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## Protocol Section ### Identification Module **NCT ID:** NCT04456179 **Brief Title:** Continuous Non-Invasive Blood Pressure System Data Collection in Comparison to Invasive Radial Arterial Pressure **Official Title:** Evaluation of Sensifree's PPG Based Continuous & Non-Invasive Blood Pressure Monitoring System in Comparison to Invasive Radial Arterial Line #### Organization Study ID Info **ID:** PR2020-363 #### Organization **Class:** INDUSTRY **Full Name:** Sensifree Ltd. ### Status Module #### Completion Date **Date:** 2020-02-06 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2020-07-02 **Type:** ACTUAL **Last Update Submit Date:** 2020-06-29 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2020-02-06 **Type:** ACTUAL #### Start Date **Date:** 2020-02-03 **Type:** ACTUAL **Status Verified Date:** 2020-06 #### Study First Post Date **Date:** 2020-07-02 **Type:** ACTUAL **Study First Submit Date:** 2020-06-03 **Study First Submit QC Date:** 2020-06-29 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Sensifree Ltd. #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** True **Is FDA Regulated Drug:** False **Is Unapproved Device:** True **Oversight Has DMC:** False ### Description Module **Brief Summary:** The purpose of this study is to evaluate methods to modify blood pressure in humans and measure the effectiveness of such methods. A secondary outcome is to evaluate the performance of an investigational continuous non-invasive blood pressure (cNIBP) device created by Sensifree. The tests will per performed in non-hospitalized subjects under varied controlled conditions that include resting blood pressure and non-pharmacologically induced blood pressure changes. **Detailed Description:** On a first visit a screening procedure to verify inclusion / exclusion criteria are met will be conducted. On the primary procedure visit, data collection will begin with the subjects having the investigational device, ECG sensors, and 1 or more pulse oximetry sensors placed on them for data collection and to monitor their safety for the duration of the study. A physician will place an arterial line in the radial artery. The Sensifree cNIBP system will be calibrated with an oscillometric and/or auscultatory blood pressure cuff measurement taken on the arm opposite the arterial line. A series of blood pressure changes will be induced, including various combinations of methods. ### Conditions Module **Conditions:** - Blood Pressure Measurement ### Design Module #### Design Info **Allocation:** NON_RANDOMIZED **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** OTHER #### Enrollment Info **Count:** 6 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module ### Interventions #### Intervention 1 **Description:** PPG based, fingertip mounted sensor, that measures the oxygen level (oxygen saturation) of the blood and generates a waveform **Name:** GE Datex-Ohmeda Oxy-F Finger Clip Pulse Oximeter Sensor **Type:** DEVICE #### Intervention 2 **Description:** Invasive monitoring of blood pressure via catheterization of the radial artery, displaying a continuous pressure waveform **Name:** Arrow® arterial catheterization kit (Teleflex) **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Description:** Measure the effect of a combination of the following isometric efforts on a subject's blood pressure (measured in mmHg): 1. Hand grip 2. Weight lifting 3. Leg static effort **Measure:** Evaluation of the magnitude of blood pressure change (measured in mmHg) cause by different isometric efforts in humans **Time Frame:** 3-4 hours per subject #### Secondary Outcomes **Description:** Comparison of BP values (Systolic, Diastolic, MAP) that are calculated by the investigational device to the BP values measured by the arterial line during isometric effort comprising a combination of the following isometric efforts on a subject's blood pressure: 1. Hand grip 2. Weight lifting 3. Leg static effort **Measure:** Measure the accuracy of an investigational continuous non-invasive blood pressure (cNIBP) device **Time Frame:** 3-4 hours per subject ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Subject must have the ability to understand and provide written informed consent * Subject must be willing and able to comply with study procedures and duration Exclusion Criteria: * Subject with a BMI over 39 * Deformities or abnormalities that may prevent proper application of the device under test * Lateral difference in blood pressure greater than 5mmHg diastolic and 9mmHg systolic * Tachycardia or resting heart rate less than 45 bpm * Females who are pregnant, who are trying to get pregnant, (confirmed by positive urine pregnancy test unless the subject is known to be not of child-bearing potential) * Subjects with known respiratory conditions such as: (self-reported) * uncontrolled / severe asthma, * flu, * pneumonia / bronchitis, * shortness of breath / respiratory distress, * respiratory or lung surgery, * emphysema, COPD, lung disease * Subjects with known heart or cardiovascular conditions such as: (self-reported, except for blood pressure and ECG review) * have had cardiovascular surgery * have cardiac pacemakers and/or automatic internal cardio-defibrillator * Chest pain (angina) * Abnormal pulse pressure * previous heart attack * blocked artery * unexplained shortness of breath * congestive heart failure (CHF) * history of stroke * transient ischemic attack * carotