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## Protocol Section ### Identification Module **NCT ID:** NCT01419379 **Acronym:** EPOCH **Brief Title:** This is a Multicenter, Prospective and Retrospective and Descriptive Epidemiology Study in Patients With Chronic Obstructive Pulmonary Disease (COPD) in Korea **Official Title:** Epidemiologic Review and Prospective Observation of COPD and Health in Korea #### Organization Study ID Info **ID:** RO-2455-401-KR #### Organization **Class:** INDUSTRY **Full Name:** Takeda #### Secondary ID Infos **Domain:** WHO **ID:** U1111-1142-0154 **Type:** REGISTRY ### Status Module #### Completion Date **Date:** 2013-01 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2013-04-18 **Type:** ESTIMATED **Last Update Submit Date:** 2013-04-16 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2013-01 **Type:** ACTUAL #### Start Date **Date:** 2011-07 **Status Verified Date:** 2013-04 #### Study First Post Date **Date:** 2011-08-18 **Type:** ESTIMATED **Study First Submit Date:** 2011-08-17 **Study First Submit QC Date:** 2011-08-17 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Takeda #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** This study is designed as a multicenter, prospective and retrospective and descriptive epidemiology study. This study is planned to evaluate 2 years of exacerbation in COPD patients and to investigate correlation of COPD disease progress and its exacerbation. This study is designed with 6 months of subject enrollments, 12 months of retrospective study, and 12 months of prospective study. Hence, each patient will be participating in the study for 12 months, while the actual data collections from the patients will take a total of 24 months. The statistical analysis of this study will be done twice, at the completion of 1 year retrospective data collection and at the completion of next 1 year follow-up. The 1st statistical analysis of retrospective study includes exacerbation rate, duration of hospitalization for exacerbation and lung function test for the past 1 year from the enrollment and comorbidities, COPD assessment (CAT) and COPD medication at the enrollment will be analyzed. The 2nd statistical analysis of prospective 1-year follow-up includes changes in exacerbation rates, comparison of lung function test results, comorbidities, COPD assessments (CAT) and COPD medications of retrospective and prospective studies for the 2 years as well as mortality rate. ### Conditions Module **Conditions:** - COPD **Keywords:** - COPD exacerbation rate ### Design Module #### Design Info **Observational Model:** COHORT #### Enrollment Info **Count:** 1118 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Label:** 1 ### Outcomes Module #### Primary Outcomes **Description:** A total of 2 years of data will be evaluated based on annual evaluations: * 1 year-before the enrollment (past 1 year) and * 1 year-after the enrollment (1 year from the enrollment) **Measure:** To investigate exacerbation rate in patients suffering from COPD **Time Frame:** 24 months #### Secondary Outcomes **Measure:** To investigate comorbidities of COPD **Time Frame:** At screening and after 12 months **Description:** Lung function test data will be collected at the time of enrollment, 1 year before the enrollment (if available) and 1 year after the enrollment. For lung function data, the closest ones to the evaluation date among those obtained from ±3 months will be used. Items to be collected are pre/post bronchodilator FEV1, FVC, FEV1/FVC. **Measure:** To determine airflow obstruction through lung function test **Time Frame:** 24 months **Description:** Patients will complete CAT (COPD Assessment Test) questionnaire. **Measure:** To assess COPD (through CAT) **Time Frame:** At screening and after 12 months **Description:** Medications for COPD treatment at the time of enrollment will be investigated. **Measure:** To know the current use of medications for COPD treatment **Time Frame:** At screening and after 12 months **Measure:** To investigate mortality of COPD patients for 1 year period **Time Frame:** 12 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Over 40 years old 2. Patient with at least 1 year of medical history of COPD as defined by GOLD criteria 3. Patient with having past 1 year medical record at the investigational site 4. Patient who signed Informed Consent Form Exclusion Criteria: 1. Patients who are currently involved in any other interventional studies or possible to be involved for the next 1 year 2. Patients currently diagnosed with cancer **Minimum Age:** 40 Years **Sampling Method:** PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Patients with COPD ### Contacts Locations Module #### Locations **Location 1:** **City:** Busan **Country:** Korea, Republic of **Facility:** Nycomed Investigational Site **Location 2:** **City:** Chungcheongnam-do **Country:** Korea, Republic of **Facility:** Nycomed Investigational Site **Location 3:** **City:** Daegu **Country:** Korea, Republic of **Facility:** Nycomed Investigational Site **Location 4:** **City:** Daejon **Country:** Korea, Republic of **Facility:** Nycomed Investigational Site **Location 5:** **City:** Gangwon-do **Country:** Korea, Republic of **Facility:** Nycomed Investigational Site **Location 6:** **City:** Gwangju **Country:** Korea, Republic of **Facility:** Nycomed Investigational Site **Location 7:** **City:** Gyeongbuk **Country:** Korea, Republic of **Facility:** Nycomed Investigational Site **Location 8:** **City:** Gyeonggi-do **Country:** Korea, Republic of **Facility:** Nycomed Investigational Site **Location 9:** **City:** Gyeongsangnam-do **Country:** Korea, Republic of **Facility:** Nycomed Investigational Site **Location 10:** **City:** Incheon **Country:** Korea, Republic of **Facility:** Nycomed Investigational Site **Location 11:** **City:** Jeollanam-do **Country:** Korea, Republic of **Facility:** Nycomed Investigational Site **Location 12:** **City:** Jeonbuk **Country:** Korea, Republic of **Facility:** Nycomed Investigational Site **Location 13:** **City:** Seoul **Country:** Korea, Republic of **Facility:** Nycomed Investigational Site **Location 14:** **City:** Ulsan **Country:** Korea, Republic of **Facility:** Nycomed Investigational Site ## Derived Section ### Condition Browse Module - Browse Branches - Abbrev: BC08 - Name: Respiratory Tract (Lung and Bronchial) Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M11168 - Name: Lung Diseases - Relevance: LOW - As Found: Unknown - ID: M11170 - Name: Lung Diseases, Obstructive - Relevance: LOW - As Found: Unknown - ID: M23449 - Name: Pulmonary Disease, Chronic Obstructive - Relevance: LOW - As Found: Unknown - ID: T1303 - Name: Chronic Graft Versus Host Disease - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03864679 **Acronym:** FATOX **Brief Title:** Investigation of Fat Oxidation During Moderate Versus Vigorous Intensity Exercise **Official Title:** Investigation of Fat and Carbohydrate Oxidation During Moderate Versus Vigorous Intensity Exercise in Healthy Volunteers With Sedentary Lifestyle #### Organization Study ID Info **ID:** Exercise 2018-1 #### Organization **Class:** OTHER **Full Name:** Latvian Institute of Organic Synthesis ### Status Module #### Completion Date **Date:** 2018-08-30 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2019-03-06 **Type:** ACTUAL **Last Update Submit Date:** 2019-03-05 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2018-08-15 **Type:** ACTUAL #### Start Date **Date:** 2018-06-18 **Type:** ACTUAL **Status Verified Date:** 2019-03 #### Study First Post Date **Date:** 2019-03-06 **Type:** ACTUAL **Study First Submit Date:** 2018-06-22 **Study First Submit QC Date:** 2019-03-05 ### Sponsor Collaborators Module #### Collaborators **Class:** UNKNOWN **Name:** Riga East University Hospital **Class:** OTHER **Name:** University of Latvia **Class:** OTHER **Name:** Riga Stradins University #### Lead Sponsor **Class:** OTHER **Name:** Latvian Institute of Organic Synthesis #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Exercise is widely suggested as an important lifestyle change for weight loss, however, the optimal level of intensity moderate versus vigorous remains unclear. It is known that in athletes, during very high-intensity exercise, fat oxidation is decreased and energy is gained mainly from carbohydrate utilization. The aim of this study is to find an optimal workload based on fat oxidation rate during exercise in volunteers with a sedentary lifestyle. **Detailed Description:** It is planned to recruit 12 healthy volunteers with a sedentary lifestyle in the study group. Since different regimens (fed, fasted and moderate versus vigorous) will be compared in the same subjects, no control group is necessary. Subjects will perform a cycling test with 5 min incremental intensity exercise and 1 h cycling test exercising at a moderate-intensity (load will be selected after the incremental intensity exercise). The expiration of carbon dioxide (CO2) and consumption of oxygen (O2) will be measured, to determine the total fatty acid and carbohydrate oxidation during cycling. Concomitantly, it is planned to measure blood lactate and glucose concentrations during exercise experiments as well as a wide range of blood biochemistry parameters before and after exercise. The investigators expect to find optimal conditions for the sedentary population for burning of fat, which is the major source of energy during moderate-intensity exercise. Measurements of the fat and carbohydrate oxidation in healthy volunteers with a sedentary lifestyle will contribute to the understanding of exercise regimens for the most effective fat oxidation. ### Conditions Module **Conditions:** - Healthy - Sedentary Lifestyle **Keywords:** - exercise - fed - fasted - fat - carbohydrate ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** BASIC_SCIENCE #### Enrollment Info **Count:** 12 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Subjects will perform a cycling tests **Intervention Names:** - Other: Exercise **Label:** Exercise **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Exercise **Description:** Subjects will perform a cycling test with 5 min incremental intensity exercise and 1 h cycling test exercising at a moderate-intensity (load will be selected in incremental intensity exercise). **Name:** Exercise **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** The exercise workload (W) for optimal fat burning during exercise **Measure:** Optimal workload **Time Frame:** 30 min accelerated load cycling exercise **Description:** Change in heart rate (BPM) from rest to the optimal workload **Measure:** Heart rate change **Time Frame:** 30 min accelerated load cycling exercise and 60 min optimal intensity cycling exercise #### Secondary Outcomes **Description:** The influence of fed and fasted state on maximal whole body fat oxidation rate during exercise **Measure:** Influence of fed and fasted state **Time Frame:** 30 min accelerated load cycling exercise ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Healthy * Sedentary lifestyle * BMI 20 - 30 kg/m2 * Be able to attend the laboratory and willing to participate in necessary protocols * Be willing to undertake the duration of the exercise protocol (3 x 1 hour) * Have the capacity and willingness to provide informed consent (oral and written) Exclusion Criteria: * athletes * Individuals with chronic cardiovascular disease such as hypertension, valve disease, coronary artery disease, cardiac conduction abnormalities, etc. * History of pneumothorax or chronic lung disease such as asthma, COPD, bronchiectasis * Active Smokers * Pregnant women **Healthy Volunteers:** True **Maximum Age:** 55 Years **Minimum Age:** 20 Years **Sex:** ALL **Standard Ages:** - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Riga **Country:** Latvia **Facility:** Latvian University **Zip:** LV-1004 #### Overall Officials **Official 1:** **Affiliation:** Riga East University Hospital **Name:** Ilze Konrade **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Annotation Section ### Unposted Annotation #### Event: RELEASE - Date: 2019-04-08 - Date Unknown: Unknown #### Event: RESET - Date: 2019-06-28 - Date Unknown: Unknown ## Derived Section ### Misc Info Module #### Submission Tracking - Estimated Results First Submit Date: 2019-04-08 ##### Submission Infos - MCP Release N: Unknown - Release Date: 2019-04-08 - Reset Date: 2019-06-28 - Unrelease Date: Unknown - Unrelease Date Unknown: Unknown - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05015179 **Brief Title:** Mixed Reality Technology in Laparoscopic Partial Nephrectomy **Official Title:** Using Mixed Reality Technology to Facilitate Laparoscopic Partial Nephrectomy #### Organization Study ID Info **ID:** 38/124-25 #### Organization **Class:** OTHER **Full Name:** St. Petersburg State Pavlov Medical University ### Status Module #### Completion Date **Date:** 2021-03-01 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2021-08-20 **Type:** ACTUAL **Last Update Submit Date:** 2021-08-14 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2021-02-01 **Type:** ACTUAL #### Start Date **Date:** 2020-06-01 **Type:** ACTUAL **Status Verified Date:** 2021-08 #### Study First Post Date **Date:** 2021-08-20 **Type:** ACTUAL **Study First Submit Date:** 2021-08-07 **Study First Submit QC Date:** 2021-08-14 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** Saint Petersburg State University, Russia #### Lead Sponsor **Class:** OTHER **Name:** St. Petersburg State Pavlov Medical University #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** The aim of our study was: a) to evaluate the usefulness of the MR model for renal pedicle exposure and identification of the tumor's exact location during LPN, and b) to evaluate the subjective utility of the MR model as an intraoperative reference tool. Investigators prospectively enrolled 47 patients with LPN between June 2020 and February 2021. Patients were randomly assigned into two groups: the control group (24 patients), who underwent operation with an intraoperative ultrasound (US) control and the experimental group (23 patients), who underwent operation with the aid of the MR model. Randomization was performed using a computerized randomization program and sealed envelopes. Patients were included in the study if they were 18 years of age or older, were able to sign informed consent, and had T1a renal tumors amenable to LPN. Patients were excluded if they were unwilling to participate or did not meet the inclusion criteria. For each patient, investigators prospectively collected demographic data including age, body mass index, clinical tumor size, side, location, and complexity score according to the PADUA scoring system; perioperative data (including time for renal pedicle exposure and time for renal tumor detection and duration of ischemia); pathological data; data on postoperative functional outcome and complications, classified according to the Clavien-Dindo system. ### Conditions Module **Conditions:** - Kidney Tumor ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** SINGLE **Who Masked:** - INVESTIGATOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 47 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Laparoscopic partial nephrectomy is performed with an intraoperative ultrasound (US) control **Label:** Control **Type:** NO_INTERVENTION #### Arm Group 2 **Description:** Underwent Laparoscopic partial nephrectomy with the aid of the mixed reality model **Intervention Names:** - Procedure: mixed reality technology in laparoscopic partial nephrectomy **Label:** Experimental **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Experimental **Description:** All patients undergo contrast-enhanced computed tomography before surgery. DICOM files are converted to a 3D model. This model is then sent to HoloLens 2 smart glasses using HLOIA software **Name:** mixed reality technology in laparoscopic partial nephrectomy **Type:** PROCEDURE ### Outcomes Module #### Primary Outcomes **Measure:** time required to expose renal pedicle during laparoscopic partial nephrectomy **Time Frame:** during operation completion, min **Measure:** time required to get from renal pedicle to tumor during laparoscopic partial nephrectomy **Time Frame:** during operation completion, min ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * able to sign informed consent * had T1a renal tumors amenable to LPN Exclusion Criteria: * were unwilling to participate * did not meet the inclusion criteria **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Saint Petersburg **Country:** Russian Federation **Facility:** Saint Petersburg State University Hospital ### IPD Sharing Statement Module **IPD Sharing:** UNDECIDED ## Derived Section ### Condition Browse Module - Ancestors - ID: D000014571 - Term: Urologic Neoplasms - ID: D000014565 - Term: Urogenital Neoplasms - ID: D000009371 - Term: Neoplasms by Site - ID: D000009369 - Term: Neoplasms - ID: D000052776 - Term: Female Urogenital Diseases - ID: D000005261 - Term: Female Urogenital Diseases and Pregnancy Complications - ID: D000091642 - Term: Urogenital Diseases - ID: D000007674 - Term: Kidney Diseases - ID: D000014570 - Term: Urologic Diseases - ID: D000052801 - Term: Male Urogenital Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BXS - Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M10703 - Name: Kidney Neoplasms - Relevance: HIGH - As Found: Kidney tumors - ID: M17320 - Name: Urologic Neoplasms - Relevance: LOW - As Found: Unknown - ID: M17315 - Name: Urogenital Neoplasms - Relevance: LOW - As Found: Unknown - ID: M2875 - Name: Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M27093 - Name: Female Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M14127 - Name: Pregnancy Complications - Relevance: LOW - As Found: Unknown - ID: M8399 - Name: Female Urogenital Diseases and Pregnancy Complications - Relevance: LOW - As Found: Unknown - ID: M10698 - Name: Kidney Diseases - Relevance: LOW - As Found: Unknown - ID: M17319 - Name: Urologic Diseases - Relevance: LOW - As Found: Unknown - ID: M27095 - Name: Male Urogenital Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000007680 - Term: Kidney Neoplasms ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT01973179 **Acronym:** ReKo **Brief Title:** Re-irradiation of Recurrent Head and Neck Cancer **Official Title:** Observational Study to Re-irradiation for Recurrent Head and Neck Cancer #### Organization Study ID Info **ID:** STR-ReKo-2013 #### Organization **Class:** OTHER **Full Name:** Technische Universität Dresden ### Status Module #### Completion Date **Date:** 2026-12 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-01-17 **Type:** ACTUAL **Last Update Submit Date:** 2024-01-15 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2024-12 **Type:** ESTIMATED #### Start Date **Date:** 2015-07 **Status Verified Date:** 2024-01 #### Study First Post Date **Date:** 2013-10-31 **Type:** ESTIMATED **Study First Submit Date:** 2013-10-25 **Study First Submit QC Date:** 2013-10-25 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Technische Universität Dresden #### Responsible Party **Investigator Affiliation:** Technische Universität Dresden **Investigator Full Name:** Mechthild Krause **Investigator Title:** Prof. Dr. med. **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** The goal of this observational study is to evaluate the toxicity and local tumor control of proton therapy for patients with head and neck cancer in a previously irradiated field. Standard of care for recurrent or secondary malignancies in a previously irradiated field is surgery. For inoperable patients or residual tumor after surgery, standard of care would be palliative chemotherapy. For a small subset of patients (good performance status, small radiation fields) re-irradiation can be performed. In this study the established concept of re-irradiation with photons will be transferred to proton radiotherapy. Proton therapy has the advantage of a steeper dose gradient to normal tissues, thus-theoretical advantages for lower toxicity. **Detailed Description:** OBJECTIVES: Primary: Evaluation of late toxicity of re-irradiation with protons, for patients with head and neck cancer in a previously (\> 50 Gy) irradiated field. Secondary: Evaluation of the efficacy (local control) and acute toxicity (after 24 Months) of re-irradiation with protons up to a dose of 60 Gy, for patients with head and neck cancer in a previously (\> 50 Gy) irradiated field. OUTLINE This is a single center observational study. In-house standard of care for patients (good performance status and with small tumors) with head and neck cancer in a previously (\> 50 Gy) irradiated field is to irradiate the tumor with a hyperfractionated schedule and concurrent cisplatin up to a dose of 66 Gy. Dose limiting for this schedule is the incidence of acute and late toxicity induced by radiation. The purpose of the study is the evaluation of the safety of a treatment schedule based on the use of protons. Proton beam treatments will be delivered in 2 Gy fractions, 5 days per week, to a total dose of 60-66 Gy equivalent. Study visits are performed: During proton therapy once per week. Follow-up visits are scheduled every 3 months for the first 24 months after proton therapy. Primary endpoint is late toxicity 24 months after proton treatment. ### Conditions Module **Conditions:** - Head-and-neck Carcinoma ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 50 **Type:** ESTIMATED **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Radiotherapy with protons in patients with head and neck carcinoma **Intervention Names:** - Radiation: Radiation therapy **Label:** Radiation therapy ### Interventions #### Intervention 1 **Arm Group Labels:** - Radiation therapy **Description:** Radiation therapy with protons **Name:** Radiation therapy **Type:** RADIATION ### Outcomes Module #### Primary Outcomes **Description:** measured from the first day of treatment **Measure:** late toxicity **Time Frame:** 24 months after therapy #### Secondary Outcomes **Description:** measured from the first day of treatment **Measure:** acute toxicity **Time Frame:** 3 months after treatment **Description:** measured from the first day of treatment **Measure:** local recurrence free survival **Time Frame:** 24 months after therapy **Description:** measured from the first day of treatment **Measure:** overall survival **Time Frame:** 24 months after therapy **Description:** measured from the first day of treatment **Measure:** quality of life **Time Frame:** 24 months after therapy ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * tumor is located in a previously irradiated area with at least 50 Gy or there is an overlap of radiation fields with resulting total doses greater than 90 Gy to expect * tumor size and localization allow high dose re-irradiation (individual decision) * exclusion of distant metastases * Time interval between pre-irradiation and re- irradiation at least 1 year for local recurrence; at least 6 months for secondary tumor disease * age ≥ 18 years * previous radiotherapy treatment plans available * pre-treatment imaging (pre re-irradiation) available * good general condition (ECOG 0-1) * dental treatment performed, if necessary * in case of surgery before re-irradiation: resection status is R-1 or R-2 * clinical suspicion of residual tumor by very scarce surgical margins (\<1 mm) * pathological secured extracapsular extension (ECE) * indications by an interdisciplinary tumor board * patient able to understand the intention and procedures of the trial, written informed consent Exclusion Criteria: * no description of the R- status after resection of the tumour * pregnancy * no written informed consent * distant metastases * interval between first and second irradiation \< 6 months at secondary tumor or \<1 year when local recurrence of previously irradiated tumor * simultaneous participation in another intervention study , if further treatment must be carried out **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Patients with a recurrent or secondary head and neck carcinoma ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Mechthild Krause, Prof. **Role:** CONTACT #### Locations **Location 1:** **City:** Dresden **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Mechthild Krause, Prof. - **Role:** CONTACT ***Contact 2:*** - **Name:** Mechthild Krause, Prof. - **Role:** PRINCIPAL_INVESTIGATOR **Country:** Germany **Facility:** Dresden University of Technology, University Hospital Carl Gustav Carus, Department of Radiation Therapy and Radiation Oncology; and DKTK partner site Dresden **State:** Saxony **Status:** RECRUITING **Zip:** 01307 #### Overall Officials **Official 1:** **Affiliation:** Dresden University of Technology, University Hospital Carl Gustav Carus, Department of Radiation Therapy and Radiation Oncology; and DKTK partner site Dresden **Name:** Mechthild Krause, Prof. **Role:** STUDY_CHAIR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009371 - Term: Neoplasms by Site - ID: D000009369 - Term: Neoplasms ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology ### Condition Browse Module - Browse Leaves - ID: M9348 - Name: Head and Neck Neoplasms - Relevance: HIGH - As Found: Head and Neck Cancer - ID: M5534 - Name: Carcinoma - Relevance: LOW - As Found: Unknown - ID: M14850 - Name: Recurrence - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000006258 - Term: Head and Neck Neoplasms ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT02238379 **Brief Title:** Intranasal Oxytocin Administration and the Neural Correlates of Social and Non-Social Visual Perception **Official Title:** Oxytocin Pilot: Oxytocin and Face Perception #### Organization Study ID Info **ID:** 1309012677 #### Organization **Class:** OTHER **Full Name:** Yale University ### Status Module #### Completion Date **Date:** 2015-12 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2018-01-17 **Type:** ACTUAL **Last Update Submit Date:** 2018-01-12 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2015-12 **Type:** ACTUAL #### Results First Post Date **Date:** 2017-05-25 **Type:** ACTUAL **Results First Submit Date:** 2016-11-28 **Results First Submit QC Date:** 2017-05-19 #### Start Date **Date:** 2014-09 **Status Verified Date:** 2018-01 #### Study First Post Date **Date:** 2014-09-12 **Type:** ESTIMATED **Study First Submit Date:** 2014-09-04 **Study First Submit QC Date:** 2014-09-09 ### Sponsor Collaborators Module #### Collaborators **Class:** UNKNOWN **Name:** Anna Freud Centre #### Lead Sponsor **Class:** OTHER **Name:** Yale University #### Responsible Party **Type:** SPONSOR ### Description Module **Brief Summary:** The objective of this study is to investigate the effects of oxytocin on social behavior and brain activity using EEG and the event-related potential (ERP) technique. The value of EEG is its high temporal specificity, enabling precision in the timing of social behavior to be addressed. In order to elicit social responses in the human brain, a variety of social and emotional visual stimuli will be presented during EEG recording, namely infant and adult faces and houses. Brain responses after intranasal oxytocin will then be compared with placebo, to examine the effect of intranasal oxytocin on central nervous system activity. We hypothesize that intranasal oxytocin will enhance the neural response to social stimuli (infant and adult faces) but not to non-social stimuli (houses). ### Conditions Module **Conditions:** - Social Perception **Keywords:** - Intranasal oxytocin - Social perception - EEG/ERP ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** CROSSOVER ##### Masking Info **Masking:** DOUBLE **Who Masked:** - PARTICIPANT - INVESTIGATOR **Primary Purpose:** BASIC_SCIENCE #### Enrollment Info **Count:** 26 **Type:** ACTUAL **Phases:** - EARLY_PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Each participant will receive both the oxytocin nasal spray in one visit AND the placebo nasal spray in another visit (randomized) in this design. **Intervention Names:** - Drug: Oxytocin **Label:** Oxytocin **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Each participant will receive both the oxytocin nasal spray in one visit AND the placebo nasal spray in another visit (randomized) in this design. **Intervention Names:** - Other: Placebo **Label:** Placebo **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Oxytocin **Description:** 24 International Units of Oxytocin in a Nasal Spray **Name:** Oxytocin **Other Names:** - Pitocin **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Placebo **Description:** Placebo will contain all ingredients except the active oxytocin in the Nasal Spray. **Name:** Placebo **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** The investigators will analyze the amplitude (i.e., size) of visually elicited event-related potential (ERP) components to the social stimuli (infant and adult faces). This assessment will be completed after administration of the intervention (oxytocin) and the placebo to compare the neural response. The investigators hypothesize that the intervention will modulate the amplitude of the neural response to social stimuli given its previously identified role in social interactions, most likely increasing the size of the ERPs. **Measure:** Amplitude Social **Time Frame:** Duration of 30 minutes **Description:** The investigators analyze the amplitude (i.e., size) of visually elicited event-related potential (ERP) components to the non-social stimuli (houses). This assessment will be completed after administration of the intervention (oxytocin) and the placebo to compare the neural response. The investigators hypothesize that there will be no difference between the intervention and placebo during the non-social condition on the amplitude of the ERPs. **Measure:** Amplitude Non-Social **Time Frame:** Duration of 30 minutes **Description:** The investigators analyze the latency (i.e., efficiency of processing) of visually elicited ERP components to the social stimuli (infant and adult faces). This assessment will be completed after administration of the intervention (oxytocin) and the placebo to compare the neural response. The investigators hypothesize that there will be more efficient processing (i.e., earlier latency) of ERPs during the social condition following administration of the intervention relative to the placebo condition. **Measure:** Latency Social **Time Frame:** Duration of 30 minutes **Description:** The investigators will analyze the latency (i.e., efficiency of processing) of visually elicited ERP components to the non-social stimuli (houses). This assessment will be completed after administration of the intervention (oxytocin) and the placebo to compare the neural response. The investigators hypothesize that there will be no difference between the intervention and placebo on ERP latency measures in the non-social condition. **Measure:** Latency Non-Social **Time Frame:** Duration of 30 minutes #### Secondary Outcomes **Description:** The investigators will assess depression by employing the Beck Depression Inventory (Beck et al., 1961). Specifically addressing whether the level of depression symptomatology in participants and whether this is associated with the neural correlates of social and non-social perception during both intervention and placebo visits. It is not yet known the extent to which variation in depression symptoms are associated with this methodology, although prior research has suggested depression modulates the neural response to social cues. This measure includes a question regarding suicidal ideation and therefore it is acknowledged there may be a safety issue in response to the questionnaire. Scores range from 0-63, with higher scores indicating greater levels of depression (scores 29+ indicates severe depression). **Measure:** Depression **Time Frame:** Within 20 minutes of study visit commencing **Description:** Participants will complete a CO breathalyzer and the Fagerstrom Test for Nicotine Dependence (Heatherton, Kozlowski, Frecker, \& Fagerstrom, 1991) to assess smoking behavior. These measures are included to characterize the sample in respect of substance use. **Measure:** Smoking **Time Frame:** Within 30 minutes of study visit commencing **Description:** The investigators will assess anxiety using the State-Trait Anxiety Inventory (Spielberger et al., 1970). Specifically, it will be explored whether participant anxiety symptoms are associated with the neural correlates of social and non-social perception during both intervention and placebo visits. It is not yet known the extent to which variation in anxiety symptoms are associated with this methodology, although prior research has suggested anxiety modulates the neural response to social cues. Scores range from 20-80 and a higher score on both state and trait measures indicate higher levels of anxiety. A potential clinical cut off has been proposed for participants scoring over 39-40 as being high anxious. **Measure:** Anxiety **Time Frame:** Within 20 minutes of study visit commencing **Description:** The investigators will measure current levels of stress by using the Perceived Stress Scale (Cohen et al., 1983). It is not yet known the extent to which variation in perceived stress is associated with this methodology, but it is anticipated stress will be associated with levels of depression and anxiety in the sample. The PSS consists of 14 items, with scores ranging from 0 to 42, with higher scores indicating higher levels of perceived stress. A score of 21+ is considered to indicate that participants have higher than average stress. **Measure:** Stress **Time Frame:** Within 20 minutes of study visit commencing **Description:** The investigators will employ the Parental Bonding Instrument (Parker, Tupling, \& Brown, 1979) to assess the early relationship experiences participants have with their caregivers. Existing research employing intranasal oxytocin suggests that the quality of early relationships may impact the strength of any modulation of brain or behavior by oxytocin administration and therefore this variable will be included in the analyses in support of this hypothesis. There are 12 items that capture parental care and 13 items that capture parental overprotection. Items are scored on a 4-point likert scale from "very like" to "very unlike". The PBI is typically scored by identifying optimal (High Care Scores, Low Protection Scores) and less optimal (Low Care Scores, Low Protection Scores) scores on the mother and father subscales (NB: protection refers to overprotection). For the care items, scores can range from 0 to 36; for overprotection items, scores can range from 0 to 39. **Measure:** Early Experience **Time Frame:** Within 20 minutes of study visit commencing **Description:** The investigators will employ the ASI Lite (McLellan, Luborsky, Woody, \& O'Brien, 1980) to assess for current substance use. This measure is included to characterize the sample in respect of substance use; however the ASI Lite did not provide a measure of substance dependance and therefore we report the data from the Mini International Neuropsychiatric Interview substance dependance module (Sheehan et al., 1998) to provide a specific indication of the presence of absence of substance dependance. **Measure:** Number of Participants Endorsing Substance Use **Time Frame:** Within 30 minutes of study visit commencing **Description:** Participants will complete an alcohol breathalyzer to characterize the alcohol use status of the sample. **Measure:** Number of Participants Testing Positive for Alcohol Use Following a Breathalyzer **Time Frame:** Within 30 minutes of study visit commencing ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Adults ages 18-64 * Good medical health * Ability to understand and speak English Exclusion Criteria: * Pregnancy * Medical Illnesses: Moderate or severe acute or chronic medical illnesses (e.g. cardiac disease, diabetes, epilepsy, influenza). * Cardiovascular risk factors: History of hypertension with baseline blood pressure above 140 mm Hg (systolic) over 90 mm Hg (diastolic). Also any history of syncope and/or baseline blood pressure below 100 mm Hg (systolic). * CNS disease: Known history of brain abnormalities (e.g., neoplasms, subarachnoid cysts), cerebrovascular disease, infectious disease (e.g., abscess), other central nervous system disease, or history of head trauma which resulted in a persistent neurologic deficit or loss of consciousness \> 3 minutes. * Medication status: Individuals on stable doses of a neuroleptic and/or an antidepressant medication for at least the past 6 weeks will be allowed to participate in this study. The use of other psychotropic medications will not be allowed. Females taking contraceptive hormones will not be able to participate in the study. * A history of seizures or current use of anticonvulsants; history of head injury with loss of consciousness **Healthy Volunteers:** True **Maximum Age:** 64 Years **Minimum Age:** 18 Years **Sex:** FEMALE **Standard Ages:** - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** New Haven **Country:** United States **Facility:** Yale Child Study Center **State:** Connecticut **Zip:** 06520 #### Overall Officials **Official 1:** **Affiliation:** Yale University **Name:** Linda C Mayes, MD **Role:** PRINCIPAL_INVESTIGATOR **Official 2:** **Affiliation:** Yale University **Name:** Helena JV Rutherford, PhD **Role:** STUDY_DIRECTOR ## Derived Section ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M21089 - Name: Facies - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Ancestors - ID: D000010120 - Term: Oxytocics - ID: D000012102 - Term: Reproductive Control Agents - ID: D000045505 - Term: Physiological Effects of Drugs ### Intervention Browse Module - Browse Branches - Abbrev: Repr - Name: Reproductive Control Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M13041 - Name: Oxytocin - Relevance: HIGH - As Found: Joint ### Intervention Browse Module - Meshes - ID: D000010121 - Term: Oxytocin ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module #### Event Groups **Group ID:** EG000 **Title:** Oxytocin **Description:** Each participant will receive both the oxytocin nasal spray in one visit AND the placebo nasal spray in another visit (randomized) in this design. Oxytocin: 24 International Units of Oxytocin in a Nasal Spray **ID:** EG000 **Other Num at Risk:** 26 **Serious Number At Risk:** 26 **Title:** Oxytocin **Group ID:** EG001 **Title:** Placebo **Description:** Each participant will receive both the oxytocin nasal spray in one visit AND the placebo nasal spray in another visit (randomized) in this design. Placebo: Placebo will contain all ingredients except the active oxytocin in the Nasal Spray. **ID:** EG001 **Other Num at Risk:** 25 **Serious Number At Risk:** 25 **Title:** Placebo **Frequency Threshold:** 0 ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 12 **Group ID:** BG001 **Value:** 14 **Group ID:** BG002 **Value:** 26 **Units:** Participants ### Group **ID:** BG000 **Title:** Oxytocin **Description:** Each participant will receive both the oxytocin nasal spray in one visit AND the placebo nasal spray in another visit (randomized) in this design. Oxytocin: 24 International Units of Oxytocin in a Nasal Spray ### Group **ID:** BG001 **Title:** Placebo **Description:** Each participant will receive both the oxytocin nasal spray in one visit AND the placebo nasal spray in another visit (randomized) in this design. Placebo: Placebo will contain all ingredients except the active oxytocin in the Nasal Spray. ### Group **ID:** BG002 **Title:** Total **Description:** Total of all reporting groups ### Measure #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** <=18 years #### Measurement **Group ID:** BG000 **Value:** 12 #### Measurement **Group ID:** BG001 **Value:** 14 #### Measurement **Group ID:** BG002 **Value:** 26 **Category Title:** Between 18 and 65 years #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** >=65 years **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Spread:** 3 **Value:** 24 #### Measurement **Group ID:** BG001 **Spread:** 3 **Value:** 23 #### Measurement **Group ID:** BG002 **Spread:** 3 **Value:** 24 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 12 #### Measurement **Group ID:** BG001 **Value:** 14 #### Measurement **Group ID:** BG002 **Value:** 26 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** Male **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 12 #### Measurement **Group ID:** BG001 **Value:** 14 #### Measurement **Group ID:** BG002 **Value:** 26 **Class Title:** United States **Denomination Units Selected:** ## Results Section - Baseline Characteristics Module ### Measure 1 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Age, Categorical **Unit of Measure:** Participants ### Measure 2 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** Age, Continuous **Unit of Measure:** years ### Measure 3 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Sex: Female, Male **Unit of Measure:** Participants ### Measure 4 **Parameter Type:** NUMBER **Title:** Region of Enrollment **Unit of Measure:** participants **Population Description:** 1 participant was lost to follow up for their placebo visit (determined after blind was broken). ## Results Section - More Information Module ### Certain Agreement **PI Sponsor Employee:** True ### Limitations and Caveats **Description:** Small sample size limiting the interpretations of ERP differences between oxytocin and placebo conditions and individual difference measures. ### Point of Contact **Email:** [email protected] **Organization:** Yale University **Phone:** 203-737-3408 **Title:** Dr. Helena Rutherford ## Results Section - Outcome Measures Module ### Outcome Measure 1 #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** N170 Analysis **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** .003 **P-Value Comment:** Main Effect of Emotion **Parameter Type:** **Parameter Value:** **Statistical Comment:** Spray (Oxytocin, Placebo) by Face Type (Infant, Adult) by Emotion (Distress, Neutral) by Hemisphere (Left, Right) ANOVA **Statistical Method:** ANOVA **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** N170 Analysis **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** .034 **P-Value Comment:** Main Effect of Face Type **Parameter Type:** **Parameter Value:** **Statistical Comment:** Spray (Oxytocin, Placebo) by Face Type (Infant, Adult) by Emotion (Distress, Neutral) by Hemisphere (Left, Right) ANOVA **Statistical Method:** ANOVA **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** P300 Analysis **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** .03 **P-Value Comment:** Main Effect of Face Type **Parameter Type:** **Parameter Value:** **Statistical Comment:** Spray Type (Oxytocin, Placebo) by Face Type (Infant, Adult) by Emotion (Distress, Neutral) ANOVA **Statistical Method:** ANOVA **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** P300 Analysis **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** .03 **P-Value Comment:** Spray Type by Face Type Interaction **Parameter Type:** **Parameter Value:** **Statistical Comment:** Spray Type (Oxytocin, Placebo) by Face Type (Infant, Adult) by Emotion (Distress, Neutral) ANOVA **Statistical Method:** ANOVA **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** LPP Analysis **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** >.22 **P-Value Comment:** No Main Effects or Interactions **Parameter Type:** **Parameter Value:** **Statistical Comment:** Spray Type (Oxytocin, Placebo) by Face Type (Infant, Adult) by Emotion (Distress, Neutral) ANOVA **Statistical Method:** ANOVA **Tested Non-Inferiority:** ### Outcome Measure 2 #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** N170 Analysis **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** >.14 **P-Value Comment:** No Main Effects or Interactions **Parameter Type:** **Parameter Value:** **Statistical Comment:** Spray Type (Oxytocin, Placebo) and Hemisphere (left, right) ANOVA **Statistical Method:** ANOVA **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** P300 Analysis **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** >.17 **P-Value Comment:** No difference between Spray Types **Parameter Type:** **Parameter Value:** **Statistical Comment:** Paired samples t-test comparing Spray Type (Oxytocin vs Placebo) **Statistical Method:** t-test, 2 sided **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** LPP Analysis **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** >.27 **P-Value Comment:** No difference between Spray Types **Parameter Type:** **Parameter Value:** **Statistical Comment:** Paired samples t-test comparing Spray Type (Oxytocin vs Placebo) **Statistical Method:** t-test, 2 sided **Tested Non-Inferiority:** ### Outcome Measure 3 #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Only relevant for N170 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** .006 **P-Value Comment:** Main Effect of Emotion **Parameter Type:** **Parameter Value:** **Statistical Comment:** Spray Type (Oxytocin, Placebo), Face Type (Infant, Adult), Emotion (Neutral, Distressed), and Hemisphere (left, right) ANOVA **Statistical Method:** ANOVA **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Only relevant for N170 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** .01 **P-Value Comment:** Main Effect of Hemisphere **Parameter Type:** **Parameter Value:** **Statistical Comment:** Spray Type (Oxytocin, Placebo), Face Type (Infant, Adult), Emotion (Neutral, Distressed), and Hemisphere (left, right) ANOVA **Statistical Method:** ANOVA **Tested Non-Inferiority:** ### Outcome Measure 4 #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Only relevant for N170 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** .03 **P-Value Comment:** Main Effect of Spray **Parameter Type:** **Parameter Value:** **Statistical Comment:** Spray (oxytocin, placebo) by Hemisphere (left, right) ANOVA **Statistical Method:** ANOVA **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Only relevant for N170 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** .008 **P-Value Comment:** Main Effect of Hemisphere **Parameter Type:** **Parameter Value:** **Statistical Comment:** Spray (oxytocin, placebo) by Hemisphere (left, right) ANOVA **Statistical Method:** ANOVA **Tested Non-Inferiority:** ### Outcome Measure 5 #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** .05 **P-Value Comment:** **Parameter Type:** **Parameter Value:** **Statistical Comment:** **Statistical Method:** correlation **Tested Non-Inferiority:** ### Outcome Measure 6 ### Outcome Measure 7 #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** .05 **P-Value Comment:** **Parameter Type:** **Parameter Value:** **Statistical Comment:** **Statistical Method:** correlation **Tested Non-Inferiority:** ### Outcome Measure 8 #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** .05 **P-Value Comment:** **Parameter Type:** **Parameter Value:** **Statistical Comment:** **Statistical Method:** correlation **Tested Non-Inferiority:** ### Outcome Measure 9 #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** .05 **P-Value Comment:** **Parameter Type:** **Parameter Value:** **Statistical Comment:** **Statistical Method:** correlation **Tested Non-Inferiority:** ### Outcome Measure 10 ### Outcome Measure 11 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 2.81 - **Upper Limit:** - **Value:** -3.72 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 2.64 - **Upper Limit:** - **Value:** -3.55 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 24 - **Group ID:** OG001 - **Value:** 24 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 2.55 - **Upper Limit:** - **Value:** -3.28 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 2.94 - **Upper Limit:** - **Value:** -3.30 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 24 - **Group ID:** OG001 - **Value:** 24 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 2.72 - **Upper Limit:** - **Value:** -3.70 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 2.64 - **Upper Limit:** - **Value:** -3.27 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 24 - **Group ID:** OG001 - **Value:** 24 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 2.48 - **Upper Limit:** - **Value:** -3.23 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 2.33 - **Upper Limit:** - **Value:** -2.87 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 24 - **Group ID:** OG001 - **Value:** 24 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.26 - **Upper Limit:** - **Value:** 0.94 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.21 - **Upper Limit:** - **Value:** 0.50 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 24 - **Group ID:** OG001 - **Value:** 24 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.47 - **Upper Limit:** - **Value:** 1.10 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.34 - **Upper Limit:** - **Value:** 0.55 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 24 - **Group ID:** OG001 - **Value:** 24 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.22 - **Upper Limit:** - **Value:** 0.65 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.91 - **Upper Limit:** - **Value:** 0.39 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 24 - **Group ID:** OG001 - **Value:** 24 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.38 - **Upper Limit:** - **Value:** 0.52 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.09 - **Upper Limit:** - **Value:** 0.61 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 24 - **Group ID:** OG001 - **Value:** 24 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.53 - **Upper Limit:** - **Value:** -0.56 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.94 - **Upper Limit:** - **Value:** -0.50 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 23 - **Group ID:** OG001 - **Value:** 23 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.40 - **Upper Limit:** - **Value:** -0.24 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.51 - **Upper Limit:** - **Value:** -0.54 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 23 - **Group ID:** OG001 - **Value:** 23 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.33 - **Upper Limit:** - **Value:** -0.38 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.40 - **Upper Limit:** - **Value:** -0.57 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 23 - **Group ID:** OG001 - **Value:** 23 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.49 - **Upper Limit:** - **Value:** -0.71 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.27 - **Upper Limit:** - **Value:** -0.40 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 23 - **Group ID:** OG001 - **Value:** 23 **Units:** Participants #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.71 - **Upper Limit:** - **Value:** -1.15 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.35 - **Upper Limit:** - **Value:** -1.15 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.47 - **Upper Limit:** - **Value:** 1.21 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.91 - **Upper Limit:** - **Value:** 0.86 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.12 - **Upper Limit:** - **Value:** -0.58 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.06 - **Upper Limit:** - **Value:** -0.32 **Title:** #### Outcome Measure 3 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 8 - **Upper Limit:** - **Value:** 164 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 10 - **Upper Limit:** - **Value:** 164 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 9 - **Upper Limit:** - **Value:** 163 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 9 - **Upper Limit:** - **Value:** 161 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 10 - **Upper Limit:** - **Value:** 164 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 12 - **Upper Limit:** - **Value:** 163 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 9 - **Upper Limit:** - **Value:** 161 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 11 - **Upper Limit:** - **Value:** 161 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 9 - **Upper Limit:** - **Value:** 165 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 10 - **Upper Limit:** - **Value:** 166 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 8 - **Upper Limit:** - **Value:** 164 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 9 - **Upper Limit:** - **Value:** 162 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 11 - **Upper Limit:** - **Value:** 165 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 10 - **Upper Limit:** - **Value:** 163 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 7 - **Upper Limit:** - **Value:** 161 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 9 - **Upper Limit:** - **Value:** 160 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 11 - **Upper Limit:** - **Value:** 166 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 14 - **Upper Limit:** - **Value:** 165 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 9 - **Upper Limit:** - **Value:** 162 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 9 - **Upper Limit:** - **Value:** 161 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 10 - **Upper Limit:** - **Value:** 163 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 13 - **Upper Limit:** - **Value:** 162 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 8 - **Upper Limit:** - **Value:** 159 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 10 - **Upper Limit:** - **Value:** 160 **Title:** #### Outcome Measure 4 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 13 - **Upper Limit:** - **Value:** 171 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 14 - **Upper Limit:** - **Value:** 174 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 9 - **Upper Limit:** - **Value:** 166 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 13 - **Upper Limit:** - **Value:** 169 **Title:** #### Outcome Measure 5 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 6.06 - **Upper Limit:** - **Value:** 4.00 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 5.75 - **Upper Limit:** - **Value:** 4.33 **Title:** #### Outcome Measure 6 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** #### Outcome Measure 7 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 10.67 - **Upper Limit:** - **Value:** 31.54 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 11.27 - **Upper Limit:** - **Value:** 35.50 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 10.11 - **Upper Limit:** - **Value:** 30.58 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 7.82 - **Upper Limit:** - **Value:** 30.79 **Title:** #### Outcome Measure 8 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 8.28 - **Upper Limit:** - **Value:** 17.54 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 8.23 - **Upper Limit:** - **Value:** 18.13 **Title:** #### Outcome Measure 9 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 6.69 - **Upper Limit:** - **Value:** 30.13 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 6.79 - **Upper Limit:** - **Value:** 29.50 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 24 - **Group ID:** OG001 - **Value:** 24 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 8.67 - **Upper Limit:** - **Value:** 27.74 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 8.95 - **Upper Limit:** - **Value:** 28.13 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 23 - **Group ID:** OG001 - **Value:** 23 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 8.01 - **Upper Limit:** - **Value:** 13.71 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 8.51 - **Upper Limit:** - **Value:** 13.75 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 24 - **Group ID:** OG001 - **Value:** 24 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 8.30 - **Upper Limit:** - **Value:** 11.91 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 9.34 - **Upper Limit:** - **Value:** 10.91 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 23 - **Group ID:** OG001 - **Value:** 23 **Units:** Participants #### Outcome Measure 10 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 **Title:** #### Outcome Measure 11 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** The investigators will analyze the amplitude (i.e., size) of visually elicited event-related potential (ERP) components to the social stimuli (infant and adult faces). This assessment will be completed after administration of the intervention (oxytocin) and the placebo to compare the neural response. The investigators hypothesize that the intervention will modulate the amplitude of the neural response to social stimuli given its previously identified role in social interactions, most likely increasing the size of the ERPs. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** 1 participant was lost to follow-up (did not complete placebo); 1 participant's data was lost (removed then from placebo and oxytocin arms); for LPP analysis, 1 participant was a statistical outlier and removed from oxytocin and placebo arms **Reporting Status:** POSTED **Time Frame:** Duration of 30 minutes **Title:** Amplitude Social **Type:** PRIMARY **Unit of Measure:** microvolts ##### Group **Description:** Each participant will receive both the oxytocin nasal spray in one visit AND the placebo nasal spray in another visit (randomized) in this design. Oxytocin: 24 International Units of Oxytocin in a Nasal Spray **ID:** OG000 **Title:** Oxytocin ##### Group **Description:** Each participant will receive both the oxytocin nasal spray in one visit AND the placebo nasal spray in another visit (randomized) in this design. Placebo: Placebo will contain all ingredients except the active oxytocin in the Nasal Spray. **ID:** OG001 **Title:** Placebo #### Outcome Measure 2 **Description:** The investigators analyze the amplitude (i.e., size) of visually elicited event-related potential (ERP) components to the non-social stimuli (houses). This assessment will be completed after administration of the intervention (oxytocin) and the placebo to compare the neural response. The investigators hypothesize that there will be no difference between the intervention and placebo during the non-social condition on the amplitude of the ERPs. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** 1 participant was lost to follow-up (did not complete placebo); 1 participant's data was lost (removed then from placebo and oxytocin arms) **Reporting Status:** POSTED **Time Frame:** Duration of 30 minutes **Title:** Amplitude Non-Social **Type:** PRIMARY **Unit of Measure:** microvolts ##### Group **Description:** Each participant will receive both the oxytocin nasal spray in one visit AND the placebo nasal spray in another visit (randomized) in this design. Oxytocin: 24 International Units of Oxytocin in a Nasal Spray **ID:** OG000 **Title:** Oxytocin ##### Group **Description:** Each participant will receive both the oxytocin nasal spray in one visit AND the placebo nasal spray in another visit (randomized) in this design. Placebo: Placebo will contain all ingredients except the active oxytocin in the Nasal Spray. **ID:** OG001 **Title:** Placebo #### Outcome Measure 3 **Description:** The investigators analyze the latency (i.e., efficiency of processing) of visually elicited ERP components to the social stimuli (infant and adult faces). This assessment will be completed after administration of the intervention (oxytocin) and the placebo to compare the neural response. The investigators hypothesize that there will be more efficient processing (i.e., earlier latency) of ERPs during the social condition following administration of the intervention relative to the placebo condition. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** 1 participant was lost to follow-up (did not complete placebo); 1 participant's data was lost (removed then from placebo and oxytocin arms); for LPP analysis, 1 participants were statistical outliers and removed from oxytocin and placebo arms for N170 latency analysis **Reporting Status:** POSTED **Time Frame:** Duration of 30 minutes **Title:** Latency Social **Type:** PRIMARY **Unit of Measure:** milliseconds ##### Group **Description:** Each participant will receive both the oxytocin nasal spray in one visit AND the placebo nasal spray in another visit (randomized) in this design. Oxytocin: 24 International Units of Oxytocin in a Nasal Spray **ID:** OG000 **Title:** Oxytocin ##### Group **Description:** Each participant will receive both the oxytocin nasal spray in one visit AND the placebo nasal spray in another visit (randomized) in this design. Placebo: Placebo will contain all ingredients except the active oxytocin in the Nasal Spray. **ID:** OG001 **Title:** Placebo #### Outcome Measure 4 **Description:** The investigators will analyze the latency (i.e., efficiency of processing) of visually elicited ERP components to the non-social stimuli (houses). This assessment will be completed after administration of the intervention (oxytocin) and the placebo to compare the neural response. The investigators hypothesize that there will be no difference between the intervention and placebo on ERP latency measures in the non-social condition. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** 1 participant was lost to follow-up (did not complete placebo); 1 participant's data was lost (removed then from placebo and oxytocin arms); 2 participants were statistical outliers and removed from oxytocin and placebo arms for N170 latency analysis **Reporting Status:** POSTED **Time Frame:** Duration of 30 minutes **Title:** Latency Non-Social **Type:** PRIMARY **Unit of Measure:** milliseconds ##### Group **Description:** Each participant will receive both the oxytocin nasal spray in one visit AND the placebo nasal spray in another visit (randomized) in this design. Oxytocin: 24 International Units of Oxytocin in a Nasal Spray **ID:** OG000 **Title:** Oxytocin ##### Group **Description:** Each participant will receive both the oxytocin nasal spray in one visit AND the placebo nasal spray in another visit (randomized) in this design. Placebo: Placebo will contain all ingredients except the active oxytocin in the Nasal Spray. **ID:** OG001 **Title:** Placebo #### Outcome Measure 5 **Description:** The investigators will assess depression by employing the Beck Depression Inventory (Beck et al., 1961). Specifically addressing whether the level of depression symptomatology in participants and whether this is associated with the neural correlates of social and non-social perception during both intervention and placebo visits. It is not yet known the extent to which variation in depression symptoms are associated with this methodology, although prior research has suggested depression modulates the neural response to social cues. This measure includes a question regarding suicidal ideation and therefore it is acknowledged there may be a safety issue in response to the questionnaire. Scores range from 0-63, with higher scores indicating greater levels of depression (scores 29+ indicates severe depression). **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Only participants included that have ERP data to analyze (excluding participant lost to follow-up and data loss) **Reporting Status:** POSTED **Time Frame:** Within 20 minutes of study visit commencing **Title:** Depression **Type:** SECONDARY **Unit of Measure:** units on a scale ##### Group **Description:** Each participant will receive both the oxytocin nasal spray in one visit AND the placebo nasal spray in another visit (randomized) in this design. Oxytocin: 24 International Units of Oxytocin in a Nasal Spray **ID:** OG000 **Title:** Oxytocin ##### Group **Description:** Each participant will receive both the oxytocin nasal spray in one visit AND the placebo nasal spray in another visit (randomized) in this design. Placebo: Placebo will contain all ingredients except the active oxytocin in the Nasal Spray. **ID:** OG001 **Title:** Placebo #### Outcome Measure 6 **Description:** Participants will complete a CO breathalyzer and the Fagerstrom Test for Nicotine Dependence (Heatherton, Kozlowski, Frecker, \& Fagerstrom, 1991) to assess smoking behavior. These measures are included to characterize the sample in respect of substance use. **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** 1 participant was lost to follow-up **Reporting Status:** POSTED **Time Frame:** Within 30 minutes of study visit commencing **Title:** Smoking **Type:** SECONDARY **Unit of Measure:** Participants ##### Group **Description:** Each participant will receive both the oxytocin nasal spray in one visit AND the placebo nasal spray in another visit (randomized) in this design. Oxytocin: 24 International Units of Oxytocin in a Nasal Spray **ID:** OG000 **Title:** Oxytocin ##### Group **Description:** Each participant will receive both the oxytocin nasal spray in one visit AND the placebo nasal spray in another visit (randomized) in this design. Placebo: Placebo will contain all ingredients except the active oxytocin in the Nasal Spray. **ID:** OG001 **Title:** Placebo #### Outcome Measure 7 **Description:** The investigators will assess anxiety using the State-Trait Anxiety Inventory (Spielberger et al., 1970). Specifically, it will be explored whether participant anxiety symptoms are associated with the neural correlates of social and non-social perception during both intervention and placebo visits. It is not yet known the extent to which variation in anxiety symptoms are associated with this methodology, although prior research has suggested anxiety modulates the neural response to social cues. Scores range from 20-80 and a higher score on both state and trait measures indicate higher levels of anxiety. A potential clinical cut off has been proposed for participants scoring over 39-40 as being high anxious. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Only participants included that have ERP data to analyze (excluding participant lost to follow-up and data loss) **Reporting Status:** POSTED **Time Frame:** Within 20 minutes of study visit commencing **Title:** Anxiety **Type:** SECONDARY **Unit of Measure:** units on a scale ##### Group **Description:** Each participant will receive both the oxytocin nasal spray in one visit AND the placebo nasal spray in another visit (randomized) in this design. Oxytocin: 24 International Units of Oxytocin in a Nasal Spray **ID:** OG000 **Title:** Oxytocin ##### Group **Description:** Each participant will receive both the oxytocin nasal spray in one visit AND the placebo nasal spray in another visit (randomized) in this design. Placebo: Placebo will contain all ingredients except the active oxytocin in the Nasal Spray. **ID:** OG001 **Title:** Placebo #### Outcome Measure 8 **Description:** The investigators will measure current levels of stress by using the Perceived Stress Scale (Cohen et al., 1983). It is not yet known the extent to which variation in perceived stress is associated with this methodology, but it is anticipated stress will be associated with levels of depression and anxiety in the sample. The PSS consists of 14 items, with scores ranging from 0 to 42, with higher scores indicating higher levels of perceived stress. A score of 21+ is considered to indicate that participants have higher than average stress. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Only participants included that have ERP data to analyze (excluding participant lost to follow-up and data loss) **Reporting Status:** POSTED **Time Frame:** Within 20 minutes of study visit commencing **Title:** Stress **Type:** SECONDARY **Unit of Measure:** units on a scale ##### Group **Description:** Each participant will receive both the oxytocin nasal spray in one visit AND the placebo nasal spray in another visit (randomized) in this design. Oxytocin: 24 International Units of Oxytocin in a Nasal Spray **ID:** OG000 **Title:** Oxytocin ##### Group **Description:** Each participant will receive both the oxytocin nasal spray in one visit AND the placebo nasal spray in another visit (randomized) in this design. Placebo: Placebo will contain all ingredients except the active oxytocin in the Nasal Spray. **ID:** OG001 **Title:** Placebo #### Outcome Measure 9 **Description:** The investigators will employ the Parental Bonding Instrument (Parker, Tupling, \& Brown, 1979) to assess the early relationship experiences participants have with their caregivers. Existing research employing intranasal oxytocin suggests that the quality of early relationships may impact the strength of any modulation of brain or behavior by oxytocin administration and therefore this variable will be included in the analyses in support of this hypothesis. There are 12 items that capture parental care and 13 items that capture parental overprotection. Items are scored on a 4-point likert scale from "very like" to "very unlike". The PBI is typically scored by identifying optimal (High Care Scores, Low Protection Scores) and less optimal (Low Care Scores, Low Protection Scores) scores on the mother and father subscales (NB: protection refers to overprotection). For the care items, scores can range from 0 to 36; for overprotection items, scores can range from 0 to 39. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Only participants included that have ERP data to analyze (excluding participant lost to follow-up and data loss); 1 participant did not know their father and did not complete the measure for paternal assessment **Reporting Status:** POSTED **Time Frame:** Within 20 minutes of study visit commencing **Title:** Early Experience **Type:** SECONDARY **Unit of Measure:** units on a scale ##### Group **Description:** Each participant will receive both the oxytocin nasal spray in one visit AND the placebo nasal spray in another visit (randomized) in this design. Oxytocin: 24 International Units of Oxytocin in a Nasal Spray **ID:** OG000 **Title:** Oxytocin ##### Group **Description:** Each participant will receive both the oxytocin nasal spray in one visit AND the placebo nasal spray in another visit (randomized) in this design. Placebo: Placebo will contain all ingredients except the active oxytocin in the Nasal Spray. **ID:** OG001 **Title:** Placebo #### Outcome Measure 10 **Description:** The investigators will employ the ASI Lite (McLellan, Luborsky, Woody, \& O'Brien, 1980) to assess for current substance use. This measure is included to characterize the sample in respect of substance use; however the ASI Lite did not provide a measure of substance dependance and therefore we report the data from the Mini International Neuropsychiatric Interview substance dependance module (Sheehan et al., 1998) to provide a specific indication of the presence of absence of substance dependance. **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** 1 participant lost to follow-up; count of participants where substance dependence indicated **Reporting Status:** POSTED **Time Frame:** Within 30 minutes of study visit commencing **Title:** Number of Participants Endorsing Substance Use **Type:** SECONDARY **Unit of Measure:** Participants ##### Group **Description:** Each participant will receive both the oxytocin nasal spray in one visit AND the placebo nasal spray in another visit (randomized) in this design. Oxytocin: 24 International Units of Oxytocin in a Nasal Spray **ID:** OG000 **Title:** Oxytocin ##### Group **Description:** Each participant will receive both the oxytocin nasal spray in one visit AND the placebo nasal spray in another visit (randomized) in this design. Placebo: Placebo will contain all ingredients except the active oxytocin in the Nasal Spray. **ID:** OG001 **Title:** Placebo #### Outcome Measure 11 **Description:** Participants will complete an alcohol breathalyzer to characterize the alcohol use status of the sample. **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** 1 participant lost to follow-up; data indicates number of participants with alcohol in their system **Reporting Status:** POSTED **Time Frame:** Within 30 minutes of study visit commencing **Title:** Number of Participants Testing Positive for Alcohol Use Following a Breathalyzer **Type:** SECONDARY **Unit of Measure:** Participants ##### Group **Description:** Each participant will receive both the oxytocin nasal spray in one visit AND the placebo nasal spray in another visit (randomized) in this design. Oxytocin: 24 International Units of Oxytocin in a Nasal Spray **ID:** OG000 **Title:** Oxytocin ##### Group **Description:** Each participant will receive both the oxytocin nasal spray in one visit AND the placebo nasal spray in another visit (randomized) in this design. Placebo: Placebo will contain all ingredients except the active oxytocin in the Nasal Spray. **ID:** OG001 **Title:** Placebo ### Participant Flow Module #### Group **Description:** Each participant will receive both the oxytocin nasal spray in one visit AND the placebo nasal spray in another visit (randomized) in this design. Oxytocin: 24 International Units of Oxytocin in a Nasal Spray **ID:** FG000 **Title:** Oxytocin First, Then Placebo #### Group **Description:** Each participant will receive both the oxytocin nasal spray in one visit AND the placebo nasal spray in another visit (randomized) in this design. Placebo: Placebo will contain all ingredients except the active oxytocin in the Nasal Spray. **ID:** FG001 **Title:** Placebo First, Then Oxytocin #### Period **Title:** Overall Study ##### Withdraw **Type:** Lost to Follow-up ###### Reason **Group ID:** FG000 **Number of Subjects:** 1 ###### Reason **Group ID:** FG001 **Number of Subjects:** 0 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 12 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 14 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 11 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 14 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 1 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 0 **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT02928679 **Acronym:** IM-LOSEIT-II **Brief Title:** Multi-parametric Imaging of the Knee in Obese Patients With Knee Osteoarthritis; Weight Maintenance **Official Title:** Multi-parametric Imaging of the Knee in Obese Patients With Knee Osteoarthritis Following Liraglutide Treatment, Investigating the Impact on Inflammation #### Organization Study ID Info **ID:** 137.05 #### Organization **Class:** OTHER **Full Name:** Parker Research Institute ### Status Module #### Completion Date **Date:** 2019-03-20 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2019-03-25 **Type:** ACTUAL **Last Update Submit Date:** 2019-03-21 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2019-02-20 **Type:** ACTUAL #### Start Date **Date:** 2016-11 **Status Verified Date:** 2019-03 #### Study First Post Date **Date:** 2016-10-10 **Type:** ESTIMATED **Study First Submit Date:** 2016-10-07 **Study First Submit QC Date:** 2016-10-07 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Henrik Gudbergsen #### Responsible Party **Investigator Affiliation:** Parker Research Institute **Investigator Full Name:** Henrik Gudbergsen **Investigator Title:** MD, PhD **Type:** SPONSOR_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** This is a substudy to a randomised trial investigating the effect of liraglutide on body weight and pain in overweight or obese patients with knee osteoarthritis (NCT02905864). In the parent trial, patients will be subjected to an 8-week diet intervention phase including a low-calorie diet and dietetic counseling, after which patients will be randomised to receive either liraglutide 3 mg or liraglutide 3 mg placebo as an add-on to dietetic guidance on re-introducing regular foods and a focus on continued motivation to engage in a healthy lifestyle. This substudy aims to investigate the impact of, and subsequent change of, joint inflammation, articular cartilage composition, overall knee morphology, and clinical symptoms, in obese patients with knee osteoarthritis following a randomisation to Liraglutide 3 mg or Liraglutide 3 mg placebo treatment between weeks 0-52. ### Conditions Module **Conditions:** - Osteoarthritis - Obesity **Keywords:** - Magnetic resonance imaging - Dynamic contrast enhanced MRI - Liraglutide 3 mg - Liraglutide - Obesity - Osteoarthritis ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** QUADRUPLE **Who Masked:** - PARTICIPANT - CARE_PROVIDER - INVESTIGATOR - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 150 **Type:** ESTIMATED **Phases:** - PHASE4 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Arm description: Subjects will be up titrated to liraglutide 3 mg QD and stay on that dose for the remainder of the 52-week drug intervention period. Drug: Liraglutide 3 mg QD administered in a 6 mg/mL, 3 mL pen for subcutaneous injection. Dose escalation scheme: Initial dosage of 0.6 mg per day, escalated bi-weekly by 0.6 mg to 3 mg per day over a total of 8 weeks. **Intervention Names:** - Drug: Liraglutide 3 mg (Saxenda) **Label:** Liraglutide 3 mg **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Arm description: Subjects will be up titrated to liraglutide 3 mg placebo QD and stay on that dose for the remainder of the 52-week drug intervention period. Drug: Liraglutide 3 mg placebo QD administered in a 6 mg/mL drug equivalent volumes, 3 mL pen for subcutaneous injection. Dose escalation scheme: Initial dosage of a 0.6 mg drug equivalent volume per day, escalated bi-weekly by an 0.6 mg drug equivalent volume per day to a 3 mg drug equivalent volume per day over a total of 8 weeks. **Intervention Names:** - Drug: Liraglutide 3 mg placebo **Label:** Liraglutide 3 mg placebo **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Liraglutide 3 mg **Name:** Liraglutide 3 mg (Saxenda) **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Liraglutide 3 mg placebo **Name:** Liraglutide 3 mg placebo **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Change will be assessed via a dynamic contrast enhanced MRI evaluation of corpus hoffa (Ballegaard C et al. and Riis RG et al.) **Measure:** Change in the degree of inflammation in the knee-joint (DCE-MRI) **Time Frame:** Week 0 to 52 #### Secondary Outcomes **Description:** Change will be assessed via a static contrast enhanced MRI evaluation of the level of synovitis in the knee-joint (11 sites scored 0-2, ad modum Guermazi et al.) **Measure:** Change in the degree of inflammation in the knee-joint (CE-MRI) **Time Frame:** Week 0 to 52 **Description:** Change will be assessed via a conventional MRI evaluation of the level of synovitis and effusion (combined) in the knee-joint (MOAKS) **Measure:** Change in the degree of inflammation in the knee-joint (MRI) **Time Frame:** Week 0 to 52 **Description:** Change will be assessed via T2-maps of cartilage in the weight-bearing parts of the knee-joint (ROI) **Measure:** Change in cartilage composition **Time Frame:** Week 0 to 52 **Description:** Change will be assessed via the MRI knee scoring system MOAKS; BML sum-score **Measure:** Change in bone marrow lesions **Time Frame:** Week 0 to 52 ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Same as parent trial (NCT02905864) Further Exclusion Criteria: * Same as parent trial (NCT02905864) * Usual exclusion criteria for MRI (i.e. pacemakers etc.) **Maximum Age:** 74 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Frederiksberg **Country:** Denmark **Facility:** The Parker Institute and Department of Radiology at Bispebjerg and Frederiksberg Hospital **State:** Capital Region **Zip:** 2000 ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000001168 - Term: Arthritis - ID: D000007592 - Term: Joint Diseases - ID: D000009140 - Term: Musculoskeletal Diseases - ID: D000012216 - Term: Rheumatic Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC05 - Name: Musculoskeletal Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: BC18 - Name: Nutritional and Metabolic Diseases - Abbrev: BC17 - Name: Skin and Connective Tissue Diseases ### Condition Browse Module - Browse Leaves - ID: M12926 - Name: Osteoarthritis - Relevance: HIGH - As Found: Osteoarthritis - ID: M22168 - Name: Osteoarthritis, Knee - Relevance: HIGH - As Found: Knee Osteoarthritis - ID: M10293 - Name: Inflammation - Relevance: LOW - As Found: Unknown - ID: M5114 - Name: Body Weight - Relevance: LOW - As Found: Unknown - ID: M12701 - Name: Obesity - Relevance: LOW - As Found: Unknown - ID: M4476 - Name: Arthritis - Relevance: LOW - As Found: Unknown - ID: M10621 - Name: Joint Diseases - Relevance: LOW - As Found: Unknown - ID: M12097 - Name: Musculoskeletal Diseases - Relevance: LOW - As Found: Unknown - ID: M15045 - Name: Rheumatic Diseases - Relevance: LOW - As Found: Unknown - ID: M6323 - Name: Collagen Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000010003 - Term: Osteoarthritis - ID: D000020370 - Term: Osteoarthritis, Knee ### Intervention Browse Module - Ancestors - ID: D000097789 - Term: Glucagon-Like Peptide-1 Receptor Agonists - ID: D000007004 - Term: Hypoglycemic Agents - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000054795 - Term: Incretins - ID: D000006728 - Term: Hormones - ID: D000006730 - Term: Hormones, Hormone Substitutes, and Hormone Antagonists ### Intervention Browse Module - Browse Branches - Abbrev: Hypo - Name: Hypoglycemic Agents - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Gast - Name: Gastrointestinal Agents ### Intervention Browse Module - Browse Leaves - ID: M419 - Name: Liraglutide - Relevance: HIGH - As Found: Ascending - ID: M9043 - Name: Glucagon - Relevance: LOW - As Found: Unknown - ID: M3401 - Name: Glucagon-Like Peptide-1 Receptor Agonists - Relevance: LOW - As Found: Unknown - ID: M26997 - Name: Glucagon-Like Peptide 1 - Relevance: LOW - As Found: Unknown - ID: M10054 - Name: Hypoglycemic Agents - Relevance: LOW - As Found: Unknown - ID: M27905 - Name: Incretins - Relevance: LOW - As Found: Unknown - ID: M9789 - Name: Hormones - Relevance: LOW - As Found: Unknown - ID: M9788 - Name: Hormone Antagonists - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000069450 - Term: Liraglutide ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04564079 **Brief Title:** An Observational Study to Evaluate the Clinical Utility of the Oncomine Precision Assay Within the Exactis Network **Official Title:** A Multi-Centre Observational Study to Evaluate the Clinical Utility of Returning Genomic Aberration Results Using the Oncomine Precision Assay in Advanced or Metastatic Non-Small Cell Lung Cancer Within the Exactis Network #### Organization Study ID Info **ID:** Exactis-01 #### Organization **Class:** OTHER **Full Name:** Exactis Innovation ### Status Module #### Completion Date **Date:** 2023-08-01 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2023-05-16 **Type:** ACTUAL **Last Update Submit Date:** 2023-05-12 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2023-07-01 **Type:** ESTIMATED #### Start Date **Date:** 2021-06-01 **Type:** ACTUAL **Status Verified Date:** 2023-05 #### Study First Post Date **Date:** 2020-09-25 **Type:** ACTUAL **Study First Submit Date:** 2020-08-28 **Study First Submit QC Date:** 2020-09-18 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Exactis Innovation #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** A Multi-centre Observational Study to Evaluate the Clinical Utility of Returning Genomic Aberration results Using the Oncomine Precision Assay in Advanced or Metastatic Non-Small Cell Lung Cancer Patients within the Exactis Network **Detailed Description:** This prospective multi-center observational study will evaluate the clinical utility of returning genomic aberration results in blood and/or tissue using the Oncomine Precision Assay in non-small cell lung cancer (NSCLC) patients. Up to 100 patients with stage IIIb/IV NSCLC will consent to have their blood and tissue profiled on the Oncomine Precision Assay. A baseline plasma sample will be collected for all patients, of which up to 50 patients will have a tissue sample collected from pathology archives or planned biopsy or surgery. ### Conditions Module **Conditions:** - NSCLC **Keywords:** - Genomic Aberrations - Exactis Network - Advanced or Metastatic Non-Small Cell Lung Cancer - Liquid Biopsy ### Design Module #### Bio Spec **Description:** Blood samples and/or tissue **Retention:** SAMPLES_WITH_DNA #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 100 **Type:** ESTIMATED **Study Type:** OBSERVATIONAL ### Outcomes Module #### Other Outcomes **Description:** Number of genomic aberrations concordant and discordant between tissue and blood using the Oncomine Precision Assay **Measure:** Exploratory - Analytical validity of Oncomine Precision Assay **Time Frame:** 2 years **Description:** Compare the sensitivity and specificity of mutation detection in extracellular vesicles (EV) total nucleic acids and circulating tumor total nucleic acids **Measure:** Exploratory- Sensitivity and specificity of mutation detection analysis of extracellular vesicles (EV) total nucleic acids **Time Frame:** 2 years **Description:** Small RNA extracted from plasma EV at baseline and at progression will be analyzed using RNA sequencing. Potential association between expression profiles and clinical parameters such as treatment response will be explored and candidate patterns predictive of treatment response will be tested using artificial intelligence algorithms. **Measure:** Exploratory- Explore the response patterns to treatment based on EV RNAs **Time Frame:** 2 years #### Primary Outcomes **Description:** Proportion of patients for whom an actionable genomic aberration is detected in at least one of the eight genes (ROS1, ERBB2, MET, BRAF, KRAS, RET, ALK, EGFR) using the Oncomine Precision Assay vs. study site's standard of care **Measure:** To compare the number of genomic aberrations detected by the Oncomine Precision Assay vs Standard of Care **Time Frame:** 1 year #### Secondary Outcomes **Measure:** Clinical utility of returning genomic aberration results by quantifying the number of patients who received targeted therapy based on results returned from the Oncomine Precision Assay genomic aberration results in blood and/or tissue **Time Frame:** 2 years **Measure:** Clinical utility of returning genomic aberration results by quantifying the number of patients enrolled on a clinical trial based on results returned from the Oncomine Precision Assay in blood and/or tissue **Time Frame:** 2 years ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Patients with NSCLC, which is (i) advanced or metastatic (stage IIIb/IV), (ii) non- squamous histology NSCLC as confirmed by local histopathology (mixed squamous and adenocarcinoma is allowed), and has (iii) radiographically measurable disease with at least one bidimensionally measurable lesion of \> 1 cm by CT scan * No prior treatment for advanced or metastatic NSCLC, except for palliative radiation therapy to non-lung or non-thorax metastases. Patients who received palliative radiation therapy to metastases located within or approximately to the lung or thorax must be evaluated for eligibility. * Willing and able to provide adequate blood sample prior to starting treatment. * Willing to provide primary or metastatic tissue, if available. * Signed and dated Research Ethics Board (REB)-approved informed consent form for Exactis-01 or PMT. * Not pregnant or breastfeeding Exclusion Criteria: • Patients who have a history of another active cancer within the past 2 years from date of consent except cervical cancer in situ, basal cell carcinoma of the skin or another in situ carcinoma that is considered cured by the investigator. **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Patients with NSCLC, which is i) advanced or metastatic (stage IIIb/IV), ii) non-squamous histology NSCLC as confirmed by local histopathology (mixed squamous and adenocarcinoma is allowed). ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Irine Islam **Phone:** 514-282-4523 **Phone Ext:** 212 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Dina Della Rocca **Phone:** 514-282-4523 **Phone Ext:** 207 **Role:** CONTACT #### Locations **Location 1:** **City:** Moncton **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Stéphanie Crapoulet - **Phone:** 506-862-4221 - **Role:** CONTACT ***Contact 2:*** - **Name:** Nicholas Finn, MD - **Role:** PRINCIPAL_INVESTIGATOR **Country:** Canada **Facility:** Centre hospitalier universitaire Dr-Georges-L.-Dumont **State:** New Brunswick **Status:** RECRUITING **Zip:** E1C 2Z3 **Location 2:** **City:** Moncton **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Ian Chute - **Role:** CONTACT ***Contact 2:*** - **Name:** Mahmoud Abdelsalam, MD - **Role:** PRINCIPAL_INVESTIGATOR **Country:** Canada **Facility:** The Moncton Hospital **State:** New Brunswick **Status:** RECRUITING **Zip:** E1C 6Z8 **Location 3:** **City:** Ottawa **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Nathalie Tremblay - **Role:** CONTACT ***Contact 2:*** - **Name:** Arif Awan, MD - **Role:** PRINCIPAL_INVESTIGATOR **Country:** Canada **Facility:** The Ottawa Hospital **State:** Ontario **Status:** RECRUITING **Zip:** K1H 8L6 **Location 4:** **City:** Toronto **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Roxanne Fernandes - **Phone:** 416-946-4501 - **Phone Ext:** 3592 - **Role:** CONTACT ***Contact 2:*** - **Name:** Natasha Leighl, MD - **Role:** PRINCIPAL_INVESTIGATOR **Country:** Canada **Facility:** Princess Margaret Cancer Centre **State:** Ontario **Status:** RECRUITING **Zip:** M5G 2C1 **Location 5:** **City:** Montreal **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Caterina Marcangione - **Role:** CONTACT ***Contact 2:*** - **Email:** [email protected] - **Name:** Benedicte Foveau - **Role:** CONTACT ***Contact 3:*** - **Name:** Jason Agulnik, MD - **Role:** PRINCIPAL_INVESTIGATOR **Country:** Canada **Facility:** Jewish General Hospital **State:** Quebec **Status:** RECRUITING **Zip:** H3T 1E2 **Location 6:** **City:** Sherbrooke **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Noemie Poirier - **Role:** CONTACT ***Contact 2:*** - **Email:** [email protected] - **Name:** Suzanne Maltais - **Role:** CONTACT ***Contact 3:*** - **Name:** Nicole Bouchard, MD - **Role:** PRINCIPAL_INVESTIGATOR **Country:** Canada **Facility:** Centre hospitalier universitaire de Sherbrooke (CHUS) **State:** Quebec **Status:** RECRUITING **Zip:** J1H 5H3 #### Overall Officials **Official 1:** **Affiliation:** Principal Investigator **Name:** Jason Agulnik, MD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **Description:** As in the PMT registry, data and samples will be collected, coded and stored in secure and protected installations. Information and samples provided to researchers will be double-coded so that they cannot be traced back to you. Exactis takes great care to protect participants' data and samples, to minimize security risks and the possibility of a confidentiality breach. **IPD Sharing:** YES ### References Module #### See Also Links **Label:** exactis.ca **URL:** https://www.exactis.ca **Label:** PMT registry **URL:** http://clinicaltrials.gov/ct2/show/NCT02355171?term=personalize+me+treatment&draw=2&rank=9 ## Derived Section ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC08 - Name: Respiratory Tract (Lung and Bronchial) Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M11172 - Name: Lung Neoplasms - Relevance: LOW - As Found: Unknown - ID: M5546 - Name: Carcinoma, Non-Small-Cell Lung - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT02836379 **Acronym:** CAVIDIOR **Brief Title:** Quality of Life Study Breakthrough Cancer Pain Treated in Radiation Oncology Services With Palliative Intent **Official Title:** Quality of Life Study in Patients With Breakthrough Cancer Pain Treated in Radiation Oncology Services With Palliative Intent #### Organization Study ID Info **ID:** ANG-DOL-2016-01 (CAVIDIOR) #### Organization **Class:** INDUSTRY **Full Name:** Angelini Farmacéutica ### Status Module #### Completion Date **Date:** 2018-02-28 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2018-03-05 **Type:** ACTUAL **Last Update Submit Date:** 2018-03-02 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2017-11 **Type:** ACTUAL #### Start Date **Date:** 2016-07-08 **Type:** ACTUAL **Status Verified Date:** 2018-03 #### Study First Post Date **Date:** 2016-07-19 **Type:** ESTIMATED **Study First Submit Date:** 2016-07-11 **Study First Submit QC Date:** 2016-07-14 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Angelini Farmacéutica #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** In the context of radiotherapy, control of breakthrough pain represents a special challenge. Patients undergoing radiotherapy may experience different situations of pain that may be due to the need to remain immobilized during radiotherapy session, the need to wear an immobilization mask (head and neck cancer), the odynophagia caused by mucositis, defecation after the development of proctitis, or sudden pain during the night causing sleep disturbances. In a survey conducted in radiation oncology services more than half of patients treated with radiotherapy experienced pain, and 39% of patients reported that their pain was not treated properly. This situation may increase the patient's anxiety, dissatisfaction with treatment, affect their quality of life and can even come to refuse radiotherapy treatment. This post-authorization observational study will assess the quality of life of cancer patients with breakthrough cancer pain treated in radiotherapy services in Spanish hospitals. ### Conditions Module **Conditions:** - Breakthrough Pain **Keywords:** - Breakthrough Cancer Pain - Quality of life - Radiotherapy ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 79 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** No intervention (Non-interventional study) **Intervention Names:** - Other: No intervention **Label:** Breakthrough Cancer Pain ### Interventions #### Intervention 1 **Arm Group Labels:** - Breakthrough Cancer Pain **Description:** No intervention **Name:** No intervention **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** Change in punctuation of the SF-12 questionnaire between end of radiotherapy treatment and baseline. **Measure:** Change in quality of life according SF-12 questionnaire **Time Frame:** Baseline and 4-6 weeks (estimated end of radiotherapy treatment) #### Secondary Outcomes **Description:** Percentage of patients with neuropathic, visceral, somatic and mixed pain **Measure:** Percentage of patients with neuropathic, visceral, somatic and mixed pain **Time Frame:** Baseline (the day that patient sign the informed consent form) **Description:** Percentage of patients with each comorbidity **Measure:** Comorbidities associated with patients **Time Frame:** Baseline (the day that patient sign the informed consent form) **Description:** Time from the start of the episode until the relief of breakthrough pain **Measure:** Mean time to relief of breakthrough pain **Time Frame:** Up to 6 weeks, from date of inclusion until the end of radiotherapy treatment **Description:** Time from the start of the episode until the pain ends **Measure:** Mean duration of the episodes of breakthrough pain **Time Frame:** Up to 6 weeks, from date of inclusion until the end of radiotherapy treatment **Description:** Number of patients indicating each of the possible answers of the Clinical Global Impression of improvement scale **Measure:** Clinical Global improvement **Time Frame:** 4-6 weeks (estimated end of radiotherapy treatment) **Description:** Number of patients indicating each of the possible answers of the Patient Global Impression of improvement scale **Measure:** Patient Global improvement **Time Frame:** 4-6 weeks (estimated end of radiotherapy treatment) **Description:** Difference in percentage of patients with punctuation ≥ 17 points at end of radiotherapy treatment and baseline. **Measure:** Change in assessment (percentage) of family claudication **Time Frame:** Baseline and 4-6 weeks (estimated end of radiotherapy treatment) **Description:** Intensity of breakthrough cancer pain assessed with a Visual Analog Scale (VAS). VAS will be compared at each study visit. **Measure:** Change in mean Intensity of breakthrough cancer pain at each study visit **Time Frame:** Up to 6 weeks, from date of inclusion until the end of radiotherapy treatment **Description:** Change in MOS Sleep Scale scores between end of radiotherapy treatment and baseline **Measure:** Change in MOS Sleep Scale scores **Time Frame:** Baseline and 4-6 weeks (estimated end of radiotherapy treatment) ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Patients \> 18 years * Cancer Patients * Patients attended in radiation oncology consultations with palliative intent * Life expectancy \> 6 months * Written informed consent * Patients with baseline controlled cancer pain with opioids who are diagnosed of breakthrough cancer pain by Davies algorithm Exclusion Criteria: * Untreated patients with opioids for baseline pain * Patients who are not opioid tolerant * Serious psychiatric disorder or any disease or condition that prevents the collection of data * Patients with evidence of opioid addiction or history of drug or alcohol abuse **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Patients with breakthrough cancer pain treated in Radiation Oncology services with palliative intent will be included ### Contacts Locations Module #### Locations **Location 1:** **City:** Santiago de Compostela **Country:** Spain **Facility:** Complejo Hospitalario Universitario de Santiago **State:** A Coruña **Zip:** 15706 **Location 2:** **City:** Terrassa **Country:** Spain **Facility:** Hospital de Terrassa **State:** Barcelona **Zip:** 08227 **Location 3:** **City:** Majadahonda **Country:** Spain **Facility:** Hospital Puerta de Hierro **State:** Madrid **Zip:** 28222 **Location 4:** **City:** Vigo **Country:** Spain **Facility:** Hospital Do Meixoeiro **State:** Pontevedra **Zip:** 36200 **Location 5:** **City:** A Coruña **Country:** Spain **Facility:** Centro Oncológico de galicia **Zip:** 15009 **Location 6:** **City:** Barcelona **Country:** Spain **Facility:** Hospital de l'Esperança **Zip:** 08024 **Location 7:** **City:** Barcelona **Country:** Spain **Facility:** ICO Hospitalet **Zip:** 08908 **Location 8:** **City:** Madrid **Country:** Spain **Facility:** Hospital Ramón y Cajal **Zip:** 28034 **Location 9:** **City:** Madrid **Country:** Spain **Facility:** Hospital La Paz **Zip:** 28046 **Location 10:** **City:** Málaga **Country:** Spain **Facility:** Hospital Regional de Málaga **Zip:** 29010 **Location 11:** **City:** Sevilla **Country:** Spain **Facility:** Hospital Virgen Macarena **Zip:** 41007 #### Overall Officials **Official 1:** **Affiliation:** IMONCOLOGY, Hospital la Milagrosa. Madrid **Name:** Ana Mañas, MD **Role:** STUDY_DIRECTOR ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Hernanz de Lucas R, Nunez Fernandez M, Gomez-Caamano A, Morera Lopez R, Fortes de la Torre I, de la Torre Tomas A, Munoz-Garzon V, Lopez Bermudo C, Manas Rueda A. Quality of life in patients with breakthrough cancer pain in radiation oncology departments in Spain: the CAVIDIOR study. Future Oncol. 2021 Mar;17(8):943-954. doi: 10.2217/fon-2020-1063. Epub 2020 Dec 8. **PMID:** 33289432 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000010146 - Term: Pain - ID: D000009461 - Term: Neurologic Manifestations ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: BXM - Name: Behaviors and Mental Disorders ### Condition Browse Module - Browse Leaves - ID: M13066 - Name: Pain - Relevance: LOW - As Found: Unknown - ID: M1091 - Name: Cancer Pain - Relevance: HIGH - As Found: Cancer Pain - ID: M29458 - Name: Breakthrough Pain - Relevance: HIGH - As Found: Breakthrough Pain - ID: M12404 - Name: Neurologic Manifestations - Relevance: LOW - As Found: Unknown - ID: T6034 - Name: Quality of Life - Relevance: HIGH - As Found: Quality of Life ### Condition Browse Module - Meshes - ID: D000072716 - Term: Cancer Pain - ID: D000059390 - Term: Breakthrough Pain ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT02368379 **Brief Title:** Diagnosis of Central Adrenal Insufficiency in Patients With Prader-Willi Syndrome **Official Title:** Diagnosis of Central Adrenal Insufficiency in Patients With Prader-Willi Syndrome #### Organization Study ID Info **ID:** 293113 #### Organization **Class:** OTHER **Full Name:** Nationwide Children's Hospital ### Status Module #### Completion Date **Date:** 2016-08 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2018-01-29 **Type:** ACTUAL **Last Update Submit Date:** 2018-01-25 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2016-08 **Type:** ACTUAL #### Start Date **Date:** 2014-03 **Status Verified Date:** 2018-01 #### Study First Post Date **Date:** 2015-02-23 **Type:** ESTIMATED **Study First Submit Date:** 2015-02-05 **Study First Submit QC Date:** 2015-02-16 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Nationwide Children's Hospital #### Responsible Party **Investigator Affiliation:** Nationwide Children's Hospital **Investigator Full Name:** Manmohan Kamboj **Investigator Title:** Associate Professor of Pediatrics, Section of Endocrinology, Metabolism and Diabetes **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** The purpose of this study is to determine presence of central adrenal insufficiency in children with Prader Willi Syndrome using low dose (1 mcg) ACTH stimulation test compared to results of overnight metyrapone test. ### Conditions Module **Conditions:** - Prader Willi Syndrome - Adrenal Insufficiency **Keywords:** - Metyrapone - ACTH stimulation test ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** DIAGNOSTIC #### Enrollment Info **Count:** 23 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Patients will undergo low dose ACTH stimulation test followed by overnight metyrapone test to assess for central adrenal insufficiency. **Intervention Names:** - Other: Low dose (1 mcg) ACTH stimulation test - Other: Overnight metyrapone test **Label:** Assessment of Central Adrenal Insufficiency **Type:** OTHER ### Interventions #### Intervention 1 **Arm Group Labels:** - Assessment of Central Adrenal Insufficiency **Description:** Subjects will have baseline cortisol and ACTH drawn followed by administration of 1 mcg/m2 (max 1 mcg) of cortrosyn. Blood will be drawn at 20 and 40 minutes post cortrosyn for peak cortisol assessment of central adrenal insufficiency. **Name:** Low dose (1 mcg) ACTH stimulation test **Type:** OTHER #### Intervention 2 **Arm Group Labels:** - Assessment of Central Adrenal Insufficiency **Description:** Subjects will receive metyrapone 30 mg/kg (max 3 grams) by mouth at midnight. Blood will be drawn at 0800 AM the following morning for ACTH, cortisol and 11 deoxycortisol for assessment of central adrenal insufficiency. **Name:** Overnight metyrapone test **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Measure:** Presence of central adrenal insufficiency using low dose (1 mcg) ACTH stimulation test **Time Frame:** 40 minutes **Measure:** Prescence of central adrenal insufficiency using overnight metyrapone test **Time Frame:** 8 hours #### Secondary Outcomes **Measure:** Determine peak cortisol value on low dose (1 mcg) ACTH stimulation test that can accurately predict central adrenal insufficiency based on overnight metyrapone test with good sensitivity and specificity. **Time Frame:** 0 ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Individuals with Prader Willi Syndrome ages 2 years and older Exclusion Criteria: * Individuals who are ill at the time of study * Individuals who are pregnant at the time of study * Individuals who it is deemed unsafe to stop taking medications known to affect the results of they study (hydrocortisone, phenytoin, estrogen, acetaminophen, oral anti-diabetic agents). **Healthy Volunteers:** True **Minimum Age:** 2 Years **Sex:** ALL **Standard Ages:** - CHILD - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Columbus **Country:** United States **Facility:** Nationwide Children's Hospital **State:** Ohio **Zip:** 43205 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000004194 - Term: Disease - ID: D000010335 - Term: Pathologic Processes - ID: D000008607 - Term: Intellectual Disability - ID: D000019954 - Term: Neurobehavioral Manifestations - ID: D000009461 - Term: Neurologic Manifestations - ID: D000009422 - Term: Nervous System Diseases - ID: D000000015 - Term: Abnormalities, Multiple - ID: D000000013 - Term: Congenital Abnormalities - ID: D000025063 - Term: Chromosome Disorders - ID: D000030342 - Term: Genetic Diseases, Inborn - ID: D000096803 - Term: Imprinting Disorders - ID: D000009765 - Term: Obesity - ID: D000050177 - Term: Overweight - ID: D000044343 - Term: Overnutrition - ID: D000009748 - Term: Nutrition Disorders - ID: D000000307 - Term: Adrenal Gland Diseases - ID: D000004700 - Term: Endocrine System Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: BC16 - Name: Diseases and Abnormalities at or Before Birth - Abbrev: BC18 - Name: Nutritional and Metabolic Diseases - Abbrev: BC19 - Name: Gland and Hormone Related Diseases - Abbrev: BXM - Name: Behaviors and Mental Disorders - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M16355 - Name: Syndrome - Relevance: HIGH - As Found: Syndrome - ID: M14099 - Name: Prader-Willi Syndrome - Relevance: HIGH - As Found: Prader-Willi Syndrome - ID: M3661 - Name: Adrenal Insufficiency - Relevance: HIGH - As Found: Adrenal Insufficiency - ID: M11589 - Name: Intellectual Disability - Relevance: LOW - As Found: Unknown - ID: M21826 - Name: Neurobehavioral Manifestations - Relevance: LOW - As Found: Unknown - ID: M12404 - Name: Neurologic Manifestations - Relevance: LOW - As Found: Unknown - ID: M12 - Name: Congenital Abnormalities - Relevance: LOW - As Found: Unknown - ID: M14 - Name: Abnormalities, Multiple - Relevance: LOW - As Found: Unknown - ID: M23023 - Name: Chromosome Disorders - Relevance: LOW - As Found: Unknown - ID: M23686 - Name: Genetic Diseases, Inborn - Relevance: LOW - As Found: Unknown - ID: M12701 - Name: Obesity - Relevance: LOW - As Found: Unknown - ID: M26186 - Name: Overweight - Relevance: LOW - As Found: Unknown - ID: M25307 - Name: Overnutrition - Relevance: LOW - As Found: Unknown - ID: M12684 - Name: Nutrition Disorders - Relevance: LOW - As Found: Unknown - ID: M3659 - Name: Adrenal Gland Diseases - Relevance: LOW - As Found: Unknown - ID: M7862 - Name: Endocrine System Diseases - Relevance: LOW - As Found: Unknown - ID: T4665 - Name: Prader-Willi Syndrome - Relevance: HIGH - As Found: Prader-Willi Syndrome - ID: T5162 - Name: Secondary Adrenal Insufficiency - Relevance: HIGH - As Found: Central Adrenal Insufficiency ### Condition Browse Module - Meshes - ID: D000011218 - Term: Prader-Willi Syndrome - ID: D000000309 - Term: Adrenal Insufficiency - ID: D000013577 - Term: Syndrome ### Intervention Browse Module - Ancestors - ID: D000000963 - Term: Antimetabolites - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000004791 - Term: Enzyme Inhibitors ### Intervention Browse Module - Browse Branches - Abbrev: VaCoAg - Name: Vasoconstrictor Agents - Abbrev: Resp - Name: Respiratory System Agents - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Infl - Name: Anti-Inflammatory Agents ### Intervention Browse Module - Browse Leaves - ID: M7992 - Name: Epinephrine - Relevance: LOW - As Found: Unknown - ID: M9912 - Name: Hydrocortisone - Relevance: LOW - As Found: Unknown - ID: M155245 - Name: Hydrocortisone 17-butyrate 21-propionate - Relevance: LOW - As Found: Unknown - ID: M228609 - Name: Hydrocortisone acetate - Relevance: LOW - As Found: Unknown - ID: M263259 - Name: Hydrocortisone hemisuccinate - Relevance: LOW - As Found: Unknown - ID: M30371 - Name: Racepinephrine - Relevance: LOW - As Found: Unknown - ID: M211043 - Name: Epinephryl borate - Relevance: LOW - As Found: Unknown - ID: M6585 - Name: Cosyntropin - Relevance: LOW - As Found: Unknown - ID: M11769 - Name: Metyrapone - Relevance: HIGH - As Found: Amenorrhea - ID: M4281 - Name: Antimetabolites - Relevance: LOW - As Found: Unknown - ID: M7951 - Name: Enzyme Inhibitors - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000008797 - Term: Metyrapone ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04246879 **Brief Title:** MRI Following Stereotactic Radiosurgery (SRS) for Brain Metastases **Official Title:** Diagnostic Accuracy of Delayed MRI Contrast Enhancement Characteristics and Radiation Necrosis Following Stereotactic Radiosurgery (SRS) for Brain Metastases #### Organization Study ID Info **ID:** Pro00103163 #### Organization **Class:** OTHER **Full Name:** Duke University ### Status Module #### Completion Date **Date:** 2025-07 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-04-02 **Type:** ACTUAL **Last Update Submit Date:** 2024-04-01 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2025-07 **Type:** ESTIMATED #### Start Date **Date:** 2021-07-19 **Type:** ACTUAL **Status Verified Date:** 2024-04 #### Study First Post Date **Date:** 2020-01-29 **Type:** ACTUAL **Study First Submit Date:** 2020-01-28 **Study First Submit QC Date:** 2020-01-28 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Duke University #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** The purpose of this study is to test whether an additional magnetic resonance image (MRI) sequence can improve the ability to distinguish radiation damage from tumor recurrence in participants with brain metastasis who have previously been treated with stereotactic radiosurgery (SRS). ### Conditions Module **Conditions:** - Brain Metastases **Keywords:** - Laser Interstitial Thermal Therapy (LITT) - Stereotactic radiosurgery (SRS) - Magnetic resonance image (MRI) ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** OTHER #### Enrollment Info **Count:** 37 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Intervention Names:** - Other: MRI **Label:** MRI **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - MRI **Description:** Subjects undergo one additional delayed MRI sequence **Name:** MRI **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** true tumor will be detected by delayed MRI as determined by biopsy **Measure:** number of positive MRI sequences along with positive tumor biopsies **Time Frame:** baseline **Description:** absence of tumor will be detected by delayed MRI as determined by biopsy **Measure:** number of negative MRI sequences along with negative tumor biopsies **Time Frame:** baseline ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Adult patients, age ≥18 * Metastatic malignancy with at least 1 brain metastasis previously treated with SRS * Patients may have also received whole brain radiation therapy (WBRT) for management of brain metastatic disease but this is not required for study participation * Patients must have been diagnosed with a metastatic solid tumor of any histological type except small cell lung cancer (SCLC), or lymphoma. * Radiographic progression on post-SRS imaging at previously treated SRS site(s) * Must be a candidate for brain surgery as determined by treating neurosurgeon and/or anesthesia team * Patients must sign study-specific informed consent prior to study entry Exclusion Criteria: * Poor surgical candidate as determined by treating neurosurgeon and/or anesthesia team * Unable to undergo contrasted MRI (e.g. incompatible medical device, inadequate renal function per standard institutional clinical protocol, contrast allergy) * Small cell lung cancer (SCLC) or lymphoma histology **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Eileen Duffy, RN OCN **Phone:** 919 668 3726 **Role:** CONTACT #### Locations **Location 1:** **City:** Durham **Contacts:** ***Contact 1:*** - **Name:** Eileen Duffy, BNS RN OCN - **Phone:** 919-668-3726 - **Role:** CONTACT ***Contact 2:*** - **Name:** Scott Floyd, MD PhD - **Role:** PRINCIPAL_INVESTIGATOR **Country:** United States **Facility:** Duke University Health System **State:** North Carolina **Status:** RECRUITING **Zip:** 27710 #### Overall Officials **Official 1:** **Affiliation:** Duke Health **Name:** Scott Floyd, M.D. Ph.D. **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009385 - Term: Neoplastic Processes - ID: D000009369 - Term: Neoplasms - ID: D000010335 - Term: Pathologic Processes - ID: D000016543 - Term: Central Nervous System Neoplasms - ID: D000009423 - Term: Nervous System Neoplasms - ID: D000009371 - Term: Neoplasms by Site - ID: D000001927 - Term: Brain Diseases - ID: D000002493 - Term: Central Nervous System Diseases - ID: D000009422 - Term: Nervous System Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC10 - Name: Nervous System Diseases ### Condition Browse Module - Browse Leaves - ID: M12307 - Name: Neoplasm Metastasis - Relevance: HIGH - As Found: Metastases - ID: M12284 - Name: Necrosis - Relevance: LOW - As Found: Unknown - ID: M5209 - Name: Brain Neoplasms - Relevance: HIGH - As Found: Brain Metastases - ID: M12330 - Name: Neoplastic Processes - Relevance: LOW - As Found: Unknown - ID: M18937 - Name: Central Nervous System Neoplasms - Relevance: LOW - As Found: Unknown - ID: M12367 - Name: Nervous System Neoplasms - Relevance: LOW - As Found: Unknown - ID: M5204 - Name: Brain Diseases - Relevance: LOW - As Found: Unknown - ID: M5742 - Name: Central Nervous System Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000009362 - Term: Neoplasm Metastasis - ID: D000001932 - Term: Brain Neoplasms ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04895579 **Acronym:** LCD **Brief Title:** Lung Cancer With Copanlisib and Durvalumab **Official Title:** Boosting Immune Response With Copanlisib in Locally Advanced Unresectable Non-Small Cell Lung Cancer Receiving Durvalumab, A Phase Ib Study #### Organization Study ID Info **ID:** MCC-20-LUN-119-PMC #### Organization **Class:** OTHER **Full Name:** University of Kentucky ### Status Module #### Completion Date **Date:** 2025-06 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-02-13 **Type:** ACTUAL **Last Update Submit Date:** 2024-02-12 **Overall Status:** ACTIVE_NOT_RECRUITING #### Primary Completion Date **Date:** 2025-06 **Type:** ESTIMATED #### Start Date **Date:** 2021-05-12 **Type:** ACTUAL **Status Verified Date:** 2024-02 #### Study First Post Date **Date:** 2021-05-20 **Type:** ACTUAL **Study First Submit Date:** 2021-05-17 **Study First Submit QC Date:** 2021-05-17 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** Bayer #### Lead Sponsor **Class:** OTHER **Name:** Zhonglin Hao #### Responsible Party **Investigator Affiliation:** University of Kentucky **Investigator Full Name:** Zhonglin Hao **Investigator Title:** Professor **Type:** SPONSOR_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** True **Oversight Has DMC:** True ### Description Module **Brief Summary:** The current study focuses on unresectable stage III non-small cell lung cancer (NSCLC) patients who are starting Durvalumab consolidation after concurrent chemoradiation with a goal of cure. The overall hypothesis of this study is that the addition of Copanlisib to Durvalumab will be well-tolerated at a biweekly schedule. It will test whether the addition of Copanlisib to Durvalumab can overcome resistance to Durvalumab. **Detailed Description:** Treatment will be administered in outpatient settings. Durvalumab will be administered as infusion intravenously once every two weeks on D1 and D15, every 28 days (10 mg/Kg based on body weight) or 1500mg on D1 every 28 days. Copanlisib will be given as infusion intravenously on D1, D15 in a 28-day cycle (flat dose). The starting dose of Copalisib will be 60 mg D1 and D15. It will be reduced to 45 mg for the first dose reduction and to 30 mg for the second dose reduction. The Durvalumab dose will remain constant when Copanlisib is reduced. Once the appropriate dose is determined, e.g. Copanlisib 60 mg iv d1, 15, q4w, in the dose-finding phase, this will become the recommended dose for the dose-expansion phase. Patients will be treated at the dose-expansion phase to increase our understanding of pharmacokinetics and to confirm safety as well as initial efficacy in this population. ### Conditions Module **Conditions:** - Non Small Cell Lung Cancer **Keywords:** - Stage 3A, 3B - Chemoradiation therapy - Durvalumab consolidation/maintenance - Copanlisib ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP **Intervention Model Description:** Dose finding cohort and dose expansion cohort up to 18 patients ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 11 **Type:** ACTUAL **Phases:** - PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Patients in the group will receive Durvalumab at 10mg/kg (IV infusion on days 1 and 15, q28 days or 1500mg day 1 q28d). They will also receive Copanlisib ranging from 30mg to 60mg (IV infusion on days 1 and 15, q 28 days). **Intervention Names:** - Drug: Durvalumab - Drug: Copanlisib **Label:** Copanlisib (30-60mg iv) **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Copanlisib (30-60mg iv) **Description:** Durvalumab will be delivered at 10mg/kg via IV infusion at days 1 and 15 every 28 days or 1500 mg on D1, q4w. **Name:** Durvalumab **Other Names:** - Imfinzi **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Copanlisib (30-60mg iv) **Description:** Copanlisib will be delivered at various doses (30-60mg/kg) via IV infusion at days 1 and 15 every 28 days. **Name:** Copanlisib **Other Names:** - Aliqopa **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** The number of dose limiting toxicities will be counted for each cohort. **Measure:** Dose Limiting Toxicity **Time Frame:** 28 days #### Secondary Outcomes **Description:** The objective response rate is evaluated by iRECIST 1.1, which includes all patients with partial response (iPR) or complete response (iCR). **Measure:** Objective Response Rate **Time Frame:** approximately 10 years **Description:** Progression-free survival (PFS) is defined as the time interval between the date patients are started on Copanlisib treatment to the date of disease progression, death or last follow-up, whichever occurs first. Patients who are intolerant to treatment and removed from study by the principal investigator or withdraw from the study will be treated as censored data for the PFS analysis. **Measure:** Progression-Free Survival **Time Frame:** approximately 10 years **Description:** Duration of response (DOR) is defined as the time interval between the initial response to therapy and subsequent disease progression or relapse. Non-responders will be assigned a DOR equal to zero. **Measure:** Duration of Response **Time Frame:** approximately 10 years ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Histologically confirmed NSCLC (e.g., adenocarcinoma, squamous cell) deemed unresectable or inoperable who have received concurrent chemoradiation. * Durvalumab will be started as consolidation therapy * Have at least one measurable lesion. * ECOG performance status ≤2. * Adequate organ and marrow function. * Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: * Mixed Non-small cell and small cell histology; known EGFR and/or ALK driver mutations. * Treated with sequential chemoradiation therapy. * Autoimmune disease, such as rheumatoid arthritis, systemic lupus erythematosus, requiring systemic treatment with immunosuppressant in the past two years. * Patients who are receiving any other investigational agents orally or intravenously. * Systemic steroid for other purpose exceeding 10 mg prednisone a day except local injection at the discretion of the investigator. * Solid organ or bone marrow transplant recipients. * History or concurrent condition of interstitial lung disease of any severity and/or severely impaired lung function. * Patients with uncontrolled inter-current illness. * Patients with psychiatric illness/social situations that would limit compliance with study requirements and patients with seizure disorder not well controlled. * Received live vaccine in the past 4 weeks. * Pregnant or breast-feeding/lactating women. * Receiving medications prohibited by the study. * New York Heart Association Class 3 or above. * Myocardial infarction within the last 6 months. * Unstable angina. * Venous thromboembolism within last 3 months. * Evidence or history of bleeding diathesis. Any hemorrhage or bleeding event ≥ CTCAE Grade 3 within 4 weeks. * Proteinuria of ≥ CTCAE Grade 3 or estimated by urine protein: creatinine ratio \> 3.5 * Major surgeries within the last 28 days. * Any illness or medical conditions that are unstable or could jeopardize the safety of patients and their compliance in the study. **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Lexington **Country:** United States **Facility:** Markey Cancer Center **State:** Kentucky **Zip:** 40536 #### Overall Officials **Official 1:** **Affiliation:** University of Kentucky **Name:** Zhonglin Hao, MD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000012142 - Term: Respiratory Tract Neoplasms - ID: D000013899 - Term: Thoracic Neoplasms - ID: D000009371 - Term: Neoplasms by Site - ID: D000009369 - Term: Neoplasms - ID: D000008171 - Term: Lung Diseases - ID: D000012140 - Term: Respiratory Tract Diseases - ID: D000002283 - Term: Carcinoma, Bronchogenic - ID: D000001984 - Term: Bronchial Neoplasms ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC08 - Name: Respiratory Tract (Lung and Bronchial) Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M11172 - Name: Lung Neoplasms - Relevance: HIGH - As Found: Lung Cancer - ID: M5546 - Name: Carcinoma, Non-Small-Cell Lung - Relevance: HIGH - As Found: Non-Small Cell Lung Cancer - ID: M5534 - Name: Carcinoma - Relevance: LOW - As Found: Unknown - ID: M14979 - Name: Respiratory Tract Neoplasms - Relevance: LOW - As Found: Unknown - ID: M16658 - Name: Thoracic Neoplasms - Relevance: LOW - As Found: Unknown - ID: M11168 - Name: Lung Diseases - Relevance: LOW - As Found: Unknown - ID: M14977 - Name: Respiratory Tract Diseases - Relevance: LOW - As Found: Unknown - ID: M5540 - Name: Carcinoma, Bronchogenic - Relevance: LOW - As Found: Unknown - ID: M5260 - Name: Bronchial Neoplasms - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000008175 - Term: Lung Neoplasms - ID: D000002289 - Term: Carcinoma, Non-Small-Cell Lung ### Intervention Browse Module - Ancestors - ID: D000074322 - Term: Antineoplastic Agents, Immunological - ID: D000000970 - Term: Antineoplastic Agents ### Intervention Browse Module - Browse Branches - Abbrev: ANeo - Name: Antineoplastic Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M272500 - Name: Durvalumab - Relevance: HIGH - As Found: Non-Small Cell - ID: M1346 - Name: Antineoplastic Agents, Immunological - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: C000613593 - Term: Durvalumab ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05051579 **Brief Title:** A Study of LY3502970 in Participants With Obesity or Overweight With Weight-related Comorbidities **Official Title:** A Phase 2 Study of Once-Daily LY3502970 Compared With Placebo in Participants Who Have Obesity or Are Overweight With Weight-Related Comorbidities #### Organization Study ID Info **ID:** 18210 #### Organization **Class:** INDUSTRY **Full Name:** Eli Lilly and Company #### Secondary ID Infos **Domain:** Eli Lilly and Company **ID:** J2A-MC-GZGI **Type:** OTHER **ID:** 2021-002805-88 **Type:** EUDRACT_NUMBER ### Status Module #### Completion Date **Date:** 2022-11-22 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2023-09-13 **Type:** ACTUAL **Last Update Submit Date:** 2023-08-23 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2022-08-25 **Type:** ACTUAL #### Results First Post Date **Date:** 2023-09-13 **Type:** ACTUAL **Results First Submit Date:** 2023-08-23 **Results First Submit QC Date:** 2023-08-23 #### Start Date **Date:** 2021-09-29 **Type:** ACTUAL **Status Verified Date:** 2023-08 #### Study First Post Date **Date:** 2021-09-21 **Type:** ACTUAL **Study First Submit Date:** 2021-09-17 **Study First Submit QC Date:** 2021-09-17 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Eli Lilly and Company #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** True **Oversight Has DMC:** False ### Description Module **Brief Summary:** The main purpose of the study was to assess the effect of LY3502970 in participants who have obesity or are overweight. ### Conditions Module **Conditions:** - Obesity - Overweight and Obesity ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** DOUBLE **Who Masked:** - PARTICIPANT - INVESTIGATOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 272 **Type:** ACTUAL **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Participants received maintenance dose 12 mg with dose escalation starting from 3 mg,6 mg and then 12 mg LY3502970 administered orally once daily until 36 weeks. **Intervention Names:** - Drug: LY3502970 **Label:** 12 milligram (mg) LY3502970 **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Participants received maintenance dose 24 mg with dose escalation starting from 3 mg, 6 mg, 8 mg,12 mg and then 24 mg LY3502970 administered orally once daily until 36 weeks. **Intervention Names:** - Drug: LY3502970 **Label:** 24 mg LY3502970 **Type:** EXPERIMENTAL #### Arm Group 3 **Description:** Participants received maintenance dose 36 mg with dose escalation starting from 2 mg, 3 mg, 6 mg, 8 mg, 12 mg, 24 mg and then 36 mg LY3502970 administered orally once daily until 36 weeks. **Intervention Names:** - Drug: LY3502970 **Label:** 36 mg-1 LY3502970 **Type:** EXPERIMENTAL #### Arm Group 4 **Description:** Participants received maintenance dose 36 mg with dose escalation starting from 3 mg, 6 mg,12 mg, 24 mg and then 36 mg LY3502970 administered orally once daily until 36 weeks. **Intervention Names:** - Drug: LY3502970 **Label:** 36 mg-2 LY3502970 **Type:** EXPERIMENTAL #### Arm Group 5 **Description:** Participants received maintenance dose 45 mg with dose escalation starting from 3 mg, 6 mg, 8 mg, 12 mg, 24 mg, 36 mg and then 45 mg LY3502970 administered orally once daily until 36 weeks. **Intervention Names:** - Drug: LY3502970 **Label:** 45 mg-1 LY3502970 **Type:** EXPERIMENTAL #### Arm Group 6 **Description:** Participants received maintenance dose 45 mg with dose escalation starting from 2 mg, 3 mg, 6 mg, 12 mg, 24 mg, 36 mg and then 45 mg LY3502970 administered orally once daily until 36 weeks. **Intervention Names:** - Drug: LY3502970 **Label:** 45 mg-2 LY3502970 **Type:** EXPERIMENTAL #### Arm Group 7 **Description:** Participants received placebo administered orally once daily until 36 weeks. **Intervention Names:** - Drug: Placebo **Label:** Placebo **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - 12 milligram (mg) LY3502970 - 24 mg LY3502970 - 36 mg-1 LY3502970 - 36 mg-2 LY3502970 - 45 mg-1 LY3502970 - 45 mg-2 LY3502970 **Description:** Administered orally **Name:** LY3502970 **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Placebo **Description:** Administered orally **Name:** Placebo **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Least Squares (LS) mean was determined by mixed model repeated measures (MMRM) model with Baseline + Baseline BMI Group + Sex + Treatment + Time + Treatment\*Time (Type III sum of squares) as variables. Variance-Covariance structure (Actual Value) = Unstructured. Variance-Covariance structure (Percent Change from Baseline) = Unstructured. **Measure:** Percent Change From Baseline in Body Weight in LY3502970 and Placebo **Time Frame:** Baseline, Week 26 #### Secondary Outcomes **Description:** LS mean was determined by MMRM model with Baseline + Baseline BMI Group + Sex + Treatment + Time + Treatment\*Time (Type III sum of squares) as variables. Variance-Covariance structure (Actual Value) = Unstructured. Variance-Covariance structure (Percent Change from Baseline) = Unstructured. **Measure:** Percent Change From Baseline in Body Weight in LY3502970 and Placebo **Time Frame:** Baseline, Week 36 **Description:** LS mean was determined by MMRM model with Baseline + Baseline BMI Group + Sex + Treatment + Time + Treatment\*Time (Type III sum of squares) as variables. Variance-Covariance structure (Actual Value) = Unstructured. Variance-Covariance structure (Percent Change from Baseline) = Unstructured. **Measure:** Change From Baseline in Body Weight in LY3502970 and Placebo **Time Frame:** Baseline, Week 26 **Description:** LS mean was determined by MMRM model with Baseline + Baseline BMI Group + Sex + Treatment + Time + Treatment\*Time (Type III sum of squares) as variables. Variance-Covariance structure (Actual Value) = Unstructured. Variance-Covariance structure (Percent Change from Baseline) = Unstructured. **Measure:** Change From Baseline in Body Weight in LY3502970 and Placebo **Time Frame:** Baseline, Week 36 **Description:** LS mean was determined by MMRM model with Baseline + Baseline BMI Group + Sex + Treatment + Time + Treatment\*Time (Type III sum of squares) as variables. Variance-Covariance structure (Actual Value) = Unstructured. Variance-Covariance structure (Percent Change from Baseline) = Unstructured. **Measure:** Change From Baseline in Waist Circumference in LY3502970 and Placebo **Time Frame:** Baseline, Week 26 **Description:** LS mean was determined by MMRM model with Baseline + Baseline BMI Group + Sex + Treatment + Time + Treatment\*Time (Type III sum of squares) as variables. Variance-Covariance structure (Actual Value) = Unstructured. Variance-Covariance structure (Percent Change from Baseline) = Unstructured. **Measure:** Change From Baseline in Waist Circumference in LY3502970 and Placebo **Time Frame:** Baseline, Week 36 **Description:** LS mean was determined by MMRM model with Baseline + Baseline BMI Group + Sex + Treatment + Time + Treatment\*Time (Type III sum of squares) as variables. Variance-Covariance structure (Actual Value) = Unstructured. Variance-Covariance structure (Percent Change from Baseline) = Unstructured. **Measure:** Change From Baseline in BMI in LY3502970 and Placebo **Time Frame:** Baseline, Week 26 **Description:** LS mean was determined by MMRM model with Baseline + Baseline BMI Group + Sex + Treatment + Time + Treatment\*Time (Type III sum of squares) as variables. Variance-Covariance structure (Actual Value) = Unstructured. Variance-Covariance structure (Percent Change from Baseline) = Unstructured. **Measure:** Change From Baseline in BMI in LY3502970 and Placebo **Time Frame:** Baseline, Week 36 **Description:** Percentage of participants with \>=5% body weight loss was reported. **Measure:** Percentage of Participants With >=5% Body Weight Loss **Time Frame:** Week 26 **Description:** Percentage of participants with \>=10% body weight loss was reported. **Measure:** Percentage of Participants With >=10% Body Weight Loss **Time Frame:** Week 26 **Description:** Percentage of participants with \>=5% body weight loss was reported. **Measure:** Percentage of Participants With >=5% Body Weight Loss **Time Frame:** Week 36 **Description:** Percentage of participants with \>=10% body weight loss was reported. **Measure:** Percentage of Participants With >=10% Body Weight Loss **Time Frame:** Week 36 ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Have a body mass index (BMI) of ≥30-kilogram square meter (kg/m²) * Have a BMI ≥27 kg/m² and \<30 kg/m² with at least 1 of the following weight-related comorbidities eg; \[Have hypertension, or dyslipidemia, cardiovascular disease\] * Have had a stable body weight for the 3 months prior to randomization (not more than 5% body weight gain and/or loss) Exclusion Criteria: * Have any prior diagnosis of diabetes * Have a prior or planned surgical treatment for obesity * Have obesity induced by other endocrinological disorders or diagnosed monogenetic or syndromic forms of obesity * Have renal impairment measured as estimated glomerular filtration rate (eGFR) \<30 milliliter (mL)/minute (min)/1.73 m² * Have a history of acute chronic pancreatitis * Have a history of significant active or unstable Major Depressive Disorder (MDD) or other severe psychiatric disorder (for example, schizophrenia, bipolar disorder, or other serious mood or anxiety disorder) within the last 2 years Note: Participants with MDD or generalized anxiety disorder whose disease state is considered stable for the past 2 years and expected to remain stable throughout the course of the study, may be considered for inclusion if they are not on excluded medications. Within 3 months prior to screening: * Have poorly controlled hypertension * Have history of acute myocardial infarction * Have history of cerebrovascular accident (stroke) * Had hospitalization due to congestive heart failure (CHF) * Have cancer * Have human immunodeficiency virus (HIV) and/or positive HIV antibodies historically or at screening * Have hepatitis B and/or positive hepatitis B surface antigen **Maximum Age:** 75 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Anaheim **Country:** United States **Facility:** Anaheim Clinical Trials, LLC **State:** California **Zip:** 92801 **Location 2:** **City:** Concord **Country:** United States **Facility:** John Muir Physician Network Research Center **State:** California **Zip:** 94520 **Location 3:** **City:** Greenbrae **Country:** United States **Facility:** NorCal Medical Research, Inc **State:** California **Zip:** 94904 **Location 4:** **City:** Northridge **Country:** United States **Facility:** Valley Clinical Trials, Inc. **State:** California **Zip:** 91325 **Location 5:** **City:** San Ramon **Country:** United States **Facility:** Norcal Endocrinology & Internal Medicine **State:** California **Zip:** 94583 **Location 6:** **City:** Blackfoot **Country:** United States **Facility:** Elite Clinical Trials **State:** Idaho **Zip:** 83221 **Location 7:** **City:** Idaho Falls **Country:** United States **Facility:** Rocky Mountain Clinical Research **State:** Idaho **Zip:** 83404 **Location 8:** **City:** Saint Peters **Country:** United States **Facility:** StudyMetrix Research **State:** Missouri **Zip:** 63303 **Location 9:** **City:** Trenton **Country:** United States **Facility:** Premier Research **State:** New Jersey **Zip:** 08611 **Location 10:** **City:** Fargo **Country:** United States **Facility:** Lillestol Research **State:** North Dakota **Zip:** 58104 **Location 11:** **City:** Norman **Country:** United States **Facility:** Intend Research, LLC **State:** Oklahoma **Zip:** 73069 **Location 12:** **City:** Camp Hill **Country:** United States **Facility:** Capital Area Research, LLC **State:** Pennsylvania **Zip:** 17011 **Location 13:** **City:** Pittsburgh **Country:** United States **Facility:** Preferred Primary Care Physicians, Preferred Clinical Research-St. Clair **State:** Pennsylvania **Zip:** 15243 **Location 14:** **City:** Dallas **Country:** United States **Facility:** Dallas Diabetes Research Center **State:** Texas **Zip:** 75230 **Location 15:** **City:** Fort Worth **Country:** United States **Facility:** Diabetes and Thyroid Center of Fort Worth **State:** Texas **Zip:** 76132 **Location 16:** **City:** Round Rock **Country:** United States **Facility:** Texas Diabetes & Endocrinology, P.A. **State:** Texas **Zip:** 78681 **Location 17:** **City:** Richmond **Country:** United States **Facility:** National Clinical Research, Inc **State:** Virginia **Zip:** 23294 **Location 18:** **City:** Green Bay **Country:** United States **Facility:** St. Vincent Hospital d/b/a Prevea Health **State:** Wisconsin **Zip:** 54303 **Location 19:** **City:** Calgary **Country:** Canada **Facility:** C-health Research **State:** Alberta **Zip:** T2V 4J2 **Location 20:** **City:** Hamilton **Country:** Canada **Facility:** Wharton Medical Clinic **State:** Ontario **Zip:** L8L 5G8 **Location 21:** **City:** Sarnia **Country:** Canada **Facility:** Bluewater Clinical Research Group Inc. **State:** Ontario **Zip:** N7T 4X3 **Location 22:** **City:** Saint Marc des Carrières **Country:** Canada **Facility:** Centre Médical et Professionnel de l'Ouest de Portneuf **State:** Quebec **Zip:** G0A 4B0 **Location 23:** **City:** Quebec **Country:** Canada **Facility:** Alpha Recherche Clinique **Zip:** G2J 0C4 **Location 24:** **City:** Quebec **Country:** Canada **Facility:** ALPHA Recherche Clinique **Zip:** G3K 2P8 **Location 25:** **City:** Kalocsa **Country:** Hungary **Facility:** Studium Egeszseghaz Kft **State:** Bács-Kiskun **Zip:** 6300 **Location 26:** **City:** Gyongyos **Country:** Hungary **Facility:** Bugát Pál Kórház **State:** Heves **Zip:** 3200 **Location 27:** **City:** Balatonfüred **Country:** Hungary **Facility:** DRC Gyógyszervizsgáló Központ **State:** Veszprém **Zip:** 8230 **Location 28:** **City:** Nagykanizsa **Country:** Hungary **Facility:** Kanizsai Dorottya Korhaz **State:** Zala **Zip:** 8800 **Location 29:** **City:** Budapest **Country:** Hungary **Facility:** Szent Margit Rendelőintézet Nonprofit Kft **Zip:** 1032 **Location 30:** **City:** Budapest **Country:** Hungary **Facility:** Clinexpert Kft. **Zip:** 1033 **Location 31:** **City:** Budapest **Country:** Hungary **Facility:** TRANTOR'99 Bt. Anyagcsere Centrum **Zip:** 1213 **Location 32:** **City:** Budapest **Country:** Hungary **Facility:** Strazsahegy Medicina Bt. **Zip:** H1171 **Location 33:** **City:** Debrecen **Country:** Hungary **Facility:** Debreceni Egyetem Klinikai Kozpont **Zip:** 4032 **Location 34:** **City:** Ponce **Country:** Puerto Rico **Facility:** Puerto Rico Medical Research **Zip:** 00717 **Location 35:** **City:** Ponce **Country:** Puerto Rico **Facility:** Research and Cardiovascular Corp. **Zip:** 00717 #### Overall Officials **Official 1:** **Affiliation:** Eli Lilly and Company **Name:** Call 1-877-CTLILLY (1-877-285-4559) or 1-317-5615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) **Role:** STUDY_DIRECTOR ### IPD Sharing Statement Module **Access Criteria:** A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement. **Description:** Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement. **Info Types:** - STUDY_PROTOCOL - SAP - CSR **IPD Sharing:** YES **Time Frame:** Data are available 6 months after the primary publication and approval of the indication studied in the US and European Union (EU), whichever is later. Data will be indefinitely available for requesting. **URL:** https://vivli.org/ ### References Module #### See Also Links **Label:** A Study of LY3502970 in Participants With Obesity or Overweight With Weight-related Comorbidities **URL:** https://trials.lillytrialguide.com/en-US/trial/1R7BP1Yw5t6roV3ZWFGzYQ ## Document Section ### Large Document Module #### Large Docs - Date: 2021-09-27 - Filename: Prot_000.pdf - Has ICF: False - Has Protocol: True - Has SAP: False - Label: Study Protocol - Size: 5864017 - Type Abbrev: Prot - Upload Date: 2023-08-08T01:56 - Date: 2022-10-03 - Filename: SAP_001.pdf - Has ICF: False - Has Protocol: False - Has SAP: True - Label: Statistical Analysis Plan - Size: 1191356 - Type Abbrev: SAP - Upload Date: 2023-08-08T01:57 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000044343 - Term: Overnutrition - ID: D000009748 - Term: Nutrition Disorders - ID: D000001835 - Term: Body Weight ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC18 - Name: Nutritional and Metabolic Diseases ### Condition Browse Module - Browse Leaves - ID: M5114 - Name: Body Weight - Relevance: LOW - As Found: Unknown - ID: M12701 - Name: Obesity - Relevance: HIGH - As Found: Obesity - ID: M26186 - Name: Overweight - Relevance: HIGH - As Found: Overweight - ID: M25307 - Name: Overnutrition - Relevance: LOW - As Found: Unknown - ID: M12684 - Name: Nutrition Disorders - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000009765 - Term: Obesity - ID: D000050177 - Term: Overweight ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module **Description:** All randomized participants who received at least one dose of study drug regardless of adherence to study drug. Gender specific events occurring only in male or female participants have had the number of participants at risk adjusted accordingly. #### Event Groups **Group ID:** EG000 **Title:** 12 mg LY3502970 **Deaths Num At Risk:** 50 **Description:** Participants received maintenance dose 12 mg with dose escalation starting from 3 mg,6 mg and then 12 mg LY3502970 administered orally once daily until 36 weeks. **ID:** EG000 **Other Num Affected:** 35 **Other Num at Risk:** 50 **Serious Number At Risk:** 50 **Title:** 12 mg LY3502970 **Group ID:** EG001 **Title:** 24 mg LY3502970 **Deaths Num At Risk:** 53 **Description:** Participants received maintenance dose 24 mg with dose escalation starting from 3 mg, 6 mg, 8 mg,12 mg and then 24 mg LY3502970 administered orally once daily until 36 weeks. **ID:** EG001 **Other Num Affected:** 46 **Other Num at Risk:** 53 **Serious Number Affected:** 2 **Serious Number At Risk:** 53 **Title:** 24 mg LY3502970 **Group ID:** EG002 **Title:** 36 Mg-1 LY3502970 **Deaths Num At Risk:** 29 **Description:** Participants received maintenance dose 36 mg with dose escalation starting from 2 mg, 3 mg, 6 mg, 8 mg, 12 mg, 24 mg and then 36 mg LY3502970 administered orally once daily until 36 weeks. **ID:** EG002 **Other Num Affected:** 23 **Other Num at Risk:** 29 **Serious Number At Risk:** 29 **Title:** 36 Mg-1 LY3502970 **Group ID:** EG003 **Title:** 36 Mg-2 LY3502970 **Deaths Num At Risk:** 29 **Description:** Participants received maintenance dose 36 mg with dose escalation starting from 3 mg, 6 mg,12 mg, 24 mg and then 36 mg LY3502970 administered orally once daily until 36 weeks. **ID:** EG003 **Other Num Affected:** 25 **Other Num at Risk:** 29 **Serious Number Affected:** 3 **Serious Number At Risk:** 29 **Title:** 36 Mg-2 LY3502970 **Group ID:** EG004 **Title:** 45 Mg-1 LY3502970 **Deaths Num At Risk:** 31 **Description:** Participants received maintenance dose 45 mg with dose escalation starting from 3 mg, 6 mg, 8 mg, 12 mg, 24 mg, 36 mg and then 45 mg LY3502970 administered orally once daily until 36 weeks. **ID:** EG004 **Other Num Affected:** 26 **Other Num at Risk:** 31 **Serious Number Affected:** 2 **Serious Number At Risk:** 31 **Title:** 45 Mg-1 LY3502970 **Group ID:** EG005 **Title:** 45 Mg-2 LY3502970 **Deaths Num At Risk:** 30 **Description:** Participants received maintenance dose 45 mg with dose escalation starting from 2 mg, 3 mg, 6 mg, 12 mg, 24 mg, 36 mg and then 45 mg LY3502970 administered orally once daily until 36 weeks. **ID:** EG005 **Other Num Affected:** 24 **Other Num at Risk:** 30 **Serious Number At Risk:** 30 **Title:** 45 Mg-2 LY3502970 **Group ID:** EG006 **Title:** Placebo **Deaths Num At Risk:** 50 **Description:** Participants received placebo administered orally once daily until 36 weeks. **ID:** EG006 **Other Num Affected:** 27 **Other Num at Risk:** 50 **Serious Number At Risk:** 50 **Title:** Placebo **Frequency Threshold:** 5 #### Other Events **Term:** Atrioventricular block first degree **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Abdominal discomfort **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Abdominal distension **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Abdominal pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Abdominal pain upper **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Constipation **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Diarrhoea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Dyspepsia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Eructation **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Flatulence **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Gastrooesophageal reflux disease **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Nausea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Vomiting **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Chills **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Fatigue **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Covid-19 **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 25.1 **Term:** Nasopharyngitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 25.1 **Term:** Sinusitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 25.1 **Term:** Upper respiratory tract infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 25.1 **Term:** Urinary tract infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 25.1 **Term:** Decreased appetite **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Arthralgia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Back pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Muscle spasms **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Myalgia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Pain in extremity **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Dizziness **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Headache **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Dysuria **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Balanoposthitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Reproductive system and breast disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Erectile dysfunction **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Reproductive system and breast disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Postmenopausal haemorrhage **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Reproductive system and breast disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Vulvovaginal pruritus **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Reproductive system and breast disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Oropharyngeal pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Alopecia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA 25.1 **Term:** Hypotension **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA 25.1 #### Serious Events **Term:** Coronary artery disease **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 50 **Group ID:** EG001 **Num At Risk:** 53 **Group ID:** EG002 **Num At Risk:** 29 **Group ID:** EG003 **Num At Risk:** 29 **Group ID:** EG004 **Num Affected:** 1 **Num At Risk:** 31 **Num Events:** 1 **Group ID:** EG005 **Num At Risk:** 30 **Group ID:** EG006 **Num At Risk:** 50 **Term:** Retinal vein thrombosis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Eye disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 50 **Group ID:** EG001 **Num At Risk:** 53 **Group ID:** EG002 **Num At Risk:** 29 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 29 **Num Events:** 1 **Group ID:** EG004 **Num At Risk:** 31 **Group ID:** EG005 **Num At Risk:** 30 **Group ID:** EG006 **Num At Risk:** 50 **Term:** Vitreoretinal traction syndrome **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Eye disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 50 **Group ID:** EG001 **Num At Risk:** 53 **Group ID:** EG002 **Num At Risk:** 29 **Group ID:** EG003 **Num At Risk:** 29 **Group ID:** EG004 **Num Affected:** 1 **Num At Risk:** 31 **Num Events:** 1 **Group ID:** EG005 **Num At Risk:** 30 **Group ID:** EG006 **Num At Risk:** 50 **Term:** Diverticulum intestinal **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 50 **Group ID:** EG001 **Num At Risk:** 53 **Group ID:** EG002 **Num At Risk:** 29 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 29 **Num Events:** 1 **Group ID:** EG004 **Num At Risk:** 31 **Group ID:** EG005 **Num At Risk:** 30 **Group ID:** EG006 **Num At Risk:** 50 **Term:** Gastrointestinal polyp haemorrhage **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 50 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 53 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 29 **Group ID:** EG003 **Num At Risk:** 29 **Group ID:** EG004 **Num At Risk:** 31 **Group ID:** EG005 **Num At Risk:** 30 **Group ID:** EG006 **Num At Risk:** 50 **Term:** Cholecystitis acute **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 50 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 53 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 29 **Group ID:** EG003 **Num At Risk:** 29 **Group ID:** EG004 **Num At Risk:** 31 **Group ID:** EG005 **Num At Risk:** 30 **Group ID:** EG006 **Num At Risk:** 50 **Term:** Hypercalcaemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 50 **Group ID:** EG001 **Num At Risk:** 53 **Group ID:** EG002 **Num At Risk:** 29 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 29 **Num Events:** 1 **Group ID:** EG004 **Num At Risk:** 31 **Group ID:** EG005 **Num At Risk:** 30 **Group ID:** EG006 **Num At Risk:** 50 **Term:** Hepatic cancer metastatic **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA 25.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 50 **Group ID:** EG001 **Num At Risk:** 53 **Group ID:** EG002 **Num At Risk:** 29 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 29 **Num Events:** 1 **Group ID:** EG004 **Num At Risk:** 31 **Group ID:** EG005 **Num At Risk:** 30 **Group ID:** EG006 **Num At Risk:** 50 **Time Frame:** Baseline through Week 38 (36 weeks with 2 weeks safety follow up) ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 50 **Group ID:** BG001 **Value:** 53 **Group ID:** BG002 **Value:** 29 **Group ID:** BG003 **Value:** 29 **Group ID:** BG004 **Value:** 31 **Group ID:** BG005 **Value:** 30 **Group ID:** BG006 **Value:** 50 **Group ID:** BG007 **Value:** 272 **Units:** Participants ### Group **ID:** BG000 **Title:** 12 mg LY3502970 **Description:** Participants received maintenance dose 12 mg with dose escalation starting from 3 mg,6 mg and then 12 mg LY3502970 administered orally once daily until 36 weeks. ### Group **ID:** BG001 **Title:** 24 mg LY3502970 **Description:** Participants received maintenance dose 24 mg with dose escalation starting from 3 mg, 6 mg, 8 mg,12 mg and then 24 mg LY3502970 administered orally once daily until 36 weeks. ### Group **ID:** BG002 **Title:** 36 mg -1 LY3502970 **Description:** Participants received maintenance dose 36 mg with dose escalation starting from 2 mg, 3 mg, 6 mg, 8 mg, 12 mg, 24 mg and then 36 mg LY3502970 administered orally once daily until 36 weeks. ### Group **ID:** BG003 **Title:** 36 mg -2 LY3502970 **Description:** Participants received maintenance dose 36 mg with dose escalation starting from 3 mg, 6 mg,12 mg, 24 mg and then 36 mg LY3502970 administered orally once daily until 36 weeks. ### Group **ID:** BG004 **Title:** 45 mg -1 LY3502970 **Description:** Participants received maintenance dose 45 mg with dose escalation starting from 3 mg, 6 mg, 8 mg, 12 mg, 24 mg, 36 mg and then 45 mg LY3502970 administered orally once daily until 36 weeks. ### Group **ID:** BG005 **Title:** 45 mg -2 LY3502970 **Description:** Participants received maintenance dose 45 mg with dose escalation starting from 2 mg, 3 mg, 6 mg, 12 mg, 24 mg, 36 mg and then 45 mg LY3502970 administered orally once daily until 36 weeks. ### Group **ID:** BG006 **Title:** Placebo **Description:** Participants received placebo administered orally once daily until 36 weeks. ### Group **ID:** BG007 **Title:** Total **Description:** Total of all reporting groups ### Measure #### Measurement **Group ID:** BG000 **Spread:** 10.51 **Value:** 49.80 #### Measurement **Group ID:** BG001 **Spread:** 9.09 **Value:** 57.00 #### Measurement **Group ID:** BG002 **Spread:** 11.83 **Value:** 56.30 #### Measurement **Group ID:** BG003 **Spread:** 10.93 **Value:** 55.40 #### Measurement **Group ID:** BG004 **Spread:** 10.74 **Value:** 56.50 #### Measurement **Group ID:** BG005 **Spread:** 12.58 **Value:** 50.90 #### Measurement **Group ID:** BG006 **Spread:** 8.82 **Value:** 54.00 #### Measurement **Group ID:** BG007 **Spread:** 10.67 **Value:** 54.20 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 31 #### Measurement **Group ID:** BG001 **Value:** 30 #### Measurement **Group ID:** BG002 **Value:** 18 #### Measurement **Group ID:** BG003 **Value:** 18 #### Measurement **Group ID:** BG004 **Value:** 19 #### Measurement **Group ID:** BG005 **Value:** 16 #### Measurement **Group ID:** BG006 **Value:** 29 #### Measurement **Group ID:** BG007 **Value:** 161 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 19 #### Measurement **Group ID:** BG001 **Value:** 23 #### Measurement **Group ID:** BG002 **Value:** 11 #### Measurement **Group ID:** BG003 **Value:** 11 #### Measurement **Group ID:** BG004 **Value:** 12 #### Measurement **Group ID:** BG005 **Value:** 14 #### Measurement **Group ID:** BG006 **Value:** 21 #### Measurement **Group ID:** BG007 **Value:** 111 **Category Title:** Male **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 11 #### Measurement **Group ID:** BG001 **Value:** 6 #### Measurement **Group ID:** BG002 **Value:** 4 #### Measurement **Group ID:** BG003 **Value:** 2 #### Measurement **Group ID:** BG004 **Value:** 4 #### Measurement **Group ID:** BG005 **Value:** 7 #### Measurement **Group ID:** BG006 **Value:** 5 #### Measurement **Group ID:** BG007 **Value:** 39 **Category Title:** Hispanic or Latino #### Measurement **Group ID:** BG000 **Value:** 38 #### Measurement **Group ID:** BG001 **Value:** 46 #### Measurement **Group ID:** BG002 **Value:** 23 #### Measurement **Group ID:** BG003 **Value:** 26 #### Measurement **Group ID:** BG004 **Value:** 25 #### Measurement **Group ID:** BG005 **Value:** 22 #### Measurement **Group ID:** BG006 **Value:** 43 #### Measurement **Group ID:** BG007 **Value:** 223 **Category Title:** Not Hispanic or Latino #### Measurement **Group ID:** BG000 **Value:** 1 #### Measurement **Group ID:** BG001 **Value:** 1 #### Measurement **Group ID:** BG002 **Value:** 2 #### Measurement **Group ID:** BG003 **Value:** 1 #### Measurement **Group ID:** BG004 **Value:** 2 #### Measurement **Group ID:** BG005 **Value:** 1 #### Measurement **Group ID:** BG006 **Value:** 2 #### Measurement **Group ID:** BG007 **Value:** 10 **Category Title:** Unknown or Not Reported **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 1 #### Measurement **Group ID:** BG002 **Value:** 0 #### Measurement **Group ID:** BG003 **Value:** 0 #### Measurement **Group ID:** BG004 **Value:** 0 #### Measurement **Group ID:** BG005 **Value:** 0 #### Measurement **Group ID:** BG006 **Value:** 0 #### Measurement **Group ID:** BG007 **Value:** 1 **Category Title:** American Indian or Alaska Native #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 #### Measurement **Group ID:** BG003 **Value:** 0 #### Measurement **Group ID:** BG004 **Value:** 0 #### Measurement **Group ID:** BG005 **Value:** 0 #### Measurement **Group ID:** BG006 **Value:** 2 #### Measurement **Group ID:** BG007 **Value:** 2 **Category Title:** Asian #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 #### Measurement **Group ID:** BG003 **Value:** 0 #### Measurement **Group ID:** BG004 **Value:** 0 #### Measurement **Group ID:** BG005 **Value:** 0 #### Measurement **Group ID:** BG006 **Value:** 0 #### Measurement **Group ID:** BG007 **Value:** 0 **Category Title:** Native Hawaiian or Other Pacific Islander #### Measurement **Group ID:** BG000 **Value:** 3 #### Measurement **Group ID:** BG001 **Value:** 6 #### Measurement **Group ID:** BG002 **Value:** 4 #### Measurement **Group ID:** BG003 **Value:** 4 #### Measurement **Group ID:** BG004 **Value:** 1 #### Measurement **Group ID:** BG005 **Value:** 0 #### Measurement **Group ID:** BG006 **Value:** 1 #### Measurement **Group ID:** BG007 **Value:** 19 **Category Title:** Black or African American #### Measurement **Group ID:** BG000 **Value:** 47 #### Measurement **Group ID:** BG001 **Value:** 46 #### Measurement **Group ID:** BG002 **Value:** 25 #### Measurement **Group ID:** BG003 **Value:** 25 #### Measurement **Group ID:** BG004 **Value:** 29 #### Measurement **Group ID:** BG005 **Value:** 30 #### Measurement **Group ID:** BG006 **Value:** 45 #### Measurement **Group ID:** BG007 **Value:** 247 **Category Title:** White #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 #### Measurement **Group ID:** BG003 **Value:** 0 #### Measurement **Group ID:** BG004 **Value:** 0 #### Measurement **Group ID:** BG005 **Value:** 0 #### Measurement **Group ID:** BG006 **Value:** 2 #### Measurement **Group ID:** BG007 **Value:** 2 **Category Title:** More than one race #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 #### Measurement **Group ID:** BG003 **Value:** 0 #### Measurement **Group ID:** BG004 **Value:** 1 #### Measurement **Group ID:** BG005 **Value:** 0 #### Measurement **Group ID:** BG006 **Value:** 0 #### Measurement **Group ID:** BG007 **Value:** 1 **Category Title:** Unknown or Not Reported **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 9 #### Measurement **Group ID:** BG001 **Value:** 11 #### Measurement **Group ID:** BG002 **Value:** 5 #### Measurement **Group ID:** BG003 **Value:** 3 #### Measurement **Group ID:** BG004 **Value:** 9 #### Measurement **Group ID:** BG005 **Value:** 5 #### Measurement **Group ID:** BG006 **Value:** 6 #### Measurement **Group ID:** BG007 **Value:** 48 **Class Title:** Canada #### Measurement **Group ID:** BG000 **Value:** 6 #### Measurement **Group ID:** BG001 **Value:** 5 #### Measurement **Group ID:** BG002 **Value:** 3 #### Measurement **Group ID:** BG003 **Value:** 6 #### Measurement **Group ID:** BG004 **Value:** 3 #### Measurement **Group ID:** BG005 **Value:** 3 #### Measurement **Group ID:** BG006 **Value:** 5 #### Measurement **Group ID:** BG007 **Value:** 31 **Class Title:** Hungary #### Measurement **Group ID:** BG000 **Value:** 35 #### Measurement **Group ID:** BG001 **Value:** 37 #### Measurement **Group ID:** BG002 **Value:** 21 #### Measurement **Group ID:** BG003 **Value:** 20 #### Measurement **Group ID:** BG004 **Value:** 19 #### Measurement **Group ID:** BG005 **Value:** 22 #### Measurement **Group ID:** BG006 **Value:** 39 #### Measurement **Group ID:** BG007 **Value:** 193 **Class Title:** United States ### Measure #### Measurement **Group ID:** BG000 **Spread:** 25.34 **Value:** 107.49 #### Measurement **Group ID:** BG001 **Spread:** 30.18 **Value:** 112.05 #### Measurement **Group ID:** BG002 **Spread:** 22.45 **Value:** 107.78 #### Measurement **Group ID:** BG003 **Spread:** 28.52 **Value:** 108.84 #### Measurement **Group ID:** BG004 **Spread:** 20.40 **Value:** 105.23 #### Measurement **Group ID:** BG005 **Spread:** 28.11 **Value:** 110.85 #### Measurement **Group ID:** BG006 **Spread:** 25.24 **Value:** 107.57 #### Measurement **Group ID:** BG007 **Spread:** 26.03 **Value:** 108.68 **Class Title:** **Denomination Units Selected:** ## Results Section - Baseline Characteristics Module ### Measure 1 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** Age, Continuous **Unit of Measure:** years ### Measure 2 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Sex: Female, Male **Unit of Measure:** Participants ### Measure 3 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Ethnicity (NIH/OMB) **Unit of Measure:** Participants ### Measure 4 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Race (NIH/OMB) **Unit of Measure:** Participants ### Measure 5 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Region of Enrollment **Unit of Measure:** Participants ### Measure 6 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** Baseline Body Weight **Unit of Measure:** Kilograms (kg) **Population Description:** All randomized participants. ## Results Section - More Information Module ### Certain Agreement **Restriction Type:** GT60 **Restrictive Agreement:** True ### Point of Contact **Email:** [email protected] **Organization:** Eli Lilly and Company **Phone:** 800-545-5979 **Title:** Chief Medical Officer ## Results Section - Outcome Measures Module ### Outcome Measure 1 #### Analysis **CI Lower Limit:** -8.9 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -4.2 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** <0.001 **P-Value Comment:** **Parameter Type:** LS Mean difference (Final Values) **Parameter Value:** -6.5 **Statistical Comment:** **Statistical Method:** Mixed Models Analysis **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** -11.5 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -6.9 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** <0.001 **P-Value Comment:** **Parameter Type:** LS Mean difference (Final Values) **Parameter Value:** -9.2 **Statistical Comment:** **Statistical Method:** Mixed Models Analysis **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** -12.4 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -8.0 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** <0.001 **P-Value Comment:** **Parameter Type:** LS Mean difference (Final Values) **Parameter Value:** -10.2 **Statistical Comment:** **Statistical Method:** Mixed Models Analysis **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** -12.7 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -8.4 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** <0.001 **P-Value Comment:** **Parameter Type:** LS Mean difference (Final Values) **Parameter Value:** -10.6 **Statistical Comment:** **Statistical Method:** Mixed Models Analysis **Tested Non-Inferiority:** ### Outcome Measure 2 #### Analysis **CI Lower Limit:** -9.9 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -4.2 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** OTHER **Other Analysis Description:** **P-Value:** <0.001 **P-Value Comment:** **Parameter Type:** LS Mean difference (Final Values) **Parameter Value:** -7.1 **Statistical Comment:** **Statistical Method:** Mixed Models Analysis **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** -12.9 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -7.3 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** OTHER **Other Analysis Description:** **P-Value:** <0.001 **P-Value Comment:** **Parameter Type:** LS Mean difference (Final Values) **Parameter Value:** -10.1 **Statistical Comment:** **Statistical Method:** Mixed Models Analysis **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** -13.8 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -8.4 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** OTHER **Other Analysis Description:** **P-Value:** <0.001 **P-Value Comment:** **Parameter Type:** LS Mean difference (Final Values) **Parameter Value:** -11.1 **Statistical Comment:** **Statistical Method:** Mixed Models Analysis **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** -15.0 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -9.6 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** OTHER **Other Analysis Description:** **P-Value:** <0.001 **P-Value Comment:** **Parameter Type:** LS Mean difference (Final Values) **Parameter Value:** -12.3 **Statistical Comment:** **Statistical Method:** Mixed Models Analysis **Tested Non-Inferiority:** ### Outcome Measure 3 #### Analysis **CI Lower Limit:** -9.3 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -4.4 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** OTHER **Other Analysis Description:** **P-Value:** <0.001 **P-Value Comment:** **Parameter Type:** LS Mean difference (Final Values) **Parameter Value:** -6.9 **Statistical Comment:** **Statistical Method:** Mixed Models Analysis **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** -12.5 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -7.8 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** OTHER **Other Analysis Description:** **P-Value:** <0.001 **P-Value Comment:** **Parameter Type:** LS Mean difference (Final Values) **Parameter Value:** -10.2 **Statistical Comment:** **Statistical Method:** Mixed Models Analysis **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** -13.1 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -8.5 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** OTHER **Other Analysis Description:** **P-Value:** <0.001 **P-Value Comment:** **Parameter Type:** LS Mean difference (Final Values) **Parameter Value:** -10.8 **Statistical Comment:** **Statistical Method:** Mixed Models Analysis **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** -13.5 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -8.9 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** OTHER **Other Analysis Description:** **P-Value:** <0.001 **P-Value Comment:** **Parameter Type:** LS Mean difference (Final Values) **Parameter Value:** -11.2 **Statistical Comment:** **Statistical Method:** Mixed Models Analysis **Tested Non-Inferiority:** ### Outcome Measure 4 #### Analysis **CI Lower Limit:** -10.4 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -4.3 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** OTHER **Other Analysis Description:** **P-Value:** <0.001 **P-Value Comment:** **Parameter Type:** LS Mean difference (Final Values) **Parameter Value:** -7.4 **Statistical Comment:** **Statistical Method:** Mixed Models Analysis **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** -14.2 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -8.3 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** OTHER **Other Analysis Description:** **P-Value:** <0.001 **P-Value Comment:** **Parameter Type:** LS Mean difference (Final Values) **Parameter Value:** -11.2 **Statistical Comment:** **Statistical Method:** Mixed Models Analysis **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** -14.7 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -9.0 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** OTHER **Other Analysis Description:** **P-Value:** <0.001 **P-Value Comment:** **Parameter Type:** LS Mean difference (Final Values) **Parameter Value:** -11.8 **Statistical Comment:** **Statistical Method:** Mixed Models Analysis **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** -15.8 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -10.2 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** OTHER **Other Analysis Description:** **P-Value:** <0.001 **P-Value Comment:** **Parameter Type:** LS Mean difference (Final Values) **Parameter Value:** -13.0 **Statistical Comment:** **Statistical Method:** Mixed Models Analysis **Tested Non-Inferiority:** ### Outcome Measure 5 #### Analysis **CI Lower Limit:** -7.2 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -1.6 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** OTHER **Other Analysis Description:** **P-Value:** 0.002 **P-Value Comment:** **Parameter Type:** LS Mean difference (Final Values) **Parameter Value:** -4.4 **Statistical Comment:** **Statistical Method:** Mixed Models Analysis **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** -8.0 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -2.4 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** OTHER **Other Analysis Description:** **P-Value:** <0.001 **P-Value Comment:** **Parameter Type:** LS Mean difference (Final Values) **Parameter Value:** -5.2 **Statistical Comment:** **Statistical Method:** Mixed Models Analysis **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** -9.2 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -3.8 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** OTHER **Other Analysis Description:** **P-Value:** <0.001 **P-Value Comment:** **Parameter Type:** LS Mean difference (Final Values) **Parameter Value:** -6.5 **Statistical Comment:** **Statistical Method:** Mixed Models Analysis **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** -11.3 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -6.0 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** OTHER **Other Analysis Description:** **P-Value:** <0.001 **P-Value Comment:** **Parameter Type:** LS Mean difference (Final Values) **Parameter Value:** -8.7 **Statistical Comment:** **Statistical Method:** Mixed Models Analysis **Tested Non-Inferiority:** ### Outcome Measure 6 #### Analysis **CI Lower Limit:** -8.8 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -2.4 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** OTHER **Other Analysis Description:** **P-Value:** <0.001 **P-Value Comment:** **Parameter Type:** LS Mean difference (Final Values) **Parameter Value:** -5.6 **Statistical Comment:** **Statistical Method:** Mixed Models Analysis **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** -10.3 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -4.0 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** OTHER **Other Analysis Description:** **P-Value:** <0.001 **P-Value Comment:** **Parameter Type:** LS Mean difference (Final Values) **Parameter Value:** -7.2 **Statistical Comment:** **Statistical Method:** Mixed Models Analysis **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** -9.7 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -3.6 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** OTHER **Other Analysis Description:** **P-Value:** <0.001 **P-Value Comment:** **Parameter Type:** LS Mean difference (Final Values) **Parameter Value:** -6.6 **Statistical Comment:** **Statistical Method:** Mixed Models Analysis **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** -12.7 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -6.6 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** OTHER **Other Analysis Description:** **P-Value:** <0.001 **P-Value Comment:** **Parameter Type:** LS Mean difference (Final Values) **Parameter Value:** -9.6 **Statistical Comment:** **Statistical Method:** Mixed Models Analysis **Tested Non-Inferiority:** ### Outcome Measure 7 #### Analysis **CI Lower Limit:** -3.2 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -1.6 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** OTHER **Other Analysis Description:** **P-Value:** <0.001 **P-Value Comment:** **Parameter Type:** LS Mean difference (Final Values) **Parameter Value:** -2.4 **Statistical Comment:** **Statistical Method:** Mixed Models Analysis **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** -4.3 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -2.6 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** OTHER **Other Analysis Description:** **P-Value:** <0.001 **P-Value Comment:** **Parameter Type:** LS Mean difference (Final Values) **Parameter Value:** -3.5 **Statistical Comment:** **Statistical Method:** Mixed Models Analysis **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** -4.6 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 3.0 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** OTHER **Other Analysis Description:** **P-Value:** <0.001 **P-Value Comment:** **Parameter Type:** LS Mean difference (Final Values) **Parameter Value:** -3.8 **Statistical Comment:** **Statistical Method:** Mixed Models Analysis **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** -4.7 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -3.1 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** OTHER **Other Analysis Description:** **P-Value:** <0.001 **P-Value Comment:** **Parameter Type:** LS Mean difference (Final Values) **Parameter Value:** -3.9 **Statistical Comment:** **Statistical Method:** Mixed Models Analysis **Tested Non-Inferiority:** ### Outcome Measure 8 #### Analysis **CI Lower Limit:** -3.6 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -1.5 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** OTHER **Other Analysis Description:** **P-Value:** <0.001 **P-Value Comment:** **Parameter Type:** LS Mean difference (Final Values) **Parameter Value:** -2.5 **Statistical Comment:** **Statistical Method:** Mixed Models Analysis **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** -4.8 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -2.8 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** OTHER **Other Analysis Description:** **P-Value:** <0.001 **P-Value Comment:** **Parameter Type:** LS Mean difference (Final Values) **Parameter Value:** -3.8 **Statistical Comment:** **Statistical Method:** Mixed Models Analysis **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** -5.2 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -3.2 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** OTHER **Other Analysis Description:** **P-Value:** <0.001 **P-Value Comment:** **Parameter Type:** LS Mean difference (Final Values) **Parameter Value:** -4.2 **Statistical Comment:** **Statistical Method:** Mixed Models Analysis **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** -5.6 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -3.6 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** OTHER **Other Analysis Description:** **P-Value:** <0.001 **P-Value Comment:** **Parameter Type:** LS Mean difference (Final Values) **Parameter Value:** -4.6 **Statistical Comment:** **Statistical Method:** Mixed Models Analysis **Tested Non-Inferiority:** ### Outcome Measure 9 #### Analysis **CI Lower Limit:** 3.61 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 27.44 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** OTHER **Other Analysis Description:** **P-Value:** <0.001 **P-Value Comment:** **Parameter Type:** Odds Ratio (OR) **Parameter Value:** 9.96 **Statistical Comment:** **Statistical Method:** Regression, Logistic **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 8.15 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 96.01 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** OTHER **Other Analysis Description:** **P-Value:** <0.001 **P-Value Comment:** **Parameter Type:** Odds Ratio (OR) **Parameter Value:** 27.97 **Statistical Comment:** **Statistical Method:** Regression, Logistic **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 8.71 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 85.91 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** OTHER **Other Analysis Description:** **P-Value:** <0.001 **P-Value Comment:** **Parameter Type:** Odds Ratio (OR) **Parameter Value:** 27.36 **Statistical Comment:** **Statistical Method:** Regression, Logistic **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 7.65 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 72.77 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** OTHER **Other Analysis Description:** **P-Value:** <0.001 **P-Value Comment:** **Parameter Type:** Odds Ratio (OR) **Parameter Value:** 23.59 **Statistical Comment:** **Statistical Method:** Regression, Logistic **Tested Non-Inferiority:** ### Outcome Measure 10 #### Analysis **CI Lower Limit:** 3.47 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 114.40 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** OTHER **Other Analysis Description:** **P-Value:** <0.001 **P-Value Comment:** **Parameter Type:** Odds Ratio (OR) **Parameter Value:** 19.93 **Statistical Comment:** **Statistical Method:** Regression, Logistic **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 6.95 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 224.83 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** OTHER **Other Analysis Description:** **P-Value:** <0.001 **P-Value Comment:** **Parameter Type:** Odds Ratio (OR) **Parameter Value:** 39.52 **Statistical Comment:** **Statistical Method:** Regression, Logistic **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 13.16 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 427.18 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** OTHER **Other Analysis Description:** **P-Value:** <0.001 **P-Value Comment:** **Parameter Type:** Odds Ratio (OR) **Parameter Value:** 74.97 **Statistical Comment:** **Statistical Method:** Regression, Logistic **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 12.62 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 413.21 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** OTHER **Other Analysis Description:** **P-Value:** <0.001 **P-Value Comment:** **Parameter Type:** Odds Ratio (OR) **Parameter Value:** 72.23 **Statistical Comment:** **Statistical Method:** Regression, Logistic **Tested Non-Inferiority:** ### Outcome Measure 11 #### Analysis **CI Lower Limit:** 2.90 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 20.92 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** OTHER **Other Analysis Description:** **P-Value:** <0.001 **P-Value Comment:** **Parameter Type:** Odds Ratio (OR) **Parameter Value:** 7.79 **Statistical Comment:** **Statistical Method:** Regression, Logistic **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 7.49 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 83.91 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** OTHER **Other Analysis Description:** **P-Value:** <0.001 **P-Value Comment:** **Parameter Type:** Odds Ratio (OR) **Parameter Value:** 25.07 **Statistical Comment:** **Statistical Method:** Regression, Logistic **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 8.17 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 147.86 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** OTHER **Other Analysis Description:** **P-Value:** <0.001 **P-Value Comment:** **Parameter Type:** Odds Ratio (OR) **Parameter Value:** 34.76 **Statistical Comment:** **Statistical Method:** Regression, Logistic **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 8.15 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 96.29 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** OTHER **Other Analysis Description:** **P-Value:** <0.001 **P-Value Comment:** **Parameter Type:** Odds Ratio (OR) **Parameter Value:** 28.01 **Statistical Comment:** **Statistical Method:** Regression, Logistic **Tested Non-Inferiority:** ### Outcome Measure 12 #### Analysis **CI Lower Limit:** 2.59 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 26.45 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** OTHER **Other Analysis Description:** **P-Value:** <0.001 **P-Value Comment:** **Parameter Type:** Odds Ratio (OR) **Parameter Value:** 8.27 **Statistical Comment:** **Statistical Method:** Regression, Logistic **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 4.83 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 50.68 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** OTHER **Other Analysis Description:** **P-Value:** <0.001 **P-Value Comment:** **Parameter Type:** Odds Ratio (OR) **Parameter Value:** 15.64 **Statistical Comment:** **Statistical Method:** Regression, Logistic **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 8.39 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 88.38 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** OTHER **Other Analysis Description:** **P-Value:** <0.001 **P-Value Comment:** **Parameter Type:** Odds Ratio (OR) **Parameter Value:** 27.24 **Statistical Comment:** **Statistical Method:** Regression, Logistic **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 6.59 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 66.17 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** OTHER **Other Analysis Description:** **P-Value:** <0.001 **P-Value Comment:** **Parameter Type:** Odds Ratio (OR) **Parameter Value:** 20.88 **Statistical Comment:** **Statistical Method:** Regression, Logistic **Tested Non-Inferiority:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.85 - **Upper Limit:** - **Value:** -8.6 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.82 - **Upper Limit:** - **Value:** -11.2 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 0.77 - **Upper Limit:** - **Value:** -12.3 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** 0.75 - **Upper Limit:** - **Value:** -12.6 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** 0.81 - **Upper Limit:** - **Value:** -2.0 **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.05 - **Upper Limit:** - **Value:** -9.4 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.01 - **Upper Limit:** - **Value:** -12.5 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 0.95 - **Upper Limit:** - **Value:** -13.5 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** 0.94 - **Upper Limit:** - **Value:** -14.7 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** 1.00 - **Upper Limit:** - **Value:** -2.3 **Title:** #### Outcome Measure 3 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.90 - **Upper Limit:** - **Value:** -9.0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.86 - **Upper Limit:** - **Value:** -12.3 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 0.82 - **Upper Limit:** - **Value:** -12.9 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** 0.79 - **Upper Limit:** - **Value:** -13.3 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** 0.86 - **Upper Limit:** - **Value:** -2.1 **Title:** #### Outcome Measure 4 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.10 - **Upper Limit:** - **Value:** -9.8 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.06 - **Upper Limit:** - **Value:** -13.6 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 1.00 - **Upper Limit:** - **Value:** -14.2 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** 0.98 - **Upper Limit:** - **Value:** -15.4 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** 1.05 - **Upper Limit:** - **Value:** -2.4 **Title:** #### Outcome Measure 5 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.03 - **Upper Limit:** - **Value:** -8.0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.00 - **Upper Limit:** - **Value:** -8.8 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 0.94 - **Upper Limit:** - **Value:** -10.1 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** 0.93 - **Upper Limit:** - **Value:** -12.2 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** 0.99 - **Upper Limit:** - **Value:** -3.6 **Title:** #### Outcome Measure 6 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.18 - **Upper Limit:** - **Value:** -9.6 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.15 - **Upper Limit:** - **Value:** -11.2 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 1.06 - **Upper Limit:** - **Value:** -10.6 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** 1.07 - **Upper Limit:** - **Value:** -13.6 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** 1.12 - **Upper Limit:** - **Value:** -4.0 **Title:** #### Outcome Measure 7 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.31 - **Upper Limit:** - **Value:** -3.2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.30 - **Upper Limit:** - **Value:** -4.2 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 0.28 - **Upper Limit:** - **Value:** -4.6 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** 0.27 - **Upper Limit:** - **Value:** -4.7 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** 0.29 - **Upper Limit:** - **Value:** -0.8 **Title:** #### Outcome Measure 8 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.38 - **Upper Limit:** - **Value:** -3.4 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.36 - **Upper Limit:** - **Value:** -4.7 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 0.34 - **Upper Limit:** - **Value:** -5.0 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** 0.34 - **Upper Limit:** - **Value:** -5.5 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** 0.36 - **Upper Limit:** - **Value:** -0.9 **Title:** #### Outcome Measure 9 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 74.39 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 88.84 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 89.46 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 87.26 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 22.88 **Title:** #### Outcome Measure 10 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 39.39 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 56.61 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 71.30 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 69.86 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2.25 **Title:** #### Outcome Measure 11 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 72.00 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 89.47 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 92.05 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 90.44 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 24.02 **Title:** #### Outcome Measure 12 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 46.50 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 61.88 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 74.75 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 69.07 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 8.85 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** Least Squares (LS) mean was determined by mixed model repeated measures (MMRM) model with Baseline + Baseline BMI Group + Sex + Treatment + Time + Treatment\*Time (Type III sum of squares) as variables. Variance-Covariance structure (Actual Value) = Unstructured. Variance-Covariance structure (Percent Change from Baseline) = Unstructured. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** All randomized participants who received at least one dose of study drug and had baseline and at least one post-baseline body weight value. **Reporting Status:** POSTED **Time Frame:** Baseline, Week 26 **Title:** Percent Change From Baseline in Body Weight in LY3502970 and Placebo **Type:** PRIMARY **Unit of Measure:** Percent change ##### Group **Description:** Participants received maintenance dose 12 mg with dose escalation starting from 3 mg,6 mg and then 12 mg LY3502970 administered orally once daily until 36 weeks. **ID:** OG000 **Title:** 12 mg LY3502970 ##### Group **Description:** Participants received maintenance dose 24 mg with dose escalation starting from 3 mg, 6 mg, 8 mg,12 mg and then 24 mg LY3502970 administered orally once daily until 36 weeks. **ID:** OG001 **Title:** 24 mg LY3502970 ##### Group **Description:** Participants received maintenance dose 36 mg with dose escalation starting from 2 mg, 3 mg, 6 mg, 8 mg, 12 mg, 24 mg and then 36 mg LY3502970 in LY 36mg-1 and dose escalation starting from 3 mg, 6 mg,12 mg, 24 mg and then 36 mg LY3502970 in LY 36mg-2 administered orally once daily until 36 weeks. **ID:** OG002 **Title:** 36 mg LY3502970 ##### Group **Description:** Participants received maintenance dose 45 mg with dose escalation starting from 3 mg, 6 mg, 8 mg, 12 mg, 24 mg, 36 mg and then 45 mg LY3502970 in LY 45mg-1 and dose escalation starting from 2 mg, 3 mg, 6 mg, 12 mg, 24 mg, 36 mg and then 45 mg LY3502970 in LY 45mg-2 administered orally once daily until 36 weeks. **ID:** OG003 **Title:** 45 mg LY3502970 ##### Group **Description:** Participants received placebo administered orally once daily until 36 weeks. **ID:** OG004 **Title:** Placebo #### Outcome Measure 2 **Description:** LS mean was determined by MMRM model with Baseline + Baseline BMI Group + Sex + Treatment + Time + Treatment\*Time (Type III sum of squares) as variables. Variance-Covariance structure (Actual Value) = Unstructured. Variance-Covariance structure (Percent Change from Baseline) = Unstructured. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** All randomized participants who received at least one dose of study drug and had baseline and at least one post-baseline body weight value. **Reporting Status:** POSTED **Time Frame:** Baseline, Week 36 **Title:** Percent Change From Baseline in Body Weight in LY3502970 and Placebo **Type:** SECONDARY **Unit of Measure:** Percent change ##### Group **Description:** Participants received maintenance dose 12 mg with dose escalation starting from 3 mg,6 mg and then 12 mg LY3502970 administered orally once daily until 36 weeks. **ID:** OG000 **Title:** 12 mg LY3502970 ##### Group **Description:** Participants received maintenance dose 24 mg with dose escalation starting from 3 mg, 6 mg, 8 mg,12 mg and then 24 mg LY3502970 administered orally once daily until 36 weeks. **ID:** OG001 **Title:** 24 mg LY3502970 ##### Group **Description:** Participants received maintenance dose 36 mg with dose escalation starting from 2 mg, 3 mg, 6 mg, 8 mg, 12 mg, 24 mg and then 36 mg LY3502970 in LY 36mg-1 and dose escalation starting from 3 mg, 6 mg,12 mg, 24 mg and then 36 mg LY3502970 in LY 36mg-2 administered orally once daily until 36 weeks. **ID:** OG002 **Title:** 36 mg LY3502970 ##### Group **Description:** Participants received maintenance dose 45 mg with dose escalation starting from 3 mg, 6 mg, 8 mg, 12 mg, 24 mg, 36 mg and then 45 mg LY3502970 in LY 45mg-1 and dose escalation starting from 2 mg, 3 mg, 6 mg, 12 mg, 24 mg, 36 mg and then 45 mg LY3502970 in LY 45mg-2 administered orally once daily until 36 weeks. **ID:** OG003 **Title:** 45 mg LY3502970 ##### Group **Description:** Participants received placebo administered orally once daily until 36 weeks. **ID:** OG004 **Title:** Placebo #### Outcome Measure 3 **Description:** LS mean was determined by MMRM model with Baseline + Baseline BMI Group + Sex + Treatment + Time + Treatment\*Time (Type III sum of squares) as variables. Variance-Covariance structure (Actual Value) = Unstructured. Variance-Covariance structure (Percent Change from Baseline) = Unstructured. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** All randomized participants who received at least one dose of study drug and had baseline and at least one post-baseline body weight value. **Reporting Status:** POSTED **Time Frame:** Baseline, Week 26 **Title:** Change From Baseline in Body Weight in LY3502970 and Placebo **Type:** SECONDARY **Unit of Measure:** kg ##### Group **Description:** Participants received maintenance dose 12 mg with dose escalation starting from 3 mg,6 mg and then 12 mg LY3502970 administered orally once daily until 36 weeks. **ID:** OG000 **Title:** 12 mg LY3502970 ##### Group **Description:** Participants received maintenance dose 24 mg with dose escalation starting from 3 mg, 6 mg, 8 mg,12 mg and then 24 mg LY3502970 administered orally once daily until 36 weeks. **ID:** OG001 **Title:** 24 mg LY3502970 ##### Group **Description:** Participants received maintenance dose 36 mg with dose escalation starting from 2 mg, 3 mg, 6 mg, 8 mg, 12 mg, 24 mg and then 36 mg LY3502970 in LY 36mg-1 and dose escalation starting from 3 mg, 6 mg,12 mg, 24 mg and then 36 mg LY3502970 in LY 36mg-2 administered orally once daily until 36 weeks. **ID:** OG002 **Title:** 36 mg LY3502970 ##### Group **Description:** Participants received maintenance dose 45 mg with dose escalation starting from 3 mg, 6 mg, 8 mg, 12 mg, 24 mg, 36 mg and then 45 mg LY3502970 in LY 45mg-1 and dose escalation starting from 2 mg, 3 mg, 6 mg, 12 mg, 24 mg, 36 mg and then 45 mg LY3502970 in LY 45mg-2 administered orally once daily until 36 weeks. **ID:** OG003 **Title:** 45 mg LY3502970 ##### Group **Description:** Participants received placebo administered orally once daily until 36 weeks. **ID:** OG004 **Title:** Placebo #### Outcome Measure 4 **Description:** LS mean was determined by MMRM model with Baseline + Baseline BMI Group + Sex + Treatment + Time + Treatment\*Time (Type III sum of squares) as variables. Variance-Covariance structure (Actual Value) = Unstructured. Variance-Covariance structure (Percent Change from Baseline) = Unstructured. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** All randomized participants who received at least one dose of study drug and had baseline and at least one post-baseline body weight value. **Reporting Status:** POSTED **Time Frame:** Baseline, Week 36 **Title:** Change From Baseline in Body Weight in LY3502970 and Placebo **Type:** SECONDARY **Unit of Measure:** kg ##### Group **Description:** Participants received maintenance dose 12 mg with dose escalation starting from 3 mg,6 mg and then 12 mg LY3502970 administered orally once daily until 36 weeks. **ID:** OG000 **Title:** 12 mg LY3502970 ##### Group **Description:** Participants received maintenance dose 24 mg with dose escalation starting from 3 mg, 6 mg, 8 mg,12 mg and then 24 mg LY3502970 administered orally once daily until 36 weeks. **ID:** OG001 **Title:** 24 mg LY3502970 ##### Group **Description:** Participants received maintenance dose 36 mg with dose escalation starting from 2 mg, 3 mg, 6 mg, 8 mg, 12 mg, 24 mg and then 36 mg LY3502970 in LY 36mg-1 and dose escalation starting from 3 mg, 6 mg,12 mg, 24 mg and then 36 mg LY3502970 in LY 36mg-2 administered orally once daily until 36 weeks. **ID:** OG002 **Title:** 36 mg LY3502970 ##### Group **Description:** Participants received maintenance dose 45 mg with dose escalation starting from 3 mg, 6 mg, 8 mg, 12 mg, 24 mg, 36 mg and then 45 mg LY3502970 in LY 45mg-1 and dose escalation starting from 2 mg, 3 mg, 6 mg, 12 mg, 24 mg, 36 mg and then 45 mg LY3502970 in LY 45mg-2 administered orally once daily until 36 weeks. **ID:** OG003 **Title:** 45 mg LY3502970 ##### Group **Description:** Participants received placebo administered orally once daily until 36 weeks. **ID:** OG004 **Title:** Placebo #### Outcome Measure 5 **Description:** LS mean was determined by MMRM model with Baseline + Baseline BMI Group + Sex + Treatment + Time + Treatment\*Time (Type III sum of squares) as variables. Variance-Covariance structure (Actual Value) = Unstructured. Variance-Covariance structure (Percent Change from Baseline) = Unstructured. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** All randomized participants who received at least one dose of study drug and had baseline and at least one post-baseline body waist circumference value. **Reporting Status:** POSTED **Time Frame:** Baseline, Week 26 **Title:** Change From Baseline in Waist Circumference in LY3502970 and Placebo **Type:** SECONDARY **Unit of Measure:** centimeter (cm) ##### Group **Description:** Participants received maintenance dose 12 mg with dose escalation starting from 3 mg,6 mg and then 12 mg LY3502970 administered orally once daily until 36 weeks. **ID:** OG000 **Title:** 12 mg LY3502970 ##### Group **Description:** Participants received maintenance dose 24 mg with dose escalation starting from 3 mg, 6 mg, 8 mg,12 mg and then 24 mg LY3502970 administered orally once daily until 36 weeks. **ID:** OG001 **Title:** 24 mg LY3502970 ##### Group **Description:** Participants received maintenance dose 36 mg with dose escalation starting from 2 mg, 3 mg, 6 mg, 8 mg, 12 mg, 24 mg and then 36 mg LY3502970 in LY 36mg-1 and dose escalation starting from 3 mg, 6 mg,12 mg, 24 mg and then 36 mg LY3502970 in LY 36mg-2 administered orally once daily until 36 weeks. **ID:** OG002 **Title:** 36 mg LY3502970 ##### Group **Description:** Participants received maintenance dose 45 mg with dose escalation starting from 3 mg, 6 mg, 8 mg, 12 mg, 24 mg, 36 mg and then 45 mg LY3502970 in LY 45mg-1 and dose escalation starting from 2 mg, 3 mg, 6 mg, 12 mg, 24 mg, 36 mg and then 45 mg LY3502970 in LY 45mg-2 administered orally once daily until 36 weeks. **ID:** OG003 **Title:** 45 mg LY3502970 ##### Group **Description:** Participants received placebo administered orally once daily until 36 weeks. **ID:** OG004 **Title:** Placebo #### Outcome Measure 6 **Description:** LS mean was determined by MMRM model with Baseline + Baseline BMI Group + Sex + Treatment + Time + Treatment\*Time (Type III sum of squares) as variables. Variance-Covariance structure (Actual Value) = Unstructured. Variance-Covariance structure (Percent Change from Baseline) = Unstructured. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** All randomized participants who received at least one dose of study drug and had baseline and at least one post-baseline body waist circumference value. **Reporting Status:** POSTED **Time Frame:** Baseline, Week 36 **Title:** Change From Baseline in Waist Circumference in LY3502970 and Placebo **Type:** SECONDARY **Unit of Measure:** cm ##### Group **Description:** Participants received maintenance dose 12 mg with dose escalation starting from 3 mg,6 mg and then 12 mg LY3502970 administered orally once daily until 36 weeks. **ID:** OG000 **Title:** 12 mg LY3502970 ##### Group **Description:** Participants received maintenance dose 24 mg with dose escalation starting from 3 mg, 6 mg, 8 mg,12 mg and then 24 mg LY3502970 administered orally once daily until 36 weeks. **ID:** OG001 **Title:** 24 mg LY3502970 ##### Group **Description:** Participants received maintenance dose 36 mg with dose escalation starting from 2 mg, 3 mg, 6 mg, 8 mg, 12 mg, 24 mg and then 36 mg LY3502970 in LY 36mg-1 and dose escalation starting from 3 mg, 6 mg,12 mg, 24 mg and then 36 mg LY3502970 in LY 36mg-2 administered orally once daily until 36 weeks. **ID:** OG002 **Title:** 36 mg LY3502970 ##### Group **Description:** Participants received maintenance dose 45 mg with dose escalation starting from 3 mg, 6 mg, 8 mg, 12 mg, 24 mg, 36 mg and then 45 mg LY3502970 in LY 45mg-1 and dose escalation starting from 2 mg, 3 mg, 6 mg, 12 mg, 24 mg, 36 mg and then 45 mg LY3502970 in LY 45mg-2 administered orally once daily until 36 weeks. **ID:** OG003 **Title:** 45 mg LY3502970 ##### Group **Description:** Participants received placebo administered orally once daily until 36 weeks. **ID:** OG004 **Title:** Placebo #### Outcome Measure 7 **Description:** LS mean was determined by MMRM model with Baseline + Baseline BMI Group + Sex + Treatment + Time + Treatment\*Time (Type III sum of squares) as variables. Variance-Covariance structure (Actual Value) = Unstructured. Variance-Covariance structure (Percent Change from Baseline) = Unstructured. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** All randomized participants who received at least one dose of study drug and had baseline and at least one post-baseline BMI value. **Reporting Status:** POSTED **Time Frame:** Baseline, Week 26 **Title:** Change From Baseline in BMI in LY3502970 and Placebo **Type:** SECONDARY **Unit of Measure:** kilograms per meter square (kg/m^2) ##### Group **Description:** Participants received maintenance dose 12 mg with dose escalation starting from 3 mg,6 mg and then 12 mg LY3502970 administered orally once daily until 36 weeks. **ID:** OG000 **Title:** 12 mg LY3502970 ##### Group **Description:** Participants received maintenance dose 24 mg with dose escalation starting from 3 mg, 6 mg, 8 mg,12 mg and then 24 mg LY3502970 administered orally once daily until 36 weeks. **ID:** OG001 **Title:** 24 mg LY3502970 ##### Group **Description:** Participants received maintenance dose 36 mg with dose escalation starting from 2 mg, 3 mg, 6 mg, 8 mg, 12 mg, 24 mg and then 36 mg LY3502970 in LY 36mg-1 and dose escalation starting from 3 mg, 6 mg,12 mg, 24 mg and then 36 mg LY3502970 in LY 36mg-2 administered orally once daily until 36 weeks. **ID:** OG002 **Title:** 36 mg LY3502970 ##### Group **Description:** Participants received maintenance dose 45 mg with dose escalation starting from 3 mg, 6 mg, 8 mg, 12 mg, 24 mg, 36 mg and then 45 mg LY3502970 in LY 45mg-1 and dose escalation starting from 2 mg, 3 mg, 6 mg, 12 mg, 24 mg, 36 mg and then 45 mg LY3502970 in LY 45mg-2 administered orally once daily until 36 weeks. **ID:** OG003 **Title:** 45 mg LY3502970 ##### Group **Description:** Participants received placebo administered orally once daily until 36 weeks. **ID:** OG004 **Title:** Placebo #### Outcome Measure 8 **Description:** LS mean was determined by MMRM model with Baseline + Baseline BMI Group + Sex + Treatment + Time + Treatment\*Time (Type III sum of squares) as variables. Variance-Covariance structure (Actual Value) = Unstructured. Variance-Covariance structure (Percent Change from Baseline) = Unstructured. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** All randomized participants who received at least one dose of study drug and had baseline and at least one post-baseline BMI value. **Reporting Status:** POSTED **Time Frame:** Baseline, Week 36 **Title:** Change From Baseline in BMI in LY3502970 and Placebo **Type:** SECONDARY **Unit of Measure:** kg/m^2 ##### Group **Description:** Participants received maintenance dose 12 mg with dose escalation starting from 3 mg,6 mg and then 12 mg LY3502970 administered orally once daily until 36 weeks. **ID:** OG000 **Title:** 12 mg LY3502970 ##### Group **Description:** Participants received maintenance dose 24 mg with dose escalation starting from 3 mg, 6 mg, 8 mg,12 mg and then 24 mg LY3502970 administered orally once daily until 36 weeks. **ID:** OG001 **Title:** 24 mg LY3502970 ##### Group **Description:** Participants received maintenance dose 36 mg with dose escalation starting from 2 mg, 3 mg, 6 mg, 8 mg, 12 mg, 24 mg and then 36 mg LY3502970 in LY 36mg-1 and dose escalation starting from 3 mg, 6 mg,12 mg, 24 mg and then 36 mg LY3502970 in LY 36mg-2 administered orally once daily until 36 weeks. **ID:** OG002 **Title:** 36 mg LY3502970 ##### Group **Description:** Participants received maintenance dose 45 mg with dose escalation starting from 3 mg, 6 mg, 8 mg, 12 mg, 24 mg, 36 mg and then 45 mg LY3502970 in LY 45mg-1 and dose escalation starting from 2 mg, 3 mg, 6 mg, 12 mg, 24 mg, 36 mg and then 45 mg LY3502970 in LY 45mg-2 administered orally once daily until 36 weeks. **ID:** OG003 **Title:** 45 mg LY3502970 ##### Group **Description:** Participants received placebo administered orally once daily until 36 weeks. **ID:** OG004 **Title:** Placebo #### Outcome Measure 9 **Description:** Percentage of participants with \>=5% body weight loss was reported. **Parameter Type:** NUMBER **Population Description:** All randomized participants who received at least one dose of study drug and had baseline and at least one post-baseline value for ≥5% body weight reduction. **Reporting Status:** POSTED **Time Frame:** Week 26 **Title:** Percentage of Participants With >=5% Body Weight Loss **Type:** SECONDARY **Unit of Measure:** percentage of participants ##### Group **Description:** Participants received maintenance dose 12 mg with dose escalation starting from 3 mg,6 mg and then 12 mg LY3502970 administered orally once daily until 36 weeks. **ID:** OG000 **Title:** 12 mg LY3502970 ##### Group **Description:** Participants received maintenance dose 24 mg with dose escalation starting from 3 mg, 6 mg, 8 mg,12 mg and then 24 mg LY3502970 administered orally once daily until 36 weeks. **ID:** OG001 **Title:** 24 mg LY3502970 ##### Group **Description:** Participants received maintenance dose 36 mg with dose escalation starting from 2 mg, 3 mg, 6 mg, 8 mg, 12 mg, 24 mg and then 36 mg LY3502970 in LY 36mg-1 and dose escalation starting from 3 mg, 6 mg,12 mg, 24 mg and then 36 mg LY3502970 in LY 36mg-2 administered orally once daily until 36 weeks. **ID:** OG002 **Title:** 36 mg LY3502970 ##### Group **Description:** Participants received maintenance dose 45 mg with dose escalation starting from 3 mg, 6 mg, 8 mg, 12 mg, 24 mg, 36 mg and then 45 mg LY3502970 in LY 45mg-1 and dose escalation starting from 2 mg, 3 mg, 6 mg, 12 mg, 24 mg, 36 mg and then 45 mg LY3502970 in LY 45mg-2 administered orally once daily until 36 weeks. **ID:** OG003 **Title:** 45 mg LY3502970 ##### Group **Description:** Participants received placebo administered orally once daily until 36 weeks. **ID:** OG004 **Title:** Placebo #### Outcome Measure 10 **Description:** Percentage of participants with \>=10% body weight loss was reported. **Parameter Type:** NUMBER **Population Description:** All randomized participants who received at least one dose of study drug and had baseline and at least one post-baseline value for ≥10% body weight reduction. **Reporting Status:** POSTED **Time Frame:** Week 26 **Title:** Percentage of Participants With >=10% Body Weight Loss **Type:** SECONDARY **Unit of Measure:** percentage of participants ##### Group **Description:** Participants received maintenance dose 12 mg with dose escalation starting from 3 mg,6 mg and then 12 mg LY3502970 administered orally once daily until 36 weeks. **ID:** OG000 **Title:** 12 mg LY3502970 ##### Group **Description:** Participants received maintenance dose 24 mg with dose escalation starting from 3 mg, 6 mg, 8 mg,12 mg and then 24 mg LY3502970 administered orally once daily until 36 weeks. **ID:** OG001 **Title:** 24 mg LY3502970 ##### Group **Description:** Participants received maintenance dose 36 mg with dose escalation starting from 2 mg, 3 mg, 6 mg, 8 mg, 12 mg, 24 mg and then 36 mg LY3502970 in LY 36mg-1 and dose escalation starting from 3 mg, 6 mg,12 mg, 24 mg and then 36 mg LY3502970 in LY 36mg-2 administered orally once daily until 36 weeks. **ID:** OG002 **Title:** 36 mg LY3502970 ##### Group **Description:** Participants received maintenance dose 45 mg with dose escalation starting from 3 mg, 6 mg, 8 mg, 12 mg, 24 mg, 36 mg and then 45 mg LY3502970 in LY 45mg-1 and dose escalation starting from 2 mg, 3 mg, 6 mg, 12 mg, 24 mg, 36 mg and then 45 mg LY3502970 in LY 45mg-2 administered orally once daily until 36 weeks. **ID:** OG003 **Title:** 45 mg LY3502970 ##### Group **Description:** Participants received placebo administered orally once daily until 36 weeks. **ID:** OG004 **Title:** Placebo #### Outcome Measure 11 **Description:** Percentage of participants with \>=5% body weight loss was reported. **Parameter Type:** NUMBER **Population Description:** All randomized participants who received at least one dose of study drug and had baseline and at least one post-baseline value for ≥5% body weight reduction. **Reporting Status:** POSTED **Time Frame:** Week 36 **Title:** Percentage of Participants With >=5% Body Weight Loss **Type:** SECONDARY **Unit of Measure:** percentage of participants ##### Group **Description:** Participants received maintenance dose 12 mg with dose escalation starting from 3 mg,6 mg and then 12 mg LY3502970 administered orally once daily until 36 weeks. **ID:** OG000 **Title:** 12 mg LY3502970 ##### Group **Description:** Participants received maintenance dose 24 mg with dose escalation starting from 3 mg, 6 mg, 8 mg,12 mg and then 24 mg LY3502970 administered orally once daily until 36 weeks. **ID:** OG001 **Title:** 24 mg LY3502970 ##### Group **Description:** Participants received maintenance dose 36 mg with dose escalation starting from 2 mg, 3 mg, 6 mg, 8 mg, 12 mg, 24 mg and then 36 mg LY3502970 in LY 36mg-1 and dose escalation starting from 3 mg, 6 mg,12 mg, 24 mg and then 36 mg LY3502970 in LY 36mg-2 administered orally once daily until 36 weeks. **ID:** OG002 **Title:** 36 mg LY3502970 ##### Group **Description:** Participants received maintenance dose 45 mg with dose escalation starting from 3 mg, 6 mg, 8 mg, 12 mg, 24 mg, 36 mg and then 45 mg LY3502970 in LY 45mg-1 and dose escalation starting from 2 mg, 3 mg, 6 mg, 12 mg, 24 mg, 36 mg and then 45 mg LY3502970 in LY 45mg-2 administered orally once daily until 36 weeks. **ID:** OG003 **Title:** 45 mg LY3502970 ##### Group **Description:** Participants received placebo administered orally once daily until 36 weeks. **ID:** OG004 **Title:** Placebo #### Outcome Measure 12 **Description:** Percentage of participants with \>=10% body weight loss was reported. **Parameter Type:** NUMBER **Population Description:** All randomized participants who received at least one dose of study drug and had baseline and at least one post-baseline value for ≥10% body weight reduction. **Reporting Status:** POSTED **Time Frame:** Week 36 **Title:** Percentage of Participants With >=10% Body Weight Loss **Type:** SECONDARY **Unit of Measure:** percentage of participants ##### Group **Description:** Participants received maintenance dose 12 mg with dose escalation starting from 3 mg,6 mg and then 12 mg LY3502970 administered orally once daily until 36 weeks. **ID:** OG000 **Title:** 12 mg LY3502970 ##### Group **Description:** Participants received maintenance dose 24 mg with dose escalation starting from 3 mg, 6 mg, 8 mg,12 mg and then 24 mg LY3502970 administered orally once daily until 36 weeks. **ID:** OG001 **Title:** 24 mg LY3502970 ##### Group **Description:** Participants received maintenance dose 36 mg with dose escalation starting from 2 mg, 3 mg, 6 mg, 8 mg, 12 mg, 24 mg and then 36 mg LY3502970 in LY 36mg-1 and dose escalation starting from 3 mg, 6 mg,12 mg, 24 mg and then 36 mg LY3502970 in LY 36mg-2 administered orally once daily until 36 weeks. **ID:** OG002 **Title:** 36 mg LY3502970 ##### Group **Description:** Participants received maintenance dose 45 mg with dose escalation starting from 3 mg, 6 mg, 8 mg, 12 mg, 24 mg, 36 mg and then 45 mg LY3502970 in LY 45mg-1 and dose escalation starting from 2 mg, 3 mg, 6 mg, 12 mg, 24 mg, 36 mg and then 45 mg LY3502970 in LY 45mg-2 administered orally once daily until 36 weeks. **ID:** OG003 **Title:** 45 mg LY3502970 ##### Group **Description:** Participants received placebo administered orally once daily until 36 weeks. **ID:** OG004 **Title:** Placebo ### Participant Flow Module #### Group **Description:** Participants received maintenance dose 12 mg with dose escalation starting from 3 mg, 6 mg and then 12 mg LY3502970 administered orally once daily until 36 weeks. **ID:** FG000 **Title:** 12 mg LY3502970 #### Group **Description:** Participants received maintenance dose 24 mg with dose escalation starting from 3 mg, 6 mg, 8 mg,12 mg and then 24 mg LY3502970 administered orally once daily until 36 weeks. **ID:** FG001 **Title:** 24 mg LY3502970 #### Group **Description:** Participants received maintenance dose 36 mg with dose escalation starting from 2 mg, 3 mg, 6 mg, 8 mg, 12 mg, 24 mg and then 36 mg LY3502970 administered orally once daily until 36 weeks. **ID:** FG002 **Title:** 36 mg -1 LY3502970 #### Group **Description:** Participants received maintenance dose 36 mg with dose escalation starting from 3 mg, 6 mg,12 mg, 24 mg and then 36 mg LY3502970 administered orally once daily until 36 weeks. **ID:** FG003 **Title:** 36 mg -2 LY3502970 #### Group **Description:** Participants received maintenance dose 45 mg with dose escalation starting from 3 mg, 6 mg, 8 mg, 12 mg, 24 mg, 36 mg and then 45 mg LY3502970 administered orally once daily until 36 weeks. **ID:** FG004 **Title:** 45 mg -1 LY3502970 #### Group **Description:** Participants received maintenance dose 45 mg with dose escalation starting from 2 mg, 3 mg, 6 mg, 12 mg, 24 mg, 36 mg and then 45 mg LY3502970 administered orally once daily until 36 weeks. **ID:** FG005 **Title:** 45 mg -2 LY3502970 #### Group **Description:** Participants received placebo administered orally once daily until 36 weeks. **ID:** FG006 **Title:** Placebo #### Period **Title:** Overall Study ##### Withdraw **Type:** Withdrawal by Subject ###### Reason **Group ID:** FG000 **Number of Subjects:** 3 ###### Reason **Group ID:** FG001 **Number of Subjects:** 5 ###### Reason **Group ID:** FG002 **Number of Subjects:** 2 ###### Reason **Group ID:** FG003 **Number of Subjects:** 1 ###### Reason **Group ID:** FG004 **Number of Subjects:** 4 ###### Reason **Group ID:** FG005 **Number of Subjects:** 0 ###### Reason **Group ID:** FG006 **Number of Subjects:** 4 ##### Withdraw **Type:** Lost to Follow-up ###### Reason **Group ID:** FG000 **Number of Subjects:** 1 ###### Reason **Group ID:** FG001 **Number of Subjects:** 0 ###### Reason **Group ID:** FG002 **Number of Subjects:** 0 ###### Reason **Group ID:** FG003 **Number of Subjects:** 0 ###### Reason **Group ID:** FG004 **Number of Subjects:** 1 ###### Reason **Group ID:** FG005 **Number of Subjects:** 0 ###### Reason **Group ID:** FG006 **Number of Subjects:** 1 ##### Withdraw **Type:** Subject Unable to Visit Due to Working Out of Town ###### Reason **Group ID:** FG000 **Number of Subjects:** 0 ###### Reason **Group ID:** FG001 **Number of Subjects:** 0 ###### Reason **Group ID:** FG002 **Number of Subjects:** 0 ###### Reason **Group ID:** FG003 **Number of Subjects:** 0 ###### Reason **Group ID:** FG004 **Number of Subjects:** 0 ###### Reason **Group ID:** FG005 **Number of Subjects:** 0 ###### Reason **Group ID:** FG006 **Number of Subjects:** 1 ##### Withdraw **Type:** Adverse Event ###### Reason **Group ID:** FG000 **Number of Subjects:** 2 ###### Reason **Group ID:** FG001 **Number of Subjects:** 1 ###### Reason **Group ID:** FG002 **Number of Subjects:** 0 ###### Reason **Group ID:** FG003 **Number of Subjects:** 4 ###### Reason **Group ID:** FG004 **Number of Subjects:** 1 ###### Reason **Group ID:** FG005 **Number of Subjects:** 2 ###### Reason **Group ID:** FG006 **Number of Subjects:** 0 ##### Withdraw **Type:** Inadvertent Enrollment ###### Reason **Group ID:** FG000 **Number of Subjects:** 0 ###### Reason **Group ID:** FG001 **Number of Subjects:** 0 ###### Reason **Group ID:** FG002 **Number of Subjects:** 0 ###### Reason **Group ID:** FG003 **Number of Subjects:** 0 ###### Reason **Group ID:** FG004 **Number of Subjects:** 0 ###### Reason **Group ID:** FG005 **Number of Subjects:** 0 ###### Reason **Group ID:** FG006 **Number of Subjects:** 1 ##### Withdraw **Type:** Subject Could not Tolerate Investigational Product (IP) and was Taken Off ###### Reason **Group ID:** FG000 **Number of Subjects:** 0 ###### Reason **Group ID:** FG001 **Number of Subjects:** 1 ###### Reason **Group ID:** FG002 **Number of Subjects:** 0 ###### Reason **Group ID:** FG003 **Number of Subjects:** 0 ###### Reason **Group ID:** FG004 **Number of Subjects:** 0 ###### Reason **Group ID:** FG005 **Number of Subjects:** 0 ###### Reason **Group ID:** FG006 **Number of Subjects:** 0 ##### Withdraw **Type:** Sponsor Decision ###### Reason **Group ID:** FG000 **Number of Subjects:** 0 ###### Reason **Group ID:** FG001 **Number of Subjects:** 0 ###### Reason **Group ID:** FG002 **Number of Subjects:** 0 ###### Reason **Group ID:** FG003 **Number of Subjects:** 0 ###### Reason **Group ID:** FG004 **Number of Subjects:** 1 ###### Reason **Group ID:** FG005 **Number of Subjects:** 0 ###### Reason **Group ID:** FG006 **Number of Subjects:** 0 ##### Withdraw **Type:** Patient was Initially Long Term Follow-up But Contacted and came to Site After Follow-up ###### Reason **Group ID:** FG000 **Number of Subjects:** 0 ###### Reason **Group ID:** FG001 **Number of Subjects:** 0 ###### Reason **Group ID:** FG002 **Number of Subjects:** 0 ###### Reason **Group ID:** FG003 **Number of Subjects:** 0 ###### Reason **Group ID:** FG004 **Number of Subjects:** 1 ###### Reason **Group ID:** FG005 **Number of Subjects:** 0 ###### Reason **Group ID:** FG006 **Number of Subjects:** 0 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 50 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 53 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 29 ###### Achievement **Group ID:** FG003 **Number of Subjects:** 29 ###### Achievement **Group ID:** FG004 **Number of Subjects:** 31 ###### Achievement **Group ID:** FG005 **Number of Subjects:** 30 ###### Achievement **Group ID:** FG006 **Number of Subjects:** 50 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 44 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 46 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 27 ###### Achievement **Group ID:** FG003 **Number of Subjects:** 24 ###### Achievement **Group ID:** FG004 **Number of Subjects:** 23 ###### Achievement **Group ID:** FG005 **Number of Subjects:** 28 ###### Achievement **Group ID:** FG006 **Number of Subjects:** 43 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 6 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 7 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 2 ###### Achievement **Group ID:** FG003 **Number of Subjects:** 5 ###### Achievement **Group ID:** FG004 **Number of Subjects:** 8 ###### Achievement **Group ID:** FG005 **Number of Subjects:** 2 ###### Achievement **Group ID:** FG006 **Number of Subjects:** 7 **Pre-Assignment Details:** For maintenance doses of LY3502970: 12, 24, 36, and 45 milligram (mg), the initial dose will be 2 or 3 mg followed by additional escalation steps as appropriate. The dose-escalation varied by dose group where the target maintenance dose was achieved between Weeks 5 and 16. **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT05948579 **Brief Title:** Department of Defense PTSD Adaptive Platform Trial - Intervention B - Vilazodone **Official Title:** A Phase 2, Multi-center, Multi-arm, Randomized, Placebo-controlled, Double-blind, Adaptive Platform Study to Evaluate the Safety, Tolerability, and Efficacy of Potential Pharmacotherapeutic Interventions in Active-Duty Service Members and Veterans With PTSD #### Organization Study ID Info **ID:** S-21-02 (Vilazodone) #### Organization **Class:** FED **Full Name:** U.S. Army Medical Research and Development Command ### Status Module #### Completion Date **Date:** 2026-09 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-01-29 **Type:** ACTUAL **Last Update Submit Date:** 2024-01-25 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2026-03 **Type:** ESTIMATED #### Start Date **Date:** 2024-03 **Type:** ESTIMATED **Status Verified Date:** 2024-01 #### Study First Post Date **Date:** 2023-07-17 **Type:** ACTUAL **Study First Submit Date:** 2023-07-05 **Study First Submit QC Date:** 2023-07-05 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** PPD **Class:** OTHER **Name:** Berry Consultants **Class:** INDUSTRY **Name:** Idorsia Pharmaceuticals Ltd. **Class:** INDUSTRY **Name:** Cambridge Cognition Ltd **Class:** UNKNOWN **Name:** Citeline #### Lead Sponsor **Class:** FED **Name:** U.S. Army Medical Research and Development Command #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** True **Oversight Has DMC:** True ### Description Module **Brief Summary:** This is a Phase 2 randomized, double-blinded, placebo-controlled study that will evaluate multiple potential pharmacotherapeutic interventions for PTSD utilizing an adaptive platform trial design. Intervention B - Vilazodone will assess the safety and efficacy of vilzodone in participants with PTSD. Please see NCT05422612 for information on the S-21-02 Master Protocol. **Detailed Description:** The general structure of this Adaptive Platform Trial (APT) consists of a 30-day Screening Period, a 12-week Platform Treatment Period, and a 4-week Safety Follow-up. The S-21-02 Platform Trial will evaluate the safety and efficacy of multiple investigational products for the treatment of PTSD (see NCT05422612 for Master Protocol information). Participants are randomized among the multiple cohorts in the study and the resulting randomization enables sharing/pooling of control subjects, where all interventions may be compared to a common control (placebo). This record only includes information relevant to the vilazodone cohort. Once a participant meets all eligibility criteria for the Master Protocol, eligibility for each currently enrolling intervention cohort is assessed. Eligible participants will be randomized with equal probability into a cohort. Participants randomized to the vilazodone cohort are then randomly assigned to receive either vilazodone or placebo in a ratio defined by the number of cohorts for which they are eligible, for the duration of the 12-week treatment period. Parties interested in having their intervention considered for testing within the DOD PTSD APT should complete a request for information form using this webpage https://citeline.qualtrics.com/jfe/form/SV_0oDoJXvIL7EFM1M. ### Conditions Module **Conditions:** - Post Traumatic Stress Disorder ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** Vilazodone is one of multiple interventions that will be tested in this adaptive platform trial (NCT05422612). ##### Masking Info **Masking:** QUADRUPLE **Masking Description:** The overall 2-stage randomization scheme will be implemented by an unblinded statistician who is otherwise uninvolved in study operations. Participants will be assigned a study number at Screening (Subject ID). In the first stage of randomization, eligible participants who complete screening will be randomly assigned to an open platform cohort for which they are eligible (both site PIs and participants are aware of the cohort assignment) and, within that cohort, the second stage of randomization is to intervention vs placebo (double-blind) using Interactive Response Technology (IRT). For this APT, participant assignment to a cohort will not be blinded. The tablets/capsules used in the cohorts may not be visually similar between cohorts and blinding to cohort assignment is not necessary to avoid bias. However, within each cohort, participants, site personnel, contract research personnel and the sponsor will be blind to treatment assignment (intervention vs. placebo). **Who Masked:** - PARTICIPANT - CARE_PROVIDER - INVESTIGATOR - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 200 **Type:** ESTIMATED **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Intervention Names:** - Drug: Intervention B Vilazodone Hydrochloride (HCl) **Label:** Intervention B Vilazodone **Type:** EXPERIMENTAL #### Arm Group 2 **Intervention Names:** - Drug: Intervention B Placebo **Label:** Intervention B Placebo **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Intervention B Vilazodone **Description:** Vilazodone HCl will be administered at 10 mg once daily for 7 days, followed by 20 mg for 7 days, followed by 40 mg for the remainder of the trial. There must be a minimum of 7 days between dosage increases. One reduction in dose due to tolerability will be allowed. After Week 8, dose reduction for tolerability is allowed, but dose increase is not allowed. **Name:** Intervention B Vilazodone Hydrochloride (HCl) **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Intervention B Placebo **Description:** A matching placebo will be administered at 10 to 40 mg daily in the same regimen as the intervention. **Name:** Intervention B Placebo **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** A change in PTSD symptom severity from baseline as measured by CAPS-5-R Past Month. The range of the scale is 0-200. The higher the score at baseline, the worse the PTSD severity. The larger the decrease in score from baseline, the better the outcome. **Measure:** Absolute change in the Clinician-Administered PTSD Scale-5-Revised (CAPS-5-R) Past Month total score at Week 12 (Final/Early termination Visit). **Time Frame:** 12 Weeks **Description:** The C-SSRS is an assessment of suicidal ideation and behavior in clinical and research settings. The C-SSRS consists of 16 questions that ask about suicidal ideation and behaviors (the first 10 questions comprise the ideation subscale and the last 6 comprise the behavior subscale). This 5-item subscale ranges from a minimum of 0 (corresponding to no suicidal ideation) to a maximum of 5 (representing active suicidal ideation with plan and intent). **Measure:** Incidence of new or worsening suicidal thoughts or behaviors as measured by change in Columbia Suicide Severity Rating Scale (C-SSRS) score from baseline. **Time Frame:** 12 Weeks #### Secondary Outcomes **Description:** The TEAEs recorded during the study will be summarized by system organ class, preferred term, and treatment group. Adverse events and medical history will be coded using the most current version of MedDRA. **Measure:** Frequency of treatment-emergent adverse events (TEAEs). **Time Frame:** 12 Weeks **Description:** The TEAEs recorded during the study will be summarized by system organ class, preferred term, and treatment group. Adverse events and medical history will be coded using the most current version of MedDRA. **Measure:** Severity of treatment-emergent adverse events (TEAEs). **Time Frame:** 12 Weeks **Description:** The SAEs recorded during the study will be summarized by system organ class, preferred term, and treatment group. Adverse events and medical history will be coded using the most current version of MedDRA. **Measure:** Frequency of serious adverse events (SAEs). **Time Frame:** 12 Weeks **Description:** The SAEs recorded during the study will be summarized by system organ class, preferred term, and treatment group. Adverse events and medical history will be coded using the most current version of MedDRA. **Measure:** Severity of serious adverse events (SAEs). **Time Frame:** 12 Weeks **Description:** A relative change in PTSD symptom severity from baseline as measured by CAPS-5-R Past Month. The range of the scale is 0-200. The higher the score at baseline, the worse the PTSD severity. The larger the decrease in score from baseline, the better the outcome. **Measure:** Relative change from Baseline to Week 12 in the Clinician-Administered PTSD Scale for DSM-5 Revised (CAPS-5-R), Past Month total score. **Time Frame:** 12 Weeks **Description:** ≥30% reduction from Baseline to 12 Weeks in the Clinician-Administered PTSD Scale for DSM-5 Revised (CAPS-5-R), Past Month total score. The range of the scale is 0-200. The higher the score, the worse the PTSD severity. The larger the decrease in score from baseline, the better the outcome. **Measure:** Number of participants with a Response Rate ≥30% **Time Frame:** 12 Weeks **Description:** ≥50% reduction from Baseline to 12 Weeks in the Clinician-Administered PTSD Scale for DSM-5 Revised (CAPS-5-R), Past Month total score. The range of the scale is 0-200. The higher the score, the worse the PTSD severity. The larger the decrease in score from baseline, the better the outcome. **Measure:** Number of participants with a Response Rate ≥50% **Time Frame:** 12 Weeks **Description:** Achieving remission: defined as the Clinician-Administered PTSD Scale for DSM-5 Revised (CAPS-5-R), Past Month total score \<18. The range of the scale is 0-200. The higher the score, the worse the PTSD severity. **Measure:** Number of participants Achieving Remission. **Time Frame:** 12 Weeks ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: No additional inclusion criteria beyond the inclusion criteria specified in the Master Protocol (NCT05422612). Exclusion Criteria: The following exclusion criteria are in addition to the exclusion criteria specified in the Master Protocol (NCT05422612). 1. History of treatment for PTSD with vilazodone at doses of 20 to 40 mg daily, for at least 4 weeks. **Gender Based:** True **Gender Description:** Participants who have undergone or plans to undergo gender reassignment surgery are not eligible. Participants who are currently undergoing stable hormone replacement therapy are eligible for inclusion in the study. **Healthy Volunteers:** True **Maximum Age:** 65 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Dr. Kimberly del Carmen **Phone:** Please reach out by email **Role:** CONTACT ### References Module #### References **Citation:** Viele K. Allocation in platform trials to maintain comparability across time and eligibility. Stat Med. 2023 Jul 20;42(16):2811-2818. doi: 10.1002/sim.9750. Epub 2023 Apr 23. **PMID:** 37088912 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000068099 - Term: Trauma and Stressor Related Disorders - ID: D000001523 - Term: Mental Disorders ### Condition Browse Module - Browse Branches - Abbrev: BXM - Name: Behaviors and Mental Disorders - Abbrev: All - Name: All Conditions - Abbrev: BC26 - Name: Wounds and Injuries ### Condition Browse Module - Browse Leaves - ID: M16103 - Name: Stress Disorders, Post-Traumatic - Relevance: HIGH - As Found: Post Traumatic Stress Disorder - ID: M24916 - Name: Stress Disorders, Traumatic - Relevance: HIGH - As Found: Traumatic Stress Disorder - ID: M17685 - Name: Wounds and Injuries - Relevance: LOW - As Found: Unknown - ID: M222 - Name: Trauma and Stressor Related Disorders - Relevance: LOW - As Found: Unknown - ID: M4815 - Name: Mental Disorders - Relevance: LOW - As Found: Unknown - ID: M14473 - Name: Psychotic Disorders - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000040921 - Term: Stress Disorders, Traumatic - ID: D000013313 - Term: Stress Disorders, Post-Traumatic ### Intervention Browse Module - Ancestors - ID: D000000928 - Term: Antidepressive Agents - ID: D000011619 - Term: Psychotropic Drugs - ID: D000017367 - Term: Selective Serotonin Reuptake Inhibitors - ID: D000014179 - Term: Neurotransmitter Uptake Inhibitors - ID: D000049990 - Term: Membrane Transport Modulators - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000018377 - Term: Neurotransmitter Agents - ID: D000018490 - Term: Serotonin Agents - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000058825 - Term: Serotonin 5-HT1 Receptor Agonists - ID: D000017366 - Term: Serotonin Receptor Agonists ### Intervention Browse Module - Browse Branches - Abbrev: PsychDr - Name: Psychotropic Drugs - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M453 - Name: Vilazodone Hydrochloride - Relevance: HIGH - As Found: Moxifloxacin Ophthalmic - ID: M4247 - Name: Antidepressive Agents - Relevance: LOW - As Found: Unknown - ID: M14474 - Name: Psychotropic Drugs - Relevance: LOW - As Found: Unknown - ID: M19649 - Name: Selective Serotonin Reuptake Inhibitors - Relevance: LOW - As Found: Unknown - ID: M15512 - Name: Serotonin - Relevance: LOW - As Found: Unknown - ID: M20504 - Name: Neurotransmitter Agents - Relevance: LOW - As Found: Unknown - ID: M29240 - Name: Serotonin 5-HT1 Receptor Agonists - Relevance: LOW - As Found: Unknown - ID: M19648 - Name: Serotonin Receptor Agonists - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000069503 - Term: Vilazodone Hydrochloride ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03873779 **Acronym:** CRT **Brief Title:** CoolSculpting and RF for the Submental **Official Title:** A Feasibility Study to Explore the Safety and Efficacy of Cryolipolysis Followed by Radiofrequency Treatment for Submental and Submandibular Contouring #### Organization Study ID Info **ID:** ZA18-002 #### Organization **Class:** INDUSTRY **Full Name:** Zeltiq Aesthetics ### Status Module #### Completion Date **Date:** 2020-11 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** ACTIVE_NOT_RECRUITING #### Last Update Post Date **Date:** 2020-08-18 **Type:** ACTUAL **Last Update Submit Date:** 2020-08-14 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2020-08 **Type:** ESTIMATED #### Start Date **Date:** 2018-12-18 **Type:** ACTUAL **Status Verified Date:** 2020-08 #### Study First Post Date **Date:** 2019-03-13 **Type:** ACTUAL **Study First Submit Date:** 2018-12-18 **Study First Submit QC Date:** 2019-03-11 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Zeltiq Aesthetics #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** True **Is FDA Regulated Drug:** False **Is US Export:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** The purpose of this study is to evaluate the safety and efficacy of sequential use of CoolSculpting (Cryolipolysis) and radiofrequency treatment of the submental and submandibular area. ### Conditions Module **Conditions:** - Body Fat Disorder ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** OTHER #### Enrollment Info **Count:** 25 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** The treatments are designed to see if the fat can be reduced in the submental/submandibular area. **Intervention Names:** - Device: The ZELTIQ System **Label:** Fat Reduction **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Fat Reduction **Description:** The CoolSculpting machine will be used to perform the treatments. **Name:** The ZELTIQ System **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Description:** The primary safety endpoint is measurement of unanticipated adverse device effects. All adverse events reported during and following the treatment will be included in the safety analysis. The frequency and proportion of subjects reporting each type of adverse event will be tabulated by relationship with the treatment and severity of the event. **Measure:** Incidence of unanticipated adverse device effects (UADE). It is expected there will be zero UADE's. **Time Frame:** 12-weeks post final treatment #### Secondary Outcomes **Description:** Overall improvement in the targeted area will be assessed by the subject using the GAIS at 12-weeks post-final treatment. The assessment will consist of writing the outcome as: Very much improved; much improved; improved; no change; worse; much worse; very much worse. **Measure:** Assessment of overall treatment outcome in submental and submandibular area using Subject-graded GAIS (SGAIS) **Time Frame:** 12-weeks post final treatment ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria * Male or female subjects ≥22 years of age and ≤65 years of age. * Treatment area skin fold thickness \> 1cm (measured by caliper). * Dissatisfaction with the treatment area expressed by the subject as a rating of 0, 1 or 2 using the Subject Self Rating Scale (SSRS) as determined at Screening visit. * No weight change exceeding 5% of body weight in the preceding month. * Agreement to maintain his/her weight (i.e., within 5%) by not making any major changes in diet or exercise routine during the course of the study. * Subject has signed a written informed consent form Exclusion Criteria * Body Mass Index ≥ 46.2 as determined at screening. * Excessive skin laxity in the treatment area for which reduction of subcutaneous fat may, in the opinion of the investigator, result in an unacceptable aesthetic result. * Prominent platysmal bands at rest which may interfere with assessment of treatment area. * Evidence of any cause of enlargement in the treatment area other than localized subcutaneous fat, such as swollen lymph nodes or ptotic submandibular glands. * Significant enlargement on the anterior neck that may prevent the proper placement of the applicator e.g. enlarged thyroid glands. * Treatment with dermal fillers, chemical peels, radiofrequency or laser procedures that may affect contour in the treatment area within the past 6 months. * Botulinum toxin, deoxycholic acid, or other aesthetic drug injections within the treatment area in the past 6 months. * History of facial nerve paresis or paralysis (such as Bell's palsy). * History of a fat reduction procedure (e.g., liposuction, surgery, lipolytic agents, etc.) or implant in or adjacent to the area of intended treatment. * History of prior neck surgery, or prior surgery in the area of intended treatment. * Current infection in and adjacent to treatment area. * Known history of cryoglobulinemia, cold urticaria, cold agglutinin disease or paroxysmal cold hemoglobinuria. * Known history of Raynaud's disease, or any known condition with a response to cold exposure that limits blood flow to the skin. * History of bleeding disorder or is taking any medication that in the investigator's opinion may increase the subject's risk of bruising. * Currently taking or has taken diet pills or weight control supplements within the past month. * Any dermatological conditions, such as scars in the location of the treatment area that may interfere with the treatment or evaluation. * Active implanted device such as a pacemaker, automatic implantable cardioverter/defibrillator (AICD), drug delivery system, or any other implantable electrical device. * Pregnant or intending to become pregnant in the next 6 months. * Lactating or has been lactating in the past 6 months. * Unable or unwilling to comply with the study requirements including remaining clean shaven for all study visits. * Currently enrolled in a clinical study of an unapproved investigational drug or device. * Any other condition or laboratory value that would, in the professional opinion of the investigator, potentially affect the subject's response or the integrity of the data or would pose an unacceptable risk to the subject. **Healthy Volunteers:** True **Maximum Age:** 65 Years **Minimum Age:** 22 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Pleasanton **Country:** United States **Facility:** Innovation Research Center **State:** California **Zip:** 94588 #### Overall Officials **Official 1:** **Affiliation:** Zeltiq Aesthetics **Name:** Kerrie Jiang, NP **Role:** STUDY_DIRECTOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000008659 - Term: Metabolic Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC18 - Name: Nutritional and Metabolic Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M27029 - Name: Lipid Metabolism Disorders - Relevance: HIGH - As Found: Fat Disorder - ID: M11639 - Name: Metabolic Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000052439 - Term: Lipid Metabolism Disorders ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT01142479 **Brief Title:** Compound Herbal Formula (TPE-1) for Leukopenia and Cancer-related Fatigue in Breast Cancer Patients With Radiotherapy **Official Title:** The Effects of Compound Herbal Formula(TPE-1) for Leukopenia and Cancer-related Fatigue in Breast Cancer Patients With Radiotherapy #### Organization Study ID Info **ID:** TPE-1-breast Ca #### Organization **Class:** OTHER_GOV **Full Name:** Taipei City Hospital ### Status Module #### Expanded Access Info #### Last Update Post Date **Date:** 2014-05-29 **Type:** ESTIMATED **Last Update Submit Date:** 2014-05-28 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2011-04 **Type:** ACTUAL #### Start Date **Date:** 2010-05 **Status Verified Date:** 2014-05 #### Study First Post Date **Date:** 2010-06-11 **Type:** ESTIMATED **Study First Submit Date:** 2010-06-10 **Study First Submit QC Date:** 2010-06-10 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** Taipei Medical University Shuang Ho Hospital #### Lead Sponsor **Class:** OTHER_GOV **Name:** Taipei City Hospital #### Responsible Party **Investigator Affiliation:** Taipei City Hospital **Investigator Full Name:** Chung-Hua Hsu **Investigator Title:** vice superintendent **Type:** PRINCIPAL_INVESTIGATOR ### Description Module **Brief Summary:** Many breast cancer patients will taking Chinese herbal medicine during receiving radiotherapy. The investigators conducted the pilot study showing Compound Herbal Formula (TPE-1) have the effect of improving the fatigue and leukopenia during radiotherapy. So the investigators designed this double blind and controlled trial to evaluate whether TPE-1 have the effects for leukopenia and cancer-related fatigue in breast cancer patients with radiotherapy. From our initial observation for 2 years, TPE-1 is safety. The study is also designed to evaluate the safety when patients taking this formula. **Detailed Description:** TPE-1 is designed according to TCM concept. It is not anti-cancer directly, it is enhancing the Qi flow and immunity of breast cancer when they are just finishing chemotherapy and on going radiotherapy. Many Chinese population will seeking Chinese herbal medicine under the same condition. ### Conditions Module **Conditions:** - Breast Cancer - Radiotherapy - Chinese Herbal Medicine **Keywords:** - Breast Cancer - Radiotherapy - Chinese herbal medicine - TPE-1 - Leukopenia ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** DOUBLE **Who Masked:** - PARTICIPANT - CARE_PROVIDER **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 60 **Type:** ACTUAL **Phases:** - PHASE2 - PHASE3 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** dilute of (TPE-1) decoction. **Intervention Names:** - Drug: Chinese herbal medicine decoction **Label:** herbal A **Type:** PLACEBO_COMPARATOR #### Arm Group 2 **Description:** TPE-1 decoction (100 ml) **Intervention Names:** - Drug: Chinese herbal medicine decoction **Label:** herbal B **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - herbal A - herbal B **Description:** 100 ml /Qd for 6 weeks(42 days) **Name:** Chinese herbal medicine decoction **Other Names:** - TPE-1 **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** WBC will be checked before taking TPE ans after taking TPE-1. **Measure:** the % change of white blood cell(WBC) count **Time Frame:** 6 weeks #### Secondary Outcomes **Description:** The Hb will be checked before and after kaking TPE-1 **Measure:** Hemoglobin (Hb) **Time Frame:** 6 weeks ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * breast cancer * age between 18 to 70 yrs * finished chemotherapy (adriamycin ), will receiving radiotherapy * Chinese population * KP$ between 40-100 * ECOG \< 2 * WBC \>4X10(9)／L and Hb \> 10g/dl * Assigned informed concent. Exclusion Criteria: * receiving operation during 14 days * blood transfusion during one month. * ALT \>100mg/dL * Creatinine \>2.0mg/dL * Total bilirubin \>2.0mg/dL * Infection * prolation * Taking anti-seizure , psychological drugs or any drugs not suitable patients * AIDS or any disease diagnosed by physician and not suitable patients. **Maximum Age:** 70 Years **Minimum Age:** 18 Years **Sex:** FEMALE **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Taipei **Country:** Taiwan **Facility:** Shuang Ho Hospital **Zip:** 886 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009371 - Term: Neoplasms by Site - ID: D000009369 - Term: Neoplasms - ID: D000001941 - Term: Breast Diseases - ID: D000012871 - Term: Skin Diseases - ID: D000095542 - Term: Cytopenia - ID: D000006402 - Term: Hematologic Diseases - ID: D000007960 - Term: Leukocyte Disorders ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC17 - Name: Skin and Connective Tissue Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: BC15 - Name: Blood and Lymph Conditions ### Condition Browse Module - Browse Leaves - ID: M5220 - Name: Breast Neoplasms - Relevance: HIGH - As Found: Breast Cancer - ID: M8364 - Name: Fatigue - Relevance: LOW - As Found: Unknown - ID: M10973 - Name: Leukopenia - Relevance: HIGH - As Found: Leukopenia - ID: M5218 - Name: Breast Diseases - Relevance: LOW - As Found: Unknown - ID: M15674 - Name: Skin Diseases - Relevance: LOW - As Found: Unknown - ID: M3170 - Name: Cytopenia - Relevance: LOW - As Found: Unknown - ID: M9490 - Name: Hematologic Diseases - Relevance: LOW - As Found: Unknown - ID: M10963 - Name: Leukocyte Disorders - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000001943 - Term: Breast Neoplasms - ID: D000007970 - Term: Leukopenia ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT01074879 **Acronym:** IceProQualita **Brief Title:** Protein Ingestion and Resistance Exercise in Elderly **Official Title:** Effects of Protein Quantity and Quality in Combination With Resistance Exercise on Muscle Mass and -Strength in Icelandic Elderly. #### Organization Study ID Info **ID:** 071323007 #### Organization **Class:** OTHER **Full Name:** University of Iceland ### Status Module #### Completion Date **Date:** 2009-12 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2010-02-24 **Type:** ESTIMATED **Last Update Submit Date:** 2010-02-23 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2009-12 **Type:** ACTUAL #### Start Date **Date:** 2008-08 **Status Verified Date:** 2010-02 #### Study First Post Date **Date:** 2010-02-24 **Type:** ESTIMATED **Study First Submit Date:** 2010-02-23 **Study First Submit QC Date:** 2010-02-23 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** Landspitali University Hospital Research Fund #### Lead Sponsor **Class:** OTHER **Name:** University of Iceland #### Responsible Party **Old Name Title:** Prof. Inga Thorsdottir ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** The mail goal of this randomized controlled, dietary intervention study is to investigate whether protein supplementation in combination with resistance exercise can increase muscle mass and strength in elderly. Loss of muscle mass and -strength is frequent in this group. Participants (N = 220, equal distribution between men and women) are randomized to one of three groups receiving different quantities and qualities of protein supplementation after exercise. The results of this study will be used to form recommendations regarding diet and exercise for the prevention of this frequent health problem in elderly. ### Conditions Module **Conditions:** - Healthy **Keywords:** - Elderly - protein consumption - resistance exercise - muscle mass ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** TRIPLE **Who Masked:** - PARTICIPANT - INVESTIGATOR - OUTCOMES_ASSESSOR **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 220 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** 20 g whey protein + 20 g carbohydrates **Intervention Names:** - Dietary Supplement: Whey protein **Label:** Whey protein **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** 20 g milk protein + 20 g carbohydrates **Intervention Names:** - Dietary Supplement: Milk protein **Label:** Milk protein **Type:** EXPERIMENTAL #### Arm Group 3 **Description:** 40 g carbohydrates **Intervention Names:** - Dietary Supplement: Carbohydrates **Label:** Carbohydrates **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Whey protein **Description:** Dietary supplement after training **Name:** Whey protein **Type:** DIETARY_SUPPLEMENT #### Intervention 2 **Arm Group Labels:** - Milk protein **Description:** Dietary supplement after training **Name:** Milk protein **Type:** DIETARY_SUPPLEMENT #### Intervention 3 **Arm Group Labels:** - Carbohydrates **Description:** Dietary supplement after training **Name:** Carbohydrates **Type:** DIETARY_SUPPLEMENT ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * 65 years and older Exclusion Criteria: * uncontrolled coronary heart disease * pharmacological interventions with drugs known to affect muscle mass * major orthopedic disease * low cognitive function. **Healthy Volunteers:** True **Minimum Age:** 65 Years **Sex:** ALL **Standard Ages:** - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Reykjavik **Country:** Iceland **Facility:** Unit for Nutrition Research **Zip:** 101 ### References Module #### References **Citation:** Og G, M C, Pv J, I T, A R. Associations of physical activity with vitamin D status depends on obesity status in old adults. Clin Nutr ESPEN. 2020 Oct;39:222-226. doi: 10.1016/j.clnesp.2020.06.009. Epub 2020 Jul 12. **PMID:** 32859321 **Citation:** Geirsdottir OG, Chang M, Jonsson PV, Thorsdottir I, Ramel A. Obesity, Physical Function, and Training Success in Community-Dwelling Nonsarcopenic Old Adults. J Aging Res. 2019 Feb 18;2019:5340328. doi: 10.1155/2019/5340328. eCollection 2019. **PMID:** 30906596 **Citation:** Geirsdottir OG, Chang M, Briem K, Jonsson PV, Thorsdottir I, Ramel A. Gender, Success, and Drop-Out during a Resistance Exercise Program in Community Dwelling Old Adults. J Aging Res. 2017;2017:5841083. doi: 10.1155/2017/5841083. Epub 2017 Aug 14. **PMID:** 28890833 **Citation:** Arnarson A, Gudny Geirsdottir O, Ramel A, Jonsson PV, Thorsdottir I. Insulin-Like Growth Factor-1 and Resistance Exercise in Community Dwelling Old Adults. J Nutr Health Aging. 2015 Oct;19(8):856-60. doi: 10.1007/s12603-015-0547-3. **PMID:** 26412290 **Citation:** Ramel A, Geirsdottir OG, Jonsson PV, Thorsdottiri I. C-Reactive Protein and Resistance Exercise in Community Dwelling Old Adults. J Nutr Health Aging. 2015 Aug;19(7):792-6. doi: 10.1007/s12603-015-0548-2. **PMID:** 26193865 **Citation:** Geirsdottir OG, Arnarson A, Ramel A, Briem K, Jonsson PV, Thorsdottir I. Muscular strength and physical function in elderly adults 6-18 months after a 12-week resistance exercise program. Scand J Public Health. 2015 Feb;43(1):76-82. doi: 10.1177/1403494814560842. Epub 2014 Nov 27. **PMID:** 25431460 **Citation:** Arnarson A, Ramel A, Geirsdottir OG, Jonsson PV, Thorsdottir I. Changes in body composition and use of blood cholesterol lowering drugs predict changes in blood lipids during 12 weeks of resistance exercise training in old adults. Aging Clin Exp Res. 2014 Jun;26(3):287-92. doi: 10.1007/s40520-013-0172-0. Epub 2013 Dec 1. **PMID:** 24293371 **Citation:** Geirsdottir OG, Arnarson A, Ramel A, Jonsson PV, Thorsdottir I. Dietary protein intake is associated with lean body mass in community-dwelling older adults. Nutr Res. 2013 Aug;33(8):608-12. doi: 10.1016/j.nutres.2013.05.014. Epub 2013 Jun 27. **PMID:** 23890349 **Citation:** Arnarson A, Gudny Geirsdottir O, Ramel A, Briem K, Jonsson PV, Thorsdottir I. Effects of whey proteins and carbohydrates on the efficacy of resistance training in elderly people: double blind, randomised controlled trial. Eur J Clin Nutr. 2013 Aug;67(8):821-6. doi: 10.1038/ejcn.2013.40. Epub 2013 Mar 13. **PMID:** 23486511 **Citation:** Ramel A, Arnarson A, Geirsdottir OG, Jonsson PV, Thorsdottir I. Glomerular filtration rate after a 12-wk resistance exercise program with post-exercise protein ingestion in community dwelling elderly. Nutrition. 2013 May;29(5):719-23. doi: 10.1016/j.nut.2012.10.002. Epub 2013 Jan 11. **PMID:** 23317926 **Citation:** Geirsdottir OG, Arnarson A, Briem K, Ramel A, Jonsson PV, Thorsdottir I. Effect of 12-week resistance exercise program on body composition, muscle strength, physical function, and glucose metabolism in healthy, insulin-resistant, and diabetic elderly Icelanders. J Gerontol A Biol Sci Med Sci. 2012 Nov;67(11):1259-65. doi: 10.1093/gerona/gls096. Epub 2012 Apr 10. **PMID:** 22496538 **Citation:** Geirsdottir OG, Arnarson A, Briem K, Ramel A, Tomasson K, Jonsson PV, Thorsdottir I. Physical function predicts improvement in quality of life in elderly Icelanders after 12 weeks of resistance exercise. J Nutr Health Aging. 2012 Jan;16(1):62-6. doi: 10.1007/s12603-011-0076-7. **PMID:** 22238003 ## Derived Section ### Intervention Browse Module - Ancestors - ID: D000002614 - Term: Chelating Agents - ID: D000064449 - Term: Sequestering Agents - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action ### Intervention Browse Module - Browse Branches - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Ot - Name: Other Dietary Supplements ### Intervention Browse Module - Browse Leaves - ID: M5616 - Name: Caseins - Relevance: HIGH - As Found: Subacute - ID: M5860 - Name: Chelating Agents - Relevance: LOW - As Found: Unknown - ID: T435 - Name: Whey Protein - Relevance: HIGH - As Found: Ingredients ### Intervention Browse Module - Meshes - ID: D000002364 - Term: Caseins ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT01536379 **Brief Title:** A Study of Belimumab in the Prevention of Kidney Transplant Rejection **Official Title:** BEL114424: A Phase 2 Pilot, Multicentered, Randomised, Double Blind, Placebo-Controlled Study to Evaluate the Potential for Efficacy and the Safety of Belimumab Plus Standard of Care Versus Placebo Plus Standard of Care in the Prevention of Allograft Rejection in Adult Subjects After Renal Transplantation #### Organization Study ID Info **ID:** 114424 #### Organization **Class:** INDUSTRY **Full Name:** GlaxoSmithKline ### Status Module #### Completion Date **Date:** 2016-02 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2017-04-25 **Type:** ACTUAL **Last Update Submit Date:** 2017-03-14 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2016-02 **Type:** ACTUAL #### Results First Post Date **Date:** 2017-04-25 **Type:** ACTUAL **Results First Submit Date:** 2016-10-05 **Results First Submit QC Date:** 2017-03-14 #### Start Date **Date:** 2013-09 **Status Verified Date:** 2017-03 #### Study First Post Date **Date:** 2012-02-22 **Type:** ESTIMATED **Study First Submit Date:** 2012-02-16 **Study First Submit QC Date:** 2012-02-16 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** GlaxoSmithKline #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** Kidney transplantation is the best treatment for many patients with kidney failure. Sometimes a transplanted kidney is rejected by the patient's immune system. Many types of immune system cells, including B cells, are active in rejection. B cells produce antibodies against anything the body sees as non-self, like germs or a transplanted kidney. Most medicines that help prevent transplant rejection affect cells other than B cells. Belimumab is a medication used to treat a disease called lupus. Belimumab slows development of antibody-producing B cells. This study will test whether belimumab works on parts of the immune system that cause rejection. Twenty to thirty adults getting a kidney transplant will be in this study. Like flipping a coin, a computer will randomly assign half to be given belimumab and half to be given placebo (a fake medicine). Patients and doctors will not know which medicine was assigned until the study is over. A total of 7 doses of study medicine will be given through a vein. One dose will be given during transplant surgery, and the other 6 will be given 2, 4, 8, 12, 16 and 20 weeks after transplant surgery. Usual transplant medicines will also be given. After all of the doses have been given, patients will be watched and tested at 24, 36, and 52 weeks after the transplant surgery. Blood samples will be tested to see what study medicines do to the immune system in transplant patients. If patients get a kidney biopsy, the samples will be tested to see if belimumab had any effect. Patients will be asked many questions to see if they are having any side effects. The study will be done at Addenbrooke's Hospital in Cambridge and Guys \&St Thomas Hospital in London, United Kingdom. A pharmaceutical company, GlaxoSmithKline, is funding the study. ### Conditions Module **Conditions:** - Transplantation, Organ **Keywords:** - Infection - Quality of Life ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** DOUBLE **Who Masked:** - PARTICIPANT - INVESTIGATOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 30 **Type:** ACTUAL **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Subjects will receive belimumab 10 mg/ Kilogram (kg) infusion on Days 0, 14, 28 and every 4 weeks thereafter for a total of 7 infusions. The last dose of investigational product will be administered at the Week 20 visit; In addition to investigational product, all subjects will receive standard of care. **Intervention Names:** - Drug: Belimumab **Label:** Belimumab 10 mg **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Subjects will receive placebo infusion on Days 0, 14, 28 and every 4 weeks thereafter for a total of 7 infusions. The last dose of investigational product will be administered at the Week 20 visit; In addition to investigational product, all subjects will receive standard of care **Intervention Names:** - Drug: Placebo **Label:** Placebo **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Belimumab 10 mg **Description:** Belimumab (10 mg/kg) will be given as an intravenous solution over a 1 hour time period administered every 4 weeks for 24 weeks (with an additional dose at Week 2) **Name:** Belimumab **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Placebo **Description:** Placebo will be given as an intravenous solution over a 1 hour time period administered every 4 weeks for 24 weeks (with an additional dose at Week 2) **Name:** Placebo **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Naive B cell is cell that is not exposed to antigen. Naïve B cell count is CD20+CD27 concentration of cells (conc-cell)/cubic millimeter (cumm). Change from Baseline in naïve B cells was calculated as the value at Week 24 minus the value at Baseline. MITT Population consisted of all participants randomized to treatment, who have had taken at least one dose of study. Participants analyzed included those who had data at Week 24 for naïve B cells count (MITT Population). Baseline value used in the analysis was of Day 0 (Day of transplant). Adjusted mean differences (treatment-placebo) and 95% confidence intervals for differences were obtained from mixed-models repeated-measures (MMRM) model, with fixed categorical effects of treatment, visit, donor type and treatment-by-visit interaction and fixed continuous covariates of Baseline and Baseline-by-visit interaction. A compound symmetry variance structure was used to model the within-participant errors, shared across treatments. **Measure:** Change From Baseline in naïve B Cells From Baseline to Week 24 **Time Frame:** Baseline and Week 24 **Description:** Number of participants with AEs, SAEs and AESI are summarized. The On-treatment (OT) phase started on the day and time of receiving the start of the first infusion and ended on the last dose date plus 28 days. The Post-treatment (PT) phase started 29 days after day of last dose up to 1 year. An AE is any untoward medical occurrence, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that at any dose results in, death, is life threatening, Requires hospitalization or prolongation of existing hospitalization, Results in disability/incapacity, Is a congenital anomaly/birth defect or event that but may jeopardize the subject or may require medical or surgical intervention to prevent one of the other outcomes listed. AESI included malignant neoplasms, infusion/anaphylaxis/hypersensitivity reactions, all infections, depression/suicide/self-injury, deaths. **Measure:** Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESI) **Time Frame:** Up to 1 year **Description:** All infections included: 1. Opportunistic infections per-clinical assessment, 2. Herpes Zoster, a. Recurrent, b. Disseminated, 3. Sepsis. Opportunistic infections were identified using list of preferred terms as per Medical Dictionary for Regulatory Activities (MedDRA) version 18.1. Any events falling under these preferred terms were adjudicated to determine if criteria was met for an opportunistic infection. **Measure:** Number of Incidence of All Infections and Serious Infections **Time Frame:** Up to 1 year **Description:** Change from Baseline in SBP and DBP were assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Change from Baseline was calculated as the value at Week 24 and Week 52 minus the value at Baseline. Baseline value used in the analysis was of Day 0 (Day of transplant). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). **Measure:** Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 24 and Week 52 **Time Frame:** Baseline, Week 24 and Week 52 **Description:** Change from Baseline in heart rate was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Change from Baseline was calculated as the value at Week 24 and Week 52 minus the value at Baseline. Baseline value used in the analysis was of Day 0 (Day of transplant). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). **Measure:** Change From Baseline in Heart Rate From Baseline at Week 24 and Week 52 **Time Frame:** Baseline, Week 24 and Week 52 **Description:** Change from Baseline in body temperature was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Change from Baseline was calculated as the value at Week 24 and Week 52 minus the value at Baseline. Baseline value used in the analysis was of Day 0 (Day of transplant). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). **Measure:** Change From Baseline in Body Temperature From Baseline at Week 24 and Week 52 **Time Frame:** Baseline, Week 24 and Week 52 **Description:** Number of participants outside the normal range (NR) for SBP and DBP was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Number of participants outside the normal range are summarized by less than (\<) normal range and greater than (\>) normal range categories at Week 24 and Week 52. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). **Measure:** Number of Participants Outside the Normal Range (NR) for SBP and DBP at Week 24 and Week 52 **Time Frame:** Week 24 and Week 52 **Description:** Number of participants outside the normal range (NR) for heart rate was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Number of participants outside the normal range are summarized by less than (\<) normal range and greater than (\>) normal range categories at Week 24 and Week 52. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). **Measure:** Number of Participants Outside the Normal Range (NR) for Heart Rate at Week 24 and Week 52 **Time Frame:** Week 24 and Week 52 **Description:** Number of participants outside the normal range (NR) for body temperature was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Number of participants outside the normal range are summarized by less than (\<) normal range and greater than (\>) normal range categories at Week 24 and Week 52. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). **Measure:** Number of Participants Outside the Normal Range (NR) for Body Temperature at Week 24 and Week 52 **Time Frame:** Week 24 and Week 52 **Description:** Hematology parameters included: basophils (B), eosinophils (E), lymphocytes (L), monocytes (M), total neutrophils (N), platelet count (PC) and white blood cells (WBC). Change from Baseline in haematology parameter was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Change from Baseline was calculated as the value on Week 24 and Week 52 minus the value at Baseline. Baseline value used in the analysis was of Day 0 (Day of transplant). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). **Measure:** Change From Baseline in the Indicated Hematology Parameters at Week 24 and Week 52 **Time Frame:** Baseline, Week 24 and Week 52 **Description:** Change from Baseline in hemoglobin was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Change from Baseline was calculated as the value on Week 24 and Week 52 minus the value at Baseline. Baseline value used in the analysis was of Day 0 (Day of transplant). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). **Measure:** Change From Baseline in the Haematology Parameter- Hemoglobin at Week 24 and Week 52 **Time Frame:** Baseline, Week 24 and Week 52 **Description:** Endpoint was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Change from Baseline was calculated as the value on Week 24 and Week 52 minus the value at Baseline. Baseline value used in the analysis was of Day 0 (Day of transplant). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). **Measure:** Change From Baseline in the Hematology Parameter- Hematocrit at Week 24 and Week 52 **Time Frame:** Baseline, Week 24 and Week 52 **Description:** Change from Baseline in MCH was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Change from Baseline was calculated as the value on Week 24 and Week 52 minus the value at Baseline. Baseline value used in the analysis was of Day 0 (Day of transplant). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). **Measure:** Change From Baseline in Haematology Parameter- Mean Corposcular Hemoglobin (MCH) at Week 24 and Week 52 **Time Frame:** Baseline, Week 24 and Week 52 **Description:** Change from Baseline in MCV was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Change from Baseline was calculated as the value on Week 24 and Week 52 minus the value at Baseline. Baseline value used in the analysis was of Day 0 (Day of transplant). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). **Measure:** Change From Baseline in Haematology Parameter- Mean Corposcular Volume (MCV) at Week 24 and Week 52 **Time Frame:** Baseline, Week 24 and Week 52 **Description:** Change from Baseline in RBC was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Change from Baseline was calculated as the value on Week 24 and Week 52 minus the value at Baseline. Baseline value used in the analysis was of Day 0 (Day of transplant). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). **Measure:** Change From Baseline in Haematology Parameter- Red Blood Cell (RBC) at Week 24 and Week 52 **Time Frame:** Baseline, Week 24 and Week 52 **Description:** Change from Baseline in albumin was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Change from Baseline was calculated as the value on Week 24 and Week 52 minus the value at Baseline. Baseline value used in the analysis was of Day 0 (Day of transplant). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). **Measure:** Change From Baseline in Clinical Chemistry Parameter- Albumin at Week 24 and Week 52 **Time Frame:** Baseline, Week 24 and Week 52 **Description:** Clinical chemistry parameter included alkaline phosphatase (ALP), alanine amino Transferase (ALT) and aspartate amino transferase (AST). Endpoint was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Change from Baseline was calculated as the value on Week 24 and Week 52 minus the value at Baseline. Baseline value used in the analysis was of Day 0 (Day of transplant). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). **Measure:** Change From Baseline in Clinical Chemistry Parameter- ALP, ALT, AST at Week 24 and Week 52 **Time Frame:** Baseline, Week 24 and Week 52 **Description:** Clinical chemistry parameters included direct bilirubin (DB), total bilirubin (TB) and creatinine (C). Endpoint was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Change from Baseline was calculated as the value on Week 24 and Week 52 minus the value at Baseline. Baseline value used in the analysis was of Day 0 (Day of transplant). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). **Measure:** Change From Baseline in Clinical Chemistry Parameter- Direct Bilirubin, Total Bilirubin and Creatinine at Week 24 and Week 52 **Time Frame:** Baseline, Week 24 and Week 52 **Description:** Clinical chemistry parameters included calcium (Ca), carbon dioxide content/bicarbonate (CO2/Bicar), glucose (Gl), potassium (K), sodium (Na), phosphorus inorganic (PhI), urea/blood urine nitrogen (U/BUN). Endpoint was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Change from Baseline was calculated as the value on Week 24 and Week 52 minus the value at Baseline. Baseline value used in the analysis was of Day 0 (Day of transplant). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). **Measure:** Change From Baseline in Clinical Chemistry Parameter- Ca, CO2/Bicar, Gl, K, Na, PhI, U/BUN at Week 24 and Week 52 **Time Frame:** Baseline, Week 24 and Week 52 **Description:** Change from Baseline in GFR was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Change from Baseline was calculated as the value on Week 24 and Week 52 minus the value at Baseline. Baseline value used in the analysis was of Day 0 (Day of transplant). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). **Measure:** Change From Baseline in Clinical Chemistry Parameter- Glomerular Filtration Rate (GFR) at Week 24 and Week 52 **Time Frame:** Baseline, Week 24 and Week 52 **Description:** Change from Baseline in immunoglobulins IgA, IgG and IgM was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Change from Baseline was calculated as the value on Week 24 and Week 52 minus the value at Baseline. Baseline value used in the analysis was of Day 0 (Day of transplant). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). **Measure:** Change From Baseline in Immunoglobulin A (IgA), Immunoglobulin G (IgG) and Immunoglobulin M (IgM) at Week 24 and Week 52 **Time Frame:** Baseline, Week 24 and Week 52 #### Secondary Outcomes **Description:** Memory B cells are B cell sub-type that are formed within germinal centres following primary infection and are important in generating an accelerated and more robust antibody-mediated immune response in the case of re-infection. Memory B cell count included CD20+CD27+ cells/mm\^3. Baseline value used in the analysis was of Day 0 (Day of transplant). Endpoint was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Percent change from Baseline in Memory B cell count was calculated as the value at Week 24 and Week 52 minus the value at Baseline multiplied by 100. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Median Difference and 95% confidence interval of difference obtained using the Hodges-Lehmann method. **Measure:** Median Percent Change From Baseline in Memory B Cell Count at Week 24 and Week 52 **Time Frame:** Baseline, Week 24 and Week 52 **Description:** Activated memory B cell-CD95% count is CD19+CD27+CD95 conc-cells/mL. Adjusted mean difference (treatment-placebo) and 95% confidence intervals for differences were obtained from MMRM model, with fixed categorical effects of treatment, visit, donor type and treatment-by-visit interaction and fixed continuous covariates of Baseline and Baseline-by-visit interaction. A compound symmetry variance structure was used to model the within-participant errors, shared across treatments. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). **Measure:** Activated Memory B Cells Count at Week 24 and Week 52 **Time Frame:** Week 24 and Week 52 **Description:** Activated memory B cell-CD95% percentage is CD19+CD27+CD95+ (%CD19/CD27). Adjusted mean difference (treatment-placebo) and 95% confidence intervals for differences were obtained from MMRM model, with fixed categorical effects of treatment, visit, donor type and treatment-by-visit interaction and fixed continuous covariates of Baseline and Baseline-by-visit interaction. A compound symmetry variance structure was used to model the within-participant errors, shared across treatments. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). **Measure:** Activated Memory B Cells Percentage at Week 24 and Week 52 **Time Frame:** Week 24 and Week 52 **Description:** Transitional B cell count (Newell) is CD19+CD24b+CD38b+IgD+ (Conc-cells/mL). Adjusted mean difference (treatment-placebo) and 95% confidence intervals for differences were obtained from MMRM model, with fixed categorical effects of treatment, visit, donor type and treatment-by-visit interaction and fixed continuous covariates of Baseline and Baseline-by-visit interaction. A compound symmetry variance structure was used to model the within-participant errors, shared across treatments. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). **Measure:** Transitional B Cells Count at Week 24 and Week 52 **Time Frame:** Week 24 and Week 52 **Description:** Transitional B cell percentage (Newell) is CD19+CD24b+CD38b+IgD+ (%CD19+). Adjusted mean difference (treatment-placebo) and 95% confidence intervals for differences were obtained from MMRM model, with fixed categorical effects of treatment, visit, donor type and treatment-by-visit interaction and fixed continuous covariates of Baseline and Baseline-by-visit interaction. A compound symmetry variance structure was used to model the within-participant errors, shared across treatments. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). **Measure:** Transitional B Cells Percentage at Week 24 and Week 52 **Time Frame:** Week 24 and Week 52 **Description:** A T cell is a type of lymphocyte that plays a central role in cell-mediated immunity. Activated T cell count Codarri is CD4+ CD25hi CD45RA- IL 7Rhi (Conc-cells/mL). Adjusted mean difference (treatment-placebo) and 95% confidence intervals for differences were obtained from MMRM model, with fixed categorical effects of treatment, visit, donor type and treatment-by-visit interaction and fixed continuous covariates of Baseline and Baseline-by-visit interaction. A compound symmetry variance structure was used to model the within-participant errors, shared across treatments. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). **Measure:** Activated T Cell Count at Week 24 and Week 52 **Time Frame:** Week 24 and Week 52 **Description:** Activated T cell percentage (Codarri)= CD4+ CD25hi CD45RA- IL 7Rhi (% of CD4+). Adjusted mean difference (treatment-placebo) and 95% confidence intervals for differences were obtained from MMRM model, with fixed categorical effects of treatment, visit, donor type and treatment-by-visit interaction and fixed continuous covariates of Baseline and Baseline-by-visit interaction. A compound symmetry variance structure was used to model the within-participant errors, shared across treatments. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). **Measure:** Activated T Cell Percentage at Week 24 and Week 52 **Time Frame:** Week 24 and Week 52 **Description:** Regulatory T cell count is CD4+ CD25hi IL-7Rlo (Conc-cells/mL). Adjusted mean difference (treatment-placebo) and 95% confidence intervals for differences were obtained from MMRM model, with fixed categorical effects of treatment, visit, donor type and treatment-by-visit interaction and fixed continuous covariates of Baseline and Baseline-by-visit interaction. A compound symmetry variance structure was used to model the within-participant errors, shared across treatments. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). **Measure:** Regulatory T Cell Count at Week 24 and Week 52 **Time Frame:** Week 24 and Week 52 **Description:** Regulatory T cell (%CD4) = CD4+ CD25hi IL-7Rlo (% of CD4+). Adjusted mean difference (treatment-placebo) and 95% confidence intervals for differences were obtained from MMRM model, with fixed categorical effects of treatment, visit, donor type and treatment-by-visit interaction and fixed continuous covariates of Baseline and Baseline-by-visit interaction. A compound symmetry variance structure was used to model the within-participant errors, shared across treatments. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). **Measure:** Regulatory T Cell (%CD4) at Week 24 and Week 52 **Time Frame:** Week 24 and Week 52 **Description:** Activated: regulatory T cell ratio is Activated T cell CD4+CD25hi CD45RA IL 7Rhi (absolute number)/ Regulatory T cell CD4+CD25hi CD45RA IL 7Rlo (absolute number). Adjusted mean difference (treatment-placebo) and 95% confidence intervals for differences were obtained from MMRM model, with fixed categorical effects of treatment, visit, donor type and treatment-by-visit interaction and fixed continuous covariates of Baseline and Baseline-by-visit interaction. A compound symmetry variance structure was used to model the within-participant errors, shared across treatments. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). **Measure:** Mean Activated: Regulatory T Cell Ratio at Week 24 and Week 52 **Time Frame:** Week 24 and Week 52 **Description:** The endpoint diagnosis was made by a proven biopsy result. Number of rejections only counted once per participant. The proportion of participants with episodes of acute rejection was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). **Measure:** Proportion of Participants With Episodes of Acute Rejection at Week 24 and Week 52 **Time Frame:** Week 24 and Week 52 **Description:** Adjusted mean difference for serum creatinine values (treatment-placebo) and 95% confidence intervals for differences were obtained from MMRM model, with fixed categorical effects of treatment, visit, donor type and treatment-by-visit interaction and fixed continuous covariates of Baseline and Baseline-by-visit interaction, at Week 24 and Week 52. A compound symmetry variance structure was used to model the within-participant errors, shared across treatments. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). **Measure:** Mean Serum Creatinine at Week 24 and Week 52 **Time Frame:** Week 24 and Week 52 **Description:** The estimated glomerular filtration rate (eGFR) were calculated by the abbreviated Modification of Diet in Renal Disease (MDRD) equation. Adjusted mean difference(treatment-placebo) and 95% confidence intervals for differences were obtained from MMRM model, with fixed categorical effects of treatment, visit, donor type and treatment-by-visit interaction and fixed continuous covariates of Baseline and Baseline-by-visit interaction at Week 24 and Week 52. A compound symmetry variance structure was used to model the within-participant errors, shared across treatments. Only those participants available at the indicated time points were analyzed (represented by n= X, X in the category titles). **Measure:** Mean eGFR at Week 24 and Week 52 **Time Frame:** Week 24 and Week 52 **Description:** Adjusted mean difference (treatment-placebo) for Prednisolone use and 95% confidence intervals for differences were obtained from MMRM model, with fixed categorical effects of treatment, visit, donor type and treatment-by-visit interaction and fixed continuous covariates of Baseline and Baseline-by-visit interaction at Week 24. A compound symmetry variance structure was used to model the within-participant errors, shared across treatments Only those participants available at indicated timepoints were analyzed (represented by n=X, X in the category titles). **Measure:** Mean Prednisolone Use at Week 24 **Time Frame:** Week 24 ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Eligible for kidney transplantation: Considered eligible for transplantation after undergoing multidisciplinary evaluation at the institution at which the transplantation will be performed * Donor characteristics: Receiving a deceased donor kidney or a living donor kidney allograft * Age \& Gender: Male or female between 18 and 75 years of age, inclusive, at the time of signing the informed consent * Female Subjects: Not pregnant or nursing and at least one of the following conditions apply: a. Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy or postmenopausal defined as 12 months of spontaneous amenorrhea. In the absence of confirmatory laboratory assessments \[(a blood sample with simultaneous follicle stimulating hormone (FSH) \> 40 million international units per milliliter (MIU/mL) and estradiol \< 40 picogram per milliliter (pg/mL) (\<147 picomole per liter \[pmol/L\])\] in questionable cases, female subjects will be required to use one of the contraception methods as described by the investigator or designee, until confirmatory results become available; b. Questionable post-menopausal status and agrees to use one of the contraception methods as described by the investigator or designee, from Day 0 until 16 weeks after the last dose of investigational product or until postmenopausal status is confirmed with a blood sample with simultaneous follicle stimulating hormone (FSH) \> 40 MIU/mL and estradiol status who are using hormone replacement therapy (HRT) will be required to use one of the contraception methods as described by the investigator or designee, until post-menopausal status is confirmed. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method; c. Child-bearing potential and agrees to use one of the contraception methods as described by the investigator or designee, from Day 0 until 16 weeks after the last dose of investigational product. * Liver function (most recent values available before transplantation): alanine aminotransferase (ALT) \< 2x upper limit of normal (ULN); bilirubin \<= 1.5xULN (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%). * Immunosuppressants: at the time of transplantation, planned to receive a combination of immunosuppressants including basiliximab, mycophenolate mofetil, tacrolimus, prednisolone Exclusion Criteria: * Donor characteristics: receiving a kidney allograft from a donor with any of the following characteristics: a) cold ischemic time exceeding 36 hours; b) age \< 5 years old; c) for donors after brain death (DBD), age \>70 years old; d) for donors after cardiac death (DCD) age \>70 years old; e) ABO blood type incompatible against the recipient; f) 0 0 0 HLA-A -B -DR mismatch against the recipient by National Health Service Blood and Transplant (NHSBT criteria; g) T- and/or B-cell positive crossmatch by complement dependent cytotoxicity or flow cytometry against the recipient. Note :- (In some situations it may be that a pre-existing T- and/or B-cell positive crossmatch by complement dependent cytotoxicity or flow cytometry against the recipient will only be fully revealed immediately after the transplant; in such situations they will be recorded as having met exclusion criteria and withdraw from further involvement in the study; h) serology positive for hepatitis B (except hepatitis B surface antibody and prior vaccination), hepatitis C or human immunodeficiency virus (HIV) * Transplant other than kidney: has previously received a hematopoietic stem cell/marrow transplant or an organ transplant other than a kidney (with the exception of corneal transplantation) * Planned immunosuppressant regimen: are being considered for steroid-free or alemtuzumab induction * Prior therapy at any time: has ever received any of the following: a) B-cell targeted therapy (e.g., rituximab, other anti-CD20 agents, anti-CD22 \[epratuzumab\], anti-CD52 \[alemtuzumab\], BLyS-receptor fusion protein \[BR3\], TACI fragment, crystallizable (Fc), or belimumab) * 364 Day prior therapy: has received any of the following within 364 days before Day 0: a) Cyclophosphamide; b) Abatacept; c) A biologic investigational agent other than B-cell targeted therapy \[e.g., abetimus sodium, anti CD40L antibody (e.g., BG9588/ IDEC 131; investigational agent applies to any drug not approved for sale in the country in which it is being used\] * 90 Day prior therapy: has received any of the following within 90 days before Day 0: a) Anti- Tumor necrosis factor (TNF) or anti-Interleukin (IL)-6 therapy (e.g., adalimumab, etanercept, infliximab, tocilizumab); b) Interleukin-1 receptor antagonists (e.g., anakinra); c) Intravenous immunoglobulin (IVIG); d) Plasmapheresis, leukapheresis * 60 Day prior therapy: has received any of the following within 60 days before Day 0: a) A non-biologic investigational agent (investigational agent applies to any drug not approved for sale in the country in which it is being used); b) Any new immunosuppressive/immunomodulatory agent; tacrolimus, Mycophenolate mofetil (MMF), and corticosteroids are permitted. Inhaled steroids and new topical immunosuppressive agents (e.g., eye drops, topical creams) are also allowed. * 30 Day prior therapy: has received any of the following within 30 days before Day 0: a) A live vaccine; b) An increase in dose of an immunosuppressive/immunomodulatory agent (decreases in dose or discontinuations are permitted). Increases in doses of tacrolimus, MMF, and corticosteroids are permitted. * Malignancy: has a history of malignancy in the past 5 years except for adequately treated cancers of the skin (basal or squamous cell) or carcinoma in situ of the uterine cervix. * Acute or chronic infection: has required management of acute or chronic infections (excludes prophylaxis of infections), as follows: a) Currently receiving any suppressive therapy for a chronic infection (such as tuberculosis, pneumocystis, cytomegalovirus, herpes simplex virus, herpes zoster and atypical mycobacteria), which, in the opinion of the investigator, could put the subject at undue risk; b) Hospitalized for treatment of infection within 30 days before Day 0, which, in the opinion of the investigator, could put the subject at undue risk ; c) Treated for an infection with parenteral (intravenous or intramuscular)\] antibiotics (antibacterials, antivirals, anti-fungals, or anti-parasitic agents) within 30 days before Day 0, which, in the opinion of the investigator, could put the subject at undue risk * Other disease/conditions: has any of the following: a) clinical evidence of significant unstable or uncontrolled acute or chronic diseases (i.e., cardiovascular, pulmonary, hematologic, gastrointestinal, hepatic, neurological, malignancy or infectious diseases) which, in the opinion of the investigator, could confound the results of the study or put the subject at undue risk; b) a surgical procedure planned in the 6 months after Day 0, other than kidney transplantation or related procedure; c) a known history of any other medical disease (e.g., cardiopulmonary), laboratory abnormality, or condition (e.g., poor venous access) that, in the opinion of the investigator, makes the subject unsuitable for the study * Hepatitis: known to have serologic evidence of hepatitis B infection based on the results of testing for hepatitis B surface antigen (HBsAg), or antibodies against hepatitis B core antigen (HBc) and/or hepatitis B surface antigen (HBs) as follows: a) Patients positive for HBsAg are excluded; ) Patients negative for HBsAg and anti-HBc antibody but positive for anti-HBs antibody and with no history of hepatitis B vaccination are excluded; c) Patients negative for HBsAg but positive for both anti-HBc and anti-HBs antibodies are excluded; d) Patients negative for HBsAg and anti-HBs antibody but positive for anti-HBc antibody are excluded; e) Or has known serologic evidence of hepatitis C infection based on the results of testing for hepatitis C antibody and hepatitis C recombinant immunoblot assay (RIBA) as follows: Patients with a positive test for Hepatitis C antibody confirmed on the same sample with a Hepatitis C RIBA immunoblot assay. Patients who are positive for Hepatitis C antibody, and who are negative when the Hepatitis C RIBA immunoblot assay is performed on the same sample, will be eligible to participate. Patients who are positive for Hepatitis C antibody and who have a positive or indeterminate result when the Hepatitis C RIBA immunoblot assay is performed on the same sample, will not be eligible to participate. * HIV: known to have a historically positive HIV test or tests positive at screening for HIV. * Immunodeficiency: recipient with a history of immunodeficiency (defined as Immunoglobulin A isotype (IgA) level \<10 milligrams per deciliter (mg/dL) or have Immunoglobulin G isotype (IgG) level \<400 mg/dL). * Laboratory abnormalities: has an abnormal laboratory assessment, which is judged clinically significant by the investigator. * Lymphopenia: has a lymphocyte count \<500/ millimeter (mm)\^3. * Drug Sensitivity: has a history of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy including a previous anaphylactic reaction to parenteral administration contrast agents, human or murine proteins or monoclonal antibodies that, in the opinion of the investigator or Medical Monitor, contraindicates their participation. * Substance abuse: has evidence of current drug or alcohol abuse or dependence. * Blood donation: where participation in the study would result in donation of blood or blood products in excess of 700 mL within a 56-day period * Venous access: has venous access limitations likely to preclude monthly infusions * Compliance: is unlikely to comply with scheduled study visits based on investigator judgment or has a history of substance abuse, psychiatric disorder or condition that may compromise communication with the investigator **Maximum Age:** 75 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Cambridge **Country:** United Kingdom **Facility:** GSK Investigational Site **Zip:** CB2 0QQ **Location 2:** **City:** London **Country:** United Kingdom **Facility:** GSK Investigational Site **Zip:** SE1 9RT #### Overall Officials **Official 1:** **Affiliation:** GlaxoSmithKline **Name:** GSK Clinical Trials **Role:** STUDY_DIRECTOR ### References Module #### References **Citation:** Banham GD, Flint SM, Torpey N, Lyons PA, Shanahan DN, Gibson A, Watson CJE, O'Sullivan AM, Chadwick JA, Foster KE, Jones RB, Devey LR, Richards A, Erwig LP, Savage CO, Smith KGC, Henderson RB, Clatworthy MR. Belimumab in kidney transplantation: an experimental medicine, randomised, placebo-controlled phase 2 trial. Lancet. 2018 Jun 30;391(10140):2619-2630. doi: 10.1016/S0140-6736(18)30984-X. Epub 2018 Jun 14. **PMID:** 29910042 ## Derived Section ### Condition Browse Module - Browse Branches - Abbrev: BC01 - Name: Infections - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: BXM - Name: Behaviors and Mental Disorders ### Condition Browse Module - Browse Leaves - ID: M10283 - Name: Infections - Relevance: LOW - As Found: Unknown - ID: M6368 - Name: Communicable Diseases - Relevance: LOW - As Found: Unknown - ID: T6034 - Name: Quality of Life - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Ancestors - ID: D000007166 - Term: Immunosuppressive Agents - ID: D000007155 - Term: Immunologic Factors - ID: D000045505 - Term: Physiological Effects of Drugs ### Intervention Browse Module - Browse Branches - Abbrev: PhSol - Name: Pharmaceutical Solutions - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M21860 - Name: Pharmaceutical Solutions - Relevance: LOW - As Found: Unknown - ID: M287398 - Name: Belimumab - Relevance: HIGH - As Found: Inject - ID: M10212 - Name: Immunosuppressive Agents - Relevance: LOW - As Found: Unknown - ID: M10201 - Name: Immunologic Factors - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: C000511911 - Term: Belimumab ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module **Description:** On-treatment SAEs and non-serious AEs are reported for MITT Population. #### Event Groups **Group ID:** EG000 **Title:** Placebo **Description:** Participants received normal saline (0.9% sodium chloride) via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) in addition to standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** EG000 **Other Num Affected:** 9 **Other Num at Risk:** 13 **Serious Number Affected:** 7 **Serious Number At Risk:** 13 **Title:** Placebo **Group ID:** EG001 **Title:** Belimumab 10mg/kg **Description:** Participants received 10 milligram (mg) /kilogram (kg) belimumab in 250 milliliter (mL) normal saline via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** EG001 **Other Num Affected:** 9 **Other Num at Risk:** 12 **Serious Number Affected:** 5 **Serious Number At Risk:** 12 **Title:** Belimumab 10mg/kg **Frequency Threshold:** 5 #### Other Events **Term:** Diarrhoea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA version 18.1 **Term:** Leukopenia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA version 18.1 **Term:** Urinary tract infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA version 18.1 **Term:** Anaemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA version 18.1 **Term:** Dyspepsia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA version 18.1 **Term:** Alanine aminotransferase increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA version 18.1 **Term:** Lower respiratory tract infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA version 18.1 **Term:** Nasopharyngitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA version 18.1 **Term:** Polyomavirus test positive **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA version 18.1 **Term:** Diabetes mellitus **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA version 18.1 **Term:** Dizziness **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA version 18.1 **Term:** Oesophagitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA version 18.1 **Term:** Tonsillitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA version 18.1 **Term:** Vomiting **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA version 18.1 **Term:** Wound infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA version 18.1 **Term:** Anaemia vitamin B12 deficiency **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA version 18.1 **Term:** Cold sweat **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA version 18.1 **Term:** Cough **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA version 18.1 **Term:** Cytomegalovirus test positive **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA version 18.1 **Term:** Duodenal ulcer **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA version 18.1 **Term:** Duodenitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA version 18.1 **Term:** Epstein-Barr virus test positive **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA version 18.1 **Term:** Headache **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA version 18.1 **Term:** Hip fracture **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA version 18.1 **Term:** Hyperhidrosis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA version 18.1 **Term:** Hypertension **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA version 18.1 **Term:** Infusion related reaction **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA version 18.1 **Term:** Iron deficiency anaemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA version 18.1 **Term:** Migraine **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA version 18.1 **Term:** Mouth ulceration **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA version 18.1 **Term:** Myalgia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA version 18.1 **Term:** Onychomycosis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA version 18.1 **Term:** Oral candidiasis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA version 18.1 **Term:** Palpitations **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA version 18.1 **Term:** Paraesthesia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA version 18.1 **Term:** Pneumonia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA version 18.1 **Term:** Polycythaemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA version 18.1 **Term:** Polyomavirus-associated nephropathy **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA version 18.1 **Term:** Renal artery stenosis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA version 18.1 **Term:** Renal cyst infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA version 18.1 **Term:** Respiratory disorder **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA version 18.1 **Term:** Tachycardia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA version 18.1 **Term:** Thrombocytopenia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA version 18.1 **Term:** Tremor **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA version 18.1 **Term:** Ulcerative gastritis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA version 18.1 **Term:** Upper respiratory tract infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA version 18.1 **Term:** Urinary tract infection enterococcal **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA version 18.1 **Term:** Vasculitic rash **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA version 18.1 **Term:** Vertigo **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Ear and labyrinth disorders **Source Vocabulary:** MedDRA version 18.1 **Term:** Vulvovaginal candidiasis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA version 18.1 #### Serious Events **Term:** Acute myocardial infarction **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA version 18.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 13 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 12 **Term:** Alanine aminotransferase increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA version 18.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 13 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 12 **Term:** Anaemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA version 18.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 13 **Num Events:** 3 **Group ID:** EG001 **Num At Risk:** 12 **Term:** Blood creatinine increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA version 18.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 13 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 12 **Num Events:** 1 **Term:** Cardiac failure acute **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA version 18.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 13 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 12 **Term:** Cellulitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA version 18.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 13 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 12 **Term:** Clostridium difficile colitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA version 18.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 13 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 12 **Num Events:** 1 **Term:** Colitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA version 18.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 13 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 12 **Num Events:** 1 **Term:** Dehydration **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA version 18.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 13 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 12 **Num Events:** 1 **Term:** Delirium **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA version 18.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 13 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 12 **Num Events:** 1 **Term:** Diarrhoea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA version 18.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 13 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 12 **Num Events:** 1 **Term:** Escherichia urinary tract infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA version 18.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 13 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 12 **Term:** Focal segmental glomerulosclerosis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA version 18.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 13 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 12 **Num Events:** 1 **Term:** Glomerulonephritis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA version 18.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 13 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 12 **Term:** Hip fracture **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA version 18.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 13 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 12 **Term:** Lymphocele **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA version 18.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 13 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 12 **Num Events:** 1 **Term:** Pneumonia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA version 18.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 13 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 12 **Num Events:** 1 **Term:** Pulmonary oedema **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA version 18.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 13 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 12 **Term:** Renal cyst infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA version 18.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 13 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 12 **Term:** Tonsillitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA version 18.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 13 **Num Events:** 2 **Group ID:** EG001 **Num At Risk:** 12 **Term:** Transplant rejection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Immune system disorders **Source Vocabulary:** MedDRA version 18.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 13 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 12 **Num Events:** 1 **Term:** Urinary tract infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA version 18.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 13 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 12 **Term:** Urosepsis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA version 18.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 13 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 12 **Num Events:** 1 **Term:** Wound infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA version 18.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 13 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 12 **Num Events:** 1 **Time Frame:** Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until follow-up (up to 52 weeks). ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 13 **Group ID:** BG001 **Value:** 12 **Group ID:** BG002 **Value:** 25 **Units:** Participants ### Group **ID:** BG000 **Title:** Placebo **Description:** Participants received normal saline (0.9% sodium chloride) via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) in addition to standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. ### Group **ID:** BG001 **Title:** Belimumab 10mg/kg **Description:** Participants received 10 milligram (mg) /kilogram (kg) belimumab in 250 milliliter (mL) normal saline via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. ### Group **ID:** BG002 **Title:** Total **Description:** Total of all reporting groups ### Measure #### Measurement **Group ID:** BG000 **Spread:** 14.02 **Value:** 51.0 #### Measurement **Group ID:** BG001 **Spread:** 11.02 **Value:** 54.3 #### Measurement **Group ID:** BG002 **Spread:** 12.52 **Value:** 52.6 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 4 #### Measurement **Group ID:** BG001 **Value:** 7 #### Measurement **Group ID:** BG002 **Value:** 11 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 9 #### Measurement **Group ID:** BG001 **Value:** 5 #### Measurement **Group ID:** BG002 **Value:** 14 **Category Title:** Male **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 12 #### Measurement **Group ID:** BG001 **Value:** 11 #### Measurement **Group ID:** BG002 **Value:** 23 **Class Title:** White/Caucasian #### Measurement **Group ID:** BG000 **Value:** 1 #### Measurement **Group ID:** BG001 **Value:** 1 #### Measurement **Group ID:** BG002 **Value:** 2 **Class Title:** Asian **Denomination Units Selected:** ## Results Section - Baseline Characteristics Module ### Measure 1 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** Age, Continuous **Unit of Measure:** Years ### Measure 2 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Sex: Female, Male **Unit of Measure:** Participants ### Measure 3 **Parameter Type:** NUMBER **Title:** Race/Ethnicity, Customized **Unit of Measure:** Participants ## Results Section - More Information Module ### Certain Agreement **Other Details:** GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial. **Restriction Type:** OTHER **Restrictive Agreement:** True ### Point of Contact **Organization:** GlaxoSmithKline **Phone:** 866-435-7343 **Title:** GSK Response Center ## Results Section - Outcome Measures Module ### Outcome Measure 1 #### Analysis **CI Lower Limit:** -109.5 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 40.7 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 37.24 **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** -34.4 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** ### Outcome Measure 2 ### Outcome Measure 3 ### Outcome Measure 4 ### Outcome Measure 5 ### Outcome Measure 6 ### Outcome Measure 7 ### Outcome Measure 8 ### Outcome Measure 9 ### Outcome Measure 10 ### Outcome Measure 11 ### Outcome Measure 12 ### Outcome Measure 13 ### Outcome Measure 14 ### Outcome Measure 15 ### Outcome Measure 16 ### Outcome Measure 17 ### Outcome Measure 18 ### Outcome Measure 19 ### Outcome Measure 20 ### Outcome Measure 21 ### Outcome Measure 22 #### Analysis **CI Lower Limit:** 90.00 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 550.00 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** Week 24 comparison **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Median Difference (Final Values) **Parameter Value:** 204.35 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** -169.84 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 25.00 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** Week 52 comparison **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Median Difference (Final Values) **Parameter Value:** -33.06 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** ### Outcome Measure 23 #### Analysis **CI Lower Limit:** -50457.0 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 52921.8 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 25735.56 **Estimate Comment:** Week 24 comparison **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 1232.40 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** -61868.9 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 35612.2 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 24165.18 **Estimate Comment:** Week 52 comparison **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** -13128.35 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** ### Outcome Measure 24 #### Analysis **CI Lower Limit:** -31.3 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 3.7 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 8.78 **Estimate Comment:** Week 24 comparison **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** -13.8 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** -8.6 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 22.2 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 7.68 **Estimate Comment:** Week 52 comparison **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 6.8 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** ### Outcome Measure 25 #### Analysis **CI Lower Limit:** -12105 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 6524 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 4651.1 **Estimate Comment:** Week 24 comparison **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** -2791 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** -9487 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 8572 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 4501.8 **Estimate Comment:** Week 52 comparison **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** -458 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** ### Outcome Measure 26 #### Analysis **CI Lower Limit:** -3.59 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 1.01 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 1.156 **Estimate Comment:** Week 24 comparison **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** -1.29 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** -1.24 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 2.82 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 1.017 **Estimate Comment:** Week 52 comparison **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 0.79 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** ### Outcome Measure 27 #### Analysis **CI Lower Limit:** -100559.1 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 39905.3 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 34677.86 **Estimate Comment:** Week 24 comparison **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** -30326.9 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** -113218.9 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 19308.3 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 32594.81 **Estimate Comment:** Week 52 comparison **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** -46955.3 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** ### Outcome Measure 28 #### Analysis **CI Lower Limit:** -10.1 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 4.2 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 3.54 **Estimate Comment:** Week 24 comparison **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** -3.0 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** -7.2 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 6.3 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 3.35 **Estimate Comment:** Week 52 comparison **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** -0.4 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** ### Outcome Measure 29 #### Analysis **CI Lower Limit:** -24661.1 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 25957.7 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 12618.44 **Estimate Comment:** Week 24 comparison **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 648.3 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** -29994.8 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 18757.0 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 12153.03 **Estimate Comment:** Week 52 comparison **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** -5618.9 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** ### Outcome Measure 30 #### Analysis **CI Lower Limit:** -3.2 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 3.5 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 1.67 **Estimate Comment:** Week 24 comparison **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 0.1 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** -3.5 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 2.3 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 1.45 **Estimate Comment:** Week 52 comparison **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** -0.6 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** ### Outcome Measure 31 #### Analysis **CI Lower Limit:** -4.07 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 0.98 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 1.255 **Estimate Comment:** Week 24 comparison **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** -1.54 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** -3.68 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 1.67 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 1.329 **Estimate Comment:** Week 52 comparison **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** -1.01 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** ### Outcome Measure 32 #### Analysis **CI Lower Limit:** -0.638 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 0.505 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** Week 24 comparison **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Difference in Proportion **Parameter Value:** -0.067 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** -0.838 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 0.305 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** Week 52 comparison **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Difference in Proportion **Parameter Value:** -0.267 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** ### Outcome Measure 33 #### Analysis **CI Lower Limit:** -105.9 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 100.3 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 52.06 **Estimate Comment:** Week 24 comparison **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** -2.8 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** -107.1 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 81.4 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 47.52 **Estimate Comment:** Week 52 comparison **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** -12.9 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** ### Outcome Measure 34 #### Analysis **CI Lower Limit:** -31.56 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 5.71 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 9.440 **Estimate Comment:** Week 24 comparison **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** -12.92 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** -19.11 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 13.72 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 8.315 **Estimate Comment:** Week 52 comparison **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** -2.70 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** ### Outcome Measure 35 #### Analysis **CI Lower Limit:** -4.84 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 3.96 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 2.225 **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** -0.44 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 25.55 - **Upper Limit:** - **Value:** 4.0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 27.50 - **Upper Limit:** - **Value:** -30.4 **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 10 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 11 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 9 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 10 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 7 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 5 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 6 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 7 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** #### Outcome Measure 3 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 8 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 7 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 7 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 5 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** #### Outcome Measure 4 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 14.3275 - **Upper Limit:** - **Value:** -4.444 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 13.8289 - **Upper Limit:** - **Value:** 7.286 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 13.9668 - **Upper Limit:** - **Value:** -6.545 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 8.5479 - **Upper Limit:** - **Value:** 4.200 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 26.0960 - **Upper Limit:** - **Value:** 2.000 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 35.9444 - **Upper Limit:** - **Value:** 10.000 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 27.2046 - **Upper Limit:** - **Value:** -2.909 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 27.9008 - **Upper Limit:** - **Value:** 3.300 **Title:** #### Outcome Measure 5 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 16.8983 - **Upper Limit:** - **Value:** 5.125 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 13.6345 - **Upper Limit:** - **Value:** 1.500 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 11.5065 - **Upper Limit:** - **Value:** 2.000 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 15.4200 - **Upper Limit:** - **Value:** -2.444 **Title:** #### Outcome Measure 6 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.7025 - **Upper Limit:** - **Value:** 0.025 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.5007 - **Upper Limit:** - **Value:** -0.233 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.4803 - **Upper Limit:** - **Value:** -0.045 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.5417 - **Upper Limit:** - **Value:** 0.030 **Title:** #### Outcome Measure 7 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 5 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 5 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** #### Outcome Measure 8 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** #### Outcome Measure 9 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 5 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 **Title:** #### Outcome Measure 10 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.0215 - **Upper Limit:** - **Value:** -0.001 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.0207 - **Upper Limit:** - **Value:** -0.015 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.1024 - **Upper Limit:** - **Value:** 0.033 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.0357 - **Upper Limit:** - **Value:** -0.005 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.0250 - **Upper Limit:** - **Value:** -0.531 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.1274 - **Upper Limit:** - **Value:** -0.140 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.8048 - **Upper Limit:** - **Value:** -0.392 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.1489 - **Upper Limit:** - **Value:** -0.127 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.6457 - **Upper Limit:** - **Value:** -0.218 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.3467 - **Upper Limit:** - **Value:** -0.347 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.5841 - **Upper Limit:** - **Value:** 0.085 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.3357 - **Upper Limit:** - **Value:** -0.245 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.2231 - **Upper Limit:** - **Value:** -0.097 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.3509 - **Upper Limit:** - **Value:** -0.365 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.1799 - **Upper Limit:** - **Value:** 0.001 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.3892 - **Upper Limit:** - **Value:** -0.111 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 2.6602 - **Upper Limit:** - **Value:** 0.946 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 2.4752 - **Upper Limit:** - **Value:** -0.083 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 3.5533 - **Upper Limit:** - **Value:** 1.657 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 3.3406 - **Upper Limit:** - **Value:** -0.606 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 59.64 - **Upper Limit:** - **Value:** 15.9 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 40.35 - **Upper Limit:** - **Value:** 7.3 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 55.81 - **Upper Limit:** - **Value:** 18.1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 54.14 - **Upper Limit:** - **Value:** -10.0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 3.483 - **Upper Limit:** - **Value:** 0.10 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 2.868 - **Upper Limit:** - **Value:** -0.95 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 3.572 - **Upper Limit:** - **Value:** 1.47 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 3.557 - **Upper Limit:** - **Value:** -1.11 **Title:** #### Outcome Measure 11 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 24.84 - **Upper Limit:** - **Value:** 5.4 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 28.90 - **Upper Limit:** - **Value:** 13.2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 22.69 - **Upper Limit:** - **Value:** 12.6 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 23.48 - **Upper Limit:** - **Value:** 6.3 **Title:** #### Outcome Measure 12 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.06625 - **Upper Limit:** - **Value:** 0.0216 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.09540 - **Upper Limit:** - **Value:** 0.0477 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.06813 - **Upper Limit:** - **Value:** 0.0434 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.07045 - **Upper Limit:** - **Value:** 0.0238 **Title:** #### Outcome Measure 13 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 2.173 - **Upper Limit:** - **Value:** -0.79 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 2.683 - **Upper Limit:** - **Value:** -1.37 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.516 - **Upper Limit:** - **Value:** -1.59 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 2.743 - **Upper Limit:** - **Value:** -1.93 **Title:** #### Outcome Measure 14 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 6.430 - **Upper Limit:** - **Value:** -1.73 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 8.198 - **Upper Limit:** - **Value:** -2.55 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 4.340 - **Upper Limit:** - **Value:** -3.58 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 7.041 - **Upper Limit:** - **Value:** -4.61 **Title:** #### Outcome Measure 15 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.6716 - **Upper Limit:** - **Value:** 0.298 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.8097 - **Upper Limit:** - **Value:** 0.645 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.7064 - **Upper Limit:** - **Value:** 0.635 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.5884 - **Upper Limit:** - **Value:** 0.468 **Title:** #### Outcome Measure 16 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 2.62 - **Upper Limit:** - **Value:** 4.1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 4.91 - **Upper Limit:** - **Value:** 2.9 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 3.00 - **Upper Limit:** - **Value:** 2.9 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 4.98 - **Upper Limit:** - **Value:** 1.8 **Title:** #### Outcome Measure 17 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 26.14 - **Upper Limit:** - **Value:** -16.0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 60.03 - **Upper Limit:** - **Value:** -5.0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 35.25 - **Upper Limit:** - **Value:** -17.5 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 80.63 - **Upper Limit:** - **Value:** 19.9 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 15.86 - **Upper Limit:** - **Value:** 1.0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 7.56 - **Upper Limit:** - **Value:** 5.1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 11.16 - **Upper Limit:** - **Value:** -2.5 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 5.80 - **Upper Limit:** - **Value:** 2.1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 7.91 - **Upper Limit:** - **Value:** 3.2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 4.04 - **Upper Limit:** - **Value:** 7.3 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 5.68 - **Upper Limit:** - **Value:** 3.3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 3.86 - **Upper Limit:** - **Value:** 9.3 **Title:** #### Outcome Measure 18 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.51 - **Upper Limit:** - **Value:** 0.6 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 3.06 - **Upper Limit:** - **Value:** -0.7 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.54 - **Upper Limit:** - **Value:** 0.9 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.30 - **Upper Limit:** - **Value:** 0.2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 6.50 - **Upper Limit:** - **Value:** 3.0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 5.22 - **Upper Limit:** - **Value:** 2.7 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 5.26 - **Upper Limit:** - **Value:** 2.9 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 3.38 - **Upper Limit:** - **Value:** 2.9 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 317.54 - **Upper Limit:** - **Value:** -471.1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 183.53 - **Upper Limit:** - **Value:** -571.3 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 310.54 - **Upper Limit:** - **Value:** -468.4 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 271.89 - **Upper Limit:** - **Value:** -609.8 **Title:** #### Outcome Measure 19 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.1344 - **Upper Limit:** - **Value:** 0.116 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.1942 - **Upper Limit:** - **Value:** 0.167 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.1013 - **Upper Limit:** - **Value:** 0.116 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.1386 - **Upper Limit:** - **Value:** 0.128 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 5.951 - **Upper Limit:** - **Value:** -3.73 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 3.449 - **Upper Limit:** - **Value:** 1.70 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 5.142 - **Upper Limit:** - **Value:** -2.68 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 3.588 - **Upper Limit:** - **Value:** 0.77 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 3.093 - **Upper Limit:** - **Value:** 0.20 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 2.003 - **Upper Limit:** - **Value:** -0.04 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 2.483 - **Upper Limit:** - **Value:** -0.32 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 4.107 - **Upper Limit:** - **Value:** 1.79 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.723 - **Upper Limit:** - **Value:** 0.06 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.923 - **Upper Limit:** - **Value:** -0.63 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.535 - **Upper Limit:** - **Value:** -0.02 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.877 - **Upper Limit:** - **Value:** -0.44 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 4.03 - **Upper Limit:** - **Value:** -0.6 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 5.01 - **Upper Limit:** - **Value:** 5.9 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 3.71 - **Upper Limit:** - **Value:** -0.7 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 4.71 - **Upper Limit:** - **Value:** 2.2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.3843 - **Upper Limit:** - **Value:** -0.225 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.5862 - **Upper Limit:** - **Value:** -0.913 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.4234 - **Upper Limit:** - **Value:** -0.227 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.5453 - **Upper Limit:** - **Value:** -0.726 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 12.164 - **Upper Limit:** - **Value:** -5.91 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 9.128 - **Upper Limit:** - **Value:** -9.47 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 14.967 - **Upper Limit:** - **Value:** -8.13 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 7.323 - **Upper Limit:** - **Value:** -9.01 **Title:** #### Outcome Measure 20 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 23.604 - **Upper Limit:** - **Value:** 42.80 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 10.731 - **Upper Limit:** - **Value:** 44.36 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 29.140 - **Upper Limit:** - **Value:** 42.33 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 15.176 - **Upper Limit:** - **Value:** 53.75 **Title:** #### Outcome Measure 21 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.2828 - **Upper Limit:** - **Value:** -0.500 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.6429 - **Upper Limit:** - **Value:** -0.433 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.0000 - **Upper Limit:** - **Value:** -0.300 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.5292 - **Upper Limit:** - **Value:** -0.500 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.184 - **Upper Limit:** - **Value:** -1.02 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.731 - **Upper Limit:** - **Value:** -2.40 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 3.595 - **Upper Limit:** - **Value:** 0.78 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.702 - **Upper Limit:** - **Value:** -2.13 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.0000 - **Upper Limit:** - **Value:** -0.100 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.3512 - **Upper Limit:** - **Value:** -0.133 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.0000 - **Upper Limit:** - **Value:** 0.0000 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.4933 - **Upper Limit:** - **Value:** -0.333 **Title:** #### Outcome Measure 22 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -88 - **Spread:** - **Upper Limit:** 320 - **Value:** -12.5 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 40 - **Spread:** - **Upper Limit:** 800 - **Value:** 177.8 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -67 - **Spread:** - **Upper Limit:** 340 - **Value:** 2.4 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** -80 - **Spread:** - **Upper Limit:** 44 - **Value:** -33.3 **Title:** #### Outcome Measure 23 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 16664.42 - **Upper Limit:** - **Value:** 37157.2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 18682.83 - **Upper Limit:** - **Value:** 38389.6 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 15744.17 - **Upper Limit:** - **Value:** 24220.8 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 17711.36 - **Upper Limit:** - **Value:** 11092.5 **Title:** #### Outcome Measure 24 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 5.94 - **Upper Limit:** - **Value:** 32.8 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 6.06 - **Upper Limit:** - **Value:** 19.0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 5.07 - **Upper Limit:** - **Value:** 32.0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 5.48 - **Upper Limit:** - **Value:** 38.8 **Title:** #### Outcome Measure 25 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 2910.9 - **Upper Limit:** - **Value:** 5470 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 3518.4 - **Upper Limit:** - **Value:** 2679 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 2836.7 - **Upper Limit:** - **Value:** 7110 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 3291.5 - **Upper Limit:** - **Value:** 6652 **Title:** #### Outcome Measure 26 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.776 - **Upper Limit:** - **Value:** 2.43 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.869 - **Upper Limit:** - **Value:** 1.14 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.713 - **Upper Limit:** - **Value:** 2.61 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.731 - **Upper Limit:** - **Value:** 3.41 **Title:** #### Outcome Measure 27 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 22998.02 - **Upper Limit:** - **Value:** 109279.5 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 26155.19 - **Upper Limit:** - **Value:** 78952.7 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 21898.24 - **Upper Limit:** - **Value:** 122304.7 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 24313.62 - **Upper Limit:** - **Value:** 75349.4 **Title:** #### Outcome Measure 28 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 2.29 - **Upper Limit:** - **Value:** 17.0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 2.58 - **Upper Limit:** - **Value:** 14.0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 2.15 - **Upper Limit:** - **Value:** 15.2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 2.33 - **Upper Limit:** - **Value:** 14.7 **Title:** #### Outcome Measure 29 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 8427.77 - **Upper Limit:** - **Value:** 23586.2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 9238.41 - **Upper Limit:** - **Value:** 24234.5 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 7676.99 - **Upper Limit:** - **Value:** 33038.7 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 9093.84 - **Upper Limit:** - **Value:** 27419.8 **Title:** #### Outcome Measure 30 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.12 - **Upper Limit:** - **Value:** 4.4 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.25 - **Upper Limit:** - **Value:** 4.6 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.01 - **Upper Limit:** - **Value:** 5.0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.04 - **Upper Limit:** - **Value:** 4.4 **Title:** #### Outcome Measure 31 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.832 - **Upper Limit:** - **Value:** 4.88 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.915 - **Upper Limit:** - **Value:** 3.33 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.779 - **Upper Limit:** - **Value:** 4.62 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.942 - **Upper Limit:** - **Value:** 3.61 **Title:** #### Outcome Measure 32 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0.4 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0.33 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0.6 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0.33 **Title:** #### Outcome Measure 33 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 35.24 - **Upper Limit:** - **Value:** 115.1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 38.20 - **Upper Limit:** - **Value:** 112.3 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 33.50 - **Upper Limit:** - **Value:** 135.4 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 33.37 - **Upper Limit:** - **Value:** 122.6 **Title:** #### Outcome Measure 34 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 6.119 - **Upper Limit:** - **Value:** 62.25 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 6.897 - **Upper Limit:** - **Value:** 49.33 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 5.732 - **Upper Limit:** - **Value:** 58.99 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 5.765 - **Upper Limit:** - **Value:** 56.29 **Title:** #### Outcome Measure 35 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.438 - **Upper Limit:** - **Value:** 5.71 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.713 - **Upper Limit:** - **Value:** 5.27 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** Naive B cell is cell that is not exposed to antigen. Naïve B cell count is CD20+CD27 concentration of cells (conc-cell)/cubic millimeter (cumm). Change from Baseline in naïve B cells was calculated as the value at Week 24 minus the value at Baseline. MITT Population consisted of all participants randomized to treatment, who have had taken at least one dose of study. Participants analyzed included those who had data at Week 24 for naïve B cells count (MITT Population). Baseline value used in the analysis was of Day 0 (Day of transplant). Adjusted mean differences (treatment-placebo) and 95% confidence intervals for differences were obtained from mixed-models repeated-measures (MMRM) model, with fixed categorical effects of treatment, visit, donor type and treatment-by-visit interaction and fixed continuous covariates of Baseline and Baseline-by-visit interaction. A compound symmetry variance structure was used to model the within-participant errors, shared across treatments. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** Modified Intent to treat (MITT) Population **Reporting Status:** POSTED **Time Frame:** Baseline and Week 24 **Title:** Change From Baseline in naïve B Cells From Baseline to Week 24 **Type:** PRIMARY **Unit of Measure:** cells/mm^3 ##### Group **Description:** Participants received normal saline (0.9% sodium chloride) via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) in addition to standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** OG000 **Title:** Placebo ##### Group **Description:** Participants received 10 milligram (mg) /kilogram (kg) belimumab in 250 milliliter (mL) normal saline via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** OG001 **Title:** Belimumab 10mg/kg #### Outcome Measure 2 **Description:** Number of participants with AEs, SAEs and AESI are summarized. The On-treatment (OT) phase started on the day and time of receiving the start of the first infusion and ended on the last dose date plus 28 days. The Post-treatment (PT) phase started 29 days after day of last dose up to 1 year. An AE is any untoward medical occurrence, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that at any dose results in, death, is life threatening, Requires hospitalization or prolongation of existing hospitalization, Results in disability/incapacity, Is a congenital anomaly/birth defect or event that but may jeopardize the subject or may require medical or surgical intervention to prevent one of the other outcomes listed. AESI included malignant neoplasms, infusion/anaphylaxis/hypersensitivity reactions, all infections, depression/suicide/self-injury, deaths. **Parameter Type:** NUMBER **Population Description:** mITT Population **Reporting Status:** POSTED **Time Frame:** Up to 1 year **Title:** Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESI) **Type:** PRIMARY **Unit of Measure:** Participants ##### Group **Description:** Participants received normal saline (0.9% sodium chloride) via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) in addition to standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** OG000 **Title:** Placebo ##### Group **Description:** Participants received 10 milligram (mg) /kilogram (kg) belimumab in 250 milliliter (mL) normal saline via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** OG001 **Title:** Belimumab 10mg/kg #### Outcome Measure 3 **Description:** All infections included: 1. Opportunistic infections per-clinical assessment, 2. Herpes Zoster, a. Recurrent, b. Disseminated, 3. Sepsis. Opportunistic infections were identified using list of preferred terms as per Medical Dictionary for Regulatory Activities (MedDRA) version 18.1. Any events falling under these preferred terms were adjudicated to determine if criteria was met for an opportunistic infection. **Parameter Type:** NUMBER **Population Description:** mITT Population **Reporting Status:** POSTED **Time Frame:** Up to 1 year **Title:** Number of Incidence of All Infections and Serious Infections **Type:** PRIMARY **Unit of Measure:** Infections ##### Group **Description:** Participants received normal saline (0.9% sodium chloride) via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) in addition to standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** OG000 **Title:** Placebo ##### Group **Description:** Participants received 10 milligram (mg) /kilogram (kg) belimumab in 250 milliliter (mL) normal saline via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** OG001 **Title:** Belimumab 10mg/kg #### Outcome Measure 4 **Description:** Change from Baseline in SBP and DBP were assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Change from Baseline was calculated as the value at Week 24 and Week 52 minus the value at Baseline. Baseline value used in the analysis was of Day 0 (Day of transplant). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** mITT Population **Reporting Status:** POSTED **Time Frame:** Baseline, Week 24 and Week 52 **Title:** Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 24 and Week 52 **Type:** PRIMARY **Unit of Measure:** millimeter of mercury (mmHg) ##### Group **Description:** Participants received normal saline (0.9% sodium chloride) via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) in addition to standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** OG000 **Title:** Placebo ##### Group **Description:** Participants received 10 milligram (mg) /kilogram (kg) belimumab in 250 milliliter (mL) normal saline via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** OG001 **Title:** Belimumab 10mg/kg #### Outcome Measure 5 **Description:** Change from Baseline in heart rate was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Change from Baseline was calculated as the value at Week 24 and Week 52 minus the value at Baseline. Baseline value used in the analysis was of Day 0 (Day of transplant). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** mITT Population **Reporting Status:** POSTED **Time Frame:** Baseline, Week 24 and Week 52 **Title:** Change From Baseline in Heart Rate From Baseline at Week 24 and Week 52 **Type:** PRIMARY **Unit of Measure:** Beats per minute (BPM) ##### Group **Description:** Participants received normal saline (0.9% sodium chloride) via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) in addition to standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** OG000 **Title:** Placebo ##### Group **Description:** Participants received 10 milligram (mg) /kilogram (kg) belimumab in 250 milliliter (mL) normal saline via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** OG001 **Title:** Belimumab 10mg/kg #### Outcome Measure 6 **Description:** Change from Baseline in body temperature was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Change from Baseline was calculated as the value at Week 24 and Week 52 minus the value at Baseline. Baseline value used in the analysis was of Day 0 (Day of transplant). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** mITT Population **Reporting Status:** POSTED **Time Frame:** Baseline, Week 24 and Week 52 **Title:** Change From Baseline in Body Temperature From Baseline at Week 24 and Week 52 **Type:** PRIMARY **Unit of Measure:** Degree Centigrade ##### Group **Description:** Participants received normal saline (0.9% sodium chloride) via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) in addition to standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** OG000 **Title:** Placebo ##### Group **Description:** Participants received 10 milligram (mg) /kilogram (kg) belimumab in 250 milliliter (mL) normal saline via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** OG001 **Title:** Belimumab 10mg/kg #### Outcome Measure 7 **Description:** Number of participants outside the normal range (NR) for SBP and DBP was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Number of participants outside the normal range are summarized by less than (\<) normal range and greater than (\>) normal range categories at Week 24 and Week 52. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). **Parameter Type:** NUMBER **Population Description:** mITT Population **Reporting Status:** POSTED **Time Frame:** Week 24 and Week 52 **Title:** Number of Participants Outside the Normal Range (NR) for SBP and DBP at Week 24 and Week 52 **Type:** PRIMARY **Unit of Measure:** Participants ##### Group **Description:** Participants received normal saline (0.9% sodium chloride) via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) in addition to standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** OG000 **Title:** Placebo ##### Group **Description:** Participants received 10 milligram (mg) /kilogram (kg) belimumab in 250 milliliter (mL) normal saline via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** OG001 **Title:** Belimumab 10mg/kg #### Outcome Measure 8 **Description:** Number of participants outside the normal range (NR) for heart rate was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Number of participants outside the normal range are summarized by less than (\<) normal range and greater than (\>) normal range categories at Week 24 and Week 52. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). **Parameter Type:** NUMBER **Population Description:** mITT Population **Reporting Status:** POSTED **Time Frame:** Week 24 and Week 52 **Title:** Number of Participants Outside the Normal Range (NR) for Heart Rate at Week 24 and Week 52 **Type:** PRIMARY **Unit of Measure:** Participants ##### Group **Description:** Participants received normal saline (0.9% sodium chloride) via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) in addition to standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** OG000 **Title:** Placebo ##### Group **Description:** Participants received 10 milligram (mg) /kilogram (kg) belimumab in 250 milliliter (mL) normal saline via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** OG001 **Title:** Belimumab 10mg/kg #### Outcome Measure 9 **Description:** Number of participants outside the normal range (NR) for body temperature was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Number of participants outside the normal range are summarized by less than (\<) normal range and greater than (\>) normal range categories at Week 24 and Week 52. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). **Parameter Type:** NUMBER **Population Description:** mITT Population **Reporting Status:** POSTED **Time Frame:** Week 24 and Week 52 **Title:** Number of Participants Outside the Normal Range (NR) for Body Temperature at Week 24 and Week 52 **Type:** PRIMARY **Unit of Measure:** Participants ##### Group **Description:** Participants received normal saline (0.9% sodium chloride) via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) in addition to standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** OG000 **Title:** Placebo ##### Group **Description:** Participants received 10 milligram (mg) /kilogram (kg) belimumab in 250 milliliter (mL) normal saline via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** OG001 **Title:** Belimumab 10mg/kg #### Outcome Measure 10 **Description:** Hematology parameters included: basophils (B), eosinophils (E), lymphocytes (L), monocytes (M), total neutrophils (N), platelet count (PC) and white blood cells (WBC). Change from Baseline in haematology parameter was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Change from Baseline was calculated as the value on Week 24 and Week 52 minus the value at Baseline. Baseline value used in the analysis was of Day 0 (Day of transplant). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** mITT Population **Reporting Status:** POSTED **Time Frame:** Baseline, Week 24 and Week 52 **Title:** Change From Baseline in the Indicated Hematology Parameters at Week 24 and Week 52 **Type:** PRIMARY **Unit of Measure:** Gills/Liter (GI/L) ##### Group **Description:** Participants received normal saline (0.9% sodium chloride) via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) in addition to standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** OG000 **Title:** Placebo ##### Group **Description:** Participants received 10 milligram (mg) /kilogram (kg) belimumab in 250 milliliter (mL) normal saline via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** OG001 **Title:** Belimumab 10mg/kg #### Outcome Measure 11 **Description:** Change from Baseline in hemoglobin was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Change from Baseline was calculated as the value on Week 24 and Week 52 minus the value at Baseline. Baseline value used in the analysis was of Day 0 (Day of transplant). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** mITT Population **Reporting Status:** POSTED **Time Frame:** Baseline, Week 24 and Week 52 **Title:** Change From Baseline in the Haematology Parameter- Hemoglobin at Week 24 and Week 52 **Type:** PRIMARY **Unit of Measure:** Grams per Liter (G/L) ##### Group **Description:** Participants received normal saline (0.9% sodium chloride) via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) in addition to standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** OG000 **Title:** Placebo ##### Group **Description:** Participants received 10 milligram (mg) /kilogram (kg) belimumab in 250 milliliter (mL) normal saline via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** OG001 **Title:** Belimumab 10mg/kg #### Outcome Measure 12 **Description:** Endpoint was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Change from Baseline was calculated as the value on Week 24 and Week 52 minus the value at Baseline. Baseline value used in the analysis was of Day 0 (Day of transplant). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** mITT Population **Reporting Status:** POSTED **Time Frame:** Baseline, Week 24 and Week 52 **Title:** Change From Baseline in the Hematology Parameter- Hematocrit at Week 24 and Week 52 **Type:** PRIMARY **Unit of Measure:** Percentage of blood ##### Group **Description:** Participants received normal saline (0.9% sodium chloride) via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) in addition to standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** OG000 **Title:** Placebo ##### Group **Description:** Participants received 10 milligram (mg) /kilogram (kg) belimumab in 250 milliliter (mL) normal saline via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** OG001 **Title:** Belimumab 10mg/kg #### Outcome Measure 13 **Description:** Change from Baseline in MCH was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Change from Baseline was calculated as the value on Week 24 and Week 52 minus the value at Baseline. Baseline value used in the analysis was of Day 0 (Day of transplant). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** mITT Population **Reporting Status:** POSTED **Time Frame:** Baseline, Week 24 and Week 52 **Title:** Change From Baseline in Haematology Parameter- Mean Corposcular Hemoglobin (MCH) at Week 24 and Week 52 **Type:** PRIMARY **Unit of Measure:** Picogram (pg) ##### Group **Description:** Participants received normal saline (0.9% sodium chloride) via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) in addition to standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** OG000 **Title:** Placebo ##### Group **Description:** Participants received 10 milligram (mg) /kilogram (kg) belimumab in 250 milliliter (mL) normal saline via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** OG001 **Title:** Belimumab 10mg/kg #### Outcome Measure 14 **Description:** Change from Baseline in MCV was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Change from Baseline was calculated as the value on Week 24 and Week 52 minus the value at Baseline. Baseline value used in the analysis was of Day 0 (Day of transplant). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** mITT Population **Reporting Status:** POSTED **Time Frame:** Baseline, Week 24 and Week 52 **Title:** Change From Baseline in Haematology Parameter- Mean Corposcular Volume (MCV) at Week 24 and Week 52 **Type:** PRIMARY **Unit of Measure:** Femtoliter (FL) ##### Group **Description:** Participants received normal saline (0.9% sodium chloride) via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) in addition to standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** OG000 **Title:** Placebo ##### Group **Description:** Participants received 10 milligram (mg) /kilogram (kg) belimumab in 250 milliliter (mL) normal saline via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** OG001 **Title:** Belimumab 10mg/kg #### Outcome Measure 15 **Description:** Change from Baseline in RBC was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Change from Baseline was calculated as the value on Week 24 and Week 52 minus the value at Baseline. Baseline value used in the analysis was of Day 0 (Day of transplant). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** mITT Population **Reporting Status:** POSTED **Time Frame:** Baseline, Week 24 and Week 52 **Title:** Change From Baseline in Haematology Parameter- Red Blood Cell (RBC) at Week 24 and Week 52 **Type:** PRIMARY **Unit of Measure:** Tera (TI)/L ##### Group **Description:** Participants received normal saline (0.9% sodium chloride) via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) in addition to standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** OG000 **Title:** Placebo ##### Group **Description:** Participants received 10 milligram (mg) /kilogram (kg) belimumab in 250 milliliter (mL) normal saline via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** OG001 **Title:** Belimumab 10mg/kg #### Outcome Measure 16 **Description:** Change from Baseline in albumin was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Change from Baseline was calculated as the value on Week 24 and Week 52 minus the value at Baseline. Baseline value used in the analysis was of Day 0 (Day of transplant). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** mITT Population **Reporting Status:** POSTED **Time Frame:** Baseline, Week 24 and Week 52 **Title:** Change From Baseline in Clinical Chemistry Parameter- Albumin at Week 24 and Week 52 **Type:** PRIMARY **Unit of Measure:** G/L ##### Group **Description:** Participants received normal saline (0.9% sodium chloride) via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) in addition to standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** OG000 **Title:** Placebo ##### Group **Description:** Participants received 10 milligram (mg) /kilogram (kg) belimumab in 250 milliliter (mL) normal saline via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** OG001 **Title:** Belimumab 10mg/kg #### Outcome Measure 17 **Description:** Clinical chemistry parameter included alkaline phosphatase (ALP), alanine amino Transferase (ALT) and aspartate amino transferase (AST). Endpoint was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Change from Baseline was calculated as the value on Week 24 and Week 52 minus the value at Baseline. Baseline value used in the analysis was of Day 0 (Day of transplant). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** mITT Population **Reporting Status:** POSTED **Time Frame:** Baseline, Week 24 and Week 52 **Title:** Change From Baseline in Clinical Chemistry Parameter- ALP, ALT, AST at Week 24 and Week 52 **Type:** PRIMARY **Unit of Measure:** International Unit (IU)/L ##### Group **Description:** Participants received normal saline (0.9% sodium chloride) via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) in addition to standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** OG000 **Title:** Placebo ##### Group **Description:** Participants received 10 milligram (mg) /kilogram (kg) belimumab in 250 milliliter (mL) normal saline via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** OG001 **Title:** Belimumab 10mg/kg #### Outcome Measure 18 **Description:** Clinical chemistry parameters included direct bilirubin (DB), total bilirubin (TB) and creatinine (C). Endpoint was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Change from Baseline was calculated as the value on Week 24 and Week 52 minus the value at Baseline. Baseline value used in the analysis was of Day 0 (Day of transplant). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** mITT Population **Reporting Status:** POSTED **Time Frame:** Baseline, Week 24 and Week 52 **Title:** Change From Baseline in Clinical Chemistry Parameter- Direct Bilirubin, Total Bilirubin and Creatinine at Week 24 and Week 52 **Type:** PRIMARY **Unit of Measure:** Micromole per Liter (umol/L) ##### Group **Description:** Participants received normal saline (0.9% sodium chloride) via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) in addition to standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** OG000 **Title:** Placebo ##### Group **Description:** Participants received 10 milligram (mg) /kilogram (kg) belimumab in 250 milliliter (mL) normal saline via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** OG001 **Title:** Belimumab 10mg/kg #### Outcome Measure 19 **Description:** Clinical chemistry parameters included calcium (Ca), carbon dioxide content/bicarbonate (CO2/Bicar), glucose (Gl), potassium (K), sodium (Na), phosphorus inorganic (PhI), urea/blood urine nitrogen (U/BUN). Endpoint was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Change from Baseline was calculated as the value on Week 24 and Week 52 minus the value at Baseline. Baseline value used in the analysis was of Day 0 (Day of transplant). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** mITT Population **Reporting Status:** POSTED **Time Frame:** Baseline, Week 24 and Week 52 **Title:** Change From Baseline in Clinical Chemistry Parameter- Ca, CO2/Bicar, Gl, K, Na, PhI, U/BUN at Week 24 and Week 52 **Type:** PRIMARY **Unit of Measure:** Millimole (MMOL)/L ##### Group **Description:** Participants received normal saline (0.9% sodium chloride) via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) in addition to standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** OG000 **Title:** Placebo ##### Group **Description:** Participants received 10 milligram (mg) /kilogram (kg) belimumab in 250 milliliter (mL) normal saline via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** OG001 **Title:** Belimumab 10mg/kg #### Outcome Measure 20 **Description:** Change from Baseline in GFR was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Change from Baseline was calculated as the value on Week 24 and Week 52 minus the value at Baseline. Baseline value used in the analysis was of Day 0 (Day of transplant). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** mITT Population **Reporting Status:** POSTED **Time Frame:** Baseline, Week 24 and Week 52 **Title:** Change From Baseline in Clinical Chemistry Parameter- Glomerular Filtration Rate (GFR) at Week 24 and Week 52 **Type:** PRIMARY **Unit of Measure:** milliliter (mL)/Minute (min) ##### Group **Description:** Participants received normal saline (0.9% sodium chloride) via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) in addition to standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** OG000 **Title:** Placebo ##### Group **Description:** Participants received 10 milligram (mg) /kilogram (kg) belimumab in 250 milliliter (mL) normal saline via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** OG001 **Title:** Belimumab 10mg/kg #### Outcome Measure 21 **Description:** Change from Baseline in immunoglobulins IgA, IgG and IgM was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Change from Baseline was calculated as the value on Week 24 and Week 52 minus the value at Baseline. Baseline value used in the analysis was of Day 0 (Day of transplant). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** mITT Population **Reporting Status:** POSTED **Time Frame:** Baseline, Week 24 and Week 52 **Title:** Change From Baseline in Immunoglobulin A (IgA), Immunoglobulin G (IgG) and Immunoglobulin M (IgM) at Week 24 and Week 52 **Type:** PRIMARY **Unit of Measure:** G/L ##### Group **Description:** Participants received normal saline (0.9% sodium chloride) via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) in addition to standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** OG000 **Title:** Placebo ##### Group **Description:** Participants received 10 milligram (mg) /kilogram (kg) belimumab in 250 milliliter (mL) normal saline via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** OG001 **Title:** Belimumab 10mg/kg #### Outcome Measure 22 **Description:** Memory B cells are B cell sub-type that are formed within germinal centres following primary infection and are important in generating an accelerated and more robust antibody-mediated immune response in the case of re-infection. Memory B cell count included CD20+CD27+ cells/mm\^3. Baseline value used in the analysis was of Day 0 (Day of transplant). Endpoint was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Percent change from Baseline in Memory B cell count was calculated as the value at Week 24 and Week 52 minus the value at Baseline multiplied by 100. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Median Difference and 95% confidence interval of difference obtained using the Hodges-Lehmann method. **Dispersion Type:** Full Range **Parameter Type:** MEDIAN **Population Description:** mITT Population **Reporting Status:** POSTED **Time Frame:** Baseline, Week 24 and Week 52 **Title:** Median Percent Change From Baseline in Memory B Cell Count at Week 24 and Week 52 **Type:** SECONDARY **Unit of Measure:** Percent change ##### Group **Description:** Participants received normal saline (0.9% sodium chloride) via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) in addition to standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** OG000 **Title:** Placebo ##### Group **Description:** Participants received 10 milligram (mg) /kilogram (kg) belimumab in 250 milliliter (mL) normal saline via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** OG001 **Title:** Belimumab 10mg/kg #### Outcome Measure 23 **Description:** Activated memory B cell-CD95% count is CD19+CD27+CD95 conc-cells/mL. Adjusted mean difference (treatment-placebo) and 95% confidence intervals for differences were obtained from MMRM model, with fixed categorical effects of treatment, visit, donor type and treatment-by-visit interaction and fixed continuous covariates of Baseline and Baseline-by-visit interaction. A compound symmetry variance structure was used to model the within-participant errors, shared across treatments. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** mITT Population **Reporting Status:** POSTED **Time Frame:** Week 24 and Week 52 **Title:** Activated Memory B Cells Count at Week 24 and Week 52 **Type:** SECONDARY **Unit of Measure:** cells/mL ##### Group **Description:** Participants received normal saline (0.9% sodium chloride) via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) in addition to standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** OG000 **Title:** Placebo ##### Group **Description:** Participants received 10 milligram (mg) /kilogram (kg) belimumab in 250 milliliter (mL) normal saline via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** OG001 **Title:** Belimumab 10mg/kg #### Outcome Measure 24 **Description:** Activated memory B cell-CD95% percentage is CD19+CD27+CD95+ (%CD19/CD27). Adjusted mean difference (treatment-placebo) and 95% confidence intervals for differences were obtained from MMRM model, with fixed categorical effects of treatment, visit, donor type and treatment-by-visit interaction and fixed continuous covariates of Baseline and Baseline-by-visit interaction. A compound symmetry variance structure was used to model the within-participant errors, shared across treatments. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** mITT Population **Reporting Status:** POSTED **Time Frame:** Week 24 and Week 52 **Title:** Activated Memory B Cells Percentage at Week 24 and Week 52 **Type:** SECONDARY **Unit of Measure:** Percentage of activated memory B cells ##### Group **Description:** Participants received normal saline (0.9% sodium chloride) via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) in addition to standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** OG000 **Title:** Placebo ##### Group **Description:** Participants received 10 milligram (mg) /kilogram (kg) belimumab in 250 milliliter (mL) normal saline via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** OG001 **Title:** Belimumab 10mg/kg #### Outcome Measure 25 **Description:** Transitional B cell count (Newell) is CD19+CD24b+CD38b+IgD+ (Conc-cells/mL). Adjusted mean difference (treatment-placebo) and 95% confidence intervals for differences were obtained from MMRM model, with fixed categorical effects of treatment, visit, donor type and treatment-by-visit interaction and fixed continuous covariates of Baseline and Baseline-by-visit interaction. A compound symmetry variance structure was used to model the within-participant errors, shared across treatments. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** mITT Population **Reporting Status:** POSTED **Time Frame:** Week 24 and Week 52 **Title:** Transitional B Cells Count at Week 24 and Week 52 **Type:** SECONDARY **Unit of Measure:** cells/mL ##### Group **Description:** Participants received normal saline (0.9% sodium chloride) via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) in addition to standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** OG000 **Title:** Placebo ##### Group **Description:** Participants received 10 milligram (mg) /kilogram (kg) belimumab in 250 milliliter (mL) normal saline via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** OG001 **Title:** Belimumab 10mg/kg #### Outcome Measure 26 **Description:** Transitional B cell percentage (Newell) is CD19+CD24b+CD38b+IgD+ (%CD19+). Adjusted mean difference (treatment-placebo) and 95% confidence intervals for differences were obtained from MMRM model, with fixed categorical effects of treatment, visit, donor type and treatment-by-visit interaction and fixed continuous covariates of Baseline and Baseline-by-visit interaction. A compound symmetry variance structure was used to model the within-participant errors, shared across treatments. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** mITT Population **Reporting Status:** POSTED **Time Frame:** Week 24 and Week 52 **Title:** Transitional B Cells Percentage at Week 24 and Week 52 **Type:** SECONDARY **Unit of Measure:** Percentage of transitional B cells ##### Group **Description:** Participants received normal saline (0.9% sodium chloride) via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) in addition to standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** OG000 **Title:** Placebo ##### Group **Description:** Participants received 10 milligram (mg) /kilogram (kg) belimumab in 250 milliliter (mL) normal saline via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** OG001 **Title:** Belimumab 10mg/kg #### Outcome Measure 27 **Description:** A T cell is a type of lymphocyte that plays a central role in cell-mediated immunity. Activated T cell count Codarri is CD4+ CD25hi CD45RA- IL 7Rhi (Conc-cells/mL). Adjusted mean difference (treatment-placebo) and 95% confidence intervals for differences were obtained from MMRM model, with fixed categorical effects of treatment, visit, donor type and treatment-by-visit interaction and fixed continuous covariates of Baseline and Baseline-by-visit interaction. A compound symmetry variance structure was used to model the within-participant errors, shared across treatments. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** mITT Population **Reporting Status:** POSTED **Time Frame:** Week 24 and Week 52 **Title:** Activated T Cell Count at Week 24 and Week 52 **Type:** SECONDARY **Unit of Measure:** cells/mL ##### Group **Description:** Participants received normal saline (0.9% sodium chloride) via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) in addition to standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** OG000 **Title:** Placebo ##### Group **Description:** Participants received 10 milligram (mg) /kilogram (kg) belimumab in 250 milliliter (mL) normal saline via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** OG001 **Title:** Belimumab 10mg/kg #### Outcome Measure 28 **Description:** Activated T cell percentage (Codarri)= CD4+ CD25hi CD45RA- IL 7Rhi (% of CD4+). Adjusted mean difference (treatment-placebo) and 95% confidence intervals for differences were obtained from MMRM model, with fixed categorical effects of treatment, visit, donor type and treatment-by-visit interaction and fixed continuous covariates of Baseline and Baseline-by-visit interaction. A compound symmetry variance structure was used to model the within-participant errors, shared across treatments. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** mITT Population **Reporting Status:** POSTED **Time Frame:** Week 24 and Week 52 **Title:** Activated T Cell Percentage at Week 24 and Week 52 **Type:** SECONDARY **Unit of Measure:** Percentage of activated T cell ##### Group **Description:** Participants received normal saline (0.9% sodium chloride) via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) in addition to standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** OG000 **Title:** Placebo ##### Group **Description:** Participants received 10 milligram (mg) /kilogram (kg) belimumab in 250 milliliter (mL) normal saline via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** OG001 **Title:** Belimumab 10mg/kg #### Outcome Measure 29 **Description:** Regulatory T cell count is CD4+ CD25hi IL-7Rlo (Conc-cells/mL). Adjusted mean difference (treatment-placebo) and 95% confidence intervals for differences were obtained from MMRM model, with fixed categorical effects of treatment, visit, donor type and treatment-by-visit interaction and fixed continuous covariates of Baseline and Baseline-by-visit interaction. A compound symmetry variance structure was used to model the within-participant errors, shared across treatments. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** mITT Population **Reporting Status:** POSTED **Time Frame:** Week 24 and Week 52 **Title:** Regulatory T Cell Count at Week 24 and Week 52 **Type:** SECONDARY **Unit of Measure:** cells/mL ##### Group **Description:** Participants received normal saline (0.9% sodium chloride) via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) in addition to standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** OG000 **Title:** Placebo ##### Group **Description:** Participants received 10 milligram (mg) /kilogram (kg) belimumab in 250 milliliter (mL) normal saline via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** OG001 **Title:** Belimumab 10mg/kg #### Outcome Measure 30 **Description:** Regulatory T cell (%CD4) = CD4+ CD25hi IL-7Rlo (% of CD4+). Adjusted mean difference (treatment-placebo) and 95% confidence intervals for differences were obtained from MMRM model, with fixed categorical effects of treatment, visit, donor type and treatment-by-visit interaction and fixed continuous covariates of Baseline and Baseline-by-visit interaction. A compound symmetry variance structure was used to model the within-participant errors, shared across treatments. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** mITT Population **Reporting Status:** POSTED **Time Frame:** Week 24 and Week 52 **Title:** Regulatory T Cell (%CD4) at Week 24 and Week 52 **Type:** SECONDARY **Unit of Measure:** Percentage of Regulatory T cell ##### Group **Description:** Participants received normal saline (0.9% sodium chloride) via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) in addition to standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** OG000 **Title:** Placebo ##### Group **Description:** Participants received 10 milligram (mg) /kilogram (kg) belimumab in 250 milliliter (mL) normal saline via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** OG001 **Title:** Belimumab 10mg/kg #### Outcome Measure 31 **Description:** Activated: regulatory T cell ratio is Activated T cell CD4+CD25hi CD45RA IL 7Rhi (absolute number)/ Regulatory T cell CD4+CD25hi CD45RA IL 7Rlo (absolute number). Adjusted mean difference (treatment-placebo) and 95% confidence intervals for differences were obtained from MMRM model, with fixed categorical effects of treatment, visit, donor type and treatment-by-visit interaction and fixed continuous covariates of Baseline and Baseline-by-visit interaction. A compound symmetry variance structure was used to model the within-participant errors, shared across treatments. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** mITT Population **Reporting Status:** POSTED **Time Frame:** Week 24 and Week 52 **Title:** Mean Activated: Regulatory T Cell Ratio at Week 24 and Week 52 **Type:** SECONDARY **Unit of Measure:** Ratio ##### Group **Description:** Participants received normal saline (0.9% sodium chloride) via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) in addition to standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** OG000 **Title:** Placebo ##### Group **Description:** Participants received 10 milligram (mg) /kilogram (kg) belimumab in 250 milliliter (mL) normal saline via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** OG001 **Title:** Belimumab 10mg/kg #### Outcome Measure 32 **Description:** The endpoint diagnosis was made by a proven biopsy result. Number of rejections only counted once per participant. The proportion of participants with episodes of acute rejection was assessed at Week 24 (at the end of therapy) and at Week 52 (at study end). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). **Parameter Type:** NUMBER **Population Description:** mITT Population. Participants analyzed had at least one biopsy. **Reporting Status:** POSTED **Time Frame:** Week 24 and Week 52 **Title:** Proportion of Participants With Episodes of Acute Rejection at Week 24 and Week 52 **Type:** SECONDARY **Unit of Measure:** Proportion of participants ##### Group **Description:** Participants received normal saline (0.9% sodium chloride) via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) in addition to standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** OG000 **Title:** Placebo ##### Group **Description:** Participants received 10 milligram (mg) /kilogram (kg) belimumab in 250 milliliter (mL) normal saline via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** OG001 **Title:** Belimumab 10mg/kg #### Outcome Measure 33 **Description:** Adjusted mean difference for serum creatinine values (treatment-placebo) and 95% confidence intervals for differences were obtained from MMRM model, with fixed categorical effects of treatment, visit, donor type and treatment-by-visit interaction and fixed continuous covariates of Baseline and Baseline-by-visit interaction, at Week 24 and Week 52. A compound symmetry variance structure was used to model the within-participant errors, shared across treatments. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** mITT Population **Reporting Status:** POSTED **Time Frame:** Week 24 and Week 52 **Title:** Mean Serum Creatinine at Week 24 and Week 52 **Type:** SECONDARY **Unit of Measure:** micromole/L ##### Group **Description:** Participants received normal saline (0.9% sodium chloride) via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) in addition to standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** OG000 **Title:** Placebo ##### Group **Description:** Participants received 10 milligram (mg) /kilogram (kg) belimumab in 250 milliliter (mL) normal saline via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** OG001 **Title:** Belimumab 10mg/kg #### Outcome Measure 34 **Description:** The estimated glomerular filtration rate (eGFR) were calculated by the abbreviated Modification of Diet in Renal Disease (MDRD) equation. Adjusted mean difference(treatment-placebo) and 95% confidence intervals for differences were obtained from MMRM model, with fixed categorical effects of treatment, visit, donor type and treatment-by-visit interaction and fixed continuous covariates of Baseline and Baseline-by-visit interaction at Week 24 and Week 52. A compound symmetry variance structure was used to model the within-participant errors, shared across treatments. Only those participants available at the indicated time points were analyzed (represented by n= X, X in the category titles). **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** mITT Population **Reporting Status:** POSTED **Time Frame:** Week 24 and Week 52 **Title:** Mean eGFR at Week 24 and Week 52 **Type:** SECONDARY **Unit of Measure:** mL/minute/1.73 square meter (m^2) ##### Group **Description:** Participants received normal saline (0.9% sodium chloride) via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) in addition to standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** OG000 **Title:** Placebo ##### Group **Description:** Participants received 10 milligram (mg) /kilogram (kg) belimumab in 250 milliliter (mL) normal saline via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** OG001 **Title:** Belimumab 10mg/kg #### Outcome Measure 35 **Description:** Adjusted mean difference (treatment-placebo) for Prednisolone use and 95% confidence intervals for differences were obtained from MMRM model, with fixed categorical effects of treatment, visit, donor type and treatment-by-visit interaction and fixed continuous covariates of Baseline and Baseline-by-visit interaction at Week 24. A compound symmetry variance structure was used to model the within-participant errors, shared across treatments Only those participants available at indicated timepoints were analyzed (represented by n=X, X in the category titles). **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** mITT Population **Reporting Status:** POSTED **Time Frame:** Week 24 **Title:** Mean Prednisolone Use at Week 24 **Type:** SECONDARY **Unit of Measure:** mg/day ##### Group **Description:** Participants received normal saline (0.9% sodium chloride) via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) in addition to standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** OG000 **Title:** Placebo ##### Group **Description:** Participants received 10 milligram (mg) /kilogram (kg) belimumab in 250 milliliter (mL) normal saline via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** OG001 **Title:** Belimumab 10mg/kg ### Participant Flow Module #### Group **Description:** Participants received normal saline (0.9% sodium chloride) via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) in addition to standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** FG000 **Title:** Placebo #### Group **Description:** Participants received 10 milligram (mg) /kilogram (kg) belimumab in 250 milliliter (mL) normal saline via intravenous infusion over 1 hour, every 4 weeks for 24 weeks (with an additional dose at week 2) standard of care assessments, treatment and other interventions according to institutional protocols from the time of transplantation throughout the study. **ID:** FG001 **Title:** Belimumab 10mg/kg #### Period **Title:** Overall Study ##### Withdraw **Type:** Adverse Event ###### Reason **Group ID:** FG000 **Number of Subjects:** 1 ###### Reason **Group ID:** FG001 **Number of Subjects:** 2 ##### Withdraw **Type:** Withdrawal by Subject ###### Reason **Group ID:** FG000 **Number of Subjects:** 1 ###### Reason **Group ID:** FG001 **Number of Subjects:** 1 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 13 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 12 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 11 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 9 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 2 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 3 **Pre-Assignment Details:** Participants were randomized to 1 of the 2 treatments groups in a 1:1 ratio and received standard of care in addition to investigational products (IPs). Participants received IP infusion on Day 0, Day 14, Day 28 and every 4 weeks thereafter for a total of 7 infusions. **Recruitment Details:** A total of 30 renal transplant recipients were enrolled, of which 28 were randomized and 25 were transplanted. **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT02256579 **Brief Title:** Utility of Urinary beta2 Microglobulin as an Early Marker of Renal Dysfunction in Vietnamese HIV-Infected Patients **Official Title:** Vietnam-Japan Cooperative Research on Prognosis of HIV-1-infection -Clinical Utility of Urinary beta2 Microglobulin as an Early Marker of Renal Dysfunction Caused by Use of Tenofovir in Vietnamese HIV-Infected Patients- #### Organization Study ID Info **ID:** NCGM-G-001074-01 #### Organization **Class:** OTHER_GOV **Full Name:** National Center for Global Health and Medicine, Japan ### Status Module #### Completion Date **Date:** 2017-03 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** ENROLLING_BY_INVITATION #### Last Update Post Date **Date:** 2014-10-03 **Type:** ESTIMATED **Last Update Submit Date:** 2014-10-01 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2016-11 **Type:** ESTIMATED #### Start Date **Date:** 2014-10 **Status Verified Date:** 2014-04 #### Study First Post Date **Date:** 2014-10-03 **Type:** ESTIMATED **Study First Submit Date:** 2014-10-01 **Study First Submit QC Date:** 2014-10-01 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER_GOV **Name:** National Center for Global Health and Medicine, Japan #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** This study is to investigate clinical utility of beta2 microglobulin as an early marker for renal dysfunction caused by Tenofovir in Vietnamese HIV-infected patients. **Detailed Description:** An observational study to investigate clinical utility of beta2 microglobulin as an early marker for renal dysfunction caused by Tenofovir in Vietnamese HIV-infected patients. ### Conditions Module **Conditions:** - HIV Infection - Renal Function Disorder - Renal Tubular Disorder **Keywords:** - TDF:Tenofovir, Urine beta2microglobulin ### Design Module #### Bio Spec **Description:** Complete blood cell count, CD4+ cell count, AST, ALT, Serum-creatinine, HIV-1 plasma viral loads, HBs antigen, anti-HBc antibody, anti-HBs antibody, anti-HCV antibody, Urine-protein, Urine-creatinine and urine beta2microglobulin. **Retention:** SAMPLES_WITHOUT_DNA #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 1800 **Type:** ESTIMATED **Study Type:** OBSERVATIONAL ### Outcomes Module #### Primary Outcomes **Description:** Follow up Vietnamese HIV-infected patients, for their renal function including urinary beta2microglobulin, urinary protein and serum creatinine for 3 years **Measure:** Evaluation of urinary beta2microglobulin, urinary protein and serum creatinine among Vietnamese HIV-infected patients **Time Frame:** 3 years #### Secondary Outcomes **Description:** Risk factors for renal and tubular dysfunction were evaluated. Risk factors including: Age, sex, body weight, history of ART, AIDS or non-AIDS complication and concomitant use of cotrimoxazole, Hepatitis C virus antibody and Hepatitis B virus Ag antigen, CD4 positive cell count and HIV viral load. **Measure:** Evaluation of risk factors for renal dysfunction and tubular dysfunction **Time Frame:** 3 years ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * HIV-infected patients in the NHTD -ACC cohort who are under cART or will start cART and can provide written informed consents. Exclusion Criteria: * HIV-infected patients who drop out of treatment within 6 months from the entry. **Minimum Age:** 20 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Vietnamese HIV-infected patients who are registered in the NHTD (National Hospital of Tropical Diseases) -ACC (AIDS Clinical Center, NCGM) cohort. ### Contacts Locations Module #### Overall Officials **Official 1:** **Affiliation:** National Center for Global Health and Medicine **Name:** Shinichi Oka, MD. PhD **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000091642 - Term: Urogenital Diseases - ID: D000007674 - Term: Kidney Diseases - ID: D000014570 - Term: Urologic Diseases - ID: D000052776 - Term: Female Urogenital Diseases - ID: D000005261 - Term: Female Urogenital Diseases and Pregnancy Complications - ID: D000052801 - Term: Male Urogenital Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC01 - Name: Infections - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: BXS - Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions - Abbrev: BC20 - Name: Immune System Diseases ### Condition Browse Module - Browse Leaves - ID: M10283 - Name: Infections - Relevance: HIGH - As Found: Infection - ID: M6368 - Name: Communicable Diseases - Relevance: LOW - As Found: Unknown - ID: M3522 - Name: Acquired Immunodeficiency Syndrome - Relevance: LOW - As Found: Unknown - ID: M18250 - Name: HIV Infections - Relevance: LOW - As Found: Unknown - ID: M26718 - Name: Renal Insufficiency - Relevance: HIGH - As Found: Renal Dysfunction - ID: M2875 - Name: Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M10698 - Name: Kidney Diseases - Relevance: LOW - As Found: Unknown - ID: M17319 - Name: Urologic Diseases - Relevance: LOW - As Found: Unknown - ID: M27093 - Name: Female Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M14127 - Name: Pregnancy Complications - Relevance: LOW - As Found: Unknown - ID: M8399 - Name: Female Urogenital Diseases and Pregnancy Complications - Relevance: LOW - As Found: Unknown - ID: M27095 - Name: Male Urogenital Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000007239 - Term: Infections - ID: D000051437 - Term: Renal Insufficiency ### Intervention Browse Module - Browse Branches - Abbrev: Infe - Name: Anti-Infective Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M296 - Name: Tenofovir - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03187379 **Brief Title:** Efficacy of Exparel (TM) on Post-operative Pain After Laparoscopic Gastric Bypass Using Circular EEA Stapler **Official Title:** Efficacy of Exparel (TM) on Post-operative Pain After Laparoscopic Gastric Bypass Using Circular EEA Stapler #### Organization Study ID Info **ID:** 16-1571 #### Organization **Class:** OTHER **Full Name:** The Cleveland Clinic ### Status Module #### Completion Date **Date:** 2021-02-01 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2022-06-21 **Type:** ACTUAL **Last Update Submit Date:** 2022-06-16 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2021-01-26 **Type:** ACTUAL #### Results First Post Date **Date:** 2022-06-21 **Type:** ACTUAL **Results First Submit Date:** 2022-04-27 **Results First Submit QC Date:** 2022-06-16 #### Start Date **Date:** 2017-06-01 **Type:** ACTUAL **Status Verified Date:** 2022-06 #### Study First Post Date **Date:** 2017-06-14 **Type:** ACTUAL **Study First Submit Date:** 2017-06-01 **Study First Submit QC Date:** 2017-06-12 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Matthew Kroh #### Responsible Party **Investigator Affiliation:** The Cleveland Clinic **Investigator Full Name:** Matthew Kroh **Investigator Title:** Principal investigator **Type:** SPONSOR_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** True **Is US Export:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** This will be a comparative study between two cohorts of patients undergoing Roux-en-Y Gastric bypass. One cohort (75 patients) will receive FDA approved Exparel® (liposome bupivacaine injection solution) injections intra-operatively at time of incision site closure. The control cohort (75 patients) will receive 0.25% bupivacaine injection solution at the time of incision site closure. The medication for the control group is our current standard of care. The primary end point is post-operative pain at 24 and 48 hours measured by the Visual Analog Scale (VAS). Comparison will be made between cohorts. All subjects enrolled in the study will be evaluated per nursing protocol with the verbal numerical analog scale. At 24 and 48 hours a member of the research team will administer a 2-part questionnaire containing the VAS and the Revised American Pain Society Post-Operative Questionnaire (APS-POQ-R). The latter is validated for assessment of the patient's experience of pain and it hindrance to daily activity in the post operative period. **Detailed Description:** The study will include up to 150 patients, and will consist of two cohort. The study cohort will include 75 patients who receive intraoperative Exparel® injections at the incision locations in addition to our standard multimodality post-operative analgesia. The control arm will include 75 patients who meet inclusion criteria but receive standard 0.25% bupivacaine and our standard multimodality post-operative analgesia. Patients will be randomized by REDCap™ database system in collaboration with Cleveland Clinic Pharmacy to receive either Exparel® or the control medication (0.25% Bupivacaine). Consent from patients will be obtained and documented by a dedicated research personnel prior to any enrollment. ### Conditions Module **Conditions:** - Post-operative Pain Management ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** SINGLE **Who Masked:** - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 102 **Type:** ACTUAL **Phases:** - PHASE4 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Subjects in this arm will receive Exparel® liposomal bupivacaine injected concurrently with 0.25% bupivacaine at the incisional sites prior to closing **Intervention Names:** - Drug: Exparel **Label:** Exparel, Liposomal Bupivacaine **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Subjects in this arm will receive 0.25% bupivacaine alone **Intervention Names:** - Drug: Bupivacaine **Label:** Control **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Exparel, Liposomal Bupivacaine **Description:** Exparel liposomal bupivacaine - 20cc Exparel® + 60cc Bupivicaine **Name:** Exparel **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Control **Description:** 60cc Bupivacaine **Name:** Bupivacaine **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Patient-reported pain levels, on a 0-100 Visual Analog Scale (VAS) with 0 representing less pain and 100 representing more pain. **Measure:** Post-Operative Pain **Time Frame:** 24 hours post-surgery #### Secondary Outcomes **Description:** Patient-reported pain levels, on a 0-100 Visual Analog Scale (VAS) with 0 representing less pain and 100 representing more pain. **Measure:** Post-Operative Pain **Time Frame:** 48 hours post-surgery ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * bariatric surgery patients * laparoscopic roux-en-y gastric bypass * use of EEA stapler anastomosis Exclusion Criteria: * age \<18 years * previous history of roux-en-y gastric bypass * patients undergoing other bariatric procedures * pre-operative opioid analgesics **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Cleveland **Country:** United States **Facility:** Cleveland Clinic **State:** Ohio **Zip:** 44195 #### Overall Officials **Official 1:** **Affiliation:** Staff **Name:** Alisan Fathalizadeh, M.D **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Document Section ### Large Document Module #### Large Docs - Date: 2020-03-23 - Filename: Prot_SAP_000.pdf - Has ICF: False - Has Protocol: True - Has SAP: True - Label: Study Protocol and Statistical Analysis Plan - Size: 1496210 - Type Abbrev: Prot_SAP - Upload Date: 2022-02-17T15:56 - Date: 2020-04-15 - Filename: ICF_001.pdf - Has ICF: True - Has Protocol: False - Has SAP: False - Label: Informed Consent Form - Size: 272624 - Type Abbrev: ICF - Upload Date: 2022-02-17T16:03 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000011183 - Term: Postoperative Complications - ID: D000010335 - Term: Pathologic Processes - ID: D000010146 - Term: Pain - ID: D000009461 - Term: Neurologic Manifestations ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC10 - Name: Nervous System Diseases ### Condition Browse Module - Browse Leaves - ID: M13069 - Name: Pain, Postoperative - Relevance: HIGH - As Found: Post Operative Pain - ID: M13066 - Name: Pain - Relevance: LOW - As Found: Unknown - ID: M14065 - Name: Postoperative Complications - Relevance: LOW - As Found: Unknown - ID: M12404 - Name: Neurologic Manifestations - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000010149 - Term: Pain, Postoperative ### Intervention Browse Module - Ancestors - ID: D000000779 - Term: Anesthetics, Local - ID: D000000777 - Term: Anesthetics - ID: D000002492 - Term: Central Nervous System Depressants - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000018689 - Term: Sensory System Agents - ID: D000018373 - Term: Peripheral Nervous System Agents ### Intervention Browse Module - Browse Branches - Abbrev: CNSDep - Name: Central Nervous System Depressants - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M5315 - Name: Bupivacaine - Relevance: HIGH - As Found: Following - ID: M4107 - Name: Anesthetics - Relevance: LOW - As Found: Unknown - ID: M4109 - Name: Anesthetics, Local - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000002045 - Term: Bupivacaine ### Misc Info Module #### Submission Tracking ##### First MCP Info ###### Post Date - Date: 2022-05-17 - Type: ACTUAL - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module #### Event Groups **Group ID:** EG000 **Title:** Exparel, Liposomal Bupivacaine **Deaths Num At Risk:** 50 **Description:** Subjects in this arm will receive Exparel® liposomal bupivacaine injected concurrently with 0.25% bupivacaine at the incisional sites prior to closing Exparel: Exparel liposomal bupivacaine - 20cc Exparel® + 60cc Bupivicaine **ID:** EG000 **Other Num Affected:** 14 **Other Num at Risk:** 50 **Serious Number Affected:** 10 **Serious Number At Risk:** 50 **Title:** Exparel, Liposomal Bupivacaine **Group ID:** EG001 **Title:** Control **Deaths Num At Risk:** 52 **Description:** Subjects in this arm will receive 0.25% bupivacaine alone Bupivacaine: 60cc Bupivacaine **ID:** EG001 **Other Num Affected:** 27 **Other Num at Risk:** 52 **Serious Number Affected:** 15 **Serious Number At Risk:** 52 **Title:** Control **Frequency Threshold:** 0 #### Other Events **Term:** Bleeding **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** **Term:** Abdominal Pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** **Term:** Diarrhea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** **Term:** Nausea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** **Term:** Vomiting **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** **Term:** Pain- Not otherwise Specified **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** **Term:** Cellulitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** **Term:** Wound Drainage **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** **Term:** Shortness of Breath **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** **Term:** Chest Pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** **Term:** Pelvic Pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** **Term:** Knee Pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** **Term:** Vaginal Bleed **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Reproductive system and breast disorders **Source Vocabulary:** **Term:** Leg Burn **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** **Term:** Left Ankle Pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** **Term:** Foot Pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** **Term:** Dehydration **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** **Term:** Dizziness **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** **Term:** Back Pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** **Term:** Abnormal labs **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** **Term:** Black Stool **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** **Term:** Headache **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** **Term:** Left Side Pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** **Term:** Swollen Leg **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** **Term:** Right Eye Complaint **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Eye disorders **Source Vocabulary:** **Term:** Infection- Not otherwise Specified **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** **Term:** Hip Pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** **Term:** Congestion **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** **Term:** Cough **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** #### Serious Events **Term:** Nausea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders ##### Stats **Group ID:** EG000 **Num Affected:** 3 **Num At Risk:** 50 **Num Events:** 3 **Group ID:** EG001 **Num Affected:** 3 **Num At Risk:** 52 **Num Events:** 3 **Term:** Vomiting **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders ##### Stats **Group ID:** EG000 **Num Affected:** 3 **Num At Risk:** 50 **Num Events:** 3 **Group ID:** EG001 **Num Affected:** 4 **Num At Risk:** 52 **Num Events:** 4 **Term:** Pneumonia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 50 **Num Events:** 1 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 52 **Num Events:** 1 **Term:** Small Bowel Obstruction **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 50 **Num Events:** 1 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 52 **Num Events:** 1 **Term:** Stroke **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 50 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 52 **Term:** Abdominal Pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 50 **Num Events:** 2 **Group ID:** EG001 **Num Affected:** 5 **Num At Risk:** 52 **Num Events:** 5 **Term:** Bleeding **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders ##### Stats **Group ID:** EG000 **Num At Risk:** 50 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 52 **Num Events:** 1 **Term:** Dehydration **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 50 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 52 **Term:** Ileus **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders ##### Stats **Group ID:** EG000 **Num At Risk:** 50 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 52 **Num Events:** 2 **Term:** Chest Pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 50 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 52 **Term:** Left Side Pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders ##### Stats **Group ID:** EG000 **Num At Risk:** 50 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 52 **Num Events:** 1 **Term:** Right Flank Pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders ##### Stats **Group ID:** EG000 **Num At Risk:** 50 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 52 **Num Events:** 1 **Term:** Chills **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders ##### Stats **Group ID:** EG000 **Num At Risk:** 50 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 52 **Num Events:** 1 **Term:** Fever **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders ##### Stats **Group ID:** EG000 **Num At Risk:** 50 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 52 **Num Events:** 1 **Term:** Abdominal Abscess **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations ##### Stats **Group ID:** EG000 **Num At Risk:** 50 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 52 **Num Events:** 1 **Term:** Wound Infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 50 **Num Events:** 1 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 52 **Num Events:** 1 **Term:** Post Operative Complications **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 50 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 52 **Term:** Shortness of Breath **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders ##### Stats **Group ID:** EG000 **Num At Risk:** 50 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 52 **Num Events:** 1 **Time Frame:** 1 year ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 50 **Group ID:** BG001 **Value:** 52 **Group ID:** BG002 **Value:** 102 **Units:** Participants ### Group **ID:** BG000 **Title:** Exparel, Liposomal Bupivacaine **Description:** Subjects in this arm will receive Exparel® liposomal bupivacaine injected concurrently with 0.25% bupivacaine at the incisional sites prior to closing Exparel: Exparel liposomal bupivacaine - 20cc Exparel® + 60cc Bupivicaine ### Group **ID:** BG001 **Title:** Control **Description:** Subjects in this arm will receive 0.25% bupivacaine alone Bupivacaine: 60cc Bupivacaine ### Group **ID:** BG002 **Title:** Total **Description:** Total of all reporting groups ### Measure #### Measurement **Group ID:** BG000 **Lower Limit:** 37.1 **Upper Limit:** 56.2 **Value:** 48.4 #### Measurement **Group ID:** BG001 **Lower Limit:** 36.3 **Upper Limit:** 52.2 **Value:** 41.2 #### Measurement **Group ID:** BG002 **Lower Limit:** 36.7 **Upper Limit:** 55.3 **Value:** 44.6 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 50 **Group ID:** BG001 **Value:** 52 **Group ID:** BG002 **Value:** 102 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 40 #### Measurement **Group ID:** BG001 **Value:** 42 #### Measurement **Group ID:** BG002 **Value:** 82 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 10 #### Measurement **Group ID:** BG001 **Value:** 10 #### Measurement **Group ID:** BG002 **Value:** 20 **Category Title:** Male #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 50 **Group ID:** BG001 **Value:** 52 **Group ID:** BG002 **Value:** 102 **Class Title:** ### Measure #### Measurement **Group ID:** BG002 **Value:** 0 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 0 **Group ID:** BG001 **Value:** 0 **Group ID:** BG002 **Value:** 0 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 50 #### Measurement **Group ID:** BG001 **Value:** 52 #### Measurement **Group ID:** BG002 **Value:** 102 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 50 **Group ID:** BG001 **Value:** 52 **Group ID:** BG002 **Value:** 102 **Class Title:** United States **Denomination Units Selected:** ## Results Section - Baseline Characteristics Module ### Measure 1 **Dispersion Type:** INTER_QUARTILE_RANGE **Parameter Type:** MEDIAN **Title:** Age, Continuous **Unit of Measure:** Years ### Measure 2 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Sex: Female, Male **Unit of Measure:** Participants ### Measure 3 **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Race and Ethnicity were not collected from any participant. **Title:** Race and Ethnicity Not Collected **Unit of Measure:** Participants ### Measure 4 **Parameter Type:** NUMBER **Title:** Region of Enrollment **Unit of Measure:** participants ## Results Section - More Information Module ### Certain Agreement **PI Sponsor Employee:** True ### Point of Contact **Email:** [email protected] **Organization:** Cleveland Clinic Foundation **Phone:** 12164457410 **Title:** Dr. Matthew Kroh ## Results Section - Outcome Measures Module ### Outcome Measure 1 ### Outcome Measure 2 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 29 - **Upper Limit:** - **Value:** 49.4 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 26.4 - **Upper Limit:** - **Value:** 56.6 **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 30 - **Upper Limit:** - **Value:** 42.2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 31.4 - **Upper Limit:** - **Value:** 51.5 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** Patient-reported pain levels, on a 0-100 Visual Analog Scale (VAS) with 0 representing less pain and 100 representing more pain. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Reporting Status:** POSTED **Time Frame:** 24 hours post-surgery **Title:** Post-Operative Pain **Type:** PRIMARY **Unit of Measure:** units on a Visual Analog Scale (VAS) ##### Group **Description:** Subjects in this arm will receive Exparel® liposomal bupivacaine injected concurrently with 0.25% bupivacaine at the incisional sites prior to closing Exparel: Exparel liposomal bupivacaine - 20cc Exparel® + 60cc Bupivicaine **ID:** OG000 **Title:** Exparel, Liposomal Bupivacaine ##### Group **Description:** Subjects in this arm will receive 0.25% bupivacaine alone Bupivacaine: 60cc Bupivacaine **ID:** OG001 **Title:** Control #### Outcome Measure 2 **Description:** Patient-reported pain levels, on a 0-100 Visual Analog Scale (VAS) with 0 representing less pain and 100 representing more pain. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Reporting Status:** POSTED **Time Frame:** 48 hours post-surgery **Title:** Post-Operative Pain **Type:** SECONDARY **Unit of Measure:** units on a Visual Analog Scale (VAS) ##### Group **Description:** Subjects in this arm will receive Exparel® liposomal bupivacaine injected concurrently with 0.25% bupivacaine at the incisional sites prior to closing Exparel: Exparel liposomal bupivacaine - 20cc Exparel® + 60cc Bupivicaine **ID:** OG000 **Title:** Exparel, Liposomal Bupivacaine ##### Group **Description:** Subjects in this arm will receive 0.25% bupivacaine alone Bupivacaine: 60cc Bupivacaine **ID:** OG001 **Title:** Control ### Participant Flow Module #### Group **Description:** Subjects in this arm will receive Exparel® liposomal bupivacaine injected concurrently with 0.25% bupivacaine at the incisional sites prior to closing Exparel: Exparel liposomal bupivacaine - 20cc Exparel® + 60cc Bupivicaine **ID:** FG000 **Title:** Exparel, Liposomal Bupivacaine #### Group **Description:** Subjects in this arm will receive 0.25% bupivacaine alone Bupivacaine: 60cc Bupivacaine **ID:** FG001 **Title:** Control #### Period **Title:** Overall Study ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 50 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 52 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 50 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 52 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 0 **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT06142279 **Acronym:** MUCOVID **Brief Title:** Development and Qualification of Methods for Analyzing the Mucosal Immune Response to COVID-19 **Official Title:** Development and Qualification of Methods for Analyzing the Mucosal Immune Response to COVID-19 #### Organization Study ID Info **ID:** DR230062-MUCOVID #### Organization **Class:** OTHER **Full Name:** University Hospital, Tours ### Status Module #### Completion Date **Date:** 2024-11 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2023-11-21 **Type:** ACTUAL **Last Update Submit Date:** 2023-11-17 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2024-11 **Type:** ESTIMATED #### Start Date **Date:** 2023-11 **Type:** ESTIMATED **Status Verified Date:** 2023-11 #### Study First Post Date **Date:** 2023-11-21 **Type:** ACTUAL **Study First Submit Date:** 2023-11-14 **Study First Submit QC Date:** 2023-11-17 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** University Hospital, Tours #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** The pandemic associated with the SARS-CoV-2 coronavirus has affected over 760 million individuals worldwide, resulting in more than 6.9 million deaths. France has also been heavily impacted, with over 39.8 million infections and 167,000 deaths. SARS-CoV-2 primarily causes an upper respiratory tract infection transmitted through the air. When it reaches the lungs, it leads to a severe acute respiratory illness called COVID-19. The body's response to this viral assault primarily occurs at the level of the respiratory mucosa. This mucosal response is complex, involving various levels of activity. Mucosal immunity is therefore essential for an adequate and long-term immune response against viral respiratory infections, including SARS-CoV-2 infection. Infection with SARS-CoV-2 triggers a humoral immune response with the production of antibodies in the blood (serum antibodies) and antibodies in the upper respiratory tract (mucosal antibodies). It also induces a cellular immune response by activating specific blood T lymphocytes. Tests used to measure the humoral blood response against SARS-CoV-2 and their neutralizing capacity are now well identified, as are tests for assessing the serum cellular T lymphocyte response. However, tests for measuring mucosal immune responses are not routinely used. Our study aims to develop and qualify methods for analyzing mucosal immunity directed against SARS-CoV-2. These methods will be essential for a more precise analysis of the body's mucosal response to this virus. Once these analytical methods are validated, they will enable the study of mucosal responses to infection, as well as mucosal responses induced by vaccination against SARS-CoV-2, particularly in the context of future nasal vaccine use. **Detailed Description:** SARS-CoV-2 is initially responsible for an airborne infection of the upper respiratory tract which, on reaching the lungs, causes a severe acute respiratory illness known as COVID-19. The organism's response to this viral aggression is initially directed at the respiratory mucosa. This mucosal response is complex, with different levels of activity interacting: mechanical activity, with the secretion of mucus that acts as a barrier to the infectious agent; physico-chemical activity, with the production of enzymes and cytokines that contribute to the degradation of viral particles; and specific humoral immune activity, with the production of secretory IgA-type immunoglobulins at the mucosal level, with neutralizing activity that blocks viral entry into the host cell. These innate and adaptive immune mechanisms, together with their humoral and cellular components, play an essential role in mucosal barrier function. Mucosal immunity is therefore essential for an adequate, early and long-term immune response against respiratory viral infections. SARS-CoV-2 is an enveloped virus with a helical capsid and a genome consisting of approximately 30,000 nucleotides. This genome codes for several proteins essential for virion formation, including the S protein for Spike and the N protein for nucleocapsid. The viral S protein binds to the host cell's angiotensin-converting enzyme 2 (ACE2). ACE2 thus acts as a viral receptor mediating viral entry into the cell and the triggering an immune response in the host. This protein S is the main target of the neutralizing antibody response. Mutations in protein S have been responsible for the emergence of variants of SARS-CoV-2 with different phenotypes affecting transmission and susceptibility to antibody. The N protein is a highly immunogenic glycoprotein also involved in viral replication and in the modulation of cellular signalling pathways. During virion assembly virion, the N protein binds to viral RNA and leads to the formation of the helical nucleocapsid. This N protein is highly conserved in all SARS-CoV-2 variants and may therefore be an interesting target in the universal defense against this virus. In the event of a respiratory infection, stimulation of the mucosal immune system triggers on the one hand, a humoral response with the release of secretory immunoglobulins, mainly secretory IgA. The main role of IgA is to prevent the virus from spreading throughout the body. On the other hand, respiratory infection will also trigger a mucosal cellular response primarily mediated by T lymphocytes. Infection with SARS-CoV-2 triggers an immune response involving antibody production in the blood (serum antibodies), stimulation of blood lymphocytes and antibody production in the upper respiratory tract (mucosal antibodies). The quantitative anti-SARS-CoV-2 humoral response in the blood (serum antibodies) has been assessed by various tests. For the time being, however, it relies mainly on EIA-type tests, with blood levels of anti-S IgG (directed against the Spike protein) and anti-N IgG (directed against the nucleocapsid protein). Qualitative analysis of this response is based on the ability of these antibodies to have neutralizing activity (neutralizing antibodies). The anti-SARS-CoV-2 T lymphocyte cellular response also appears to be important in controlling infection. The most rapid test for assessing this T lymphocyte response is the ELISPOT IFN-γ As for the mucosal humoral response, several studies have documented the presence of virus-specific anti-S IgA antibodies (directed against the Spike protein) in the nasopharyngeal secretions or saliva of infected individuals. To date, there is no routinely-used test for measuring mucosal antibodies to SARS-CoV-2, notably secretory anti-S IgA, and to analyze their neutralizing activity. Our study will thus enable us to develop and qualify methods for analyzing mucosal immunity to SARS-CoV-2. These methods will be essential for analyzing mucosal response to this virus. Once these analytical methods have been validated, they will make it possible to study the mucosal response to infection but also the mucosal response induced by vaccination against SARS-CoV-2, particularly when using nasal vaccines. Indeed, the vaccines currently used to combat SARS-CoV-2 induce serum neutralizing activity against protein S (Spike). Their intramuscular route of administration will induce systemic immunity, providing protection against severe forms of the infection. Nevertheless, mucosal immunity induced by current vaccines remains low. The development of a nasally-administered vaccine is an interesting avenue, as it would provide more complete protection, notably by controlling virus replication in the upper respiratory tract, thus inducing upper respiratory tract, thereby inducing herd immunity and reducing transmission of the virus. ### Conditions Module **Conditions:** - Certain Disorders Involving the Immune Mechanism ### Design Module #### Design Info **Allocation:** NON_RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** Multicenter cross-sectional study comparing short-term mucosal response in individuals recently infected with SARS-CoV-2 versus recently non-infected individuals. The study will consist of two parts: 1. Part A, which focuses on developing the technique, involves prospective data collection and the collection of biological samples (nasal, salivary, and blood samples). 2. Part B, which aims to qualify the analysis method, also includes prospective data collection and the collection of biological samples. Once the threshold is reached in one of the two groups in Phase A, Phase B will begin concurrently. ##### Masking Info **Masking:** NONE **Primary Purpose:** HEALTH_SERVICES_RESEARCH #### Enrollment Info **Count:** 240 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** participant with a positive SARS-CoV-2 PCR test **Intervention Names:** - Biological: Sampling - Biological: PCR (polymerase chain reaction) SARS-CoV-2 **Label:** COVID + **Type:** OTHER #### Arm Group 2 **Description:** participant with a negative SARS-CoV-2 PCR test **Intervention Names:** - Biological: Sampling - Biological: PCR (polymerase chain reaction) SARS-CoV-2 **Label:** COVID - **Type:** OTHER ### Interventions #### Intervention 1 **Arm Group Labels:** - COVID + - COVID - **Description:** At baseline, nasal, salivary and blood sampling will be taken for the participants. **Name:** Sampling **Type:** BIOLOGICAL #### Intervention 2 **Arm Group Labels:** - COVID + - COVID - **Description:** At baseline, this PCR SARS-CoV-2 will be taken for the participants. **Name:** PCR (polymerase chain reaction) SARS-CoV-2 **Type:** BIOLOGICAL ### Outcomes Module #### Primary Outcomes **Description:** The level of secretory IgA (immunoglobulin A) in nasal secretions, expressed in picograms per milliliter equivalent. **Measure:** To study the anti-Spike mucosal humoral immune response by measuring secretory IgA in nasal secretions **Time Frame:** Baseline - Day 0 **Description:** The neutralizing capacity of secretory nasal IgA assessed in neutralization titer (PRNT 50). **Measure:** Analysis of the neutralizing capacity of anti-Spike IgA in nasal secretions **Time Frame:** Baseline - Day 0 #### Secondary Outcomes **Description:** Secretory IgA levels in saliva expressed in picograms per milliliter Eq **Measure:** Determination of secretory anti-Spike IgA in salivary secretions **Time Frame:** Baseline - Day 0 **Description:** Salivary IgA neutralizing capacity assessed by neutralizing titer (PRNT 50) **Measure:** Analysis of the neutralizing capacity of anti-Spike IgA in salivary secretions **Time Frame:** Baseline - Day 0 **Description:** Blood anti-S IgG (immunoglobulin G) levels expressed in Binding Antibody Units per milliliter (BAU/ml) **Measure:** Determination of serum anti-Spike IgG **Time Frame:** Baseline - Day 0 **Description:** Blood IgG neutralizing capacity assessed by neutralizing titer (PRNT 50) **Measure:** Analysis of the neutralizing capacity of serum anti-Spike IgG **Time Frame:** Baseline - Day 0 **Description:** Blood anti-N IgG levels expressed as an index **Measure:** Assay serum anti-N IgG **Time Frame:** Baseline - Day 0 **Description:** T-cell reactivity expressed in the number of Spot Forming Units per 106 Peripheral Blood Mononuclear Cells (SFU: Spot Forming Unit) **Measure:** Study the systemic cellular immune response by measuring interferon-gamma production **Time Frame:** Baseline - Day 0 ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * ≥18 years old * Participant affiliated with a social security scheme * Participant willing to take part in the study and having provided consent * Participant in good health or with a stable chronic condition for more than 6 months Exclusion Criteria: * Contraindication for nasopharyngeal sampling * Pregnant or breastfeeding women * Participants benefiting from a legal protection measure as referred to in articles L1121-5 to L1121-8 of the Public Health Code (guardianship, trusteeship, etc.) * Participant with an acute condition unrelated to SARS-CoV-2 infection * Participant with an unstable chronic condition **Healthy Volunteers:** True **Maximum Age:** 100 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Zoha MAAKAROUN-VERMESSE, MD-PHD **Phone:** 0247476972 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Valérie Gissot, MD-PHD **Phone:** 0247476972 **Role:** CONTACT #### Locations **Location 1:** **City:** Tours **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Zoha MAAKAROUN-VERMESSE, MD-PHD - **Phone:** 0247476972 - **Phone Ext:** Investigator - **Role:** CONTACT **Country:** France **Facility:** CHRU de Tours **Zip:** 37044 #### Overall Officials **Official 1:** **Affiliation:** CHRU de TOURS **Name:** Zoha MAAKAROUN-VERMESSE, MD-PHD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Haute autorité de santé. Aspect immunologiques et virologiques de l'infection par le SARS-CoV-2 ; Rapport HAS 25 Novembre 2020 **Citation:** Alu A, Chen L, Lei H, Wei Y, Tian X, Wei X. Intranasal COVID-19 vaccines: From bench to bed. EBioMedicine. 2022 Feb;76:103841. doi: 10.1016/j.ebiom.2022.103841. Epub 2022 Jan 24. **PMID:** 35085851 **Citation:** Y. Jouan · M. Si-Tahar · A. Guillon. Immunité de la muqueuse respiratoire : physiologie et implications en réanimation. Méd. Intensive Réa 2017 ; 26 :11-20 **Citation:** Smith N, Goncalves P, Charbit B, Grzelak L, Beretta M, Planchais C, Bruel T, Rouilly V, Bondet V, Hadjadj J, Yatim N, Pere H, Merkling SH, Ghozlane A, Kerneis S, Rieux-Laucat F, Terrier B, Schwartz O, Mouquet H, Duffy D, Di Santo JP. Distinct systemic and mucosal immune responses during acute SARS-CoV-2 infection. Nat Immunol. 2021 Nov;22(11):1428-1439. doi: 10.1038/s41590-021-01028-7. Epub 2021 Sep 1. **PMID:** 34471264 **Citation:** Chavda VP, Vora LK, Pandya AK, Patravale VB. Intranasal vaccines for SARS-CoV-2: From challenges to potential in COVID-19 management. Drug Discov Today. 2021 Nov;26(11):2619-2636. doi: 10.1016/j.drudis.2021.07.021. Epub 2021 Jul 29. **PMID:** 34332100 **Citation:** Denis F, Alain S, Hantz S, Lagrange P. [Antiviral vaccination and respiratory mucosal immunity: still disappointing results from a seductive idea]. Presse Med. 2005 Oct 8;34(17):1245-53. doi: 10.1016/s0755-4982(05)84165-x. French. **PMID:** 16230967 **Citation:** Russell MW, Mestecky J. Mucosal immunity: The missing link in comprehending SARS-CoV-2 infection and transmission. Front Immunol. 2022 Aug 17;13:957107. doi: 10.3389/fimmu.2022.957107. eCollection 2022. **PMID:** 36059541 **Citation:** Tang J, Zeng C, Cox TM, Li C, Son YM, Cheon IS, Wu Y, Behl S, Taylor JJ, Chakaraborty R, Johnson AJ, Shiavo DN, Utz JP, Reisenauer JS, Midthun DE, Mullon JJ, Edell ES, Alameh MG, Borish L, Teague WG, Kaplan MH, Weissman D, Kern R, Hu H, Vassallo R, Liu SL, Sun J. Respiratory mucosal immunity against SARS-CoV-2 after mRNA vaccination. Sci Immunol. 2022 Oct 28;7(76):eadd4853. doi: 10.1126/sciimmunol.add4853. Epub 2022 Oct 21. **PMID:** 35857583 **Citation:** Yaugel-Novoa M, Bourlet T, Paul S. Role of the humoral immune response during COVID-19: guilty or not guilty? Mucosal Immunol. 2022 Jun;15(6):1170-1180. doi: 10.1038/s41385-022-00569-w. Epub 2022 Oct 4. **PMID:** 36195658 ## Derived Section ### Condition Browse Module - Browse Branches - Abbrev: BC01 - Name: Infections - Abbrev: BC08 - Name: Respiratory Tract (Lung and Bronchial) Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC20 - Name: Immune System Diseases ### Condition Browse Module - Browse Leaves - ID: M2561 - Name: COVID-19 - Relevance: LOW - As Found: Unknown - ID: M10200 - Name: Immune System Diseases - Relevance: HIGH - As Found: Disorders Involving the Immune Mechanism ### Condition Browse Module - Meshes - ID: D000007154 - Term: Immune System Diseases ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT02157779 **Acronym:** TOTRA **Brief Title:** Treatment of Trauma-Related Anger in OEF/OIF/OND Veterans **Official Title:** Treatment of Trauma-Related Anger in OEF/OIF/OND Veterans #### Organization Study ID Info **ID:** D1146-R #### Organization **Class:** FED **Full Name:** VA Office of Research and Development #### Secondary ID Infos **Domain:** VA RR&D **ID:** Rx 001146 **Type:** OTHER_GRANT ### Status Module #### Completion Date **Date:** 2019-02-28 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2021-11-18 **Type:** ACTUAL **Last Update Submit Date:** 2021-10-20 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2019-02-28 **Type:** ACTUAL #### Results First Post Date **Date:** 2020-03-16 **Type:** ACTUAL **Results First Submit Date:** 2020-02-26 **Results First Submit QC Date:** 2020-02-26 #### Start Date **Date:** 2015-01-01 **Type:** ACTUAL **Status Verified Date:** 2021-10 #### Study First Post Date **Date:** 2014-06-06 **Type:** ESTIMATED **Study First Submit Date:** 2014-05-06 **Study First Submit QC Date:** 2014-06-03 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** FED **Name:** VA Office of Research and Development #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Is US Export:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Excessive and poorly controlled anger is one of the most common problems experienced by war Veterans. The consequences can be severe, including increased risk for divorce, domestic violence, job loss and instability, and other serious impairments in family, social, and occupational functioning. Availability of effective treatments is critical to reducing the adverse effects of anger in Veterans. The investigators propose to conduct a controlled study to determine whether a cognitive behavior treatment that has been adapted for treating anger problems in Veterans of Iraq and Afghanistan results in improved outcomes compared to a supportive therapy. Results will be examined for improvement in anger, functioning, and quality of life at end of 12 weekly sessions, and at 3 and 6 months following treatment. **Detailed Description:** Poorly controlled anger is a common problem with often devastating effects in Veterans who have served in a warzone. Adverse consequences include increased risk for divorce, domestic violence, job loss and instability, and other serious impairments in family, social, and occupational functioning. Recent evidence indicates that anger and aggression are likely to be problems for a significant proportion of Veterans of Iraq (Operation Iraqi Freedom, OIF; Operation New Dawn, OND) and Afghanistan (Operation Enduring Freedom, OEF). A survey of reintegration problems among 754 OEF/OIF combat Veterans receiving VA Medical care showed that anger was the most commonly reported problem, with 57% reporting increased problems in controlling anger. Despite encouraging evidence for efficacy of cognitive behavioral interventions in treating anger in civilian samples, much less is known about the efficacy of such treatments for anger problems in military personnel following exposure to war zone trauma. Promising preliminary findings for individually based cognitive behavioral treatment have been reported, and there is evidence that a group anger management treatment delivered by teleconferencing is as effective as the same treatment delivered in person, but to date there is not a single adequately powered randomized trial designed to test the efficacy of an anger treatment compared to an active control condition in Veterans. Building on findings from the investigators' randomized pilot study, the objective of the current proposal is to conduct a randomized clinical trial with sufficient statistical power to test the effectiveness of a manualized cognitive behavioral intervention (CBI) that has been adapted from an existing treatment (Anger Control Therapy; Novaco, 1994, 2001) for the treatment of anger problems in OEF/OIF/OND Veterans, compared to a manualized supportive therapy intervention (SI) control condition. Ninety OEF/OIF/OND Veterans reporting significant problems with anger will be randomized to receive 12 individual sessions of one of the two study conditions. Outcomes including measures of anger and aggression; interpersonal, social and occupational functioning; and quality of life will be assessed during and at the end of treatment and at 3 and 6 month follow-ups. Exploratory analyses will examine 1) whether a diagnosis of PTSD impacts treatment effectiveness and 2) potential mediators of treatment outcome with CBI. ### Conditions Module **Conditions:** - Anger Problems **Keywords:** - Veterans - Anger - Cognitive Behavioral Therapy - Treatment ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** SINGLE **Who Masked:** - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 112 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** 12 weekly individual sessions consisting of psychoeducation, and cognitive and behavioral anger management strategies **Intervention Names:** - Behavioral: Cognitive Behavioral Intervention **Label:** Cognitive Behavioral Intervention (CBI) **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** 12 weekly individual sessions consisting of psychoeducation, problem-solving strategies, and support **Intervention Names:** - Behavioral: Supportive Intervention **Label:** Supportive Intervention (SI) **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Cognitive Behavioral Intervention (CBI) **Description:** Includes individual therapy sessions using cognitive and behavioral strategies addressing problems with anger intensity / frequency / management **Name:** Cognitive Behavioral Intervention **Other Names:** - CBI **Type:** BEHAVIORAL #### Intervention 2 **Arm Group Labels:** - Supportive Intervention (SI) **Description:** Includes individual therapy sessions using supportive and problem-solving strategies. **Name:** Supportive Intervention **Type:** BEHAVIORAL ### Outcomes Module #### Other Outcomes **Description:** The ACQ is a brief self-report measure developed to assess the frequency of negative anger-related behavioral consequences. Internal consistencies of .75 to .91 have been reported. This scale includes items not covered by the other anger measures, including for example, trouble with the law, driving recklessly, getting into an accident, damaging relationships, etc. There are 50 items; minimum and maximum Values range from 0 to 200. Higher scores means more anger. **Measure:** Least Squares Mean Total Score on the Anger Consequences Questionnaire (ACQ) Using a Repeated Measures ANCOVA Adjusted for Baseline Scores and Time Effects **Time Frame:** Baseline, Week 12, 3 and 6 months Post-treatment #### Primary Outcomes **Description:** The STAXI-2 is a revision of Spielberger's State-Trait Anger Expression Inventory (STAXI), expanded from 44 to 57 items. It is a self-report questionnaire consisting of six scales and an Anger Expression Index (AX). Scales include State Anger, Trait Anger, Anger Expression-Out, Anger Expression-In, Anger Control-Out and Anger Expression-In. The Anger Expression Index is an overall measure of the expression and control of anger based on responses to the two anger expression and the two anger control subscales. Minimum and Maximum Values range from 0 to 96, higher scores mean more anger. **Measure:** Least Squares Mean Anger Expression Index Score on the State Trait Anger Inventory 2 (STAXI-2) Using a Repeated Measures ANCOVA Adjusted for Baseline and Time Effects **Time Frame:** Baseline, Weeks 4, 8,12, 3 and 6 months post-treatment **Description:** Structured Interview that assesses verbal and physical aggressive behaviors. Minimum and Maximum Values range from 0 to no maximum, higher scores mean more anger. **Measure:** Least Squares Mean Aggression Scale Score on the Overt Aggression Scale-Modified (OAS-M) Using a Repeated Measures ANCOVA Adjusted for Baseline Scores and Time Effects **Time Frame:** Baseline, Weeks 4, 8,12 (end of treatment), 3 and 6 months post-treatment #### Secondary Outcomes **Description:** Psychosocial functioning scales from the clinician administered Longitudinal Interval Follow-up Evaluation (LIFE) provides assessment of functioning in areas of work (employment, household, or student), various aspects of interpersonal functioning, recreation and satisfaction. The global social adjustment score is based upon a 5 point scale. Ratings are based on the past month. The psychosocial functioning ratings have been found to be of generally high reliability. Minimum and Maximum Values range from 1 to 5, higher scores mean worse functioning. **Measure:** Least Squares Mean Global Social Adjustment Score on the Longitudinal Interval Follow-up Evaluation (LIFE) Using a Repeated Measures ANCOVA Adjusted for Baseline Scores and Time Effects **Time Frame:** Baseline, 12 weeks (end of treatment), 3 and 6 months post-treatment **Description:** Psychosocial functioning scales from the clinician administered Longitudinal Interval Follow-up Evaluation (LIFE) provides assessment of functioning in areas of work (employment, household, or student), various aspects of interpersonal functioning, recreation, satisfaction and global social adjustment. Ratings are based on the past month. The psychosocial functioning ratings have been found to be of generally high reliability. Minimum and Maximum Values for the work functioning global score range from 1 to 5, higher scores mean worse functioning. **Measure:** Least Squares Mean Global Work Functioning Score on the Longitudinal Interval Follow-up Evaluation (LIFE) Using a Repeated Measures ANCOVA Adjusted for Baseline Scores and Time Effects **Time Frame:** Baseline, 12 weeks (end of treatment), 3 and 6 months post-treatment **Description:** The OQ is a self report measure that assesses functioning and includes three subscales: symptom distress, interpersonal relations, and social role functioning. Concurrent validity has been demonstrated in relation to internal consistency and reliability. Additionally, the OQ has been shown to be fairly stable in untreated individuals and sensitive to change in those individuals in treatment. Minimum and Maximum Values range from 0 to 180, higher scores mean worse functioning. **Measure:** Least Squares Mean Total Score on the Outcomes Questionnaire (OQ) Using a Repeated Measures ANCOVA Adjusted for Baseline Scores and Time Effects **Time Frame:** Baseline, 12 weeks, 3 and 6 months post-treatment **Description:** The World Health Organization Quality of Life (WHOQOL-BREF), is 26 item self-report measure used to assess quality of life in multiple domains (i.e., physical, psychological, social, and environment). Psychometric properties suggest that the measure is valid and reliable across cultures and nations. Ratings are made on a 5 point scale. The psychological subscale, which consists of 6 items, was used in this study. Minimum and Maximum Values for the psychological domain range from 6 to 30, higher scores mean better quality of life. **Measure:** Least Squares Mean Psychological Domain Score on the WHO Quality of Life (WHOQOL) Using a Repeated Measures ANCOVA Adjusted for Baseline Scores and Time Effects **Time Frame:** Baseline, 12 weeks (end of treatment), 3 and 6 months post-treatment **Description:** The CAPS-5 (updated for DSM-5) is a clinician administered structured interview for the assessment of DSM-5 PTSD. The CAPS has excellent reliability and validity and is widely used in PTSD treatment research. Each one of the DSM-5 PTSD symptoms is rated on a 0-4 (low to high) scale to determine symptom severity. The cutoff used to establish the presence of an individual symptom is a score of 2 or greater. Overall PTSD severity is computed by summing the totals for all items. Minimum and Maximum Values range from 0 to 80, higher scores mean higher levels of symptomatology. **Measure:** Least Squares Mean PTSD Severity Score on the Clinician-Administered PTSD Scale (CAPS) for DSM-5 Using a Repeated Measures ANCOVA Adjusted for Baseline Scores and Time Effects **Time Frame:** Baseline,12 weeks (end of treatment), 3 and 6 months post-treatment ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Male or Female current or former member of the military (active duty, National Guard or Reserve) Deployed to Iraq or Afghanistan * Experience trauma during deployment * Clinically significant anger * At least 2 additional symptoms of PTSD hyperarousal * If on medication, no changes within prior 4 weeks Exclusion Criteria: * Current severe substance use disorder or prior severe substance use disorder not in remission for at least 3 months * Current psychotic symptoms * current Mania or Bipolar Disorder * Current suicidal or homicidal ideation requiring hospitalization * Any severe cognitive impairment or history of Organic Mental Disorder **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Providence **Country:** United States **Facility:** Providence VA Medical Center, Providence, RI **State:** Rhode Island **Zip:** 02908 #### Overall Officials **Official 1:** **Affiliation:** Providence VA Medical Center, Providence, RI **Name:** Tracie M. Shea, PhD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **Description:** I anticipate sharing the data, but have not yet developed a specific plan. **Info Types:** - STUDY_PROTOCOL - SAP - CSR **IPD Sharing:** YES **Time Frame:** April 1 2021 ### References Module #### References **Citation:** Shea MT, Lambert J, Reddy MK, Presseau C, Sevin E, Stout RL. Treatment of trauma related anger in operation enduring freedom, operation Iraqi freedom, and operation New Dawn veterans: Rationale and study protocol. Contemp Clin Trials Commun. 2018 Aug 24;12:26-31. doi: 10.1016/j.conctc.2018.08.011. eCollection 2018 Dec. Erratum In: Contemp Clin Trials Commun. 2020 Dec 10;20:100688. **PMID:** 30225391 ## Document Section ### Large Document Module #### Large Docs - Date: 2018-11-28 - Filename: Prot_SAP_000.pdf - Has ICF: False - Has Protocol: True - Has SAP: True - Label: Study Protocol and Statistical Analysis Plan - Size: 761946 - Type Abbrev: Prot_SAP - Upload Date: 2020-02-10T11:08 - Date: 2017-09-18 - Filename: ICF_001.pdf - Has ICF: True - Has Protocol: False - Has SAP: False - Label: Informed Consent Form - Size: 145085 - Type Abbrev: ICF - Upload Date: 2020-02-10T11:22 ## Derived Section ### Condition Browse Module - Browse Branches - Abbrev: BC26 - Name: Wounds and Injuries - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M17685 - Name: Wounds and Injuries - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module #### Event Groups **Group ID:** EG000 **Title:** Cognitive Behavioral Intervention **Deaths Num Affected:** 1 **Deaths Num At Risk:** 47 **Description:** 12 weekly individual sessions consisting of psychoeducation, and cognitive and behavioral anger management strategies Cognitive Behavioral Intervention: Includes individual therapy sessions using cognitive and behavioral strategies addressing problems with anger intensity / frequency / management. **ID:** EG000 **Other Num at Risk:** 47 **Serious Number Affected:** 3 **Serious Number At Risk:** 47 **Title:** Cognitive Behavioral Intervention **Group ID:** EG001 **Title:** Supportive Intervention **Deaths Num Affected:** 1 **Deaths Num At Risk:** 45 **Description:** 12 weekly individual sessions consisting of psychoeducation, problem-solving strategies, and support Supportive Intervention: Includes individual therapy sessions using supportive and problem-solving strategies. **ID:** EG001 **Other Num at Risk:** 45 **Serious Number Affected:** 1 **Serious Number At Risk:** 45 **Title:** Supportive Intervention **Frequency Threshold:** 5 #### Serious Events **Term:** Panic Attack **Assessment Type:** SYSTEMATIC_ASSESSMENT **Notes:** Panic Attack **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA (10.0) ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 47 **Num Events:** 2 **Group ID:** EG001 **Num At Risk:** 45 **Term:** Death **Assessment Type:** SYSTEMATIC_ASSESSMENT **Notes:** Cardiac attack **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA (10.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 47 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 45 **Term:** Death **Assessment Type:** SYSTEMATIC_ASSESSMENT **Notes:** Veteran accidentally overdosed on cocaine and fentanyl **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA (10.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 47 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 45 **Num Events:** 1 **Time Frame:** 4 years ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 47 **Group ID:** BG001 **Value:** 45 **Group ID:** BG002 **Value:** 92 **Units:** Participants ### Group **ID:** BG000 **Title:** Cognitive Behavioral Intervention **Description:** 12 weekly individual sessions consisting of psychoeducation, and cognitive and behavioral anger management strategies Cognitive Behavioral Intervention: Includes individual therapy sessions using cognitive and behavioral strategies addressing problems with anger intensity / frequency / management ### Group **ID:** BG001 **Title:** Supportive Intervention **Description:** 12 weekly individual sessions consisting of psychoeducation, problem-solving strategies, and support Supportive Intervention: Includes individual therapy sessions using supportive and problem-solving strategies. ### Group **ID:** BG002 **Title:** Total **Description:** Total of all reporting groups ### Measure #### Measurement **Group ID:** BG000 **Spread:** 9.11 **Value:** 35.30 #### Measurement **Group ID:** BG001 **Spread:** 9.77 **Value:** 36.5 #### Measurement **Group ID:** BG002 **Spread:** 9.41 **Value:** 35.90 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 1 #### Measurement **Group ID:** BG001 **Value:** 2 #### Measurement **Group ID:** BG002 **Value:** 3 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 46 #### Measurement **Group ID:** BG001 **Value:** 43 #### Measurement **Group ID:** BG002 **Value:** 89 **Category Title:** Male **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 7 #### Measurement **Group ID:** BG001 **Value:** 12 #### Measurement **Group ID:** BG002 **Value:** 19 **Category Title:** Hispanic or Latino #### Measurement **Group ID:** BG000 **Value:** 40 #### Measurement **Group ID:** BG001 **Value:** 33 #### Measurement **Group ID:** BG002 **Value:** 73 **Category Title:** Not Hispanic or Latino #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** Unknown or Not Reported **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 1 #### Measurement **Group ID:** BG001 **Value:** 3 #### Measurement **Group ID:** BG002 **Value:** 4 **Category Title:** American Indian or Alaska Native #### Measurement **Group ID:** BG000 **Value:** 1 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 1 **Category Title:** Asian #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** Native Hawaiian or Other Pacific Islander #### Measurement **Group ID:** BG000 **Value:** 1 #### Measurement **Group ID:** BG001 **Value:** 4 #### Measurement **Group ID:** BG002 **Value:** 5 **Category Title:** Black or African American #### Measurement **Group ID:** BG000 **Value:** 42 #### Measurement **Group ID:** BG001 **Value:** 35 #### Measurement **Group ID:** BG002 **Value:** 77 **Category Title:** White #### Measurement **Group ID:** BG000 **Value:** 2 #### Measurement **Group ID:** BG001 **Value:** 3 #### Measurement **Group ID:** BG002 **Value:** 5 **Category Title:** More than one race #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** Unknown or Not Reported **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 22 #### Measurement **Group ID:** BG001 **Value:** 27 #### Measurement **Group ID:** BG002 **Value:** 49 **Category Title:** Full Time #### Measurement **Group ID:** BG000 **Value:** 5 #### Measurement **Group ID:** BG001 **Value:** 15 #### Measurement **Group ID:** BG002 **Value:** 20 **Category Title:** Part Time #### Measurement **Group ID:** BG000 **Value:** 14 #### Measurement **Group ID:** BG001 **Value:** 3 #### Measurement **Group ID:** BG002 **Value:** 17 **Category Title:** Unemployed #### Measurement **Group ID:** BG000 **Value:** 6 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 6 **Category Title:** Retired **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 11 #### Measurement **Group ID:** BG001 **Value:** 11 #### Measurement **Group ID:** BG002 **Value:** 22 **Category Title:** High School Graduate/GED #### Measurement **Group ID:** BG000 **Value:** 30 #### Measurement **Group ID:** BG001 **Value:** 24 #### Measurement **Group ID:** BG002 **Value:** 54 **Category Title:** Some College/Technical School #### Measurement **Group ID:** BG000 **Value:** 4 #### Measurement **Group ID:** BG001 **Value:** 7 #### Measurement **Group ID:** BG002 **Value:** 11 **Category Title:** College Graduate #### Measurement **Group ID:** BG000 **Value:** 2 #### Measurement **Group ID:** BG001 **Value:** 3 #### Measurement **Group ID:** BG002 **Value:** 5 **Category Title:** Post Graduate **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Spread:** 12.98 **Value:** 55.67 #### Measurement **Group ID:** BG001 **Spread:** 11.86 **Value:** 54.77 #### Measurement **Group ID:** BG002 **Spread:** 12.39 **Value:** 55.24 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Spread:** 0.525 **Value:** 1.335 #### Measurement **Group ID:** BG001 **Spread:** 0.500 **Value:** 1.396 #### Measurement **Group ID:** BG002 **Spread:** 0.511 **Value:** 1.365 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Spread:** 0.54 **Value:** 3.57 #### Measurement **Group ID:** BG001 **Spread:** 0.71 **Value:** 3.64 #### Measurement **Group ID:** BG002 **Spread:** 0.63 **Value:** 3.61 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Spread:** 1.22 **Value:** 3.17 #### Measurement **Group ID:** BG001 **Spread:** 1.08 **Value:** 2.98 #### Measurement **Group ID:** BG002 **Spread:** 1.15 **Value:** 3.08 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Spread:** 26.50 **Value:** 82.45 #### Measurement **Group ID:** BG001 **Spread:** 22.93 **Value:** 88.31 #### Measurement **Group ID:** BG002 **Spread:** 24.86 **Value:** 85.32 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Spread:** 3.17 **Value:** 11.54 #### Measurement **Group ID:** BG001 **Spread:** 2.61 **Value:** 10.97 #### Measurement **Group ID:** BG002 **Spread:** 2.91 **Value:** 11.26 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Spread:** 10.62 **Value:** 30.02 #### Measurement **Group ID:** BG001 **Spread:** 9.52 **Value:** 32.38 #### Measurement **Group ID:** BG002 **Spread:** 10.11 **Value:** 31.17 **Class Title:** **Denomination Units Selected:** ## Results Section - Baseline Characteristics Module ### Measure 1 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** Age, Continuous **Unit of Measure:** years ### Measure 2 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Sex: Female, Male **Unit of Measure:** Participants ### Measure 3 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Ethnicity (NIH/OMB) **Unit of Measure:** Participants ### Measure 4 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Race (NIH/OMB) **Unit of Measure:** Participants ### Measure 5 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Employment Status **Unit of Measure:** Participants ### Measure 6 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Education **Unit of Measure:** Participants ### Measure 7 **Description:** STAXI-2 is a self-report questionnaire consisting of six scales and an Anger Expression Index. The Anger Expression Index is an overall measure of the expression and control of anger based on responses to two anger expression and two anger control subscales. Score range is 0 to 96; higher scores means more anger. **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** State Trait Anger Inventory 2 (STAXI-2) Anger Expression Index Score **Unit of Measure:** units on a scale ### Measure 8 **Description:** Structured Interview that assesses verbal and physical aggressive behaviors. Four subscores are calculated by multiplying frequency by severity of specific behaviors within that category. Subscores are also weighted for severity. The Aggression Scale Score is the total of subscores. Minimum score is zero; no maximum score specified as scores are determined by unlimited frequency counts of behavior. Higher scores indicate more frequent and severe aggressive behaviors. **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** Overt Anger Scale-Modified Aggression Scale **Unit of Measure:** units on a scale ### Measure 9 **Description:** LIFE psychosocial functioning scales assess functioning in multiple areas, including work, interpersonal relationships, recreation, and global social adjustment. The global social adjustment score ranges from 1 to 5, with higher scores reflecting poorer functioning. **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** Longitudinal Interval Follow up (LIFE) social functioning global score **Unit of Measure:** units on a scale ### Measure 10 **Description:** The LIFE Work Functioning Score assess functioning in work (employment, household, or student). The work global score ranges from 1 to 5; higher scores indicate worse functioning. **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** LIFE Work Functioning Global Score **Unit of Measure:** units on a scale ### Measure 11 **Description:** The Outcomes questionnaire is a self report measure that assesses functioning and includes three subscales: symptom distress, interpersonal relations, and social role functioning. The total score is the sum of the scores for the three scales. Total scores can range from 0 to 180; higher scores mean worse functioning. **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** Outcomes Questionnaire **Unit of Measure:** units on a scale ### Measure 12 **Description:** The WHOQOL is a 26 item self report measure used to assess quality of life in multiple domains. The psychological domain includes 6 items, each rated on a scale from 1 to 5. The score is obtained by computing the means of each item of the scale, and multiplying the mean by 4. Scores can range from 4 to 20. Higher scores reflect better quality of life. **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** WHO Quality of Life (WHOQOL) Psychological Domain **Unit of Measure:** units on a scale ### Measure 13 **Description:** The CAPS-5 is a clinician administered structured interview assessing the DSM-5 PTSD symptoms. Each of the 20 symptoms is rated on a 0 to 4 scale; the range for the total score is 0 to 80. Higher scores reflect more severe PTSD. **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** Clinician Administered PTSD Scale (CAPS) **Unit of Measure:** units on a scale **Population Description:** Number of participants varies slightly for some measures due to missing data. ## Results Section - More Information Module ### Certain Agreement **PI Sponsor Employee:** True ### Point of Contact **Email:** [email protected] **Organization:** Providence VA Medical Center **Phone:** 401-273-7100 **Phone Extension:** 6248 **Title:** M. Tracie Shea, PhD ## Results Section - Outcome Measures Module ### Outcome Measure 1 #### Analysis **CI Lower Limit:** -10.32 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -1.01 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** A negative difference means that the adjusted mean for CBI is numerically lower than that for SI. **Group Description:** All randomized participants with at least one post-baseline assessment (4wk, 8wk, end of treatment, 3 mo f/u, and/or 6 mo f/u) were used in the HLM analyses. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** .017 **P-Value Comment:** Threshold for statistical significance was 0.025. **Parameter Type:** Least Squares Mean Difference **Parameter Value:** -5.68 **Statistical Comment:** Method used: Hierarchical Linear Model (HLM) Repeated Measures Analysis of Covariance, Controlling for Baseline Score. **Statistical Method:** ANCOVA **Tested Non-Inferiority:** ### Outcome Measure 2 #### Analysis **CI Lower Limit:** -0.33 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 0.06 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Population Description: All randomized participants with at least one post-baseline assessment (4wk, 8wk, end of treatment, 3 mo f/u, and/or 6 mo f/u) were used in the statistical analysis. Data were winsorized and log10 transformed to counter high levels of skewness. Full Information Maximum Likelihood was used to account for missing data. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** A negative difference means that the adjusted mean for CBI is numerically lower than that for SI. **P-Value:** 0.19 **P-Value Comment:** The threshold for statistical significance was p=0.025 **Parameter Type:** Least Squares Mean Difference **Parameter Value:** -0.14 **Statistical Comment:** Hierarchical Linear Model (HLM) Repeated Measures Analysis of Covariance, Controlling for Baseline Score. **Statistical Method:** ANCOVA **Tested Non-Inferiority:** ### Outcome Measure 3 #### Analysis **CI Lower Limit:** -0.75 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -0.09 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Population Description: All randomized participants with at least one post-baseline assessment were used in the statistical analysis process. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** A negative difference means that the adjusted mean for CBI is numerically lower than that for SI. **P-Value:** .011 **P-Value Comment:** Threshold for statistical significance was 0.025. **Parameter Type:** Least Squares Mean Difference **Parameter Value:** -0.42 **Statistical Comment:** Hierarchical Linear Model (HLM) Repeated Measures Analysis of Covariance, Controlling for Baseline Score **Statistical Method:** ANCOVA **Tested Non-Inferiority:** ### Outcome Measure 4 #### Analysis **CI Lower Limit:** -0.63 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 0.11 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** A negative difference means that the adjusted mean for CBI is numerically lower than that for SI. **Group Description:** All randomized participants with at least one post-baseline assessment (12 weeks (end of treatment, 3 month and/or 6 month follow-up) were included in the analyses. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.16 **P-Value Comment:** Threshold for statistical significance was 0.025. **Parameter Type:** Least Squares Mean Difference **Parameter Value:** -0.26 **Statistical Comment:** Hierarchical Linear Model (HLM) Repeated Measures Analysis of Covariance, Controlling for Baseline Score. **Statistical Method:** ANCOVA **Tested Non-Inferiority:** ### Outcome Measure 5 #### Analysis **CI Lower Limit:** -22.20 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -1.09 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** A negative difference means that the adjusted mean for CBI is numerically lower than that for SI. **Group Description:** All randomized participants with at least one post-baseline assessment (12 weeks (end of treatment), 3 month and/or 6 month follow-up) were included in the statistical analyses. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** .031 **P-Value Comment:** Threshold for statistical significance was 0.025. **Parameter Type:** Least Squares Mean Difference **Parameter Value:** -11.65 **Statistical Comment:** Hierarchical Linear Model (HLM) Repeated Measures Analysis of Covariance, Controlling for Baseline Score. **Statistical Method:** ANCOVA **Tested Non-Inferiority:** ### Outcome Measure 6 #### Analysis **CI Lower Limit:** 0.51 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 2.60 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** All randomized participants with at least one post-baseline assessment (week 12 (end of treatment), 3 month, and/or 6 month follow-up) were used in the statistical analysis. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** A positive difference means that the adjusted mean for CBI is numerically higher than that for SI. **P-Value:** 0.004 **P-Value Comment:** Threshold for statistical significance was 0.025. **Parameter Type:** Least Squares Mean Difference **Parameter Value:** 1.56 **Statistical Comment:** Hierarchical Linear Model (HLM) Repeated Measures Analysis of Covariance, Controlling for Baseline Score. **Statistical Method:** ANCOVA **Tested Non-Inferiority:** ### Outcome Measure 7 #### Analysis **CI Lower Limit:** -7.37 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 3.07 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** A negative difference means that the adjusted mean for CBI is numerically lower than that for SI **Group Description:** All randomized participants with at least one post-baseline assessment were used in the statistical analysis process. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.416 **P-Value Comment:** Threshold for statistical significance was 0.025. **Parameter Type:** Least Squares Mean Difference **Parameter Value:** -2.15 **Statistical Comment:** Hierarchical Linear Model (HLM) Repeated Measures Analysis of Covariance, Controlling for Baseline Score **Statistical Method:** ANCOVA **Tested Non-Inferiority:** ### Outcome Measure 8 #### Analysis **CI Lower Limit:** -25.94 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -1.50 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** A negative difference means that the adjusted mean for CBI is numerically lower than that for SI. **Group Description:** All randomized participants with at least one post-baseline assessment were used in the analyses. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.028 **P-Value Comment:** Threshold for significance was 0.025 **Parameter Type:** Least Squares Mean Difference **Parameter Value:** -13.72 **Statistical Comment:** Hierarchical Linear Model (HLM) Repeated Measures Analysis of Covariance controlling for baseline score. **Statistical Method:** ANCOVA **Tested Non-Inferiority:** ### Outcome Measure 9 #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** All randomized participants with at least one DAR completed in each time frame (sessions 1-4, 5-8, and 9-12) were included in the analyses. The mean DAR scores for sessions 1-4, 5-8, and 9-12 were calculated and used as outcome variables in the GLM repeated measures ANOVA. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.13 **P-Value Comment:** **Parameter Type:** **Parameter Value:** **Statistical Comment:** GLM Repeated Measures Analysis of Variance of means grouped by sessions 1-4, 5-8, and 9-12 **Statistical Method:** ANOVA **Tested Non-Inferiority:** ### Outcome Measure 10 #### Analysis **CI Lower Limit:** -1.578 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -0.063 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** A negative difference means that the adjusted mean for CBI is numerically lower than that for SI. **Group Description:** All randomized participants with at least one post-baseline assessment (week 4, week 8, week 12 (end of treatment), 3 mo and/or 6 month follow-up) were included in the HLM analyses. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.030 **P-Value Comment:** Threshold for statistical significance was 0.025. **Parameter Type:** Least Squares Mean Difference **Parameter Value:** -0.82 **Statistical Comment:** Hierarchical Linear Model (HLM) Repeated Measures Analysis of Covariance, Controlling for Baseline Score **Statistical Method:** ANCOVA **Tested Non-Inferiority:** ### Outcome Measure 11 #### Analysis **CI Lower Limit:** -0.158 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -0.011 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** A negative difference means that the adjusted mean for CBI is numerically lower than that for SI. **Group Description:** All randomized participants with at least one post-baseline assessment (4 week, 8 week, 12 week, 3 month and/or 6 month follow-up) were included in the HLM analysis. Data were winsorized and log10 transformed to counter high levels of skewness. Full Information Maximum Likelihood was used to account for missing data. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.021 **P-Value Comment:** Threshold for statistical significance was 0.025. **Parameter Type:** Least Squares Mean Difference **Parameter Value:** -0.085 **Statistical Comment:** Hierarchical Linear Model (HLM) Repeated Measures Analysis of Covariance, Controlling for Baseline Score **Statistical Method:** ANCOVA **Tested Non-Inferiority:** ### Outcome Measure 12 #### Analysis **CI Lower Limit:** -0.283 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 0.073 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** A negative difference means that the adjusted mean for CBI is numerically lower than that for SI. **Group Description:** All randomized participants with at least one post-baseline assessment (4 week, 8 week, 12 week, 3 month and/or 6 month follow-up) were used in the HLM analysis. Data were winsorized and log10 transformed to counter high levels of skewness. Full Information Maximum Likelihood was used to account for missing data. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.246 **P-Value Comment:** Threshold for significance was 0.025 **Parameter Type:** Least Squares Mean Difference **Parameter Value:** -0.10 **Statistical Comment:** Hierarchical Linear Model (HLM) Repeated Measures Analysis of Covariance, Controlling for Baseline Score. **Statistical Method:** ANCOVA **Tested Non-Inferiority:** ### Outcome Measure 13 #### Analysis **CI Lower Limit:** -0.27 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -0.01 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** A negative difference means that the adjusted mean for CBI is numerically lower than that for SI. **Group Description:** All randomized participants with at least one post-baseline assessment were used in the statistical analysis. Data were winsorized and log 10 transformed to counter high levels of skewness. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.036 **P-Value Comment:** Threshold for statistical significance was 0.025. **Parameter Type:** Least Squares Mean Difference **Parameter Value:** -0.14 **Statistical Comment:** Hierarchical Linear Model (HLM) Repeated Measures Analysis of Covariance, Controlling for Baseline Score **Statistical Method:** ANCOVA **Tested Non-Inferiority:** ### Outcome Measure 14 #### Analysis **CI Lower Limit:** -0.213 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 0.1614 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** A negative difference means that the adjusted mean for CBI is numerically lower than that for SI. **Group Description:** All randomized participants with at least one post-baseline assessment (4 week, 8 week, 12 week, 3 month and/or 6 month follow-up) were included in the HLM analysis. Data were winsorized and log10 transformed to counter high levels of skewness. Full Information Maximum Likelihood was used to account for missing data. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.786 **P-Value Comment:** Threshold for statistical significance was 0.025 **Parameter Type:** Least Squares Mean Difference **Parameter Value:** -0.026 **Statistical Comment:** Hierarchical Linear Model (HLM) Repeated Measures Analysis of Covariance, controlling for baseline score. **Statistical Method:** ANCOVA **Tested Non-Inferiority:** ### Outcome Measure 15 #### Analysis **CI Lower Limit:** -0.18 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 0.13 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** A negative difference means that the adjusted mean for CBI is numerically lower than that for SI. **Group Description:** All randomized participants with at least one post-baseline assessment (4 week, 8 week, 12 week, 3 month and/or 6 month follow-up) were included in the HLM analysis. Data were winsorized and log10 transformed to counter high levels of skewness. Full Information Maximum Likelihood was used to account for missing data. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.744 **P-Value Comment:** Threshold for significance was 0.025. **Parameter Type:** Least Squares Mean Difference **Parameter Value:** -0.02 **Statistical Comment:** Hierarchical Linear Model (HLM) Repeated Measures Analysis of Covariance, controlling for baseline score. **Statistical Method:** ANCOVA **Tested Non-Inferiority:** ### Outcome Measure 16 #### Analysis **CI Lower Limit:** -3.038 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -0.663 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** A negative difference means that the adjusted mean for CBI is numerically lower than that for SI. **Group Description:** All randomized participants with at least one post-baseline assessment (4 week, 8 week, 12 week, 3 month and/or 6 month follow-up) were included in the HLM analysis. Full Information Maximum Likelihood was used to account for missing data. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.002 **P-Value Comment:** Threshold for significance was 0.025 **Parameter Type:** Least Squares Mean Difference **Parameter Value:** -1.85 **Statistical Comment:** Hierarchical Linear Model (HLM) Repeated Measures Analysis of Covariance, controlling for baseline score. **Statistical Method:** ANCOVA **Tested Non-Inferiority:** ### Outcome Measure 17 #### Analysis **CI Lower Limit:** -2.518 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 0.524 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** A negative difference means that the adjusted mean for CBI is numerically lower than that for SI. **Group Description:** All randomized participants with at least one post-baseline assessment (4wk, 8wk, 12 week (end of treatment), 3 mo and/or 6 mo follow-up) were included in the HLM analysis. Full Information Maximum Likelihood was used to account for missing data. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.186 **P-Value Comment:** Threshold for significance was 0.025 **Parameter Type:** Least Squares Mean Difference **Parameter Value:** -1.0 **Statistical Comment:** Hierarchical Linear Model (HLM) Repeated Measures Analysis of Covariance, controlling for baseline score. **Statistical Method:** ANCOVA **Tested Non-Inferiority:** ### Outcome Measure 18 #### Analysis **CI Lower Limit:** -0.560 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 3.09 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** A positive difference means that the adjusted mean for CBI is numerically higher than that for SI. **Group Description:** All randomized participants with at least one post-baseline assessment (4wk, 8wk, 12 week (end of treatment), 3 mo and/or 6 mo follow-up) were included in the HLM analysis. Full Information Maximum Likelihood was used to account for missing data. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.164 **P-Value Comment:** Threshold for significance was 0.025 **Parameter Type:** Least Squares Mean Difference **Parameter Value:** 1.26 **Statistical Comment:** Hierarchical Linear Model (HLM) Repeated Measures Analysis of Covariance, controlling for baseline score. **Statistical Method:** ANCOVA **Tested Non-Inferiority:** ### Outcome Measure 19 #### Analysis **CI Lower Limit:** -0.26 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 2.92 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** A positive difference means that the adjusted mean for CBI is numerically higher than that for SI. **Group Description:** All randomized participants with at least one post-baseline assessment (4wk, 8wk, 12 week (end of treatment), 3 mo and/or 6 mo follow-up) were included in the HLM analysis. Full Information Maximum Likelihood was used to account for missing data. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.100 **P-Value Comment:** Threshold for statistical significance was 0.025. **Parameter Type:** Least Squares Mean Difference **Parameter Value:** 1.33 **Statistical Comment:** Hierarchical Linear Model (HLM) Repeated Measures Analysis of Covariance, Controlling for Baseline Score **Statistical Method:** ANCOVA **Tested Non-Inferiority:** ### Outcome Measure 20 #### Analysis **CI Lower Limit:** -12.85 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 0.27 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** All randomized participants with at least one post-baseline assessment (12 week (end of treatment), 3 mo and/or 6 mo follow-up) were included in the HLM analysis. Full Information Maximum Likelihood was used to account for missing data. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** A negative difference means that the adjusted mean for CBI is numerically lower than that for SI, indicating less symptomatic distress. **P-Value:** 0.060 **P-Value Comment:** Threshold for significance was 0.025 **Parameter Type:** Least Squares Mean Difference **Parameter Value:** -6.29 **Statistical Comment:** Hierarchical Linear Model (HLM) Repeated Measures Analysis of Covariance, controlling for baseline score. **Statistical Method:** ANCOVA **Tested Non-Inferiority:** ### Outcome Measure 21 #### Analysis **CI Lower Limit:** -6.083 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -0.458 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** A negative difference means that the adjusted mean for CBI is numerically lower than that for SI. **Group Description:** All randomized participants with at least one post-baseline assessment (12 week (end of treatment), 3 mo and/or 6 mo follow-up) were included in the HLM analysis. Full Information Maximum Likelihood was used to account for missing data. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.023 **P-Value Comment:** Threshold for significance was 0.025 **Parameter Type:** Least Squares Mean Difference **Parameter Value:** -3.271 **Statistical Comment:** Hierarchical Linear Model (HLM) Repeated Measures Analysis of Covariance, controlling for baseline score. **Statistical Method:** ANCOVA **Tested Non-Inferiority:** ### Outcome Measure 22 #### Analysis **CI Lower Limit:** -3.39 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 0.82 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** A negative difference means that the adjusted mean for CBI is numerically lower than that for SI. **Group Description:** All randomized participants with at least one post-baseline assessment (12 week (end of treatment), 3 mo and/or 6 mo follow-up) were included in the HLM analysis. Full Information Maximum Likelihood was used to account for missing data. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.23 **P-Value Comment:** Threshold for significance was 0.025 **Parameter Type:** Least Squares Mean Difference **Parameter Value:** -1.28 **Statistical Comment:** Hierarchical Linear Model (HLM) Repeated Measures Analysis of Covariance, controlling for baseline score. **Statistical Method:** ANCOVA **Tested Non-Inferiority:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.77 - **Upper Limit:** - **Value:** 41.42 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.65 - **Upper Limit:** - **Value:** 47.09 **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.08 - **Upper Limit:** - **Value:** 1.00 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.07 - **Upper Limit:** - **Value:** 1.14 **Title:** #### Outcome Measure 3 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.13 - **Upper Limit:** - **Value:** 2.85 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.10 - **Upper Limit:** - **Value:** 3.28 **Title:** #### Outcome Measure 4 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.14 - **Upper Limit:** - **Value:** 2.78 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.12 - **Upper Limit:** - **Value:** 3.04 **Title:** #### Outcome Measure 5 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 4.11 - **Upper Limit:** - **Value:** 60.69 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 3.27 - **Upper Limit:** - **Value:** 72.34 **Title:** #### Outcome Measure 6 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.40 - **Upper Limit:** - **Value:** 13.64 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.33 - **Upper Limit:** - **Value:** 12.09 **Title:** #### Outcome Measure 7 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 2.01 - **Upper Limit:** - **Value:** 22.56 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.69 - **Upper Limit:** - **Value:** 24.71 **Title:** #### Outcome Measure 8 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 4.71 - **Upper Limit:** - **Value:** 30.48 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 3.75 - **Upper Limit:** - **Value:** 44.20 **Title:** #### Outcome Measure 9 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 4.91 - **Upper Limit:** - **Value:** 14.35 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 5.65 - **Upper Limit:** - **Value:** 15.43 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 5.77 - **Upper Limit:** - **Value:** 10.76 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 5.99 - **Upper Limit:** - **Value:** 12.96 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 5.80 - **Upper Limit:** - **Value:** 8.60 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 6.53 - **Upper Limit:** - **Value:** 11.88 **Title:** #### Outcome Measure 10 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.29 - **Upper Limit:** - **Value:** 4.02 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.26 - **Upper Limit:** - **Value:** 4.84 **Title:** #### Outcome Measure 11 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.03 - **Upper Limit:** - **Value:** 0.26 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.02 - **Upper Limit:** - **Value:** 0.34 **Title:** #### Outcome Measure 12 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.07 - **Upper Limit:** - **Value:** 0.85 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.06 - **Upper Limit:** - **Value:** 0.96 **Title:** #### Outcome Measure 13 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.05 - **Upper Limit:** - **Value:** 0.19 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.04 - **Upper Limit:** - **Value:** 0.33 **Title:** #### Outcome Measure 14 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.06 - **Upper Limit:** - **Value:** 0.11 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.05 - **Upper Limit:** - **Value:** 0.14 **Title:** #### Outcome Measure 15 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.06 - **Upper Limit:** - **Value:** 0.11 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.05 - **Upper Limit:** - **Value:** 0.14 **Title:** #### Outcome Measure 16 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.44 - **Upper Limit:** - **Value:** 16.42 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.41 - **Upper Limit:** - **Value:** 18.27 **Title:** #### Outcome Measure 17 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.55 - **Upper Limit:** - **Value:** 18.31 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.52 - **Upper Limit:** - **Value:** 19.31 **Title:** #### Outcome Measure 18 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.68 - **Upper Limit:** - **Value:** 20.07 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.62 - **Upper Limit:** - **Value:** 18.80 **Title:** #### Outcome Measure 19 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.68 - **Upper Limit:** - **Value:** 20.71 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.54 - **Upper Limit:** - **Value:** 19.38 **Title:** #### Outcome Measure 20 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 2.56 - **Upper Limit:** - **Value:** 35.29 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 2.08 - **Upper Limit:** - **Value:** 41.58 **Title:** #### Outcome Measure 21 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.09 - **Upper Limit:** - **Value:** 14.66 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.86 - **Upper Limit:** - **Value:** 17.93 **Title:** #### Outcome Measure 22 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.82 - **Upper Limit:** - **Value:** 11.39 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.67 - **Upper Limit:** - **Value:** 12.68 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** The STAXI-2 is a revision of Spielberger's State-Trait Anger Expression Inventory (STAXI), expanded from 44 to 57 items. It is a self-report questionnaire consisting of six scales and an Anger Expression Index (AX). Scales include State Anger, Trait Anger, Anger Expression-Out, Anger Expression-In, Anger Control-Out and Anger Expression-In. The Anger Expression Index is an overall measure of the expression and control of anger based on responses to the two anger expression and the two anger control subscales. Minimum and Maximum Values range from 0 to 96, higher scores mean more anger. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** Participants were randomly assigned to CBI or SI. Those with one or more post-baseline assessments were included in Hierarchical Linear Model (HLM) analyses. Not all participants had post-baseline data; some treatment noncompleters had one or more post-baseline assessments. Least Square Means and differences adjusted for baseline and time effects from repeated measures ANCOVA are shown. Full Information Maximum Likelihood was used to account for missing data. **Reporting Status:** POSTED **Time Frame:** Baseline, Weeks 4, 8,12, 3 and 6 months post-treatment **Title:** Least Squares Mean Anger Expression Index Score on the State Trait Anger Inventory 2 (STAXI-2) Using a Repeated Measures ANCOVA Adjusted for Baseline and Time Effects **Type:** PRIMARY **Unit of Measure:** score on a scale ##### Group **Description:** 12 weekly individual sessions consisting of psychoeducation, and cognitive and behavioral anger management strategies Cognitive Behavioral Intervention: Includes individual therapy sessions using cognitive and behavioral strategies addressing problems with anger intensity / frequency / management **ID:** OG000 **Title:** Cognitive Behavioral Intervention (CBI) ##### Group **Description:** 12 weekly individual sessions consisting of psychoeducation, problem-solving strategies, and support Supportive Intervention: Includes individual therapy sessions using supportive and problem-solving strategies. **ID:** OG001 **Title:** Supportive Intervention (SI) #### Outcome Measure 2 **Description:** Structured Interview that assesses verbal and physical aggressive behaviors. Minimum and Maximum Values range from 0 to no maximum, higher scores mean more anger. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** Participants were randomly assigned to CBI or SI. Participants with at least one post-baseline measure (4wk, 8wk, 12 wk, 3 mo and/or 6 mo f/u) were included in HLM analysis. Not all participants had post-baseline data, and some non-completers had one or more post-baseline assessments. Least Square means and differences adjusted for baseline and time effects from repeated analyses of covariance are shown. Full Information Maximum Likelihood was used to account for missing data. **Reporting Status:** POSTED **Time Frame:** Baseline, Weeks 4, 8,12 (end of treatment), 3 and 6 months post-treatment **Title:** Least Squares Mean Aggression Scale Score on the Overt Aggression Scale-Modified (OAS-M) Using a Repeated Measures ANCOVA Adjusted for Baseline Scores and Time Effects **Type:** PRIMARY **Unit of Measure:** units on a scale ##### Group **Description:** 12 weekly individual sessions consisting of psychoeducation, and cognitive and behavioral anger management strategies Cognitive Behavioral Intervention: Includes individual therapy sessions using cognitive and behavioral strategies addressing problems with anger intensity / frequency / management **ID:** OG000 **Title:** Cognitive Behavioral Intervention ##### Group **Description:** 12 weekly individual sessions consisting of psychoeducation, problem-solving strategies, and support Supportive Intervention: Includes individual therapy sessions using supportive and problem-solving strategies. **ID:** OG001 **Title:** Supportive Intervention #### Outcome Measure 3 **Description:** Psychosocial functioning scales from the clinician administered Longitudinal Interval Follow-up Evaluation (LIFE) provides assessment of functioning in areas of work (employment, household, or student), various aspects of interpersonal functioning, recreation and satisfaction. The global social adjustment score is based upon a 5 point scale. Ratings are based on the past month. The psychosocial functioning ratings have been found to be of generally high reliability. Minimum and Maximum Values range from 1 to 5, higher scores mean worse functioning. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** Participants were randomly assigned to CBI or SI. Those with at least one post-baseline measure (12 wk (end of treatment), 3 mo f/u, and/or 6 mo f/u) were included in HLM analysis. Not all had post-baseline data, and some who didn't complete treatment had one or more post-baseline assessments. Least Square means and differences adjusted for baseline and time effects from repeated measures ANCOVA are shown. Full Information Maximum Likelihood was used to account for missing data. **Reporting Status:** POSTED **Time Frame:** Baseline, 12 weeks (end of treatment), 3 and 6 months post-treatment **Title:** Least Squares Mean Global Social Adjustment Score on the Longitudinal Interval Follow-up Evaluation (LIFE) Using a Repeated Measures ANCOVA Adjusted for Baseline Scores and Time Effects **Type:** SECONDARY **Unit of Measure:** units on a scale ##### Group **Description:** 12 weekly individual sessions consisting of psychoeducation, and cognitive and behavioral anger management strategies Cognitive Behavioral Intervention: Includes individual therapy sessions using cognitive and behavioral strategies addressing problems with anger intensity / frequency / management. **ID:** OG000 **Title:** Cognitive Behavioral Intervention ##### Group **Description:** 12 weekly individual sessions consisting of psychoeducation, problem-solving strategies, and support Supportive Intervention: Includes individual therapy sessions using supportive and problem-solving strategies. **ID:** OG001 **Title:** Supportive Intervention #### Outcome Measure 4 **Description:** Psychosocial functioning scales from the clinician administered Longitudinal Interval Follow-up Evaluation (LIFE) provides assessment of functioning in areas of work (employment, household, or student), various aspects of interpersonal functioning, recreation, satisfaction and global social adjustment. Ratings are based on the past month. The psychosocial functioning ratings have been found to be of generally high reliability. Minimum and Maximum Values for the work functioning global score range from 1 to 5, higher scores mean worse functioning. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** Participants were randomly assigned to CBI or SI. Those with at least one post-baseline measure (12 wk (end of treatment), 3 mo f/u, and/or 6 mo f/u) were included in HLM analysis. Not all had post-baseline data, and some who didn't complete treatment had one or more post-baseline assessments. Least Square means and differences adjusted for baseline and time effects from repeated measures ANCOVA are shown. Full Information Maximum Likelihood was used to account for missing data. **Reporting Status:** POSTED **Time Frame:** Baseline, 12 weeks (end of treatment), 3 and 6 months post-treatment **Title:** Least Squares Mean Global Work Functioning Score on the Longitudinal Interval Follow-up Evaluation (LIFE) Using a Repeated Measures ANCOVA Adjusted for Baseline Scores and Time Effects **Type:** SECONDARY **Unit of Measure:** units on a scale ##### Group **Description:** 12 weekly individual sessions consisting of psychoeducation, and cognitive and behavioral anger management strategies Cognitive Behavioral Intervention: Includes individual therapy sessions using cognitive and behavioral strategies addressing problems with anger intensity / frequency / management. **ID:** OG000 **Title:** Cognitive Behavioral Intervention ##### Group **Description:** 12 weekly individual sessions consisting of psychoeducation, problem-solving strategies, and support Supportive Intervention: Includes individual therapy sessions using supportive and problem-solving strategies. **ID:** OG001 **Title:** Supportive Intervention #### Outcome Measure 5 **Description:** The OQ is a self report measure that assesses functioning and includes three subscales: symptom distress, interpersonal relations, and social role functioning. Concurrent validity has been demonstrated in relation to internal consistency and reliability. Additionally, the OQ has been shown to be fairly stable in untreated individuals and sensitive to change in those individuals in treatment. Minimum and Maximum Values range from 0 to 180, higher scores mean worse functioning. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** Participants were randomly assigned to CBI or SI. Those with at least one post-baseline measure (12 wk (end of treatment), 3 mo f/u, and/or 6 mo f/u) were included in HLM analysis. Not all had post-baseline data, and some who didn't complete treatment had one or more post-baseline assessments. Least Square means and differences adjusted for baseline and time effects from repeated measures ANCOVA are shown. Full Information Maximum Likelihood was used to account for missing data. **Reporting Status:** POSTED **Time Frame:** Baseline, 12 weeks, 3 and 6 months post-treatment **Title:** Least Squares Mean Total Score on the Outcomes Questionnaire (OQ) Using a Repeated Measures ANCOVA Adjusted for Baseline Scores and Time Effects **Type:** SECONDARY **Unit of Measure:** score on a scale ##### Group **Description:** 12 weekly individual sessions consisting of psychoeducation, and cognitive and behavioral anger management strategies Cognitive Behavioral Intervention: Includes individual therapy sessions using cognitive and behavioral strategies addressing problems with anger intensity / frequency / management. **ID:** OG000 **Title:** Cognitive Behavioral Intervention ##### Group **Description:** 12 weekly individual sessions consisting of psychoeducation, problem-solving strategies, and support Supportive Intervention: Includes individual therapy sessions using supportive and problem-solving strategies. **ID:** OG001 **Title:** Supportive Intervention #### Outcome Measure 6 **Description:** The World Health Organization Quality of Life (WHOQOL-BREF), is 26 item self-report measure used to assess quality of life in multiple domains (i.e., physical, psychological, social, and environment). Psychometric properties suggest that the measure is valid and reliable across cultures and nations. Ratings are made on a 5 point scale. The psychological subscale, which consists of 6 items, was used in this study. Minimum and Maximum Values for the psychological domain range from 6 to 30, higher scores mean better quality of life. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** Participants were randomly assigned to CBI or SI. Those with at least one post-baseline measure (12 wk (end of treatment), 3 mo f/u, and/or 6 mo f/u) were included in HLM analysis. Not all had post-baseline data, and some who didn't complete treatment had one or more post-baseline assessments. Least Square means and differences adjusted for baseline and time effects from repeated measures ANCOVA are shown. Full Information Maximum Likelihood was used to account for missing data. **Reporting Status:** POSTED **Time Frame:** Baseline, 12 weeks (end of treatment), 3 and 6 months post-treatment **Title:** Least Squares Mean Psychological Domain Score on the WHO Quality of Life (WHOQOL) Using a Repeated Measures ANCOVA Adjusted for Baseline Scores and Time Effects **Type:** SECONDARY **Unit of Measure:** score on a scale ##### Group **Description:** 12 weekly individual sessions consisting of psychoeducation, and cognitive and behavioral anger management strategies Cognitive Behavioral Intervention: Includes individual therapy sessions using cognitive and behavioral strategies addressing problems with anger intensity / frequency / management. **ID:** OG000 **Title:** Cognitive Behavioral Intervention ##### Group **Description:** 12 weekly individual sessions consisting of psychoeducation, problem-solving strategies, and support Supportive Intervention: Includes individual therapy sessions using supportive and problem-solving strategies. **ID:** OG001 **Title:** Supportive Intervention #### Outcome Measure 7 **Description:** The CAPS-5 (updated for DSM-5) is a clinician administered structured interview for the assessment of DSM-5 PTSD. The CAPS has excellent reliability and validity and is widely used in PTSD treatment research. Each one of the DSM-5 PTSD symptoms is rated on a 0-4 (low to high) scale to determine symptom severity. The cutoff used to establish the presence of an individual symptom is a score of 2 or greater. Overall PTSD severity is computed by summing the totals for all items. Minimum and Maximum Values range from 0 to 80, higher scores mean higher levels of symptomatology. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** Participants were randomly assigned to CBI or SI. Those with at least one post-baseline measure (12 wk (end of treatment), 3 mo f/u, and/or 6 mo f/u) were included in HLM analysis. Not all had post-baseline data, and some who didn't complete treatment had one or more post-baseline assessments. Least Square means and differences adjusted for baseline and time effects from repeated measures ANCOVA are shown. Full Information Maximum Likelihood was used to account for missing data. **Reporting Status:** POSTED **Time Frame:** Baseline,12 weeks (end of treatment), 3 and 6 months post-treatment **Title:** Least Squares Mean PTSD Severity Score on the Clinician-Administered PTSD Scale (CAPS) for DSM-5 Using a Repeated Measures ANCOVA Adjusted for Baseline Scores and Time Effects **Type:** SECONDARY **Unit of Measure:** score on a scale ##### Group **Description:** 12 weekly individual sessions consisting of psychoeducation, and cognitive and behavioral anger management strategies Cognitive Behavioral Intervention: Includes individual therapy sessions using cognitive and behavioral strategies addressing problems with anger intensity / frequency / management. **ID:** OG000 **Title:** Cognitive Behavioral Intervention ##### Group **Description:** 12 weekly individual sessions consisting of psychoeducation, problem-solving strategies, and support Supportive Intervention: Includes individual therapy sessions using supportive and problem-solving strategies. **ID:** OG001 **Title:** Supportive Intervention #### Outcome Measure 8 **Description:** The ACQ is a brief self-report measure developed to assess the frequency of negative anger-related behavioral consequences. Internal consistencies of .75 to .91 have been reported. This scale includes items not covered by the other anger measures, including for example, trouble with the law, driving recklessly, getting into an accident, damaging relationships, etc. There are 50 items; minimum and maximum Values range from 0 to 200. Higher scores means more anger. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** Participants were randomly assigned to CBI or SI. Those with one or more post-baseline assessments (week 12, 3- and/or 6-month follow-up) were included in HLM analyses. Not all participants had post-baseline data, and some who didn't complete treatment had one or more post-baseline assessments. Least Square means and differences adjusted for baseline and time effects from repeated measures ANCOVA are shown. Full Information Maximum Likelihood was used to account for missing data. **Reporting Status:** POSTED **Time Frame:** Baseline, Week 12, 3 and 6 months Post-treatment **Title:** Least Squares Mean Total Score on the Anger Consequences Questionnaire (ACQ) Using a Repeated Measures ANCOVA Adjusted for Baseline Scores and Time Effects **Type:** OTHER_PRE_SPECIFIED **Unit of Measure:** score on a scale ##### Group **Description:** 12 weekly individual sessions consisting of psychoeducation, and cognitive and behavioral anger management strategies Cognitive Behavioral Intervention: Includes individual therapy sessions using cognitive and behavioral strategies addressing problems with anger intensity / frequency / management **ID:** OG000 **Title:** Cognitive Behavioral Intervention (CBI) ##### Group **Description:** 12 weekly individual sessions consisting of psychoeducation, problem-solving strategies, and support Supportive Intervention: Includes individual therapy sessions using supportive and problem-solving strategies. **ID:** OG001 **Title:** Supportive Intervention (SI) #### Outcome Measure 9 **Description:** The DAR is a 7 item self-report measure of anger reactions. It has been found to be reliable and sensitive to change. Higher scores reflect more severe anger. Scores can range from 0 to 28. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Participants were randomly assigned to CBI or SI. Participants with at one or more DARs completed during each of the time frames (sessions 1-4, 5-8, 9-12) were included in the analyses. Not all randomized participants had one or more DARs in all time frames. Some who did not complete treatment did have at least one DAR in all time frames. **Reporting Status:** POSTED **Time Frame:** The DAR was administered at each weekly 75-minute treatment session (up to 12 sessions). The mean DAR scores for sessions 1-4, 5-8, and 9-12 were calculated and used as outcome variables in the GLM repeated measures ANOVA. **Title:** Mean Scores for Sessions 1-4, 5-8, and 9-12 on the Dimensions of Anger Response (DAR) Measure Using a Generalized Linear Model (GLM) Repeated Measures ANOVA **Type:** POST_HOC **Unit of Measure:** score on a scale ##### Group **Description:** 12 weekly individual sessions consisting of psychoeducation, and cognitive and behavioral anger management strategies Cognitive Behavioral Intervention: Includes individual therapy sessions using cognitive and behavioral strategies addressing problems with anger intensity / frequency / management **ID:** OG000 **Title:** Cognitive Behavioral Intervention ##### Group **Description:** 12 weekly individual sessions consisting of psychoeducation, problem-solving strategies, and support Supportive Intervention: Includes individual therapy sessions using supportive and problem-solving strategies. **ID:** OG001 **Title:** Supportive Intervention #### Outcome Measure 10 **Description:** The OAS-M is a structured Interview that assesses verbal and physical aggressive behaviors. The Global Anger and Aggression Score consists of two items - subjective experience and overt expression of anger, each rated on a scale from 0 to 5. Minimum and Maximum Values range from 0 to 10, higher scores means more anger. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** Participants were randomly assigned to the CBI or SI. Those with at least one post-baseline measure (4wk, 8wk, 12 wk, 3 mo and/or 6 mo f/u) were included in HLM analysis. . Not all participants had post-baseline data, and some non-completers had one or more post-baseline assessments. Least Square means and differences adjusted for baseline and time effects from repeated analyses of covariance are shown. Full Information Maximum Likelihood was used to account for missing data. **Reporting Status:** POSTED **Time Frame:** Baseline, Weeks 4, 8,12, 3 and 6 months post-treatment **Title:** Least Squares Mean Global Anger and Aggression Score on the Overt Aggression Scale-Modified (OAS-M) Using a Repeated Measures ANCOVA Adjusted for Baseline Scores and Time Effects **Type:** POST_HOC **Unit of Measure:** score on a scale ##### Group **Description:** 12 weekly individual sessions consisting of psychoeducation, and cognitive and behavioral anger management strategies Cognitive Behavioral Intervention: Includes individual therapy sessions using cognitive and behavioral strategies addressing problems with anger intensity / frequency / management **ID:** OG000 **Title:** Cognitive Behavioral Intervention ##### Group **Description:** 12 weekly individual sessions consisting of psychoeducation, problem-solving strategies, and support Supportive Intervention: Includes individual therapy sessions using supportive and problem-solving strategies. **ID:** OG001 **Title:** Supportive Intervention #### Outcome Measure 11 **Description:** The OAS-M is a structured Interview that assesses verbal and physical aggressive behaviors. Aggressive Outbursts is a measure of the frequency and severity of all aggressive outbursts over the past week.Minimum and Maximum Values range from 0 to no maximum, higher scores means more anger. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** Participants were randomly assigned to CBI or SI. Participants with at least one post-baseline measure (4wk, 8wk, 12 wk, 3 mo and/or 6 mo f/u) were included in HLM analysis. Not all had post-baseline data, and some who didn't complete treatment had one or more post-baseline assessments. Least Square means and differences adjusted for baseline and time effects from repeated measures ANCOVA are shown. Full Information Maximum Likelihood was used to account for missing data. **Reporting Status:** POSTED **Time Frame:** Baseline, Weeks 4, 8,12, 3 and 6 months post-treatment **Title:** Least Squares Mean Aggressive Outbursts Score From the Overt Aggression Scale-Modified (OAS-M) Using a Repeated Measures ANCOVA Adjusted for Baseline Scores and Time Effects **Type:** POST_HOC **Unit of Measure:** units on a scale ##### Group **Description:** 12 weekly individual sessions consisting of psychoeducation, and cognitive and behavioral anger management strategies Cognitive Behavioral Intervention: Includes individual therapy sessions using cognitive and behavioral strategies addressing problems with anger intensity / frequency / management **ID:** OG000 **Title:** Cognitive Behavioral Intervention ##### Group **Description:** 12 weekly individual sessions consisting of psychoeducation, problem-solving strategies, and support Supportive Intervention: Includes individual therapy sessions using supportive and problem-solving strategies. **ID:** OG001 **Title:** Supportive Intervention #### Outcome Measure 12 **Description:** The OAS-M is a structured interview that assesses frequency of anger and aggression. The verbal assault subscale measures the frequency and severity of verbal assaults over the previous week. Minimum and Maximum Values range from 0 to no maximum, higher scores means more anger. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** Participants were randomly assigned to CBI or SI. Those with at least one post-baseline measure (12 wk (end of treatment), 3 mo f/u, and/or 6 mo f/u) were included in HLM analysis. Not all had post-baseline data, and some who didn't complete treatment had one or more post-baseline assessments. Least Square means and differences adjusted for baseline and time effects from repeated measures ANCOVA are shown. Full Information Maximum Likelihood was used to account for missing data. **Reporting Status:** POSTED **Time Frame:** Baseline, 4 weeks, 8 weeks, 12 weeks (end of treatment), 3 month and 6 month follow-ups **Title:** Least Squares Mean Verbal Assault Score on the Overt Aggression Scale-Modified (OAS-M) Using a Repeated Measures ANCOVA Adjusted for Baseline Scores and Time Effects **Type:** POST_HOC **Unit of Measure:** units on a scale ##### Group **Description:** 12 weekly individual sessions consisting of psychoeducation, and cognitive and behavioral anger management strategies Cognitive Behavioral Intervention: Includes individual therapy sessions using cognitive and behavioral strategies addressing problems with anger intensity / frequency / management **ID:** OG000 **Title:** Cognitive Behavioral Intervention ##### Group **Description:** 12 weekly individual sessions consisting of psychoeducation, problem-solving strategies, and support Supportive Intervention: Includes individual therapy sessions using supportive and problem-solving strategies. **ID:** OG001 **Title:** Supportive Intervention #### Outcome Measure 13 **Description:** The OAS-M is a structured interview that assesses anger and aggressive behaviors. The Assaults on Objects Subscale assesses the frequency and severity of assaults against objects over the past week. Minimum and Maximum Values range from 0 to no maximum, higher scores means more assaults. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** Participants were randomly assigned to CBI or SI. Those with at least one post-baseline measure (12 wk (end of treatment), 3 mo f/u, and/or 6 mo f/u) were included in HLM analysis. Not all had post-baseline data, and some who didn't complete treatment had one or more post-baseline assessments. Least Square means and differences adjusted for baseline and time effects from repeated measures ANCOVA are shown. Full Information Maximum Likelihood was used to account for missing data. **Reporting Status:** POSTED **Time Frame:** Baseline, weeks 4, 8, 12 (post-treatment), 3 and 6 month post-treatment follow-ups **Title:** Least Squares Mean Assaults on Objects Score on the Overt Aggression Scale-Modified (OAS-M) Using a Repeated Measures ANCOVA Adjusted for Baseline Scores and Time Effects **Type:** POST_HOC **Unit of Measure:** units on a scale ##### Group **Description:** 12 weekly individual sessions consisting of psychoeducation, and cognitive and behavioral anger management strategies Cognitive Behavioral Intervention: Includes individual therapy sessions using cognitive and behavioral strategies addressing problems with anger intensity / frequency / management **ID:** OG000 **Title:** Cognitive Behavioral Intervention ##### Group **Description:** 12 weekly individual sessions consisting of psychoeducation, problem-solving strategies, and support Supportive Intervention: Includes individual therapy sessions using supportive and problem-solving strategies. **ID:** OG001 **Title:** Supportive Intervention #### Outcome Measure 14 **Description:** The Assault Against Others Subscale assesses the frequency and severity of aggressive behaviors towards others. Minimum and Maximum Values range from 0 to no maximum, higher scores means more anger. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** Participants were randomly assigned to CBI or SI. Those with at least one post-baseline measure (12 wk (end of treatment), 3 mo f/u, and/or 6 mo f/u) were included in HLM analysis. Not all had post-baseline data, and some who didn't complete treatment had one or more post-baseline assessments. Least Square means and differences adjusted for baseline and time effects from repeated measures ANCOVA are shown. Full Information Maximum Likelihood was used to account for missing data. **Reporting Status:** POSTED **Time Frame:** Baseline, weeks 4, 8, 12 (post-treatment), 3 and 6 month post-treatment **Title:** Least Squares Mean Assault Against Others Score on the Overt Aggression Scale-Modified Using a Repeated Measures ANCOVA Adjusted for Baseline Scores and Time Effects **Type:** POST_HOC **Unit of Measure:** units on a scale ##### Group **Description:** 12 weekly individual sessions consisting of psychoeducation, and cognitive and behavioral anger management strategies Cognitive Behavioral Intervention: Includes individual therapy sessions using cognitive and behavioral strategies addressing problems with anger intensity / frequency / management **ID:** OG000 **Title:** Cognitive Behavioral Intervention ##### Group **Description:** 12 weekly individual sessions consisting of psychoeducation, problem-solving strategies, and support Supportive Intervention: Includes individual therapy sessions using supportive and problem-solving strategies. **ID:** OG001 **Title:** Supportive Intervention #### Outcome Measure 15 **Description:** The OAS-M is a structured interview assessing anger and aggression. The Assault against Self Subscale assesses the frequency and severity of aggression towards oneself during the past week. Minimum and Maximum Values range from 0 to no maximum, higher scores means more anger. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** All randomized participants with at least one post-baseline assessment (4wk, 8wk, end of treatment, 3 mo f/u, and/or 6 mo f/u) were included in the analyses. Data were winsorized and log 10 transformed to counter high levels of skewness. Least Square means and differences adjusted for baseline and time effects from repeated analyses of covariance are shown. Full Information Maximum Likelihood was used to account for missing data. **Reporting Status:** POSTED **Time Frame:** Baseline, weeks 4, 8, 12 (posttreatment), 3 and 6 months posttreatment **Title:** Least Squares Mean Assault Against Self Scale on the Overt Aggression Scale-Modified Using a Repeated Measures ANCOVA Adjusted for Baseline Scores and Time Effects **Type:** POST_HOC **Unit of Measure:** units on a scale ##### Group **Description:** 12 weekly individual sessions consisting of psychoeducation, and cognitive and behavioral anger management strategies Cognitive Behavioral Intervention: Includes individual therapy sessions using cognitive and behavioral strategies addressing problems with anger intensity / frequency / management **ID:** OG000 **Title:** Cognitive Behavioral Intervention ##### Group **Description:** 12 weekly individual sessions consisting of psychoeducation, problem-solving strategies, and support Supportive Intervention: Includes individual therapy sessions using supportive and problem-solving strategies. **ID:** OG001 **Title:** Supportive Intervention #### Outcome Measure 16 **Description:** The revised STAXI-2 is a 57 item self-report questionnaire that consists of five subscales and an anger expression index. The Anger Expression Out (AX-O) subscale measures how often angry feelings are expressed in verbally or physically aggressive behavior. It consists of 8 items, with a subscale range of 8 to 32. Higher scores indicate higher levels of expressed anger. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** Participants were randomly assigned to CBI or SI. Those with at least one post-baseline measure (4 wk, 8wk,12 wk (end of tx), 3 mo and/or 6 mo f/u) were included in HLM analysis. Not all had post-baseline data, and some who didn't complete treatment had one or more post-baseline assessments. Least Square means and differences adjusted for baseline and time effects from repeated measures ANCOVA are shown. Full Information Maximum Likelihood was used to account for missing data. **Reporting Status:** POSTED **Time Frame:** Baseline, weeks 4, 8, 12 (post-treatment), 3 and 6 month post-treatment **Title:** Least Squares Mean Anger Expression Out Scale Score on the State Trait Anger Inventory 2 (STAXI-2) Using a Repeated Measures ANCOVA Adjusted for Baseline Scores and Time Effects **Type:** POST_HOC **Unit of Measure:** score on a scale ##### Group **Description:** 12 weekly individual sessions consisting of psychoeducation, and cognitive and behavioral anger management strategies Cognitive Behavioral Intervention: Includes individual therapy sessions using cognitive and behavioral strategies addressing problems with anger intensity / frequency / management **ID:** OG000 **Title:** Cognitive Behavioral Intervention ##### Group **Description:** 12 weekly individual sessions consisting of psychoeducation, problem-solving strategies, and support Supportive Intervention: Includes individual therapy sessions using supportive and problem-solving strategies. **ID:** OG001 **Title:** Supportive Intervention #### Outcome Measure 17 **Description:** The revised STAXI-2 is a 57 item self-report questionnaire that consists of five subscales and an anger expression index. The Anger Expression In subscale measures how often angry feelings are experienced but not expressed (suppressed). It consists of 8 items with a score range of 8-32. Higher scores indicate higher levels of experienced anger. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** Participants were randomly assigned to CBI or SI. Those with at least one post-baseline measure (4 wk, 8 wk, 12 wk (posttreatment), 3 mo and/or 6 mo f/u) were included in HLM analysis. Not all had post-baseline data, and some who didn't complete treatment had one or more post-baseline measures. Least Square means and differences adjusted for baseline and time effects from repeated measures ANCOVA are shown. Full Information Maximum Likelihood was used to account for missing data. **Reporting Status:** POSTED **Time Frame:** Baseline, weeks 4, 8, 12 (post-treatment), 3 and 6 month post-treatment **Title:** Least Squares Mean Anger Expression Scale Score on the State-Trait Anger Inventory Using a Repeated Measures ANCOVA Adjusted for Baseline Scores and Time Effects **Type:** POST_HOC **Unit of Measure:** score on a scale ##### Group **Description:** 12 weekly individual sessions consisting of psychoeducation, and cognitive and behavioral anger management strategies Cognitive Behavioral Intervention: Includes individual therapy sessions using cognitive and behavioral strategies addressing problems with anger intensity / frequency / management **ID:** OG000 **Title:** Cognitive Behavioral Intervention ##### Group **Description:** 12 weekly individual sessions consisting of psychoeducation, problem-solving strategies, and support Supportive Intervention: Includes individual therapy sessions using supportive and problem-solving strategies. **ID:** OG001 **Title:** Supportive Intervention #### Outcome Measure 18 **Description:** The STAXI-2 Anger Control Out subscale measures how often a person controls the outward expression of angry feelings. It consists of 8 items with a score range of 8 to 32. Higher scores reflect more effort in monitoring and preventing the outward expression of anger. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** Participants were randomly assigned to CBI or SI. Those with at least one post-baseline measure (posttreatment), 3 mo and/or 6 mo f/u) were included in HLM analysis. Not all had post-baseline data, and some who didn't complete treatment had one or more post-baseline measures. Least Square means and differences adjusted for baseline and time effects from repeated measures ANCOVA are shown. Full Information Maximum Likelihood was used to account for missing data. **Reporting Status:** POSTED **Time Frame:** Baseline, weeks 4, 8, 12 (post-treatment), 3 and 6 month post-treatment Baseline, weeks 4, 8, 12 (post-treatment), 3 and 6 month post-treatment **Title:** Least Squares Mean Score on the Anger Control Out Scale From the State Trait Anger Inventory-2 (STAXI-2) Using a Repeated Measures ANCOVA Adjusted for Baseline Scores and Time Effects **Type:** POST_HOC **Unit of Measure:** score on a scale ##### Group **Description:** 12 weekly individual sessions consisting of psychoeducation, and cognitive and behavioral anger management strategies Cognitive Behavioral Intervention: Includes individual therapy sessions using cognitive and behavioral strategies addressing problems with anger intensity / frequency / management **ID:** OG000 **Title:** Cognitive Behavioral Intervention ##### Group **Description:** 12 weekly individual sessions consisting of psychoeducation, problem-solving strategies, and support Supportive Intervention: Includes individual therapy sessions using supportive and problem-solving strategies. **ID:** OG001 **Title:** Supportive Intervention #### Outcome Measure 19 **Description:** The STAXI-2 Anger Control-In subscale measures how often a person attempts to control angry feelings by calming down or cooling off. It has 8 items with a score range of 8 to 32. Higher scores indicate more frequent attempts to control internal experiences of anger. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** Participants were randomly assigned to CBI or SI. Those with at least one post-baseline measure (4 wk, 8 wk, 12 wk (posttreatment), 3 mo and/or 6 mo f/u) were included in HLM analysis. Not all had post-baseline data, and some who didn't complete treatment had one or more post-baseline measures. Least Square means and differences adjusted for baseline and time effects from repeated measures ANCOVA are shown. Full Information Maximum Likelihood was used to account for missing data **Reporting Status:** POSTED **Time Frame:** Baseline, weeks 4, 8, 12 (post-treatment), 3 and 6 month post-treatment **Title:** Least Squares Mean Anger Control-In Score on the State-Trait Anger Expression Inventory-2 (STAXI-2) Using a Repeated Measures ANCOVA Adjusted for Baseline Scores and Time Effects **Type:** POST_HOC **Unit of Measure:** score on a scale ##### Group **Description:** 12 weekly individual sessions consisting of psychoeducation, and cognitive and behavioral anger management strategies Cognitive Behavioral Intervention: Includes individual therapy sessions using cognitive and behavioral strategies addressing problems with anger intensity / frequency / management **ID:** OG000 **Title:** Cognitive Behavioral Intervention ##### Group **Description:** 12 weekly individual sessions consisting of psychoeducation, problem-solving strategies, and support Supportive Intervention: Includes individual therapy sessions using supportive and problem-solving strategies. **ID:** OG001 **Title:** Supportive Intervention #### Outcome Measure 20 **Description:** The Symptom Distress subscale assesses symptoms of affective disorders, anxiety disorders, adjustment disorders and stress related illness. It consists of 25 items, with a score range from 0 to 100. Higher scores indicate more symptoms and distress. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** Participants were randomly assigned to CBI or SI. Those with one or more post-baseline assessments (wk 12, 3- and/or 6-mo follow-up) were included in HLM analyses. Not all participants had post-baseline data, and some who didn't complete treatment had one or more post-baseline measures. Least Square means and differences adjusted for baseline and time effects from repeated measures ANCOVA are shown. Full Information Maximum Likelihood was used to account for missing data. **Reporting Status:** POSTED **Time Frame:** Baseline, week 12 (end of treatment), 3 and 6 months post-treatment **Title:** Least Squares Mean Symptom Distress Score on the Outcomes Questionnaire Using a Repeated Measures ANCOVA Adjusted for Baseline Scores and Time Effects **Type:** POST_HOC **Unit of Measure:** score on a scale ##### Group **Description:** 12 weekly individual sessions consisting of psychoeducation, and cognitive and behavioral anger management strategies Cognitive Behavioral Intervention: Includes individual therapy sessions using cognitive and behavioral strategies addressing problems with anger intensity / frequency / management **ID:** OG000 **Title:** Cognitive Behavioral Intervention ##### Group **Description:** 12 weekly individual sessions consisting of psychoeducation, problem-solving strategies, and support Supportive Intervention: Includes individual therapy sessions using supportive and problem-solving strategies. **ID:** OG001 **Title:** Supportive Intervention #### Outcome Measure 21 **Description:** The OQ Interpersonal Relations subscale assesses complaints such as loneliness, conflicts with others, family and marriage problems. High scores reflect more difficulties in these areas. This subscale contains 11 items with a range of 0 to 44. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** Participants were randomly assigned to CBI or SI. Those with one or more post-baseline assessments (week 12, 3- and/or 6-month follow-up) were included in HLM analyses. Not all participants had post-baseline data, and some who didn't complete treatment had one or more post-baseline assessments. Least Square means and differences adjusted for baseline and time effects from repeated measures ANCOVA are shown. Full Information Maximum Likelihood was used to account for missing data. **Reporting Status:** POSTED **Time Frame:** Baseline, Week 12 (End of Treatment), 3 and 6 months post-treatment **Title:** Least Squares Mean Interpersonal Relations Scale Score on the Outcomes Questionnaire Using a Repeated Measures ANCOVA Adjusted for Baseline Scores and Time Effects **Type:** POST_HOC **Unit of Measure:** score on a scale ##### Group **Description:** 12 weekly individual sessions consisting of psychoeducation, and cognitive and behavioral anger management strategies Cognitive Behavioral Intervention: Includes individual therapy sessions using cognitive and behavioral strategies addressing problems with anger intensity / frequency / management **ID:** OG000 **Title:** Cognitive Behavioral Intervention ##### Group **Description:** 12 weekly individual sessions consisting of psychoeducation, problem-solving strategies, and support Supportive Intervention: Includes individual therapy sessions using supportive and problem-solving strategies. **ID:** OG001 **Title:** Supportive Intervention #### Outcome Measure 22 **Description:** The Social Role scale measures the extent to which difficulties in the social roles of worker, homemaker, or student are present. This subscale contains 9 items with a range of 0 to 36. Higher scores indicate more conflicts at work, overwork, distress, and inefficiency in these roles. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** Participants were randomly assigned to CBI or SI. Those with one or more post-baseline assessments (week 12, 3- and/or 6-month follow-up) were included in HLM analyses. Not all participants had post-baseline data, and some who didn't complete treatment had one or more post-baseline assessments. Least Square means and differences adjusted for baseline and time effects from repeated measures ANCOVA are shown. Full Information Maximum Likelihood was used to account for missing data. **Reporting Status:** POSTED **Time Frame:** Baseline, Week 12 (End of Treatment), 3 and 6 months post-treatment. **Title:** Mean Social Role Scale on the Outcomes Questionnaire Using a Repeated Measures ANCOVA Adjusted for Baseline Scores and Time Effects **Type:** POST_HOC **Unit of Measure:** units on a scale ##### Group **Description:** 12 weekly individual sessions consisting of psychoeducation, and cognitive and behavioral anger management strategies Cognitive Behavioral Intervention: Includes individual therapy sessions using cognitive and behavioral strategies addressing problems with anger intensity / frequency / management **ID:** OG000 **Title:** Cognitive Behavioral Intervention ##### Group **Description:** 12 weekly individual sessions consisting of psychoeducation, problem-solving strategies, and support Supportive Intervention: Includes individual therapy sessions using supportive and problem-solving strategies. **ID:** OG001 **Title:** Supportive Intervention ### Participant Flow Module #### Group **Description:** 12 weekly individual sessions consisting of psychoeducation, and cognitive and behavioral anger management strategies Cognitive Behavioral Intervention: Includes individual therapy sessions using cognitive and behavioral strategies addressing problems with anger intensity / frequency / management **ID:** FG000 **Title:** Cognitive Behavioral Intervention #### Group **Description:** 12 weekly individual sessions consisting of psychoeducation, problem-solving strategies, and support Supportive Intervention: Includes individual therapy sessions using supportive and problem-solving strategies. **ID:** FG001 **Title:** Supportive Intervention #### Period **Title:** Overall Study ##### Withdraw **Type:** Logistical ###### Reason **Group ID:** FG000 **Number of Subjects:** 9 ###### Reason **Group ID:** FG001 **Number of Subjects:** 3 ##### Withdraw **Type:** Stopped attending, reason unknown ###### Reason **Group ID:** FG000 **Number of Subjects:** 11 ###### Reason **Group ID:** FG001 **Number of Subjects:** 7 ##### Withdraw **Type:** No response to outreach after Baseline ###### Reason **Group ID:** FG000 **Number of Subjects:** 1 ###### Reason **Group ID:** FG001 **Number of Subjects:** 1 ##### Withdraw **Type:** Moved ###### Reason **Group ID:** FG000 **Number of Subjects:** 1 ###### Reason **Group ID:** FG001 **Number of Subjects:** 0 ##### Withdraw **Type:** Medical ###### Reason **Group ID:** FG000 **Number of Subjects:** 1 ###### Reason **Group ID:** FG001 **Number of Subjects:** 0 ##### Withdraw **Type:** Legal issue ###### Reason **Group ID:** FG000 **Number of Subjects:** 1 ###### Reason **Group ID:** FG001 **Number of Subjects:** 0 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 47 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 45 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 23 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 34 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 24 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 11 **Pre-Assignment Details:** Of the 112 enrolled, 94 completed both the first and second baseline assessments and were deemed eligible for the study. Of the 94 who completed their second baseline and were deemed eligible for the study, 92 were randomized to treatment. Two of the 92 randomized participants did not respond to outreach and did not start treatment. **Recruitment Details:** Participants were recruited from a wide range of sources during the time period of January 1, 2015 through January 31, 2018. The primary recruitment source was the Providence Veterans Affairs Medical Center, including the OEF/OIF specialty primary care clinic, the Returning Veterans Outreach Program (REVOC) and the PTSD Clinic. **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT01436279 **Acronym:** SaMi2 **Brief Title:** Mifepristone Versus Osmotic Dilator Insertion for Cervical Preparation Prior to Surgical Abortion at 15-18 Weeks **Official Title:** Mifepristone Versus Osmotic Dilator Insertion for Cervical Preparation Prior to Surgical Abortion at 15-18 Weeks #### Organization Study ID Info **ID:** H-31032 #### Organization **Class:** OTHER **Full Name:** Boston University #### Secondary ID Infos **Domain:** Society of Family Planning **ID:** AU 6003109 **Type:** OTHER_GRANT ### Status Module #### Completion Date **Date:** 2013-08 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2017-06-14 **Type:** ACTUAL **Last Update Submit Date:** 2017-05-16 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2013-08 **Type:** ACTUAL #### Results First Post Date **Date:** 2017-06-14 **Type:** ACTUAL **Results First Submit Date:** 2017-04-11 **Results First Submit QC Date:** 2017-05-16 #### Start Date **Date:** 2011-07 **Status Verified Date:** 2017-05 #### Study First Post Date **Date:** 2011-09-19 **Type:** ESTIMATED **Study First Submit Date:** 2011-09-15 **Study First Submit QC Date:** 2011-09-16 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** Society of Family Planning #### Lead Sponsor **Class:** OTHER **Name:** Boston University #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** True **Is US Export:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** In this study the investigators plan to compare mifepristone and misoprostol use to osmotic dilator use for cervical preparation for 15-18 week surgical abortion. Mifepristone would be given 24 hours prior to abortion, and misoprostol 400 mcg would be administered buccally 2 hours prior to abortion. Osmotic dilators are the method currently used in our institution, and are placed 24 hours prior to abortion. The primary outcome will be the length of the procedure. Secondary outcomes will include amount of dilation achieved, ease of procedure, participant's assessment of discomfort before mifepristone or dilators, discomfort during the abortion procedure, acceptability to participants, and acceptability to staff. ### Conditions Module **Conditions:** - Cervical Preparation ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 50 **Type:** ACTUAL **Phases:** - PHASE3 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Mifepristone 200 mg PO given 20-24 hours prior to procedure, misoprostol 400 mcg given 2 hours prior to procedure **Intervention Names:** - Drug: Mifepristone **Label:** Mifepristone + misoprostol **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Placed 20-24 hours prior to procedure **Intervention Names:** - Device: osmotic dilators **Label:** Osmotic dilators **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Mifepristone + misoprostol **Description:** 200 mg po 20-24 hours prior to the procedure **Name:** Mifepristone **Other Names:** - Mifeprex - RU-486 - Mifegyne **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Osmotic dilators **Description:** osmotic dilators placed in the cervix 20-24 hours prior to the procedure **Name:** osmotic dilators **Other Names:** - Laminaria - Dilapan-S - Dilapan **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Description:** Interval from speculum insertion to speculum removal **Measure:** Length of Procedure **Time Frame:** Subjects will be followed from the administration of mifepristone/misoprostol or laminaria, until the end of their procedure, a total of two days. #### Secondary Outcomes **Description:** Interval from initiation of vacuum aspiration to speculum removal **Measure:** Operative Time **Time Frame:** Subjects will be followed from the administration of mifepristone/misoprostol, or laminaria, until the end of their procedure, a total of two days. **Description:** Pain was subjectively described by the subjects as : None, Mild, Moderate, Severe **Measure:** Subject Discomfort Before the Abortion **Time Frame:** Subjects will be followed from the administration of mifepristone/misoprostol, or laminaria, until the end of their procedure, a total of two days. **Description:** Amount of pain medication used during the procedure: reported as micrograms of fentanyl **Measure:** Pain Medication (Fentanyl) During the Abortion **Time Frame:** Subjects will be followed from the administration of mifepristone/misoprostol, or laminaria, until the end of their procedure, a total of two days. **Description:** Amount of pain medication used during the procedure: reported as milligrams of midazolam **Measure:** Pain Medication (Midazolam) During the Abortion **Time Frame:** Subjects will be followed from the administration of mifepristone/misoprostol, or laminaria, until the end of their procedure, a total of two days. **Description:** Cervical dilation at start of procedure **Measure:** Cervical Dilation Achieved **Time Frame:** At time of abortion **Description:** Patient was asked whether they would choose to be in the same group again if they had a similar procedure again. The number of participants whose response was "yes" is being reported. **Measure:** Acceptability to Patient **Time Frame:** After procedure completion **Description:** Outcome measure is the number and percentage of participants where the provider rated the procedure as "difficult or very difficult". Provider assessment of difficulty of procedure categories were: "very easy", "easy", "moderate", "difficult", or "very difficult." **Measure:** Difficulty of Procedure **Time Frame:** After completion of procedure ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Women 18-50 years of age undergoing surgical termination of pregnancy * English or Spanish speaking * Gestational age between 15 and 18 weeks gestation on day of abortion (inclusive), by ultrasound dating * Eligible for a dilation and evacuation abortion with local anesthesia and sedation * Ultrasound for dating purposes done within the last two weeks Exclusion Criteria: * Intrauterine infection * Fetal demise * Ruptured membranes * Multiple gestation * Uterine anomaly or significant distortion of the uterus with fibroids * BMI greater than 45 * Inability to place osmotic dilators * Active substance abuse or intoxication * Adrenal failure, chronic corticosteroid use, anticoagulant usage * Severe cervicitis, until treated and resolved * Prior Cesarean section **Maximum Age:** 50 Years **Minimum Age:** 18 Years **Sex:** FEMALE **Standard Ages:** - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Boston **Country:** United States **Facility:** Boston University **State:** Massachusetts **Zip:** 02130 #### Overall Officials **Official 1:** **Affiliation:** Boston Medical Center **Name:** Sarita Sonalkar, MD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Intervention Browse Module - Ancestors - ID: D000000021 - Term: Abortifacient Agents, Steroidal - ID: D000000019 - Term: Abortifacient Agents - ID: D000012102 - Term: Reproductive Control Agents - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000003280 - Term: Contraceptives, Oral, Synthetic - ID: D000003276 - Term: Contraceptives, Oral - ID: D000003271 - Term: Contraceptive Agents, Female - ID: D000003270 - Term: Contraceptive Agents - ID: D000003283 - Term: Contraceptives, Postcoital, Synthetic - ID: D000003281 - Term: Contraceptives, Postcoital - ID: D000006727 - Term: Hormone Antagonists - ID: D000006730 - Term: Hormones, Hormone Substitutes, and Hormone Antagonists - ID: D000008186 - Term: Luteolytic Agents - ID: D000080066 - Term: Contraceptive Agents, Hormonal - ID: D000008600 - Term: Menstruation-Inducing Agents ### Intervention Browse Module - Browse Branches - Abbrev: Repr - Name: Reproductive Control Agents - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Gast - Name: Gastrointestinal Agents ### Intervention Browse Module - Browse Leaves - ID: M18300 - Name: Mifepristone - Relevance: HIGH - As Found: Debridement - ID: M18979 - Name: Misoprostol - Relevance: LOW - As Found: Unknown - ID: M6494 - Name: Contraceptive Agents - Relevance: LOW - As Found: Unknown - ID: M6500 - Name: Contraceptives, Oral - Relevance: LOW - As Found: Unknown - ID: M6495 - Name: Contraceptive Agents, Female - Relevance: LOW - As Found: Unknown - ID: M6505 - Name: Contraceptives, Postcoital - Relevance: LOW - As Found: Unknown - ID: M9789 - Name: Hormones - Relevance: LOW - As Found: Unknown - ID: M9788 - Name: Hormone Antagonists - Relevance: LOW - As Found: Unknown - ID: M2116 - Name: Contraceptive Agents, Hormonal - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000015735 - Term: Mifepristone ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module #### Event Groups **Group ID:** EG000 **Title:** Mifepristone + Misoprostol **Deaths Num At Risk:** 30 **Description:** Mifepristone 200 mg PO given 20-24 hours prior to procedure, misoprostol 400 mcg given 2 hours prior to procedure Mifepristone: 200 mg po 20-24 hours prior to the procedure **ID:** EG000 **Other Num at Risk:** 30 **Serious Number At Risk:** 30 **Title:** Mifepristone + Misoprostol **Group ID:** EG001 **Title:** Osmotic Dilators **Deaths Num At Risk:** 20 **Description:** Placed 20-24 hours prior to procedure osmotic dilators: osmotic dilators placed in the cervix 20-24 hours prior to the procedure **ID:** EG001 **Other Num at Risk:** 20 **Serious Number At Risk:** 20 **Title:** Osmotic Dilators **Frequency Threshold:** 0 **Time Frame:** 12 months ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 30 **Group ID:** BG001 **Value:** 20 **Group ID:** BG002 **Value:** 50 **Units:** Participants ### Group **ID:** BG000 **Title:** Mifepristone + Misoprostol **Description:** Mifepristone 200 mg PO given 20-24 hours prior to procedure, misoprostol 400 mcg given 2 hours prior to procedure ### Group **ID:** BG001 **Title:** Osmotic Dilators **Description:** Placed 20-24 hours prior to procedure ### Group **ID:** BG002 **Title:** Total **Description:** Total of all reporting groups ### Measure #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** <=18 years #### Measurement **Group ID:** BG000 **Value:** 30 #### Measurement **Group ID:** BG001 **Value:** 20 #### Measurement **Group ID:** BG002 **Value:** 50 **Category Title:** Between 18 and 65 years #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** >=65 years **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 30 #### Measurement **Group ID:** BG001 **Value:** 20 #### Measurement **Group ID:** BG002 **Value:** 50 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** Male **Class Title:** **Denomination Units Selected:** ## Results Section - Baseline Characteristics Module ### Measure 1 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Age, Categorical **Unit of Measure:** Participants ### Measure 2 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Sex: Female, Male **Unit of Measure:** Participants ## Results Section - More Information Module ### Certain Agreement **PI Sponsor Employee:** True ### Point of Contact **Email:** [email protected] **Organization:** Boston Medical Center **Phone:** 617 414 7304 **Title:** Olivera Vragovic ## Results Section - Outcome Measures Module ### Outcome Measure 1 ### Outcome Measure 2 ### Outcome Measure 3 ### Outcome Measure 4 ### Outcome Measure 5 ### Outcome Measure 6 ### Outcome Measure 7 ### Outcome Measure 8 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 12 - **Spread:** - **Upper Limit:** 17 - **Value:** 14 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 11 - **Spread:** - **Upper Limit:** 16 - **Value:** 13.5 **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 7 - **Spread:** - **Upper Limit:** 12 - **Value:** 9 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 7 - **Spread:** - **Upper Limit:** 9.5 - **Value:** 8.5 **Title:** #### Outcome Measure 3 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 18 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 7 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 7 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 6 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 5 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4 **Title:** #### Outcome Measure 4 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.34 - **Upper Limit:** - **Value:** 3.1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1 - **Upper Limit:** - **Value:** 2.9 **Title:** #### Outcome Measure 5 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 31 - **Upper Limit:** - **Value:** 104 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 26 - **Upper Limit:** - **Value:** 105 **Title:** #### Outcome Measure 6 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 11 - **Upper Limit:** - **Value:** 42 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 5 - **Upper Limit:** - **Value:** 56 **Title:** #### Outcome Measure 7 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 26 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 11 **Title:** #### Outcome Measure 8 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 5 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** Interval from speculum insertion to speculum removal **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEAN **Reporting Status:** POSTED **Time Frame:** Subjects will be followed from the administration of mifepristone/misoprostol or laminaria, until the end of their procedure, a total of two days. **Title:** Length of Procedure **Type:** PRIMARY **Unit of Measure:** minutes ##### Group **Description:** Mifepristone 200 mg PO given 20-24 hours prior to procedure, misoprostol 400 mcg given 2 hours prior to procedure **ID:** OG000 **Title:** Mifepristone + Misoprostol ##### Group **Description:** Placed 20-24 hours prior to procedure **ID:** OG001 **Title:** Osmotic Dilators #### Outcome Measure 2 **Description:** Interval from initiation of vacuum aspiration to speculum removal **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEDIAN **Reporting Status:** POSTED **Time Frame:** Subjects will be followed from the administration of mifepristone/misoprostol, or laminaria, until the end of their procedure, a total of two days. **Title:** Operative Time **Type:** SECONDARY **Unit of Measure:** minutes ##### Group **Description:** Mifepristone 200 mg PO given 20-24 hours prior to procedure, misoprostol 400 mcg given 2 hours prior to procedure Mifepristone: 200 mg po 20-24 hours prior to the procedure **ID:** OG000 **Title:** Mifepristone + Misoprostol ##### Group **Description:** Placed 20-24 hours prior to procedure osmotic dilators: osmotic dilators placed in the cervix 20-24 hours prior to the procedure **ID:** OG001 **Title:** Osmotic Dilators #### Outcome Measure 3 **Description:** Pain was subjectively described by the subjects as : None, Mild, Moderate, Severe **Parameter Type:** NUMBER **Reporting Status:** POSTED **Time Frame:** Subjects will be followed from the administration of mifepristone/misoprostol, or laminaria, until the end of their procedure, a total of two days. **Title:** Subject Discomfort Before the Abortion **Type:** SECONDARY **Unit of Measure:** participants ##### Group **Description:** Mifepristone 200 mg PO given 20-24 hours prior to procedure, misoprostol 400 mcg given 2 hours prior to procedure Mifepristone: 200 mg po 20-24 hours prior to the procedure **ID:** OG000 **Title:** Mifepristone + Misoprostol ##### Group **Description:** Placed 20-24 hours prior to procedure osmotic dilators: osmotic dilators placed in the cervix 20-24 hours prior to the procedure **ID:** OG001 **Title:** Osmotic Dilators #### Outcome Measure 4 **Description:** Amount of pain medication used during the procedure: reported as micrograms of fentanyl **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Reporting Status:** POSTED **Time Frame:** Subjects will be followed from the administration of mifepristone/misoprostol, or laminaria, until the end of their procedure, a total of two days. **Title:** Pain Medication (Fentanyl) During the Abortion **Type:** SECONDARY **Unit of Measure:** mcg ##### Group **Description:** Mifepristone 200 mg PO given 20-24 hours prior to procedure, misoprostol 400 mcg given 2 hours prior to procedure **ID:** OG000 **Title:** Mifepristone + Misoprostol ##### Group **Description:** Placed 20-24 hours prior to procedure **ID:** OG001 **Title:** Osmotic Dilators #### Outcome Measure 5 **Description:** Amount of pain medication used during the procedure: reported as milligrams of midazolam **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Reporting Status:** POSTED **Time Frame:** Subjects will be followed from the administration of mifepristone/misoprostol, or laminaria, until the end of their procedure, a total of two days. **Title:** Pain Medication (Midazolam) During the Abortion **Type:** SECONDARY **Unit of Measure:** mg ##### Group **Description:** Mifepristone 200 mg PO given 20-24 hours prior to procedure, misoprostol 400 mcg given 2 hours prior to procedure **ID:** OG000 **Title:** Mifepristone + Misoprostol ##### Group **Description:** Placed 20-24 hours prior to procedure **ID:** OG001 **Title:** Osmotic Dilators #### Outcome Measure 6 **Description:** Cervical dilation at start of procedure **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Reporting Status:** POSTED **Time Frame:** At time of abortion **Title:** Cervical Dilation Achieved **Type:** SECONDARY **Unit of Measure:** mm ##### Group **Description:** Mifepristone 200 mg PO given 20-24 hours prior to procedure, misoprostol 400 mcg given 2 hours prior to procedure Mifepristone: 200 mg po 20-24 hours prior to the procedure **ID:** OG000 **Title:** Mifepristone + Misoprostol ##### Group **Description:** Placed 20-24 hours prior to procedure osmotic dilators: osmotic dilators placed in the cervix 20-24 hours prior to the procedure **ID:** OG001 **Title:** Osmotic Dilators #### Outcome Measure 7 **Description:** Patient was asked whether they would choose to be in the same group again if they had a similar procedure again. The number of participants whose response was "yes" is being reported. **Parameter Type:** COUNT_OF_PARTICIPANTS **Reporting Status:** POSTED **Time Frame:** After procedure completion **Title:** Acceptability to Patient **Type:** SECONDARY **Unit of Measure:** Participants ##### Group **Description:** Mifepristone 200 mg PO given 20-24 hours prior to procedure, misoprostol 400 mcg given 2 hours prior to procedure Mifepristone: 200 mg po 20-24 hours prior to the procedure **ID:** OG000 **Title:** Mifepristone + Misoprostol ##### Group **Description:** Placed 20-24 hours prior to procedure osmotic dilators: osmotic dilators placed in the cervix 20-24 hours prior to the procedure **ID:** OG001 **Title:** Osmotic Dilators #### Outcome Measure 8 **Description:** Outcome measure is the number and percentage of participants where the provider rated the procedure as "difficult or very difficult". Provider assessment of difficulty of procedure categories were: "very easy", "easy", "moderate", "difficult", or "very difficult." **Parameter Type:** COUNT_OF_PARTICIPANTS **Reporting Status:** POSTED **Time Frame:** After completion of procedure **Title:** Difficulty of Procedure **Type:** SECONDARY **Unit of Measure:** Participants ##### Group **Description:** Mifepristone 200 mg PO given 20-24 hours prior to procedure, misoprostol 400 mcg given 2 hours prior to procedure Mifepristone: 200 mg po 20-24 hours prior to the procedure **ID:** OG000 **Title:** Mifepristone + Misoprostol ##### Group **Description:** Placed 20-24 hours prior to procedure osmotic dilators: osmotic dilators placed in the cervix 20-24 hours prior to the procedure **ID:** OG001 **Title:** Osmotic Dilators ### Participant Flow Module #### Group **Description:** Mifepristone 200 mg PO given 20-24 hours prior to procedure, misoprostol 400 mcg given 2 hours prior to procedure Mifepristone: 200 mg po 20-24 hours prior to the procedure **ID:** FG000 **Title:** Mifepristone + Misoprostol #### Group **Description:** Placed 20-24 hours prior to procedure osmotic dilators: osmotic dilators placed in the cervix 20-24 hours prior to the procedure **ID:** FG001 **Title:** Osmotic Dilators #### Period **Title:** Overall Study ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 30 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 20 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 30 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 20 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 0 **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT04314479 **Brief Title:** Improving Adherence to ACS Guidelines on Nutrition and Physical Activity in Latinas With Cancer and Their Informal Caregivers **Official Title:** Improving Adherence to American Cancer Society (ACS) Guidelines on Nutrition and Physical Activity Through Integrated Symptom Management in Latinas With Cancer and Their Informal Caregivers #### Organization Study ID Info **ID:** 1801209654 #### Organization **Class:** OTHER **Full Name:** University of Arizona ### Status Module #### Completion Date **Date:** 2019-06-16 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2020-03-19 **Type:** ACTUAL **Last Update Submit Date:** 2020-03-17 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2019-06-08 **Type:** ACTUAL #### Start Date **Date:** 2018-03-15 **Type:** ACTUAL **Status Verified Date:** 2020-03 #### Study First Post Date **Date:** 2020-03-19 **Type:** ACTUAL **Study First Submit Date:** 2020-03-16 **Study First Submit QC Date:** 2020-03-17 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** University of Arizona #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** This research study is testing the feasibility and acceptability of a 12-week intervention that integrates telephone coaching and printed materials about the ACS guidelines and healthy lifestyle behaviors in order to manage symptoms after treatment for cancer. We will recruit 57 dyads (the survivor plus one identified informal caregiver) from the community. **Detailed Description:** This research study is testing the feasibility and acceptability of a 12-week intervention that integrates telephone coaching and printed materials about the ACS guidelines and healthy lifestyle behaviors in order to manage symptoms after treatment for cancer. The study population is 36 Latinas who have recently completed treatment for solid tumor cancers and their informal caregiver (36 dyads). Research suggests that family members can be facilitators to behavior change more specifically, Latinos rely on family support more than non-Hispanic Whites. Fewer than 20% of Latina cancer survivors meet the American Cancer Society's (ACS) Guidelines on Nutrition and Physical Activity. Healthier lifestyle behaviors (such as diet and physical activity) would result in an immediate benefit of reduced symptoms and long-term benefit of improved health while lowering cancer risk. This pilot study tests an intervention that will help in lessening survivors' symptoms to improve adherence to the ACS guidelines for cancer prevention ultimately improving overall health. A telephone-based intervention does not require any in-person meetings (outside of initial recruitment) and lessens participant burden. The Specific Aims of this project are to evaluate this intervention among 36 survivors who have recently completed treatment for solid tumor cancers and their informal caregivers to 1) Determine the feasibility and acceptability of the intervention 2) Establish the preliminary efficacy for improvement in diet, physical activity, and quality of life for the dyads, and symptom burden for survivors through surveys given at baseline and study completion as well as a weekly symptom distress survey. ### Conditions Module **Conditions:** - Cancer **Keywords:** - Cancer - Cancer symptoms - Cancer survivors - Latina - Nutrition - Healthy lifestyle ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 144 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** The intervention condition will involve weekly symptom assessment and health coaching to manage symptoms and to meet the ACS cancer prevention guidelines provided over the telephone by trained health coaches. Participants will be completing the same forms/assessments throughout the study. The content will be built around the Symptom Management Toolkit. The coaching will be dictated by the symptoms the survivor or the support person is experiencing the week of the intervention call. All calls begin with the symptom assessments, only the intervention arm includes intervention coaching that focuses on physical activity, stress management, or eating a healthy diet to improve adherence to the ACS guidelines for cancer prevention. We anticipate coaching sessions will last approximately 20 - 45 minutes **Intervention Names:** - Behavioral: Symptom Assessment and Health Coaching **Label:** Symptom Assessment and Health Coaching **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** For participants randomized to the control condition weekly symptom assessment telephone calls will be completed by staff at the University of Arizona Cancer Center Behavioral Measurements Interventions Shared Resource (BMISR). At week 13 an exit interview will be completed by the study coordinator to record participants feedback regarding study intervention, length, coaches, etc... In addition, staff from BMISR will call to repeat all baseline measures with the exception of the demographic questionnaires. Symptom assessment calls will take approximately 15 minutes. **Intervention Names:** - Behavioral: Symptom Assessment and Health Coaching **Label:** Symptom Assessment Only **Type:** OTHER ### Interventions #### Intervention 1 **Arm Group Labels:** - Symptom Assessment Only - Symptom Assessment and Health Coaching **Description:** The intervention condition will involve weekly symptom assessment and health coaching to manage symptoms and to meet the ACS cancer prevention guidelines provided over the telephone by trained health coaches. Participants will be completing the same forms/assessments throughout the study. The content will be built around the Symptom Management Toolkit. The coaching will be dictated by the symptoms the survivor or the support person is experiencing the week of the intervention call. All calls begin with the symptom assessments, only the intervention arm includes intervention coaching that focuses on physical activity, stress management, or eating a healthy diet to improve adherence to the ACS guidelines for cancer prevention. We anticipate coaching sessions will last approximately 20 - 45 minutes. **Name:** Symptom Assessment and Health Coaching **Type:** BEHAVIORAL ### Outcomes Module #### Primary Outcomes **Description:** Feasibility assessed by consent rate of 50% and 2) completion rate of intervention of 80% Acceptability assessed by open-ended questions as part of exit interview/satisfaction survey at end of study (80% benchmark for dyads considering intervention helpful). **Measure:** Determine the feasibility **Time Frame:** 12 weeks **Description:** Acceptability assessed by completion rate of intervention of 80%. Acceptability assessed by open-ended questions as part of exit interview/satisfaction survey at end of study (80% benchmark for dyads considering intervention helpful). **Measure:** Determine acceptability **Time Frame:** 12 weeks **Description:** Preliminary efficacy for improvement assessed utilizing NCI Dietary Screener Questionnaire for diet. **Measure:** Establish preliminary efficacy in diet adherence. **Time Frame:** 12 weeks **Description:** Preliminary efficacy for improvement assessed utilizing Women's Health Initiative (WHI) Physical Activity Questionnaire for physical activity. **Measure:** Establish preliminary efficacy in physical activity adherence. **Time Frame:** 12 weeks **Description:** Preliminary efficacy for improvement assessed utilizing General Symptom Distress Scale for symptoms/QoL and Patient Reported Outcomes Measurement Information System (PROMIS) Self-Efficacy Short Form for self-efficacy for symptom management. **Measure:** Establish preliminary efficacy via symptom improvement. **Time Frame:** 12 weeks ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: Patients * Female * at least 18 years of age * diagnosis of cancer * speak and understand English or Spanish * are finishing (or have finished) curative intent cancer treatment and do not have any subsequent cancer treatments planned, except for hormonal therapy or trastuzumab for breast cancer. * Patients must also have at least 1 of the 5 most common cancer-related symptoms (pain, sleep disturbance, anxiety, depression and/or fatigue) with a severity score of 4 or higher (2 or higher for depression) on a 0-10 rating scale which is based on the National Comprehensive Cancer Network guidelines for symptom monitoring. Caregivers * must be 18 years or older * able to speak and understand English or Spanish * not currently treated for cancer preserving the distinction between survivor and caregiver. **Gender Based:** True **Gender Description:** Patients must be female; caregiver may be male or female **Minimum Age:** 18 Years **Sex:** FEMALE **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Tucson **Country:** United States **Facility:** University of Arizona Cancer Center **State:** Arizona **Zip:** 85724 #### Overall Officials **Official 1:** **Affiliation:** University of Arizona **Name:** Tracy E. Crane, PhD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT02006979 **Brief Title:** Acute Exercise Cardioprotection From Doxorubicin **Official Title:** The Effects of Exercise Before Doxorubicin Chemotherapy on Cardiac Function #### Organization Study ID Info **ID:** H13-03090 #### Organization **Class:** OTHER **Full Name:** University of British Columbia ### Status Module #### Completion Date **Date:** 2016-05-25 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2019-10-25 **Type:** ACTUAL **Last Update Submit Date:** 2019-10-23 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2016-05-25 **Type:** ACTUAL #### Results First Post Date **Date:** 2019-10-25 **Type:** ACTUAL **Results First Submit Date:** 2017-11-08 **Results First Submit QC Date:** 2019-10-23 #### Start Date **Date:** 2016-01-15 **Type:** ACTUAL **Status Verified Date:** 2019-10 #### Study First Post Date **Date:** 2013-12-10 **Type:** ESTIMATED **Study First Submit Date:** 2013-12-05 **Study First Submit QC Date:** 2013-12-05 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** British Columbia Cancer Agency #### Lead Sponsor **Class:** OTHER **Name:** University of British Columbia #### Responsible Party **Investigator Affiliation:** University of British Columbia **Investigator Full Name:** Kristin Campbell **Investigator Title:** Dr. Kristin Campbell **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** In rodents, a single bout of exercise prior to injection of a chemotherapy agent used to treat breast cancer prevents or attenuates a number of markers of cardiac injury. This study will investigate whether this finding translates to human breast cancer patients. Participants scheduled to receive chemotherapy for breast cancer will be randomized to exercise or no exercise 24 hours prior to every chemotherapy treatment. The effect on cardiac function will be compared between groups noninvasively by echocardiography and electrocardiography and a venous blood draw at baseline before chemotherapy, after the first treatment and at the end of chemotherapy. **Detailed Description:** 1. Purpose The purpose of this study is to investigate whether performing a single bout of exercise 24 hours prior to receiving infusions of the anthracycline chemotherapy agent doxorubicin for breast cancer can prevent some of the damaging cardiac effects. Currently, doxorubicin is the most effective chemotherapy agent for breast cancer but is also the most damaging. As such, increased risk of cardiovascular disease is a growing concern in doxorubicin-treated patients. Current strategies for minimizing cardiac injury are dose reduction and discontinuation of therapy, which compromise the effectiveness of the treatment. Interventions that can minimize the cardiac injury associated with doxorubicin could reduce cancer-related and cardiovascular disease-related mortality in women diagnosed with breast cancer. 2. Hypotheses 1. Performing an acute bout of exercise within 24 hours before anthracycline infusion will decrease the acute negative change in subclinical markers of cardiotoxicity after the first anthracycline infusion seen in those who do not exercise for 72 hours prior. 2. Performing exercise within 24 hours before every infusion of anthracycline will decrease the negative change in markers of cardiac dysfunction seen at the end of chemotherapy in those who do not exercise for 72 hours prior to each infusion. 3) Justification An acute exercise bout prior to induction of a myocardial infarction in animals provides cardioprotective benefit by reducing the size of the infarct relative to control animals. Recently, acute exercise performed 24 hours before anthracycline injection in rodents has also provided a cardioprotective benefit. Oxidative stress and apoptosis of cardiomyocyte mitochondria are primary mechanisms of anthracycline-induced cardiotoxicity. The single acute bout of exercise prevented or attenuated some of the anthracycline-induced negative effects on cardiomyocytes including oxidative stress, apoptosis, mitochondrial dysfunction, as well as systolic dysfunction. There are no studies to date that have investigated the cardiac effects of an acute bout of exercise in close proximity to anthracycline infusion in humans. Aerobic exercise training is recommended throughout chemotherapy treatment, but there are no guidelines in place in terms of the timing of exercise in relation to receipt of chemotherapy infusions. 4) Objectives 1. To compare the acute effect of performing exercise (within 24 hours before the first infusion) compared to no exercise (no exercise for 72 hours prior to the first infusion) on markers of subclinical cardiotoxicity 24-48 hours after the first anthracycline infusion. 2. To compare the chronic effect of performing exercise (within 24 hours before every infusion) compared to no exercise (no exercise for 72 hours prior to every infusion) on markers of cardiotoxicity 7 to 14 days after the final anthracycline infusion 5) Research Method This study will be a two-arm randomized control trial. Twenty-four women aged 18 or older newly diagnosed with stage I-IIIA breast cancer, and scheduled to receive neoadjuvant or adjuvant doxorubicin chemotherapy in cycles of 2-3 weeks will be recruited by oncologist referral and posters. Participants will be randomized to one of two conditions: i) an acute bout of exercise performed ≤24 hours prior to each cycle of anthracyclines and no exercise for 48 hours post; or ii) no exercise for 72 hours prior or 48 hours post each cycle of anthracyclines. 6) Statistical Analysis The primary outcome will be global longitudinal strain measured by echocardiography. The secondary outcomes will be the NT-proBNP and cardiac troponin T cardiac biomarkers measured with an assay of blood taken via venous blood draw, echocardiography-derived left ventricular twist. The exploratory outcome measure will be treatment symptoms as reported by the Rotterdam Symptom Checklist. Cardiac outcome measures will be performed at the following time points: 1) Post diagnosis and prior to the first cycle of anthracyclines; 2) 24-48 hours after the first cycle; 3) at least one week after the last cycle of anthracyclines, but before subsequent chemotherapy treatments. The Rotterdam will be performed at baseline and within the last few days of each treatment cycle. Baseline characteristics of the two groups will be compared with independent t-tests. Descriptive statistics and frequencies will be calculated for all continuous and categorical variables. The acute effect will be determined by the difference between time points 1) and 2). The chronic effect will be determined by the difference between time points 1) and 3). For each analysis, a linear mixed model with time as a fixed and repeated effect, group as a fixed effect, and a time by condition (2 x 2) interaction will be used. If the interaction effect is not statistically significant, the main effects of time and condition will be explored. An alpha of 0.05 will be used for all analyses. ### Conditions Module **Conditions:** - Breast Cancer **Keywords:** - cardiotoxicity - Chemotherapy, Adjuvant - Breast Neoplasms - Exercise - Cardiotoxins - Echocardiography - Speckle tracking - Biological Markers - Electrocardiography ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** SINGLE **Who Masked:** - OUTCOMES_ASSESSOR **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 27 **Type:** ACTUAL **Phases:** - PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** an acute bout of exercise performed ≤24 hours prior to each cycle of anthracyclines and no exercise for 48 hours post **Intervention Names:** - Other: exercise **Label:** Exercise **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** no exercise for 72 hours prior or 48 hours post each cycle of anthracyclines **Label:** No exercise **Type:** NO_INTERVENTION ### Interventions #### Intervention 1 **Arm Group Labels:** - Exercise **Description:** An acute bout of exercise performed 24 hours prior to every anthracycline infusion. **Name:** exercise **Type:** OTHER ### Outcomes Module #### Other Outcomes **Description:** As assessed by standardized scores of physical and psychological distress by the Rotterdam Symptom Checklist **Measure:** Patient-reported Symptoms **Time Frame:** <1 week before the first doxorubicin, <3 days before the 2nd, 3rd, and 4th doxorubicin, 7-14 days after completion of the last doxorubicin cycle #### Primary Outcomes **Description:** Assessed with 2D speckle tracking echocardiography **Measure:** Global Longitudinal Strain **Time Frame:** 24-48 hours after first doxorubicin and 7-14 days after completion of last doxorubicin cycle #### Secondary Outcomes **Description:** biomarker of cardiac injury **Measure:** NT-proBNP **Time Frame:** 24-48 hours after first doxorubicin and 7-14 days after completion of last doxorubicin cycle **Description:** biomarker of cardiac injury **Measure:** Cardiac Troponin T **Time Frame:** 24-48 hours after first doxorubicin and 7-14 days after completion of last doxorubicin cycle **Description:** Assessed with 2D speckle tracking echocardiography **Measure:** LV Twist **Time Frame:** 24-48 hours after first doxorubicin and 7-14 days after completion of last doxorubicin cycle ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * newly diagnosed with stage I-IIIA breast cancer * scheduled to receive neoadjuvant or adjuvant doxorubicin chemotherapy in cycles of 2-3 weeks long * receive their oncologist's approval to exercise * be able to complete first time point of data collection prior to first chemotherapy cycle * be able to understand and provide written informed consent in English Exclusion Criteria: * concurrent participation in a structured exercise program or study * have orthopedic limitations to exercise * pre-existing cardiovascular disease * uncontrolled hypertension (blood pressure ≥ 140/90 mmHg) * uncontrolled diabetes * respiratory disease * current smoking status **Minimum Age:** 18 Years **Sex:** FEMALE **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Vancouver **Country:** Canada **Facility:** University of British Columbia Breast Cancer Research Exercise Gym **State:** British Columbia **Zip:** V5Z 4C2 #### Overall Officials **Official 1:** **Affiliation:** University of British Columbia **Name:** Kristin L Campbell, PhD **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC17 - Name: Skin and Connective Tissue Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: BC25 - Name: Substance Related Disorders - Abbrev: BC26 - Name: Wounds and Injuries - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M5220 - Name: Breast Neoplasms - Relevance: LOW - As Found: Unknown - ID: M30670 - Name: Cardiotoxicity - Relevance: LOW - As Found: Unknown - ID: T170 - Name: Acute Graft Versus Host Disease - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Browse Branches - Abbrev: ANeo - Name: Antineoplastic Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M7492 - Name: Doxorubicin - Relevance: LOW - As Found: Unknown - ID: M227339 - Name: Liposomal doxorubicin - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module **Description:** Serious adverse events related to the study intervention. #### Event Groups **Group ID:** EG000 **Title:** Exercise **Description:** an acute bout of exercise performed ≤24 hours prior to each cycle of anthracyclines and no exercise for 48 hours post exercise **ID:** EG000 **Other Num at Risk:** 13 **Serious Number At Risk:** 13 **Title:** Exercise **Group ID:** EG001 **Title:** Usual Care **Description:** no exercise for 72 hours prior or 48 hours post each cycle of anthracyclines **ID:** EG001 **Other Num at Risk:** 11 **Serious Number At Risk:** 11 **Title:** Usual Care **Frequency Threshold:** 0 **Time Frame:** During intervention period which lasted from shortly prior to the first doxorubicin treatment to 7-14 days after the last doxorubicin treatment. ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 13 **Group ID:** BG001 **Value:** 11 **Group ID:** BG002 **Value:** 24 **Units:** Participants ### Group **ID:** BG000 **Title:** Exercise **Description:** an acute bout of exercise performed ≤24 hours prior to each cycle of anthracyclines and no exercise for 48 hours post exercise ### Group **ID:** BG001 **Title:** Usual Care **Description:** no exercise for 72 hours prior or 48 hours post each cycle of anthracyclines ### Group **ID:** BG002 **Title:** Total **Description:** Total of all reporting groups ### Measure #### Measurement **Group ID:** BG000 **Spread:** 9 **Value:** 50 #### Measurement **Group ID:** BG001 **Spread:** 10 **Value:** 50 #### Measurement **Group ID:** BG002 **Spread:** 9 **Value:** 50 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 13 #### Measurement **Group ID:** BG001 **Value:** 11 #### Measurement **Group ID:** BG002 **Value:** 24 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** Male **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** American Indian or Alaska Native #### Measurement **Group ID:** BG000 **Value:** 2 #### Measurement **Group ID:** BG001 **Value:** 3 #### Measurement **Group ID:** BG002 **Value:** 5 **Category Title:** Asian #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** Native Hawaiian or Other Pacific Islander #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** Black or African American #### Measurement **Group ID:** BG000 **Value:** 11 #### Measurement **Group ID:** BG001 **Value:** 7 #### Measurement **Group ID:** BG002 **Value:** 18 **Category Title:** White #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** More than one race #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 1 #### Measurement **Group ID:** BG002 **Value:** 1 **Category Title:** Unknown or Not Reported **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 13 #### Measurement **Group ID:** BG001 **Value:** 11 #### Measurement **Group ID:** BG002 **Value:** 24 **Class Title:** Canada ### Measure #### Measurement **Group ID:** BG000 **Spread:** 11.7 **Value:** 69.7 #### Measurement **Group ID:** BG001 **Spread:** 12.7 **Value:** 72.2 #### Measurement **Group ID:** BG002 **Spread:** 12.7 **Value:** 71.9 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Spread:** 1.0 **Value:** 13.0 #### Measurement **Group ID:** BG001 **Spread:** 1.1 **Value:** 12.7 #### Measurement **Group ID:** BG002 **Spread:** 1.0 **Value:** 12.8 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Lower Limit:** 0 **Upper Limit:** 701 **Value:** 214 #### Measurement **Group ID:** BG001 **Lower Limit:** 0 **Upper Limit:** 619 **Value:** 124 #### Measurement **Group ID:** BG002 **Lower Limit:** 0 **Upper Limit:** 701 **Value:** 165 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Spread:** 4 **Value:** 57 #### Measurement **Group ID:** BG001 **Spread:** 3 **Value:** 58 #### Measurement **Group ID:** BG002 **Spread:** 3 **Value:** 58 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Spread:** 0.6 **Value:** 3.2 #### Measurement **Group ID:** BG001 **Spread:** 0.5 **Value:** 3.0 #### Measurement **Group ID:** BG002 **Spread:** 0.5 **Value:** 3.1 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Spread:** 11 **Value:** 69 #### Measurement **Group ID:** BG001 **Spread:** 12 **Value:** 69 #### Measurement **Group ID:** BG002 **Spread:** 11 **Value:** 69 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Spread:** 445 **Value:** 1933 #### Measurement **Group ID:** BG001 **Spread:** 514 **Value:** 2074 #### Measurement **Group ID:** BG002 **Spread:** 472 **Value:** 1998 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Spread:** 0.37 **Value:** 1.20 #### Measurement **Group ID:** BG001 **Spread:** 0.32 **Value:** 1.27 #### Measurement **Group ID:** BG002 **Spread:** 0.34 **Value:** 1.23 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Spread:** 10 **Value:** 75 #### Measurement **Group ID:** BG001 **Spread:** 11 **Value:** 76 #### Measurement **Group ID:** BG002 **Spread:** 11 **Value:** 76 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Spread:** 4.8 **Value:** 25.0 #### Measurement **Group ID:** BG001 **Spread:** 5.1 **Value:** 26.7 #### Measurement **Group ID:** BG002 **Spread:** 4.9 **Value:** 25.8 **Class Title:** **Denomination Units Selected:** ## Results Section - Baseline Characteristics Module ### Measure 1 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** Age, Continuous **Unit of Measure:** years ### Measure 2 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Sex: Female, Male **Unit of Measure:** Participants ### Measure 3 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Race (NIH/OMB) **Unit of Measure:** Participants ### Measure 4 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Region of Enrollment **Unit of Measure:** Participants ### Measure 5 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** Body weight **Unit of Measure:** kg ### Measure 6 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** Hemoglobin **Unit of Measure:** g/dL ### Measure 7 **Dispersion Type:** FULL_RANGE **Parameter Type:** MEDIAN **Title:** 6-month MVPA **Unit of Measure:** average weekly minutes ### Measure 8 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** LVEF **Unit of Measure:** % ### Measure 9 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** Cardiac output **Unit of Measure:** L/min ### Measure 10 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** Resting HR **Unit of Measure:** beats per minute ### Measure 11 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** Systemic vascular resistance **Unit of Measure:** dynes·sec·cm-5 ### Measure 12 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** E/A ratio **Unit of Measure:** no units ### Measure 13 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** Mean arterial pressure **Unit of Measure:** mmHg ### Measure 14 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** Body mass index **Unit of Measure:** kg/m2 **Population Description:** One participant in the usual care group did not complete baseline assessment. One participant in usual care group completed baseline assessment before protocol violation (did not receive any of study drug) and was excluded. One participant in the exercise group withdrew immediately after the baseline assessment and did not start the intervention. ## Results Section - More Information Module ### Certain Agreement ### Point of Contact **Email:** [email protected] **Organization:** University of Alberta **Phone:** 7804926874 **Title:** Dr. Amy Kirkham, Postdoctoral Research Fellow ## Results Section - Outcome Measures Module ### Outcome Measure 1 ### Outcome Measure 2 ### Outcome Measure 3 ### Outcome Measure 4 ### Outcome Measure 5 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.9 - **Upper Limit:** - **Value:** 19.2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.9 - **Upper Limit:** - **Value:** -19.6 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.8 - **Upper Limit:** - **Value:** 21.4 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.6 - **Upper Limit:** - **Value:** -21.5 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.4 - **Upper Limit:** - **Value:** -18.7 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.6 - **Upper Limit:** - **Value:** -20.3 **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 30 - **Upper Limit:** - **Value:** 52 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 35 - **Upper Limit:** - **Value:** 59 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 77 - **Upper Limit:** - **Value:** 214 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 151 - **Upper Limit:** - **Value:** 323 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 78 - **Upper Limit:** - **Value:** 106 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 39 - **Upper Limit:** - **Value:** 77 **Title:** #### Outcome Measure 3 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 2.1 - **Upper Limit:** - **Value:** 1.3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 2.3 - **Upper Limit:** - **Value:** 1.5 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 3.2 - **Upper Limit:** - **Value:** 2.6 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 2.6 - **Upper Limit:** - **Value:** 1.9 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 11.2 - **Upper Limit:** - **Value:** 13.6 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 8.3 - **Upper Limit:** - **Value:** 11.6 **Title:** #### Outcome Measure 4 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 7.6 - **Upper Limit:** - **Value:** 16.4 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 5.9 - **Upper Limit:** - **Value:** 16.4 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 8.5 - **Upper Limit:** - **Value:** 20.3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 7.8 - **Upper Limit:** - **Value:** 22.4 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 6.5 - **Upper Limit:** - **Value:** 15.7 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 6.6 - **Upper Limit:** - **Value:** 15.6 **Title:** #### Outcome Measure 5 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** Assessed with 2D speckle tracking echocardiography **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Reporting Status:** POSTED **Time Frame:** 24-48 hours after first doxorubicin and 7-14 days after completion of last doxorubicin cycle **Title:** Global Longitudinal Strain **Type:** PRIMARY **Unit of Measure:** % deformation ##### Group **Description:** an acute bout of exercise performed ≤24 hours prior to each cycle of anthracyclines and no exercise for 48 hours post exercise **ID:** OG000 **Title:** Exercise ##### Group **Description:** no exercise for 72 hours prior or 48 hours post each cycle of anthracyclines **ID:** OG001 **Title:** Usual Care #### Outcome Measure 2 **Description:** biomarker of cardiac injury **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Reporting Status:** POSTED **Time Frame:** 24-48 hours after first doxorubicin and 7-14 days after completion of last doxorubicin cycle **Title:** NT-proBNP **Type:** SECONDARY **Unit of Measure:** pg/mL ##### Group **Description:** an acute bout of exercise performed ≤24 hours prior to each cycle of anthracyclines and no exercise for 48 hours post exercise **ID:** OG000 **Title:** Exercise ##### Group **Description:** no exercise for 72 hours prior or 48 hours post each cycle of anthracyclines **ID:** OG001 **Title:** Usual Care #### Outcome Measure 3 **Description:** biomarker of cardiac injury **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Reporting Status:** POSTED **Time Frame:** 24-48 hours after first doxorubicin and 7-14 days after completion of last doxorubicin cycle **Title:** Cardiac Troponin T **Type:** SECONDARY **Unit of Measure:** pg/mL ##### Group **Description:** an acute bout of exercise performed ≤24 hours prior to each cycle of anthracyclines and no exercise for 48 hours post exercise **ID:** OG000 **Title:** Exercise ##### Group **Description:** no exercise for 72 hours prior or 48 hours post each cycle of anthracyclines **ID:** OG001 **Title:** Usual Care #### Outcome Measure 4 **Description:** Assessed with 2D speckle tracking echocardiography **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Reporting Status:** POSTED **Time Frame:** 24-48 hours after first doxorubicin and 7-14 days after completion of last doxorubicin cycle **Title:** LV Twist **Type:** SECONDARY **Unit of Measure:** degrees ##### Group **Description:** an acute bout of exercise performed ≤24 hours prior to each cycle of anthracyclines and no exercise for 48 hours post exercise **ID:** OG000 **Title:** Exercise ##### Group **Description:** no exercise for 72 hours prior or 48 hours post each cycle of anthracyclines **ID:** OG001 **Title:** Usual Care #### Outcome Measure 5 **Description:** As assessed by standardized scores of physical and psychological distress by the Rotterdam Symptom Checklist **Reporting Status:** NOT_POSTED **Time Frame:** <1 week before the first doxorubicin, <3 days before the 2nd, 3rd, and 4th doxorubicin, 7-14 days after completion of the last doxorubicin cycle **Title:** Patient-reported Symptoms **Type:** OTHER_PRE_SPECIFIED ### Participant Flow Module #### Group **Description:** an acute bout of exercise performed ≤24 hours prior to each cycle of anthracyclines and no exercise for 48 hours post exercise: An acute bout of exercise performed 24 hours prior to every anthracycline infusion. **ID:** FG000 **Title:** Exercise #### Group **Description:** no exercise for 72 hours prior or 48 hours post each cycle of anthracyclines **ID:** FG001 **Title:** Usual Care #### Period **Title:** Overall Study ##### Withdraw **Type:** Withdrawal by Subject ###### Reason **Group ID:** FG000 **Number of Subjects:** 1 ###### Reason **Group ID:** FG001 **Number of Subjects:** 1 ##### Withdraw **Type:** Protocol Violation ###### Reason **Group ID:** FG000 **Number of Subjects:** 0 ###### Reason **Group ID:** FG001 **Number of Subjects:** 1 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 14 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 13 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 13 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 11 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 1 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 2 **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT03173079 **Brief Title:** Geriatric Assessment and Outcome in Patients Undergoing Transcatheter Aortic Valve Replacement **Official Title:** Geriatric Assessment and Outcome in Patients Undergoing Transcatheter Aortic Valve Replacement #### Organization Study ID Info **ID:** CampusBN #### Organization **Class:** OTHER **Full Name:** Campus Bad Neustadt ### Status Module #### Completion Date **Date:** 2020-09-15 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2021-02-01 **Type:** ACTUAL **Last Update Submit Date:** 2021-01-27 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2019-03-15 **Type:** ACTUAL #### Start Date **Date:** 2017-03-15 **Type:** ACTUAL **Status Verified Date:** 2021-01 #### Study First Post Date **Date:** 2017-06-01 **Type:** ACTUAL **Study First Submit Date:** 2017-05-30 **Study First Submit QC Date:** 2017-05-31 ### Sponsor Collaborators Module #### Collaborators **Class:** UNKNOWN **Name:** Rhönklinikum AG #### Lead Sponsor **Class:** OTHER **Name:** Campus Bad Neustadt #### Responsible Party **Investigator Affiliation:** Campus Bad Neustadt **Investigator Full Name:** Sebastian Barth **Investigator Title:** PI **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** A geriatric assessment is becoming increasingly important in the treatment of patients with a percutaneous aortic valve replacement due to their comorbidities. The aim of this multimodal therapy concept is to examine the influence on the postoperative outcome. In addition to a comprehensive assessment of the individual frailty score, the subjective condition before and after TAVI is also evaluated using a standardized questionnaire ("Minnesota living with heart failure questionnaire"). ### Conditions Module **Conditions:** - Influence of Geriatric Functional State on the Outcome After TAVI - Possible Change in Geriatric Assessment After TAVI ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 220 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module ### Interventions #### Intervention 1 **Description:** geriatric assessment **Name:** pre- and postinterventional geriatric assessment in patients undergoing TAVI **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** self reported quality of life **Measure:** Quality of Live score in the "Minnesota living with heart failure questionnaire" **Time Frame:** 6 month **Description:** multimodal geriatric assessment including cognitive Status (MMST, clock test, Tinetti test, stand up and go-test) **Measure:** frailty score **Time Frame:** 6 month **Description:** phone call follow-up **Measure:** mortality after TAVI **Time Frame:** 6 month ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * all patients with indication for TAVI according to the current guidelines Exclusion Criteria: * no indication for TAVI, indication for cardiac surgery, mentally disabled patients, patients with endocarditis or life expectancy of less than 2 years **Minimum Age:** 70 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - OLDER_ADULT **Study Population:** all-comers cohort ### Contacts Locations Module #### Locations **Location 1:** **City:** Bad Neustadt an der Saale **Country:** Germany **Facility:** Cardiovascular Center Bad Neustadt **State:** Bavaria **Zip:** 97616 #### Overall Officials **Official 1:** **Affiliation:** Cardiovascular Center Bad Neustadt **Name:** Sebastian Barth, MD **Role:** PRINCIPAL_INVESTIGATOR **Official 2:** **Affiliation:** Cardiovascular Center Bad Neustadt **Name:** Karsten Hamm, MD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** UNDECIDED ## Derived Section ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT02243579 **Brief Title:** Pembrolizumab in Treating Patients With Relapsed or Refractory Stage IB-IVB Mycosis Fungoides or Sezary Syndrome **Official Title:** A Phase 2 Study of MK-3475 for the Treatment of Relapsed/Refractory Mycosis Fungoides/Sezary Syndrome #### Organization Study ID Info **ID:** NCI-2014-00709 #### Organization **Class:** NIH **Full Name:** National Cancer Institute (NCI) #### Secondary ID Infos **Domain:** CTRP (Clinical Trial Reporting Program) **ID:** NCI-2014-00709 **Type:** REGISTRY **Domain:** Cancer Immunotherapy Trials Network **ID:** CITN-10 **Type:** OTHER **Domain:** CTEP **ID:** CITN-10 **Type:** OTHER **ID:** P30CA015704 **Link:** https://reporter.nih.gov/quickSearch/P30CA015704 **Type:** NIH **ID:** U01CA154967 **Link:** https://reporter.nih.gov/quickSearch/U01CA154967 **Type:** NIH ### Status Module #### Completion Date **Date:** 2019-04-01 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2019-09-20 **Type:** ACTUAL **Last Update Submit Date:** 2019-08-29 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2018-01-04 **Type:** ACTUAL #### Results First Post Date **Date:** 2019-02-05 **Type:** ACTUAL **Results First Submit Date:** 2019-01-07 **Results First Submit QC Date:** 2019-01-11 #### Start Date **Date:** 2014-10-15 **Type:** ACTUAL **Status Verified Date:** 2019-08 #### Study First Post Date **Date:** 2014-09-18 **Type:** ESTIMATED **Study First Submit Date:** 2014-09-16 **Study First Submit QC Date:** 2014-09-16 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** NIH **Name:** National Cancer Institute (NCI) #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** This phase II trial studies how well pembrolizumab works in treating patients with stage IB-IVB mycosis fungoides or Sezary syndrome that has returned after a period of improvement or has not responded to at least one type of treatment. Monoclonal antibodies, such as pembrolizumab, may block cancer growth in different ways by targeting certain cells. **Detailed Description:** PRIMARY OBJECTIVES: I. To assess the response rate of MK-3475 (pembrolizumab) in subjects with relapsed/refractory mycosis fungoides/Sezary syndrome (MF/SS). SECONDARY OBJECTIVES: I. To explore the clinical activity of MK-3475 in subjects with relapsed/refractory MF and SS with respect to the following endpoints: duration of response (DOR); progression-free survival (PFS); overall survival (OS). OUTLINE: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Courses repeat every 3 weeks for up to 2 years (6 months for patients achieving complete response \[CR\]) in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 30 days and then every 12 weeks. ### Conditions Module **Conditions:** - Recurrent Mycosis Fungoides and Sezary Syndrome - Refractory Mycosis Fungoides and Sezary Syndrome - Stage IB Mycosis Fungoides and Sezary Syndrome AJCC v7 - Stage IIA Mycosis Fungoides and Sezary Syndrome AJCC v7 - Stage IIB Mycosis Fungoides and Sezary Syndrome AJCC v7 - Stage IIIA Mycosis Fungoides and Sezary Syndrome AJCC v7 - Stage IIIB Mycosis Fungoides and Sezary Syndrome AJCC v7 - Stage IVA Mycosis Fungoides and Sezary Syndrome AJCC v7 - Stage IVB Mycosis Fungoides and Sezary Syndrome AJCC v7 ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 24 **Type:** ACTUAL **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Patients receive pembrolizumab IV over 30 minutes on day 1. Courses repeat every 3 weeks for up to 2 years (6 months for patients achieving CR) in the absence of disease progression or unacceptable toxicity. **Intervention Names:** - Other: Laboratory Biomarker Analysis - Biological: Pembrolizumab **Label:** Treatment (pembrolizumab) **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Treatment (pembrolizumab) **Description:** Correlative studies **Name:** Laboratory Biomarker Analysis **Type:** OTHER #### Intervention 2 **Arm Group Labels:** - Treatment (pembrolizumab) **Description:** Given IV **Name:** Pembrolizumab **Other Names:** - Keytruda - Lambrolizumab - MK-3475 - SCH 900475 **Type:** BIOLOGICAL ### Outcomes Module #### Primary Outcomes **Description:** A generalized linear model for the objective response rate used a binominal error distribution. The model included as covariates all available baseline predictors of the missing outcomes. **Measure:** Objective Response Rate (ORR), Defined as a Confirmed Partial Response (PR) or Complete Response (CR) Using Global Assessment Standard Response Criteria for Mycosis Fungoides and Sezary Syndrome **Time Frame:** Up to 3.2 years #### Secondary Outcomes **Description:** Was estimated using the Kaplan-Meier method (Duration of Response Probability). **Measure:** Duration of Response **Time Frame:** The time interval between the date of first response (CR/PR) and the date of progression as assessed by standard Mycosis Fungoides and Sezary Syndrome response criteria, assessed at 26 and 52 weeks **Description:** Was estimated using the Kaplan-Meier method (Progression Free Survival Probability). **Measure:** Progression Free Survival (PFS) **Time Frame:** The time from allocation to the first documented disease progression or death due to any cause, whichever occurs first, assessed at 26 and 52 weeks **Description:** Was estimated using the Kaplan-Meier method (Overall Survival Probability). **Measure:** Overall Survival (OS) **Time Frame:** The time from randomization to death due to any cause, assessed at 52, 104 and 156 weeks **Description:** Summary statistics (mean and SD) for time to onset of first drug-related toxicity was provided. **Measure:** Time to Onset of First Drug-related Toxicity **Time Frame:** Up to 4 years **Description:** Adverse events were summarized as counts and frequencies by toxicity grade. **Measure:** Incidence of Adverse Events Graded Using the Common Terminology Criteria for Adverse Events Version 5.0 **Time Frame:** Up to 4 years ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * This trial will include subjects with stage IB-IVB MF/SS (maximal stage since diagnosis will determine eligibility), and who have relapsed, are refractory, or progressed after at least one standard systemic therapy; current disease stage at time of entry will also be documented but will not be used for eligibility * Subjects must have the following minimum wash-out and adverse event (AE) recovery period from previous treatments without treatment between documentation of relapse/progression and enrollment of specifically: * \>= 2 weeks for local radiation therapy * \>= 4 weeks for systemic cytotoxic anticancer agents, anticancer investigational agents that are not defined as immunotherapy, or for tumor-targeting monoclonal antibodies (mAbs) with the exception of alemtuzumab for which the washout is at least 8 weeks * \>= 15 weeks for anti-cluster of differentiation (CD)137 or anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways) * \>= 2 weeks from resolution (i.e., =\< grade 1 or at baseline) from AEs due to procedures performed or therapeutic agents administered * \>= 2 weeks for retinoids, interferons, vorinostat, romidepsin, denileukin diftitox, and therapeutic doses of oral corticosteroids (physiologic replacement doses of oral corticosteroids are allowed, topical corticosteroids are allowed) * \>= 2 weeks for phototherapy * \>= 1 week for topical therapy (including retinoid, nitrogen mustard, or imiquimod) * Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale * Life expectancy of at least 6 months * Performed within 10 days of treatment initiation: Leukocytes \>= 2,000/mcL * Performed within 10 days of treatment initiation: Absolute neutrophil count \>= 1,500/mcL * Performed within 10 days of treatment initiation: Platelets \>= 100,000/mcL * Performed within 10 days of treatment initiation: Hemoglobin \>= 9 g/dL OR \>= 5.6 mmol/L * Performed within 10 days of treatment initiation: Serum total bilirubin =\< 1.5 x upper limit of normal (ULN) OR direct bilirubin =\< ULN for subjects with total bilirubin levels \> 1.5 ULN * Performed within 10 days of treatment initiation: Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x ULN OR =\< 5 x ULN for patients with liver metastases * Performed within 10 days of treatment initiation: Serum creatinine =\< 1.5 x ULN OR measured or calculated creatinine clearance \>= 60 mL/min for subject with creatinine clearance (CrCl) levels \> 1.5 x institutional ULN (glomerular filtration rate \[GFR\] can also be used in place of creatinine or CrCl) * Performed within 10 days of treatment initiation: International normalized ratio (INR) or prothrombin time (PT) =\< 1.5 x ULN unless subject is receiving anticoagulant therapy in which case the INR or PT must be within the therapeutic range of intended use for the anticoagulant * Performed within 10 days of treatment initiation: Activated partial thromboplastin time (aPTT) =\< 1.5 x ULN unless subject is receiving anticoagulant therapy in which case the aPTT must be within the therapeutic range of intended use for the anticoagulant * Performed within 10 days of treatment initiation: Thyroid stimulating hormone (TSH) within institutional limits (ie: normal); if TSH is greater or less than institutional limits patients may participate if their thyroxine (T4) is within normal limits (WNL); patients may be on a stable dose of replacement thyroid medication; dose adjustments are allowed if needed * Patients must provide tissue from a punch biopsy of the skin at baseline, at the time of a clinical event (at the time of response, progression or appearance of a new lesion) and at the end of treatment; additional punch biopsies every 3 cycles are optional; an archival tissue sample is optional * Have measurable disease based on modified severity-weighted assessment tool (mSWAT); tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions * Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) from the time of the pre-study visit, through the course of the study and for 120 days after the last dose of study medication * Female patients of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication; if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required * Female patients of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity from the time of the pre-study visit, through the course of the study and for 120 days after the last dose of study medication; patients of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \> 1 year * Should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of MK-3475 administration * Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: * Patients who have had chemotherapy or targeted small molecule therapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier * Note: patients with =\< grade 2 neuropathy are an exception to this criterion and may qualify for the study * Note: if patients received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy * Patients who are currently participating in or have participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment * Has a diagnosis of immunodeficiency or is receiving therapeutic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment * Has had a prior monoclonal antibody within 4 weeks prior to study day 1 or who has not recovered (i.e., =\< grade 1 or at baseline) from AEs due to agents administered more than 4 weeks earlier * Has a known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy * Patients with known brain metastases should be excluded from this clinical trial * Patients with carcinomatous meningitis should also be excluded * Patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 4 weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment * History of allergic reactions attributed to compounds of similar chemical or biologic composition to MK-3475 * Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents; patients with vitiligo or resolved childhood asthma/atopy would be an exception to this rule; patients that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study; the use of physiologic doses of corticosteroids may be approved after consultation with the protocol principal investigator (PI) and Cancer Immunotherapy Trials Network (CITN); patients with hypothyroidism stable on hormone replacement or Sjogren's syndrome will not be excluded from the study * Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating investigator * Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial * Has received prior therapy with an anti-programmed cell death (PD)-1, anti-PD-ligand (L)1, anti-PD-L2 * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, interstitial lung disease or active, non-infectious pneumonitis, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements * History of other pulmonary disease such as emphysema or chronic obstructive pulmonary disease, (forced expiratory volume in one second \[FEV1\] \< 60% of predicted for height and age); pulmonary function tests (PFTs) are required in patients with prolonged smoking history or symptoms of respiratory dysfunction * Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-study visit through 120 days after the last dose of trial treatment; breastfeeding should be discontinued if the mother is treated with MK-3475 * Men and non-pregnant, non-breast-feeding women may be enrolled if they are willing to use 2 methods of birth control or are considered highly unlikely to conceive; highly unlikely to conceive is defined as 1) surgically sterilized, or 2) postmenopausal (a woman who is \>= 45 years of age and has not had menses for greater than 1 year will be considered postmenopausal), or 3) not heterosexually active for the duration of the study; the two birth control methods can be barrier method or a barrier method plus a hormonal method to prevent pregnancy; patients should start using birth control from the time of the pre-study visit, through the course of the study and for 120 days after the last dose of study medication; the following are considered adequate barrier methods of contraception: diaphragm, condom (by the partner), copper intrauterine device, sponge, or spermicide; appropriate hormonal contraceptives will include any registered and marketed contraceptive agent that contains an estrogen and/or a progestational agent (including oral, subcutaneous, intrauterine, or intramuscular agents) * Patients should be informed that taking the study medication may involve unknown risks to the fetus (unborn baby) if pregnancy were to occur during the study; in order to participate in the study they must adhere to the contraception requirement (described above) for the duration of the study and during the follow-up period; if there is any question that a patient will not reliably comply with the requirements for contraception, that patient should not be entered into the study * If a patient inadvertently becomes pregnant while on treatment with MK-3475, the patient will immediately be removed from the study; the site will contact the patient at least monthly and document the patient's status until the pregnancy has been completed or terminated; the outcome of the pregnancy will be reported without delay and within 24 hours if the outcome is a serious adverse experience (e.g., death, abortion, congenital anomaly, or other disabling or life-threatening complication to the mother or newborn); the study investigator will make every effort to obtain permission to follow the outcome of the pregnancy and report the condition of the fetus or newborn; if a male patient impregnates his female partner the study personnel at the site must be informed immediately and the pregnancy reported and followed * Patients who are human immunodeficiency virus (HIV) positive may participate IF they meet the following eligibility requirements: * They must be stable on their anti-retroviral regimen, and they must be healthy from an HIV perspective * They must have a CD4 count of greater than 250 cells/mcL * They must not be receiving prophylactic therapy for an opportunistic infection * Has known active hepatitis B (e.g., hepatitis B surface antigen \[HBsAg\] reactive) or hepatitis C (e.g., hepatitis C virus \[HCV\] ribonucleic acid \[RNA\] \[qualitative\] is detected) * Has received a live vaccine within 30 days prior to the first dose of trial treatment * Has a known human T-lymphotropic virus type 1 (HTLV) infection * Patient has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Palo Alto **Country:** United States **Facility:** Stanford Cancer Institute Palo Alto **State:** California **Zip:** 94304 **Location 2:** **City:** New Haven **Country:** United States **Facility:** Yale University **State:** Connecticut **Zip:** 06520 **Location 3:** **City:** Tampa **Country:** United States **Facility:** Moffitt Cancer Center **State:** Florida **Zip:** 33612 **Location 4:** **City:** Baltimore **Country:** United States **Facility:** Johns Hopkins University/Sidney Kimmel Cancer Center **State:** Maryland **Zip:** 21287 **Location 5:** **City:** New York **Country:** United States **Facility:** Memorial Sloan Kettering Cancer Center **State:** New York **Zip:** 10065 **Location 6:** **City:** Columbus **Country:** United States **Facility:** Ohio State University Comprehensive Cancer Center **State:** Ohio **Zip:** 43210 **Location 7:** **City:** Philadelphia **Country:** United States **Facility:** University of Pennsylvania/Abramson Cancer Center **State:** Pennsylvania **Zip:** 19104 **Location 8:** **City:** Seattle **Country:** United States **Facility:** Seattle Cancer Care Alliance **State:** Washington **Zip:** 98109 #### Overall Officials **Official 1:** **Affiliation:** Cancer Immunotherapy Trials Network **Name:** Youn Kim **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### References **Citation:** Phillips D, Matusiak M, Gutierrez BR, Bhate SS, Barlow GL, Jiang S, Demeter J, Smythe KS, Pierce RH, Fling SP, Ramchurren N, Cheever MA, Goltsev Y, West RB, Khodadoust MS, Kim YH, Schurch CM, Nolan GP. Immune cell topography predicts response to PD-1 blockade in cutaneous T cell lymphoma. Nat Commun. 2021 Nov 18;12(1):6726. doi: 10.1038/s41467-021-26974-6. **PMID:** 34795254 **Citation:** Khodadoust MS, Rook AH, Porcu P, Foss F, Moskowitz AJ, Shustov A, Shanbhag S, Sokol L, Fling SP, Ramchurren N, Pierce R, Davis A, Shine R, Li S, Fong S, Kim J, Yang Y, Blumenschein WM, Yearley JH, Das B, Patidar R, Datta V, Cantu E, McCutcheon JN, Karlovich C, Williams PM, Subrahmanyam PB, Maecker HT, Horwitz SM, Sharon E, Kohrt HE, Cheever MA, Kim YH. Pembrolizumab in Relapsed and Refractory Mycosis Fungoides and Sezary Syndrome: A Multicenter Phase II Study. J Clin Oncol. 2020 Jan 1;38(1):20-28. doi: 10.1200/JCO.19.01056. Epub 2019 Sep 18. **PMID:** 31532724 ## Document Section ### Large Document Module #### Large Docs - Date: 2018-03-08 - Filename: Prot_SAP_000.pdf - Has ICF: False - Has Protocol: True - Has SAP: True - Label: Study Protocol and Statistical Analysis Plan - Size: 3990042 - Type Abbrev: Prot_SAP - Upload Date: 2018-10-23T10:16 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000004194 - Term: Disease - ID: D000010335 - Term: Pathologic Processes - ID: D000001423 - Term: Bacterial Infections and Mycoses - ID: D000007239 - Term: Infections - ID: D000016410 - Term: Lymphoma, T-Cell, Cutaneous - ID: D000016399 - Term: Lymphoma, T-Cell - ID: D000008228 - Term: Lymphoma, Non-Hodgkin - ID: D000008223 - Term: Lymphoma - ID: D000009370 - Term: Neoplasms by Histologic Type - ID: D000009369 - Term: Neoplasms - ID: D000008232 - Term: Lymphoproliferative Disorders - ID: D000008206 - Term: Lymphatic Diseases - ID: D000007160 - Term: Immunoproliferative Disorders - ID: D000007154 - Term: Immune System Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC01 - Name: Infections - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC15 - Name: Blood and Lymph Conditions - Abbrev: BC20 - Name: Immune System Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M16355 - Name: Syndrome - Relevance: HIGH - As Found: Syndrome - ID: M12136 - Name: Mycoses - Relevance: HIGH - As Found: Mycosis - ID: M12137 - Name: Mycosis Fungoides - Relevance: HIGH - As Found: Mycosis Fungoides - ID: M14850 - Name: Recurrence - Relevance: LOW - As Found: Unknown - ID: M15560 - Name: Sezary Syndrome - Relevance: HIGH - As Found: Sezary syndrome - ID: M10283 - Name: Infections - Relevance: LOW - As Found: Unknown - ID: M6368 - Name: Communicable Diseases - Relevance: LOW - As Found: Unknown - ID: M4722 - Name: Bacterial Infections - Relevance: LOW - As Found: Unknown - ID: M4721 - Name: Bacterial Infections and Mycoses - Relevance: LOW - As Found: Unknown - ID: M11220 - Name: Lymphoma - Relevance: LOW - As Found: Unknown - ID: M18829 - Name: Lymphoma, T-Cell - Relevance: LOW - As Found: Unknown - ID: M18832 - Name: Lymphoma, T-Cell, Cutaneous - Relevance: LOW - As Found: Unknown - ID: M11222 - Name: Lymphoma, Non-Hodgkin - Relevance: LOW - As Found: Unknown - ID: M12315 - Name: Neoplasms by Histologic Type - Relevance: LOW - As Found: Unknown - ID: M11225 - Name: Lymphoproliferative Disorders - Relevance: LOW - As Found: Unknown - ID: M11203 - Name: Lymphatic Diseases - Relevance: LOW - As Found: Unknown - ID: M10206 - Name: Immunoproliferative Disorders - Relevance: LOW - As Found: Unknown - ID: M10200 - Name: Immune System Diseases - Relevance: LOW - As Found: Unknown - ID: T3986 - Name: Mycosis Fungoides - Relevance: HIGH - As Found: Mycosis Fungoides - ID: T5200 - Name: Sezary Syndrome - Relevance: HIGH - As Found: Sezary syndrome - ID: T3543 - Name: Lymphosarcoma - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000009181 - Term: Mycoses - ID: D000009182 - Term: Mycosis Fungoides - ID: D000012751 - Term: Sezary Syndrome - ID: D000013577 - Term: Syndrome ### Intervention Browse Module - Ancestors - ID: D000074322 - Term: Antineoplastic Agents, Immunological - ID: D000000970 - Term: Antineoplastic Agents - ID: D000082082 - Term: Immune Checkpoint Inhibitors - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action ### Intervention Browse Module - Browse Branches - Abbrev: ANeo - Name: Antineoplastic Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M349416 - Name: Pembrolizumab - Relevance: HIGH - As Found: Blind - ID: M1346 - Name: Antineoplastic Agents, Immunological - Relevance: LOW - As Found: Unknown - ID: M2342 - Name: Immune Checkpoint Inhibitors - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: C000582435 - Term: Pembrolizumab ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module #### Event Groups **Group ID:** EG000 **Title:** Treatment (Pembrolizumab) **Deaths Num Affected:** 7 **Deaths Num At Risk:** 24 **Description:** Patients receive pembrolizumab IV over 30 minutes on day 1. Courses repeat every 3 weeks for up to 2 years (6 months for patients achieving CR) in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pembrolizumab: Given IV **ID:** EG000 **Other Num Affected:** 24 **Other Num at Risk:** 24 **Serious Number Affected:** 11 **Serious Number At Risk:** 24 **Title:** Treatment (Pembrolizumab) **Frequency Threshold:** 1 #### Other Events **Term:** Anemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** **Term:** Low Hemoglobin **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** **Term:** Vertigo **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Ear and labyrinth disorders **Source Vocabulary:** **Term:** Blurred Vision **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Eye disorders **Source Vocabulary:** **Term:** Keratitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Eye disorders **Source Vocabulary:** **Term:** Abdominal Pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** **Term:** Colonic hemorrhage **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** **Term:** Constipation **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** **Term:** Diarrhea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** **Term:** Nausia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** **Term:** Vomiting **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** **Term:** Chills **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** **Term:** Edema face **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** **Term:** Edema limbs **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** **Term:** Edema trunk **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** **Term:** Fatigue **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** **Term:** Fever **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** **Term:** Weakness **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** **Term:** Weakness (grade decrease) **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** **Term:** Firm tender lump on his left lateral thigh, no trauma to the area **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** **Term:** Generalized edema **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** **Term:** Malaise **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** **Term:** Pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** **Term:** Inflammation/Flare reaction **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Immune system disorders **Source Vocabulary:** **Term:** Conjunctivitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** **Term:** Esophageal infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** **Term:** Eye infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** **Term:** Infection S/P scheduled Mohs surgery **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** **Term:** Right lower leg infection related to approved radiation and wound care **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** **Term:** Mucosal infection (thrush) **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** **Term:** Mucosal infection - thrush **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** **Term:** Upper eyelid infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** **Term:** otitis externa **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** **Term:** rash pustular **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** **Term:** Skin infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** **Term:** Soft tissue infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** **Term:** Upper respiratory infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** **Term:** Urinary tract infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** **Term:** Fall **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** **Term:** Infusion related reaction **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** **Term:** Alanine aminotransferase increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** **Term:** Alkaline phosphatase inceased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** **Term:** Aspartate aminotransferase increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** **Term:** Blood bilirubin increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** **Term:** Cardiac troponin T increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** **Term:** Creatinine increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** **Term:** Investigations **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** **Term:** Lymphocyte count decreased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** **Term:** Neutrophil count decreased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** **Term:** Weight gain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** **Term:** Weight loss **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** **Term:** white blood cell decreased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** **Term:** Hyperglycemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** **Term:** Hyperkalemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** **Term:** Hyperuricemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** **Term:** Hypoalbuminemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** **Term:** Hypocalcemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** **Term:** Hypokalemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** **Term:** Hyponatremia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** **Term:** Hypophosphatemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** **Term:** Arthralgia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** **Term:** Arthritis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** **Term:** Back pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** **Term:** Muscle weakness lower limb **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** **Term:** Herniated disc **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** **Term:** neck pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** **Term:** Pain in extremity **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** **Term:** BCC right leg **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** **Term:** SCC forehead **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** **Term:** Ataxia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** **Term:** Syncope **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** **Term:** Tremor **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** **Term:** Anxiety **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** **Term:** Confusion **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** **Term:** Insomnia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** **Term:** Nephrolithiasis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** **Term:** Acute kidney injury **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** **Term:** Allergic rhinitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** **Term:** Cough **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** **Term:** Dyspnea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** **Term:** Horseness **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Reproductive system and breast disorders **Source Vocabulary:** **Term:** Hypoxia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** **Term:** Pneumonitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** **Term:** Postnasal drip **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** **Term:** Bilateral pulmonary infiltrates **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** **Term:** Sinus inflammation **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** **Term:** Alopecia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** **Term:** Dry skin **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** **Term:** Erythroderma **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** **Term:** Hyperhidrosis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** **Term:** Pruritus **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** **Term:** Rash maculo-papular **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** **Term:** Skin eruption/flare, rash **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** **Term:** immune mediated flare reaction on the face **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** **Term:** pustular rash **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** **Term:** Mild skin peeling **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** **Term:** Erythroderma **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** **Term:** Night sweats **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** **Term:** Skin flare **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** **Term:** Excess skin peeling **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** **Term:** Urticaria **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** **Term:** Scheduled Mohs surgery **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Surgical and medical procedures **Source Vocabulary:** **Term:** Hot flashes **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** **Term:** Hypertension **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** **Term:** Hypotension **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** #### Serious Events **Term:** Atrial Fibrillation **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 24 **Term:** Heart Failure **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 24 **Term:** Corneal Ulcer **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Eye disorders ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 24 **Term:** Periorbital Edema **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Eye disorders ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 24 **Term:** Colitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 24 **Term:** Colonic obstruction **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 24 **Term:** Duodenitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 24 **Term:** Edema face **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 24 **Term:** Fatigue **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 24 **Term:** Anaphylaxis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Immune system disorders ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 24 **Term:** Lung Infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 24 **Term:** Sepsis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 24 **Term:** Urinary Tract Infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 24 **Term:** Alanine Aminotransferase increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 24 **Term:** Aspartate Aminotransferase increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 24 **Term:** Hyperuricemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 24 **Term:** Arthralgia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 24 **Term:** Confusion **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 24 **Term:** Epistaxis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 24 **Term:** Hypoxia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 24 **Term:** Pneuminitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 24 **Term:** Pulmonary Edema **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 24 **Term:** Hypertension **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 24 **Time Frame:** Up to 4 years ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 24 **Units:** Participants ### Group **ID:** BG000 **Title:** Treatment (Pembrolizumab) **Description:** Patients receive pembrolizumab IV over 30 minutes on day 1. Courses repeat every 3 weeks for up to 2 years (6 months for patients achieving CR) in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pembrolizumab: Given IV ### Measure #### Measurement **Group ID:** BG000 **Value:** 0 **Category Title:** <=18 years #### Measurement **Group ID:** BG000 **Value:** 9 **Category Title:** Between 18 and 65 years #### Measurement **Group ID:** BG000 **Value:** 15 **Category Title:** >=65 years **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 6 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 18 **Category Title:** Male **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 0 **Category Title:** American Indian or Alaska Native #### Measurement **Group ID:** BG000 **Value:** 0 **Category Title:** Asian #### Measurement **Group ID:** BG000 **Value:** 0 **Category Title:** Native Hawaiian or Other Pacific Islander #### Measurement **Group ID:** BG000 **Value:** 3 **Category Title:** Black or African American #### Measurement **Group ID:** BG000 **Value:** 20 **Category Title:** White #### Measurement **Group ID:** BG000 **Value:** 0 **Category Title:** More than one race #### Measurement **Group ID:** BG000 **Value:** 1 **Category Title:** Unknown or Not Reported **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 24 **Class Title:** United States **Denomination Units Selected:** ## Results Section - Baseline Characteristics Module ### Measure 1 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Age, Categorical **Unit of Measure:** Participants ### Measure 2 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Sex: Female, Male **Unit of Measure:** Participants ### Measure 3 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Race (NIH/OMB) **Unit of Measure:** Participants ### Measure 4 **Parameter Type:** NUMBER **Title:** Region of Enrollment **Unit of Measure:** participants ## Results Section - More Information Module ### Certain Agreement **Restriction Type:** LTE60 **Restrictive Agreement:** True ### Point of Contact **Email:** [email protected] **Organization:** Fred Hutchinson Cancer Research Center **Phone:** 206-667-5300 **Title:** Asa Davis ## Results Section - Outcome Measures Module ### Outcome Measure 1 ### Outcome Measure 2 ### Outcome Measure 3 ### Outcome Measure 4 ### Outcome Measure 5 ### Outcome Measure 6 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 **Title:** Confirmed Complete Response ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 7 **Title:** Confirmed Partial Response ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 9 **Title:** Stable Disease ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 6 **Title:** Progressive Disease #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1.0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0.8571 **Title:** #### Outcome Measure 3 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0.7380 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0.6457 **Title:** #### Outcome Measure 4 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0.95 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0.7917 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0.5429 **Title:** #### Outcome Measure 5 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 121.3 - **Upper Limit:** - **Value:** 64.5 **Title:** #### Outcome Measure 6 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 **Title:** Maximum Toxicity Grade 1 ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 7 **Title:** Maximum Toxicity Grade 2 ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 9 **Title:** Maximum Toxicity Grade 3 ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 6 **Title:** Maximum Toxicity Grade 4 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** A generalized linear model for the objective response rate used a binominal error distribution. The model included as covariates all available baseline predictors of the missing outcomes. **Parameter Type:** COUNT_OF_PARTICIPANTS **Reporting Status:** POSTED **Time Frame:** Up to 3.2 years **Title:** Objective Response Rate (ORR), Defined as a Confirmed Partial Response (PR) or Complete Response (CR) Using Global Assessment Standard Response Criteria for Mycosis Fungoides and Sezary Syndrome **Type:** PRIMARY **Unit of Measure:** Participants ##### Group **Description:** Patients receive pembrolizumab IV over 30 minutes on day 1. Courses repeat every 3 weeks for up to 2 years (6 months for patients achieving CR) in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pembrolizumab: Given IV **ID:** OG000 **Title:** Treatment (Pembrolizumab) #### Outcome Measure 2 **Description:** Was estimated using the Kaplan-Meier method (Duration of Response Probability). **Parameter Type:** NUMBER **Reporting Status:** POSTED **Time Frame:** The time interval between the date of first response (CR/PR) and the date of progression as assessed by standard Mycosis Fungoides and Sezary Syndrome response criteria, assessed at 26 and 52 weeks **Title:** Duration of Response **Type:** SECONDARY **Unit of Measure:** Duration of Response Probability ##### Group **Description:** Patients receive pembrolizumab IV over 30 minutes on day 1. Courses repeat every 3 weeks for up to 2 years (6 months for patients achieving CR) in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pembrolizumab: Given IV **ID:** OG000 **Title:** Treatment (Pembrolizumab) #### Outcome Measure 3 **Description:** Was estimated using the Kaplan-Meier method (Progression Free Survival Probability). **Parameter Type:** NUMBER **Reporting Status:** POSTED **Time Frame:** The time from allocation to the first documented disease progression or death due to any cause, whichever occurs first, assessed at 26 and 52 weeks **Title:** Progression Free Survival (PFS) **Type:** SECONDARY **Unit of Measure:** Progression Free Survival Probability ##### Group **Description:** Patients receive pembrolizumab IV over 30 minutes on day 1. Courses repeat every 3 weeks for up to 2 years (6 months for patients achieving CR) in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pembrolizumab: Given IV **ID:** OG000 **Title:** Treatment (Pembrolizumab) #### Outcome Measure 4 **Description:** Was estimated using the Kaplan-Meier method (Overall Survival Probability). **Parameter Type:** NUMBER **Reporting Status:** POSTED **Time Frame:** The time from randomization to death due to any cause, assessed at 52, 104 and 156 weeks **Title:** Overall Survival (OS) **Type:** SECONDARY **Unit of Measure:** Overall Survival Probability ##### Group **Description:** Patients receive pembrolizumab IV over 30 minutes on day 1. Courses repeat every 3 weeks for up to 2 years (6 months for patients achieving CR) in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pembrolizumab: Given IV **ID:** OG000 **Title:** Treatment (Pembrolizumab) #### Outcome Measure 5 **Description:** Summary statistics (mean and SD) for time to onset of first drug-related toxicity was provided. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Patients with drug-related toxicities included in the analysis **Reporting Status:** POSTED **Time Frame:** Up to 4 years **Title:** Time to Onset of First Drug-related Toxicity **Type:** SECONDARY **Unit of Measure:** Days ##### Group **Description:** Patients receive pembrolizumab IV over 30 minutes on day 1. Courses repeat every 3 weeks for up to 2 years (6 months for patients achieving CR) in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pembrolizumab: Given IV **ID:** OG000 **Title:** Treatment (Pembrolizumab) #### Outcome Measure 6 **Description:** Adverse events were summarized as counts and frequencies by toxicity grade. **Parameter Type:** COUNT_OF_PARTICIPANTS **Reporting Status:** POSTED **Time Frame:** Up to 4 years **Title:** Incidence of Adverse Events Graded Using the Common Terminology Criteria for Adverse Events Version 5.0 **Type:** SECONDARY **Unit of Measure:** Participants ##### Group **Description:** Patients receive pembrolizumab IV over 30 minutes on day 1. Courses repeat every 3 weeks for up to 2 years (6 months for patients achieving CR) in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pembrolizumab: Given IV **ID:** OG000 **Title:** Treatment (Pembrolizumab) ### Participant Flow Module #### Group **Description:** Patients receive pembrolizumab IV over 30 minutes on day 1. Courses repeat every 3 weeks for up to 2 years (6 months for patients achieving CR) in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pembrolizumab: Given IV **ID:** FG000 **Title:** Treatment (Pembrolizumab) #### Period **Title:** Overall Study ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 24 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 4 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 20 **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT04387279 **Brief Title:** The Impact of COVID-19 on the Health Care Utilization of Inflammatory Bowel Disease **Official Title:** The Effect of Patient's Perceptions for COVID-19 on the Inflammatory Bowel Disease-related Healthcare Utilization in the Hyperepidemic Area #### Organization Study ID Info **ID:** 2020-04-070 #### Organization **Class:** OTHER **Full Name:** Keimyung University Dongsan Medical Center ### Status Module #### Completion Date **Date:** 2021-03-30 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** RECRUITING #### Last Update Post Date **Date:** 2020-05-13 **Type:** ACTUAL **Last Update Submit Date:** 2020-05-12 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2021-03-30 **Type:** ESTIMATED #### Start Date **Date:** 2020-04-24 **Type:** ACTUAL **Status Verified Date:** 2020-05 #### Study First Post Date **Date:** 2020-05-13 **Type:** ACTUAL **Study First Submit Date:** 2020-05-12 **Study First Submit QC Date:** 2020-05-12 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** Yeungnam University College of Medicine #### Lead Sponsor **Class:** OTHER **Name:** Keimyung University Dongsan Medical Center #### Responsible Party **Investigator Affiliation:** Keimyung University Dongsan Medical Center **Investigator Full Name:** YooJin Lee **Investigator Title:** Professor **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** The rapid spread of COVID-19 is expected to have a significant impact on medicine as well as all sectors worldwide. In particular, inflammatory bowel disease (IBD) is a chronic immune disease in which remission and activation are repeated and must be treated consistently throughout life. In addition, patients with IBD may be vulnerable to various infectious diseases due to the immuno-compromised state due to the use of immuno-suppressants or biological agents. During a pandemic, patients with IBD may postpone hospital visits due to concerns about infection with COVID-19, and if they cannot continue drug treatment, there is a concern about the flare up IBD disease activity. Therefore, in this study, we would like to investigate the current status of hospital utilization of IBD patients in Daegu, the epidemic area of COVID-19, and to investigate the effect of patient perception of COVID-19 on hospital ultilization. **Detailed Description:** Background: In the epidemic area of COVID-19, emergency treatment of chronic diseases other than COVID-19 can be limited. Therefore, it is important to reduce the risk of exposure to COVID-19 in patients with chronic immune diseases such as IBD, but it is most important to manage well so that the underlying diseases are not exacerbated at times when emergency medical treatment may be difficult. However, there is a lack of evidence on the management policy of chronic immune diseases in the current epidemic, and only expert opinions are being presented. Aim: To investigate the current status of hospital utilization of IBD patients in Daegu, the epidemic area of COVID-19, and to investigate the effect of patient perception of COVID-19 on hospital utilization. Material and method: This study is a multicenter, prospective, cross-sectional survey which will be consulted in Keimyung University Dongsan Medical Center and Yeungnam University Hospital. Patients with IBD aged above 18 will enrolled and surveyed about their perception about COVID-19 and status of hospital utilization during pandemic period. Patients' demographics and disease-related variables will be evaluated to identify clinical significances. ### Conditions Module **Conditions:** - COVID-19 - Perception, Self - Facilities and Services Utilization ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** CROSS_SECTIONAL #### Enrollment Info **Count:** 800 **Type:** ESTIMATED **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Patients with inflammatory bowel disease who live in COVID-19 hyperemic area **Intervention Names:** - Other: Interview **Label:** Inflammatory bowel disease ### Interventions #### Intervention 1 **Arm Group Labels:** - Inflammatory bowel disease **Description:** Surveys on medical use patterns and patient's perceptions about COVID-19 **Name:** Interview **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** Correlation between patient's perception of COVID-19 and medical use patterns during the pandemic period **Measure:** Patient's perception of COVID-19 and medical use patterns **Time Frame:** 1day #### Secondary Outcomes **Description:** Exacerbation of symptoms in patients with IBD during the pandemic period **Measure:** Exacerbation of symptoms **Time Frame:** 1day ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Patients with inflammatory growth disease, those who agreed to participate in this study Exclusion Criteria: * Those who are unable to understand or answer the questionnaire * Those who declined to participate in this study **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** This study population will comprise the sample of all patients with inflammatory bowel disease, living in the Daegu city ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Yoojin Lee, M.D. **Phone:** 82-53-258-7739 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Kyeong Ok Kim, Ph.D. **Role:** CONTACT #### Locations **Location 1:** **City:** Daegu **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Yoo Jin Lee - **Phone:** +82-250-7088 - **Role:** CONTACT **Country:** Korea, Republic of **Facility:** KeimyungUniversity **State:** Jung-gu **Status:** RECRUITING **Zip:** 700-712 #### Overall Officials **Official 1:** **Affiliation:** Keimyung University Dongsan Medical Center **Name:** Yoojin Lee, M.D. **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000011024 - Term: Pneumonia, Viral - ID: D000011014 - Term: Pneumonia - ID: D000012141 - Term: Respiratory Tract Infections - ID: D000007239 - Term: Infections - ID: D000014777 - Term: Virus Diseases - ID: D000018352 - Term: Coronavirus Infections - ID: D000003333 - Term: Coronaviridae Infections - ID: D000030341 - Term: Nidovirales Infections - ID: D000012327 - Term: RNA Virus Infections - ID: D000008171 - Term: Lung Diseases - ID: D000012140 - Term: Respiratory Tract Diseases - ID: D000007410 - Term: Intestinal Diseases - ID: D000005767 - Term: Gastrointestinal Diseases - ID: D000004066 - Term: Digestive System Diseases - ID: D000005759 - Term: Gastroenteritis ### Condition Browse Module - Browse Branches - Abbrev: BC01 - Name: Infections - Abbrev: BC08 - Name: Respiratory Tract (Lung and Bronchial) Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC06 - Name: Digestive System Diseases - Abbrev: BC23 - Name: Symptoms and General Pathology ### Condition Browse Module - Browse Leaves - ID: M2561 - Name: COVID-19 - Relevance: HIGH - As Found: COVID-19 - ID: M10444 - Name: Intestinal Diseases - Relevance: LOW - As Found: Unknown - ID: M17917 - Name: Inflammatory Bowel Diseases - Relevance: HIGH - As Found: Inflammatory Bowel Disease - ID: M13904 - Name: Pneumonia - Relevance: LOW - As Found: Unknown - ID: M13914 - Name: Pneumonia, Viral - Relevance: LOW - As Found: Unknown - ID: M10283 - Name: Infections - Relevance: LOW - As Found: Unknown - ID: M6368 - Name: Communicable Diseases - Relevance: LOW - As Found: Unknown - ID: M14978 - Name: Respiratory Tract Infections - Relevance: LOW - As Found: Unknown - ID: M17522 - Name: Virus Diseases - Relevance: LOW - As Found: Unknown - ID: M20490 - Name: Coronavirus Infections - Relevance: LOW - As Found: Unknown - ID: M6555 - Name: Coronaviridae Infections - Relevance: LOW - As Found: Unknown - ID: M23685 - Name: Nidovirales Infections - Relevance: LOW - As Found: Unknown - ID: M15149 - Name: RNA Virus Infections - Relevance: LOW - As Found: Unknown - ID: M11168 - Name: Lung Diseases - Relevance: LOW - As Found: Unknown - ID: M14977 - Name: Respiratory Tract Diseases - Relevance: LOW - As Found: Unknown - ID: M7255 - Name: Digestive System Diseases - Relevance: LOW - As Found: Unknown - ID: M8883 - Name: Gastrointestinal Diseases - Relevance: LOW - As Found: Unknown - ID: M8875 - Name: Gastroenteritis - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000086382 - Term: COVID-19 - ID: D000015212 - Term: Inflammatory Bowel Diseases ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03613779 **Acronym:** CLUSTER-HF **Brief Title:** CLUSTER-HF: Lung Ultrasound Guided Therapy in Heart Failure **Official Title:** Efficacy of Lung Ultrasound Guided Therapy to Prevent Rehospitalizations in Heart Failure (CLUSTER-HF): a Randomized Controlled Trial #### Organization Study ID Info **ID:** PT-18-078 #### Organization **Class:** OTHER **Full Name:** Instituto Nacional de Cardiologia Ignacio Chavez ### Status Module #### Completion Date **Date:** 2019-12-07 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2019-12-11 **Type:** ACTUAL **Last Update Submit Date:** 2019-12-09 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2019-12-06 **Type:** ACTUAL #### Start Date **Date:** 2018-04-10 **Type:** ACTUAL **Status Verified Date:** 2019-12 #### Study First Post Date **Date:** 2018-08-03 **Type:** ACTUAL **Study First Submit Date:** 2018-07-29 **Study First Submit QC Date:** 2018-08-02 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Instituto Nacional de Cardiologia Ignacio Chavez #### Responsible Party **Investigator Affiliation:** Instituto Nacional de Cardiologia Ignacio Chavez **Investigator Full Name:** Diego Araiza-Garaygordobil **Investigator Title:** Principal Investigator **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Introduction: Heart failure is the leading cause of hospitalization among adults \>65 years of age. Discharge from a heart failure hospitalization is followed by a 30 day readmission rate of ≈24%. Readmissions for heart failure are typically preceded by a gradual rise in ventricular filling pressures that begins days or weeks before any detectable changes in clinical status. Lung ultrasound (LUS) is a tool that is easily available at bedside and shows superior sensitivity for the detection of pulmonary congestion when compared with X ray or physical examination, even in the absence of symptoms. Pulmonary congestion assessed by LUS identifies a subgroup with worse prognosis and a higher rate of readmission and mortality. Whether the implementation of lung ultrasound in the follow up of heart failure patients may reduce the rate of readmissions is unknown. Objective: The aim of this study is to evaluate a protocol of lung ultrasound guided therapy to prevent readmissions in heart failure outpatients. Study design: the design of the investigator's study is a single center, single blinded, randomized controlled clinical trial. Eligibility criteria: patients older than 18 years of age, who have been hospitalized for an acute heart failure syndrome. Exclusion criteria are life expectancy of less than 6 months, a surgically correctable cause of heart failure or uninterpretable lung ultrasound. Eligible patients will be randomized into either "LUS-guided therapy group" or "control group" at hospital discharge. Follow-up visits will be scheduled at 15 days, 45 days, 3 months and 6 months after hospital discharge. LUS will be performed in all patients at hospital discharge and in every follow-up visit, but only in those allocated to the "LUS-guided therapy group" the information will be provided to the treating physician. In the "LUS-guided therapy group", a prespecified diuretic dose will be administered to patients depending on the degree of ultrasonographic pulmonary congestion: if congestive (3 or more B lines, in total) a high dose (80-120mg furosemide PO/day) will be prescribed; if no congestive (less than 3 B lines, in total) a low dose (up to 40mg PO/day) will be prescribed. Primary outcome will be the composite of hospital readmission + mortality. This study complies with the Declaration of Helsinki and the study protocol is being evaluated by the Ethic Committee of our institution. ### Conditions Module **Conditions:** - Heart Failure **Keywords:** - Lung ultrasound - Heart failure - Management ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** DOUBLE **Who Masked:** - PARTICIPANT - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 130 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** LUS-guided therapy group. Patients randomly allocated to this arm will receive standard of care + LUS examination accessible to treating physician in every visit. Depending on the results of LUS examination, a low dose or high dose of diuretics will be administered. A standardized algorithm will be provided to ensure compliance to guideline-recommended medical therapy for heart failure. **Intervention Names:** - Combination Product: LUS-guided therapy - Other: Standard of Care **Label:** LUS-guided therapy group **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Control group. Patients randomly allocated to this arm will receive standard of care + LUS examination blinded to the treating physician in every visit. Diuretic titration will be based on standard practice (physical examination, symptoms and lab results). A standardized algorithm will be provided to ensure compliance to guideline-recommended medical therapy for heart failure. **Intervention Names:** - Other: Standard of Care **Label:** Control group. **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - LUS-guided therapy group **Description:** Lung ultrasound guided therapy; if pulmonary congestion (more or equal than 3 B-lines), high dose (80-120mg PO/day furosemide) will be prescribed until next follow up re-assessment. If no congestion (less than 3 B-lines), low dose (0-40mg PO/day furosemide) will be prescribed until next follow up re-assessment **Name:** LUS-guided therapy **Type:** COMBINATION_PRODUCT #### Intervention 2 **Arm Group Labels:** - Control group. - LUS-guided therapy group **Description:** Standard of care will be provided. **Name:** Standard of Care **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** Hospital readmission: urgent hospital non scheduled visit and stay of more than 24 hours, requiring medical interventions. Mortality: patient's death. **Measure:** Number of patients with the composite outcome of hospital readmission + mortality. **Time Frame:** 6 months. **Description:** Hospital readmission: urgent hospital non scheduled visit and stay of more than 24 hours, requiring medical interventions. Mortality: patient's death. Urgent visits for worsening HF: non-scheduled visit to day care or ED that prompted increased oral / IV therapy, less than 24 hours stay. **Measure:** Number of patients with the composite outcome of hospital readmission + mortality + urgent visits for worsening HF **Time Frame:** 6 months #### Secondary Outcomes **Description:** Quality of life at 6 months assessed by KCCQ **Measure:** Quality of life measured by kansas city cardiomyopathy questionnaire (KCCQ) **Time Frame:** 6 months **Description:** NTproBNP concentrations and change by last visit **Measure:** NTproBNP concentrations **Time Frame:** 6 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Patients admitted to the hospital with the primary or secondary diagnosis of heart failure * The intra-hospital stay extends for at least 24 hours. * The patient shows new symptoms (or worsening of known symptoms) due to the presentation of heart failure, including at least one of the following: dyspnea (dyspnea at rest, at exertion, orthopnea, nocturnal paroxysmal dyspnea), decreased exercise capacity, fatigue or other symptoms of target organ hypoperfusion or volume overload. * The patient has at least two physical examination findings; or at least one finding to the physical examination and at least one complementary criterion, including: physical examination findings that are considered to be due to heart failure (peripheral edema, increase in the abdominal perimeter or ascites in the absence of primary liver disease, signs of pulmonary congestion including crackles, subcrepitant rales or decrease in vesicular murmur, increase in jugular venous pressure and / or hepatojugular reflux, gallop by third sound (S3) or rapid weight gain, clinically significant, attributed to water retention); and/or complementary findings that are considered to be due to heart failure, including Increase in levels of N-terminal-pro-BNP (NT-proBNP) compatible with decompensation of heart failure (\> 2,000 pg / mL), radiographic evidence of pulmonary congestion, or invasive or non-invasive evidence of significant increase in ventricular filling pressures or decreased cardiac output. Exclusion Criteria: * Non interpretable lung ultrasound imaging or false positive findings (chronic lung interstitial disease, pneumonia, large pleural effusion). * Lack of willing to provide informed consent * Life expectancy lesser than 6 months * Surgically correctable cause of heart failure (aortic stenosis, mitral regurgitation, multi-vessel coronary artery disease). * Chronic kidney injury with an estimated or measured creatinine clearance rate lower than 15ml/min/1.73m2. **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Mexico City **Country:** Mexico **Facility:** Instituto Nacional de Cardiología "Ignacio Chavez" **Zip:** 14030 #### Overall Officials **Official 1:** **Affiliation:** Instituto Nacional de Cardiología "Ignacio Chavez" **Name:** Diego Araiza-Garaygordobil, MD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **Access Criteria:** Via direct PI contact **Info Types:** - STUDY_PROTOCOL - SAP - ICF - CSR - ANALYTIC_CODE **IPD Sharing:** YES **Time Frame:** Second semester or 2020 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000006331 - Term: Heart Diseases - ID: D000002318 - Term: Cardiovascular Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M9421 - Name: Heart Failure - Relevance: HIGH - As Found: Heart Failure - ID: M9419 - Name: Heart Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000006333 - Term: Heart Failure ### Intervention Browse Module - Browse Branches - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: NaAg - Name: Natriuretic Agents ### Intervention Browse Module - Browse Leaves - ID: M7411 - Name: Diuretics - Relevance: LOW - As Found: Unknown - ID: M8784 - Name: Furosemide - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05523479 **Acronym:** METEOR **Brief Title:** The Maximizing Extubation Outcomes Through Educational and Organizational Research (METEOR) Trial **Official Title:** The Maximizing Extubation Outcomes Through Educational and Organizational Research (METEOR) Trial #### Organization Study ID Info **ID:** STUDY20100469 #### Organization **Class:** OTHER **Full Name:** University of Pittsburgh #### Secondary ID Infos **ID:** U01HL159882 **Link:** https://reporter.nih.gov/quickSearch/U01HL159882 **Type:** NIH ### Status Module #### Completion Date **Date:** 2026-02 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-04-15 **Type:** ACTUAL **Last Update Submit Date:** 2024-04-11 **Overall Status:** ENROLLING_BY_INVITATION #### Primary Completion Date **Date:** 2025-11 **Type:** ESTIMATED #### Start Date **Date:** 2023-03-01 **Type:** ACTUAL **Status Verified Date:** 2024-04 #### Study First Post Date **Date:** 2022-08-31 **Type:** ACTUAL **Study First Submit Date:** 2022-08-29 **Study First Submit QC Date:** 2022-08-29 ### Sponsor Collaborators Module #### Collaborators **Class:** NIH **Name:** National Heart, Lung, and Blood Institute (NHLBI) #### Lead Sponsor **Class:** OTHER **Name:** University of Pittsburgh #### Responsible Party **Investigator Affiliation:** University of Pittsburgh **Investigator Full Name:** Timothy Girard, MD, MSCI **Investigator Title:** Professor of Critical Care Medicine **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** The METEOR Trial will compare four implementation strategies-traditional online education, protocol-directed care, interprofessional education, and a combination of protocol-directed care and interprofessional education-to test the hypotheses that interprofessional education is superior to traditional online education as an implementation strategy in the intensive care unit (ICU) and the benefits of interprofessional education are increased when interprofessional education is paired with a clinical protocol. Additionally, the trial will also test the hypothesis that preventive post-extubation NIV for high-risk patients and preventive post-extubation HFNC for low-risk patients are both superior to current clinical practice (i.e., conventional post-extubation oxygen therapy). **Detailed Description:** Nearly one million patients require invasive mechanical ventilation for acute respiratory failure in the United States each year. Most of these patients will recover to the point of extubation, yet even those who are extubated remain vulnerable to complications and poor outcomes. Multiple high-profile randomized controlled trials have shown that two preventive post-extubation respiratory therapies-noninvasive ventilation (NIV) and high-flow nasal cannula oxygen (HFNC)-can prevent recurrent respiratory failure, reintubation, and death in this population. Despite this evidence, however, these therapies remain severely underutilized, leading to preventable morbidity and mortality. To address this implementation gap, the investigators will conduct the Maximizing Extubation outcomes Through Educational and Organizational Research (METEOR) Trial, a cluster-randomized, stepped-wedge, type 2 hybrid effectiveness-implementation trial of interprofessional education about preventive post-extubation NIV and HFNC with and without clinical protocols. The METEOR Trial was designed based on extensive preliminary studies, during which the investigators identified barriers to adoption of preventive post-extubation respiratory care and pilot tested interprofessional education as an implementation strategy in the ICU. These studies revealed that a major barrier to implementation is the lack of a shared understanding about the value of these therapies within the interprofessional ICU team; a theory-based interprofessional education intervention designed to create a shared understanding and support "transactive memory" among team members is both feasible and acceptable; and interprofessional education can be strengthened by linking it with a clinical protocol. During the METEOR Trial, the investigators will randomize ICUs to one of four implementation strategies: an active control, protocol-directed care, interprofessional education, or a combination of protocol-directed care and interprofessional education. In parallel, the investigators will randomize ICUs to one of two clinical strategies, one emphasizing either post- extubation NIV or HFNC based on patient risk vs. one emphasizing post-extubation HFNC for all patients. ### Conditions Module **Conditions:** - Acute Respiratory Failure - Airway Extubation **Keywords:** - Interprofessional Education - Clinical Protocols - Noninvasive Ventilation - Oxygen Inhalation Therapy ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** FACTORIAL **Intervention Model Description:** The METEOR Trial is a batched stepped wedge cluster randomized type 2 hybrid implementation-effectiveness trial. ICUs are randomized rather than individuals, and each ICU will cross over from control to intervention at a randomized timepoint. The trial will employ three variations on the traditional stepped wedge design: 1. A factorial design will be used to estimate the effects of two implementation strategies (IPE and a clinical protocol) separately as well as together. 2. A concurrent design will be used to compare two post-extubation strategies (HFNC for all patients vs. NIV for high-risk patients and HFNC for low-risk patients) with conventional post-extubation oxygen therapy and with each other. 3. A batched design allows for the recruitment of clusters (i.e., ICUs) throughout the duration of the trial rather than requiring that all clusters commence participation in the trial at the same time. ##### Masking Info **Masking:** NONE **Primary Purpose:** HEALTH_SERVICES_RESEARCH #### Enrollment Info **Count:** 16800 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** During this period, ICU providers receive traditional online education that demonstrates the evidence supporting use of preventive post-extubation respiratory support (NIV or HFNC) over conventional post-extubation oxygen and supports the implementation of risk-stratified, preventive post-extubation NIV/HFNC. **Intervention Names:** - Behavioral: Traditional online education - Other: Risk-stratified preventive post-extubation noninvasive ventilation (NIV) or high-flow nasal cannula oxygen (HFNC) **Label:** Online education about risk-stratified post-extubation NIV/HFNC **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** During this period, ICU providers receive interprofessional education that demonstrates the evidence supporting use of preventive post-extubation respiratory support (NIV or HFNC) over conventional post-extubation oxygen and supports the implementation of risk-stratified, preventive post-extubation NIV/HFNC. **Intervention Names:** - Behavioral: Interprofessional education - Other: Risk-stratified preventive post-extubation noninvasive ventilation (NIV) or high-flow nasal cannula oxygen (HFNC) **Label:** Interprofessional education about risk-stratified post-extubation NIV/HFNC **Type:** ACTIVE_COMPARATOR #### Arm Group 3 **Description:** During this period, ICU providers deploy a clinical protocol that supports the implementation of risk-stratified, preventive post-extubation NIV/HFNC. **Intervention Names:** - Behavioral: Clinical protocol - Other: Risk-stratified preventive post-extubation noninvasive ventilation (NIV) or high-flow nasal cannula oxygen (HFNC) **Label:** Clinical protocol about risk-stratified post-extubation NIV/HFNC **Type:** ACTIVE_COMPARATOR #### Arm Group 4 **Description:** During this period, ICU providers receive interprofessional education and use a clinical protocol that supports the implementation of risk-stratified, preventive post-extubation NIV/HFNC. **Intervention Names:** - Behavioral: Interprofessional education - Behavioral: Clinical protocol - Other: Risk-stratified preventive post-extubation noninvasive ventilation (NIV) or high-flow nasal cannula oxygen (HFNC) **Label:** Interprofessional education plus clinical protocol about risk-stratified post-extubation NIV/HFNC **Type:** ACTIVE_COMPARATOR #### Arm Group 5 **Description:** During this period, ICU providers receive traditional online education that demonstrates the evidence supporting use of preventive post-extubation respiratory support (NIV or HFNC) over conventional post-extubation oxygen and supports the implementation of preventive post-extubation HFNC for all eligible patients. **Intervention Names:** - Behavioral: Traditional online education - Other: Preventive post-extubation high-flow nasal cannula oxygen (HFNC) **Label:** Online education about post-extubation HFNC **Type:** ACTIVE_COMPARATOR #### Arm Group 6 **Description:** During this period, ICU providers receive interprofessional education that demonstrates the evidence supporting use of preventive post-extubation respiratory support (NIV or HFNC) over conventional post-extubation oxygen and supports the implementation of preventive post-extubation HFNC for all eligible patients. **Intervention Names:** - Behavioral: Interprofessional education - Other: Preventive post-extubation high-flow nasal cannula oxygen (HFNC) **Label:** Interprofessional education about post-extubation HFNC **Type:** ACTIVE_COMPARATOR #### Arm Group 7 **Description:** During this period, ICU providers deploy a clinical protocol that supports the implementation of preventive post-extubation HFNC for all eligible patients. **Intervention Names:** - Behavioral: Clinical protocol - Other: Preventive post-extubation high-flow nasal cannula oxygen (HFNC) **Label:** Clinical protocol about post-extubation HFNC **Type:** ACTIVE_COMPARATOR #### Arm Group 8 **Description:** During this period, ICU providers receive interprofessional education and use a clinical protocol that supports the implementation of preventive post-extubation HFNC for all eligible patients. **Intervention Names:** - Behavioral: Interprofessional education - Behavioral: Clinical protocol - Other: Preventive post-extubation high-flow nasal cannula oxygen (HFNC) **Label:** Interprofessional education plus clinical protocol about post-extubation HFNC **Type:** ACTIVE_COMPARATOR #### Arm Group 9 **Description:** During this period, ICU providers receive no structured education about preventive, post-extubation respiratory support therapies **Label:** Usual care **Type:** NO_INTERVENTION ### Interventions #### Intervention 1 **Arm Group Labels:** - Online education about post-extubation HFNC - Online education about risk-stratified post-extubation NIV/HFNC **Description:** A 30-60 minute, online, interactive, educational video that is customized to each provider type and offered with provider-specific continuing education credits **Name:** Traditional online education **Type:** BEHAVIORAL #### Intervention 2 **Arm Group Labels:** - Interprofessional education about post-extubation HFNC - Interprofessional education about risk-stratified post-extubation NIV/HFNC - Interprofessional education plus clinical protocol about post-extubation HFNC - Interprofessional education plus clinical protocol about risk-stratified post-extubation NIV/HFNC **Description:** Interprofessional education (IPE) consists of both classroom-based IPE and just-in-time IPE. In classroom-based IPE, a trained physician educator with content expertise who works in the ICU leads a 60-to-90-minute, in-person, IPE workshop consisting of a 30-minute didactic session and a 30-to-60-minute small group session, during which participants work together to apply the content to authentic cases. The workshops, which are designed according to modern principles of adult learning and IPE, present the rationale and evidence supporting the preventive, post-extubation therapies. They are specifically designed to foster authenticity, reinforce role identity, and relate the content to life experience. In just-in-time IPE, trained local champions meet with the interprofessional ICU team each morning to identify eligible patients and, as needed, briefly review the evidence supporting proper use of the assigned preventive, post-extubation strategy. **Name:** Interprofessional education **Type:** BEHAVIORAL #### Intervention 3 **Arm Group Labels:** - Clinical protocol about post-extubation HFNC - Clinical protocol about risk-stratified post-extubation NIV/HFNC - Interprofessional education plus clinical protocol about post-extubation HFNC - Interprofessional education plus clinical protocol about risk-stratified post-extubation NIV/HFNC **Description:** An "adequately explicit" protocol provides specific rules for use of the preventive, post-extubation therapy based on patient data. A "ready-to-customize" version of the protocol with instructions to work with key local stakeholders to revise the protocol, accounting for local needs and resources, is provided. After local customization, a local champion then disseminates the protocol based on local practices. **Name:** Clinical protocol **Type:** BEHAVIORAL #### Intervention 4 **Arm Group Labels:** - Clinical protocol about risk-stratified post-extubation NIV/HFNC - Interprofessional education about risk-stratified post-extubation NIV/HFNC - Interprofessional education plus clinical protocol about risk-stratified post-extubation NIV/HFNC - Online education about risk-stratified post-extubation NIV/HFNC **Description:** Preventive post-extubation NIV for high-risk patients and preventive post-extubation HFNC for low-risk patients **Name:** Risk-stratified preventive post-extubation noninvasive ventilation (NIV) or high-flow nasal cannula oxygen (HFNC) **Type:** OTHER #### Intervention 5 **Arm Group Labels:** - Clinical protocol about post-extubation HFNC - Interprofessional education about post-extubation HFNC - Interprofessional education plus clinical protocol about post-extubation HFNC - Online education about post-extubation HFNC **Description:** Preventive post-extubation HFNC for all eligible patients (without risk stratification) **Name:** Preventive post-extubation high-flow nasal cannula oxygen (HFNC) **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** Defined the number of participants who received post-extubation NIV or HFNC divided by the number of participants eligible for post-extubation NIV or HFNC **Measure:** Rate of use of post-extubation NIV or HFNC among eligible participants (primary implementation outcome) **Time Frame:** 60 days after initiating invasive mechanical ventilation **Description:** Defined as the number of participants who died during hospitalization **Measure:** In-hospital mortality truncated at 60 days from intubation (primary clinical outcome) **Time Frame:** 60 days after initiating invasive mechanical ventilation #### Secondary Outcomes **Description:** Defined as the total number of participants who received care from ICU providers (physicians, nurses, and/or respiratory therapists) who completed an implementation intervention (traditional online education, interprofessional education, and/or clinical protocol) **Measure:** Number of eligible participants receiving care from providers who completed an implementation intervention **Time Frame:** Up to 3 years **Description:** Defined the number of participants who received post-extubation NIV or HFNC divided by the number of participants eligible for post-extubation NIV or HFNC during the one-month period beginning 6 months after the implementation intervention (IPE plus protocol) is fully deployed **Measure:** Use of post-extubation NIV or HFNC among eligible participants 6 months after the implementation intervention (IPE plus protocol) is fully deployed **Time Frame:** 6 months after the implementation intervention (IPE plus protocol) is fully deployed **Description:** Defined as time from initiating invasive mechanical ventilation to the date of death from any cause or last known follow-up (censored) **Measure:** 90-day survival **Time Frame:** 90 days after initiating invasive mechanical ventilation **Description:** Defined as time from the time of initiating invasive mechanical ventilation to successful discharge from the ICU, where "successful" indicates that discharge was followed by at least 48 hours alive without ICU readmission **Measure:** ICU length of stay **Time Frame:** 60 days after initiating invasive mechanical ventilation **Description:** Defined as time from the time of initiating invasive mechanical ventilation to successful hospital discharge, where "successful" indicates that discharge was followed by at least 48 hours alive without hospital readmission **Measure:** Hospital length of stay **Time Frame:** 60 days after initiating invasive mechanical ventilation **Description:** Defined as reintubation and resumption of invasive mechanical ventilation during the 48 hours after extubation **Measure:** Post-extubation respiratory failure **Time Frame:** 60 days after initiating invasive mechanical ventilation **Description:** Defined as time from the time of initiating invasive mechanical ventilation to successful extubation, where "successful" indicates that extubation was followed by at least 48 hours alive without reintubation **Measure:** Duration of mechanical ventilation **Time Frame:** 60 days after initiating invasive mechanical ventilation **Description:** Defined as the number of days a participant was breathing without assistance from the day they of intubation (initiating invasive mechanical ventilation) to 28 days later, where "breathing without assistance" indicates that discontinuation of assisted breathing was followed by at least 48 hours alive without reintubation **Measure:** 28-day ventilator-free days (VFDs) **Time Frame:** 28 days after initiating invasive mechanical ventilation **Description:** Defined as the number of participants who have a VAE according to Centers of Disease Control and Prevention (CDC) criteria divided by the number of participants who received invasive mechanical ventilation **Measure:** Ventilator-associated events (VAEs) **Time Frame:** Up to 60 days after initiating invasive mechanical ventilation **Description:** Defined as mean daily sequential organ failure assessment (SOFA) score from initiating invasive mechanical ventilation to up to 60 days later **Measure:** Organ failure (daily SOFA) **Time Frame:** Up to 60 days after initiating invasive mechanical ventilation ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * All adults treated with invasive mechanical ventilation \>24 hours in participating ICUs Exclusion Criteria: * None **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Pittsburgh **Country:** United States **Facility:** University of Pittsburgh **State:** Pennsylvania **Zip:** 15213 #### Overall Officials **Official 1:** **Affiliation:** University of Pittsburgh **Name:** Timothy D Girard, MD, MSCI **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **Access Criteria:** Proposals should be directed to Timothy Girard at [email protected]. To gain access, data requestors will need to sign a data use agreement. **Description:** The University of Pittsburgh will comply with applicable NIH guidelines on data sharing as published online. The investigators will make scientific data as widely and freely available as possible while safeguarding the privacy of participants and protecting confidential and proprietary data. Data will be shared as elements that meet or exceed the HIPAA Privacy Rule definition of "safe harbor de-identified" data, so that the rights and privacy of human subjects who participate in research are protected at all times. Principles and guidelines as outlined by the NIH Office of Technology Transfer will be observed in sharing all scientific resources. **Info Types:** - STUDY_PROTOCOL - SAP **IPD Sharing:** YES **Time Frame:** Deidentified individual participant data will be made available to investigators who provide a methodologically sound proposal to achieve the aims of the approved proposal. Data will be available as soon as possible but no later than within one year of the completion of the funded project period or upon acceptance of the data for publication, whichever is earlier. ### References Module #### References **Citation:** Ouellette DR, Patel S, Girard TD, Morris PE, Schmidt GA, Truwit JD, Alhazzani W, Burns SM, Epstein SK, Esteban A, Fan E, Ferrer M, Fraser GL, Gong MN, Hough CL, Mehta S, Nanchal R, Pawlik AJ, Schweickert WD, Sessler CN, Strom T, Kress JP. Liberation From Mechanical Ventilation in Critically Ill Adults: An Official American College of Chest Physicians/American Thoracic Society Clinical Practice Guideline: Inspiratory Pressure Augmentation During Spontaneous Breathing Trials, Protocols Minimizing Sedation, and Noninvasive Ventilation Immediately After Extubation. Chest. 2017 Jan;151(1):166-180. doi: 10.1016/j.chest.2016.10.036. Epub 2016 Nov 3. **PMID:** 27818331 **Citation:** Rochwerg B, Brochard L, Elliott MW, Hess D, Hill NS, Nava S, Navalesi P Members Of The Steering Committee, Antonelli M, Brozek J, Conti G, Ferrer M, Guntupalli K, Jaber S, Keenan S, Mancebo J, Mehta S, Raoof S Members Of The Task Force. Official ERS/ATS clinical practice guidelines: noninvasive ventilation for acute respiratory failure. Eur Respir J. 2017 Aug 31;50(2):1602426. doi: 10.1183/13993003.02426-2016. Print 2017 Aug. **PMID:** 28860265 **Citation:** Granton D, Chaudhuri D, Wang D, Einav S, Helviz Y, Mauri T, Mancebo J, Frat JP, Jog S, Hernandez G, Maggiore SM, Hodgson CL, Jaber S, Brochard L, Trivedi V, Ricard JD, Goligher EC, Burns KEA, Rochwerg B. High-Flow Nasal Cannula Compared With Conventional Oxygen Therapy or Noninvasive Ventilation Immediately Postextubation: A Systematic Review and Meta-Analysis. Crit Care Med. 2020 Nov;48(11):e1129-e1136. doi: 10.1097/CCM.0000000000004576. **PMID:** 32947472 **Citation:** Sang L, Nong L, Zheng Y, Xu Y, Chen S, Zhang Y, Huang Y, Liu X, Li Y. Effect of high-flow nasal cannula versus conventional oxygen therapy and non-invasive ventilation for preventing reintubation: a Bayesian network meta-analysis and systematic review. J Thorac Dis. 2020 Jul;12(7):3725-3736. doi: 10.21037/jtd-20-1050. **PMID:** 32802452 **Citation:** Fernando SM, Tran A, Sadeghirad B, Burns KEA, Fan E, Brodie D, Munshi L, Goligher EC, Cook DJ, Fowler RA, Herridge MS, Cardinal P, Jaber S, Moller MH, Thille AW, Ferguson ND, Slutsky AS, Brochard LJ, Seely AJE, Rochwerg B. Noninvasive respiratory support following extubation in critically ill adults: a systematic review and network meta-analysis. Intensive Care Med. 2022 Feb;48(2):137-147. doi: 10.1007/s00134-021-06581-1. Epub 2021 Nov 25. **PMID:** 34825256 **Citation:** Argote L, Miron-Spektor E. Organizational learning: From experience to knowledge. Organization Science 2011;22:1123-37. **Citation:** Kasza J, Bowden R, Hooper R, Forbes AB. The batched stepped wedge design: A design robust to delays in cluster recruitment. Stat Med. 2022 Aug 15;41(18):3627-3641. doi: 10.1002/sim.9438. Epub 2022 May 21. **PMID:** 35596691 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000012120 - Term: Respiration Disorders - ID: D000012140 - Term: Respiratory Tract Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC08 - Name: Respiratory Tract (Lung and Bronchial) Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M14968 - Name: Respiratory Insufficiency - Relevance: HIGH - As Found: Respiratory Failure - ID: M27137 - Name: Respiratory Aspiration - Relevance: LOW - As Found: Unknown - ID: M14957 - Name: Respiration Disorders - Relevance: LOW - As Found: Unknown - ID: M14977 - Name: Respiratory Tract Diseases - Relevance: LOW - As Found: Unknown - ID: T170 - Name: Acute Graft Versus Host Disease - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000012131 - Term: Respiratory Insufficiency ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03838679 **Brief Title:** Imaging of the Angiofibrotic Switch in Neovascular AMD **Official Title:** Multimodal Imaging of Subretinal Fibrosis in Neovascular AMD #### Organization Study ID Info **ID:** 2019-02-0051 #### Organization **Class:** OTHER **Full Name:** Medical University of Vienna ### Status Module #### Completion Date **Date:** 2022-04-28 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** RECRUITING #### Last Update Post Date **Date:** 2020-02-20 **Type:** ACTUAL **Last Update Submit Date:** 2020-02-19 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2022-04-28 **Type:** ESTIMATED #### Start Date **Date:** 2019-05-01 **Type:** ACTUAL **Status Verified Date:** 2020-02 #### Study First Post Date **Date:** 2019-02-12 **Type:** ACTUAL **Study First Submit Date:** 2019-02-10 **Study First Submit QC Date:** 2019-02-10 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Medical University of Vienna #### Responsible Party **Investigator Affiliation:** Medical University of Vienna **Investigator Full Name:** Philipp Roberts **Investigator Title:** Principal investigator **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** The content of this research project is to identify the angiofibrotic switch, the transition from angiogenesis to fibrosis, in neovascular age-related macular degeneration (nAMD) longitudinally. Despite optimal treatment about 50% of eyes with nAMD develop fibrosis within 2 years, causing irreversible damage to the retina and functional loss. Objective measurement of fibrosis, however, is challenging, since clinical staging is subjective and current imaging modalities such as color fundus photography (CFP), fluorescein angiography (FA) and optical coherence tomography (OCT) often do not allow clear delineation. Novel imaging modalities such as polarization-sensitive OCT (PS-OCT), OCT angiography (OCTA) and adaptive-optics OCT (AO-OCT) offer identification of fibrous components and microvasculature of fibrotic lesions non-invasively with highest precision and shall thus be used in this study. Hypotheses: The investigators hypothesize to detect and quantify subclinical (i.e. not detectable on dilated fundus examination) areas of fibrosis using PS-OCT and determine the rate and exact location within the neovascular lesion. Furthermore, the investigators expect neuroretinal and microvascular changes, which will be assessed by AO-OCT and OCTA. Methods: Eighty eyes of 80 patients with chronic nAMD will be included and examined cross- sectionally to evaluate the accuracy of PS-OCT to detect and quantify fibrosis in comparison to gold standard imaging modalities. In addition, OCTA and AO-OCT will be performed to analyze the relationship between fibrous, neovascular and neuroretinal structures. Furthermore, forty eyes of 40 participants with treatment-naïve nAMD will be included and followed over 12 months with predefined follow-up intervals. Novel non-invasive imaging will be applied to objectively determine the exact time and extent of the angiofibrotic switch in nAMD during state-of-the- art therapy. This approach has not been done before and is clinically relevant for multiple reasons: Firstly, only little is known about the development of fibrosis in AMD during therapy. Secondly, the clinical diagnosis of subretinal fibrosis is subjective and does not allow reliable quantification. Thirdly, current gold standard imaging modalities (i.e. CFP and FA) for detection of fibrosis involve invasive and time-consuming procedures and do not allow three-dimensional analysis. Finally, our study may identify objective endpoints for future interventional trials. **Detailed Description:** Research questions/hypotheses: Age-related macular degeneration (AMD) is the main cause of legal blindness among elderly patients in industrialized countries. The main reason for severe and irreversible visual impairment among these patients is subretinal fibrosis (SF). Large-scale interventional trials (e.g. CATT) have shown that half of all eyes affected by choroidal neovascularization (CNV) develop clinically visible fibrotic scarring over two years despite optimal treatment, causing irreversible retinal damage and functional loss. Thus, prevention of fibrosis in AMD is currently the focus of researchers worldwide. Clearly defined end points for interventional trials, however, are lacking because detection and quantification of SF is challenging. Clinical staging of SF is subjective and current gold standard imaging modalities such as color fundus photography (CFP), fluorescein angiography (FA) and optical coherence tomography (OCT), even in concert, do not allow a distinct and early delineation of SF. Novel imaging modalities such as polarization-sensitive OCT (PS-OCT), OCT angiography (OCTA) and adaptive optics (AO)-OCT are promising means to objectively detect SF and provide detailed insights into the biology of the microvascular and neurosensory compartments. Our group recently demonstrated that PS-OCT offers automated identification and quantification of SF in AMD based on tissue-specific contrast. Aim of the proposed research project is to detect and characterize the angiofibrotic switch, i.e. the transition from active and reversible neovascularization to irreversible fibrosis, in neovascular AMD under anti-VEGF treatment. We hypothesize to detect the initiating events of fibrotic conversion including even subclinical stages of fibrosis by non-invasive PS-OCT and identify the association with fibrovascular and retinal changes by OCTA and AO-OCT, respectively. Scientific/scholarly innovation/originality of the project: The combination of PS-OCT, OCTA and AO-OCTA to non-invasively detect pathognomonic features of fibrovascular conversion is a novel and unprecedented approach towards objective visualization and quantification of disease pathomechanisms. Outcomes of this study may provide clearly defined morphological endpoints for future interventional trials. Methods: Eighty eyes of 80 patients with chronic nAMD will be included and examined cross-sectionally to evaluate the accuracy of PS-OCT to detect and quantify fibrosis in comparison to gold standard imaging. In addition, OCTA and AO-OCT will be performed to analyze the relationship between fibrous, vascular and retinal structures. Furthermore, forty eyes of 40 participants with treatment-naïve nAMD will be included in a prospective study and followed for one year under treatment. PS-OCT, AO-OCT and OCTA imaging will be performed according to a standardized protocol at predefined visits. Gold standard imaging will be performed for validation. ### Conditions Module **Conditions:** - Age-related Macular Degeneration - Choroidal Neovascularization ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 120 **Type:** ESTIMATED **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** 80 participants with neovascular AMD and a minimum history of 12 months of anti- VEGF therapy will be included in cohort 1 and examined only once (1 study visit). **Intervention Names:** - Diagnostic Test: Best-corrected Visual acuity testing (BCVA) - Diagnostic Test: Optical coherence tomography (OCT) - Diagnostic Test: Color fundus photography (CFP) - Diagnostic Test: Optical coherence tomography angiography (OCTA) - Diagnostic Test: Polarization-sensitive optical coherence tomography (PS-OCT) - Diagnostic Test: Microperimetry (MP) - Diagnostic Test: Adaptive-optics optical coherence tomography (AO-OCT) - Diagnostic Test: Fluorescein angiography (FA) **Label:** Cohort 1 #### Arm Group 2 **Description:** 40 participants with treatment-naive neovascular AMD receiving standardized anti- VEGF therapy will be included in cohort 2 and followed for 12 months (6 study visits). **Intervention Names:** - Diagnostic Test: Best-corrected Visual acuity testing (BCVA) - Diagnostic Test: Optical coherence tomography (OCT) - Diagnostic Test: Color fundus photography (CFP) - Diagnostic Test: Optical coherence tomography angiography (OCTA) - Diagnostic Test: Polarization-sensitive optical coherence tomography (PS-OCT) - Diagnostic Test: Microperimetry (MP) - Diagnostic Test: Adaptive-optics optical coherence tomography (AO-OCT) - Diagnostic Test: Fluorescein angiography (FA) **Label:** Cohort 2 ### Interventions #### Intervention 1 **Arm Group Labels:** - Cohort 1 - Cohort 2 **Description:** Best-corrected visual acuity (BCVA) will be measured using Early Treatment of Diabetic Retinopathy Study (ETDRS) charts at 4 meters and 1 meter, respectively. **Name:** Best-corrected Visual acuity testing (BCVA) **Type:** DIAGNOSTIC_TEST #### Intervention 2 **Arm Group Labels:** - Cohort 1 - Cohort 2 **Description:** Optical Coherence Tomography (OCT) is a non-invasive diagnostic technique that renders an in vivo cross sectional view of the retina. **Name:** Optical coherence tomography (OCT) **Type:** DIAGNOSTIC_TEST #### Intervention 3 **Arm Group Labels:** - Cohort 1 - Cohort 2 **Description:** Color fundus photography is a non-invasive, fast and reliable imaging method providing a true-to-life depiction of the ocular fundus. **Name:** Color fundus photography (CFP) **Type:** DIAGNOSTIC_TEST #### Intervention 4 **Arm Group Labels:** - Cohort 1 - Cohort 2 **Description:** OCTA, an extension of conventional OCT, offers noninvasive imaging of the retinal and choroidal vasculature. **Name:** Optical coherence tomography angiography (OCTA) **Type:** DIAGNOSTIC_TEST #### Intervention 5 **Arm Group Labels:** - Cohort 1 - Cohort 2 **Description:** PS-OCT, a functional exten- sion of conventional OCT technology, enables differentiation of retinal layers based on their distinct interference with the polarization state of the probing light beam, as opposed to mere light intensity. **Name:** Polarization-sensitive optical coherence tomography (PS-OCT) **Type:** DIAGNOSTIC_TEST #### Intervention 6 **Arm Group Labels:** - Cohort 1 - Cohort 2 **Description:** Microperimetry allows testing of retinal sensitivity at specific locations in the area of the fovea, parafovea or even more peipheral areas of the macula. **Name:** Microperimetry (MP) **Type:** DIAGNOSTIC_TEST #### Intervention 7 **Arm Group Labels:** - Cohort 1 - Cohort 2 **Description:** AO-OCT, an extension of conventional OCT, offers non-invasive imaging of the retina with improved lateral resolution of up to 2-3 μm. **Name:** Adaptive-optics optical coherence tomography (AO-OCT) **Type:** DIAGNOSTIC_TEST #### Intervention 8 **Arm Group Labels:** - Cohort 1 - Cohort 2 **Description:** FA imaging is a standard imaging technique used for the diagnosis of vascular pathologies of the retina such as choroidal neovascularization. **Name:** Fluorescein angiography (FA) **Type:** DIAGNOSTIC_TEST ### Outcomes Module #### Other Outcomes **Description:** In cohort 1 (eyes with a minimum history of 12 months of anti- VEGF), we will compare imaging data assessed by PS-OCT with image data from OCTA for morphological analyses. In cohort 2 the same analyses will be performed. Cohort 2 will provide detailed follow-up information about morphological changes over time. Outcome measures in eyes with and without fibrosis (vessel configuration in OCTA) will be compared using chi-square tests (categorical variables), t-tests (metric variables that can be assumed to be normally distributed) and Wilcoxon tests (metric variables that cannot be assumed to be normally distributed). ANOVA and paired t-tests will be used to investigate the longitudinal changes in cohort 2. P values \< 0.05 will be considered statistically significant. Due to the exploratory nature of these analyses, no correction for multiplicity will be used. **Measure:** Correlation of fibrosis and co-localized vascular changes (comparison between OCTA and PS-OCT) **Time Frame:** 36 months **Description:** For a morphological-functional analysis areas of functional loss in microperimetry will be analyzed in detail using multimodal imaging (including PS-OCT, OCTA, OCT and AO-OCT) and relevant morphological changes associated with reduced retinal sensitivity will be assessed and described. In cohort 1 and cohort 2 the same analyses will be performed. Additionally, cohort 2 will provide detailed follow-up information about morphological and functional changes over time. **Measure:** Correlation of fibrosis localization and co-localized retinal function (comparison between MP, PS-OCT, OCTA, OCT and AO-OCT) **Time Frame:** 36 months **Description:** Descriptive analysis will be performed for patient demographics of both cohort 1 and cohort 2, as well as for morphological parameters and visual acuity (for metric variables mean, standard deviation, min, max, median and for categorical variables absolute and relative frequencies will be computed). Outcomes of BCVA testing in eyes with and without subretinal fibrosis will be analyzed cross-sectionally (cohort 1) and longitudinally (cohort 2). **Measure:** Correlation of morphology (fibrosis) and visual outcome (comparison between BCVA and PS-OCT, OCTA, AO-OCT, OCT) **Time Frame:** 36 months **Description:** Condition of the RPE assessed by PS-OCT will be graded as continuous, RPE porosity, focal RPE atrophy, RPE thickening or pigment migration in areas with and without fibrosis and described. RPE condition in eyes with and without subretinal fibrosis will be analyzed cross-sectionally (cohort 1) and longitudinally (cohort 2). **Measure:** Condition of the retinal pigment epithelium (RPE) assessed by PS-OCT in areas of fibrosis. **Time Frame:** 36 months **Description:** Condition of the photoreceptor layer assessed by AO-OCT in areas with and without fibrosis (particularly areas at the border zone of subretinal fibrosis) will be assessed and described. RPE condition in eyes with and without subretinal fibrosis will be analyzed cross-sectionally (cohort 1) and longitudinally (cohort 2). **Measure:** Correlation of fibrosis localization and co-localized photoreceptor status (comparison between AO-OCT and PS-OCT) **Time Frame:** 36 months #### Primary Outcomes **Description:** The primary objective is to determine how well the fibrosis present/not present classification of the novel PS-OCT imaging works compared to gold standard imaging techniques. To assess the primary objective, a 95% confidence interval for the proportion of correct fibrosis yes/no classifications by the novel PS-OCT imaging compared to the gold standard will be computed. To assess this objective, data from cohort 1 will be used. **Measure:** Detection of subretinal fibrosis by PS-OCT **Time Frame:** 15 months #### Secondary Outcomes **Description:** The secondary objective is to determine how well the fibrosis area detection of the novel PS-OCT imaging works compared to gold standard imaging techniques. To assess the secondary objective, a Bland-Altman plot will be drawn. Furthermore, a 95% confidence interval for the mean difference in detected area and the mean absolute difference in detected area will be computed. To assess this objective, two analysis sets will be used: Firstly, data from cohort 1 and baseline data of cohort 2, and secondly data from the 1 year follow-up examination of patients in cohort 2. **Measure:** Extension of fibrosis area quantified on PS-OCT and correlated to standard imaging modalities **Time Frame:** 33 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Chronic neovascular AMD with anti-VEGF treatment of a minimum duration of 12 months (cohort 1) * Treatment-naïve active neovascular AMD (cohort 2) * 50 years of age or older * Visual acuity 20/25-20/320 * At least one druse (\>63μm) in either eye or late AMD in the fellow eye * Fibrosis \<50% of total lesion area at baseline (cohort 2) Exclusion Criteria: * Previous treatment for CNV in the study eye (cohort 2) * Presence of other progressive retinal disease likely to affect visual acuity * Contraindications for treatment with anti-VEGF * Pregnancy * Dyslexia **Minimum Age:** 50 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** There will be two study cohorts in this trial: 1. 80 participants with neovascular AMD and a minimum history of 12 months of anti- VEGF therapy will be included in cohort 1 and examined only once (1 study visit). 2. 40 participants with treatment-naive neovascular AMD receiving standardized anti- VEGF therapy will be included in cohort 2 and followed for 12 months (6 study visits). ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Philipp Roberts, MD PhD **Phone:** +4314040079400 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Markus Schranz, MD **Phone:** +4314040079400 **Role:** CONTACT #### Locations **Location 1:** **City:** Vienna **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Philipp Roberts, MD PhD - **Phone:** +4314040079400 - **Role:** CONTACT ***Contact 2:*** - **Email:** [email protected] - **Name:** Markus Schranz, MD - **Phone:** +4314040079400 - **Role:** CONTACT **Country:** Austria **Facility:** Medical University of Vienna **Status:** RECRUITING **Zip:** 1090 #### Overall Officials **Official 1:** **Affiliation:** Medical University of Vienna **Name:** Philipp Roberts, MD PhD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** UNDECIDED ## Derived Section ### Condition Browse Module - Ancestors - ID: D000012162 - Term: Retinal Degeneration - ID: D000012164 - Term: Retinal Diseases - ID: D000005128 - Term: Eye Diseases - ID: D000008679 - Term: Metaplasia - ID: D000010335 - Term: Pathologic Processes - ID: D000015862 - Term: Choroid Diseases - ID: D000014603 - Term: Uveal Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC11 - Name: Eye Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M8485 - Name: Fibrosis - Relevance: LOW - As Found: Unknown - ID: M12334 - Name: Neovascularization, Pathologic - Relevance: HIGH - As Found: Neovascularization - ID: M11260 - Name: Macular Degeneration - Relevance: HIGH - As Found: Age-related Macular Degeneration - ID: M22078 - Name: Choroidal Neovascularization - Relevance: HIGH - As Found: Choroidal Neovascularization - ID: M14997 - Name: Retinal Degeneration - Relevance: LOW - As Found: Unknown - ID: M14999 - Name: Retinal Diseases - Relevance: LOW - As Found: Unknown - ID: M8271 - Name: Eye Diseases - Relevance: LOW - As Found: Unknown - ID: M11659 - Name: Metaplasia - Relevance: LOW - As Found: Unknown - ID: M18406 - Name: Choroid Diseases - Relevance: LOW - As Found: Unknown - ID: M17351 - Name: Uveal Diseases - Relevance: LOW - As Found: Unknown - ID: T5824 - Name: Uveal Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000008268 - Term: Macular Degeneration - ID: D000020256 - Term: Choroidal Neovascularization - ID: D000009389 - Term: Neovascularization, Pathologic ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04510779 **Brief Title:** Apple Watch Heart Failure Study **Official Title:** Monitoring Heart Failure Patients Using Heart Rate Variability Measured by the Apple Watch #### Organization Study ID Info **ID:** AppleWatch #### Organization **Class:** OTHER **Full Name:** Tufts Medical Center ### Status Module #### Completion Date **Date:** 2023-12-31 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2023-03-28 **Type:** ACTUAL **Last Update Submit Date:** 2023-03-27 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2023-11-30 **Type:** ESTIMATED #### Start Date **Date:** 2022-05-09 **Type:** ACTUAL **Status Verified Date:** 2023-03 #### Study First Post Date **Date:** 2020-08-12 **Type:** ACTUAL **Study First Submit Date:** 2020-08-10 **Study First Submit QC Date:** 2020-08-10 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Tufts Medical Center #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Is US Export:** False ### Description Module **Brief Summary:** This is a pilot/feasibility study on the accuracy of HRV as measured by the Apple Watch on heart failure patients who are admitted to the hospital with heart failure exacerbation. The primary aim is to observe a statistically significant improvement in the HRV of acutely decompensated heart failure patients upon discharge when compared to admission, implying the utility of HRV measured by Apple Watch as a monitor for cardiovascular health. **Detailed Description:** Heart failure (HF) is a complex clinical syndrome. It is caused by structural or functional impairments, which interfere with the ability of heart muscles to fill or eject blood. The prevalence of HF exceeds 7 million in the United States alone.(1) Despite improving survival, HF hospitalization rates has remained stable, which reflects persisting difficulties in managing existing disease. (2) Specifically, readmission rates may be as high as 50% by 6 months after an admission for HF management. (2) Caring for HF patients exceeds 30 billion annually and is largely driven by hospitalizations.2 Innovative, at-home surveillance tools are needed to reduce hospital admissions and to drive down the overall societal burden of this disease. (3) HF is characterized by periodic exacerbations due to volume overload and fluid congestion that impairs perfusion to the organs.(2) Accurate assessment of volume status is, therefore, key for early detection of impending exacerbation. Currently, there is no single, objective method of assessment, relying on a combination of tools including physical examination, weight, pulmonary artery catheter or echocardiography.(4) However, these measures are subjective, invasive, or impractical for monitoring patients at home. Unique body habitus and comorbidities of individual patient further complicates assessment of volume status.(4) The future of heart failure management, therefore, lies in the development of a telemonitoring system that is convenient to use and accessible for patients at home, while quantitatively understanding individual characteristics.(4) Cardiovascular health is closely related to the imbalances of the autonomic nervous system.(5) Heart rate variability (HRV), the degree of fluctuation in the interval between consecutive heartbeats, has been recognized as a reliable marker of autonomic activity.(5) HRV has been shown to be depressed in patients with congestive heart failure (CHF) and to correlate with disease severity. (6) Furthermore, abnormal HRV parameters are independently associated with incident CHF in asymptomatic, older adults. (7) HRV is conventionally measured using a 24-hour Holter monitor, which is sensitive, but inconvenient and impractical for home monitoring.(5) Newer studies have shown not only the reliability of short term (5-minute) or ultra-short term (\<5 minute) analysis of electrocardiographic recordings, but also that of wearable monitors amenable for use at home.(9-11) In particular, HRV parameters measured by Apple Watch (Cupertino, California) were shown to agree with those measured by a validated chest best heart rate monitor.(12) The usefulness of the study is to validate the utility of wearable heart monitors such as the Apple Watch in accurately measuring heart rate variability, a dynamic marker of cardiovascular health, and correlating it with the health status specifically of heart failure patients. Validating this will allow wearable monitors to record HRV remotely from home, facilitating telemonitoring and preventing hospitalizations. ### Conditions Module **Conditions:** - Heart Failure ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** DIAGNOSTIC #### Enrollment Info **Count:** 40 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** This will be a single arm study of heart failure patients with acute decompensation **Intervention Names:** - Device: Apple Watch **Label:** Heart Failure Patients **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Heart Failure Patients **Description:** Apple Watch is a smartwatch developed by Apple Inc. The heart rate variability function will be used. **Name:** Apple Watch **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Description:** Standard Deviation of NN Intervals is a time domain heart rate variability parameter. The value upon discharge after medical management should be statistically greater compared to admission value. **Measure:** Difference of Standard Deviation of NN Intervals upon Discharge Compared to Admission **Time Frame:** 1-2 Weeks ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Age \> or = 22 * Patients admitted to Tufts Medical Center for acute decompensated heart failure * Left ventricular ejection fraction greater than 35% * Able to consent Exclusion Criteria: * Pacemaker rhythm * Arrhythmia, e.g. atrial fibrillation, atrial flutter, frequent ectopic beats * prior history of heart transplant or ventricular assist device * pregnant **Minimum Age:** 22 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Edward Hong, MD **Phone:** 2015759009 **Role:** CONTACT #### Locations **Location 1:** **City:** Boston **Contacts:** ***Contact 1:*** - **Name:** Edward Hong, MD - **Role:** CONTACT **Country:** United States **Facility:** Tufts Medical Center **State:** Massachusetts **Status:** RECRUITING **Zip:** 02111 ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Roger VL. Epidemiology of heart failure. Circ Res. 2013 Aug 30;113(6):646-59. doi: 10.1161/CIRCRESAHA.113.300268. **PMID:** 23989710 **Citation:** Desai AS. Home monitoring heart failure care does not improve patient outcomes: looking beyond telephone-based disease management. Circulation. 2012 Feb 14;125(6):828-36. doi: 10.1161/CIRCULATIONAHA.111.031179. No abstract available. **PMID:** 22331920 **Citation:** Murray CM, Agha SA, Rathi S, Germany RE. The evaluation and monitoring of volume status in congestive heart failure. Congest Heart Fail. 2008 May-Jun;14(3):135-40. doi: 10.1111/j.1751-7133.2008.05640.x. **PMID:** 18550924 **Citation:** Heart rate variability. Standards of measurement, physiological interpretation, and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Eur Heart J. 1996 Mar;17(3):354-81. No abstract available. **PMID:** 8737210 **Citation:** Musialik-Lydka A, Sredniawa B, Pasyk S. Heart rate variability in heart failure. Kardiol Pol. 2003 Jan;58(1):10-6. **PMID:** 14502297 **Citation:** Patel VN, Pierce BR, Bodapati RK, Brown DL, Ives DG, Stein PK. Association of Holter-Derived Heart Rate Variability Parameters With the Development of Congestive Heart Failure in the Cardiovascular Health Study. JACC Heart Fail. 2017 Jun;5(6):423-431. doi: 10.1016/j.jchf.2016.12.015. Epub 2017 Apr 5. **PMID:** 28396041 **Citation:** Ferrario M, Moissl U, Garzotto F, Cruz DN, Clementi A, Brendolan A, Tetta C, Gatti E, Signorini MG, Cerutti S, Ronco C. Effects of fluid overload on heart rate variability in chronic kidney disease patients on hemodialysis. BMC Nephrol. 2014 Feb 4;15:26. doi: 10.1186/1471-2369-15-26. **PMID:** 24490775 **Citation:** Nussinovitch U, Elishkevitz KP, Katz K, Nussinovitch M, Segev S, Volovitz B, Nussinovitch N. Reliability of Ultra-Short ECG Indices for Heart Rate Variability. Ann Noninvasive Electrocardiol. 2011 Apr;16(2):117-22. doi: 10.1111/j.1542-474X.2011.00417.x. **PMID:** 21496161 **Citation:** Karp E, Shiyovich A, Zahger D, Gilutz H, Grosbard A, Katz A. Ultra-short-term heart rate variability for early risk stratification following acute ST-elevation myocardial infarction. Cardiology. 2009;114(4):275-83. doi: 10.1159/000235568. Epub 2009 Aug 18. **PMID:** 19690410 **Citation:** Hernando D, Roca S, Sancho J, Alesanco A, Bailon R. Validation of the Apple Watch for Heart Rate Variability Measurements during Relax and Mental Stress in Healthy Subjects. Sensors (Basel). 2018 Aug 10;18(8):2619. doi: 10.3390/s18082619. **PMID:** 30103376 **Citation:** Tanindi A, Olgun H, Celik B, Boyaci B. Heart rate variability in patients hospitalized for decompensated diastolic heart failure at admission and after clinical stabilization. Future Cardiol. 2012 May;8(3):473-82. doi: 10.2217/fca.12.24. **PMID:** 22642636 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000006331 - Term: Heart Diseases - ID: D000002318 - Term: Cardiovascular Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M9421 - Name: Heart Failure - Relevance: HIGH - As Found: Heart Failure - ID: M9419 - Name: Heart Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000006333 - Term: Heart Failure ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT01008579 **Brief Title:** Assessing Patient Care Through Routine Use of Patient-Reported Outcomes **Official Title:** Routine Use of Patient Reported Outcomes Among Older Adults at High Risk of Falls: A 12-Month Cohort Study #### Organization Study ID Info **ID:** H09-01655 #### Organization **Class:** OTHER **Full Name:** University of British Columbia ### Status Module #### Completion Date **Date:** 2011-04 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2017-11-06 **Type:** ACTUAL **Last Update Submit Date:** 2017-11-02 **Overall Status:** WITHDRAWN #### Primary Completion Date **Date:** 2011-04 **Type:** ACTUAL #### Start Date **Date:** 2009-12 **Status Verified Date:** 2017-11 #### Study First Post Date **Date:** 2009-11-06 **Type:** ESTIMATED **Study First Submit Date:** 2009-11-04 **Study First Submit QC Date:** 2009-11-05 **Why Stopped:** Redundant with another study ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** University of British Columbia #### Responsible Party **Investigator Affiliation:** University of British Columbia **Investigator Full Name:** Teresa Liu-Ambrose **Investigator Title:** Principal Investigator **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** Patient reported outcome measures (PROMs) are assessments of health status or health-related quality of life. The EuroQol-5D (EQ5D) is an example of a generic instrument to assess health-related quality of life. The investigators will use the EQ5D in the Falls Prevention Clinic as part of routine clinical assessment at baseline, 6 months and 12 months to track patient care in a cohort of 300 older adults who are at high-risk of falls. **Detailed Description:** 1. Purpose: We will use the EQ5D in the Falls Prevention Clinic as part of routine clinical assessment at baseline, 6-months and 12-months to track patient care in a cohort of 300 older adults who are at high-risk of falls. 2. Objectives: O1: Our primary objective is to use a routinely administered patient reported outcomes measure, the EuroQol-5D (EQ-5D), in older adults at high risk of falls to determine patients self-reported health status over a 12-month followup period. O2: Our secondary objective is to develop an explanatory model and a predictive model of covariates that explain significant gains or losses in health related quality of life. ### Conditions Module **Conditions:** - Falls **Keywords:** - Patient Reported Outcome Measures - falls - older adults ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Referred to falls clinic for assessment by general practitioner or emergency department physician. 2. Index fall presentation not due to overwhelming force resulting in presentation to Emergency Department or general practitioner (including syncopal presentation, see below). 3. At least 70 years of age. 4. No progressive neurological disorder (e.g. Dementia, Parkinson's, Alzheimer's). 5. Community dwelling (within Vancouver and Burnaby only). 6. Mini Mental State Examination Score of at least 24. 7. Walk at least 3 meters. 8. Has at least one of the following 'high-risk' criteria: * At least one other non-syncopal fall in the past 12 months * PPA of at least 1.0 (using dominant score for strength test) * TUG of at least 15 seconds 9. Life expectancy of greater than 12 months as determined by the geriatrician. Exclusion Criteria: 1. Any patients who do not meet the inclusion criteria specified above will be excluded from assessment at the Falls Prevention Clinic. **Minimum Age:** 60 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Falls Prevention Clinic ### Contacts Locations Module #### Locations **Location 1:** **City:** Vancouver **Country:** Canada **Facility:** Vancouver General Hospital **State:** British Columbia #### Overall Officials **Official 1:** **Affiliation:** University of British Columbia **Name:** Karim Khan **Role:** STUDY_DIRECTOR **Official 2:** **Affiliation:** University of British Columbia **Name:** Teresa Liu-Ambrose **Role:** STUDY_DIRECTOR **Official 3:** **Affiliation:** University of British Columbia **Name:** Stirling Bryan **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04636879 **Brief Title:** Dry Needling and Patients Treatment Expectations **Official Title:** Influence of Induced Expectations on the Autonomic Nervous System During a Dry Needling Intervention for Patients With Neck Pain. A Randomized Clinical Trial. #### Organization Study ID Info **ID:** CEI20/009 #### Organization **Class:** OTHER **Full Name:** University of Alcala ### Status Module #### Completion Date **Date:** 2024-05-05 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-04-08 **Type:** ACTUAL **Last Update Submit Date:** 2024-04-04 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2024-05-05 **Type:** ESTIMATED #### Start Date **Date:** 2021-02-23 **Type:** ACTUAL **Status Verified Date:** 2024-04 #### Study First Post Date **Date:** 2020-11-19 **Type:** ACTUAL **Study First Submit Date:** 2020-11-15 **Study First Submit QC Date:** 2020-11-15 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** University of Alcala #### Responsible Party **Investigator Affiliation:** University of Alcala **Investigator Full Name:** Prof. Dr. Daniel Pecos Martín **Investigator Title:** PhD. Daniel Pecos Martín **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Objectives The aim of this study is to compare the effects of inducing positive expectations against negative or neutral induced expectations on the activation of the Autonomic Nervous System and the analgesic response, after a dry needling technique in upper trapezius fibers in patients with unspecific neck pain. Summary Theoretical framework: Dry needling has proven its efficacy for the treatment of myofascial trigger points. Moreover, it has proven its effects over the Central Nervous System and the Autonomic Nervous System (ANS). Despite that previous studies have researched the role of patient's expectations and their relationship with the results of treatment, there is insufficient information concerning the effects of inducing expectations and the activation of the ANS during the application of widely used therapies, such as dry needling. **Detailed Description:** The aim of this study will be to research the effects of induced expectations combined with a dry needling technique on the activation of the ANS and on the results of the treatment. Hypothesis: The induction of a positive expectation shall cause a greater analgesic response associated with a response in the ANS compared to the induction of neutral or negative expectations. Methods: Patients with neck pain will participated in this randomized clinical trial, which will be randomly assigned into 3 groups in order to receive positive, neutral or negative expectations concerning the treatment, by means of an individual informative talk. All subjects will received treatment using dry needling in the upper trapezius fibers. The main variables measured will be the following: Analogic Visual Scale, Pressure Pain Threshold using a mechanical Force Gage (before and after) and the activation of the ANS measuring the skin conductance, skin temperature, heart rate and breathing rate (monitored for 5 minutes before the intervention, during and 20 minutes afterwards). ### Conditions Module **Conditions:** - Neck Pain; Dry Needling; Motivation ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** TRIPLE **Who Masked:** - PARTICIPANT - INVESTIGATOR - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 45 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** "Dry needling is a very effective tool used in the treatment of nonspecific neck pain, which we hope will reduce your neck pain." **Intervention Names:** - Other: Positive expectation AND dry needling in the upper trapezius fibers, at the most painful point **Label:** • Group 1. Positive expectation **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** "Dry needling is an indicated tool used in the treatment of nonspecific neck pain, but its efficacy is unknown". **Intervention Names:** - Other: Neutral expectation AND dry needling in the upper trapezius fibers, at the most painful point **Label:** • Group 2. Neutral Expectation **Type:** ACTIVE_COMPARATOR #### Arm Group 3 **Description:** "Dry needling is not a very effective treatment tool for nonspecific neck pain, so we expect your neck pain to increase a bit." **Intervention Names:** - Other: Negative expectation AND dry needling in the upper trapezius fibers, at the most painful point **Label:** • Group 3. Negative Expectation **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - • Group 1. Positive expectation **Description:** The subjects will received the same treatment, using dry needling in the upper trapezius fibers, at the most painful point after receiving the corresponding message. **Name:** Positive expectation AND dry needling in the upper trapezius fibers, at the most painful point **Type:** OTHER #### Intervention 2 **Arm Group Labels:** - • Group 2. Neutral Expectation **Description:** The subjects will received the same treatment, using dry needling in the upper trapezius fibers, at the most painful point after receiving the corresponding **Name:** Neutral expectation AND dry needling in the upper trapezius fibers, at the most painful point **Type:** OTHER #### Intervention 3 **Arm Group Labels:** - • Group 3. Negative Expectation **Description:** The subjects will received the same treatment, using dry needling in the upper trapezius fibers, at the most painful point after receiving the corresponding **Name:** Negative expectation AND dry needling in the upper trapezius fibers, at the most painful point **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** It is the measure of the variations in the electrical resistance of the skin, caused by the excitation of the sweat glands, controlled by the Sympathetic Nervous System (SNS) **Measure:** Skin conductance (µS). **Time Frame:** Change from baseline at twenty minutes #### Secondary Outcomes **Description:** This variable is defined as the variation of the heartbeat in a previously defined period in an analysis of consecutive circadian periods. It measures the time in milliseconds between the R waves of two consecutive beats (known as the RR interval) and is widely used in the field of Cardiology for the stratification of patients after an acute myocardial infarction. It has also been shown to be a useful tool in detecting ANS activation. **Measure:** Heart rate variability **Time Frame:** Change from baseline at twenty minutes **Description:** It will be collected through the Visual Analogue Scale (VAS). It is a continuous scale, which consists of a 100 mm horizontal straight line, so that zero is equivalent to "total absence of pain" and 100 to "more bearable pain. **Measure:** Pain intensity **Time Frame:** Change from baseline at twenty minutes **Description:** The pressure pain threshold is defined as the minimum amount of pressure necessary to cause pain. It has been measured through a Force Dial FDK using a mechanical Force Gage (Wagner Instruments). **Measure:** Pressure pain threshold **Time Frame:** Change from baseline at twenty minutes. ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Neck pain. * Hiperalgesic point in Upper trapezius muscle. Exclusion Criteria: * Pain Irradiation toward upper limb * Psychological disorders * Whiplash. * Neuropathic symptoms * Cervical and / or Shoulder Spine Surgery **Maximum Age:** 65 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Daniel Pecos-Martín, PhD **Phone:** + 34 918855142 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Daniel Somkereki, Master **Phone:** 636869373 **Role:** CONTACT #### Locations **Location 1:** **City:** Alcala de Henares **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Patricia Martinez-Merinero, Dr - **Phone:** +34 918855142 - **Role:** CONTACT **Country:** Spain **Facility:** Clinical University **State:** Madrid **Status:** RECRUITING **Zip:** 2805 #### Overall Officials **Official 1:** **Affiliation:** Alcala University **Name:** Daniel Pecos-Martin, PhD **Role:** STUDY_CHAIR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000010146 - Term: Pain - ID: D000009461 - Term: Neurologic Manifestations ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC10 - Name: Nervous System Diseases ### Condition Browse Module - Browse Leaves - ID: M13066 - Name: Pain - Relevance: LOW - As Found: Unknown - ID: M21485 - Name: Neck Pain - Relevance: HIGH - As Found: Neck Pain - ID: M12404 - Name: Neurologic Manifestations - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000019547 - Term: Neck Pain ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT02370979 **Acronym:** DRONE **Brief Title:** Impact of Starting a Dolutegravir-based Regimen on HIV-1 Proviral DNA Reservoir Of Treatment Naïve and Experienced Patients **Official Title:** Impact of Starting a Dolutegravir-based Regimen on HIV-1 Proviral DNA Reservoir Of Treatment Naïve and Experienced Patients #### Organization Study ID Info **ID:** 5973 #### Organization **Class:** OTHER **Full Name:** University Hospital, Strasbourg, France ### Status Module #### Completion Date **Date:** 2017-07 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** RECRUITING #### Last Update Post Date **Date:** 2015-08-07 **Type:** ESTIMATED **Last Update Submit Date:** 2015-08-06 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2017-07 **Type:** ESTIMATED #### Start Date **Date:** 2015-02 **Status Verified Date:** 2015-08 #### Study First Post Date **Date:** 2015-02-25 **Type:** ESTIMATED **Study First Submit Date:** 2015-01-26 **Study First Submit QC Date:** 2015-02-18 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** University Hospital, Strasbourg, France #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** This is a multi-center prospective study. The primary objective of DRONE study is to investigate the change of the size of HIV-1 DNA reservoir in blood from baseline to week 48 (W48) in participants treated by DTG-based regimen. Secondary objectives include: DTG pharmacokinetic and analysis of biomarkers of immune activation from baseline to W48. ### Conditions Module **Conditions:** - HIV-1 Infection **Keywords:** - Dolutegravir - Proviral HIV-1 DNA - Reservoir ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 202 **Type:** ESTIMATED **Phases:** - PHASE4 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Intervention Names:** - Biological: Blood samples **Label:** Dolutegravir **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Dolutegravir **Name:** Blood samples **Type:** BIOLOGICAL ### Outcomes Module #### Primary Outcomes **Measure:** Change from baseline in Proviral HIV-1 DNA at Week 48 **Time Frame:** baseline (Day 0) and Week 48 #### Secondary Outcomes **Measure:** Dolutegravir pharmacokinetic (dolutegravir pharmacological blood levels) **Time Frame:** Week 4, Week 24 and Week 48 **Description:** CRPus, IL-6, neopterin, D-dimer, CD14s **Measure:** Quantification of biomarkers of immune activation **Time Frame:** baseline (Day 0), Week 24 and Week 48 ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Male or female aged from de 18 to 80 years * Patient starting a DTG-regimen * Patients agreeing to use methods of birthcontrol while on the study and during the 6 weeks after stopping DTG treatment * Signed and dated written informed consent is obtained from the subject or the subject's legal representative prior to screening Exclusion Criteria: * Women who are pregnant or breastfeeding * HBV or HCV coinfection * Participation in another clinical drug or device trial where the last dose of drug was within the past 30 days or an investigational medical device is currently implanted * An active AIDS-defining condition at Screening * Documented resistance to DTG * Allergy or intolerance to the study drugs or their components or drugs of their class * Any acute or verified Grade 4 laboratory abnormality (with the exception of Grade 4 lipids) at Screening. * Coadministration with Dofelitide **Maximum Age:** 80 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Samira FAFI-KREMER, PhD **Phone:** +33369551438 **Role:** CONTACT #### Locations **Location 1:** **City:** Belfort **Country:** France **Facility:** Centre hospitalier de Belfort-Montbéliard **Status:** ACTIVE_NOT_RECRUITING **Zip:** 90000 **Location 2:** **City:** Colmar **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Martin MARTINOT, MD - **Role:** CONTACT **Country:** France **Facility:** Centre hospitalier de Colmar **Status:** RECRUITING **Zip:** 68024 **Location 3:** **City:** Mulhouse Cedex **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Geneviève BECK WIRTH, MD - **Role:** CONTACT **Country:** France **Facility:** Centre hospitalier de Mulhouse **Status:** RECRUITING **Zip:** 68070 **Location 4:** **City:** Strasbourg Cedex **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** David REY, PhD - **Role:** CONTACT **Country:** France **Facility:** Hôpitaux Universitaire de Strasbourg **Status:** RECRUITING **Zip:** 67091 #### Overall Officials **Official 1:** **Affiliation:** Hôpitaux Universitaires de Strasbourg **Name:** David REY, PhD **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Browse Branches - Abbrev: BC01 - Name: Infections - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: BXS - Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions - Abbrev: BC20 - Name: Immune System Diseases ### Condition Browse Module - Browse Leaves - ID: M10283 - Name: Infections - Relevance: LOW - As Found: Unknown - ID: M6368 - Name: Communicable Diseases - Relevance: LOW - As Found: Unknown - ID: M3522 - Name: Acquired Immunodeficiency Syndrome - Relevance: LOW - As Found: Unknown - ID: M18250 - Name: HIV Infections - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Browse Branches - Abbrev: Infe - Name: Anti-Infective Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M347662 - Name: Dolutegravir - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00001579 **Brief Title:** A Phase I Trial of 5-Fluorouracil Given With 776C85 (GW776) and Low-Dose Leucovorin in Adult Patients With Solid Tumors **Official Title:** A Phase I Trial of 5-Fluorouracil Given With 776C85 (GW776) and Low-Dose Leucovorin in Adult Patients With Solid Tumors #### Organization Study ID Info **ID:** 970136 #### Organization **Class:** NIH **Full Name:** National Institutes of Health Clinical Center (CC) #### Secondary ID Infos **ID:** 97-C-0136 ### Status Module #### Completion Date **Date:** 2001-03 #### Expanded Access Info #### Last Update Post Date **Date:** 2006-07-17 **Type:** ESTIMATED **Last Update Submit Date:** 2006-07-14 **Overall Status:** COMPLETED #### Start Date **Date:** 1997-06 **Status Verified Date:** 2000-05 #### Study First Post Date **Date:** 2002-12-10 **Type:** ESTIMATED **Study First Submit Date:** 1999-11-03 **Study First Submit QC Date:** 2002-12-09 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** NIH **Name:** National Cancer Institute (NCI) ### Description Module **Brief Summary:** This is a dose escalation study. During the first period of this study, an initial pharmacological assessment of fluorouracil administered intravenously along with oral leucovorin calcium is made. Leucovorin calcium is given orally bid on days 1-3. Fluorouracil is given as a 24 hour infusion on day 2. After a 2 week rest period and resolution of any toxicities experienced during the first period of treatment, patients are given an escalating dose of fluorouracil with fixed doses of leucovorin calcium and ethynyluracil. Ethynyluracil and leucovorin calcium are given bid orally on days 1-3 of each week. Fluorouracil is given bid orally on day 2 of each week. Treatment is repeated for three weeks followed by a one week rest period. 3 to 6 patients are enrolled at each dose level. Dose escalation proceeds until the maximum tolerated dose (MTD) is determined. MTD is defined as the dose preceding that at which 2 or more patients experience dose limiting toxicity. **Detailed Description:** The primary purpose of this Phase I protocol is to develop an orally administered regimen of fluorouracil (5-FU) given with fixed doses of leucovorin (LV) and 776C85 (GW776), a mechanism-based inhibitor of dihydropyrimidine dehydrogenase (DPD), the rate-limiting enzyme involved in the catabolism of 5-FU. In the presence of 776C85, 5-FU is cleared by renal mechanisms. The schedule employed is intended to mimic the pharmacologic profile associated with a 24 hour weekly continuous infusion of 5-FU without the need for an indwelling central venous catheter. The target population is adult cancer patients with solid tumors. The first week, each patient will receive a single dose of 5-FU given by 24 hour continuous IV infusion at its recommended Phase II dose with low-dose oral LV. In the third week, the patient will begin 776C85 (GW776) and LV PO on days 1, 2, 3 at fixed doses. Oral 5-FU will be given on day 2, and the dose will be escalated in successive cohorts of patients. Treatment will be repeated weekly for three weeks, followed by a one week break. The dose of 5-FU will be adjusted according to individual tolerance. Cohorts of three patients will be entered at each dose level of 5-FU, which will be escalated until dose-limiting toxicity is seen (guidelines are outlined in the following schema). Treatment will be continued indefinitely until evidence of disease progression, provided the patient is tolerating therapy and wishes to continue. Biochemical monitoring suggests that there is profound and sustained inhibition of DPD with a single dose of 20 mg PO 776C85 days 1-3 each week for three of four weeks. Once the MTD has been defined for the once daily dosing on days 1, 2, 3 schedule, a simplified schedule will be evaluated in which a single dose of 776C85 on day 1 in the evening, with oral leucovorin days 1 and 2, and 5-FU given day 2 as a single dose. Since the pharmaceutical company has decided to go with a combined tablet of eniluracil/5-FU for future studies, the new schedule will be oral leucovorin on days 1 \& 2, with 776C85 and 5-FU both given day 2 as a single dose. ### Conditions Module **Conditions:** - Lymphoma - Neoplasms **Keywords:** - Biochemical Modulation - Dihydropyrimidine Dehydrogenase - Oral Administration - Pharmacokinetics ### Design Module #### Design Info **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 50 **Phases:** - PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module ### Interventions #### Intervention 1 **Name:** 5-Fluorouracil **Type:** DRUG #### Intervention 2 **Name:** Ethynyluracil **Type:** DRUG #### Intervention 3 **Name:** Leucovorin **Type:** DRUG ### Eligibility Module **Eligibility Criteria:** DISEASE CHARACTERISTICS: Histologically proven solid tumor that has failed standard therapy or for which no such therapy exists. Tumor may be locally advanced and unresectable, recurrent and/or metastatic. Lymphomas with minimal or no involvement of bone marrow are also eligible. No primary malignancies or metastatic disease of the CNS. No symptomatic pre-existing peripheral neuropathy. PRIOR/CURRENT THERAPY: BIOLOGIC THERAPY: No immunotherapy within past 4 weeks. Recovered from toxic effects. CHEMOTHERAPY: No chemotherapy within past 4 weeks (6 weeks for nitrosoureas). No mitomycin within past 12 weeks. Recovered from toxic effects. ENDOCRINE THERAPY: Not specified. RADIOTHERAPY: No radiotherapy within past 2 weeks (8 weeks for strontium therapy). Recovered from toxic effects. SURGERY: Recovered from prior surgery. OTHER: No concurrent cimetidine. PATIENT CHARACTERISTICS: AGE: 18 and over. PERFORMANCE STATUS: ECOG 0-2. LIFE EXPECTANCY: Not specified. HEMATOPOIETIC: Absolute granulocyte count at least 2000/mm(3); Platelet count at least 100,000/mm(3). HEPATIC: Bilirubin no greater than 2 times upper normal limit; SGOT/SGPT no greater than 4 times upper normal limit. RENAL: Creatinine no greater than 1.6 mg/dL; Creatinine clearance greater than 55 mL/min. OTHER: Not pregnant or nursing. Fertile patients must use effective contraception. Not HIV positive. No active infections requiring intravenous antibiotic therapy. No other serious concurrent illness. No evidence of hemolytic uremic syndrome. **Sex:** ALL **Standard Ages:** - CHILD - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Bethesda **Country:** United States **Facility:** National Cancer Institute (NCI) **State:** Maryland **Zip:** 20892 ### References Module #### References **Citation:** Evans RM, Laskin JD, Hakala MT. Assessment of growth-limiting events caused by 5-fluorouracil in mouse cells and in human cells. Cancer Res. 1980 Nov;40(11):4113-22. No abstract available. **PMID:** 6162543 **Citation:** Spears CP, Shani J, Shahinian AH, Wolf W, Heidelberger C, Danenberg PV. Assay and time course of 5-fluorouracil incorporation into RNA of L1210/0 ascites cells in vivo. Mol Pharmacol. 1985 Feb;27(2):302-7. **PMID:** 2578605 **Citation:** Calabro-Jones PM, Byfield JE, Ward JF, Sharp TR. Time-dose relationships for 5-fluorouracil cytotoxicity against human epithelial cancer cells in vitro. Cancer Res. 1982 Nov;42(11):4413-20. No abstract available. **PMID:** 7127282 ## Derived Section ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC15 - Name: Blood and Lymph Conditions - Abbrev: BC20 - Name: Immune System Diseases - Abbrev: All - Name: All Conditions - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M11220 - Name: Lymphoma - Relevance: LOW - As Found: Unknown - ID: T3543 - Name: Lymphosarcoma - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Ancestors - ID: D000000963 - Term: Antimetabolites - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000000964 - Term: Antimetabolites, Antineoplastic - ID: D000000970 - Term: Antineoplastic Agents - ID: D000007166 - Term: Immunosuppressive Agents - ID: D000007155 - Term: Immunologic Factors - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000000931 - Term: Antidotes - ID: D000020011 - Term: Protective Agents - ID: D000014803 - Term: Vitamin B Complex - ID: D000014815 - Term: Vitamins - ID: D000018977 - Term: Micronutrients - ID: D000004791 - Term: Enzyme Inhibitors ### Intervention Browse Module - Browse Branches - Abbrev: Micro - Name: Micronutrients - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: ANeo - Name: Antineoplastic Agents - Abbrev: Hemat - Name: Hematinics - Abbrev: Vi - Name: Vitamins ### Intervention Browse Module - Browse Leaves - ID: M6191 - Name: Leucovorin - Relevance: HIGH - As Found: Stem Cell - ID: M8600 - Name: Fluorouracil - Relevance: HIGH - As Found: According - ID: M229917 - Name: Eniluracil - Relevance: HIGH - As Found: Generalized Pustular Psoriasis - ID: M4281 - Name: Antimetabolites - Relevance: LOW - As Found: Unknown - ID: M10212 - Name: Immunosuppressive Agents - Relevance: LOW - As Found: Unknown - ID: M10201 - Name: Immunologic Factors - Relevance: LOW - As Found: Unknown - ID: M4250 - Name: Antidotes - Relevance: LOW - As Found: Unknown - ID: M21869 - Name: Protective Agents - Relevance: LOW - As Found: Unknown - ID: M8618 - Name: Folic Acid - Relevance: LOW - As Found: Unknown - ID: M17558 - Name: Vitamins - Relevance: LOW - As Found: Unknown - ID: M17546 - Name: Vitamin B Complex - Relevance: LOW - As Found: Unknown - ID: M21009 - Name: Micronutrients - Relevance: LOW - As Found: Unknown - ID: M16885 - Name: Trace Elements - Relevance: LOW - As Found: Unknown - ID: M7951 - Name: Enzyme Inhibitors - Relevance: LOW - As Found: Unknown - ID: T446 - Name: Folic Acid - Relevance: LOW - As Found: Unknown - ID: T448 - Name: Folate - Relevance: LOW - As Found: Unknown - ID: T475 - Name: Vitamin B9 - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000002955 - Term: Leucovorin - ID: D000005472 - Term: Fluorouracil - ID: C000073482 - Term: Eniluracil ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT06191679 **Acronym:** DECIDES B+ **Brief Title:** Decision Aid for Education and Support About Cancer Treatment **Official Title:** Decision Aid for Education and Support About Cancer Treatment #### Organization Study ID Info **ID:** 20-017521 #### Organization **Class:** OTHER **Full Name:** Children's Hospital of Philadelphia ### Status Module #### Completion Date **Date:** 2023-04-13 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2024-02-14 **Type:** ACTUAL **Last Update Submit Date:** 2024-02-12 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2023-04-13 **Type:** ACTUAL #### Start Date **Date:** 2020-07-08 **Type:** ACTUAL **Status Verified Date:** 2024-02 #### Study First Post Date **Date:** 2024-01-05 **Type:** ACTUAL **Study First Submit Date:** 2023-12-20 **Study First Submit QC Date:** 2023-12-20 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Children's Hospital of Philadelphia #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** The goals of this clinical trial are to evaluate DECIDES, a web-based decision support application that provides education about cancer and cancer treatment and provides support to encourage adolescent and young adult (AYA) patients, their caregivers, and oncology health care providers to make informed decisions about cancer treatment together. The main questions this study aims to answer are: * Is DECIDES acceptable, usable, and feasible for AYA, caregivers, and oncology health care providers? * Is DECIDES helpful for AYA, caregivers, and oncology health care providers that are making cancer treatment decisions together? AYA and caregiver participants will complete a questionnaire and be randomly assigned to participate in one of three groups: (1) Usual Care, (2) DECIDES, or (3) DECIDES + Coach. Participants in 'Usual Care' will continue to have access to their oncology health care team for questions related to cancer and cancer treatment, as per usual standard of care. Participants in both 'DECIDES' and 'DECIDES + Coach' groups will receive access to DECIDES, and those in 'DECIDES + Coach' will receive additional live, coach-assisted support. After 8 weeks, AYA and caregivers will complete a follow-up questionnaire and those in the 'DECIDES' and 'DECIDES + Coach' groups will complete a semi-structured qualitative interview. Oncology health care providers of participating AYA will be invited to participate in a questionnaire and semi-structured qualitative interview. Researchers will compare groups to see if AYA and caregivers that receive access to DECIDES (with and without coach-assisted support) report more positive decision-making processes compared to those that receive usual standard of care. **Detailed Description:** DECIDES is a developmentally appropriate, engaging, and interactive web-based decision support application that has been designed to address health literacy and includes: * Education on cancer and cancer treatments, including clinical trials * An exercise to identify perceived barriers and benefits to treatment options * An exercise to clarify personal goals for treatment that align with life goals * Resources to support communication with the oncology health care team ### Conditions Module **Conditions:** - Cancer - Childhood Cancer **Keywords:** - AYA ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** Family Units (AYA and caregiver participants) are randomized to one of three arms: (1) Usual Care \[no intervention\], (2) DECIDES \[access to web-based decision aid\], or (3) DECIDES + Coach \[access to web-based decision aid with coach-assisted support\]. Oncology health care providers of participating AYA are not enrolled in an intervention arm. ##### Masking Info **Masking:** NONE **Primary Purpose:** SUPPORTIVE_CARE #### Enrollment Info **Count:** 117 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Subjects will have access to their oncology health care providers and other members of the health care team for questions related to cancer and cancer treatment (as per usual). **Label:** Usual Care **Type:** NO_INTERVENTION #### Arm Group 2 **Description:** Subjects will receive access to DECIDES with an informational handout that includes goals of the decision support intervention and instructions for accessing the application independently. **Intervention Names:** - Behavioral: Decision Aid for Education and Support about Cancer Treatment (DECIDES) **Label:** DECIDES **Type:** EXPERIMENTAL #### Arm Group 3 **Description:** Subjects will receive access to DECIDES with live, coach-assisted support. **Intervention Names:** - Behavioral: Decision Aid for Education and Support about Cancer Treatment with Coach-Assisted Support (DECIDES + coach) **Label:** DECIDES + coach **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - DECIDES **Description:** DECIDES is a developmentally appropriate, engaging and interactive web-based decision support application designed to address health literacy through education about cancer and cancer treatment, and provide support for AYA patients, their caregivers, and oncology health care providers to make informed decisions about cancer treatment together. **Name:** Decision Aid for Education and Support about Cancer Treatment (DECIDES) **Type:** BEHAVIORAL #### Intervention 2 **Arm Group Labels:** - DECIDES + coach **Description:** Live support in the form of a coach is provided to support navigation of DECIDES and promote involvement in decision-making. DECIDES is a developmentally appropriate, engaging and interactive web-based decision support application designed to address health literacy through education about cancer and cancer treatment, and provide support for AYA patients, their caregivers, and oncology health care providers to make informed decisions about cancer treatment together. **Name:** Decision Aid for Education and Support about Cancer Treatment with Coach-Assisted Support (DECIDES + coach) **Type:** BEHAVIORAL ### Outcomes Module #### Primary Outcomes **Description:** This is a 12-item study-team developed measure used to obtain acceptability ratings from AYA and caregivers (that completed participation in DECIDES or DECIDES + Coach). This measure is based on The Ottawa Hospital's measure of acceptability regarding comprehension of components of a decision aid, its length, pace, amount of information, balance in presentation of information about options, and overall suitability for decision-making. Items are rated on a 5-point Likert scale (1=strongly disagree to 5=strongly agree). The average across 12 items is calculated to produce a total score that ranges from 1-5. Higher scores reflect greater acceptability. **Measure:** Acceptability of Decision Aid **Time Frame:** 8 weeks post-enrollment **Description:** This is a 10-item scale collected from AYA and caregivers (that completed participation in DECIDES or DECIDES + coach) and oncology health care providers to measure perceptions of DECIDES usability. Items are rated on a 5-point Likert scale (1=strongly disagree to 5=strongly agree) and summed to produce a total score that ranges from 0 to 100. Scores are normalized to produce a percentile ranking. A score \>80.3 reflects letter grade "A" (adjective rating "excellent"); 68-80.3 reflects letter grade "B" (adjective rating "good"), 68 reflects letter grade "C" (adjective rating "OK"); 51-67 reflects letter grade "D" (adjective rating "poor"); and \<51 reflects letter grade "F" (adjective rating "awful"). **Measure:** Systems Usability Scale **Time Frame:** 8 weeks post-enrollment **Description:** A semi-structured qualitative interview is conducted with AYA, caregivers, and oncology health care providers to assess the acceptability, feasibility, and usability of DECIDES. Interview data is used to inform implementation strategies for future dissemination. **Measure:** Semi-Structured Qualitative Interview **Time Frame:** 8 weeks post-enrollment #### Secondary Outcomes **Description:** This is a 25-item true/false questionnaire collected to measure AYA and caregiver knowledge of clinical trials. Items are scored (correct versus incorrect) and an overall knowledge score that ranges from 0-100 is calculated based on % correct. **Measure:** Knowledge of Cancer Clinical Trials **Time Frame:** 0 weeks post-enrollment and 8 weeks post-enrollment **Description:** This is a 35-item measure of AYA and caregiver attitudes toward clinical trials. Higher scores reflect more support for participation (range = 6-30), perceived incentives for participation (range = 3-15), trust in participation (range = 11-55), barriers/costs to participation (range = 9-45) and greater decision balance about participation \[range = -3 (negative) - 3 (positive) valence\]. **Measure:** Attitudes toward Cancer Clinical Trials **Time Frame:** 0 weeks post-enrollment and 8 weeks post-enrollment **Description:** This is a valid and reliable 16-item scale collected from AYA and caregivers to measure uncertainty in making cancer treatment decisions, including factors that contribute to uncertainty about cancer treatment options and perceptions of effective decision-making. Total scores range from 0 (no decisional conflict) to 100 (extremely high decisional conflict). **Measure:** Uncertainty in Cancer Treatment Decision-Making Process **Time Frame:** 8 weeks post-enrollment **Description:** This is a valid and reliable 5-item scale collected from AYA and caregivers to measure distress or remorse about a cancer treatment decision. Total scores range from 0 (no regret) to 100 (high regret). **Measure:** Regret about Cancer Treatment Decision-Making Process **Time Frame:** 8 weeks post-enrollment **Description:** This is a valid and reliable 11-item scale collected from AYA and caregivers to measure self-confidence in decision-making abilities. Total scores range from 0 (not confident) to 100 (extremely confident). **Measure:** Self-confidence in Cancer Treatment Decision-Making Abilities **Time Frame:** 8 weeks post-enrollment **Description:** This is a valid and reliable 6-item scale collected from AYA and caregivers to measure satisfaction with the cancer treatment decision that was made. Total scores range from 6 to 30, with higher scores reflecting higher satisfaction. **Measure:** Satisfaction with Cancer Treatment Decision-Making Process **Time Frame:** 8 weeks post-enrollment **Description:** This is a 5-item scale that measures AYA and caregiver perceptions of the extent to which clinicians engaged in five key elements of the decision-making process (e.g., discuss the available options with you in a way you could understand?, encourage you to ask questions or express any concerns you had about the available options?, involve you as much as you wanted in the decision making process?). The overall physician style score ranges from 0-100. Higher scores reflect more optimal communication with physician. **Measure:** Perceptions of Physician Engagement in Decision-Making Process **Time Frame:** 8 weeks post-enrollment **Description:** The SDM-Q-9 is a valid and reliable 9-item patient-reported questionnaire collected from AYA to measure their perceived involvement in the process of shared treatment decision-making with their oncology clinician. The physician version of the SDM-Q-9 (SDM-Q-Doc) was adapted for use with caregivers in this study to measure AYA involvement in shared decision-making with their oncology clinician, from the caregiver's perspective. Total scores range from 0 to 100. Higher scores reflect greater degree to which AYA were involved in a shared treatment decision-making process. **Measure:** Perceived Involvement in Shared Treatment Decision-Making Process **Time Frame:** 8 weeks post-enrollment ### Eligibility Module **Eligibility Criteria:** Adolescent and Young Adults (AYA) INCLUSION CRITERIA: * Ages 15-24 years old * Newly diagnosed or relapsed with leukemia/lymphoma, solid tumor, or brain tumor within 6 weeks of enrollment * Ability to read and speak English * If \<18 Years Old: Parental/guardian permission to participate (informed consent) EXCLUSION CRITERIA: * Inability to read or speak English * Pre-existing cognitive deficits (based on provider assessment) that result in impaired reading or decision-making capacity * AYA is a ward of the state or any other agency, institution, or entity * If \<18 Years Old: No Parental/Guardian permission to participate (informed consent) Caregivers INCLUSION CRITERIA: * Parent or Legal Guardian of a participating AYA * Ability to read and speak English EXCLUSION CRITERIA: * Foster parent or child advocate (i.e., caregiver is not biological parent or legal guardian) * Inability to read or speak English Oncology Health Care Providers INCLUSION CRITERIA: * Oncology health care provider involved in decision-making about cancer treatment with enrolled AYA patients and caregiver(s) * Ability to read and speak English EXCLUSION CRITERIA: * Oncology health care provider that is not involved in decision-making about cancer treatment with enrolled AYA patients and caregiver(s) * Inability to read or speak English **Healthy Volunteers:** True **Maximum Age:** 24 Years **Minimum Age:** 15 Years **Sex:** ALL **Standard Ages:** - CHILD - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Philadelphia **Country:** United States **Facility:** Children's Hospital of Philadelphia **State:** Pennsylvania **Zip:** 19104 #### Overall Officials **Official 1:** **Affiliation:** Children's Hospital of Philadelphia **Name:** Lamia Barakat, PhD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Misc Info Module #### Submission Tracking - Estimated Results First Submit Date: 2024-04-12 ##### Submission Infos - MCP Release N: Unknown - Release Date: 2024-04-12 - Reset Date: Unknown - Unrelease Date: Unknown - Unrelease Date Unknown: Unknown - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT02576379 **Brief Title:** The Impact of a Helicopter Emergency Medical System on Prognosis in Stroke Patients **Official Title:** The Impact of a Helicopter Emergency Medical System on Prognosis in Stroke Patients #### Organization Study ID Info **ID:** ALH3-KF-2015 #### Organization **Class:** OTHER **Full Name:** Rigshospitalet, Denmark ### Status Module #### Completion Date **Date:** 2015-05 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2016-07-11 **Type:** ESTIMATED **Last Update Submit Date:** 2016-07-08 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2015-05 **Type:** ACTUAL #### Start Date **Date:** 2010-01 **Status Verified Date:** 2016-07 #### Study First Post Date **Date:** 2015-10-15 **Type:** ESTIMATED **Study First Submit Date:** 2015-10-13 **Study First Submit QC Date:** 2015-10-13 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Rigshospitalet, Denmark #### Responsible Party **Investigator Affiliation:** Rigshospitalet, Denmark **Investigator Full Name:** Kamilia S. Funder **Investigator Title:** MD. **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** Stroke is a leading cause of death and disability, and 15 million people suffer a stroke each year; one-third die and one-third are left permanently disabled. Because the risk of stroke increases with age, it has been considered a disease of the elderly, but stroke also occurs in middle-aged people. Thrombolysis with tissue plasminogen activator (tPA) is the preferred choice of reperfusion therapy of ischemic stroke if performed within 4.5 hours from symptom onset. Time to thrombolysis is associated with improved outcome: the sooner the treatment, the less risk of serious - and possibly permanent - damage to the brain. Unfortunately, only a small fraction of stroke patients make it to thrombolysis within the 4.5-hour; one explanation may be system delays including prolonged transportation. In May 2010, the first physician-staffed Helicopter Emergency Medical Service (HEMS) was implemented in the Eastern part of Denmark. An observational study evaluating the short-term effects of HEMS implementation compared patients transported by conventional ground ambulance (Ground Emergency Medical Service (GEMS)) to patients transported by HEMS. Patients transported by helicopter had increased time to specialized care. However, both 30-day and 1-year mortality was slightly lower in patients transported by HEMS, although not significant, as was the degree of disability at three months measured by the modified Rankin Scale (mRS). ### Conditions Module **Conditions:** - Thrombolysis **Keywords:** - Helicopter Emergency Medical System - Mortality - Labour market affiliation - Modified Rankin Scale ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 1068 **Type:** ACTUAL **Patient Registry:** True **Study Type:** OBSERVATIONAL **Target Duration:** 2 Years ### Arms Interventions Module #### Arm Group 1 **Description:** Patients suspected of suffering from a vascular condition within the geographical area covered by both HEMS and GEMS, and were transported by Helicopter Emergency Medical System (HEMS) to the regional stroke unit at Copenhagen University Hospital Roskilde in a 36-month period from May 1st 2010 until April 30th 2013. **Label:** HEMS patients #### Arm Group 2 **Description:** Patients suspected of suffering from a vascular condition within the geographical area covered by both HEMS and GEMS, and were transported by Ground Emergency Medical System (GEMS) to the regional stroke unit at Copenhagen University Hospital Roskilde in a 40-month period from January 1st 2010 until April 30th 2013. **Label:** GEMS patients ### Outcomes Module #### Primary Outcomes **Description:** Mortality during the follow-up period will be analysed for differences between GEMS and HEMS. Follow-up period is until May 1st 2015. Because of varying access to information on covariates depending on the diagnosis and treatment of the patient, we conduct the analysis as follows: 1) the whole study population; adjusted for sex and age, 2) patients who were suspected of suffering from a vascular condition; adjusted for sex, age and comorbidity (defined as one of the following conditions; diabetes, atrial fibrillation, hypertension, previous myocardial infarction, and previous stroke), and 3) patients who underwent thrombolysis; adjustment for sex, age, comorbidity, and initial National Institutes of Health Stroke Scale (NIHSS) score. **Measure:** Risk of death during follow-up **Time Frame:** 2 - 5.5 years after admission to the stroke unit. #### Secondary Outcomes **Description:** Patients are divided into the same three sub-groups and adjusted for the same potential confounders as described in the primary outcome analysis. **Measure:** The risk of death at 30 day. **Time Frame:** 30 days after admission to the stroke unit. **Description:** Assessed in patients who underwent thrombolysis. **Measure:** Modified Rankin Scale (mRS) after three months. **Time Frame:** Three months **Description:** Assessed in all patients suspected of suffering from a vascular condition between 18 and 60 years of age to ensure a sample that was at risk of involuntary early retirement during the full follow-up period. **Measure:** The risk of involuntary early retirement during the follow-up period. **Time Frame:** 2 - 5.5 years after admission to the stroke unit. **Description:** Assessed in all patients suspected of suffering from a vascular condition between 18 and 60 years of age to ensure a sample that was at risk of involuntary early retirement during the full follow-up period. **Measure:** The risk of reduced workability two years after the vascular event **Time Frame:** Two years after admission to the stroke unit **Description:** Assessed in all patients suspected of suffering from a vascular condition between 18 and 60 years of age to ensure a sample that was at risk of involuntary early retirement during the full follow-up period. **Measure:** The percentage of time on social transfer payments during the first two years. **Time Frame:** Two years after admission to the stroke unit ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * All patients arriving at the regional stroke unit at Copenhagen University Hospital, Roskilde, suspected of an acute vascular condition within the geographical area covered by both HEMS and GEMS in a 40-month period from January 1st 2010 until April 30th 2013. Exclusion Criteria: * For patients with multiple contacts; only the first contact is included in the data for analysis. **Sampling Method:** PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - CHILD - ADULT - OLDER_ADULT **Study Population:** All patients arriving at the regional stroke unit at Copenhagen University Hospital, Roskilde, suspected of an acute vascular condition within the geographical area covered by both HEMS and GEMS in a 40-month period from January 1st 2010 until April 30th 2013. The geographical catchment area is defined as the area from where HEMS transported patients the first year of implementation. We compare stroke patients transported by HEMS with stroke patients transported by GEMS. ### Contacts Locations Module #### Overall Officials **Official 1:** **Affiliation:** Department of Anesthesia, Center of Head and Orthopedics, section 4231, Copenhagen University Hospital, Rigshospitalet **Name:** Kamilia S. Funder, MD **Role:** PRINCIPAL_INVESTIGATOR **Official 2:** **Affiliation:** Department of Anesthesia, Center of Head and Orthopedics, section 4231, Copenhagen University Hospital, Rigshospitalet **Name:** Jacob Steinmetz, MD, PhD **Role:** STUDY_DIRECTOR ### References Module #### References **Citation:** Wahlgren N, Ahmed N, Davalos A, Hacke W, Millan M, Muir K, Roine RO, Toni D, Lees KR; SITS investigators. Thrombolysis with alteplase 3-4.5 h after acute ischaemic stroke (SITS-ISTR): an observational study. Lancet. 2008 Oct 11;372(9646):1303-9. doi: 10.1016/S0140-6736(08)61339-2. Epub 2008 Sep 12. **PMID:** 18790527 **Citation:** Hesselfeldt R, Gyllenborg J, Steinmetz J, Do HQ, Hejselbaek J, Rasmussen LS. Is air transport of stroke patients faster than ground transport? A prospective controlled observational study. Emerg Med J. 2014 Apr;31(4):268-72. doi: 10.1136/emermed-2012-202270. Epub 2013 Feb 6. **PMID:** 23389831 **Citation:** Funder KS, Rasmussen LS, Lohse N, Hesselfeldt R, Siersma V, Gyllenborg J, Wulffeld S, Hendriksen OM, Lippert FK, Steinmetz J. The impact of a physician-staffed helicopter on outcome in patients admitted to a stroke unit: a prospective observational study. Scand J Trauma Resusc Emerg Med. 2017 Feb 23;25(1):18. doi: 10.1186/s13049-017-0363-3. **PMID:** 28231814 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000020969 - Term: Disease Attributes - ID: D000010335 - Term: Pathologic Processes ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: BC14 - Name: Heart and Blood Diseases ### Condition Browse Module - Browse Leaves - ID: M7796 - Name: Emergencies - Relevance: HIGH - As Found: Emergency - ID: M22306 - Name: Stroke - Relevance: LOW - As Found: Unknown - ID: M22700 - Name: Disease Attributes - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000004630 - Term: Emergencies ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT01667679 **Acronym:** COMPASS **Brief Title:** Efficacy and Safety of 20 mg Sumatriptan Powder Delivered Intranasally With the Bi-directional Device Compared With 100 mg Sumatriptan Tablets in Adults With Acute Migraine With or Without Aura **Official Title:** A Randomized, Double-Blind, Double-Dummy, Active-Controlled, Cross-Over Study Evaluating the Efficacy and Safety of 20 mg Sumatriptan Powder Delivered Intranasally With the Bi-directional Device Compared With 100 mg Sumatriptan Tablets in Adults With Acute Migraine With or Without Aura #### Organization Study ID Info **ID:** OPN-SUM-MIG-3302 #### Organization **Class:** INDUSTRY **Full Name:** Avanir Pharmaceuticals ### Status Module #### Completion Date **Date:** 2014-06 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2017-04-12 **Type:** ACTUAL **Last Update Submit Date:** 2017-03-14 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2014-03 **Type:** ACTUAL #### Results First Post Date **Date:** 2017-03-14 **Type:** ACTUAL **Results First Submit Date:** 2016-10-13 **Results First Submit QC Date:** 2017-01-24 #### Start Date **Date:** 2012-08 **Status Verified Date:** 2017-03 #### Study First Post Date **Date:** 2012-08-17 **Type:** ESTIMATED **Study First Submit Date:** 2012-08-06 **Study First Submit QC Date:** 2012-08-16 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Avanir Pharmaceuticals #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** This study is being conducted to determine if OPTINOSE SUMATRIPTAN delivered nasally (through the nose) using the OPTINOSE SUMATRIPTAN DEVICE can reduce the pain associated with migraine headaches in 30 minutes after use. **Detailed Description:** The primary objective for this study is to compare the proportion of attacks in which pain reduction (defined as a decrease in pain intensity of at least 1 point) is achieved at 30 minutes following 20 mg OPTINOSE SUMATRIPTAN treatment with 100 mg Sumatriptan Tablets ### Conditions Module **Conditions:** - Migraine - Headaches **Keywords:** - Migraine - Headaches - Sumatriptan ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** CROSSOVER ##### Masking Info **Masking:** QUADRUPLE **Who Masked:** - PARTICIPANT - CARE_PROVIDER - INVESTIGATOR - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 275 **Type:** ACTUAL **Phases:** - PHASE3 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** 20 mg OPTINOSE SUMATRIPTAN Powder Delivered Intranasally With the Bi-directional Device nasally and Placebo Tablet **Intervention Names:** - Drug: OPTINOSE SUMATRIPTAN delivered nasally and placebo tablet **Label:** OPTINOSE SUMATRIPTAN and Placebo **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** 100 mg Sumatriptan Tablet and OPTINOSE Placebo delivered nasally **Intervention Names:** - Drug: 100 mg Sumatriptan Tablet and OPTINOSE Placebo delivered nasally **Label:** 100mg Sumatriptan and OPTINOSE Placebo **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - 100mg Sumatriptan and OPTINOSE Placebo **Name:** 100 mg Sumatriptan Tablet and OPTINOSE Placebo delivered nasally **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - OPTINOSE SUMATRIPTAN and Placebo **Name:** OPTINOSE SUMATRIPTAN delivered nasally and placebo tablet **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** SPID-30 is defined as the sum of the pain intensity differences (measured as area under the curve) from dosing (Baseline) through 30 minutes post-dose for headaches with a Baseline intensity of mild, moderate, or severe. The range of possible scores is -60 to +90. A higher number indicates a greater reduction in pain intensity. Negative values indicate worsening pain. A value of "0" indicates that there was no change in pain intensity from Baseline through 30 minutes. Results are from an analysis of covariance (ANCOVA) model with treatment, period, and treatment sequence as fixed effects and participant as a random effect. The Last Observation Carried Forward (LOCF) imputation method (missing values were replaced by carrying forward the preceding value) was used for this analysis. **Measure:** Mean Sum of Migraine Pain Intensity Differences (SPID)-30 **Time Frame:** Baseline and 30 minutes post-dose (up to 24 weeks) #### Secondary Outcomes **Description:** SPID-30 is defined as the sum of the pain intensity differences (measured as area under the curve) from dosing (Baseline) through 30 minutes post-dose for headaches with a Baseline intensity of mild and moderate/severe (rated on a 4-point scale: 0=none, 1=mild, 2=moderate, and 3=severe). The range of possible scores for all participants is -60 to +90. For participants with a mild headache at Baseline, the SPID range is -60 to +30. For participants with a moderate/severe headache at Baseline, the SPID range is -30 to +90. A higher number indicates a greater reduction in pain intensity. Negative values indicate worsening pain. A value of "0" indicates that there was no change in pain intensity from Baseline through 30 minutes. Results are from an ANCOVA model with treatment, period, and treatment sequence as fixed effects and participant as a random effect. The LOCF imputation method (missing values were replaced by carrying forward the preceding value) was used for this analysis. **Measure:** Mean Sum of Migraine Pain Intensity Differences (SPID)-30 for Headaches With a Baseline Intensity of Mild and Moderate/Severe **Time Frame:** Baseline and 30 minutes post-dose (up to 24 weeks) **Description:** Percentage of attacks in which pain reduction (defined as a decrease in pain intensity of at least one point on the following scale: 0, none; 1, mild; 2, moderate; 3, severe) was achieved at 10, 15, 30, 45, 60, 90, and 120 minutes after the initial dose for all attacks. **Measure:** Percentage of Attacks in Which Pain Reduction Was Achieved **Time Frame:** 10, 15, 30, 45, 60, 90, and 120 minutes **Description:** Percentage of attacks in which pain freedom (defined as pain level reduced to none \[Grade 0\]) was achieved at 10, 15, 30, 45, 60, 90, and 120 minutes after the initial dose for all attacks. **Measure:** Percentage of Attacks in Which Pain Freedom Was Achieved **Time Frame:** Baseline and 10, 15, 30, 45, 60, 90, and 120 minutes post-dose (up to 24 weeks) **Description:** Percentage of attacks treated at a severity of moderate (Grade 2) or severe (Grade 3) in which pain relief (defined as pain level reduced to none \[Grade 0\] or mild \[Grade 1\]) was achieved at 10, 15, 30, 45, 60, 90, and 120 minutes after the initial dose for all attacks. **Measure:** Percentage of Attacks in Which Pain Relief Was Achieved **Time Frame:** Baseline and 10, 15, 30, 45, 60, 90, and 120 minutes post-dose (up to 24 weeks) **Description:** Pain freedom is defined as a pain level reduced to none (Grade 0). **Measure:** Median Time to Pain Freedom **Time Frame:** 120 minutes post-dose (up to 24 weeks) **Description:** Participants were required to record their headache severity score in their e-diaries immediately before intake of study medication (Baseline) and at 10, 15, 30, 45, 60, 90, and 120 minutes post-dose. Participants graded their headaches on the following severity scale: 0, none; 1, mild; 2, moderate; 3, severe. Mean change from Baseline was calculated as the post-Baseline value minus the Baseline value. **Measure:** Mean Change in Headache Severity From Baseline to 10, 15, 30, 45, 60, 90, and 120 Minutes Post-dose **Time Frame:** Baseline and 10, 15, 30, 45, 60, 90, and 120 minutes post-dose (up to 24 weeks) **Description:** Participants were required to record their clinical disability score in their e-diaries immediately before intake of study medication (Baseline) and at 10, 15, 30, 45, 60, 90, and 120 minutes post-dose. Participants graded their disability on the following scale: 0, no disability, able to function normally; 1, performance of daily activities mildly impaired, can still do everything but with difficulty; 2, performance of daily activities moderately impaired, unable to do some things; 3, performance of daily activities severely impaired, cannot do all or most things, bed rest may be necessary. Mean change from Baseline was calculated as the post-Baseline value minus the Baseline value. **Measure:** Mean Change From Baseline in Clinical Disability Score at 10, 15, 30, 45, 60, 90, and 120 Minutes Post-dose **Time Frame:** Baseline and 10, 15, 30, 45, 60, 90, and 120 minutes post-dose (up to 24 weeks) **Description:** An adverse event is defined as any untoward medical occurrence associated with the use of an investigational product in humans, whether or not it is considered related to the investigational product. This includes any occurrence that was new in onset or aggravated in severity or frequency from the Baseline condition. **Measure:** Number of Participants With Any Treatment-emergent Non-serious and Serious Adverse Event **Time Frame:** Baseline compared to Vist 2, 3 and 4 **Description:** Change from Baseline in hemoglobin was assessed at Visit 3 (the start of Treatment Period 2) and Visit 4 (the end-of-study visit). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The Baseline value is the last non-missing value prior to or on the start date of Treatment Period 1. **Measure:** Change From Baseline in Hemoglobin at Visit 3 (up to 12 Weeks) and Visit 4 (up to 24 Weeks) **Time Frame:** Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks) **Description:** Change from Baseline in hematocrit (proportion of total blood volume that is composed of red blood cells) was assessed at Visit 3 (the start of Treatment Period 2) and Visit 4 (the end-of-study visit). Change from Baseline was calculated as the post-Baseline value minus the Baseline value.The Baseline value is the last non-missing value prior to or on the start date of Treatment Period 1. **Measure:** Change From Baseline in Hematocrit at Visit 3 (up to 12 Weeks) and Visit 4 (up to 24 Weeks) **Time Frame:** Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks) **Description:** Change from Baseline in red blood cell count was assessed at Visit 3 (the start of Treatment Period 2) and Visit 4 (the end-of-study visit). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The Baseline value is the last non-missing value prior to or on the start date of Treatment Period 1. **Measure:** Change From Baseline in Red Blood Cell Count at Visit 3 (up to Week 12) and Visit 4 (up to Week 24) **Time Frame:** Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks) **Description:** Change from Baseline in white blood cell (WBC) count, basinophils, monocytes, neutrophils, lymphocytes, eosinophils, and platelets was assessed at Visit 3 (the start of Treatment Period 2) and Visit 4 (the end-of-study visit). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The Baseline value is the last non-missing value prior to or on the start date of Treatment Period 1. **Measure:** Change From Baseline in White Blood Cell Count, Basinophils, Monocytes, Neutrophils, Lymphocytes, Eosinophils, and Platelets at Visit 3 (up to Week 12) and Visit 4 (up to Week 24) **Time Frame:** Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks) **Description:** Change from Baseline in urea was assessed at Visit 3 (the start of Treatment Period 2) and Visit 4 (the end-of-study visit). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The Baseline value is the last non-missing value prior to or on the start date of Treatment Period 1. **Measure:** Change From Baseline in Urea at Visit 3 (up to Week 12) and Visit 4 (up to Week 24) **Time Frame:** Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks) **Description:** Change from Baseline in creatinine was assessed at Visit 3 (the start of Treatment Period 2) and Visit 4 (the end-of-study visit). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The Baseline value is the last non-missing value prior to or on the start date of Treatment Period 1. **Measure:** Change From Baseline in Creatinine at Visit 3 (up to Week 12) and Visit 4 (up to Week 24) **Time Frame:** Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks) **Description:** Change from Baseline in ALP and ALT was assessed at Visit 3 (the start of Treatment Period 2) and Visit 4 (the end-of-study visit). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The Baseline value is the last non-missing value prior to or on the start date of Treatment Period 1. **Measure:** Change From Baseline in Alkaline Phosphatase (ALP) and Alanine Aminotransferase (ALT) at Visit 3 (up to Week 12) and Visit 4 (up to Week 24) **Time Frame:** Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks) **Description:** Change from Baseline in AST and GGT was assessed at Visit 3 (the start of Treatment Period 2) and Visit 4 (the end-of-study visit). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The Baseline value is the last non-missing value prior to or on the start date of Treatment Period 1. **Measure:** Change From Baseline in Aspartate Aminotransferase (AST) and Gamma Glutamyl Transferase (GGT) at Visit 3 (up to Week 12) and Visit 4 (up to Week 24) **Time Frame:** Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks) **Description:** Change from Baseline in total bilirubin was assessed at Visit 3 (the start of Treatment Period 2) and Visit 4 (the end-of-study visit). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The Baseline value is the last non-missing value prior to or on the start date of Treatment Period 1. **Measure:** Change From Baseline in Total Bilirubin at Visit 3 (up to Week 12) and Visit 4 (up to Week 24) **Time Frame:** Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks) **Description:** Change from Baseline in albumin and total protein was assessed at Visit 3 (the start of Treatment Period 2) and Visit 4 (the end-of-study visit). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The Baseline value is the last non-missing value prior to or on the start date of Treatment Period 1. **Measure:** Change From Baseline in Albumin and Total Protein at Visit 3 (up to Week 12) and Visit 4 (up to Week 24) **Time Frame:** Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks) **Description:** Change from Baseline in sodium, potassium, chloride, calcium, and glucose was assessed at Visit 3 (the start of Treatment Period 2) and Visit 4 (the end-of-study visit). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The Baseline value is the last non-missing value prior to or on the start date of Treatment Period 1. **Measure:** Change From Baseline in Sodium, Potassium, Chloride, Calcium, and Glucose at Visit 3 (up to Week 12) and Visit 4 (up to Week 24) **Time Frame:** Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks) **Description:** Change from Baseline in urinalysis values was assessed at Visit 3 (the start of Treatment Period 2) and Visit 4 (the end-of-study visit). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The Baseline value is the last non-missing value prior to or on the start date of Treatment Period 1. **Measure:** Change From Baseline in Urinalysis Values by Dipstick Method at Visit 3 (up to Week 12) and Visit 4 (up to Week 24) **Time Frame:** Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks) **Description:** The Baseline value is the last non-missing value prior to or on the start date of Treatment Period 1. Data are based on standard reads, with "1+," "2+," and "3+" indicating increasing amounts of metabolites in urine. **Measure:** Number of Participants With the Indicated Amounts of Protein, Glucose, Ketones, Blood, and White Blood Cells (WBCs) in Urine at Baseline, Visit 3 (up to Week 12), and Visit 4 (up to Week 24) **Time Frame:** Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks) **Description:** Change from Baseline in SBP and DBP was assessed at Visit 3 (the start of Treatment Period 2) and Visit 4 (the end-of-study visit). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The Baseline value is the last non-missing value prior to or on the start date of Treatment Period 1. **Measure:** Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Visit 3 (up to Week 12) and Visit 4 (up to Week 24) **Time Frame:** Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks) **Description:** Change from Baseline in pulse was assessed at Visit 3 (the start of Treatment Period 2) and Visit 4 (the end-of-study visit). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The Baseline value is the last non-missing value prior to or on the start date of Treatment Period 1. **Measure:** Change From Baseline in Pulse at Visit 3 (up to Week 12) and Visit 4 (up to Week 24) **Time Frame:** Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks) **Description:** The Baseline value is the last non-missing value prior to or on the start date of Treatment Period 1. Clinical significance was determined by the Investigator (per clinical judgement). A categorization of "normal" or "abnormal" was made per the investigators' clinical judgment of the ECG, taking the participants' demographic characteristics and other medical conditions into account. CS = clinically significant. CNS = clinically not significant. **Measure:** Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Findings at Baseline, Visit 3 (up to Week 12), and Visit 4 (up to Week 24) **Time Frame:** Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks) **Description:** The Baseline value is the last non-missing value prior to or on the start date of Treatment Period 1. Clinical significance was determined by the Investigator (per clinical judgement). CS = clinically significant. CNS = clinically not significant. **Measure:** Number of Participants With the Indicated Physical Examination Abnormalities at Baseline, Visit 3 (up to Week 12), and Visit 4 (up to Week 24) **Time Frame:** Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks) **Description:** Concomitant medications are defined as non-study medications with a start or stop date between the first dose of study medication and the end of safety follow-up, inclusive. Derm. = dermatologic; incl. - including. **Measure:** Number of Participants With the Indicated Concomitant Medications **Time Frame:** up to 24 weeks ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Man or woman, between the ages of 18 to 65 years, inclusive at screening * Have a diagnosis of episodic migraine, with or without aura according to InternationalClassification of Headache Disorders (2nd Edition) (ICHD-2) for at least 1 year prior to screening * Experiences between 2 and 8 migraine attacks per month for the past 12 months * Women of child bearing potential must be practicing an effective method of birth control * Women of child-bearing potential must have a negative urine pregnancy test at the screening visit and a negative urine pregnancy test at the randomization visit * Demonstrate the ability to use the bi-directional delivery device correctly * Able and willing to read and comprehend written instructions and complete the electronic diary information required by the protocol * Must be capable, in the opinion of the Investigator, of providing informed consent to participate in the study. Subjects (and their legally acceptable representatives, if applicable) must sign an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study Exclusion Criteria: * Inability to distinguish other headaches from migraine * Experiences headache of any kind at a frequency greater than or equal to 15 days per month * History of resistance to sumatriptan, or non-response to 2 or more other triptans, defined as subjects who have not responded to an adequate dose and duration of treatment * Current use of medication for migraine prophylaxis that has not been stable (no dose adjustment) for 30 days prior to screening * Chronic opioid therapy (\>3 consecutive days in the 30 days prior to screening) * Current treatment with monoamine oxidase A (MAO-A) inhibitors or use within 4 weeks before randomization * Have hemiplegic or basilar migraine * History, symptoms or signs of ischemic cardiac, cerebrovascular or peripheral vascular syndromes. Ischemic cardiac syndromes include, but are not limited to, angina pectoris of any type (e.g., stable angina of effort, vasospastic forms of angina such as the Prinzmetal variant), all forms of myocardial infarction and silent myocardial ischemia. Cerebrovascular syndromes include, but are not limited to, strokes of any type as well as transient ischemic attacks. Peripheral vascular disease includes, but is not limited to, ischemic bowel disease, Raynaud syndrome * Uncontrolled hypertension (screening systolic/diastolic blood pressure \>140/95 mmHg) * Have severe hepatic impairment * Have history of epilepsy or conditions associated with a lowered seizure threshold * History (within 2 years) of drug or alcohol abuse as defined by Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-IV) criteria **Maximum Age:** 65 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** San Francisco **Country:** United States **Facility:** San Francisco Clinical Research Center **State:** California **Zip:** 94109 **Location 2:** **City:** Santa Monica **Country:** United States **Facility:** California Medical Clinic for Headache **State:** California **Zip:** 90404 **Location 3:** **City:** Fairfied **Country:** United States **Facility:** Associated Neurologists of Southern CT, P.C. **State:** Connecticut **Zip:** 06824 **Location 4:** **City:** West Palm Beach **Country:** United States **Facility:** Premiere Research Institute **State:** Florida **Zip:** 33407 **Location 5:** **City:** Watertown **Country:** United States **Facility:** MedVadis **State:** Massachusetts **Zip:** 02472 **Location 6:** **City:** Ann Arbor **Country:** United States **Facility:** Michigan Head and Pain Institute **State:** Michigan **Zip:** 48104-5199 **Location 7:** **City:** Springfield **Country:** United States **Facility:** ClinVest **State:** Missouri **Zip:** 65807 **Location 8:** **City:** St. Louis **Country:** United States **Facility:** Mercy Health Research **State:** Missouri **Zip:** 63141 **Location 9:** **City:** Amherst **Country:** United States **Facility:** DENT Neurologic Institute **State:** New York **Zip:** 14226 **Location 10:** **City:** Greensboro **Country:** United States **Facility:** Headache Welness Center **State:** North Carolina **Zip:** 27405 **Location 11:** **City:** Winston Salem **Country:** United States **Facility:** PMG Research of Winston Salem, LLC **State:** North Carolina **Zip:** 27103 **Location 12:** **City:** Philadelphia **Country:** United States **Facility:** Jefferson Headache Center **State:** Pennsylvania **Zip:** 19107 **Location 13:** **City:** Mt. Pleasant **Country:** United States **Facility:** Coastal Carolina Research Center **State:** South Carolina **Zip:** 29464 ### References Module #### References **Citation:** Lipton RB, McGinley JS, Shulman KJ, Wirth RJ, Buse DC. Faster Improvement in Migraine Pain Intensity and Migraine-Related Disability at Early Time Points with AVP-825 (Sumatriptan Nasal Powder Delivery System) versus Oral Sumatriptan: A Comparative Randomized Clinical Trial Across Multiple Attacks from the COMPASS Study. Headache. 2017 Nov;57(10):1570-1582. doi: 10.1111/head.13165. Epub 2017 Sep 7. **PMID:** 28880380 **Citation:** Tepper SJ, Cady RK, Silberstein S, Messina J, Mahmoud RA, Djupesland PG, Shin P, Siffert J. AVP-825 breath-powered intranasal delivery system containing 22 mg sumatriptan powder vs 100 mg oral sumatriptan in the acute treatment of migraines (The COMPASS study): a comparative randomized clinical trial across multiple attacks. Headache. 2015 May;55(5):621-35. doi: 10.1111/head.12583. Epub 2015 May 4. **PMID:** 25941016 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000051270 - Term: Headache Disorders, Primary - ID: D000020773 - Term: Headache Disorders - ID: D000001927 - Term: Brain Diseases - ID: D000002493 - Term: Central Nervous System Diseases - ID: D000009422 - Term: Nervous System Diseases - ID: D000010146 - Term: Pain - ID: D000009461 - Term: Neurologic Manifestations ### Condition Browse Module - Browse Branches - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M11852 - Name: Migraine Disorders - Relevance: HIGH - As Found: Migraine - ID: M9351 - Name: Headache - Relevance: HIGH - As Found: Headache - ID: M22529 - Name: Headache Disorders - Relevance: LOW - As Found: Unknown - ID: M26657 - Name: Headache Disorders, Primary - Relevance: LOW - As Found: Unknown - ID: M5204 - Name: Brain Diseases - Relevance: LOW - As Found: Unknown - ID: M5742 - Name: Central Nervous System Diseases - Relevance: LOW - As Found: Unknown - ID: M13066 - Name: Pain - Relevance: LOW - As Found: Unknown - ID: M12404 - Name: Neurologic Manifestations - Relevance: LOW - As Found: Unknown - ID: T170 - Name: Acute Graft Versus Host Disease - Relevance: LOW - As Found: Unknown - ID: T4202 - Name: Oculocerebral Syndrome With Hypopigmentation - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000008881 - Term: Migraine Disorders - ID: D000006261 - Term: Headache ### Intervention Browse Module - Ancestors - ID: D000014662 - Term: Vasoconstrictor Agents - ID: D000058825 - Term: Serotonin 5-HT1 Receptor Agonists - ID: D000017366 - Term: Serotonin Receptor Agonists - ID: D000018490 - Term: Serotonin Agents - ID: D000018377 - Term: Neurotransmitter Agents - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000045505 - Term: Physiological Effects of Drugs ### Intervention Browse Module - Browse Branches - Abbrev: VaCoAg - Name: Vasoconstrictor Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M20316 - Name: Sumatriptan - Relevance: HIGH - As Found: Stage IIIB - ID: M17409 - Name: Vasoconstrictor Agents - Relevance: LOW - As Found: Unknown - ID: M15512 - Name: Serotonin - Relevance: LOW - As Found: Unknown - ID: M29240 - Name: Serotonin 5-HT1 Receptor Agonists - Relevance: LOW - As Found: Unknown - ID: M19648 - Name: Serotonin Receptor Agonists - Relevance: LOW - As Found: Unknown - ID: M20504 - Name: Neurotransmitter Agents - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000018170 - Term: Sumatriptan ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module **Description:** Adverse events were collected in members of the Safety Analysis Set, comprised of all randomized participants who received at least 1 dose of either 20 mg sumatriptan nasal powder or 100 mg sumatriptan tablet. #### Event Groups **Group ID:** EG000 **Title:** 20 mg Sumatriptan Nasal Powder **Description:** Participants received 20 mg sumatriptan nasal powder delivered intranasally with a bi-directional device in Treatment Period 1 or Treatment Period 2. **ID:** EG000 **Other Num Affected:** 98 **Other Num at Risk:** 219 **Serious Number At Risk:** 219 **Title:** 20 mg Sumatriptan Nasal Powder **Group ID:** EG001 **Title:** 100 mg Sumatriptan Tablet **Description:** Participants received a 100 mg sumatriptan tablet taken orally in Treatment Period 1 or Treatment Period 2. **ID:** EG001 **Other Num Affected:** 35 **Other Num at Risk:** 228 **Serious Number At Risk:** 228 **Title:** 100 mg Sumatriptan Tablet **Frequency Threshold:** 1 #### Other Events **Term:** Nausea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA (14.1) **Term:** Product taste abnormal **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA (14.1) **Term:** Ear infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (14.1) **Term:** Gastroenteritis viral **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (14.1) **Term:** Sinusitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (14.1) **Term:** Upper respiratory tract infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (14.1) **Term:** Neck pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA (14.1) **Term:** Headache **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA (14.1) **Term:** Nasal discomfort **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA (14.1) **Term:** Rhinalgia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA (14.1) **Term:** Throat irritation **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA (14.1) **Term:** Upper-airway cough syndrome **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA (14.1) **Time Frame:** Treatment-emergent adverse events were collected from the first dose of investigational product through up to 24 weeks. ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 133 **Group ID:** BG001 **Value:** 129 **Group ID:** BG002 **Value:** 262 **Units:** Participants ### Group **ID:** BG000 **Title:** 20 mg Sumatriptan+PBO (TP1)/100 mg Sumatriptan+PBO (TP2) **Description:** In Treatment Period 1 (\<=12 weeks), participants received 20 milligrams (mg) sumatriptan nasal powder delivered intranasally with a bi-directional device and a placebo (PBO) tablet taken orally. After completing Treatment Period 1, participants entered Treatment Period 2 (\<=12 weeks), during which they received a 100 mg sumatriptan tablet taken orally and placebo (lactose) as a nasal powder administered into the nostril on the side of the migraine, followed by another administration into the other nostril. ### Group **ID:** BG001 **Title:** 100 mg Sumatriptan+PBO (TP1)/20 mg Sumatriptan+PBO (TP2) **Description:** In Treatment Period 1 (\<=12 weeks), participants received a 100 mg sumatriptan tablet taken orally and placebo (lactose) as a nasal powder administered into the nostril on the side of the migraine, followed by another administration into the other nostril. After completing Treatment Period 1, participants entered Treatment Period 2 (\<=12 weeks), during which they received 20 mg sumatriptan nasal powder delivered intranasally with a bi-directional device and a placebo tablet taken orally. ### Group **ID:** BG002 **Title:** Total **Description:** Total of all reporting groups ### Measure #### Measurement **Group ID:** BG000 **Spread:** 12.55 **Value:** 39.5 #### Measurement **Group ID:** BG001 **Spread:** 11.93 **Value:** 40.7 #### Measurement **Group ID:** BG002 **Spread:** 12.24 **Value:** 40.1 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 107 #### Measurement **Group ID:** BG001 **Value:** 115 #### Measurement **Group ID:** BG002 **Value:** 222 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 26 #### Measurement **Group ID:** BG001 **Value:** 14 #### Measurement **Group ID:** BG002 **Value:** 40 **Category Title:** Male **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** American Indian or Alaska Native #### Measurement **Group ID:** BG000 **Value:** 3 #### Measurement **Group ID:** BG001 **Value:** 1 #### Measurement **Group ID:** BG002 **Value:** 4 **Category Title:** Asian #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** Native Hawaiian or Other Pacific Islander #### Measurement **Group ID:** BG000 **Value:** 24 #### Measurement **Group ID:** BG001 **Value:** 26 #### Measurement **Group ID:** BG002 **Value:** 50 **Category Title:** Black or African American #### Measurement **Group ID:** BG000 **Value:** 104 #### Measurement **Group ID:** BG001 **Value:** 100 #### Measurement **Group ID:** BG002 **Value:** 204 **Category Title:** White #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** More than one race #### Measurement **Group ID:** BG000 **Value:** 2 #### Measurement **Group ID:** BG001 **Value:** 2 #### Measurement **Group ID:** BG002 **Value:** 4 **Category Title:** Unknown or Not Reported **Class Title:** **Denomination Units Selected:** ## Results Section - Baseline Characteristics Module ### Measure 1 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** Age, Continuous **Unit of Measure:** Years ### Measure 2 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Sex: Female, Male **Unit of Measure:** Participants ### Measure 3 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Race (NIH/OMB) **Unit of Measure:** Participants **Population Description:** Baseline data are reported for participants in the Safety Analysis Set, defined as all randomized participants who received at least one dose of sumatriptan (20 mg nasal powder or 100 mg tablet). ## Results Section - More Information Module ### Certain Agreement **Restriction Type:** OTHER **Restrictive Agreement:** True ### Point of Contact **Email:** [email protected] **Organization:** Avanir Pharmaceuticals **Phone:** 1-949-268-8972 **Title:** Nadine Knowles; Executive Director, Research & Development Operations ## Results Section - Outcome Measures Module ### Outcome Measure 1 #### Analysis **CI Lower Limit:** 1.76 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 5.01 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.824 **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** <0.0001 **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 3.39 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** ### Outcome Measure 2 #### Analysis **CI Lower Limit:** 1.47 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 5.85 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 1.105 **Estimate Comment:** mild attacks **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0013 **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 3.66 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 1.84 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 5.68 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.971 **Estimate Comment:** moderate/severe attacks **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0002 **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 3.76 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** ### Outcome Measure 3 #### Analysis **CI Lower Limit:** 0.85 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 1.60 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** 10 minutes post-dose **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.3549 **P-Value Comment:** **Parameter Type:** Odds Ratio (OR) **Parameter Value:** 1.16 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 1.20 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 1.90 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** 15 minutes post-dose **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0005 **P-Value Comment:** **Parameter Type:** Odds Ratio (OR) **Parameter Value:** 1.51 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 1.45 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 2.21 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** 30 minutes post-dose **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** <0.0001 **P-Value Comment:** **Parameter Type:** Odds Ratio (OR) **Parameter Value:** 1.79 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 1.24 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 1.96 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** 45 minutes post-dose **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0002 **P-Value Comment:** **Parameter Type:** Odds Ratio (OR) **Parameter Value:** 1.56 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 1.10 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 1.71 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** 60 minutes post-dose **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0057 **P-Value Comment:** **Parameter Type:** Odds Ratio (OR) **Parameter Value:** 1.37 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 0.99 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 1.61 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** 90 minutes post-dose **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0654 **P-Value Comment:** **Parameter Type:** Odds Ratio (OR) **Parameter Value:** 1.26 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 0.89 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 1.49 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** 120 minutes post-dose **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.2894 **P-Value Comment:** **Parameter Type:** Odds Ratio (OR) **Parameter Value:** 1.15 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** ### Outcome Measure 4 #### Analysis **CI Lower Limit:** 0.76 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 4.54 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** 10 minutes post-dose **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.1771 **P-Value Comment:** **Parameter Type:** Odds Ratio (OR) **Parameter Value:** 1.85 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 1.21 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 3.42 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** 15 minutes post-dose **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0077 **P-Value Comment:** **Parameter Type:** Odds Ratio (OR) **Parameter Value:** 2.03 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 1.32 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 2.50 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** 30 minutes post-dose **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0003 **P-Value Comment:** **Parameter Type:** Odds Ratio (OR) **Parameter Value:** 1.82 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 1.29 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 2.09 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** 45 minutes post-dose **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** <0.0001 **P-Value Comment:** **Parameter Type:** Odds Ratio (OR) **Parameter Value:** 1.64 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 1.14 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 1.74 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** 60 minutes post-dose **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0016 **P-Value Comment:** **Parameter Type:** Odds Ratio (OR) **Parameter Value:** 1.41 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 1.09 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 1.69 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** 90 minutes post-dose **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0059 **P-Value Comment:** **Parameter Type:** Odds Ratio (OR) **Parameter Value:** 1.36 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 0.91 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 1.42 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** 120 minutes post-dose **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.2717 **P-Value Comment:** **Parameter Type:** Odds Ratio (OR) **Parameter Value:** 1.14 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** ### Outcome Measure 5 #### Analysis **CI Lower Limit:** 0.87 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 1.77 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** 10 minutes post-dose **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.2426 **P-Value Comment:** **Parameter Type:** Odds Ratio (OR) **Parameter Value:** 1.24 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 1.12 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 1.99 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** 15 minutes post-dose **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0069 **P-Value Comment:** **Parameter Type:** Odds Ratio (OR) **Parameter Value:** 1.49 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 1.47 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 2.56 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** 30 minutes post-dose **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** <0.0001 **P-Value Comment:** **Parameter Type:** Odds Ratio (OR) **Parameter Value:** 1.94 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 1.26 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 2.23 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** 45 minutes post-dose **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0004 **P-Value Comment:** **Parameter Type:** Odds Ratio (OR) **Parameter Value:** 1.68 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 1.22 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 2.11 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** 60 minutes post-dose **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0008 **P-Value Comment:** **Parameter Type:** Odds Ratio (OR) **Parameter Value:** 1.60 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 1.04 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 1.83 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** 90 minutes post-dose **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0272 **P-Value Comment:** **Parameter Type:** Odds Ratio (OR) **Parameter Value:** 1.38 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 0.90 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 1.62 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** 120 minutes post-dose **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.2085 **P-Value Comment:** **Parameter Type:** Odds Ratio (OR) **Parameter Value:** 1.21 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** ### Outcome Measure 6 ### Outcome Measure 7 #### Analysis **CI Lower Limit:** -0.06 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 0.02 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.021 **Estimate Comment:** 10 minutes post-dose **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.3562 **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** -0.02 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** -0.14 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 94 **CI Upper Limit:** -0.02 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.029 **Estimate Comment:** 15 minutes post-dose **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0063 **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** -0.08 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** -0.26 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -0.11 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.039 **Estimate Comment:** 30 minutes post-dose **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** < 0.0001 **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** -0.19 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** -0.26 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -0.07 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.046 **Estimate Comment:** 45 minutes post-dose **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0005 **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** -0.17 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** -0.24 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -0.05 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.048 **Estimate Comment:** 60 minutes post-dose **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0040 **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** -0.14 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** -0.21 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -0.01 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.052 **Estimate Comment:** 90 minutes post-dose **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0333 **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** -0.11 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** -0.15 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 0.06 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.052 **Estimate Comment:** 120 minutes post-dose **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.4031 **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** -0.04 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** ### Outcome Measure 8 #### Analysis **CI Lower Limit:** -0.08 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -0.01 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.019 **Estimate Comment:** 10 minutes post-dose **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0181 **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** -0.04 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** -0.14 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -0.04 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.026 **Estimate Comment:** 15 minutes post-dose **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0003 **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** -0.09 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** -0.23 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -0.09 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.035 **Estimate Comment:** 30 minutes post-dose **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** < 0.0001 **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** -0.16 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** -0.25 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -0.08 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.043 **Estimate Comment:** 45 minutes post-dose **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0001 **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** -0.17 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** -0.26 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -0.07 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.047 **Estimate Comment:** 60 minutes post-dose **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0006 **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** -0.16 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** -0.21 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -0.02 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.048 **Estimate Comment:** 90 minutes post-dose **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0189 **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** -0.11 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** -0.17 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 0.03 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.050 **Estimate Comment:** 120 minutes post-dose **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.1704 **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** -0.07 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** ### Outcome Measure 9 ### Outcome Measure 10 ### Outcome Measure 11 ### Outcome Measure 12 ### Outcome Measure 13 ### Outcome Measure 14 ### Outcome Measure 15 ### Outcome Measure 16 ### Outcome Measure 17 ### Outcome Measure 18 ### Outcome Measure 19 ### Outcome Measure 20 ### Outcome Measure 21 ### Outcome Measure 22 ### Outcome Measure 23 ### Outcome Measure 24 ### Outcome Measure 25 ### Outcome Measure 26 ### Outcome Measure 27 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.880 - **Upper Limit:** - **Value:** 10.80 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.880 - **Upper Limit:** - **Value:** 7.41 **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.921 - **Upper Limit:** - **Value:** 3.90 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.931 - **Upper Limit:** - **Value:** 0.24 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.022 - **Upper Limit:** - **Value:** 13.83 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.997 - **Upper Limit:** - **Value:** 10.07 **Title:** #### Outcome Measure 3 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 11.5 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 10.2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 26.4 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 19.6 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 49.0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 35.2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 60.7 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 49.9 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 67.2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 59.8 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 74.6 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 69.8 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 78.0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 75.2 **Title:** #### Outcome Measure 4 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2.5 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1.3 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 7.2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3.7 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 18.2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 10.8 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 31.0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 21.3 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 41.2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 32.9 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 52.8 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 44.9 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 60.4 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 56.3 **Title:** #### Outcome Measure 5 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 13.8 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 11.5 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 27.9 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 20.9 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 53.8 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 38.7 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 65.0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 53.9 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 72.1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 62.6 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 77.4 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 72.0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 79.6 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 76.9 **Title:** #### Outcome Measure 6 **Class:** ##### Category **Measurements:** - **Comment:** The confidence interval is un-estimable due to the number of participants who were observed pain free at the post-dose time points. - **Group ID:** OG000 - **Lower Limit:** NA - **Spread:** - **Upper Limit:** NA - **Value:** 91 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 91 - **Spread:** - **Upper Limit:** 121 - **Value:** 121 **Title:** #### Outcome Measure 7 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.018 - **Upper Limit:** - **Value:** -0.11 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.018 - **Upper Limit:** - **Value:** -0.09 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.029 - **Upper Limit:** - **Value:** -0.26 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.029 - **Upper Limit:** - **Value:** -0.18 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.042 - **Upper Limit:** - **Value:** -0.56 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.042 - **Upper Limit:** - **Value:** -0.38 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.049 - **Upper Limit:** - **Value:** -0.77 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.049 - **Upper Limit:** - **Value:** -0.60 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.051 - **Upper Limit:** - **Value:** -0.93 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.051 - **Upper Limit:** - **Value:** -0.79 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.052 - **Upper Limit:** - **Value:** -1.09 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.052 - **Upper Limit:** - **Value:** -0.98 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.053 - **Upper Limit:** - **Value:** -1.19 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.053 - **Upper Limit:** - **Value:** -1.15 **Title:** #### Outcome Measure 8 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.017 - **Upper Limit:** - **Value:** -0.08 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.017 - **Upper Limit:** - **Value:** -0.03 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.025 - **Upper Limit:** - **Value:** -0.18 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.025 - **Upper Limit:** - **Value:** -0.09 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.038 - **Upper Limit:** - **Value:** -0.42 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.038 - **Upper Limit:** - **Value:** -0.26 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.046 - **Upper Limit:** - **Value:** -0.60 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.046 - **Upper Limit:** - **Value:** -0.43 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.049 - **Upper Limit:** - **Value:** -0.73 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.049 - **Upper Limit:** - **Value:** -0.56 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.052 - **Upper Limit:** - **Value:** -0.83 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.052 - **Upper Limit:** - **Value:** -0.72 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.054 - **Upper Limit:** - **Value:** -0.92 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.054 - **Upper Limit:** - **Value:** -0.85 **Title:** #### Outcome Measure 9 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 118 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 73 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** #### Outcome Measure 10 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 6.07 - **Upper Limit:** - **Value:** -1.3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 6.66 - **Upper Limit:** - **Value:** -1.3 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 109 - **Group ID:** OG001 - **Value:** 95 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 6.58 - **Upper Limit:** - **Value:** -2.7 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 6.63 - **Upper Limit:** - **Value:** -0.8 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 124 - **Group ID:** OG001 - **Value:** 110 **Units:** Participants #### Outcome Measure 11 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.0204 - **Upper Limit:** - **Value:** -0.002 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.0222 - **Upper Limit:** - **Value:** -0.005 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.0222 - **Upper Limit:** - **Value:** -0.005 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.0198 - **Upper Limit:** - **Value:** -0.002 **Title:** #### Outcome Measure 12 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.227 - **Upper Limit:** - **Value:** -0.02 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.280 - **Upper Limit:** - **Value:** -0.04 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.228 - **Upper Limit:** - **Value:** -0.05 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.209 - **Upper Limit:** - **Value:** -0.02 **Title:** #### Outcome Measure 13 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.398 - **Upper Limit:** - **Value:** -0.10 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.381 - **Upper Limit:** - **Value:** -0.19 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.477 - **Upper Limit:** - **Value:** -0.05 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.464 - **Upper Limit:** - **Value:** -0.09 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.0301 - **Upper Limit:** - **Value:** 0.000 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.0297 - **Upper Limit:** - **Value:** 0.000 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.0283 - **Upper Limit:** - **Value:** 0.000 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.0235 - **Upper Limit:** - **Value:** -0.001 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.1356 - **Upper Limit:** - **Value:** -0.030 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.1160 - **Upper Limit:** - **Value:** -0.022 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.1504 - **Upper Limit:** - **Value:** -0.014 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.1281 - **Upper Limit:** - **Value:** -0.026 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.2553 - **Upper Limit:** - **Value:** -0.052 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.1600 - **Upper Limit:** - **Value:** -0.134 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.4270 - **Upper Limit:** - **Value:** -0.059 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.2885 - **Upper Limit:** - **Value:** -0.057 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.4702 - **Upper Limit:** - **Value:** -0.049 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.3892 - **Upper Limit:** - **Value:** -0.038 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.4252 - **Upper Limit:** - **Value:** 0.012 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.3925 - **Upper Limit:** - **Value:** -0.020 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.0766 - **Upper Limit:** - **Value:** -0.001 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.0493 - **Upper Limit:** - **Value:** 0.006 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.1068 - **Upper Limit:** - **Value:** 0.012 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.0824 - **Upper Limit:** - **Value:** 0.013 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 29.14 - **Upper Limit:** - **Value:** -1.9 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 46.92 - **Upper Limit:** - **Value:** -8.2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 27.92 - **Upper Limit:** - **Value:** -4.0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 43.40 - **Upper Limit:** - **Value:** -7.5 **Title:** #### Outcome Measure 14 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.2118 - **Upper Limit:** - **Value:** 0.070 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.2227 - **Upper Limit:** - **Value:** 0.079 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.2840 - **Upper Limit:** - **Value:** 0.156 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.3674 - **Upper Limit:** - **Value:** 0.308 **Title:** #### Outcome Measure 15 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 10.73 - **Upper Limit:** - **Value:** -1.9 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 6.59 - **Upper Limit:** - **Value:** -0.7 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 11.77 - **Upper Limit:** - **Value:** -1.3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 8.24 - **Upper Limit:** - **Value:** -0.6 **Title:** #### Outcome Measure 16 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 8.92 - **Upper Limit:** - **Value:** -0.5 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 6.78 - **Upper Limit:** - **Value:** 0.0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 9.92 - **Upper Limit:** - **Value:** -1.7 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 9.45 - **Upper Limit:** - **Value:** -1.0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 7.08 - **Upper Limit:** - **Value:** 0.4 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 8.86 - **Upper Limit:** - **Value:** 0.0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 6.83 - **Upper Limit:** - **Value:** 0.4 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 7.16 - **Upper Limit:** - **Value:** -0.9 **Title:** #### Outcome Measure 17 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 5.26 - **Upper Limit:** - **Value:** -0.2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 14.39 - **Upper Limit:** - **Value:** 0.5 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 7.88 - **Upper Limit:** - **Value:** 0.6 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 5.84 - **Upper Limit:** - **Value:** -1.2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 10.09 - **Upper Limit:** - **Value:** 0.8 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 7.05 - **Upper Limit:** - **Value:** 0.0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 10.31 - **Upper Limit:** - **Value:** 0.4 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 7.35 - **Upper Limit:** - **Value:** -0.7 **Title:** #### Outcome Measure 18 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 4.26 - **Upper Limit:** - **Value:** 0.2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 2.96 - **Upper Limit:** - **Value:** -0.2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 4.09 - **Upper Limit:** - **Value:** -0.6 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 4.01 - **Upper Limit:** - **Value:** 0.2 **Title:** #### Outcome Measure 19 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 2.82 - **Upper Limit:** - **Value:** -0.8 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 2.84 - **Upper Limit:** - **Value:** -0.9 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 2.98 - **Upper Limit:** - **Value:** -0.9 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 2.62 - **Upper Limit:** - **Value:** -0.5 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 3.75 - **Upper Limit:** - **Value:** -1.0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 3.61 - **Upper Limit:** - **Value:** -1.2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 4.20 - **Upper Limit:** - **Value:** -1.2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 3.35 - **Upper Limit:** - **Value:** -1.0 **Title:** #### Outcome Measure 20 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 2.62 - **Upper Limit:** - **Value:** -0.3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 2.24 - **Upper Limit:** - **Value:** -0.5 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 2.76 - **Upper Limit:** - **Value:** -0.3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 2.25 - **Upper Limit:** - **Value:** -0.2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.440 - **Upper Limit:** - **Value:** -0.08 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.404 - **Upper Limit:** - **Value:** -0.04 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.411 - **Upper Limit:** - **Value:** -0.10 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.406 - **Upper Limit:** - **Value:** -0.00 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 2.95 - **Upper Limit:** - **Value:** -0.1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 2.39 - **Upper Limit:** - **Value:** 0.0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 2.62 - **Upper Limit:** - **Value:** 0.2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 2.51 - **Upper Limit:** - **Value:** 0.2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.1017 - **Upper Limit:** - **Value:** -0.019 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.1043 - **Upper Limit:** - **Value:** -0.016 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.1058 - **Upper Limit:** - **Value:** -0.011 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.0886 - **Upper Limit:** - **Value:** -0.006 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.316 - **Upper Limit:** - **Value:** 0.34 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.930 - **Upper Limit:** - **Value:** 0.05 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.063 - **Upper Limit:** - **Value:** 0.20 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.135 - **Upper Limit:** - **Value:** 0.24 **Title:** #### Outcome Measure 21 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.603 - **Upper Limit:** - **Value:** -0.04 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.720 - **Upper Limit:** - **Value:** -0.03 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.664 - **Upper Limit:** - **Value:** 0.01 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.658 - **Upper Limit:** - **Value:** -0.07 **Title:** #### Outcome Measure 22 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 112 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 105 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 16 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 19 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 5 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 92 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 75 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 11 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 15 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 5 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 104 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 90 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 17 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 12 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 6 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 132 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 126 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 107 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 94 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 122 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 108 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 124 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 121 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 7 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 7 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 102 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 88 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 5 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 6 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 119 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 101 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 8 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 116 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 116 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 7 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 5 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 5 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 94 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 78 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 6 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 5 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 5 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 111 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 94 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 6 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 5 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 5 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 99 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 101 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 12 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 8 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 12 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 11 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 7 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 5 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 90 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 75 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 8 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 7 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 5 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 6 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 105 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 85 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 5 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 7 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 5 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 8 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 8 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4 **Title:** #### Outcome Measure 23 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 11.58 - **Upper Limit:** - **Value:** 0.1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 11.46 - **Upper Limit:** - **Value:** 1.5 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 11.52 - **Upper Limit:** - **Value:** 1.6 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 11.94 - **Upper Limit:** - **Value:** 2.0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 7.17 - **Upper Limit:** - **Value:** -0.2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 8.89 - **Upper Limit:** - **Value:** 1.0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 7.42 - **Upper Limit:** - **Value:** 0.2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 7.90 - **Upper Limit:** - **Value:** -0.2 **Title:** #### Outcome Measure 24 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 8.63 - **Upper Limit:** - **Value:** 0.1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 9.24 - **Upper Limit:** - **Value:** 0.1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 9.07 - **Upper Limit:** - **Value:** -2.2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 10.96 - **Upper Limit:** - **Value:** -0.2 **Title:** #### Outcome Measure 25 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 96 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 99 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 36 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 30 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 79 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 70 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 31 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 25 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 90 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 73 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 34 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 37 **Title:** #### Outcome Measure 26 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 132 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 129 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 109 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 93 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 124 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 111 **Title:** #### Outcome Measure 27 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 218 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 226 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 12 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 14 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 143 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 148 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 6 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 6 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 18 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 20 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 13 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 17 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 7 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 6 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 11 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 12 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 5 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 38 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 39 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 135 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 143 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 8 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 8 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 18 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 15 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 9 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 8 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 7 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 8 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 8 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 9 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 6 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 7 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 22 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 23 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 5 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 20 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 26 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 7 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 9 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 23 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 20 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 20 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 22 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 12 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 16 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 25 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 27 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 7 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 6 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 5 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 5 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 21 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 21 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 57 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 60 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 31 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 31 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 62 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 59 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 18 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 16 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 11 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 12 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 57 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 56 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** SPID-30 is defined as the sum of the pain intensity differences (measured as area under the curve) from dosing (Baseline) through 30 minutes post-dose for headaches with a Baseline intensity of mild, moderate, or severe. The range of possible scores is -60 to +90. A higher number indicates a greater reduction in pain intensity. Negative values indicate worsening pain. A value of "0" indicates that there was no change in pain intensity from Baseline through 30 minutes. Results are from an analysis of covariance (ANCOVA) model with treatment, period, and treatment sequence as fixed effects and participant as a random effect. The Last Observation Carried Forward (LOCF) imputation method (missing values were replaced by carrying forward the preceding value) was used for this analysis. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** Full Analysis Set (FAS): all participants who experienced at least 1 headache attack per treatment period, received at least 1 dose of study medication (sumatriptan nasal powder or tablet) in each treatment period, and had at least 1 post-Baseline assessment for a treated attack in each treatment period. **Reporting Status:** POSTED **Time Frame:** Baseline and 30 minutes post-dose (up to 24 weeks) **Title:** Mean Sum of Migraine Pain Intensity Differences (SPID)-30 **Type:** PRIMARY **Unit of Measure:** scores on a scale ##### Group **Description:** Participants received 20 mg sumatriptan nasal powder delivered intranasally with a bi-directional device in Treatment Period 1 or Treatment Period 2. **ID:** OG000 **Title:** 20 mg Sumatriptan Nasal Powder ##### Group **Description:** Participants received a 100 mg sumatriptan tablet taken orally in Treatment Period 1 or Treatment Period 2. **ID:** OG001 **Title:** 100 mg Sumatriptan Tablet #### Outcome Measure 2 **Description:** SPID-30 is defined as the sum of the pain intensity differences (measured as area under the curve) from dosing (Baseline) through 30 minutes post-dose for headaches with a Baseline intensity of mild and moderate/severe (rated on a 4-point scale: 0=none, 1=mild, 2=moderate, and 3=severe). The range of possible scores for all participants is -60 to +90. For participants with a mild headache at Baseline, the SPID range is -60 to +30. For participants with a moderate/severe headache at Baseline, the SPID range is -30 to +90. A higher number indicates a greater reduction in pain intensity. Negative values indicate worsening pain. A value of "0" indicates that there was no change in pain intensity from Baseline through 30 minutes. Results are from an ANCOVA model with treatment, period, and treatment sequence as fixed effects and participant as a random effect. The LOCF imputation method (missing values were replaced by carrying forward the preceding value) was used for this analysis. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** FAS. Only those participants with the type of attack specified were analyzed (specified by n=X, X in the corresponding category title). A single participant could have had both a mild and a moderate/severe attack. **Reporting Status:** POSTED **Time Frame:** Baseline and 30 minutes post-dose (up to 24 weeks) **Title:** Mean Sum of Migraine Pain Intensity Differences (SPID)-30 for Headaches With a Baseline Intensity of Mild and Moderate/Severe **Type:** SECONDARY **Unit of Measure:** scores on a scale ##### Group **Description:** Participants received 20 mg sumatriptan nasal powder delivered intranasally with a bi-directional device in Treatment Period 1 or Treatment Period 2. **ID:** OG000 **Title:** 20 mg Sumatriptan Nasal Powder ##### Group **Description:** Participants received a 100 mg sumatriptan tablet taken orally in Treatment Period 1 or Treatment Period 2. **ID:** OG001 **Title:** 100 mg Sumatriptan Tablet #### Outcome Measure 3 **Description:** Percentage of attacks in which pain reduction (defined as a decrease in pain intensity of at least one point on the following scale: 0, none; 1, mild; 2, moderate; 3, severe) was achieved at 10, 15, 30, 45, 60, 90, and 120 minutes after the initial dose for all attacks. **Parameter Type:** NUMBER **Population Description:** FAS. The LOCF imputation method was used in this analysis. **Reporting Status:** POSTED **Time Frame:** 10, 15, 30, 45, 60, 90, and 120 minutes **Title:** Percentage of Attacks in Which Pain Reduction Was Achieved **Type:** SECONDARY **Type Units Analyzed:** number of attacks **Unit of Measure:** percentage of attacks ##### Group **Description:** Participants received 20 mg sumatriptan nasal powder delivered intranasally with a bi-directional device in Treatment Period 1 or Treatment Period 2. **ID:** OG000 **Title:** 20 mg Sumatriptan Nasal Powder ##### Group **Description:** Participants received a 100 mg sumatriptan tablet taken orally in Treatment Period 1 or Treatment Period 2. **ID:** OG001 **Title:** 100 mg Sumatriptan Tablet #### Outcome Measure 4 **Description:** Percentage of attacks in which pain freedom (defined as pain level reduced to none \[Grade 0\]) was achieved at 10, 15, 30, 45, 60, 90, and 120 minutes after the initial dose for all attacks. **Parameter Type:** NUMBER **Population Description:** FAS. The LOCF imputation method was used for this analysis. **Reporting Status:** POSTED **Time Frame:** Baseline and 10, 15, 30, 45, 60, 90, and 120 minutes post-dose (up to 24 weeks) **Title:** Percentage of Attacks in Which Pain Freedom Was Achieved **Type:** SECONDARY **Type Units Analyzed:** number of attacks **Unit of Measure:** percentage of attacks ##### Group **Description:** Participants received 20 mg sumatriptan nasal powder delivered intranasally with a bi-directional device in Treatment Period 1 or Treatment Period 2. **ID:** OG000 **Title:** 20 mg Sumatriptan Nasal Powder ##### Group **Description:** Participants received a 100 mg sumatriptan tablet taken orally in Treatment Period 1 or Treatment Period 2. **ID:** OG001 **Title:** 100 mg Sumatriptan Tablet #### Outcome Measure 5 **Description:** Percentage of attacks treated at a severity of moderate (Grade 2) or severe (Grade 3) in which pain relief (defined as pain level reduced to none \[Grade 0\] or mild \[Grade 1\]) was achieved at 10, 15, 30, 45, 60, 90, and 120 minutes after the initial dose for all attacks. **Parameter Type:** NUMBER **Population Description:** FAS. The LOCF imputation method was used in this analysis. **Reporting Status:** POSTED **Time Frame:** Baseline and 10, 15, 30, 45, 60, 90, and 120 minutes post-dose (up to 24 weeks) **Title:** Percentage of Attacks in Which Pain Relief Was Achieved **Type:** SECONDARY **Type Units Analyzed:** number of moderate or severe attacks **Unit of Measure:** percentage of attacks ##### Group **Description:** Participants received 20 mg sumatriptan nasal powder delivered intranasally with a bi-directional device in Treatment Period 1 or Treatment Period 2. **ID:** OG000 **Title:** 20 mg Sumatriptan Nasal Powder ##### Group **Description:** Participants received a 100 mg sumatriptan tablet taken orally in Treatment Period 1 or Treatment Period 2. **ID:** OG001 **Title:** 100 mg Sumatriptan Tablet #### Outcome Measure 6 **Description:** Pain freedom is defined as a pain level reduced to none (Grade 0). **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEDIAN **Population Description:** FAS. If the participant did not report pain freedom within 120 minutes post-dose, he/she was considered to be censored at the last non-missing result prior to the 120-minute time point. **Reporting Status:** POSTED **Time Frame:** 120 minutes post-dose (up to 24 weeks) **Title:** Median Time to Pain Freedom **Type:** SECONDARY **Unit of Measure:** minutes ##### Group **Description:** Participants received 20 mg sumatriptan nasal powder delivered intranasally with a bi-directional device in Treatment Period 1 or Treatment Period 2. **ID:** OG000 **Title:** 20 mg Sumatriptan Nasal Powder ##### Group **Description:** Participants received a 100 mg sumatriptan tablet taken orally in Treatment Period 1 or Treatment Period 2. **ID:** OG001 **Title:** 100 mg Sumatriptan Tablet #### Outcome Measure 7 **Description:** Participants were required to record their headache severity score in their e-diaries immediately before intake of study medication (Baseline) and at 10, 15, 30, 45, 60, 90, and 120 minutes post-dose. Participants graded their headaches on the following severity scale: 0, none; 1, mild; 2, moderate; 3, severe. Mean change from Baseline was calculated as the post-Baseline value minus the Baseline value. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** FAS. The LOCF imputation method was used for this analysis. Results are from an ANCOVA model with treatment, period, and treatment sequence as fixed effects and participant as a random effect. **Reporting Status:** POSTED **Time Frame:** Baseline and 10, 15, 30, 45, 60, 90, and 120 minutes post-dose (up to 24 weeks) **Title:** Mean Change in Headache Severity From Baseline to 10, 15, 30, 45, 60, 90, and 120 Minutes Post-dose **Type:** SECONDARY **Unit of Measure:** scores on a scale ##### Group **Description:** Participants received 20 mg sumatriptan nasal powder delivered intranasally with a bi-directional device in Treatment Period 1 or Treatment Period 2. **ID:** OG000 **Title:** 20 mg Sumatriptan Nasal Powder ##### Group **Description:** Participants received a 100 mg sumatriptan tablet taken orally in Treatment Period 1 or Treatment Period 2. **ID:** OG001 **Title:** 100 mg Sumatriptan Tablet #### Outcome Measure 8 **Description:** Participants were required to record their clinical disability score in their e-diaries immediately before intake of study medication (Baseline) and at 10, 15, 30, 45, 60, 90, and 120 minutes post-dose. Participants graded their disability on the following scale: 0, no disability, able to function normally; 1, performance of daily activities mildly impaired, can still do everything but with difficulty; 2, performance of daily activities moderately impaired, unable to do some things; 3, performance of daily activities severely impaired, cannot do all or most things, bed rest may be necessary. Mean change from Baseline was calculated as the post-Baseline value minus the Baseline value. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** FAS. The LOCF imputation method was used for this analysis. Results are from an ANCOVA model with treatment, period, and treatment sequence as fixed effects and participant as a random effect. **Reporting Status:** POSTED **Time Frame:** Baseline and 10, 15, 30, 45, 60, 90, and 120 minutes post-dose (up to 24 weeks) **Title:** Mean Change From Baseline in Clinical Disability Score at 10, 15, 30, 45, 60, 90, and 120 Minutes Post-dose **Type:** SECONDARY **Unit of Measure:** scores on a scale ##### Group **Description:** Participants received 20 mg sumatriptan nasal powder delivered intranasally with a bi-directional device in Treatment Period 1 or Treatment Period 2. **ID:** OG000 **Title:** 20 mg Sumatriptan Nasal Powder ##### Group **Description:** Participants received a 100 mg sumatriptan tablet taken orally in Treatment Period 1 or Treatment Period 2. **ID:** OG001 **Title:** 100 mg Sumatriptan Tablet #### Outcome Measure 9 **Description:** An adverse event is defined as any untoward medical occurrence associated with the use of an investigational product in humans, whether or not it is considered related to the investigational product. This includes any occurrence that was new in onset or aggravated in severity or frequency from the Baseline condition. **Parameter Type:** NUMBER **Population Description:** Safety Analysis Set: all randomized participants who received at least 1 dose of either 20 mg sumatriptan nasal powder or 100 mg sumatriptan tablet **Reporting Status:** POSTED **Time Frame:** Baseline compared to Vist 2, 3 and 4 **Title:** Number of Participants With Any Treatment-emergent Non-serious and Serious Adverse Event **Type:** SECONDARY **Unit of Measure:** participants ##### Group **Description:** Participants received 20 mg sumatriptan nasal powder delivered intranasally with a bi-directional device in Treatment Period 1 or Treatment Period 2. **ID:** OG000 **Title:** 20 mg Sumatriptan Nasal Powder ##### Group **Description:** Participants received a 100 mg sumatriptan tablet taken orally in Treatment Period 1 or Treatment Period 2. **ID:** OG001 **Title:** 100 mg Sumatriptan Tablet #### Outcome Measure 10 **Description:** Change from Baseline in hemoglobin was assessed at Visit 3 (the start of Treatment Period 2) and Visit 4 (the end-of-study visit). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The Baseline value is the last non-missing value prior to or on the start date of Treatment Period 1. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Safety Analysis Set. Only those participants with data available at Visit 3 and Visit 4 were assessed at that respective visit (indicated by n=X, X in the category titles). **Reporting Status:** POSTED **Time Frame:** Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks) **Title:** Change From Baseline in Hemoglobin at Visit 3 (up to 12 Weeks) and Visit 4 (up to 24 Weeks) **Type:** SECONDARY **Unit of Measure:** grams per Liter (g/L) ##### Group **Description:** In Treatment Period 1 (\<=12 weeks), participants received 20 milligrams (mg) sumatriptan nasal powder delivered intranasally with a bi-directional device and a placebo (PBO) tablet taken orally. After completing Treatment Period 1 (upon reaching 12 weeks or treating the fifth qualifying migraine headache in the treatment period, whichever came first), participants entered Treatment Period 2 (\<=12 weeks), during which they received a 100 mg sumatriptan tablet taken orally and placebo (lactose) as a nasal powder administered into the nostril on the side of the migraine, followed by another administration into the other nostril. Participants were to treat \<=5 qualifying migraine headaches during Treatment Period 2. **ID:** OG000 **Title:** 20 mg Sumatriptan+PBO (TP1)/100 mg Sumatriptan+PBO (TP2) ##### Group **Description:** In Treatment Period 1 (\<=12 weeks), participants received a 100 mg sumatriptan tablet taken orally and placebo (lactose) as a nasal powder administered into the nostril on the side of the migraine, followed by another administration into the other nostril. After completing Treatment Period 1 (upon reaching 12 weeks or treating the fifth qualifying migraine headache in the treatment period, whichever came first), participants entered Treatment Period 2 (\<=12 weeks), during which they received 20 mg sumatriptan nasal powder delivered intranasally with a bi-directional device and a placebo tablet taken orally. Participants were to treat \<=5 qualifying migraine headaches during Treatment Period 2. **ID:** OG001 **Title:** 100 mg Sumatriptan+PBO (TP1)/20 mg Sumatriptan+PBO (TP2) #### Outcome Measure 11 **Description:** Change from Baseline in hematocrit (proportion of total blood volume that is composed of red blood cells) was assessed at Visit 3 (the start of Treatment Period 2) and Visit 4 (the end-of-study visit). Change from Baseline was calculated as the post-Baseline value minus the Baseline value.The Baseline value is the last non-missing value prior to or on the start date of Treatment Period 1. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Safety Analysis Set. Only those participants with data available at Visit 3 and Visit 4 were assessed at that respective visit (indicated by n=X, X in the category titles). **Reporting Status:** POSTED **Time Frame:** Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks) **Title:** Change From Baseline in Hematocrit at Visit 3 (up to 12 Weeks) and Visit 4 (up to 24 Weeks) **Type:** SECONDARY **Unit of Measure:** proportion ##### Group **Description:** In Treatment Period 1 (\<=12 weeks), participants received 20 milligrams (mg) sumatriptan nasal powder delivered intranasally with a bi-directional device and a placebo (PBO) tablet taken orally. After completing Treatment Period 1 (upon reaching 12 weeks or treating the fifth qualifying migraine headache in the treatment period, whichever came first), participants entered Treatment Period 2 (\<=12 weeks), during which they received a 100 mg sumatriptan tablet taken orally and placebo (lactose) as a nasal powder administered into the nostril on the side of the migraine, followed by another administration into the other nostril. Participants were to treat \<=5 qualifying migraine headaches during Treatment Period 2. **ID:** OG000 **Title:** 20 mg Sumatriptan+PBO (TP1)/100 mg Sumatriptan+PBO (TP2) ##### Group **Description:** In Treatment Period 1 (\<=12 weeks), participants received a 100 mg sumatriptan tablet taken orally and placebo (lactose) as a nasal powder administered into the nostril on the side of the migraine, followed by another administration into the other nostril. After completing Treatment Period 1 (upon reaching 12 weeks or treating the fifth qualifying migraine headache in the treatment period, whichever came first), participants entered Treatment Period 2 (\<=12 weeks), during which they received 20 mg sumatriptan nasal powder delivered intranasally with a bi-directional device and a placebo tablet taken orally. Participants were to treat \<=5 qualifying migraine headaches during Treatment Period 2. **ID:** OG001 **Title:** 100 mg Sumatriptan+PBO (TP1)/20 mg Sumatriptan+PBO (TP2) #### Outcome Measure 12 **Description:** Change from Baseline in red blood cell count was assessed at Visit 3 (the start of Treatment Period 2) and Visit 4 (the end-of-study visit). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The Baseline value is the last non-missing value prior to or on the start date of Treatment Period 1. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Safety Analysis Set. Only those participants with data available at Visit 3 and Visit 4 were assessed at that respective visit (indicated by n=X, X in the category titles). **Reporting Status:** POSTED **Time Frame:** Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks) **Title:** Change From Baseline in Red Blood Cell Count at Visit 3 (up to Week 12) and Visit 4 (up to Week 24) **Type:** SECONDARY **Unit of Measure:** 10^12 cells per Liter ##### Group **Description:** In Treatment Period 1 (\<=12 weeks), participants received 20 milligrams (mg) sumatriptan nasal powder delivered intranasally with a bi-directional device and a placebo (PBO) tablet taken orally. After completing Treatment Period 1 (upon reaching 12 weeks or treating the fifth qualifying migraine headache in the treatment period, whichever came first), participants entered Treatment Period 2 (\<=12 weeks), during which they received a 100 mg sumatriptan tablet taken orally and placebo (lactose) as a nasal powder administered into the nostril on the side of the migraine, followed by another administration into the other nostril. Participants were to treat \<=5 qualifying migraine headaches during Treatment Period 2. **ID:** OG000 **Title:** 20 mg Sumatriptan+PBO (TP1)/100 mg Sumatriptan+PBO (TP2) ##### Group **Description:** In Treatment Period 1 (\<=12 weeks), participants received a 100 mg sumatriptan tablet taken orally and placebo (lactose) as a nasal powder administered into the nostril on the side of the migraine, followed by another administration into the other nostril. After completing Treatment Period 1 (upon reaching 12 weeks or treating the fifth qualifying migraine headache in the treatment period, whichever came first), participants entered Treatment Period 2 (\<=12 weeks), during which they received 20 mg sumatriptan nasal powder delivered intranasally with a bi-directional device and a placebo tablet taken orally. Participants were to treat \<=5 qualifying migraine headaches during Treatment Period 2. **ID:** OG001 **Title:** 100 mg Sumatriptan+PBO (TP1)/20 mg Sumatriptan+PBO (TP2) #### Outcome Measure 13 **Description:** Change from Baseline in white blood cell (WBC) count, basinophils, monocytes, neutrophils, lymphocytes, eosinophils, and platelets was assessed at Visit 3 (the start of Treatment Period 2) and Visit 4 (the end-of-study visit). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The Baseline value is the last non-missing value prior to or on the start date of Treatment Period 1. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Safety Analysis Set. Only those participants with data available at Visit 3 and Visit 4 were assessed at that respective visit (indicated by n=X, X in the category titles). **Reporting Status:** POSTED **Time Frame:** Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks) **Title:** Change From Baseline in White Blood Cell Count, Basinophils, Monocytes, Neutrophils, Lymphocytes, Eosinophils, and Platelets at Visit 3 (up to Week 12) and Visit 4 (up to Week 24) **Type:** SECONDARY **Unit of Measure:** 10^9 cells per Liter ##### Group **Description:** In Treatment Period 1 (\<=12 weeks), participants received 20 milligrams (mg) sumatriptan nasal powder delivered intranasally with a bi-directional device and a placebo (PBO) tablet taken orally. After completing Treatment Period 1 (upon reaching 12 weeks or treating the fifth qualifying migraine headache in the treatment period, whichever came first), participants entered Treatment Period 2 (\<=12 weeks), during which they received a 100 mg sumatriptan tablet taken orally and placebo (lactose) as a nasal powder administered into the nostril on the side of the migraine, followed by another administration into the other nostril. Participants were to treat \<=5 qualifying migraine headaches during Treatment Period 2. **ID:** OG000 **Title:** 20 mg Sumatriptan+PBO (TP1)/100 mg Sumatriptan+PBO (TP2) ##### Group **Description:** In Treatment Period 1 (\<=12 weeks), participants received a 100 mg sumatriptan tablet taken orally and placebo (lactose) as a nasal powder administered into the nostril on the side of the migraine, followed by another administration into the other nostril. After completing Treatment Period 1 (upon reaching 12 weeks or treating the fifth qualifying migraine headache in the treatment period, whichever came first), participants entered Treatment Period 2 (\<=12 weeks), during which they received 20 mg sumatriptan nasal powder delivered intranasally with a bi-directional device and a placebo tablet taken orally. Participants were to treat \<=5 qualifying migraine headaches during Treatment Period 2. **ID:** OG001 **Title:** 100 mg Sumatriptan+PBO (TP1)/20 mg Sumatriptan+PBO (TP2) #### Outcome Measure 14 **Description:** Change from Baseline in urea was assessed at Visit 3 (the start of Treatment Period 2) and Visit 4 (the end-of-study visit). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The Baseline value is the last non-missing value prior to or on the start date of Treatment Period 1. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Safety Analysis Set. Only those participants with data available at Visit 3 and Visit 4 were assessed at that respective visit (indicated by n=X, X in the category titles). **Reporting Status:** POSTED **Time Frame:** Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks) **Title:** Change From Baseline in Urea at Visit 3 (up to Week 12) and Visit 4 (up to Week 24) **Type:** SECONDARY **Unit of Measure:** millimoles per Liter (mmol/L) ##### Group **Description:** In Treatment Period 1 (\<=12 weeks), participants received 20 milligrams (mg) sumatriptan nasal powder delivered intranasally with a bi-directional device and a placebo (PBO) tablet taken orally. After completing Treatment Period 1 (upon reaching 12 weeks or treating the fifth qualifying migraine headache in the treatment period, whichever came first), participants entered Treatment Period 2 (\<=12 weeks), during which they received a 100 mg sumatriptan tablet taken orally and placebo (lactose) as a nasal powder administered into the nostril on the side of the migraine, followed by another administration into the other nostril. Participants were to treat \<=5 qualifying migraine headaches during Treatment Period 2. **ID:** OG000 **Title:** 20 mg Sumatriptan+PBO (TP1)/100 mg Sumatriptan+PBO (TP2) ##### Group **Description:** In Treatment Period 1 (\<=12 weeks), participants received a 100 mg sumatriptan tablet taken orally and placebo (lactose) as a nasal powder administered into the nostril on the side of the migraine, followed by another administration into the other nostril. After completing Treatment Period 1 (upon reaching 12 weeks or treating the fifth qualifying migraine headache in the treatment period, whichever came first), participants entered Treatment Period 2 (\<=12 weeks), during which they received 20 mg sumatriptan nasal powder delivered intranasally with a bi-directional device and a placebo tablet taken orally. Participants were to treat \<=5 qualifying migraine headaches during Treatment Period 2. **ID:** OG001 **Title:** 100 mg Sumatriptan+PBO (TP1)/20 mg Sumatriptan+PBO (TP2) #### Outcome Measure 15 **Description:** Change from Baseline in creatinine was assessed at Visit 3 (the start of Treatment Period 2) and Visit 4 (the end-of-study visit). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The Baseline value is the last non-missing value prior to or on the start date of Treatment Period 1. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Safety Analysis Set. Only those participants with data available at Visit 3 and Visit 4 were assessed at that respective visit (indicated by n=X, X in the category titles). **Reporting Status:** POSTED **Time Frame:** Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks) **Title:** Change From Baseline in Creatinine at Visit 3 (up to Week 12) and Visit 4 (up to Week 24) **Type:** SECONDARY **Unit of Measure:** micromoles per Liter (µmol/L) ##### Group **Description:** In Treatment Period 1 (\<=12 weeks), participants received 20 milligrams (mg) sumatriptan nasal powder delivered intranasally with a bi-directional device and a placebo (PBO) tablet taken orally. After completing Treatment Period 1 (upon reaching 12 weeks or treating the fifth qualifying migraine headache in the treatment period, whichever came first), participants entered Treatment Period 2 (\<=12 weeks), during which they received a 100 mg sumatriptan tablet taken orally and placebo (lactose) as a nasal powder administered into the nostril on the side of the migraine, followed by another administration into the other nostril. Participants were to treat \<=5 qualifying migraine headaches during Treatment Period 2. **ID:** OG000 **Title:** 20 mg Sumatriptan+PBO (TP1)/100 mg Sumatriptan+PBO (TP2) ##### Group **Description:** In Treatment Period 1 (\<=12 weeks), participants received a 100 mg sumatriptan tablet taken orally and placebo (lactose) as a nasal powder administered into the nostril on the side of the migraine, followed by another administration into the other nostril. After completing Treatment Period 1 (upon reaching 12 weeks or treating the fifth qualifying migraine headache in the treatment period, whichever came first), participants entered Treatment Period 2 (\<=12 weeks), during which they received 20 mg sumatriptan nasal powder delivered intranasally with a bi-directional device and a placebo tablet taken orally. Participants were to treat \<=5 qualifying migraine headaches during Treatment Period 2. **ID:** OG001 **Title:** 100 mg Sumatriptan+PBO (TP1)/20 mg Sumatriptan+PBO (TP2) #### Outcome Measure 16 **Description:** Change from Baseline in ALP and ALT was assessed at Visit 3 (the start of Treatment Period 2) and Visit 4 (the end-of-study visit). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The Baseline value is the last non-missing value prior to or on the start date of Treatment Period 1. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Safety Analysis Set. Only those participants with data available at Visit 3 and Visit 4 were assessed at that respective visit (indicated by n=X, X in the category titles). **Reporting Status:** POSTED **Time Frame:** Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks) **Title:** Change From Baseline in Alkaline Phosphatase (ALP) and Alanine Aminotransferase (ALT) at Visit 3 (up to Week 12) and Visit 4 (up to Week 24) **Type:** SECONDARY **Unit of Measure:** International Units per Liter (IU/L) ##### Group **Description:** In Treatment Period 1 (\<=12 weeks), participants received 20 milligrams (mg) sumatriptan nasal powder delivered intranasally with a bi-directional device and a placebo (PBO) tablet taken orally. After completing Treatment Period 1 (upon reaching 12 weeks or treating the fifth qualifying migraine headache in the treatment period, whichever came first), participants entered Treatment Period 2 (\<=12 weeks), during which they received a 100 mg sumatriptan tablet taken orally and placebo (lactose) as a nasal powder administered into the nostril on the side of the migraine, followed by another administration into the other nostril. Participants were to treat \<=5 qualifying migraine headaches during Treatment Period 2. **ID:** OG000 **Title:** 20 mg Sumatriptan+PBO (TP1)/100 mg Sumatriptan+PBO (TP2) ##### Group **Description:** In Treatment Period 1 (\<=12 weeks), participants received a 100 mg sumatriptan tablet taken orally and placebo (lactose) as a nasal powder administered into the nostril on the side of the migraine, followed by another administration into the other nostril. After completing Treatment Period 1 (upon reaching 12 weeks or treating the fifth qualifying migraine headache in the treatment period, whichever came first), participants entered Treatment Period 2 (\<=12 weeks), during which they received 20 mg sumatriptan nasal powder delivered intranasally with a bi-directional device and a placebo tablet taken orally. Participants were to treat \<=5 qualifying migraine headaches during Treatment Period 2. **ID:** OG001 **Title:** 100 mg Sumatriptan+PBO (TP1)/20 mg Sumatriptan+PBO (TP2) #### Outcome Measure 17 **Description:** Change from Baseline in AST and GGT was assessed at Visit 3 (the start of Treatment Period 2) and Visit 4 (the end-of-study visit). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The Baseline value is the last non-missing value prior to or on the start date of Treatment Period 1. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Safety Analysis Set. Only those participants with data available at Visit 3 and Visit 4 were assessed at that respective visit (indicated by n=X, X in the category titles). **Reporting Status:** POSTED **Time Frame:** Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks) **Title:** Change From Baseline in Aspartate Aminotransferase (AST) and Gamma Glutamyl Transferase (GGT) at Visit 3 (up to Week 12) and Visit 4 (up to Week 24) **Type:** SECONDARY **Unit of Measure:** International Units per Liter (IU/L) ##### Group **Description:** In Treatment Period 1 (\<=12 weeks), participants received 20 milligrams (mg) sumatriptan nasal powder delivered intranasally with a bi-directional device and a placebo (PBO) tablet taken orally. After completing Treatment Period 1 (upon reaching 12 weeks or treating the fifth qualifying migraine headache in the treatment period, whichever came first), participants entered Treatment Period 2 (\<=12 weeks), during which they received a 100 mg sumatriptan tablet taken orally and placebo (lactose) as a nasal powder administered into the nostril on the side of the migraine, followed by another administration into the other nostril. Participants were to treat \<=5 qualifying migraine headaches during Treatment Period 2. **ID:** OG000 **Title:** 20 mg Sumatriptan+PBO (TP1)/100 mg Sumatriptan+PBO (TP2) ##### Group **Description:** In Treatment Period 1 (\<=12 weeks), participants received a 100 mg sumatriptan tablet taken orally and placebo (lactose) as a nasal powder administered into the nostril on the side of the migraine, followed by another administration into the other nostril. After completing Treatment Period 1 (upon reaching 12 weeks or treating the fifth qualifying migraine headache in the treatment period, whichever came first), participants entered Treatment Period 2 (\<=12 weeks), during which they received 20 mg sumatriptan nasal powder delivered intranasally with a bi-directional device and a placebo tablet taken orally. Participants were to treat \<=5 qualifying migraine headaches during Treatment Period 2. **ID:** OG001 **Title:** 100 mg Sumatriptan+PBO (TP1)/20 mg Sumatriptan+PBO (TP2) #### Outcome Measure 18 **Description:** Change from Baseline in total bilirubin was assessed at Visit 3 (the start of Treatment Period 2) and Visit 4 (the end-of-study visit). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The Baseline value is the last non-missing value prior to or on the start date of Treatment Period 1. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Safety Analysis Set. Only those participants with data available at Visit 3 and Visit 4 were assessed at that respective visit (indicated by n=X, X in the category titles). **Reporting Status:** POSTED **Time Frame:** Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks) **Title:** Change From Baseline in Total Bilirubin at Visit 3 (up to Week 12) and Visit 4 (up to Week 24) **Type:** SECONDARY **Unit of Measure:** Units per Liter (U/L) ##### Group **Description:** In Treatment Period 1 (\<=12 weeks), participants received 20 milligrams (mg) sumatriptan nasal powder delivered intranasally with a bi-directional device and a placebo (PBO) tablet taken orally. After completing Treatment Period 1 (upon reaching 12 weeks or treating the fifth qualifying migraine headache in the treatment period, whichever came first), participants entered Treatment Period 2 (\<=12 weeks), during which they received a 100 mg sumatriptan tablet taken orally and placebo (lactose) as a nasal powder administered into the nostril on the side of the migraine, followed by another administration into the other nostril. Participants were to treat \<=5 qualifying migraine headaches during Treatment Period 2. **ID:** OG000 **Title:** 20 mg Sumatriptan+PBO (TP1)/100 mg Sumatriptan+PBO (TP2) ##### Group **Description:** In Treatment Period 1 (\<=12 weeks), participants received a 100 mg sumatriptan tablet taken orally and placebo (lactose) as a nasal powder administered into the nostril on the side of the migraine, followed by another administration into the other nostril. After completing Treatment Period 1 (upon reaching 12 weeks or treating the fifth qualifying migraine headache in the treatment period, whichever came first), participants entered Treatment Period 2 (\<=12 weeks), during which they received 20 mg sumatriptan nasal powder delivered intranasally with a bi-directional device and a placebo tablet taken orally. Participants were to treat \<=5 qualifying migraine headaches during Treatment Period 2. **ID:** OG001 **Title:** 100 mg Sumatriptan+PBO (TP1)/20 mg Sumatriptan+PBO (TP2) #### Outcome Measure 19 **Description:** Change from Baseline in albumin and total protein was assessed at Visit 3 (the start of Treatment Period 2) and Visit 4 (the end-of-study visit). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The Baseline value is the last non-missing value prior to or on the start date of Treatment Period 1. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Safety Analysis Set. Only those participants with data available at Visit 3 and Visit 4 were assessed at that respective visit (indicated by n=X, X in the category titles). **Reporting Status:** POSTED **Time Frame:** Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks) **Title:** Change From Baseline in Albumin and Total Protein at Visit 3 (up to Week 12) and Visit 4 (up to Week 24) **Type:** SECONDARY **Unit of Measure:** grams per Liter (grams/L) ##### Group **Description:** In Treatment Period 1 (\<=12 weeks), participants received 20 milligrams (mg) sumatriptan nasal powder delivered intranasally with a bi-directional device and a placebo (PBO) tablet taken orally. After completing Treatment Period 1 (upon reaching 12 weeks or treating the fifth qualifying migraine headache in the treatment period, whichever came first), participants entered Treatment Period 2 (\<=12 weeks), during which they received a 100 mg sumatriptan tablet taken orally and placebo (lactose) as a nasal powder administered into the nostril on the side of the migraine, followed by another administration into the other nostril. Participants were to treat \<=5 qualifying migraine headaches during Treatment Period 2. **ID:** OG000 **Title:** 20 mg Sumatriptan+PBO (TP1)/100 mg Sumatriptan+PBO (TP2) ##### Group **Description:** In Treatment Period 1 (\<=12 weeks), participants received a 100 mg sumatriptan tablet taken orally and placebo (lactose) as a nasal powder administered into the nostril on the side of the migraine, followed by another administration into the other nostril. After completing Treatment Period 1 (upon reaching 12 weeks or treating the fifth qualifying migraine headache in the treatment period, whichever came first), participants entered Treatment Period 2 (\<=12 weeks), during which they received 20 mg sumatriptan nasal powder delivered intranasally with a bi-directional device and a placebo tablet taken orally. Participants were to treat \<=5 qualifying migraine headaches during Treatment Period 2. **ID:** OG001 **Title:** 100 mg Sumatriptan+PBO (TP1)/20 mg Sumatriptan+PBO (TP2) #### Outcome Measure 20 **Description:** Change from Baseline in sodium, potassium, chloride, calcium, and glucose was assessed at Visit 3 (the start of Treatment Period 2) and Visit 4 (the end-of-study visit). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The Baseline value is the last non-missing value prior to or on the start date of Treatment Period 1. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Safety Analysis Set. Only those participants with data available at Visit 3 and Visit 4 were assessed at that respective visit (indicated by n=X, X in the category titles). **Reporting Status:** POSTED **Time Frame:** Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks) **Title:** Change From Baseline in Sodium, Potassium, Chloride, Calcium, and Glucose at Visit 3 (up to Week 12) and Visit 4 (up to Week 24) **Type:** SECONDARY **Unit of Measure:** mmoles/L ##### Group **Description:** In Treatment Period 1 (\<=12 weeks), participants received 20 milligrams (mg) sumatriptan nasal powder delivered intranasally with a bi-directional device and a placebo (PBO) tablet taken orally. After completing Treatment Period 1 (upon reaching 12 weeks or treating the fifth qualifying migraine headache in the treatment period, whichever came first), participants entered Treatment Period 2 (\<=12 weeks), during which they received a 100 mg sumatriptan tablet taken orally and placebo (lactose) as a nasal powder administered into the nostril on the side of the migraine, followed by another administration into the other nostril. Participants were to treat \<=5 qualifying migraine headaches during Treatment Period 2. **ID:** OG000 **Title:** 20 mg Sumatriptan+PBO (TP1)/100 mg Sumatriptan+PBO (TP2) ##### Group **Description:** In Treatment Period 1 (\<=12 weeks), participants received a 100 mg sumatriptan tablet taken orally and placebo (lactose) as a nasal powder administered into the nostril on the side of the migraine, followed by another administration into the other nostril. After completing Treatment Period 1 (upon reaching 12 weeks or treating the fifth qualifying migraine headache in the treatment period, whichever came first), participants entered Treatment Period 2 (\<=12 weeks), during which they received 20 mg sumatriptan nasal powder delivered intranasally with a bi-directional device and a placebo tablet taken orally. Participants were to treat \<=5 qualifying migraine headaches during Treatment Period 2. **ID:** OG001 **Title:** 100 mg Sumatriptan+PBO (TP1)/20 mg Sumatriptan+PBO (TP2) #### Outcome Measure 21 **Description:** Change from Baseline in urinalysis values was assessed at Visit 3 (the start of Treatment Period 2) and Visit 4 (the end-of-study visit). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The Baseline value is the last non-missing value prior to or on the start date of Treatment Period 1. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Safety Analysis Set. Only those participants with data available at Visit 3 and Visit 4 were assessed at that respective visit (indicated by n=X, X in the category titles). **Reporting Status:** POSTED **Time Frame:** Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks) **Title:** Change From Baseline in Urinalysis Values by Dipstick Method at Visit 3 (up to Week 12) and Visit 4 (up to Week 24) **Type:** SECONDARY **Unit of Measure:** pH ##### Group **Description:** In Treatment Period 1 (\<=12 weeks), participants received 20 milligrams (mg) sumatriptan nasal powder delivered intranasally with a bi-directional device and a placebo (PBO) tablet taken orally. After completing Treatment Period 1 (upon reaching 12 weeks or treating the fifth qualifying migraine headache in the treatment period, whichever came first), participants entered Treatment Period 2 (\<=12 weeks), during which they received a 100 mg sumatriptan tablet taken orally and placebo (lactose) as a nasal powder administered into the nostril on the side of the migraine, followed by another administration into the other nostril. Participants were to treat \<=5 qualifying migraine headaches during Treatment Period 2. **ID:** OG000 **Title:** 20 mg Sumatriptan+PBO (TP1)/100 mg Sumatriptan+PBO (TP2) ##### Group **Description:** In Treatment Period 1 (\<=12 weeks), participants received a 100 mg sumatriptan tablet taken orally and placebo (lactose) as a nasal powder administered into the nostril on the side of the migraine, followed by another administration into the other nostril. After completing Treatment Period 1 (upon reaching 12 weeks or treating the fifth qualifying migraine headache in the treatment period, whichever came first), participants entered Treatment Period 2 (\<=12 weeks), during which they received 20 mg sumatriptan nasal powder delivered intranasally with a bi-directional device and a placebo tablet taken orally. Participants were to treat \<=5 qualifying migraine headaches during Treatment Period 2. **ID:** OG001 **Title:** 100 mg Sumatriptan+PBO (TP1)/20 mg Sumatriptan+PBO (TP2) #### Outcome Measure 22 **Description:** The Baseline value is the last non-missing value prior to or on the start date of Treatment Period 1. Data are based on standard reads, with "1+," "2+," and "3+" indicating increasing amounts of metabolites in urine. **Parameter Type:** NUMBER **Population Description:** Safety Analysis Set **Reporting Status:** POSTED **Time Frame:** Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks) **Title:** Number of Participants With the Indicated Amounts of Protein, Glucose, Ketones, Blood, and White Blood Cells (WBCs) in Urine at Baseline, Visit 3 (up to Week 12), and Visit 4 (up to Week 24) **Type:** SECONDARY **Unit of Measure:** participants ##### Group **Description:** In Treatment Period 1 (\<=12 weeks), participants received 20 milligrams (mg) sumatriptan nasal powder delivered intranasally with a bi-directional device and a placebo (PBO) tablet taken orally. After completing Treatment Period 1 (upon reaching 12 weeks or treating the fifth qualifying migraine headache in the treatment period, whichever came first), participants entered Treatment Period 2 (\<=12 weeks), during which they received a 100 mg sumatriptan tablet taken orally and placebo (lactose) as a nasal powder administered into the nostril on the side of the migraine, followed by another administration into the other nostril. Participants were to treat \<=5 qualifying migraine headaches during Treatment Period 2. **ID:** OG000 **Title:** 20 mg Sumatriptan+PBO (TP1)/100 mg Sumatriptan+PBO (TP2) ##### Group **Description:** In Treatment Period 1 (\<=12 weeks), participants received a 100 mg sumatriptan tablet taken orally and placebo (lactose) as a nasal powder administered into the nostril on the side of the migraine, followed by another administration into the other nostril. After completing Treatment Period 1 (upon reaching 12 weeks or treating the fifth qualifying migraine headache in the treatment period, whichever came first), participants entered Treatment Period 2 (\<=12 weeks), during which they received 20 mg sumatriptan nasal powder delivered intranasally with a bi-directional device and a placebo tablet taken orally. Participants were to treat \<=5 qualifying migraine headaches during Treatment Period 2. **ID:** OG001 **Title:** 100 mg Sumatriptan+PBO (TP1)/20 mg Sumatriptan+PBO (TP2) #### Outcome Measure 23 **Description:** Change from Baseline in SBP and DBP was assessed at Visit 3 (the start of Treatment Period 2) and Visit 4 (the end-of-study visit). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The Baseline value is the last non-missing value prior to or on the start date of Treatment Period 1. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Safety Analysis Set. Only those participants with data available at Visit 3 and Visit 4 were assessed at that respective visit (indicated by n=X, X in the category titles). **Reporting Status:** POSTED **Time Frame:** Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks) **Title:** Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Visit 3 (up to Week 12) and Visit 4 (up to Week 24) **Type:** SECONDARY **Unit of Measure:** millimeters of mercury (mmHg) ##### Group **Description:** In Treatment Period 1 (\<=12 weeks), participants received 20 milligrams (mg) sumatriptan nasal powder delivered intranasally with a bi-directional device and a placebo (PBO) tablet taken orally. After completing Treatment Period 1 (upon reaching 12 weeks or treating the fifth qualifying migraine headache in the treatment period, whichever came first), participants entered Treatment Period 2 (\<=12 weeks), during which they received a 100 mg sumatriptan tablet taken orally and placebo (lactose) as a nasal powder administered into the nostril on the side of the migraine, followed by another administration into the other nostril. Participants were to treat \<=5 qualifying migraine headaches during Treatment Period 2. **ID:** OG000 **Title:** 20 mg Sumatriptan+PBO (TP1)/100 mg Sumatriptan+PBO (TP2) ##### Group **Description:** In Treatment Period 1 (\<=12 weeks), participants received a 100 mg sumatriptan tablet taken orally and placebo (lactose) as a nasal powder administered into the nostril on the side of the migraine, followed by another administration into the other nostril. After completing Treatment Period 1 (upon reaching 12 weeks or treating the fifth qualifying migraine headache in the treatment period, whichever came first), participants entered Treatment Period 2 (\<=12 weeks), during which they received 20 mg sumatriptan nasal powder delivered intranasally with a bi-directional device and a placebo tablet taken orally. Participants were to treat \<=5 qualifying migraine headaches during Treatment Period 2. **ID:** OG001 **Title:** 100 mg Sumatriptan+PBO (TP1)/20 mg Sumatriptan+PBO (TP2) #### Outcome Measure 24 **Description:** Change from Baseline in pulse was assessed at Visit 3 (the start of Treatment Period 2) and Visit 4 (the end-of-study visit). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The Baseline value is the last non-missing value prior to or on the start date of Treatment Period 1. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Safety Analysis Set. Only those participants with data available at Visit 3 and Visit 4 were assessed at that respective visit (indicated by n=X, X in the category titles). **Reporting Status:** POSTED **Time Frame:** Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks) **Title:** Change From Baseline in Pulse at Visit 3 (up to Week 12) and Visit 4 (up to Week 24) **Type:** SECONDARY **Unit of Measure:** beats per minute ##### Group **Description:** In Treatment Period 1 (\<=12 weeks), participants received 20 milligrams (mg) sumatriptan nasal powder delivered intranasally with a bi-directional device and a placebo (PBO) tablet taken orally. After completing Treatment Period 1 (upon reaching 12 weeks or treating the fifth qualifying migraine headache in the treatment period, whichever came first), participants entered Treatment Period 2 (\<=12 weeks), during which they received a 100 mg sumatriptan tablet taken orally and placebo (lactose) as a nasal powder administered into the nostril on the side of the migraine, followed by another administration into the other nostril. Participants were to treat \<=5 qualifying migraine headaches during Treatment Period 2. **ID:** OG000 **Title:** 20 mg Sumatriptan+PBO (TP1)/100 mg Sumatriptan+PBO (TP2) ##### Group **Description:** In Treatment Period 1 (\<=12 weeks), participants received a 100 mg sumatriptan tablet taken orally and placebo (lactose) as a nasal powder administered into the nostril on the side of the migraine, followed by another administration into the other nostril. After completing Treatment Period 1 (upon reaching 12 weeks or treating the fifth qualifying migraine headache in the treatment period, whichever came first), participants entered Treatment Period 2 (\<=12 weeks), during which they received 20 mg sumatriptan nasal powder delivered intranasally with a bi-directional device and a placebo tablet taken orally. Participants were to treat \<=5 qualifying migraine headaches during Treatment Period 2. **ID:** OG001 **Title:** 100 mg Sumatriptan+PBO (TP1)/20 mg Sumatriptan+PBO (TP2) #### Outcome Measure 25 **Description:** The Baseline value is the last non-missing value prior to or on the start date of Treatment Period 1. Clinical significance was determined by the Investigator (per clinical judgement). A categorization of "normal" or "abnormal" was made per the investigators' clinical judgment of the ECG, taking the participants' demographic characteristics and other medical conditions into account. CS = clinically significant. CNS = clinically not significant. **Parameter Type:** NUMBER **Population Description:** Safety Analysis Set **Reporting Status:** POSTED **Time Frame:** Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks) **Title:** Number of Participants With the Indicated 12-lead Electrocardiogram (ECG) Findings at Baseline, Visit 3 (up to Week 12), and Visit 4 (up to Week 24) **Type:** SECONDARY **Unit of Measure:** participants ##### Group **Description:** In Treatment Period 1 (\<=12 weeks), participants received 20 milligrams (mg) sumatriptan nasal powder delivered intranasally with a bi-directional device and a placebo (PBO) tablet taken orally. After completing Treatment Period 1 (upon reaching 12 weeks or treating the fifth qualifying migraine headache in the treatment period, whichever came first), participants entered Treatment Period 2 (\<=12 weeks), during which they received a 100 mg sumatriptan tablet taken orally and placebo (lactose) as a nasal powder administered into the nostril on the side of the migraine, followed by another administration into the other nostril. Participants were to treat \<=5 qualifying migraine headaches during Treatment Period 2. **ID:** OG000 **Title:** 20 mg Sumatriptan+PBO (TP1)/100 mg Sumatriptan+PBO (TP2) ##### Group **Description:** In Treatment Period 1 (\<=12 weeks), participants received a 100 mg sumatriptan tablet taken orally and placebo (lactose) as a nasal powder administered into the nostril on the side of the migraine, followed by another administration into the other nostril. After completing Treatment Period 1 (upon reaching 12 weeks or treating the fifth qualifying migraine headache in the treatment period, whichever came first), participants entered Treatment Period 2 (\<=12 weeks), during which they received 20 mg sumatriptan nasal powder delivered intranasally with a bi-directional device and a placebo tablet taken orally. Participants were to treat \<=5 qualifying migraine headaches during Treatment Period 2. **ID:** OG001 **Title:** 100 mg Sumatriptan+PBO (TP1)/20 mg Sumatriptan+PBO (TP2) #### Outcome Measure 26 **Description:** The Baseline value is the last non-missing value prior to or on the start date of Treatment Period 1. Clinical significance was determined by the Investigator (per clinical judgement). CS = clinically significant. CNS = clinically not significant. **Parameter Type:** NUMBER **Population Description:** Safety Analysis Set **Reporting Status:** POSTED **Time Frame:** Baseline and Visits 3 (up to 12 weeks) and 4 (up to 24 weeks) **Title:** Number of Participants With the Indicated Physical Examination Abnormalities at Baseline, Visit 3 (up to Week 12), and Visit 4 (up to Week 24) **Type:** SECONDARY **Unit of Measure:** participants ##### Group **Description:** In Treatment Period 1 (\<=12 weeks), participants received 20 milligrams (mg) sumatriptan nasal powder delivered intranasally with a bi-directional device and a placebo (PBO) tablet taken orally. After completing Treatment Period 1 (upon reaching 12 weeks or treating the fifth qualifying migraine headache in the treatment period, whichever came first), participants entered Treatment Period 2 (\<=12 weeks), during which they received a 100 mg sumatriptan tablet taken orally and placebo (lactose) as a nasal powder administered into the nostril on the side of the migraine, followed by another administration into the other nostril. Participants were to treat \<=5 qualifying migraine headaches during Treatment Period 2. **ID:** OG000 **Title:** 20 mg Sumatriptan+PBO (TP1)/100 mg Sumatriptan+PBO (TP2) ##### Group **Description:** In Treatment Period 1 (\<=12 weeks), participants received a 100 mg sumatriptan tablet taken orally and placebo (lactose) as a nasal powder administered into the nostril on the side of the migraine, followed by another administration into the other nostril. After completing Treatment Period 1 (upon reaching 12 weeks or treating the fifth qualifying migraine headache in the treatment period, whichever came first), participants entered Treatment Period 2 (\<=12 weeks), during which they received 20 mg sumatriptan nasal powder delivered intranasally with a bi-directional device and a placebo tablet taken orally. Participants were to treat \<=5 qualifying migraine headaches during Treatment Period 2. **ID:** OG001 **Title:** 100 mg Sumatriptan+PBO (TP1)/20 mg Sumatriptan+PBO (TP2) #### Outcome Measure 27 **Description:** Concomitant medications are defined as non-study medications with a start or stop date between the first dose of study medication and the end of safety follow-up, inclusive. Derm. = dermatologic; incl. - including. **Parameter Type:** NUMBER **Population Description:** Safety Analysis Set **Reporting Status:** POSTED **Time Frame:** up to 24 weeks **Title:** Number of Participants With the Indicated Concomitant Medications **Type:** SECONDARY **Unit of Measure:** participants ##### Group **Description:** In Treatment Period 1 (\<=12 weeks), participants received 20 milligrams (mg) sumatriptan nasal powder delivered intranasally with a bi-directional device and a placebo (PBO) tablet taken orally. After completing Treatment Period 1 (upon reaching 12 weeks or treating the fifth qualifying migraine headache in the treatment period, whichever came first), participants entered Treatment Period 2 (\<=12 weeks), during which they received a 100 mg sumatriptan tablet taken orally and placebo (lactose) as a nasal powder administered into the nostril on the side of the migraine, followed by another administration into the other nostril. Participants were to treat \<=5 qualifying migraine headaches during Treatment Period 2. **ID:** OG000 **Title:** 20 mg Sumatriptan+PBO (TP1)/100 mg Sumatriptan+PBO (TP2) ##### Group **Description:** In Treatment Period 1 (\<=12 weeks), participants received a 100 mg sumatriptan tablet taken orally and placebo (lactose) as a nasal powder administered into the nostril on the side of the migraine, followed by another administration into the other nostril. After completing Treatment Period 1 (upon reaching 12 weeks or treating the fifth qualifying migraine headache in the treatment period, whichever came first), participants entered Treatment Period 2 (\<=12 weeks), during which they received 20 mg sumatriptan nasal powder delivered intranasally with a bi-directional device and a placebo tablet taken orally. Participants were to treat \<=5 qualifying migraine headaches during Treatment Period 2. **ID:** OG001 **Title:** 100 mg Sumatriptan+PBO (TP1)/20 mg Sumatriptan+PBO (TP2) ### Participant Flow Module #### Group **Description:** In Treatment Period (TP) 1 (\<=12 weeks), participants received 20 milligrams (mg) sumatriptan nasal powder delivered intranasally with a bi-directional device and a placebo (PBO) tablet taken orally. After completing Treatment Period 1 (upon reaching 12 weeks or treating the fifth qualifying migraine headache in the treatment period, whichever came first), participants entered Treatment Period 2 (\<=12 weeks), during which they received a 100 mg sumatriptan tablet taken orally and placebo (lactose) as a nasal powder administered into the nostril on the side of the migraine, followed by another administration into the other nostril. Participants were to treat \<=5 qualifying migraine headaches during Treatment Period 2. **ID:** FG000 **Title:** 20 mg Sumatriptan+PBO (TP1)/100 mg Sumatriptan+PBO (TP2) #### Group **Description:** In Treatment Period 1 (\<=12 weeks), participants received a 100 mg sumatriptan tablet taken orally and placebo (lactose) as a nasal powder administered into the nostril on the side of the migraine, followed by another administration into the other nostril. After completing Treatment Period 1 (upon reaching 12 weeks or treating the fifth qualifying migraine headache in the treatment period, whichever came first), participants entered Treatment Period 2 (\<=12 weeks), during which they received 20 mg sumatriptan nasal powder delivered intranasally with a bi-directional device and a placebo tablet taken orally. Participants were to treat \<=5 qualifying migraine headaches during Treatment Period 2. **ID:** FG001 **Title:** 100 mg Sumatriptan+PBO (TP1)/20 mg Sumatriptan+PBO (TP2) #### Period **Title:** Treatment Period 1 (<=12 Weeks) ##### Withdraw **Type:** Failure to Treat Migraine Headache ###### Reason **Group ID:** FG000 **Number of Subjects:** 2 ###### Reason **Group ID:** FG001 **Number of Subjects:** 6 ##### Withdraw **Type:** Dosed Incorrectly ###### Reason **Group ID:** FG000 **Number of Subjects:** 2 ###### Reason **Group ID:** FG001 **Number of Subjects:** 0 ##### Withdraw **Type:** Lack of Efficacy ###### Reason **Group ID:** FG000 **Number of Subjects:** 2 ###### Reason **Group ID:** FG001 **Number of Subjects:** 0 ##### Withdraw **Type:** Could Not Tolerate Diary ###### Reason **Group ID:** FG000 **Number of Subjects:** 1 ###### Reason **Group ID:** FG001 **Number of Subjects:** 0 ##### Withdraw **Type:** Withdrawal by Subject ###### Reason **Group ID:** FG000 **Number of Subjects:** 6 ###### Reason **Group ID:** FG001 **Number of Subjects:** 13 ##### Withdraw **Type:** Adverse Event ###### Reason **Group ID:** FG000 **Number of Subjects:** 3 ###### Reason **Group ID:** FG001 **Number of Subjects:** 3 ##### Withdraw **Type:** Lost to Follow-up ###### Reason **Group ID:** FG000 **Number of Subjects:** 0 ###### Reason **Group ID:** FG001 **Number of Subjects:** 2 ##### Withdraw **Type:** Protocol Violation ###### Reason **Group ID:** FG000 **Number of Subjects:** 0 ###### Reason **Group ID:** FG001 **Number of Subjects:** 2 ##### Withdraw **Type:** Non-compliance ###### Reason **Group ID:** FG000 **Number of Subjects:** 0 ###### Reason **Group ID:** FG001 **Number of Subjects:** 3 ##### Withdraw **Type:** Moved Out of State ###### Reason **Group ID:** FG000 **Number of Subjects:** 0 ###### Reason **Group ID:** FG001 **Number of Subjects:** 1 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 138 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 137 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 122 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 107 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 16 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 30 #### Period **Title:** Treatment Period 2 (<=12 Weeks) ##### Withdraw **Type:** Withdrawal by Subject ###### Reason **Group ID:** FG000 **Number of Subjects:** 6 ###### Reason **Group ID:** FG001 **Number of Subjects:** 4 ##### Withdraw **Type:** Non-compliance with Electronic Diary ###### Reason **Group ID:** FG000 **Number of Subjects:** 2 ###### Reason **Group ID:** FG001 **Number of Subjects:** 0 ##### Withdraw **Type:** Lost to Follow-up ###### Reason **Group ID:** FG000 **Number of Subjects:** 8 ###### Reason **Group ID:** FG001 **Number of Subjects:** 10 ##### Withdraw **Type:** Non-compliance ###### Reason **Group ID:** FG000 **Number of Subjects:** 3 ###### Reason **Group ID:** FG001 **Number of Subjects:** 4 ##### Withdraw **Type:** Sponsor Decision ###### Reason **Group ID:** FG000 **Number of Subjects:** 1 ###### Reason **Group ID:** FG001 **Number of Subjects:** 0 ##### Withdraw **Type:** Failure to Treat Migraine Headache ###### Reason **Group ID:** FG000 **Number of Subjects:** 1 ###### Reason **Group ID:** FG001 **Number of Subjects:** 0 ##### Withdraw **Type:** Adverse Event ###### Reason **Group ID:** FG000 **Number of Subjects:** 1 ###### Reason **Group ID:** FG001 **Number of Subjects:** 0 ##### Withdraw **Type:** Significant Improvement in Migraine ###### Reason **Group ID:** FG000 **Number of Subjects:** 0 ###### Reason **Group ID:** FG001 **Number of Subjects:** 1 ##### Withdraw **Type:** Partially Dosed ###### Reason **Group ID:** FG000 **Number of Subjects:** 0 ###### Reason **Group ID:** FG001 **Number of Subjects:** 1 ##### Withdraw **Type:** Brought in before 12 Weeks/5 Migraines ###### Reason **Group ID:** FG000 **Number of Subjects:** 0 ###### Reason **Group ID:** FG001 **Number of Subjects:** 1 ##### Withdraw **Type:** Refused Last Day of Visit 4 Procedures ###### Reason **Group ID:** FG000 **Number of Subjects:** 0 ###### Reason **Group ID:** FG001 **Number of Subjects:** 1 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 122 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 107 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 100 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 85 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 22 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 22 **Pre-Assignment Details:** A total of 334 participants were assessed for eligibility; of these, 275 participants were randomized. **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT00968279 **Brief Title:** Coronary CT Angiography Using 320-Row Volume CT in Patients With Atrial Fibrillation **Official Title:** Coronary CT Angiography Using 320-Row Volume CT in Patients With Atrial Fibrillation #### Organization Study ID Info **ID:** EA1/134/08 #### Organization **Class:** OTHER **Full Name:** Charite University, Berlin, Germany ### Status Module #### Completion Date **Date:** 2012-09 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2013-05-03 **Type:** ESTIMATED **Last Update Submit Date:** 2013-05-02 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2012-09 **Type:** ACTUAL #### Start Date **Date:** 2009-08 **Status Verified Date:** 2013-04 #### Study First Post Date **Date:** 2009-08-28 **Type:** ESTIMATED **Study First Submit Date:** 2009-08-27 **Study First Submit QC Date:** 2009-08-27 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Charite University, Berlin, Germany #### Responsible Party **Old Name Title:** Marc Dewey **Old Organization:** Charité ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** The primary objective of this study is to analyze the diagnostic accuracy of coronary CT angiography using 320 simultaneous detector results in patients with atrial fibrillation. ### Conditions Module **Conditions:** - Atrial Fibrillation **Keywords:** - Patients with atrial fibrillation ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 54 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Label:** Atrial Fibrillation ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Suspected coronary artery disease based on clinical findings or findings on other noninvasive imaging tests and planned coronary angiography within the next 14 days. * Able to understand and willing to sign the Informed CF. Exclusion Criteria: * Creatinine of above 2.0 mg/dl * Age below 50 years * Women of child bearing potential (no hysterectomy, no menopause, or menopause since less than 12 months) must demonstrate a negative pregnancy test performed within 24 hours before CT. * Inability to hold the breath for 10 seconds **Minimum Age:** 50 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Patients with atrial fibrillation scheduled to undergo coronary angiography due to suspected coronary artery disease. ### Contacts Locations Module #### Locations **Location 1:** **City:** Berlin **Country:** Germany **Facility:** Charité **Zip:** 10117 #### Overall Officials **Official 1:** **Affiliation:** Charité **Name:** Marc Dewey, MD, PhD **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### References **Citation:** Zimmermann E, Dewey M. Whole-heart 320-row computed tomography: reduction of radiation dose via prior coronary calcium scanning. Rofo. 2011 Jan;183(1):54-9. doi: 10.1055/s-0029-1245629. Epub 2010 Aug 19. **PMID:** 20725881 **Citation:** Dewey M, Zimmermann E, Deissenrieder F, Laule M, Dubel HP, Schlattmann P, Knebel F, Rutsch W, Hamm B. Noninvasive coronary angiography by 320-row computed tomography with lower radiation exposure and maintained diagnostic accuracy: comparison of results with cardiac catheterization in a head-to-head pilot investigation. Circulation. 2009 Sep 8;120(10):867-75. doi: 10.1161/CIRCULATIONAHA.109.859280. Epub 2009 Aug 24. **PMID:** 19704093 **Citation:** Dewey M, Oncel D, Oncel G, Tastan A. Coronary CT angiography in patients with atrial fibrillation. Radiology. 2008 Aug;248(2):701; author reply 701-2. doi: 10.1148/radiol.2482080062. No abstract available. **PMID:** 18641260 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000001145 - Term: Arrhythmias, Cardiac - ID: D000006331 - Term: Heart Diseases - ID: D000002318 - Term: Cardiovascular Diseases - ID: D000010335 - Term: Pathologic Processes ### Condition Browse Module - Browse Branches - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M4586 - Name: Atrial Fibrillation - Relevance: HIGH - As Found: Atrial Fibrillation - ID: M4453 - Name: Arrhythmias, Cardiac - Relevance: LOW - As Found: Unknown - ID: M9419 - Name: Heart Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000001281 - Term: Atrial Fibrillation ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT02684279 **Brief Title:** Dasotraline Binge Eating Disorder Extension Study **Official Title:** An Open-label, Flexibly-dosed, Multicenter, Extension Study of Dasotraline to Evaluate Long-term Safety and Tolerability in Adults With Binge-eating Disorder #### Organization Study ID Info **ID:** SEP360-322 #### Organization **Class:** INDUSTRY **Full Name:** Sumitomo Pharma America, Inc. ### Status Module #### Completion Date **Date:** 2019-06-24 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2020-08-12 **Type:** ACTUAL **Last Update Submit Date:** 2020-07-28 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2019-06-24 **Type:** ACTUAL #### Results First Post Date **Date:** 2020-08-12 **Type:** ACTUAL **Results First Submit Date:** 2020-06-17 **Results First Submit QC Date:** 2020-07-28 #### Start Date **Date:** 2016-02-29 **Type:** ACTUAL **Status Verified Date:** 2020-07 #### Study First Post Date **Date:** 2016-02-17 **Type:** ESTIMATED **Study First Submit Date:** 2016-01-28 **Study First Submit QC Date:** 2016-02-11 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Sumitomo Pharma America, Inc. #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** Binge Eating Disorder Extension Study. **Detailed Description:** This is a Phase 3, 12 month, multicenter, open-label, flexibly-dosed, safety study in adults with Binge Eating Disorder. ### Conditions Module **Conditions:** - Binge Eating Disorder ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Masking Description:** open-label **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 533 **Type:** ACTUAL **Phases:** - PHASE3 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** 4, 6, 8 mg flexibly dosed **Intervention Names:** - Drug: Dasotraline **Label:** Dasotraline **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Dasotraline **Description:** Dasotraline 4, 6, 8 mg flexibly dosed once daily **Name:** Dasotraline **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Columbia-suicide severity rating scale (C-SSRS) Severity of suicidal ideation is rated on a 6-point scale from 0='No ideation present' to 5='Active ideation with plan and intent'. A score of 4 or 5 on this scale indicates serious suicidal ideation. Suicidal behavior is collected as presence/absence of actual attempts, non-suicidal self-injurious behavior, interrupted attempts, aborted attempts, preparatory acts or behavior, and any suicidal behavior **Measure:** Frequency and Severity of Suicidal Ideation Using the Columbia-suicide Severity Rating Scale (C-SSRS) **Time Frame:** Baseline to Week 52 **Description:** Columbia-suicide severity rating scale (C-SSRS) Severity of suicidal ideation is rated on a 6-point scale from 0='No ideation present' to 5='Active ideation with plan and intent'. A score of 4 or 5 on this scale indicates serious suicidal ideation. Suicidal behavior is collected as presence/absence of actual attempts, non-suicidal self-injurious behavior, interrupted attempts, aborted attempts, preparatory acts or behavior, and any suicidal behavior **Measure:** Frequency and Severity of Suicidal Behavior Using the C-SSRS **Time Frame:** Baseline to Week 52 #### Secondary Outcomes **Description:** Change in body weight **Measure:** Change in Body Weight **Time Frame:** Baseline, Week 52 **Description:** Percent change in body weight (kg) **Measure:** Percent Change in Body Weight (kg) **Time Frame:** Baseline, Week 52 **Description:** Change in Body Mass Index **Measure:** Change in Body Mass Index **Time Frame:** Baseline, Week 52 **Description:** Percent change in Body Mass Index (kg/m\^2) **Measure:** Percent Change in Body Mass Index (kg/m^2) **Time Frame:** Baseline, Week 52 **Description:** Change in fasting lipid panel, Triglyceride's **Measure:** Change in Fasting Lipid Panel, Triglyceride's **Time Frame:** Baseline, Week 52 **Description:** Change in fasting lipid panel , total cholesterol **Measure:** Change in Fasting Lipid Panel , Total Cholesterol **Time Frame:** Baseline, Week 52 **Description:** Change in fasting lipid panel, high-density lipoprotein \[HDL\] cholesterol, **Measure:** Change in Fasting Lipid Panel , High-density Lipoprotein [HDL] Cholesterol, **Time Frame:** Baseline, Week 52 **Description:** Change in fasting lipid panel, low-density lipoprotein \[LDL\] cholesterol) **Measure:** Change in Fasting Lipid Panel, Low-density Lipoprotein [LDL] Cholesterol) **Time Frame:** Baseline, Week 52 **Description:** Change in hemoglobin A1c levels **Measure:** Change in Hemoglobin A1c Levels **Time Frame:** Baseline, Week 52 **Description:** Change in fasting glucose levels **Measure:** Change in Fasting Glucose Levels **Time Frame:** Baseline, Week 52 **Description:** Eating Disorder Examination Questionnaire (EDE-Q) Modified global and subscale scores 4 subscale scores (Restraint, Eating Concern, Shape Concern, and Weight Concern) range from 0- 6, where 0 represents absence of the feature and 6 represents an extreme degree. An EDE-Q global score is calculated as average of 4 EDE-Q subscale scores. **Measure:** Change in Eating Disorder Examination Questionnaire (EDE Q) Modified Global Score and Subscale Scores (Restraint, Shape, Concern, Weight Concern), and Items 4-6 Scores **Time Frame:** Baseline, Week 52 **Description:** Eating Disorder Examination Questionnaire (EDE-Q) Modified global and subscale scores 4 subscale scores (Restraint, Eating Concern, Shape Concern, and Weight Concern) range from 0- 6, where 0 represents absence of the feature and 6 represents an extreme degree. An EDE-Q global score is calculated as average of 4 EDE-Q subscale scores. Item 4: Over the past 28 days, how many times have you eaten what other people would regard as an unusually large amount of food (given the circumstances)? Item 5: On how many of these times did you have a sense of having lost control over your eating (at the time that you were eating)? **Measure:** Change in Eating Disorder Examination Questionnaire (EDE Q) Modified Global Score and Subscale Scores (Restraint, Shape, Concern, Weight Concern), and Items 4-6 Scores **Time Frame:** Baseline, Week 52 **Description:** Eating Disorder Examination Questionnaire (EDE-Q) Modified global and subscale scores 4 subscale scores (Restraint, Eating Concern, Shape Concern, and Weight Concern) range from 0- 6, where 0 represents absence of the feature and 6 represents an extreme degree. An EDE-Q global score is calculated as average of 4 EDE-Q subscale scores. Item 6: Over the past 28 days, on how many DAYS have such episodes of overeating occurred (i.e., you have eaten an unusually large amount of food and have had a sense of loss of control at the time)? **Measure:** Change in Eating Disorder Examination Questionnaire (EDE Q) Modified Global Score and Subscale Scores (Restraint, Shape, Concern, Weight Concern), and Items 4-6 Scores **Time Frame:** Baseline, Week 52 **Description:** Binge-eating Clinical Global Impression-Severity (BE-CGI-S) The BE-CGI-S is a single value, clinician-rated assessment of illness severity, and 7-point scale with range from 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; 7 = among the most extremely ill subjects. A higher score is associated with greater illness severity. **Measure:** Change in Binge Eating Clinical Global Impression-Severity (BE-CGI S) Score **Time Frame:** Baseline, Week 52 **Description:** The Sheehan Disability Scale (SDS) 3 subscales (work/school, social life, home life) are rated on the following scale: 0 = not at all; 1-3 = mildly; 4-6 = moderately; 7-9 =markedly; 10 = extremely. The 3 items can be combined into a single global measure of impairment (SDS total score) that ranges from 0 (unimpaired) to 30 (highly impaired). A higher subscale score and total score are associated with greater illness severity. **Measure:** Change in Sheehan Disability Scale (SDS) Total Score and Subscale Scores (School/Work Disability, Social Life Disability, and Family Life Disability) **Time Frame:** Baseline, Week 52 **Description:** Hamilton Anxiety Rating Scale (HAM-A) total score HAM-A total score ranges from 0 to 56. A higher score is associated with a greater degree of anxiety. **Measure:** Change From Baseline in Hamilton Anxiety Rating Scale (HAM-A) Total Score **Time Frame:** Baseline, Week 52 **Description:** Montgomery-Asberg Depression Rating Scale (MADRS) total score The MADRS total score ranges from 0 to 60, with higher scores indicating increased depressive symptoms **Measure:** Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score **Time Frame:** Baseline, Week 52 **Description:** Change in SF-12 two component scores (physical, mental health) for Subjects Continued from Study SEP360-221 The SF-12 is a 12-item self-report questionnaire. Physical Component Summary (PCS) and Mental Component Summary (MCS) are computed using the scores of twelve questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health. **Measure:** Change in SF-12 Two Component Scores (Physical, Mental Health) **Time Frame:** Baseline, Week 52 ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Completion of the treatment period of a dasotraline core study (ie, SEP360 221 or SEP360-321) for the treatment of BED. * Subject has agreed to participate by providing written informed consent and is willing and able to comply with the protocol, in the opinion of the investigator. * Subject has not taken any medication other than the study drug for the purpose of controlling BED symptoms during the core study. * Female subject must have a negative urine pregnancy test at open label (OL) Baseline; females who are post-menopausal (defined as at least 12 months of spontaneous amenorrhea) and those who have undergone hysterectomy or bilateral oophorectomy will be exempted from the pregnancy test. * Female subject of childbearing potential and male subject with female partner of childbearing potential must agree to use an effective and medically acceptable form of birth control (see Section 22, Appendix III) throughout the study period. Note: Continued use of an effective and medically acceptable form of birth control is recommended for 30 days after study completion. * Subject is judged by the investigator to be suitable for participation in a 12 month clinical trial involving open-label dasotraline treatment. * Subject can read well enough to understand the informed consent form and other subject materials. Exclusion Criteria: * Subject is considered by the investigator to be at imminent risk of suicide, injury to self or to others, or damage to property. * Subject is considered a suicide risk in the investigator's opinion or has any previous history of suicide attempt within the past 12 months. * Subject answers "yes" to "suicidal ideation" item 4 (active suicidal ideation with some intent to act, without specific plan) or item 5 (active suicidal ideation with specific plan and intent) on the C SSRS assessment at OL Baseline. Subjects who answer "yes" to this question must be referred to the Investigator for follow up evaluation. * Subject has a clinically significant abnormality including physical examination, vital signs, ECG, or laboratory tests that the investigator in consultation with the medical monitor considers to be inappropriate to allow participation in the study. * Subject has a positive urine drug screen (UDS) or breath alcohol test at OL Baseline. * Subject is breastfeeding. * Subject is at high risk of non-compliance in the investigator's opinion. **Maximum Age:** 56 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Phoenix **Country:** United States **Facility:** Noesis Parma **State:** Arizona **Zip:** 85032 **Location 2:** **City:** Beverly Hills **Country:** United States **Facility:** Southern California Research **State:** California **Zip:** 90210 **Location 3:** **City:** Encino **Country:** United States **Facility:** Pharmacology Research Institute **State:** California **Zip:** 91316 **Location 4:** **City:** Garden Grove **Country:** United States **Facility:** Collaborative NeuroScience Network Inc. **State:** California **Zip:** 92845 **Location 5:** **City:** Newport Beach **Country:** United States **Facility:** Pharmacology Research Institute **State:** California **Zip:** 92660 **Location 6:** **City:** San Marcos **Country:** United States **Facility:** Artemis Institute for Clinical Research **State:** California **Zip:** 92078 **Location 7:** **City:** Santa Ana **Country:** United States **Facility:** Syrentis Clinical Research **State:** California **Zip:** 92705 **Location 8:** **City:** Colorado Springs **Country:** United States **Facility:** MCB Clinical Research Centers, LLC **State:** Colorado **Zip:** 80910 **Location 9:** **City:** Denver **Country:** United States **Facility:** Weiss and Lytle, PLLC **State:** Colorado **Zip:** 80209* **Location 10:** **City:** Cromwell **Country:** United States **Facility:** CT Clinical Research **State:** Connecticut **Zip:** 06416 **Location 11:** **City:** Fort Myers **Country:** United States **Facility:** Gulfcoast Clinical Research Center **State:** Florida **Zip:** 33912 **Location 12:** **City:** Jacksonville **Country:** United States **Facility:** Clinical Neuroscience Solutions, Inc. **State:** Florida **Zip:** 32256 **Location 13:** **City:** North Miami **Country:** United States **Facility:** Segal Institute for Clinical Research **State:** Florida **Zip:** 33161 **Location 14:** **City:** Orlando **Country:** United States **Facility:** Clinical Neuroscience Solutions, Inc. **State:** Florida **Zip:** 32801 **Location 15:** **City:** South Miami **Country:** United States **Facility:** Miami Research Associates **State:** Florida **Zip:** 33143 **Location 16:** **City:** Alpharetta **Country:** United States **Facility:** Institute of Advanced Medical Research **State:** Georgia **Zip:** 30005 **Location 17:** **City:** Atlanta **Country:** United States **Facility:** Neuotrials Research, Inc. **State:** Georgia **Zip:** 30342 **Location 18:** **City:** Marietta **Country:** United States **Facility:** Northwest Behavioral Research Center **State:** Georgia **Zip:** 30060 **Location 19:** **City:** Libertyville **Country:** United States **Facility:** Capstone Clinical Research **State:** Illinois **Zip:** 60048 **Location 20:** **City:** Indianapolis **Country:** United States **Facility:** Goldpoint Clinical Research, Inc. **State:** Indiana **Zip:** 46260 **Location 21:** **City:** Prairie Village **Country:** United States **Facility:** Phoenix Medical Research, Inc. Suite 135 **State:** Kansas **Zip:** 66208 **Location 22:** **City:** Wichita **Country:** United States **Facility:** Cyress Medical Research Center, LLC **State:** Kansas **Zip:** 67226 **Location 23:** **City:** Belmont **Country:** United States **Facility:** McLean Hospital **State:** Massachusetts **Zip:** 02478 **Location 24:** **City:** Boston **Country:** United States **Facility:** Boston Clinical Trials **State:** Massachusetts **Zip:** 02131 **Location 25:** **City:** Methuen **Country:** United States **Facility:** ActivMed Practices & Research, Inc. **State:** Massachusetts **Zip:** 01844 **Location 26:** **City:** Watertown **Country:** United States **Facility:** Adams Clinical Trials, LLC **State:** Massachusetts **Zip:** 02472 **Location 27:** **City:** Saint Charles **Country:** United States **Facility:** St. Charles Psychiatric Associates - Midwest Research Group **State:** Missouri **Zip:** 63304 **Location 28:** **City:** Portsmouth **Country:** United States **Facility:** ActivMed Practices and Research, Inc. **State:** New Hampshire **Zip:** 03801 **Location 29:** **City:** Cherry Hill **Country:** United States **Facility:** Center for Emotional Fitness **State:** New Jersey **Zip:** 08002 **Location 30:** **City:** Princeton **Country:** United States **Facility:** Princeton Medical Institute, LCC **State:** New Jersey **Zip:** 08540 **Location 31:** **City:** Mount Kisco **Country:** United States **Facility:** Bioscience Research, LLC **State:** New York **Zip:** 10549 **Location 32:** **City:** New York **Country:** United States **Facility:** Manhattan Behavioral Medicine, PLLC **State:** New York **Zip:** 10036 **Location 33:** **City:** New York **Country:** United States **Facility:** The Medical Research Network, LLC **State:** New York **Zip:** 10128 **Location 34:** **City:** Raleigh **Country:** United States **Facility:** Wake Research Associates **State:** North Carolina **Zip:** 27612 **Location 35:** **City:** Akron **Country:** United States **Facility:** Radiant Research, Inc. **State:** Ohio **Zip:** 44311 **Location 36:** **City:** Cincinnati **Country:** United States **Facility:** Patient Priority Clinical Sites **State:** Ohio **Zip:** 45215 **Location 37:** **City:** Dayton **Country:** United States **Facility:** Midwest Clinical Research Center **State:** Ohio **Zip:** 45417 **Location 38:** **City:** Mason **Country:** United States **Facility:** Lindner Center Of Hope **State:** Ohio **Zip:** 45040 **Location 39:** **City:** Oklahoma City **Country:** United States **Facility:** IPS Research Company **State:** Oklahoma **Zip:** 73103 **Location 40:** **City:** Medford **Country:** United States **Facility:** Sunstone Medical Research, LLC **State:** Oregon **Zip:** 97504 **Location 41:** **City:** Portland **Country:** United States **Facility:** Oregon Center for Clinical Investigatons, INC. **State:** Oregon **Zip:** 97214 **Location 42:** **City:** Salem **Country:** United States **Facility:** Oregon Center for Clinical Investigations, Inc. **State:** Oregon **Zip:** 97301 **Location 43:** **City:** Allentown **Country:** United States **Facility:** Lehigh Center For Clinical Research **State:** Pennsylvania **Zip:** 18104 **Location 44:** **City:** Anderson **Country:** United States **Facility:** Radiant Research, Inc. **State:** South Carolina **Zip:** 29621 **Location 45:** **City:** Greer **Country:** United States **Facility:** Radient Research, Inc. **State:** South Carolina **Zip:** 29650 **Location 46:** **City:** Mount Pleasant **Country:** United States **Facility:** Coastal Carolina Research Center **State:** South Carolina **Zip:** 29464 **Location 47:** **City:** Memphis **Country:** United States **Facility:** Clinical Neuroscience Solutons, Inc. **State:** Tennessee **Zip:** 38119 **Location 48:** **City:** Nashville **Country:** United States **Facility:** Clinical Research Associates, Inc. **State:** Tennessee **Zip:** 37203 **Location 49:** **City:** Austin **Country:** United States **Facility:** Donald J. Garcia Jr., MD **State:** Texas **Zip:** 78737 **Location 50:** **City:** Houston **Country:** United States **Facility:** Texas Center for Drug Development, Inc. **State:** Texas **Zip:** 77081 **Location 51:** **City:** Plano **Country:** United States **Facility:** Psychiatric Medical Associates **State:** Texas **Zip:** 75023 **Location 52:** **City:** San Antonio **Country:** United States **Facility:** Clinical Trials of Texas, Inc. **State:** Texas **Zip:** 78229 **Location 53:** **City:** San Antonio **Country:** United States **Facility:** Radient Research, Inc. **State:** Texas **Zip:** 78229 **Location 54:** **City:** Murray **Country:** United States **Facility:** Radiant Research, Inc. **State:** Utah **Zip:** 84123 **Location 55:** **City:** Woodstock **Country:** United States **Facility:** Neuropsychiatric Associates **State:** Vermont **Zip:** 05091 **Location 56:** **City:** Herndon **Country:** United States **Facility:** NeuroScience, Inc. **State:** Virginia **Zip:** 20170 **Location 57:** **City:** Seattle **Country:** United States **Facility:** Summitt Research Network(Seattle) LLC **State:** Washington **Zip:** 98104 #### Overall Officials **Official 1:** **Affiliation:** Sumitomo Pharma America, Inc. **Name:** Dasotraline Medical Director **Role:** STUDY_DIRECTOR ## Document Section ### Large Document Module #### Large Docs - Date: 2017-06-13 - Filename: Prot_000.pdf - Has ICF: False - Has Protocol: True - Has SAP: False - Label: Study Protocol - Size: 1750464 - Type Abbrev: Prot - Upload Date: 2020-06-17T09:29 - Date: 2019-06-20 - Filename: SAP_001.pdf - Has ICF: False - Has Protocol: False - Has SAP: True - Label: Statistical Analysis Plan - Size: 492541 - Type Abbrev: SAP - Upload Date: 2020-06-17T09:32 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000001523 - Term: Mental Disorders - ID: D000006963 - Term: Hyperphagia - ID: D000012817 - Term: Signs and Symptoms, Digestive ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BXM - Name: Behaviors and Mental Disorders ### Condition Browse Module - Browse Leaves - ID: M5304 - Name: Bulimia - Relevance: HIGH - As Found: Binge Eating - ID: M28641 - Name: Binge-Eating Disorder - Relevance: HIGH - As Found: Binge Eating Disorder - ID: M26956 - Name: Bulimia Nervosa - Relevance: LOW - As Found: Unknown - ID: M4380 - Name: Feeding and Eating Disorders - Relevance: HIGH - As Found: Eating Disorders - ID: M4815 - Name: Mental Disorders - Relevance: LOW - As Found: Unknown - ID: M14473 - Name: Psychotic Disorders - Relevance: LOW - As Found: Unknown - ID: M10014 - Name: Hyperphagia - Relevance: LOW - As Found: Unknown - ID: M15622 - Name: Signs and Symptoms, Digestive - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000002032 - Term: Bulimia - ID: D000001068 - Term: Feeding and Eating Disorders - ID: D000056912 - Term: Binge-Eating Disorder ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module **Description:** Treatment-emergent adverse events (TEAEs) are those reported adverse events with onset date on or after the first day of the open-label treatment period through 7 days after study drug discontinuation (14 days for serious adverse events and deaths). #### Event Groups **Group ID:** EG000 **Title:** Dasotraline **Deaths Num At Risk:** 528 **Description:** 4, 6, 8 mg flexibly dosed **ID:** EG000 **Other Num Affected:** 295 **Other Num at Risk:** 528 **Serious Number Affected:** 21 **Serious Number At Risk:** 528 **Title:** Dasotraline **Frequency Threshold:** 5 #### Other Events **Term:** Dry mouth **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 19.0 **Term:** Nausea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 19.0 **Term:** Nasopharyngitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 19.0 **Term:** Upper respiratory tract infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 19.0 **Term:** Weight decreased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA 19.0 **Term:** Headache **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 19.0 **Term:** Anxiety **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA 19.0 **Term:** Insomnia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA 19.0 **Term:** Irritability **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA 19.0 #### Serious Events **Term:** Anaemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA 19.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Term:** Iron deficiency anaemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA 19.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Term:** Abdominal adhesions **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 19.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Term:** Colitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 19.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Term:** Rectal haemorrhage **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 19.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Term:** Cholecystitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA 19.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Term:** Cholelithiasis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA 19.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Term:** Hypersensitivity **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Immune system disorders **Source Vocabulary:** MedDRA 19.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Term:** Cellulitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 19.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Term:** Localised infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 19.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Term:** Laceration **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 19.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Term:** Lumbar vertebral fracture **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 19.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Term:** Post procedural inflammation **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 19.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Term:** Osteoarthritis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 19.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Term:** Uterine leiomyoma **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA 19.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Term:** Hemiplegic migraine **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 19.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Term:** Partial seizures **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 19.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Term:** Seizure **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 19.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Term:** Panic attack **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA 19.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Term:** Paranoia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA 19.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Term:** Psychotic disorder **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA 19.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Term:** Substance-induced mood disorder **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA 19.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Term:** Suicide attempt **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA 19.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Term:** Nephrolithiasis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA 19.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Term:** Menorrhagia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Reproductive system and breast disorders **Source Vocabulary:** MedDRA 19.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 528 **Num Events:** 1 **Time Frame:** An AE onset on or after the start of the open-label treatment period (treatment duration: 52 weeks) through 7 days after study drug discontinuation (14 days for serious adverse events and deaths) ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 528 **Units:** Participants ### Group **ID:** BG000 **Title:** Dasotraline **Description:** 4, 6, 8 mg flexibly dosed ### Measure #### Measurement **Group ID:** BG000 **Value:** 2 **Category Title:** <=18 years #### Measurement **Group ID:** BG000 **Value:** 526 **Category Title:** Between 18 and 65 years #### Measurement **Group ID:** BG000 **Value:** 0 **Category Title:** >=65 years **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Spread:** 9.81 **Value:** 38.8 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 440 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 88 **Category Title:** Male **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 85 **Category Title:** Hispanic or Latino #### Measurement **Group ID:** BG000 **Value:** 443 **Category Title:** Not Hispanic or Latino #### Measurement **Group ID:** BG000 **Value:** 0 **Category Title:** Unknown or Not Reported **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 1 **Category Title:** American Indian or Alaska Native #### Measurement **Group ID:** BG000 **Value:** 14 **Category Title:** Asian #### Measurement **Group ID:** BG000 **Value:** 0 **Category Title:** Native Hawaiian or Other Pacific Islander #### Measurement **Group ID:** BG000 **Value:** 82 **Category Title:** Black or African American #### Measurement **Group ID:** BG000 **Value:** 420 **Category Title:** White #### Measurement **Group ID:** BG000 **Value:** 11 **Category Title:** More than one race #### Measurement **Group ID:** BG000 **Value:** 0 **Category Title:** Unknown or Not Reported **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Spread:** 8.77 **Value:** 167.4 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Spread:** 21.52 **Value:** 95.1 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Spread:** 6.348 **Value:** 33.8 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Spread:** 0.54 **Value:** 4.5 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Spread:** 1.38 **Value:** 2.4 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Spread:** 1.522 **Value:** 3.7 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Spread:** 2.007 **Value:** 2.21 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Spread:** 1.721 **Value:** 4.38 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Spread:** 1.655 **Value:** 4.5 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Spread:** 1.687 **Value:** 2.9 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Spread:** 1.961 **Value:** 1.71 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Spread:** 1.944 **Value:** 3.44 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Spread:** 1.912 **Value:** 3.55 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 53 **Class Title:** Underweight/Normal (<25) #### Measurement **Group ID:** BG000 **Value:** 104 **Class Title:** Overweight (25 to <30) #### Measurement **Group ID:** BG000 **Value:** 134 **Class Title:** Obesity Class I (30 to <35) #### Measurement **Group ID:** BG000 **Value:** 136 **Class Title:** Obesity Class II (35 to <40) #### Measurement **Group ID:** BG000 **Value:** 101 **Class Title:** Obesity Class III (>=40) **Denomination Units Selected:** ## Results Section - Baseline Characteristics Module ### Measure 1 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Age, Categorical **Unit of Measure:** Participants ### Measure 2 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** Age, Continuous **Unit of Measure:** Years ### Measure 3 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Sex: Female, Male **Unit of Measure:** Participants ### Measure 4 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Ethnicity (NIH/OMB) **Unit of Measure:** Participants ### Measure 5 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Race (NIH/OMB) **Unit of Measure:** Participants ### Measure 6 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** Height (cm) **Unit of Measure:** cm ### Measure 7 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** Weight (kg) **Unit of Measure:** kg ### Measure 8 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** BMI (kg/m^2) **Unit of Measure:** kg/m^2 ### Measure 9 **Description:** DB Baseline (ie, Baseline assessment of the double-blind core studies \[SEP 360-221, or SEP360-321\]) is defined as the last assessment made on or before the 1st dose of double-blind study medication as described in the SAPs of the core studies. **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** Binge-eating Clinical Global Impression-Severity (BE-CGI-S) Score at Double-Blind (DB) Baseline **Unit of Measure:** Score ### Measure 10 **Description:** The OL Baseline is defined as the last assessment made on or before Day 1 of the extension study (ie, Baseline assessment in the open-label study \[SEP 360-322\] for demographic and EDE-Q modified, and height at the screening and the Endpoint assessment of the double-blind studies \[SEP 360-221, or SEP 360-321\], otherwise). **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** Binge-eating Clinical Global Impression-Severity (BE-CGI-S) Score at Open Label (OL) Baseline **Unit of Measure:** Score ### Measure 11 **Description:** DB Baseline (ie, Baseline assessment of the double-blind core studies \[SEP 360-221, or SEP360-321\]) is defined as the last assessment made on or before the 1st dose of double-blind study medication as described in the SAPs of the core studies. **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** Eating Disorder Examination Question(EDE-QM) Modified Score at DB Baseline - Global Score **Unit of Measure:** Score ### Measure 12 **Description:** DB Baseline (ie, Baseline assessment of the double-blind core studies \[SEP 360-221, or SEP360-321\]) is defined as the last assessment made on or before the 1st dose of double-blind study medication as described in the SAPs of the core studies. **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** Eating Disorder Examination Question(EDE-QM) Modified Score at DB Baseline - Restraint **Unit of Measure:** Score ### Measure 13 **Description:** DB Baseline (ie, Baseline assessment of the double-blind core studies \[SEP 360-221, or SEP360-321\]) is defined as the last assessment made on or before the 1st dose of double-blind study medication as described in the SAPs of the core studies. **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** Eating Disorder Examination Question(EDE-QM) Modified Score at DB Baseline - Shape Concern **Unit of Measure:** Score ### Measure 14 **Description:** DB Baseline (ie, Baseline assessment of the double-blind core studies \[SEP 360-221, or SEP360-321\]) is defined as the last assessment made on or before the 1st dose of double-blind study medication as described in the SAPs of the core studies. **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** EDE-QM Modified Score at DB Baseline - Weight Concern **Unit of Measure:** Score ### Measure 15 **Description:** The OL Baseline is defined as the last assessment made on or before Day 1 of the extension study (ie, Baseline assessment in the open-label study \[SEP 360-322\] for demographic and EDE-Q modified, and height at the screening and the Endpoint assessment of the double-blind studies \[SEP 360-221, or SEP 360-321\], otherwise). **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** EDE-QM Modified Score at OL Baseline - Global Score **Unit of Measure:** Score ### Measure 16 **Description:** The OL Baseline is defined as the last assessment made on or before Day 1 of the extension study (ie, Baseline assessment in the open-label study \[SEP 360-322\] for demographic and EDE-Q modified, and height at the screening and the Endpoint assessment of the double-blind studies \[SEP 360-221, or SEP 360-321\], otherwise). **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** EDE-QM Modified Score at OL Baseline - Restraint **Unit of Measure:** Score ### Measure 17 **Description:** The OL Baseline is defined as the last assessment made on or before Day 1 of the extension study (ie, Baseline assessment in the open-label study \[SEP 360-322\] for demographic and EDE-Q modified, and height at the screening and the Endpoint assessment of the double-blind studies \[SEP 360-221, or SEP 360-321\], otherwise). **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** EDE-QM Modified Score at OL Baseline - Shape Concern **Unit of Measure:** Score ### Measure 18 **Description:** The OL Baseline is defined as the last assessment made on or before Day 1 of the extension study (ie, Baseline assessment in the open-label study \[SEP 360-322\] for demographic and EDE-Q modified, and height at the screening and the Endpoint assessment of the double-blind studies \[SEP 360-221, or SEP 360-321\], otherwise). **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** Eating Disorder Examination Question(EDE-QM) Modified Score at OL Baseline - Weight Concern **Unit of Measure:** Score ### Measure 19 **Description:** The OL Baseline is defined as the last assessment made on or before Day 1 of the extension study (ie, Baseline assessment in the open-label study \[SEP 360-322\] for demographic and EDE-Q modified, and height at the screening and the Endpoint assessment of the double-blind studies \[SEP 360-221, or SEP 360-321\], otherwise). **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** summary for Body Mass Index (BMI) category at open label baseline **Unit of Measure:** Participants **Population Description:** safety ## Results Section - More Information Module ### Certain Agreement **Other Details:** In the event the Study is part of a multi-center study, the first publication of the results of the Study shall be made in conjunction with the results of other participating study sites as a multi-center publication; provided however, if a multi-center publication is not forthcoming within twenty-four (24) months following completion of the Study at all sites, Institution and Investigator shall be free to publish. **Restriction Type:** OTHER **Restrictive Agreement:** True ### Point of Contact **Email:** [email protected] **Organization:** Sunovion Pharmaceuticals Inc. **Phone:** 1-866-503-6351 **Title:** CNS Medical Director ## Results Section - Outcome Measures Module ### Outcome Measure 1 ### Outcome Measure 2 ### Outcome Measure 3 ### Outcome Measure 4 ### Outcome Measure 5 ### Outcome Measure 6 ### Outcome Measure 7 ### Outcome Measure 8 ### Outcome Measure 9 ### Outcome Measure 10 ### Outcome Measure 11 ### Outcome Measure 12 ### Outcome Measure 13 ### Outcome Measure 14 ### Outcome Measure 15 ### Outcome Measure 16 ### Outcome Measure 17 ### Outcome Measure 18 ### Outcome Measure 19 ### Outcome Measure 20 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 515 **Title:** 0: No suicidal ideation ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 7 **Title:** 1: Wish to be dead ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 **Title:** 2: Non-specific active suicidal thoughts ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** 3: ideation with any methods , no intent to act ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** 4: ideation with some intent to act, no plan ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** 5: Active ideation with specific plan and intent #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** #### Outcome Measure 3 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -5.36 - **Spread:** - **Upper Limit:** -3.93 - **Value:** -4.65 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -2.77 - **Spread:** - **Upper Limit:** -1.49 - **Value:** -2.13 **Title:** #### Outcome Measure 4 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -5.35 - **Spread:** - **Upper Limit:** -3.95 - **Value:** -4.65 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -2.71 - **Spread:** - **Upper Limit:** -1.43 - **Value:** -2.07 **Title:** #### Outcome Measure 5 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -1.89 - **Spread:** - **Upper Limit:** -1.39 - **Value:** -1.64 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -0.97 - **Spread:** - **Upper Limit:** -0.53 - **Value:** -0.75 **Title:** #### Outcome Measure 6 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -5.35 - **Spread:** - **Upper Limit:** -3.95 - **Value:** -4.65 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -2.71 - **Spread:** - **Upper Limit:** -1.43 - **Value:** -2.07 **Title:** #### Outcome Measure 7 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -17.5 - **Spread:** - **Upper Limit:** -6.3 - **Value:** -11.9 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -10.4 - **Spread:** - **Upper Limit:** -0.3 - **Value:** -5.3 **Title:** #### Outcome Measure 8 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -9.3 - **Spread:** - **Upper Limit:** -4.8 - **Value:** -7.0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -5.6 - **Spread:** - **Upper Limit:** -1.4 - **Value:** -3.5 **Title:** #### Outcome Measure 9 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -2.0 - **Spread:** - **Upper Limit:** -0.2 - **Value:** -1.1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0.2 - **Spread:** - **Upper Limit:** 1.9 - **Value:** 1.1 **Title:** #### Outcome Measure 10 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -5.5 - **Spread:** - **Upper Limit:** -1.6 - **Value:** -3.6 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -5.2 - **Spread:** - **Upper Limit:** -1.5 - **Value:** -3.4 **Title:** #### Outcome Measure 11 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -0.02 - **Spread:** - **Upper Limit:** 0.02 - **Value:** 0.00 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -0.02 - **Spread:** - **Upper Limit:** 0.02 - **Value:** 0.00 **Title:** #### Outcome Measure 12 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0.9 - **Spread:** - **Upper Limit:** 3.5 - **Value:** 2.2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0.3 - **Spread:** - **Upper Limit:** 3.1 - **Value:** 1.7 **Title:** #### Outcome Measure 13 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -1.30 - **Spread:** - **Upper Limit:** -1.02 - **Value:** -1.16 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -0.48 - **Spread:** - **Upper Limit:** -0.26 - **Value:** -0.37 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -0.81 - **Spread:** - **Upper Limit:** -0.45 - **Value:** -0.63 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -0.27 - **Spread:** - **Upper Limit:** 0.01 - **Value:** -0.13 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -1.54 - **Spread:** - **Upper Limit:** -1.22 - **Value:** -1.38 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -0.57 - **Spread:** - **Upper Limit:** -0.31 - **Value:** -0.44 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -1.63 - **Spread:** - **Upper Limit:** -1.31 - **Value:** -1.47 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -0.66 - **Spread:** - **Upper Limit:** -0.39 - **Value:** -0.53 **Title:** #### Outcome Measure 14 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -18.2 - **Spread:** - **Upper Limit:** -16.6 - **Value:** -17.4 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -4.6 - **Spread:** - **Upper Limit:** -3.1 - **Value:** -3.9 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -17.4 - **Spread:** - **Upper Limit:** -15.8 - **Value:** -16.6 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -4.2 - **Spread:** - **Upper Limit:** -2.8 - **Value:** -3.5 **Title:** #### Outcome Measure 15 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -15.9 - **Spread:** - **Upper Limit:** -14.7 - **Value:** -15.3 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -3.8 - **Spread:** - **Upper Limit:** -2.7 - **Value:** -3.3 **Title:** #### Outcome Measure 16 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -2.8 - **Spread:** - **Upper Limit:** -2.6 - **Value:** -2.7 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -0.8 - **Spread:** - **Upper Limit:** -0.5 - **Value:** -0.7 **Title:** #### Outcome Measure 17 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -9.0 - **Spread:** - **Upper Limit:** -7.4 - **Value:** -8.2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -2.1 - **Spread:** - **Upper Limit:** -0.9 - **Value:** -1.5 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -2.3 - **Spread:** - **Upper Limit:** -1.8 - **Value:** -2.0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -0.6 - **Spread:** - **Upper Limit:** -0.2 - **Value:** -0.4 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -3.5 - **Spread:** - **Upper Limit:** -2.9 - **Value:** -3.2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -0.7 - **Spread:** - **Upper Limit:** -0.3 - **Value:** -0.5 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -3.2 - **Spread:** - **Upper Limit:** -2.6 - **Value:** -2.9 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -0.6 - **Spread:** - **Upper Limit:** -0.2 - **Value:** -0.4 **Title:** #### Outcome Measure 18 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0.0 - **Spread:** - **Upper Limit:** 0.9 - **Value:** 0.4 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0.2 - **Spread:** - **Upper Limit:** 1.0 - **Value:** 0.6 **Title:** #### Outcome Measure 19 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -1.1 - **Spread:** - **Upper Limit:** -0.1 - **Value:** -0.6 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0.0 - **Spread:** - **Upper Limit:** 0.8 - **Value:** 0.4 **Title:** #### Outcome Measure 20 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -0.44 - **Spread:** - **Upper Limit:** 2.95 - **Value:** 1.25 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -3.27 - **Spread:** - **Upper Limit:** -0.40 - **Value:** -1.84 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 1.32 - **Spread:** - **Upper Limit:** 3.80 - **Value:** 2.56 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -0.16 - **Spread:** - **Upper Limit:** 1.90 - **Value:** 0.87 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** Columbia-suicide severity rating scale (C-SSRS) Severity of suicidal ideation is rated on a 6-point scale from 0='No ideation present' to 5='Active ideation with plan and intent'. A score of 4 or 5 on this scale indicates serious suicidal ideation. Suicidal behavior is collected as presence/absence of actual attempts, non-suicidal self-injurious behavior, interrupted attempts, aborted attempts, preparatory acts or behavior, and any suicidal behavior **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Safety- please note: one subject had no value for Suicidal Ideation or Suicidal Behavior **Reporting Status:** POSTED **Time Frame:** Baseline to Week 52 **Title:** Frequency and Severity of Suicidal Ideation Using the Columbia-suicide Severity Rating Scale (C-SSRS) **Type:** PRIMARY **Unit of Measure:** Participants ##### Group **Description:** 4, 6, 8 mg flexibly dosed **ID:** OG000 **Title:** Dasotraline #### Outcome Measure 2 **Description:** Columbia-suicide severity rating scale (C-SSRS) Severity of suicidal ideation is rated on a 6-point scale from 0='No ideation present' to 5='Active ideation with plan and intent'. A score of 4 or 5 on this scale indicates serious suicidal ideation. Suicidal behavior is collected as presence/absence of actual attempts, non-suicidal self-injurious behavior, interrupted attempts, aborted attempts, preparatory acts or behavior, and any suicidal behavior **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Safety **Reporting Status:** POSTED **Time Frame:** Baseline to Week 52 **Title:** Frequency and Severity of Suicidal Behavior Using the C-SSRS **Type:** PRIMARY **Unit of Measure:** Participants ##### Group **Description:** 4, 6, 8 mg flexibly dosed **ID:** OG000 **Title:** Dasotraline #### Outcome Measure 3 **Description:** Change in body weight **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEAN **Population Description:** Safety **Reporting Status:** POSTED **Time Frame:** Baseline, Week 52 **Title:** Change in Body Weight **Type:** SECONDARY **Unit of Measure:** kg ##### Group **Description:** 4, 6, 8 mg flexibly dosed **ID:** OG000 **Title:** Dasotraline #### Outcome Measure 4 **Description:** Percent change in body weight (kg) **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEAN **Population Description:** Safety **Reporting Status:** POSTED **Time Frame:** Baseline, Week 52 **Title:** Percent Change in Body Weight (kg) **Type:** SECONDARY **Unit of Measure:** percent change ##### Group **Description:** 4, 6, 8 mg flexibly dosed **ID:** OG000 **Title:** Dasotraline #### Outcome Measure 5 **Description:** Change in Body Mass Index **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEAN **Population Description:** Safety **Reporting Status:** POSTED **Time Frame:** Baseline, Week 52 **Title:** Change in Body Mass Index **Type:** SECONDARY **Unit of Measure:** kg/m^2 ##### Group **Description:** 4, 6, 8 mg flexibly dosed **ID:** OG000 **Title:** Dasotraline #### Outcome Measure 6 **Description:** Percent change in Body Mass Index (kg/m\^2) **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEAN **Population Description:** Safety **Reporting Status:** POSTED **Time Frame:** Baseline, Week 52 **Title:** Percent Change in Body Mass Index (kg/m^2) **Type:** SECONDARY **Unit of Measure:** percent change ##### Group **Description:** 4, 6, 8 mg flexibly dosed **ID:** OG000 **Title:** Dasotraline #### Outcome Measure 7 **Description:** Change in fasting lipid panel, Triglyceride's **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEAN **Population Description:** Safety **Reporting Status:** POSTED **Time Frame:** Baseline, Week 52 **Title:** Change in Fasting Lipid Panel, Triglyceride's **Type:** SECONDARY **Unit of Measure:** mg/dL ##### Group **Description:** 4, 6, 8 mg flexibly dosed **ID:** OG000 **Title:** Dasotraline #### Outcome Measure 8 **Description:** Change in fasting lipid panel , total cholesterol **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEAN **Population Description:** Safety **Reporting Status:** POSTED **Time Frame:** Baseline, Week 52 **Title:** Change in Fasting Lipid Panel , Total Cholesterol **Type:** SECONDARY **Unit of Measure:** mg/dL ##### Group **Description:** 4, 6, 8 mg flexibly dosed **ID:** OG000 **Title:** Dasotraline #### Outcome Measure 9 **Description:** Change in fasting lipid panel, high-density lipoprotein \[HDL\] cholesterol, **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEAN **Population Description:** Safety **Reporting Status:** POSTED **Time Frame:** Baseline, Week 52 **Title:** Change in Fasting Lipid Panel , High-density Lipoprotein [HDL] Cholesterol, **Type:** SECONDARY **Unit of Measure:** mg/dL ##### Group **Description:** 4, 6, 8 mg flexibly dosed **ID:** OG000 **Title:** Dasotraline #### Outcome Measure 10 **Description:** Change in fasting lipid panel, low-density lipoprotein \[LDL\] cholesterol) **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEAN **Population Description:** Safety **Reporting Status:** POSTED **Time Frame:** Baseline, Week 52 **Title:** Change in Fasting Lipid Panel, Low-density Lipoprotein [LDL] Cholesterol) **Type:** SECONDARY **Unit of Measure:** mg/dL ##### Group **Description:** 4, 6, 8 mg flexibly dosed **ID:** OG000 **Title:** Dasotraline #### Outcome Measure 11 **Description:** Change in hemoglobin A1c levels **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEAN **Population Description:** Safety **Reporting Status:** POSTED **Time Frame:** Baseline, Week 52 **Title:** Change in Hemoglobin A1c Levels **Type:** SECONDARY **Unit of Measure:** Percent change ##### Group **Description:** 4, 6, 8 mg flexibly dosed **ID:** OG000 **Title:** Dasotraline #### Outcome Measure 12 **Description:** Change in fasting glucose levels **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEAN **Population Description:** Safety **Reporting Status:** POSTED **Time Frame:** Baseline, Week 52 **Title:** Change in Fasting Glucose Levels **Type:** SECONDARY **Unit of Measure:** mg/dL ##### Group **Description:** 4, 6, 8 mg flexibly dosed **ID:** OG000 **Title:** Dasotraline #### Outcome Measure 13 **Description:** Eating Disorder Examination Questionnaire (EDE-Q) Modified global and subscale scores 4 subscale scores (Restraint, Eating Concern, Shape Concern, and Weight Concern) range from 0- 6, where 0 represents absence of the feature and 6 represents an extreme degree. An EDE-Q global score is calculated as average of 4 EDE-Q subscale scores. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEAN **Population Description:** Safety **Reporting Status:** POSTED **Time Frame:** Baseline, Week 52 **Title:** Change in Eating Disorder Examination Questionnaire (EDE Q) Modified Global Score and Subscale Scores (Restraint, Shape, Concern, Weight Concern), and Items 4-6 Scores **Type:** SECONDARY **Unit of Measure:** units on a scale ##### Group **Description:** 4, 6, 8 mg flexibly dosed **ID:** OG000 **Title:** Dasotraline #### Outcome Measure 14 **Description:** Eating Disorder Examination Questionnaire (EDE-Q) Modified global and subscale scores 4 subscale scores (Restraint, Eating Concern, Shape Concern, and Weight Concern) range from 0- 6, where 0 represents absence of the feature and 6 represents an extreme degree. An EDE-Q global score is calculated as average of 4 EDE-Q subscale scores. Item 4: Over the past 28 days, how many times have you eaten what other people would regard as an unusually large amount of food (given the circumstances)? Item 5: On how many of these times did you have a sense of having lost control over your eating (at the time that you were eating)? **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEAN **Population Description:** Safety **Reporting Status:** POSTED **Time Frame:** Baseline, Week 52 **Title:** Change in Eating Disorder Examination Questionnaire (EDE Q) Modified Global Score and Subscale Scores (Restraint, Shape, Concern, Weight Concern), and Items 4-6 Scores **Type:** SECONDARY **Unit of Measure:** events ##### Group **Description:** 4, 6, 8 mg flexibly dosed **ID:** OG000 **Title:** Dasotraline #### Outcome Measure 15 **Description:** Eating Disorder Examination Questionnaire (EDE-Q) Modified global and subscale scores 4 subscale scores (Restraint, Eating Concern, Shape Concern, and Weight Concern) range from 0- 6, where 0 represents absence of the feature and 6 represents an extreme degree. An EDE-Q global score is calculated as average of 4 EDE-Q subscale scores. Item 6: Over the past 28 days, on how many DAYS have such episodes of overeating occurred (i.e., you have eaten an unusually large amount of food and have had a sense of loss of control at the time)? **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEAN **Population Description:** Safety **Reporting Status:** POSTED **Time Frame:** Baseline, Week 52 **Title:** Change in Eating Disorder Examination Questionnaire (EDE Q) Modified Global Score and Subscale Scores (Restraint, Shape, Concern, Weight Concern), and Items 4-6 Scores **Type:** SECONDARY **Unit of Measure:** number of days ##### Group **Description:** 4, 6, 8 mg flexibly dosed **ID:** OG000 **Title:** Dasotraline #### Outcome Measure 16 **Description:** Binge-eating Clinical Global Impression-Severity (BE-CGI-S) The BE-CGI-S is a single value, clinician-rated assessment of illness severity, and 7-point scale with range from 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; 7 = among the most extremely ill subjects. A higher score is associated with greater illness severity. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEAN **Population Description:** Safety **Reporting Status:** POSTED **Time Frame:** Baseline, Week 52 **Title:** Change in Binge Eating Clinical Global Impression-Severity (BE-CGI S) Score **Type:** SECONDARY **Unit of Measure:** units on a scale ##### Group **Description:** 4, 6, 8 mg flexibly dosed **ID:** OG000 **Title:** Dasotraline #### Outcome Measure 17 **Description:** The Sheehan Disability Scale (SDS) 3 subscales (work/school, social life, home life) are rated on the following scale: 0 = not at all; 1-3 = mildly; 4-6 = moderately; 7-9 =markedly; 10 = extremely. The 3 items can be combined into a single global measure of impairment (SDS total score) that ranges from 0 (unimpaired) to 30 (highly impaired). A higher subscale score and total score are associated with greater illness severity. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEAN **Population Description:** Safety **Reporting Status:** POSTED **Time Frame:** Baseline, Week 52 **Title:** Change in Sheehan Disability Scale (SDS) Total Score and Subscale Scores (School/Work Disability, Social Life Disability, and Family Life Disability) **Type:** SECONDARY **Unit of Measure:** units on a scale ##### Group **Description:** 4, 6, 8 mg flexibly dosed **ID:** OG000 **Title:** Dasotraline #### Outcome Measure 18 **Description:** Hamilton Anxiety Rating Scale (HAM-A) total score HAM-A total score ranges from 0 to 56. A higher score is associated with a greater degree of anxiety. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEAN **Population Description:** Safety **Reporting Status:** POSTED **Time Frame:** Baseline, Week 52 **Title:** Change From Baseline in Hamilton Anxiety Rating Scale (HAM-A) Total Score **Type:** SECONDARY **Unit of Measure:** units on a scale ##### Group **Description:** 4, 6, 8 mg flexibly dosed **ID:** OG000 **Title:** Dasotraline #### Outcome Measure 19 **Description:** Montgomery-Asberg Depression Rating Scale (MADRS) total score The MADRS total score ranges from 0 to 60, with higher scores indicating increased depressive symptoms **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEAN **Population Description:** Safety **Reporting Status:** POSTED **Time Frame:** Baseline, Week 52 **Title:** Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score **Type:** SECONDARY **Unit of Measure:** units on a scale ##### Group **Description:** 4, 6, 8 mg flexibly dosed **ID:** OG000 **Title:** Dasotraline #### Outcome Measure 20 **Description:** Change in SF-12 two component scores (physical, mental health) for Subjects Continued from Study SEP360-221 The SF-12 is a 12-item self-report questionnaire. Physical Component Summary (PCS) and Mental Component Summary (MCS) are computed using the scores of twelve questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEAN **Population Description:** Safety **Reporting Status:** POSTED **Time Frame:** Baseline, Week 52 **Title:** Change in SF-12 Two Component Scores (Physical, Mental Health) **Type:** SECONDARY **Unit of Measure:** units on a scale ##### Group **Description:** 4, 6, 8 mg flexibly dosed **ID:** OG000 **Title:** Dasotraline ### Participant Flow Module #### Group **Description:** 4, 6, 8 mg flexibly dosed **ID:** FG000 **Title:** Dasotraline #### Period **Title:** Overall Study ##### Withdraw **Type:** Adverse Event ###### Reason **Group ID:** FG000 **Number of Subjects:** 87 ##### Withdraw **Type:** Lack of Efficacy ###### Reason **Group ID:** FG000 **Number of Subjects:** 4 ##### Withdraw **Type:** Lost to Follow-up ###### Reason **Group ID:** FG000 **Number of Subjects:** 61 ##### Withdraw **Type:** Protocol Violation ###### Reason **Group ID:** FG000 **Number of Subjects:** 6 ##### Withdraw **Type:** Pregnancy ###### Reason **Group ID:** FG000 **Number of Subjects:** 8 ##### Withdraw **Type:** Withdrawal by Subject ###### Reason **Group ID:** FG000 **Number of Subjects:** 92 ##### Withdraw **Type:** non-compliance with study drug ###### Reason **Group ID:** FG000 **Number of Subjects:** 9 ##### Withdraw **Type:** non compliance with study visits ###### Reason **Group ID:** FG000 **Number of Subjects:** 2 ##### Withdraw **Type:** subject to have surgery ###### Reason **Group ID:** FG000 **Number of Subjects:** 1 ##### Withdraw **Type:** family emergency ###### Reason **Group ID:** FG000 **Number of Subjects:** 1 ##### Withdraw **Type:** Site closures ###### Reason **Group ID:** FG000 **Number of Subjects:** 7 ##### Withdraw **Type:** Physician Decision ###### Reason **Group ID:** FG000 **Number of Subjects:** 1 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 528 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 249 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 279 **Pre-Assignment Details:** A total 533 subjects were enrolled in this study. Five subjects did not receive any dose of study medication. **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT01540279 **Brief Title:** Clinical Outcome in View of Surgical Site Infection (SSI) With Antibacterial Skin Sutures **Official Title:** Do Antibacterial Skin Sutures Reduce Surgical Site Infections After Open Abdominal Surgery? #### Organization Study ID Info **ID:** University Hospital Basel #### Organization **Class:** OTHER **Full Name:** University Hospital, Basel, Switzerland ### Status Module #### Completion Date **Date:** 2014-07 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2015-03-18 **Type:** ESTIMATED **Last Update Submit Date:** 2015-03-17 **Overall Status:** TERMINATED #### Primary Completion Date **Date:** 2014-07 **Type:** ACTUAL #### Start Date **Date:** 2011-07 **Status Verified Date:** 2015-03 #### Study First Post Date **Date:** 2012-02-28 **Type:** ESTIMATED **Study First Submit Date:** 2012-02-22 **Study First Submit QC Date:** 2012-02-27 **Why Stopped:** insufficient enrollment ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** University Hospital, Basel, Switzerland #### Responsible Party **Type:** SPONSOR ### Description Module **Brief Summary:** Background: Poor wound healing and the development of surgical site infection (SSI) continue to occur and remain a significant cause of disability among operated patients. In spite of the substantial advances in our understanding of the epidemiology, pathogenesis and prevention it remains one of the most common complications in conventional abdominal surgery with an incidence in the literature between 4% and 17%. As it is known that surgical sutures potentiate the development of wound infection the search for an ideal suture material, suitable for all purposes has been pursued by surgeons for decades. Hypothesis: In line with in-vitro results the investigators hypothesize that the use of antibacterial skin sutures with triclosan poliglecaprone 25 reduces the rate of SSI after open abdominal surgery Methods: To prevent microbial colonization of suture material in operative wounds and therefore to prevent SSI, triclosan-coated poliglecaprone 25 suture materials with antibacterial activity will be tested against un-coated suture material for skin closure after open abdominal surgery of 200 patients. The study is planed as a single center, randomized controlled trial. After ethical approval the patients will be consecutively enrolled from 2011 to 2012 in the Department of Visceral Surgery, University Hospital Basel, Switzerland. The patients will be followed for 30 days (day 3,7 and 30) to detect and document wound complications. Wound complications will be classified according to Center for Disease Control and Prevention Standard guidelines. Data will be collected and the rate of SSI will be analysed in both groups. Expected value of the proposed project: If the investigators can confirm the proposed hypothesis in our study this could be a promising and feasible approach to lower SSI after open abdominal surgery and might be also used in other surgical fields. By lowering the rate of SSI the investigators might offer a new and cost saving procedure to the surgical community. ### Conditions Module **Conditions:** - Wound Infection, Surgical ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 52 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Label:** Cohort one with abdominal wall closure with Monocryl #### Arm Group 2 **Label:** Cohort two with abdominal wall closure with Monocryl plus ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * All patients from the Visceral Department of Basel University Hospital requiring open abdominal surgery. Open abdominal surgery is defined as: opened peritoneal cavity Exclusion Criteria: * factors limiting the ability to co-operate in the study; * absence of signed informed consent before entering the study; * people with mental disorders; * pregnant women; * participants under 18 years **Minimum Age:** 18 Years **Sampling Method:** PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** All patients with required open abdominal surgery will be consecutively enrolled.Data of emergency patients are recorded separately as well as patients with a contaminated or dirty-infected (class III-IV) operative wound classified according to CDC guidelines on surgical wound classification1 further Patients with implanted foreign material such as mesh or vascular prosthesis. ### Contacts Locations Module #### Locations **Location 1:** **City:** Basel **Country:** Switzerland **Facility:** Surgical Department of University Hospital Basel, Switzerland **State:** Basel-Stadt **Zip:** 4031 #### Overall Officials **Official 1:** **Affiliation:** Surgical Department of University Hospital Basel, Switzerland **Name:** Heidi Misteli, MD **Role:** STUDY_CHAIR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000020969 - Term: Disease Attributes - ID: D000010335 - Term: Pathologic Processes - ID: D000011183 - Term: Postoperative Complications ### Condition Browse Module - Browse Branches - Abbrev: BC01 - Name: Infections - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: BC26 - Name: Wounds and Injuries ### Condition Browse Module - Browse Leaves - ID: M10283 - Name: Infections - Relevance: HIGH - As Found: Infection - ID: M6368 - Name: Communicable Diseases - Relevance: HIGH - As Found: Infection - ID: M17685 - Name: Wounds and Injuries - Relevance: LOW - As Found: Unknown - ID: M17684 - Name: Wound Infection - Relevance: HIGH - As Found: Wound Infection - ID: M16310 - Name: Surgical Wound Infection - Relevance: HIGH - As Found: Wound Infection, Surgical - ID: M1112 - Name: Surgical Wound - Relevance: LOW - As Found: Unknown - ID: M22700 - Name: Disease Attributes - Relevance: LOW - As Found: Unknown - ID: M14065 - Name: Postoperative Complications - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000007239 - Term: Infections - ID: D000003141 - Term: Communicable Diseases - ID: D000013530 - Term: Surgical Wound Infection - ID: D000014946 - Term: Wound Infection ### Intervention Browse Module - Browse Branches - Abbrev: Infe - Name: Anti-Infective Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M4222 - Name: Anti-Bacterial Agents - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00257179 **Brief Title:** The Serum Tissue Factor Level in Lung Cancer Patients as a Prognostic Factor #### Organization Study ID Info **ID:** 9461700609 #### Organization **Class:** OTHER **Full Name:** National Taiwan University Hospital ### Status Module #### Expanded Access Info **Last Known Status:** RECRUITING #### Last Update Post Date **Date:** 2006-03-14 **Type:** ESTIMATED **Last Update Submit Date:** 2006-03-13 **Overall Status:** UNKNOWN #### Start Date **Date:** 2005-06 **Status Verified Date:** 2005-06 #### Study First Post Date **Date:** 2005-11-22 **Type:** ESTIMATED **Study First Submit Date:** 2005-11-21 **Study First Submit QC Date:** 2005-11-21 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** National Taiwan University Hospital ### Description Module **Brief Summary:** This study uses serum tissue factor and tissue factor inhibitor and factor VII to monitor the pre-coagulation status in lung cancer patients and to correlate the pre-coagulation status with clinical staging and prognosis. **Detailed Description:** The staging of lung cancer was according to tumor size, involvement of lymph node and metastatic status. But there is a different prognosis in cancer patients of the same stage. The coagulation status of cancer patients was considered as an important possible prognostic factor. So in this study, we want to evaluate patients' coagulation status and find the relation of coagulation status and cancer status. We thus propose a prospective study using coagulation factors in order to search for the relationship between cancer stage and pre-coagulation status in Taiwanese lung cancer patients. We will also evaluate the potential use of tissue factor as a prognosis predictor in lung cancer patients. ### Conditions Module **Conditions:** - Lung Cancer **Keywords:** - Tissue factor - Lung cancer - Tissue factor protein inhibitor - Factor VII - Factor X ### Design Module #### Design Info **Observational Model:** NATURAL_HISTORY **Time Perspective:** OTHER #### Enrollment Info **Count:** 200 **Study Type:** OBSERVATIONAL ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Patients with newly-diagnosed lung cancer * Serum from cancer-free healthy volunteers Exclusion Criteria: * Chronic renal failure or end-stage renal disease \[ESRD\] (creatinine \[Cr\] \> 2 ) * Hyperlipidemia on statin therapy * Acute myocardial infarction * Tapal or Plavix use * Active thromboembolic event * Severe liver disease (\> child B) **Minimum Age:** 16 Years **Sex:** ALL **Standard Ages:** - CHILD - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Chong-Jen Yu, M.D., Ph.D. **Phone:** 886-2-2356-2905 **Role:** CONTACT #### Locations **Location 1:** **City:** Taipei **Contacts:** ***Contact 1:*** - **Name:** Chong-Jen Yu, M.D., Ph.D. - **Phone:** 886-2-2356-2905 - **Role:** CONTACT **Country:** Taiwan **Facility:** National Taiwan University Hospital **Status:** RECRUITING #### Overall Officials **Official 1:** **Affiliation:** National Taiwan University Hospital **Name:** Chong-Jen Yu, M.D., Ph.D. **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000012142 - Term: Respiratory Tract Neoplasms - ID: D000013899 - Term: Thoracic Neoplasms - ID: D000009371 - Term: Neoplasms by Site - ID: D000009369 - Term: Neoplasms - ID: D000008171 - Term: Lung Diseases - ID: D000012140 - Term: Respiratory Tract Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC08 - Name: Respiratory Tract (Lung and Bronchial) Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M11172 - Name: Lung Neoplasms - Relevance: HIGH - As Found: Lung Cancer - ID: M14979 - Name: Respiratory Tract Neoplasms - Relevance: LOW - As Found: Unknown - ID: M16658 - Name: Thoracic Neoplasms - Relevance: LOW - As Found: Unknown - ID: M11168 - Name: Lung Diseases - Relevance: LOW - As Found: Unknown - ID: M14977 - Name: Respiratory Tract Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000008175 - Term: Lung Neoplasms ### Intervention Browse Module - Browse Branches - Abbrev: Coag - Name: Coagulants - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M16684 - Name: Thromboplastin - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05869279 **Brief Title:** Allogeneic CARCIK-CD19 in Adults/Pediatric B-cell NHL or Chronic Lymphocytic Leukemia **Official Title:** Phase I/II Trial to Determine the in Vivo Engraftment, Safety and Clinical Activity of Allogeneic CIK Cells Transduced With a Transposon CD19-chimeric Antigen Receptor (CARCIK-CD19) Gene in Adult and Pediatric Patients With Relapsed/Refractory B-cell Non-Hodgkin Lymphoma #### Organization Study ID Info **ID:** FT04CARCIK #### Organization **Class:** OTHER **Full Name:** Fondazione Matilde Tettamanti Menotti De Marchi Onlus ### Status Module #### Completion Date **Date:** 2027-09-01 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-03 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-02 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2026-09-01 **Type:** ESTIMATED #### Start Date **Date:** 2023-12-01 **Type:** ACTUAL **Status Verified Date:** 2023-05 #### Study First Post Date **Date:** 2023-05-22 **Type:** ACTUAL **Study First Submit Date:** 2023-05-03 **Study First Submit QC Date:** 2023-05-19 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Fondazione Matilde Tettamanti Menotti De Marchi Onlus #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** This is a single arm, open-label, multi-center, phase I/II study to determine the engraftment, safety and clinical activity of allogeneic CARCIK-CD19 cells in adult and pediatric patients with relapsed/refractory mature B-cell neoplasia expected to express CD19 i.e. B-cell NHL and CLL. CARCIK-CD19 will be produced from the peripheral blood of an at least haploidentical familial donor. ### Conditions Module **Conditions:** - B-cell NHL - CLL ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 29 **Type:** ESTIMATED **Phases:** - PHASE1 - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Gene therapy product composed of T lymphocytes differentiated according CIK-cell protocol (leading to production of CD3+ cells also expressing CD8 and to a lesser extent CD4 or CD56) that have been genetically modified to express CAR with specificity for targeting CD19 molecule expressed on the surface of B cells. The CARCIK-CD19 contains cells that express the anti-CD19 single chain fragment variable (scFV) linked to an intracellular signaling domain comprising the TCR CD3 ζ chain and tandem costimulatory domains as the CD28 and OX40 (CD19-CD28OX40). **Intervention Names:** - Biological: CARCIK-CD19 **Label:** CARCIK-CD19 **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - CARCIK-CD19 **Description:** allogeneic cytokine induced killer cells transduced with a transposon CD19-chimeric antigen receptor (CARCIK-CD19) gene **Name:** CARCIK-CD19 **Type:** BIOLOGICAL ### Outcomes Module #### Primary Outcomes **Description:** Dose Limiting Toxicity **Measure:** Dose Limiting Toxicity **Time Frame:** 28 day after CARCIK infusion **Description:** overall response rate (complete + partial remission) **Measure:** overall response rate **Time Frame:** month 3 after CARCIK-CD19 infusion #### Secondary Outcomes **Description:** Incidence of Adverse event **Measure:** Adverse event (AE) **Time Frame:** up to 12 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: criteria apply: 1. Able and willing to provide written informed consent and to comply with the study protocol according to International Conference on Harmonization (ICH) and local regulations. 2. Ineligibility to commercially available CAR-T cells 3. Age limits: children (1-17 years old) and adults (≥18 years old) 4. Availability of an at least haploidentical (i.e. 4/8 HLA matched by allele typing) familial donor willing to and eligible for blood donation 5. Histologically-confirmed mature B-cell neoplasia (NHL), according to according to WHO 2021 classification: • Eligible histologies include: indolent \[follicular lymphoma (FL) or marginal zone lymphoma (MZL) nodal; extra-nodal; or splenic\] or aggressive \[diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma (PMBL), high-grade B cell lymphoma with MYC and BCL2 rearrangements (double-hit lymphoma), mantle cell lymphoma (MCL), including transformed B-cell NHL\], CLL or lymphocytic lymphoma (LL). high-grade B cell lymphoma (HGBCL) NOS. Additional histologies including Burkitt lymphoma and Richter syndrome will be considered upon review with Sponsor. 6. Relapsed after or refractory to at least two prior lines of treatment, and no available treatment options that are expected to prolong survival (e.g. chemotherapy or high-dose chemotherapy/stem cell transplantation, commercially available CART cell therapy or other standard treatment) or patients refusing such treatments 7. At least one measurable target lesion, measurable as defined by Lugano 2014 classification (nodal: \> 1.5 cm longest transverse diameter; extra-nodal: \> 1 cm longest transverse diameter) by computerized tomography (CT) scan or presence of assessable disease (i.e. bone marrow or spleen) 8. Eastern Cooperative Oncology Group (ECOG) performance status equal to 2 or less for subject ≥ 16 years of age, or Lansky \>50 for subjects \< 16 years of age 9. Adequate cardiac and pulmonary function: ejection fraction (EF) by echo or MUGA \>40% and radial artery (RA) oxygen saturation \>92%. 10. Life expectancy (in the opinion of the Investigator) of \> 12 weeks 11. Adequate liver function: * Total bilirubin ≤ 2.0x ULN (≤ 3x ULN in patients with Gilbert's syndrome or documented liver involvement) * AST (aspartate aminotransferase) /ALT (alanine aminotransferase) 3x ULN or 5x for patients with evidence of liver involvement with lymphoma 12. Adequate bone marrow function to receive lymphodepleting chemotherapy at investigator judgment. 13. Adequate renal function: creatinine ≤1.5x ULN or creatinine clearance (CrCl) calculated by Cockcroft-Gault formula of ≥50 mL/min for adult patients in whom, in the Investigator's judgment, serum creatinine levels do not adequately reflect renal function. For children, CrCl will be calculated by local institutional standard. 14. Females of childbearing potential (FCBP) subjects must: * Have a negative pregnancy test as verified by the local investigator * Either commit to true abstinence from heterosexual contact or agree to use, and be able to comply with, effective contraception without interruption from screening until at least 12 months following CARCIK-CD19 infusion and until CAR positive viable T cells are no longer present by quantitative polymerase chain reaction (qPCR) on two consecutive tests. * Contraception methods must include one highly effective method including: surgical female sterilization, use of oral (estrogen and progesterone), injected, or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS), or other forms of hormonal contraception that have comparable efficacy (failure rate \<1%) * Agree to abstain from breastfeeding during study participation and for at least 12 months following CARCIK-CD19 infusion and until CAR positive viable T cells are no longer present by quantitative polymerase chain reaction (qPCR) on two consecutive tests. 15. Male subjects must: * Practice true abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential for 12 months after following CARCIK-CD19 infusion and until CAR positive viable T cells are no longer present by quantitative polymerase chain reaction (qPCR) on two consecutive tests. Exclusion Criteria: 1. Patients with clinically significant active viral, bacterial or fungal infection or any major episode of infection requiring hospitalization or treatment with IV antibiotics (for IV antibiotics this pertains to completion of last course of antibiotic treatment) within 2 weeks prior to CARCIK-CD19 infusion. 2. Patients with an active infection with Hepatitis B. However, patients with a controlled (treated) hepatitis will be allowed if the all the following criteria are met: * Anti-viral therapy for hepatitis B virus (HBV) must be given for at least 1 month prior to time of informed consent; * HBV viral load must be \<2000 IU/mL (104 copies/mL) prior to time of informed consent; and * those on active HBV therapy with viral load \<2000 IU/mL (104 copies/mL) should stay on the same anti-viral therapy throughout study treatment 3. Patients with an active hepatitis C virus (HCV) infection. However, patients with successfully treated chronic HCV infection will be allowed if they show a sustained virologic response at 12 weeks (SVR12) or 24 weeks (SVR24), and if there is a 4-week period between achieving sustained viral response (SVR12 or SVR24) and time of informed consent. 4. Patients with a positive serologic test or a positive molecular PCR test for human immunodeficiency virus (HIV) are eligible if asymptomatic, well controlled by the HAART therapy and no medically significant active infection is present 5. Rapidly progressive disease that in the estimation of the investigator and sponsor could affect compliance with the protocol or interpretation of results 6. Active CNS lymphoma 7. Major surgery or significant traumatic injury 28 days prior to CARCIK-CD19 infusion (excluding biopsies) or anticipation of the need for major surgery during study treatment 8. Patients with another active invasive malignancy with a life expectancy of less than 3 years 9. Significant cardiovascular disease (such as New York Heart Association (NYHA) Class II cardiac disease, congestive heart failure, myocardial infarction or cerebrovascular accident within 30 days prior to CARCIK-CD19 infusion, unstable arrhythmias, or unstable angina) 10. Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results, including diabetes mellitus, history of relevant pulmonary disorders (bronchospasm, obstructive pulmonary disease) and known autoimmune diseases 11. Treatment with any other standard anti-cancer radiotherapy / chemotherapy including investigational therapy (defined as treatment for which there is currently no regulatory authority approved indication) within 2 weeks prior to CARCIK-CD19 infusion 12. Allogeneic or autologous Stem Cell Transplantation within 3 months prior to CARCIK-CD19 infusion, or Donor Lymphocytes (DLI) 13. Active GvHD Grades II-IV or extensive chronic Graft-versus-Host Disease (for patients who had previously been allotransplanted) 14. Prior treatment with CART cell therapy within 30 days before first study treatment administration (lymphodepletion) 15. Toxicities from prior anti-cancer therapy including immunotherapy that did not resolve to ≤ Grade 1 with the exception of alopecia, endocrinopathy managed with replacement therapy and stable vitiligo. 16. Ongoing corticosteroid use 25 mg/day (\> or 0.3 mg/kg for children) of prednisone or equivalent within 1 weeks prior to CARCIK-CD19 infusion 17. Administration of a live, attenuated vaccine within 4 weeks prior to CARCIK-CD19 infusion **Minimum Age:** 1 Year **Sex:** ALL **Standard Ages:** - CHILD - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Andrea Biondi, MD **Phone:** +39039233 **Phone Ext:** 6816 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Alessandro Rambaldi, MD **Phone:** +39035267 **Phone Ext:** 3684 **Role:** CONTACT #### Locations **Location 1:** **City:** Bergamo **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Alessandro Rambaldi, MD - **Role:** CONTACT ***Contact 2:*** - **Email:** [email protected] - **Name:** Federico Lussana, MD - **Role:** CONTACT **Country:** Italy **Facility:** Ospedale Papa Giovanni XXIII **State:** BG **Status:** RECRUITING **Zip:** 24127 #### Overall Officials **Official 1:** **Affiliation:** IRCCS San Gerardo dei Tintori **Name:** Andrea Biondi, MD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC15 - Name: Blood and Lymph Conditions - Abbrev: All - Name: All Conditions - Abbrev: BC20 - Name: Immune System Diseases - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M10945 - Name: Leukemia - Relevance: LOW - As Found: Unknown - ID: M10951 - Name: Leukemia, Lymphoid - Relevance: LOW - As Found: Unknown - ID: M18116 - Name: Leukemia, Lymphocytic, Chronic, B-Cell - Relevance: LOW - As Found: Unknown - ID: M11220 - Name: Lymphoma - Relevance: LOW - As Found: Unknown - ID: M18828 - Name: Lymphoma, B-Cell - Relevance: LOW - As Found: Unknown - ID: T1308 - Name: Chronic Lymphocytic Leukemia - Relevance: LOW - As Found: Unknown - ID: T1303 - Name: Chronic Graft Versus Host Disease - Relevance: LOW - As Found: Unknown - ID: T3543 - Name: Lymphosarcoma - Relevance: LOW - As Found: Unknown - ID: T640 - Name: B-cell Lymphoma - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05450679 **Brief Title:** Cervical Paraspinal Muscle Twitching and Cervical Facet Radiofrequency Ablation Outcomes **Official Title:** The Predictive Value of Cervical Paraspinal Muscle Twitching During Motor Stimulation Testing on Cervical Facet Joint Radiofrequency Ablation Outcomes #### Organization Study ID Info **ID:** IRB00323880 #### Organization **Class:** OTHER **Full Name:** Johns Hopkins University ### Status Module #### Completion Date **Date:** 2026-02-01 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2023-09-13 **Type:** ACTUAL **Last Update Submit Date:** 2023-09-11 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2025-08-01 **Type:** ESTIMATED #### Start Date **Date:** 2022-09-13 **Type:** ACTUAL **Status Verified Date:** 2023-09 #### Study First Post Date **Date:** 2022-07-11 **Type:** ACTUAL **Study First Submit Date:** 2022-07-05 **Study First Submit QC Date:** 2022-07-05 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Johns Hopkins University #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** The investigators aim to determine whether cervical paravertebral muscle twitching during motor testing as part of performing cervical RFAs is associated with a greater likelihood of treatment success, and greater magnitude or duration of analgesia. The investigators propose a straightforward grading scale based on visual and tactile information readily available during RFA procedures as part of routine practice (per radiofrequency electrode: 0 = no twitches palpated or observed; 1 = twitches palpated but not observed; 2 = twitches palpated and observed at 1-2 levels; 3= twitches palpated and observed at \>2 levels). If a higher weighted score (total score divided by number of radiofrequency lesion sites) correlates with a greater likelihood of treatment success, or magnitude or duration of analgesia following cervical RFA, cervical paraspinal muscle twitching may serve as a readily obtainable prognostic factor (marker) for effectiveness. **Detailed Description:** Approximately 60 patients with cervical facet arthropathy who are undergoing cervical radiofrequency ablation (RFA) will be recruited for this study. Only patients who have already been deemed candidates by their primary pain physician for cervical RFA (e.g. \> 50% relief from a diagnostic cervical medial branch block) will be recruited. During the cervical RFA procedure, all patients will undergo sensory and motor stimulation testing prior to receiving radiofrequency lesioning, which is a standard and recommended practice. The investigators will align the electrodes to optimize sensory testing. During the motor stimulation testing step, the pain physicians performing the procedure (e.g. attending, fellows, residents, etc.) will assess the presence or absence of cervical paraspinal muscle twitching by using a standardized grading scale (per radiofrequency electrode: 0 = no twitches observed or palpated; 1 = twitches palpated but not observed; 2 = twitches observed and palpated at 1-2 levels; 3 = twitches observed at \> 2 levels). A total score and a weighted score (total score divided by the number of radiofrequency lesion sites), will be recorded for each patient, and the RFA procedure will be completed per usual practice. The interventional procedure used in this study (radiofrequency ablation) will be performed in the usual manner and as per "standard of care." The use of the grading scale described above to assess the presence/absence and magnitude of cervical paraspinal muscle twitching will be unique to this research study. The investigators will also obtain the following data immediately pre-procedurally, from electronic health record review and also a standardized set of questionnaires provided to study participants: * Information routinely obtained as standard practice: age, sex, average and worst neck pain score over the past week on numeric rating scale (NRS), percent pain relief from diagnostic block, duration of pain, inciting event, MRI findings if available, obesity (defined as BMI \> 30), smoking, co-existing pain conditions, co-existing psychiatric conditions, and potential sources of secondary gain (e.g. worker's compensation claim, ongoing litigation, etc.) * Information obtained as part of the research study: Neck Disability Index (NDI) score, Athens Insomnia Scale (AIS) score, Hospital Anxiety and Depression Scale (HADS) scores. At a 1-month post-procedural follow-up timepoint, the investigators will obtain the following data, from electronic health record review and also a standardized set of questionnaires provided to study participants: * Information routinely obtained as standard practice: categorical binary outcome (positive outcome defined as \>/= 2-point decrease in average neck pain score coupled with PGIC score \>/= 5/7) analgesic medications and doses; status of medication reduction (yes or no); average and worst NRS pain score over the past week; description of any procedural complications * Information obtained as part of the research study: NDI, AIS, and HADS scores; Patient Global Impression of Change Scale (PGIC) score * Exiting the trial: patients may choose to exit the study at any time for any reason. A patient will exit the study to receive alternative care if the patient reports a PGIC score \<5 or \< 2-point reduction in average NRS pain score. This would indicate that the RFA treatment was unsuccessful. At a 3-month post-procedural follow-up timepoint, the investigators will obtain the following data, from electronic health record review and also a standardized set of questionnaires provided to study participants: * Information routinely obtained as standard practice: categorical binary outcome, analgesic medications and doses; status of medication reduction (yes or no); average and worst NRS pain score over the past week; description of any procedural complications * Information obtained as part of the research study: NDI, AIS, and HADS scores; Patient Global Impression of Change Scale (PGIC) score on 7-point Likert scale * Exiting the trial: patients may choose to exit the study at any time for any reason. A patient will exit the study to receive alternative treatment if the patient reports a PGIC score \<5 or \< 2-point reduction in average NRS pain score. This would indicate that the analgesic and functional benefit of the RFA procedure has now been exhausted. At a 6-month post-procedural follow-up timepoint, the investigators will obtain the following data, from electronic health record review and also a standardized set of questionnaires provided to study participants: * Information routinely obtained as standard practice: binary categorical outcome, analgesic medications and doses; status of medication reduction (yes or no); average and worst NRS pain score over the past week; description of any procedural complications * Information obtained as part of the research study: NDI, AIS, and HADS scores; Patient Global Impression of Change Scale (PGIC) score * Exiting the trial: All patients who remain in the study will exit at 6 months. ### Conditions Module **Conditions:** - Cervical Facet Joint Pain - Chronic Pain - Neck Pain **Keywords:** - facet arthropathy - cervicalgia - radiofrequency ablation ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 60 **Type:** ESTIMATED **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Only patients who have already been deemed candidates by their primary pain physician for cervical RFA will be recruited to the study. During the cervical RFA procedure, all patients will undergo sensory and motor stimulation testing prior to receiving radiofrequency lesioning, which is a standard and recommended practice. **Intervention Names:** - Procedure: Cervical Radiofrequency Ablation (RFA) **Label:** Cervical Radiofrequency Ablation (RFA)-treated group ### Interventions #### Intervention 1 **Arm Group Labels:** - Cervical Radiofrequency Ablation (RFA)-treated group **Description:** During the cervical RFA procedure, all patients will undergo sensory and motor stimulation testing prior to receiving radiofrequency lesioning, which is a standard and recommended practice. During the motor stimulation testing step, the pain physicians performing the procedure will assess the presence or absence of cervical paraspinal muscle twitching by using a standardized grading scale (per radiofrequency electrode: 0 = no twitches observed or palpated; 1 = twitches palpated but not observed; 2 = twitches observed and palpated at 1-2 levels; 3 = twitches observed at \> 2 levels). A total score and a weighted score (total score divided by the number of radiofrequency lesion sites), will be recorded for each patient, and the RFA procedure will be completed per usual practice. RFAs will be performed in the usual manner and as per "standard of care." Providers will not use any new or experimental devices to perform the RFA. **Name:** Cervical Radiofrequency Ablation (RFA) **Type:** PROCEDURE ### Outcomes Module #### Primary Outcomes **Description:** Definition of success: a \>/= 2-point decrease in average neck pain (measured over the past week) coupled with a score of \>/= 5/7 on a patient global impression of change (PGIC) scale where 1= "no change or worsened symptoms", 5= "moderately better, a slight but noticeable change", and 7= "a great deal better." **Measure:** Categorical number of participants with treatment success or failure **Time Frame:** 3 months #### Secondary Outcomes **Description:** Definition of success: a \>/= 2-point decrease in average neck pain (measured over the past week) coupled with a score of \>/= 5/7 on a patient global impression of change (PGIC) scale where 1= "no change or worsened symptoms", 5= "moderately better, a slight but noticeable change", and 7= "a great deal better." **Measure:** Categorical number of participants with treatment success or failure **Time Frame:** 1 month **Description:** Definition of success: a \>/= 2-point decrease in average neck pain (measured over the past week) coupled with a score of \>/= 5/7 on a patient global impression of change (PGIC) scale where 1= "no change or worsened symptoms", 5= "moderately better, a slight but noticeable change", and 7= "a great deal better." **Measure:** Categorical number of participants with treatment success or failure **Time Frame:** 6 months **Description:** Pain scores measured on 0-10 numeric rating scale (NRS) **Measure:** Average neck pain score **Time Frame:** 1 month **Description:** Pain scores measured on 0-10 numeric rating scale (NRS) **Measure:** Average neck pain score **Time Frame:** 3 months **Description:** Pain scores measured on 0-10 numeric rating scale (NRS) **Measure:** Average neck pain score **Time Frame:** 6 months **Description:** Pain scores measured on 0-10 numeric rating scale (NRS) **Measure:** Worst neck pain score **Time Frame:** 1 month **Description:** Pain scores measured on 0-10 numeric rating scale (NRS) **Measure:** Worst neck pain score **Time Frame:** 3 months **Description:** Pain scores measured on 0-10 numeric rating scale (NRS) **Measure:** Worst neck pain score **Time Frame:** 6 months **Description:** Neck disability index (NDI) score (0-100%, higher numbers indicate poorer function) **Measure:** Functional outcome as measured using the Neck disability index (NDI) **Time Frame:** 1 month **Description:** Neck disability index (NDI) score (0-100%, higher numbers indicate poorer function) **Measure:** Functional outcome as measured using the Neck disability index (NDI) **Time Frame:** 3 months **Description:** Neck disability index (NDI) score (0-100%, higher numbers indicate poorer function) **Measure:** Functional outcome as measured using the Neck disability index (NDI) **Time Frame:** 6 months **Description:** Athens Insomnia Scale (AIS) score (0-24, with higher scores indicate greater dysfunction) **Measure:** Sleep quality as assessed by the Athens Insomnia Scale (AIS) **Time Frame:** 1 month **Description:** Athens Insomnia Scale (AIS) score (0-24, with higher scores indicate greater dysfunction) **Measure:** Sleep quality as assessed by the Athens Insomnia Scale (AIS) **Time Frame:** 3 months **Description:** Athens Insomnia Scale (AIS) score (0-24, with higher scores indicate greater dysfunction) **Measure:** Sleep quality as assessed by the Athens Insomnia Scale (AIS) **Time Frame:** 6 months **Description:** Hospital anxiety and depression scale (HADS) score (Depression and anxiety scored from 0-21 with higher scores indicating greater depression and anxiety) **Measure:** Mood and anxiety as assessed by the Hospital anxiety and depression scale (HADS) **Time Frame:** 1 month **Description:** Hospital anxiety and depression scale (HADS) score (Depression and anxiety scored from 0-21 with higher scores indicating greater depression and anxiety) **Measure:** Mood and anxiety as assessed by the Hospital anxiety and depression scale **Time Frame:** 3 months **Description:** Hospital anxiety and depression scale (HADS) score (Depression and anxiety scored from 0-21 with higher scores indicating greater depression and anxiety) **Measure:** Mood and anxiety as assessed by the Hospital anxiety and depression scale **Time Frame:** 6 months **Description:** Defined as cessation of a non-opioid analgesic or \> 20% decrease in pre-existing opioid consumption **Measure:** Medication reduction as assessed by follow-up visit or telephone call, and Prescription Drug Monitoring Program data review **Time Frame:** 1 month **Description:** Defined as cessation of a non-opioid analgesic or \> 20% decrease in pre-existing opioid consumption **Measure:** Medication reduction as assessed by follow-up visit or telephone call, and Prescription Drug Monitoring Program data review **Time Frame:** 3 months **Description:** Defined as cessation of a non-opioid analgesic or \> 20% decrease in pre-existing opioid consumption **Measure:** Medication reduction as assessed by follow-up visit or telephone call, and Prescription Drug Monitoring Program data review **Time Frame:** 6 months **Description:** Any reported adverse events or complications directly related to the cervical radiofrequency ablation (RFA) procedure. **Measure:** Procedural complications **Time Frame:** Any time point up to the 6-month post-procedural follow-up visit or up to the patient exiting the trial (whichever occurs first) ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Age 18 years or older * Cervical facet arthropathy based on history and physical exam (e.g. axial cervical neck pain, paraspinal tenderness, no pain referral below the ipsilateral shoulder) * Radiologic evidence of cervical pathology consistent with symptoms if MRI is available * Pain duration of greater than 3 months * Obtained 50% or greater pain relief from at least 1 diagnostic cervical medial branch block of the identical medial branch nerves targeted for RFA Exclusion Criteria: * Untreated coagulopathy * Signs or symptoms of cervical myelopathy * Signs or symptoms of cervical radiculitis/radiculopathy * Allergic reactions to local anesthetics * Serious psychiatric disorder (e.g. uncontrolled or refractory depression) that might preclude optimal outcome * Poorly controlled medical condition (e.g. pacemaker that cannot be switched off, unstable angina) * Pregnancy **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Only patients who have already been deemed candidates by their primary pain physician for a cervical radiofrequency ablation (RFA) (e.g. \>/= 50% relief from a diagnostic cervical medial branch block) will be recruited. ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Eric Wang, MD **Phone:** 410-955-7246 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Steven Cohen, MD **Phone:** 410-955-7246 **Role:** CONTACT #### Locations **Location 1:** **City:** Baltimore **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Eric Wang, MD - **Phone:** 410-955-7246 - **Role:** CONTACT ***Contact 2:*** - **Email:** [email protected] - **Name:** Steven Cohen, MD - **Phone:** 410-955-7246 - **Role:** CONTACT ***Contact 3:*** - **Name:** Eric Wang, MD - **Role:** PRINCIPAL_INVESTIGATOR ***Contact 4:*** - **Name:** Steven Cohen, MD - **Role:** SUB_INVESTIGATOR ***Contact 5:*** - **Name:** Michael Erdek - **Role:** SUB_INVESTIGATOR **Country:** United States **Facility:** Johns Hopkins Hospital **State:** Maryland **Status:** RECRUITING **Zip:** 21287 #### Overall Officials **Official 1:** **Affiliation:** Johns Hopkins University **Name:** Eric Wang, MD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **Description:** There is not a plan to make individual participant data available. **IPD Sharing:** NO ### References Module #### References **Citation:** GBD 2015 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet. 2016 Oct 8;388(10053):1545-1602. doi: 10.1016/S0140-6736(16)31678-6. Erratum In: Lancet. 2017 Jan 7;389(10064):e1. **PMID:** 27733282 **Citation:** Aprill C, Bogduk N. The prevalence of cervical zygapophyseal joint pain. A first approximation. Spine (Phila Pa 1976). 1992 Jul;17(7):744-7. doi: 10.1097/00007632-199207000-00003. **PMID:** 1502636 **Citation:** Manchikanti L, Singh V, Rivera J, Pampati V. Prevalence of cervical facet joint pain in chronic neck pain. Pain Physician. 2002 Jul;5(3):243-9. Erratum In: Pain Physician. 2002 Oct;5(4):445. **PMID:** 16902649 **Citation:** Schaerer JP. Radiofrequency facet rhizotomy in the treatment of chronic neck and low back pain. Int Surg. 1978 Sep-Dec;63(6):53-9. **PMID:** 155664 **Citation:** Lord SM, Barnsley L, Wallis BJ, McDonald GJ, Bogduk N. Percutaneous radio-frequency neurotomy for chronic cervical zygapophyseal-joint pain. N Engl J Med. 1996 Dec 5;335(23):1721-6. doi: 10.1056/NEJM199612053352302. **PMID:** 8929263 **Citation:** Huygen F, Kallewaard JW, van Tulder M, Van Boxem K, Vissers K, van Kleef M, Van Zundert J. "Evidence-Based Interventional Pain Medicine According to Clinical Diagnoses": Update 2018. Pain Pract. 2019 Jul;19(6):664-675. doi: 10.1111/papr.12786. Epub 2019 May 2. **PMID:** 30957944 **Citation:** Hurley RW, Adams MCB, Barad M, Bhaskar A, Bhatia A, Chadwick A, Deer TR, Hah J, Hooten WM, Kissoon NR, Lee DW, Mccormick Z, Moon JY, Narouze S, Provenzano DA, Schneider BJ, van Eerd M, Van Zundert J, Wallace MS, Wilson SM, Zhao Z, Cohen SP. Consensus practice guidelines on interventions for cervical spine (facet) joint pain from a multispecialty international working group. Reg Anesth Pain Med. 2022 Jan;47(1):3-59. doi: 10.1136/rapm-2021-103031. Epub 2021 Nov 11. **PMID:** 34764220 **Citation:** Lord SM, McDonald GJ, Bogduk N. Percutaneous Radiofrequency Neurotomy of the Cervical Medial Branches. Neurosurgery Quarterly. 1998;8(4):288-308. doi:10.1097/00013414-199812000-00004 **Citation:** MacVicar J, Borowczyk JM, MacVicar AM, Loughnan BM, Bogduk N. Cervical medial branch radiofrequency neurotomy in New Zealand. Pain Med. 2012 May;13(5):647-54. doi: 10.1111/j.1526-4637.2012.01351.x. Epub 2012 Mar 28. **PMID:** 22458772 **Citation:** Manchikanti L, Sanapati MR, Pampati V, Soin A, Atluri S, Kaye AD, Subramanian J, Hirsch JA. Update of Utilization Patterns of Facet Joint Interventions in Managing Spinal Pain from 2000 to 2018 in the US Fee-for-Service Medicare Population. Pain Physician. 2020 Mar;23(2):E133-E149. **PMID:** 32214289 **Citation:** International Spine Intervention Society. ISIS Practice Guidelines for Spinal Diagnostic and Treatment Procedures: 2nd Edition.; 2013. https://books.google.com/books/about/ISIS_Practice_Guidelines_for_Spinal_Diag.html?hl=&id=ikWhoAEACAAJ **Citation:** Cohen SP, Strassels SA, Kurihara C, Lesnick IK, Hanling SR, Griffith SR, Buckenmaier CC 3rd, Nguyen C. Does sensory stimulation threshold affect lumbar facet radiofrequency denervation outcomes? A prospective clinical correlational study. Anesth Analg. 2011 Nov;113(5):1233-41. doi: 10.1213/ANE.0b013e31822dd379. Epub 2011 Sep 14. **PMID:** 21918166 **Citation:** Dreyfuss P, Halbrook B, Pauza K, Joshi A, McLarty J, Bogduk N. Efficacy and validity of radiofrequency neurotomy for chronic lumbar zygapophysial joint pain. Spine (Phila Pa 1976). 2000 May 15;25(10):1270-7. doi: 10.1097/00007632-200005150-00012. **PMID:** 10806505 **Citation:** Koh JC, Kim DH, Lee YW, Choi JB, Ha DH, An JW. Relationship between paravertebral muscle twitching and long-term effects of radiofrequency medial branch neurotomy. Korean J Pain. 2017 Oct;30(4):296-303. doi: 10.3344/kjp.2017.30.4.296. Epub 2017 Sep 29. **PMID:** 29123625 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000010146 - Term: Pain - ID: D000009461 - Term: Neurologic Manifestations - ID: D000007592 - Term: Joint Diseases - ID: D000009140 - Term: Musculoskeletal Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC05 - Name: Musculoskeletal Diseases - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M29442 - Name: Chronic Pain - Relevance: HIGH - As Found: Chronic Pain - ID: M13066 - Name: Pain - Relevance: LOW - As Found: Unknown - ID: M10621 - Name: Joint Diseases - Relevance: LOW - As Found: Unknown - ID: M21485 - Name: Neck Pain - Relevance: HIGH - As Found: Neck Pain - ID: M20833 - Name: Arthralgia - Relevance: HIGH - As Found: Joint Pain - ID: M8350 - Name: Fasciculation - Relevance: LOW - As Found: Unknown - ID: M12404 - Name: Neurologic Manifestations - Relevance: LOW - As Found: Unknown - ID: M12097 - Name: Musculoskeletal Diseases - Relevance: LOW - As Found: Unknown - ID: T1303 - Name: Chronic Graft Versus Host Disease - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000018771 - Term: Arthralgia - ID: D000059350 - Term: Chronic Pain - ID: D000019547 - Term: Neck Pain ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT06033079 **Acronym:** ICE-CAP2 **Brief Title:** Improving CarE for Community Acquired Pneumonia 1 (ICE-CAP2) **Official Title:** Improving CarE for Community Acquired Pneumonia 1 (ICE-CAP1): Prognostic Decision Support #### Organization Study ID Info **ID:** R01AI125642pt2 #### Organization **Class:** OTHER **Full Name:** Vanderbilt University Medical Center #### Secondary ID Infos **ID:** R01AI125642 **Link:** https://reporter.nih.gov/quickSearch/R01AI125642 **Type:** NIH ### Status Module #### Completion Date **Date:** 2022-11-30 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2023-12-05 **Type:** ACTUAL **Last Update Submit Date:** 2023-11-13 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2022-11-30 **Type:** ACTUAL #### Results First Post Date **Date:** 2023-12-05 **Type:** ACTUAL **Results First Submit Date:** 2023-10-19 **Results First Submit QC Date:** 2023-11-13 #### Start Date **Date:** 2020-11-20 **Type:** ACTUAL **Status Verified Date:** 2023-11 #### Study First Post Date **Date:** 2023-09-13 **Type:** ACTUAL **Study First Submit Date:** 2023-08-23 **Study First Submit QC Date:** 2023-09-07 ### Sponsor Collaborators Module #### Collaborators **Class:** NIH **Name:** National Institute of Allergy and Infectious Diseases (NIAID) **Class:** OTHER **Name:** University of Pittsburgh Medical Center #### Lead Sponsor **Class:** OTHER **Name:** Vanderbilt University Medical Center #### Responsible Party **Investigator Affiliation:** Vanderbilt University Medical Center **Investigator Full Name:** Derek Williams **Investigator Title:** Associate Professor of Pediatrics **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** Children with pneumonia presenting to the emergency department at Monroe Carell Jr. Children's Hospital at Vanderbilt or Children's Hospital of Pittsburgh will be potentially eligible for study. During intervention periods, providers caring for enrolled children will be presented with a detailed decision support strategy that emphasizes management in accordance with national guideline recommendations. The anticipated study duration is 24 months and, as this study does not include direct contact with enrolled subjects, there is no anticipated follow up. **Detailed Description:** Pneumonia is the most common serious infection in childhood. In the United States (US), pneumonia accounts for 1-4% of all emergency department (ED) visits in children (3-28 per 1,000 US children per year) and ranks among the top 3 reasons for pediatric hospitalization with \>100,000 hospitalizations per year (15-22 per 100,000 US children per year). Pneumonia also accounts for more days of antibiotic use in US children's hospitals than any other condition. Emergency care for childhood pneumonia, including hospitalization rates, varies widely across the nation. A study examining hospital admission rates at 35 US children's hospitals from 2009-12 showed marked differences in severity-adjusted pneumonia hospital admission rates (median 31%; range 19-69%). Provider preferences and inaccurate risk perceptions contribute to these differences in hospitalization rates. Within the Intermountain Healthcare System in Utah, Dean et al. exposed large differences in admission rates (range 38-79%) among 18 individual ED providers providing care for \>2,000 adults with pneumonia. Differences were not explained by patient characteristics or illness severity and higher rates of hospitalization did not reduce hospital readmissions or mortality. In another multicenter study of 472 adults with pneumonia at \<4% risk of 30-day mortality estimated using objective severity scores, providers overestimated the risk of mortality in 5% of outpatients (range across institutions 0-12%) and 41% of inpatients (range across institutions 36-48%). These studies suggest that risk perceptions are often inaccurate, and potentially lead to unnecessary or prolonged hospitalizations and intensive therapies. Similar studies have not been performed in children because no valid prognostic tools exist to reliably predict pediatric pneumonia severity. ### Conditions Module **Conditions:** - Pneumonia Childhood ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** We will conduct a randomized controlled trial comparing our prognostic tool (intervention arm) to usual care (control arm) over a period of 24 months. Randomization will occur at the patient level. Allocation to intervention or control will be based on medical record number (even vs. odd) or similar strategy and will be assigned automatically once a provider confirms the diagnosis of pneumonia. Importantly, all standard of care treatment options will be available and decision-making will not be restricted in any way in either group. ##### Masking Info **Masking:** NONE **Primary Purpose:** HEALTH_SERVICES_RESEARCH #### Enrollment Info **Count:** 536 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** The prognostic decision support application will be provided to those randomized to the intervention arm. Due to the nature of the intervention, blinding of treating providers will not be possible. All children will receive usual care and all treatment decisions will be made by the clinical providers and will not be restricted or altered in any way. **Intervention Names:** - Behavioral: Clinical Decision Support **Label:** CDS Intervention **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** No experimental decision support will be provided to those randomized to the control arm. All children will receive usual care and treatment will not be restricted or altered in any way by the study. **Label:** Control **Type:** NO_INTERVENTION ### Interventions #### Intervention 1 **Arm Group Labels:** - CDS Intervention **Description:** For enrolled subjects assigned to the decision support arm, providers will receive prognostic information derived using our previously validated and best performing model. The decision support application will automatically calculate predicted risk for moderate (intensive care) and severe (respiratory failure or shock) outcomes using the parameters derived from the prognostic tool's regression equation. Outcome probabilities will be integrated into the decision support application and displayed within the EHR. **Name:** Clinical Decision Support **Type:** BEHAVIORAL ### Outcomes Module #### Other Outcomes **Description:** This outcome reports the number of participants who died as a result of their pneumonia-related illness within 30 days discharge from the index encounter. **Measure:** Death **Time Frame:** 30 days #### Primary Outcomes **Description:** Number of participants who were disposed from the ED and experienced a change in level of care within 24 hours unless objective criteria present. Appropriate dispositions were defined as follows. 1. Disposition: Discharged to home, Appropriate if no subsequent hospitalization within 24h 2. Disposition: Inpatient Ward, Appropriate if hospital length of stay (LOS) ≥ 24h OR hospital LOS \< 24h with objective criteria for admission present (eg, need for supplemental oxygen) PLUS no transfer to intensive care (ICU) within 24h 3. Disposition: ICU, ICU LOS ≥ 24h OR ICU LOS \< 24h with objective criteria for ICU admission present (eg, respiratory failure) Encounters NOT meeting these criteria were defined as Inappropriate. **Measure:** Inappropriate Disposition **Time Frame:** 24 Hours #### Secondary Outcomes **Description:** This outcome reports the total number of participants who were initially discharged from the ED, admitted to the inpatient ward, or admitted to the ICU. **Measure:** Overall Site-of-care Disposition **Time Frame:** ED Disposition **Description:** This outcome reports the number of participants who presented to the ED for care within 72 hours of the index discharge. **Measure:** ED Revisits (72 Hours) **Time Frame:** 72 hours **Description:** This outcome reports the number of participants who presented to the ED for care within 7 days of the index discharge. **Measure:** ED Revisits (7 Days) **Time Frame:** 7 days **Description:** This outcome reports the number of participants who were readmitted to the hospital for pneumonia-related illness within 72 hours of the index discharge. **Measure:** Rehospitalizations (72 Hours) **Time Frame:** 72 hours **Description:** This outcome reports the number of participants who were readmitted to the hospital for pneumonia-related illness within 7 days of the index discharge. **Measure:** Rehospitalizations (7 Days) **Time Frame:** 7 days ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Six months to \<18 years of age 2. Radiographic evidence of pneumonia in ED 3. Provider-confirmed diagnosis of pneumonia Exclusion Criteria: 1. Children with tracheostomy, cystic fibrosis, immunosuppression 2. Inter-hospital transfers 3. Hospitalization within preceding 7 days 4. Previously enrolled within preceding 28 days 5. Provider preference for any reason **Maximum Age:** 18 Years **Minimum Age:** 6 Months **Sex:** ALL **Standard Ages:** - CHILD - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Nashville **Country:** United States **Facility:** Monroe Carell Jr. Children's Hospital - Vanderbilt University Medical Center **State:** Tennessee **Zip:** 37232 #### Overall Officials **Official 1:** **Affiliation:** Vanderbilt University Medical Center **Name:** Derek J Williams, MD, MPH **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Document Section ### Large Document Module #### Large Docs - Date: 2022-10-26 - Filename: Prot_000.pdf - Has ICF: False - Has Protocol: True - Has SAP: False - Label: Study Protocol - Size: 353554 - Type Abbrev: Prot - Upload Date: 2023-08-23T15:01 - Date: 2022-10-26 - Filename: SAP_001.pdf - Has ICF: False - Has Protocol: False - Has SAP: True - Label: Statistical Analysis Plan - Size: 356050 - Type Abbrev: SAP - Upload Date: 2023-08-23T15:02 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000012141 - Term: Respiratory Tract Infections - ID: D000007239 - Term: Infections - ID: D000008171 - Term: Lung Diseases - ID: D000012140 - Term: Respiratory Tract Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC01 - Name: Infections - Abbrev: BC08 - Name: Respiratory Tract (Lung and Bronchial) Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M13904 - Name: Pneumonia - Relevance: HIGH - As Found: Pneumonia - ID: M10283 - Name: Infections - Relevance: LOW - As Found: Unknown - ID: M6368 - Name: Communicable Diseases - Relevance: LOW - As Found: Unknown - ID: M14978 - Name: Respiratory Tract Infections - Relevance: LOW - As Found: Unknown - ID: M11168 - Name: Lung Diseases - Relevance: LOW - As Found: Unknown - ID: M14977 - Name: Respiratory Tract Diseases - Relevance: LOW - As Found: Unknown - ID: T3897 - Name: Muckle-Wells Syndrome - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000011014 - Term: Pneumonia ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module #### Event Groups **Group ID:** EG000 **Title:** Control **Deaths Num Affected:** 3 **Deaths Num At Risk:** 269 **Description:** No experimental decision support will be provided to those randomized to the control arm. All children will receive usual care and treatment will not be restricted or altered in any way by the study. **ID:** EG000 **Other Num at Risk:** 269 **Serious Number At Risk:** 269 **Title:** Control **Group ID:** EG001 **Title:** CDS Intervention **Deaths Num Affected:** 4 **Deaths Num At Risk:** 267 **Description:** The prognostic decision support application will be provided to those randomized to the intervention arm. Due to the nature of the intervention, blinding of treating providers will not be possible. All children will receive usual care and all treatment decisions will be made by the clinical providers and will not be restricted or altered in any way. Clinical Decision Support: For enrolled subjects assigned to the decision support arm, providers will receive prognostic information derived using our previously validated and best performing model. The decision support application will automatically calculate predicted risk for moderate (intensive care) and severe (respiratory failure or shock) outcomes using the parameters derived from the prognostic tool's regression equation. Outcome probabilities will be integrated into the decision support application and displayed within the EHR. **ID:** EG001 **Other Num at Risk:** 267 **Serious Number At Risk:** 267 **Title:** CDS Intervention **Frequency Threshold:** 0 **Time Frame:** 30 days ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 269 **Group ID:** BG001 **Value:** 267 **Group ID:** BG002 **Value:** 536 **Units:** Participants ### Group **ID:** BG000 **Title:** Control **Description:** No experimental decision support will be provided to those randomized to the control arm. All children will receive usual care and treatment will not be restricted or altered in any way by the study. ### Group **ID:** BG001 **Title:** CDS Intervention **Description:** The prognostic decision support application will be provided to those randomized to the intervention arm. Due to the nature of the intervention, blinding of treating providers will not be possible. All children will receive usual care and all treatment decisions will be made by the clinical providers and will not be restricted or altered in any way. Clinical Decision Support: For enrolled subjects assigned to the decision support arm, providers will receive prognostic information derived using our previously validated and best performing model. The decision support application will automatically calculate predicted risk for moderate (intensive care) and severe (respiratory failure or shock) outcomes using the parameters derived from the prognostic tool's regression equation. Outcome probabilities will be integrated into the decision support application and displayed within the EHR. ### Group **ID:** BG002 **Title:** Total **Description:** Total of all reporting groups ### Measure #### Measurement **Group ID:** BG000 **Lower Limit:** 2.1 **Upper Limit:** 7.0 **Value:** 4.4 #### Measurement **Group ID:** BG001 **Lower Limit:** 2.1 **Upper Limit:** 7.2 **Value:** 4.3 #### Measurement **Group ID:** BG002 **Lower Limit:** 2.1 **Upper Limit:** 7.4 **Value:** 4.4 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 269 **Group ID:** BG001 **Value:** 267 **Group ID:** BG002 **Value:** 536 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 126 #### Measurement **Group ID:** BG001 **Value:** 141 #### Measurement **Group ID:** BG002 **Value:** 267 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 143 #### Measurement **Group ID:** BG001 **Value:** 126 #### Measurement **Group ID:** BG002 **Value:** 269 **Category Title:** Male #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 269 **Group ID:** BG001 **Value:** 267 **Group ID:** BG002 **Value:** 536 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 184 #### Measurement **Group ID:** BG001 **Value:** 177 #### Measurement **Group ID:** BG002 **Value:** 361 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 269 **Group ID:** BG001 **Value:** 267 **Group ID:** BG002 **Value:** 536 **Class Title:** White #### Measurement **Group ID:** BG000 **Value:** 36 #### Measurement **Group ID:** BG001 **Value:** 50 #### Measurement **Group ID:** BG002 **Value:** 86 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 269 **Group ID:** BG001 **Value:** 267 **Group ID:** BG002 **Value:** 536 **Class Title:** Black #### Measurement **Group ID:** BG000 **Value:** 4 #### Measurement **Group ID:** BG001 **Value:** 2 #### Measurement **Group ID:** BG002 **Value:** 6 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 269 **Group ID:** BG001 **Value:** 267 **Group ID:** BG002 **Value:** 536 **Class Title:** Asian #### Measurement **Group ID:** BG000 **Value:** 15 #### Measurement **Group ID:** BG001 **Value:** 7 #### Measurement **Group ID:** BG002 **Value:** 22 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 269 **Group ID:** BG001 **Value:** 267 **Group ID:** BG002 **Value:** 536 **Class Title:** Other #### Measurement **Group ID:** BG000 **Value:** 30 #### Measurement **Group ID:** BG001 **Value:** 31 #### Measurement **Group ID:** BG002 **Value:** 61 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 269 **Group ID:** BG001 **Value:** 267 **Group ID:** BG002 **Value:** 536 **Class Title:** Unknown ### Measure #### Measurement **Group ID:** BG000 **Value:** 150 #### Measurement **Group ID:** BG001 **Value:** 132 #### Measurement **Group ID:** BG002 **Value:** 282 **Category Title:** Non-chronic #### Measurement **Group ID:** BG000 **Value:** 26 #### Measurement **Group ID:** BG001 **Value:** 25 #### Measurement **Group ID:** BG002 **Value:** 51 **Category Title:** Non-complex chronic #### Measurement **Group ID:** BG000 **Value:** 80 #### Measurement **Group ID:** BG001 **Value:** 83 #### Measurement **Group ID:** BG002 **Value:** 163 **Category Title:** Complex chronic #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 256 **Group ID:** BG001 **Value:** 240 **Group ID:** BG002 **Value:** 496 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 153 #### Measurement **Group ID:** BG001 **Value:** 142 #### Measurement **Group ID:** BG002 **Value:** 295 **Category Title:** Public #### Measurement **Group ID:** BG000 **Value:** 95 #### Measurement **Group ID:** BG001 **Value:** 101 #### Measurement **Group ID:** BG002 **Value:** 196 **Category Title:** Private #### Measurement **Group ID:** BG000 **Value:** 16 #### Measurement **Group ID:** BG001 **Value:** 20 #### Measurement **Group ID:** BG002 **Value:** 36 **Category Title:** Multiple #### Measurement **Group ID:** BG000 **Value:** 5 #### Measurement **Group ID:** BG001 **Value:** 4 #### Measurement **Group ID:** BG002 **Value:** 9 **Category Title:** None #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 269 **Group ID:** BG001 **Value:** 267 **Group ID:** BG002 **Value:** 536 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Lower Limit:** 36.9 **Upper Limit:** 38.2 **Value:** 37.5 #### Measurement **Group ID:** BG001 **Lower Limit:** 36.8 **Upper Limit:** 38.08 **Value:** 37.2 #### Measurement **Group ID:** BG002 **Lower Limit:** 36.8 **Upper Limit:** 38.1 **Value:** 37.3 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 269 **Group ID:** BG001 **Value:** 267 **Group ID:** BG002 **Value:** 536 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Lower Limit:** 121.0 **Upper Limit:** 154.0 **Value:** 138.5 #### Measurement **Group ID:** BG001 **Lower Limit:** 117.0 **Upper Limit:** 155.0 **Value:** 135.0 #### Measurement **Group ID:** BG002 **Lower Limit:** 118.0 **Upper Limit:** 155.0 **Value:** 136.0 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 269 **Group ID:** BG001 **Value:** 267 **Group ID:** BG002 **Value:** 536 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Lower Limit:** 24.0 **Upper Limit:** 40.0 **Value:** 30.0 #### Measurement **Group ID:** BG001 **Lower Limit:** 24.0 **Upper Limit:** 40.5 **Value:** 32.0 #### Measurement **Group ID:** BG002 **Lower Limit:** 24.0 **Upper Limit:** 40.0 **Value:** 31.0 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 269 **Group ID:** BG001 **Value:** 267 **Group ID:** BG002 **Value:** 536 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Lower Limit:** 99.0 **Upper Limit:** 117.0 **Value:** 108.0 #### Measurement **Group ID:** BG001 **Lower Limit:** 100.0 **Upper Limit:** 117.0 **Value:** 108.0 #### Measurement **Group ID:** BG002 **Lower Limit:** 100.0 **Upper Limit:** 117.0 **Value:** 108.0 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 269 **Group ID:** BG001 **Value:** 267 **Group ID:** BG002 **Value:** 536 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Lower Limit:** 442.9 **Upper Limit:** 466.7 **Value:** 457.1 #### Measurement **Group ID:** BG001 **Lower Limit:** 447.6 **Upper Limit:** 466.7 **Value:** 457.1 #### Measurement **Group ID:** BG002 **Lower Limit:** 447.6 **Upper Limit:** 466.7 **Value:** 457.1 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 220 **Group ID:** BG001 **Value:** 227 **Group ID:** BG002 **Value:** 447 **Class Title:** **Denomination Units Selected:** ## Results Section - Baseline Characteristics Module ### Measure 1 **Dispersion Type:** INTER_QUARTILE_RANGE **Parameter Type:** MEDIAN **Title:** Age, Continuous **Unit of Measure:** years ### Measure 2 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Sex: Female, Male **Unit of Measure:** Participants ### Measure 3 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Race/Ethnicity, Customized **Unit of Measure:** Participants ### Measure 4 **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Data for this measure not available for all patients. **Title:** Comorbidity **Unit of Measure:** Participants ### Measure 5 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Insurance **Unit of Measure:** Participants ### Measure 6 **Dispersion Type:** INTER_QUARTILE_RANGE **Parameter Type:** MEDIAN **Title:** Triage temperature **Unit of Measure:** degrees Celsius ### Measure 7 **Dispersion Type:** INTER_QUARTILE_RANGE **Parameter Type:** MEDIAN **Title:** Triage heart rate **Unit of Measure:** beats per minute ### Measure 8 **Dispersion Type:** INTER_QUARTILE_RANGE **Parameter Type:** MEDIAN **Title:** Triage respiratory rate **Unit of Measure:** respirations per minute ### Measure 9 **Dispersion Type:** INTER_QUARTILE_RANGE **Parameter Type:** MEDIAN **Title:** Triage systolic blood pressure **Unit of Measure:** mmHg ### Measure 10 **Dispersion Type:** INTER_QUARTILE_RANGE **Parameter Type:** MEDIAN **Population Description:** Data for this measure not available for all patients. **Title:** SpO2:FiO2 ratio **Unit of Measure:** ratio ## Results Section - More Information Module ### Certain Agreement **PI Sponsor Employee:** True ### Point of Contact **Email:** [email protected] **Organization:** Vanderbilt University Medical Center **Phone:** 615-322-2744 **Title:** Derek J. Williams, MD, MPH ## Results Section - Outcome Measures Module ### Outcome Measure 1 #### Analysis **CI Lower Limit:** 0.32 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 2.95 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Odds Ratio (OR) **Parameter Value:** 0.99 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** ### Outcome Measure 2 #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.233 **P-Value Comment:** **Parameter Type:** **Parameter Value:** **Statistical Comment:** **Statistical Method:** Fisher Exact **Tested Non-Inferiority:** ### Outcome Measure 3 #### Analysis **CI Lower Limit:** 0.30 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 2.37 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Odds Ratio (OR) **Parameter Value:** 0.86 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** ### Outcome Measure 4 #### Analysis **CI Lower Limit:** 0.32 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 1.82 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Hazard Ratio (HR) **Parameter Value:** 0.78 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** ### Outcome Measure 5 #### Analysis **CI Lower Limit:** 0.34 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 7.51 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Odds Ratio (OR) **Parameter Value:** 1.42 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** ### Outcome Measure 6 #### Analysis **CI Lower Limit:** 0.13 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 1.42 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Hazard Ratio (HR) **Parameter Value:** 0.46 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** ### Outcome Measure 7 #### Analysis **CI Lower Limit:** 0.41 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 7.90 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Odds Ratio (OR) **Parameter Value:** 1.72 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 7 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 6 **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 107 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 109 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 113 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 96 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 49 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 62 **Title:** #### Outcome Measure 3 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 10 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 6 **Title:** #### Outcome Measure 4 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 15 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 9 **Title:** #### Outcome Measure 5 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 9 **Title:** #### Outcome Measure 6 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 8 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 5 **Title:** #### Outcome Measure 7 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** Number of participants who were disposed from the ED and experienced a change in level of care within 24 hours unless objective criteria present. Appropriate dispositions were defined as follows. 1. Disposition: Discharged to home, Appropriate if no subsequent hospitalization within 24h 2. Disposition: Inpatient Ward, Appropriate if hospital length of stay (LOS) ≥ 24h OR hospital LOS \< 24h with objective criteria for admission present (eg, need for supplemental oxygen) PLUS no transfer to intensive care (ICU) within 24h 3. Disposition: ICU, ICU LOS ≥ 24h OR ICU LOS \< 24h with objective criteria for ICU admission present (eg, respiratory failure) Encounters NOT meeting these criteria were defined as Inappropriate. **Parameter Type:** COUNT_OF_PARTICIPANTS **Reporting Status:** POSTED **Time Frame:** 24 Hours **Title:** Inappropriate Disposition **Type:** PRIMARY **Unit of Measure:** Participants ##### Group **Description:** No experimental decision support will be provided to those randomized to the control arm. All children will receive usual care and treatment will not be restricted or altered in any way by the study. **ID:** OG000 **Title:** Control ##### Group **Description:** The prognostic decision support application will be provided to those randomized to the intervention arm. Due to the nature of the intervention, blinding of treating providers will not be possible. All children will receive usual care and all treatment decisions will be made by the clinical providers and will not be restricted or altered in any way. Clinical Decision Support: For enrolled subjects assigned to the decision support arm, providers will receive prognostic information derived using our previously validated and best performing model. The decision support application will automatically calculate predicted risk for moderate (intensive care) and severe (respiratory failure or shock) outcomes using the parameters derived from the prognostic tool's regression equation. Outcome probabilities will be integrated into the decision support application and displayed within the EHR. **ID:** OG001 **Title:** CDS Intervention #### Outcome Measure 2 **Description:** This outcome reports the total number of participants who were initially discharged from the ED, admitted to the inpatient ward, or admitted to the ICU. **Parameter Type:** COUNT_OF_PARTICIPANTS **Reporting Status:** POSTED **Time Frame:** ED Disposition **Title:** Overall Site-of-care Disposition **Type:** SECONDARY **Unit of Measure:** Participants ##### Group **Description:** No experimental decision support will be provided to those randomized to the control arm. All children will receive usual care and treatment will not be restricted or altered in any way by the study. **ID:** OG000 **Title:** Control ##### Group **Description:** The prognostic decision support application will be provided to those randomized to the intervention arm. Due to the nature of the intervention, blinding of treating providers will not be possible. All children will receive usual care and all treatment decisions will be made by the clinical providers and will not be restricted or altered in any way. Clinical Decision Support: For enrolled subjects assigned to the decision support arm, providers will receive prognostic information derived using our previously validated and best performing model. The decision support application will automatically calculate predicted risk for moderate (intensive care) and severe (respiratory failure or shock) outcomes using the parameters derived from the prognostic tool's regression equation. Outcome probabilities will be integrated into the decision support application and displayed within the EHR. **ID:** OG001 **Title:** CDS Intervention #### Outcome Measure 3 **Description:** This outcome reports the number of participants who presented to the ED for care within 72 hours of the index discharge. **Parameter Type:** COUNT_OF_PARTICIPANTS **Reporting Status:** POSTED **Time Frame:** 72 hours **Title:** ED Revisits (72 Hours) **Type:** SECONDARY **Unit of Measure:** Participants ##### Group **Description:** No experimental decision support will be provided to those randomized to the control arm. All children will receive usual care and treatment will not be restricted or altered in any way by the study. **ID:** OG000 **Title:** Control ##### Group **Description:** The prognostic decision support application will be provided to those randomized to the intervention arm. Due to the nature of the intervention, blinding of treating providers will not be possible. All children will receive usual care and all treatment decisions will be made by the clinical providers and will not be restricted or altered in any way. Clinical Decision Support: For enrolled subjects assigned to the decision support arm, providers will receive prognostic information derived using our previously validated and best performing model. The decision support application will automatically calculate predicted risk for moderate (intensive care) and severe (respiratory failure or shock) outcomes using the parameters derived from the prognostic tool's regression equation. Outcome probabilities will be integrated into the decision support application and displayed within the EHR. **ID:** OG001 **Title:** CDS Intervention #### Outcome Measure 4 **Description:** This outcome reports the number of participants who presented to the ED for care within 7 days of the index discharge. **Parameter Type:** COUNT_OF_PARTICIPANTS **Reporting Status:** POSTED **Time Frame:** 7 days **Title:** ED Revisits (7 Days) **Type:** SECONDARY **Unit of Measure:** Participants ##### Group **Description:** No experimental decision support will be provided to those randomized to the control arm. All children will receive usual care and treatment will not be restricted or altered in any way by the study. **ID:** OG000 **Title:** Control ##### Group **Description:** The prognostic decision support application will be provided to those randomized to the intervention arm. Due to the nature of the intervention, blinding of treating providers will not be possible. All children will receive usual care and all treatment decisions will be made by the clinical providers and will not be restricted or altered in any way. Clinical Decision Support: For enrolled subjects assigned to the decision support arm, providers will receive prognostic information derived using our previously validated and best performing model. The decision support application will automatically calculate predicted risk for moderate (intensive care) and severe (respiratory failure or shock) outcomes using the parameters derived from the prognostic tool's regression equation. Outcome probabilities will be integrated into the decision support application and displayed within the EHR. **ID:** OG001 **Title:** CDS Intervention #### Outcome Measure 5 **Description:** This outcome reports the number of participants who were readmitted to the hospital for pneumonia-related illness within 72 hours of the index discharge. **Parameter Type:** COUNT_OF_PARTICIPANTS **Reporting Status:** POSTED **Time Frame:** 72 hours **Title:** Rehospitalizations (72 Hours) **Type:** SECONDARY **Unit of Measure:** Participants ##### Group **Description:** No experimental decision support will be provided to those randomized to the control arm. All children will receive usual care and treatment will not be restricted or altered in any way by the study. **ID:** OG000 **Title:** Control ##### Group **Description:** The prognostic decision support application will be provided to those randomized to the intervention arm. Due to the nature of the intervention, blinding of treating providers will not be possible. All children will receive usual care and all treatment decisions will be made by the clinical providers and will not be restricted or altered in any way. Clinical Decision Support: For enrolled subjects assigned to the decision support arm, providers will receive prognostic information derived using our previously validated and best performing model. The decision support application will automatically calculate predicted risk for moderate (intensive care) and severe (respiratory failure or shock) outcomes using the parameters derived from the prognostic tool's regression equation. Outcome probabilities will be integrated into the decision support application and displayed within the EHR. **ID:** OG001 **Title:** CDS Intervention #### Outcome Measure 6 **Description:** This outcome reports the number of participants who were readmitted to the hospital for pneumonia-related illness within 7 days of the index discharge. **Parameter Type:** COUNT_OF_PARTICIPANTS **Reporting Status:** POSTED **Time Frame:** 7 days **Title:** Rehospitalizations (7 Days) **Type:** SECONDARY **Unit of Measure:** Participants ##### Group **Description:** No experimental decision support will be provided to those randomized to the control arm. All children will receive usual care and treatment will not be restricted or altered in any way by the study. **ID:** OG000 **Title:** Control ##### Group **Description:** The prognostic decision support application will be provided to those randomized to the intervention arm. Due to the nature of the intervention, blinding of treating providers will not be possible. All children will receive usual care and all treatment decisions will be made by the clinical providers and will not be restricted or altered in any way. Clinical Decision Support: For enrolled subjects assigned to the decision support arm, providers will receive prognostic information derived using our previously validated and best performing model. The decision support application will automatically calculate predicted risk for moderate (intensive care) and severe (respiratory failure or shock) outcomes using the parameters derived from the prognostic tool's regression equation. Outcome probabilities will be integrated into the decision support application and displayed within the EHR. **ID:** OG001 **Title:** CDS Intervention #### Outcome Measure 7 **Description:** This outcome reports the number of participants who died as a result of their pneumonia-related illness within 30 days discharge from the index encounter. **Parameter Type:** COUNT_OF_PARTICIPANTS **Reporting Status:** POSTED **Time Frame:** 30 days **Title:** Death **Type:** OTHER_PRE_SPECIFIED **Unit of Measure:** Participants ##### Group **Description:** No experimental decision support will be provided to those randomized to the control arm. All children will receive usual care and treatment will not be restricted or altered in any way by the study. **ID:** OG000 **Title:** Control ##### Group **Description:** The prognostic decision support application will be provided to those randomized to the intervention arm. Due to the nature of the intervention, blinding of treating providers will not be possible. All children will receive usual care and all treatment decisions will be made by the clinical providers and will not be restricted or altered in any way. Clinical Decision Support: For enrolled subjects assigned to the decision support arm, providers will receive prognostic information derived using our previously validated and best performing model. The decision support application will automatically calculate predicted risk for moderate (intensive care) and severe (respiratory failure or shock) outcomes using the parameters derived from the prognostic tool's regression equation. Outcome probabilities will be integrated into the decision support application and displayed within the EHR. **ID:** OG001 **Title:** CDS Intervention ### Participant Flow Module #### Group **Description:** No experimental decision support will be provided to those randomized to the control arm. All children will receive usual care and treatment will not be restricted or altered in any way by the study. **ID:** FG000 **Title:** Control #### Group **Description:** The prognostic decision support application will be provided to those randomized to the intervention arm. Due to the nature of the intervention, blinding of treating providers will not be possible. All children will receive usual care and all treatment decisions will be made by the clinical providers and will not be restricted or altered in any way. Clinical Decision Support: For enrolled subjects assigned to the decision support arm, providers will receive prognostic information derived using our previously validated and best performing model. The decision support application will automatically calculate predicted risk for moderate (intensive care) and severe (respiratory failure or shock) outcomes using the parameters derived from the prognostic tool's regression equation. Outcome probabilities will be integrated into the decision support application and displayed within the EHR. **ID:** FG001 **Title:** CDS Intervention #### Period **Title:** Overall Study ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 269 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 267 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 269 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 267 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 0 **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT02386579 **Brief Title:** Characterization of Local and Systemic Bone Markers in Diabetes Patients With Charcot Osteoarthropathy #### Organization Study ID Info **ID:** H-1-2014-069 #### Organization **Class:** OTHER **Full Name:** Bispebjerg Hospital ### Status Module #### Completion Date **Date:** 2017-06 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2020-03-31 **Type:** ACTUAL **Last Update Submit Date:** 2020-03-28 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2017-06 **Type:** ACTUAL #### Start Date **Date:** 2015-02 **Status Verified Date:** 2020-03 #### Study First Post Date **Date:** 2015-03-12 **Type:** ESTIMATED **Study First Submit Date:** 2015-02-27 **Study First Submit QC Date:** 2015-03-06 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Bispebjerg Hospital #### Responsible Party **Investigator Affiliation:** Bispebjerg Hospital **Investigator Full Name:** Rasmus Bo Jansen **Investigator Title:** MD **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** The study is designed to investigate biomarkers related to bone turnover in diabetics with charcot foot. This is done by measuring local blood samples in the feet, and systemically in a vene and an artery. Measurements are done before and after cooling the feet in icewater to lower the bloodflow. Patients will be compared with healthy diabetic controls. ### Conditions Module **Conditions:** - Arthropathy, Neurogenic - Diabetes Complications - Diabetes Mellitus ### Design Module #### Bio Spec **Description:** blood serum samples **Retention:** SAMPLES_WITHOUT_DNA #### Design Info **Observational Model:** CASE_CONTROL **Time Perspective:** CROSS_SECTIONAL #### Enrollment Info **Count:** 5 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Intervention Names:** - Procedure: Blood sample measurements **Label:** Diabetics with Charcot foot ### Interventions #### Intervention 1 **Arm Group Labels:** - Diabetics with Charcot foot **Description:** Blood samples are drawn in the feet and arms (a/v) before and after cooling the feet with ice water **Name:** Blood sample measurements **Type:** PROCEDURE ### Outcomes Module #### Primary Outcomes **Measure:** RANKL **Time Frame:** 10 min between measurements #### Secondary Outcomes **Measure:** osteocalcin **Time Frame:** 10 min between measurements **Measure:** CTX-I **Time Frame:** 10 min between measurements **Measure:** sRAGE **Time Frame:** 10 min between measurements **Measure:** P1NP **Time Frame:** 10 min between measurements ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Diabetes mellitus type 1 or 2 * Charcot foot diagnosed with x-ray, scintigraphy or clinical review by a specialist Exclusion Criteria: * Osteoporosis * Anti-osteoporotic treatment * Lower extremity amputation * Lower extremity infection **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - CHILD - ADULT - OLDER_ADULT **Study Population:** Diabetes patients with and without acute charcot foot ## Derived Section ### Condition Browse Module - Ancestors - ID: D000044882 - Term: Glucose Metabolism Disorders - ID: D000008659 - Term: Metabolic Diseases - ID: D000004700 - Term: Endocrine System Diseases - ID: D000007592 - Term: Joint Diseases - ID: D000009140 - Term: Musculoskeletal Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC18 - Name: Nutritional and Metabolic Diseases - Abbrev: BC19 - Name: Gland and Hormone Related Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC05 - Name: Musculoskeletal Diseases ### Condition Browse Module - Browse Leaves - ID: M7115 - Name: Diabetes Mellitus - Relevance: HIGH - As Found: Diabetes - ID: M10621 - Name: Joint Diseases - Relevance: LOW - As Found: Unknown - ID: M26004 - Name: Diabetes Complications - Relevance: HIGH - As Found: Diabetes Complications - ID: M4485 - Name: Arthropathy, Neurogenic - Relevance: HIGH - As Found: Arthropathy, Neurogenic - ID: M11639 - Name: Metabolic Diseases - Relevance: LOW - As Found: Unknown - ID: M25403 - Name: Glucose Metabolism Disorders - Relevance: LOW - As Found: Unknown - ID: M7862 - Name: Endocrine System Diseases - Relevance: LOW - As Found: Unknown - ID: M12097 - Name: Musculoskeletal Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000001177 - Term: Arthropathy, Neurogenic - ID: D000003920 - Term: Diabetes Mellitus - ID: D000048909 - Term: Diabetes Complications ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT01902979 **Acronym:** SSPANLI **Brief Title:** The Spinal Stenosis Pedometer and Nutrition e-Health Lifestyle Intervention (SSPANLI) Trial **Official Title:** The Spinal Stenosis Pedometer and Nutrition e-Health Lifestyle Intervention (SSPANLI) Randomized Trial #### Organization Study ID Info **ID:** CIHR290928 #### Organization **Class:** OTHER **Full Name:** Mount Royal University ### Status Module #### Expanded Access Info **Last Known Status:** RECRUITING #### Last Update Post Date **Date:** 2013-09-10 **Type:** ESTIMATED **Last Update Submit Date:** 2013-09-09 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2015-09 **Type:** ESTIMATED #### Start Date **Date:** 2013-09 **Status Verified Date:** 2013-09 #### Study First Post Date **Date:** 2013-07-18 **Type:** ESTIMATED **Study First Submit Date:** 2013-07-05 **Study First Submit QC Date:** 2013-07-16 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Mount Royal University #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** Obesity is one of the most important determinants of quality of life and function. People with lumbar spinal stenosis may be at increased risk of obesity given walking limitations. Spinal stenosis is a very common degenerative condition in people over 45. People with this condition have pain and numbness in the legs during walking, and therefore avoid physical activity. Lack of physical activity is related to weight gain and increased risk of chronic disease. Objective: The objective of this project is test a new e-health (online) pedometer and nutrition intervention aimed at promoting weight loss and increasing physical activity in overweight and obese individuals with spinal stenosis. Methods: The investigators will recruit 88 people with lumbar spinal stenosis who are overweight or obese. Half of these people will receive the 12-week intervention, and the other half will receive usual care (no intervention). In Weeks 1 and 6, people in the intervention group will meet with a Registered Dietitian and an Exercise Physiologist for personalized sessions. They will receive a pedometer and instructions on how to log in to the e-health site (https://sspanli.mtroyal.ca). They will wear the pedometer daily and log in to the website each week for a nutrition education session, a weekly step goal, and tips. The investigators will look to see whether people in the intervention group show greater change in physical activity, body composition and quality of life compared to the individuals who received usual care. Relevance: The increasing number of people with spinal stenosis represents a huge health care burden in Canada. This intervention could provide a new treatment option that would increase mobility, quality of life, and potentially alleviate the need for expensive treatments like surgery. E-health interventions provide an opportunity for patients to take an active role in their own health, and promote behaviour changes that will result in healthier Canadians less likely to access care in the future. ### Conditions Module **Conditions:** - Lumbar Spinal Stenosis - Obesity ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** SINGLE **Who Masked:** - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 88 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** In Weeks 1 and 6, people in the intervention group will meet with a Registered Dietitian and an Exercise Physiologist for personalized sessions. They will receive a pedometer and instructions on how to log in to the e-health site (https://sspanli.mtroyal.ca). They will wear the pedometer daily and log in to the website each week for a nutrition education session, a weekly step goal, and tips. **Intervention Names:** - Behavioral: Lifestyle intervention **Label:** Lifestyle intervention **Type:** EXPERIMENTAL #### Arm Group 2 **Label:** Usual Care **Type:** NO_INTERVENTION ### Interventions #### Intervention 1 **Arm Group Labels:** - Lifestyle intervention **Name:** Lifestyle intervention **Type:** BEHAVIORAL ### Outcomes Module #### Primary Outcomes **Description:** Fat mass will be assessed at both Baseline and 6 month follow-up using dual energy x-ray absorptiometry and presented as a percentage of total body mass. **Measure:** Change from Baseline in Percent Fat Mass at 6 months **Time Frame:** 6 months **Description:** Steps per day will be assessed at both Baseline and 6-month follow-up using a pedometer worn for 7 consecutive days **Measure:** Change from Baseline in Mean Number of Steps Per Day at 6 months **Time Frame:** 6 months **Description:** Waist circumference will be assessed at both Baseline and 6-month follow-up using a tape measure and recorded in centimetres **Measure:** Change from Baseline in Waist Circumference (Centimeters) at 6 months **Time Frame:** 6 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * All subjects will be at least 45 years of age and will have received a diagnosis of lumbar spinal stenosis (LSS) by a spine surgeon who has both examined the patient and reviewed imaging results (MRI or CT). All subjects will be required to have a BMI of 25 kg/m2 or greater (overweight) and to have maintained a stable body weight for the previous 3 months. Exclusion Criteria: * any co-morbid conditions that would make participation in a walking program medically inadvisable. * subjects currently participating in a diet or lifestyle intervention for weight loss or who are on medications known to influence bodyweight or glucoregulation (including antidepressants, sibutramine orlistate, insulin and metformin), will be excluded. If participants are scheduled for any type of surgery that could impact mobility during the intervention period, they will be removed from the study. **Minimum Age:** 45 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Calgary **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Yvette Andreas - **Phone:** 403-606-7021 - **Role:** CONTACT ***Contact 2:*** - **Name:** Christy C Tomkins-Lane, PhD - **Role:** PRINCIPAL_INVESTIGATOR **Country:** Canada **Facility:** Mount Royal University **State:** Alberta **Status:** RECRUITING **Zip:** T2N 1T1 #### Overall Officials **Official 1:** **Affiliation:** Mount Royal University **Name:** Christy Tomkins-Lane **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### References **Citation:** Tomkins-Lane CC, Lafave LM, Parnell JA, Krishnamurthy A, Rempel J, Macedo LG, Moriartey S, Stuber KJ, Wilson PM, Hu R, Andreas YM. The spinal stenosis pedometer and nutrition lifestyle intervention (SSPANLI) randomized controlled trial protocol. BMC Musculoskelet Disord. 2013 Nov 14;14:322. doi: 10.1186/1471-2474-14-322. **PMID:** 24228747 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000020763 - Term: Pathological Conditions, Anatomical - ID: D000013122 - Term: Spinal Diseases - ID: D000001847 - Term: Bone Diseases - ID: D000009140 - Term: Musculoskeletal Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC18 - Name: Nutritional and Metabolic Diseases - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC05 - Name: Musculoskeletal Diseases ### Condition Browse Module - Browse Leaves - ID: M12701 - Name: Obesity - Relevance: LOW - As Found: Unknown - ID: M6475 - Name: Constriction, Pathologic - Relevance: HIGH - As Found: Stenosis - ID: M15927 - Name: Spinal Stenosis - Relevance: HIGH - As Found: Spinal Stenosis - ID: M22519 - Name: Pathological Conditions, Anatomical - Relevance: LOW - As Found: Unknown - ID: M15919 - Name: Spinal Diseases - Relevance: LOW - As Found: Unknown - ID: M5126 - Name: Bone Diseases - Relevance: LOW - As Found: Unknown - ID: M12097 - Name: Musculoskeletal Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000013130 - Term: Spinal Stenosis - ID: D000003251 - Term: Constriction, Pathologic ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00528879 **Brief Title:** A Phase III Study of BMS-512148 (Dapagliflozin) in Patients With Type 2 Diabetes Who Are Not Well Controlled on Metformin Alone **Official Title:** A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Phase 3 Trial to Evaluate the Safety and Efficacy of Dapagliflozin in Combination With Metformin in Subjects With Type 2 Diabetes Who Have Inadequate Glycemic Control on Metformin Alone #### Organization Study ID Info **ID:** MB102-014 LT #### Organization **Class:** INDUSTRY **Full Name:** AstraZeneca #### Secondary ID Infos **Domain:** Other Study ID Numbers: **ID:** MB102-014 **Type:** OTHER ### Status Module #### Completion Date **Date:** 2010-05 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2015-10-20 **Type:** ESTIMATED **Last Update Submit Date:** 2015-09-30 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2008-11 **Type:** ACTUAL #### Results First Post Date **Date:** 2014-05-02 **Type:** ESTIMATED **Results First Submit Date:** 2014-02-06 **Results First Submit QC Date:** 2014-04-01 #### Start Date **Date:** 2007-09 **Status Verified Date:** 2015-09 #### Study First Post Date **Date:** 2007-09-12 **Type:** ESTIMATED **Study First Submit Date:** 2007-09-11 **Study First Submit QC Date:** 2007-09-11 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** Bristol-Myers Squibb #### Lead Sponsor **Class:** INDUSTRY **Name:** AstraZeneca #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** The purpose of this clinical research study is to learn whether dapagliflozin can help reduce blood sugar levels in participants with Type 2 diabetes that is not well controlled on metformin alone. The safety of this treatment will also be studied. ### Conditions Module **Conditions:** - Type 2 Diabetes **Keywords:** - Diabetes Mellitus, Type 2 - Diabetes Mellitus - Endocrine System Diseases - Glucose Metabolism Disorders - Metabolic Diseases - Metformin - Hypoglycemic Agents - Pharmacologic Actions - Physiological Effects of Drugs ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** DOUBLE **Who Masked:** - PARTICIPANT - INVESTIGATOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 915 **Type:** ACTUAL **Phases:** - PHASE3 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Participants received dapagliflozin-matching placebo once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks **Intervention Names:** - Drug: Placebo - Drug: Metformin **Label:** Placebo + Metformin **Type:** PLACEBO_COMPARATOR #### Arm Group 2 **Description:** Participants received dapagliflozin, 2.5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks **Intervention Names:** - Drug: Dapagliflozin - Drug: Metformin **Label:** Dapagliflozin, 2.5 mg + Metformin **Type:** EXPERIMENTAL #### Arm Group 3 **Description:** Participants received dapagliflozin, 5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks **Intervention Names:** - Drug: Dapagliflozin - Drug: Metformin **Label:** Dapagliflozin, 5 mg + Metformin **Type:** EXPERIMENTAL #### Arm Group 4 **Description:** Participants received dapagliflozin, 10 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks **Intervention Names:** - Drug: Dapagliflozin - Drug: Placebo - Drug: Metformin **Label:** Dapagliflozin, 10 mg + Metformin **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Dapagliflozin, 10 mg + Metformin - Dapagliflozin, 2.5 mg + Metformin - Dapagliflozin, 5 mg + Metformin **Description:** Tablets administered orally as a 2.5-, 5-, or 10-mg dose once daily for up to 102 weeks **Name:** Dapagliflozin **Other Names:** - BMS-512148 **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Dapagliflozin, 10 mg + Metformin - Placebo + Metformin **Description:** Dapagliflozin-matching placebo administered as tablets orally once daily for up to 102 weeks **Name:** Placebo **Type:** DRUG #### Intervention 3 **Arm Group Labels:** - Dapagliflozin, 10 mg + Metformin - Dapagliflozin, 2.5 mg + Metformin - Dapagliflozin, 5 mg + Metformin - Placebo + Metformin **Description:** Open-label metformin administered as ≥1500 mg per day for up to 102 weeks **Name:** Metformin **Type:** DRUG ### Outcomes Module #### Other Outcomes **Description:** AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Related=having certain, probable, possible, or missing relationship to study drug. Events captured from baseline to last dose plus 4 days for AEs and plus 30 days for SAEs during the double-blind 12-week period. Data after rescue included. **Measure:** Number of Participants With Adverse Events (AEs), Hypoglycemia Events, Related AEs, Death as Outcome, Serious AEs (SAEs), Related SAEs, SAEs Leading to Discontinuation, AEs Leading to Discontinuation, and Hypoglycemia Events Leading to Discontinuation **Time Frame:** From Baseline to end of Long-term Period (Week 102) **Description:** BUN=blood urea nitrogen; preRX=pretreatment; ULN=upper limit of normal; AST=aspartate aminotransferase; ALT=alanine aminotransferase; ALP=alkaline phosphatase. Phosphorus, inorganic (low): ages 17-65 years, ≤1.8 mg/dL; ages≥66 years, ≤2.1 mg/dL. Phosphorus, inorganic (high): ages 17-65 years, ≥5.6 mg/dL; ages≥66 years, ≥5.6 mg/dL. Phosphorus, inorganic (low) ≤1.8 mg/dL if age 17-65 or ≤2.1 mg/dL if age ≥66. Calcium, total (high): ≥1 mg/dL from ULN and ≥0.5 mg/dL from preRx value. **Measure:** Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality **Time Frame:** Day 1 to Week 102 **Description:** 12-Lead electrocardiograms (ECGs) were performed at entry into lead-in period Day -7 visit and Week 24/dnd of treatment visit (LOCF) on participants who were supine. ECGs were assessed by the investigator. Baseline was Day -7 for this parameter. Data after rescue included.The Week 102 value is the last observation, regardless of rescue prior to Week 102 if no Week 102 measurement was available. **Measure:** Number of Participants With Changes in Baseline in Electrocardiogram Findings at Week 102 (Last Observation Carried Forward [LOCF]) **Time Frame:** Baseline to Week 102 **Description:** Blood pressure values were obtained after the participant was seated quietly for 5 minutes; at least 8 hours after the last ingestion of caffeine, alcohol, or nicotine; and in the same arm (right or left) consistently through out the study. Data after rescue were also included. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. **Measure:** Mean Changes From Baseline in Seated Systolic Blood Pressure **Time Frame:** From Baseline to Week 102 **Description:** Blood pressure values were obtained after the participant was seated quietly for 5 minutes; at least 8 hours after the last ingestion of caffeine, alcohol, or nicotine; and in the same arm (right or left) consistently through out the study. Data after rescue were also included. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. **Measure:** Mean Changes From Baseline in Seated Diastolic Blood Pressure **Time Frame:** From Baseline to Week 102 **Description:** Orthostatic hypotension was defined as a decrease from supine to standing blood pressure of \>20 mm Hg in systolic blood pressure or \>10 mm Hg in diastolic blood pressure. **Measure:** Number of Participants With Orthostatic Hypotension **Time Frame:** From Baseline to Week 102 #### Primary Outcomes **Description:** HbA1c was measured as percent of hemoglobin by a central laboratory. Data after rescue medication was excluded from this analysis. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. HbA1c measurements were obtained during the qualification and lead-in periods and on Day 1 and Weeks 4, 8, 12, 16, 20, and 24 in the double-blind period. **Measure:** Adjusted Mean Change From Baseline in Hemoglobin A1C (HbA1c) at Week 24 (Last Observation Carried Forward [LOCF]) **Time Frame:** From Baseline to Week 24 #### Secondary Outcomes **Description:** Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Data after rescue medication was excluded from this analysis. Fasting plasma glucose was measured as milligrams per deciliter (mg/dL) by a central laboratory. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. **Measure:** Adjusted Mean Change From Baseline in Fasting Plasma Glucose at Week 24 (Last Observation Carried Forward [LOCF]) **Time Frame:** From Baseline to Week 24 **Description:** Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Adjusted mean change from baseline in total body weight at Week 24 (or the last postbaseline measurement prior to Week 24 if no Week 24 assessment was available was determined. Data after rescue medication was excluded from this analysis. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. Body weight measurements were obtained during the qualification and lead-in periods and on Day 1 and Weeks 1, 2, 3, 4, 6, 8, 12, 16, 20, and 24 of the double-blind period. **Measure:** Adjusted Mean Change From Baseline in Total Body Weight at Week 24 (Last Observation Carried Forward [LOCF]) **Time Frame:** From Baseline to Week 24 **Description:** Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Percent adjusted for baseline HbA1c. Therapeutic glycemic response is defined as HbA1c \<7.0%. Data after rescue medication was excluded from this analysis. HbA1c was measured as a percent of hemoglobin. **Measure:** Percentage of Participants Achieving a Therapeutic Glycemic Response (Hemoglobin A1c [HbA1C]) <7.0% at Week 24 (Last Observation Carried Forward [LOCF]) **Time Frame:** From Baseline to Week 24 **Description:** Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. HbA1c was measured as percent of hemoglobin by a central laboratory. The population included those randomized participants who received treatment and had a baseline HbA1c \> 9.0%. Data after rescue medication were excluded from this analysis. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. **Measure:** Adjusted Mean Change From Baseline in Hemoglobin A1c (HbA1c) in Participants With Baseline HbA1c ≥9.0% at Week 24 (Last Observation Carried Forward [LOCF]) **Time Frame:** From Baseline to Week 24 **Description:** Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Adjusted mean change from baseline in total body weight at Week 24 (or the last postbaseline measurement prior to Week 24 if no Week 24 assessment was available was determined.) Data after rescue medication was excluded from this analysis. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. Body weight measurements were obtained during the qualification and lead-in Periods and on Day 1 and Weeks 1, 2, 3, 4, 6, 8, 12, 16, 20, and 24 of the double-blind period. **Measure:** Adjusted Mean Change From Baseline in Total Body Weight at Week 24 in Participants With Baseline Body Mass Index (BMI) ≥27 kg/m^2 (Last Observation Carried Forward [LOCF]) **Time Frame:** From Baseline to Week 24 **Description:** Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Adjusted for baseline HbA1c. HbA1c was measured as percent of hemoglobin by a central laboratory. Data after rescue medication were excluded from this analysis. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. **Measure:** Adjusted Mean Change From Baseline in Hemoglobin A1c (HbA1c) in Participants With Baseline Body Mass Index (BMI) ≥27 kg/m^2 at Week 24 (Last Observation Carried Forward [LOCF]) **Time Frame:** From Baseline to Week 24 **Description:** Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Data after rescue medication was excluded from this analysis. Fasting plasma glucose was measured by a central laboratory. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. **Measure:** Adjusted Mean Change From Baseline in Fasting Plasma Glucose at Week 1 (Last Observation Carried Forward [LOCF]) **Time Frame:** From Baseline to Week 1 **Description:** Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Percent adjusted for baseline HbA1c. Data after rescue medication was excluded from this analysis. HbA1c was measured as a percent of hemoglobin. **Measure:** Adjusted Percentage of Participants Achieving Hemoglobin A1c (HbA1C) ≤6.5% at Week 24 (Last Observation Carried Forward [LOCF]) **Time Frame:** From Baseline to Week 24 ### Eligibility Module **Eligibility Criteria:** Key Inclusion Criteria * Males and females, 18 to 77 years old, with type 2 diabetes and inadequate glycemic control * Participants who have been receiving metformin at a total daily dose ≥1500 mg per day for at least 8 weeks * C-peptide ≥1.0 ng/mL * Body mass index ≤45.0 kg/m\^2 * Serum creatinine level \<1.50 mg/dL for men or \<1.40 mg/dL for women. Key Exclusion Criteria * Aspartate aminotransferase and/or alanine aminotransferase level \>3.0 times the upper limit of normal * Serum total bilirubin level \>2 mg/dL * Creatinine kinase level \>3 times upper limit of normal * Symptoms of severely uncontrolled diabetes * Serum creatinine level ≥1.50 mg/dL for men or ≥1.40 mg/dL for women * Currently unstable or serious cardiovascular, renal, hepatic, hematologic, oncologic, endocrine, psychiatric, or rheumatic diseases **Maximum Age:** 77 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Tempe **Country:** United States **Facility:** Clinical Research Advantage / Desert Clinical Res, Llc **State:** Arizona **Zip:** 85282 **Location 2:** **City:** Encino **Country:** United States **Facility:** Medical Group Of Encino **State:** California **Zip:** 91436 **Location 3:** **City:** Fresno **Country:** United States **Facility:** Valley Research **State:** California **Zip:** 93720 **Location 4:** **City:** Los Angeles **Country:** United States **Facility:** Randall Shue, D.O. **State:** California **Zip:** 90023 **Location 5:** **City:** Northridge **Country:** United States **Facility:** Diabetes Medical Center Of California **State:** California **Zip:** 91325 **Location 6:** **City:** San Diego **Country:** United States **Facility:** Ritchken & First M.D.'S **State:** California **Zip:** 92117 **Location 7:** **City:** Spring Valley **Country:** United States **Facility:** Encompass Clinical Research **State:** California **Zip:** 91978 **Location 8:** **City:** Torrance **Country:** United States **Facility:** Raikhel, Marina **State:** California **Zip:** 90505 **Location 9:** **City:** Colorado Springs **Country:** United States **Facility:** Express Care Clinical Res **State:** Colorado **Zip:** 80909 **Location 10:** **City:** Denver **Country:** United States **Facility:** Denver Internal Medicine **State:** Colorado **Zip:** 80209 **Location 11:** **City:** Golden **Country:** United States **Facility:** New West Physicians **State:** Colorado **Zip:** 80401 **Location 12:** **City:** Altamonte Springs **Country:** United States **Facility:** Central Florida Clinical Trials, Inc. **State:** Florida **Zip:** 32701 **Location 13:** **City:** Chipley **Country:** United States **Facility:** Family Care Associates Of Nw Florida **State:** Florida **Zip:** 32428 **Location 14:** **City:** Minneapolis **Country:** United States **Facility:** Health Partners Research Foundation **State:** Minnesota **Zip:** 56440 **Location 15:** **City:** Chesterfield **Country:** United States **Facility:** Woodlake Research **State:** Missouri **Zip:** 63017 **Location 16:** **City:** Las Vegas **Country:** United States **Facility:** Nevada Alliance Against Diabetes **State:** Nevada **Zip:** 89101 **Location 17:** **City:** Morehead City **Country:** United States **Facility:** Diabetes & Endocrinology Consultants, Pc **State:** North Carolina **Zip:** 28557 **Location 18:** **City:** Newark **Country:** United States **Facility:** Newark Physician Associates **State:** Ohio **Zip:** 43055 **Location 19:** **City:** Oklahoma City **Country:** United States **Facility:** Integris Family Care S. Penn **State:** Oklahoma **Zip:** 73159 **Location 20:** **City:** Carlisle **Country:** United States **Facility:** Cumberland Valley Endocrinology Center, Llc **State:** Pennsylvania **Zip:** 17013 **Location 21:** **City:** Pittsburgh **Country:** United States **Facility:** Banksville Medical Pc **State:** Pennsylvania **Zip:** 15216 **Location 22:** **City:** Summerville **Country:** United States **Facility:** Palmetto Clinical Research **State:** South Carolina **Zip:** 29485 **Location 23:** **City:** Taylors **Country:** United States **Facility:** Southeastern Research Assoc **State:** South Carolina **Zip:** 29687 **Location 24:** **City:** Houston **Country:** United States **Facility:** Texas Center For Drug Development, P.A. **State:** Texas **Zip:** 77081 **Location 25:** **City:** San Antonio **Country:** United States **Facility:** Diabetes & Glandular Disease Research Associates, Inc. **State:** Texas **Zip:** 78229 **Location 26:** **City:** San Antonio **Country:** United States **Facility:** S.A.M. Clinical Research Center **State:** Texas **Zip:** 78229 **Location 27:** **City:** Salt Lake City **Country:** United States **Facility:** Optimum Clinical Research **State:** Utah **Zip:** 84102 **Location 28:** **City:** Spokane **Country:** United States **Facility:** Office Of Dr. Gray **State:** Washington **Zip:** 99216 **Location 29:** **City:** Capital Federal **Country:** Argentina **Facility:** Local Institution **State:** Buenos Aires **Zip:** 1034 **Location 30:** **City:** Capital Federal **Country:** Argentina **Facility:** Local Institution **State:** Buenos Aires **Zip:** 1429 **Location 31:** **City:** Capital Federal **Country:** Argentina **Facility:** Local Institution **State:** Buenos Aires **Zip:** C1056ABJ **Location 32:** **City:** Capital Federal **Country:** Argentina **Facility:** Local Institution **State:** Buenos Aires **Zip:** C1425AGC **Location 33:** **City:** Ciudad Auton. **Country:** Argentina **Facility:** Local Institution **State:** Buenos Aires **Zip:** C1505CWB **Location 34:** **City:** Ciudad Auton **Country:** Argentina **Facility:** Local Institution **State:** Buenos Aires **Zip:** C1408INH **Location 35:** **City:** Mar Del Plata **Country:** Argentina **Facility:** Local Institution **State:** Buenos Aires **Zip:** 7600 **Location 36:** **City:** Zarate **Country:** Argentina **Facility:** Local Institution **State:** Buenos Aires **Zip:** 2800 **Location 37:** **City:** Villa Carlos Paz **Country:** Argentina **Facility:** Local Institution **State:** Cordoba **Zip:** 5152 **Location 38:** **City:** Buenos Aires **Country:** Argentina **Facility:** Local Institution **Zip:** 1431 **Location 39:** **City:** Cordoba **Country:** Argentina **Facility:** Local Institution **Zip:** 5000 **Location 40:** **City:** Fortaleza **Country:** Brazil **Facility:** Local Institution **State:** Ceara **Zip:** 60021 **Location 41:** **City:** Itajuba **Country:** Brazil **Facility:** Local Institution **State:** Minas Gerais **Zip:** 37502 **Location 42:** **City:** Belem **Country:** Brazil **Facility:** Local Institution **State:** Para **Zip:** 66073 **Location 43:** **City:** Caxias Do Sul **Country:** Brazil **Facility:** Local Institution **State:** Rio Grande Do Sul **Zip:** 95070 **Location 44:** **City:** Porto Alegre **Country:** Brazil **Facility:** Local Institution **State:** Rio Grande Do Sul **Zip:** 90020090 **Location 45:** **City:** Porto Alegre **Country:** Brazil **Facility:** Local Institution **State:** Rio Grande Do Sul **Zip:** 90035 **Location 46:** **City:** Marilia **Country:** Brazil **Facility:** Local Institution **State:** Sao Paulo **Zip:** 17519 **Location 47:** **City:** Rio De Janeiro **Country:** Brazil **Facility:** Local Institution **Zip:** 20211 **Location 48:** **City:** Calgary **Country:** Canada **Facility:** Local Institution **State:** Alberta **Zip:** T2R 0X7 **Location 49:** **City:** Kelowna **Country:** Canada **Facility:** Local Institution **State:** British Columbia **Zip:** V1Y 2H4 **Location 50:** **City:** Winnipeg **Country:** Canada **Facility:** Local Institution **State:** Manitoba **Zip:** R3E 3P4 **Location 51:** **City:** Bathurst **Country:** Canada **Facility:** Local Institution **State:** New Brunswick **Zip:** E2A 4X7 **Location 52:** **City:** Mount Pearl **Country:** Canada **Facility:** Local Institution **State:** Newfoundland and Labrador **Zip:** A1N 1W7 **Location 53:** **City:** St-John **Country:** Canada **Facility:** Local Institution **State:** Newfoundland and Labrador **Zip:** A1E 2E2 **Location 54:** **City:** Sarnia **Country:** Canada **Facility:** Local Institution **State:** Ontario **Zip:** N7T 4X3 **Location 55:** **City:** Thornhill **Country:** Canada **Facility:** Local Institution **State:** Ontario **Zip:** L4J 8L7 **Location 56:** **City:** Toronto **Country:** Canada **Facility:** Local Institution **State:** Ontario **Zip:** M4R 2G4 **Location 57:** **City:** Toronto **Country:** Canada **Facility:** Local Institution **State:** Ontario **Zip:** M9W 4L6 **Location 58:** **City:** Charlottetown **Country:** Canada **Facility:** Local Institution **State:** Prince Edward Island **Zip:** C1A 5Y9 **Location 59:** **City:** Drummondville **Country:** Canada **Facility:** Local Institution **State:** Quebec **Zip:** J2B 7T1 **Location 60:** **City:** Granby **Country:** Canada **Facility:** Local Institution **State:** Quebec **Zip:** J2G 8Z9 **Location 61:** **City:** L'Ancienne Lorette **Country:** Canada **Facility:** Local Institution **State:** Quebec **Zip:** G2E 2X1 **Location 62:** **City:** Mirabel **Country:** Canada **Facility:** Local Institution **State:** Quebec **Zip:** J7J 2K8 **Location 63:** **City:** St-Leonard **Country:** Canada **Facility:** Local Institution **State:** Quebec **Zip:** H1S 3A9 **Location 64:** **City:** Saskatoon **Country:** Canada **Facility:** Local Institution **State:** Saskatchewan **Zip:** S7K 3H3 **Location 65:** **City:** Saskatoon **Country:** Canada **Facility:** Local Institution **State:** Saskatchewan **Zip:** S7K 7H9 **Location 66:** **City:** Df **Country:** Mexico **Facility:** Local Institution **State:** Distrito Federal **Zip:** 11800 **Location 67:** **City:** Guadalajara **Country:** Mexico **Facility:** Local Institution **State:** Distrito Federal **Zip:** 44670 **Location 68:** **City:** Zapopan **Country:** Mexico **Facility:** Local Institution **State:** Distrito Federal **Zip:** 45150 **Location 69:** **City:** Guadalajara **Country:** Mexico **Facility:** Local Institution **State:** Jalisco **Zip:** 44650 **Location 70:** **City:** Guadalajara **Country:** Mexico **Facility:** Local Institution **State:** Jalisco **Zip:** 44670 **Location 71:** **City:** Monterrey **Country:** Mexico **Facility:** Local Institution **State:** Nuevo Leon **Zip:** 64460 **Location 72:** **City:** Monterrey **Country:** Mexico **Facility:** Local Institution **State:** Nuevo Leon **Zip:** 64710 **Location 73:** **City:** Monterrrey **Country:** Mexico **Facility:** Local Institution **State:** Nuevo Leon **Zip:** 64700 **Location 74:** **City:** Tampico **Country:** Mexico **Facility:** Local Institution **State:** Tamaulipas **Zip:** 89109 **Location 75:** **City:** Durango **Country:** Mexico **Facility:** Local Institution **Zip:** 64710 #### Overall Officials **Official 1:** **Affiliation:** Bristol-Myers Squibb **Name:** Bristol-Myers Squibb **Role:** STUDY_DIRECTOR ### References Module #### References **Citation:** Shah M, Stolbov L, Yakovleva T, Tang W, Sokolov V, Penland RC, Boulton D, Parkinson J. A model-based approach to investigating the relationship between glucose-insulin dynamics and dapagliflozin treatment effect in patients with type 2 diabetes. Diabetes Obes Metab. 2021 Apr;23(4):991-1000. doi: 10.1111/dom.14305. Epub 2021 Jan 25. **PMID:** 33368935 **Citation:** Bailey CJ, Del Prato S, Wei C, Reyner D, Saraiva G. Durability of glycaemic control with dapagliflozin, an SGLT2 inhibitor, compared with saxagliptin, a DPP4 inhibitor, in patients with inadequately controlled type 2 diabetes. Diabetes Obes Metab. 2019 Nov;21(11):2564-2569. doi: 10.1111/dom.13841. Epub 2019 Aug 26. **PMID:** 31364269 **Citation:** Mellander A, Billger M, Johnsson E, Traff AK, Yoshida S, Johnsson K. Hypersensitivity Events, Including Potentially Hypersensitivity-Related Skin Events, with Dapagliflozin in Patients with Type 2 Diabetes Mellitus: A Pooled Analysis. Clin Drug Investig. 2016 Nov;36(11):925-933. doi: 10.1007/s40261-016-0438-3. **PMID:** 27461213 **Citation:** Kohan DE, Fioretto P, Johnsson K, Parikh S, Ptaszynska A, Ying L. The effect of dapagliflozin on renal function in patients with type 2 diabetes. J Nephrol. 2016 Jun;29(3):391-400. doi: 10.1007/s40620-016-0261-1. Epub 2016 Feb 19. **PMID:** 26894924 **Citation:** Bailey CJ, Gross JL, Hennicken D, Iqbal N, Mansfield TA, List JF. Dapagliflozin add-on to metformin in type 2 diabetes inadequately controlled with metformin: a randomized, double-blind, placebo-controlled 102-week trial. BMC Med. 2013 Feb 20;11:43. doi: 10.1186/1741-7015-11-43. Erratum In: BMC Med. 2013;11:193. **PMID:** 23425012 **Citation:** Bailey CJ, Gross JL, Pieters A, Bastien A, List JF. Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemic control with metformin: a randomised, double-blind, placebo-controlled trial. Lancet. 2010 Jun 26;375(9733):2223-33. doi: 10.1016/S0140-6736(10)60407-2. **PMID:** 20609968 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000044882 - Term: Glucose Metabolism Disorders - ID: D000008659 - Term: Metabolic Diseases - ID: D000004700 - Term: Endocrine System Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC18 - Name: Nutritional and Metabolic Diseases - Abbrev: BC19 - Name: Gland and Hormone Related Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M7115 - Name: Diabetes Mellitus - Relevance: HIGH - As Found: Diabetes - ID: M7119 - Name: Diabetes Mellitus, Type 2 - Relevance: HIGH - As Found: Type 2 Diabetes - ID: M11639 - Name: Metabolic Diseases - Relevance: LOW - As Found: Unknown - ID: M25403 - Name: Glucose Metabolism Disorders - Relevance: LOW - As Found: Unknown - ID: M7862 - Name: Endocrine System Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000003920 - Term: Diabetes Mellitus - ID: D000003924 - Term: Diabetes Mellitus, Type 2 ### Intervention Browse Module - Ancestors - ID: D000007004 - Term: Hypoglycemic Agents - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000077203 - Term: Sodium-Glucose Transporter 2 Inhibitors - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action ### Intervention Browse Module - Browse Branches - Abbrev: Hypo - Name: Hypoglycemic Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M11667 - Name: Metformin - Relevance: HIGH - As Found: Assessment - ID: M348449 - Name: Dapagliflozin - Relevance: HIGH - As Found: Intramuscular - ID: M10054 - Name: Hypoglycemic Agents - Relevance: LOW - As Found: Unknown - ID: M1691 - Name: Sodium-Glucose Transporter 2 Inhibitors - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000008687 - Term: Metformin - ID: C000529054 - Term: Dapagliflozin ### Misc Info Module #### Removed Countries - Country: Russian Federation - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module #### Event Groups **Group ID:** EG000 **Title:** Placebo + Metformin **Description:** Participants received dapagliflozin-matching placebo once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks **ID:** EG000 **Other Num Affected:** 84 **Other Num at Risk:** 137 **Serious Number Affected:** 14 **Serious Number At Risk:** 137 **Title:** Placebo + Metformin **Group ID:** EG001 **Title:** Dapagliflozin, 2.5 mg + Metformin **Description:** Participants received dapagliflozin, 2.5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks **ID:** EG001 **Other Num Affected:** 87 **Other Num at Risk:** 137 **Serious Number Affected:** 15 **Serious Number At Risk:** 137 **Title:** Dapagliflozin, 2.5 mg + Metformin **Group ID:** EG002 **Title:** Dapagliflozin, 5.0 mg + Metformin **Description:** Participants received dapagliflozin, 5.0 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks **ID:** EG002 **Other Num Affected:** 77 **Other Num at Risk:** 137 **Serious Number Affected:** 9 **Serious Number At Risk:** 137 **Title:** Dapagliflozin, 5.0 mg + Metformin **Group ID:** EG003 **Title:** Dapagliflozin, 10 mg + Metformin **Description:** Participants received dapagliflozin, 10 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks **ID:** EG003 **Other Num Affected:** 83 **Other Num at Risk:** 135 **Serious Number Affected:** 14 **Serious Number At Risk:** 135 **Title:** Dapagliflozin, 10 mg + Metformin **Frequency Threshold:** 5 #### Other Events **Term:** Headache **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 13.0 **Term:** Hypertension **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA 13.0 **Term:** Influenza **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 13.0 **Term:** Vomiting **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 13.0 **Term:** Bronchitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 13.0 **Term:** Cough **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 13.0 **Term:** Diarrhoea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 13.0 **Term:** Dizziness **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 13.0 **Term:** Back pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 13.0 **Term:** Dyslipidaemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 13.0 **Term:** Gastroenteritis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 13.0 **Term:** Nasopharyngitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 13.0 **Term:** Pain in extremity **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 13.0 **Term:** Upper respiratory tract infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 13.0 **Term:** Urinary tract infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 13.0 **Term:** Arthralgia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 13.0 **Term:** Pharyngitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 13.0 **Term:** Depression **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA 13.0 **Term:** Nausea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 13.0 #### Serious Events **Term:** Breast cancer **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA 13.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 137 **Group ID:** EG001 **Num At Risk:** 137 **Group ID:** EG002 **Num At Risk:** 137 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 135 **Term:** Cerebrovascular accident **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 13.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 137 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 137 **Group ID:** EG002 **Num At Risk:** 137 **Group ID:** EG003 **Num At Risk:** 135 **Term:** Cervical cord compression **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 13.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 137 **Group ID:** EG001 **Num At Risk:** 137 **Group ID:** EG002 **Num At Risk:** 137 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 135 **Term:** Dengue fever **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 13.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 137 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 137 **Group ID:** EG002 **Num At Risk:** 137 **Group ID:** EG003 **Num At Risk:** 135 **Term:** Face injury **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 13.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 137 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 137 **Group ID:** EG002 **Num At Risk:** 137 **Group ID:** EG003 **Num At Risk:** 135 **Term:** Intervertebral disc protrusion **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 13.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 137 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 137 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 137 **Group ID:** EG003 **Num At Risk:** 135 **Term:** Loss of consciousness **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 13.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 137 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 137 **Group ID:** EG002 **Num At Risk:** 137 **Group ID:** EG003 **Num At Risk:** 135 **Term:** Malignant melanoma **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA 13.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 137 **Group ID:** EG001 **Num At Risk:** 137 **Group ID:** EG002 **Num At Risk:** 137 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 135 **Term:** Necrobiosis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 13.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 137 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 137 **Group ID:** EG002 **Num At Risk:** 137 **Group ID:** EG003 **Num At Risk:** 135 **Term:** Renal cell carcinoma **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA 13.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 137 **Group ID:** EG001 **Num At Risk:** 137 **Group ID:** EG002 **Num At Risk:** 137 **Group ID:** EG003 **Num At Risk:** 135 **Term:** Rotator cuff syndrome **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 13.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 137 **Group ID:** EG001 **Num At Risk:** 137 **Group ID:** EG002 **Num At Risk:** 137 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 135 **Term:** Spinal cord injury cervical **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 13.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 137 **Group ID:** EG001 **Num At Risk:** 137 **Group ID:** EG002 **Num At Risk:** 137 **Group ID:** EG003 **Num At Risk:** 135 **Term:** Transient ischaemic attack **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 13.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 137 **Group ID:** EG001 **Num At Risk:** 137 **Group ID:** EG002 **Num At Risk:** 137 **Group ID:** EG003 **Num At Risk:** 135 **Term:** Angina pectoris **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 13.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 137 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 137 **Group ID:** EG002 **Num At Risk:** 137 **Group ID:** EG003 **Num At Risk:** 135 **Term:** Bacteraemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 13.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 137 **Group ID:** EG001 **Num At Risk:** 137 **Group ID:** EG002 **Num At Risk:** 137 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 135 **Term:** Fall **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 13.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 137 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 137 **Group ID:** EG002 **Num At Risk:** 137 **Group ID:** EG003 **Num At Risk:** 135 **Term:** Lymphocytic leukaemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA 13.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 137 **Group ID:** EG001 **Num At Risk:** 137 **Group ID:** EG002 **Num At Risk:** 137 **Group ID:** EG003 **Num At Risk:** 135 **Term:** Myocardial infarction **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 13.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 137 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 137 **Group ID:** EG002 **Num At Risk:** 137 **Group ID:** EG003 **Num At Risk:** 135 **Term:** Angina unstable **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 13.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 137 **Group ID:** EG001 **Num At Risk:** 137 **Group ID:** EG002 **Num At Risk:** 137 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 135 **Term:** Calculus ureteric **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA 13.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 137 **Group ID:** EG001 **Num At Risk:** 137 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 137 **Group ID:** EG003 **Num At Risk:** 135 **Term:** Cholecystitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA 13.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 137 **Group ID:** EG001 **Num At Risk:** 137 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 137 **Group ID:** EG003 **Num At Risk:** 135 **Term:** Diverticulitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 13.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 137 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 137 **Group ID:** EG002 **Num At Risk:** 137 **Group ID:** EG003 **Num At Risk:** 135 **Term:** Spinal osteoarthritis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 13.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 137 **Group ID:** EG001 **Num At Risk:** 137 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 137 **Group ID:** EG003 **Num At Risk:** 135 **Term:** Urethral injury **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 13.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 137 **Group ID:** EG001 **Num At Risk:** 137 **Group ID:** EG002 **Num At Risk:** 137 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 135 **Term:** Appendicitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 13.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 137 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 137 **Group ID:** EG002 **Num At Risk:** 137 **Group ID:** EG003 **Num At Risk:** 135 **Term:** Atrial fibrillation **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 13.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 137 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 137 **Group ID:** EG002 **Num At Risk:** 137 **Group ID:** EG003 **Num At Risk:** 135 **Term:** Coronary artery stenosis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 13.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 137 **Group ID:** EG001 **Num At Risk:** 137 **Group ID:** EG002 **Num At Risk:** 137 **Group ID:** EG003 **Num At Risk:** 135 **Term:** Head injury **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 13.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 137 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 137 **Group ID:** EG002 **Num At Risk:** 137 **Group ID:** EG003 **Num At Risk:** 135 **Term:** Inguinal hernia, obstructive **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 13.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 137 **Group ID:** EG001 **Num At Risk:** 137 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 137 **Group ID:** EG003 **Num At Risk:** 135 **Term:** Myocardial ischaemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 13.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 137 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 137 **Group ID:** EG002 **Num At Risk:** 137 **Group ID:** EG003 **Num At Risk:** 135 **Term:** Open fracture **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 13.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 137 **Group ID:** EG001 **Num At Risk:** 137 **Group ID:** EG002 **Num At Risk:** 137 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 135 **Term:** Osteoarthritis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 13.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 137 **Group ID:** EG001 **Num At Risk:** 137 **Group ID:** EG002 **Num At Risk:** 137 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 135 **Term:** Rectosigmoid cancer **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA 13.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 137 **Group ID:** EG001 **Num At Risk:** 137 **Group ID:** EG002 **Num At Risk:** 137 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 135 **Term:** Urinary tract infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 13.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 137 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 137 **Group ID:** EG002 **Num At Risk:** 137 **Group ID:** EG003 **Num At Risk:** 135 **Term:** Abdominal pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 13.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 137 **Group ID:** EG001 **Num At Risk:** 137 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 137 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 135 **Term:** Arteriosclerosis coronary artery **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 13.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 137 **Group ID:** EG001 **Num At Risk:** 137 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 137 **Group ID:** EG003 **Num At Risk:** 135 **Term:** Arthralgia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 13.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 137 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 137 **Group ID:** EG002 **Num At Risk:** 137 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 135 **Term:** Bladder transitional cell carcinoma **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA 13.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 137 **Group ID:** EG001 **Num At Risk:** 137 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 137 **Group ID:** EG003 **Num At Risk:** 135 **Term:** Cardiac arrest **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 13.0 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 137 **Group ID:** EG001 **Num At Risk:** 137 **Group ID:** EG002 **Num At Risk:** 137 **Group ID:** EG003 **Num At Risk:** 135 **Term:** Diabetic gastroparesis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 13.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 137 **Group ID:** EG001 **Num At Risk:** 137 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 137 **Group ID:** EG003 **Num At Risk:** 135 **Term:** Ischaemic stroke **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 13.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 137 **Group ID:** EG001 **Num At Risk:** 137 **Group ID:** EG002 **Num At Risk:** 137 **Group ID:** EG003 **Num At Risk:** 135 **Term:** Lung neoplasm malignant **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA 13.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 137 **Group ID:** EG001 **Num At Risk:** 137 **Group ID:** EG002 **Num At Risk:** 137 **Group ID:** EG003 **Num At Risk:** 135 **Term:** Pneumonia aspiration **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 13.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 137 **Group ID:** EG001 **Num At Risk:** 137 **Group ID:** EG002 **Num At Risk:** 137 **Group ID:** EG003 **Num At Risk:** 135 **Term:** Urinary incontinence **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA 13.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 137 **Group ID:** EG001 **Num At Risk:** 137 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 137 **Group ID:** EG003 **Num At Risk:** 135 **Term:** Cardio-respiratory arrest **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 13.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 137 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 137 **Group ID:** EG002 **Num At Risk:** 137 **Group ID:** EG003 **Num At Risk:** 135 **Term:** Dyspnoea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 13.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 137 **Group ID:** EG001 **Num At Risk:** 137 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 137 **Group ID:** EG003 **Num At Risk:** 135 **Term:** Renal failure acute **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA 13.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 137 **Group ID:** EG001 **Num At Risk:** 137 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 137 **Group ID:** EG003 **Num At Risk:** 135 **Term:** Syncope **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 13.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 137 **Group ID:** EG001 **Num At Risk:** 137 **Group ID:** EG002 **Num At Risk:** 137 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 135 **Term:** Thrombocytopenia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA 13.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 137 **Group ID:** EG001 **Num At Risk:** 137 **Group ID:** EG002 **Num At Risk:** 137 **Group ID:** EG003 **Num At Risk:** 135 **Term:** Acute myocardial infarction **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 13.0 ##### Stats **Group ID:** EG000 **Num Affected:** 3 **Num At Risk:** 137 **Group ID:** EG001 **Num At Risk:** 137 **Group ID:** EG002 **Num At Risk:** 137 **Group ID:** EG003 **Num At Risk:** 135 **Term:** Atrioventricular block second degree **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 13.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 137 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 137 **Group ID:** EG002 **Num At Risk:** 137 **Group ID:** EG003 **Num At Risk:** 135 **Term:** Basal cell carcinoma **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA 13.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 137 **Group ID:** EG001 **Num At Risk:** 137 **Group ID:** EG002 **Num At Risk:** 137 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 135 **Term:** Breast mass **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Reproductive system and breast disorders **Source Vocabulary:** MedDRA 13.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 137 **Group ID:** EG001 **Num At Risk:** 137 **Group ID:** EG002 **Num At Risk:** 137 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 135 **Term:** Chest pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 13.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 137 **Group ID:** EG001 **Num At Risk:** 137 **Group ID:** EG002 **Num At Risk:** 137 **Group ID:** EG003 **Num Affected:** 2 **Num At Risk:** 135 **Term:** Postoperative wound infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 13.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 137 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 137 **Group ID:** EG002 **Num At Risk:** 137 **Group ID:** EG003 **Num At Risk:** 135 ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 137 **Group ID:** BG001 **Value:** 137 **Group ID:** BG002 **Value:** 137 **Group ID:** BG003 **Value:** 135 **Group ID:** BG004 **Value:** 546 **Units:** Participants ### Group **ID:** BG000 **Title:** Placebo + Metformin **Description:** Participants received dapagliflozin-matching placebo once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks ### Group **ID:** BG001 **Title:** Dapagliflozin, 2.5 mg + Metformin **Description:** Participants received dapagliflozin, 2.5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks ### Group **ID:** BG002 **Title:** Dapagliflozin, 5 mg + Metformin **Description:** Participants received dapagliflozin, 5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks ### Group **ID:** BG003 **Title:** Dapagliflozin, 10 mg + Metformin **Description:** Participants received dapagliflozin, 10 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks ### Group **ID:** BG004 **Title:** Total **Description:** Total of all reporting groups ### Measure #### Measurement **Group ID:** BG000 **Lower Limit:** 30 **Upper Limit:** 74 **Value:** 53.7 #### Measurement **Group ID:** BG001 **Lower Limit:** 30 **Upper Limit:** 76 **Value:** 55.0 #### Measurement **Group ID:** BG002 **Lower Limit:** 33 **Upper Limit:** 75 **Value:** 54.3 #### Measurement **Group ID:** BG003 **Lower Limit:** 29 **Upper Limit:** 76 **Value:** 52.7 #### Measurement **Group ID:** BG004 **Lower Limit:** 29 **Upper Limit:** 76 **Value:** 53.9 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 114 #### Measurement **Group ID:** BG001 **Value:** 116 #### Measurement **Group ID:** BG002 **Value:** 119 #### Measurement **Group ID:** BG003 **Value:** 118 #### Measurement **Group ID:** BG004 **Value:** 467 **Class Title:** Younger than 65 years #### Measurement **Group ID:** BG000 **Value:** 23 #### Measurement **Group ID:** BG001 **Value:** 19 #### Measurement **Group ID:** BG002 **Value:** 17 #### Measurement **Group ID:** BG003 **Value:** 16 #### Measurement **Group ID:** BG004 **Value:** 75 **Class Title:** 65 to younger than 75 years #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 2 #### Measurement **Group ID:** BG002 **Value:** 1 #### Measurement **Group ID:** BG003 **Value:** 1 #### Measurement **Group ID:** BG004 **Value:** 4 **Class Title:** 75 years and older ### Measure #### Measurement **Group ID:** BG000 **Value:** 61 #### Measurement **Group ID:** BG001 **Value:** 67 #### Measurement **Group ID:** BG002 **Value:** 68 #### Measurement **Group ID:** BG003 **Value:** 58 #### Measurement **Group ID:** BG004 **Value:** 254 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 76 #### Measurement **Group ID:** BG001 **Value:** 70 #### Measurement **Group ID:** BG002 **Value:** 69 #### Measurement **Group ID:** BG003 **Value:** 77 #### Measurement **Group ID:** BG004 **Value:** 292 **Category Title:** Male **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 124 #### Measurement **Group ID:** BG001 **Value:** 117 #### Measurement **Group ID:** BG002 **Value:** 118 #### Measurement **Group ID:** BG003 **Value:** 121 #### Measurement **Group ID:** BG004 **Value:** 480 **Class Title:** White #### Measurement **Group ID:** BG000 **Value:** 2 #### Measurement **Group ID:** BG001 **Value:** 5 #### Measurement **Group ID:** BG002 **Value:** 6 #### Measurement **Group ID:** BG003 **Value:** 4 #### Measurement **Group ID:** BG004 **Value:** 17 **Class Title:** Black/African American #### Measurement **Group ID:** BG000 **Value:** 3 #### Measurement **Group ID:** BG001 **Value:** 3 #### Measurement **Group ID:** BG002 **Value:** 4 #### Measurement **Group ID:** BG003 **Value:** 1 #### Measurement **Group ID:** BG004 **Value:** 11 **Class Title:** Asian #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 1 #### Measurement **Group ID:** BG003 **Value:** 0 #### Measurement **Group ID:** BG004 **Value:** 1 **Class Title:** Native Hawaiian/Other Pacific Islander #### Measurement **Group ID:** BG000 **Value:** 1 #### Measurement **Group ID:** BG001 **Value:** 2 #### Measurement **Group ID:** BG002 **Value:** 2 #### Measurement **Group ID:** BG003 **Value:** 4 #### Measurement **Group ID:** BG004 **Value:** 9 **Class Title:** American Indian/Alaskan Native #### Measurement **Group ID:** BG000 **Value:** 7 #### Measurement **Group ID:** BG001 **Value:** 10 #### Measurement **Group ID:** BG002 **Value:** 6 #### Measurement **Group ID:** BG003 **Value:** 5 #### Measurement **Group ID:** BG004 **Value:** 28 **Class Title:** Other ### Measure #### Measurement **Group ID:** BG000 **Value:** 25 #### Measurement **Group ID:** BG001 **Value:** 18 #### Measurement **Group ID:** BG002 **Value:** 22 #### Measurement **Group ID:** BG003 **Value:** 22 #### Measurement **Group ID:** BG004 **Value:** 87 **Class Title:** 50 Years and younger #### Measurement **Group ID:** BG000 **Value:** 36 #### Measurement **Group ID:** BG001 **Value:** 49 #### Measurement **Group ID:** BG002 **Value:** 46 #### Measurement **Group ID:** BG003 **Value:** 36 #### Measurement **Group ID:** BG004 **Value:** 167 **Class Title:** Older than 50 years ### Measure #### Measurement **Group ID:** BG000 **Value:** 9 #### Measurement **Group ID:** BG001 **Value:** 4 #### Measurement **Group ID:** BG002 **Value:** 12 #### Measurement **Group ID:** BG003 **Value:** 12 #### Measurement **Group ID:** BG004 **Value:** 37 **Class Title:** <25 kg/m^2 #### Measurement **Group ID:** BG000 **Value:** 128 #### Measurement **Group ID:** BG001 **Value:** 133 #### Measurement **Group ID:** BG002 **Value:** 125 #### Measurement **Group ID:** BG003 **Value:** 123 #### Measurement **Group ID:** BG004 **Value:** 509 **Class Title:** ≥25 kg/m^2 #### Measurement **Group ID:** BG000 **Value:** 115 #### Measurement **Group ID:** BG001 **Value:** 120 #### Measurement **Group ID:** BG002 **Value:** 111 #### Measurement **Group ID:** BG003 **Value:** 106 #### Measurement **Group ID:** BG004 **Value:** 452 **Class Title:** ≥27 kg/m^2 #### Measurement **Group ID:** BG000 **Value:** 79 #### Measurement **Group ID:** BG001 **Value:** 77 #### Measurement **Group ID:** BG002 **Value:** 81 #### Measurement **Group ID:** BG003 **Value:** 75 #### Measurement **Group ID:** BG004 **Value:** 312 **Class Title:** ≥30 kg/m^2 **Denomination Units Selected:** ## Results Section - Baseline Characteristics Module ### Measure 1 **Dispersion Type:** FULL_RANGE **Parameter Type:** MEAN **Title:** Age, Continuous **Unit of Measure:** Years ### Measure 2 **Parameter Type:** NUMBER **Title:** Age, Customized **Unit of Measure:** Participants ### Measure 3 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Sex: Female, Male **Unit of Measure:** Participants ### Measure 4 **Parameter Type:** NUMBER **Title:** Race/Ethnicity, Customized **Unit of Measure:** Participants ### Measure 5 **Parameter Type:** NUMBER **Title:** Female Age **Unit of Measure:** Participants ### Measure 6 **Parameter Type:** NUMBER **Title:** Body Mass Index **Unit of Measure:** Participants **Population Description:** All randomized participants who received at least 1 dose of study medication ## Results Section - More Information Module ### Certain Agreement **Other Details:** Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication. **Restriction Type:** OTHER **Restrictive Agreement:** True ### Point of Contact **Email:** [email protected] **Organization:** Bristol-Myers Squibb **Title:** Bristol-Myers Squibb Study Director ## Results Section - Outcome Measures Module ### Outcome Measure 1 #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.1014 **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0002 **P-Value Comment:** Tested at alpha=0.019, applying the Dunnett adjustment **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** -0.38 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.1016 **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** <0.0001 **P-Value Comment:** Tested at alpha=0.019, applying the Dunnett adjustment **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** -0.41 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.1021 **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** <0.0001 **P-Value Comment:** Tested at alpha=0.019, applying the Dunnett adjustment **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** -0.54 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** False ### Outcome Measure 2 #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 3.774 **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** <0.0019 **P-Value Comment:** Statistically significant according to hierarchical testing procedure (p\<0.05). **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** -11.8 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 3.781 **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** <0.0001 **P-Value Comment:** Statistically significant according to hierarchical testing procedure (p\<0.05). **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** -15.5 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 3.819 **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** <0.0001 **P-Value Comment:** Statistically significant according to hierarchical testing procedure (p\<0.05). **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** -17.5 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** False ### Outcome Measure 3 #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.3344 **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** <0.0001 **P-Value Comment:** Statistically significant according to hierarchical testing procedure (p\<0.05). **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** -1.32 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.3344 **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** <0.0001 **P-Value Comment:** Statistically significant according to hierarchical testing procedure (p\<0.05). **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** -2.16 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.3365 **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** <0.0001 **P-Value Comment:** Statistically significant according to hierarchical testing procedure (p\<0.05). **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** -1.97 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** False ### Outcome Measure 4 #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.1775 **P-Value Comment:** Statistically significant according to hierarchical testing procedure (p\<0.05). **Parameter Type:** Median Difference (Final Values) **Parameter Value:** 7.1 **Statistical Comment:** **Statistical Method:** Modified logistic regression **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0275 **P-Value Comment:** Statistically significant according to hierarchical testing procedure (p\<0.05). **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 11.7 **Statistical Comment:** **Statistical Method:** Modified logistic regression **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0062 **P-Value Comment:** Statistically significant according to hierarchical testing procedure (p\<0.05). **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 14.7 **Statistical Comment:** **Statistical Method:** Modified logistic regression **Tested Non-Inferiority:** False ### Outcome Measure 5 #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.3515 **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** **P-Value Comment:** Sequential testing procedures were used, and no test was performed for this comparison due to the fact that the previous comparison was not significant. **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** -0.68 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.3022 **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0068 **P-Value Comment:** Statistically significant according to hierarchical testing procedure (p\<0.05). **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** -0.84 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.3535 **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0290 **P-Value Comment:** Statistically significant according to hierarchical testing procedure (p\<0.05). **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** -0.78 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** False ### Outcome Measure 6 #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.3681 **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** **P-Value Comment:** Sequential testing procedures were used, and no test was performed for this comparison due to the fact that the previous comparison was not significant. **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** -1.38 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.3745 **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** <0.0001 **P-Value Comment:** Statistically significant according to hierarchical testing procedure (p\<0.05). **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** -2.19 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.3791 **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** <0.0001 **P-Value Comment:** Statistically significant according to hierarchical testing procedure (p\<0.05). **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** -2.08 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** False ### Outcome Measure 7 ### Outcome Measure 8 ### Outcome Measure 9 ### Outcome Measure 10 ### Outcome Measure 11 ### Outcome Measure 12 ### Outcome Measure 13 #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.1109 **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** **P-Value Comment:** Sequential testing procedures were used, and no test was performed for this comparison due to the fact that the previous comparison was not significant. **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** -0.38 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.1129 **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0004 **P-Value Comment:** Statistically significant according to hierarchical testing procedure (p\<0.05). **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** -0.40 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.1146 **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** <0.0001 **P-Value Comment:** Statistically significant according to hierarchical testing procedure (p\<0.05). **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** -0.57 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** False ### Outcome Measure 14 #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 2.769 **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** **P-Value Comment:** Sequential testing procedures were used, and no test was performed for this comparison due to the fact that the previous comparison was not significant. **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** -7.1 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 2.762 **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** <0.0001 **P-Value Comment:** Statistically significant according to hierarchical testing procedure (p\<0.05). **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** -13.1 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 2.808 **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** <0.0001 **P-Value Comment:** Statistically significant according to hierarchical testing procedure (p\<0.05). **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** -17.7 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** False ### Outcome Measure 15 #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** **P-Value Comment:** Sequential testing procedures were used, and no test was performed for this comparison due to the fact that the previous comparison was not significant. **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 6.9 **Statistical Comment:** **Statistical Method:** Modified logistic regression **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.8627 **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 0.7 **Statistical Comment:** **Statistical Method:** Modified logistic regression **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0149 **P-Value Comment:** Statistically significant according to hierarchical testing procedure (p\<0.05). **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 11.3 **Statistical Comment:** **Statistical Method:** Modified logistic regression **Tested Non-Inferiority:** False ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.0718 - **Upper Limit:** - **Value:** -0.30 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.0715 - **Upper Limit:** - **Value:** -0.67 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 0.0722 - **Upper Limit:** - **Value:** -0.70 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** 0.0724 - **Upper Limit:** - **Value:** -0.84 **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 2.673 - **Upper Limit:** - **Value:** -6.0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 2.663 - **Upper Limit:** - **Value:** -17.8 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 2.679 - **Upper Limit:** - **Value:** -21.5 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** 2.721 - **Upper Limit:** - **Value:** -23.5 **Title:** #### Outcome Measure 3 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.2368 - **Upper Limit:** - **Value:** -0.89 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.2357 - **Upper Limit:** - **Value:** -2.21 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 0.2358 - **Upper Limit:** - **Value:** -3.04 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** 0.2392 - **Upper Limit:** - **Value:** -2.86 **Title:** #### Outcome Measure 4 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 25.9 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 33.0 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 37.5 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 40.6 **Title:** #### Outcome Measure 5 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.2345 - **Upper Limit:** - **Value:** -0.53 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.2660 - **Upper Limit:** - **Value:** -1.21 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 0.1875 - **Upper Limit:** - **Value:** -1.37 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** 0.2595 - **Upper Limit:** - **Value:** -1.32 **Title:** #### Outcome Measure 6 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.2630 - **Upper Limit:** - **Value:** -1.01 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.2564 - **Upper Limit:** - **Value:** -2.39 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 0.2661 - **Upper Limit:** - **Value:** -3.21 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** 0.2737 - **Upper Limit:** - **Value:** -3.09 **Title:** #### Outcome Measure 7 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 111 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 111 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 111 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 111 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 8 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 5 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 7 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 7 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 28 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 36 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 33 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 45 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 14 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 15 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 9 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 14 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 6 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 9 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 7 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 5 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 6 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** #### Outcome Measure 8 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 5 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 6 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 5 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 5 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 5 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 **Title:** #### Outcome Measure 9 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 74 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 80 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 79 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 82 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 7 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 14 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 9 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 8 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 9 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 6 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 5 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 9 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 17 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 11 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 20 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 10 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 26 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 24 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 20 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 25 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** #### Outcome Measure 10 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.216 - **Upper Limit:** - **Value:** -0.1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.380 - **Upper Limit:** - **Value:** -1.6 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 1.206 - **Upper Limit:** - **Value:** -4.0 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** 1.230 - **Upper Limit:** - **Value:** -3.0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.229 - **Upper Limit:** - **Value:** -0.2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.126 - **Upper Limit:** - **Value:** -2.1 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 1.270 - **Upper Limit:** - **Value:** -4.3 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** 1.329 - **Upper Limit:** - **Value:** -5.1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.440 - **Upper Limit:** - **Value:** 1.0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.281 - **Upper Limit:** - **Value:** -0.1 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 1.314 - **Upper Limit:** - **Value:** -2.1 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** 1.472 - **Upper Limit:** - **Value:** -1.9 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.610 - **Upper Limit:** - **Value:** 1.5 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.825 - **Upper Limit:** - **Value:** 0.7 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 1.412 - **Upper Limit:** - **Value:** -1.1 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** 1.544 - **Upper Limit:** - **Value:** -0.3 **Title:** #### Outcome Measure 11 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.763 - **Upper Limit:** - **Value:** -0.9 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.794 - **Upper Limit:** - **Value:** -1.3 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 0.714 - **Upper Limit:** - **Value:** -2.3 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** 0.758 - **Upper Limit:** - **Value:** -1.0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.744 - **Upper Limit:** - **Value:** -0.1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.863 - **Upper Limit:** - **Value:** -1.8 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 0.769 - **Upper Limit:** - **Value:** -2.5 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** 0.842 - **Upper Limit:** - **Value:** -1.8 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.861 - **Upper Limit:** - **Value:** 0.1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.714 - **Upper Limit:** - **Value:** -0.2 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 0.840 - **Upper Limit:** - **Value:** -2.4 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** 0.921 - **Upper Limit:** - **Value:** -1.2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.929 - **Upper Limit:** - **Value:** -1.0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.914 - **Upper Limit:** - **Value:** -0.1 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 0.861 - **Upper Limit:** - **Value:** -1.5 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** 1.041 - **Upper Limit:** - **Value:** -1.2 **Title:** #### Outcome Measure 12 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 28 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 26 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 21 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 19 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 6 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 8 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 5 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 10 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 6 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 5 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 10 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 6 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 7 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 6 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 **Title:** #### Outcome Measure 13 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.0792 - **Upper Limit:** - **Value:** -0.31 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.0774 - **Upper Limit:** - **Value:** -0.69 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 0.0806 - **Upper Limit:** - **Value:** -0.71 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** 0.0826 - **Upper Limit:** - **Value:** -0.88 **Title:** #### Outcome Measure 14 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.934 - **Upper Limit:** - **Value:** 1.2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.981 - **Upper Limit:** - **Value:** -6.0 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 1.976 - **Upper Limit:** - **Value:** -12.0 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** 2.030 - **Upper Limit:** - **Value:** -16.5 **Title:** #### Outcome Measure 15 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 13.8 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 20.7 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 14.5 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 25.2 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** HbA1c was measured as percent of hemoglobin by a central laboratory. Data after rescue medication was excluded from this analysis. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. HbA1c measurements were obtained during the qualification and lead-in periods and on Day 1 and Weeks 4, 8, 12, 16, 20, and 24 in the double-blind period. **Dispersion Type:** Standard Error **Parameter Type:** MEAN **Population Description:** All randomized participants who received study medication and had nonmissing HbA1c values at baseline and Week 24 (LOCF) **Reporting Status:** POSTED **Time Frame:** From Baseline to Week 24 **Title:** Adjusted Mean Change From Baseline in Hemoglobin A1C (HbA1c) at Week 24 (Last Observation Carried Forward [LOCF]) **Type:** PRIMARY **Unit of Measure:** Percent ##### Group **Description:** Participants received dapagliflozin-matching placebo once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks **ID:** OG000 **Title:** Placebo + Metformin ##### Group **Description:** Participants received dapagliflozin, 2.5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks **ID:** OG001 **Title:** Dapagliflozin, 2.5 mg + Metformin ##### Group **Description:** Participants received dapagliflozin, 5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks **ID:** OG002 **Title:** Dapagliflozin, 5 mg + Metformin ##### Group **Description:** Participants received dapagliflozin, 10 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks **ID:** OG003 **Title:** Dapagliflozin, 10 mg + Metformin #### Outcome Measure 2 **Description:** Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Data after rescue medication was excluded from this analysis. Fasting plasma glucose was measured as milligrams per deciliter (mg/dL) by a central laboratory. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. **Dispersion Type:** Standard Error **Parameter Type:** MEAN **Population Description:** All randomized participants who received study medication and who had nonmissing fasting plasma glucose values at baseline and Week 24 (LOCF) **Reporting Status:** POSTED **Time Frame:** From Baseline to Week 24 **Title:** Adjusted Mean Change From Baseline in Fasting Plasma Glucose at Week 24 (Last Observation Carried Forward [LOCF]) **Type:** SECONDARY **Unit of Measure:** mg/dL ##### Group **Description:** Participants received dapagliflozin-matching placebo once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks **ID:** OG000 **Title:** Placebo + Metformin ##### Group **Description:** Participants received dapagliflozin, 2.5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks **ID:** OG001 **Title:** Dapagliflozin, 2.5 mg + Metformin ##### Group **Description:** Participants received dapagliflozin, 5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks **ID:** OG002 **Title:** Dapagliflozin, 5 mg + Metformin ##### Group **Description:** Participants received dapagliflozin, 10 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks **ID:** OG003 **Title:** Dapagliflozin, 10 mg + Metformin #### Outcome Measure 3 **Description:** Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Adjusted mean change from baseline in total body weight at Week 24 (or the last postbaseline measurement prior to Week 24 if no Week 24 assessment was available was determined. Data after rescue medication was excluded from this analysis. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. Body weight measurements were obtained during the qualification and lead-in periods and on Day 1 and Weeks 1, 2, 3, 4, 6, 8, 12, 16, 20, and 24 of the double-blind period. **Dispersion Type:** Standard Error **Parameter Type:** MEAN **Population Description:** All randomized participants who received study medication and had nonmissing total body weights at baseline and Week 24 (LOCF) **Reporting Status:** POSTED **Time Frame:** From Baseline to Week 24 **Title:** Adjusted Mean Change From Baseline in Total Body Weight at Week 24 (Last Observation Carried Forward [LOCF]) **Type:** SECONDARY **Unit of Measure:** Kilograms ##### Group **Description:** Participants received dapagliflozin-matching placebo once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks **ID:** OG000 **Title:** Placebo + Metformin ##### Group **Description:** Participants received dapagliflozin, 2.5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks **ID:** OG001 **Title:** Dapagliflozin, 2.5 mg + Metformin ##### Group **Description:** Participants received dapagliflozin, 5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks **ID:** OG002 **Title:** Dapagliflozin, 5 mg + Metformin ##### Group **Description:** Participants received dapagliflozin, 10 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks **ID:** OG003 **Title:** Dapagliflozin, 10 mg + Metformin #### Outcome Measure 4 **Description:** Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Percent adjusted for baseline HbA1c. Therapeutic glycemic response is defined as HbA1c \<7.0%. Data after rescue medication was excluded from this analysis. HbA1c was measured as a percent of hemoglobin. **Parameter Type:** NUMBER **Population Description:** All randomized participants who received study medication and were not missing baseline and Week 24 (LOCF) values **Reporting Status:** POSTED **Time Frame:** From Baseline to Week 24 **Title:** Percentage of Participants Achieving a Therapeutic Glycemic Response (Hemoglobin A1c [HbA1C]) <7.0% at Week 24 (Last Observation Carried Forward [LOCF]) **Type:** SECONDARY **Unit of Measure:** Percentage of participants ##### Group **Description:** Participants received dapagliflozin-matching placebo once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks **ID:** OG000 **Title:** Placebo + Metformin ##### Group **Description:** Participants received dapagliflozin, 2.5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks **ID:** OG001 **Title:** Dapagliflozin, 2.5 mg + Metformin ##### Group **Description:** Participants received dapagliflozin, 5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks **ID:** OG002 **Title:** Dapagliflozin, 5 mg + Metformin ##### Group **Description:** Participants received dapagliflozin, 10 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks **ID:** OG003 **Title:** Dapagliflozin, 10 mg + Metformin #### Outcome Measure 5 **Description:** Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. HbA1c was measured as percent of hemoglobin by a central laboratory. The population included those randomized participants who received treatment and had a baseline HbA1c \> 9.0%. Data after rescue medication were excluded from this analysis. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. **Dispersion Type:** Standard Error **Parameter Type:** MEAN **Population Description:** All randomized participants who received study medication, who had baseline HbA1c ≥9.0%, and who had nonmissing HbA1c values at Week 24 (LOCF) **Reporting Status:** POSTED **Time Frame:** From Baseline to Week 24 **Title:** Adjusted Mean Change From Baseline in Hemoglobin A1c (HbA1c) in Participants With Baseline HbA1c ≥9.0% at Week 24 (Last Observation Carried Forward [LOCF]) **Type:** SECONDARY **Unit of Measure:** Percent ##### Group **Description:** Participants received dapagliflozin-matching placebo once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks **ID:** OG000 **Title:** Placebo + Metformin ##### Group **Description:** Participants received dapagliflozin, 2.5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks **ID:** OG001 **Title:** Dapagliflozin, 2.5 mg + Metformin ##### Group **Description:** Participants received dapagliflozin, 5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks **ID:** OG002 **Title:** Dapagliflozin, 5 mg + Metformin ##### Group **Description:** Participants received dapagliflozin, 10 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks **ID:** OG003 **Title:** Dapagliflozin, 10 mg + Metformin #### Outcome Measure 6 **Description:** Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Adjusted mean change from baseline in total body weight at Week 24 (or the last postbaseline measurement prior to Week 24 if no Week 24 assessment was available was determined.) Data after rescue medication was excluded from this analysis. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. Body weight measurements were obtained during the qualification and lead-in Periods and on Day 1 and Weeks 1, 2, 3, 4, 6, 8, 12, 16, 20, and 24 of the double-blind period. **Dispersion Type:** Standard Error **Parameter Type:** MEAN **Population Description:** All randomized participants who received study medication, who had baseline BMI ≥27 kg/m\^2, and who had nonmissing total body weight measurements at Week 24 (LOCF) **Reporting Status:** POSTED **Time Frame:** From Baseline to Week 24 **Title:** Adjusted Mean Change From Baseline in Total Body Weight at Week 24 in Participants With Baseline Body Mass Index (BMI) ≥27 kg/m^2 (Last Observation Carried Forward [LOCF]) **Type:** SECONDARY **Unit of Measure:** Kilograms ##### Group **Description:** Participants received dapagliflozin-matching placebo once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks **ID:** OG000 **Title:** Placebo + Metformin ##### Group **Description:** Participants received dapagliflozin, 2.5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks **ID:** OG001 **Title:** Dapagliflozin, 2.5 mg + Metformin ##### Group **Description:** Participants received dapagliflozin, 5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks **ID:** OG002 **Title:** Dapagliflozin, 5 mg + Metformin ##### Group **Description:** Participants received dapagliflozin, 10 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks **ID:** OG003 **Title:** Dapagliflozin, 10 mg + Metformin #### Outcome Measure 7 **Description:** AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Related=having certain, probable, possible, or missing relationship to study drug. Events captured from baseline to last dose plus 4 days for AEs and plus 30 days for SAEs during the double-blind 12-week period. Data after rescue included. **Parameter Type:** NUMBER **Population Description:** All randomized participants who received at least 1 dose of blinded study medication **Reporting Status:** POSTED **Time Frame:** From Baseline to end of Long-term Period (Week 102) **Title:** Number of Participants With Adverse Events (AEs), Hypoglycemia Events, Related AEs, Death as Outcome, Serious AEs (SAEs), Related SAEs, SAEs Leading to Discontinuation, AEs Leading to Discontinuation, and Hypoglycemia Events Leading to Discontinuation **Type:** OTHER_PRE_SPECIFIED **Unit of Measure:** Participants ##### Group **Description:** Participants received dapagliflozin-matching placebo once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks **ID:** OG000 **Title:** Placebo + Metformin ##### Group **Description:** Participants received dapagliflozin, 2.5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks **ID:** OG001 **Title:** Dapagliflozin, 2.5 mg + Metformin ##### Group **Description:** Participants received dapagliflozin, 5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks **ID:** OG002 **Title:** Dapagliflozin, 5 mg + Metformin ##### Group **Description:** Participants received dapagliflozin, 10 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks **ID:** OG003 **Title:** Dapagliflozin, 10 mg + Metformin #### Outcome Measure 8 **Description:** BUN=blood urea nitrogen; preRX=pretreatment; ULN=upper limit of normal; AST=aspartate aminotransferase; ALT=alanine aminotransferase; ALP=alkaline phosphatase. Phosphorus, inorganic (low): ages 17-65 years, ≤1.8 mg/dL; ages≥66 years, ≤2.1 mg/dL. Phosphorus, inorganic (high): ages 17-65 years, ≥5.6 mg/dL; ages≥66 years, ≥5.6 mg/dL. Phosphorus, inorganic (low) ≤1.8 mg/dL if age 17-65 or ≤2.1 mg/dL if age ≥66. Calcium, total (high): ≥1 mg/dL from ULN and ≥0.5 mg/dL from preRx value. **Parameter Type:** NUMBER **Population Description:** All randomized participants who received at least 1 dose of study medication and who had nonmissing laboratory values at baseline and Week 102. **Reporting Status:** POSTED **Time Frame:** Day 1 to Week 102 **Title:** Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality **Type:** OTHER_PRE_SPECIFIED **Unit of Measure:** Participants ##### Group **Description:** Participants received dapagliflozin-matching placebo once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks **ID:** OG000 **Title:** Placebo + Metformin ##### Group **Description:** Participants received dapagliflozin, 2.5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks **ID:** OG001 **Title:** Dapagliflozin, 2.5 mg + Metformin ##### Group **Description:** Participants received dapagliflozin, 5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks **ID:** OG002 **Title:** Dapagliflozin, 5 mg + Metformin ##### Group **Description:** Participants received dapagliflozin, 10 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks **ID:** OG003 **Title:** Dapagliflozin, 10 mg + Metformin #### Outcome Measure 9 **Description:** 12-Lead electrocardiograms (ECGs) were performed at entry into lead-in period Day -7 visit and Week 24/dnd of treatment visit (LOCF) on participants who were supine. ECGs were assessed by the investigator. Baseline was Day -7 for this parameter. Data after rescue included.The Week 102 value is the last observation, regardless of rescue prior to Week 102 if no Week 102 measurement was available. **Parameter Type:** NUMBER **Population Description:** All randomized participants who received at least 1 dose of study medication and who had nonmissing baseline and Week 102 (LOCF) values **Reporting Status:** POSTED **Time Frame:** Baseline to Week 102 **Title:** Number of Participants With Changes in Baseline in Electrocardiogram Findings at Week 102 (Last Observation Carried Forward [LOCF]) **Type:** OTHER_PRE_SPECIFIED **Unit of Measure:** Participants ##### Group **Description:** Participants received dapagliflozin-matching placebo once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks **ID:** OG000 **Title:** Placebo + Metformin ##### Group **Description:** Participants received dapagliflozin, 2.5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks **ID:** OG001 **Title:** Dapagliflozin, 2.5 mg + Metformin ##### Group **Description:** Participants received dapagliflozin, 5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks **ID:** OG002 **Title:** Dapagliflozin, 5 mg + Metformin ##### Group **Description:** Participants received dapagliflozin, 10 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks **ID:** OG003 **Title:** Dapagliflozin, 10 mg + Metformin #### Outcome Measure 10 **Description:** Blood pressure values were obtained after the participant was seated quietly for 5 minutes; at least 8 hours after the last ingestion of caffeine, alcohol, or nicotine; and in the same arm (right or left) consistently through out the study. Data after rescue were also included. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. **Dispersion Type:** Standard Error **Parameter Type:** MEAN **Population Description:** All randomized participants who received study medication. n=the number of participants not missing baseline and Week t values. **Reporting Status:** POSTED **Time Frame:** From Baseline to Week 102 **Title:** Mean Changes From Baseline in Seated Systolic Blood Pressure **Type:** OTHER_PRE_SPECIFIED **Unit of Measure:** mm Hg ##### Group **Description:** Participants received dapagliflozin-matching placebo once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks **ID:** OG000 **Title:** Placebo + Metformin ##### Group **Description:** Participants received dapagliflozin, 2.5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks **ID:** OG001 **Title:** Dapagliflozin, 2.5 mg + Metformin ##### Group **Description:** Participants received dapagliflozin, 5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks **ID:** OG002 **Title:** Dapagliflozin, 5 mg + Metformin ##### Group **Description:** Participants received dapagliflozin, 10 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks **ID:** OG003 **Title:** Dapagliflozin, 10 mg + Metformin #### Outcome Measure 11 **Description:** Blood pressure values were obtained after the participant was seated quietly for 5 minutes; at least 8 hours after the last ingestion of caffeine, alcohol, or nicotine; and in the same arm (right or left) consistently through out the study. Data after rescue were also included. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. **Dispersion Type:** Standard Error **Parameter Type:** MEAN **Population Description:** All randomized participants who received study medication. n=the number of participants not missing baseline and Week t values. **Reporting Status:** POSTED **Time Frame:** From Baseline to Week 102 **Title:** Mean Changes From Baseline in Seated Diastolic Blood Pressure **Type:** OTHER_PRE_SPECIFIED **Unit of Measure:** mm Hg ##### Group **Description:** Participants received dapagliflozin-matching placebo once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks **ID:** OG000 **Title:** Placebo + Metformin ##### Group **Description:** Participants received dapagliflozin, 2.5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks **ID:** OG001 **Title:** Dapagliflozin, 2.5 mg + Metformin ##### Group **Description:** Participants received dapagliflozin, 5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks **ID:** OG002 **Title:** Dapagliflozin, 5 mg + Metformin ##### Group **Description:** Participants received dapagliflozin, 10 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks **ID:** OG003 **Title:** Dapagliflozin, 10 mg + Metformin #### Outcome Measure 12 **Description:** Orthostatic hypotension was defined as a decrease from supine to standing blood pressure of \>20 mm Hg in systolic blood pressure or \>10 mm Hg in diastolic blood pressure. **Parameter Type:** NUMBER **Population Description:** All randomized participants who received treatment; n=the number of participants who were not missing blood pressure measurements. **Reporting Status:** POSTED **Time Frame:** From Baseline to Week 102 **Title:** Number of Participants With Orthostatic Hypotension **Type:** OTHER_PRE_SPECIFIED **Unit of Measure:** Participants ##### Group **Description:** Participants received dapagliflozin-matching placebo once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks **ID:** OG000 **Title:** Placebo + Metformin ##### Group **Description:** Participants received dapagliflozin, 2.5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks **ID:** OG001 **Title:** Dapagliflozin, 2.5 mg + Metformin ##### Group **Description:** Participants received dapagliflozin, 5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks **ID:** OG002 **Title:** Dapagliflozin, 5 mg + Metformin ##### Group **Description:** Participants received dapagliflozin, 10 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks **ID:** OG003 **Title:** Dapagliflozin, 10 mg + Metformin #### Outcome Measure 13 **Description:** Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Adjusted for baseline HbA1c. HbA1c was measured as percent of hemoglobin by a central laboratory. Data after rescue medication were excluded from this analysis. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. **Dispersion Type:** Standard Error **Parameter Type:** MEAN **Population Description:** All randomized participants who received study medication, who had a BMI ≥27 kg/m\^2 at baseline, and who had nonmissing HbA1c values at Week 24 (LOCF) **Reporting Status:** POSTED **Time Frame:** From Baseline to Week 24 **Title:** Adjusted Mean Change From Baseline in Hemoglobin A1c (HbA1c) in Participants With Baseline Body Mass Index (BMI) ≥27 kg/m^2 at Week 24 (Last Observation Carried Forward [LOCF]) **Type:** SECONDARY **Unit of Measure:** Percent ##### Group **Description:** Participants received dapagliflozin-matching placebo once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks **ID:** OG000 **Title:** Placebo + Metformin ##### Group **Description:** Participants received dapagliflozin, 2.5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks **ID:** OG001 **Title:** Dapagliflozin, 2.5 mg + Metformin ##### Group **Description:** Participants received dapagliflozin, 5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks **ID:** OG002 **Title:** Dapagliflozin, 5 mg + Metformin ##### Group **Description:** Participants received dapagliflozin, 10 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks **ID:** OG003 **Title:** Dapagliflozin, 10 mg + Metformin #### Outcome Measure 14 **Description:** Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Data after rescue medication was excluded from this analysis. Fasting plasma glucose was measured by a central laboratory. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. **Dispersion Type:** Standard Error **Parameter Type:** MEAN **Population Description:** All randomized participants who received study medication and who had nonmissing fasting plasma glucose values at baseline and Week 1 (LOCF) **Reporting Status:** POSTED **Time Frame:** From Baseline to Week 1 **Title:** Adjusted Mean Change From Baseline in Fasting Plasma Glucose at Week 1 (Last Observation Carried Forward [LOCF]) **Type:** SECONDARY **Unit of Measure:** mg/dL ##### Group **Description:** Participants received dapagliflozin-matching placebo once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks **ID:** OG000 **Title:** Placebo + Metformin ##### Group **Description:** Participants received dapagliflozin, 2.5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks **ID:** OG001 **Title:** Dapagliflozin, 2.5 mg + Metformin ##### Group **Description:** Participants received dapagliflozin, 5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks **ID:** OG002 **Title:** Dapagliflozin, 5 mg + Metformin ##### Group **Description:** Participants received dapagliflozin, 10 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks **ID:** OG003 **Title:** Dapagliflozin, 10 mg + Metformin #### Outcome Measure 15 **Description:** Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Percent adjusted for baseline HbA1c. Data after rescue medication was excluded from this analysis. HbA1c was measured as a percent of hemoglobin. **Parameter Type:** NUMBER **Population Description:** All randomized participants who received study medication and who had HbA1c values at Baseline and Week 24 (LOCF) **Reporting Status:** POSTED **Time Frame:** From Baseline to Week 24 **Title:** Adjusted Percentage of Participants Achieving Hemoglobin A1c (HbA1C) ≤6.5% at Week 24 (Last Observation Carried Forward [LOCF]) **Type:** SECONDARY **Unit of Measure:** Percentage of participants ##### Group **Description:** Participants received dapagliflozin-matching placebo once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks **ID:** OG000 **Title:** Placebo + Metformin ##### Group **Description:** Participants received dapagliflozin, 2.5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks **ID:** OG001 **Title:** Dapagliflozin, 2.5 mg + Metformin ##### Group **Description:** Participants received dapagliflozin, 5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks **ID:** OG002 **Title:** Dapagliflozin, 5 mg + Metformin ##### Group **Description:** Participants received dapagliflozin, 10 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks **ID:** OG003 **Title:** Dapagliflozin, 10 mg + Metformin ### Participant Flow Module #### Group **Description:** Participants received dapagliflozin-matching placebo once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks **ID:** FG000 **Title:** Placebo + Metformin #### Group **Description:** Participants received dapagliflozin, 2.5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks **ID:** FG001 **Title:** Dapagliflozin, 2.5 mg + Metformin #### Group **Description:** Participants received dapagliflozin, 5 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks **ID:** FG002 **Title:** Dapagliflozin, 5 mg + Metformin #### Group **Description:** Participants received dapagliflozin, 10 mg, once daily plus open-label metformin ≥1500 mg per day for up to 102 weeks **ID:** FG003 **Title:** Dapagliflozin, 10 mg + Metformin #### Period **Title:** Short-term Period (Day 1 to Week 24) ##### Withdraw **Type:** Lack of Efficacy ###### Reason **Group ID:** FG000 **Number of Subjects:** 3 ###### Reason **Group ID:** FG001 **Number of Subjects:** 0 ###### Reason **Group ID:** FG002 **Number of Subjects:** 1 ###### Reason **Group ID:** FG003 **Number of Subjects:** 0 ##### Withdraw **Type:** Adverse Event ###### Reason **Group ID:** FG000 **Number of Subjects:** 4 ###### Reason **Group ID:** FG001 **Number of Subjects:** 4 ###### Reason **Group ID:** FG002 **Number of Subjects:** 2 ###### Reason **Group ID:** FG003 **Number of Subjects:** 4 ##### Withdraw **Type:** Withdrawal by Subject ###### Reason **Group ID:** FG000 **Number of Subjects:** 7 ###### Reason **Group ID:** FG001 **Number of Subjects:** 5 ###### Reason **Group ID:** FG002 **Number of Subjects:** 5 ###### Reason **Group ID:** FG003 **Number of Subjects:** 3 ##### Withdraw **Type:** Lost to Follow-up ###### Reason **Group ID:** FG000 **Number of Subjects:** 5 ###### Reason **Group ID:** FG001 **Number of Subjects:** 4 ###### Reason **Group ID:** FG002 **Number of Subjects:** 4 ###### Reason **Group ID:** FG003 **Number of Subjects:** 5 ##### Withdraw **Type:** Poor compliance/noncompliance ###### Reason **Group ID:** FG000 **Number of Subjects:** 0 ###### Reason **Group ID:** FG001 **Number of Subjects:** 0 ###### Reason **Group ID:** FG002 **Number of Subjects:** 2 ###### Reason **Group ID:** FG003 **Number of Subjects:** 0 ##### Withdraw **Type:** No longer meets study criteria ###### Reason **Group ID:** FG000 **Number of Subjects:** 2 ###### Reason **Group ID:** FG001 **Number of Subjects:** 3 ###### Reason **Group ID:** FG002 **Number of Subjects:** 0 ###### Reason **Group ID:** FG003 **Number of Subjects:** 2 ##### Withdraw **Type:** Administrative reason by author ###### Reason **Group ID:** FG000 **Number of Subjects:** 1 ###### Reason **Group ID:** FG001 **Number of Subjects:** 1 ###### Reason **Group ID:** FG002 **Number of Subjects:** 0 ###### Reason **Group ID:** FG003 **Number of Subjects:** 1 ##### Withdraw **Type:** Other ###### Reason **Group ID:** FG000 **Number of Subjects:** 0 ###### Reason **Group ID:** FG001 **Number of Subjects:** 0 ###### Reason **Group ID:** FG002 **Number of Subjects:** 1 ###### Reason **Group ID:** FG003 **Number of Subjects:** 1 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 137 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 137 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 137 ###### Achievement **Group ID:** FG003 **Number of Subjects:** 135 ##### Milestone **Type:** Completed the Period ###### Achievement **Group ID:** FG000 **Number of Subjects:** 119 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 121 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 122 ###### Achievement **Group ID:** FG003 **Number of Subjects:** 121 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 115 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 120 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 122 ###### Achievement **Group ID:** FG003 **Number of Subjects:** 119 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 22 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 17 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 15 ###### Achievement **Group ID:** FG003 **Number of Subjects:** 16 #### Period **Title:** Long-term Period (Weeks 24 to 102) ##### Withdraw **Type:** Lack of Efficacy ###### Reason **Group ID:** FG000 **Number of Subjects:** 27 ###### Reason **Group ID:** FG001 **Number of Subjects:** 16 ###### Reason **Group ID:** FG002 **Number of Subjects:** 17 ###### Reason **Group ID:** FG003 **Number of Subjects:** 9 ##### Withdraw **Type:** Adverse Event ###### Reason **Group ID:** FG000 **Number of Subjects:** 5 ###### Reason **Group ID:** FG001 **Number of Subjects:** 4 ###### Reason **Group ID:** FG002 **Number of Subjects:** 3 ###### Reason **Group ID:** FG003 **Number of Subjects:** 2 ##### Withdraw **Type:** Withdrawal by Subject ###### Reason **Group ID:** FG000 **Number of Subjects:** 4 ###### Reason **Group ID:** FG001 **Number of Subjects:** 6 ###### Reason **Group ID:** FG002 **Number of Subjects:** 8 ###### Reason **Group ID:** FG003 **Number of Subjects:** 4 ##### Withdraw **Type:** Death ###### Reason **Group ID:** FG000 **Number of Subjects:** 0 ###### Reason **Group ID:** FG001 **Number of Subjects:** 1 ###### Reason **Group ID:** FG002 **Number of Subjects:** 0 ###### Reason **Group ID:** FG003 **Number of Subjects:** 0 ##### Withdraw **Type:** Lost to Follow-up ###### Reason **Group ID:** FG000 **Number of Subjects:** 4 ###### Reason **Group ID:** FG001 **Number of Subjects:** 5 ###### Reason **Group ID:** FG002 **Number of Subjects:** 3 ###### Reason **Group ID:** FG003 **Number of Subjects:** 7 ##### Withdraw **Type:** Poor compliance/noncompliance ###### Reason **Group ID:** FG000 **Number of Subjects:** 0 ###### Reason **Group ID:** FG001 **Number of Subjects:** 5 ###### Reason **Group ID:** FG002 **Number of Subjects:** 1 ###### Reason **Group ID:** FG003 **Number of Subjects:** 2 ##### Withdraw **Type:** Pregnancy ###### Reason **Group ID:** FG000 **Number of Subjects:** 1 ###### Reason **Group ID:** FG001 **Number of Subjects:** 0 ###### Reason **Group ID:** FG002 **Number of Subjects:** 0 ###### Reason **Group ID:** FG003 **Number of Subjects:** 0 ##### Withdraw **Type:** No longer meets study criteria ###### Reason **Group ID:** FG000 **Number of Subjects:** 1 ###### Reason **Group ID:** FG001 **Number of Subjects:** 1 ###### Reason **Group ID:** FG002 **Number of Subjects:** 1 ###### Reason **Group ID:** FG003 **Number of Subjects:** 0 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 115 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 120 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 122 ###### Achievement **Group ID:** FG003 **Number of Subjects:** 119 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 73 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 82 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 89 ###### Achievement **Group ID:** FG003 **Number of Subjects:** 95 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 42 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 38 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 33 ###### Achievement **Group ID:** FG003 **Number of Subjects:** 24 **Pre-Assignment Details:** Of 915 participants enrolled, 562 completed a qualification period. Of these 562 participants, 546 were randomized and received treatment and 16 were excluded due to adverse events (1), no longer meeting study criteria (7), poor compliance or noncompliance (3), withdrawn consent (4), and lost to follow-up (1). **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT00690079 **Acronym:** MAD **Brief Title:** Study to Investigate the Safety, Tolerability and Pharmacokinetics of AZD1386 **Official Title:** A Phase I, Randomised, Double-blind, Placebo-controlled Study to Assess the Safety, Tolerability and Pharmacokinetics of AZD1386 in Healthy Caucasian Young and Elderly Subjects After Oral Multiple Doses. #### Organization Study ID Info **ID:** D5090C00008 #### Organization **Class:** INDUSTRY **Full Name:** AstraZeneca #### Secondary ID Infos **ID:** EudraCT No. 2007-005470-31 ### Status Module #### Completion Date **Date:** 2008-10 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2010-12-10 **Type:** ESTIMATED **Last Update Submit Date:** 2010-12-08 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2008-10 **Type:** ACTUAL #### Start Date **Date:** 2008-02 **Status Verified Date:** 2009-01 #### Study First Post Date **Date:** 2008-06-04 **Type:** ESTIMATED **Study First Submit Date:** 2008-06-02 **Study First Submit QC Date:** 2008-06-03 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** AstraZeneca #### Responsible Party **Old Name Title:** Rolf Karlsten, MD, PhD Medical Science Director **Old Organization:** AstraZeneca R&D Södertälje SE-151 85 Södertälje, Sweden ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** The study is being performed in order to learn more about the safety and tolerability of AZD1386. AZD1386 is primary intended for treatment of chronic pain. ### Conditions Module **Conditions:** - Chronic Pain **Keywords:** - MAD - Multiple ascending dose - Chronic pain - pain ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** QUADRUPLE **Who Masked:** - PARTICIPANT - CARE_PROVIDER - INVESTIGATOR - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 69 **Type:** ESTIMATED **Phases:** - PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** 7 groups receiving a specified volume of the active component AZD1386 at different points of time. **Intervention Names:** - Drug: AZD1386 **Label:** AZD1386 **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** 7 groups receiving a specified volume of placebo at different points of time **Intervention Names:** - Drug: Placebo **Label:** Placebo **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - AZD1386 **Description:** Oral admin. of doses at 11 days through a 12 days period. Cmax = 16 mikromol/L and AUCmax = 98 mikromol\*h/L **Name:** AZD1386 **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Placebo **Description:** Oral admin. of doses at 11 days through a 12 days period. **Name:** Placebo **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Measure:** Safety AEs and vital signs **Time Frame:** During the whole study **Measure:** ECG-recordings **Time Frame:** ECGs (5 minutes) Days 1 and 12. 2 ECGs (5 minutes) Days 3, 6 and 10. 1 ECG (5 minutes) Days 2 and 13. #### Secondary Outcomes **Measure:** PK **Time Frame:** Days 1, 5 and 12, 12 times each day. Days 4, 6, 8, 10 and 14, once. Days 2, 3, 7, 9, 11 and 13 twice. ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Healthy Caucasians, males or females aged ≥20 and ≤ 45 years or between 65 80 years. Female subjects must be surgically sterile or post-menopausal for at least 12 months prior to the enrolment visit. * Body Mass Index (BMI) of ≥18 to ≤ 30 kg/m2 and weight of ≥50 to ≤100 kg * Clinically normal physical findings including heart rate \> 45 bpm and laboratory values and normal resting ECG Exclusion Criteria: * History of somatic or psychiatric disease/condition, which may interfere with the objectives of the study. * History of severe allergy/hypersensitivity or symptoms/signs of ongoing allergy/hypersensitivity. * Subjects with a high decrease in blood pressure within 5 minutes when going from a supine to standing position. **Healthy Volunteers:** True **Maximum Age:** 80 Years **Minimum Age:** 20 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Macclesfield **Country:** United Kingdom **Facility:** Research Site **State:** Cheshire #### Overall Officials **Official 1:** **Affiliation:** Emerging Analgesia TA AstraZeneca R&D Södertälje, Sweden **Name:** Rolf Karlsten **Role:** STUDY_DIRECTOR **Official 2:** **Affiliation:** AstraZeneca Alderly Park1G61 Mereside, Alderly Park, Macclesfeld, Cheshire, England SK104TG **Name:** Ray Chetty **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000010146 - Term: Pain - ID: D000009461 - Term: Neurologic Manifestations ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M29442 - Name: Chronic Pain - Relevance: HIGH - As Found: Chronic Pain - ID: M13066 - Name: Pain - Relevance: LOW - As Found: Unknown - ID: M12404 - Name: Neurologic Manifestations - Relevance: LOW - As Found: Unknown - ID: T1303 - Name: Chronic Graft Versus Host Disease - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000059350 - Term: Chronic Pain ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT02868879 **Brief Title:** Anatomical and Structural Connectivity in Two Psychotic Phenotypes : Periodic Catatonia and Cataphasia **Official Title:** Anatomical and Structural Connectivity in Schizophrenias #### Organization Study ID Info **ID:** 2898 #### Organization **Class:** OTHER **Full Name:** University Hospital, Strasbourg, France ### Status Module #### Completion Date **Date:** 2019-09 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2019-10-21 **Type:** ACTUAL **Last Update Submit Date:** 2019-10-18 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2019-09 **Type:** ACTUAL #### Start Date **Date:** 2006-09-25 **Type:** ACTUAL **Status Verified Date:** 2019-10 #### Study First Post Date **Date:** 2016-08-16 **Type:** ESTIMATED **Study First Submit Date:** 2016-08-05 **Study First Submit QC Date:** 2016-08-11 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** University Hospital, Strasbourg, France #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** The different subtypes of Schizophrenia might have a disordered connectivity as their final common pathways. The investigators will use multimodal structural MRI to assess anatomical connectivity on the one side and its functional consequence on functional connectivity on the other side to assess two phenotypes of psychosis : periodic catatonia and cataphasia in comparison with control subjects. The coherence between structural and functional anomalies will be especially studied. ### Conditions Module **Conditions:** - Schizophrenia - Catatonia ### Design Module #### Design Info **Observational Model:** CASE_CONTROL **Time Perspective:** CROSS_SECTIONAL #### Enrollment Info **Count:** 162 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Intervention Names:** - Other: Quantitative multiparametric and functional MRI **Label:** Schizophrenia #### Arm Group 2 **Intervention Names:** - Other: Quantitative multiparametric and functional MRI **Label:** Normal controls. ### Interventions #### Intervention 1 **Arm Group Labels:** - Normal controls. - Schizophrenia **Description:** Structural connectivity assessed in the cortex and the white matter using multimodal quantitative parametric imaging (R1, R2, R2\*, DTI, susceptibility, macromolecular proton fraction, cortical thickness, VBM). Functional connectivity assessed using simple BOLD and combined ASL-BOLD sequences during multiple tasks including motor, language and working memory tasks. **Name:** Quantitative multiparametric and functional MRI **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** Statistical parametric mapping (SPM) will be applied on quantitative maps : rCBF (ml/100g/min), susceptibility (part per billion), R1, R2, R2\* (all expressed in ms-1), fractional anisotropy (fraction), averaged diffusivity (μm²/sec), macromolecular proton fraction (percentage), cortical thickness (mm), VBM (probability of grey and white matter) and contrast maps (BOLD signal correlation with the anterior cingulate ROI). **Measure:** Changes in structural and functional connectivity according to the phenotype. Correlation between these changes **Time Frame:** Subjects will be assessed only once. #### Secondary Outcomes **Description:** Symptomatic scales : PANSS, SANS, SAPS, Calgary, Bush and Francis catatonia scale, the psychological experimental test operationalized for cataphasia, Clinician-rated dimension of psychosis symptom severity questionnaire assessing handedness, anhedonia, vigilance, QoL, activity, handicap, ruminations, depression and personality. Cognitive tests : grammar tests, semantic priming, implicit memory, CPT, fNART, Mill-Hill (part B) **Measure:** Changes in rCBF and cognition according to the phenotype. Correlation between the different changes and the symptomatic scales. **Time Frame:** Subjects will be assessed only once. ### Eligibility Module **Eligibility Criteria:** Inclusion criteria (controls): * Aged from 18-65 Y * Right handed Additional inclusion criteria for patients: * Schizophrenia according to the DSM5 * Either periodic catatonia or cataphasia according to the WKL classification * Under stable medication regimen (\> 1M) Exclusion criteria: * Current substance abuse * Contraindication to MRI * Past records susceptible to affect brain integrity * Severe, unstable medical condition * Pregnancy * Patients deprived of their rights **Healthy Volunteers:** True **Maximum Age:** 65 Years **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Schizophrenia patients (subdivided in periodic catatonia and cataphasia) and normal controls, both having the same procedure. ### Contacts Locations Module #### Locations **Location 1:** **City:** Strasbourg **Country:** France **Facility:** Service de Psychiatrie, Hôpital Civil, Hôpitaux Universitaires de Strasbourg **Zip:** 67091 ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Foucher JR, Zhang YF, Roser M, Lamy J, De Sousa PL, Weibel S, Vidailhet P, Mainberger O, Berna F. A double dissociation between two psychotic phenotypes: Periodic catatonia and cataphasia. Prog Neuropsychopharmacol Biol Psychiatry. 2018 Aug 30;86:363-369. doi: 10.1016/j.pnpbp.2018.03.008. Epub 2018 Mar 17. **PMID:** 29559372 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000019967 - Term: Schizophrenia Spectrum and Other Psychotic Disorders - ID: D000001523 - Term: Mental Disorders - ID: D000019954 - Term: Neurobehavioral Manifestations - ID: D000009461 - Term: Neurologic Manifestations - ID: D000009422 - Term: Nervous System Diseases - ID: D000001526 - Term: Behavioral Symptoms ### Condition Browse Module - Browse Branches - Abbrev: BXM - Name: Behaviors and Mental Disorders - Abbrev: All - Name: All Conditions - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: BC23 - Name: Symptoms and General Pathology ### Condition Browse Module - Browse Leaves - ID: M15376 - Name: Schizophrenia - Relevance: HIGH - As Found: Schizophrenia - ID: M4815 - Name: Mental Disorders - Relevance: LOW - As Found: Unknown - ID: M14473 - Name: Psychotic Disorders - Relevance: LOW - As Found: Unknown - ID: M5641 - Name: Catatonia - Relevance: HIGH - As Found: Catatonia - ID: M21838 - Name: Schizophrenia Spectrum and Other Psychotic Disorders - Relevance: LOW - As Found: Unknown - ID: M21826 - Name: Neurobehavioral Manifestations - Relevance: LOW - As Found: Unknown - ID: M12404 - Name: Neurologic Manifestations - Relevance: LOW - As Found: Unknown - ID: M4818 - Name: Behavioral Symptoms - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000002389 - Term: Catatonia - ID: D000012559 - Term: Schizophrenia ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05427279 **Brief Title:** Effects of Vitamin C Enriched Hydrolyzed Collagen, PrimaColl™, Whey Protein, or Placebo on Collagen Synthesis **Official Title:** Investigating the Effects of 24-hours of Repeated Doses of Vitamin C Enriched Hydrolyzed Collagen, PrimaColl™, Whey Protein, or Placebo on Collagen Synthesis #### Organization Study ID Info **ID:** 220518 #### Organization **Class:** OTHER **Full Name:** University of California, Davis ### Status Module #### Completion Date **Date:** 2024-08-31 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-09 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-07 **Overall Status:** ACTIVE_NOT_RECRUITING #### Primary Completion Date **Date:** 2023-06-30 **Type:** ACTUAL #### Start Date **Date:** 2022-10-05 **Type:** ACTUAL **Status Verified Date:** 2023-08 #### Study First Post Date **Date:** 2022-06-22 **Type:** ACTUAL **Study First Submit Date:** 2022-06-09 **Study First Submit QC Date:** 2022-06-16 ### Sponsor Collaborators Module #### Collaborators **Class:** UNKNOWN **Name:** Geltor #### Lead Sponsor **Class:** OTHER **Name:** University of California, Davis #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** The purpose of this study is to determine the effects of repeated dosing vitamin C enriched hydrolyzed collagen (HC) over a 24hr period, compared to PrimaColl™ (PC), whey protein (WP) and placebo (PL), with prescribed exercise on collagen synthesis. To achieve this, participants will consume a supplemental dose of HC (20g with 50mg vitamin C), PC (20g with 50mg vitamin C), whey protein (20g whey isolate with 50mg vitamin C) or a placebo (20g maltodextrin with 50mg vitamin C) 1hr prior to an exercise bout (6 minutes of jump rope), this will be repeated three times over a 24h period. The amount of collagen protein synthesized will be indirectly measured by measuring pro-collagen type I N-terminal propeptide (PINP) in the serum before and 4hrs after the last exercise bout. **Detailed Description:** The purpose of this study is to determine the effects of repeated dosing of vitamin C enriched hydrolyzed collagen (HC) over a 24hr period, compared to PrimaColl™ (PC), whey protein (WP) and placebo (PL), with prescribed exercise on collagen synthesis. To achieve this, participants will consume a supplemental dose of HC (20g with 50mg vitamin C), PC (20g with 50mg vitamin C), whey protein (20g whey isolate with 50mg vitamin C) or a placebo (20g maltodextrin with 50mg vitamin C) 1hr prior to exercise bouts (6 minutes of jump rope). The amount of collagen protein synthesized will be indirectly measured by measuring procollagen type I N-terminal propeptide (PINP) in the serum before and 4hrs after the last exercise bout. It is expected that this project will determine whether greater increases in collagen synthesis are observed with repeated doses of HC and exercise, compared with a single dose and exercise bout (from previous research). This study will also determine whether collagen synthesis is similarly stimulated with PrimaColl, or whey protein. Results from this study will help to better prescribe the use of dietary collagen and exercise training to improve collagen synthesis in healthy young people. Improved collagen synthesis has the potential to decrease ligament, tendon, and bone injuries in the general and athletic populations. Male and female participants between the ages of 18-30 years of age will be enrolled in the study. A randomized double-blind crossover design with neither the subjects nor the investigators knowing who is on which treatment (HC, PC, WP or PL). I. Baseline blood draw The subjects will arrive in the laboratory following an overnight fast. The antecubital vein will be cannulated, and an initial 5 mL baseline blood sample will be collected. II. Supplementation After baseline blood draw subjects will be provided with a supplement as shown in the table below. Subjects will be asked to consume the supplement that will be pre-mixed with 250 ml of water 60 min before the jump rope exercise. This will be repeated 3 times, separated by 12 hours over a 24h period. III. Exercise Sixty minutes after the ingestion of the supplement, each participant will complete 6 minutes of jump rope. This will be repeated on 3 occasions over a 24hr period. Subjects will be asked to abstain from vigorous exercise during the 24hr period, aside from the prescribed jump rope exercise. Subjects will be asked to ingest supplement and jump rope in lab for time point 1. Subjects will be given the option to ingest supplement and jump rope outside lab if more conducive to their scheduling restrictions at time points 2 and 3 blood draws are not required at these timepoints. Subjects will be asked to return to the lab 4 hours after last jumping session for blood sampling. Blood draws for PNIP analysis Blood samples (5 mL) at different time points: * Baseline 2 vials will be drawn (1 for PINP and the other for bioassays) * 1h after the first supplementation 1 vial will be drawn (bioassay) * 4hrs post-exercise session number 3 the last vial will be drawn (PINP) Blood will be collected in 5 mL serum separating tubes and allowed to clot for 1hr before centrifugation at 1000 x g for 10 minutes and the serum will be frozen and kept at -30°C until processed. PINP levels will be determined by electrochemiluminescence (ECL; Roche Diagnostics, Indianapolis, IN) according to the manufacturer's instructions. The total number of blood draws will be 12 (3 per intervention with 4 interventions). Treatments will be randomized to avoid an order effect and a washout period of about 72h between trials will be used to minimize the effect of the previous treatment ### Conditions Module **Conditions:** - Effect of Food Supplement **Keywords:** - Collagen synthesis - Exercise - Supplementation - Engineered ligaments ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** CROSSOVER **Intervention Model Description:** Participants will consume a supplemental dose of hydrolyzed collagen (20g with 50mg vitamin C), PrimaColl (20g with 50mg vitamin C), whey protein (20g whey isolate with 50mg vitamin C) or a placebo (20g maltodextrin with 50mg vitamin C) 1hr prior to exercise bouts (6 minutes of jump rope). The type of consumed supplementation will be randomized where neither the participant nor investigator will know which supplement is being consumed. Each participant will repeat the protocol four times. ##### Masking Info **Masking:** TRIPLE **Masking Description:** A randomized double-blind crossover design with neither the subjects nor the investigators knowing who is on which treatment. The interventions will be coded using a blinded alphabetical letter code (A, B, C, D). A delegate researcher (independent party not further involved in the study) will randomize all interventions using a computer-generated randomization list. The delegate will hand in the code-breaker to the principal investigator in a sealed envelope. The envelope will be stored in a locked filing cabinet in the principal investigator's office, which will also be locked when unoccupied. The envelope will be opened by the principal investigator after completing the analysis of blood samples. **Who Masked:** - PARTICIPANT - INVESTIGATOR - OUTCOMES_ASSESSOR **Primary Purpose:** OTHER #### Enrollment Info **Count:** 20 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** This arm will be given a placebo (20g maltodextrin with 50mg vitamin C) **Intervention Names:** - Dietary Supplement: Placebo **Label:** Placebo **Type:** PLACEBO_COMPARATOR #### Arm Group 2 **Description:** This arm will be given Hydrolized Collagen (20g with 50mg vitamin C) **Intervention Names:** - Dietary Supplement: Hydrolized Collagen **Label:** Hydrolized Collagen **Type:** EXPERIMENTAL #### Arm Group 3 **Description:** This arm will be given PrimaColl, a vegan collagen supplementation (20g with 50mg vitamin C) **Intervention Names:** - Dietary Supplement: PrimaColl **Label:** PrimaColl **Type:** EXPERIMENTAL #### Arm Group 4 **Description:** This arm will be given whey protein (20g with 50mg vitamin C) **Intervention Names:** - Dietary Supplement: Whey protein **Label:** Whey Protein **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Placebo **Description:** The participant will consume a supplemental dose of a placebo (20g maltodextrin with 50mg vitamin C) **Name:** Placebo **Other Names:** - maltodextrin **Type:** DIETARY_SUPPLEMENT #### Intervention 2 **Arm Group Labels:** - Hydrolized Collagen **Description:** The participant will consume a supplemental dose of Hydrolized collagen (20g with 50mg vitamin C) **Name:** Hydrolized Collagen **Type:** DIETARY_SUPPLEMENT #### Intervention 3 **Arm Group Labels:** - PrimaColl **Description:** The participant will consume a supplemental dose of PrimaColl, a vegan collagen supplementation (20g with 50mg vitamin C) **Name:** PrimaColl **Type:** DIETARY_SUPPLEMENT #### Intervention 4 **Arm Group Labels:** - Whey Protein **Description:** The participant will consume a supplemental dose of whey protein (20g whey isolate with 50mg vitamin C) **Name:** Whey protein **Type:** DIETARY_SUPPLEMENT ### Outcomes Module #### Primary Outcomes **Description:** Collagen protein synthesis will be indirectly measured by measuring pro-collagen type I N-terminal propeptide (PINP) in the serum before and 4 hours after the last exercise bout (at 28 hours of the protocol) **Measure:** Collagen protein synthesis **Time Frame:** Baseline (0 hour) to 4 hours after last exercise bout (at 28 hour of the protocol) #### Secondary Outcomes **Description:** Serum from participants will be used to treat engineered ligaments in order to assess the effect of the different supplementation on the ligament collagen content using a hydroxyproline assay kit. **Measure:** Ligament collagen content **Time Frame:** Baseline (0 hour) to directly after consumption of supplementation (1 hour) **Description:** Serum from participants will be used to treat engineered ligaments in order to measure the effect of the different supplementation on the strength of the ligaments, the strength will be measured using the Instron bio puls 68SC-1 tension and compression machine. **Measure:** Strength of engineered ligaments **Time Frame:** Baseline (0 hour) to directly after consumption of supplementation (1 hour) ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * healthy active male or female * normal weight (BMI between 18 and 25 kg/m2) Exclusion Criteria: * taking any medication that may interfere with the study * have a history of more than 3 musculoskeletal injuries within the past 12 months * have any health or dietary restriction that would be affected by the supplementation protocol **Healthy Volunteers:** True **Maximum Age:** 30 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Davis **Country:** United States **Facility:** Hickey Laboratory **State:** California **Zip:** 95616 #### Overall Officials **Official 1:** **Affiliation:** UC Davis **Name:** Keith Baar, PhD **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Intervention Browse Module - Browse Branches - Abbrev: Micro - Name: Micronutrients - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Vi - Name: Vitamins - Abbrev: Ot - Name: Other Dietary Supplements ### Intervention Browse Module - Browse Leaves - ID: M4513 - Name: Ascorbic Acid - Relevance: LOW - As Found: Unknown - ID: M17558 - Name: Vitamins - Relevance: LOW - As Found: Unknown - ID: T477 - Name: Vitamin C - Relevance: LOW - As Found: Unknown - ID: T437 - Name: Ascorbic Acid - Relevance: LOW - As Found: Unknown - ID: T435 - Name: Whey Protein - Relevance: HIGH - As Found: Ingredients ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT02447679 **Brief Title:** Oral Thalidomide and Tegafur-uracil to Decrease Hepatocellular Carcinoma Recurrence **Official Title:** Oral Thalidomide and Tegafur-uracil to Decrease Hepatocellular Carcinoma Recurrent After Hepatectomy in High Risk Patients -A Phase II Study #### Organization Study ID Info **ID:** CGMF-IRB-97-1291A #### Organization **Class:** OTHER **Full Name:** Chang Gung Memorial Hospital ### Status Module #### Completion Date **Date:** 2017-02-02 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2017-02-07 **Type:** ESTIMATED **Last Update Submit Date:** 2017-02-05 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2017-01-31 **Type:** ACTUAL #### Start Date **Date:** 2010-08 **Status Verified Date:** 2016-12 #### Study First Post Date **Date:** 2015-05-19 **Type:** ESTIMATED **Study First Submit Date:** 2014-12-16 **Study First Submit QC Date:** 2015-05-14 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Chang Gung Memorial Hospital #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** This single-centered phase II clinical study is to obtain preliminary information on 1-year recurrence-free survival rate, recurrence-free survival and safety profile of thalidomide in combination with tegafur-uracil in hepatocellular carcinoma after hepatectomy and explore biomarkers(VEGF/bFGF) for thalidomide response. **Detailed Description:** After liver resection to remove the hepatocellular carcinioma completely, the patients with high risk of tumor recurrence will be enrolled into this study. The high risk of tumor recurrence depends on tumor characteristics. The risk factors of tumor characteristics included tumor size \>5 cm in diameter, abscence of encapsulation, vascular invasion and presence of daughter nodules. The patients with high risk of tumor recurrence will have 1 to 3 risk factors. When the patients are enrolled into the study, oral thalidomide in combination with tegafur-uracil will be applied to prevent tumor recurrence. The patients will be fillowed uo erevy 3 mnoths. ### Conditions Module **Conditions:** - Adult Hepatocellular Carcinoma - Recurrent Hepatocellular Carcinoma - Adverse Reaction to Drug - Vascular Endothelial Growth Factor Overexpression ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 40 **Type:** ACTUAL **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** 1. Thalidomide 400mg/day for 1 year 2. tegafur-uracil 2 tables for 1 year. **Intervention Names:** - Drug: thalidomine - Drug: tegafur-uracil **Label:** thalidomine **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - thalidomine **Description:** thalidomine (400mg/day) for 1 year to prevent HCC recurrence **Name:** thalidomine **Other Names:** - thado **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - thalidomine **Description:** tegafur-uracil (2 tablelet twice a day) for 1 year to prevent HCC recurrence **Name:** tegafur-uracil **Other Names:** - ufur **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Measure a-fetoprotein and perform liver echo to find out tumor recurrence every 3 month. Then, if a tumor/tumors are found in liver echo, tumor recurrence will be confirmed by CT scan. The imaging on CT shows typical HCC pattern. The pilot study is to obtain preliminary information on: * 3-year recurrence-free survival rate * Recurrence-free survival * Safety profile of the treatment * Biomarkers response(VEGF/bFGF) **Measure:** tumor recurrence **Time Frame:** every 3 months, up to 5 years ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. stage I-III（TNM: T1-T3） hepatocellular carcinoma 2. previously received curative surgery 3. presence at least one and no more than three of the following risk factors , i.Tumor size ≧ 5 cm ii.presence of microscopic or macrovascular venous invasion iii.presence of satellite nodules/addition nodules iv.no capsular formation v.multiple tumors d.performance status of ECOG 0, 1 e.age between 20 and 75 years f.no residual or recurrent tumors detected by computed tomography (CT) or echo within 3-6 weeks after surgery g.written informed consent to participate in the trial Exclusion Criteria: 1. other malignancy with the exception of curative treated non-melanoma skin cancer or cervical carcinoma in situ prior to the entry of study 2. previously received chemotherapy 3. less than 2 weeks since previous radiotherapy/surgery 4. white blood cell (WBC) less than 3,000/mm3 and absolute neutrophil count (ANC) less than 1,500/mm3, and platelets less than 100,000/mm3 5. serum bilirubin greater than 1.5 times the upper limit of normal range (ULN) 6. alanine aminotransferase (ALT) or aspartate transaminase (AST) greater than 5 times the ULN 7. alkaline phosphatase greater than 5 times the ULN 8. presence of serious concomitant illness which might be aggravated by study medication:uncontrolled infection (active serious infections that are not controlled by antibiotics) 9. hypersensitivity to thalidomide or compounds pregnant or breast feeding women, or women of child-bearing potential unless using two reliable and appropriate contraceptive method **Maximum Age:** 75 Years **Minimum Age:** 20 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Taoyuan **Country:** Taiwan **Facility:** Chang Gung Memorial Hospital #### Overall Officials **Official 1:** **Affiliation:** Chang Gung Memorial Hospital **Name:** Wei-Chen Lee **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009375 - Term: Neoplasms, Glandular and Epithelial - ID: D000009370 - Term: Neoplasms by Histologic Type - ID: D000009369 - Term: Neoplasms - ID: D000000230 - Term: Adenocarcinoma - ID: D000008113 - Term: Liver Neoplasms - ID: D000004067 - Term: Digestive System Neoplasms - ID: D000009371 - Term: Neoplasms by Site - ID: D000004066 - Term: Digestive System Diseases - ID: D000008107 - Term: Liver Diseases - ID: D000064419 - Term: Chemically-Induced Disorders ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: All - Name: All Conditions - Abbrev: BC25 - Name: Substance Related Disorders - Abbrev: BC06 - Name: Digestive System Diseases - Abbrev: BC23 - Name: Symptoms and General Pathology ### Condition Browse Module - Browse Leaves - ID: M5534 - Name: Carcinoma - Relevance: HIGH - As Found: Carcinoma - ID: M30303 - Name: Drug-Related Side Effects and Adverse Reactions - Relevance: HIGH - As Found: Adverse Reaction to Drug - ID: M9613 - Name: Carcinoma, Hepatocellular - Relevance: HIGH - As Found: Hepatocellular Carcinoma - ID: M14850 - Name: Recurrence - Relevance: LOW - As Found: Unknown - ID: M12320 - Name: Neoplasms, Glandular and Epithelial - Relevance: LOW - As Found: Unknown - ID: M12315 - Name: Neoplasms by Histologic Type - Relevance: LOW - As Found: Unknown - ID: M3585 - Name: Adenocarcinoma - Relevance: LOW - As Found: Unknown - ID: M11113 - Name: Liver Neoplasms - Relevance: LOW - As Found: Unknown - ID: M8886 - Name: Gastrointestinal Neoplasms - Relevance: LOW - As Found: Unknown - ID: M7256 - Name: Digestive System Neoplasms - Relevance: LOW - As Found: Unknown - ID: M7255 - Name: Digestive System Diseases - Relevance: LOW - As Found: Unknown - ID: M8883 - Name: Gastrointestinal Diseases - Relevance: LOW - As Found: Unknown - ID: M11107 - Name: Liver Diseases - Relevance: LOW - As Found: Unknown - ID: M30302 - Name: Chemically-Induced Disorders - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000002277 - Term: Carcinoma - ID: D000006528 - Term: Carcinoma, Hepatocellular - ID: D000064420 - Term: Drug-Related Side Effects and Adverse Reactions ### Intervention Browse Module - Ancestors - ID: D000000964 - Term: Antimetabolites, Antineoplastic - ID: D000000963 - Term: Antimetabolites - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000000970 - Term: Antineoplastic Agents ### Intervention Browse Module - Browse Branches - Abbrev: ANeo - Name: Antineoplastic Agents - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Infe - Name: Anti-Infective Agents ### Intervention Browse Module - Browse Leaves - ID: M8760 - Name: Tegafur - Relevance: HIGH - As Found: Fasted state - ID: M16559 - Name: Thalidomide - Relevance: LOW - As Found: Unknown - ID: M4281 - Name: Antimetabolites - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000005641 - Term: Tegafur ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT06316479 **Brief Title:** Safety and Performance of PTMC Dermal Filler **Official Title:** A Prospective, Multi-Centre, Single-Arm First-In-Man Study to Evaluate the Safety and Performance of PTMC Dermal Filler for the Correction of Moderate to Severe Nasolabial Folds #### Organization Study ID Info **ID:** CI-001-23 #### Organization **Class:** INDUSTRY **Full Name:** Aqpha Medical B.V. ### Status Module #### Completion Date **Date:** 2025-12 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-03-18 **Type:** ACTUAL **Last Update Submit Date:** 2024-03-12 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2024-12 **Type:** ESTIMATED #### Start Date **Date:** 2024-08 **Type:** ESTIMATED **Status Verified Date:** 2024-03 #### Study First Post Date **Date:** 2024-03-18 **Type:** ACTUAL **Study First Submit Date:** 2024-03-12 **Study First Submit QC Date:** 2024-03-12 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Aqpha Medical B.V. #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** The goal of this clinical trial is to assess the safety and performance of the PTMC Dermal filler for treating moderate to severe nasolabial folds in adult men and women. The main questions it aims to answer are: * Does the PTMC dermal filler maintain its performance for a minimum of 6 months? * Is the treatment considered safe for participants? Participants will: * Before treatment, the investigator will assess your medical history, medication usage, and satisfaction with your wrinkles/folds. * You'll receive one injection of the PTMC Dermal filler during your initial visit. * For 30 days post-injection, you'll keep a diary to note any reactions like pain, redness, or swelling at the injection site. * At the 1-month follow-up, you can request a 'touch-up' of the filler, extending your participation in the study. * Participants will visit the clinic a total of 8 times, including the initial treatment and 7 follow-up visits, spanning up to 18 months. * Each visit will last approximately 60-90 minutes. The visits will be conducted in person. ### Conditions Module **Conditions:** - Moderate to Severe Nasolabial Fold ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 120 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** All participants will receive PTMC Dermal Filler. **Intervention Names:** - Device: PTMC Dermal Filler **Label:** Treatment group **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Treatment group **Description:** A total of 120 subjects will receive treatment with PTMC Dermal Filler. The volume of filler injected will vary depending on the severity of the nasolabial fold. Injections will be administered by the investigator at the beginning of the study, with the injection technique, plane, and volume recorded. Touch-up treatments are permitted at the 1-month follow-up visit, if necessary. **Name:** PTMC Dermal Filler **Type:** DEVICE ### Outcomes Module #### Other Outcomes **Description:** Evaluation of pain by the participant using Visual Analog Scale (VAS) **Measure:** Visual Analog Scale (VAS) for pain **Time Frame:** After each injection and at the 2-weeks follow-up visit **Description:** Treatment satisfaction evaluated by the subject using a questionnaire. **Measure:** Treatment satisfaction **Time Frame:** 1, 3, 6, 9, 12, and 18 months after treatment **Description:** Ease of use of the device evaluated by the investigator using a questionnaire. **Measure:** Ease of use **Time Frame:** After injection of the device on day 0 #### Primary Outcomes **Description:** The nasolabial fold severity is measured using the Wrinkles Severity Rating Scale (WSRS) by the investigator. **Measure:** Nasolabial fold severity **Time Frame:** 6 months after treatment #### Secondary Outcomes **Description:** Safety is assessed by the collection of adverse events (incidence and severity), and through subject assessment of injection site responses (ISRs) up to 4 weeks after treatment. **Measure:** Safety (Adverse events) **Time Frame:** until 18 months after treatment **Description:** Mean change from baseline of the nasolabial fold severity measured using the WSRS by the investigator. **Measure:** Nasolabial fold severity **Time Frame:** 1, 3, 9, 12, and 18 months after treatment **Description:** Number of subjects having at least 1-point improvement in the WSRS score compared to the baseline. **Measure:** Responder rate **Time Frame:** 1, 3, 6, 9, 12, and 18 months after treatment **Description:** Overall aesthetic improvement is assessed by the investigator using the Global Aesthetic Improvement Scale (GAIS). **Measure:** Overall aesthetic improvement (by the investigator) **Time Frame:** 1, 3, 6, 9, 12, and 18 months after treatment **Description:** Overall aesthetic improvement assessed by the subject using the Global Aesthetic Improvement Scale (GAIS). **Measure:** Overall aesthetic improvement (by the subject) **Time Frame:** 1, 3, 6, 9, 12, and 18 months after treatment **Description:** Subject satisfaction is measured using a FACE-Q questionnaire. **Measure:** Subject satisfaction **Time Frame:** 1, 3, 6, 9, 12, and 18 months after treatment ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Male or female ≥18 years and £67 old. 2. Two fully visible bilateral nasolabial folds each with a Wrinkle Severity Rating Scale (WSRS) score of 3 or 4 that may be corrected with an injectable dermal filler. 3. If female and of childbearing potential: a negative urine pregnancy test + agreement to use adequate contraception. 4. Ability to understand and comply with the study requirements. 5. Willingness and ability to provide written informed consent. 6. Agree to refrain from seeking other treatment of nasolabial folds during the study. 7. Over the counter (OTC) wrinkle products or prescription wrinkle treatments, if used, shall be continued throughout the study in similar manner as performed prior to participation. Exclusion Criteria: 1. Wrinkle Severity Rating Scale (WSRS) score of ≤ 2 on the right or left nasolabial fold. 2. Women who are pregnant or lactating or planning to become pregnant during the study. 3. Evidence of scar-related disease or delayed healing activity within the past 1 year. 4. History of keloid formation or hypertrophic scars. 5. Scars at the intended treatment sites. 6. Any infection or wound on the face. 7. Facial tattoo that may interfere with diagnosis. 8. Allergic history including anaphylaxis or multiple severe allergies to natural rubber latex or lidocaine. 9. Clinically significant organic disease including clinically significant cardiovascular, hepatic, pulmonary, neurologic, or renal disease or other medical condition, serious intercurrent illness, or extenuating circumstance that, in the opinion of the investigator preclude participation in the trial. 10. Aspirin, or nonsteroidal anti-inflammatory drugs within 1 week (7 days) prior to treatment. 11. Systemic (oral/injectable) corticosteroids or immunosuppressive medications within 30 days prior to treatment and topical steroids on the face within 14 days prior to trial start and throughout the study. 12. Concomitant anticoagulant therapy, antiplatelet therapy, biotherapy or history of bleeding disorders or connective tissue disorders. 13. Immunocompromised or immunosuppressed. 14. History of autoimmune diseases. 15. Anti-covid vaccination (RNA-based vaccines) within 2 weeks (14 days) prior to treatment. 16. Received any investigational product within 30 days prior to treatment. 17. Received prior dermabrasion, or botulinum toxins under the orbital rim (tear through) within 6 months (180 days) prior to entry into the study. 18. Received facelift within 2 years prior to treatment. 19. Previous tissue augmentation (bulking agents) for facial wrinkles and scars within 6 months at the mid-face. 20. Previous tissue augmentation with permanent implants. 21. Treatment of microdermabrasion or micro needling within the whole facial area within 3 months prior to treatment. 22. Laser treatment within the whole facial area within 6 months prior to treatment. **Healthy Volunteers:** True **Maximum Age:** 67 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ## Derived Section ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03091179 **Brief Title:** Transnasal Humidified Rapid-Insufflation Ventilatory Exchange (THRIVE) and Short Laryngologic Surgery **Official Title:** The Safety and Efficacy of the Transnasal Humidified Rapid-Insufflation Ventilatory Exchange (THRIVE) for Short Laryngologic Surgical Procedures. #### Organization Study ID Info **ID:** 39202 #### Organization **Class:** OTHER **Full Name:** Stanford University ### Status Module #### Completion Date **Date:** 2018-07-18 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2020-03-04 **Type:** ACTUAL **Last Update Submit Date:** 2020-02-25 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2018-07-18 **Type:** ACTUAL #### Results First Post Date **Date:** 2019-07-17 **Type:** ACTUAL **Results First Submit Date:** 2019-06-21 **Results First Submit QC Date:** 2019-06-21 #### Start Date **Date:** 2017-03-17 **Type:** ACTUAL **Status Verified Date:** 2020-02 #### Study First Post Date **Date:** 2017-03-27 **Type:** ACTUAL **Study First Submit Date:** 2017-03-05 **Study First Submit QC Date:** 2017-03-21 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Stanford University #### Responsible Party **Investigator Affiliation:** Stanford University **Investigator Full Name:** Vladimir Nekhendzy **Investigator Title:** Clinical Professor of Anesthesiology and Otolaryngology **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** True **Is FDA Regulated Drug:** False **Is US Export:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** The purpose of this study is to investigate whether selected, short laryngologic surgical procedures can be safely and potentially more effectively performed without the use of endotracheal tube or jet ventilation, under completely tubeless conditions. The patient's gas exchange will be supported by rapid insufflation of high-flow oxygen through specialized nasal cannulae: the so called Transnasal Humidified Rapid- Insufflation Ventilatory Exchange (THRIVE). ### Conditions Module **Conditions:** - Laryngologic Surgical Procedures **Keywords:** - airway management - high flow nasal oxygen - high flow nasal cannula - THRIVE ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** DOUBLE **Who Masked:** - PARTICIPANT - CARE_PROVIDER **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 20 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** high flow nasal oxygen **Intervention Names:** - Device: THRIVE **Label:** THRIVE **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** tracheal intubation **Intervention Names:** - Device: Endotracheal tube **Label:** Endotracheal tube **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - THRIVE **Description:** active nasal oxygen delivery system **Name:** THRIVE **Type:** DEVICE #### Intervention 2 **Arm Group Labels:** - Endotracheal tube **Description:** a plastic tube for mechanical ventilation **Name:** Endotracheal tube **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Measure:** Average Oxygen Saturation by Pulse Oximetry (SpO2) (Primary Anesthesia Outcome) **Time Frame:** intraoperative (up to one hour) **Description:** time from end of surgery to responding to commands/extubation **Measure:** Time to Awakening From Anesthesia (Primary Anesthesia Outcome) **Time Frame:** intraoperative (up to 20 min) **Description:** Time required for the surgeon to position the patient's head and expose the surgical field for surgery using operating laryngoscope **Measure:** Suspension Time (Primary Surgical Outcome) **Time Frame:** intraoperative (up to 5 min) **Description:** Number of attempts required for the surgeon to reposition the patient's head for optimal surgical exposure using operating laryngoscope **Measure:** Number of Suspension Repositioning Maneuvers (Primary Surgical Outcome) **Time Frame:** intraoperative (up to 5 min) **Measure:** Duration of Surgery (Primary Surgical Outcome) **Time Frame:** intraoperative (up to one hour) #### Secondary Outcomes **Description:** Time required for the patient to become fully alert and oriented per standard recovery room evaluation **Measure:** Alertness **Time Frame:** Recovery room admission (up to 30 min following admission to recovery room) **Measure:** Recovery Room Time **Time Frame:** Up to 2 hours after procedure **Description:** A score from 0 to 10, higher scores corresponding to higher pain **Measure:** Numerical Pain Rating Scores **Time Frame:** Recovery room admission and discharge (up to 2 hours) **Description:** Total oral opioid consumption in morphine milligram equivalents **Measure:** Opioid Consumption **Time Frame:** Recovery room admission and discharge (up to 2 hours) **Description:** numerical scale, range from 0 to 40, with higher scores corresponding to worse outcome **Measure:** Change in Voice Handicap Index (VHI) **Time Frame:** Preoperative assessment and one month after surgery **Description:** 15-question survey, with each question scored from 0 to 10. Overall range 0-150, higher scores correspond to better outcome. **Measure:** Quality of Recovery **Time Frame:** One week after surgery ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Patients presenting for short, non-laser laryngologic surgery Exclusion Criteria: 1. Patients with significantly decreased myocardial function (ejection fraction \< 50%) 2. Patients with abnormal cardiac rhythm and conduction abnormalities, except for patients with isolated, asymptomatic premature atrial and ventricular contractions. 3. Patients with significant peripheral vascular disease, such as those with the symptoms of intermittent claudication. 4. Patients with known significant cerebrovascular disease, such as history of cerebrovascular accidents (CVAs) and transient ischemic attacks (TIAs). 5. Patients with significant renal insufficiency, as manifested by estimated glomerular filtration rate (eGFR) \< 60 ml/min/1.73 m2. 6. Patients with electrolyte (K+, Ca++) abnormalities, as determined by the lab values outside of a normal range. 7. Patients with the history or symptoms of increased intracranial pressure or reduced intracranial compliance (e.g. headaches, nausea and vomiting, visual changes, mental changes). 8. Patients with skull base defects. 9. Patients with pulmonary hypertension who have pulmonary artery pressures above the normal range. 10. Patients with significant chronic obstructive or restrictive lung diseases, as manifested by known history of baseline chronic hypoxia and/or hypercapnia, and/or baseline room air SpO2 \< 95%. 11. Obese patients with BMI above 35 kg/m2. 13. Patients with severe and poorly controlled gastroesophageal reflux disease despite medical treatment. 14. Patients with hiatal hernia and full stomach patients. 15. Patient's refusal to participate in the study. 16. Patients who do not understand English or mentally handicapped. 17. Pregnant or breastfeeding patients. **Maximum Age:** 80 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Stanford **Country:** United States **Facility:** Stanford Hospital and Clinics **State:** California **Zip:** 94305 #### Overall Officials **Official 1:** **Affiliation:** Stanford University **Name:** Vladimir Nekhendzy, MD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Nekhendzy V, Saxena A, Mittal B, Sun E, Sung K, Dewan K, Damrose EJ. The Safety and Efficacy of Transnasal Humidified Rapid-Insufflation Ventilatory Exchange for Laryngologic Surgery. Laryngoscope. 2020 Dec;130(12):E874-E881. doi: 10.1002/lary.28562. Epub 2020 Feb 20. **PMID:** 32078170 ## Document Section ### Large Document Module #### Large Docs - Date: 2019-06-20 - Filename: SAP_000.pdf - Has ICF: False - Has Protocol: False - Has SAP: True - Label: Statistical Analysis Plan - Size: 365669 - Type Abbrev: SAP - Upload Date: 2019-06-20T13:17 - Date: 2017-02-15 - Filename: Prot_001.pdf - Has ICF: False - Has Protocol: True - Has SAP: False - Label: Study Protocol - Size: 328212 - Type Abbrev: Prot - Upload Date: 2019-06-21T00:46 ## Derived Section ### Intervention Browse Module - Browse Branches - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M12478 - Name: Nicotine - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module #### Event Groups **Group ID:** EG000 **Title:** THRIVE **Deaths Num At Risk:** 10 **Description:** THRIVE: active nasal oxygen delivery system **ID:** EG000 **Other Num at Risk:** 10 **Serious Number At Risk:** 10 **Title:** THRIVE **Group ID:** EG001 **Title:** Control Group **Deaths Num At Risk:** 10 **Description:** Endotracheal tube or Supraglottic jet ventilation **ID:** EG001 **Other Num at Risk:** 10 **Serious Number At Risk:** 10 **Title:** Control Group **Frequency Threshold:** 0 **Time Frame:** one month ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 10 **Group ID:** BG001 **Value:** 10 **Group ID:** BG002 **Value:** 20 **Units:** Participants ### Group **ID:** BG000 **Title:** THRIVE **Description:** THRIVE: active nasal oxygen delivery system ### Group **ID:** BG001 **Title:** Control Group **Description:** Endotracheal tube or Supraglottic jet ventilation ### Group **ID:** BG002 **Title:** Total **Description:** Total of all reporting groups ### Measure #### Measurement **Group ID:** BG000 **Spread:** 12.42 **Value:** 50.9 #### Measurement **Group ID:** BG001 **Spread:** 17.29 **Value:** 55.2 #### Measurement **Group ID:** BG002 **Spread:** 14.82 **Value:** 53.1 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 10 **Group ID:** BG001 **Value:** 10 **Group ID:** BG002 **Value:** 20 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 8 #### Measurement **Group ID:** BG001 **Value:** 6 #### Measurement **Group ID:** BG002 **Value:** 14 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 2 #### Measurement **Group ID:** BG001 **Value:** 4 #### Measurement **Group ID:** BG002 **Value:** 6 **Category Title:** Male #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 10 **Group ID:** BG001 **Value:** 10 **Group ID:** BG002 **Value:** 20 **Class Title:** ### Measure #### Measurement **Group ID:** BG002 **Value:** 0 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 0 **Group ID:** BG001 **Value:** 0 **Group ID:** BG002 **Value:** 0 **Class Title:** **Denomination Units Selected:** ## Results Section - Baseline Characteristics Module ### Measure 1 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** Age, Continuous **Unit of Measure:** years ### Measure 2 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Sex: Female, Male **Unit of Measure:** Participants ### Measure 3 **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Race and Ethnicity were not collected from any participant. **Title:** Race and Ethnicity Not Collected **Unit of Measure:** Participants ## Results Section - More Information Module ### Certain Agreement **PI Sponsor Employee:** True ### Point of Contact **Email:** [email protected] **Organization:** Stanford University **Phone:** 650-498-4055 **Title:** Vladimir Nekhendzy ## Results Section - Outcome Measures Module ### Outcome Measure 1 #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** P value was calculated using the means and standard deviations for each of the patient characteristics. **Non-Inferiority Type:** EQUIVALENCE **Other Analysis Description:** **P-Value:** 0.006 **P-Value Comment:** **Parameter Type:** **Parameter Value:** **Statistical Comment:** **Statistical Method:** t-test, 2 sided **Tested Non-Inferiority:** ### Outcome Measure 2 ### Outcome Measure 3 ### Outcome Measure 4 ### Outcome Measure 5 ### Outcome Measure 6 ### Outcome Measure 7 ### Outcome Measure 8 ### Outcome Measure 9 ### Outcome Measure 10 ### Outcome Measure 11 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 5.66 - **Upper Limit:** - **Value:** 93 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.57 - **Upper Limit:** - **Value:** 98.7 **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 4.0 - **Upper Limit:** - **Value:** 10.3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 3.4 - **Upper Limit:** - **Value:** 9.4 **Title:** #### Outcome Measure 3 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.1 - **Upper Limit:** - **Value:** 1.8 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 2.1 - **Upper Limit:** - **Value:** 4.3 **Title:** #### Outcome Measure 4 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.52 - **Upper Limit:** - **Value:** 0.4 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.95 - **Upper Limit:** - **Value:** 1.7 **Title:** #### Outcome Measure 5 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 10.82 - **Upper Limit:** - **Value:** 19.1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 8.85 - **Upper Limit:** - **Value:** 20.9 **Title:** #### Outcome Measure 6 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 6.3 - **Upper Limit:** - **Value:** 4.3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 7.4 - **Upper Limit:** - **Value:** 4.8 **Title:** #### Outcome Measure 7 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 43.41 - **Upper Limit:** - **Value:** 65.7 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 42.84 - **Upper Limit:** - **Value:** 77.7 **Title:** #### Outcome Measure 8 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.95 - **Upper Limit:** - **Value:** 1.3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 2.91 - **Upper Limit:** - **Value:** 3.7 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.29 - **Upper Limit:** - **Value:** 0.9 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.77 - **Upper Limit:** - **Value:** 2.7 **Title:** #### Outcome Measure 9 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 11.0 - **Upper Limit:** - **Value:** 8.8 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 22.1 - **Upper Limit:** - **Value:** 22.5 **Title:** #### Outcome Measure 10 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 12.63 - **Upper Limit:** - **Value:** 12.8 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 12.06 - **Upper Limit:** - **Value:** 22.7 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 12.19 - **Upper Limit:** - **Value:** 7.6 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 13.22 - **Upper Limit:** - **Value:** 13.6 **Title:** #### Outcome Measure 11 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 15.7 - **Upper Limit:** - **Value:** 142.5 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 17.9 - **Upper Limit:** - **Value:** 131.2 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Reporting Status:** POSTED **Time Frame:** intraoperative (up to one hour) **Title:** Average Oxygen Saturation by Pulse Oximetry (SpO2) (Primary Anesthesia Outcome) **Type:** PRIMARY **Unit of Measure:** percentage of saturation (SpO2) ##### Group **Description:** THRIVE: active nasal oxygen delivery system **ID:** OG000 **Title:** THRIVE ##### Group **Description:** Endotracheal tube or Supraglottic jet ventilation **ID:** OG001 **Title:** Control Group #### Outcome Measure 2 **Description:** time from end of surgery to responding to commands/extubation **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Reporting Status:** POSTED **Time Frame:** intraoperative (up to 20 min) **Title:** Time to Awakening From Anesthesia (Primary Anesthesia Outcome) **Type:** PRIMARY **Unit of Measure:** minutes ##### Group **Description:** THRIVE: active nasal oxygen delivery system **ID:** OG000 **Title:** THRIVE ##### Group **Description:** Endotracheal tube or Supraglottic jet ventilation **ID:** OG001 **Title:** Control Group #### Outcome Measure 3 **Description:** Time required for the surgeon to position the patient's head and expose the surgical field for surgery using operating laryngoscope **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Reporting Status:** POSTED **Time Frame:** intraoperative (up to 5 min) **Title:** Suspension Time (Primary Surgical Outcome) **Type:** PRIMARY **Unit of Measure:** minutes ##### Group **Description:** THRIVE: active nasal oxygen delivery system **ID:** OG000 **Title:** THRIVE ##### Group **Description:** Endotracheal tube or Supraglottic jet ventilation **ID:** OG001 **Title:** Control Group #### Outcome Measure 4 **Description:** Number of attempts required for the surgeon to reposition the patient's head for optimal surgical exposure using operating laryngoscope **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Reporting Status:** POSTED **Time Frame:** intraoperative (up to 5 min) **Title:** Number of Suspension Repositioning Maneuvers (Primary Surgical Outcome) **Type:** PRIMARY **Unit of Measure:** maneuvers ##### Group **Description:** THRIVE: active nasal oxygen delivery system **ID:** OG000 **Title:** THRIVE ##### Group **Description:** Endotracheal tube or Supraglottic jet ventilation **ID:** OG001 **Title:** Control Group #### Outcome Measure 5 **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Reporting Status:** POSTED **Time Frame:** intraoperative (up to one hour) **Title:** Duration of Surgery (Primary Surgical Outcome) **Type:** PRIMARY **Unit of Measure:** minutes ##### Group **Description:** THRIVE: active nasal oxygen delivery system **ID:** OG000 **Title:** THRIVE ##### Group **Description:** Endotracheal tube or Supraglottic jet ventilation **ID:** OG001 **Title:** Control Group #### Outcome Measure 6 **Description:** Time required for the patient to become fully alert and oriented per standard recovery room evaluation **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Reporting Status:** POSTED **Time Frame:** Recovery room admission (up to 30 min following admission to recovery room) **Title:** Alertness **Type:** SECONDARY **Unit of Measure:** minutes ##### Group **Description:** THRIVE: active nasal oxygen delivery system **ID:** OG000 **Title:** THRIVE ##### Group **Description:** Endotracheal tube or Supraglottic jet ventilation **ID:** OG001 **Title:** Control Group #### Outcome Measure 7 **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Reporting Status:** POSTED **Time Frame:** Up to 2 hours after procedure **Title:** Recovery Room Time **Type:** SECONDARY **Unit of Measure:** minutes ##### Group **Description:** THRIVE: active nasal oxygen delivery system **ID:** OG000 **Title:** THRIVE ##### Group **Description:** Endotracheal tube or Supraglottic jet ventilation **ID:** OG001 **Title:** Control Group #### Outcome Measure 8 **Description:** A score from 0 to 10, higher scores corresponding to higher pain **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Reporting Status:** POSTED **Time Frame:** Recovery room admission and discharge (up to 2 hours) **Title:** Numerical Pain Rating Scores **Type:** SECONDARY **Unit of Measure:** score on a scale ##### Group **Description:** THRIVE: active nasal oxygen delivery system **ID:** OG000 **Title:** THRIVE ##### Group **Description:** Endotracheal tube or Supraglottic jet ventilation **ID:** OG001 **Title:** Control Group #### Outcome Measure 9 **Description:** Total oral opioid consumption in morphine milligram equivalents **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Reporting Status:** POSTED **Time Frame:** Recovery room admission and discharge (up to 2 hours) **Title:** Opioid Consumption **Type:** SECONDARY **Unit of Measure:** MME: morphine milligram equivalents ##### Group **Description:** THRIVE: active nasal oxygen delivery system **ID:** OG000 **Title:** THRIVE ##### Group **Description:** Endotracheal tube or Supraglottic jet ventilation **ID:** OG001 **Title:** Control Group #### Outcome Measure 10 **Description:** numerical scale, range from 0 to 40, with higher scores corresponding to worse outcome **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Reporting Status:** POSTED **Time Frame:** Preoperative assessment and one month after surgery **Title:** Change in Voice Handicap Index (VHI) **Type:** SECONDARY **Unit of Measure:** score on a scale ##### Group **Description:** THRIVE: active nasal oxygen delivery system **ID:** OG000 **Title:** THRIVE ##### Group **Description:** Endotracheal tube or Supraglottic jet ventilation **ID:** OG001 **Title:** Control Group #### Outcome Measure 11 **Description:** 15-question survey, with each question scored from 0 to 10. Overall range 0-150, higher scores correspond to better outcome. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Reporting Status:** POSTED **Time Frame:** One week after surgery **Title:** Quality of Recovery **Type:** SECONDARY **Unit of Measure:** score on a scale ##### Group **Description:** THRIVE: active nasal oxygen delivery system **ID:** OG000 **Title:** THRIVE ##### Group **Description:** Endotracheal tube or Supraglottic jet ventilation **ID:** OG001 **Title:** Control Group ### Participant Flow Module #### Group **Description:** THRIVE: active nasal oxygen delivery system **ID:** FG000 **Title:** THRIVE #### Group **Description:** Endotracheal tube or Supraglottic jet ventilation **ID:** FG001 **Title:** Control Group #### Period **Title:** Overall Study ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 10 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 10 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 10 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 10 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 0 **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT05503979 **Acronym:** EHCUS **Brief Title:** Elimination of Hepatitis C Virus Among Users of Substances **Official Title:** Eliminación de la infección Por el Virus de la Hepatitis C en PWID en Los Estados Del Norte de México #### Organization Study ID Info **ID:** GAS-3800-21-22-1 #### Organization **Class:** OTHER **Full Name:** Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran ### Status Module #### Completion Date **Date:** 2024-05-15 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2022-09-29 **Type:** ACTUAL **Last Update Submit Date:** 2022-09-27 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2023-08-15 **Type:** ESTIMATED #### Start Date **Date:** 2022-11-15 **Type:** ESTIMATED **Status Verified Date:** 2022-09 #### Study First Post Date **Date:** 2022-08-17 **Type:** ACTUAL **Study First Submit Date:** 2022-08-03 **Study First Submit QC Date:** 2022-08-14 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** Gilead Sciences #### Lead Sponsor **Class:** OTHER **Name:** Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran #### Responsible Party **Investigator Affiliation:** Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran **Investigator Full Name:** Graciela Elia Castro Narro **Investigator Title:** Principal Investigator **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** True **Is US Export:** True **Oversight Has DMC:** True ### Description Module **Brief Summary:** Substance users are a vulnerable group that should be prioritized in HCV (Hepatitis C Virus) elimination efforts in Mexico and in which it is feasible to carry out micro-elimination programs. It is an important group to treat both because of its high prevalence and because of the dynamic spread of infection among the general population. HCV seropositivity has not been documented in this group of people in Mexico City, the metropolitan area and the northern states of the country, nor has the sustained viral response been evaluated in this group of patients in the Mexican population. **Detailed Description:** The investigators would use a work team, the program and the value proposal would be presented to the local authorities, the coordinator of the national commission against dependencies and doctors. The investigators would use an algorithm designed for the first-step diagnosis of HCV in SUs (Substances Users) , and defined the key centers for screening and linking to care. The project is planned as follows: * Screening: SUs in centers of substance users in Mexico City, the metropolitan area and states in the North of the country will be evaluated with rapid tests. Those with a positive result will be selected. * Diagnosis: Patients with a positive rapid test result will undergo a viral load test against HCV. Those with positive results will be selected. * Link-up: Those who are confirmed positive will be profiled to receive treatment at INCMNSZ. they will receive damage reduction to prevent reinfection or primary infection in negatives (granted by the rehabilitation center). * Treatment: The treatment will be received in a certified hospital (INCMNSZ) to treat patients with HCV infection, the treatment will be indicated by doctors who work in this hospital in the treatment consultations for hepatitis C or in centers with substance users with doctors trained to administer the treatment. This training will be received by telementoring. And also during the treatment, follow-up will be given with telementoring sessions if necessary. This group of people has personality characteristics that require a integral treatment, so it will be a integral and multidisciplinary treatment with psychological care and harm reduction (provided by the rehabilitation center) * Confirm SVR: A viral load test will be performed 12 weeks after the end of treatment to corroborate SVR. They will be given after this a mentorship for harm reduction and advice against reinfections The importance of this project is characterized by minimal monitoring, patients and doctors education by telementoring, multidisciplinary teams and integral treatment ### Conditions Module **Conditions:** - Hepatitis C in Substance Users **Keywords:** - HCV - Elimination - Substance Users ### Design Module #### Bio Spec **Description:** A blood sample will be taken for HCV detection by PCR (polymerase chain reaction) **Retention:** SAMPLES_WITH_DNA #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 1000 **Type:** ESTIMATED **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Substances users confirmed with Viral Load for HCV. after that will be evaluated through laboratory studies (CBC and blood chemistry), HIV/HBV (Hepatitis B Virus) serology, fibrosis status will be evaluated through APRI (AST to Platelet Ratio Index) and FIB-4. The antiviral treatment (sofosbuvir/Velpatasvir) will be chosen according to the characteristics of each patient and follow-up will be maintained according to the national plan with a visit at the end of treatment and 12 weeks after its end to assess SVR. The importance of this project is characterized by minimal monitoring, patients and doctors education by telementoring, multidisciplinary teams and integral treatment. **Intervention Names:** - Drug: Sofosbuvir 400 MG / Velpatasvir 100 MG [Epclusa] **Label:** Substances Users ### Interventions #### Intervention 1 **Arm Group Labels:** - Substances Users **Description:** 1 tab every 24 hrs for 12 weeks **Name:** Sofosbuvir 400 MG / Velpatasvir 100 MG [Epclusa] **Other Names:** - Epclusa **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Number por participants who achive SVR whit the treatment **Measure:** Sustained viral response (SVR) in people who use substances in the Mexico City metropolitan area and the northern states of the country. **Time Frame:** through study completion, an average of 1 year #### Secondary Outcomes **Description:** Number of participants with chronic HCV infection **Measure:** Seroprevalence and prevalence of HCV in people who use substances in the Mexico City metropolitan area and the northern states of the country. **Time Frame:** through study completion, an average of 1 year **Description:** Number of participants who does not achive RVS **Measure:** No Sustained viral response (SVR) in people who use Substances in the Mexico City **Time Frame:** through study completion, an average of 1 year ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Patients older than 18 years. * Active infection by hepatitis C virus. * People who use substances and who are users of rehabilitation centers in Mexico City, the metropolitan area and the northern states of the country. * Signature of informed consent Exclusion Criteria: * all those who do not fit the inclusion criteria **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Substances Users who are registered in the rehabilitation centers that comply with the applicable regulations in Mexico City, the metropolitan area and the northern states of the country. ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Graciela Castro-Narro, MD **Phone:** +52 55 5405 3670 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Valeria Cortés-Mollinedo, MD **Phone:** +52 27 1100 7484 **Role:** CONTACT #### Overall Officials **Official 1:** **Affiliation:** INCMNSZ **Name:** Graciela Castro-Narro, MD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **Access Criteria:** An Open Access journal will be searched so that the information can be consulted **Description:** all IPD that underlie results in a publication would be shared **Info Types:** - CSR **IPD Sharing:** YES **Time Frame:** By 2024, once the enrollment of patients and the analyzes have been completed, this publication will be published and can be consulted ### References Module #### References **Citation:** Yehia BR, Schranz AJ, Umscheid CA, Lo Re V 3rd. The treatment cascade for chronic hepatitis C virus infection in the United States: a systematic review and meta-analysis. PLoS One. 2014 Jul 2;9(7):e101554. doi: 10.1371/journal.pone.0101554. eCollection 2014. **PMID:** 24988388 **Citation:** Mendizabal M, Alonso C, Silva MO. Overcoming barriers to hepatitis C elimination. Frontline Gastroenterol. 2019 Jul;10(3):207-209. doi: 10.1136/flgastro-2018-101114. Epub 2019 Feb 1. No abstract available. **PMID:** 31288259 **Citation:** Lazarus JV, Safreed-Harmon K, Thursz MR, Dillon JF, El-Sayed MH, Elsharkawy AM, Hatzakis A, Jadoul M, Prestileo T, Razavi H, Rockstroh JK, Wiktor SZ, Colombo M. The Micro-Elimination Approach to Eliminating Hepatitis C: Strategic and Operational Considerations. Semin Liver Dis. 2018 Aug;38(3):181-192. doi: 10.1055/s-0038-1666841. Epub 2018 Jul 9. **PMID:** 29986353 **Citation:** Wansom T, Falade-Nwulia O, Sutcliffe CG, Mehta SH, Moore RD, Thomas DL, Sulkowski MS. Barriers to Hepatitis C Virus (HCV) Treatment Initiation in Patients With Human Immunodeficiency Virus/HCV Coinfection: Lessons From the Interferon Era. Open Forum Infect Dis. 2017 Feb 11;4(1):ofx024. doi: 10.1093/ofid/ofx024. eCollection 2017 Winter. **PMID:** 28480293 **Citation:** Vandenbroucke JP, von Elm E, Altman DG, Gotzsche PC, Mulrow CD, Pocock SJ, Poole C, Schlesselman JJ, Egger M; STROBE Initiative. Strengthening the Reporting of Observational Studies in Epidemiology (STROBE): explanation and elaboration. Int J Surg. 2014 Dec;12(12):1500-24. doi: 10.1016/j.ijsu.2014.07.014. Epub 2014 Jul 18. **PMID:** 25046751 #### See Also Links **Label:** Global Health Sector Strategy for Viral Hepatitis 2016-2021: Ending Viral Hepatitis. **URL:** https://apps.who.int/iris/handle/10665/250578 **Label:** REGISTERED ADDICTION CARE CENTERS THAT COMPLY WITH APPLICABLE REGULATIONS IN CDMX **URL:** https://www.iapa.cdmx.gob.mx/storage/app/uploads/public/5cf/6f1/886/5cf6f1886f373671287065.pdf ## Derived Section ### Condition Browse Module - Ancestors - ID: D000008107 - Term: Liver Diseases - ID: D000004066 - Term: Digestive System Diseases - ID: D000006525 - Term: Hepatitis, Viral, Human - ID: D000014777 - Term: Virus Diseases - ID: D000007239 - Term: Infections - ID: D000004769 - Term: Enterovirus Infections - ID: D000010850 - Term: Picornaviridae Infections - ID: D000012327 - Term: RNA Virus Infections - ID: D000086982 - Term: Blood-Borne Infections - ID: D000003141 - Term: Communicable Diseases - ID: D000018178 - Term: Flaviviridae Infections - ID: D000019966 - Term: Substance-Related Disorders - ID: D000064419 - Term: Chemically-Induced Disorders - ID: D000001523 - Term: Mental Disorders ### Condition Browse Module - Browse Branches - Abbrev: BC01 - Name: Infections - Abbrev: BC06 - Name: Digestive System Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC25 - Name: Substance Related Disorders - Abbrev: BXM - Name: Behaviors and Mental Disorders - Abbrev: BC23 - Name: Symptoms and General Pathology ### Condition Browse Module - Browse Leaves - ID: M9592 - Name: Hepatitis A - Relevance: HIGH - As Found: Hepatitis - ID: M9591 - Name: Hepatitis - Relevance: HIGH - As Found: Hepatitis - ID: M17522 - Name: Virus Diseases - Relevance: LOW - As Found: Unknown - ID: M9611 - Name: Hepatitis C - Relevance: HIGH - As Found: Hepatitis C - ID: M1557 - Name: Drug Misuse - Relevance: HIGH - As Found: Substance Users - ID: M11107 - Name: Liver Diseases - Relevance: LOW - As Found: Unknown - ID: M7255 - Name: Digestive System Diseases - Relevance: LOW - As Found: Unknown - ID: M8883 - Name: Gastrointestinal Diseases - Relevance: LOW - As Found: Unknown - ID: M9610 - Name: Hepatitis, Viral, Human - Relevance: LOW - As Found: Unknown - ID: M10283 - Name: Infections - Relevance: LOW - As Found: Unknown - ID: M6368 - Name: Communicable Diseases - Relevance: LOW - As Found: Unknown - ID: M7930 - Name: Enterovirus Infections - Relevance: LOW - As Found: Unknown - ID: M13745 - Name: Picornaviridae Infections - Relevance: LOW - As Found: Unknown - ID: M15149 - Name: RNA Virus Infections - Relevance: LOW - As Found: Unknown - ID: M2593 - Name: Blood-Borne Infections - Relevance: LOW - As Found: Unknown - ID: M20324 - Name: Flaviviridae Infections - Relevance: LOW - As Found: Unknown - ID: M21837 - Name: Substance-Related Disorders - Relevance: LOW - As Found: Unknown - ID: M30302 - Name: Chemically-Induced Disorders - Relevance: LOW - As Found: Unknown - ID: M4815 - Name: Mental Disorders - Relevance: LOW - As Found: Unknown - ID: M14473 - Name: Psychotic Disorders - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000006506 - Term: Hepatitis A - ID: D000006526 - Term: Hepatitis C - ID: D000006505 - Term: Hepatitis - ID: D000076064 - Term: Drug Misuse ### Intervention Browse Module - Ancestors - ID: D000000998 - Term: Antiviral Agents - ID: D000000890 - Term: Anti-Infective Agents ### Intervention Browse Module - Browse Branches - Abbrev: Infe - Name: Anti-Infective Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M341417 - Name: Sofosbuvir-velpatasvir drug combination - Relevance: HIGH - As Found: Supraclavicular - ID: M443 - Name: Sofosbuvir - Relevance: HIGH - As Found: Chronic Pain - ID: M349587 - Name: Velpatasvir - Relevance: HIGH - As Found: Photographs - ID: M4314 - Name: Antiviral Agents - Relevance: LOW - As Found: Unknown - ID: M4214 - Name: Anti-Infective Agents - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000069474 - Term: Sofosbuvir - ID: C000611331 - Term: Sofosbuvir-velpatasvir drug combination - ID: C000604171 - Term: Velpatasvir ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04963179 **Acronym:** PREG2 **Brief Title:** PREvention of Intrauterine Adhesion After Adhesiolysis With Novel Tri-block deGradable Polymer Film. **Official Title:** PREvention of Intrauterine Adhesion After Adhesiolysis With Novel Tri-block deGradable Polymer Film. #### Organization Study ID Info **ID:** PREG2 #### Organization **Class:** INDUSTRY **Full Name:** Womed ### Status Module #### Completion Date **Date:** 2025-01 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-02-14 **Type:** ACTUAL **Last Update Submit Date:** 2024-02-12 **Overall Status:** ACTIVE_NOT_RECRUITING #### Primary Completion Date **Date:** 2023-11-11 **Type:** ACTUAL #### Start Date **Date:** 2021-11-29 **Type:** ACTUAL **Status Verified Date:** 2024-02 #### Study First Post Date **Date:** 2021-07-15 **Type:** ACTUAL **Study First Submit Date:** 2021-07-05 **Study First Submit QC Date:** 2021-07-05 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Womed #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False ### Description Module **Brief Summary:** PREG2 is a randomized controlled trial that aims to evaluate efficacy in preventing intrauterine adhesion recurrence after hysteroscopic adhesiolysis of a novel intrauterine barrier film named Womed Leaf **Detailed Description:** PREG2 is a prospective, multi-center, randomized, controlled, two arm clinical study. The objective is to evaluate the efficacy of Womed Leaf in preventing intrauterine adhesion recurrence after adhesiolysis compared to adhesiolysis alone. The study will be performed on women with moderate or severe adhesions (AFS score \>=5) scheduled for adhesiolysis. Indeed, the risk of intrauterine adhesion is very high (up to 60%) in this population of patients. A follow-up diagnostic hysteroscopy will be performed 6-8 weeks after the adhesiolysis procedure to determine the presence and severity of IUAs according to the American Fertility Society and European Society of Gynecologic Endoscopy classification systems of adhesions. Fertility-related outcome will include live pregnancy at 1 year and 2 years and will be reported as secondary endpoints. 154 women are planned to be included in the PREG2 study. ### Conditions Module **Conditions:** - Asherman Syndrome - Intrauterine Adhesion **Keywords:** - Asherman Syndrome - Intrauterine adhesion - Hysteroscopy - Adhesiolysis - Adhesion prevention - Infertility ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** DOUBLE **Who Masked:** - PARTICIPANT - OUTCOMES_ASSESSOR **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 160 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** IUA prevention: The novel intrauterine barrier film (Womed Leaf) is inserted immediately after completion of the hysteroscopic adhesiolysis **Intervention Names:** - Device: Womed Leaf **Label:** Womed Leaf **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** No IUA prevention - no placebo after adhesiolysis **Label:** Control **Type:** NO_INTERVENTION ### Interventions #### Intervention 1 **Arm Group Labels:** - Womed Leaf **Description:** Womed Leaf™ device is composed of a uterine anti-adhesion film pre-loaded inside a flexible inserter. Womed Leaf™ is inserted in the uterine cavity by the gynecologist surgeon as a film folded into a 5 mm diameter flexible inserter. Once released, the film will unfold and swell into the uterine cavity to keep uterus walls separated during approximately 5 days. It is degraded and discharged naturally through the cervix and vagina in less than 30 days. **Name:** Womed Leaf **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Description:** Change of AFS score between pre-adhesiolysis and second-look hysteroscopy (AFS) score **Measure:** Efficacy - IUA severity **Time Frame:** At second look hysteroscopy between 4 and 8 weeks **Description:** Adverse events up to second look hysteroscopy. **Measure:** Safety - Adverse events **Time Frame:** At second look hysteroscopy between 4 and 8 weeks #### Secondary Outcomes **Description:** Percentage of patients who have improved from severe to mild adhesions or from severe to no adhesions or from moderate to no adhesions **Measure:** High-responder rate **Time Frame:** At second look hysteroscopy between 4 and 8 weeks **Description:** Average of AFS score component "extent of cavity involved" **Measure:** Change of "extent of cavity involved" component **Time Frame:** At second look hysteroscopy between 4 and 8 weeks **Description:** Average of AFS score component "extent of cavity involved" **Measure:** Change in "extent of cavity involved" component between post-adhesiolysis and second look hysteroscopy **Time Frame:** At second look hysteroscopy between 4 and 8 weeks **Description:** Average of AFS score **Measure:** AFS score **Time Frame:** At second look hysteroscopy between 4 and 8 weeks **Description:** Average of the change of the AFS score component "Extent of IUA" **Measure:** Change of extent of IUA AFS score component **Time Frame:** At second look hysteroscopy between 4 and 8 weeks **Description:** Average of the change of the AFS score component "type of IUA" **Measure:** Change of type of IUA AFS score component **Time Frame:** At second look hysteroscopy between 4 and 8 weeks **Description:** Average of the change of the AFS score component "Menstrual Pattern" **Measure:** Menstrual pattern AFS score component **Time Frame:** At second look hysteroscopy between 4 and 8 weeks **Description:** Percentage of patients who have AFS \< 5 **Measure:** Percentage of patients who have Mild adhesions or no adhesion **Time Frame:** At second look hysteroscopy between 4 and 8 weeks **Description:** Rate of patients who don't have adhesion **Measure:** Freedom from IUA **Time Frame:** At second look hysteroscopy between 4 and 8 weeks **Description:** Rate of ECGE stage **Measure:** ESGE stage **Time Frame:** At second look hysteroscopy between 4 and 8 weeks **Description:** Level of post-operative pain on a numeric rating scale, with 0 = no pain and 10 = the worst pain. **Measure:** Level of post-operative pain **Time Frame:** At second look hysteroscopy between 4 and 8 weeks **Description:** Level of discomfort related to vaginal discharge on a numeric rating scale, with 0 = no discomfort and 10 = extremely disturbing **Measure:** Level of discomfort related to vaginal discharge **Time Frame:** At second look hysteroscopy between 4 and 8 weeks **Description:** Timing of vaginal discharge as recalled by the patient **Measure:** Timing of vaginal discharge **Time Frame:** At second look hysteroscopy between 4 and 8 weeks **Description:** Duration of the vaginal discharge as recalled by the patient **Measure:** Duration of the vaginal discharge **Time Frame:** At second look hysteroscopy between 4 and 8 weeks **Description:** Qualitative description of the vaginal discharge as recalled by the patient **Measure:** Qualitative description of the vaginal discharge **Time Frame:** At second look hysteroscopy between 4 and 8 weeks **Description:** Change of menstrual pattern **Measure:** Change of menstrual pattern **Time Frame:** At second look hysteroscopy between 4 and 8 weeks, 1 year, 2 years **Description:** Reintervention rate, during second look hysteroscopy or scheduled later up to one year **Measure:** Reintervention rate **Time Frame:** At second look hysteroscopy or scheduled later up to one year **Description:** Number of adhesiolysis procedures after second look to one year **Measure:** Number of adhesiolysis procedures **Time Frame:** After second look to one year **Description:** Pregnancy rate defined as presence of foetal sac or heartbeat by ultrasound at 1 year and 2 years, whether spontaneous or IVF **Measure:** Pregnancy rate **Time Frame:** 1 year, 2 years **Description:** Live birth rate at 1 year and 2 years **Measure:** Live birth rate **Time Frame:** 1 year and 2 years **Description:** Pregnancy complication rate **Measure:** Pregnancy complication rate **Time Frame:** 2 years **Description:** Time to pregnancy (i.e. time between the second look hysteroscopy and pregnancy start) **Measure:** Time to pregnancy **Time Frame:** 2 years **Description:** IUA severity according to Chinese scoring system (for patients enrolled in China only) **Measure:** IUA severity according to Chinese scoring system **Time Frame:** At second look hysteroscopy between 4 and 8 weeks **Description:** Percentage of patients with an improvement of one clinical category i.e from Severe to Moderate or from Moderate to Mild **Measure:** Responder rate **Time Frame:** At second look hysteroscopy between 4 and 8 weeks ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Women with moderate or severe intrauterine adhesions according to the AFS classification, i.e AFS score \>=5, confirmed by hysteroscopy right before adhesiolysis * Scheduled for hysteroscopic adhesiolysis * Age above or equal to 18 * Subjects who are willing to provide a written informed consent. * Subjects who can comply with the study follow-up (second look hysteroscopy) and other study requirements * Subjects who agree to refrain from intercourse or use a reliable form of barrier contraception to prevent unintended pregnancy until the follow-up hysteroscopy. * Subjects who agree to avoid all intrauterine devices (IUDs) until the follow-up hysteroscopy. Exclusion Criteria: Pre-operative criteria * Post menopause * Pregnant (confirmed by a positive pregnancy test) or lactating * Abnormal uterine cavity according to ESHRE classification I to V such as unicornis, bicornis, septate, duplex * Known or suspected endometrial hyperplasia * History of cervical or endometrial cancer * Active pelvic infection or history of pelvic peritonitis * History of endometrial ablation * Known contraindication or hypersensitivity to Womed Leaf component * Current participation in another clinical investigation that has not yet received the primary endpoint. * Any other condition that makes participation in the study contrary to the patient's best interests. Intra-operative criteria, post adhesiolysis: * Perforation during adhesiolysis * Uterine depth \< 5cm or \> 10cm **Minimum Age:** 18 Years **Sex:** FEMALE **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Gent **Country:** Belgium **Facility:** Gent UZ **Zip:** 9000 **Location 2:** **City:** Guangzhou **Country:** China **Facility:** Guangdong Maternal and Child Health Hospital **Location 3:** **City:** Hangzhou **Country:** China **Facility:** Women's Hospital School Of Medicine Zhejiang University **Location 4:** **City:** Shanghai **Country:** China **Facility:** The Obstetrics & Gynecology Hospital Affiliated to Fudan University **Location 5:** **City:** Ostrava **Country:** Czechia **Facility:** Gynprenatal **Location 6:** **City:** Le Kremlin-Bicêtre **Country:** France **Facility:** CHU Bicêtre **Zip:** 94270 **Location 7:** **City:** Lille **Country:** France **Facility:** CHU de Lille **Zip:** 59000 **Location 8:** **City:** Marseille **Country:** France **Facility:** Hopital La Conception **Zip:** 13005 **Location 9:** **City:** Paris **Country:** France **Facility:** CHU Lariboisière **Zip:** 75010 **Location 10:** **City:** Rennes **Country:** France **Facility:** Clinique Mutualiste La sagesse **Zip:** 35043 **Location 11:** **City:** Napoli **Country:** Italy **Facility:** A.O.U Federico II **Zip:** 80131 **Location 12:** **City:** Torino **Country:** Italy **Facility:** Aso Mauriziano Umberto I **Location 13:** **City:** Barcelona **Country:** Spain **Facility:** Hospital Clinic Barcelonna **Location 14:** **City:** Madrid **Country:** Spain **Facility:** Ramon y Cajal Hospital **Zip:** 28034 **Location 15:** **City:** Lausanne **Country:** Switzerland **Facility:** Centre Hospitalier Universitaire Vaudois **Zip:** 1011 ### IPD Sharing Statement Module **Access Criteria:** researchers who provide a methodologically sound proposal **Description:** Individual participant data that underlie the result that will be reported in an article and study protocol may be made available to researchers who provide a methodologically sound proposal, immediately after article publication and during 5 years **Info Types:** - STUDY_PROTOCOL **IPD Sharing:** YES **Time Frame:** immediately after article publication and during 5 years ## Derived Section ### Condition Browse Module - Ancestors - ID: D000010335 - Term: Pathologic Processes - ID: D000002921 - Term: Cicatrix - ID: D000005355 - Term: Fibrosis - ID: D000005831 - Term: Genital Diseases, Female - ID: D000052776 - Term: Female Urogenital Diseases - ID: D000005261 - Term: Female Urogenital Diseases and Pregnancy Complications - ID: D000091642 - Term: Urogenital Diseases - ID: D000091662 - Term: Genital Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BXS - Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M16355 - Name: Syndrome - Relevance: LOW - As Found: Unknown - ID: M10290 - Name: Infertility - Relevance: LOW - As Found: Unknown - ID: M3620 - Name: Tissue Adhesions - Relevance: HIGH - As Found: Adhesion - ID: M9269 - Name: Gynatresia - Relevance: HIGH - As Found: Asherman Syndrome - ID: M6160 - Name: Cicatrix - Relevance: LOW - As Found: Unknown - ID: M8485 - Name: Fibrosis - Relevance: LOW - As Found: Unknown - ID: M8943 - Name: Genital Diseases, Female - Relevance: LOW - As Found: Unknown - ID: M2876 - Name: Genital Diseases - Relevance: LOW - As Found: Unknown - ID: M2875 - Name: Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M27093 - Name: Female Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M14127 - Name: Pregnancy Complications - Relevance: LOW - As Found: Unknown - ID: M8399 - Name: Female Urogenital Diseases and Pregnancy Complications - Relevance: LOW - As Found: Unknown - ID: T509 - Name: Asherman's Syndrome - Relevance: HIGH - As Found: Asherman Syndrome ### Condition Browse Module - Meshes - ID: D000006175 - Term: Gynatresia - ID: D000000267 - Term: Tissue Adhesions ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00324779 **Brief Title:** Rituximab in Treating Young Patients Who Are Receiving Chemotherapy for B-Cell Non-Hodgkin's Lymphoma or B-Cell Acute Lymphoblastic Leukemia **Official Title:** Multicenter Therapy Study for Children With Mature B-NHL or B-ALL With a Rituximab - Window Before Chemotherapy #### Organization Study ID Info **ID:** CDR0000466643 #### Organization **Class:** NIH **Full Name:** National Cancer Institute (NCI) #### Secondary ID Infos **ID:** B-NHL-BFM-Rituximab **ID:** EU-205119 **ID:** NHL-BFM-RITUXIMAB ### Status Module #### Expanded Access Info #### Last Update Post Date **Date:** 2015-09-25 **Type:** ESTIMATED **Last Update Submit Date:** 2015-09-24 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2011-04 **Type:** ACTUAL #### Start Date **Date:** 2004-03 **Status Verified Date:** 2015-09 #### Study First Post Date **Date:** 2006-05-11 **Type:** ESTIMATED **Study First Submit Date:** 2006-05-10 **Study First Submit QC Date:** 2006-05-10 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** University Hospital Erlangen ### Description Module **Brief Summary:** RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some find cancer cells and kill them or carry cancer-killing substances to them. Others interfere with the ability of cancer cells to grow and spread. Giving rituximab before chemotherapy may be an effective treatment for B-cell non-Hodgkin's lymphoma or B-cell acute lymphoblastic leukemia. PURPOSE: This phase II trial is studying how well rituximab works in treating young patients who are planning to receive chemotherapy for B-cell non-Hodgkin's lymphoma or B-cell acute lymphoblastic leukemia. **Detailed Description:** OBJECTIVES: * Determine the response rate in children and adolescents with B-cell non-Hodgkin's lymphoma (B-NHL) or B-cell acute lymphoblastic leukemia (B-ALL) treated with rituximab monotherapy as upfront window therapy before chemotherapy. * Evaluate the effect of rituximab on different histological subtypes of childhood mature B-NHL or B-ALL in patients treated with this regimen. * Investigate the rituximab response in patients treated with this regimen. * Determine the toxicity profile of rituximab in these patients. * Collect pharmacokinetic and pharmacodynamic data from patients treated with this regimen. OUTLINE: This is a multicenter study. Patients receive rituximab IV on day 1. PROJECTED ACCRUAL: A total of 79 patients will be accrued for this study. ### Conditions Module **Conditions:** - Leukemia - Lymphoma **Keywords:** - B-cell childhood acute lymphoblastic leukemia - untreated childhood acute lymphoblastic leukemia - stage I childhood large cell lymphoma - stage II childhood large cell lymphoma - stage III childhood large cell lymphoma - stage IV childhood large cell lymphoma - stage I childhood lymphoblastic lymphoma - stage II childhood lymphoblastic lymphoma - stage III childhood lymphoblastic lymphoma - stage IV childhood lymphoblastic lymphoma - stage I childhood small noncleaved cell lymphoma - stage II childhood small noncleaved cell lymphoma - stage III childhood small noncleaved cell lymphoma - stage IV childhood small noncleaved cell lymphoma ### Design Module #### Design Info ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 79 **Type:** ESTIMATED **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module ### Interventions #### Intervention 1 **Name:** rituximab **Type:** BIOLOGICAL ### Outcomes Module #### Primary Outcomes **Measure:** Response rate **Measure:** Effect of rituximab on different histological subtypes **Measure:** Rituximab response **Measure:** Toxicity **Measure:** Pharmacokinetics and pharmacodynamics ### Eligibility Module **Eligibility Criteria:** DISEASE CHARACTERISTICS: * Histologically and immunohistochemically OR cytomorphologically and immunphenotypically confirmed mature B-cell non-Hodgkin's lymphoma or B-cell acute lymphoblastic leukemia * CD20 positive disease PATIENT CHARACTERISTICS: * Not pregnant or nursing * Fertile patients must use effective contraception * Adequate general condition with sufficient organ function (hepatic, renal, and cardiac) * No known disease that would preclude protocol therapy with rituximab * No known allergies against proteins * No acute or previous hepatitis B infection PRIOR CONCURRENT THERAPY: * At least 2 weeks since prior corticosteroids * No prior radiotherapy * No prior or concurrent chemotherapy * No concurrent treatment in another investigational trial **Maximum Age:** 18 Years **Sex:** ALL **Standard Ages:** - CHILD - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Aachen **Country:** Germany **Facility:** Kinderklinik - Universitaetsklinikum Aachen **Zip:** D-52074 **Location 2:** **City:** Augsburg **Country:** Germany **Facility:** Klinikum Augsburg **Zip:** DOH-86156 **Location 3:** **City:** Berlin **Country:** Germany **Facility:** Charite - Campus Charite Mitte **Zip:** D-10117 **Location 4:** **City:** Berlin **Country:** Germany **Facility:** Helios Klinikum Berlin **Zip:** D-13125 **Location 5:** **City:** Biefeld **Country:** Germany **Facility:** Evangelisches Krankenhauus Bielfeld **Zip:** 33617 **Location 6:** **City:** Bremen **Country:** Germany **Facility:** Klinikum Bremen-Mitte **Zip:** D-28205 **Location 7:** **City:** Cologne **Country:** Germany **Facility:** Children's Hospital **Zip:** D-50924 **Location 8:** **City:** Datteln **Country:** Germany **Facility:** Vestische Kinderklinik **Zip:** 45704 **Location 9:** **City:** Dresden **Country:** Germany **Facility:** Universitatsklinikum Carl Gustav Carus **Zip:** D-01307 **Location 10:** **City:** Erfurt **Country:** Germany **Facility:** Helios Klinikum Erfurt **Zip:** 99089 **Location 11:** **City:** Erlangen **Country:** Germany **Facility:** Universitaets - Kinderklinik **Zip:** 91054 **Location 12:** **City:** Essen **Country:** Germany **Facility:** Universitaetsklinikum Essen **Zip:** D-45147 **Location 13:** **City:** Frankfurt **Country:** Germany **Facility:** Klinikum der J.W. Goethe Universitaet **Zip:** D-60590 **Location 14:** **City:** Freiburg **Country:** Germany **Facility:** Universitaetskinderklinik - Universitaetsklinikum Freiburg **Zip:** D-79106 **Location 15:** **City:** Giessen **Country:** Germany **Facility:** Kinderklinik **Zip:** D-35385 **Location 16:** **City:** Greifswald **Country:** Germany **Facility:** Klinik und Poliklinik Fuer Kinder-und Jugendmedizin - Universitaetsklinikum Greifswald **Zip:** 17475 **Location 17:** **City:** Hamburg **Country:** Germany **Facility:** University Medical Center Hamburg - Eppendorf **Zip:** D-20246 **Location 18:** **City:** Hannover **Country:** Germany **Facility:** Medizinische Hochschule Hannover **Zip:** D-30625 **Location 19:** **City:** Heidelberg **Country:** Germany **Facility:** Universitaets-Kinderklinik Heidelberg **Zip:** D-69120 **Location 20:** **City:** Homburg **Country:** Germany **Facility:** Universitaetsklinikum des Saarlandes **Zip:** 66421 **Location 21:** **City:** Jena **Country:** Germany **Facility:** Universitaets - Kinderklinik **Zip:** D-07440 **Location 22:** **City:** Karlsruhe **Country:** Germany **Facility:** Staedtisches Klinikum Karlsruhe gGmbH **Zip:** 76133 **Location 23:** **City:** Kassel **Country:** Germany **Facility:** Kinderkrankenhaus Park Schoenfeld **Zip:** D-34121 **Location 24:** **City:** Kiel **Country:** Germany **Facility:** University Hospital Schleswig-Holstein - Kiel Campus **Zip:** D-24105 **Location 25:** **City:** Leipzig **Country:** Germany **Facility:** Universitaets - Kinderklinik **Zip:** D-04317 **Location 26:** **City:** Luebeck **Country:** Germany **Facility:** Universitaets - Kinderklinik - Luebeck **Zip:** D-23538 **Location 27:** **City:** Magdeburg **Country:** Germany **Facility:** Universitatsklinikum der MA **Zip:** 39120 **Location 28:** **City:** Marburg **Country:** Germany **Facility:** Universitaets - Kinderklinik **Zip:** 35033 **Location 29:** **City:** Muenster **Country:** Germany **Facility:** Klinik und Poliklinik fuer Kinder und Jugendmedizin - Universitaetsklinikum Muenster **Zip:** D-48149 **Location 30:** **City:** Munich **Country:** Germany **Facility:** Krankenhaus Muenchen Schwabing **Zip:** 80804 **Location 31:** **City:** Munich **Country:** Germany **Facility:** Dr. von Haunersches Kinderspital der Universitaet Muenchen **Zip:** D-80337 **Location 32:** **City:** Nuremberg **Country:** Germany **Facility:** Cnopf'sche Kinderklinik **Zip:** 90419 **Location 33:** **City:** Regensburg **Country:** Germany **Facility:** Klinik St. Hedwig-Kinderklinik **Zip:** 93049 **Location 34:** **City:** Stuttgart **Country:** Germany **Facility:** Olgahospital **Zip:** D-70176 **Location 35:** **City:** Tuebingen **Country:** Germany **Facility:** Universitaetsklinikum Tuebingen **Zip:** D-72076 **Location 36:** **City:** Ulm **Country:** Germany **Facility:** Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm **Zip:** D-89075 **Location 37:** **City:** Wuerzburg **Country:** Germany **Facility:** Universitaets - Kinderklinik Wuerzburg **Zip:** D-97080 **Location 38:** **City:** Zurich **Country:** Switzerland **Facility:** University Children's Hospital **Zip:** CH-8032 #### Overall Officials **Official 1:** **Affiliation:** University Hospital Erlangen **Name:** Alfred Reiter, MD **Role:** STUDY_CHAIR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009370 - Term: Neoplasms by Histologic Type - ID: D000009369 - Term: Neoplasms - ID: D000008232 - Term: Lymphoproliferative Disorders - ID: D000008206 - Term: Lymphatic Diseases - ID: D000007160 - Term: Immunoproliferative Disorders - ID: D000007154 - Term: Immune System Diseases - ID: D000006402 - Term: Hematologic Diseases - ID: D000007945 - Term: Leukemia, Lymphoid ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC15 - Name: Blood and Lymph Conditions - Abbrev: All - Name: All Conditions - Abbrev: BC20 - Name: Immune System Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M10945 - Name: Leukemia - Relevance: HIGH - As Found: Leukemia - ID: M10951 - Name: Leukemia, Lymphoid - Relevance: LOW - As Found: Unknown - ID: M27585 - Name: Precursor Cell Lymphoblastic Leukemia-Lymphoma - Relevance: HIGH - As Found: Acute Lymphoblastic Leukemia - ID: M11220 - Name: Lymphoma - Relevance: HIGH - As Found: Lymphoma - ID: M18828 - Name: Lymphoma, B-Cell - Relevance: LOW - As Found: Unknown - ID: M12315 - Name: Neoplasms by Histologic Type - Relevance: LOW - As Found: Unknown - ID: M11225 - Name: Lymphoproliferative Disorders - Relevance: LOW - As Found: Unknown - ID: M11203 - Name: Lymphatic Diseases - Relevance: LOW - As Found: Unknown - ID: M10206 - Name: Immunoproliferative Disorders - Relevance: LOW - As Found: Unknown - ID: M10200 - Name: Immune System Diseases - Relevance: LOW - As Found: Unknown - ID: M9490 - Name: Hematologic Diseases - Relevance: LOW - As Found: Unknown - ID: T175 - Name: Acute Lymphoblastic Leukemia - Relevance: HIGH - As Found: Acute Lymphoblastic Leukemia - ID: T3533 - Name: Lymphoblastic Lymphoma - Relevance: LOW - As Found: Unknown - ID: T3543 - Name: Lymphosarcoma - Relevance: HIGH - As Found: Lymphoma - ID: T640 - Name: B-cell Lymphoma - Relevance: LOW - As Found: Unknown - ID: T170 - Name: Acute Graft Versus Host Disease - Relevance: LOW - As Found: Unknown - ID: T1134 - Name: Childhood Acute Lymphoblastic Leukemia - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000008223 - Term: Lymphoma - ID: D000007938 - Term: Leukemia - ID: D000054198 - Term: Precursor Cell Lymphoblastic Leukemia-Lymphoma ### Intervention Browse Module - Ancestors - ID: D000074322 - Term: Antineoplastic Agents, Immunological - ID: D000000970 - Term: Antineoplastic Agents - ID: D000007155 - Term: Immunologic Factors - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000018501 - Term: Antirheumatic Agents ### Intervention Browse Module - Browse Branches - Abbrev: ANeo - Name: Antineoplastic Agents - Abbrev: ARhu - Name: Antirheumatic Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M373 - Name: Rituximab - Relevance: HIGH - As Found: Healthy - ID: M1346 - Name: Antineoplastic Agents, Immunological - Relevance: LOW - As Found: Unknown - ID: M10201 - Name: Immunologic Factors - Relevance: LOW - As Found: Unknown - ID: M20604 - Name: Antirheumatic Agents - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000069283 - Term: Rituximab ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT01572779 **Brief Title:** A Study to Investigate the Effect of a New Postural Bio-feedback Device on Low Back Pain **Official Title:** A Multicentre, Cluster Randomised, Placebo-controlled, Open-label Pilot Study of Back Strain Monitor (BSM) With Feedback Compared With the BSM Without Feedback in Subjects With Moderate Lower Back Pain. #### Organization Study ID Info **ID:** ProA-BSM-001 #### Organization **Class:** INDUSTRY **Full Name:** Pro-Active Medical Pty Ltd ### Status Module #### Completion Date **Date:** 2013-06 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2015-03-25 **Type:** ESTIMATED **Last Update Submit Date:** 2015-03-23 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2013-06 **Type:** ACTUAL #### Start Date **Date:** 2009-11 **Status Verified Date:** 2015-03 #### Study First Post Date **Date:** 2012-04-06 **Type:** ESTIMATED **Study First Submit Date:** 2011-06-07 **Study First Submit QC Date:** 2012-04-04 ### Sponsor Collaborators Module #### Collaborators **Class:** UNKNOWN **Name:** Department of Business and Innovation, Victoria, Australia #### Lead Sponsor **Class:** INDUSTRY **Name:** Pro-Active Medical Pty Ltd #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** A postural bio-feedback device worn by subjects for 4-10 hours a day for 6 days spread across 6 weeks for the sub acute low back pain group and for 8 days spread across 10 weeks for the chronic group. The device records movement and muscle activity data relating to the lower back. Bio-feedback is delivered to the subject as an audible tone, visual cue or vibration and aims to prompt the subject to alter their posture or position in line with recommendations given by the treating practitioner. Four small sensors are adhered to the lower back and send data wirelessly to a data logger carried in the pocket by the subject (the size of a small mobile phone). ### Conditions Module **Conditions:** - Low Back Pain **Keywords:** - dorsavi - vimove - biofeedback - objective movement data - back pain ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 112 **Type:** ACTUAL **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** BSM device with bio-feedback **Intervention Names:** - Device: BSM device with bio-feedback **Label:** Intervention **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** The BSM device without feed-back **Intervention Names:** - Device: BSM device with no bio-feedback **Label:** Control **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Intervention **Description:** A postural bio-feedback device worn by subjects for 4-10hours a day for 6 days spread across 6 weeks for the sub acute low back pain group and for 8 days spread across 10 weeks for the chronic group. The device records movement and muscle activity data relating to the lower back. Bio-feedback is delivered to the subject as an audible tone, visual cue or vibration and aims to prompt the subject to alter their posture or position in line with recommendations given by the treating practitioner. Four small sensors are adhered to the lower back and send data wirelessly to a data logger carried in the pocket by the subject (the size of a small mobile phone). **Name:** BSM device with bio-feedback **Other Names:** - ViMove **Type:** DEVICE #### Intervention 2 **Arm Group Labels:** - Control **Description:** The BSM device is worn as a placebo with no bio-feedback given to the subject. The subjects in the control group wear the device for 4-10 hours a day for 6 days spread across 6 weeks for the sub acute low back pain group and for 8 days spread across 10 weeks for the chronic group. **Name:** BSM device with no bio-feedback **Other Names:** - ViMove with no Feedback **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Description:** Functional Outcome measure **Measure:** Roland Morris Disability Questionaire (RMDQ-23) **Time Frame:** over 12 months **Description:** Functional Outcome Measure **Measure:** Patient Specific Functional Scale (PSFS) **Time Frame:** over 12 months **Description:** Pain Scale **Measure:** Quadruple Visual Analogue Scale (QVAS) **Time Frame:** over 12 months #### Secondary Outcomes **Description:** Functional Outcome Measure **Measure:** The change over time from baseline in the range of movement, recorded by the device. Measured in degrees of movement in the three anatomical planes. **Time Frame:** over 12 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Subject provides informed consent 2. Age between 18 and 65 years of age 3. At least moderate intensity low back pain (LBP) and/or back related leg pain, as defined by a QVAS score \> 3 (Carragee, Spine 2000). 4. Initial QVAS score of \> 3 out of 10 5. Subjects must be assessed by the practitioner as Sub Acute (3 to 12 weeks post onset of low back pain (LBP) or Chronic (\> 12 weeks post onset of low back pain (LBP). Exclusion Criteria: 1. Lower back surgery within previous twelve (12) months. 2. Females who are pregnant. 3. Subjects with a severe hearing impairment. 4. Evidence of non mechanical contributing cause for lower back pain e.g. neoplasm, infection, fracture, inflammatory disorder. 5. Preceding chronic neurological changes (Sub Acute group only). 6. Implanted medical device (spinal cord stimulator, intrathecal pump or peripheral nerve stimulator) 7. Nerve block, spinal injection or anesthetic procedure for the treatment of lower back pain within 12 months of the study. 8. Significant medical abnormalities or conditions that in the opinion of the Practitioner would interfere either with the ability to complete the study or the evaluation of the investigational device's safety and efficacy. 9. Recent history of a significant medical-surgical intervention that in the judgment of the Practitioner would interfere either with the ability to complete the study or the evaluation of the investigative device's safety and efficacy. 10. Known allergic skin reaction to tapes and plasters. 11. Subject who is currently enrolled in an investigational drug or device study. **Maximum Age:** 65 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Caulfield **Country:** Australia **Facility:** Metro Spinal Clinic **State:** Victoria **Zip:** 3162 **Location 2:** **City:** Footscray **Country:** Australia **Facility:** Stanlake Specialist Centre **State:** Victoria **Zip:** 3011 **Location 3:** **City:** Geelong **Country:** Australia **Facility:** Myers Street Family Medical **State:** Victoria **Zip:** 3220 **Location 4:** **City:** Hampton **Country:** Australia **Facility:** Peak Musculoskeletal **State:** Victoria **Zip:** 3188 **Location 5:** **City:** Heidelberg **Country:** Australia **Facility:** Austin Hopsital **State:** Victoria **Zip:** 3084 **Location 6:** **City:** Melbourne **Country:** Australia **Facility:** Olympic Park Sports Medicine Centre **State:** Victoria **Zip:** 3003 **Location 7:** **City:** Richmond **Country:** Australia **Facility:** Epworth Hospital Richmond **State:** Victoria **Zip:** 3121 **Location 8:** **City:** Ringwood **Country:** Australia **Facility:** Bounce Health Group **State:** Victoria **Zip:** 3084 **Location 9:** **City:** Werribee **Country:** Australia **Facility:** The Clinic Werribee **State:** Victoria **Zip:** 3030 #### Overall Officials **Official 1:** **Affiliation:** Stanlake Specialist Centre **Name:** Steven Jensen, MB BS FAFMM **Role:** PRINCIPAL_INVESTIGATOR **Official 2:** **Affiliation:** Myers Street Family Medical **Name:** Adrian Jury, MD **Role:** PRINCIPAL_INVESTIGATOR **Official 3:** **Affiliation:** The Clinic Werribee **Name:** Joe Garra, MD **Role:** PRINCIPAL_INVESTIGATOR **Official 4:** **Affiliation:** Stanlake Specialist Centre **Name:** Peter Braun, MD **Role:** PRINCIPAL_INVESTIGATOR **Official 5:** **Affiliation:** Austin Hospital Pysiotherapy Outpatients **Name:** Robert Laird **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### References **Citation:** Kent P, Laird R, Haines T. The effect of changing movement and posture using motion-sensor biofeedback, versus guidelines-based care, on the clinical outcomes of people with sub-acute or chronic low back pain-a multicentre, cluster-randomised, placebo-controlled, pilot trial. BMC Musculoskelet Disord. 2015 May 29;16:131. doi: 10.1186/s12891-015-0591-5. **PMID:** 26022102 #### See Also Links **Label:** device description **URL:** http://www.dorsavi.com/ ## Derived Section ### Condition Browse Module - Ancestors - ID: D000010146 - Term: Pain - ID: D000009461 - Term: Neurologic Manifestations ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC10 - Name: Nervous System Diseases ### Condition Browse Module - Browse Leaves - ID: M4714 - Name: Back Pain - Relevance: HIGH - As Found: Back Pain - ID: M19433 - Name: Low Back Pain - Relevance: HIGH - As Found: Low Back Pain - ID: M13066 - Name: Pain - Relevance: LOW - As Found: Unknown - ID: M12404 - Name: Neurologic Manifestations - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000001416 - Term: Back Pain - ID: D000017116 - Term: Low Back Pain ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05376579 **Acronym:** ITASIA **Brief Title:** Impact of Mayzent on aSPMS Patients in a Long-term NIS in Italy **Official Title:** Impact of Mayzent (Siponimod) on Active Secondary Progressive Multiple Sclerosis Patients in a Long-term Non-interventional Study in Italy #### Organization Study ID Info **ID:** CBAF312AIT04 #### Organization **Class:** INDUSTRY **Full Name:** Novartis ### Status Module #### Completion Date **Date:** 2026-06-30 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2023-09-06 **Type:** ACTUAL **Last Update Submit Date:** 2023-09-04 **Overall Status:** ACTIVE_NOT_RECRUITING #### Primary Completion Date **Date:** 2026-06-30 **Type:** ESTIMATED #### Start Date **Date:** 2022-06-17 **Type:** ACTUAL **Status Verified Date:** 2023-09 #### Study First Post Date **Date:** 2022-05-17 **Type:** ACTUAL **Study First Submit Date:** 2022-05-12 **Study First Submit QC Date:** 2022-05-12 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Novartis Pharmaceuticals #### Responsible Party **Type:** SPONSOR ### Description Module **Brief Summary:** This is an observational, multicenter, single-arm, prospective study conducted in Italy **Detailed Description:** Primary data will be collected over a period of three years. Medical history of participants will be collected including EDSS, MRI outcomes, relapses and previous medication to allow the estimation of the effects of siponimod treatment on an individual basis. ### Conditions Module **Conditions:** - Active Secondary Progressive Multiple Sclerosis **Keywords:** - Secondary Progressive Multiple Sclerosis - aSPMS - NIS - Italy - Mayzent - siponimod ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 134 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** patients treated with siponimod **Intervention Names:** - Other: siponimod **Label:** siponimod ### Interventions #### Intervention 1 **Arm Group Labels:** - siponimod **Description:** Prospective observational cohort study. There is no treatment allocation. Patients will be invited to participate in the study after the independent decision by physician and patient to start siponimod treatment as routine clinical care. **Name:** siponimod **Other Names:** - mayzent **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** Confirmed disability progression (CDP) is defined as a ≥1.0-point worsening of Expanded Disability Status Scale (EDSS) score from ≤5.0 baseline or a 0.5-point worsening from \>5.0 baseline for at least 6 months OR a ≥4.0-point confirmed cognitive worsening (CCW) from baseline of Symbol Digit Modalities Test (SDMT) for at least 6 months. **Measure:** Proportion of patients with six-month CDP during 36 months of treatment **Time Frame:** 36 months #### Secondary Outcomes **Description:** ARR is the number of relapses during the period / person-years of subject Person-years for subject = period (in days) / 365.25 **Measure:** Annualized relapse rate (ARR) **Time Frame:** Month 12, month 24 and month 36 **Description:** Number of new/newly enlarging T2-hyperintense lesions and number of new 1 gadolinium-enhancing (Gd+) lesions is collected **Measure:** Number of new/newly enlarging T2 [neT2] and Gd+T1 lesions **Time Frame:** Baseline, month 3, month 6, month 12, month 18, month 24, month 30 and month 36 **Description:** Expanded Disability Status Scale (EDSS) score is composed of the overall impression and individual scores of the following functional systems: cognition, mood, fatigue, vision, brain stem, upper extremities, lower extremities, bladder-intestinal function, sexuality. Scores are on a scale of 0 (healthy) to 10 (death from MS) with 0.5 unit increments **Measure:** Expanded Disability Status Scale scores **Time Frame:** Month 12, month 24 and month 36 **Description:** EDSS trend is measured by differentiating patients who stabilize from those who experience an increase of EDSS score (increment of ≥1 or ≥0.5 point if baseline EDSS was ≤5.0 or ˃5.0, respectively). Moreover, patients with progression will be categorized as patients with continuous disability accrual (CDA) or one-step worsening (OneS-wors), defined as: * OneS-wors: the occurrence of one single episode of confirmed EDSS deterioration. * CDA: occurrence of at least two episodes of OneS-wors associated with continuous disability progression between at least two time points. **Measure:** Expanded Disability Status Scale trend **Time Frame:** Month 12, month 24 and month 36 **Description:** NEDA-3 is defined as no Confirmed disability progression (CDP), no confirmed relapse and absence of T1 gadolinium-enhancing (Gd+) lesions. **Measure:** Proportion of patients with No Evidence of Disease Activity (NEDA)-3 **Time Frame:** Month 12, month 24 and month 36 **Description:** The UKNDS is a questionnaire for recording impairments in MS from the patient's perspective and considers 12 functional systems: perception and thinking, mood, vision, speech and communication, swallowing, arm and hand function, walking ability, bladder function, bowel function, fatigue, sexuality, pain, cramps and others. Answering the questions results in a score of 0 (no disability) to 60 (maximum disability). This questionnaire will be completed by the patients during site visits. **Measure:** UK Neurological Disability Scale (UKNDS) **Time Frame:** Baseline, month 3, month 6, month 12, month 18, month 24, month 30 and month 36 **Description:** The FSMC is a patient questionnaire for the clarification of cognitive and motor fatigue, a typical symptom of MS (Penner et al., 2009), and considers a cognitive, motor and total score. Score ranges from 200 to 100, the greater the score the greater the impairment caused by fatigue. **Measure:** Fatigue Scale for Motor and Cognitive Functions (FSMC) **Time Frame:** Baseline, month 3, month 6, month 12, month 18, month 24, month 30 and month 36 **Description:** The HADS has seven items each for depression and anxiety subscales. Scoring for each item ranges from zero to three, with three denoting highest anxiety or depression level. A total subscale score of \>8 points out of a possible 21 denotes considerable symptoms of anxiety or depression. Calculations of scores: each of the 14 items is rated on a 4-point scale ('Yes, definitely', 'Yes, sometimes', 'No, not much' and 'No, not at all'). All items except 7 and 10 are scored as 'Yes, definitely' = 3 to 'No, not at all' = 0. Items 7 and 10 are scored as 'Yes, definitely' = 0 to 'No, not at all' = 3. The HADS consists of two sub-scores: the HAD-A for anxiety and HAD-D for depression; each sub-score ranges from 0 to 21 points; scores ≥11 indicate the presence of anxious or depressive disorders; scores between 8-10 points are borderline abnormal, and scores of ≤7 indicate that the disorder is not present. **Measure:** Hospital Anxiety and Depression Scale (HADS) **Time Frame:** Baseline, month 3, month 6, month 12, month 18, month 24, month 30 and month 36 **Description:** The SDMT is a sensitive and specific test to investigate attention, concentration and information processing speed, which are typically impaired in cognitively impaired MS patients. Nine numbers are shown paired with 9 corresponding individual symbols. Below this are further lines with symbols and empty boxes. The patients must assign the correct numbers to the symbols as quickly as possible. The number of correctly assigned numbers within 90 seconds gives the test score. The total duration of the test is about 5 minutes and scores range between 0 and 110 where higher scores indicate better result. A deterioration of the SDMT score by ≥4 points is considered clinically relevant **Measure:** Symbol Digit Modality test (SDMT) **Time Frame:** Baseline, month 3, month 6, month 12, month 18, month 24, month 30 and month 36 **Description:** The CGI scale represents a short, independent assessment by the treating physician of the overall condition of the patient. It incorporates patient history, psychosocial circumstances, symptoms, behavior and the influence of symptoms on the patient's functional ability. The CGI consists of three different global measures and all three will be evaluated: Severity of illness (CGI-S) ranges from 0 to 7, Global Improvement (CGI-I) ranges from 0 to 7 and Efficacy index (CGI-E) ranges from 0 to 16. A higher score means a severe impact on the disease. **Measure:** Clinical Global Impression (CGI) **Time Frame:** Baseline, month 3, month 6, month 12, month 18, month 24, month 30 and month 36 **Description:** Number of relapse, number of relapse that affects the daily activities, number of relapse that required an hospitalization and number of treated relapse to be collected **Measure:** MS activity status (MS-AS) - number of relapse **Time Frame:** Baseline, month 3, month 6, month 12, month 18, month 24, month 30 and month 36 **Description:** Number of patients with presence of symptoms to be collected **Measure:** MS activity status (MS-AS) - Number of patients with presence of symptoms **Time Frame:** Baseline, month 3, month 6, month 12, month 18, month 24, month 30 and month 36 **Description:** The T25-FW is an objective and quantitative test of the lower extremities. The time in seconds it takes a patient to walk a distance of 25 feet (7.62 m) is measured. The patient should walk as quickly and safely as possible. This test is performed twice in a row and the mean value of the time required is documented in seconds. An improvement or deterioration of 20% is considered a significant change **Measure:** T25-foot-walk **Time Frame:** Baseline, month 3, month 6, month 12, month 18, month 24, month 30 and month 36 **Description:** This test examines manual dexterity. Patients must individually remove nine pegs from a flat dish with one hand and insert them into corresponding holes in a test board. The pegs are then placed back into the dish with the same hand. Two rounds are performed per hand and the average value of the time required is documented in seconds **Measure:** 9-Hole peg test **Time Frame:** Baseline, month 3, month 6, month 12, month 18, month 24, month 30 and month 36 **Description:** The EQ-5D is a generic multidimensional measurement tool for describing health-related quality of life (EuroQol, 1999). The five domains of mobility, self-care ability, daily activities, pain/discomfort and anxiety/depression are considered. For each of the dimensions, the most appropriate answer from three given possibilities is selected (1=no problem, 2=moderate problem, 3=large problem). In addition, the patient marks the current state of health on a scale from 0 (worst conceivable state of health) to 100 (best conceivable state of health). **Measure:** EQ-5D: EuroQol five-dimensional **Time Frame:** Baseline, month 3, month 6, month 12, month 18, month 24, month 30 and month 36 **Description:** The TSQM-9 is a questionnaire to assess patient satisfaction with siponimod treatment. The TSQM-9 is a sound and valid measure of the major dimensions of patients' satisfaction with medication and also a good predictor of adherence across different types of medication and patient population. Effectiveness, side effects, simplicity and overall satisfaction are all rated between 0 and 100. Higher values mean a worse condition. Responses to items are summed and transformed so that higher scores indicate greater satisfaction. Specifically, TSQM-9 scale scores are computed by adding the items loading on each domain. The lowest possible score is subtracted from the composite score and divided by the greatest possible score range. This provides a transformed score between 0 and 1 that is then multiplied by 100. If more than one item is missing from a subscale of the TSQM-9 for a particular patient, this subscale should be considered invalid for that respondent. **Measure:** TSQM-9: Treatment Satisfaction Questionnaire for Medication **Time Frame:** Baseline, month 3, month 6, month 12, month 18, month 24, month 30 and month 36 **Description:** Exposure adjusted proportion of patients with adverse event (AE) or serious adverse event (SAE) per 100 subject-years to be collected **Measure:** Exposure adjusted proportion of patients with adverse event (AE) or serious adverse event (SAE) per 100 subject-years **Time Frame:** Up to 36 months **Description:** Discontinuation rates due to AE or other reasons to be collected **Measure:** Discontinuation rates due to AE or other reasons **Time Frame:** Up to 36 months **Description:** Proportion of patient who required first dose observation (FDO) when starting siponimod and the reason why **Measure:** Proportion of patient who required FDO when starting siponimod and the reason why **Time Frame:** Baseline ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Signed informed consent: patient must provide written informed consent before any study assessment is performed. 2. Male/female participants aged between 18 and 60. 3. Documented diagnosis of active SPMS. 4. Siponimod treatment as routine medical care: patients newly treated with siponimod (starting not more than 7 days before baseline visit), for whom the decision to start treatment has already been taken independently of study inclusion based on clinical practice and according to SmPC and AIFA criteria, and who successfully qualified for treatment with siponimod (i.e. passed the screening procedure mandated by the SmPC and Risk Management Plan (RMP) for this treatment, including genotyping for CYP2C9 to determine CYP2C9 metaboliser status). Exclusion Criteria: 1. Patients treated outside the approved siponimod label or with any controindication indicated in the SmPC. 2. Pregnant or lactating women. 3. Patients with any clinical condition that may interfere with the subject's ability to cooperate and comply with the study procedures based on the investigator's judgement. 4. Current participation in an interventional trial. 5. Treatment with siponimod prior to inclusion in this study (siponimod can be started not more than 7 days before baseline visit). **Maximum Age:** 60 Years **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT **Study Population:** patients in Italy with active SPMS treated with siponimod as per label and local clinical practice. ### Contacts Locations Module #### Locations **Location 1:** **City:** Ancona **Country:** Italy **Facility:** Novartis Investigative Site **State:** AN **Zip:** 60126 **Location 2:** **City:** L Aquila **Country:** Italy **Facility:** Novartis Investigative Site **State:** AQ **Zip:** 67100 **Location 3:** **City:** Bergamo **Country:** Italy **Facility:** Novartis Investigative Site **State:** BG **Zip:** 24128 **Location 4:** **City:** Bologna **Country:** Italy **Facility:** Novartis Investigative Site **State:** BO **Zip:** 40139 **Location 5:** **City:** Brescia **Country:** Italy **Facility:** Novartis Investigative Site **State:** BS **Zip:** 25123 **Location 6:** **City:** Como **Country:** Italy **Facility:** Novartis Investigative Site **State:** CO **Zip:** 22100 **Location 7:** **City:** Catanzaro **Country:** Italy **Facility:** Novartis Investigative Site **State:** CZ **Zip:** 88100 **Location 8:** **City:** Foggia **Country:** Italy **Facility:** Novartis Investigative Site **State:** FG **Zip:** 71100 **Location 9:** **City:** Genova **Country:** Italy **Facility:** Novartis Investigative Site **State:** GE **Zip:** 16132 **Location 10:** **City:** Messina **Country:** Italy **Facility:** Novartis Investigative Site **State:** ME **Zip:** 98121 **Location 11:** **City:** Milano **Country:** Italy **Facility:** Novartis Investigative Site **State:** MI **Zip:** 20133 **Location 12:** **City:** Palermo **Country:** Italy **Facility:** Novartis Investigative Site **State:** PA **Zip:** 90127 **Location 13:** **City:** Padova **Country:** Italy **Facility:** Novartis Investigative Site **State:** PD **Zip:** 35128 **Location 14:** **City:** Pisa **Country:** Italy **Facility:** Novartis Investigative Site **State:** PI **Zip:** 56126 **Location 15:** **City:** Pavia **Country:** Italy **Facility:** Novartis Investigative Site **State:** PV **Zip:** 27100 **Location 16:** **City:** Roma **Country:** Italy **Facility:** Novartis Investigative Site **State:** RM **Zip:** 00133 **Location 17:** **City:** Roma **Country:** Italy **Facility:** Novartis Investigative Site **State:** RM **Zip:** 00152 **Location 18:** **City:** Roma **Country:** Italy **Facility:** Novartis Investigative Site **State:** RM **Zip:** 00189 **Location 19:** **City:** Orbassano **Country:** Italy **Facility:** Novartis Investigative Site **State:** TO **Zip:** 10043 **Location 20:** **City:** Trieste **Country:** Italy **Facility:** Novartis Investigative Site **State:** TS **Zip:** 34149 **Location 21:** **City:** Vicenza **Country:** Italy **Facility:** Novartis Investigative Site **State:** VI **Zip:** 36100 **Location 22:** **City:** Napoli **Country:** Italy **Facility:** Novartis Investigative Site **Zip:** 80132 **Location 23:** **City:** Napoli **Country:** Italy **Facility:** Novartis Investigative Site **Zip:** 80138 **Location 24:** **City:** Novara **Country:** Italy **Facility:** Novartis Investigative Site **Zip:** 28100 #### Overall Officials **Official 1:** **Affiliation:** Novartis Pharmaceuticals **Name:** Novartis Pharmaceuticals **Role:** STUDY_DIRECTOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000010335 - Term: Pathologic Processes - ID: D000020278 - Term: Demyelinating Autoimmune Diseases, CNS - ID: D000020274 - Term: Autoimmune Diseases of the Nervous System - ID: D000009422 - Term: Nervous System Diseases - ID: D000003711 - Term: Demyelinating Diseases - ID: D000001327 - Term: Autoimmune Diseases - ID: D000007154 - Term: Immune System Diseases - ID: D000009385 - Term: Neoplastic Processes - ID: D000009369 - Term: Neoplasms - ID: D000002908 - Term: Chronic Disease - ID: D000020969 - Term: Disease Attributes ### Condition Browse Module - Browse Branches - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: BC20 - Name: Immune System Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: BC04 - Name: Neoplasms - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M12060 - Name: Multiple Sclerosis - Relevance: HIGH - As Found: Multiple Sclerosis - ID: M15415 - Name: Sclerosis - Relevance: HIGH - As Found: Sclerosis - ID: M12307 - Name: Neoplasm Metastasis - Relevance: HIGH - As Found: Secondary - ID: M22313 - Name: Multiple Sclerosis, Chronic Progressive - Relevance: HIGH - As Found: Secondary Progressive Multiple Sclerosis - ID: M4629 - Name: Autoimmune Diseases - Relevance: LOW - As Found: Unknown - ID: M22098 - Name: Demyelinating Autoimmune Diseases, CNS - Relevance: LOW - As Found: Unknown - ID: M22094 - Name: Autoimmune Diseases of the Nervous System - Relevance: LOW - As Found: Unknown - ID: M6909 - Name: Demyelinating Diseases - Relevance: LOW - As Found: Unknown - ID: M10200 - Name: Immune System Diseases - Relevance: LOW - As Found: Unknown - ID: M12330 - Name: Neoplastic Processes - Relevance: LOW - As Found: Unknown - ID: M6147 - Name: Chronic Disease - Relevance: LOW - As Found: Unknown - ID: M22700 - Name: Disease Attributes - Relevance: LOW - As Found: Unknown - ID: T1303 - Name: Chronic Graft Versus Host Disease - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000009362 - Term: Neoplasm Metastasis - ID: D000009103 - Term: Multiple Sclerosis - ID: D000020528 - Term: Multiple Sclerosis, Chronic Progressive - ID: D000012598 - Term: Sclerosis ### Intervention Browse Module - Ancestors - ID: D000081243 - Term: Sphingosine 1 Phosphate Receptor Modulators - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000007166 - Term: Immunosuppressive Agents - ID: D000007155 - Term: Immunologic Factors - ID: D000045505 - Term: Physiological Effects of Drugs ### Intervention Browse Module - Browse Branches - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M271068 - Name: Siponimod - Relevance: HIGH - As Found: Noncontiguous stage II marginal zone lymphoma - ID: M10212 - Name: Immunosuppressive Agents - Relevance: LOW - As Found: Unknown - ID: M10201 - Name: Immunologic Factors - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: C000578989 - Term: Siponimod ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT02005679 **Acronym:** MMS-LS **Brief Title:** Mini-Mental State (MMS-LS) and Sign Language **Official Title:** Transposition of the Mini-Mental State in Sign Language #### Organization Study ID Info **ID:** RC-P0008 #### Organization **Class:** OTHER **Full Name:** Lille Catholic University ### Status Module #### Completion Date **Date:** 2017-12-07 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2019-02-15 **Type:** ACTUAL **Last Update Submit Date:** 2019-02-12 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2017-12-07 **Type:** ACTUAL #### Start Date **Date:** 2011-06-17 **Type:** ACTUAL **Status Verified Date:** 2019-02 #### Study First Post Date **Date:** 2013-12-09 **Type:** ESTIMATED **Study First Submit Date:** 2013-11-22 **Study First Submit QC Date:** 2013-12-04 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Lille Catholic University #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** In France the prevalence of pre-lingual deafness is between 1 and 1.4 per 1000 habitants, and according to very conservative estimates, about 44 000 deaf persons use the sign language. Additionally, the prevalence of dementia in France is close to 1% (850 000 dements for a total population of 65 millions). The prevalence of dementia in pre-lingual deaf adults has also been described and is between 1 and 1.4 /100 000 habitants. The Mini Mental State Examination (MMSE) of Folstein is a test recommended to perform the cognitive evaluation for the detection of mental disorders including dementia, and a consensual French version exists prepared by GRECO (Group of Research and Cognitive Assessments). However, to date, there are no simple, rapid and validated screening tests to study cognitive disorders in deaf persons who use the sign language. The only tests available allow a late diagnosis avoiding an optimal treatment of the patients. **Detailed Description:** The objective of this study is to assess the intrinsic quality of the tool MMS-LS, a mini-mental state examination that has been adapted to the sign language in order to monitor cognitive disorders in deaf people who speak sign language. ### Conditions Module **Conditions:** - Prelingual Deafness - Retention Disorders, Cognitive **Keywords:** - Prelingual Deafness - Retention Disorders, Cognitive - Sign language - Mini-Mental State ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** DIAGNOSTIC #### Enrollment Info **Count:** 195 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Intervention Names:** - Behavioral: application of the mini-mental state test **Label:** deaf persons with potential dementia **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - deaf persons with potential dementia **Name:** application of the mini-mental state test **Type:** BEHAVIORAL ### Outcomes Module #### Primary Outcomes **Measure:** Assessment of internal consistency of MMS-LS test for the diagnosis of cognitive impairment among deaf patients by a correlation analysis followed by Cronbach's alpha test **Time Frame:** At baseline, 1 year and 2 years follow-up visits #### Secondary Outcomes **Description:** Explanatory Factors are: age, education level, characteristics of the sign language(fluency level, learning age, usage frequency, usage by other family members) **Measure:** Description of MMS-LS test results **Time Frame:** Baseline **Description:** Sensitivity, specificity, positive and negative predictive values. **Measure:** Diagnostic performance and predictive values of MMS-LS test for acquired dementia. **Time Frame:** Baseline, 1 year and 2 years follow-up visits **Description:** We also check that patients having a suspicious CDR (0.5) have a superior MMS-LS score compared to patients having a CDR ≥ 1. **Measure:** Correlation between MMS-LS score and CDR level **Time Frame:** Baseline, 1 year and 2 years follow-up visits **Description:** Sensitivity, specificity, positive and negative predictive values **Measure:** Diagnostic performance and predictive values of MMS-LS test for suspected dementia. **Time Frame:** Baseline, 1 year and 2 years follow-up visits ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Adults\> 18 years * Pre-lingual deafness * Use of French sign language Exclusion Criteria: * Refusal to sign the consent * Severe visual impairment with lower acuity (less than 0.5) * Severe motor difficulties impeding the practice of sign language **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Marseille **Country:** France **Facility:** Hôpital de la Conception, Pôle psychiatrie Centre **State:** Bouches-du-Rhône **Zip:** 13885 **Location 2:** **City:** Rennes **Country:** France **Facility:** CHU de Rennes, Hôpital de Pontchaillou **State:** Ille-et-Vilaine **Zip:** 35000 **Location 3:** **City:** Nancy **Country:** France **Facility:** Unité Régionale d'Accueil et de Soins pour Sourds et malentendants - CHRU Nancy **State:** Meurthe-et-Moselle **Zip:** 54000 **Location 4:** **City:** Lille **Country:** France **Facility:** Groupement des Hôpitaux de l'Institut Catholique de Lille **State:** Nord Pas De Calais **Zip:** 59962 #### Overall Officials **Official 1:** **Affiliation:** Groupement des Hôpitaux de l'Institut Catholique de Lille, Unité d'Accueil et de Soins des Sourds en Langue des Signes et Réseau Sourds et Santé **Name:** Benoît Drion, MD **Role:** STUDY_DIRECTOR **Official 2:** **Affiliation:** Groupement des Hôpitaux de l'Institut Catholique de Lille, Medical Research Department **Name:** Amélie Lansiaux, MD **Role:** STUDY_CHAIR **Official 3:** **Affiliation:** CHU de Rennes, Hôpital de Pontchaillou **Name:** Isabelle Ridoux, MD **Role:** PRINCIPAL_INVESTIGATOR **Official 4:** **Affiliation:** Hôpital de la Conception, Pôle psychiatrie, Marseille **Name:** Corine Gilda Scemama-Ammar, MD **Role:** PRINCIPAL_INVESTIGATOR **Official 5:** **Affiliation:** Groupement des Hôpitaux de l'Institut Catholique de Lille **Name:** Charlotte Crinquette, MD **Role:** PRINCIPAL_INVESTIGATOR **Official 6:** **Affiliation:** CHRU de Nancy, Unité Régionale d'Accueil et de Soins pour Sourds et malentendants **Name:** Isabelle Bouillevaux, MD **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000006311 - Term: Hearing Disorders - ID: D000004427 - Term: Ear Diseases - ID: D000010038 - Term: Otorhinolaryngologic Diseases - ID: D000012678 - Term: Sensation Disorders - ID: D000009461 - Term: Neurologic Manifestations - ID: D000009422 - Term: Nervous System Diseases - ID: D000019954 - Term: Neurobehavioral Manifestations ### Condition Browse Module - Browse Branches - Abbrev: BC09 - Name: Ear, Nose, and Throat Diseases - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BXM - Name: Behaviors and Mental Disorders ### Condition Browse Module - Browse Leaves - ID: M24420 - Name: Hearing Loss - Relevance: HIGH - As Found: Deafness - ID: M6840 - Name: Deafness - Relevance: HIGH - As Found: Prelingual Deafness - ID: M11552 - Name: Memory Disorders - Relevance: HIGH - As Found: Retention Disorders, Cognitive - ID: M9400 - Name: Hearing Disorders - Relevance: LOW - As Found: Unknown - ID: M7601 - Name: Ear Diseases - Relevance: LOW - As Found: Unknown - ID: M12961 - Name: Otorhinolaryngologic Diseases - Relevance: LOW - As Found: Unknown - ID: M15490 - Name: Sensation Disorders - Relevance: LOW - As Found: Unknown - ID: M12404 - Name: Neurologic Manifestations - Relevance: LOW - As Found: Unknown - ID: M21826 - Name: Neurobehavioral Manifestations - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000003638 - Term: Deafness - ID: D000034381 - Term: Hearing Loss - ID: D000008569 - Term: Memory Disorders ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03816579 **Acronym:** MAPP **Brief Title:** A Meal-based Comparison of Protein Quality, Complementary Proteins and Muscle Anabolism **Official Title:** A Meal-based Comparison of Protein Quality, Complementary Proteins and Muscle Anabolism #### Organization Study ID Info **ID:** 18-0147 #### Organization **Class:** OTHER **Full Name:** The University of Texas Medical Branch, Galveston ### Status Module #### Completion Date **Date:** 2021-01-21 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2021-04-29 **Type:** ACTUAL **Last Update Submit Date:** 2021-04-27 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2021-01-21 **Type:** ACTUAL #### Start Date **Date:** 2019-03-26 **Type:** ACTUAL **Status Verified Date:** 2020-12 #### Study First Post Date **Date:** 2019-01-25 **Type:** ACTUAL **Study First Submit Date:** 2019-01-22 **Study First Submit QC Date:** 2019-01-24 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** The University of Texas Medical Branch, Galveston #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** To highlight the importance of protein quality rather than the total protein content of a meal, the investigators will demonstrate that unlike high quality proteins, a single meal containing 30 g of an incomplete protein source does not stimulate skeletal muscle protein synthesis. Secondly, the investigators will directly challenge a prevalent, but untested, assertion that has the potential to negatively impact health. The goal is to demonstrate that complementary plant-proteins (i.e., two or more incomplete protein sources) must be consumed at the same meal to stimulate protein synthesis. **Detailed Description:** The investigators will test the following hypotheses in middle-aged men and women (45-60) years old using a randomized, cross over design. All study objectives will be met concurrently: 1. Meals containing 30 g of high quality, predominantly beef-protein (PRO-A) will stimulate acute (i.e., single meal response) and 24 h skeletal muscle protein synthesis \[confirmatory hypothesis\] 2. Meals containing 30 g of complementary plant-based proteins (PRO-B: complete essential amino acid profile at each meal) will stimulate acute and 24 h skeletal muscle protein synthesis, but to a lesser extent than beef-protein. 3. A single meal containing 30 g of an incomplete plant-based protein source (PRO-C: lacking one essential amino acid) will fail to acutely stimulate skeletal muscle protein synthesis 4. Meals containing 30 g of plant-based protein that are incomplete at each separate meal, but complementary over a 24 h period, will fail to stimulate 24 h skeletal muscle protein synthesis. 5. Beef-and plant-based meals will have a similar effect on satiety and 24 h blood glucose \[descriptive\] If these hypotheses are correct, the investigators will demonstrate that meals containing a moderate amount of high quality protein, such as beef, are an efficient and effective way to augment a largely plant based diet and stimulate skeletal muscle protein synthesis - a prerequisite for outcomes related to physical function, performance, successful aging and metabolic health. ### Conditions Module **Conditions:** - Protein - Diet - Skeletal Muscle ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** CROSSOVER ##### Masking Info **Masking:** SINGLE **Who Masked:** - PARTICIPANT **Primary Purpose:** OTHER #### Enrollment Info **Count:** 23 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Beef protein **Intervention Names:** - Other: PRO-A **Label:** PRO-A **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Complementary proteins at each meal **Intervention Names:** - Other: PRO-B **Label:** PRO-B **Type:** EXPERIMENTAL #### Arm Group 3 **Description:** Complementary proteins over 24 hours **Intervention Names:** - Other: PRO-C **Label:** PRO-C **Type:** EXPERIMENTAL #### Arm Group 4 **Description:** Low protein (\<5 g) meal **Label:** CON **Type:** NO_INTERVENTION ### Interventions #### Intervention 1 **Arm Group Labels:** - PRO-A **Description:** 30 g of beef protein will be consumed at each meal **Name:** PRO-A **Type:** OTHER #### Intervention 2 **Arm Group Labels:** - PRO-B **Description:** 30 g of complementary proteins will be consumed at each meal **Name:** PRO-B **Type:** OTHER #### Intervention 3 **Arm Group Labels:** - PRO-C **Description:** 30 g of complementary proteins will be consumed over 24 hours **Name:** PRO-C **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** Muscle protein synthesis response to PRO-A breakfast meal (%/h) **Measure:** Acute muscle protein synthesis: PRO-A **Time Frame:** 3 hours after consuming meal **Description:** Muscle protein synthesis response to PRO-B breakfast meal (%/h) **Measure:** Acute muscle protein synthesis: PRO-B **Time Frame:** 3 hours after consuming meal **Description:** Muscle protein synthesis response to PRO-C breakfast meal (%/h) **Measure:** Acute muscle protein synthesis: PRO-C **Time Frame:** 3 hours after consuming meal **Description:** Muscle protein synthesis response to CON breakfast meal (%/hour) **Measure:** Acute muscle protein synthesis: CON **Time Frame:** 3 hours after consuming meal **Description:** Muscle protein synthesis response to PRO-A diet over 24 hours (%/hour) **Measure:** 24-hour muscle protein synthesis: PRO-A **Time Frame:** Approximately 24 hours **Description:** Muscle protein synthesis response to PRO-B diet over 24 hours (%/hour) **Measure:** 24-hour muscle protein synthesis: PRO-B **Time Frame:** Approximately 24 hours **Description:** Muscle protein synthesis response to PRO-C diet over 24 hours (%/hour) **Measure:** 24-hour muscle protein synthesis: PRO-C **Time Frame:** Approximately 24 hours **Description:** Blood samples will be drawn to measure amino acid concentrations response to PRO-A breakfast (µmol/L) **Measure:** Blood amino acid response to diet: PRO-A **Time Frame:** Approximately 5 hours **Description:** Blood samples will be drawn to measure amino acid concentrations response to PRO-B breakfast (µmol/L) **Measure:** Blood amino acid response to diet: PRO-B **Time Frame:** Approximately 5 hours **Description:** Blood samples will be drawn to measure amino acid concentrations response to PRO-B C breakfast (µmol/L) **Measure:** Blood amino acid response to diet: PRO-C **Time Frame:** Approximately 5 hours **Description:** Blood samples will be drawn to measure amino acid concentrations response to CON breakfast (µmol/L) **Measure:** Blood amino acid response to diet: CON **Time Frame:** Approximately 5 hours #### Secondary Outcomes **Description:** Blood samples will be drawn to measure blood glucose response to PRO-A diet (mg/dl) **Measure:** Blood glucose response to diet: PRO-A **Time Frame:** Approximately 24 hours **Description:** Blood samples will be drawn to measure blood glucose response to PRO-B diet (mg/dl) **Measure:** Blood glucose response to diet: PRO-B **Time Frame:** Approximately 24 hours **Description:** Blood samples will be drawn to measure blood glucose response to PRO-C diet (mg/dl) **Measure:** Blood glucose response to diet: PRO-C **Time Frame:** Approximately 24 hours **Description:** Blood samples will be drawn to measure blood glucose response to CON breakfast meal (mg/dl) **Measure:** Blood glucose response to diet: CON **Time Frame:** Approximately 5 hours **Description:** Questionnaires will be given to assess hunger, fullness, desire to eat, thirst, desire to eat something sweet, desire to eat something salty, desire to eat something savory, sleepiness, physical energy, mental energy, and nausea in response to PRO-A diet. All outcomes are scored individually on a 10 pt visual analog scale using "not at all" being 0 and "extremely" being a 10. **Measure:** Appetite and Hedonic Questionnaire: PRO-A **Time Frame:** Approximately 8 hours **Description:** Questionnaires will be given to assess hunger, fullness, desire to eat, thirst, desire to eat something sweet, desire to eat something salty, desire to eat something savory, sleepiness, physical energy, mental energy, and nausea in response to PRO-B diet. All outcomes are scored individually on a 10 pt visual analog scale using "not at all" being 0 and "extremely" being a 10. **Measure:** Appetite and Hedonic Questionnaire: PRO-B **Time Frame:** Approximately 8 hours **Description:** Questionnaires will be given to assess hunger, fullness, desire to eat, thirst, desire to eat something sweet, desire to eat something salty, desire to eat something savory, sleepiness, physical energy, mental energy, and nausea in response to PRO-C diet. All outcomes are scored individually on a 10 pt visual analog scale using "not at all" being 0 and "extremely" being a 10. **Measure:** Appetite and Hedonic Questionnaire: PRO-C **Time Frame:** Approximately 8 hours **Description:** Questionnaires will be given to assess hunger, fullness, desire to eat, thirst, desire to eat something sweet, desire to eat something salty, desire to eat something savory, sleepiness, physical energy, mental energy, and nausea in response to CON diet. All outcomes are scored individually on a 10 pt visual analog scale using "not at all" being 0 and "extremely" being a 10. **Measure:** Appetite and Hedonic Questionnaire: CON **Time Frame:** Approximately 5 hours **Description:** Diet records will be collected and analyzed with ASA24 to assess habitual energy intake the week prior to PRO-A study visit **Measure:** 3 day dietary record: PRO-A **Time Frame:** Approximately 36 hours **Description:** Diet records will be collected and analyzed with ASA24 to assess habitual energy intake the week prior to PRO-B study visit **Measure:** 3 day dietary record: PRO-B **Time Frame:** Approximately 36 hours **Description:** Diet records will be collected and analyzed with ASA24 to assess habitual energy intake the week prior to PRO-C study visit **Measure:** 3 day dietary record: PRO-C **Time Frame:** Approximately 36 hours **Description:** Diet records will be collected and analyzed with ASA24 to assess habitual energy intake the week prior to CON study visit **Measure:** 3 day dietary record: CON **Time Frame:** Approximately 36 hours **Description:** Questionnaires will be given to assess palatability of the PRO-A diet. Outcomes include the participants ranking of the food appearance, aroma intensity, aroma, flavor intensity, flavor, texture and overall appeal of the food. A 10 pt visual analog scale will be used to assess the subject's response with 0 being "extremely dislike", 5 being "neither like nor dislike" and 10 being "extremely like". **Measure:** Palatability Questionnaire:PRO-A **Time Frame:** Approximately 8 hours **Description:** Questionnaires will be given to assess palatability of the PRO-B diet. Outcomes include the participants ranking of the food appearance, aroma intensity, aroma, flavor intensity, flavor, texture and overall appeal of the food. A 10 pt visual analog scale will be used to assess the subject's response with 0 being "extremely dislike", 5 being "neither like nor dislike" and 10 being "extremely like". **Measure:** Palatability Questionnaire:PRO-B **Time Frame:** Approximately 8 hours **Description:** Questionnaires will be given to assess palatability of the PRO-C diet. Outcomes include the participants ranking of the food appearance, aroma intensity, aroma, flavor intensity, flavor, texture and overall appeal of the food. A 10 pt visual analog scale will be used to assess the subject's response with 0 being "extremely dislike", 5 being "neither like nor dislike" and 10 being "extremely like". **Measure:** Palatability Questionnaire:PRO-C **Time Frame:** Approximately 8 hours **Description:** Questionnaires will be given to assess palatability of the CON diet. Outcomes include the participants ranking of the food appearance, aroma intensity, aroma, flavor intensity, flavor, texture and overall appeal of the food. A 10 pt visual analog scale will be used to assess the subject's response with 0 being "extremely dislike", 5 being "neither like nor dislike" and 10 being "extremely like". **Measure:** Palatability Questionnaire:CON **Time Frame:** Approximately 5 hours ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. All races and ethnic backgrounds 2. Men and women, age 45-60 years 3. Generally healthy (see exclusion criteria) 4. Able and willing to provide informed consent 5. Ability to speak and read English (\* the study procedures, e.g., muscle biopsy, duration of each acute study, e.g. overnight stay; and multiple dietary questionnaires require sound written and spoken English) Exclusion Criteria: 1. Sarcopenia (defined by: European Working Group on Sarcopenia in Older People, EWGSOP (44)) 2. Clinically significant heart disease (e.g. New York Heart Classification greater than grade II; ischemia) 3. Peripheral vascular disease 4. Pulmonary disease 5. History of systemic or pulmonary embolus 6. Uncontrolled blood pressure (systolic BP\>170, diastolic BP\>95 mmHg) 7. Impaired renal function (creatinine \>1.5 mg/dl) 8. Anemia (hematocrit \<33) 9. Untreated thyroid disease (abnormal TSH) 10. A recent history (\<12 months) of GI bleed 11. Diabetes mellitus or other untreated endocrine or metabolic disease 12. Electrolyte abnormalities 13. Any history of stroke, hypo- or hyper-coagulation disorders 14. Recent (3 years) treated cancer other than basal cell carcinoma 15. Systemic steroids, anabolic steroids, growth hormone or immunosuppressant use within 12 months 16. Recent (6 months) adherence to a weight-loss or weight-gain diet 17. Weight change of 5% or more in previous 6 months 18. Body mass index \>30 or excess body fat that compromises muscle biopsy collection 19. Body mass index \<20 or recent history (\<12 month) of disordered eating 20. Dietary preferences or practices that preclude the consumption of the study meals 21. Acute infectious disease or chronic infection 22. Alcohol or drug abuse 23. Any other condition or event considered exclusionary by study physician 24. Pregnancy **Healthy Volunteers:** True **Maximum Age:** 60 Years **Minimum Age:** 45 Years **Sex:** ALL **Standard Ages:** - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Galveston **Country:** United States **Facility:** Unversity of Texas Medical Branch **State:** Texas **Zip:** 77555 #### Overall Officials **Official 1:** **Affiliation:** University of Texas **Name:** Doug Paddon-Jones, PhD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT01687179 **Acronym:** SAIL **Brief Title:** Safety Study of Sirolimus and Hydroxychloroquine in Women With Lymphangioleiomyomatosis **Official Title:** Targeting Autophagy for the Treatment of TSC and LAM: a Phase I Trial of Hydroxychloroquine and Sirolimus #### Organization Study ID Info **ID:** SAIL-1100 #### Organization **Class:** OTHER **Full Name:** Brigham and Women's Hospital #### Secondary ID Infos **ID:** 1ZIAHL002541-21 **Link:** https://reporter.nih.gov/quickSearch/1ZIAHL002541-21 **Type:** NIH ### Status Module #### Completion Date **Date:** 2015-08 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2018-10-11 **Type:** ACTUAL **Last Update Submit Date:** 2018-09-13 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2015-08 **Type:** ACTUAL #### Results First Post Date **Date:** 2018-10-11 **Type:** ACTUAL **Results First Submit Date:** 2017-03-30 **Results First Submit QC Date:** 2018-09-13 #### Start Date **Date:** 2012-09 **Status Verified Date:** 2018-09 #### Study First Post Date **Date:** 2012-09-18 **Type:** ESTIMATED **Study First Submit Date:** 2012-08-02 **Study First Submit QC Date:** 2012-09-13 ### Sponsor Collaborators Module #### Collaborators **Class:** NIH **Name:** National Heart, Lung, and Blood Institute (NHLBI) #### Lead Sponsor **Class:** OTHER **Name:** Brigham and Women's Hospital #### Responsible Party **Investigator Affiliation:** Brigham and Women's Hospital **Investigator Full Name:** Elizabeth Henske **Investigator Title:** Overall Principal Investigator **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** Specific Aim 1: To investigate whether, in Lymphangioleiomyomatosis (LAM) patients, the combination of sirolimus and hydroxychloroquine is safe and well tolerated Specific Aim 2: To investigate whether, in LAM patients, 6 months of combination therapy with sirolimus and hydroxychloroquine results in improvement of indicators of disease, and whether the gains are sustained after stopping therapy. Specific Aim 3: To investigate the potential role of a LAM-specific peripheral blood signature to predict rates of disease progression and determine responsiveness to combination therapy. This will be a phase I dose escalation study of the combination of sirolimus (2 mg adjusted to keep trough levels between 5-15 ng/ml) and hydroxychloroquine (200 mg or 400 mg) taken orally daily. Up to 18 adult women with LAM will be enrolled. **Detailed Description:** This will be a phase I dose escalation study of the combination of sirolimus (2 mg adjusted to keep trough levels between 5-15 ng/ml) and hydroxychloroquine (200 mg or 400 mg) taken orally daily for 6 months. The study is to be conducted at 2 sites. Up to 18 adult women with LAM will be enrolled, and each recruiting site will recruit between 8-12 subjects. The protocol will use the following eligibility criteria. ### Conditions Module **Conditions:** - Lymphangioleiomyomatosis **Keywords:** - LAM - TSC - lymphangioleiomyomatosis ### Design Module #### Design Info **Intervention Model:** SEQUENTIAL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 14 **Type:** ACTUAL **Phases:** - PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Subjects will take Sirolimus at an initial dose of 2mg followed by dose adjustment to keep Sirolimus trough levels between 5-15ng/ml consistent with the effective dose in the MILES trial. In addition to Sirolimus subjects will receive Hydroxychloroquine at 200 mg daily for 6 months. Once safety is established at the lower dose ("Sirolimus" and "Hydroxychloroquine" 200 mg), subjects enrolled henceforth will receive Sirolimus and Hydroxychloroquine 400 mg (200 mg twice a day) for 6 months. **Intervention Names:** - Drug: "Sirolimus" and "Hydroxychloroquine" 200 mg - Drug: "Sirolimus" and "Hydroxychloroquine" 400 mg **Label:** "Sirolimus" and "Hydroxychloroquine" **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - "Sirolimus" and "Hydroxychloroquine" **Description:** This will be a phase I dose escalation study of the combination of "Sirolimus" (2 mg adjusted to keep trough levels between 5-15 ng/ml) and "Hydroxychloroquine" 200 mg taken orally daily. **Name:** "Sirolimus" and "Hydroxychloroquine" 200 mg **Other Names:** - sirolimus(rapamune), hydroxychloroquine (plaquenil) **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - "Sirolimus" and "Hydroxychloroquine" **Description:** Once safety is established with the lower dose, (Sirolimus and Hydroxychloroquine 200 mg), subjects will receive Sirolimus 2 mg (adjusted to keep trough levels between 5 to 15 ng/ml) and hydroxychloroquine 200 mg twice a day. **Name:** "Sirolimus" and "Hydroxychloroquine" 400 mg **Other Names:** - Sirolimus (Rapamune), Hydroxychloroquine (plaquenil) **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** The Primary endpoint of this study was safety. Safety was assessed based on the adverse events and serious adverse events that occurred in these patients when they were on this combination therapy. Percentage of adverse events in each system at a dose was calculated from the total adverse events at that dose. Subjects were closely monitored and adverse events were classified and graded according to the "Common Terminology Criteria for Adverse Events, (CTCAE) Version 4.0". **Measure:** Safety of Combination Therapy With Sirolimus and Hydroxychloroquine in LAM Patients **Time Frame:** 48 weeks ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Female age 18 or older * Ability to give informed consent * Diagnosis of LAM as defined as typical cystic change on CT plus: * biopsy or cytology of any tissue demonstrating LAM * angiomyolipoma, chylothorax, lymphangioleiomyoma, or tuberous sclerosis * serum VEGFD greater or equal to 800pg/ml * Post-bronchodilator FEV1 equal or less than 80% of predicted or DLCO equal equal or less than 70% of predicted, or RV \> 120% of predicted at baseline * Women of childbearing potential must agree to use 2 forms of barrier contraception during and for 8 weeks after the last dose of medication. Exclusion Criteria: * History of intolerance of mTOR inhibitors * History of intolerance to hydroxychloroquine * History of severe psoriasis * History of porphyria cutanea tarda * Uncontrolled intercurrent illness * Pregnant, breast feeding, or plan to become pregnant in the next year * Inadequate contraception * Significant hematological or hepatic abnormalities * Use of an investigational drug within 30 days of study start * Inability to attend scheduled clinic visits * Inability to perform PFTs * Creatinine \> 2.5mg/dL * Recent pneumothorax within 8 weeks of screening * History of malignancy in the last 2 years other than basal cell skin cancer * Use of estrogen containing medication within 30 days of screening * Abnormal G6PD levels at baseline * Preexisting maculopathy or retinopathy * Preexisting myopathy * Currently taking doxycycline, metformin, lupron, simvastatin * Unable to undergo CT or MRI * History of seizure within last year * Hepatitis B, C, HIV positive serology * Use of alternative medical therapies for LAM for at least 6 weeks prior to study participation * History of myocardial infarct, angina, or stroke related to atherosclerosis * History of cardiomyopathy * Previous lung transplant * Surgery (involving entry into a body cavity or requiring 3 or more stitches) within 2 months of initiation of study drug * Uncontrolled cholesterol \> 350mg/dL, triglycerides \> 400mg/dL **Maximum Age:** 85 Years **Minimum Age:** 18 Years **Sex:** FEMALE **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Boston **Country:** United States **Facility:** Brigham and Women's Hospital **State:** Massachusetts **Zip:** 02120 #### Overall Officials **Official 1:** **Affiliation:** Brigham and Women's Hospital **Name:** Elizabeth P Henske, MD **Role:** PRINCIPAL_INVESTIGATOR **Official 2:** **Affiliation:** National Heart, Lung, and Blood Institute (NHLBI) **Name:** Joel Moss, MD, PhD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Tang Y, El-Chemaly S, Taveira-Dasilva A, Goldberg HJ, Bagwe S, Rosas IO, Moss J, Priolo C, Henske EP. Alterations in Polyamine Metabolism in Patients With Lymphangioleiomyomatosis and Tuberous Sclerosis Complex 2-Deficient Cells. Chest. 2019 Dec;156(6):1137-1148. doi: 10.1016/j.chest.2019.05.038. Epub 2019 Jul 9. **PMID:** 31299246 **Citation:** Lamattina AM, Taveira-Dasilva A, Goldberg HJ, Bagwe S, Cui Y, Rosas IO, Moss J, Henske EP, El-Chemaly S. Circulating Biomarkers From the Phase 1 Trial of Sirolimus and Autophagy Inhibition for Patients With Lymphangioleiomyomatosis. Chest. 2018 Nov;154(5):1070-1082. doi: 10.1016/j.chest.2018.08.1029. Epub 2018 Aug 23. **PMID:** 30144422 **Citation:** El-Chemaly S, Taveira-Dasilva A, Goldberg HJ, Peters E, Haughey M, Bienfang D, Jones AM, Julien-Williams P, Cui Y, Villalba JA, Bagwe S, Maurer R, Rosas IO, Moss J, Henske EP. Sirolimus and Autophagy Inhibition in Lymphangioleiomyomatosis: Results of a Phase I Clinical Trial. Chest. 2017 Jun;151(6):1302-1310. doi: 10.1016/j.chest.2017.01.033. Epub 2017 Feb 10. **PMID:** 28192114 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000008203 - Term: Lymphangiomyoma - ID: D000018190 - Term: Lymphatic Vessel Tumors - ID: D000009370 - Term: Neoplasms by Histologic Type - ID: D000009369 - Term: Neoplasms - ID: D000054973 - Term: Perivascular Epithelioid Cell Neoplasms - ID: D000018204 - Term: Neoplasms, Connective and Soft Tissue - ID: D000008232 - Term: Lymphoproliferative Disorders - ID: D000008206 - Term: Lymphatic Diseases - ID: D000007160 - Term: Immunoproliferative Disorders - ID: D000007154 - Term: Immune System Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC15 - Name: Blood and Lymph Conditions - Abbrev: BC20 - Name: Immune System Diseases - Abbrev: All - Name: All Conditions - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M20338 - Name: Lymphangioleiomyomatosis - Relevance: HIGH - As Found: Lymphangioleiomyomatosis - ID: M11200 - Name: Lymphangiomyoma - Relevance: LOW - As Found: Unknown - ID: M12315 - Name: Neoplasms by Histologic Type - Relevance: LOW - As Found: Unknown - ID: M27983 - Name: Perivascular Epithelioid Cell Neoplasms - Relevance: LOW - As Found: Unknown - ID: M20350 - Name: Neoplasms, Connective and Soft Tissue - Relevance: LOW - As Found: Unknown - ID: M11225 - Name: Lymphoproliferative Disorders - Relevance: LOW - As Found: Unknown - ID: M11203 - Name: Lymphatic Diseases - Relevance: LOW - As Found: Unknown - ID: M10206 - Name: Immunoproliferative Disorders - Relevance: LOW - As Found: Unknown - ID: M10200 - Name: Immune System Diseases - Relevance: LOW - As Found: Unknown - ID: T3526 - Name: Lymphangioleiomyomatosis - Relevance: HIGH - As Found: Lymphangioleiomyomatosis ### Condition Browse Module - Meshes - ID: D000018192 - Term: Lymphangioleiomyomatosis ### Intervention Browse Module - Ancestors - ID: D000000900 - Term: Anti-Bacterial Agents - ID: D000000890 - Term: Anti-Infective Agents - ID: D000000903 - Term: Antibiotics, Antineoplastic - ID: D000000970 - Term: Antineoplastic Agents - ID: D000000935 - Term: Antifungal Agents - ID: D000007166 - Term: Immunosuppressive Agents - ID: D000007155 - Term: Immunologic Factors - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000047428 - Term: Protein Kinase Inhibitors - ID: D000004791 - Term: Enzyme Inhibitors - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000000962 - Term: Antimalarials - ID: D000000981 - Term: Antiprotozoal Agents - ID: D000000977 - Term: Antiparasitic Agents - ID: D000018501 - Term: Antirheumatic Agents ### Intervention Browse Module - Browse Branches - Abbrev: Infe - Name: Anti-Infective Agents - Abbrev: ANeo - Name: Antineoplastic Agents - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: ARhu - Name: Antirheumatic Agents ### Intervention Browse Module - Browse Leaves - ID: M21960 - Name: Sirolimus - Relevance: HIGH - As Found: Included - ID: M9940 - Name: Hydroxychloroquine - Relevance: HIGH - As Found: Bone marrow - ID: M353695 - Name: Temsirolimus - Relevance: HIGH - As Found: Included - ID: M2827 - Name: MTOR Inhibitors - Relevance: HIGH - As Found: Included - ID: M4222 - Name: Anti-Bacterial Agents - Relevance: LOW - As Found: Unknown - ID: M4214 - Name: Anti-Infective Agents - Relevance: LOW - As Found: Unknown - ID: M4224 - Name: Antibiotics, Antitubercular - Relevance: LOW - As Found: Unknown - ID: M6252 - Name: Clotrimazole - Relevance: LOW - As Found: Unknown - ID: M11796 - Name: Miconazole - Relevance: LOW - As Found: Unknown - ID: M4254 - Name: Antifungal Agents - Relevance: LOW - As Found: Unknown - ID: M10212 - Name: Immunosuppressive Agents - Relevance: LOW - As Found: Unknown - ID: M10201 - Name: Immunologic Factors - Relevance: LOW - As Found: Unknown - ID: M25820 - Name: Protein Kinase Inhibitors - Relevance: LOW - As Found: Unknown - ID: M7951 - Name: Enzyme Inhibitors - Relevance: LOW - As Found: Unknown - ID: M4280 - Name: Antimalarials - Relevance: LOW - As Found: Unknown - ID: M4298 - Name: Antiprotozoal Agents - Relevance: LOW - As Found: Unknown - ID: M4294 - Name: Antiparasitic Agents - Relevance: LOW - As Found: Unknown - ID: M20604 - Name: Antirheumatic Agents - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000020123 - Term: Sirolimus - ID: D000006886 - Term: Hydroxychloroquine - ID: C000401859 - Term: Temsirolimus - ID: D000091203 - Term: MTOR Inhibitors ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module #### Event Groups **Group ID:** EG000 **Title:** Sirolimus and Hydroxychloroquine 200 mg **Deaths Num At Risk:** 3 **Description:** This will be a phase I dose escalation study of the combination of sirolimus (2 mg adjusted to keep trough levels between 5-15 ng/ml) and hydroxychloroquine 200 mg taken orally daily. **ID:** EG000 **Other Num Affected:** 3 **Other Num at Risk:** 3 **Serious Number At Risk:** 3 **Title:** Sirolimus and Hydroxychloroquine 200 mg **Group ID:** EG001 **Title:** Sirolimus and Hydroxychloroquine 400 mg **Deaths Num At Risk:** 10 **Description:** Once safety is established with the lower dose, (Sirolimus and Hydroxychloroquine 200 mg), subjects will receive Sirolimus 2 mg (adjusted to keep trough levels between 5 to 15 ng/ml) and hydroxychloroquine 200 mg twice a day. **ID:** EG001 **Other Num Affected:** 9 **Other Num at Risk:** 10 **Serious Number Affected:** 1 **Serious Number At Risk:** 10 **Title:** Sirolimus and Hydroxychloroquine 400 mg **Frequency Threshold:** 0 #### Other Events **Term:** Rash/ Acne **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Abnormal Investigations **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** CTCAE (4.0) **Term:** Diarrhea **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Oral Mucositis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (4.0) #### Serious Events **Term:** radiculitis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** CTCAE (4.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 3 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 10 **Num Events:** 1 **Time Frame:** 48 weeks ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 14 **Units:** Participants ### Group **ID:** BG000 **Title:** Sirolimus and Hydroxychloroquine **Description:** Subjects will take sirolimus at an initial dose of 2mg followed by dose adjustment to keep sirolimus trough levels between 5-15ng/ml consistent with the effective dose in the MILES trial. In addition to sirolimus subjects will receive hydroxychloroquine at 200 mg daily or twice a day for 6 months, depending on time of enrollment into the study, following a standard phase I dose escalation. sirolimus and hydroxychloroquine: This will be a phase I dose escalation study of the combination of sirolimus (2 mg adjusted to keep trough levels between 5-15 ng/ml) and hydroxychloroquine (200 mg or 400 mg) taken orally daily. ### Measure #### Measurement **Group ID:** BG000 **Lower Limit:** 40 **Upper Limit:** 65 **Value:** 49 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 13 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 13 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 0 **Category Title:** Male #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 13 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 0 **Category Title:** American Indian or Alaska Native #### Measurement **Group ID:** BG000 **Value:** 1 **Category Title:** Asian #### Measurement **Group ID:** BG000 **Value:** 0 **Category Title:** Native Hawaiian or Other Pacific Islander #### Measurement **Group ID:** BG000 **Value:** 0 **Category Title:** Black or African American #### Measurement **Group ID:** BG000 **Value:** 12 **Category Title:** White #### Measurement **Group ID:** BG000 **Value:** 0 **Category Title:** More than one race #### Measurement **Group ID:** BG000 **Value:** 0 **Category Title:** Unknown or Not Reported #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 13 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 13 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 13 **Class Title:** United States ### Measure #### Measurement **Group ID:** BG000 **Value:** 6 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 13 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 9 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 13 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 2 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 13 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 0 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 14 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 8 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 13 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 1 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 13 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Spread:** 103 **Value:** 442 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 13 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Spread:** 19.2 **Value:** 43.8 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 13 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Spread:** 0.33 **Value:** 3.11 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 13 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Spread:** 0.7 **Value:** 1.6 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 13 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Spread:** 21 **Value:** 59 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 14 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Spread:** 0.7 **Value:** 2.8 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 13 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Spread:** 16 **Value:** 81 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 13 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Spread:** 3.1 **Value:** 9.8 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 13 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Spread:** 15 **Value:** 43 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 13 **Class Title:** **Denomination Units Selected:** ## Results Section - Baseline Characteristics Module ### Measure 1 **Dispersion Type:** FULL_RANGE **Parameter Type:** MEDIAN **Population Description:** 1 subject screen failed. **Title:** Age, Continuous **Unit of Measure:** years ### Measure 2 **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** 1 subject screen failed. **Title:** Sex: Female, Male **Unit of Measure:** Participants ### Measure 3 **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** 1 subject screen failed. **Title:** Race (NIH/OMB) **Unit of Measure:** Participants ### Measure 4 **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** 1 subject screen failed. **Title:** Region of Enrollment **Unit of Measure:** Participants ### Measure 5 **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** 1 subject screen failed. **Title:** Post-Menopause **Unit of Measure:** Participants ### Measure 6 **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** 1 subject screen failed. **Title:** Pneumothorax **Unit of Measure:** Participants ### Measure 7 **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** 1 subject screen failed. **Title:** Angiomyolipoma **Unit of Measure:** Participants ### Measure 8 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Tuberous Sclerois (TSC)- Lymphangioleiomyomatosis (LAM) **Unit of Measure:** Participants ### Measure 9 **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** 1 subject screen failed. **Title:** Lung Biopsy **Unit of Measure:** Participants ### Measure 10 **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** 1 subject screen failed **Title:** Chylothorax **Unit of Measure:** Participants ### Measure 11 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Population Description:** 1 subject screen failed. **Title:** 6 minute walk distance (6MWD) (m) **Unit of Measure:** m ### Measure 12 **Description:** The Saint George's Respiratory Questionnaire (SGRQ) is a disease-specific instrument designed to measure impact on overall health, daily life, and perceived well-being in patients with obstructive airways disease. Scores range from 0 to 100, with higher scores indicating more limitations. **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Population Description:** 1 subject screen failed. **Title:** St. George's Respiratory Questionnaire (SGRQ) **Unit of Measure:** units on a scale ### Measure 13 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Population Description:** 1 subject screen failed. **Title:** Log VEGF-D (Veascular Endothelial Growth factor) **Unit of Measure:** log(pg/ml) ### Measure 14 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Population Description:** 1 Subject Screen failed. **Title:** FEV1 **Unit of Measure:** Litres ### Measure 15 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** FEV1 (%) **Unit of Measure:** Percent predicted ### Measure 16 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Population Description:** 1 subject screen failed. **Title:** FVC (L) **Unit of Measure:** Litres ### Measure 17 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Population Description:** 1 Subject Screen failed. **Title:** FVC (%) **Unit of Measure:** Percent predicted ### Measure 18 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Population Description:** 1 Subject screen failed. **Title:** DLCO (ml/min/mmhg) **Unit of Measure:** ml/min/mmhg ### Measure 19 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Population Description:** 1 Subject screen failed. **Title:** DLCO (%) **Unit of Measure:** percent predicted **Population Description:** 1 subject failed to qualify for the study at the screening visit. Since the subject had signed consent, we considered the participant to be enrolled on the study. ## Results Section - More Information Module ### Certain Agreement ### Point of Contact **Email:** [email protected] **Organization:** Brigham and Women's Hospital **Phone:** 857-307-0782 **Title:** Elizabeth P. Henske, MD ## Results Section - Outcome Measures Module ### Outcome Measure 1 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2.27 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1.11 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1.11 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 18.18 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 22.22 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 18.18 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 6.67 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0.56 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 15.91 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 8.33 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0.56 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 6.82 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 20 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3.33 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4.44 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4.55 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 5.00 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0.56 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 7.78 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 6.82 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1.11 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2.27 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 9.44 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 25.0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 6.11 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1.67 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** The Primary endpoint of this study was safety. Safety was assessed based on the adverse events and serious adverse events that occurred in these patients when they were on this combination therapy. Percentage of adverse events in each system at a dose was calculated from the total adverse events at that dose. Subjects were closely monitored and adverse events were classified and graded according to the "Common Terminology Criteria for Adverse Events, (CTCAE) Version 4.0". **Parameter Type:** NUMBER **Reporting Status:** POSTED **Time Frame:** 48 weeks **Title:** Safety of Combination Therapy With Sirolimus and Hydroxychloroquine in LAM Patients **Type:** PRIMARY **Unit of Measure:** Percentage of adverse events ##### Group **Description:** This will be a phase I dose escalation study of the combination of sirolimus (2 mg adjusted to keep trough levels between 5-15 ng/ml) and hydroxychloroquine 200 mg taken orally daily. Safety of the drug combination was assessed by the occurrence of adverse events in these 3 patients. **ID:** OG000 **Title:** Sirolimus and Hydroxychloroquine 200 mg ##### Group **Description:** Once safety is established with the lower dose, (Sirolimus and Hydroxychloroquine 200 mg), subjects will receive Sirolimus 2 mg (adjusted to keep trough levels between 5 to 15 ng/ml) and hydroxychloroquine 200 mg twice a day. Safety of this dose was assessed by the occurrence of adverse events in these 10 patients. **ID:** OG001 **Title:** Sirolimus and Hydroxychloroquine 400 mg ### Participant Flow Module #### Group **Description:** This will be a phase I dose escalation study of the combination of sirolimus (2 mg adjusted to keep trough levels between 5-15 ng/ml) and hydroxychloroquine 200 mg taken orally daily. **ID:** FG000 **Title:** Sirolimus and Hydroxychloroquine 200 mg #### Group **Description:** Once safety is established with the lower dose, (Sirolimus and Hydroxychloroquine 200 mg), subjects will receive Sirolimus 2 mg (adjusted to keep trough levels between 5 to 15 ng/ml) and hydroxychloroquine 200 mg twice a day. **ID:** FG001 **Title:** Sirolimus and HydroxyChloroquine 400 mg #### Period **Title:** Overall Study ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 3 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 10 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 2 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 6 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 1 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 4 **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT03568279 **Brief Title:** Jaw-thrust on Postoperative Sore Throat **Official Title:** Influence of Two-handed Jaw Thrust on Postoperative Sore Throat #### Organization Study ID Info **ID:** JTPOST #### Organization **Class:** OTHER **Full Name:** Keimyung University Dongsan Medical Center ### Status Module #### Completion Date **Date:** 2019-08-01 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** ENROLLING_BY_INVITATION #### Last Update Post Date **Date:** 2018-09-28 **Type:** ACTUAL **Last Update Submit Date:** 2018-09-27 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2019-07-01 **Type:** ESTIMATED #### Start Date **Date:** 2018-07-01 **Type:** ACTUAL **Status Verified Date:** 2018-09 #### Study First Post Date **Date:** 2018-06-26 **Type:** ACTUAL **Study First Submit Date:** 2018-06-04 **Study First Submit QC Date:** 2018-06-22 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Keimyung University Dongsan Medical Center #### Responsible Party **Investigator Affiliation:** Keimyung University Dongsan Medical Center **Investigator Full Name:** Hyun-Chang Kim **Investigator Title:** Assistant professor **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** This investigation is planned to compare the incidence and severity of postoperative sore throat according to the use of two-handed jaw thrust maneuver in patients undergoing endotracheal intubation for general anesthesia. ### Conditions Module **Conditions:** - General Anesthesia ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** TRIPLE **Who Masked:** - PARTICIPANT - INVESTIGATOR - OUTCOMES_ASSESSOR **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 96 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** The attending anesthesiologist provided intubation without two-handed jaw thrust. **Intervention Names:** - Procedure: Control **Label:** Control **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** The attending anesthesiologist provided intubation with two-handed jaw thrust. **Intervention Names:** - Procedure: Two-handed jaw thrust **Label:** Two-hand **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Two-hand **Description:** The assistant applied two-handed jaw thrust for intubation. **Name:** Two-handed jaw thrust **Type:** PROCEDURE #### Intervention 2 **Arm Group Labels:** - Control **Description:** The intubation was done without two-handed jaw thrust. **Name:** Control **Type:** PROCEDURE ### Outcomes Module #### Primary Outcomes **Measure:** Number of participants with postoperative sore throat for postoperative 24 hour **Time Frame:** At postoperative 24 hour #### Secondary Outcomes **Measure:** Number of participants with postoperative sore throat **Time Frame:** At postoperative 2, 4, and 24 hour **Description:** Visual analogue scales will be used (10: most imaginable pain, 0: no pain). **Measure:** Postoperative sore throat scores **Time Frame:** At postoperative 2, 4, and 24 hour **Measure:** Number of participants with postoperative hoarseness **Time Frame:** At postoperative 2, 4, and 24 hour **Measure:** Number of participants with postoperative shivering **Time Frame:** At postoperative 2, 4, and 24 hour **Description:** Visual analogue scales will be used (10: most imaginable pain, 0: no pain). **Measure:** Wound pain scores **Time Frame:** At postoperative 2, 4, and 24 hour **Measure:** Number of participants with jaw discomfort **Time Frame:** At postoperative 2, 4, and 24 hour ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * ASA I-III * Patients scheduled for general anesthesia with endotracheal intubation Exclusion Criteria: * Difficult airway * Mallampatti scores greater than 2 * Recent sore throat * Cervical spine disease * Recent upper respiratory infection * Recent analgesics * History of head and neck surgery * Friable teeth * Multiple intubation attempts **Maximum Age:** 80 Years **Minimum Age:** 19 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Daegu **Country:** Korea, Republic of **Facility:** Hyun-Chang Kim **State:** Non-US/Canada **Zip:** 137-040 ### IPD Sharing Statement Module **IPD Sharing:** UNDECIDED ### References Module #### References **Citation:** Huh H, Go DY, Cho JE, Park J, Lee J, Kim HC. Influence of two-handed jaw thrust during tracheal intubation on postoperative sore throat: a prospective randomised study. J Int Med Res. 2021 Feb;49(2):300060520961237. doi: 10.1177/0300060520961237. **PMID:** 33535830 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000012141 - Term: Respiratory Tract Infections - ID: D000007239 - Term: Infections - ID: D000010608 - Term: Pharyngeal Diseases - ID: D000009057 - Term: Stomatognathic Diseases - ID: D000012140 - Term: Respiratory Tract Diseases - ID: D000010038 - Term: Otorhinolaryngologic Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC01 - Name: Infections - Abbrev: BC07 - Name: Mouth and Tooth Diseases - Abbrev: BC08 - Name: Respiratory Tract (Lung and Bronchial) Diseases - Abbrev: BC09 - Name: Ear, Nose, and Throat Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology ### Condition Browse Module - Browse Leaves - ID: M13519 - Name: Pharyngitis - Relevance: HIGH - As Found: Sore Throat - ID: M10283 - Name: Infections - Relevance: LOW - As Found: Unknown - ID: M6368 - Name: Communicable Diseases - Relevance: LOW - As Found: Unknown - ID: M14978 - Name: Respiratory Tract Infections - Relevance: LOW - As Found: Unknown - ID: M13515 - Name: Pharyngeal Diseases - Relevance: LOW - As Found: Unknown - ID: M12017 - Name: Stomatognathic Diseases - Relevance: LOW - As Found: Unknown - ID: M14977 - Name: Respiratory Tract Diseases - Relevance: LOW - As Found: Unknown - ID: M12961 - Name: Otorhinolaryngologic Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000010612 - Term: Pharyngitis ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT02435979 **Brief Title:** Proximal Strengthening for the Management of Wrist Pain **Official Title:** Proximal Strengthening for the Management of Wrist Pain: A Randomized Controlled Trial #### Organization Study ID Info **ID:** IRB15-00251 #### Organization **Class:** OTHER **Full Name:** Nationwide Children's Hospital ### Status Module #### Completion Date **Date:** 2019-07 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2019-07-16 **Type:** ACTUAL **Last Update Submit Date:** 2019-07-15 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2019-07 **Type:** ACTUAL #### Start Date **Date:** 2015-05 **Status Verified Date:** 2019-07 #### Study First Post Date **Date:** 2015-05-06 **Type:** ESTIMATED **Study First Submit Date:** 2015-05-01 **Study First Submit QC Date:** 2015-05-05 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Mitchell Selhorst #### Responsible Party **Investigator Affiliation:** Nationwide Children's Hospital **Investigator Full Name:** Mitchell Selhorst **Investigator Title:** Principal Investigator **Type:** SPONSOR_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** This study will be a randomized controlled trial comparing proximal strengthening vs. traditional hand therapy for patients with wrist pain. Patients will attend 2 hand therapy sessions per week for 4 weeks. Change in patient function and pain as measured by the patient rated wrist evaluation will be the primary outcome of interest **Detailed Description:** This will be a non-blinded randomized controlled trial using a sample of consecutive patients with wrist pain. Patients who are referred to Nationwide Children's Hospital Hand therapy clinics with a primary complaint of wrist pain will be considered for this study. Patients will be randomly assigned to one of two treatment groups; The proximal strengthening group or Traditional Hand Therapy Group. Both treatment groups will be evaluated and treated by the certified hand therapists for 2 sessions per week for 4 weeks. Both groups will receive similar treatment durations of 45-60 minutes per session based on each patient's individual needs. Proximal strengthening group-The experimental proximal strengthening group consists of treatment where the hand therapist address specific impairments at the wrist and hand for 20-30 minutes at each treatment session. Patients allocated to this treatment group will also perform a standardized proximal strengthening protocol consisting of cervical, periscapular, and shoulder strengthening exercises. Depending on the pace and guidance needed for these exercises 25-30 minutes will be spent on proximal strengthening exercises. As the patients endurance and strength increased the repetitions and/or resistance of these exercises will increase. Traditional Hand Therapy Group This active comparator group consists of treatment where the hand therapist address specific impairments at the wrist and hand for 45-60 minutes at each treatment session. Treatment can include stretching, motion, and strengthening exercises. As the patients endurance and strength increased the repetitions and/or resistance of these exercises will increase. Modalities for pain control and tissue mobility, and bracing or splinting if necessary. All treatments for the traditional hand therapy treatment group will occur seated at the hand therapy treatment table. ### Conditions Module **Conditions:** - Wrist Injuries **Keywords:** - wrist - proximal strengthening - hand therapy ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 38 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Patients in this group will perform traditional hand therapy for 30 minutes and proximal strengthening of the core, cervical spine, and shoulder complex for up to 30 minutes **Intervention Names:** - Other: hand therapy - Other: Proximal Strengthening **Label:** Proximal strengthening + hand therapy **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** This group will receive traditional hand therapy for 45-60 minutes each session. **Intervention Names:** - Other: hand therapy **Label:** Traditional hand therapy **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Proximal strengthening + hand therapy - Traditional hand therapy **Description:** Treatment can include stretching, motion, and strengthening exercises. As the patients endurance and strength increased the repetitions and/or resistance of these exercises will increase. Modalities for pain control and tissue mobility, and bracing or splinting if necessary. All treatments for the traditional hand therapy treatment group will occur seated at the hand therapy treatment table. **Name:** hand therapy **Type:** OTHER #### Intervention 2 **Arm Group Labels:** - Proximal strengthening + hand therapy **Description:** Patients will perform a standardized proximal strengthening protocol consisting of cervical, periscapular, and shoulder strengthening exercises. Depending on the pace and guidance needed for these exercises 25-30 minutes will be spent on proximal strengthening exercises. As the patients endurance and strength increased the repetitions and/or resistance of these exercises will increase. **Name:** Proximal Strengthening **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** The PRWE is a 15 item self-report questionnaire which measure pain and function. It has been found valid and reliable for measure changes in pain and function for patients with wrist pain. The minimal clinical important difference of this scale is 14 (Sorensen, 2013). **Measure:** Change in Patient Rated Wrist Evaluation (PRWE) score **Time Frame:** 4 weeks (From initial evaluation to discharge) #### Secondary Outcomes **Description:** Grip strength will be measured using a Jamar dynamometer on 2nd setting with elbow at 90 deg and shoulder in adduction at the patient's side, with the patient seated. Grip strength will be expressed as a percentage of body weight to account for differences in patients size and strength. **Measure:** Change in Grip Dynamometer strength **Time Frame:** 4 weeks (From initial evaluation to discharge) ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Wrist pain Exclusion Criteria: * \<8 years of age * any neurological disorder * Juvenile rheumatoid arthritis * juvenile idiopathic arthritis * Wrist fractures \< 16 weeks from date of injury or surgery * Tendon repair * Nerve injury or repair * Inability to follow directions * Inability to attend follow-up appointments **Minimum Age:** 8 Years **Sex:** ALL **Standard Ages:** - CHILD - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Columbus **Country:** United States **Facility:** Nationwide Children's Hospital Sports and Ortho PT Ortho Center **State:** Ohio **Zip:** 43205 **Location 2:** **City:** Columbus **Country:** United States **Facility:** Nationwide Children's Hospital Sports and Ortho PT East Broad **State:** Ohio **Zip:** 43213 **Location 3:** **City:** Dublin **Country:** United States **Facility:** Nationwide Children's Hospital Sports and Ortho PT Dublin **State:** Ohio **Zip:** 43017 **Location 4:** **City:** Westerville **Country:** United States **Facility:** Nationwide Children's Hospital Sports and Ortho PT Westerville **State:** Ohio **Zip:** 43082 #### Overall Officials **Official 1:** **Affiliation:** Nationwide Childrens Hospital **Name:** Mitchell Selhorst, DPT **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### References **Citation:** Alexander M, Franko OI, Makhni EC, Zurakowski D, Day CS. Validation of a modern activity hand survey with respect to reliability, construct and criterion validity. J Hand Surg Eur Vol. 2008 Oct;33(5):653-60. doi: 10.1177/1753193408093810. **PMID:** 18977836 **Citation:** Metzler W, Kessler G, Benzer W, Mahr G. [Ophthalmological significance of stenosing carotid processes]. Wien Med Wochenschr. 1990 Jul 31;140(14):387-9. German. **PMID:** 2219945 **Citation:** Emery K, De Serres SJ, McMillan A, Cote JN. The effects of a Pilates training program on arm-trunk posture and movement. Clin Biomech (Bristol, Avon). 2010 Feb;25(2):124-30. doi: 10.1016/j.clinbiomech.2009.10.003. Epub 2009 Oct 30. **PMID:** 19879677 **Citation:** Kalra N, Seitz AL, Boardman ND 3rd, Michener LA. Effect of posture on acromiohumeral distance with arm elevation in subjects with and without rotator cuff disease using ultrasonography. J Orthop Sports Phys Ther. 2010 Oct;40(10):633-40. doi: 10.2519/jospt.2010.3155. **PMID:** 20710092 **Citation:** Kong YK. The effects of co-ordinating postures with shoulder and elbow flexion angles on maximum grip strength and upper-limb muscle activity in standing and sitting postures. Int J Occup Saf Ergon. 2014;20(4):595-606. doi: 10.1080/10803548.2014.11077077. **PMID:** 25513795 **Citation:** MacDermid JC. Development of a scale for patient rating of wrist pain and disability. J Hand Ther. 1996 Apr-Jun;9(2):178-83. doi: 10.1016/s0894-1130(96)80076-7. No abstract available. **PMID:** 8784681 **Citation:** Park JK, Buchholz B. Effects of work surface height on muscle activity and posture of the upper extremity during simulated pipetting. Ergonomics. 2013;56(7):1147-58. doi: 10.1080/00140139.2013.799234. Epub 2013 Jun 6. **PMID:** 23742175 **Citation:** Sorensen AA, Howard D, Tan WH, Ketchersid J, Calfee RP. Minimal clinically important differences of 3 patient-rated outcomes instruments. J Hand Surg Am. 2013 Apr;38(4):641-9. doi: 10.1016/j.jhsa.2012.12.032. Epub 2013 Mar 6. **PMID:** 23481405 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000001134 - Term: Arm Injuries - ID: D000014947 - Term: Wounds and Injuries ### Condition Browse Module - Browse Branches - Abbrev: BC26 - Name: Wounds and Injuries - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology ### Condition Browse Module - Browse Leaves - ID: M17692 - Name: Wrist Injuries - Relevance: HIGH - As Found: Wrist Injuries - ID: M13066 - Name: Pain - Relevance: LOW - As Found: Unknown - ID: M4444 - Name: Arm Injuries - Relevance: LOW - As Found: Unknown - ID: M17685 - Name: Wounds and Injuries - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000014954 - Term: Wrist Injuries ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05788679 **Brief Title:** A Study Using Subject-specific MRD to Adopt Treatment After HSCT for Subjects With MDS **Official Title:** A Phase II Multicenter Single-armed Study Using Subject-specific Minimal Residual Disease Markers to Adopt Treatment After Allogeneic Stem Cell Transplantation for Subjects With Myelodysplastic Syndrome #### Organization Study ID Info **ID:** NMDSG14B, part 2 #### Organization **Class:** OTHER **Full Name:** Karolinska University Hospital ### Status Module #### Completion Date **Date:** 2026-12 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2023-12-05 **Type:** ACTUAL **Last Update Submit Date:** 2023-12-04 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2026-12 **Type:** ESTIMATED #### Start Date **Date:** 2022-11-22 **Type:** ACTUAL **Status Verified Date:** 2023-12 #### Study First Post Date **Date:** 2023-03-29 **Type:** ACTUAL **Study First Submit Date:** 2023-01-27 **Study First Submit QC Date:** 2023-03-27 ### Sponsor Collaborators Module #### Collaborators **Class:** NETWORK **Name:** Nordic MDS Group #### Lead Sponsor **Class:** OTHER **Name:** Karolinska University Hospital #### Responsible Party **Investigator Affiliation:** Karolinska University Hospital **Investigator Full Name:** Magnus Tobiasson **Investigator Title:** Coordinating investigator **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** True **Is US Export:** True **Oversight Has DMC:** True ### Description Module **Brief Summary:** The goal of this interventional study is to evaluate if pre-emptive intervention using Azacitidine and / or donor lymphocytes or tapering of immune suppression in measurable residual disease (MRD) positive subjects can prevent clinical relapse. Participants will undergo MRD surveillance and be subjected to intervention in case of MRD positivity. Results will be compared with NMDSG14B, part one, in which MRD was analyzed in included patients without recieving intervention. ### Conditions Module **Conditions:** - Myelodysplastic Syndromes - Acute Myeloid Leukemia With Myelodysplasia Related Disease and < 30% Blasts - Mixed Myelodysplastic/Myeloproliferative Disease ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 200 **Type:** ESTIMATED **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Azacitidine and / or Donor lymphocytes or tapering of immune suppression **Intervention Names:** - Drug: Azacitidine - Other: Donor lymphocytes - Other: Tapering of immune suppression **Label:** Intervention in MRD positive patients **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Intervention in MRD positive patients **Description:** Azacitidine **Name:** Azacitidine **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Intervention in MRD positive patients **Description:** Donor lymphocytes in patients without immune suppression **Name:** Donor lymphocytes **Type:** OTHER #### Intervention 3 **Arm Group Labels:** - Intervention in MRD positive patients **Description:** Tapering of immune suppression in patients who are on immune suppressive drugs **Name:** Tapering of immune suppression **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Measure:** Clinical event defined as relapse or death within 1 year from first MRD+ sample **Time Frame:** Within 1 year from first MRD+ sample #### Secondary Outcomes **Measure:** Number of MRD+ patients achieving MRD negativity **Time Frame:** From MRD positivity until 2y after transplantation **Measure:** Incidence and severity of graft-versus host disease **Time Frame:** From transplantation until 2y after transplantation **Measure:** Safety, adverse events reporting **Time Frame:** After start of Azacitidine until 30 days after last azacitidine injection **Measure:** Relapse-free survival **Time Frame:** From transplantation until 2y after transplantation **Measure:** Overall survival **Time Frame:** From transplantation until 2y after transplantation ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: Signed informed consent * Age ≥ 18 years * Subjects eligible for SCT * Subjects having the disease MDS, mixed myelodysplastic/myeloproliferative syndrome or AML with myelodysplasia related dysplasia and 20-29% marrow blasts * All female subjects of childbearing potential have to have negative pregnancy test within 2 weeks prior to inclusion to the study Exclusion Criteria: * No traceable genetic aberration identified either in screening next generation sequencing panel or next generation sequencing panel performed at diagnosis * Uncontrolled hypertension, heart, liver, kidney related or other uncontrolled medical or psychiatric disorders * Mental inability, reluctance or language difficulties that results in difficulty understanding the meaning of study participation **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Magnus Tobiasson, PhD **Phone:** 0046858580000 **Role:** CONTACT #### Locations **Location 1:** **City:** Stockholm **Contacts:** ***Contact 1:*** - **Name:** Magnus Tobiasson, PhD - **Role:** CONTACT ***Contact 2:*** - **Name:** Andreas Björklund - **Role:** PRINCIPAL_INVESTIGATOR **Country:** Sweden **Facility:** Department of Hematology, Karolinska University Hospital **Status:** RECRUITING #### Overall Officials **Official 1:** **Affiliation:** Karolinska University Hospital **Name:** Magnus Tobiasson, PhD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009369 - Term: Neoplasms - ID: D000006402 - Term: Hematologic Diseases - ID: D000001855 - Term: Bone Marrow Diseases - ID: D000011230 - Term: Precancerous Conditions ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC15 - Name: Blood and Lymph Conditions - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M10945 - Name: Leukemia - Relevance: LOW - As Found: Unknown - ID: M10955 - Name: Leukemia, Myeloid - Relevance: LOW - As Found: Unknown - ID: M18127 - Name: Leukemia, Myeloid, Acute - Relevance: LOW - As Found: Unknown - ID: M16355 - Name: Syndrome - Relevance: LOW - As Found: Unknown - ID: M12149 - Name: Myeloproliferative Disorders - Relevance: HIGH - As Found: Myeloproliferative Diseases - ID: M14164 - Name: Preleukemia - Relevance: HIGH - As Found: Myelodysplastic Syndrome - ID: M12145 - Name: Myelodysplastic Syndromes - Relevance: HIGH - As Found: Myelodysplastic Syndrome - ID: M20497 - Name: Neoplasm, Residual - Relevance: LOW - As Found: Unknown - ID: M27707 - Name: Myelodysplastic-Myeloproliferative Diseases - Relevance: HIGH - As Found: Myelodysplastic/myeloproliferative disease - ID: M9490 - Name: Hematologic Diseases - Relevance: LOW - As Found: Unknown - ID: M5134 - Name: Bone Marrow Diseases - Relevance: LOW - As Found: Unknown - ID: M14111 - Name: Precancerous Conditions - Relevance: LOW - As Found: Unknown - ID: T3995 - Name: Myeloid Leukemia - Relevance: LOW - As Found: Unknown - ID: T182 - Name: Acute Myeloid Leukemia - Relevance: HIGH - As Found: Acute Myeloid Leukemia - ID: T188 - Name: Acute Non Lymphoblastic Leukemia - Relevance: LOW - As Found: Unknown - ID: T170 - Name: Acute Graft Versus Host Disease - Relevance: LOW - As Found: Unknown - ID: T1311 - Name: Chronic Myeloproliferative Disorders - Relevance: HIGH - As Found: Myeloproliferative Diseases - ID: T3993 - Name: Myelodysplastic Syndromes - Relevance: HIGH - As Found: Myelodysplastic Syndrome - ID: T3994 - Name: Myelodysplastic/myeloproliferative Disease - Relevance: HIGH - As Found: Myelodysplastic/myeloproliferative disease ### Condition Browse Module - Meshes - ID: D000011289 - Term: Preleukemia - ID: D000009190 - Term: Myelodysplastic Syndromes - ID: D000009196 - Term: Myeloproliferative Disorders - ID: D000054437 - Term: Myelodysplastic-Myeloproliferative Diseases ### Intervention Browse Module - Ancestors - ID: D000000964 - Term: Antimetabolites, Antineoplastic - ID: D000000963 - Term: Antimetabolites - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000000970 - Term: Antineoplastic Agents - ID: D000004791 - Term: Enzyme Inhibitors ### Intervention Browse Module - Browse Branches - Abbrev: ANeo - Name: Antineoplastic Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M4673 - Name: Azacitidine - Relevance: HIGH - As Found: Side - ID: M4281 - Name: Antimetabolites - Relevance: LOW - As Found: Unknown - ID: M7951 - Name: Enzyme Inhibitors - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000001374 - Term: Azacitidine ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT02421679 **Acronym:** P202 **Brief Title:** Open Label Extension Safety and Efficacy Study of TNX-102 SL Tablets in Military Related PTSD and Related Conditions **Official Title:** A 12-Week, Open-Label, Multicenter, Extension Study To TNX-CY-P201 To Evaluate The Safety And Efficacy Of TNX-102 SL Taken Daily At Bedtime In Patients With Military-Related PTSD And Related Conditions #### Organization Study ID Info **ID:** TNX-CY-P202 #### Organization **Class:** INDUSTRY **Full Name:** Tonix Pharmaceuticals, Inc. ### Status Module #### Completion Date **Date:** 2016-08 **Type:** ACTUAL #### Disp First Post Date **Date:** 2017-10-31 **Type:** ACTUAL **Disp First Submit Date:** 2017-10-26 **Disp First Submit QC Date:** 2017-10-26 #### Expanded Access Info #### Last Update Post Date **Date:** 2017-10-31 **Type:** ACTUAL **Last Update Submit Date:** 2017-10-26 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2016-08 **Type:** ACTUAL #### Start Date **Date:** 2015-04 **Type:** ACTUAL **Status Verified Date:** 2017-10 #### Study First Post Date **Date:** 2015-04-21 **Type:** ESTIMATED **Study First Submit Date:** 2015-04-09 **Study First Submit QC Date:** 2015-04-20 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Tonix Pharmaceuticals, Inc. #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** This is a 12-week, multicenter, open-label extension study to evaluate the safety and efficacy of TNX-102 SL tablet taken daily at bedtime in patients with Military-Related PTSD or related condition. Patients recruited into this trial are those who have successfully completed the double-blind study, TNX-CY-P201 (AtEase Study). Patients will not be made aware of the therapy they received during the double-blind study. **Detailed Description:** The study will consist of 4 clinic visits, including Screening/Baseline Visit 1 (Day 0, which is anticipated to be the same date as the final visit in the lead-in P201 study) and visits after 2, 6 and 12 weeks of treatment. The previous requirements in the lead-in study for refraining from the use of certain concomitant medications and trauma-focused psychotherapies will be relaxed. Patients may continue to take rescue therapy for sleep, as appropriate, or they may utilize other medications as needed to help them sleep, per the judgment of the investigator. Eligible patients who provide written informed consent will take one TNX-102 SL tablet daily at bedtime sublingually (under the tongue) for 12 weeks. All patients will be assigned to receive tthe same dosage of TNX-102 SL, regardless of their treatment assignment in the lead-in study. No patients, investigators, or study staff will know the assigned study treatment from the lead-in study, P201, at the time of entry into the extension study. Patient data collected at the Week 12 visit (Visit 9) in the lead-in P201 study will be used as one of the baseline values for this study. ### Conditions Module **Conditions:** - PTSD **Keywords:** - PTSD - Military-related PTSD and other related conditions - open-label extension ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 159 **Type:** ACTUAL **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** TNX-102 SL taken daily at bedtime for 12 weeks **Intervention Names:** - Drug: TNX-102 SL **Label:** TNX-102 SL **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - TNX-102 SL **Description:** TNX-102 Sublingual tablets **Name:** TNX-102 SL **Other Names:** - cyclobenzaprine HCI **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** To evaluate the safety of the TNX-102 SL (cyclobenzaprine HCl sublingual tablets) as new treatment emergent AEs since lead-in study, change in clinical laboratory test results and vital signs **Measure:** Safety (Adverse events, change in lab test results and vital signs) **Time Frame:** Week 12 #### Secondary Outcomes **Description:** Changes in total CAPS-5 score from baseline in lead-in study and since baseline in this study **Measure:** Total CAPS-5 (Clinician Administered PTSD Scale (for Diagnostic and Statistical Manual of Mental Disorders Version 5) **Time Frame:** Weeks 2, 6 and 12 **Description:** ≥30% decrease in Total CAPS-5 score at weeks from baseline in lead-in study and since baseline in this study **Measure:** Response rates a in Total CAPS-5 score **Time Frame:** Weeks 2, 6 and 12 **Description:** Changes from baseline in lead-in study and since baseline in this study in item scores, including * intrusion symptoms (Criterion B) * CAPS-5 item 2. (B-2) (unpleasant dreams related to the trauma) * persistent avoidance (Criterion C), * negative cognitions and mood (Criterion D) * arousal and reactivity (Criterion E) **Measure:** CAPS-5 cluster score items **Time Frame:** Weeks 2, 6 and 12 **Description:** Changes from baseline in lead-in study and since baseline in this study in MADRS **Measure:** Montgomery-Asberg Depression Rating Scale **Time Frame:** Week 12 **Description:** Changes from baseline in lead-in study and since baseline in this study in PROMIS scores **Measure:** PROMIS (Patient -Reported Outcome Measurement Information System) **Time Frame:** Week 12 **Description:** Changes from baseline in lead-in study and since baseline in this study in MTRSS scores **Measure:** MTRSS (Morning Treatment-Related Sedation Scale) **Time Frame:** Week 12 **Description:** Changes from baseline in lead-in study and since baseline in this study in PGIC **Measure:** PGIC (Patient Global Impression of Change Scale) **Time Frame:** Week 12 ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Completed the lead-in study and is judged as reasonably compliant, with at least 60% compliance * Signed informed consent * Met all prior inclusion and exclusion requirements for lead-in study * No new or worsening medical conditions since starting the lead-in study that could pose a safety risk or interfere with participation in the study * Willing to refrain from use of specific medication (ask PI) * Female patients of childbearing potential continue to practice medically acceptable methods of birth control Exclusion Criteria: * None **Maximum Age:** 66 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Tuscaloosa **Country:** United States **Facility:** Tuscaloosa VA Medical Center **State:** Alabama **Zip:** 35404 **Location 2:** **City:** Phoenix **Country:** United States **Facility:** Noesis Pharma **State:** Arizona **Zip:** 85032 **Location 3:** **City:** Imperial **Country:** United States **Facility:** Sun Valley Reserach Center **State:** California **Zip:** 92251 **Location 4:** **City:** National City **Country:** United States **Facility:** Synergy Clinical Research **State:** California **Zip:** 91950 **Location 5:** **City:** Oceanside **Country:** United States **Facility:** Excell Research, Inc **State:** California **Zip:** 92506 **Location 6:** **City:** Orange **Country:** United States **Facility:** Neuropsychiatric Research Center of Orange County **State:** California **Zip:** 92868 **Location 7:** **City:** Riverside **Country:** United States **Facility:** CITRIALS **State:** California **Zip:** 92506 **Location 8:** **City:** San Diego **Country:** United States **Facility:** CESAMH **State:** California **Zip:** 92103 **Location 9:** **City:** Torrance **Country:** United States **Facility:** Cns, Inc. **State:** California **Zip:** 90502 **Location 10:** **City:** Lake City **Country:** United States **Facility:** Sarkis Clinical Trials **State:** Florida **Zip:** 32025 **Location 11:** **City:** Leesburg **Country:** United States **Facility:** Compass Research North, LLC **State:** Florida **Zip:** 34748 **Location 12:** **City:** Orlando **Country:** United States **Facility:** Clinical Neuroscience Solutions, Inc. **State:** Florida **Zip:** 32801 **Location 13:** **City:** Atlanta **Country:** United States **Facility:** Atlanta Center For Medical Research **State:** Georgia **Zip:** 30308 **Location 14:** **City:** Chicago **Country:** United States **Facility:** Great Lakes Clinical Trials **State:** Illinois **Zip:** 60640 **Location 15:** **City:** New Bedford **Country:** United States **Facility:** Novex Clinical Research **State:** Massachusetts **Zip:** 02740 **Location 16:** **City:** Lincoln **Country:** United States **Facility:** Premier Psychiatric Research Instititute, Inc. **State:** Nebraska **Zip:** 68526 **Location 17:** **City:** Las Vegas **Country:** United States **Facility:** Altea Research **State:** Nevada **Zip:** 89102 **Location 18:** **City:** Cedarhurst **Country:** United States **Facility:** Neurobehavioral Research, Inc. **State:** New York **Zip:** 11516 **Location 19:** **City:** Cincinnati **Country:** United States **Facility:** University of Cincinnati College of Medicine **State:** Ohio **Zip:** 45219 **Location 20:** **City:** Cleveland **Country:** United States **Facility:** University Hospitals Case Medical Center **State:** Ohio **Zip:** 44106 **Location 21:** **City:** San Antonio **Country:** United States **Facility:** Clinical Trials of Texas **State:** Texas **Zip:** 78229 **Location 22:** **City:** Bellevue **Country:** United States **Facility:** Northwest Clinical Research Center **State:** Washington **Zip:** 98007 #### Overall Officials **Official 1:** **Affiliation:** Premier Research Group plc **Name:** Denise Bedoya **Role:** STUDY_DIRECTOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000010335 - Term: Pathologic Processes - ID: D000040921 - Term: Stress Disorders, Traumatic - ID: D000068099 - Term: Trauma and Stressor Related Disorders - ID: D000001523 - Term: Mental Disorders ### Condition Browse Module - Browse Branches - Abbrev: BXM - Name: Behaviors and Mental Disorders - Abbrev: All - Name: All Conditions - Abbrev: BC26 - Name: Wounds and Injuries ### Condition Browse Module - Browse Leaves - ID: M16103 - Name: Stress Disorders, Post-Traumatic - Relevance: HIGH - As Found: PTSD - ID: M24916 - Name: Stress Disorders, Traumatic - Relevance: LOW - As Found: Unknown - ID: M17685 - Name: Wounds and Injuries - Relevance: LOW - As Found: Unknown - ID: M222 - Name: Trauma and Stressor Related Disorders - Relevance: LOW - As Found: Unknown - ID: M4815 - Name: Mental Disorders - Relevance: LOW - As Found: Unknown - ID: M14473 - Name: Psychotic Disorders - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000004194 - Term: Disease - ID: D000013313 - Term: Stress Disorders, Post-Traumatic ### Intervention Browse Module - Ancestors - ID: D000000929 - Term: Antidepressive Agents, Tricyclic - ID: D000000928 - Term: Antidepressive Agents - ID: D000011619 - Term: Psychotropic Drugs - ID: D000009125 - Term: Muscle Relaxants, Central - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000009465 - Term: Neuromuscular Agents - ID: D000018373 - Term: Peripheral Nervous System Agents - ID: D000014149 - Term: Tranquilizing Agents - ID: D000002492 - Term: Central Nervous System Depressants ### Intervention Browse Module - Browse Branches - Abbrev: CNSDep - Name: Central Nervous System Depressants - Abbrev: MuRelCen - Name: Muscle Relaxants, Central - Abbrev: PsychDr - Name: Psychotropic Drugs - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M228188 - Name: Cyclobenzaprine - Relevance: HIGH - As Found: Vortioxetine - ID: M4247 - Name: Antidepressive Agents - Relevance: LOW - As Found: Unknown - ID: M4248 - Name: Antidepressive Agents, Tricyclic - Relevance: LOW - As Found: Unknown - ID: M14474 - Name: Psychotropic Drugs - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: C000004704 - Term: Cyclobenzaprine ### Misc Info Module #### Submission Tracking - Estimated Results First Submit Date: 2024-04-30 ##### Submission Infos - MCP Release N: Unknown - Release Date: 2024-04-30 - Reset Date: Unknown - Unrelease Date: Unknown - Unrelease Date Unknown: Unknown - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT02656979 **Brief Title:** Blood Flow of Ophthalmic Artery and Glaucoma **Official Title:** Blood Flow of Ophthalmic Artery and Its Relationship to Structural Properties of the Optic Nerve and Intraocular Pressure in Glaucoma #### Organization Study ID Info **ID:** UmeaU #### Organization **Class:** OTHER **Full Name:** Umeå University ### Status Module #### Completion Date **Date:** 2019-09 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** RECRUITING #### Last Update Post Date **Date:** 2019-08-02 **Type:** ACTUAL **Last Update Submit Date:** 2019-08-01 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2019-09 **Type:** ESTIMATED #### Start Date **Date:** 2013-12 **Status Verified Date:** 2019-02 #### Study First Post Date **Date:** 2016-01-15 **Type:** ESTIMATED **Study First Submit Date:** 2015-12-15 **Study First Submit QC Date:** 2016-01-13 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Umeå University #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** The main purpose of this project is to investigate the blood flow of the ophthalmic artery (OA) in patients with ocular hypertension, high tension glaucoma and normal tension glaucoma. It is also to study the influence of the intraocular pressure difference on OA blood flow in the two first groups. Furthermore, the investigators want to understand the relationship between ocular dynamics, blood flow and structural alternations of the optic nerve head (ONH). The rationale behind the study is to improve knowledge of the pathogenesis of glaucoma. **Detailed Description:** The investigators will investigate the OA blood flow, intraocular pressure (IOP) and structural properties of the optic nerve. The investigators will include glaucoma patients as they believe that glaucoma may be caused by or influenced by OA blood flow. The investigators will include also patients with intraocular hypertension with and without pseudoexfoliation in order to study how changes in IOP interact with OA blood flow and the structural properties of the optic nerve in a group that does not develop glaucoma. In addition, the investigators will investigate patients that develop glaucoma in spite of a normal IOP. Therefore, the investigators will study three fundamentally different groups (G1, G2 and G3) of patients as well as a control group of healthy subjects (G4): G1: Newly diagnosed and untreated Glaucoma (optic and visual field damage exists). G2: Ocular hypertension with IOP ≥ 23 mmHg (i.e. only elevated eye pressure). G3: Normal Tension Glaucoma. G4: Healthy subjects. Each group will include 25 patients apart from G2 where 50 patients will be included, half of which have pseudoexfoliation syndrome. The study will be performed in accordance with the tenets of the Helsinki Declaration and is approved by the regional ethical board. Study protocol overview: Study protocol consists of two parts of examinations repeated with approximately one week between: Each part is divided into two examinations; one at the Department of radiology followed by one at the Department of ophthalmology. The measurements are repeated approximately one week later for G1 and G2. Day 1: First, MRI scans on the brain to measure the blood flow of OA as well as the structural and morphological properties of the ON (see method below). Second, just after MRI examination, the patient will be examined at the Department of ophthalmology. Measurement of intraocular pressure, ocular pulse amplitude, central corneal thickness, bulb length, investigation with optical coherence tomography (OCT) and blood pressure will be performed. The patients from G3 (Normal Pressure Glaucoma) will participate only in Day 1, since most cases already has pressure-lowering treatment. Also subjects in G4 vill only participate in Day 1. All other participants will receive pressure lowering drug (Latanoprost) in one eye once daily, until the protocol is repeated at Day 2. Day 2: The measurements at Day 1 are repeated approximately one week later. The measurements will be made in both eyes, which is why an eye can serve as a control. That way the investigators will have a good opportunity to assess how much of the change the investigators see in the treated eye that may be due to normal variations in OA blood flow and how much depends on the given treatment. The findings will be compared between the groups and to the normal material in G4. The investigators will be able to see whether, and if so, to what extent, eyes with glaucoma differ from normal eyes in terms of blood flow through OA as compared to the IOP measurements, and different biomechanical parameters of the eye. Thus, determine the pressure dynamics and calculate ocular compliance with the three different groups of research subjects; newly diagnosed glaucoma, ocular hypertension, normal tension glaucoma. ### Conditions Module **Conditions:** - Glaucoma **Keywords:** - Glaucoma - Blood flow - Pseudoexfoliation - Intraocular pressure - Brain perfusion - Magnetic Resonance Imaging ### Design Module #### Design Info **Allocation:** NON_RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** SINGLE **Who Masked:** - OUTCOMES_ASSESSOR **Primary Purpose:** DIAGNOSTIC #### Enrollment Info **Count:** 125 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** After measurement of blood flow with MRI and measurements of ocular parameters the patient receives the IOP lowering eye drop latanoprost once daily in one eye for approximately one week and then the measurements are are repeated in the same manner. **Intervention Names:** - Drug: Latanoprost **Label:** Blood flow pre&post IOP lowering **Type:** OTHER #### Arm Group 2 **Description:** The subjects will do blood flow measurements with MRI and measurements of ocular parameters only once. No intervention with IOP lowering drops. **Label:** Blood flow **Type:** NO_INTERVENTION ### Interventions #### Intervention 1 **Arm Group Labels:** - Blood flow pre&post IOP lowering **Description:** Between measurements on day 1 and day 2, the subjects will receive a drop of latanoprost which is an IOP lowering drug once daily in one eye. **Name:** Latanoprost **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Measure:** The blood flow (ml/min) of the ophthalmic artery in patients with different types of glaucoma/ocular hypertension and healthy individuals will be measured with MRI **Time Frame:** Up to four years #### Secondary Outcomes **Measure:** The change of ophthalmic artery blood flow (ml/min) after a reduction in IOP in glaucoma and intraocular hypertension will be measured with MRI **Time Frame:** Up to four years **Measure:** The change of structural properties (μm) of the optic nerve after a reduction in IOP in glaucoma and intraocular hypertension will be measured with MRI **Time Frame:** Up to four years **Measure:** Difference in the ophthalmic artery blood flow (ml/min) measured with MRI in patients with ocular hypertension with and without pseudoexfoliation. **Time Frame:** Up to four years ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Newly diagnosed and untreated glaucoma patients * Treated normal tension glaucoma patients * Untreated patients with ocular hypertension * Subjects with healthy eyes Exclusion Criteria: * Heart disease except treated hypertension * Intracranial pathology such as stroke, tumor, previous intracranial surgery * Insulin treated diabetes mellitus **Healthy Volunteers:** True **Maximum Age:** 85 Years **Minimum Age:** 55 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Gauti Jóhannesson, M.D., Ph.D. **Phone:** +46702200798 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Christina Lindén, M.D., Ph.D. **Phone:** +46907850000 **Role:** CONTACT #### Locations **Location 1:** **City:** Umeå **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Gauti Jóhannesson, M.D., Ph.D. - **Phone:** +46702200798 - **Role:** CONTACT **Country:** Sweden **Facility:** Department of Clinical Science, Ophthalmology, Umeå University **State:** Västerbotten **Status:** RECRUITING **Zip:** 90187 #### Overall Officials **Official 1:** **Affiliation:** Department of Clinical Science, Ophthalmology, Umeå University **Name:** Gauti Jóhannesson, M.D., Ph.D. **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009798 - Term: Ocular Hypertension - ID: D000005128 - Term: Eye Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC11 - Name: Eye Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC14 - Name: Heart and Blood Diseases ### Condition Browse Module - Browse Leaves - ID: M9013 - Name: Glaucoma - Relevance: HIGH - As Found: Glaucoma - ID: M10024 - Name: Hypertension - Relevance: LOW - As Found: Unknown - ID: M12731 - Name: Ocular Hypertension - Relevance: LOW - As Found: Unknown - ID: M8271 - Name: Eye Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000005901 - Term: Glaucoma ### Intervention Browse Module - Ancestors - ID: D000009883 - Term: Ophthalmic Solutions - ID: D000019999 - Term: Pharmaceutical Solutions ### Intervention Browse Module - Browse Branches - Abbrev: PhSol - Name: Pharmaceutical Solutions - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M12814 - Name: Ophthalmic Solutions - Relevance: LOW - As Found: Unknown - ID: M1775 - Name: Latanoprost - Relevance: HIGH - As Found: Brain Stimulation - ID: M21860 - Name: Pharmaceutical Solutions - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000077338 - Term: Latanoprost ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT02269579 **Brief Title:** Pharmacokinetic and Pharmacodynamic Assessment of Treatment With CPX-351 (Cytarabine: Daunorubicin) Liposome for Injection in Acute Leukemias and MDS Patients With Moderate Hepatic Impairment **Official Title:** An Open Label Phase II Pharmacokinetic and Pharmacodynamic Assessment of Treatment With CPX-351 (Cytarabine: Daunorubicin) Liposome for Injection in Acute Leukemias and MDS Patients With Moderate Hepatic Impairment #### Organization Study ID Info **ID:** CLTR0314-208 #### Organization **Class:** INDUSTRY **Full Name:** Jazz Pharmaceuticals ### Status Module #### Completion Date **Date:** 2017-06 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2018-03-14 **Type:** ACTUAL **Last Update Submit Date:** 2018-03-12 **Overall Status:** WITHDRAWN #### Primary Completion Date **Date:** 2017-06 **Type:** ESTIMATED #### Start Date **Date:** 2015-04 **Status Verified Date:** 2018-03 #### Study First Post Date **Date:** 2014-10-21 **Type:** ESTIMATED **Study First Submit Date:** 2014-10-14 **Study First Submit QC Date:** 2014-10-17 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Jazz Pharmaceuticals #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** To assess the impact of moderate hepatic impairment on cytarabine and daunorubicin pharmacokinetics and their metabolites following administration of CPX-351. ### Conditions Module **Conditions:** - Acute Myeloid Leukemia (AML) - Acute Lymphoblastic Leukemia (ALL) - Myelodysplastic Syndrome (MDS) **Keywords:** - Newly Diagnosed AML - Secondary AML - Relapsed/Refractory AML - Relapsed/Refractory ALL ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Type:** ACTUAL **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Study Drug CPX-351 will be given intravenously at 100u/m2 on days 1, 3 and 5 by approximately 90 minute infusion. **Intervention Names:** - Drug: CPX-351 **Label:** CPX-351 **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - CPX-351 **Name:** CPX-351 **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** The following parameters will be determined:Tmax, Cmax, AUC (0-last), AUC (0-inf), AUC (0-tau), Clast/λz, λz, t1/2, Vss and CL **Measure:** Total Drug Plasma PK **Time Frame:** Pre-dose and up to Day 21 during first induction only #### Secondary Outcomes **Description:** The following parameters will be determined:Tmax, Cmax, AUC (0-last), AUC (0-inf), AUC (0-tau), Clast/λz, λz, t1/2, Vss and CL **Measure:** Serum Copper Levels **Time Frame:** Pre-dose and up to Day 21 during the first induction only, prior to every course the patient receives, early termination or end of study and 60 day post end of study. **Measure:** Urine Sampling **Time Frame:** Days 5-10 during the first induction only. **Measure:** Efficacy and Safety **Time Frame:** Efficacy and Safety are measured up until the end of study period, SAEs are measured up to 30 days from the end of study period. ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Ability to understand and voluntarily sign an informed consent form * Age ≥ 18 to ≤ 80 years at the time of signing the informed consent form * Life expectancy of at least 3 months * Pathological confirmation by bone marrow documenting the following: * Newly Diagnosed De novo AML according to WHO criteria except for Acute Promyelocytic Leukemia or patients with known favorable cytogenetics * Newly Diagnosed Secondary AML defined as having a history of an antecedent hematologic disorder (myelodysplastic syndromes \[MDS\], myeloproliferative disease \[MPD\]or history of cytotoxic treatment for non-hematologic malignancy) * Patients with relapsed/refractory AML regardless of cytogenetic risk * Patients with relapsed/refractory ALL * Patients with MDS (IPSS score ≥ 1.5) * Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2 * Able to adhere to the study visit schedule and other protocol requirements * Laboratory values fulfilling the following: * Serum creatinine ≤ 2.0mg/dL. * Hepatic function with a score of 7-9 points according to the Child-Pugh System * Serum alanine aminotransferase or aspartate aminotransferase \< 3 times the ULN. Note:If elevated liver enzymes are related to disease; contact medical monitor to discuss. * Cardiac ejection fraction ≥50% by ECHO or MUGA * Patients with second malignancies in remission may be eligible if there is clinical evidence of disease stability for a period of greater than 6 months off cytotoxic chemotherapy, documented by imaging, tumor marker studies, etc., at screening. Patients maintained on long-term nonchemotherapy treatment, e.g., hormonal therapy, are eligible. * All men and women must agree to practice effective contraception during the study period if not otherwise documented to be infertile. Exclusion Criteria: * Patients with history of and/or current evidence of myocardial impairment (e.g. cardiomyopathy,ischemic heart disease, significant valvular dysfunction, hypertensive heart disease, and congestive heart failure) resulting in heart failure by New York Heart Association Criteria (Class III or IV staging) * Newly diagnosed patients with Acute promyelocytic leukemia \[t(15;17)\] or favorable cytogenetics, including t(8;21) or inv16 * Clinical evidence of active CNS leukemic involvement * Chemotherapy or other investigational anticancer therapeutic drugs within 1 week prior to study entry. AEs from prior therapy must have resolved or stabilized so that there is no interference with the assessment of efficacy or safety; in the event of rapidly proliferative disease, however, the use of hydroxyurea is permitted up to 12 hours before study entry. Patients with prior bone marrow or stem cell transplant, considered for inclusion, should be discussed with the medical monitor first. * Any serious medical condition or psychiatric illness that would prevent the patient from providing informed consent * Patients with prior cumulative anthracycline exposure of greater than 368 mg/m2 daunorubicin (or equivalent) * Active or uncontrolled infection. Patients with any infection receiving treatment (antibiotic,antifungal or antiviral treatment) may be entered into the study but must be afebrile and hemodynamically stable for ≥72 hrs. Patients with fevers believed to be due to leukemia or MDS are eligible provided a thorough infection work-up is negative and the patient is clinically and hemodynamically stable. * Pregnant or lactating women * Hypersensitivity to cytarabine, daunorubicin or liposomal products * History of Wilson's disease or other copper-related metabolic disorder **Maximum Age:** 80 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Los Angeles **Country:** United States **Facility:** Ronald Reagan UCLA Medical Center **State:** California **Zip:** 90095 **Location 2:** **City:** Gainesville **Country:** United States **Facility:** Shands Cancer Hospital @ University of Florida **State:** Florida **Zip:** 32610 **Location 3:** **City:** Indianapolis **Country:** United States **Facility:** Franciscan St. Francis Health **State:** Indiana **Zip:** 46237 **Location 4:** **City:** Hackensack **Country:** United States **Facility:** John Theurer Cancer Center @ Hackensack Medical University Medical Center **State:** New Jersey **Zip:** 07601 **Location 5:** **City:** Milwaukee **Country:** United States **Facility:** Medical College of Wisconsin **State:** Wisconsin **Zip:** 53226 #### Overall Officials **Official 1:** **Affiliation:** Jazz Pharmaceuticals **Name:** Clinical Trial Transparency **Role:** STUDY_DIRECTOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009370 - Term: Neoplasms by Histologic Type - ID: D000009369 - Term: Neoplasms - ID: D000006402 - Term: Hematologic Diseases - ID: D000007951 - Term: Leukemia, Myeloid - ID: D000001855 - Term: Bone Marrow Diseases - ID: D000011230 - Term: Precancerous Conditions - ID: D000007945 - Term: Leukemia, Lymphoid - ID: D000008232 - Term: Lymphoproliferative Disorders - ID: D000008206 - Term: Lymphatic Diseases - ID: D000007160 - Term: Immunoproliferative Disorders - ID: D000007154 - Term: Immune System Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC15 - Name: Blood and Lymph Conditions - Abbrev: All - Name: All Conditions - Abbrev: BC20 - Name: Immune System Diseases - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M10945 - Name: Leukemia - Relevance: HIGH - As Found: Leukemia - ID: M10955 - Name: Leukemia, Myeloid - Relevance: LOW - As Found: Unknown - ID: M18127 - Name: Leukemia, Myeloid, Acute - Relevance: HIGH - As Found: Acute Myeloid Leukemia (AML) - ID: M10951 - Name: Leukemia, Lymphoid - Relevance: LOW - As Found: Unknown - ID: M16355 - Name: Syndrome - Relevance: LOW - As Found: Unknown - ID: M27585 - Name: Precursor Cell Lymphoblastic Leukemia-Lymphoma - Relevance: HIGH - As Found: Acute Lymphoblastic Leukemia - ID: M12307 - Name: Neoplasm Metastasis - Relevance: LOW - As Found: Unknown - ID: M14164 - Name: Preleukemia - Relevance: HIGH - As Found: Myelodysplastic Syndrome (MDS) - ID: M12145 - Name: Myelodysplastic Syndromes - Relevance: HIGH - As Found: Myelodysplastic Syndrome (MDS) - ID: M11220 - Name: Lymphoma - Relevance: LOW - As Found: Unknown - ID: M12315 - Name: Neoplasms by Histologic Type - Relevance: LOW - As Found: Unknown - ID: M9490 - Name: Hematologic Diseases - Relevance: LOW - As Found: Unknown - ID: M5134 - Name: Bone Marrow Diseases - Relevance: LOW - As Found: Unknown - ID: M14111 - Name: Precancerous Conditions - Relevance: LOW - As Found: Unknown - ID: M11225 - Name: Lymphoproliferative Disorders - Relevance: LOW - As Found: Unknown - ID: M11203 - Name: Lymphatic Diseases - Relevance: LOW - As Found: Unknown - ID: M10206 - Name: Immunoproliferative Disorders - Relevance: LOW - As Found: Unknown - ID: M10200 - Name: Immune System Diseases - Relevance: LOW - As Found: Unknown - ID: T3995 - Name: Myeloid Leukemia - Relevance: LOW - As Found: Unknown - ID: T182 - Name: Acute Myeloid Leukemia - Relevance: HIGH - As Found: Acute Myeloid Leukemia (AML) - ID: T188 - Name: Acute Non Lymphoblastic Leukemia - Relevance: HIGH - As Found: Acute Myeloid Leukemia (AML) - ID: T175 - Name: Acute Lymphoblastic Leukemia - Relevance: HIGH - As Found: Acute Lymphoblastic Leukemia - ID: T3533 - Name: Lymphoblastic Lymphoma - Relevance: LOW - As Found: Unknown - ID: T170 - Name: Acute Graft Versus Host Disease - Relevance: LOW - As Found: Unknown - ID: T3993 - Name: Myelodysplastic Syndromes - Relevance: HIGH - As Found: Myelodysplastic Syndrome (MDS) - ID: T3543 - Name: Lymphosarcoma - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000007938 - Term: Leukemia - ID: D000015470 - Term: Leukemia, Myeloid, Acute - ID: D000011289 - Term: Preleukemia - ID: D000054198 - Term: Precursor Cell Lymphoblastic Leukemia-Lymphoma - ID: D000009190 - Term: Myelodysplastic Syndromes ### Intervention Browse Module - Browse Branches - Abbrev: Infe - Name: Anti-Infective Agents - Abbrev: ANeo - Name: Antineoplastic Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M6766 - Name: Cytarabine - Relevance: LOW - As Found: Unknown - ID: M6832 - Name: Daunorubicin - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03007979 **Brief Title:** Alternative Dosing Schedule of Palbociclib in Metastatic Hormone Receptor Positive Breast Cancer **Official Title:** A Phase II Clinical Trial Assessing the Safety of an Alternative Dosing Schedule of Palbociclib in Metastatic Hormone Receptor Positive Breast Cancer #### Organization Study ID Info **ID:** 201612098 #### Organization **Class:** OTHER **Full Name:** Washington University School of Medicine ### Status Module #### Completion Date **Date:** 2023-03-31 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2024-03-20 **Type:** ACTUAL **Last Update Submit Date:** 2024-02-23 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2020-03-13 **Type:** ACTUAL #### Results First Post Date **Date:** 2021-03-15 **Type:** ACTUAL **Results First Submit Date:** 2021-02-19 **Results First Submit QC Date:** 2021-02-19 #### Start Date **Date:** 2017-06-15 **Type:** ACTUAL **Status Verified Date:** 2024-02 #### Study First Post Date **Date:** 2017-01-02 **Type:** ESTIMATED **Study First Submit Date:** 2016-12-19 **Study First Submit QC Date:** 2016-12-28 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** Pfizer #### Lead Sponsor **Class:** OTHER **Name:** Washington University School of Medicine #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** True **Is US Export:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** The investigators propose to conduct a study to test an alternative dosing schedule of palbociclib. With the current three-week on and one week off schedule, a significant number of patients develop grade 3 or higher degree of neutropenia and require dose reduction and sometimes discontinuation. This potentially compromises the efficacy of the drug. In addition, as the half-life of palbociclib is 27 hours, 1 week break with the standard 3 weeks on and 1 week off dosing schedule could potentially lead to recovery of Rb phosphorylation during the off week. Hence, the investigators propose a 5 days on and 2 days off schedule each week without any weeks off drug. Although the cumulative doses each 28-day cycle is roughly the same with this schedule compared to conventional dosing, the bone marrow is not exposed to the drug continuously for 21 days and rather gets frequent breaks from therapy. The investigators hypothesize that the 5 days on and 2 days off schedule is more tolerable with less frequent high grade neutropenia and dose interruption/reduction. In addition, this schedule also provides for a more continuous drug delivery to the patient since there is not a week's break in therapy, which could ultimately prove to be more efficacious. ### Conditions Module **Conditions:** - Breast Cancer - Breast Carcinoma - Cancer of Breast - Malignant Tumor of Breast ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 55 **Type:** ACTUAL **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** * Palbociclib should be taken by mouth with food on a 5 days on/2 days off schedule (meaning: on Days 1-5, 8-12, 15-19, and 22-26 of each 28-day cycle). * Patients who are receiving letrozole will take it daily by mouth, every day of each 28-day cycle. * Patients who are receiving fulvestrant will receive it as two intramuscular injections (one into each buttock) on Days 1 and 15 of Cycle 1 and then on Day 1 of each cycle thereafter. * Goserelin is given as a subcutaneous injection every 28 days. It is preferred to be given on Day 1 of each cycle, but it may be administered on any day of the treatment cycle to accommodate its specific Q28-day cycle. It will be given to pre- or peri-menopausal women only. * Optional research biopsy at baseline and progression * Blood for research at baseline, cycle 1 day 15, cycle 2 day 1, every 2-3 months (to coincide with imaging studies), and time of progression **Intervention Names:** - Drug: Palbociclib - Drug: Letrozole - Drug: Fulvestrant - Procedure: Optional research biopsy - Drug: Goserelin - Procedure: Research blood draw - Procedure: Circulating tumor cell blood draw - Procedure: Tumor biopsy (optional) **Label:** Palbociclib + letrozole or + fulvestrant **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Palbociclib + letrozole or + fulvestrant **Description:** Palbociclib at a dose of 125 mg should be taken by mouth with food on a 5 days on/2 days off schedule **Name:** Palbociclib **Other Names:** - Ibrance **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Palbociclib + letrozole or + fulvestrant **Description:** Patients who are receiving letrozole will take it daily by mouth, every day of each 28-day cycle, at a dose of 2.5 mg. **Name:** Letrozole **Other Names:** - Femara **Type:** DRUG #### Intervention 3 **Arm Group Labels:** - Palbociclib + letrozole or + fulvestrant **Description:** Patients who are receiving fulvestrant will receive it at a dose of 500 mg as two 5 mL intramuscular injections (one into each buttock) on Days 1 and 15 of Cycle 1 and then on Day 1 of each cycle thereafter. **Name:** Fulvestrant **Other Names:** - Faslodex **Type:** DRUG #### Intervention 4 **Arm Group Labels:** - Palbociclib + letrozole or + fulvestrant **Description:** Patients may consent to paired tumor biopsies at baseline and time of progression. **Name:** Optional research biopsy **Type:** PROCEDURE #### Intervention 5 **Arm Group Labels:** - Palbociclib + letrozole or + fulvestrant **Description:** Goserelin is given as a subcutaneous injection every 28 days. It is preferred to be given on Day 1 of each cycle, but it may be administered on any day of the treatment cycle to accommodate its specific Q28-day cycle. It will be given to pre- and peri-menopausal women only. **Name:** Goserelin **Other Names:** - Zoladex **Type:** DRUG #### Intervention 6 **Arm Group Labels:** - Palbociclib + letrozole or + fulvestrant **Description:** -Blood will be drawn at the following time points for serum, plasma, cfDNA, and germline DNA (only at baseline): * Baseline * C1D15 * C2D1 * Every 2-3 months thereafter (to coincide with imaging studies) * Time of progression **Name:** Research blood draw **Type:** PROCEDURE #### Intervention 7 **Arm Group Labels:** - Palbociclib + letrozole or + fulvestrant **Description:** -Baseline, cycle 2 day 1, post 2 or 3 months of therapy (to coincide with first tumor imaging), and progression **Name:** Circulating tumor cell blood draw **Type:** PROCEDURE #### Intervention 8 **Arm Group Labels:** - Palbociclib + letrozole or + fulvestrant **Description:** -Baseline and progression **Name:** Tumor biopsy (optional) **Type:** PROCEDURE ### Outcomes Module #### Primary Outcomes **Description:** * The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting. * Grade 3 neutropenia: \<1000-500/mm\^3; \<1.0-0.5 x 10e9/L * Grade 4 neutropenia: \<500/mm\^3; \<0.5 x 10e9/L **Measure:** Rate of Grade 3 or Higher Neutropenia **Time Frame:** Through the first 29 days of treatment #### Secondary Outcomes **Description:** * The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting. * Grade 3 neutropenia: \<1000-500/mm\^3; \<1.0-0.5 x 10e9/L * Grade 4 neutropenia: \<500/mm\^3; \<0.5 x 10e9/L **Measure:** Rate of Grade 3 or Higher Neutropenia **Time Frame:** Through 30 day follow-up (estimated to be 25 months) **Description:** -Percentage of participants who have a palbociclib dose reduction during treatment **Measure:** Rate of Palbociclib Dose Reduction **Time Frame:** Through the completion of treatment (estimated to be 24 months) **Description:** -Percentage of participants who have a palbociclib dose interruption during treatment **Measure:** Rate of Palbociclib Dose Interruption **Time Frame:** Through the completion of treatment (estimated to be 24 months) **Description:** -Percentage of participants who discontinue palbociclib due to adverse event **Measure:** Rate of Palbociclib Discontinuation **Time Frame:** Through the completion of treatment (estimated to be 24 months) **Description:** * The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting. * Relationship of possible, probably, or definitely related. **Measure:** Adverse Event Profile of Palbociclib **Time Frame:** Through the 30 day follow-up (estimated to be 25 months) **Description:** * PFS will be followed from start of treatment to time of progression or death, whichever occurs first. * Progressive disease: At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions). **Measure:** Kaplan-Meier Estimate of Progression-free Survival (PFS) **Time Frame:** 1 year **Description:** * Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm, dDisappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (\<10 mm short axis). * Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters **Measure:** Overall Response Rate (Complete Response + Partial Response) **Time Frame:** Time of progression (estimated to be 24 months) **Description:** * Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm, dDisappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (\<10 mm short axis). * Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters * Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. **Measure:** Clinical Benefit Rate (Complete Response + Partial Response + Stable Disease) for at Least 6 Months) **Time Frame:** Time of progression (estimated to be 24 months) ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Histologically confirmed metastatic ER+ and/or PR+ and HER2- breast cancer who are candidates for palbociclib in combination with either letrozole or fulvestrant per treating physician. * Presence of measurable or non-measurable disease by RECIST 1.1 criteria. * One prior systemic therapy in the metastatic setting is allowed, but patients who have not had any prior systemic therapies in the metastatic setting are also eligible. \*Note: patients who were started on endocrine therapy monotherapy as their 1st line or 2nd line systemic therapy in the metastatic setting for no more than 28 days and without clinical progression prior to the initiation of the study drug therapy are allowed to enroll on the study as their 1st line or 2nd line therapy, respectively. * At least 18 years of age. * Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 * Normal bone marrow and organ function as defined below: * Absolute neutrophil count ≥ 1,500/mcl * Platelets ≥ 100,000/mcl * Total bilirubin ≤ institutional upper limit of normal (IULN) or total bilirubin ≤ 3.0 x IULN with direct bilirubin within normal range in patients with documented Gilbert's syndrome * AST(SGOT)/ALT(SGPT) ≤ 1.5 x IULN (up to 5 x IULN in patients with liver disease) * Creatinine ≤ IULN OR creatinine clearance ≥ 60 mL/min/1.73 m2 for patients with serum creatinine levels above institutional normal (calculated by Creatinine Clearance Estimate by Cockcroft-Gault Equation) * Pre- or post-menopausal women are allowed. If pre- or peri-menopausal, concurrent ovarian suppression for pre- or peri-menopausal women is required. * Women of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately. * Able to swallow and retain oral medication. * Washout of at least 3 weeks from prior chemotherapy or targeted therapy that induces myelosuppression and recovery of treatment related adverse events to grade 1 or less, with the exception of alopecia, is required prior to the start of palbociclib. * Ability to understand and willingness to sign an Institutional Review Board (IRB) approved written informed consent document (or that of legally authorized representative, if applicable). Exclusion Criteria: * Prior therapy with any CDK inhibitor. * Currently receiving any other investigational agents. * Currently receiving exogenous estrogen replacement (topical vaginal estrogen therapy is allowed). * Known brain metastases. Patients with known brain metastases must be excluded from this clinical trial because of their poor prognosis which could affect the evaluation of all-cycle adverse events. * A history of allergic reactions attributed to compounds of similar chemical or biologic composition to palbociclib or other agents used in the study. * Receiving any medications or substances that are potent inhibitors or inducers of CYP3A isoenzymes within 7 days prior to registration. * Clinically significant history of liver disease. * A condition that would interfere with enteric absorption. * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia. * Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 7 days of study entry. * Known HIV-positivity on combination antiretroviral therapy because of the potential for pharmacokinetic interactions with palbociclib. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated. **Minimum Age:** 18 Years **Sex:** FEMALE **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Saint Louis **Country:** United States **Facility:** Washington University School of Medicine **State:** Missouri **Zip:** 63110 **Location 2:** **City:** Lincoln **Country:** United States **Facility:** University of Nebraska **State:** Nebraska **Zip:** 68588 #### Overall Officials **Official 1:** **Affiliation:** Washington University School of Medicine **Name:** Cynthia X Ma, M.D., Ph.D. **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Krishnamurthy J, Luo J, Suresh R, Ademuyiwa F, Rigden C, Rearden T, Clifton K, Weilbaecher K, Frith A, Roshal A, Tandra PK, Cherian M, Summa T, Haas B, Thomas S, Hernandez-Aya L, Bergqvist M, Peterson L, Ma CX. A phase II trial of an alternative schedule of palbociclib and embedded serum TK1 analysis. NPJ Breast Cancer. 2022 Mar 21;8(1):35. doi: 10.1038/s41523-022-00399-w. **PMID:** 35314693 #### See Also Links **Label:** Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine **URL:** http://www.siteman.wustl.edu ## Document Section ### Large Document Module #### Large Docs - Date: 2019-04-12 - Filename: Prot_SAP_000.pdf - Has ICF: False - Has Protocol: True - Has SAP: True - Label: Study Protocol and Statistical Analysis Plan - Size: 737485 - Type Abbrev: Prot_SAP - Upload Date: 2021-01-15T10:17 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009371 - Term: Neoplasms by Site - ID: D000009369 - Term: Neoplasms - ID: D000001941 - Term: Breast Diseases - ID: D000012871 - Term: Skin Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC17 - Name: Skin and Connective Tissue Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M5220 - Name: Breast Neoplasms - Relevance: HIGH - As Found: Breast Cancer - ID: M5534 - Name: Carcinoma - Relevance: LOW - As Found: Unknown - ID: M5218 - Name: Breast Diseases - Relevance: LOW - As Found: Unknown - ID: M15674 - Name: Skin Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000001943 - Term: Breast Neoplasms ### Intervention Browse Module - Ancestors - ID: D000000970 - Term: Antineoplastic Agents - ID: D000047072 - Term: Aromatase Inhibitors - ID: D000065088 - Term: Steroid Synthesis Inhibitors - ID: D000004791 - Term: Enzyme Inhibitors - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000004965 - Term: Estrogen Antagonists - ID: D000006727 - Term: Hormone Antagonists - ID: D000006730 - Term: Hormones, Hormone Substitutes, and Hormone Antagonists - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000018931 - Term: Antineoplastic Agents, Hormonal - ID: D000065171 - Term: Estrogen Receptor Antagonists - ID: D000047428 - Term: Protein Kinase Inhibitors ### Intervention Browse Module - Browse Branches - Abbrev: ANeo - Name: Antineoplastic Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M1723 - Name: Fulvestrant - Relevance: HIGH - As Found: Partial - ID: M1743 - Name: Letrozole - Relevance: HIGH - As Found: Medicine - ID: M9789 - Name: Hormones - Relevance: LOW - As Found: Unknown - ID: M223893 - Name: Palbociclib - Relevance: HIGH - As Found: Youth - ID: M19568 - Name: Goserelin - Relevance: HIGH - As Found: Transcranial Direct Current Stimulation - ID: M25769 - Name: Aromatase Inhibitors - Relevance: LOW - As Found: Unknown - ID: M7951 - Name: Enzyme Inhibitors - Relevance: LOW - As Found: Unknown - ID: M8116 - Name: Estrogens - Relevance: LOW - As Found: Unknown - ID: M8114 - Name: Estrogen Antagonists - Relevance: LOW - As Found: Unknown - ID: M30483 - Name: Estrogen Receptor Antagonists - Relevance: LOW - As Found: Unknown - ID: M9788 - Name: Hormone Antagonists - Relevance: LOW - As Found: Unknown - ID: M20966 - Name: Antineoplastic Agents, Hormonal - Relevance: LOW - As Found: Unknown - ID: M25820 - Name: Protein Kinase Inhibitors - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000077289 - Term: Letrozole - ID: D000077267 - Term: Fulvestrant - ID: C000500026 - Term: Palbociclib - ID: D000017273 - Term: Goserelin ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module #### Event Groups **Group ID:** EG000 **Title:** Palbociclib + Letrozole or + Fulvestrant **Deaths Num Affected:** 3 **Deaths Num At Risk:** 54 **Description:** * Palbociclib should be taken by mouth with food on a 5 days on/2 days off schedule (meaning: on Days 1-5, 8-12, 15-19, and 22-26 of each 28-day cycle). * Patients who are receiving letrozole will take it daily by mouth, every day of each 28-day cycle. * Patients who are receiving fulvestrant will receive it as two intramuscular injections (one into each buttock) on Days 1 and 15 of Cycle 1 and then on Day 1 of each cycle thereafter. * Goserelin is given as a subcutaneous injection every 28 days. It is preferred to be given on Day 1 of each cycle, but it may be administered on any day of the treatment cycle to accommodate its specific Q28-day cycle. It will be given to pre- or peri-menopausal women only. * Optional research biopsy at baseline and progression * Blood for research at baseline, cycle 1 day 15, cycle 2 day 1, every 2-3 months (to coincide with imaging studies), and time of progression **ID:** EG000 **Other Num Affected:** 54 **Other Num at Risk:** 54 **Serious Number Affected:** 15 **Serious Number At Risk:** 54 **Title:** Palbociclib + Letrozole or + Fulvestrant **Frequency Threshold:** 0 #### Other Events **Term:** Anemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Gout **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Chest pain - cardiac **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Sinus tachycardia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Tinnitus **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Ear and labyrinth disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Vertigo **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Ear and labyrinth disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Blurred vision **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Eye disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Cataract **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Eye disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Dry eye **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Eye disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Eye lid pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Eye disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Photophobia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Eye disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Red eye **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Eye disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Watering eyes **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Eye disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Abdominal pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Broken tooth **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (4.0) **Term:** C. difficile **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Constipation **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Diarrhea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Dry lips **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Dry mouth **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Dyspepsia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Dysphagia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Gastric ulcer **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Gastroesophageal reflux disease **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Gingival pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Hematochezia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Hemorrhoidal hemorrhage **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Hemorrhoids **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Mucositis oral **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Nausea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Oral dysesthesia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Oral pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Stomach pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Toothache **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Vomiting **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Breast pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Buttock pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Chills **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Cold sensitivity **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Cold sweats **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Common cold **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Dilation of appendix with periappendiceal fat stranding seen on CT **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Edema face **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Edema limbs **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Edema trunk **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Fatigue **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Fever **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Flu-like symptoms **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Gait disturbance **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Generalized weakness **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Groin pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Intrascapular pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Leg pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Localized edema **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Non-cardiac chest pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Wrist pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Allergic reaction **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Immune system disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Bladder infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** CTCAE (4.0) **Term:** Bronchitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** CTCAE (4.0) **Term:** COVID-19 **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** CTCAE (4.0) **Term:** Diverticulitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** CTCAE (4.0) **Term:** Fungal toe infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** CTCAE (4.0) **Term:** Lung infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** CTCAE (4.0) **Term:** Otitis media **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** CTCAE (4.0) **Term:** Paronychia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** CTCAE (4.0) **Term:** Pharyngitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** CTCAE (4.0) **Term:** Respiratory syncytial virus (RSV) **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** CTCAE (4.0) **Term:** Rhinovirus **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** CTCAE (4.0) **Term:** Sepsis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** CTCAE (4.0) **Term:** Sinusitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** CTCAE (4.0) **Term:** Skin infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** CTCAE (4.0) **Term:** Tooth infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** CTCAE (4.0) **Term:** Upper respiratory infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** CTCAE (4.0) **Term:** Urinary tract infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** CTCAE (4.0) **Term:** Vaginal infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** CTCAE (4.0) **Term:** Wound infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** CTCAE (4.0) **Term:** Yeast infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** CTCAE (4.0) **Term:** Bruising **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** CTCAE (4.0) **Term:** Bug bite **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** CTCAE (4.0) **Term:** Burn **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** CTCAE (4.0) **Term:** Fall **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** CTCAE (4.0) **Term:** Fracture **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** CTCAE (4.0) **Term:** Head injury **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** CTCAE (4.0) **Term:** Puncture wound **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** CTCAE (4.0) **Term:** Radiation recall reaction (dermatologic) **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** CTCAE (4.0) **Term:** Snake bite **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** CTCAE (4.0) **Term:** Wrist fracture **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** CTCAE (4.0) **Term:** Activated partial thromboplastin time prolonged **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** CTCAE (4.0) **Term:** Alanine aminotransferase increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** CTCAE (4.0) **Term:** Alkaline phosphatase increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** CTCAE (4.0) **Term:** Aspartate aminotransferase increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** CTCAE (4.0) **Term:** Blood bilirubin increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** CTCAE (4.0) **Term:** Creatinine increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** CTCAE (4.0) **Term:** Hemoglobin increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** CTCAE (4.0) **Term:** INR increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** CTCAE (4.0) **Term:** Lymphocyte count decreased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** CTCAE (4.0) **Term:** Lymphocyte count increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** CTCAE (4.0) **Term:** Neutrophil count decreased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** CTCAE (4.0) **Term:** Platelet count decreased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** CTCAE (4.0) **Term:** Weight gain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** CTCAE (4.0) **Term:** Weight loss **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** CTCAE (4.0) **Term:** White blood cell count decreased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** CTCAE (4.0) **Term:** Anorexia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Dehydration **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Hypercalcemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Hyperglycemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Hyperkalemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Hypermagnesemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Hypernatremia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Hyperuricemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Hypoalbuminemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Hypocalcemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Hypoglycemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Hypokalemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Hypomagnesemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Hyponatremia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Hypophosphatemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Arthralgia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Arthritis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Back pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Back spasms **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Bone pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Chest wall pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Generalized muscle weakness **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Knee pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Leg stiffness **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Muscle cramp **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Muscle weakness lower limb **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Myalgia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Neck pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Osteonecrosis of jaw **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Pain in extremity **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Sacroliac joint pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Shoulder pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Lung cancer **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** CTCAE (4.0) **Term:** Dizziness **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Dysgeusia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Facial nerve disorder **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Headache **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Memory impairment **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Paresthesia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Peripheral sensory neuropathy **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Right arm numbness **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Sinus pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Spasticity **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Syncope **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Agitation **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Anxiety **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Confusion **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Depression **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Hallucinations **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Insomnia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Mood swings **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Urinary frequency **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Urinary retention **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Urine discoloration **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Vaginal discharge **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Reproductive system and breast disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Vaginal dryness **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Reproductive system and breast disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Vaginal itching **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Reproductive system and breast disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Allergic rhinitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** CTCAE (4.0) **Term:** COPD **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Cough **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Dyspnea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Epistaxis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Hoarseness **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Laryngeal inflammation **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Nasal congestion **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Nasal drainage **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Nasal dryness **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Pleural effusion **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Postnasal drip **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Productive cough **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Sinus congestion **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Sore throat **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Voice alteration **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Alopecia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Bilateral nares sores **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Blister **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Brittle nail **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Dry skin **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Erythema multiforme **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Erythema right breast **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Fever blister **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Hyperhidrosis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Itchy skin **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Nail loss **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Oral fissure **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Rash acneiform **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Rash maculopapular **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Shoulder nodule **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Skin bump **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Stomach rash **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Tender nail bed **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Hot flashes **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Hypertension **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Lymphedema **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Thromboembolic event **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** CTCAE (4.0) #### Serious Events **Term:** Chest pain - cardiac **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** CTCAE (4.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 54 **Term:** Myocardial infarction **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** CTCAE (4.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 54 **Term:** Constipation **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (4.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 54 **Term:** Dysphagia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (4.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 54 **Term:** Nausea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (4.0) ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 54 **Term:** Vomiting **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (4.0) ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 54 **Term:** Death **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (4.0) ##### Stats **Group ID:** EG000 **Num Affected:** 3 **Num At Risk:** 54 **Term:** Fever **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (4.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 54 **Term:** Generalized weakness **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (4.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 54 **Term:** Cellulitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** CTCAE (4.0) ##### Stats **Group ID:** EG000 **Num Affected:** 3 **Num At Risk:** 54 **Term:** Sepsis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** CTCAE (4.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 54 **Term:** Urinary tract infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** CTCAE (4.0) ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 54 **Term:** Alanine aminotransferase increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** CTCAE (4.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 54 **Term:** Aspartate aminotransferase increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** CTCAE (4.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 54 **Term:** Back pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** CTCAE (4.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 54 **Term:** Bone pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** CTCAE (4.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 54 **Term:** Flank pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** CTCAE (4.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 54 **Term:** Pain in extremity **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** CTCAE (4.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 54 **Term:** Cognitive disturbance **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** CTCAE (4.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 54 **Term:** Acute kidney injury **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** CTCAE (4.0) ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 54 **Term:** Dyspnea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** CTCAE (4.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 54 **Term:** Hypotension **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** CTCAE (4.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 54 **Term:** Superficial thrombophlebitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** CTCAE (4.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 54 **Term:** Thromboembolic event **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** CTCAE (4.0) ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 54 **Time Frame:** Adverse events were collected from start of treatment through 30 days following completion of treatment. ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 55 **Units:** Participants ### Group **ID:** BG000 **Title:** Palbociclib + Letrozole or + Fulvestrant **Description:** * Palbociclib should be taken by mouth with food on a 5 days on/2 days off schedule (meaning: on Days 1-5, 8-12, 15-19, and 22-26 of each 28-day cycle). * Patients who are receiving letrozole will take it daily by mouth, every day of each 28-day cycle. * Patients who are receiving fulvestrant will receive it as two intramuscular injections (one into each buttock) on Days 1 and 15 of Cycle 1 and then on Day 1 of each cycle thereafter. * Goserelin is given as a subcutaneous injection every 28 days. It is preferred to be given on Day 1 of each cycle, but it may be administered on any day of the treatment cycle to accommodate its specific Q28-day cycle. It will be given to pre- or peri-menopausal women only. * Optional research biopsy at baseline and progression * Blood for research at baseline, cycle 1 day 15, cycle 2 day 1, every 2-3 months (to coincide with imaging studies), and time of progression ### Measure #### Measurement **Group ID:** BG000 **Lower Limit:** 34 **Upper Limit:** 86 **Value:** 61 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 55 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 0 **Category Title:** Male **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 0 **Category Title:** Hispanic or Latino #### Measurement **Group ID:** BG000 **Value:** 55 **Category Title:** Not Hispanic or Latino #### Measurement **Group ID:** BG000 **Value:** 0 **Category Title:** Unknown or Not Reported **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 0 **Category Title:** American Indian or Alaska Native #### Measurement **Group ID:** BG000 **Value:** 0 **Category Title:** Asian #### Measurement **Group ID:** BG000 **Value:** 0 **Category Title:** Native Hawaiian or Other Pacific Islander #### Measurement **Group ID:** BG000 **Value:** 10 **Category Title:** Black or African American #### Measurement **Group ID:** BG000 **Value:** 45 **Category Title:** White #### Measurement **Group ID:** BG000 **Value:** 0 **Category Title:** More than one race #### Measurement **Group ID:** BG000 **Value:** 0 **Category Title:** Unknown or Not Reported **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 55 **Class Title:** United States **Denomination Units Selected:** ## Results Section - Baseline Characteristics Module ### Measure 1 **Dispersion Type:** FULL_RANGE **Parameter Type:** MEDIAN **Title:** Age, Continuous **Unit of Measure:** years ### Measure 2 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Sex: Female, Male **Unit of Measure:** Participants ### Measure 3 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Ethnicity (NIH/OMB) **Unit of Measure:** Participants ### Measure 4 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Race (NIH/OMB) **Unit of Measure:** Participants ### Measure 5 **Parameter Type:** NUMBER **Title:** Region of Enrollment **Unit of Measure:** participants ## Results Section - More Information Module ### Certain Agreement **PI Sponsor Employee:** True ### Point of Contact **Email:** [email protected] **Organization:** Washington University School of Medicine **Phone:** 314-362-9383 **Title:** Cynthia X. Ma, M.D., Ph.D. ## Results Section - Outcome Measures Module ### Outcome Measure 1 ### Outcome Measure 2 ### Outcome Measure 3 ### Outcome Measure 4 ### Outcome Measure 5 ### Outcome Measure 6 ### Outcome Measure 7 ### Outcome Measure 8 ### Outcome Measure 9 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 10 **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 23 **Title:** #### Outcome Measure 3 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 13 **Title:** #### Outcome Measure 4 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 39 **Title:** #### Outcome Measure 5 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 **Title:** #### Outcome Measure 6 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 31 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 5 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 8 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 11 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 16 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 7 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 22 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 23 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 13 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 22 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 24 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 21 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 26 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 26 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 6 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 5 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 19 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 12 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** #### Outcome Measure 7 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 52.934 - **Spread:** - **Upper Limit:** 79.025 - **Value:** 67.911 **Title:** #### Outcome Measure 8 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 18 **Title:** #### Outcome Measure 9 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 45 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** * The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting. * Grade 3 neutropenia: \<1000-500/mm\^3; \<1.0-0.5 x 10e9/L * Grade 4 neutropenia: \<500/mm\^3; \<0.5 x 10e9/L **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** The following participants were not evaluable for this outcome measure: 4 participants did not take palbociclib dose as per protocol and were without dose-limiting toxicity; 2 participants withdrew in cycle 1, and 1 participant went off treatment in cycle 1 due to adverse events unrelated to the study. **Reporting Status:** POSTED **Time Frame:** Through the first 29 days of treatment **Title:** Rate of Grade 3 or Higher Neutropenia **Type:** PRIMARY **Unit of Measure:** Participants ##### Group **Description:** * Palbociclib should be taken by mouth with food on a 5 days on/2 days off schedule (meaning: on Days 1-5, 8-12, 15-19, and 22-26 of each 28-day cycle). * Patients who are receiving letrozole will take it daily by mouth, every day of each 28-day cycle. * Patients who are receiving fulvestrant will receive it as two intramuscular injections (one into each buttock) on Days 1 and 15 of Cycle 1 and then on Day 1 of each cycle thereafter. * Goserelin is given as a subcutaneous injection every 28 days. It is preferred to be given on Day 1 of each cycle, but it may be administered on any day of the treatment cycle to accommodate its specific Q28-day cycle. It will be given to pre- or peri-menopausal women only. * Optional research biopsy at baseline and progression * Blood for research at baseline, cycle 1 day 15, cycle 2 day 1, every 2-3 months (to coincide with imaging studies), and time of progression **ID:** OG000 **Title:** Palbociclib + Letrozole or + Fulvestrant #### Outcome Measure 2 **Description:** * The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting. * Grade 3 neutropenia: \<1000-500/mm\^3; \<1.0-0.5 x 10e9/L * Grade 4 neutropenia: \<500/mm\^3; \<0.5 x 10e9/L **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** The following participants were not evaluable for this outcome measure: 4 participants did not take palbociclib dose as per protocol and were without dose-limiting toxicity; 2 participants withdrew in cycle 1, and 1 participant went off treatment in cycle 1 due to adverse events unrelated to the study. **Reporting Status:** POSTED **Time Frame:** Through 30 day follow-up (estimated to be 25 months) **Title:** Rate of Grade 3 or Higher Neutropenia **Type:** SECONDARY **Unit of Measure:** Participants ##### Group **Description:** * Palbociclib should be taken by mouth with food on a 5 days on/2 days off schedule (meaning: on Days 1-5, 8-12, 15-19, and 22-26 of each 28-day cycle). * Patients who are receiving letrozole will take it daily by mouth, every day of each 28-day cycle. * Patients who are receiving fulvestrant will receive it as two intramuscular injections (one into each buttock) on Days 1 and 15 of Cycle 1 and then on Day 1 of each cycle thereafter. * Goserelin is given as a subcutaneous injection every 28 days. It is preferred to be given on Day 1 of each cycle, but it may be administered on any day of the treatment cycle to accommodate its specific Q28-day cycle. It will be given to pre- or peri-menopausal women only. * Optional research biopsy at baseline and progression * Blood for research at baseline, cycle 1 day 15, cycle 2 day 1, every 2-3 months (to coincide with imaging studies), and time of progression **ID:** OG000 **Title:** Palbociclib + Letrozole or + Fulvestrant #### Outcome Measure 3 **Description:** -Percentage of participants who have a palbociclib dose reduction during treatment **Parameter Type:** COUNT_OF_PARTICIPANTS **Reporting Status:** POSTED **Time Frame:** Through the completion of treatment (estimated to be 24 months) **Title:** Rate of Palbociclib Dose Reduction **Type:** SECONDARY **Unit of Measure:** Participants ##### Group **Description:** * Palbociclib should be taken by mouth with food on a 5 days on/2 days off schedule (meaning: on Days 1-5, 8-12, 15-19, and 22-26 of each 28-day cycle). * Patients who are receiving letrozole will take it daily by mouth, every day of each 28-day cycle. * Patients who are receiving fulvestrant will receive it as two intramuscular injections (one into each buttock) on Days 1 and 15 of Cycle 1 and then on Day 1 of each cycle thereafter. * Goserelin is given as a subcutaneous injection every 28 days. It is preferred to be given on Day 1 of each cycle, but it may be administered on any day of the treatment cycle to accommodate its specific Q28-day cycle. It will be given to pre- or peri-menopausal women only. * Optional research biopsy at baseline and progression * Blood for research at baseline, cycle 1 day 15, cycle 2 day 1, every 2-3 months (to coincide with imaging studies), and time of progression **ID:** OG000 **Title:** Palbociclib + Letrozole or + Fulvestrant #### Outcome Measure 4 **Description:** -Percentage of participants who have a palbociclib dose interruption during treatment **Parameter Type:** COUNT_OF_PARTICIPANTS **Reporting Status:** POSTED **Time Frame:** Through the completion of treatment (estimated to be 24 months) **Title:** Rate of Palbociclib Dose Interruption **Type:** SECONDARY **Unit of Measure:** Participants ##### Group **Description:** * Palbociclib should be taken by mouth with food on a 5 days on/2 days off schedule (meaning: on Days 1-5, 8-12, 15-19, and 22-26 of each 28-day cycle). * Patients who are receiving letrozole will take it daily by mouth, every day of each 28-day cycle. * Patients who are receiving fulvestrant will receive it as two intramuscular injections (one into each buttock) on Days 1 and 15 of Cycle 1 and then on Day 1 of each cycle thereafter. * Goserelin is given as a subcutaneous injection every 28 days. It is preferred to be given on Day 1 of each cycle, but it may be administered on any day of the treatment cycle to accommodate its specific Q28-day cycle. It will be given to pre- or peri-menopausal women only. * Optional research biopsy at baseline and progression * Blood for research at baseline, cycle 1 day 15, cycle 2 day 1, every 2-3 months (to coincide with imaging studies), and time of progression **ID:** OG000 **Title:** Palbociclib + Letrozole or + Fulvestrant #### Outcome Measure 5 **Description:** -Percentage of participants who discontinue palbociclib due to adverse event **Parameter Type:** COUNT_OF_PARTICIPANTS **Reporting Status:** POSTED **Time Frame:** Through the completion of treatment (estimated to be 24 months) **Title:** Rate of Palbociclib Discontinuation **Type:** SECONDARY **Unit of Measure:** Participants ##### Group **Description:** * Palbociclib should be taken by mouth with food on a 5 days on/2 days off schedule (meaning: on Days 1-5, 8-12, 15-19, and 22-26 of each 28-day cycle). * Patients who are receiving letrozole will take it daily by mouth, every day of each 28-day cycle. * Patients who are receiving fulvestrant will receive it as two intramuscular injections (one into each buttock) on Days 1 and 15 of Cycle 1 and then on Day 1 of each cycle thereafter. * Goserelin is given as a subcutaneous injection every 28 days. It is preferred to be given on Day 1 of each cycle, but it may be administered on any day of the treatment cycle to accommodate its specific Q28-day cycle. It will be given to pre- or peri-menopausal women only. * Optional research biopsy at baseline and progression * Blood for research at baseline, cycle 1 day 15, cycle 2 day 1, every 2-3 months (to coincide with imaging studies), and time of progression **ID:** OG000 **Title:** Palbociclib + Letrozole or + Fulvestrant #### Outcome Measure 6 **Description:** * The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting. * Relationship of possible, probably, or definitely related. **Parameter Type:** COUNT_OF_PARTICIPANTS **Reporting Status:** POSTED **Time Frame:** Through the 30 day follow-up (estimated to be 25 months) **Title:** Adverse Event Profile of Palbociclib **Type:** SECONDARY **Unit of Measure:** Participants ##### Group **Description:** * Palbociclib should be taken by mouth with food on a 5 days on/2 days off schedule (meaning: on Days 1-5, 8-12, 15-19, and 22-26 of each 28-day cycle). * Patients who are receiving letrozole will take it daily by mouth, every day of each 28-day cycle. * Patients who are receiving fulvestrant will receive it as two intramuscular injections (one into each buttock) on Days 1 and 15 of Cycle 1 and then on Day 1 of each cycle thereafter. * Goserelin is given as a subcutaneous injection every 28 days. It is preferred to be given on Day 1 of each cycle, but it may be administered on any day of the treatment cycle to accommodate its specific Q28-day cycle. It will be given to pre- or peri-menopausal women only. * Optional research biopsy at baseline and progression * Blood for research at baseline, cycle 1 day 15, cycle 2 day 1, every 2-3 months (to coincide with imaging studies), and time of progression **ID:** OG000 **Title:** Palbociclib + Letrozole or + Fulvestrant #### Outcome Measure 7 **Description:** * PFS will be followed from start of treatment to time of progression or death, whichever occurs first. * Progressive disease: At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions). **Dispersion Type:** 95% Confidence Interval **Parameter Type:** NUMBER **Reporting Status:** POSTED **Time Frame:** 1 year **Title:** Kaplan-Meier Estimate of Progression-free Survival (PFS) **Type:** SECONDARY **Unit of Measure:** percentage of participants-Kaplan Meier ##### Group **Description:** * Palbociclib should be taken by mouth with food on a 5 days on/2 days off schedule (meaning: on Days 1-5, 8-12, 15-19, and 22-26 of each 28-day cycle). * Patients who are receiving letrozole will take it daily by mouth, every day of each 28-day cycle. * Patients who are receiving fulvestrant will receive it as two intramuscular injections (one into each buttock) on Days 1 and 15 of Cycle 1 and then on Day 1 of each cycle thereafter. * Goserelin is given as a subcutaneous injection every 28 days. It is preferred to be given on Day 1 of each cycle, but it may be administered on any day of the treatment cycle to accommodate its specific Q28-day cycle. It will be given to pre- or peri-menopausal women only. * Optional research biopsy at baseline and progression * Blood for research at baseline, cycle 1 day 15, cycle 2 day 1, every 2-3 months (to coincide with imaging studies), and time of progression **ID:** OG000 **Title:** Palbociclib + Letrozole or + Fulvestrant #### Outcome Measure 8 **Description:** * Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm, dDisappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (\<10 mm short axis). * Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters **Parameter Type:** COUNT_OF_PARTICIPANTS **Reporting Status:** POSTED **Time Frame:** Time of progression (estimated to be 24 months) **Title:** Overall Response Rate (Complete Response + Partial Response) **Type:** SECONDARY **Unit of Measure:** Participants ##### Group **Description:** * Palbociclib should be taken by mouth with food on a 5 days on/2 days off schedule (meaning: on Days 1-5, 8-12, 15-19, and 22-26 of each 28-day cycle). * Patients who are receiving letrozole will take it daily by mouth, every day of each 28-day cycle. * Patients who are receiving fulvestrant will receive it as two intramuscular injections (one into each buttock) on Days 1 and 15 of Cycle 1 and then on Day 1 of each cycle thereafter. * Goserelin is given as a subcutaneous injection every 28 days. It is preferred to be given on Day 1 of each cycle, but it may be administered on any day of the treatment cycle to accommodate its specific Q28-day cycle. It will be given to pre- or peri-menopausal women only. * Optional research biopsy at baseline and progression * Blood for research at baseline, cycle 1 day 15, cycle 2 day 1, every 2-3 months (to coincide with imaging studies), and time of progression **ID:** OG000 **Title:** Palbociclib + Letrozole or + Fulvestrant #### Outcome Measure 9 **Description:** * Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm, dDisappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (\<10 mm short axis). * Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters * Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. **Parameter Type:** COUNT_OF_PARTICIPANTS **Reporting Status:** POSTED **Time Frame:** Time of progression (estimated to be 24 months) **Title:** Clinical Benefit Rate (Complete Response + Partial Response + Stable Disease) for at Least 6 Months) **Type:** SECONDARY **Unit of Measure:** Participants ##### Group **Description:** * Palbociclib should be taken by mouth with food on a 5 days on/2 days off schedule (meaning: on Days 1-5, 8-12, 15-19, and 22-26 of each 28-day cycle). * Patients who are receiving letrozole will take it daily by mouth, every day of each 28-day cycle. * Patients who are receiving fulvestrant will receive it as two intramuscular injections (one into each buttock) on Days 1 and 15 of Cycle 1 and then on Day 1 of each cycle thereafter. * Goserelin is given as a subcutaneous injection every 28 days. It is preferred to be given on Day 1 of each cycle, but it may be administered on any day of the treatment cycle to accommodate its specific Q28-day cycle. It will be given to pre- or peri-menopausal women only. * Optional research biopsy at baseline and progression * Blood for research at baseline, cycle 1 day 15, cycle 2 day 1, every 2-3 months (to coincide with imaging studies), and time of progression **ID:** OG000 **Title:** Palbociclib + Letrozole or + Fulvestrant ### Participant Flow Module #### Group **Description:** * Palbociclib should be taken by mouth with food on a 5 days on/2 days off schedule (meaning: on Days 1-5, 8-12, 15-19, and 22-26 of each 28-day cycle). * Patients who are receiving letrozole will take it daily by mouth, every day of each 28-day cycle. * Patients who are receiving fulvestrant will receive it as two intramuscular injections (one into each buttock) on Days 1 and 15 of Cycle 1 and then on Day 1 of each cycle thereafter. * Goserelin is given as a subcutaneous injection every 28 days. It is preferred to be given on Day 1 of each cycle, but it may be administered on any day of the treatment cycle to accommodate its specific Q28-day cycle. It will be given to pre- or peri-menopausal women only. * Optional research biopsy at baseline and progression * Blood for research at baseline, cycle 1 day 15, cycle 2 day 1, every 2-3 months (to coincide with imaging studies), and time of progression **ID:** FG000 **Title:** Palbociclib + Letrozole or + Fulvestrant #### Period **Title:** Overall Study ##### Withdraw **Type:** Deemed not eligible prior to starting palbociclib ###### Reason **Group ID:** FG000 **Number of Subjects:** 1 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 55 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 54 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 1 **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT02833779 **Brief Title:** Trial to Compare the Effectiveness of Group Versus Individual Therapy on Alternate Days in Patients With Subacromial Impingement Syndrome #### Organization Study ID Info **ID:** SSD #### Organization **Class:** OTHER_GOV **Full Name:** Basque Health Service ### Status Module #### Expanded Access Info #### Last Update Post Date **Date:** 2016-07-15 **Type:** ESTIMATED **Last Update Submit Date:** 2016-07-14 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2013-10 **Type:** ACTUAL #### Start Date **Date:** 2010-04 **Status Verified Date:** 2016-07 #### Study First Post Date **Date:** 2016-07-14 **Type:** ESTIMATED **Study First Submit Date:** 2016-07-05 **Study First Submit QC Date:** 2016-07-12 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER_GOV **Name:** Basque Health Service #### Responsible Party **Investigator Affiliation:** Basque Health Service **Investigator Full Name:** Marcos Sanchez Garcia **Investigator Title:** Registered physiotherapist **Type:** PRINCIPAL_INVESTIGATOR ### Description Module **Brief Summary:** Pathology of the rotator cuff and subacromial bursa is considered to be the principal cause of pain and symptoms arising from the shoulder. Physiotherapy specialists often disagree about which type of exercise is most appropriate. Manual Physiotherapy combined with guided exercise is a commonly applied clinical treatment, but no proof of its effectiveness has been shown. Clinical trials comparing results of treating subacromial syndrome of the shoulder with guided self-treatment and conventional physiotherapy yielded a slightly higher improvement, basically because patients suffered from chronic tendinitis and the treatment period lasted only two weeks. That is the reason why the investigators propose a long-term follow-up study and a more complete assessment of effectiveness of the exercise prescribed to improved this pathology. Objectives: * Assessment of effectiveness of two different types of treatment of subacromial syndrome of the shoulder. * Comparison of effectiveness of both treatments in order to select that one yielding better results as the one to be applied as a routine practice. Patients will be assigned one of the following treatments: * Group 1: patients will be taught exercises in groups of six people, on a daily basis for twelve sessions. * Group 2: patients will be taught the same exercise as Group 1, individually, and will receive manual therapy consisting of muscular and joint re-centering. A modified version of the Constant scale will be used to assess mobility and pain shoulder. ### Conditions Module **Conditions:** - Mobility ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 89 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Patients will be taught exercises in groups of six persons, on a daily basis for twelve sessions. **Intervention Names:** - Other: Group exercises **Label:** Group Therapy Exercises **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** Patients will be taught the same exercises as in a Group 1, individually, and will receive manual therapy consisting of muscular and joint re-centering **Intervention Names:** - Other: Individual exercises **Label:** Individual Manual Therapy Exercises **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Individual Manual Therapy Exercises **Name:** Individual exercises **Type:** OTHER #### Intervention 2 **Arm Group Labels:** - Group Therapy Exercises **Name:** Group exercises **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Measure:** The assessment of pain with a visual analogue scale. **Time Frame:** Six Months **Measure:** The mobility (joint range of motion) with a goniometer. **Time Frame:** Six Months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * History of shoulder pain defined as at least 2 positive results in subacromial impingement tests. * Self-perceived pain reported by the patient under clinical examination of the shoulder. * A minimum of 90º mobility in flexion. Exclusion Criteria: * Luxation, a history of surgery, or evidence the current shoulder pain or other symptoms under cervical examination or other shoulder bone disease, except for acromioclavicular joint arthrosis. * Patients were receiving other physiotherapy or rehabilitation treatments. * Patients had been treated for SIS (subacromial impingement syndrome) with injection of anti-inflammatory or analgesic drugs in the last month. **Sex:** ALL **Standard Ages:** - CHILD - ADULT - OLDER_ADULT ## Derived Section ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC05 - Name: Musculoskeletal Diseases - Abbrev: BC26 - Name: Wounds and Injuries ### Condition Browse Module - Browse Leaves - ID: M16355 - Name: Syndrome - Relevance: LOW - As Found: Unknown - ID: M21476 - Name: Shoulder Impingement Syndrome - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05576779 **Brief Title:** Characterization of Early Patients Initiating Ofatumumab for Treatment of Multiple Sclerosis. **Official Title:** Characterization of Early Patients Initiating Ofatumumab for Treatment of Multiple Sclerosis in the Real-World #### Organization Study ID Info **ID:** COMB157GUS11 #### Organization **Class:** INDUSTRY **Full Name:** Novartis ### Status Module #### Completion Date **Date:** 2021-12-31 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2022-11-08 **Type:** ACTUAL **Last Update Submit Date:** 2022-11-07 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2021-12-31 **Type:** ACTUAL #### Start Date **Date:** 2020-12-03 **Type:** ACTUAL **Status Verified Date:** 2022-11 #### Study First Post Date **Date:** 2022-10-13 **Type:** ACTUAL **Study First Submit Date:** 2022-10-10 **Study First Submit QC Date:** 2022-10-10 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Novartis Pharmaceuticals #### Responsible Party **Type:** SPONSOR ### Description Module **Brief Summary:** This was a retrospective cohort study utilizing secondary data from IQVIA's open source pharmacy claims database (i.e., IQVIA LRx) selecting patients with prescription claims for ofatumumab or other DMTs of interest. **Detailed Description:** The date of first ofatumumab prescription claim or other DMT of interest was defined as the index date. No post-index requirements were imposed. Patients were linked to IQVIA's open source medical claims databases (Dx) to obtain patient clinical characteristics. The initial data were extracted in October 2020. The data and results were refreshed in April 2021 and July 2021 to allow for assessment of changes in characteristics at 6 and 9 months post-launch. ### Conditions Module **Conditions:** - Multiple Sclerosis **Keywords:** - Multiple sclerosis, - ofatumumab, - disease-modifying therapy, - COVID-19 ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** RETROSPECTIVE #### Enrollment Info **Count:** 2101 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** all eligible patients with at least 1 claim for ofatumumab observed during the index period were included in the ofatumumab cohort **Intervention Names:** - Other: Ofatunumab **Label:** Ofatumumab #### Arm Group 2 **Description:** patients with no evidence of ofatumumab during the index period were included in the non-ofatumumab cohort and included in subgroups based on the index medication: Siponimod, Ocrelizumab, Dimethyl fumarate, Glatiramer acetate **Label:** Non-ofatumumab ### Interventions #### Intervention 1 **Arm Group Labels:** - Ofatumumab **Description:** All eligible patients with at least 1 claim for ofatumumab observed during the index period were included in the ofatumumab cohort **Name:** Ofatunumab **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** The primary measure was pre-index treatment status of patients initiating ofatumumab, measured as proportion (n, %) of DMT-naïve and DMT-experienced patients among patients initiating ofatumumab based on DMT use in the 12-month pre-index period. **Measure:** Proportion of patients initiating ofatumumab based on DMT use **Time Frame:** 12-months prior to index date, where index date was defined as the date of first ofatumumab claim (or other DMT of interest for non-ofa cohorts) #### Secondary Outcomes **Description:** Age information was reported **Measure:** Age **Time Frame:** Index date, defined as the date of first ofatumumab claim (or other DMT of interest for non-ofa cohorts) **Description:** Gender information was reported **Measure:** Gender **Time Frame:** Index date, defined as the date of first ofatumumab claim (or other DMT of interest for non-ofa cohorts) **Description:** Northeast, Midwest, South, West, Unknown **Measure:** Number of patients: Geographic region **Time Frame:** Index date, defined as the date of first ofatumumab claim (or other DMT of interest for non-ofa cohorts) **Description:** The geographical heat map of ofatumumab utilization at the state level was presented. **Measure:** Number of patients: State level (Geographic region) **Time Frame:** Index date, defined as the date of first ofatumumab claim (or other DMT of interest for non-ofa cohorts) **Description:** Cash, Commercial, Medicare, Medicare Part D, Medicaid, Unknown **Measure:** Number of patients: Insurance type **Time Frame:** Index date, defined as the date of first ofatumumab claim (or other DMT of interest for non-ofa cohorts) **Description:** CVS, Aetna etc **Measure:** Number of patients: Payer **Time Frame:** Index date, defined as the date of first ofatumumab claim (or other DMT of interest for non-ofa cohorts) **Description:** Ofatumumab persistence was assessed over the variable follow-up time. **Measure:** Follow-up time **Time Frame:** Variable Post-index period, where index date was defined as date of first ofatumumab claim (or other DMT of interest for non-ofa cohorts) (01/08/2019 - 31/05/2021) **Description:** Charlson Comorbidity Index predicts the ten-year mortality for a patient who may have a range of comorbid conditions. omorbidity was assessed using the Charlson Comorbidity Index (CCI), categorized as low (0-1) and high (≥2) **Measure:** Number of patients: Pre-index Charlson comorbidity index (CCI) **Time Frame:** 12-months prior to index date, where index date was defined as the date of first ofatumumab claim (or other DMT of interest for non-ofa cohorts) **Description:** Number of patients with list of comorbidities were reported **Measure:** Number of patients: Pre-index comorbidities **Time Frame:** 12-months prior to index date, where index date was defined as the date of first ofatumumab claim (or other DMT of interest for non-ofa cohorts) **Description:** Number of patients with MS relapses were reported **Measure:** Number of patients with a relapse in inpatient settings **Time Frame:** 12-months prior to index date, where index date was defined as the date of first ofatumumab claim (or other DMT of interest for non-ofa cohorts) **Description:** Number of patients with MS relapses were reported **Measure:** Number of patients with a relapse in outpatient settings **Time Frame:** 12-months prior to index date, where index date was defined as the date of first ofatumumab claim (or other DMT of interest for non-ofa cohorts) **Description:** Number of patients with MS relapses were reported **Measure:** Number of relapses in all patients **Time Frame:** 12-months prior to index date, where index date was defined as the date of first ofatumumab claim (or other DMT of interest for non-ofa cohorts) **Description:** Number of patients with MS relapses were reported **Measure:** Number of relapses in patients with at least 1 relapse **Time Frame:** 12-months prior to index date, where index date was defined as the date of first ofatumumab claim (or other DMT of interest for non-ofa cohorts) **Description:** Pre-index MS-related symptoms and secondary conditions (n, %) based on a Claims-Based Disability Score (e.g., sensory problems, eye symptoms, pyramidal symptoms, bladder/bowel symptoms, fatigue/malaise, muscular weakness, durable medical equipment utilization. **Measure:** Claims-Based Disability Score **Time Frame:** 12-months prior to index date, where index date was defined as the date of first ofatumumab claim (or other DMT of interest for non-ofa cohorts) **Description:** Categorized as: No MRI, 1, 2, 3+ **Measure:** Number of pre-index Brain and Spinal MRI scans **Time Frame:** 12-months prior to index date, where index date was defined as the date of first ofatumumab claim (or other DMT of interest for non-ofa cohorts) **Description:** Yes/No **Measure:** Number of patients: Hepatitis B virus screening **Time Frame:** 12-months prior to index date, where index date was defined as the date of first ofatumumab claim (or other DMT of interest for non-ofa cohorts) **Description:** Yes/No **Measure:** Number of patients: Quantitative serum immunoglobulin screening **Time Frame:** 12-months prior to index date, where index date was defined as the date of first ofatumumab claim (or other DMT of interest for non-ofa cohorts) **Description:** Yes/No **Measure:** Number of patients: Pre-index flu shot **Time Frame:** 12-months prior to index date, where index date was defined as the date of first ofatumumab claim (or other DMT of interest for non-ofa cohorts) **Description:** Yes/No **Measure:** Number of patients: Post-index flu shot **Time Frame:** Variable Post-index period, where index date was defined as Date of first ofatumumab claim (or other DMT of interest for non-ofa cohorts) (01/08/2019 - 31/05/2021) **Description:** Yes/No **Measure:** Pre-index: Number of patients with COVID-19 diagnosis **Time Frame:** 12-months prior to index date, where index date was defined as the date of first ofatumumab claim (or other DMT of interest for non-ofa cohorts) **Description:** Yes/No **Measure:** Post-index: Number of patients with COVID-19 diagnosis **Time Frame:** Variable Post-index period, where index date was defined as Date of first ofatumumab claim (or other DMT of interest for non-ofa cohorts) (01/08/2019 - 31/05/2021) **Description:** Days between COVID-19 diagnosis and initiation of ofatumumab were reported **Measure:** Days between COVID-19 diagnosis and initiation of ofatumumab **Time Frame:** Variable Post-index period, where index date was defined as Date of first ofatumumab claim (or other DMT of interest for non-ofa cohorts) (01/08/2019 - 31/05/2021) **Description:** Yes/No **Measure:** Pre-index: Number of patients with COVID-19 vaccination **Time Frame:** 12-months prior to index date, where index date was defined as the date of first ofatumumab claim (or other DMT of interest for non-ofa cohorts) **Description:** Yes/No **Measure:** Post-index: Number of patients with COVID-19 vaccination **Time Frame:** Variable Post-index period, where index date was defined as Date of first ofatumumab claim (or other DMT of interest for non-ofa cohorts) (01/08/2019 - 31/05/2021) **Description:** Days between COVID-19 vaccination and initiation of ofatumumab were reported. **Measure:** Days between COVID-19 vaccination and initiation of ofatumumab **Time Frame:** Variable Post-index period, where index date was defined as Date of first ofatumumab claim (or other DMT of interest for non-ofa cohorts) (01/08/2019 - 31/05/2021) **Description:** E.g. diphenhydramine, dexamethasone and other steroids. pre-medication was defined as medication observed within two days of ofatumumab initiation. **Measure:** Proportion of patients with steroid use or antihistamine as pre-medication with ofatumumab first dose **Time Frame:** Variable Post-index period, where index date was defined as Date of first ofatumumab claim (or other DMT of interest for non-ofa cohorts) (01/08/2019 - 31/05/2021) **Description:** Number of patients with an inpatient visits were reported to report the pre-index healthcare resource utilization **Measure:** Pre-index HCRU: Number of patients with an inpatient visit **Time Frame:** 12-months prior to index date, where index date was defined as the date of first ofatumumab claim (or other DMT of interest for non-ofa cohorts) **Description:** Number of patients with an ED visit were reported to report the pre-index healthcare resource utilization **Measure:** Pre-index HCRU: Number of patients with an ED visit **Time Frame:** 12-months prior to index date, where index date was defined as the date of first ofatumumab claim (or other DMT of interest for non-ofa cohorts) **Description:** Number of patients with an outpatient visit were reported to report the pre-index healthcare resource utilization **Measure:** Pre-index HCRU: Number of patients with an outpatient visit **Time Frame:** 12-months prior to index date, where index date was defined as the date of first ofatumumab claim (or other DMT of interest for non-ofa cohorts) **Description:** Number of patients with a pharmacy claim were reported to report the pre-index healthcare resource utilization **Measure:** Pre-index HCRU: Number of patients with a pharmacy claim **Time Frame:** 12-months prior to index date, where index date was defined as the date of first ofatumumab claim (or other DMT of interest for non-ofa cohorts) **Description:** Number of patients with an inpatient visits were reported to report the post-index healthcare resource utilization accrued while on ofatumumab **Measure:** Post-index HCRU: Number of patients with an inpatient visit **Time Frame:** Variable Post-index period, where index date was defined as Date of first ofatumumab claim (or other DMT of interest for non-ofa cohorts) (01/08/2019 - 31/05/2021) **Description:** Number of patients with an ED visit were reported to report the post-index healthcare resource utilization accrued while on ofatumumab **Measure:** Post-index HCRU: Number of patients with an ED visit **Time Frame:** Variable Post-index period, where index date was defined as Date of first ofatumumab claim (or other DMT of interest for non-ofa cohorts) (01/08/2019 - 31/05/2021) **Description:** Number of patients with an outpatient visit were reported to report the post-index healthcare resource utilization accrued while on ofatumumab **Measure:** Post-index HCRU: Number of patients with an outpatient visit **Time Frame:** Variable Post-index period, where index date was defined as Date of first ofatumumab claim (or other DMT of interest for non-ofa cohorts) (01/08/2019 - 31/05/2021) **Description:** Number of patients with a pharmacy claim were reported to report the post-index healthcare resource utilization accrued while on ofatumumab **Measure:** Post-index HCRU: Number of patients with a pharmacy claim **Time Frame:** Variable Post-index period, where index date was defined as Date of first ofatumumab claim (or other DMT of interest for non-ofa cohorts) (01/08/2019 - 31/05/2021) ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Patients with ≥ 1 prescription for ofatumumab in the LRx/Dx database were included. The date of the first observed prescription within the index window served as the index date. -. Patients with a diagnosis of COVID-19 or a COVID-19 vaccination any time during the study period. * Patients with linkage to the Dx database. Exclusion criteria - No exclusion criteria were applied to patients in the study. **Maximum Age:** 99 Years **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Patients with prescription claims for ofatumumab or other DMTs of interest. ### Contacts Locations Module #### Locations **Location 1:** **City:** East Hanover **Country:** United States **Facility:** Novartis Investigative Site **State:** New Jersey **Zip:** 07936-1080 #### Overall Officials **Official 1:** **Affiliation:** Novartis Pharmaceuticals **Name:** Novartis Pharmaceuticals **Role:** STUDY_DIRECTOR ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### See Also Links **Label:** Results for COMB157GUS11 from the Novartis Clinical Trials Website **URL:** http://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=17981 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000010335 - Term: Pathologic Processes - ID: D000020278 - Term: Demyelinating Autoimmune Diseases, CNS - ID: D000020274 - Term: Autoimmune Diseases of the Nervous System - ID: D000009422 - Term: Nervous System Diseases - ID: D000003711 - Term: Demyelinating Diseases - ID: D000001327 - Term: Autoimmune Diseases - ID: D000007154 - Term: Immune System Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: BC20 - Name: Immune System Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: BC01 - Name: Infections - Abbrev: BC08 - Name: Respiratory Tract (Lung and Bronchial) Diseases ### Condition Browse Module - Browse Leaves - ID: M12060 - Name: Multiple Sclerosis - Relevance: HIGH - As Found: Multiple Sclerosis - ID: M15415 - Name: Sclerosis - Relevance: HIGH - As Found: Sclerosis - ID: M2561 - Name: COVID-19 - Relevance: LOW - As Found: Unknown - ID: M4629 - Name: Autoimmune Diseases - Relevance: LOW - As Found: Unknown - ID: M22098 - Name: Demyelinating Autoimmune Diseases, CNS - Relevance: LOW - As Found: Unknown - ID: M22094 - Name: Autoimmune Diseases of the Nervous System - Relevance: LOW - As Found: Unknown - ID: M6909 - Name: Demyelinating Diseases - Relevance: LOW - As Found: Unknown - ID: M10200 - Name: Immune System Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000009103 - Term: Multiple Sclerosis - ID: D000012598 - Term: Sclerosis ### Intervention Browse Module - Browse Branches - Abbrev: ANeo - Name: Antineoplastic Agents - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: ARhu - Name: Antirheumatic Agents - Abbrev: Derm - Name: Dermatologic Agents ### Intervention Browse Module - Browse Leaves - ID: M347498 - Name: Ofatumumab - Relevance: LOW - As Found: Unknown - ID: M288908 - Name: Ocrelizumab - Relevance: LOW - As Found: Unknown - ID: M297 - Name: Glatiramer Acetate - Relevance: LOW - As Found: Unknown - ID: M147897 - Name: (T,G)-A-L - Relevance: LOW - As Found: Unknown - ID: M431 - Name: Dimethyl Fumarate - Relevance: LOW - As Found: Unknown - ID: M271068 - Name: Siponimod - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05173779 **Brief Title:** Left Atrial Isolation by Catheter Ablation in Persistent Atrial Fibrillation With Severe Atrial Fibrosis **Official Title:** A Single-arm Study to Evaluate the Efficacy and Safety of Left Atrial Isolation Achieved by Catheter Ablation in Patients With Persistent Atrial Fibrillation and Severe Atrial Fibrosis: a Chinese Registry Study #### Organization Study ID Info **ID:** LAICA #### Organization **Class:** OTHER **Full Name:** Shanghai Chest Hospital ### Status Module #### Completion Date **Date:** 2024-12-31 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2022-08-10 **Type:** ACTUAL **Last Update Submit Date:** 2022-08-09 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2024-12-31 **Type:** ESTIMATED #### Start Date **Date:** 2023-01-01 **Type:** ESTIMATED **Status Verified Date:** 2022-08 #### Study First Post Date **Date:** 2021-12-30 **Type:** ACTUAL **Study First Submit Date:** 2021-12-14 **Study First Submit QC Date:** 2021-12-14 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Shanghai Chest Hospital #### Responsible Party **Investigator Affiliation:** Shanghai Chest Hospital **Investigator Full Name:** Xu Liu **Investigator Title:** Professor, deputy director of cardiology department of Shanghai Chest Hospital **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False ### Description Module **Brief Summary:** This is a single-arm clinical trial evaluating the efficacy and safety of left atrial isolation achieved by catheter ablation in patients with persistent atrial fibrillation with severe atrial fibrosis. **Detailed Description:** This is a single-arm clinical trial. Patients with persistent atrial fibrillation with severe atrial fibrosis are enrolled as subjects to conduct left atrial isolation by catheter ablation. Postoperative recurrence rate and other indicators are analyzed to evaluate the efficacy and safety of left atrial isolation achieved by catheter ablation in patients with persistent atrial fibrillation with severe atrial fibrosis. ### Conditions Module **Conditions:** - Persistent Atrial Fibrillation **Keywords:** - Persistent Atrial Fibrillation - Severe atrial fibrosis - Left atrial isolation - catheter ablation ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 50 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** All the enrolled subjects will receive left atrial isolation through catheter ablation. **Intervention Names:** - Procedure: Left atrial isolation by catheter ablation **Label:** Left atrial isolation arm **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Left atrial isolation arm **Description:** Procedure: Right pulmonary vein circumferential isolation + anterior left atrial line (superior mitral annulus to right superior pulmonary vein via the anterior wall) + para-septal line (para-septal mitral annulus to the right inferior pulmonary vein, including right atrial components-especially in and around the proximal coronary sinus) + posterior left atrial line (superior mitral annulus to right superior pulmonary vein via the posterior wall). **Name:** Left atrial isolation by catheter ablation **Type:** PROCEDURE ### Outcomes Module #### Primary Outcomes **Description:** AF/AFL/AT recurrence is defined as presence of documented AF/AFL/AT episodes of 30 seconds or longer duration **Measure:** Postoperative atrial fibrillation (AF)/atrial flutter (AFL)/atrial tachycardia (AT) recurrence rate **Time Frame:** up to 18 months after enrollment #### Secondary Outcomes **Description:** AF recurrence is defined as presence of documented AF episodes of 30 seconds or longer duration **Measure:** Postoperative AF recurrence rate **Time Frame:** up to 18 months after enrollment **Description:** Occurrence of AFL/AT is defined as presence of documented AFL/AT episodes of 30 seconds or longer duration **Measure:** Postoperative AFL/AT rate **Time Frame:** up to 18 months after enrollment **Description:** including death, atrio-esophageal fistula, cardiac tamponade/perforation, myocardial infarction, stroke/cerebrovascular accident, thromboembolism, diaphragmatic paralysis, pneumothorax, pleural effusion, heart block, pulmonary vein stenosis, pulmonary edema, left atrial thrombus, pericarditis and major vascular access complication or bleeding **Measure:** Incidence of complications **Time Frame:** up to 18 months after enrollment **Measure:** Changes in the diameter of the left atrium and the left ventricular ejection fraction **Time Frame:** up to 18 months after enrollment ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Aged 18 to 80 years old 2. Persistent AF with severe atrial fibrosis and left atrial anterioposterior diameter \> 50mm 3. Nonresponse or intolerance to ≥1 antiarrhythmic drug 4. CHA2DS2-VASc ≥ 3 and HAS-BLED \< 3 Exclusion Criteria: 1. With uncontrolled congestive heart failure; 2. Having significant valvular disease; 3. Having moderate-to-severe pulmonary hypertension; 4. With myocardial infarction or stroke within 6 months of screening; 5. With Significant congenital heart disease; 6. Ejection fraction was \<40% measured by echocardiography; 7. Allergic to contrast media; 8. Contraindication to anticoagulation medications; 9. Severe pulmonary disease e.g. restrictive pulmonary disease, chronic obstructive disease (COPD); 10. Left atrial thrombus; 11. Having any contraindication to right or left sided heart catheterization **Maximum Age:** 80 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Mu Qin, M.D. **Phone:** +8613052320103 **Role:** CONTACT ## Derived Section ### Condition Browse Module - Ancestors - ID: D000001145 - Term: Arrhythmias, Cardiac - ID: D000006331 - Term: Heart Diseases - ID: D000002318 - Term: Cardiovascular Diseases - ID: D000010335 - Term: Pathologic Processes ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC14 - Name: Heart and Blood Diseases ### Condition Browse Module - Browse Leaves - ID: M8485 - Name: Fibrosis - Relevance: HIGH - As Found: Fibrosis - ID: M4586 - Name: Atrial Fibrillation - Relevance: HIGH - As Found: Persistent Atrial Fibrillation - ID: M4453 - Name: Arrhythmias, Cardiac - Relevance: LOW - As Found: Unknown - ID: M9419 - Name: Heart Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000001281 - Term: Atrial Fibrillation - ID: D000005355 - Term: Fibrosis ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT02992379 **Brief Title:** Clinical Evaluation of Stabilizing Splint Versus Pivot Splint as Jaw Exercise Together With Stabilizing Splint **Official Title:** Clinical Evaluation of Stabilizing Splint Versus Pivot Splint as Jaw Exercise Together With Stabilizing Splint as Treatment for TMJ Anterior Disc Displacement Without Reduction #### Organization Study ID Info **ID:** cairo ss-ps #### Organization **Class:** OTHER **Full Name:** Cairo University ### Status Module #### Completion Date **Date:** 2017-12 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** NOT_YET_RECRUITING #### Last Update Post Date **Date:** 2016-12-14 **Type:** ESTIMATED **Last Update Submit Date:** 2016-12-10 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2017-07 **Type:** ESTIMATED #### Start Date **Date:** 2016-12 **Status Verified Date:** 2016-12 #### Study First Post Date **Date:** 2016-12-14 **Type:** ESTIMATED **Study First Submit Date:** 2016-11-29 **Study First Submit QC Date:** 2016-12-10 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Cairo University #### Responsible Party **Investigator Affiliation:** Cairo University **Investigator Full Name:** Hesham Mohamed mohamed elsayed safa **Investigator Title:** Resident at National Cancer Institute **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** To evaluate the effectiveness of the stabilizing splint versus the pivot splint as jaw exercise together with stabilizing splints for treatment of TMJ anterior disc displacement without reduction **Detailed Description:** To evaluate the effectiveness of the stabilizing splint versus the pivot splint as jaw exercise together with stabilizing splints for treatment of TMJ anterior disc displacement without reduction PICO: Population (P): Patients with symptomatic anterior disc displacement without reduction. Intervention (I): pivot splint. Comparator (C): stabilizing repositioning splint (ARS). Outcome (O): Primary outcome: Patients' subjective pain experience. Each patient will be asked to rate his or her current and worst pain intensity on numerical rating scale (NRS) of 0-10 with zero being no pain and ten corresponds to the worst pain that the patient ever had. Secondary outcome: 1. Maximum mouth opening (MMO). Assessment of MMO will be performed by measuring the distance in mm between the incisal edges of the upper and lower central incisors using a ruler. 2. Lateral excursion. Assessment of lateral excursion will be performed by measuring the distance in mm between midline of upper and lower jaws 3. Protrusion. distance in mm from the incisal edge of the maxillary central incisor to the incisor edge of the mandibular incisor will measured in the maximum protruded position. ### Conditions Module **Conditions:** - TMJ Disc Disorder **Keywords:** - Anterior disc displacement - Stabilizing splint ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 30 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Active Comparator: stabilizing splint A 2-mm-thick, hard, clear sheet of resin will be adapted to the maxillary arch . Small amount of self-curing acrylic will be added to the anterior portion of the appliance as a stop for the lower incisor. The area of this stop is approximately 4 to 6 mm. The patient is instructed to protrude the mandible slightly and to open and close the mouth In this position. Self-curing acrylic will be added to the occluding surface of the appliance. All occluding areas, except the contact on the anterior stop . Excess acrylic surrounding the centric contacts is removed with a hard rubber wheel on a lathe. intervention: pivot splint **Intervention Names:** - Device: pivot splint - Device: stabilizing splint **Label:** stabilizing splint **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** Experimental: pivot splint A 2-mm-thick, hard, clear sheet of resin will be adapted to the maxillary arch . Small amount of self-curing acrylic will be added to the anterior portion of the appliance as a stop for the lower incisor. The area of this stop is approximately 4 to 6 mm. The patient should be instructed to close in Centric relation . Self-curing acrylic will be added to the occluding surface of the appliance. All occluding areas, except the contact on the anterior stop . Excess acrylic surrounding the centric contacts is removed with a hard rubber wheel on a lathe. All areas, except labial to the mandibular canines, are flattened to the contact marks. Other Names: PS **Intervention Names:** - Device: pivot splint - Device: stabilizing splint **Label:** pivot splint **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - pivot splint - stabilizing splint **Description:** A 2-mm-thick, hard, clear sheet of resin will be adapted to the maxillary arch . Small amount of selfcuring acrylic will be added to the anterior portion of the appliance as a stop for the lower incisor. The area of this stop is approximately 4 to 6 mm. The patient is instructed to protrude the mandible slightly and to open and close the mouth In this position. Self-curing acrylic will be added to the occluding surface of the appliance. All occluding areas, except the contact on the anterior stop . Excess acrylic surrounding the centric contacts is removed with a hard rubber wheel on a lathe. **Name:** pivot splint **Other Names:** - PS **Type:** DEVICE #### Intervention 2 **Arm Group Labels:** - pivot splint - stabilizing splint **Description:** A 2-mm-thick, hard, clear sheet of resin will be adapted to the maxillary arch . Small amount of self-curing acrylic will be added to the anterior portion of the appliance as a stop for the lower incisor. The area of this stop is approximately 4 to 6 mm. The patient is instructed to protrude the mandible slightly and to open and close the mouth In this position. Self-curing acrylic will be added to the occluding surface of the appliance. All occluding areas, except the contact on the anterior stop . Excess acrylic surrounding the centric contacts is removed with a hard rubber wheel on a lathe. intervention: pivot splint **Name:** stabilizing splint **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Description:** Each patient will be asked to rate his or her current and worst pain intensity on numerical rating scale (NRS) of 0-10 with zero being no pain and ten corresponds to the worst pain that the patient ever had. **Measure:** Patients' subjective pain experience (numerical rating scale) **Time Frame:** 6 months #### Secondary Outcomes **Description:** measuring the distance between the incisal edges of the upper and lower central incisors using a ruler. Unit: mm **Measure:** Maximum mouth opening (Unit: mm) **Time Frame:** 6 months **Description:** measuring the distance between midline of upper and lower jaws. Unit: mm **Measure:** Lateral excursion (Unit: mm) **Time Frame:** 6 months **Description:** The distance in mm from the incisal edge of the maxillary central incisor to the incisor edge of the mandibular incisor will measured in the maximum protruded position. **Measure:** Protrusion (distance in mm) **Time Frame:** 6 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Adult patient from 15 to 50 years old * Report of pain in preauricular region worsened by functional activities, such as chewing and talking * Presence of disc displacement with reduction and joint clicking * Positive diagnosis of unilateral or bilateral anterior disc displacement with reduction by means of magnetic resonance imaging (MRI) Exclusion Criteria: * Individuals with systemic diseases that can affect TMJ * History of TMJ surgery * Individuals with osteoarthritis * Individuals under TMD management * Individuals wearing full or partial dentures * Reducing dislocations of the articular disc * Consequences of condyle fractures and/or fracture of another maxillofacial zone * In therapy for the same pathologies * Articular pathologies of systemic nature (e.g., rheumatoid arthritis, arthrosis, psoriasis arthritis) * Individuals with a recent history of trauma in the face and/or neck area **Healthy Volunteers:** True **Maximum Age:** 50 Years **Minimum Age:** 15 Years **Sex:** ALL **Standard Ages:** - CHILD - ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** hesham M safa, master **Phone:** 01001720677 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Omniya Abdelaziz, lecturer **Phone:** 01001203583 **Role:** CONTACT #### Overall Officials **Official 1:** **Affiliation:** Cairo University **Name:** Nadia Galal, Ass.prof **Role:** STUDY_DIRECTOR ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Ebrahim S, Montoya L, Busse JW, Carrasco-Labra A, Guyatt GH; Medically Unexplained Syndromes Research Group. The effectiveness of splint therapy in patients with temporomandibular disorders: a systematic review and meta-analysis. J Am Dent Assoc. 2012 Aug;143(8):847-57. doi: 10.14219/jada.archive.2012.0289. **PMID:** 22855899 ## Derived Section ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT02645279 **Brief Title:** Comparison of Oral 30 % Dextrose and iv Midazolam Sedation During MRI in Neonates **Official Title:** Comparison of Oral 30 % Dextrose and iv Midazolam Sedation During MRI in Neonates #### Organization Study ID Info **ID:** KA15/19 #### Organization **Class:** OTHER **Full Name:** Baskent University ### Status Module #### Completion Date **Date:** 2016-02 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** ACTIVE_NOT_RECRUITING #### Last Update Post Date **Date:** 2016-01-01 **Type:** ESTIMATED **Last Update Submit Date:** 2015-12-31 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2016-02 **Type:** ESTIMATED #### Start Date **Date:** 2015-01 **Status Verified Date:** 2015-12 #### Study First Post Date **Date:** 2016-01-01 **Type:** ESTIMATED **Study First Submit Date:** 2015-12-30 **Study First Submit QC Date:** 2015-12-31 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Baskent University #### Responsible Party **Investigator Affiliation:** Baskent University **Investigator Full Name:** H. Evren Eker **Investigator Title:** Ass Prof **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** The purpose of this study is to demonstrate the effectiveness of oral glucose administration during MRI for imaging of newborns and compare with midazolam sedation. **Detailed Description:** Motion artefacts affect the quality of MRI and in order to overcome this problem procedures are performed under sedation or general anaesthesia. The safety profile of these methods for newborns is unclear. Alternative non-pharmacological interventions are changeable and might be time consuming. Oral glucose/sucrose administration has been the most frequently studied non-pharmacologic intervention in term and preterm neonates during painful procedures. In this study investigators aimed to compare oral 30% glucose and intravenous midazolam their efficiency on sedation during MRI. ### Conditions Module **Conditions:** - Epilepsy - Trauma - Metabolic Disease **Keywords:** - newborn - MRI - oral 30% glucose ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** DOUBLE **Who Masked:** - INVESTIGATOR - OUTCOMES_ASSESSOR **Primary Purpose:** SUPPORTIVE_CARE #### Enrollment Info **Count:** 112 **Type:** ACTUAL **Phases:** - PHASE4 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** oral 30% glucose total 200 mg/kg with 0.5-1 mL increments **Intervention Names:** - Other: oral 30% glucose **Label:** oral 30% glucose **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** intravenous administration of midazolam 0.1 mg/kg **Intervention Names:** - Drug: IV midazolam **Label:** IV midazolam **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - oral 30% glucose **Description:** 30% glucose solution was administered orally through a teat. 1 mL 30% glucose solution was added following placement of the teat into the mouth of the newborn. After suckling of 0.5-1 mL glucose solution, the motionless and sleepiness of newborn was evaluated. If the target conditions was not achieved, 0.5-1 mL increments of glucose was added until the newborn kept motionless or asleep. **Name:** oral 30% glucose **Type:** OTHER #### Intervention 2 **Arm Group Labels:** - IV midazolam **Description:** IV 0.1 mg/kg midazolam was administered.MRI was routinely performed and the newborns who did not keep motionless or asleep and had motion artefacts were sedated with intravenous 0.5 mg/kg propofol. **Name:** IV midazolam **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Measure:** Success rate of the procedures to keep the neonates quietened, motionless and slept during the procedure and to consider all images qualitatively appropriate for interpretation **Time Frame:** Approximately 1 year ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Neonates requiring MR imaging for diagnosis Exclusion Criteria: * Patients with fever, cold symptoms, suspicion of difficult airway, hypovolemia, cardiac, renal, lung disease, malformations **Maximum Age:** 30 Days **Minimum Age:** 1 Day **Sex:** ALL **Standard Ages:** - CHILD ### Contacts Locations Module #### Overall Officials **Official 1:** **Affiliation:** Baskent University Department of Anesthesiology **Name:** Anis Aribogan, Prof **Role:** STUDY_CHAIR ## Derived Section ### Condition Browse Module - Browse Branches - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC26 - Name: Wounds and Injuries - Abbrev: BC18 - Name: Nutritional and Metabolic Diseases ### Condition Browse Module - Browse Leaves - ID: M7983 - Name: Epilepsy - Relevance: LOW - As Found: Unknown - ID: M17685 - Name: Wounds and Injuries - Relevance: LOW - As Found: Unknown - ID: M11639 - Name: Metabolic Diseases - Relevance: HIGH - As Found: Metabolic Diseases ### Condition Browse Module - Meshes - ID: D000008659 - Term: Metabolic Diseases ### Intervention Browse Module - Ancestors - ID: D000000759 - Term: Adjuvants, Anesthesia - ID: D000006993 - Term: Hypnotics and Sedatives - ID: D000002492 - Term: Central Nervous System Depressants - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000014151 - Term: Anti-Anxiety Agents - ID: D000014149 - Term: Tranquilizing Agents - ID: D000011619 - Term: Psychotropic Drugs - ID: D000018686 - Term: Anesthetics, Intravenous - ID: D000018681 - Term: Anesthetics, General - ID: D000000777 - Term: Anesthetics - ID: D000018757 - Term: GABA Modulators - ID: D000018682 - Term: GABA Agents - ID: D000018377 - Term: Neurotransmitter Agents - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action ### Intervention Browse Module - Browse Branches - Abbrev: CNSDep - Name: Central Nervous System Depressants - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: PhSol - Name: Pharmaceutical Solutions - Abbrev: AdjAn - Name: Adjuvants, Anesthesia - Abbrev: PsychDr - Name: Psychotropic Drugs ### Intervention Browse Module - Browse Leaves - ID: M18307 - Name: Propofol - Relevance: LOW - As Found: Unknown - ID: M21860 - Name: Pharmaceutical Solutions - Relevance: LOW - As Found: Unknown - ID: M11845 - Name: Midazolam - Relevance: HIGH - As Found: Induction - ID: M4107 - Name: Anesthetics - Relevance: LOW - As Found: Unknown - ID: M4089 - Name: Adjuvants, Anesthesia - Relevance: LOW - As Found: Unknown - ID: M10043 - Name: Hypnotics and Sedatives - Relevance: LOW - As Found: Unknown - ID: M16905 - Name: Anti-Anxiety Agents - Relevance: LOW - As Found: Unknown - ID: M14474 - Name: Psychotropic Drugs - Relevance: LOW - As Found: Unknown - ID: M20766 - Name: Anesthetics, Intravenous - Relevance: LOW - As Found: Unknown - ID: M20761 - Name: Anesthetics, General - Relevance: LOW - As Found: Unknown - ID: M20827 - Name: GABA Modulators - Relevance: LOW - As Found: Unknown - ID: M20504 - Name: Neurotransmitter Agents - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000008874 - Term: Midazolam ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05328479 **Brief Title:** Plasma Immunity of Mild SARS-CoV-2 Omicron and Delta Pandemic in Thailand **Official Title:** The Study of Treatment Outcome and Immunogenicity of mild-to Moderate COVID-19 Patients During the Delta vs. the Omicron Pandemic #### Organization Study ID Info **ID:** 769/2564(IRB1) #### Organization **Class:** OTHER **Full Name:** Mahidol University ### Status Module #### Completion Date **Date:** 2022-05-20 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2022-10-19 **Type:** ACTUAL **Last Update Submit Date:** 2022-10-17 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2022-03-15 **Type:** ACTUAL #### Start Date **Date:** 2021-11-04 **Type:** ACTUAL **Status Verified Date:** 2022-10 #### Study First Post Date **Date:** 2022-04-14 **Type:** ACTUAL **Study First Submit Date:** 2022-04-07 **Study First Submit QC Date:** 2022-04-07 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Mahidol University #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** The investigators assessed the effect of treatment for COVID and immunity of the volunteers who admitted to the home isolation. **Detailed Description:** The investigators aimed to assess the effect of treatment for COVID and immunity of the volunteers who admitted to the home isolation. The investigators compared the population between the age groups 12-18 years, 18-45 years and over 45 years to monitor the symptoms of coronavirus patients treated in home isolation and long-term symptoms including factors related to the patient's recovery in the past, present, and future. ### Conditions Module **Conditions:** - COVID-19 **Keywords:** - COVID-19 - antibody - immunity - home isolation - vaccine ### Design Module #### Bio Spec **Description:** Plasma **Retention:** SAMPLES_WITHOUT_DNA #### Design Info **Observational Model:** COHORT **Time Perspective:** RETROSPECTIVE #### Enrollment Info **Count:** 5181 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Outcomes Module #### Primary Outcomes **Description:** Anti-RBD IgG (BAU/mL) **Measure:** Anti-SARS-CoV-2 RBD IgG **Time Frame:** Baseline **Description:** Anti-SARS-CoV-2 NP (PRNT50 titer) **Measure:** Anti-SARS-CoV-2 NP **Time Frame:** Baseline **Description:** Cycle threshold (Ct) **Measure:** Cycle threshold of the first PCR test **Time Frame:** Baseline #### Secondary Outcomes **Description:** Number of vaccine injection **Measure:** Number of vaccine injection **Time Frame:** Baseline **Description:** Type of vaccine injection **Measure:** Type of vaccine injection **Time Frame:** Baseline ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. patient with infected with the novel coronavirus disease 2019 (COVID-19) who has been end of self-quarantine at Siriraj Hospital more than 21 days. 2. Thai nationality, able to read and write Thai language 3. able to use telephone and line to communicate Exclusion Criteria: 1. people who received additional vaccination after leaving quarantine before the day of the immunization test **Healthy Volunteers:** True **Minimum Age:** 12 Years **Sampling Method:** PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - CHILD - ADULT - OLDER_ADULT **Study Population:** The COVID-19 patients who confirmed by RT-PCR at Siriraj hospital since July 8, 2021 with mild to moderate symptoms and isolated in patients' own home so-called "Siriraj Home isolation". ### Contacts Locations Module #### Locations **Location 1:** **City:** Bangkok Noi **Country:** Thailand **Facility:** Faculty of Medicine Siriraj Hospital, Mahidol University **State:** Bangkok **Zip:** 10700 #### Overall Officials **Official 1:** **Affiliation:** Doctor in Family Medicine **Name:** Korapat Mayurasakorn, MD. **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000011024 - Term: Pneumonia, Viral - ID: D000011014 - Term: Pneumonia - ID: D000012141 - Term: Respiratory Tract Infections - ID: D000007239 - Term: Infections - ID: D000014777 - Term: Virus Diseases - ID: D000018352 - Term: Coronavirus Infections - ID: D000003333 - Term: Coronaviridae Infections - ID: D000030341 - Term: Nidovirales Infections - ID: D000012327 - Term: RNA Virus Infections - ID: D000008171 - Term: Lung Diseases - ID: D000012140 - Term: Respiratory Tract Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC01 - Name: Infections - Abbrev: BC08 - Name: Respiratory Tract (Lung and Bronchial) Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology ### Condition Browse Module - Browse Leaves - ID: M2561 - Name: COVID-19 - Relevance: HIGH - As Found: COVID-19 - ID: M13904 - Name: Pneumonia - Relevance: LOW - As Found: Unknown - ID: M13914 - Name: Pneumonia, Viral - Relevance: LOW - As Found: Unknown - ID: M10283 - Name: Infections - Relevance: LOW - As Found: Unknown - ID: M6368 - Name: Communicable Diseases - Relevance: LOW - As Found: Unknown - ID: M14978 - Name: Respiratory Tract Infections - Relevance: LOW - As Found: Unknown - ID: M17522 - Name: Virus Diseases - Relevance: LOW - As Found: Unknown - ID: M20490 - Name: Coronavirus Infections - Relevance: LOW - As Found: Unknown - ID: M6555 - Name: Coronaviridae Infections - Relevance: LOW - As Found: Unknown - ID: M23685 - Name: Nidovirales Infections - Relevance: LOW - As Found: Unknown - ID: M15149 - Name: RNA Virus Infections - Relevance: LOW - As Found: Unknown - ID: M11168 - Name: Lung Diseases - Relevance: LOW - As Found: Unknown - ID: M14977 - Name: Respiratory Tract Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000086382 - Term: COVID-19 ### Intervention Browse Module - Browse Branches - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M17360 - Name: Vaccines - Relevance: LOW - As Found: Unknown - ID: M4225 - Name: Antibodies - Relevance: LOW - As Found: Unknown - ID: M10184 - Name: Immunoglobulins - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT01237379 **Brief Title:** Peroxisomal Defects and Familial Risk for Bipolar Disorder **Official Title:** Peroxisomal Defects and Familial Risk for Bipolar Disorder #### Organization Study ID Info **ID:** McNamara NARSAD #### Organization **Class:** OTHER **Full Name:** University of Cincinnati ### Status Module #### Completion Date **Date:** 2013-10 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2014-12-23 **Type:** ESTIMATED **Last Update Submit Date:** 2014-12-19 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2013-10 **Type:** ACTUAL #### Start Date **Date:** 2010-10 **Status Verified Date:** 2014-12 #### Study First Post Date **Date:** 2010-11-09 **Type:** ESTIMATED **Study First Submit Date:** 2010-10-21 **Study First Submit QC Date:** 2010-11-05 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** National Alliance for Research on Schizophrenia and Depression #### Lead Sponsor **Class:** OTHER **Name:** University of Cincinnati #### Responsible Party **Investigator Affiliation:** University of Cincinnati **Investigator Full Name:** Robert McNamara **Investigator Title:** Associate Professor **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** The purpose of this study is to screen for peroxisome defects in child and adolescent offspring of Bipolar Disorder I (BD-I) parents at different stages of risk for transitioning to mania and following the onset of mania. Prediction 1: Youth with an elevated risk for developing BD-I and first-episode manic patients will exhibit graded deficits in measures of peroxisomal function compared with healthy controls. Prediction 2: Indices of peroxisomal function will be correlated with Red Blood Cells Docosahexaenoic acid (DHA) composition. Prediction 3: Graded deficits in measures of peroxisomal function will be inversely correlated with manic and depression symptom severity scores. **Detailed Description:** Overall Study Design: This study entails collecting fasting venous blood (20 ml) from, and administering the 'omega-3 questionnaire' to, subjects being recruited from ongoing National Institute of Mental Health (NIMH)-sponsored trials within the Department of Psychiatry, University of Cincinnati College of Medicine. Specifically, blood will be collected from 20 healthy controls (i.e., no personal or family history of any Axis I mood disorder according to the Diagnostic and Statistical Manual of Mental Disorders-IV \[DSM-IV\]) and 20 asymptomatic high-risk (i.e., have a biological parent with BD-I) adolescents (aged 10-18 years old) recruited for study MH077138 (UC-IRB #: 07-04-10-03, BITREC Project 3; PI: DelBello), 20 ultra-high risk (i.e., have a biological parent with BD-I and a Major Depressive Disorder (MDD) diagnosis) recruited for study MH083924 (UC-IRB #: 04-09-15-03, CO-Principal Investigators DelBello/McNamara), and 20 adolescents who are admitted for their first hospitalization and who have a diagnosis of BD-I recruited for study MH080973 (UC-IRB #: 08-10-30-01, Principal Investigator: DelBello). Blood will then be processed, and de-identified tubes sent to the Kennedy Krieger Institute, Peroxisomal Diseases Section, to determine the following measures of peroxisomal function: (1) plasma very long chain fatty acids (C24:0 \& C26:0) concentrations, (2) plasma bile acid C27 intermediate (dehydrocrepenynic acid {DHCA},tetrahydrocannabinolic acid {THCA})concentrations, (3) plasma pipecolic acid concentrations, and (4) Red Blood Cell (RBC) plasmalogen concentrations. Additionally, RBC fatty acid composition will be determined by gas chromatography, and platelet function and plasma inflammatory markers assayed using commercially available kits according to manufacturer's instructions. ### Conditions Module **Conditions:** - Bipolar Disorder - Mania ### Design Module #### Bio Spec **Description:** Laboratory methods: The gas chromatography procedure used to determine red blood cell fatty acid composition. Briefly, total fatty acid composition will be determined. Indices of peroxisome function, including (1) plasma very long chain fatty acids concentrations, (2) plasma bile acid C27 intermediate concentrations, (3) plasma pipecolic acid concentrations, and (4) RBC plasmalogen concentrations, will be determined by liquid chromatography tandem mass spectrometry and gas chromatography. Plasma cytokine and C-Reactive Protein (CRP)concentrations will be determined. All blood analyses will be performed by a technician blinded to diagnostic group identity. **Retention:** NONE_RETAINED #### Design Info **Observational Model:** CASE_CROSSOVER **Time Perspective:** RETROSPECTIVE #### Enrollment Info **Count:** 80 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Label:** Health Controls #### Arm Group 2 **Label:** Bipolar Patients with High-Risk of Mania #### Arm Group 3 **Label:** Bipolar Patients with Ultra-High Risk #### Arm Group 4 **Label:** First Manic Episode Bipolar Youth ### Outcomes Module #### Primary Outcomes **Description:** Prediction 1: Youth with an elevated risk for developing BD-I and first-episode manic patients will exhibit graded deficits in measures of peroxisomal function compared with healthy controls. **Measure:** Youth with an elevated risk for developing BD-I and first-episode manic patients will exhibit graded deficits in measures of peroxisomal function compared with healthy controls. **Time Frame:** 1 day #### Secondary Outcomes **Description:** Prediction 3: Graded deficits in measures of peroxisomal function will be inversely correlated with manic and depression symptom severity scores. **Measure:** peroxisomal function will be inversely correlated with manic and depression symptom severity scores. **Time Frame:** 1 day **Description:** Prediction 2: Indices of peroxisomal function will be correlated with RBC DHA composition. **Measure:** Indices of peroxisomal function will be correlated with RBC DHA composition. **Time Frame:** 1 day ### Eligibility Module **Eligibility Criteria:** Subject characteristics: All subjects will be 10-18 year old males and females. Up to 80 patients will be enrolled in this study. Subjects will be screened according to previously approved individual study criteria (UC-IRB #: 07-04-10-03; 04-09-15-03; 08-10-30-01). Inclusion Criteria: * 10 -18 year old males \& females * Based on currently enrolled study. Exclusion Criteria: * Based on currently enrolled study. **Healthy Volunteers:** True **Maximum Age:** 18 Years **Minimum Age:** 10 Years **Sampling Method:** PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - CHILD - ADULT **Study Population:** Subjects: In order to accomplish this aim, 20 healthy controls, 20 high-risk, 20 ultra-high risk, and 20 first-episode manic youth (ages 10-18 years old) will be recruited at a rate of 1 subject/group per month over the first 20 months. Subjects being recruited from the following IRB approved NIMH-sponsored trials: MH077138 (UC-IRB #: 07-04-10-03, BITREC Project 3; PI: DelBello), MH083924 (UC-IRB #: 04-09-15-03, CO-PIs DelBello/McNamara), and MH080973 (UC-IRB #: 08-10-30-01, PI: DelBello). ### Contacts Locations Module #### Locations **Location 1:** **City:** Cincinnati **Country:** United States **Facility:** University of Cincinnati **State:** Ohio **Zip:** 45219 #### Overall Officials **Official 1:** **Affiliation:** University of Cincinnati **Name:** Robert McNamara, PhD **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000068105 - Term: Bipolar and Related Disorders - ID: D000019964 - Term: Mood Disorders - ID: D000001523 - Term: Mental Disorders ### Condition Browse Module - Browse Branches - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: BXM - Name: Behaviors and Mental Disorders - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M2598 - Name: Mania - Relevance: LOW - As Found: Unknown - ID: M4996 - Name: Bipolar Disorder - Relevance: HIGH - As Found: Bipolar Disorder - ID: M226 - Name: Bipolar and Related Disorders - Relevance: LOW - As Found: Unknown - ID: M21835 - Name: Mood Disorders - Relevance: LOW - As Found: Unknown - ID: M4815 - Name: Mental Disorders - Relevance: LOW - As Found: Unknown - ID: M14473 - Name: Psychotic Disorders - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000001714 - Term: Bipolar Disorder ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05401279 **Brief Title:** Bladder Sparing Treatment of Tislelizumab, Gemcitabine and Cisplatin for Patients With PD-L1 Positive Muscle Invasive Bladder Cancer **Official Title:** Bladder Sparing Treatment of Tislelizumab Combined With Gemcitabine and Cisplatin for Patients With PD-L1 Positive Muscle Invasive Bladder Cancer (T2-3N0M0): a Phase II Prospective Study #### Organization Study ID Info **ID:** TICIG #### Organization **Class:** OTHER **Full Name:** RenJi Hospital ### Status Module #### Completion Date **Date:** 2025-05 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2022-08-18 **Type:** ACTUAL **Last Update Submit Date:** 2022-08-15 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2024-04 **Type:** ESTIMATED #### Start Date **Date:** 2022-06-01 **Type:** ACTUAL **Status Verified Date:** 2022-08 #### Study First Post Date **Date:** 2022-06-02 **Type:** ACTUAL **Study First Submit Date:** 2022-05-29 **Study First Submit QC Date:** 2022-05-29 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** RenJi Hospital #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False ### Description Module **Brief Summary:** This is a phase II open label single-arm prospective study aiming to investigate the efficacy of PD-1 inhibitor Tislelizumab combined with conventional gemcitabine and cisplatin as bladder sparing treatment for patients with PD-L1 positive muscle invasive bladder carcinoma (T2-3N0M0). **Detailed Description:** The study will enroll 20 patients with adequate organ function and performance status who either wish to attempt bladder preserving therapy or are ineligible for radical cystectomy. The bladder samples must be available and assessed as positive for PD-L1 expression . Patients will receive transurethral resection or partial cystectomy to remove all visible tumors with no residual disease left. After the surgery, patients will receive 8 cycles of tislelizumab combined with 4-6 cycles of gemcitabine and cisplatin. ### Conditions Module **Conditions:** - Urothelial Carcinoma Bladder - PD-1 Inhibitor ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 20 **Type:** ESTIMATED **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Patients will receive transurethral resection or partial cystectomy to remove all visible tumors with no residual disease left. 2-4 weeks after the surgery, patients will receive 8 cycles of tislelizumab combined with 4-6 cycles of gemcitabine and cisplatin. **Intervention Names:** - Drug: Tislelizumab - Drug: Gemcitabine - Drug: Cisplatin **Label:** Gemcitabine, Cisplatin and Tislelizumab **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Gemcitabine, Cisplatin and Tislelizumab **Description:** Tislelizumab 200mg will be administered on Day 1 of each 21 day cycle for 8 21-day cycles. **Name:** Tislelizumab **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Gemcitabine, Cisplatin and Tislelizumab **Description:** Gemcitabine 1000mg/m\^2 will be administered on Days 1 and 8 for four to six 21-day cycles. **Name:** Gemcitabine **Type:** DRUG #### Intervention 3 **Arm Group Labels:** - Gemcitabine, Cisplatin and Tislelizumab **Description:** Cisplatin 70mg\^m2 will be administered on Day 1 for four to six 21-day cycles. **Name:** Cisplatin **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Bladder-intact disease-free survival is defined as time from initiation of protocol therapy until the development of muscle-invasive bladder cancer recurrence, regional pelvic recurrence, distant metastases, bladder cancer-related death, or cystectomy. **Measure:** Two-year bladder-intact disease-free survival rate **Time Frame:** 2 years #### Secondary Outcomes **Description:** The adverse events are evaluated per Common Terminology Criteria for Adverse Events (CTCAE) 5. **Measure:** Adverse Events **Time Frame:** 2 years **Description:** Defined as time to death from beginning of protocol therapy **Measure:** Overall survival **Time Frame:** up to 5 years **Description:** Defined as time to the development of radiographic distant metastases from beginning of protocol therapy. **Measure:** Metastasis-free survival **Time Frame:** up to 5 years **Description:** Defined as time to recurrence, metastasis or death from beginning of protocol therapy. **Measure:** Disease-free survival **Time Frame:** up to 5 years **Description:** Defined as time to death because of bladder cancer from beginning of protocol therapy **Measure:** Disease specific survival **Time Frame:** up to 5 years ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Histologically confirmed muscle-invasive urothelial cancer of the bladder within 60 days of study enrollment. Variant histology and cis are not allowed. Patients must be willing to provide a TURBT specimen during screening and prior to enrollment if adequate specimen (FFPE tissue block or 20 unstained slides) from initial TURBT documenting muscle-invasive urothelial bladder cancer is not available. The specimen must be assessed as PD-L1 positive by two pathologists using SP263 kit. 2. Clinical stage T2-T3, N0, M0 urothelial bladder cancer. 3. Deemed to not be a candidate for radical cystectomy by attending urologic oncologist or refuse radical cystectomy. 4. Willing to receive maximal transurethral resection or partial cystectomy to remove all bladder tumors 5. Be willing and able to provide written informed consent/assent for the trial. 6. Have a performance status of 0 or 2 on the Eastern Cooperative Oncology Group Performance Scale. 7. Demonstrate adequate organ function as defined below, all screening labs should be performed within 10 days of protocol enrollment. * Absolute neutrophil count \>= 1,500 /mcL; * Platelets \>= 100,000 /mcL; * Hemoglobin \>= 9.0 g/dL; * Serum creatinine \<=1.5 x upper limit of normal (ULN) or calculated creatinine clearance \>= 30 mL/min as calculated by Cockcrof-Gault formulae or by 24 hour urine collection; * Serum total bilirubin \<=1.5 x ULN or direct bilirubin \<= ULN for subjects with total -bilirubin levels \> 1.5 x ULN; * Aspartate aminotransferase and alanine aminotransferase \<= 1.5 x ULN; * Albumin \>= 2.5 mg/dL; * International normalized ratio or prothrombin time (PT) \<= 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or partial prothrombin time (PTT) is within therapeutic range of intended use of anticoagulants; * Activated Partial Thromboplastin Time (aPTT) \<= 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants. 8. Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. 9. Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \> 1 year. 10. Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy. Exclusion Criteria: 1. Has received prior radiation therapy or systemic chemotherapy for urothelial bladder cancer including neoadjuvant chemotherapy. Prior intravesical chemotherapy or intravesical immunotherapy is permissible, however, no prior intravesical therapy is permitted within 4 weeks of study enrollment; adjuvant therapy is not permitted. 2. Has received prior pelvic radiation therapy. 3. Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment. 4. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. 5. Has a known history of active TB (Bacillus Tuberculosis). 6. Hypersensitivity to tislelizumab or any of its excipients. 7. Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier. 8. If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy. 9. Any prior history of invasive malignancy within the past 5 years except non-melanoma skin cancer, carcinoma in-situ, localized prostate cancer without biochemical recurrence following definitive treatment. 10. Has other active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. 11. History of Guillain-Barre Syndrome or Stevens-Johnson Syndrome 12. Has known history of, or any evidence of active, non-infectious pneumonitis. 13. Has an active infection requiring systemic therapy. 14. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. 15. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. 16. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment. 17. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent. 18. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies). 19. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA \[qualitative\] is detected). 20. Has received a live vaccine within 30 days of planned start of study therapy. Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed **Maximum Age:** 75 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Yunze Xu, PhD **Phone:** +8618801967501 **Role:** CONTACT #### Locations **Location 1:** **City:** Shanghai **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Yunze Xu, PhD - **Phone:** +8618801967501 - **Role:** CONTACT **Country:** China **Facility:** Renji Hospital, School of Medicine, Shanghai Jiao Tong University **State:** Shanghai **Status:** RECRUITING **Zip:** 200127 #### Overall Officials **Official 1:** **Affiliation:** Renji Hospital, School of Medicine, Shanghai Jiao Tong University **Name:** Wei Xue, PhD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000014571 - Term: Urologic Neoplasms - ID: D000014565 - Term: Urogenital Neoplasms - ID: D000009371 - Term: Neoplasms by Site - ID: D000009369 - Term: Neoplasms - ID: D000052776 - Term: Female Urogenital Diseases - ID: D000005261 - Term: Female Urogenital Diseases and Pregnancy Complications - ID: D000091642 - Term: Urogenital Diseases - ID: D000001745 - Term: Urinary Bladder Diseases - ID: D000014570 - Term: Urologic Diseases - ID: D000052801 - Term: Male Urogenital Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: All - Name: All Conditions - Abbrev: BXS - Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M5534 - Name: Carcinoma - Relevance: LOW - As Found: Unknown - ID: M5551 - Name: Carcinoma, Transitional Cell - Relevance: LOW - As Found: Unknown - ID: M5030 - Name: Urinary Bladder Neoplasms - Relevance: HIGH - As Found: Carcinoma Bladder - ID: M17320 - Name: Urologic Neoplasms - Relevance: LOW - As Found: Unknown - ID: M17315 - Name: Urogenital Neoplasms - Relevance: LOW - As Found: Unknown - ID: M2875 - Name: Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M27093 - Name: Female Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M14127 - Name: Pregnancy Complications - Relevance: LOW - As Found: Unknown - ID: M8399 - Name: Female Urogenital Diseases and Pregnancy Complications - Relevance: LOW - As Found: Unknown - ID: M5026 - Name: Urinary Bladder Diseases - Relevance: LOW - As Found: Unknown - ID: M17319 - Name: Urologic Diseases - Relevance: LOW - As Found: Unknown - ID: M27095 - Name: Male Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: T5693 - Name: Transitional Cell Carcinoma - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000001749 - Term: Urinary Bladder Neoplasms ### Intervention Browse Module - Ancestors - ID: D000000970 - Term: Antineoplastic Agents - ID: D000000964 - Term: Antimetabolites, Antineoplastic - ID: D000000963 - Term: Antimetabolites - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000074322 - Term: Antineoplastic Agents, Immunological ### Intervention Browse Module - Browse Branches - Abbrev: ANeo - Name: Antineoplastic Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M137899 - Name: Tislelizumab - Relevance: HIGH - As Found: Healthcare - ID: M6182 - Name: Cisplatin - Relevance: LOW - As Found: Unknown - ID: M2985 - Name: Gemcitabine - Relevance: HIGH - As Found: Activity - ID: M4281 - Name: Antimetabolites - Relevance: LOW - As Found: Unknown - ID: M1346 - Name: Antineoplastic Agents, Immunological - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000093542 - Term: Gemcitabine - ID: C000707970 - Term: Tislelizumab ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00994279 **Brief Title:** Yoga or Educational Wellness Class for Women With Stage I, Stage II, or Stage III Breast Cancer Undergoing Chemotherapy **Official Title:** Yoga or Wellness Education During Breast Cancer Treatment: Establishing Community-Based Partnerships #### Organization Study ID Info **ID:** IRB00011383 #### Organization **Class:** OTHER **Full Name:** Wake Forest University Health Sciences #### Secondary ID Infos **ID:** U10CA081851 **Link:** https://reporter.nih.gov/quickSearch/U10CA081851 **Type:** NIH **Domain:** NCI **ID:** REBACCCWFU97309 **Type:** OTHER ### Status Module #### Completion Date **Date:** 2011-10-14 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2021-10-20 **Type:** ACTUAL **Last Update Submit Date:** 2021-09-27 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2011-10-14 **Type:** ACTUAL #### Results First Post Date **Date:** 2017-03-09 **Type:** ACTUAL **Results First Submit Date:** 2015-07-15 **Results First Submit QC Date:** 2017-01-18 #### Start Date **Date:** 2010-01 **Type:** ACTUAL **Status Verified Date:** 2021-09 #### Study First Post Date **Date:** 2009-10-14 **Type:** ESTIMATED **Study First Submit Date:** 2009-10-13 **Study First Submit QC Date:** 2009-10-13 ### Sponsor Collaborators Module #### Collaborators **Class:** NIH **Name:** National Cancer Institute (NCI) #### Lead Sponsor **Class:** OTHER **Name:** Wake Forest University Health Sciences #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** RATIONALE: Yoga and wellness classes may reduce fatigue and improve mood, sleep, and quality of life in women receiving chemotherapy for breast cancer. It is not yet known whether yoga is more effective than wellness education for women with breast cancer who are undergoing chemotherapy. PURPOSE: This randomized phase II trial is studying a community-based yoga class to see how well it works compared with an educational wellness class for women with stage I, stage II, or stage III breast cancer undergoing chemotherapy. **Detailed Description:** OBJECTIVES: Primary * To estimate the participation rate, accrual, adherence, and retention to a community-based study of yoga vs an active control (wellness education) in women with stage I-III breast cancer undergoing chemotherapy. Secondary * To obtain estimates of the variability of women's self-reported fatigue and depressive symptoms, sleep quality, and health-related quality of life from baseline to the end of the intervention at 10 weeks. * To obtain estimates of the efficacy of a community-based yoga intervention in women with breast cancer. * To standardize the yoga protocol for use in multiple community settings with breast cancer patients, and ascertain that yoga teachers can adhere to a uniform protocol. OUTLINE: This is a multicenter study. Patients are stratified according to CCOP site and chemotherapy-treatment status (planning vs started). Patients are randomized to 1 of 2 intervention arms. Patients must begin their class or group within 3 weeks of starting chemotherapy. All women enter their class or group on a rolling basis so that their class or group coincides with the weeks that they receive chemotherapy treatments. * Arm I (Yoga intervention): In weeks 1-10, patients attend a community-based weekly 75-minute Integral Yoga class led by an experienced yoga teacher specifically trained in adapting yoga for people with cancer. The yoga class includes postures, deep relaxation, breathing practices, and meditation to create a profound experience of peace and well-being. Women are asked to attend ≥ 8 of 10 classes over a 12-week period to allow for missed classes. Women are also provided with a yoga mat, associated yoga props (bolster, strap), and a 45-minute cancer-specific yoga DVD for home practice. Women are asked to practice yoga outside of the class at least twice per week, and are encouraged to practice more frequently than that. * Arm II (Active control): Patients meet for a weekly 75-minute wellness education group in weeks 1-10 (women may make-up missed classes during weeks 11 and 12). The group focuses on issues that women with breast cancer face as they undergo treatment; topics include symptom management, financial and insurance issues, emotional issues/coping with cancer, communicating with healthcare providers/navigating the healthcare system, healthful eating/cooking demonstrations, sexual issues/fertility/body image, mobilizing social support/impact of cancer on family and friends, survivorship (advocacy) opportunities, and common concerns/fear of recurrence. Women are provided with reading materials relevant to the topics that will be covered in each group meeting and are asked to spend approximately 45 minutes twice weekly reading these materials and incorporating any relevant principles/ideas into their daily lives. Women may request additional reading materials in further topics of interest from the group facilitators. Patients complete questionnaires at baseline and at weeks 5, 10, and 14 to assess fatigue (FACIT-Fatigue), depressive symptoms (Center for Epidemiologic Studies-Depression Scale \[CES-D\]), treatment-related symptoms (M.D. Anderson Symptom Inventory \[MDASI\]), sleep disturbance (Medical Outcomes Study Sleep Measure \[MOS-Sleep\]), and health-related quality of life (Functional Assessment of Cancer Therapy-Breast \[FACT-B\]). Patients also track time spent on all home-yoga practice (arm I) or wellness-group homework (arm II). After the intervention (week 10), patients are asked to provide feedback on the program. Yoga/Wellness teachers will completion intervention feedback forms 6 months from the start of the first intervention and at completion of the study. ### Conditions Module **Conditions:** - Breast Cancer - Depression - Fatigue - Sleep Disorders **Keywords:** - fatigue - depression - sleep disorders - stage IA breast cancer - stage IB breast cancer - stage II breast cancer - stage IIIA breast cancer - stage IIIB breast cancer - stage IIIC breast cancer - recurrent breast cancer ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** SUPPORTIVE_CARE #### Enrollment Info **Count:** 40 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Yoga Intervention **Intervention Names:** - Behavioral: Yoga **Label:** Arm 1: Yoga Intervention **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** Educational Wellness Group **Intervention Names:** - Behavioral: Education **Label:** Arm 2: Educational Wellness Group **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Arm 1: Yoga Intervention **Description:** Yoga sessions **Name:** Yoga **Type:** BEHAVIORAL #### Intervention 2 **Arm Group Labels:** - Arm 2: Educational Wellness Group **Description:** Educational Wellness Group **Name:** Education **Type:** BEHAVIORAL ### Outcomes Module #### Primary Outcomes **Description:** Proportion of participants completing the 10 week study **Measure:** Retention **Time Frame:** 10 weeks #### Secondary Outcomes **Description:** FACIT-Fatigue patient reported outcome. This questionnaire consists of 13 questions answered on a 0 to 4 scale with a min of 0 and a max of 52. Higher scores indicate less fatigue. **Measure:** Fatigue at 10 Weeks **Time Frame:** 10 weeks ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: Women will be eligible if they are: * Scheduled to begin chemotherapy treatment within 3 weeks of study registration, or able to start Yoga/Wellness sessions prior to second chemotherapy treatment. * ≥18 years of age. * Physically able to attend yoga classes (simply meaning that they can physically make it to the intervention session and are able to sit on a chair or lie on the floor) (ECOG Performance Status rating 0-2; Zubrod et al., 1960). * Diagnosed with breast cancer Stages I-III. * Chemotherapy is anticipated to continue during the 10 weeks of the study intervention. * 2-8 weeks post-completion of breast surgery (unless receiving neoadjuvant chemotherapy). * Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: * Have practiced yoga on a regular basis (at least once a week) within the past 4 weeks to recruit women who are not already regularly practicing yoga. Given that the benefits of yoga are likely more immediate than long-term, however, we will enroll women who have previously had a yoga practice. * Are being treated with surgery and/or radiation therapy and/or hormonal treatment only and/or Herceptin therapy only (no chemotherapy). * Anticipate undergoing surgery related to their breast cancer or receipt of radiation therapy during the study period. * Have regularly engaged in moderate (activity that makes you breathe somewhat harder than normal; may include carrying light loads, bicycling at a regular pace, fast walking, tennis, easy swimming, or popular or folk dancing) or vigorous (activity that causes heavy breathing, sweating, rapid fatigue; it can only be sustained for very short periods of time, like running or swimming strongly) physical activity at least 3-5 days per week (on average) within the past 4 weeks. Pregnant women will not be excluded from this study because the study intervention(s) pose no risk of potential for teratogenic or abortifacient effects. In fact, gentle yoga practice is quite safe for pregnant women and poses can be slightly modified, if needed. The anticipated number of pregnant women eligible to enroll is minimal. **Minimum Age:** 18 Years **Sex:** FEMALE **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Winston-Salem **Country:** United States **Facility:** Wake Forest University Comprehensive Cancer Center **State:** North Carolina **Zip:** 27157-1096 #### Overall Officials **Official 1:** **Affiliation:** Wake Forest University Health Sciences **Name:** Edward G. Shaw, MD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009371 - Term: Neoplasms by Site - ID: D000009369 - Term: Neoplasms - ID: D000001941 - Term: Breast Diseases - ID: D000012871 - Term: Skin Diseases - ID: D000001526 - Term: Behavioral Symptoms - ID: D000001523 - Term: Mental Disorders - ID: D000009422 - Term: Nervous System Diseases - ID: D000009461 - Term: Neurologic Manifestations ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC17 - Name: Skin and Connective Tissue Diseases - Abbrev: All - Name: All Conditions - Abbrev: BXM - Name: Behaviors and Mental Disorders - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: BC10 - Name: Nervous System Diseases ### Condition Browse Module - Browse Leaves - ID: M5220 - Name: Breast Neoplasms - Relevance: HIGH - As Found: Breast Cancer - ID: M7058 - Name: Depression - Relevance: HIGH - As Found: Depression - ID: M7061 - Name: Depressive Disorder - Relevance: LOW - As Found: Unknown - ID: M8364 - Name: Fatigue - Relevance: HIGH - As Found: Fatigue - ID: M22242 - Name: Parasomnias - Relevance: HIGH - As Found: Sleep Disorders - ID: M14850 - Name: Recurrence - Relevance: LOW - As Found: Unknown - ID: M15696 - Name: Sleep Wake Disorders - Relevance: HIGH - As Found: Sleep Disorders - ID: M5218 - Name: Breast Diseases - Relevance: LOW - As Found: Unknown - ID: M15674 - Name: Skin Diseases - Relevance: LOW - As Found: Unknown - ID: M4818 - Name: Behavioral Symptoms - Relevance: LOW - As Found: Unknown - ID: M4815 - Name: Mental Disorders - Relevance: LOW - As Found: Unknown - ID: M14473 - Name: Psychotic Disorders - Relevance: LOW - As Found: Unknown - ID: M12404 - Name: Neurologic Manifestations - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000001943 - Term: Breast Neoplasms - ID: D000012893 - Term: Sleep Wake Disorders - ID: D000020447 - Term: Parasomnias - ID: D000005221 - Term: Fatigue - ID: D000003863 - Term: Depression ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module **Description:** Sample includes all patients with follow-up toxicity assessments. This number is different from the sample size in other analyses because some participants provided follow-up toxicity assessments before they went off study. Patients were asked about adverse events at each assessment visit. #### Event Groups **Group ID:** EG000 **Title:** Arm 1: Yoga Intervention **Description:** Yoga Intervention Yoga: Yoga sessions **ID:** EG000 **Other Num Affected:** 11 **Other Num at Risk:** 21 **Serious Number Affected:** 1 **Serious Number At Risk:** 21 **Title:** Arm 1: Yoga Intervention **Group ID:** EG001 **Title:** Arm 2: Educational Wellness Group **Description:** Educational Wellness Group Education: Educational Wellness Group **ID:** EG001 **Other Num Affected:** 8 **Other Num at Risk:** 17 **Serious Number Affected:** 1 **Serious Number At Risk:** 17 **Title:** Arm 2: Educational Wellness Group **Frequency Threshold:** 5 #### Other Events **Term:** Back Pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Fatigue **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Infections and Infestations **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** CTCAE (4.0) **Term:** Mucositis oral **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Musculoskeletal/Soft tissue = Cartilage Tears **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Myalgia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Nausea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Neck Pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Pain in Extremity **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Palmar-plantar erythrodysesthesia syndrome **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Peripheral nerve infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** CTCAE (4.0) **Term:** Peripheral sensory neuropathy **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Rash acneiform **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Sore Throat **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** CTCAE (4.0) **Term:** Urinary tract infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** CTCAE (4.0) #### Serious Events **Term:** Febrile Neutropenia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** CTCAE (4.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 21 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 17 **Num Events:** 1 **Term:** Heart Failure **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** CTCAE (4.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 21 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 17 **Time Frame:** 14 weeks ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 22 **Group ID:** BG001 **Value:** 18 **Group ID:** BG002 **Value:** 40 **Units:** Participants ### Group **ID:** BG000 **Title:** Arm 1: Yoga Intervention **Description:** Yoga Intervention Yoga: Yoga sessions ### Group **ID:** BG001 **Title:** Arm 2: Educational Wellness Group **Description:** Educational Wellness Group Education: Educational Wellness Group ### Group **ID:** BG002 **Title:** Total **Description:** Total of all reporting groups ### Measure #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** <=18 years #### Measurement **Group ID:** BG000 **Value:** 19 #### Measurement **Group ID:** BG001 **Value:** 18 #### Measurement **Group ID:** BG002 **Value:** 37 **Category Title:** Between 18 and 65 years #### Measurement **Group ID:** BG000 **Value:** 3 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 3 **Category Title:** >=65 years **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Lower Limit:** 29 **Upper Limit:** 83 **Value:** 50 #### Measurement **Group ID:** BG001 **Lower Limit:** 29 **Upper Limit:** 64 **Value:** 45 #### Measurement **Group ID:** BG002 **Lower Limit:** 29 **Upper Limit:** 83 **Value:** 47 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 22 #### Measurement **Group ID:** BG001 **Value:** 18 #### Measurement **Group ID:** BG002 **Value:** 40 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** Male **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** Hispanic or Latino #### Measurement **Group ID:** BG000 **Value:** 22 #### Measurement **Group ID:** BG001 **Value:** 18 #### Measurement **Group ID:** BG002 **Value:** 40 **Category Title:** Not Hispanic or Latino #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** Unknown or Not Reported **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** American Indian or Alaska Native #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** Asian #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** Native Hawaiian or Other Pacific Islander #### Measurement **Group ID:** BG000 **Value:** 2 #### Measurement **Group ID:** BG001 **Value:** 3 #### Measurement **Group ID:** BG002 **Value:** 5 **Category Title:** Black or African American #### Measurement **Group ID:** BG000 **Value:** 20 #### Measurement **Group ID:** BG001 **Value:** 15 #### Measurement **Group ID:** BG002 **Value:** 35 **Category Title:** White #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** More than one race #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** Unknown or Not Reported **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 22 #### Measurement **Group ID:** BG001 **Value:** 18 #### Measurement **Group ID:** BG002 **Value:** 40 **Class Title:** United States **Denomination Units Selected:** ## Results Section - Baseline Characteristics Module ### Measure 1 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Age, Categorical **Unit of Measure:** Participants ### Measure 2 **Dispersion Type:** FULL_RANGE **Parameter Type:** MEDIAN **Title:** Age, Continuous **Unit of Measure:** years ### Measure 3 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Sex: Female, Male **Unit of Measure:** Participants ### Measure 4 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Ethnicity (NIH/OMB) **Unit of Measure:** Participants ### Measure 5 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Race (NIH/OMB) **Unit of Measure:** Participants ### Measure 6 **Parameter Type:** NUMBER **Title:** Region of Enrollment **Unit of Measure:** participants **Population Description:** All randomized participants ## Results Section - More Information Module ### Certain Agreement **PI Sponsor Employee:** True ### Limitations and Caveats **Description:** There were no limitations. ### Point of Contact **Email:** [email protected] **Organization:** Wake Forest NCI NCORP Research Base **Phone:** (336) 716-1048 **Title:** Dr. Doug Case ## Results Section - Outcome Measures Module ### Outcome Measure 1 #### Analysis **CI Lower Limit:** **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Null hypothesis is that the two arms will not differ in retention at 14 weeks. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER_LEGACY **Other Analysis Description:** **P-Value:** .53 **P-Value Comment:** **Parameter Type:** **Parameter Value:** **Statistical Comment:** **Statistical Method:** Chi-squared **Tested Non-Inferiority:** ### Outcome Measure 2 #### Analysis **CI Lower Limit:** **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Null hypothesis is that the two groups would not differ in fatigue at 10 weeks. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER_LEGACY **Other Analysis Description:** **P-Value:** .98 **P-Value Comment:** **Parameter Type:** **Parameter Value:** **Statistical Comment:** **Statistical Method:** Mixed Models Analysis **Tested Non-Inferiority:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 60 - **Spread:** - **Upper Limit:** 95 - **Value:** 82 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 65 - **Spread:** - **Upper Limit:** 99 - **Value:** 89 **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 2.6 - **Upper Limit:** - **Value:** 30.2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 2.9 - **Upper Limit:** - **Value:** 30.1 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** Proportion of participants completing the 10 week study **Dispersion Type:** 95% Confidence Interval **Parameter Type:** NUMBER **Population Description:** All randomized participants **Reporting Status:** POSTED **Time Frame:** 10 weeks **Title:** Retention **Type:** PRIMARY **Unit of Measure:** percentage of participants ##### Group **Description:** Yoga Intervention Yoga: Yoga sessions **ID:** OG000 **Title:** Arm 1: Yoga Intervention ##### Group **Description:** Educational Wellness Group Education: Educational Wellness Group **ID:** OG001 **Title:** Arm 2: Educational Wellness Group #### Outcome Measure 2 **Description:** FACIT-Fatigue patient reported outcome. This questionnaire consists of 13 questions answered on a 0 to 4 scale with a min of 0 and a max of 52. Higher scores indicate less fatigue. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** Participants with 10 week outcome data. Note that one participant in the Wellness group was missing this outcome even though they completed the study. **Reporting Status:** POSTED **Time Frame:** 10 weeks **Title:** Fatigue at 10 Weeks **Type:** SECONDARY **Unit of Measure:** units on a scale ##### Group **Description:** Yoga Intervention Yoga: Yoga sessions **ID:** OG000 **Title:** Arm 1: Yoga Intervention ##### Group **Description:** Educational Wellness Group Education: Educational Wellness Group **ID:** OG001 **Title:** Arm 2: Educational Wellness Group ### Participant Flow Module #### Group **Description:** Yoga Intervention Yoga: Yoga sessions **ID:** FG000 **Title:** Arm 1: Yoga Intervention #### Group **Description:** Educational Wellness Group Education: Educational Wellness Group **ID:** FG001 **Title:** Arm 2: Educational Wellness Group #### Period **Title:** Overall Study ##### Withdraw **Type:** Withdrawal by Subject ###### Reason **Group ID:** FG000 **Number of Subjects:** 2 ###### Reason **Group ID:** FG001 **Number of Subjects:** 2 ##### Withdraw **Type:** Toxicity ###### Reason **Group ID:** FG000 **Number of Subjects:** 1 ###### Reason **Group ID:** FG001 **Number of Subjects:** 0 ##### Withdraw **Type:** Multiple reasons ###### Reason **Group ID:** FG000 **Number of Subjects:** 1 ###### Reason **Group ID:** FG001 **Number of Subjects:** 3 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 22 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 18 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 18 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 13 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 4 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 5 **Recruitment Details:** Participants were recruited from three NCI CCOP sites between 1/2010 and 8/2011 **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT05380479 **Brief Title:** Mirtazapine Versus Megestrol Acetate in Treatment of Anorexia-cachexia in Advanced Cancer Patients. **Official Title:** Mirtazapine Versus Megestrol Acetate in Treatment of Anorexia-cachexia in Advanced Cancer Patients: A Randomized, Double-Blind Trail. #### Organization Study ID Info **ID:** BSMMU/2022/4193 #### Organization **Class:** OTHER **Full Name:** Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh ### Status Module #### Completion Date **Date:** 2023-02-01 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** RECRUITING #### Last Update Post Date **Date:** 2022-05-18 **Type:** ACTUAL **Last Update Submit Date:** 2022-05-17 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2023-01-01 **Type:** ESTIMATED #### Start Date **Date:** 2022-06-01 **Type:** ESTIMATED **Status Verified Date:** 2022-05 #### Study First Post Date **Date:** 2022-05-18 **Type:** ACTUAL **Study First Submit Date:** 2022-05-10 **Study First Submit QC Date:** 2022-05-17 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh #### Responsible Party **Investigator Affiliation:** Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh **Investigator Full Name:** Dr. Iftekhar Hossain Chowdhury **Investigator Title:** Principal Investigator **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Is US Export:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** This study was 8 weeks randomized, double-blind trail to assess the effect of mirtazapine versus megestrol acetate in treatment of anorexia-cachexia in advanced cancer patients in 80 patients. Participants were assessed at baseline, 4 weeks and 8 weeks. Subject were randomized to receive either mirtazapine 15 mg tablet daily or megestrol acetate 160 mg tablet daily for 8 weeks. The primary outcome was the measure of FAACT(A/C) score and the secondary measure includes weight, BMI, quality of life and evaluate adverse effects. **Detailed Description:** Cancer-related cachexia and anorexia (CRCA) comprises one of the most common syndrome of advanced cancers characterize by anorexia, tissue wasting and loss of body weight accompanied by a decrease in muscle mass and adipose tissue and by poor performance status that often precedes death . Death usually occurs when there is a 30% weight loss. The prevalence of CRCA increases from 50 to 80% before death, and in more than 20% of cancer patients, it is the cause of death. Cancer-related cachexia and anorexia (CRCA) is associated not only with impaired quality of life in patients and family members but also with shorter survival. The management of cancer-related cachexia and anorexia (CRCA) is a great challenge in clinical practice. To date, practice guidelines for the prevention and treatment of CRCA are lacking. Although megestrol acetate and dexamethasone have shown benefits for CRCA in terms of weight gain. There is no definitive evidence that these agents improve patient quality of life. This proposed study is therefore an effort whether there is any role of mirtazapine to improvement of anorexia in cancer patients. This study will be a randomized, double-blind, clinical trial. It will be conducted in the department of pharmacology, BSMMU in collaboration with the department of clinical oncology, BSMMU, NIRCH \& Delta Hospital from the day of approval by the IRB to June, 2022. A total of eighty (80) patients attend in the outpatient department of clinical oncology, BSMMU, NIRCH \& Delta Hospital diagnosed as cancer anorexia will be selected for the study according to inclusion and exclusion criteria. Then participants will randomly be assigned into two intervention groups. The cancer anorexia of each participant will be assessed by Functional Assessment of Anorexia/Cachexia Therapy at baseline. The group A (40) will receive mirtazapine15mg tablet and other group B (40) will receive megestrol acetate160mg tablet orally once a day for 8 weeks. After 4 and 8 weeks each participant will be assessed once again by Functional Assessment of Anorexia/Cachexia Therapy. The quality of life of CRAC each participant will be assessed by EORTC QLQ-C30. ### Conditions Module **Conditions:** - Anorexia **Keywords:** - Cancer - Anorexia - Cachexia - Mirtazapine - Megestrol Acetate ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** DOUBLE **Who Masked:** - PARTICIPANT - INVESTIGATOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 80 **Type:** ESTIMATED **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Tablets of 15mg mirtazapine will be used according to randomization. At the first visit, patients will be instructed to take one tablet at night. This group will consist of 40 patients with anorexia in advanced cancer patients. **Intervention Names:** - Drug: Mirtazapine **Label:** Mirtazapine **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Tablets of 160mg megestrol will be used according to randomization. At the first visit, patients will be instructed to take one tablet at night This group will consist of 40 patients with anorexia in advanced cancer patients. **Intervention Names:** - Drug: Megestrol Acetate **Label:** Megestrol Acetate **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Mirtazapine **Description:** mirtazaine15 mg tablet daily for 8 weeks. **Name:** Mirtazapine **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Megestrol Acetate **Description:** megestrol acetate 160 mg tablet daily for 8 weeks. **Name:** Megestrol Acetate **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** The primary endpoint will assess the percentage of patients who continue to present anorexia after 8 weeks of treatment. Anorexia will be defined as the lack of desire to eat, lack of appetite, as measured using the validated version of the Anorexia / Cachexia Scale from the Functional Assessment of Anorexia Cachexia Therapy (FAACT). A score of less than or equal to 24 will be considered diagnostic for anorexia **Measure:** Percentage of patients with Anorexia **Time Frame:** From the baseline assessment to 8 weeks] #### Secondary Outcomes **Description:** Sum of all the components of the organism and represents the total body mass. **Measure:** Weight **Time Frame:** From the baseline assessment to 8 weeks] **Description:** It is an index of the weight of a person in relation to his height BMI = Weight (Kg.) / \[height (m) \* height) (m)\] **Measure:** Body Mass Index **Time Frame:** From the baseline assessment to 8 weeks] **Description:** The physical functioning will be evaluated using the validated Bangla version of the European Organization for the Research and Treatment of Cancer (EORTC) Quality of life questionnaires specific for cancer using the physical functioning scale (from QLQ-C30 version 3.0).The Change over time as well as the difference between groups will be analyzed. **Measure:** Quality of life - physical functioning **Time Frame:** From the baseline assessment to 8 weeks] **Description:** The questioning about the occurrence of treatment-related adverse events will also be performed at the outpatient clinic at baseline and weeks 4 and 8 during the follow-up. **Measure:** Incidence of treatment-related Adverse Events [Time Frame: 8 weeks] **Time Frame:** Time Frame: 8 weeks ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Patients aged ≥ 18 years, with a histologically diagnosed advanced-stage tumor at any site. * Assumptive or documented loss of \>5% of pre-illness or ideal body weight (body mass index) in the previous 3 months. * Patients could be receiving concomitant chemotherapy, radiotherapy and/or palliative supportive care. * Patients ECOG Performance Status 0-3. Exclusion Criteria: * Patients with a mechanical obstruction to feeding. * Patients with high doses of corticosteroids. * Patients with clinically bulky ascites and generalized edema. * Patients with inability to take oral medications. * History of uncontrolled diabetes mellitus and hypertension. **Maximum Age:** 70 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Iftekhar Chowdhury, MD **Phone:** +8801816197635 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Prof.Md.Sayedur Rahman, FCPS.M Phil **Phone:** +8801712205305 **Role:** CONTACT #### Locations **Location 1:** **City:** Dhaka **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Registrar - **Phone:** +889661064 - **Role:** CONTACT **Country:** Bangladesh **Facility:** Bangabandhu Sheikh Mujib Medical University **Status:** RECRUITING **Zip:** 1000 ### IPD Sharing Statement Module **Description:** The result of this research will be published as an article in a journal **Info Types:** - STUDY_PROTOCOL - SAP - ICF **IPD Sharing:** YES **Time Frame:** After the publication of the results of study ## Derived Section ### Condition Browse Module - Ancestors - ID: D000012817 - Term: Signs and Symptoms, Digestive - ID: D000015431 - Term: Weight Loss - ID: D000001836 - Term: Body Weight Changes - ID: D000001835 - Term: Body Weight - ID: D000013851 - Term: Thinness - ID: D000008659 - Term: Metabolic Diseases - ID: D000009748 - Term: Nutrition Disorders ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC18 - Name: Nutritional and Metabolic Diseases ### Condition Browse Module - Browse Leaves - ID: M4181 - Name: Anorexia - Relevance: HIGH - As Found: Anorexia - ID: M21265 - Name: Wasting Syndrome - Relevance: HIGH - As Found: Cachexia - ID: M5363 - Name: Cachexia - Relevance: HIGH - As Found: Cachexia - ID: M16355 - Name: Syndrome - Relevance: LOW - As Found: Unknown - ID: M15622 - Name: Signs and Symptoms, Digestive - Relevance: LOW - As Found: Unknown - ID: M5114 - Name: Body Weight - Relevance: LOW - As Found: Unknown - ID: M18102 - Name: Weight Loss - Relevance: LOW - As Found: Unknown - ID: M5115 - Name: Body Weight Changes - Relevance: LOW - As Found: Unknown - ID: M16614 - Name: Thinness - Relevance: LOW - As Found: Unknown - ID: M11639 - Name: Metabolic Diseases - Relevance: LOW - As Found: Unknown - ID: M12684 - Name: Nutrition Disorders - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000019282 - Term: Wasting Syndrome - ID: D000000855 - Term: Anorexia - ID: D000002100 - Term: Cachexia ### Intervention Browse Module - Ancestors - ID: D000000928 - Term: Antidepressive Agents - ID: D000011619 - Term: Psychotropic Drugs - ID: D000006634 - Term: Histamine H1 Antagonists - ID: D000006633 - Term: Histamine Antagonists - ID: D000018494 - Term: Histamine Agents - ID: D000018377 - Term: Neurotransmitter Agents - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000014151 - Term: Anti-Anxiety Agents - ID: D000014149 - Term: Tranquilizing Agents - ID: D000002492 - Term: Central Nervous System Depressants - ID: D000058669 - Term: Adrenergic alpha-2 Receptor Antagonists - ID: D000000317 - Term: Adrenergic alpha-Antagonists - ID: D000018674 - Term: Adrenergic Antagonists - ID: D000018663 - Term: Adrenergic Agents - ID: D000058830 - Term: Serotonin 5-HT2 Receptor Antagonists - ID: D000012702 - Term: Serotonin Antagonists - ID: D000018490 - Term: Serotonin Agents - ID: D000058831 - Term: Serotonin 5-HT3 Receptor Antagonists - ID: D000003278 - Term: Contraceptives, Oral, Hormonal - ID: D000003276 - Term: Contraceptives, Oral - ID: D000003271 - Term: Contraceptive Agents, Female - ID: D000003270 - Term: Contraceptive Agents - ID: D000012102 - Term: Reproductive Control Agents - ID: D000080066 - Term: Contraceptive Agents, Hormonal - ID: D000003280 - Term: Contraceptives, Oral, Synthetic - ID: D000018931 - Term: Antineoplastic Agents, Hormonal - ID: D000000970 - Term: Antineoplastic Agents - ID: D000019167 - Term: Appetite Stimulants - ID: D000000697 - Term: Central Nervous System Stimulants ### Intervention Browse Module - Browse Branches - Abbrev: ANeo - Name: Antineoplastic Agents - Abbrev: Repr - Name: Reproductive Control Agents - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: CNSSti - Name: Central Nervous System Stimulants - Abbrev: CNSDep - Name: Central Nervous System Depressants - Abbrev: PsychDr - Name: Psychotropic Drugs ### Intervention Browse Module - Browse Leaves - ID: M11518 - Name: Megestrol - Relevance: HIGH - As Found: January - ID: M21272 - Name: Megestrol Acetate - Relevance: HIGH - As Found: Caucasian - ID: M2007 - Name: Mirtazapine - Relevance: HIGH - As Found: Inadequate - ID: M4247 - Name: Antidepressive Agents - Relevance: LOW - As Found: Unknown - ID: M14474 - Name: Psychotropic Drugs - Relevance: LOW - As Found: Unknown - ID: M9710 - Name: Histamine H1 Antagonists - Relevance: LOW - As Found: Unknown - ID: M9708 - Name: Histamine - Relevance: LOW - As Found: Unknown - ID: M212144 - Name: Histamine phosphate - Relevance: LOW - As Found: Unknown - ID: M9709 - Name: Histamine Antagonists - Relevance: LOW - As Found: Unknown - ID: M20504 - Name: Neurotransmitter Agents - Relevance: LOW - As Found: Unknown - ID: M16905 - Name: Anti-Anxiety Agents - Relevance: LOW - As Found: Unknown - ID: M20746 - Name: Adrenergic Agents - Relevance: LOW - As Found: Unknown - ID: M29195 - Name: Adrenergic alpha-2 Receptor Antagonists - Relevance: LOW - As Found: Unknown - ID: M3669 - Name: Adrenergic alpha-Antagonists - Relevance: LOW - As Found: Unknown - ID: M20755 - Name: Adrenergic Antagonists - Relevance: LOW - As Found: Unknown - ID: M15512 - Name: Serotonin - Relevance: LOW - As Found: Unknown - ID: M29246 - Name: Serotonin 5-HT3 Receptor Antagonists - Relevance: LOW - As Found: Unknown - ID: M6494 - Name: Contraceptive Agents - Relevance: LOW - As Found: Unknown - ID: M6500 - Name: Contraceptives, Oral - Relevance: LOW - As Found: Unknown - ID: M6502 - Name: Contraceptives, Oral, Hormonal - Relevance: LOW - As Found: Unknown - ID: M6495 - Name: Contraceptive Agents, Female - Relevance: LOW - As Found: Unknown - ID: M2116 - Name: Contraceptive Agents, Hormonal - Relevance: LOW - As Found: Unknown - ID: M20966 - Name: Antineoplastic Agents, Hormonal - Relevance: LOW - As Found: Unknown - ID: M4029 - Name: Central Nervous System Stimulants - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000008535 - Term: Megestrol - ID: D000019290 - Term: Megestrol Acetate - ID: D000078785 - Term: Mirtazapine ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03802279 **Acronym:** EFFORHAB **Brief Title:** Evaluate the Effort Test as a Therapeutic Monitoring Tool in Acute Rhabdomyolyses **Official Title:** Study of the Correlation Between the Effort Test, With the Assessment of Peripheral Oxygen Consumption and Cardiac Output in Patients With Acute Rhabdomyolysis Related to a Hereditary Disease of Metabolism, and the Biochemical Flux on Myoblasts: Evaluate the Effort Test as a Therapeutic Monitoring Tool in Acute Rhabdomyolyses #### Organization Study ID Info **ID:** APHP 180 009 #### Organization **Class:** OTHER **Full Name:** Assistance Publique - Hôpitaux de Paris #### Secondary ID Infos **Domain:** ID-RCB **ID:** 2018-A01771-54 **Type:** REGISTRY ### Status Module #### Completion Date **Date:** 2021-12-31 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2022-10-12 **Type:** ACTUAL **Last Update Submit Date:** 2022-10-10 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2021-12-31 **Type:** ACTUAL #### Start Date **Date:** 2019-10-25 **Type:** ACTUAL **Status Verified Date:** 2022-10 #### Study First Post Date **Date:** 2019-01-14 **Type:** ACTUAL **Study First Submit Date:** 2018-12-06 **Study First Submit QC Date:** 2019-01-10 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Assistance Publique - Hôpitaux de Paris #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** The prognosis of rhabdomyolyses related to hereditary diseases of metabolism is poor and treatments are only symptomatic. Rhabdomyolysis outbreaks are frequently precipitated by fever and fasting. They are unpredictable. In spite of the care of patient in an intensive care unit, the occurrence of renal failure and heart rhythm disorders explains a significant acute-phase mortality rate. There is an urgent need to understand the pathophysiological mechanisms of rhabdomyolyses related to hereditary diseases of metabolism, in order to identify specific treatments. Patients with rhabdomyolyses have few clinical signs outside of access. So there is a methodological difficulty in following a treatment test. There is an urgency to identify follow-up parameters in anticipation of new therapies. The objective of this study is to validate the hypothesis that effort test and cardiac function parameters are usable in the treatment monitoring for patients with acute rhabdomyolysis linked to a hereditary disease of metabolism and thus propose the effort test as an assessment tool for future clinical trials. In order to do so, the correlation between the results of the effort tests, performed to each patient with rhabdomyolysis related to a hereditary disease of metabolism, with the severity of the disease will be evaluated. This study is original because it opens up innovative prospects for monitoring in the field of hereditary diseases of metabolism, with the identification of new monitoring tools. **Detailed Description:** Rhabdomyolysis is a poorly known symptom associated with the destruction of skeletal muscle cells. The diagnosis of rhabdomyolyses is carried when the dosage of muscle enzymes, in particular creatine phosphate kinase (KPC), is greater than 1000 U/L (normal \< 160 U/L). Rhabdomyolyses may be of viral origin, but fever and viruses are also triggers of genetic diseases. Also, the incidence of genetic rhabdomyolyses, representing 10 to 15% of all rhabdomyolyses, is underestimated. Genetic causes are heterogeneous. They are mainly attributed to hereditary diseases of metabolism, in particular fatty acid oxidation defects, Lipin-1 deficiency, muscle glycogenoses, TANGO2 deficiency, mitochondrial cytopathies and calcium channels anomalies of in particular RYR1. Whatever the cause, traumatic, infectious or genetic, the rhabdomyolyses cause an alteration of the metabolism of adenosine triphosphate and a deregulation of the ionic channels, with the consequences of an intracytoplasmic calcium release and the destruction of muscle cells. The prognosis of rhabdomyolyses related to hereditary diseases of metabolism is poor and treatments are only symptomatic. Rhabdomyolysis outbreaks are frequently precipitated by fever and fasting. They are unpredictable. In spite of the care of patient in an intensive care unit, the occurrence of renal failure and heart rhythm disorders explains a significant acute-phase mortality rate. There is an urgent need to understand the pathophysiological mechanisms of rhabdomyolyses related to hereditary diseases of metabolism, in order to identify specific treatments. The pathophysiological mechanism of rhabdomyolyses related to Lipin-1 deficiency has been identified. Two patients with Lipin-1 deficiency treated in vivo by Hydroxychloroquine (Plaquenil ®, 6 mg/kg/day by one oral intake) rapidly standardized their serum inflammatory profile and corrected their clinical phenotype: Plasma creatine phosphokinase levels, Amount of mitochondrial DNA in plasma, number of myolyses, muscular pain, quality of life. One of these two patients, suffering from cardiac dysfunction already reported in Lipin-1 deficiency (left ventricular ejection fraction or LVEF 45%), significantly and durably improved cardiac function after one month of treatment (LVEF 62%). In addition, his fatigability and sleep disturbances have dramatically improved. Disruption of mitophagy and immunity could be a common denominator for rhabdomyolyses linked to hereditary diseases of metabolism, which could, despite their heterogeneity, benefit from a common therapeutic approach, Now non-existent. There could be a role of inflammation in rhabdomyolyses outbreaks of metabolic origin and new therapeutic approaches could be imagined as in the Lipin-1 deficiency. Patients with rhabdomyolyses have few clinical signs outside of access. So there is a methodological difficulty in following a treatment test. There is an urgency to identify follow-up parameters in anticipation of new therapies. In the Lipin deficiency, an anomaly of the effort tests with measurement of oxygen consumption and cardiac output was characterized. These effort tests were carried out in the context of care, in order to recognize for a given patient whether the practice of sport is a factor triggering rhabdomyolysis. The objective of this study is to validate the hypothesis that effort test and cardiac function parameters are usable in the treatment monitoring for patients with acute rhabdomyolysis linked to a hereditary disease of metabolism and thus propose the effort test as an assessment tool for future clinical trials. To date, no tests are available for clinical trials. In order to do so, the correlation between the results of the effort tests, performed to each patient with rhabdomyolysis related to a hereditary disease of metabolism, with the severity of the disease will be assessed, including: 1) Metabolic flux on myoblasts, 2) clinical severity (onset of disease, number of rhabdomyolyses, cardiomyopathy), 3) genotype. This study is original because it opens up innovative prospects for monitoring in the field of hereditary diseases of metabolism, with the identification of new monitoring tools. ### Conditions Module **Conditions:** - Rhabdomyolysis Linked to a Hereditary Disease of Metabolism **Keywords:** - Rhabdomyolysis linked to a hereditary disease of metabolism - Correlation between the effort test and the severity of the disease and biochemical flux on myoblasts ### Design Module #### Design Info **Observational Model:** CASE_CONTROL **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 27 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Patients with a rhabdomyolysis linked to a hereditary disease of metabolism who have benefited from a diagnostically muscle biopsy and whose myoblasts are available. Patients benefit from an effort test as part of their care. **Intervention Names:** - Other: Effort test - Other: Functional tests on fibroblasts **Label:** Rhabdomyolysis with myoblasts back up #### Arm Group 2 **Description:** Patients with a rhabdomyolysis linked to a hereditary disease of metabolism who have benefited or not from a diagnostically muscle biopsy but whose myoblasts are not available. Patients benefit from an effort test as part of their care. **Intervention Names:** - Other: Effort test **Label:** Rhabdomyolysis #### Arm Group 3 **Description:** 10 patient-matched healthy controls for age and sex having performed an effort test and cardiac exploration as part of their care. **Intervention Names:** - Other: Effort test **Label:** Witness patients : effort test #### Arm Group 4 **Description:** 6 healthy controls matched by age and sex having performed a muscle biopsy as part of their care and whose myoblasts are kept. **Intervention Names:** - Other: Functional tests on fibroblasts **Label:** Witness patients : myoblasts ### Interventions #### Intervention 1 **Arm Group Labels:** - Rhabdomyolysis - Rhabdomyolysis with myoblasts back up - Witness patients : effort test **Description:** Cardiac function: Echocardiography: left ventricular ejection fraction and global longitudinal strain will be measured. Cardiopulmonary exercise test (CPET): left ventricular stroke volume was assessed noninvasively using a thoracic bioelectrical impedance device : maximal stroke volume at the peak of effort will be considered. Peripheral muscle function: * CPET: Oxygen uptake (VO2) (and carbon dioxide) output are measured. The slope of the relationship (dQ/dVO2) will be calculated between cardiac output (Q) and VO2 using measurements of Q (using measure of the stroke volume by thoracic bioelectrical impedance device) and VO2 at rest as well as during submaximal and maximal exercise * Muscle oxygenation is measured using a near-infrared spectroscopy device. * VO2 et Q will be measured : dQ/dVO2 is high in case of oxydation defect; If Q is low because of a concommittant cardiac impairement, the DAV = VO2/Q, and DO = (Q x DAV) / (200 - DAV) will be calculated. **Name:** Effort test **Type:** OTHER #### Intervention 2 **Arm Group Labels:** - Rhabdomyolysis with myoblasts back up - Witness patients : myoblasts **Description:** Functional tests performed on fibroblasts in primary culture, using as tracers of stable isotope-labeled substrates. The metabolites of interest are assayed in mass spectrometry. **Name:** Functional tests on fibroblasts **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** Effort test **Measure:** Measurement of cardiac output (Q) **Time Frame:** Day 0 **Description:** Effort test **Measure:** Measurement of oxygen consumption (VO2) **Time Frame:** Day 0 **Description:** Effort test **Measure:** Calculation of the slope of the relationship heart rate-oxygen consumed (dQ/dVO2) **Time Frame:** Day 0 **Description:** Effort test **Measure:** Calculation of the maximum arteriovenous difference (DAV) : DAV=VO2/Q **Time Frame:** Day 0 **Description:** Effort test **Measure:** Calculation of maximum muscle diffusion (DM) using the equation of Fick: DM = (Q x DAV)/(200-DAV) **Time Frame:** Day 0 **Description:** Measurement of peripheral muscular oxygenation during the effort test. **Measure:** Peripheral muscular oxygenation **Time Frame:** Day 0 **Description:** Evaluation of cardiac performance by the value of the systolic ejection volume at the peak of the effort. The systolic ejection volume is measured beat per beat during the effort test. **Measure:** Systolic ejection volume at the peak of the effort during the effort test **Time Frame:** Day 0 **Description:** Measurement of the ejection fraction of the left ventricle in Simpson biplane and the longitudinal strain of the left ventricle in echocardiography. **Measure:** Ejection fraction of the left ventricle **Time Frame:** Day 0 **Description:** Myoblasts will be incubated in the presence of stable isotope-labeled tracers. The natural metabolites labelled with stable isotopes will be dosed. The acylcarnitines will be dosed on a mass spectrometer. The Krebs cycle intermediates will be measured in gas chromatography coupled with mass spectrometry. **Measure:** Metabolic pathways of myoblasts **Time Frame:** From study start until 26 months #### Secondary Outcomes **Description:** Clinical severity of rhabdomyolysis linked to a hereditary disease of metabolism. **Measure:** Presence of cardiomyopathy **Time Frame:** Day 0 **Description:** Clinical severity of rhabdomyolysis linked to a hereditary disease of metabolism. **Measure:** Age of onset of disease (neonatal, < 2 years, 2 - 10 years, > 10 years) **Time Frame:** Day 0 **Description:** Clinical severity of rhabdomyolysis linked to a hereditary disease of metabolism. **Measure:** Number of acute episodes of rhabdomyolyses **Time Frame:** Day 0 **Description:** Genotypic severity of rhabdomyolysis linked to a hereditary disease of metabolism. Information available in the patient medical record. **Measure:** Character of mutations nonsense or missense of the hereditary disease of metabolism **Time Frame:** Day 0 ### Eligibility Module **Eligibility Criteria:** subjects with metabolic rhabdomyolysis related to a hereditary metabolic disease : Inclusion Criteria: * pathology characterized on the biochemical and molecular level * patients who can make an effort test * patients who benefited from a diagnostically targeted muscle biopsy with backup of myoblasts (group 1) * patients who have benefited from a diagnostically targeted muscle biopsy but whose myoblasts are not available (group 2) Exclusion Criteria * inability or refusal of compliance to the requirements of the research * patients with contraindications for the effort test in particular heart failure and acute rhabdomyolysis * Patients without biochemical and/or molecular diagnosis Criteria for inclusion of witness patients : * holders of parental authority and/or patients not opposed to the use of their cardio-respiratory analysis results for this study or to the use of their myoblasts for this study * normal cardio-respiratory analysis results * normal myoblasts (group 4). **Maximum Age:** 75 Years **Minimum Age:** 6 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - CHILD - ADULT - OLDER_ADULT **Study Population:** The population to be studied consists of 40 patients with metabolic rhabdomyolyses followed by the centre of reference for metabolic diseases of the child and adult of the Necker Hospital. ### Contacts Locations Module #### Locations **Location 1:** **City:** Paris **Country:** France **Facility:** Hôpital Necker-Enfants Malades **Zip:** 75015 #### Overall Officials **Official 1:** **Affiliation:** Assistance Publique - Hôpitaux de Paris **Name:** Pascale de Lonlay **Role:** PRINCIPAL_INVESTIGATOR **Official 2:** **Affiliation:** Assistance Publique - Hôpitaux de Paris **Name:** Antoine Legendre, MD, PhD **Role:** STUDY_CHAIR **Official 3:** **Affiliation:** Assistance Publique - Hôpitaux de Paris **Name:** Florence Habarou, MD, PhD **Role:** STUDY_CHAIR **Official 4:** **Affiliation:** Assistance Publique - Hôpitaux de Paris **Name:** Caroline Tuchmann-Durand, Pharm. D, PhD **Role:** STUDY_CHAIR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009135 - Term: Muscular Diseases - ID: D000009140 - Term: Musculoskeletal Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC05 - Name: Musculoskeletal Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC16 - Name: Diseases and Abnormalities at or Before Birth - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M15035 - Name: Rhabdomyolysis - Relevance: HIGH - As Found: Rhabdomyolysis - ID: M23686 - Name: Genetic Diseases, Inborn - Relevance: HIGH - As Found: Hereditary Diseases - ID: M12092 - Name: Muscular Diseases - Relevance: LOW - As Found: Unknown - ID: M12097 - Name: Musculoskeletal Diseases - Relevance: LOW - As Found: Unknown - ID: T170 - Name: Acute Graft Versus Host Disease - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000012206 - Term: Rhabdomyolysis - ID: D000030342 - Term: Genetic Diseases, Inborn ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT01401179 **Acronym:** PPROM **Brief Title:** Antibiotics Study in Preterm Premature Rupture of the Membranes **Official Title:** Randomized Phase III Trial of Cefazolin or Combination of Cefazolin and Erythromycin or Cefazolin and Clarithromycin in Women With Preterm Premature Rupture of the Membranes #### Organization Study ID Info **ID:** 2005-04-003 #### Organization **Class:** OTHER **Full Name:** Samsung Medical Center ### Status Module #### Completion Date **Date:** 2010-04 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2011-08-08 **Type:** ESTIMATED **Last Update Submit Date:** 2011-08-05 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2010-04 **Type:** ACTUAL #### Start Date **Date:** 2005-04 **Status Verified Date:** 2011-07 #### Study First Post Date **Date:** 2011-07-25 **Type:** ESTIMATED **Study First Submit Date:** 2011-07-19 **Study First Submit QC Date:** 2011-07-22 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Samsung Medical Center #### Responsible Party **Old Name Title:** Soo-young Oh, M.D. PhD **Old Organization:** Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** The purpose of this study is to compare the efficacy on maternal infection, chorioamnionitis and neonatal morbidity and mortality, and to review the evidence and provide recommendations on the use of antibiotics in PPROM. **Detailed Description:** Despite major advances in perinatal care, preterm delivery is still the predominant cause of perinatal mortality and a major cause of neurological morbidity and mortality. Although the determinants of preterm labor and delivery are uncertain, evidence suggests intrauterine infection is a contributing factor. Antibiotic therapy for women in preterm premature rupture of membranes has been a routine practice. However the optimal regimen remains unclear and the choice of latency antibiotic regimen is at the discretion of admitting physician. The group 1 is treated only with cefazolin (1.0mg iv every 6 hours for 7 days). The group 2 is given a combination of cefazolin(1.0mg iv every 6 hours for 7 days) and erythromycin(250mg p.o. four times a day for 7 days). In group 3, clarithromycin (500mg p.o. 4 times a day for 7 days) was treated with cefazolin(1.0mg iv every 6 hours for 7 days). This study is designed to compare the efficacy on maternal infection, chorioamnionitis and neonatal morbidity and mortality and to review the evidence and provide recommendations on the use of antibiotics, especially by comparing the combination regimen in PPROM. ### Conditions Module **Conditions:** - Preterm Premature Rupture of the Membranes **Keywords:** - Preterm Premature Rupture of Fetal Membranes - antibiotic therapy ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** FACTORIAL ##### Masking Info **Masking:** SINGLE **Who Masked:** - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 101 **Type:** ACTUAL **Phases:** - PHASE3 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Intervention Names:** - Drug: cefazolin, erythromycin, clarithromycin **Label:** cefazolin **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** cefazolin, erythromycin **Intervention Names:** - Drug: cefazolin, erythromycin, clarithromycin **Label:** cefazolin plus erythromycin **Type:** ACTIVE_COMPARATOR #### Arm Group 3 **Intervention Names:** - Drug: cefazolin, erythromycin, clarithromycin **Label:** cefazolin plus clarithromycin **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - cefazolin - cefazolin plus clarithromycin - cefazolin plus erythromycin **Description:** Antibiotics regimen was one of cefazolin or cefazolin plus erythromycin or cefazolin plus clarithromycin. Intravenous 1g cefazolin was given every 6 hours after negative result skin test for allergic reaction. With cefazolin plus erythromycin group or cefazolin plus clarithromycin, cefazolin was given with same protocol and 250mg oral erythromycin every 6 hours or 500mg oral clarithromycin every 12 hours was added. All antibiotics were given for 7 days or until delivery. **Name:** cefazolin, erythromycin, clarithromycin **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** 1. respiratory distress syndrome(RDS) 2. bronchopulmonary dysplasia(BPD) 3. intraventricular hemorrhage(IVH,≥grade 3) 4. retinopathy of prematurity(ROP,≥grade 3) 5. necrotizing enterocolitis(NEC,≥stage 2) 6. proven neonatal sepsis **Measure:** Neonatal composite morbidity **Time Frame:** Participants will be followed for duration of hospital day after delivery, an expected average of 8 weeks. #### Secondary Outcomes **Measure:** the incidence of abnormal brain sonography **Time Frame:** Participants will be followed for duration of hospital day after delivery, an expected average of 8 weeks. **Description:** The outcome was evaluated in five sub-domains (development, neurologic examination, Bayley Scales of Infant Development-II, vision, and hearing). The final outcome scale was divided into normal, mild, moderate, and severe disability. **Measure:** infantile neurologic outcome **Time Frame:** at 6 months and 1 year of corrected age ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * PPROM, PA 23+0\~33+0wks * ROM \<48 hrs before randomization * singleton * Cervical dilatation \<3cm * uterine contraction less than 4 times per 1 hr Exclusion Criteria: * Major fetal malformation * Multifetal pregnancy * Rupture of the membrane \>8hrs before randomization * Prior antibiotics use at local clinic before referral * Vaginal bleeding * IIOC (incompetent internal os of cervix) * Placenta previa * Gestational diabetes or overt diabetes * Hypertensive disorders in pregnancy * Liver cirrhosis * Acute renal failure * IUGR(Intrauterine growth restriction) **Sex:** FEMALE **Standard Ages:** - CHILD - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Seoul **Country:** Korea, Republic of **Facility:** Samsung Medical center **Zip:** 135-710 #### Overall Officials **Official 1:** **Affiliation:** Samsung Medical Center **Name:** Soo-Young Oh, M.D., PhD **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000007752 - Term: Obstetric Labor, Premature - ID: D000007744 - Term: Obstetric Labor Complications - ID: D000011248 - Term: Pregnancy Complications - ID: D000005261 - Term: Female Urogenital Diseases and Pregnancy Complications - ID: D000091642 - Term: Urogenital Diseases - ID: D000014947 - Term: Wounds and Injuries ### Condition Browse Module - Browse Branches - Abbrev: BXS - Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions - Abbrev: All - Name: All Conditions - Abbrev: BC26 - Name: Wounds and Injuries ### Condition Browse Module - Browse Leaves - ID: M25869 - Name: Premature Birth - Relevance: HIGH - As Found: Premature - ID: M15241 - Name: Rupture - Relevance: HIGH - As Found: Rupture - ID: M8452 - Name: Fetal Membranes, Premature Rupture - Relevance: HIGH - As Found: Preterm Premature Rupture of the Membranes - ID: M10772 - Name: Obstetric Labor, Premature - Relevance: LOW - As Found: Unknown - ID: M10764 - Name: Obstetric Labor Complications - Relevance: LOW - As Found: Unknown - ID: M14127 - Name: Pregnancy Complications - Relevance: LOW - As Found: Unknown - ID: M2875 - Name: Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M27093 - Name: Female Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M8399 - Name: Female Urogenital Diseases and Pregnancy Complications - Relevance: LOW - As Found: Unknown - ID: M17685 - Name: Wounds and Injuries - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000047928 - Term: Premature Birth - ID: D000005322 - Term: Fetal Membranes, Premature Rupture - ID: D000012421 - Term: Rupture ### Intervention Browse Module - Ancestors - ID: D000000900 - Term: Anti-Bacterial Agents - ID: D000000890 - Term: Anti-Infective Agents - ID: D000011500 - Term: Protein Synthesis Inhibitors - ID: D000004791 - Term: Enzyme Inhibitors - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000065692 - Term: Cytochrome P-450 CYP3A Inhibitors - ID: D000065607 - Term: Cytochrome P-450 Enzyme Inhibitors - ID: D000005765 - Term: Gastrointestinal Agents ### Intervention Browse Module - Browse Branches - Abbrev: Infe - Name: Anti-Infective Agents - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Gast - Name: Gastrointestinal Agents ### Intervention Browse Module - Browse Leaves - ID: M5687 - Name: Cefazolin - Relevance: HIGH - As Found: EUS- - ID: M4222 - Name: Anti-Bacterial Agents - Relevance: LOW - As Found: Unknown - ID: M4224 - Name: Antibiotics, Antitubercular - Relevance: LOW - As Found: Unknown - ID: M19585 - Name: Clarithromycin - Relevance: HIGH - As Found: Prescription - ID: M8068 - Name: Erythromycin - Relevance: HIGH - As Found: 1 or 2 - ID: M8069 - Name: Erythromycin Estolate - Relevance: HIGH - As Found: 1 or 2 - ID: M18236 - Name: Erythromycin Ethylsuccinate - Relevance: HIGH - As Found: 1 or 2 - ID: M195803 - Name: Erythromycin stearate - Relevance: HIGH - As Found: 1 or 2 - ID: M4214 - Name: Anti-Infective Agents - Relevance: LOW - As Found: Unknown - ID: M7951 - Name: Enzyme Inhibitors - Relevance: LOW - As Found: Unknown - ID: M30564 - Name: Cytochrome P-450 CYP3A Inhibitors - Relevance: LOW - As Found: Unknown - ID: M30537 - Name: Cytochrome P-450 Enzyme Inhibitors - Relevance: LOW - As Found: Unknown - ID: M8881 - Name: Gastrointestinal Agents - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000017291 - Term: Clarithromycin - ID: D000002437 - Term: Cefazolin - ID: D000004917 - Term: Erythromycin - ID: D000004918 - Term: Erythromycin Estolate - ID: D000015643 - Term: Erythromycin Ethylsuccinate - ID: C000011462 - Term: Erythromycin stearate ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05277779 **Brief Title:** EARLY Assessment of MYOcardial Tissue Characteristics in OBESITY (EARLY-MYO-OBESITY) **Official Title:** EARLY Assessment of MYOcardial Tissue Characteristics in OBESITY (EARLY-MYO-OBESITY) #### Organization Study ID Info **ID:** ACFO2021 #### Organization **Class:** OTHER **Full Name:** RenJi Hospital ### Status Module #### Completion Date **Date:** 2022-12-30 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2023-06-01 **Type:** ACTUAL **Last Update Submit Date:** 2023-05-30 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2022-12-30 **Type:** ACTUAL #### Start Date **Date:** 2019-01-01 **Type:** ACTUAL **Status Verified Date:** 2022-02 #### Study First Post Date **Date:** 2022-03-14 **Type:** ACTUAL **Study First Submit Date:** 2022-03-03 **Study First Submit QC Date:** 2022-03-03 ### Sponsor Collaborators Module #### Collaborators **Class:** UNKNOWN **Name:** Ningbo Hangzhou Bay Hospital **Class:** UNKNOWN **Name:** Shanghai Jiading Central Hospital #### Lead Sponsor **Class:** OTHER **Name:** RenJi Hospital #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False ### Description Module **Brief Summary:** EARLY-MYO-OBESITY-CMR is a prospective, three-center, cardiac imaging study to investigate cardiac morphology, function, and tissue phenotypes in a cohort of non-diabetic obese adults, and compare with metabolically healthy non-obese controls. **Detailed Description:** 1. Transthoracic echocardiography was performed to analyze the LV morphology and function. 2. CMR was performed within 24 hours of the echocardiographic examination to assess the cardiac morphology , cardiac function, and myocardial tissue characteristics. Standard cine images were acquired to quantify LV function and volume. T1 mapping-derived ECV values were used to detect subtle diffuse fibrosis , and late gadolinium-enhanced (LGE) imaging was used to identify focal fibrosis. Native T2 values were obtained to quantify myocardial edema . Global longitudinal peak systolic strain (GLS) and e' SR were assessed by tissue tracking analysis to detect subclinical systolic and diastolic dysfunction. ### Conditions Module **Conditions:** - Obese ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 120 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** non-obese （BMI\<25kg/m2）controls without known endocrine diseases, cardiac disease, or other comorbidities, and with unremarkable imaging results. **Intervention Names:** - Diagnostic Test: cardiac magnetic resonance(CMR) **Label:** control #### Arm Group 2 **Description:** obese individuals having no more than one of the metabolic syndrome components (with exception of increased waist circumference) and without impaired glucose tolerance (defined as a 2-hour post loading glucose level of 7.7-11.1mmol/L ) **Intervention Names:** - Diagnostic Test: cardiac magnetic resonance(CMR) **Label:** metabolically healthy obese #### Arm Group 3 **Description:** obese individuals with more than one metabolic syndrome components or impaired glucose tolerance **Intervention Names:** - Diagnostic Test: cardiac magnetic resonance(CMR) **Label:** metabolically unhealthy obese ### Interventions #### Intervention 1 **Arm Group Labels:** - control - metabolically healthy obese - metabolically unhealthy obese **Description:** CMR was performed to assess myocardial tissue characteristics in the study population **Name:** cardiac magnetic resonance(CMR) **Type:** DIAGNOSTIC_TEST ### Outcomes Module #### Primary Outcomes **Description:** cardiac morphology and function were assessed by CMR steady-state free precession sequences **Measure:** investigate cardiac morphology and function by CMR **Time Frame:** 24 hours within recruitment **Description:** myocardial edema and fibrosis were assessed by CMR T2 mapping and ECV **Measure:** investigate cardiac tissue characteristics by CMR **Time Frame:** 24 hours within recruitment ### Eligibility Module **Eligibility Criteria:** Inclusion criteria: * age 18-75 years without cardiac symptoms or known cardiac diseas; * body mass index ≥25 kg/m2 Exclusion criteria: * coronary artery disease (coronary artery stenosis \>50% on angiography or coronary computed tomography, documented myocardial infarction, or a history of coronary artery bypass graft surgery or percutaneous coronary intervention) * non-ischemic cardiovascular disease, such as idiopathic cardiomyopathy, valvular disease, congenital heart disease, or pulmonary heart diseas * a left ventricular (LV) ejection fraction of\<50% on echocardiography or a history of heart failure * arrhythmia or the presence of bundle branch block on electrocardiography * pacemaker or defibrillator implantation * renal dysfunction with an estimated glomerular filtration rate of \<60 mL/min/1.73 m2 * contraindications to cardiac magnetic resonance (CMR) imaging * malignancy or life expectancy of less than 2 year * inability to provide written informed consent **Healthy Volunteers:** True **Maximum Age:** 75 Years **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Adult obese participants without cardiac symptoms or known cardiac disease ### Contacts Locations Module #### Locations **Location 1:** **City:** Shanghai **Country:** China **Facility:** Renji Hospital **State:** Shanghai **Zip:** 200127 #### Overall Officials **Official 1:** **Affiliation:** Renji Hospital, Shanghai **Name:** Meng Jiang **Role:** STUDY_DIRECTOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000050177 - Term: Overweight - ID: D000044343 - Term: Overnutrition - ID: D000009748 - Term: Nutrition Disorders - ID: D000001835 - Term: Body Weight ### Condition Browse Module - Browse Branches - Abbrev: BC18 - Name: Nutritional and Metabolic Diseases - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M12701 - Name: Obesity - Relevance: HIGH - As Found: Obesity - ID: M26186 - Name: Overweight - Relevance: LOW - As Found: Unknown - ID: M25307 - Name: Overnutrition - Relevance: LOW - As Found: Unknown - ID: M12684 - Name: Nutrition Disorders - Relevance: LOW - As Found: Unknown - ID: M5114 - Name: Body Weight - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000009765 - Term: Obesity ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03618979 **Brief Title:** A Trial Comparing Three Orthobiologic Therapies on Atrophied Multifidus Muscles in Patients With Low Back Pain **Official Title:** A Randomized Controlled Trial to Assess the Effects of Autologous Platelet Rich Plasma, Platelet Lysate, and Platelet Poor Plasma on Atrophied Multifidus Muscles in Patients With Axial Lower Back Pain #### Organization Study ID Info **ID:** RGX2018-RCT01 #### Organization **Class:** INDUSTRY **Full Name:** Regenexx, LLC ### Status Module #### Completion Date **Date:** 2022-06-29 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2022-07-08 **Type:** ACTUAL **Last Update Submit Date:** 2022-07-06 **Overall Status:** TERMINATED #### Primary Completion Date **Date:** 2022-06-29 **Type:** ACTUAL #### Start Date **Date:** 2019-05-02 **Type:** ACTUAL **Status Verified Date:** 2022-07 #### Study First Post Date **Date:** 2018-08-07 **Type:** ACTUAL **Study First Submit Date:** 2018-08-02 **Study First Submit QC Date:** 2018-08-02 **Why Stopped:** Low enrollment ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Regenexx, LLC #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** To evaluate and compare the effectiveness of 3 different injection treatments on multifidus atrophy and lower back pain. **Detailed Description:** This study is a prospective, randomized controlled study of patients with atrophied multifidus muscles and axial lower back pain that are randomized to one of 3 treatment groups. Group 1 receives a series of 6 injections (1 time per week for 6 weeks) of platelet poor plasma into multifidus. Group 2 receives a series of 6 injections (1 time per week for 6 weeks) of platelet rich plasma (PRP) into multifidus. Group 3 receives a series of 3 injections (1 time every 2 weeks for 6 weeks) of PRP to multifidus, as well as PRP into facet joint, as well as an epidural injection of platelet lysate (PL). Prior to procedure patient will undergo evaluation of medical history, back pain history, lumbar examination, medication use and review MRI of lumbar spine. While lying prone, the patient's back will be exposed and prepped sterilely. While maintaining sterile technique, the physician will utilize US, x-ray or a combination of the two to guide the needles bilaterally into the multifidus, specifically the area of treatment using ultrasound, x-ray or a combination of the two. Once the lamina is reached the physician will either inject autologous 2.5 cc PPP (group 1) or will inject autologous 2.5 cc of 5x PRP into the multifidus muscle on one side and then repeat this on the opposite side for each level (group 2 \& 3). Additionally, for patients in group 3, using sterile technique under fluoroscopic guidance, the physician will guide a needle into the supraneural transforaminal space to perform an epidural injection with 2cc of 3x PL and 1 cc of 0.5% ropivacaine. Next, a needle will then be guided into the facet joint to perform an intra-articular injection with 1cc of 14x PRP. After the procedure, the patient will be cleaned and bandaged. The patient will be given standard rehab protocols to perform at home. Patients will have follow-up visits with patient reported outcomes or pain and function at 3 months, 6 months and 12 months. A post-treatment MRI at 6 months will be compared to baseline MRI to measure changes to multifidus atrophy. ### Conditions Module **Conditions:** - Low Back Pain **Keywords:** - regenerative medicine - low back pain - multifidus - platelet rich plasma ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 8 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Platelet Poor Plasma (PPP) into the multifidus on each side and at each level 1 time per week for 6 weeks (series of 6 injections) **Intervention Names:** - Biological: PPP treatment **Label:** PPP treatment **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** 5x concentration Platelet Rich Plasma (PRP) injected into the multifidus on each side and at each level 1 time per week for 6 weeks (series of 6 injections) **Intervention Names:** - Biological: PRP treatment **Label:** PRP treatment **Type:** EXPERIMENTAL #### Arm Group 3 **Description:** 5x concentration PRP injected into the multifidus, along with a facet joint injection with 14x PRP into each joint and capsule, and transforaminal epidural injection with of 3x concentrated platelet lysate (PL) and 0.5% ropivacaine on each side and at each level 1 time every 2 weeks for 6 weeks total (series of 3 injections) **Intervention Names:** - Biological: PRP and PL Combo treatment **Label:** PRP and PL Combo treatment **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - PPP treatment **Description:** The day prior to or the morning of the procedure, patient will have their blood drawn by a phlebotomist and processed into 5 or 10 cc of PPP depending on if there is lumbar multifidus atrophy in one or two levels. Using sterile technique and ultrasound guidance, once touching the lamina the physician will inject 2.5 cc of PPP. The physician will then repeat the procedure on the opposite side. **Name:** PPP treatment **Type:** BIOLOGICAL #### Intervention 2 **Arm Group Labels:** - PRP treatment **Description:** The day prior to or the morning of the procedure, patient will have their blood drawn by a phlebotomist and processed into 5 or 10 cc of 5x PRP depending on if there is lumbar multifidus atrophy in one or two levels. Using sterile technique and ultrasound guidance, once touching the lamina the physician will inject 2.5 cc of PRP and remove the needle. The physician will then repeat the procedure on the opposite side and at the next level if indicated. **Name:** PRP treatment **Type:** BIOLOGICAL #### Intervention 3 **Arm Group Labels:** - PRP and PL Combo treatment **Description:** The day prior to or the morning of the procedure patient will have their blood drawn by a phlebotomist and processed into 5 or 10 cc of 5x PRP and 5 or 10 cc of PL and 2 or 4 cc of 14x PRP depending on if there will be one or two levels injected. Using sterile technique, under ultrasound visualization into the lumbar multifidus and onto the lamina, the physician will inject the PRP and remove the needle. Under intermittent x-ray, epidural flow is confirmed with contrast, the physician will inject 2cc of the PL and 1cc of 0.5% ropivacaine into the epidural space. Once flow is confirmed for the epidural injection and facet with contrast, 1cc of the 14x PRP is injected into the facet joint. Procedure repeated on the opposite side and next level if indicated. **Name:** PRP and PL Combo treatment **Type:** BIOLOGICAL ### Outcomes Module #### Primary Outcomes **Description:** Change in multifidus atrophy from baseline MRI **Measure:** Post-treatment MRI **Time Frame:** 6 months #### Secondary Outcomes **Description:** Difference between groups for mean improvement scores where -100=100% worse from baseline and 100=100% improved from baseline **Measure:** Single Assessment Numeric Evaluation Improvement Rating-modified **Time Frame:** 3 months, 6 months, 12 months **Description:** Difference between groups for numeric pain scores where 0=no pain and 10=worst pain possible **Measure:** Numeric Pain Scale **Time Frame:** 3 months, 6 months, 12 months **Description:** Difference between groups for function scores where 0=minimal disability and 100=severe disability **Measure:** Functional Rating Index **Time Frame:** 3 months, 6 months, 12 months **Description:** Difference between groups for function scores where 0=minimal disability and 100=severe crippling disability **Measure:** Oswestry Low Back Disability Index **Time Frame:** 3 months, 6 months, 12 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Voluntary signature of the Informed Consent 2. Axial low back pain for a minimum of 3 months 3. Male or female ages 18-75 4. Recent MRI (within last 6 months) consistent Kader grade 2 or 3 multifidus atrophy at 1 or 2 levels 5. Is independent, ambulatory, and can comply with all post-operative evaluations and visits Exclusion Criteria: 1. Mild multifidus atrophy Kader grade 1 2. Multifidus atrophy at more than 2 levels 3. Symptomatic spinal stenosis (e.g. pseudoclaudication with moderate or severe MRI findings of stenosis) 4. Radicular symptoms (e.g. lower extremity radiating numbness, tingling, paresthesia, etc) 5. Fracture, previous spine surgery, neuromuscular disease of the trunk, malignancy, infection, or pregnancy 6. Radiofrequency ablation within the previous 12 months 7. Corticosteroid injection (epidural or facet) within the past 3 months 8. Contraindications for MRI 9. Condition represents a worker's compensation case 10. Currently involved in a health-related litigation procedure 11. Bleeding disorders 12. Allergy or intolerance to study medication 13. Use of chronic opioid 14. Documented history of drug abuse within six months of treatment 15. Any other condition, that in the opinion of the investigator, that would preclude the patient from enrollment **Maximum Age:** 75 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Broomfield **Country:** United States **Facility:** Centeno-Schultz Clinic **State:** Colorado **Zip:** 80021 **Location 2:** **City:** Lone Tree **Country:** United States **Facility:** Centeno-Schultz Clinic **State:** Colorado **Zip:** 80124 #### Overall Officials **Official 1:** **Affiliation:** Centeno-Schultz Clinic **Name:** Christopher Centeno, MD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Aure OF, Nilsen JH, Vasseljen O. Manual therapy and exercise therapy in patients with chronic low back pain: a randomized, controlled trial with 1-year follow-up. Spine (Phila Pa 1976). 2003 Mar 15;28(6):525-31; discussion 531-2. doi: 10.1097/01.BRS.0000049921.04200.A6. **PMID:** 12642755 **Citation:** Suni J, Rinne M, Natri A, Statistisian MP, Parkkari J, Alaranta H. Control of the lumbar neutral zone decreases low back pain and improves self-evaluated work ability: a 12-month randomized controlled study. Spine (Phila Pa 1976). 2006 Aug 15;31(18):E611-20. doi: 10.1097/01.brs.0000231701.76452.05. **PMID:** 16915076 **Citation:** Freeman MD, Woodham MA, Woodham AW. The role of the lumbar multifidus in chronic low back pain: a review. PM R. 2010 Feb;2(2):142-6; quiz 1 p following 167. doi: 10.1016/j.pmrj.2009.11.006. **PMID:** 20193941 **Citation:** Hodges PW, James G, Blomster L, Hall L, Schmid A, Shu C, Little C, Melrose J. Multifidus Muscle Changes After Back Injury Are Characterized by Structural Remodeling of Muscle, Adipose and Connective Tissue, but Not Muscle Atrophy: Molecular and Morphological Evidence. Spine (Phila Pa 1976). 2015 Jul 15;40(14):1057-71. doi: 10.1097/BRS.0000000000000972. **PMID:** 25943090 **Citation:** Kader DF, Wardlaw D, Smith FW. Correlation between the MRI changes in the lumbar multifidus muscles and leg pain. Clin Radiol. 2000 Feb;55(2):145-9. doi: 10.1053/crad.1999.0340. **PMID:** 10657162 **Citation:** Hussein M, Hussein T. Effect of autologous platelet leukocyte rich plasma injections on atrophied lumbar multifidus muscle in low back pain patients with monosegmental degenerative disc disease. SICOT J. 2016 Mar 22;2:12. doi: 10.1051/sicotj/2016002. **PMID:** 27163101 **Citation:** Sicari BM, Agrawal V, Siu BF, Medberry CJ, Dearth CL, Turner NJ, Badylak SF. A murine model of volumetric muscle loss and a regenerative medicine approach for tissue replacement. Tissue Eng Part A. 2012 Oct;18(19-20):1941-8. doi: 10.1089/ten.TEA.2012.0475. Erratum In: Tissue Eng Part A. 2018 May 1;24(9-10):861. **PMID:** 22906411 **Citation:** Miroshnychenko O, Chang WT, Dragoo JL. The Use of Platelet-Rich and Platelet-Poor Plasma to Enhance Differentiation of Skeletal Myoblasts: Implications for the Use of Autologous Blood Products for Muscle Regeneration. Am J Sports Med. 2017 Mar;45(4):945-953. doi: 10.1177/0363546516677547. Epub 2016 Dec 27. **PMID:** 28027451 **Citation:** Gentile NE, Stearns KM, Brown EH, Rubin JP, Boninger ML, Dearth CL, Ambrosio F, Badylak SF. Targeted rehabilitation after extracellular matrix scaffold transplantation for the treatment of volumetric muscle loss. Am J Phys Med Rehabil. 2014 Nov;93(11 Suppl 3):S79-87. doi: 10.1097/PHM.0000000000000145. **PMID:** 25133624 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000010146 - Term: Pain - ID: D000009461 - Term: Neurologic Manifestations ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC10 - Name: Nervous System Diseases ### Condition Browse Module - Browse Leaves - ID: M4714 - Name: Back Pain - Relevance: HIGH - As Found: Back Pain - ID: M19433 - Name: Low Back Pain - Relevance: HIGH - As Found: Low Back Pain - ID: M13066 - Name: Pain - Relevance: LOW - As Found: Unknown - ID: M4589 - Name: Atrophy - Relevance: LOW - As Found: Unknown - ID: M12404 - Name: Neurologic Manifestations - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000001416 - Term: Back Pain - ID: D000017116 - Term: Low Back Pain ### Intervention Browse Module - Browse Branches - Abbrev: CNSDep - Name: Central Nervous System Depressants - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M1700 - Name: Ropivacaine - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00560079 **Brief Title:** Efficacy of Allopurinol and Dypiridamole in Acute Mania **Official Title:** A Double-blind, Randomized, Placebo-controlled 4-week Study on the Efficacy and Safety of the Purinergic Agents Allopurinol and Dipyridamole in Acute Bipolar Mania. #### Organization Study ID Info **ID:** 03T-356 #### Organization **Class:** OTHER **Full Name:** Hospital Espirita de Porto Alegre ### Status Module #### Completion Date **Date:** 2006-04 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2016-08-16 **Type:** ESTIMATED **Last Update Submit Date:** 2016-08-15 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2005-04 **Type:** ACTUAL #### Start Date **Date:** 2003-11 **Status Verified Date:** 2016-08 #### Study First Post Date **Date:** 2007-11-19 **Type:** ESTIMATED **Study First Submit Date:** 2007-11-15 **Study First Submit QC Date:** 2007-11-15 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** Stanley Medical Research Institute #### Lead Sponsor **Class:** OTHER **Name:** Hospital Espirita de Porto Alegre #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** This study aims to evaluate the potential antimanic efficacy, safety and tolorability of the purinergic agents allopurinol and dipyridamole as an add-on treatment to lithium in a sample of 180 drug-free manic patients enrolled in a double-blind, placebo-controlled design. **Detailed Description:** Men and women ages 18 to 65 years, who were inpatients with a diagnosis of manic episode were recruited at the emergency room of Espirita Hospital of Porto Alegre (HEPA), Brazil (n=180) between September 2004 and 2006. The presence of manic episode was confirmed using SCID-I and the severity of episode was evaluated using the Young Mania Rating Scale (YMRS) and the Clinical Global Impression scale (CGI). Patients were required to present a score\>22 on the YMRS at screening to be included. Subjects presenting rapid cycling, mixed episodes and comorbidities with axis I psychiatric disorders were not considered for inclusion. All subjects presented good physical health determined by physical exam, medical history, blood screening and electrocardiogram. Patients were randomly assigned to allopurinol 600 mg/day, dipyridamole 200mg or placebo as add-on medication lithium treatment for a 4-week, double-blind trial. The use of adjunctive antipsychotic agents (typical or second-generation drugs) was not allowed during the double-blind period. Adjunctive diazepam was used when necessary (maximum dose=20mg/day). Raters (psychiatrists) were trained together to establish reliability (YMRS =0.90). This study was approved by the Espirita Hospital Ethics Committee-IRB. Written informed consent was obtained from all patients and/or family member. Possible adverse events were monitored weekly during the follow-up period. Regarding primary outcome measures, we compared the percentage of responders according YMRS score decrease of at least 50% among allopurinol, dipyridamole and placebo groups, using fisher exact test. Also, the percentage of improvement from baseline to endpoint was obtained and compared among groups using analysis of variances (one-way ANOVA) with Duncan post-hoc test. Remission rates (YMRS scores \< 12) were also analyzed. P values \< 0.05 were considered statistically significant. Besides completers analysis, intention to treat and LOCF were employed to include data from drop-out patients who were evaluated at visit 3. Possible correlations were measured using Pearson test. Fischer exact test and X2 evaluated response and remission rates. Data are presented as mean ± standard deviation. ### Conditions Module **Conditions:** - Mania ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** QUADRUPLE **Who Masked:** - PARTICIPANT - CARE_PROVIDER - INVESTIGATOR - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 180 **Type:** ACTUAL **Phases:** - PHASE4 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Lithium 900mg/day plus allopurinol 600mg/day **Intervention Names:** - Drug: Allopurinol **Label:** 1 **Type:** EXPERIMENTAL #### Arm Group 2 **Intervention Names:** - Drug: Dipyridamole **Label:** 2 **Type:** ACTIVE_COMPARATOR #### Arm Group 3 **Intervention Names:** - Drug: Placebo **Label:** 3 **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - 1 **Description:** Allopurinol 600mg/day bid for 28 days **Name:** Allopurinol **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - 2 **Description:** Dipyridamole 200mg/day bid for 28 days **Name:** Dipyridamole **Type:** DRUG #### Intervention 3 **Arm Group Labels:** - 3 **Description:** Placebo **Name:** Placebo **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Measure:** This study aimed to evaluate the potential antimanic efficacy, safety and tolerability **Time Frame:** 28 days #### Secondary Outcomes **Measure:** Plasma uric acid levels **Time Frame:** 28 days ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * The presence of manic episode was confirmed using SCID-I and the severity of episode was evaluated using the Young Mania Rating Scale (YMRS) and the Clinical Global Impression scale (CGI). Patients were required to present a score\>22 on the YMRS at screening to be included.All subjects presented good physical health determined by physical exam, medical history, blood screening and electrocardiogram Exclusion Criteria: * Subjects presenting rapid cycling, mixed episodes and comorbidities with axis I psychiatric disorders were not considered for inclusion. . **Maximum Age:** 65 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Porto Alegre **Country:** Brazil **Facility:** Hospital Espirita de Porto Alegre **State:** RS **Zip:** 91720-440 #### Overall Officials **Official 1:** **Affiliation:** Staff Member **Name:** Rodrigo Machado-Vieira, MD, MSc, PhD **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### References **Citation:** Machado-Vieira R, Soares JC, Lara DR, Luckenbaugh DA, Busnello JV, Marca G, Cunha A, Souza DO, Zarate CA Jr, Kapczinski F. A double-blind, randomized, placebo-controlled 4-week study on the efficacy and safety of the purinergic agents allopurinol and dipyridamole adjunctive to lithium in acute bipolar mania. J Clin Psychiatry. 2008 Aug;69(8):1237-45. doi: 10.4088/jcp.v69n0806. **PMID:** 18681754 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000019954 - Term: Neurobehavioral Manifestations - ID: D000009461 - Term: Neurologic Manifestations - ID: D000009422 - Term: Nervous System Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: BXM - Name: Behaviors and Mental Disorders - Abbrev: All - Name: All Conditions - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M2598 - Name: Mania - Relevance: HIGH - As Found: Mania - ID: M21826 - Name: Neurobehavioral Manifestations - Relevance: LOW - As Found: Unknown - ID: M12404 - Name: Neurologic Manifestations - Relevance: LOW - As Found: Unknown - ID: T170 - Name: Acute Graft Versus Host Disease - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000087122 - Term: Mania ### Intervention Browse Module - Ancestors - ID: D000000963 - Term: Antimetabolites - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000004791 - Term: Enzyme Inhibitors - ID: D000006074 - Term: Gout Suppressants - ID: D000018501 - Term: Antirheumatic Agents - ID: D000016166 - Term: Free Radical Scavengers - ID: D000000975 - Term: Antioxidants - ID: D000020011 - Term: Protective Agents - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000010726 - Term: Phosphodiesterase Inhibitors - ID: D000010975 - Term: Platelet Aggregation Inhibitors - ID: D000014665 - Term: Vasodilator Agents ### Intervention Browse Module - Browse Branches - Abbrev: CNSDep - Name: Central Nervous System Depressants - Abbrev: PsychDr - Name: Psychotropic Drugs - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: ARhu - Name: Antirheumatic Agents - Abbrev: VaDiAg - Name: Vasodilator Agents - Abbrev: PlAggInh - Name: Platelet Aggregation Inhibitors ### Intervention Browse Module - Browse Leaves - ID: M19022 - Name: Lithium Carbonate - Relevance: LOW - As Found: Unknown - ID: M3834 - Name: Allopurinol - Relevance: HIGH - As Found: BIA - ID: M7358 - Name: Dipyridamole - Relevance: HIGH - As Found: Positive control - ID: M4281 - Name: Antimetabolites - Relevance: LOW - As Found: Unknown - ID: M7951 - Name: Enzyme Inhibitors - Relevance: LOW - As Found: Unknown - ID: M20604 - Name: Antirheumatic Agents - Relevance: LOW - As Found: Unknown - ID: M4292 - Name: Antioxidants - Relevance: LOW - As Found: Unknown - ID: M21869 - Name: Protective Agents - Relevance: LOW - As Found: Unknown - ID: M13629 - Name: Phosphodiesterase Inhibitors - Relevance: LOW - As Found: Unknown - ID: M13865 - Name: Platelet Aggregation Inhibitors - Relevance: LOW - As Found: Unknown - ID: M17412 - Name: Vasodilator Agents - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000000493 - Term: Allopurinol - ID: D000004176 - Term: Dipyridamole ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05596279 **Brief Title:** PANOVISION: Feasibility and Safety of Hybrid IVUS-OCT System **Official Title:** Clinical Performance of a Novel Hybrid Intravascular Ultrasound-Optical Coherence Tomography System: a Prospective Randomized Controlled Clinical Trial #### Organization Study ID Info **ID:** VP-3003-1901 #### Organization **Class:** OTHER **Full Name:** Harbin Medical University ### Status Module #### Completion Date **Date:** 2021-07-30 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2023-02-13 **Type:** ACTUAL **Last Update Submit Date:** 2023-02-10 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2020-08-12 **Type:** ACTUAL #### Start Date **Date:** 2019-11-20 **Type:** ACTUAL **Status Verified Date:** 2023-02 #### Study First Post Date **Date:** 2022-10-27 **Type:** ACTUAL **Study First Submit Date:** 2022-10-20 **Study First Submit QC Date:** 2022-10-25 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** Second Hospital of Jilin University **Class:** OTHER **Name:** Wuhan Asia Heart Hospital **Class:** UNKNOWN **Name:** Panorama Hengsheng (Beijing) Science and Technology Co., Ltd. #### Lead Sponsor **Class:** OTHER **Name:** Harbin Medical University #### Responsible Party **Investigator Affiliation:** The Second Affiliated Hospital of Harbin Medical University **Investigator Full Name:** Yu Bo **Investigator Title:** Director of Department of Cardiology **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Intravascular ultrasound (IVUS) and optical coherence tomography (OCT) were all recommended for percutaneous coronary intervention (PCI) optimization in the latest guidelines, however, which imaging modality was more suitable as either a diagnostic or guidance tool was still unknown. Recently, a novel, well-designed hybrid imaging system was approved for clinical use, allowing the accurate co-registration of two imaging modalities and immediate, simultaneous image review. For testing each modality in the hybrid imaging system, the investigators conducted this prospective, multicentre, non-inferiority trial. In this study, all participants achieved hybrid IVUS-OCT imaging after stenting, at meanwhile, patients randomly assigned to the IVUS arm were performed control IVUS (OptiCross, Boston Scientific, Natick, MA), and patients randomly assigned to the OCT arm were performed control OCT (C7 Dragonfly Duo, St. Jude Medical, St. Paul, MN). In this study, the investigators evaluated the non-inferiority of standalone IVUS versus control IVUS or standalone OCT versus control OCT in clinical feasibility using clear stent capture rate (CSCR) and safety using perioperative device-related adverse cardiovascular events. ### Conditions Module **Conditions:** - Coronary Artery Disease - Intravascular Imaging Device **Keywords:** - Hybrid imaging - Intravascular ultrasound - Optical coherence tomography ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** DIAGNOSTIC #### Enrollment Info **Count:** 100 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Hybrid IVUS-OCT and control IVUS were performed after stenting **Intervention Names:** - Diagnostic Test: Intravascular ultrasound **Label:** Intravascular ultrasound **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Hybrid IVUS-OCT and control OCT were performed after stenting **Intervention Names:** - Diagnostic Test: Optical coherence tomography **Label:** Optical coherence tomography **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Intravascular ultrasound **Description:** Hybrid IVUS-OCT and control IVUS were performed after stenting **Name:** Intravascular ultrasound **Type:** DIAGNOSTIC_TEST #### Intervention 2 **Arm Group Labels:** - Optical coherence tomography **Description:** Hybrid IVUS-OCT and control OCT were performed after stenting **Name:** Optical coherence tomography **Type:** DIAGNOSTIC_TEST ### Outcomes Module #### Primary Outcomes **Description:** The CSCR detected was defined as the ratio of the clear stent length to the total stent length **Measure:** Clear stent capture rate (CSCR) **Time Frame:** During the procedure #### Secondary Outcomes **Description:** Measured by IVUS, OCT and hybrid IVUS-OCT **Measure:** Proportion of patients with clear image length ≥ 24mm **Time Frame:** During the procedure **Description:** Assessed by IVUS, OCT and hybrid IVUS-OCT **Measure:** Detection rate of edge dissection, tissue prolapse and stent malapposition **Time Frame:** During the procedure **Description:** Device success is defined as well-manipulated and capable of acquiring intravascular images **Measure:** Device success rate **Time Frame:** During the procedure **Description:** Coronary spasm, acute vessel occlusion, coronary dissection, or thrombosis **Measure:** Adverse procedure-related adverse cardiovascular events **Time Frame:** Periprocedure ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Age 18-75 years * Patients eligible for elective percutaneous coronary intervention * Understand and voluntarily sign the informed consent form Exclusion Criteria: The lesion-related exclusion criteria: * More than 1 stent was planned to deploy in culprit lesion * In-stent restenosis * Bifurcation lesion with proposed double stent implantation * The length of the reference vessel segment proximal or distal to the lesion was less than 5mm * The length of the implanted stent was larger than 33mm * The diameter of reference vessel was less than 2 mm or larger than 4 mm * Lesions were in left main or ostium of right coronary artery * The distance between either end of the lesion and the lateral branches larger than 2 mm in diameter was less than 5 mm * Angiography revealed thrombosis in culprit vessel * Severely calcified lesions or tortuous coronary arteries * Decreased blood flow (thrombolysis in myocardial infarction score ≤ 2) Patients-level exclusion criteria: * Breastfeeding or pregnant women, the subject (or his partner) who had a pregnancy plan during the trial or within 6 months after the end of the trial, and subject who did not agree to use contraception during the trial * Participants who had withdrawn from other clinical studies within 3 months or are participating in other clinical trials * Acute myocardial infarction occurred within one week prior to screening * Cardiac troponin I or cardiac troponin T levels exceed the upper limit of normal reference values within 72 hours of procedure and were of clinical significance * Renal insufficiency with creatinine \> 200μmol/L * Unsuitable for coronary artery bypass grafting (CABG) * Unsuitable for percutaneous coronary intervention; * Coronary spasm * Chronic total occlusion or subtotal occlusion * Severe hemodynamic disturbances or shock * History of CABG * Coagulation is abnormal and clinically significant * Severe heart failure (NYHA III, IV or Left ventricular ejection fraction \< 30%) * History of contrast allergy * Multi-vessel disease * Chemotherapy or planned chemotherapy * Investigators consider unsuitable for participants selected for this study **Maximum Age:** 75 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Harbin **Country:** China **Facility:** The Second Affiliated Hospital of Harbin Medical University **State:** Heilongjiang **Zip:** 150086 **Location 2:** **City:** Wuhan **Country:** China **Facility:** Wuhan Asia Heart Hospital **State:** Hubei **Zip:** 430010 **Location 3:** **City:** Changchun **Country:** China **Facility:** The Second Hospital of Jilin University **State:** Jilin **Zip:** 150056 #### Overall Officials **Official 1:** **Affiliation:** The Second Affiliated Hospital of Harbin Medical University **Name:** Bo Yu, MD, PhD **Role:** STUDY_CHAIR **Official 2:** **Affiliation:** Second Hospital of Jilin University **Name:** Bin Liu, MD, PhD **Role:** PRINCIPAL_INVESTIGATOR **Official 3:** **Affiliation:** Wuhan Asia Heart Hospital **Name:** Xi Su, MD, PhD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000003327 - Term: Coronary Disease - ID: D000017202 - Term: Myocardial Ischemia - ID: D000006331 - Term: Heart Diseases - ID: D000002318 - Term: Cardiovascular Diseases - ID: D000001161 - Term: Arteriosclerosis - ID: D000001157 - Term: Arterial Occlusive Diseases - ID: D000014652 - Term: Vascular Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology ### Condition Browse Module - Browse Leaves - ID: M6549 - Name: Coronary Disease - Relevance: LOW - As Found: Unknown - ID: M6546 - Name: Coronary Artery Disease - Relevance: HIGH - As Found: Coronary Artery Disease - ID: M19506 - Name: Myocardial Ischemia - Relevance: LOW - As Found: Unknown - ID: M10543 - Name: Ischemia - Relevance: LOW - As Found: Unknown - ID: M9419 - Name: Heart Diseases - Relevance: LOW - As Found: Unknown - ID: M4469 - Name: Arteriosclerosis - Relevance: LOW - As Found: Unknown - ID: M4465 - Name: Arterial Occlusive Diseases - Relevance: LOW - As Found: Unknown - ID: M17400 - Name: Vascular Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000003324 - Term: Coronary Artery Disease ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04864379 **Brief Title:** Clinical Study of a Personalized Neoantigen Cancer Vaccine Combined With Anti-PD-1 and RFA in Patients With Solid Tumors **Official Title:** Safety, Tolerability and Immunogenicity of a Personalized Neoantigen Cancer Vaccine Combined With Anti-PD-1 and Radiofrequency Ablation in Patients With Advanced Solid Tumors #### Organization Study ID Info **ID:** INEO-P-003 #### Organization **Class:** OTHER **Full Name:** Sir Run Run Shaw Hospital ### Status Module #### Completion Date **Date:** 2025-08-03 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2021-04-28 **Type:** ACTUAL **Last Update Submit Date:** 2021-04-25 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2025-08-03 **Type:** ESTIMATED #### Start Date **Date:** 2020-09-03 **Type:** ACTUAL **Status Verified Date:** 2021-04 #### Study First Post Date **Date:** 2021-04-28 **Type:** ACTUAL **Study First Submit Date:** 2021-04-25 **Study First Submit QC Date:** 2021-04-25 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** Hangzhou Neoantigen Therapeutics Co., Ltd. #### Lead Sponsor **Class:** OTHER **Name:** Sir Run Run Shaw Hospital #### Responsible Party **Investigator Affiliation:** Sir Run Run Shaw Hospital **Investigator Full Name:** Yong Fang **Investigator Title:** Chief Physician **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False ### Description Module **Brief Summary:** This research study is evaluating a new type of personalized neoantigen cancer vaccine（iNeo-Vac-P01）combined with anti-PD-1 antibody and radiofrequency ablation as a possible treatment for patients with advanced solid tumors. The primary objective of this trial is to evaluate safety, tolerability and immunogenicity of iNeo-Vac-P01 in combination with anti-PD-1 and radiofrequency ablation, so as to provide a new personalized therapeutic strategy for patients. It is known that cancer patients have mutations (changes in genetic material) that are specific to an individual patient and tumor. These mutations can cause the tumor cells to produce proteins that appear very different from the body's own cells. It is possible that these proteins used in a vaccine may induce strong immune responses, which may help the participant's body fight any tumor cells that could cause the cancer to come back in the future. The study will examine the safety of the vaccine when given at several different time points and will examine the participant's blood cells for signs that the vaccine induced an immune response. ### Conditions Module **Conditions:** - Advanced Malignant Solid Tumor ### Design Module #### Design Info **Allocation:** NON_RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 30 **Type:** ESTIMATED **Phases:** - PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Patients will undergo radiofrequency ablation. At Week 3, patients will receive PD-1 at a dose of 200mg administered by intravenous infusion (IV) every 2 weeks. At Week 12,all patients,regardless of their disease status,iNeo-Vac-P01(300mcg per peptide)+ GM-CSF (40mcg) on days 1, 4, 8, 15, 22, 52, and 82 from week 12. Additional booster vaccines might be administered depending on ethics and patients' potential benefit. **Intervention Names:** - Biological: iNeo-Vac-P01 - Other: GM-CSF - Drug: PD-1 - Procedure: RFA **Label:** RFA+PD-1+iNeo-Vac-P01 **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Patients will undergo radiofrequency ablation. At Week 12, patients will receive iNeo-Vac-P01(300mcg per peptide)+ GM-CSF (40mcg) on days 1, 4, 8, 15, 22, 52, and 82 from week 12. Additional booster vaccines might be administered depending on ethics and patients' potential benefit. At Week 16, patients,regard of their disease status,will receive PD-1 at a dose of 200mg administered by intravenous infusion (IV) every 2 weeks. **Intervention Names:** - Biological: iNeo-Vac-P01 - Other: GM-CSF - Drug: PD-1 - Procedure: RFA **Label:** RFA+iNeo-Vac-P01+PD-1 **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - RFA+PD-1+iNeo-Vac-P01 - RFA+iNeo-Vac-P01+PD-1 **Description:** iNeo-Vac-P01: 300 mcg per peptide **Name:** iNeo-Vac-P01 **Other Names:** - Neoantigen peptides **Type:** BIOLOGICAL #### Intervention 2 **Arm Group Labels:** - RFA+PD-1+iNeo-Vac-P01 - RFA+iNeo-Vac-P01+PD-1 **Description:** GM-CSF: 40 mcg **Name:** GM-CSF **Other Names:** - immune adjuvant - granulocyte-macrophage colony stimulating factor **Type:** OTHER #### Intervention 3 **Arm Group Labels:** - RFA+PD-1+iNeo-Vac-P01 - RFA+iNeo-Vac-P01+PD-1 **Description:** PD-1: 200mg administered by intravenous infusion every 2 weeks. **Name:** PD-1 **Other Names:** - PD-1 inhibitor **Type:** DRUG #### Intervention 4 **Arm Group Labels:** - RFA+PD-1+iNeo-Vac-P01 - RFA+iNeo-Vac-P01+PD-1 **Description:** Radiofrequency ablation surgery **Name:** RFA **Other Names:** - Radiofrequency ablation **Type:** PROCEDURE ### Outcomes Module #### Primary Outcomes **Description:** Adverse events will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events v5.0. **Measure:** Number of participants experiencing clinical and laboratory adverse events (AEs) **Time Frame:** 1 year **Description:** ORR is defined as the number of patients achieving a complete response (CR) or partial response (PR) based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) at any time during the study. **Measure:** Objective Response Rate **Time Frame:** 5 years **Description:** CD4/CD8 T lymphocyte subsets were detected by flow cytometry. **Measure:** Measurement of CD4/CD8 T lymphocyte subsets. **Time Frame:** 3 years **Description:** The response of IFN-γ T cells induced by neoantigen was detected by ELispot. **Measure:** The IFN-γ T cells responses induced by neoantigen **Time Frame:** 2 years #### Secondary Outcomes **Description:** Time from surgery to death or last follow-up. **Measure:** Overall Survival(OS) **Time Frame:** 5 years **Description:** Time from surgery to any progression. **Measure:** Progression-free Survival(PFS) **Time Frame:** 3 years **Description:** The diversity and clonability of T cells were analyzed by peripheral blood T cell receptor sequencing. **Measure:** Peripheral blood T cell receptor sequencing analysis **Time Frame:** 2 years ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Must freely sign informed consent; 2. Aged 18 to 75 years old; 3. Life expectancy of greater than 3 months. 4. At least one measurable lesion according to RECIST 1.1 criteria(Radiofrequency ablation of lesions was excluded). 5. histologically confirmed Advanced solid tumors, 6. have failed standard treatment, or unsuitable to receive standard treatment 7. Liver metastases are present and are suitable for radiofrequency ablation； 8. agreeable to allow tumor and normal samples to be submitted for complete exome and transcription sequencing. 9. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1; 10. Good hematopoietic function ， defined as absolute neutrophils count ≥1.5×109 /L, platelet count ≥100 ×109 /L, and hemoglobin ≥90g/L； 11. Good liver function, defined as total bilirubin levels ≤1.5 times the upper normal limit (ULN), and glutamic-oxalacetic transaminase (AST) and glutamic-pyruvic transaminase (ALT) levels ≤5 times ULN; 12. Good renal function, defined as serum creatinine ≤1.5 times ULN or calculated creatinine clearance ≥ 60 mL /min (Cockcroft-Gault formula); Routine urine examination urine protein less than 2+, or 24 hours urine protein quantitative \<1g; 13. Good coagulation function, defined as INR or prothrombin time (PT) ≤1.5 times ULN; If the subject is receiving anticoagulant therapy, PT is acceptable as long as it is within the range of anticoagulant drug use； 14. Pregnant, lactating women and women of child-bearing age must have a negative pregnancy test within 7 days before entering the group, and short-term have no fertility plan, and are willing to take protective measures (contraception or other birth control methods) before and during the clinical trial; Exclusion Criteria: 1. Currently participating in an interventional clinical study treatment or has received other investigational drugs or used investigational devices within 4 weeks prior to the first administration; 2. Major surgical treatment within 3 weeks prior to first administration; 3. Completed palliative radiotherapy within 7 days prior to first administration; 4. Clinical active diverticulitis, abdominal abscess, and gastrointestinal obstruction; 5. Have none suitable neoantigen; 6. Have been bone marrow or stem cell transplants; 7. Clinically uncontrollable pleural effusion/peritoneal effusion/pericardial effusion; 8. Severe known allergic reactions (≥ grade 3) to the active ingredient and/or any excipient of PD-1 monoclonal antibody； 9. Active autoimmune disease requiring systemic treatment occurred within 2 years prior to initial administration； 10. Diagnosed with immunodeficiency or was receiving systemic glucocorticoid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dosing of the study； 11. Full recovery from toxicity and/or complications associated with any intervention has not been achieved prior to the commencement of treatment； 12. Other tumors diagnosed within 5 years prior to initial administration, exceptions include radical basal cell carcinoma of the skin, squamous cell carcinoma of the skin, and/or radical resection of carcinoma in situ; 13. Symptoms of central nervous metastasis 14. A history of noninfectious pneumonia requiring glucocorticoid therapy or current interstitial lung disease within 1 year prior to initial administration; 15. Active infections that require systemic treatment; 16. A known presence of mental illness or substance abuse conditions that may affect compliance with the test requirements; 17. Human immunodeficiency virus (HIV) infection； 18. Untreated active hepatitis B； 19. Active subjects with HCV infection； 20. vaccine was administered within 30 days prior to initial administration (cycle 1, day 1)； 21. Medical history or evidence of disease, abnormal values of treatment or laboratory tests, or other conditions deemed inappropriate by the Investigator to interfere with the results of the study, prevent subjects from participating fully in the study; 22. breastfeeding women. Patients with previous and current objective evidence of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonia, drug-related pneumonia, severe pulmonary impairment, etc.; 23. Patients whose cardiopulmonary function cannot tolerate anesthesia； 24. The investigator evaluates other circumstances that may affect the conduct of the clinical study and the judgment of the study results. **Maximum Age:** 75 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Fang Yong, MD, PhD **Phone:** +86-571-87887821 **Role:** CONTACT #### Locations **Location 1:** **City:** Hangzhou **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Fang Yong, MD, PhD - **Phone:** +86-571-87887821 - **Role:** CONTACT ***Contact 2:*** - **Name:** Fang Yong, MD, PhD - **Role:** PRINCIPAL_INVESTIGATOR **Country:** China **Facility:** Run Run Shaw Hospital Affiliated to Zhejiang University School of Medicine **State:** Zhejiang **Status:** RECRUITING **Zip:** 310000 ### References Module #### References **Citation:** Fang Y, Mo F, Shou J, Wang H, Luo K, Zhang S, Han N, Li H, Ye S, Zhou Z, Chen R, Chen L, Liu L, Wang H, Pan H, Chen S. A Pan-cancer Clinical Study of Personalized Neoantigen Vaccine Monotherapy in Treating Patients with Various Types of Advanced Solid Tumors. Clin Cancer Res. 2020 Sep 1;26(17):4511-4520. doi: 10.1158/1078-0432.CCR-19-2881. Epub 2020 May 21. **PMID:** 32439700 **Citation:** Ott PA, Hu-Lieskovan S, Chmielowski B, Govindan R, Naing A, Bhardwaj N, Margolin K, Awad MM, Hellmann MD, Lin JJ, Friedlander T, Bushway ME, Balogh KN, Sciuto TE, Kohler V, Turnbull SJ, Besada R, Curran RR, Trapp B, Scherer J, Poran A, Harjanto D, Barthelme D, Ting YS, Dong JZ, Ware Y, Huang Y, Huang Z, Wanamaker A, Cleary LD, Moles MA, Manson K, Greshock J, Khondker ZS, Fritsch E, Rooney MS, DeMario M, Gaynor RB, Srinivasan L. A Phase Ib Trial of Personalized Neoantigen Therapy Plus Anti-PD-1 in Patients with Advanced Melanoma, Non-small Cell Lung Cancer, or Bladder Cancer. Cell. 2020 Oct 15;183(2):347-362.e24. doi: 10.1016/j.cell.2020.08.053. **PMID:** 33064988 ## Derived Section ### Condition Browse Module - Meshes - ID: D000009369 - Term: Neoplasms ### Intervention Browse Module - Ancestors - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000074322 - Term: Antineoplastic Agents, Immunological - ID: D000000970 - Term: Antineoplastic Agents - ID: D000007155 - Term: Immunologic Factors - ID: D000045505 - Term: Physiological Effects of Drugs ### Intervention Browse Module - Browse Branches - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: ANeo - Name: Antineoplastic Agents ### Intervention Browse Module - Browse Leaves - ID: M17360 - Name: Vaccines - Relevance: LOW - As Found: Unknown - ID: M257633 - Name: Molgramostim - Relevance: HIGH - As Found: Button - ID: M219218 - Name: Sargramostim - Relevance: HIGH - As Found: Button - ID: M3628 - Name: Adjuvants, Immunologic - Relevance: LOW - As Found: Unknown - ID: M2342 - Name: Immune Checkpoint Inhibitors - Relevance: HIGH - As Found: Escitalopram - ID: M1346 - Name: Antineoplastic Agents, Immunological - Relevance: LOW - As Found: Unknown - ID: M10201 - Name: Immunologic Factors - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000082082 - Term: Immune Checkpoint Inhibitors - ID: C000082430 - Term: Molgramostim - ID: C000081222 - Term: Sargramostim ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05003479 **Brief Title:** Clinical Trial of SARS-CoV-2 Vaccine (Vero Cells), Inactivated in Healthy Population Aged 3 to 17 Years(COVID-19) **Official Title:** A Randomized, Double-blind, Placebo-controlled Phase Ⅰ Clinical Study to Evaluate the Safety and Immunogenicity of SARS-CoV-2 Vaccine (Vero Cells), Inactivated in Healthy Population Aged 3 to 17 Years #### Organization Study ID Info **ID:** 2020L001-2A #### Organization **Class:** INDUSTRY **Full Name:** Shenzhen Kangtai Biological Products Co., LTD ### Status Module #### Completion Date **Date:** 2022-10 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** NOT_YET_RECRUITING #### Last Update Post Date **Date:** 2021-08-18 **Type:** ACTUAL **Last Update Submit Date:** 2021-08-11 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2022-09 **Type:** ESTIMATED #### Start Date **Date:** 2021-08 **Type:** ESTIMATED **Status Verified Date:** 2021-08 #### Study First Post Date **Date:** 2021-08-12 **Type:** ACTUAL **Study First Submit Date:** 2021-08-10 **Study First Submit QC Date:** 2021-08-10 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** Beijing Minhai Biotechnology Co., Ltd **Class:** OTHER **Name:** Hunan Provincial Center for Disease Control and Prevention #### Lead Sponsor **Class:** INDUSTRY **Name:** Shenzhen Kangtai Biological Products Co., LTD #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False ### Description Module **Brief Summary:** This study is a randomized, double-blinded, and placebo controlled phase Ⅰ clinical trial of the SARS-CoV-2 inactivated vaccine to evaluate the safety and immunogenicity of the experimental vaccine in healthy population aged 3 to 17 years. ### Conditions Module **Conditions:** - COVID-19 ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** DOUBLE **Who Masked:** - PARTICIPANT - INVESTIGATOR **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 84 **Type:** ESTIMATED **Phases:** - PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Intervention Names:** - Biological: SARS-CoV-2 Vaccine (Vero Cells), Inactivated **Label:** candidate vaccine **Type:** EXPERIMENTAL #### Arm Group 2 **Intervention Names:** - Biological: Placebo **Label:** Placebo **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - candidate vaccine **Description:** 2 doses of SARS-CoV-2 Vaccine (Vero Cells), Inactivated should be administered as an intramuscular injection into the lateral deltoid of the upper arm with a 28-day interval. **Name:** SARS-CoV-2 Vaccine (Vero Cells), Inactivated **Type:** BIOLOGICAL #### Intervention 2 **Arm Group Labels:** - Placebo **Description:** 2 doses of Placebo should be administered as an intramuscular injection into the lateral deltoid of the upper arm with a 28-day interval. **Name:** Placebo **Type:** BIOLOGICAL ### Outcomes Module #### Primary Outcomes **Measure:** Incidence of adverse reactions/events **Time Frame:** 0-28 days after each vaccination #### Secondary Outcomes **Measure:** Incidence of Serious Adverse Events (SAE) **Time Frame:** within 12 months post full vaccination **Measure:** Incidence of abnormal indicators of laboratory safety examinations(including blood routine, blood biochemistry, urine routine, thyroid function and coagulation function) **Time Frame:** Day 3 after each dose of vaccination **Measure:** Geometric mean titer of SARS-CoV-2 neutralizing antibody **Time Frame:** 28 days, 3 months, 6 months and 12 months post full vaccination **Measure:** Geometric mean titer of SARS-CoV-2 IgG binding antibody **Time Frame:** 28 days, 3 months, 6 months and 12 months post full vaccination **Measure:** Seroconversion rate of SARS-CoV-2 neutralizing antibody **Time Frame:** 28 days post full vaccination **Measure:** Seroconversion rate of SARS-CoV-2 IgG binding antibody **Time Frame:** 28 days post full vaccination **Measure:** Seropositive rate of SARS-CoV-2 neutralizing antibody **Time Frame:** 3 months, 6 months and 12 months post full vaccination **Measure:** Seropositive rate of SARS-CoV-2 IgG binding antibody **Time Frame:** 3 months, 6 months and 12 months post full vaccination ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Healthy residents aged 3 to 17 years at the time of consent * Subjects and/or their guardian agree to sign the informed consent forms voluntarily. * Be able to comply with study requirements/procedures. * Axillary temperature ≤ 37.0℃ Exclusion Criteria: * Within 14 days before vaccination, subjects have been abroad and to villages/communities experienced COVID-19 epidemics, and in contact with COVID-19 cases or suspected cases. Subjects are under isolation observation, or living in the villages/communities with COVID-19 cases or suspected cases; * Confirmed cases, suspected cases or asymptomatic cases with COVID-19 (refer to Information System of China Disease Prevention and Control); * Subjects with history of SARS virus infection by self-reported; * Positive in throat swab through RT-PCR; * History of vaccination of various COVID-19 vaccines or positive in SARS-CoV-2 antibody test; * Positive urine pregnancy test for females with menarche * With abnormal indicators, such as blood biochemistry, blood routine, urine routine, thyroid function and coagulation function which might show clinical meaning, before administration; * History of severe allergic reactions (such as acute anaphylaxis, urticaria, skin eczema, dyspnea, angioneurotic edema or abdominal pain) or allergy to known composition of inactivated SARS-CoV-2 vaccine; * History or family history of convulsion, epilepsy, encephalopathy or mental illness; * Subjects with congenital malformations or developmental disorders, genetic defects, severe malnutrition, etc.; * Subjects with known or suspected diseases include: severe respiratory diseases, severe cardiovascular diseases, severe liver and kidney diseases, drug-uncontrollable hypertension, diabetic complications, malignant tumors, various acute diseases or acute onset of chronic diseases; * Diagnosed with congenital or acquired immunodeficiency, HIV infection, lymphoma, leukemia or other autoimmune diseases; * History of coagulation dysfunction (e.g. Coagulation factor deficiency, coagulation disease); * Subjects receiving anti-TB treatment; * Subjects receiving other research drugs within 6 months before vaccination; * Subjects receiving immunotherapy or inhibitor therapy within 3 months (consistently oral or infusion for more than 14 days); * Subjects receiving blood products within 3 months before administration; * Subjects vaccinated with live attenuated vaccine within 14 days before vaccination; * Subjects vaccinated with other vaccine within 7 days before vaccination; * The researchers shall judge the other conditions which might be not in compliance with the requirements of this clinical trial. **Healthy Volunteers:** True **Maximum Age:** 17 Years **Minimum Age:** 3 Years **Sex:** ALL **Standard Ages:** - CHILD ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Guifan Li, M.S **Phone:** +861059613591 **Role:** CONTACT #### Locations **Location 1:** **City:** Changsha **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Tao Huang - **Phone:** +8673184305935 - **Role:** CONTACT **Country:** China **Facility:** Hunan Provincial Center for Diseases Control and Prevention **State:** Hunan **Zip:** 410005 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000011024 - Term: Pneumonia, Viral - ID: D000011014 - Term: Pneumonia - ID: D000012141 - Term: Respiratory Tract Infections - ID: D000007239 - Term: Infections - ID: D000014777 - Term: Virus Diseases - ID: D000018352 - Term: Coronavirus Infections - ID: D000003333 - Term: Coronaviridae Infections - ID: D000030341 - Term: Nidovirales Infections - ID: D000012327 - Term: RNA Virus Infections - ID: D000008171 - Term: Lung Diseases - ID: D000012140 - Term: Respiratory Tract Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC01 - Name: Infections - Abbrev: BC08 - Name: Respiratory Tract (Lung and Bronchial) Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology ### Condition Browse Module - Browse Leaves - ID: M2561 - Name: COVID-19 - Relevance: HIGH - As Found: COVID-19 - ID: M13904 - Name: Pneumonia - Relevance: LOW - As Found: Unknown - ID: M13914 - Name: Pneumonia, Viral - Relevance: LOW - As Found: Unknown - ID: M10283 - Name: Infections - Relevance: LOW - As Found: Unknown - ID: M6368 - Name: Communicable Diseases - Relevance: LOW - As Found: Unknown - ID: M14978 - Name: Respiratory Tract Infections - Relevance: LOW - As Found: Unknown - ID: M17522 - Name: Virus Diseases - Relevance: LOW - As Found: Unknown - ID: M20490 - Name: Coronavirus Infections - Relevance: LOW - As Found: Unknown - ID: M6555 - Name: Coronaviridae Infections - Relevance: LOW - As Found: Unknown - ID: M23685 - Name: Nidovirales Infections - Relevance: LOW - As Found: Unknown - ID: M15149 - Name: RNA Virus Infections - Relevance: LOW - As Found: Unknown - ID: M11168 - Name: Lung Diseases - Relevance: LOW - As Found: Unknown - ID: M14977 - Name: Respiratory Tract Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000086382 - Term: COVID-19 ### Intervention Browse Module - Browse Branches - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M17360 - Name: Vaccines - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT01813279 **Brief Title:** Assessment of the Subcutaneous Reinjection of Human Autologous Adipose-derived Stromal Vascular Fraction (Celution® System) in the Hands of Patients Suffering From Systemic Sclerosis **Official Title:** Assessment of the Subcutaneous Reinjection of Human Autologous Adipose-derived Stromal Vascular Fraction (Celution® System) in the Hands of Patients Suffering From Systemic Sclerosis #### Organization Study ID Info **ID:** 2011-A01228-33 #### Organization **Class:** OTHER **Full Name:** Assistance Publique Hopitaux De Marseille #### Secondary ID Infos **Domain:** AP HM **ID:** 2011-28 **Type:** OTHER ### Status Module #### Completion Date **Date:** 2014-03 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2014-09-01 **Type:** ESTIMATED **Last Update Submit Date:** 2014-08-29 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2013-11 **Type:** ACTUAL #### Start Date **Date:** 2012-11 **Status Verified Date:** 2014-08 #### Study First Post Date **Date:** 2013-03-18 **Type:** ESTIMATED **Study First Submit Date:** 2013-02-22 **Study First Submit QC Date:** 2013-03-13 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Assistance Publique Hopitaux De Marseille #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** Systemic sclerosis is an autoimmune disease characterized by skin lesions and visceral responsible for significant morbidity. Microcirculatory disorders and tissue fibrosis are excessive severity of the disease. This condition can affect the hands with a major functional consequence severely impairing the quality of life of patients. Adipose tissue is used in plastic surgery for over a century for the filling of depressions in the skin. In addition to the volume effect, a trophic effect on the surrounding tissue was noted. It is shown that the stromal vascular fraction is responsible for this regenerative effect. In a previous study the investigators have demonstrated in a mouse model that the subcutaneous adipose tissue provides a trophic effect on SSc skin lesions by reducing the fibrosis of the dermis and providing a pro angiogenic. Objectives and means: This is a clinical study evaluating an innovative cell therapy procedure. The objective of this study was to evaluate the effects of injection of autologous stromal vascular fraction of adipose origin according to the system Celution ® (Cytori Therapeutics, Inc.., United Kingdom) in digital in patients with scleroderma cutaneous hands. Eleven patients with scleroderma with the hands will be included in the study. Due to the nature of the orphan disease, a longitudinal study be conducted, where each patient will have own control. The evaluation will be pre and post operative for a period of six months. This evaluation will be based on clinical criteria (trophic balance, functional) and laboratory (capillaroscopy, Doppler ultrasound of the arteries of the forearm, laser-Doppler tissue). Project schedule and implementation phases: The project will run over a period of twelve months. Patients will be followed for a period of six months. Analyzes clinical, paraclinical, and exploitation of results will be achieved over a period of six months. Expected Results: This study will validate the functional and trophic effects of reinjection of autologous stromal vascular fraction of adipose tissue issue on the fingers of patients with scleroderma. Conclusion: This innovative cell therapy could represent an alternative treatment for patients with scleroderma in check, intolerant or insufficiently relieved by medical treatment currently available in the scleroderma hand ### Conditions Module **Conditions:** - Systemic Sclerosis ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 12 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Intervention Names:** - Other: the cell therapy **Label:** patients **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - patients **Description:** the reinjection of autologous stromal vascular fraction of adipose tissue issue on the fingers of patients with scleroderma. **Name:** the cell therapy **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Measure:** The improvement of the functional index of Cochin **Time Frame:** 2 years #### Secondary Outcomes **Measure:** Analog visual scale ( EVA ) **Time Frame:** 24 MONTHS **Measure:** Evaluation of the severity of the syndrome of Raynaud **Time Frame:** 24 months **Measure:** The test HAMIS **Time Frame:** 24 months **Measure:** The score of Rodnan modified in the hand **Time Frame:** 24 months **Measure:** -The test HAMIS **Time Frame:** 24 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Men and women of more than 18 years old wishing a therapeutic alternative. * Functional Disability of the hand authenticated by a functional index of the hand of Cochin upper to 20. Exclusion Criteria: * Persons participating simultaneously in another biomedical search(research) * Minors * Pregnant or breast-feeding Women * Major Persons protected by the law (under guardianship or guardianship) * Persons staying in a sanitary or social establishment * Persons in emergency situation * Private persons of freedom **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Marseille **Country:** France **Facility:** Assistance Publique Hopitaux de Marseille **Zip:** 13354 #### Overall Officials **Official 1:** **Affiliation:** Assistance Publique Hopitaux De Marseille **Name:** loic MONDOLONI **Role:** STUDY_DIRECTOR ### References Module #### References **Citation:** Granel B, Daumas A, Jouve E, Harle JR, Nguyen PS, Chabannon C, Colavolpe N, Reynier JC, Truillet R, Mallet S, Baiada A, Casanova D, Giraudo L, Arnaud L, Veran J, Sabatier F, Magalon G. Safety, tolerability and potential efficacy of injection of autologous adipose-derived stromal vascular fraction in the fingers of patients with systemic sclerosis: an open-label phase I trial. Ann Rheum Dis. 2015 Dec;74(12):2175-82. doi: 10.1136/annrheumdis-2014-205681. Epub 2014 Aug 11. **PMID:** 25114060 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000010335 - Term: Pathologic Processes - ID: D000003240 - Term: Connective Tissue Diseases - ID: D000012871 - Term: Skin Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC17 - Name: Skin and Connective Tissue Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M15415 - Name: Sclerosis - Relevance: HIGH - As Found: Sclerosis - ID: M15412 - Name: Scleroderma, Systemic - Relevance: HIGH - As Found: Systemic Sclerosis - ID: M25560 - Name: Scleroderma, Diffuse - Relevance: HIGH - As Found: Systemic Sclerosis - ID: M6464 - Name: Connective Tissue Diseases - Relevance: LOW - As Found: Unknown - ID: M15674 - Name: Skin Diseases - Relevance: LOW - As Found: Unknown - ID: T5565 - Name: Systemic Scleroderma - Relevance: HIGH - As Found: Systemic Sclerosis ### Condition Browse Module - Meshes - ID: D000012595 - Term: Scleroderma, Systemic - ID: D000045743 - Term: Scleroderma, Diffuse - ID: D000012598 - Term: Sclerosis ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT02582879 **Acronym:** informCLL **Brief Title:** informCLL™: A Disease Registry for Patients With Chronic Lymphocytic Leukemia **Official Title:** informCLL™: A Disease Registry for Patients With Chronic Lymphocytic Leukemia #### Organization Study ID Info **ID:** PCYC-1134M-CA #### Organization **Class:** INDUSTRY **Full Name:** Pharmacyclics LLC. ### Status Module #### Completion Date **Date:** 2021-07-21 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2022-07-22 **Type:** ACTUAL **Last Update Submit Date:** 2022-07-19 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2021-07-21 **Type:** ACTUAL #### Start Date **Date:** 2015-09 **Status Verified Date:** 2022-07 #### Study First Post Date **Date:** 2015-10-21 **Type:** ESTIMATED **Study First Submit Date:** 2015-09-08 **Study First Submit QC Date:** 2015-10-19 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** Janssen, LP #### Lead Sponsor **Class:** INDUSTRY **Name:** Pharmacyclics LLC. #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** The study is designed as a multicenter, prospective, observational registry of CLL/SLL patients who are initiating approved oral kinase inhibitors, BCL-2 inhibitors or other approved anti-CLL therapies/regimens. The study will characterize treatment patterns and their association with patient characteristics, healthcare resource utilization, and clinical outcomes, as well as patient-reported outcome (PRO) measures. **Detailed Description:** This multicenter, prospective, observational registry of CLL patients is designed to characterize and describe treatment patterns for those initiating treatment with approved oral kinase inhibitors and other approved anti-CLL therapies/ regimens. The registry will provide information on regimens used to treat first-line and later lines of CLL as well as the sequencing of treatment regimens. The registry will also evaluate the association of these treatment patterns with patient characteristics, healthcare resource utilization, and functional outcomes including patient-reported HRQoL. These data will provide information to physicians that may help guide clinical practice and appropriate use of therapies, and will also provide information on HRQoL and healthcare resource utilization that will be of interest to healthcare decision makers. ### Conditions Module **Conditions:** - Chronic Lymphocytic Leukemia (CLL) **Keywords:** - Chronic Lymphocytic Leukemia - CLL - Small Lymphocytic Leukemia - SLL ### Design Module #### Bio Spec **Description:** blood samples **Retention:** SAMPLES_WITH_DNA #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 1504 **Type:** ACTUAL **Patient Registry:** True **Study Type:** OBSERVATIONAL **Target Duration:** 2 Years ### Arms Interventions Module #### Arm Group 1 **Description:** Patients with CLL/SLL in a real-world setting initiating treatment with approved oral kinase inhibitors, BCL-2 inhibitors and other approved anti-CLL therapies/regimens. **Label:** Patient with CLL/SLL ### Outcomes Module #### Primary Outcomes **Description:** - Summarize baseline characteristics of study participants **Measure:** Summarize baseline characteristics of study population, among CLL patients in a real-world setting **Time Frame:** up to 7 years **Description:** * Summarize number of participants on various initial and subsequent treatments * Summarize proportion of patients switching therapies at each follow up time point **Measure:** Summarize treatment patterns among CLL patients in a real-world setting **Time Frame:** up to 7 years **Description:** - Measures of effectiveness used will include survival status, ECOG Health status, response assessments as evaluated by the investigator such as: complete response, partial response, stable disease, progressive disease **Measure:** Summarize clinical outcomes among CLL patients in a real-world setting **Time Frame:** up to 7 years **Description:** - Summarize health care resource utilization among study participants **Measure:** Summarize health care resource utilization among CLL patients in a real-world setting **Time Frame:** up to 7 years #### Secondary Outcomes **Description:** - Summarize frequencies and percentages of AEs, that led to discontinuation/modification/interruption of therapy or death in CLL patients **Measure:** Summarize non serious adverse events (AEs) that led to discontinuation/modification/interruption of therapy and all serious adverse events in CLL patients **Time Frame:** up to 7 years **Description:** - Summarize HRQoL scores as measured by FACT-G and additional questions from other PRO instruments at baseline and each follow-up **Measure:** Summarize patient-reported HRQoL scores **Time Frame:** up to 7 years ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Age of at least 18 years * Clinical diagnosis of CLL/SLL that meets published diagnostic criteria (Hallek 2008) * Initiating anti-CLL/SLL treatment regimen (excluding clinical trials) within ±45 days of enrollment * Availability of documentation of previous CLL/SLL treatment and duration of response in the patient's medical records if patient has received prior line(s) of treatment (i.e. NOT treatment naïve) * Willing and able to provide informed consent * Willing and able to complete PRO instrument * Willing and able to provide information on patient survey questionnaire * Willing and able to provide a blood sample at time of enrollment prior to receiving treatment, as possible Exclusion Criteria: * Diagnosis of B-cell malignancies other than CLL/SLL * Estimated life expectancy \<6 months * Currently receiving treatment in an interventional clinical trial at time of entry into this study \* Note- Exceptions: 1) Patients may enroll in interventional clinical trials for indications other than CLL/SLL, 2) The interventional clinical trial treatment is not the treatment used for meeting Inclusion Criteria #2 (or "Index Treatment"), 3) Patients may enroll in an interventional clinical trial indicated for CLL/SLL as later line of treatment after discontinuing the Index Treatment **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** The registry will aim to enroll approximately 1500 patients with CLL/SLL from a total of 200 sites in the US over a 45 month enrollment period. In order to best capture real-world treatment patterns, site recruitment will aim to include approximately 85% of sites from the community hematology-oncology setting. ### Contacts Locations Module #### Locations **Location 1:** **City:** Huntsville **Country:** United States **Facility:** Clearview Cancer Institute **State:** Alabama **Zip:** 35805 **Location 2:** **City:** Muscle Shoals **Country:** United States **Facility:** Northwest Alabama Cancer Center, PC **State:** Alabama **Zip:** 35661 **Location 3:** **City:** Glendale **Country:** United States **Facility:** Arizona Oncology Associates, PC - HAL **State:** Arizona **Zip:** 85308 **Location 4:** **City:** Phoenix **Country:** United States **Facility:** Arizona Oncology Associates, PC - HAL **State:** Arizona **Zip:** 85016 **Location 5:** **City:** Phoenix **Country:** United States **Facility:** Arizona Oncology Associates, PC - HAL **State:** Arizona **Zip:** 85027 **Location 6:** **City:** Tempe **Country:** United States **Facility:** Arizona Oncology Associates, PC - HAL-Scottsdale **State:** Arizona **Zip:** 85284 **Location 7:** **City:** Fort Smith **Country:** United States **Facility:** Mercy Research **State:** Arkansas **Zip:** 72903 **Location 8:** **City:** Hot Springs **Country:** United States **Facility:** Genesis Cancer Center **State:** Arkansas **Zip:** 71913 **Location 9:** **City:** Jonesboro **Country:** United States **Facility:** Clopton Clinic of Jonesboro, Inc. **State:** Arkansas **Zip:** 72401 **Location 10:** **City:** Little Rock **Country:** United States **Facility:** CARTI - Central Arkansas Radiation Therapy Institute **State:** Arkansas **Zip:** 72205 **Location 11:** **City:** Concord **Country:** United States **Facility:** John Muir Health **State:** California **Zip:** 94520 **Location 12:** **City:** Oceanside **Country:** United States **Facility:** North County Oncology Medical Clinic **State:** California **Zip:** 92056 **Location 13:** **City:** Saint Helena **Country:** United States **Facility:** Gregory Smith, MD (Private Practice) **State:** California **Zip:** 94574 **Location 14:** **City:** Santa Barbara **Country:** United States **Facility:** Sansum Clinic **State:** California **Zip:** 93105 **Location 15:** **City:** Santa Rosa **Country:** United States **Facility:** St Joseph Heritage Healthcare **State:** California **Zip:** 95403 **Location 16:** **City:** Solvang **Country:** United States **Facility:** Sansum Clinic **State:** California **Zip:** 93463 **Location 17:** **City:** Vallejo **Country:** United States **Facility:** Solano Hematology Oncology **State:** California **Zip:** 94589 **Location 18:** **City:** Aurora **Country:** United States **Facility:** Rocky Mountain Cancer Centers, LLP- Aurora **State:** Colorado **Zip:** 80012 **Location 19:** **City:** Boulder **Country:** United States **Facility:** Rocky Mountain Cancer Centers, LLP- Boulder **State:** Colorado **Zip:** 80303 **Location 20:** **City:** Colorado Springs **Country:** United States **Facility:** Rocky Mountain Cancer Centers **State:** Colorado **Zip:** 80907 **Location 21:** **City:** Denver **Country:** United States **Facility:** Rocky Mountain Cancer Centers, LLP **State:** Colorado **Zip:** 80218 **Location 22:** **City:** Denver **Country:** United States **Facility:** Rocky Mountain Cancer Centers, LLP **State:** Colorado **Zip:** 80220 **Location 23:** **City:** Lakewood **Country:** United States **Facility:** Rocky Mountain Cancer Centers, LLP- Lakewood **State:** Colorado **Zip:** 80228 **Location 24:** **City:** Littleton **Country:** United States **Facility:** Rocky Mountain Cancer Centers, LLP- Littleton **State:** Colorado **Zip:** 80120-4413 **Location 25:** **City:** Lone Tree **Country:** United States **Facility:** Rocky Mountain Cancer Centers, LLP- Sky Ridge **State:** Colorado **Zip:** 80124 **Location 26:** **City:** Longmont **Country:** United States **Facility:** Rocky Mountain Cancer Centers, LLP- Longmont **State:** Colorado **Zip:** 80501 **Location 27:** **City:** Parker **Country:** United States **Facility:** Rocky Mountain Cancer Centers, LLP- Parker **State:** Colorado **Zip:** 80138 **Location 28:** **City:** Pueblo **Country:** United States **Facility:** Rocky Mountain Cancer Centers, LLP- Pueblo **State:** Colorado **Zip:** 81008 **Location 29:** **City:** Thornton **Country:** United States **Facility:** Rocky Mountain Cancer Centers, LLP- Thornton **State:** Colorado **Zip:** 80260 **Location 30:** **City:** Boynton Beach **Country:** United States **Facility:** University Cancer Institute, LLC **State:** Florida **Zip:** 33426 **Location 31:** **City:** Fort Lauderdale **Country:** United States **Facility:** Broward Oncology Associates, PA **State:** Florida **Zip:** 33308 **Location 32:** **City:** Jacksonville **Country:** United States **Facility:** Cancer Specialists, LLC **State:** Florida **Zip:** 32082 **Location 33:** **City:** Jacksonville **Country:** United States **Facility:** Baptist MD Anderson Cancer Center **State:** Florida **Zip:** 32207 **Location 34:** **City:** Lakeland **Country:** United States **Facility:** Lakeland Regional Health Systems Inc **State:** Florida **Zip:** 33805 **Location 35:** **City:** Lakeland **Country:** United States **Facility:** Watson Clinic Cancer and Research Center **State:** Florida **Zip:** 33805 **Location 36:** **City:** Pensacola **Country:** United States **Facility:** Sacred Heart Cancer Center **State:** Florida **Zip:** 32504 **Location 37:** **City:** Albany **Country:** United States **Facility:** Phoebe Putney Memorial Hospital **State:** Georgia **Zip:** 31701 **Location 38:** **City:** Augusta **Country:** United States **Facility:** Georgia Cancer Center at Augusta University **State:** Georgia **Zip:** 30912 **Location 39:** **City:** Brunswick **Country:** United States **Facility:** Southeast Georgia Physician Associates Hematology & Oncology **State:** Georgia **Zip:** 31520 **Location 40:** **City:** Chicago **Country:** United States **Facility:** The University of Chicago **State:** Illinois **Zip:** 60637 **Location 41:** **City:** Harvey **Country:** United States **Facility:** Ingalls Memorial Hospital **State:** Illinois **Zip:** 60426 **Location 42:** **City:** Normal **Country:** United States **Facility:** Mid-Illinois Hematology & Oncology Associates,Ltd. **State:** Illinois **Zip:** 61761 **Location 43:** **City:** Peoria **Country:** United States **Facility:** Illinois Cancer Care, P.C. **State:** Illinois **Zip:** 61615-7828 **Location 44:** **City:** Rockford **Country:** United States **Facility:** OSF Saint Anthony Medical Center **State:** Illinois **Zip:** 61108 **Location 45:** **City:** Skokie **Country:** United States **Facility:** Orchard Healthcare Research Inc. **State:** Illinois **Zip:** 60077 **Location 46:** **City:** Tinley Park **Country:** United States **Facility:** Healthcare Research Network III, LLC **State:** Illinois **Zip:** 60487 **Location 47:** **City:** Anderson **Country:** United States **Facility:** St. Vincent Anderson Regional Hospital **State:** Indiana **Zip:** 46016 **Location 48:** **City:** Indianapolis **Country:** United States **Facility:** Community Health Network **State:** Indiana **Zip:** 46219 **Location 49:** **City:** Indianapolis **Country:** United States **Facility:** Investigative Clinical Research of Indiana, LLC **State:** Indiana **Zip:** 46260 **Location 50:** **City:** Lafayette **Country:** United States **Facility:** Horizon Oncology Research, Inc **State:** Indiana **Zip:** 47905 **Location 51:** **City:** South Bend **Country:** United States **Facility:** Memorial Medical Group Clinical Research Institute **State:** Indiana **Zip:** 46601 **Location 52:** **City:** Vincennes **Country:** United States **Facility:** Good Samaritan Hospital **State:** Indiana **Zip:** 47591 **Location 53:** **City:** Ames **Country:** United States **Facility:** McFarland Clinic, P.C. **State:** Iowa **Zip:** 50010-3014 **Location 54:** **City:** Cedar Rapids **Country:** United States **Facility:** Physicians Clinic of Iowa **State:** Iowa **Zip:** 52402 **Location 55:** **City:** Waterloo **Country:** United States **Facility:** Covenant Clinic **State:** Iowa **Zip:** 50702 **Location 56:** **City:** Topeka **Country:** United States **Facility:** Cotton-O'Neil Clinical Research Center, Hematology and Oncology **State:** Kansas **Zip:** 66606 **Location 57:** **City:** Mount Sterling **Country:** United States **Facility:** Montgomery Cancer Center **State:** Kentucky **Zip:** 40353 **Location 58:** **City:** Paducah **Country:** United States **Facility:** West Ky Hematology & Oncology Group, PSC **State:** Kentucky **Zip:** 42003 **Location 59:** **City:** Covington **Country:** United States **Facility:** Pontchartrain Cancer Center **State:** Louisiana **Zip:** 70433 **Location 60:** **City:** New Orleans **Country:** United States **Facility:** Tulane University **State:** Louisiana **Zip:** 70112 **Location 61:** **City:** Shreveport **Country:** United States **Facility:** Willis-Knighton Cancer Center **State:** Louisiana **Zip:** 71103 **Location 62:** **City:** Shreveport **Country:** United States **Facility:** Christus Cancer Treatment Center **State:** Louisiana **Zip:** 71105 **Location 63:** **City:** Lewiston **Country:** United States **Facility:** Maine Research Associates **State:** Maine **Zip:** 04240 **Location 64:** **City:** Rockport **Country:** United States **Facility:** Penobscot Bay Medical Center **State:** Maine **Zip:** 04856 **Location 65:** **City:** Scarborough **Country:** United States **Facility:** Maine Center for Cancer Medicine **State:** Maine **Zip:** 04074 **Location 66:** **City:** Cumberland **Country:** United States **Facility:** Western Maryland Health System **State:** Maryland **Zip:** 21502 **Location 67:** **City:** Hagerstown **Country:** United States **Facility:** Antietam Oncology and Hematology Group PC **State:** Maryland **Zip:** 21740 **Location 68:** **City:** Pittsfield **Country:** United States **Facility:** Berkshire Hematology Oncology, PC **State:** Massachusetts **Zip:** 01201 **Location 69:** **City:** Plymouth **Country:** United States **Facility:** Beth Israel Deaconess Hospital- Plymouth **State:** Massachusetts **Zip:** 02360 **Location 70:** **City:** Kalamazoo **Country:** United States **Facility:** West Michigan Cancer Center **State:** Michigan **Zip:** 49007 **Location 71:** **City:** Novi **Country:** United States **Facility:** St John Providence Hospital **State:** Michigan **Zip:** 48374-1233 **Location 72:** **City:** Saint Cloud **Country:** United States **Facility:** Coborn Cancer Center **State:** Minnesota **Zip:** 56303 **Location 73:** **City:** Jackson **Country:** United States **Facility:** Jackson Oncology Associates **State:** Mississippi **Zip:** 39202 **Location 74:** **City:** Bolivar **Country:** United States **Facility:** Central Cancer Care Center **State:** Missouri **Zip:** 65613 **Location 75:** **City:** Jefferson City **Country:** United States **Facility:** Jefferson City Medical Group **State:** Missouri **Zip:** 65109 **Location 76:** **City:** Saint Joseph **Country:** United States **Facility:** Heartland Regional Medical Center d/b/a Cancer Care St. Joseph Mosaic Life Care **State:** Missouri **Zip:** 64506 **Location 77:** **City:** Billings **Country:** United States **Facility:** St. Vincent Frontier Cancer Center **State:** Montana **Zip:** 59102 **Location 78:** **City:** Hastings **Country:** United States **Facility:** Mary Lanning Healthcare Morrison Cancer Center **State:** Nebraska **Zip:** 68901 **Location 79:** **City:** Lincoln **Country:** United States **Facility:** Nebraska Hematology-Oncology, P.C **State:** Nebraska **Zip:** 68506 **Location 80:** **City:** Lincoln **Country:** United States **Facility:** Southeast Nebraska Cancer Center **State:** Nebraska **Zip:** 68510 **Location 81:** **City:** Omaha **Country:** United States **Facility:** Cancer Alliance of Nebraska **State:** Nebraska **Zip:** 68106 **Location 82:** **City:** Elizabeth **Country:** United States **Facility:** Trinitas Hospital **State:** New Jersey **Zip:** 07207 **Location 83:** **City:** Englewood **Country:** United States **Facility:** Hematology Oncology Physicians of Englewood, PA **State:** New Jersey **Zip:** 07631 **Location 84:** **City:** Neptune **Country:** United States **Facility:** Meridian Health Systems **State:** New Jersey **Zip:** 07753 **Location 85:** **City:** New Brunswick **Country:** United States **Facility:** Saint Peter's University Hospital **State:** New Jersey **Zip:** 08901 **Location 86:** **City:** Paramus **Country:** United States **Facility:** The Valley Hospital **State:** New Jersey **Zip:** 07652 **Location 87:** **City:** Williamstown **Country:** United States **Facility:** Southern Oncology Hematology Associates **State:** New Jersey **Zip:** 08360 **Location 88:** **City:** Farmington **Country:** United States **Facility:** San Juan Oncology Associates **State:** New Mexico **Zip:** 87401 **Location 89:** **City:** Bronx **Country:** United States **Facility:** Eastchester Center for Cancer Care **State:** New York **Zip:** 10469 **Location 90:** **City:** East Hills **Country:** United States **Facility:** St. Francis Hospital **State:** New York **Zip:** 11548 **Location 91:** **City:** East Setauket **Country:** United States **Facility:** North Shore Hematology Oncology Associates, PC **State:** New York **Zip:** 11733 **Location 92:** **City:** East Syracuse **Country:** United States **Facility:** Hematology Oncology Associates Of Central New York **State:** New York **Zip:** 13057 **Location 93:** **City:** Glens Falls **Country:** United States **Facility:** Glen Falls Hospital Cancer Center **State:** New York **Zip:** 12801 **Location 94:** **City:** Manhasset **Country:** United States **Facility:** North Shore Long Island Jewish Hospital **State:** New York **Zip:** 11030 **Location 95:** **City:** Mount Kisco **Country:** United States **Facility:** Northern Westchester Hospital **State:** New York **Zip:** 10549 **Location 96:** **City:** New York **Country:** United States **Facility:** MHO Research Foundation, Inc. **State:** New York **Zip:** 10016 **Location 97:** **City:** Nyack **Country:** United States **Facility:** Hematology Oncology Associates of Rockland **State:** New York **Zip:** 10960 **Location 98:** **City:** Syracuse **Country:** United States **Facility:** SUNY Upstate Medical Center **State:** New York **Zip:** 13210 **Location 99:** **City:** White Plains **Country:** United States **Facility:** White Plains Hospital **State:** New York **Zip:** 10601 **Location 100:** **City:** Williamsville **Country:** United States **Facility:** CCS Oncology **State:** New York **Zip:** 14221 **Location 101:** **City:** Cary **Country:** United States **Facility:** Waverly Hematology Oncology **State:** North Carolina **Zip:** 27518 **Location 102:** **City:** Charlotte **Country:** United States **Facility:** Levine Cancer Institute **State:** North Carolina **Zip:** 28204 **Location 103:** **City:** Greenville **Country:** United States **Facility:** Leo Jenkins Cancer Center/ECU School of Medicine **State:** North Carolina **Zip:** 27834 **Location 104:** **City:** Morehead City **Country:** United States **Facility:** Raab Clinic **State:** North Carolina **Zip:** 28557 **Location 105:** **City:** Cleveland **Country:** United States **Facility:** Cleveland Clinic **State:** Ohio **Zip:** 44195 **Location 106:** **City:** Columbus **Country:** United States **Facility:** Mid Ohio Oncology Hematology, DBA The Mark H. Zangmeister Center **State:** Ohio **Zip:** 43219 **Location 107:** **City:** Middletown **Country:** United States **Facility:** Wright State University **State:** Ohio **Zip:** 45005 **Location 108:** **City:** Toledo **Country:** United States **Facility:** Toledo Community Hospital Oncology Program - CCOP Toledo **State:** Ohio **Zip:** 43623 **Location 109:** **City:** Youngstown **Country:** United States **Facility:** St. Elizabeth Hospital **State:** Ohio **Zip:** 44501 **Location 110:** **City:** Oklahoma City **Country:** United States **Facility:** Mercy Research - Mercy Clinic Oncology and Hematology **State:** Oklahoma **Zip:** 73120 **Location 111:** **City:** Eugene **Country:** United States **Facility:** Willamette Valley Cancer Institute and Research Center **State:** Oregon **Zip:** 97401 **Location 112:** **City:** Medford **Country:** United States **Facility:** Hematology Oncology Associates, PC **State:** Oregon **Zip:** 97504 **Location 113:** **City:** Medford **Country:** United States **Facility:** Hematology Oncology Associates **State:** Oregon **Zip:** 97504 **Location 114:** **City:** Portland **Country:** United States **Facility:** Compass Oncology- Hoyt **State:** Oregon **Zip:** 97213-2982 **Location 115:** **City:** Portland **Country:** United States **Facility:** Compass Oncology- Barnes **State:** Oregon **Zip:** 97225 **Location 116:** **City:** Portland **Country:** United States **Facility:** Compass Oncology- Broadway **State:** Oregon **Zip:** 97227 **Location 117:** **City:** Springfield **Country:** United States **Facility:** Willamette Valley Cancer Institute and Research Center **State:** Oregon **Zip:** 97477 **Location 118:** **City:** Tualatin **Country:** United States **Facility:** Compass Oncology- Tualatin **State:** Oregon **Zip:** 97062 **Location 119:** **City:** Lancaster **Country:** United States **Facility:** Lancaster Cancer Center **State:** Pennsylvania **Zip:** 17605 **Location 120:** **City:** Monroeville **Country:** United States **Facility:** University Cancer Institute, LLC **State:** Pennsylvania **Zip:** 15232 **Location 121:** **City:** Philadelphia **Country:** United States **Facility:** Einstein Medical Center **State:** Pennsylvania **Zip:** 19141 **Location 122:** **City:** Scranton **Country:** United States **Facility:** Hematology & Oncology Associates of Northeastern PA **State:** Pennsylvania **Zip:** 18510 **Location 123:** **City:** Williamsport **Country:** United States **Facility:** Susquehanna Cancer Center **State:** Pennsylvania **Zip:** 17701 **Location 124:** **City:** York **Country:** United States **Facility:** Cancer Care Associates of York **State:** Pennsylvania **Zip:** 17403 **Location 125:** **City:** Charleston **Country:** United States **Facility:** Charleston Cancer Center **State:** South Carolina **Zip:** 29406 **Location 126:** **City:** Easley **Country:** United States **Facility:** Cancer Centers of the Carolinas- Easley **State:** South Carolina **Zip:** 29640 **Location 127:** **City:** Greenville **Country:** United States **Facility:** Cancer Centers of the Carolinas- Butternut **State:** South Carolina **Zip:** 29605 **Location 128:** **City:** Greenville **Country:** United States **Facility:** Hematology and Oncology Associates of SC, LLC **State:** South Carolina **Zip:** 29605 **Location 129:** **City:** Greenville **Country:** United States **Facility:** Greenville Hospital System Medical Center **State:** South Carolina **Zip:** 29615 **Location 130:** **City:** Greer **Country:** United States **Facility:** Greenville Health System **State:** South Carolina **Zip:** 29650 **Location 131:** **City:** Hilton Head Island **Country:** United States **Facility:** South Carolina Cancer Specialists **State:** South Carolina **Zip:** 29926 **Location 132:** **City:** Rock Hill **Country:** United States **Facility:** Carolina Blood and Cancer Care Associates **State:** South Carolina **Zip:** 29732 **Location 133:** **City:** Seneca **Country:** United States **Facility:** Cancer Centers of the Carolinas - Seneca **State:** South Carolina **Zip:** 29672 **Location 134:** **City:** Spartanburg **Country:** United States **Facility:** Spartanburg Regional Healthcare System **State:** South Carolina **Zip:** 29303 **Location 135:** **City:** Spartanburg **Country:** United States **Facility:** Cancer Centers of the Carolinas- Spartanburg **State:** South Carolina **Zip:** 29307 **Location 136:** **City:** Watertown **Country:** United States **Facility:** Prairie Lakes Hospital **State:** South Dakota **Zip:** 57201 **Location 137:** **City:** Cookeville **Country:** United States **Facility:** Cookeville Regional Medical Center **State:** Tennessee **Zip:** 38501 **Location 138:** **City:** Jackson **Country:** United States **Facility:** Jackson Madison County General Hospital **State:** Tennessee **Zip:** 38301 **Location 139:** **City:** Nashville **Country:** United States **Facility:** Meharry Medical College **State:** Tennessee **Zip:** 37208 **Location 140:** **City:** Nashville **Country:** United States **Facility:** Vanderbilt University Medical Center **State:** Tennessee **Zip:** 37232 **Location 141:** **City:** Abilene **Country:** United States **Facility:** Hendrick Cancer Center **State:** Texas **Zip:** 79601 **Location 142:** **City:** Abilene **Country:** United States **Facility:** Texas Oncology - Abilene **State:** Texas **Zip:** 79606-5208 **Location 143:** **City:** Allen **Country:** United States **Facility:** Texas Oncology- Allen **State:** Texas **Zip:** 75013 **Location 144:** **City:** Amarillo **Country:** United States **Facility:** Texas Oncology - Amarillo **State:** Texas **Zip:** 79106 **Location 145:** **City:** Arlington **Country:** United States **Facility:** Texas Oncoogy - Arlington North **State:** Texas **Zip:** 76012 **Location 146:** **City:** Arlington **Country:** United States **Facility:** Texas Oncology- Arlington South **State:** Texas **Zip:** 76014 **Location 147:** **City:** Austin **Country:** United States **Facility:** Texas Oncology - Austin Midtown **State:** Texas **Zip:** 78705 **Location 148:** **City:** Austin **Country:** United States **Facility:** Texas Oncology - P.A.- Austin **State:** Texas **Zip:** 78731 **Location 149:** **City:** Austin **Country:** United States **Facility:** South Austin Cancer Center **State:** Texas **Zip:** 78745 **Location 150:** **City:** Beaumont **Country:** United States **Facility:** Texas Oncology - PA **State:** Texas **Zip:** 77701 **Location 151:** **City:** Beaumont **Country:** United States **Facility:** Texas Oncology, P.A - Beaumont **State:** Texas **Zip:** 77702 **Location 152:** **City:** Bedford **Country:** United States **Facility:** Texas Oncology-Bedford **State:** Texas **Zip:** 76022 **Location 153:** **City:** Carrollton **Country:** United States **Facility:** Texas Oncology - Carrollton **State:** Texas **Zip:** 75010 **Location 154:** **City:** Dallas **Country:** United States **Facility:** Texas Oncology - Dallas Presbyterian **State:** Texas **Zip:** 75231 **Location 155:** **City:** Dallas **Country:** United States **Facility:** Baylor Charles A. Sammons Cancer Center **State:** Texas **Zip:** 75246 **Location 156:** **City:** El Paso **Country:** United States **Facility:** El Paso Cancer Treatment Center- West **State:** Texas **Zip:** 79902 **Location 157:** **City:** El Paso **Country:** United States **Facility:** Texas Oncology - P.A. - El Paso **State:** Texas **Zip:** 79915 **Location 158:** **City:** El Paso **Country:** United States **Facility:** Texas Oncology - El Paso **State:** Texas **Zip:** 79939 **Location 159:** **City:** Flower Mound **Country:** United States **Facility:** Texas Oncology, P.A.- Flower Mound **State:** Texas **Zip:** 75028 **Location 160:** **City:** Grapevine **Country:** United States **Facility:** Texas Oncology-Grapevine **State:** Texas **Zip:** 76051 **Location 161:** **City:** Harlingen **Country:** United States **Facility:** Texas Oncology PA **State:** Texas **Zip:** 78550 **Location 162:** **City:** Longview **Country:** United States **Facility:** Texas Oncology - P.A.- Longview **State:** Texas **Zip:** 75601 **Location 163:** **City:** McAllen **Country:** United States **Facility:** Texas Oncology - P.A.-McAllen **State:** Texas **Zip:** 78503 **Location 164:** **City:** McKinney **Country:** United States **Facility:** Texas Oncology- McKinney **State:** Texas **Zip:** 75071 **Location 165:** **City:** Mesquite **Country:** United States **Facility:** Texas Oncology -P.A.- Mesquite **State:** Texas **Zip:** 75150 **Location 166:** **City:** Midland **Country:** United States **Facility:** Texas Oncology - P.A.- Midland **State:** Texas **Zip:** 79701 **Location 167:** **City:** Odessa **Country:** United States **Facility:** Texas Oncology - P.A.- Odessa **State:** Texas **Zip:** 79761 **Location 168:** **City:** Paris **Country:** United States **Facility:** Texas Oncology - P.A.- Paris **State:** Texas **Zip:** 75460-5004 **Location 169:** **City:** Plano **Country:** United States **Facility:** Texas Oncology - P.A.- Plano **State:** Texas **Zip:** 75075-7787 **Location 170:** **City:** Plano **Country:** United States **Facility:** Texas Oncology- Plano West **State:** Texas **Zip:** 75093 **Location 171:** **City:** Rockwall **Country:** United States **Facility:** Texas Oncology - Rockwall **State:** Texas **Zip:** 75032 **Location 172:** **City:** San Antonio **Country:** United States **Facility:** Texas Oncology- San Antonio Downtown **State:** Texas **Zip:** 78212 **Location 173:** **City:** San Antonio **Country:** United States **Facility:** Texas Oncology- San Antonio Northeast **State:** Texas **Zip:** 78217 **Location 174:** **City:** San Antonio **Country:** United States **Facility:** Texas Oncology- San Antonio Stone Oak **State:** Texas **Zip:** 78258 **Location 175:** **City:** Sherman **Country:** United States **Facility:** Texas Oncology - P.A.-Sherman **State:** Texas **Zip:** 75090 **Location 176:** **City:** Sugar Land **Country:** United States **Facility:** Texas Oncology - P.A.-Sugar Land **State:** Texas **Zip:** 77479 **Location 177:** **City:** Tyler **Country:** United States **Facility:** Tyler Hematology Oncology **State:** Texas **Zip:** 75701 **Location 178:** **City:** Tyler **Country:** United States **Facility:** Texas Oncology-P.A-Tyler **State:** Texas **Zip:** 75702 **Location 179:** **City:** Waco **Country:** United States **Facility:** Texas Oncology, P.A. - Horizon Circle **State:** Texas **Zip:** 76712 **Location 180:** **City:** Waco **Country:** United States **Facility:** Texas Oncology, P.A. - Waco **State:** Texas **Zip:** 76712 **Location 181:** **City:** Webster **Country:** United States **Facility:** Texas Oncology-P.A.- Webster **State:** Texas **Zip:** 77598-4420 **Location 182:** **City:** Weslaco **Country:** United States **Facility:** Texas Oncology-Weslaco **State:** Texas **Zip:** 78596 **Location 183:** **City:** Newport News **Country:** United States **Facility:** Cancer Specialists of Tidewater **State:** Virginia **Zip:** 23601 **Location 184:** **City:** Winchester **Country:** United States **Facility:** Shenandoah Oncology, P.C. **State:** Virginia **Zip:** 22601 **Location 185:** **City:** Everett **Country:** United States **Facility:** Providence Everett Medical Center **State:** Washington **Zip:** 98201 **Location 186:** **City:** Seattle **Country:** United States **Facility:** Swedish Cancer Institute **State:** Washington **Zip:** 98104 **Location 187:** **City:** Tacoma **Country:** United States **Facility:** Multicare Institute for Research and Innovation **State:** Washington **Zip:** 98405 **Location 188:** **City:** Vancouver **Country:** United States **Facility:** Compass oncology **State:** Washington **Zip:** 98684 **Location 189:** **City:** Walla Walla **Country:** United States **Facility:** Providence St. Mary Regional Cancer Center **State:** Washington **Zip:** 99362 **Location 190:** **City:** Yakima **Country:** United States **Facility:** Yakima Valley Memorial Hospital/North Star Lodge **State:** Washington **Zip:** 98902 **Location 191:** **City:** Green Bay **Country:** United States **Facility:** HSHS St. Vincent Hospital Regional Cancer Center **State:** Wisconsin **Zip:** 54301 **Location 192:** **City:** Waukesha **Country:** United States **Facility:** ProHealth Care **State:** Wisconsin **Zip:** 53188 #### Overall Officials **Official 1:** **Affiliation:** Pharmacyclics LLC. **Name:** Alex Young **Role:** STUDY_DIRECTOR ### References Module #### References **Citation:** Hallek M, Cheson BD, Catovsky D, Caligaris-Cappio F, Dighiero G, Dohner H, Hillmen P, Keating MJ, Montserrat E, Rai KR, Kipps TJ; International Workshop on Chronic Lymphocytic Leukemia. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines. Blood. 2008 Jun 15;111(12):5446-56. doi: 10.1182/blood-2007-06-093906. Epub 2008 Jan 23. Erratum In: Blood. 2008 Dec 15;112(13):5259. **PMID:** 18216293 #### See Also Links **Label:** clinical study report synopsis **URL:** https://www.abbvieclinicaltrials.com/study/?id=PCYC-1134M-CA&Latitude=&Longitude=&LocationName=#additional-resources-section ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009370 - Term: Neoplasms by Histologic Type - ID: D000009369 - Term: Neoplasms - ID: D000006402 - Term: Hematologic Diseases - ID: D000008232 - Term: Lymphoproliferative Disorders - ID: D000008206 - Term: Lymphatic Diseases - ID: D000007160 - Term: Immunoproliferative Disorders - ID: D000007154 - Term: Immune System Diseases - ID: D000015448 - Term: Leukemia, B-Cell - ID: D000002908 - Term: Chronic Disease - ID: D000020969 - Term: Disease Attributes - ID: D000010335 - Term: Pathologic Processes ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC15 - Name: Blood and Lymph Conditions - Abbrev: All - Name: All Conditions - Abbrev: BC20 - Name: Immune System Diseases - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M10945 - Name: Leukemia - Relevance: HIGH - As Found: Leukemia - ID: M10951 - Name: Leukemia, Lymphoid - Relevance: HIGH - As Found: Lymphocytic Leukemia - ID: M18116 - Name: Leukemia, Lymphocytic, Chronic, B-Cell - Relevance: HIGH - As Found: Chronic Lymphocytic Leukemia - ID: M12315 - Name: Neoplasms by Histologic Type - Relevance: LOW - As Found: Unknown - ID: M9490 - Name: Hematologic Diseases - Relevance: LOW - As Found: Unknown - ID: M11225 - Name: Lymphoproliferative Disorders - Relevance: LOW - As Found: Unknown - ID: M11203 - Name: Lymphatic Diseases - Relevance: LOW - As Found: Unknown - ID: M10206 - Name: Immunoproliferative Disorders - Relevance: LOW - As Found: Unknown - ID: M10200 - Name: Immune System Diseases - Relevance: LOW - As Found: Unknown - ID: M18115 - Name: Leukemia, B-Cell - Relevance: LOW - As Found: Unknown - ID: M6147 - Name: Chronic Disease - Relevance: LOW - As Found: Unknown - ID: M22700 - Name: Disease Attributes - Relevance: LOW - As Found: Unknown - ID: T1308 - Name: Chronic Lymphocytic Leukemia - Relevance: HIGH - As Found: Chronic Lymphocytic Leukemia - ID: T1303 - Name: Chronic Graft Versus Host Disease - Relevance: HIGH - As Found: Chronic ### Condition Browse Module - Meshes - ID: D000007938 - Term: Leukemia - ID: D000007945 - Term: Leukemia, Lymphoid - ID: D000015451 - Term: Leukemia, Lymphocytic, Chronic, B-Cell ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT02779179 **Acronym:** ESPERA **Brief Title:** Therapeutic Management of Periodontitis and Clinical Manifestations of Rheumatoid Arthritis **Official Title:** Efficacy of Therapeutic Management of Periodontitis on the Clinical Manifestations of Rheumatoid Arthritis: the Randomized, Controlled ESPERA Trial. #### Organization Study ID Info **ID:** 10 046 08 #### Organization **Class:** OTHER **Full Name:** University Hospital, Toulouse #### Secondary ID Infos **Domain:** National Agency of Drug Safety and Health Products **ID:** 2010-A01193-36 **Type:** REGISTRY ### Status Module #### Completion Date **Date:** 2016-11 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2018-12-03 **Type:** ACTUAL **Last Update Submit Date:** 2018-11-29 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2016-11 **Type:** ACTUAL #### Start Date **Date:** 2010-11 **Type:** ACTUAL **Status Verified Date:** 2018-11 #### Study First Post Date **Date:** 2016-05-20 **Type:** ESTIMATED **Study First Submit Date:** 2015-07-10 **Study First Submit QC Date:** 2016-05-17 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** University Hospital, Toulouse #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** Although RA pathomechanisms remains incompletely understood, periodontitis and RA share pathogenic features : genetic and environmental influences, chronic inflammatory disease, immunoregulatory imbalance, bacterial factors, persistence of antigen/peptide and clinical factors (conjunctive and hard tissues destruction). Several hypothesis can be evocated : Gram negative bacterial systemic spreading, inflammatory transmitter substance systemic spreading (IL1, IL6, IL17, PGE2), systemic spreading of bacterial degradation products (LPS for example). Currently Porphyromonas gingivalis (PG) might be a susceptibility factor to RA because PG has an enzyme, the peptidylarginine deiminase leading to auto antibodies creation and RA increasing. As periodontitis, RA is chronic disease with a cyclic increase evolution, needing a complex pluridisciplinary treatment approach. Recent studies have reported an increased prevalence of RA patients with periodontal disease. Others studies show that periodontal treatment induces a significant decrease of the sedimentation rate and of the DAS28. Periodontitis is suspected to be an independent, aggravating factor in patients with RA (given the definition from NIH : an aggravating factor is something that makes a condition worse). So periodontal treatment cannot be considered as a RA treatment per se. But it is hypothesised that treating periodontitis in RA patients showing signs of periodontitis could result in improvement in RA disease activity. To date the role of periodontitis as an aggravating factor in these patients remains unclear, and only RCT designs can reasonably be used to test this causal hypothesis. There still remains some RA patients who have persistent symptoms and frequent exacerbations despite specialist care and continuous treatment, so results of treating aggravating factors are needed. As the majority of patients will benefit from a systematic evaluation and treatment of aggravating factors, the periodontal treatment strategy need to be tested. The aim of this randomised controlled trial is to assess the effectiveness of periodontal treatment for rheumatoid arthritis patients. To assess the effectiveness of periodontal treatment to reduce the severity of rheumatoid arthritis (RA), in patients suffering from both periodontitis and rheumatoid arthritis. The hypothesis is that periodontal treatment reduce the severity of rheumatoid arthritis. ### Conditions Module **Conditions:** - Periodontitis - Rheumatoid Arthritis ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 22 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Intervention Names:** - Procedure: Periodontal treatment **Label:** Immediate Periodontal treatment group **Type:** EXPERIMENTAL #### Arm Group 2 **Intervention Names:** - Procedure: Periodontal treatment **Label:** Delayed Periodontal treatment Group **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Delayed Periodontal treatment Group - Immediate Periodontal treatment group **Description:** * Mechanical debridement (scaling, root planning, subgingival curettage) * Antimicrobial therapy (systematically administered: amoxicillin or clindamycin). * Antiseptic mouthrinses, gel or dentifrice * Oral hygiene instructions (to educate and motivate patients to control the accumulation of plaque and calculus) **Name:** Periodontal treatment **Type:** PROCEDURE ### Outcomes Module #### Primary Outcomes **Measure:** Evaluation of parodontitis therapeutic care as assessed by variation in DAS28 score **Time Frame:** Day 15 and day 90 #### Secondary Outcomes **Measure:** Evaluation of parodontitis therapeutic care as assessed by variation in ACR 20 score **Time Frame:** Day 15 and day 90 **Measure:** Evaluation of parodontitis therapeutic care as assessed by variation in HAQ score **Time Frame:** Day 15 and day 90 **Measure:** Evaluation of parodontitis therapeutic care as assessed by variation in GOHAI score **Time Frame:** Day 15 and day 90 ### Eligibility Module **Eligibility Criteria:** INCLUSION CRITERIA: * rheumatoid arthritis diagnosed for at least one year * DAS28 score between 3.2 and 5.1 * no change to medication, dosage or formulation in RA treatment during the 3 months preceding the screening visit * subject available for all study visits over three months in the Dental Care Departments (V1 to V4) * subjects with at least six natural teeth with root * subject with periodontitis, defined by the presence of one site with periodontal probing depth ≥ 4 mm and clinical attachment level ≥ 3 mm on at least 4 teeth. * subject has given his informed consent: 1 week cooling-off period EXCLUSION CRITERIA: * subject will not qualify for enrolment if he presents at least one of the following: acute oral infection, acute oral pain (including pulpitis), suspicious oral mucosal lesion, severe oral inflammation unrelated to periodontal conditions, or need for immediate tooth extractions * have a planned hospitalization within 4 months after the screening visit * subject suffering from one or more known infectious diseases (HIV, hepatitis, infectious mononucleosis), * subject suffering from known clinically significant renal disease (creatinine clearance \<60 ml/min), or liver disease, * unbalanced diabetes * have a known risk of endocarditis, * have a permanent pacemaker, * subject taking antithrombotic treatment, * subject having severe difficulties in understanding written and spoken French * for females: are pregnant or intending to become pregnant, or lactating * subject suffering from a chronic disorder that requires chronic or intermittent use of antibiotics, * subject having known hypersensitivity to chlorhexidine gluconate * are participating in another intervention study * have known contraindications to both amoxicillin and clindamycin * have known contraindications to dental local anesthetic. **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Bordeaux **Country:** France **Facility:** CHU de Bordeaux **Zip:** 33000 **Location 2:** **City:** Toulouse **Country:** France **Facility:** Pôle Odontologie Hôpital Purpan - Pavillon Rayer **Zip:** 31059 #### Overall Officials **Official 1:** **Affiliation:** Faculté de chirurgie dentaire - Toulouse **Name:** Paul MONSARRAT, MD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000007592 - Term: Joint Diseases - ID: D000009140 - Term: Musculoskeletal Diseases - ID: D000012216 - Term: Rheumatic Diseases - ID: D000003240 - Term: Connective Tissue Diseases - ID: D000001327 - Term: Autoimmune Diseases - ID: D000007154 - Term: Immune System Diseases - ID: D000010510 - Term: Periodontal Diseases - ID: D000009059 - Term: Mouth Diseases - ID: D000009057 - Term: Stomatognathic Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC07 - Name: Mouth and Tooth Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC05 - Name: Musculoskeletal Diseases - Abbrev: BC17 - Name: Skin and Connective Tissue Diseases - Abbrev: BC20 - Name: Immune System Diseases ### Condition Browse Module - Browse Leaves - ID: M13427 - Name: Periodontitis - Relevance: HIGH - As Found: Periodontitis - ID: M4476 - Name: Arthritis - Relevance: HIGH - As Found: Arthritis - ID: M4480 - Name: Arthritis, Rheumatoid - Relevance: HIGH - As Found: Rheumatoid Arthritis - ID: M10621 - Name: Joint Diseases - Relevance: LOW - As Found: Unknown - ID: M12097 - Name: Musculoskeletal Diseases - Relevance: LOW - As Found: Unknown - ID: M15045 - Name: Rheumatic Diseases - Relevance: LOW - As Found: Unknown - ID: M6323 - Name: Collagen Diseases - Relevance: LOW - As Found: Unknown - ID: M6464 - Name: Connective Tissue Diseases - Relevance: LOW - As Found: Unknown - ID: M4629 - Name: Autoimmune Diseases - Relevance: LOW - As Found: Unknown - ID: M10200 - Name: Immune System Diseases - Relevance: LOW - As Found: Unknown - ID: M13419 - Name: Periodontal Diseases - Relevance: LOW - As Found: Unknown - ID: M12019 - Name: Mouth Diseases - Relevance: LOW - As Found: Unknown - ID: M12017 - Name: Stomatognathic Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000001168 - Term: Arthritis - ID: D000001172 - Term: Arthritis, Rheumatoid - ID: D000010518 - Term: Periodontitis ### Intervention Browse Module - Browse Branches - Abbrev: Infe - Name: Anti-Infective Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M3995 - Name: Amoxicillin - Relevance: LOW - As Found: Unknown - ID: M4222 - Name: Anti-Bacterial Agents - Relevance: LOW - As Found: Unknown - ID: M6214 - Name: Clindamycin - Relevance: LOW - As Found: Unknown - ID: M220697 - Name: Clindamycin palmitate - Relevance: LOW - As Found: Unknown - ID: M231711 - Name: Clindamycin phosphate - Relevance: LOW - As Found: Unknown - ID: M4214 - Name: Anti-Infective Agents - Relevance: LOW - As Found: Unknown - ID: M4215 - Name: Anti-Infective Agents, Local - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT06230679 **Brief Title:** Effectiveness of NESA in the Treatment of Cancer Survivors **Official Title:** Effectiveness of NESA in the Treatment of Sleep Problems, Fatigue, and Neuromuscular Pain in Cancer Survivors. #### Organization Study ID Info **ID:** NESABiel #### Organization **Class:** OTHER **Full Name:** University of Las Palmas de Gran Canaria ### Status Module #### Completion Date **Date:** 2024-09-19 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-16 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-13 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2024-06-19 **Type:** ESTIMATED #### Start Date **Date:** 2024-01-19 **Type:** ACTUAL **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2024-01-30 **Type:** ACTUAL **Study First Submit Date:** 2024-01-19 **Study First Submit QC Date:** 2024-01-19 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Aníbal Báez Suárez #### Responsible Party **Investigator Affiliation:** University of Las Palmas de Gran Canaria **Investigator Full Name:** Aníbal Báez Suárez **Investigator Title:** Clinical Professor **Type:** SPONSOR_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Cancer is a disease, or a set of diseases, that increased in our society. However, improvements in their detection and treatment increase the number of patients who survive. Every year 2.6 million people are diagnosed in the European Union and 1.4 million become cancer survivors. However, these people suffer the late adverse effects of treatment that can seriously affect their quality of life. the most common late effects are pain, fatigue, and sleeping difficulties. These are estimated between 58-90%. The autonomic nervous system (ANS) appears to play an important role in the manifestation and perpetuation of these symptoms. **Detailed Description:** This study aims to evaluate NESA (or NESA non-invasive neuromodulation) to treat the most common long-term side effects in cancer survivors, due to the most used treatments. It will be compared between two groups of cancer survivors. The intervention group, with electrical stimulation, and the sham group, without electrical stimulation emission. The subjects will be assigned randomly. Neither the patient, the therapist, nor the analysts/researchers will know the assignment. Finally, this project aims to add a passive tool to the therapeutic arsenal of health professionals in the oncology field for the treatment of late side effects. ### Conditions Module **Conditions:** - Cancer Survivors **Keywords:** - cancer - physical therapy modality - Electric Stimulation Therapy ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** QUADRUPLE **Who Masked:** - PARTICIPANT - CARE_PROVIDER - INVESTIGATOR - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 40 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Intervention with electrical stimulation: application of 6 electrodes per extremity and an adhesive electrode at C7 level. **Intervention Names:** - Device: Non-invasive Neuromodulation **Label:** Non-invasive Neuromodulation **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Intervention with electrical stimulation: application of 6 electrodes per extremity and an adhesive electrode at C7 level. **Intervention Names:** - Device: Placebo Non-invasive Neuromodulation **Label:** Placebo Non-invasive Neuromodulation **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Non-invasive Neuromodulation **Description:** Patients receive non-invasive neurostimulation through the Nesa device **Name:** Non-invasive Neuromodulation **Type:** DEVICE #### Intervention 2 **Arm Group Labels:** - Placebo Non-invasive Neuromodulation **Description:** The same protocol described for the experimental group will be applied, but electrical stimulation device which will be previously manipulated and tested with an oscilloscope so that they do not emit electrical currents. **Name:** Placebo Non-invasive Neuromodulation **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Description:** The investigators want to see if there are improvements in the quality, efficiency, and quantity of sleep. The Pittsburgh Sleep Quality Index (PSQI) will be combined to report changes in the patient's sleep quality. Each of the sleep components yields a score ranging from 0 to 3, with 3 indicating the greatest dysfunction. The sleep component scores are summed to yield a total score ranging from 0 to 21 with the higher total score (referred to as global score) indicating worse sleep quality. Adding up the average scores of the seven factors gives a global PSQI score from 0 to 21, with 0-4 indicating "good" sleep and 5-21 indicating "poor" sleep **Measure:** Change in sleep quality assessed by Pittsburgh Sleep Quality Index (PSQI) **Time Frame:** Measurement of change: before treatment (baseline), at two months (end of treatment), and at 1 months of treatment (follow-up period). **Description:** The Short Form 36 (SF-36) health questionnaire will be used. It is a generic scale that provides a profile of health status and is applicable to both patients and the general population. It is composed of 36 questions (items) that assess both positive and negative states of health. The scores for each of the 8 dimensions of the SF-36 range from 0 to 100, with 100 indicating optimal health and 0 reflecting very poor health. **Measure:** Change in quality of life assessed by The Short Form 36 (SF-36) health questionnaire **Time Frame:** Measurement of change: before treatment (baseline), at two months (end of treatment), and at 1 months of treatment (follow-up period). **Description:** It is a self-report questionnaire that allows to give a good description of the quality and intensity of the pain they are experiencing. of the quality and intensity of the pain they are experiencing. It consists of a list of 78 words in 20 sections related to pain. Users mark the words that best describe their pain. users mark the words that best describe their pain. These words correlate with different aspects of pain different aspects of pain, including a sensory section (sections 1 to 10), an affective section (sections 11 to 15), an evaluative section (sections 11 to 15), and a 10), an affective section (sections 11 to 15), an evaluative section (section 16), and finally a miscellaneous section (section 16). and, finally, a miscellaneous section (sections 17 to 20). The main component of the McGill Pain questionnaire consists of 15 descriptors (11 sensory; 4 affective) which are rated on an intensity scale as 0 = none, 1 = mild, 2 = moderate or 3 = severe **Measure:** Change in Pain assessed by McGill Pain questionnaire **Time Frame:** Measurement of change: before treatment (baseline), at two months (end of treatment), and at 1 months of treatment (follow-up period). ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Be a cancer survivor (5 years after discharge) * Have 1 of the 3 symptoms of the most common cluster: sleep problems, chronic fatigue, chronic neuro-muscular pain. Exclusion Criteria: * Not have an active oncological process * Present any of the contraindications of the NESA-XSignal device: pacemaker, internal bleeding, skin in poor condition (ulcerations or wounds), acute febrile processes, acute thrombophlebitis, pregnancy, phobia of electricity. **Maximum Age:** 80 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Gabriel Amengual Jaume, MSc **Phone:** +34 971 07 86 67 **Role:** CONTACT #### Locations **Location 1:** **City:** Santa Maria Del Camí **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Gabriel Amengual Jaume, MSc - **Phone:** +34 971 07 86 67 - **Role:** CONTACT ***Contact 2:*** - **Name:** Raquel Medina -Ramírez, PhD - **Role:** SUB_INVESTIGATOR ***Contact 3:*** - **Name:** David Alamo-Arce, MSc - **Role:** SUB_INVESTIGATOR ***Contact 4:*** - **Name:** Rafael Arteaga-Ortiz, PhD - **Role:** SUB_INVESTIGATOR ***Contact 5:*** - **Name:** Aníbal Báez-Suárez, PhD - **Role:** SUB_INVESTIGATOR ***Contact 6:*** - **Name:** Fabiola Molina Cedrés, MSc - **Role:** SUB_INVESTIGATOR ***Contact 7:*** - **Name:** María del Pino Quintana-Montesdeoca, PhD - **Role:** SUB_INVESTIGATOR **Country:** Spain **Facility:** Gutmotion **State:** Balearic **Status:** RECRUITING **Zip:** 07320 #### Overall Officials **Official 1:** **Affiliation:** University of Las Palmas de Gran Canaria **Name:** Gabriel Amengual Jaume, MSc **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Rick O, Dauelsberg T, Kalusche-Bontemps EM. Oncological Rehabilitation. Oncol Res Treat. 2017;40(12):772-777. doi: 10.1159/000481709. Epub 2017 Nov 29. **PMID:** 29183040 **Citation:** Paltrinieri S, Fugazzaro S, Bertozzi L, Bassi MC, Pellegrini M, Vicentini M, Mazzini E, Costi S. Return to work in European Cancer survivors: a systematic review. Support Care Cancer. 2018 Sep;26(9):2983-2994. doi: 10.1007/s00520-018-4270-6. Epub 2018 May 29. **PMID:** 29845421 **Citation:** Boland EG, Ahmedzai SH. Persistent pain in cancer survivors. Curr Opin Support Palliat Care. 2017 Sep;11(3):181-190. doi: 10.1097/SPC.0000000000000292. **PMID:** 28700361 **Citation:** Kline-Quiroz C, Nori P, Stubblefield MD. Cancer Rehabilitation: Acute and Chronic Issues, Nerve Injury, Radiation Sequelae, Surgical and Chemo-Related, Part 1. Med Clin North Am. 2020 Mar;104(2):239-250. doi: 10.1016/j.mcna.2019.10.004. Epub 2019 Nov 23. **PMID:** 32035566 ## Derived Section ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: BXM - Name: Behaviors and Mental Disorders ### Condition Browse Module - Browse Leaves - ID: M13066 - Name: Pain - Relevance: LOW - As Found: Unknown - ID: M8364 - Name: Fatigue - Relevance: LOW - As Found: Unknown - ID: M22242 - Name: Parasomnias - Relevance: LOW - As Found: Unknown - ID: M22655 - Name: Dyssomnias - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT02451579 **Brief Title:** A Clinical Trial Evaluating the Role of Systemic Antihistamine Therapy in the Reduction of Adverse Effects Associated With Topical 5-aminolevulinic Acid Photodynamic Therapy **Official Title:** A Randomized, Double-blind, Placebo-controlled, Prospective Clinical Trial Evaluating the Role of Systemic Antihistamine Therapy in the Reduction of Adverse Effects Associated With Topical 5-aminolevulinic Acid Photodynamic Therapy #### Organization Study ID Info **ID:** PDT-2015-01 #### Organization **Class:** OTHER **Full Name:** Goldman, Butterwick, Fitzpatrick and Groff ### Status Module #### Completion Date **Date:** 2017-01 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2017-03-01 **Type:** ACTUAL **Last Update Submit Date:** 2017-02-27 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2016-12 **Type:** ACTUAL #### Start Date **Date:** 2015-02 **Status Verified Date:** 2017-02 #### Study First Post Date **Date:** 2015-05-22 **Type:** ESTIMATED **Study First Submit Date:** 2015-05-12 **Study First Submit QC Date:** 2015-05-21 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** DUSA Pharmaceuticals, Inc. #### Lead Sponsor **Class:** OTHER **Name:** Goldman, Butterwick, Fitzpatrick and Groff #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** A double-blind, placebo controlled study conducted at a single study site. Evaluating the role of systemic antihistamine therapy in the reduction of adverse effects associated with topical 5-aminolevulinic acid photodynamic therapy. ### Conditions Module **Conditions:** - Actinic Keratoses **Keywords:** - Actinic Keratoses - Photodynamic Therapy - PDT - Blue Light ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** DOUBLE **Who Masked:** - PARTICIPANT - INVESTIGATOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 20 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Prophylactic use of cetirizine hydrochloride prior to and after Topical 5-aminolevulinic Acid Photodynamic Therapy **Intervention Names:** - Drug: Antihistamine Cetirizine Hydrochloride **Label:** Cetirizine Hydrochloride **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** Prophylactic use of placebo prior to and after Topical 5-aminolevulinic Acid Photodynamic Therapy **Intervention Names:** - Other: Placebo **Label:** Placebo **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Cetirizine Hydrochloride **Description:** Prophylactic use of antihistamine prior to and following topical 5-aminolevulonic acid photodynamic therapy **Name:** Antihistamine Cetirizine Hydrochloride **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Placebo **Description:** Use of placebo prior to and following topical 5-aminolevulonic acid photodynamic therapy **Name:** Placebo **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** Localized Skin Response consisting of erythema, edema, crusting, exudation, Vesiculation/Pustulation and erosion/ ulceration Investigator evaluated on a standardized scale **Measure:** Localized Skin Response **Time Frame:** Up to day 180 ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Age \> 18 * Subjects with 5-20 actinic keratosis of the face * Patients undergoing photodynamic therapy (PDT) to the face for AK with 5-aminolevulinic acid (ALA) activated by blue light. * Must be willing to give and sign a HIPPA form, photo consent and informed consent form. * Must be willing to comply with study dosing and complete the entire course of the study. * Female patients will be either of non-childbearing potential defined as: 1. Having no uterus 2. No menses for at least 12 months. Or; (WOCBP) women of childbearing potential must agree to use an effective method of birth control during the course of the study, such as: 1. Oral contraceptive pill, injection, implant, patch, vaginal ring, intrauterine device 2. Intrauterine coil 3. Bilateral tubal ligation 4. Barrier method used with an additional form of contraception (e.g., sponge, spermicide or condom) 5. Abstinence (If practicing abstinence must agree to use barrier method described above (d) if becomes sexually active). 6. Vasectomized partner g. Negative urine pregnancy test results Baseline prior to study entry (if applicable) Exclusion Criteria: * Presence of incompletely healed wound in treatment area * Presence of known or suspected BCC or SCC in treatment area * Previous PDT or treatment of the face with any topical cytotoxic or immunomodulatory agent for AKs within the past 6 months * Co-existing potentially confounding skin condition within treatment area (e.g. eczema, psoriasis, XP, rosacea) at investigator's discretion * Presence of tattoo and/or scar in the treatment area that in the investigators opinion would interfere with study assessments * Subjects with known photosensitivity or taking photosensitizing medications listed below: 1. Oral diabetes medicines 2. Griseofulvin 3. Thiazide diuretics 4. Sulfonylureas 5. Phenothiazines 6. Tetracycline's 7. St. John's Wort * Use of oral/topical retinoids within 1 month of Baseline * Subjects with a history of sensitivity to porphyrins * Subjects with recently excessive exposure of the treatment area to sunlight or artificial UV light (e.g.: use of tanning beds/booths and/or sunbathing) or expectations of tanning during the time of the study * Female subjects who are pregnant, nursing an infant or planning a pregnancy during the study \[throughout the course of the study * Presence or evidence of any conditions that in the opinion of the investigator might impede the subject's ability to give consent or comply with protocol requirements. * Current participation or participation within 30 days prior to the start of this study in a drug or other investigational research study * History of non-compliance with clinical research protocols * Ablative laser resurfacing to on their face within 12 months * Non-ablative laser or light procedures to their face within the past 3 months * Microdermabrasion (light or medium skin peel) treatment on their face within the past 30 days **Healthy Volunteers:** True **Minimum Age:** 19 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** San Diego **Country:** United States **Facility:** Cosmetic Laser Dermatology **State:** California **Zip:** 92121 #### Overall Officials **Official 1:** **Affiliation:** Cosmetic Laser Dermatology **Name:** Mitchel P Goldman, MD **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### References **Citation:** Vanaman Wilson MJ, Jones IT, Wu DC, Goldman MP. A randomized, double-blind, placebo-controlled clinical trial evaluating the role of systemic antihistamine therapy for the reduction of adverse effects associated with topical 5-aminolevulinic acid photodynamic therapy. Lasers Surg Med. 2017 Oct;49(8):738-742. doi: 10.1002/lsm.22682. Epub 2017 May 10. **PMID:** 28489298 ## Annotation Section ### Unposted Annotation #### Event: RELEASE - Date: 2019-05-01 - Date Unknown: Unknown #### Event: RESET - Date: 2019-05-22 - Date Unknown: Unknown #### Event: RELEASE - Date: 2019-08-15 - Date Unknown: Unknown #### Event: RESET - Date: 2019-09-04 - Date Unknown: Unknown ## Derived Section ### Condition Browse Module - Ancestors - ID: D000012871 - Term: Skin Diseases - ID: D000011230 - Term: Precancerous Conditions - ID: D000009369 - Term: Neoplasms ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC17 - Name: Skin and Connective Tissue Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M28268 - Name: Keratosis, Actinic - Relevance: HIGH - As Found: Actinic Keratosis - ID: M10668 - Name: Keratosis - Relevance: HIGH - As Found: Keratosis - ID: M15674 - Name: Skin Diseases - Relevance: LOW - As Found: Unknown - ID: M14111 - Name: Precancerous Conditions - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000055623 - Term: Keratosis, Actinic - ID: D000007642 - Term: Keratosis ### Intervention Browse Module - Ancestors - ID: D000018926 - Term: Anti-Allergic Agents - ID: D000039563 - Term: Histamine H1 Antagonists, Non-Sedating - ID: D000018494 - Term: Histamine Agents - ID: D000018377 - Term: Neurotransmitter Agents - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000045505 - Term: Physiological Effects of Drugs ### Intervention Browse Module - Browse Branches - Abbrev: Derm - Name: Dermatologic Agents - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: AAll - Name: Anti-Allergic Agents ### Intervention Browse Module - Browse Leaves - ID: M3960 - Name: Aminolevulinic Acid - Relevance: LOW - As Found: Unknown - ID: M9709 - Name: Histamine Antagonists - Relevance: HIGH - As Found: Diathermy - ID: M9710 - Name: Histamine H1 Antagonists - Relevance: HIGH - As Found: Diathermy - ID: M19620 - Name: Cetirizine - Relevance: HIGH - As Found: Hearing loss - ID: M9708 - Name: Histamine - Relevance: LOW - As Found: Unknown - ID: M212144 - Name: Histamine phosphate - Relevance: LOW - As Found: Unknown - ID: M20962 - Name: Anti-Allergic Agents - Relevance: LOW - As Found: Unknown - ID: M24826 - Name: Histamine H1 Antagonists, Non-Sedating - Relevance: LOW - As Found: Unknown - ID: M20504 - Name: Neurotransmitter Agents - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000017332 - Term: Cetirizine - ID: D000006633 - Term: Histamine Antagonists - ID: D000006634 - Term: Histamine H1 Antagonists ### Misc Info Module #### Submission Tracking - Estimated Results First Submit Date: 2019-05-01 ##### Submission Infos - MCP Release N: Unknown - Release Date: 2019-05-01 - Reset Date: 2019-05-22 - Unrelease Date: Unknown - Unrelease Date Unknown: Unknown - MCP Release N: Unknown - Release Date: 2019-08-15 - Reset Date: 2019-09-04 - Unrelease Date: Unknown - Unrelease Date Unknown: Unknown - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05871879 **Brief Title:** Association Between Frailty and Postoperative Adverse Outcomes in Patients Undergoing Urological Surgery **Official Title:** Association Between Frailty and Postoperative Adverse Outcomes in Patients Undergoing Urological Surgery #### Organization Study ID Info **ID:** 202305015 #### Organization **Class:** OTHER **Full Name:** Taipei Medical University Hospital ### Status Module #### Completion Date **Date:** 2023-05-15 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2023-05-23 **Type:** ACTUAL **Last Update Submit Date:** 2023-05-15 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2023-03-16 **Type:** ACTUAL #### Start Date **Date:** 2023-01-01 **Type:** ACTUAL **Status Verified Date:** 2023-05 #### Study First Post Date **Date:** 2023-05-23 **Type:** ACTUAL **Study First Submit Date:** 2023-05-15 **Study First Submit QC Date:** 2023-05-15 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Taipei Medical University Hospital #### Responsible Party **Investigator Affiliation:** Taipei Medical University Hospital **Investigator Full Name:** Chao-Shun Lin **Investigator Title:** Attending physician of anesthesiology, clinical professor **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Frailty is a clinical condition associated with aging that is characterized by a decline in physiological capacity involving multiple organ systems. Previous research has established a strong correlation between frailty and increased mortality and morbidity risk after surgery. The 5-item modified frailty index (mFI-5) is a recent tool used to assess frailty. The aim of the present study was to use the mFI-5 to identify frailty and its association with postoperative adverse outcomes, including mortality and morbidity, among patients who underwent urologic procedures. **Detailed Description:** Frailty is a clinical condition that often develops with age and is characterized by a decline in physiological capacity and dysfunction across multiple organ systems. This decline results in reduced physical reserve and an increased vulnerability to acute stressors, such as surgical interventions. The prevalence of frailty varies based on the definition used, with 15% of the nonnursing home population in the US experiencing frailty and 45% experiencing prefrailty. Frailty is more common in individuals with certain comorbidities, such as HIV infection, chronic obstructive pulmonary disease, and end-stage renal disease, and it is more prevalent with increasing age. Previous studies have established a link between urologic issues and frailty. In fact, more than 40% of patients with lower urologic symptoms exhibit frailty-related features such as sarcopenia, dysmotility, multimorbidity, and a heightened risk of malnutrition. Additionally, common geriatric ailments, such as benign prostate hypertrophy, dementia, spinal disc herniation, and cerebral infarction, are also associated with neurogenic bladder and other voiding difficulties. Consequently, surgical intervention is often necessary for these populations. However, even minimally invasive procedures may be risky due to the vulnerability of frail individuals. Prior studies have shown a strong correlation between frailty and the likelihood of postoperative mortality and morbidity. Patients classified as very frail have 30-day and 180-day mortality rates of approximately 10% and 40%, respectively, even following minor surgeries. A new tool for assessing frailty, the 5-item modified frailty index (mFI-5), has recently been developed using data from the National Surgical Quality Improvement Program (NSQIP) database. This simplified scale, which consists of only five items, has demonstrated superior predictive ability compared to previously utilized tools. The mFI-5 has been studied across various surgical populations and has been found to be associated with unfavorable postoperative outcomes. However, there are limited studies examining its utility in urologic surgery, and no reports has investigated the association between frailty and minimally invasive urologic procedures. Therefore, the present study aimed to investigate the correlation between the modified 5-item frailty index and postoperative mortality and complications among frail patients who undergo urologic surgery. ### Conditions Module **Conditions:** - Frailty - Postoperative Complications **Keywords:** - Frailty - Postoperative Complications - Urologic Surgery ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** RETROSPECTIVE #### Enrollment Info **Count:** 317076 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** The included procedures included all urologic oncology surgeries, suburethral sling placement, laparoscopic pyeloplasty, transurethral resection of the prostate, transurethral resection of the bladder tumor, ureteroscopy, hydrocelectomy, orchiectomy, spermatocelectomy, epididymectomy, and varicocelectomy. **Intervention Names:** - Diagnostic Test: The 5-item modified frailty index **Label:** All adult patients who underwent urologic procedures ### Interventions #### Intervention 1 **Arm Group Labels:** - All adult patients who underwent urologic procedures **Description:** The mFI-5 contains five items, including hypertension, diabetes, congestive heart failure (CHF), chronic obstructive lung disease (COPD), and physical function status, with each item attributing 1 point. Patients with an mFI-5 score greater than or equal to 2 were considered frail, while those with an mFI-5 score of 0 or 1 were considered nonfrail. **Name:** The 5-item modified frailty index **Other Names:** - mFI-5 **Type:** DIAGNOSTIC_TEST ### Outcomes Module #### Primary Outcomes **Description:** postoperative in-hospital mortality **Measure:** postoperative mortality **Time Frame:** within 30 days after the primary procedure #### Secondary Outcomes **Description:** cardiovascular events, cerebrovascular events, pneumonia, surgical site infection, sepsis, bleeding, mechanical ventilation \>48 hrs, reoperation, readmission, and length of hospital stay. **Measure:** postoperative complications **Time Frame:** within 30 days after the primary procedure ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * All adult patients who underwent urologic procedures were recruited (Included procedures : all urologic oncology surgeries, suburethral sling placement and laparoscopic pyeloplasty, transurethral resection of the prostate, transurethral resection of the bladder tumor, ureteroscopy, hydrocelectomy, orchiectomy, spermatocelectomy, epididymectomy, and varicocelectomy.) Exclusion Criteria: * Incomplete information of baseline parameters **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Surgical cases from 2015 to 2020 NSQIP dataset ### Contacts Locations Module #### Locations **Location 1:** **City:** Taipei **Country:** Taiwan **Facility:** Taipei Medical University Hospital **Zip:** 110 #### Overall Officials **Official 1:** **Affiliation:** Department of Anesthesiology, Taipei Medical University Hospital, 252 Wuxing St., Taipei 110 Taiwan **Name:** Chao-Shun Lin, PhD **Role:** STUDY_CHAIR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000010335 - Term: Pathologic Processes ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M14065 - Name: Postoperative Complications - Relevance: HIGH - As Found: Postoperative Complications - ID: M1175 - Name: Frailty - Relevance: HIGH - As Found: Frailty ### Condition Browse Module - Meshes - ID: D000073496 - Term: Frailty - ID: D000011183 - Term: Postoperative Complications ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT01891279 **Brief Title:** Elemental Formula in Neonates Post Small Bowel Resection: Improved Weaning From Total Parenteral Nutrition? **Official Title:** The Use of Elemental Formula in Neonates Post Small Bowel Resection: Improved Success to Wean From Total Parenteral Nutrition? #### Organization Study ID Info **ID:** HSC-MS-09-0260 #### Organization **Class:** OTHER **Full Name:** The University of Texas Health Science Center, Houston ### Status Module #### Completion Date **Date:** 2013-09-17 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2021-05-07 **Type:** ACTUAL **Last Update Submit Date:** 2021-05-04 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2013-08-13 **Type:** ACTUAL #### Start Date **Date:** 2011-09-26 **Type:** ACTUAL **Status Verified Date:** 2021-05 #### Study First Post Date **Date:** 2013-07-03 **Type:** ESTIMATED **Study First Submit Date:** 2012-05-01 **Study First Submit QC Date:** 2013-07-02 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** The University of Texas Health Science Center, Houston #### Responsible Party **Investigator Affiliation:** The University of Texas Health Science Center, Houston **Investigator Full Name:** Amir Mustafa Khan **Investigator Title:** Professor of Pediatrics **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** In neonates with recent small bowel resection or congenital bowel anomalies (gastroschisis or omphalocele), does an elemental formula as compared to a partially hydrolyzed formula allowed the infant to wean off Total Parenteral Nutrition (TPN) earlier? **Detailed Description:** Neonates with short bowel syndrome (SBS) due to recent small bowel resection or congenital bowel anomalies (gastroschisis or omphalocele) can have inability to adequately digest and absorb enteral feedings resulting in prolonged Parenteral Nutrition (PN) dependence for nutrition and growth. Prolonged PN dependence can result in Parenteral Nutrition Associated Liver Disease (PNALD) and intestinal failure requiring small bowel or small bowel/liver transplantation for survival. After bowel resection, the bowel has an ability to compensate for significant loss by going through a process called intestinal adaptation. Enteral feeding is the key factor for initiating and maintaining the adaptation of the intestine. Whole protein formulas or partially hydrolyzed formulas provide either the full protein or dipeptides/tripeptides respectively, and are thought to confer the best benefit in inducing intestinal adaptation and increasing paracrine stimulation. However, in small studies of adults and children with SBS,an amino acid based (elemental) formula demonstrated improved feeding tolerance and ability to wean off TPN. In a small study, babies fed breast milk or elemental formula appeared to have shorter duration of TPN. This is a randomized, blinded clinical trial to determine if elemental formula, Elecare® (vs. partially hydrolyzed formula, Pregestimil®) is better tolerated and allows a higher proportion of neonates with small bowel resection or congenital bowel anomalies to successfully wean off TPN. ### Conditions Module **Conditions:** - Short Bowel Syndrome **Keywords:** - short bowel syndrome - Elemental formula - partially hydrolyzed formula - Enteral feeding - TPN dependency - Intestinal adaptation - TPN cholestasis ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** TRIPLE **Who Masked:** - PARTICIPANT - CARE_PROVIDER - INVESTIGATOR **Primary Purpose:** OTHER #### Enrollment Info **Count:** 35 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Babies will receive elemental formula, Elecare®, if breast milk is not available. **Intervention Names:** - Other: elemental formula Elecare® **Label:** elemental formula, Elecare® **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Babies will receive partially hydrolyzed formula, Pregestimil®, if breast milk is not available. **Intervention Names:** - Other: partially hydrolyzed formula **Label:** part hydrolyzed formula, Pregestimil® **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - elemental formula, Elecare® **Description:** Babies will be randomized to received either elemental formula (Elecare®) or partially hydrolyzed formula (Pregestimil®) if breast milk is not available. **Name:** elemental formula Elecare® **Other Names:** - Elecare® **Type:** OTHER #### Intervention 2 **Arm Group Labels:** - part hydrolyzed formula, Pregestimil® **Description:** Babies will be randomized to received either partially hydrolyzed formula (Pregestimil®) or elemental formula (Elecare®)if breast milk is not available. **Name:** partially hydrolyzed formula **Other Names:** - Pregestimil® **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** At 6 wks post intervention, if they are tolerating \< 40 enteral Kcal/k/day, this will be considered a failure to establish adaptation with the formula; if they are tolerating 41-90 enteral Kcal/k/day, this formula will be continued for 2 weeks longer;if they are tolerating \>90 enteral Kcal/k/day, this will be considered a weaning success. At 8 wks post intervention, if they are tolerating \<90 enteral Kcal/k/day, this will be considered a failure to establish adaptation; At 8 wks post intervention, if they are tolerating \>90 enteral Kcal/k/day, this will be considered a weaning success. **Measure:** tolerance of TPN use **Time Frame:** 6 weeks and 8 weeks after initiation of feeding #### Secondary Outcomes **Description:** number of hospital days from birth to hospital discharge, up to 1 year of age **Measure:** Length of hospital stay **Time Frame:** from birth (admission) to discharge (up to 1 year of age) **Description:** The highest and lowest direct bilirubin levels during hospitalization and direct bilirubin level at hospital discharge **Measure:** Direct bilirubin levels **Time Frame:** From birth (admission) to discharge (up to 1 year of age) **Description:** Assessment for signs of infection (e.g. CBC, CRP, blood cultures, UA, stool studies, C. diff) is routine. **Measure:** Blood stream infections **Time Frame:** From birth (admission) to discharge (up to 1 year of age) ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Term or pre-term neonates with either surgical resection of the small bowel or congenital bowel anomalies (gastroschisis, omphalocele) unable to tolerate 90kcal/kg/day of enteral feedings by 1 month of age Exclusion Criteria: * Term or preterm neonates with NEC totalis, * Inborn Errors of Metabolism, or * Known or suspected congenital syndromes **Maximum Age:** 1 Year **Sex:** ALL **Standard Ages:** - CHILD ### Contacts Locations Module #### Locations **Location 1:** **City:** Houston **Country:** United States **Facility:** The University of Texas Health Science Center at Houston **State:** Texas **Zip:** 77030 #### Overall Officials **Official 1:** **Affiliation:** The University of Texas Health Science Center, Houston **Name:** Amir M Khan, MD **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### References **Citation:** Vanderhoof JA. Short bowel syndrome in children and small intestinal transplantation. Pediatr Clin North Am. 1996 Apr;43(2):533-50. doi: 10.1016/s0031-3955(05)70419-3. **PMID:** 8614614 **Citation:** Vanderhoof JA. Short bowel syndrome. Clin Perinatol. 1996 Jun;23(2):377-86. **PMID:** 8780910 **Citation:** Bines JE, Taylor RG, Justice F, Paris MC, Sourial M, Nagy E, Emselle S, Catto-Smith AG, Fuller PJ. Influence of diet complexity on intestinal adaptation following massive small bowel resection in a preclinical model. J Gastroenterol Hepatol. 2002 Nov;17(11):1170-9. doi: 10.1046/j.1440-1746.2002.02872.x. **PMID:** 12453276 **Citation:** Bines J, Francis D, Hill D. Reducing parenteral requirement in children with short bowel syndrome: impact of an amino acid-based complete infant formula. J Pediatr Gastroenterol Nutr. 1998 Feb;26(2):123-8. doi: 10.1097/00005176-199802000-00001. **PMID:** 9481624 **Citation:** Lai HS, Chen WJ, Chen KM, Lee YN. Effects of monomeric and polymeric diets on small intestine following massive resection. Taiwan Yi Xue Hui Za Zhi. 1989 Oct;88(10):982-8. **PMID:** 2634733 **Citation:** Cosnes J, Evard D, Beaugerie L, Gendre JP, Le Quintrec Y. Improvement in protein absorption with a small-peptide-based diet in patients with high jejunostomy. Nutrition. 1992 Nov-Dec;8(6):406-11. **PMID:** 1486247 **Citation:** Andorsky DJ, Lund DP, Lillehei CW, Jaksic T, Dicanzio J, Richardson DS, Collier SB, Lo C, Duggan C. Nutritional and other postoperative management of neonates with short bowel syndrome correlates with clinical outcomes. J Pediatr. 2001 Jul;139(1):27-33. doi: 10.1067/mpd.2001.114481. **PMID:** 11445790 **Citation:** Rhoads JM, Plunkett E, Galanko J, Lichtman S, Taylor L, Maynor A, Weiner T, Freeman K, Guarisco JL, Wu GY. Serum citrulline levels correlate with enteral tolerance and bowel length in infants with short bowel syndrome. J Pediatr. 2005 Apr;146(4):542-7. doi: 10.1016/j.jpeds.2004.12.027. **PMID:** 15812462 **Citation:** Jianfeng G, Weiming Z, Ning L, Fangnan L, Li T, Nan L, Jieshou L. Serum citrulline is a simple quantitative marker for small intestinal enterocytes mass and absorption function in short bowel patients. J Surg Res. 2005 Aug;127(2):177-82. doi: 10.1016/j.jss.2005.04.004. **PMID:** 15921697 **Citation:** Crenn P, Vahedi K, Lavergne-Slove A, Cynober L, Matuchansky C, Messing B. Plasma citrulline: A marker of enterocyte mass in villous atrophy-associated small bowel disease. Gastroenterology. 2003 May;124(5):1210-9. doi: 10.1016/s0016-5085(03)00170-7. **PMID:** 12730862 **Citation:** Crenn P, Coudray-Lucas C, Thuillier F, Cynober L, Messing B. Postabsorptive plasma citrulline concentration is a marker of absorptive enterocyte mass and intestinal failure in humans. Gastroenterology. 2000 Dec;119(6):1496-505. doi: 10.1053/gast.2000.20227. **PMID:** 11113071 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000010335 - Term: Pathologic Processes - ID: D000008286 - Term: Malabsorption Syndromes - ID: D000007410 - Term: Intestinal Diseases - ID: D000005767 - Term: Gastrointestinal Diseases - ID: D000004066 - Term: Digestive System Diseases - ID: D000011183 - Term: Postoperative Complications ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC06 - Name: Digestive System Diseases - Abbrev: BC18 - Name: Nutritional and Metabolic Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M16355 - Name: Syndrome - Relevance: LOW - As Found: Unknown - ID: M15586 - Name: Short Bowel Syndrome - Relevance: HIGH - As Found: Short Bowel Syndrome - ID: M6019 - Name: Cholestasis - Relevance: LOW - As Found: Unknown - ID: M11278 - Name: Malabsorption Syndromes - Relevance: LOW - As Found: Unknown - ID: M10444 - Name: Intestinal Diseases - Relevance: LOW - As Found: Unknown - ID: M7255 - Name: Digestive System Diseases - Relevance: LOW - As Found: Unknown - ID: M8883 - Name: Gastrointestinal Diseases - Relevance: LOW - As Found: Unknown - ID: M14065 - Name: Postoperative Complications - Relevance: LOW - As Found: Unknown - ID: T5206 - Name: Short Bowel Syndrome - Relevance: HIGH - As Found: Short Bowel Syndrome ### Condition Browse Module - Meshes - ID: D000012778 - Term: Short Bowel Syndrome ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05032079 **Brief Title:** Subzero and Scorpion Trial **Official Title:** Pilot Study for the Cryoablation of Ductal Carcinoma In Situ: Subzero and Scorpion Trial #### Organization Study ID Info **ID:** LCH-112020 #### Organization **Class:** OTHER **Full Name:** Larkin Community Hospital ### Status Module #### Completion Date **Date:** 2023-09-01 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2023-10-16 **Type:** ACTUAL **Last Update Submit Date:** 2023-10-12 **Overall Status:** WITHDRAWN #### Primary Completion Date **Date:** 2023-09-01 **Type:** ACTUAL #### Start Date **Date:** 2020-11-16 **Type:** ACTUAL **Status Verified Date:** 2023-10 #### Study First Post Date **Date:** 2021-09-02 **Type:** ACTUAL **Study First Submit Date:** 2021-08-27 **Study First Submit QC Date:** 2021-08-27 **Why Stopped:** Study Period Ended / Not Completed ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Larkin Community Hospital #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** This is a prospective single-institution pilot study examining the feasibility of performing ultrasound-guided cryoablation to completely ablate breast ductal carcinoma in situ (DCIS). The study is designed such that patients meeting selection criteria will undergo cryoablation followed by surgical resection. The pathology of the surgical specimen will be used to determine the rate of complete tumor ablation. Standard adjuvant therapies otherwise remained unchanged. ### Conditions Module **Conditions:** - Ductal Carcinoma in Situ ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Intervention Names:** - Procedure: cryoablation **Label:** Treatment Arm **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Treatment Arm **Description:** single probe ultrasound guided cryoablation **Name:** cryoablation **Other Names:** - cryosurgery **Type:** PROCEDURE ### Outcomes Module #### Primary Outcomes **Description:** rate of complete tumor ablation defined as no remaining invasive or in situ carcinoma present upon pathological examination of excised tissue **Measure:** complete tumor ablation **Time Frame:** 2 years ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Age \>= 18 2. Pre-registration core biopsy: Unifocal primary ductal carcinoma in situ (DCIS) or atypical ductal hyperplasia (ADH) bordering on DCIS or DCIS with microinvasion diagnosed by core needle biopsy. NOTE: Patients with lobular carcinoma, multifocal and/or multicentric ipsilateral breast cancer are NOT eligible. Patients with contralateral disease will remain eligible. 3. Tumor size \< 1.5 cm in greatest diameter. Specifically, the tumor must measure \< 1.5 cm in the axis parallel to the treatment probe and \< 1.5 cm in the axis anti-parallel to the treatment probe. Largest size measured by required pre-treatment scans (mammogram, ultrasound and MRI) will be used to determine eligibility. 4. An ultrasound visible target for cryoablation: Ultrasound-visible mass or nonmass finding corresponding to the tumor or An ultrasound-visible biopsy marker placed within 1cm of the biopsied tumor. 5. No prior or planned neoadjuvant chemotherapy for breast cancer. 6. Adequate breast size for safe cryoablation. This will be determined by the interventional radiologist using a combination of clinical exam and imaging. Site of target for cryoablation must be greater than 1 cm from the nipple and greater than 1cm from the closest skin surface. Exclusion Criteria: 1. Multifocal of multicentric carcinoma. 2. Pre-registration core biopsy with diagnosis of frank invasive carcinoma (not microinvasion) or lobular carcinoma. 3. Prior or planned neoadjuvant chemotherapy for breast cancer. 4. Retroglandular breast implants. (Please note that patients with retropectoral implants are allowed to enroll if they meet all other inclusion criteria.) **Gender Based:** True **Maximum Age:** 95 Years **Minimum Age:** 18 Years **Sex:** FEMALE **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Miami **Country:** United States **Facility:** Breast Care Center Miami **State:** Florida **Zip:** 33173 **Location 2:** **City:** Miami **Country:** United States **Facility:** Diagnostic Center for Women **State:** Florida **Zip:** 33173 #### Overall Officials **Official 1:** **Affiliation:** Diagnostic Center for Women **Name:** Michael J Plaza, MD **Role:** PRINCIPAL_INVESTIGATOR **Official 2:** **Affiliation:** Breast Care Center Miami **Name:** Ahkeel Allen, MD **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009375 - Term: Neoplasms, Glandular and Epithelial - ID: D000009370 - Term: Neoplasms by Histologic Type - ID: D000009369 - Term: Neoplasms - ID: D000000230 - Term: Adenocarcinoma - ID: D000018299 - Term: Neoplasms, Ductal, Lobular, and Medullary - ID: D000071960 - Term: Breast Carcinoma In Situ ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: All - Name: All Conditions - Abbrev: BC17 - Name: Skin and Connective Tissue Diseases ### Condition Browse Module - Browse Leaves - ID: M5534 - Name: Carcinoma - Relevance: HIGH - As Found: Carcinoma - ID: M25356 - Name: Carcinoma, Ductal - Relevance: HIGH - As Found: Ductal Carcinoma - ID: M5535 - Name: Carcinoma in Situ - Relevance: HIGH - As Found: Carcinoma in Situ - ID: M5542 - Name: Carcinoma, Intraductal, Noninfiltrating - Relevance: HIGH - As Found: Ductal Carcinoma in Situ - ID: M12320 - Name: Neoplasms, Glandular and Epithelial - Relevance: LOW - As Found: Unknown - ID: M12315 - Name: Neoplasms by Histologic Type - Relevance: LOW - As Found: Unknown - ID: M3585 - Name: Adenocarcinoma - Relevance: LOW - As Found: Unknown - ID: M5220 - Name: Breast Neoplasms - Relevance: LOW - As Found: Unknown - ID: M895 - Name: Breast Carcinoma In Situ - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000002277 - Term: Carcinoma - ID: D000002278 - Term: Carcinoma in Situ - ID: D000044584 - Term: Carcinoma, Ductal - ID: D000002285 - Term: Carcinoma, Intraductal, Noninfiltrating ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05957679 **Brief Title:** MRE Evaluation for Spinal Cord Tumor Surgery: Stiffness and Adhesion Assessment **Official Title:** Preoperative Evaluation of Tumor Stiffness and Adhesion in Spinal Cord Tumor Using Magnetic Resonance Elastography #### Organization Study ID Info **ID:** ShengjingH_brain2023 #### Organization **Class:** OTHER **Full Name:** Shengjing Hospital ### Status Module #### Completion Date **Date:** 2025-07-01 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2023-07-27 **Type:** ACTUAL **Last Update Submit Date:** 2023-07-25 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2024-07-01 **Type:** ESTIMATED #### Start Date **Date:** 2023-01-01 **Type:** ACTUAL **Status Verified Date:** 2023-07 #### Study First Post Date **Date:** 2023-07-24 **Type:** ACTUAL **Study First Submit Date:** 2023-07-15 **Study First Submit QC Date:** 2023-07-15 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Shengjing Hospital #### Responsible Party **Investigator Affiliation:** Shengjing Hospital **Investigator Full Name:** Yu Shi **Investigator Title:** Deputy director of department of radology **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** In spinal cord tumors requiring surgical intervention, the resection difficulty is determined by two significant factors: tumor stiffness and adhesion to surrounding tissue. The stiffness of the tumor dictates the complexity of removal, while strong adhesion presents additional challenges during the surgical procedure. This clinical trial aims to assess the clinical utility of magnetic resonance elastography (MRE), in evaluating the stiffness and adhesion of spinal cord tumors and guiding surgical planning to selecting the most appropriate surgical approach for patients with spinal cord tumors. **Detailed Description:** Spinal cord tumors are a common condition in neurosurgery, including neurofibroma, spinal meningioma, ependymoma, glioma, spinal lipoma, and so on. Magnetic resonance imaging (MRI) plays a crucial role in the preoperative evaluation and planning of spinal cord tumor surgery. It provides detailed information about the tumor's location, size, and relationship to adjacent structures. However, routine MRI may not always provide sufficient information about the tumor's stiffness or adhesion, which can impact surgical planning and postoperative outcomes. Magnetic resonance elastography and slip interface imaging can help measure the mechanical properties of tissues, including their stiffness or adhesion. By combining the above methods, surgeons can identify areas of potential tumor adherence or invasion into surrounding structures, allowing for more precise surgical resection and minimizing the risk of damage to critical neural tissue. ### Conditions Module **Conditions:** - Spinal Cord Tumors **Keywords:** - MRE - Slip Interface Imaging - Glioma - Magnetic Resonance Elastography - Spinal meningioma - Neurofibroma - Ependymoma - Astrocytoma - Glioblastoma - Spinal lipoma ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** DIAGNOSTIC #### Enrollment Info **Count:** 20 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Patients undergo a preoperative routine MRI scan and MRE the day before their scheduled surgery. During surgery, the tumor stiffness and adhesion are assessed and recorded by the surgeon according to established evaluation criteria. It is important to note that the surgeon does not have prior knowledge of the tumor's specific stiffness and adhesion before the surgery. This information is typically obtained through intraoperative assessment and observation. **Intervention Names:** - Diagnostic Test: Magnetic Resonance Elastography - Procedure: Assessment and Recording **Label:** Diagnostic（MRE, tumor grading of stiffness and adhesion） **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Diagnostic（MRE, tumor grading of stiffness and adhesion） **Description:** Undergo MRE and routine MRI **Name:** Magnetic Resonance Elastography **Other Names:** - MRE **Type:** DIAGNOSTIC_TEST #### Intervention 2 **Arm Group Labels:** - Diagnostic（MRE, tumor grading of stiffness and adhesion） **Description:** Undergo grading and recording of tumor stiffness and adhesion during surgery **Name:** Assessment and Recording **Type:** PROCEDURE ### Outcomes Module #### Primary Outcomes **Description:** The surgeon will score the tumor stiffness in seven aspects, ranging from 1 to 5 points: Tumor size; Shape of tumor; Tumor texture; Stiffness of the tumor's capsule; Stiffness of the tumor's central region; Primary methods of tumor removal; Features of tumor's capsule. **Measure:** Surgical assessment of tumor stiffness **Time Frame:** Baseline to 6 weeks **Description:** The surgeon will score the tumor's adhesion based on seven aspects, ranging from 1 to 4 points: Stripping instruments; Frequency of use of sharp instruments; Adhesion range; Degree of tumor resection; Cranial nerve anatomy preservation; Brain tissue anatomy preservation; Neurological function (compared with preoperative). **Measure:** Surgical assessment of tumor adhesion **Time Frame:** Baseline to 6 weeks ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * All patients undergoing spinal cord tumor resection surgery are eligible for inclusion in the study cohort. Exclusion Criteria: * Patients with metallic implants or foreign bodies in their bodies (pacemakers, artificial metallic heart valves, metal joints, metal implants, and those who cannot remove dentures, insulin pumps, or contraceptive rings) * Pregnant women in the first trimester (within three months) * Patients with severe claustrophobia or anxiety * Patients with severe fever * Patients who can not tolerate MRE * Patients with vascular malformations and aneurysms. * Patients who do not sign an informed consent **Healthy Volunteers:** True **Maximum Age:** 80 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Yu Shi, MD **Phone:** +86 189 4025 9980 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Wen Cheng, MD **Phone:** +86 150 4023 5535 **Role:** CONTACT #### Locations **Location 1:** **City:** Shenyang **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Yu Shi, MD - **Phone:** +8618940259980 - **Role:** CONTACT ***Contact 2:*** - **Email:** [email protected] - **Name:** Anhua Wu, MD - **Phone:** +8618900925766 - **Role:** CONTACT ***Contact 3:*** - **Name:** Yu Shi, MD - **Role:** PRINCIPAL_INVESTIGATOR ***Contact 4:*** - **Name:** Anhua Wu, MD - **Role:** PRINCIPAL_INVESTIGATOR ***Contact 5:*** - **Name:** Wen Cheng, MD - **Role:** PRINCIPAL_INVESTIGATOR **Country:** China **Facility:** Shengjing Hospital **State:** Liaoning **Status:** RECRUITING **Zip:** 110000 #### Overall Officials **Official 1:** **Affiliation:** Shengjing Hospital **Name:** Yu Shi, MD **Role:** PRINCIPAL_INVESTIGATOR **Official 2:** **Affiliation:** Shengjing Hospital **Name:** Anhua Wu, MD **Role:** PRINCIPAL_INVESTIGATOR **Official 3:** **Affiliation:** Shengjing Hospital **Name:** Wen Cheng, MD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Murphy MC, Huston J 3rd, Glaser KJ, Manduca A, Meyer FB, Lanzino G, Morris JM, Felmlee JP, Ehman RL. Preoperative assessment of meningioma stiffness using magnetic resonance elastography. J Neurosurg. 2013 Mar;118(3):643-8. doi: 10.3171/2012.9.JNS12519. Epub 2012 Oct 19. **PMID:** 23082888 **Citation:** Hughes JD, Fattahi N, Van Gompel J, Arani A, Meyer F, Lanzino G, Link MJ, Ehman R, Huston J. Higher-Resolution Magnetic Resonance Elastography in Meningiomas to Determine Intratumoral Consistency. Neurosurgery. 2015 Oct;77(4):653-8; discussion 658-9. doi: 10.1227/NEU.0000000000000892. **PMID:** 26197204 **Citation:** Yin Z, Lu X, Cohen Cohen S, Sui Y, Manduca A, Van Gompel JJ, Ehman RL, Huston J 3rd. A new method for quantification and 3D visualization of brain tumor adhesion using slip interface imaging in patients with meningiomas. Eur Radiol. 2021 Aug;31(8):5554-5564. doi: 10.1007/s00330-021-07918-6. Epub 2021 Apr 14. **PMID:** 33852045 **Citation:** Yin Z, Hughes JD, Trzasko JD, Glaser KJ, Manduca A, Van Gompel J, Link MJ, Romano A, Ehman RL, Huston J 3rd. Slip interface imaging based on MR-elastography preoperatively predicts meningioma-brain adhesion. J Magn Reson Imaging. 2017 Oct;46(4):1007-1016. doi: 10.1002/jmri.25623. Epub 2017 Feb 14. Erratum In: J Magn Reson Imaging. 2017 Dec;46(6):1851. **PMID:** 28194925 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000016543 - Term: Central Nervous System Neoplasms - ID: D000009423 - Term: Nervous System Neoplasms - ID: D000009371 - Term: Neoplasms by Site - ID: D000009369 - Term: Neoplasms - ID: D000013118 - Term: Spinal Cord Diseases - ID: D000002493 - Term: Central Nervous System Diseases - ID: D000009422 - Term: Nervous System Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: BC16 - Name: Diseases and Abnormalities at or Before Birth - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M9020 - Name: Glioma - Relevance: LOW - As Found: Unknown - ID: M3620 - Name: Tissue Adhesions - Relevance: LOW - As Found: Unknown - ID: M9019 - Name: Glioblastoma - Relevance: LOW - As Found: Unknown - ID: M11562 - Name: Meningioma - Relevance: LOW - As Found: Unknown - ID: M19549 - Name: Neurofibromatoses - Relevance: LOW - As Found: Unknown - ID: M12398 - Name: Neurofibroma - Relevance: LOW - As Found: Unknown - ID: M15917 - Name: Spinal Cord Neoplasms - Relevance: HIGH - As Found: Spinal Cord Tumor - ID: M4561 - Name: Astrocytoma - Relevance: LOW - As Found: Unknown - ID: M7965 - Name: Ependymoma - Relevance: LOW - As Found: Unknown - ID: M11067 - Name: Lipoma - Relevance: LOW - As Found: Unknown - ID: M18937 - Name: Central Nervous System Neoplasms - Relevance: LOW - As Found: Unknown - ID: M12367 - Name: Nervous System Neoplasms - Relevance: LOW - As Found: Unknown - ID: M15915 - Name: Spinal Cord Diseases - Relevance: LOW - As Found: Unknown - ID: M5742 - Name: Central Nervous System Diseases - Relevance: LOW - As Found: Unknown - ID: T2519 - Name: Glioma - Relevance: LOW - As Found: Unknown - ID: T2518 - Name: Glioblastoma - Relevance: LOW - As Found: Unknown - ID: T3707 - Name: Meningioma - Relevance: LOW - As Found: Unknown - ID: T4096 - Name: Neurofibromatosis - Relevance: LOW - As Found: Unknown - ID: T4095 - Name: Neurofibroma - Relevance: LOW - As Found: Unknown - ID: T2093 - Name: Ependymoma - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000013120 - Term: Spinal Cord Neoplasms ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT01811979 **Brief Title:** Efficacy of Oral Sucrose and Topical Anesthetics to Reduce Pain During Eye Examination for Retinopathy of Prematurity **Official Title:** Efficacy of Oral Sucrose and Topical Anesthetics to Reduce Pain During Eye Examination #### Organization Study ID Info **ID:** 69/04.01.2012 #### Organization **Class:** OTHER **Full Name:** Dr. Sami Ulus Children's Hospital ### Status Module #### Completion Date **Date:** 2013-05 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2013-05-09 **Type:** ESTIMATED **Last Update Submit Date:** 2013-05-07 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2013-04 **Type:** ACTUAL #### Start Date **Date:** 2012-04 **Status Verified Date:** 2013-05 #### Study First Post Date **Date:** 2013-03-15 **Type:** ESTIMATED **Study First Submit Date:** 2013-03-13 **Study First Submit QC Date:** 2013-03-13 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Dr. Sami Ulus Children's Hospital #### Responsible Party **Investigator Affiliation:** Dr. Sami Ulus Children's Hospital **Investigator Full Name:** Dilek Dilli **Investigator Title:** Assoc Prof **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** Oral sucrose reduces pain during heel sticks and venipunctures in preterm infants. The purpose of this study was to determine the effectiveness of local anesthetic eye drops and a pacifier, plus repeated doses of 24% sucrose, to relieve pain associated with eye examinations for retinopathy of prematurity. **Detailed Description:** Oral sucrose reduces pain during heel sticks and venipunctures in preterm infants. Administration of oral sucrose with and without non-nutritive sucking is the most frequently studied non-pharmacological intervention for procedural pain relief in neonates.The purpose of this study was to determine the effectiveness of local anesthetic eye drops and a pacifier, plus repeated doses of 24% sucrose, to relieve pain associated with eye examinations for retinopathy of prematurity. ### Conditions Module **Conditions:** - Investigate the Efficacy of Sucrose During Eye Examination **Keywords:** - eye examination, oral sucrose, premature infant pain scale ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** QUADRUPLE **Who Masked:** - PARTICIPANT - CARE_PROVIDER - INVESTIGATOR - OUTCOMES_ASSESSOR **Primary Purpose:** SUPPORTIVE_CARE #### Enrollment Info **Count:** 60 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** local anesthetic eye drops (Alcaine 0.5% drop) and a pacifier, plus 0.5 cc/kg of 24% sucrose, to relieve pain associated with eye examinations for retinopathy of prematurity will be given **Intervention Names:** - Dietary Supplement: Steril water **Label:** oral sucrose solution **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** steril water 0,5 cc/kg plus topical anesthetics (Alcaine %0.5 damla) before eye examination will be given **Intervention Names:** - Dietary Supplement: Oral sucrose solution **Label:** steril water **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - steril water **Description:** Oral sucrose solution plus topical anesthetics **Name:** Oral sucrose solution **Type:** DIETARY_SUPPLEMENT #### Intervention 2 **Arm Group Labels:** - oral sucrose solution **Description:** steril water plus topical anesthetics **Name:** Steril water **Type:** DIETARY_SUPPLEMENT ### Outcomes Module #### Primary Outcomes **Description:** Premature Infant Pain Profile were determined after each eye examination **Measure:** Premature Infant Pain Profile **Time Frame:** two hours #### Secondary Outcomes **Description:** Crying time will be determined after each eye examination **Measure:** Crying time **Time Frame:** two hours ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: -VLBW infants \<32 weeks of gestational age Exclusion Criteria: * infants \>32 weeks of gestational age * neuromuscular abnormality * major abnormality **Maximum Age:** 3 Months **Minimum Age:** 1 Day **Sex:** ALL **Standard Ages:** - CHILD ### Contacts Locations Module #### Locations **Location 1:** **City:** Ankara **Country:** Turkey **Facility:** Dr Sami Ulus Children Hospital #### Overall Officials **Official 1:** **Affiliation:** MD **Name:** Eda Ç İlarslan, MD **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### References **Citation:** Stevens B, Yamada J, Lee GY, Ohlsson A. Sucrose for analgesia in newborn infants undergoing painful procedures. Cochrane Database Syst Rev. 2013 Jan 31;(1):CD001069. doi: 10.1002/14651858.CD001069.pub4. **PMID:** 23440783 **Citation:** Dilli D, Ilarslan NE, Kabatas EU, Zenciroglu A, Simsek Y, Okumus N. Oral sucrose and non-nutritive sucking goes some way to reducing pain during retinopathy of prematurity eye examinations. Acta Paediatr. 2014 Feb;103(2):e76-9. doi: 10.1111/apa.12454. Epub 2013 Nov 11. **PMID:** 24730361 #### See Also Links **Label:** http://www.ncbi.nlm.nih.gov/pubmed/23440783 **URL:** http://www.ncbi.nlm.nih.gov/pubmed/23440783 ## Derived Section ### Condition Browse Module - Browse Branches - Abbrev: BXS - Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: BC11 - Name: Eye Diseases - Abbrev: BC16 - Name: Diseases and Abnormalities at or Before Birth - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M25869 - Name: Premature Birth - Relevance: LOW - As Found: Unknown - ID: M13066 - Name: Pain - Relevance: LOW - As Found: Unknown - ID: M14999 - Name: Retinal Diseases - Relevance: LOW - As Found: Unknown - ID: M15013 - Name: Retinopathy of Prematurity - Relevance: LOW - As Found: Unknown - ID: T4981 - Name: Retinopathy of Prematurity - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Browse Branches - Abbrev: CNSDep - Name: Central Nervous System Depressants - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: PhSol - Name: Pharmaceutical Solutions - Abbrev: Antipy - Name: Antipyretics - Abbrev: Analg - Name: Analgesics ### Intervention Browse Module - Browse Leaves - ID: M4107 - Name: Anesthetics - Relevance: LOW - As Found: Unknown - ID: M21860 - Name: Pharmaceutical Solutions - Relevance: LOW - As Found: Unknown - ID: M12814 - Name: Ophthalmic Solutions - Relevance: LOW - As Found: Unknown - ID: M4109 - Name: Anesthetics, Local - Relevance: LOW - As Found: Unknown - ID: M2340 - Name: Acetaminophen - Relevance: LOW - As Found: Unknown - ID: M250773 - Name: Proxymetacaine - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04240379 **Acronym:** METACOGSEP **Brief Title:** Metacognition Assessment in Patient With Multiple Sclerosis **Official Title:** Metacognition Assessment in Patient With Multiple Sclerosis #### Organization Study ID Info **ID:** 38RC19.146 #### Organization **Class:** OTHER **Full Name:** University Hospital, Grenoble #### Secondary ID Infos **Domain:** ID RCB **ID:** 2019-A01278-49 **Type:** OTHER ### Status Module #### Completion Date **Date:** 2022-04-08 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2022-06-01 **Type:** ACTUAL **Last Update Submit Date:** 2022-05-31 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2022-04-08 **Type:** ACTUAL #### Start Date **Date:** 2020-06-11 **Type:** ACTUAL **Status Verified Date:** 2022-05 #### Study First Post Date **Date:** 2020-01-27 **Type:** ACTUAL **Study First Submit Date:** 2020-01-06 **Study First Submit QC Date:** 2020-01-23 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** University Grenoble Alps #### Lead Sponsor **Class:** OTHER **Name:** University Hospital, Grenoble #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** This study will assessed the level of consciousness of MS patients suffering of cognitive and motor disorders. Understanding the awareness of the disease is crucial to allow better management of these patients. It has been shown, for other neurological pathologies, that a lack of awareness of deficits leads to inefficient rehabilitation and a disorder of understanding the impact of deficits in daily activities. Metacognition could be altered with age, so we will include participants between 18 and 60 years old. **Detailed Description:** Subject who have to do neurological assessement by the Multiple sclerosis Functional Composite (MSFC) will be enrolled. The patient will estimate the time to undergo the test. This time will be compared to the time really make by the patient to realise test. ### Conditions Module **Conditions:** - Multiple Sclerosis **Keywords:** - Multiple Sclerosis - Multiple Sclerosis Functional Composite (MSFC) - Metacognition ### Design Module #### Design Info **Observational Model:** OTHER **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 80 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Outcomes Module #### Primary Outcomes **Description:** Metacognitive precision based on Multiple Sclerosis Functional Composite (MSFC) score **Measure:** Metacognitive precision **Time Frame:** Day 1 ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Diagnosis of multiple sclerosis * Voluntary for participate to study Exclusion Criteria: * Neurological disease other than Multiple Sclerosis * psychiatric disease, other than depressiveness * illicit substance abuse * Persons referred to in Articles L1121-5 to 8 of the French Public Health Code **Maximum Age:** 60 Years **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT **Study Population:** This study will be proposed to subject : * Male or female with diagnosis of MS, * admitted in neurological unit for passing the MSFC (Multiple Sclerosis Functionnal Composite) test * who respect selection criteria. ### Contacts Locations Module #### Locations **Location 1:** **City:** Grenoble **Country:** France **Facility:** Chu Grenoble Alpes **Zip:** 38043 ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Calabrese P. Neuropsychology of multiple sclerosis--an overview. J Neurol. 2006 Feb;253 Suppl 1:I10-5. doi: 10.1007/s00415-006-1103-1. **PMID:** 16477479 **Citation:** Chiaravalloti ND, DeLuca J. Cognitive impairment in multiple sclerosis. Lancet Neurol. 2008 Dec;7(12):1139-51. doi: 10.1016/S1474-4422(08)70259-X. **PMID:** 19007738 **Citation:** Beatty WW, Monson N. Metamemory in multiple sclerosis. J Clin Exp Neuropsychol. 1991 Mar;13(2):309-27. doi: 10.1080/01688639108401046. **PMID:** 1688342 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000010335 - Term: Pathologic Processes - ID: D000020278 - Term: Demyelinating Autoimmune Diseases, CNS - ID: D000020274 - Term: Autoimmune Diseases of the Nervous System - ID: D000009422 - Term: Nervous System Diseases - ID: D000003711 - Term: Demyelinating Diseases - ID: D000001327 - Term: Autoimmune Diseases - ID: D000007154 - Term: Immune System Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: BC20 - Name: Immune System Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology ### Condition Browse Module - Browse Leaves - ID: M12060 - Name: Multiple Sclerosis - Relevance: HIGH - As Found: Multiple Sclerosis - ID: M15415 - Name: Sclerosis - Relevance: HIGH - As Found: Sclerosis - ID: M4629 - Name: Autoimmune Diseases - Relevance: LOW - As Found: Unknown - ID: M22098 - Name: Demyelinating Autoimmune Diseases, CNS - Relevance: LOW - As Found: Unknown - ID: M22094 - Name: Autoimmune Diseases of the Nervous System - Relevance: LOW - As Found: Unknown - ID: M6909 - Name: Demyelinating Diseases - Relevance: LOW - As Found: Unknown - ID: M10200 - Name: Immune System Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000009103 - Term: Multiple Sclerosis - ID: D000012598 - Term: Sclerosis ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT06009679 **Brief Title:** MISOPROSTOL FOR THE TREATMENT OF SUSPECTED POSTPARTUM RETAINED PRODUCTS OF CONCEPTION **Official Title:** MISOPROSTOL FOR THE TREATMENT OF SUSPECTED POSTPARTUM RETAINED PRODUCTS OF CONCEPTION - A RANDOMIZED TRIAL #### Organization Study ID Info **ID:** 000621AAA #### Organization **Class:** OTHER **Full Name:** Assuta Ashdod Hospital ### Status Module #### Completion Date **Date:** 2025-06-30 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2023-08-24 **Type:** ACTUAL **Last Update Submit Date:** 2023-08-20 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2024-12-31 **Type:** ESTIMATED #### Start Date **Date:** 2021-02-02 **Type:** ACTUAL **Status Verified Date:** 2023-08 #### Study First Post Date **Date:** 2023-08-24 **Type:** ACTUAL **Study First Submit Date:** 2023-08-20 **Study First Submit QC Date:** 2023-08-20 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Assuta Ashdod Hospital #### Responsible Party **Investigator Affiliation:** Assuta Ashdod Hospital **Investigator Full Name:** Oshri Barell **Investigator Title:** DR OSHRI BAREL **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** The goal of this current study is to evaluate the efficacy of treatment of postpartum patients with suspected retained products of conception (RPOC) with Misoprostol in reducing the frequency of postpartum RPOC compared to a control group of patients that will be managed expectantly, in a prospective randomized trial. **Detailed Description:** Misoprostol (Cytotec) is used widely in Obstetrics and Gynecology, whether for labor induction (1), prevention (2), and treatment (3) of early postpartum hemorrhage (ePPH), induced and missed abortions (4) and for cases suspected for having retained products of conception postabortion and postpartum (RPOC, residua). While it has been shown in previous studies that misoprostol is efficacious for most of the above-mentioned indications, it is less well-established that the treatment for suspected postpartum RPOC alters the natural course of events and reduces the number of patients requiring surgical intervention and actually having RPOC. RPOC is estimated to complicate about 1% of term pregnancies and is more prevalent than after miscarriages and termination of pregnancy (5). The diagnosis and treatment of RPOC might be challenging, as there are no clearly determined diagnostic criteria, evidence-based guidelines or treatment protocols (6). Different protocols for the follow-up and treatment of cases suspected of RPOC are in use worldwide, including expectant management, administrating uterotonics, performing suction curettage (6), and performing hysteroscopy (7, 8). Evidence in the literature supports the treatment of RPOC with operative hysteroscopy since curettage seems to increase the risk for intrauterine adhesions and Asherman syndrome (9, 10) with the possibility for menstrual abnormalities, infertility or subfertility, recurrent pregnancy losses, preterm labor, and preterm premature rupture of membranes (11). Chambers et al published in 2009 a 6-year trial (12), which shows that treatment with 200 mcg SL / PO misoprostol 3 times daily for 2 days may effectively treat RPOC and reduce repeat curettage rate by 79.6%. There was also the complete resolution of symptoms in 93%, and 77% of women reported a high level of satisfaction. The trial was retrospective and RPOC was not confirmed by hysteroscopy or histology. The main tool for diagnosis and follow-up in cases of RPOC is postpartum ultrasound, showing low, medium, and high probability for residua, with the clinical symptoms of abnormal bleeding pattern, abdominal tenderness, and persistently dilated cervix. We've decided to set the categories according to the study by Smorgick (13), although we chose to name them and treat them differently. The categories are: 1. Low probability for residua - ultrasound shows thin regular endometrial line 10 mm and below, with no intrauterine mass or Doppler vascular flow. In effect a normal ultrasound scan. 2. Medium probability for residua - ultrasound shows a cavity over 10 mm, intrauterine hypo / hyperechogenic mass, or irregular endometrial line without Doppler flow. With this group, PROC cannot be excluded. 3. High probability for residua - with the addition of Doppler vascular flow to the cavity. The natural course of the ultrasonic appearance of the uterine cavity postpartum (14) was shown to take roughly 56 days for the cavity to appear empty in 95% percent of cases not suspected of having RPOC. This study aims to test prospectively expectant management compared to misoprostol administration for a certain duration of time of cases with risk factors for RPOC, including cases undergoing revision of the uterine cavity or manual lysis of placenta postpartum, early postpartum hemorrhage, cases with a history of treated postpartum residua, having placental pathology (succenturiate, bilobed placenta), a pregnancy that started as multifetal with only one fetus reached advanced pregnancy, and patients undergoing Bumm curettage post-delivery. 2. Aims Since the literature data on this subject is scarce and the treatment is challenging, the primary aim of this study is to assess prospectively and randomly expectant management vs. misoprostol administration (PV, PO, SL) on the treatment for suspected RPOC postpartum in women with risk factors for residua along an 8-week duration as characterized by ultrasound follow-up every 2-3 weeks and divided to a 3 tier system of the low, medium and high probability of residua and the cases requiring hysteroscopy for suspected residua. Secondary aims include side effects of treatment, late postpartum hemorrhage, blood transfusion, and endomyometritis / PID and complications. 3. Hypothesis In this study, we hypothesize that the treatment with misoprostol, compared to expectant management, will be able to reduce the number of cases at medium and high probability of residua as described by ultrasound and by that reduce the number of cases requiring hysteroscopy and treatment of residua. ### Conditions Module **Conditions:** - Retained Products of Conception ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** Two arms: the intervention groups will include patients with suspected postpartum RPOC that will receive treatment with Misoprostol, and the control group will undergo conservative follow-up with ultrasound. The primary endpoint will be the number of patients with histopathology-proven retained products of conception at 8-16 weeks postpartum in each group. secondary endpoints will be the number of hysteroscopies in each group, side effects of treatment, late postpartum hemorrhage, blood transfusion, endomyometritis / PID and re-admissions to the hospital in each group. ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 150 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** The intervention group will include patients with suspected postpartum RPOC that will receive treatment with Misoprostol, 600 microgram SL/PO/PV **Intervention Names:** - Drug: Misoprostol 200mcg Tab **Label:** Intervention group **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** The control group will include women with suspected postpartum RPOC per ultrasound examination that will undergo conservative follow-up with ultrasound for a period of 6-12 weeks postpartum **Label:** Control group **Type:** NO_INTERVENTION ### Interventions #### Intervention 1 **Arm Group Labels:** - Intervention group **Description:** Patients in the intervention group with suspected postpartum RPOC will receive 600 micrograms of misoprostol up to 3 times following delivery and followed up by ultrasound and clinical examinations for 6-12 weeks post-partum **Name:** Misoprostol 200mcg Tab **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** The primary endpoint will be the number of patients with histopathology-proven retained products of conception at 8-16 weeks postpartum in each group. **Measure:** Cases of retained products of conception **Time Frame:** 8-16 weeks postpartum #### Secondary Outcomes **Description:** number of hysteroscopies in each group **Measure:** Need for hysteroscopy due to suspected RPOC **Time Frame:** 8-16 weeks postpartum **Description:** any side effects of treatments with Misoprostol **Measure:** side effects of treatment **Time Frame:** 8-16 weeks postpartum **Description:** Late postpartum hemorrhage during the followup **Measure:** Late postpartum hemorrhage **Time Frame:** 6 weeks postpartum **Description:** The need of blood transfusion during the followup **Measure:** Blood transfusions **Time Frame:** 6-18 weeks postpartum **Description:** any events of endomyometritis / PID postpartum **Measure:** endomyometritis / PID **Time Frame:** 6-18 weeks postpartum **Description:** cases that required re-admission to the hospital after discharge from tyhe postpartum ward. **Measure:** Re-admissions to the hospital **Time Frame:** up to 18 weeks ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Women between the ages of 18 years - 45 years. * Spontaneous vaginal delivery or vacuum extraction, including VBAC cases * Revision of the uterine cavity or manual lysis of the placenta postpartum * Early postpartum hemorrhage * Cases with a history of treated postpartum residua (by curettage or hysteroscopy) * Placental pathology (succenturiate placenta, bilobed placenta) * Pregnancy that started as a multifetal gestation with only one fetus reached advanced pregnancy * Bumm curettage post-delivery * Patients are able to provide written consent Exclusion Criteria: * Patients with no risk factors of RPOC * Cesarean section on index pregnancy * Cases requiring urgent curettage for late postpartum hemorrhage * Inability to consent due to cognitive or language barrier **Healthy Volunteers:** True **Maximum Age:** 45 Years **Minimum Age:** 18 Years **Sex:** FEMALE **Standard Ages:** - ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** oshri Barel, MD **Phone:** +972559382117 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Irad Burshtein, MD **Phone:** +972537345127 **Role:** CONTACT #### Locations **Location 1:** **City:** Ashdod **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Oshri Barel, MD - **Phone:** +972559382117 - **Role:** CONTACT ***Contact 2:*** - **Name:** Oshri Barel, MD - **Role:** PRINCIPAL_INVESTIGATOR **Country:** Israel **Facility:** Assuta Ashdod University Hospital **Status:** RECRUITING ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Intervention Browse Module - Ancestors - ID: D000000020 - Term: Abortifacient Agents, Nonsteroidal - ID: D000000019 - Term: Abortifacient Agents - ID: D000012102 - Term: Reproductive Control Agents - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000000897 - Term: Anti-Ulcer Agents - ID: D000005765 - Term: Gastrointestinal Agents - ID: D000010120 - Term: Oxytocics ### Intervention Browse Module - Browse Branches - Abbrev: Gast - Name: Gastrointestinal Agents - Abbrev: Repr - Name: Reproductive Control Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M18979 - Name: Misoprostol - Relevance: HIGH - As Found: Liquid - ID: M4188 - Name: Antacids - Relevance: LOW - As Found: Unknown - ID: M4219 - Name: Anti-Ulcer Agents - Relevance: LOW - As Found: Unknown - ID: M8881 - Name: Gastrointestinal Agents - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000016595 - Term: Misoprostol ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03245879 **Acronym:** SCORE **Brief Title:** Antibiotic Stewardship in Small Hospitals **Official Title:** Impact of Implementing Antibiotic Stewardship Programs in 15 Small Hospitals: A Cluster-Randomized Trial Intervention #### Organization Study ID Info **ID:** 1024823 #### Organization **Class:** OTHER **Full Name:** Intermountain Health Care, Inc. ### Status Module #### Completion Date **Date:** 2015-06 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2017-08-10 **Type:** ACTUAL **Last Update Submit Date:** 2017-08-07 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2015-06 **Type:** ACTUAL #### Start Date **Date:** 2013-07 **Type:** ACTUAL **Status Verified Date:** 2017-08 #### Study First Post Date **Date:** 2017-08-10 **Type:** ACTUAL **Study First Submit Date:** 2017-08-03 **Study First Submit QC Date:** 2017-08-07 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Intermountain Health Care, Inc. #### Responsible Party **Investigator Affiliation:** Intermountain Health Care, Inc. **Investigator Full Name:** Eddie Stenehjem **Investigator Title:** Associate Professor of Medicine **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Core elements of effective antibiotic stewardship programs (ASPs) have been identified and evidence-based guidelines have been developed for implementation. The majority of the evidence used for these guidelines are from published studies on the effectiveness of ASPs in large academic or large community hospitals. A significant portion of healthcare in the United States, however, takes place in small hospitals. In 2015, 73% of US hospitals had \< 200 beds (4,057 hospitals) and accounted for 29% of all US inpatient bed days. Limited studies on the effectiveness of antibiotic stewardship implementation have been performed in hospitals with \< 200 beds. Antibiotic use rates and selection patterns in these small hospitals are similar to that of large hospitals and the majority of small hospitals lack formal ASP that meet the CDC's core elements. The objective of this real-world implementation study was to assess the effectiveness of three ASP strategies of escalating intensity designed specifically for small hospitals within a vertically integrated healthcare delivery system. **Detailed Description:** The investigators designed a clustered randomized controlled intervention to evaluate 3 antibiotic stewardship strategies designed for small hospitals. Each hospital was randomized to one of three ASP interventions with increasing levels of intensity and intervention (Programs 1, 2, 3). The investigators felt that clinical equipoise about the effect of ASPs did not exist and randomizing to a no-intervention group was unacceptable. Antibiotic use was compared within each group before and after the intervention. In keeping with other real-world implementation studies, secondary analyses were planned to include an interrupted time series design to evaluate the impact of each strategy. Randomization of hospitals was stratified based on patient volume. Hospital administration and clinical leadership were not blinded to which ASP program they were randomly assigned to, but there were no public announcements. The intervention started March 2014 and ended June 2015. ### Conditions Module **Conditions:** - Inappropriate Prescribing - Antibiotic Stewardship - Anti-Bacterial Agents ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** HEALTH_SERVICES_RESEARCH #### Enrollment Info **Count:** 30000 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Implementation of a basic antibiotic stewardship program focusing on education, access to Infectious Diseases physicians, and availability of antibiotic use data. **Intervention Names:** - Behavioral: Program 1 **Label:** Program 1 **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** This arm increases antibiotic stewardship education and interventions. Program 2 hospitals performed audit and feedback of pre-specified antibiotics and implemented locally controlled restrictions. **Intervention Names:** - Behavioral: Program 2 **Label:** Program 2 **Type:** ACTIVE_COMPARATOR #### Arm Group 3 **Description:** This arm was the most intensive antibiotic stewardship intervention. It included signficant audit and feedback, ID controlled restrictions, and ID review of designated culture/lab results. **Intervention Names:** - Behavioral: Program 3 **Label:** Program 3 **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Program 1 **Description:** Program 1 hospitals received a basic curriculum and tools for implementation of basic antibiotic stewardship interventions. Hospitals required an indication for every antibiotic order. A daily email was sent to a designated email account when a patient had been on an antibiotic for \>48 hours. Curriculum included implementing antibiotic time-outs, IV to PO conversion, indications, evaluating for bug-drug mismatches, and recommendations on when to call the Infectious Diseases (ID) hotline. A daily antibiotic stewardship check list was created. All materials were provided to all pharmacists and remained on-site. Clinicians had access to an ID telephone hotline to answer clinical questions. Pharmacy directors and hospital leadership were provided a monthly, hospital-specific, antibiotic use dashboard. All pharmacy directors and staff received a monthly newsletter. **Name:** Program 1 **Type:** BEHAVIORAL #### Intervention 2 **Arm Group Labels:** - Program 2 **Description:** Program 2 hospitals received all the interventions of Program 1. In addition, Program 2 hospitals received more intense antibiotic stewardship education. Educational topics included audit and feedback, antibiotic de-escalation, the need for antibiotics targeting anaerobic bacteria, antibiotic allergy verification, and antibiotic restrictions. Pharmacists in Program 2 hospitals reviewed patients on vancomycin, piperacillin/tazobactam, imipenem, meropenem, and cefepime. For patients receiving one of these antibiotics, pharmacists reviewed the patients' microbiology data to identify opportunities for antibiotic de-escalation, IV to PO conversion, bug-drug mismatches, and/or indications for calling the ID hotline. Program 2 hospitals also restricted daptomycin, linezolid, imipenem, meropenem, ceftaroline, tigecycline, and all mold active antifungals. In Program 2 hospitals, the local pharmacy staff pre-authorized restricted antibiotics based on defined criteria. **Name:** Program 2 **Type:** BEHAVIORAL #### Intervention 3 **Arm Group Labels:** - Program 3 **Description:** Program 3 hospitals received all the interventions of Program 1 and Program 2. In addition, pharmacists in program 3 hospitals reviewed an expanded list of antibiotics for audit and feedback. These antibiotics included: Vancomycin, piperacillin/tazobactam, imipenem, meropenem, cefepime, ertapenem, aminoglycosides, ceftriaxone, and fluoroquinolones. Program 3 hospitals implemented the same antibiotic restrictions as Program 2 but ID pharmacists controlled pre-authorization of restricted antibiotics. In addition, an ID physician reviewed pre-specified positive cultures (e.g. all positive blood cultures, cultures with highly resistant Enterobacteraciae) and contacted providers with recommendations as needed. ID physician review occurred Monday through Friday and alerts were batched daily at 6am. **Name:** Program 3 **Type:** BEHAVIORAL ### Outcomes Module #### Primary Outcomes **Description:** Evaluated change in total antibiotic use between the baseline and intervention periods while accounting for the cluster randomized design. **Measure:** Total antibiotic use **Time Frame:** Total antibiotic use during the 15 months of Intervention (April 1, 2014 through June 30th 2015) was compared to the antibiotic use during the 12 month baseline period (Jan 1 through Dec 31 2013). #### Secondary Outcomes **Description:** Evaluated change in broad spectrum antibiotic use between the baseline and intervention periods **Measure:** Broad spectrum antibiotic use **Time Frame:** Broad spectrum antibiotic use during the 15 months of Intervention (April 1, 2014 through June 30th 2015) was compared to the broad spectrum antibiotic use during the 12 month baseline period (Jan 1 through Dec 31 2013). **Description:** Evaluated change in restricted antibiotic use between the baseline and intervention periods **Measure:** Restricted antibiotic use **Time Frame:** Restricted antibiotic use during the 15 months of Intervention (April 1, 2014 through June 30th 2015) was compared to the restricted antibiotic use during the 12 month baseline period (Jan 1 through Dec 31 2013). **Description:** Evaluated change in 30 day readmission rates between the baseline and intervention periods **Measure:** 30-day readmission **Time Frame:** 30-day readmission rate during the 15 months of Intervention (April 1, 2014 through June 30th 2015) was compared to the 30-day readmission rate during the 12 month baseline period (Jan 1 through Dec 31 2013). **Description:** Evaluated change in 30 day mortality rates between the baseline and intervention periods **Measure:** 30-day mortality **Time Frame:** 30-day mortality rate during the 15 months of Intervention (April 1, 2014 through June 30th 2015) was compared to the 30-day mortality rate during the 12 month baseline period (Jan 1 through Dec 31 2013). **Description:** Evaluated change in hospital length of stay between the baseline and intervention periods **Measure:** Hospital length of stay **Time Frame:** Average hospital length of stay during the 15 months of Intervention (April 1, 2014 through June 30th 2015) was compared to the average hospital length of stay during the 12 month baseline period (Jan 1 through Dec 31 2013). **Description:** Evaluated change in Clostridium difficile incidence between the baseline and intervention periods **Measure:** Clostridium difficile **Time Frame:** C. difficile rate during the 15 months of Intervention (April 1, 2014 through June 30th 2015) was compared to the C. difficile rate during the 12 month baseline period (Jan 1 through Dec 31 2013). ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Intermountain Healthcare acute care hospital with \< 200 licensed beds * No formal antibiotic stewardship program in place Exclusion Criteria: -All Intermountain Healthcare specialty hospitals, regardless of bed size **Sex:** ALL **Standard Ages:** - CHILD - ADULT - OLDER_ADULT ### IPD Sharing Statement Module **Description:** N/A. No individual patient level data available. **IPD Sharing:** NO ### References Module #### References **Citation:** Stenehjem E, Hersh AL, Sheng X, Jones P, Buckel WR, Lloyd JF, Howe S, Evans RS, Greene T, Pavia AT. Antibiotic Use in Small Community Hospitals. Clin Infect Dis. 2016 Nov 15;63(10):1273-1280. doi: 10.1093/cid/ciw588. Epub 2016 Sep 30. **PMID:** 27694483 **Citation:** Stenehjem E, Hersh AL, Buckel WR, Jones P, Sheng X, Evans RS, Burke JP, Lopansri BK, Srivastava R, Greene T, Pavia AT. Impact of Implementing Antibiotic Stewardship Programs in 15 Small Hospitals: A Cluster-Randomized Intervention. Clin Infect Dis. 2018 Aug 1;67(4):525-532. doi: 10.1093/cid/ciy155. **PMID:** 29790913 #### See Also Links **Label:** IDWeek 2016 SHEA Featured Oral Abstract **URL:** http://idsa.confex.com/idsa/2016/webprogram/Paper57499.html ## Derived Section ### Intervention Browse Module - Browse Branches - Abbrev: Infe - Name: Anti-Infective Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M17388 - Name: Vancomycin - Relevance: LOW - As Found: Unknown - ID: M1889 - Name: Meropenem - Relevance: LOW - As Found: Unknown - ID: M1938 - Name: Tazobactam - Relevance: LOW - As Found: Unknown - ID: M13772 - Name: Piperacillin - Relevance: LOW - As Found: Unknown - ID: M4222 - Name: Anti-Bacterial Agents - Relevance: LOW - As Found: Unknown - ID: M5693 - Name: Ceftriaxone - Relevance: LOW - As Found: Unknown - ID: M1884 - Name: Cefepime - Relevance: LOW - As Found: Unknown - ID: M4224 - Name: Antibiotics, Antitubercular - Relevance: LOW - As Found: Unknown - ID: M6252 - Name: Clotrimazole - Relevance: LOW - As Found: Unknown - ID: M11796 - Name: Miconazole - Relevance: LOW - As Found: Unknown - ID: M400 - Name: Linezolid - Relevance: LOW - As Found: Unknown - ID: M3351 - Name: Ceftaroline - Relevance: LOW - As Found: Unknown - ID: M23006 - Name: Fluoroquinolones - Relevance: LOW - As Found: Unknown - ID: M4254 - Name: Antifungal Agents - Relevance: LOW - As Found: Unknown - ID: M19824 - Name: Daptomycin - Relevance: LOW - As Found: Unknown - ID: M18061 - Name: Imipenem - Relevance: LOW - As Found: Unknown - ID: M1887 - Name: Ertapenem - Relevance: LOW - As Found: Unknown - ID: M1948 - Name: Tigecycline - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24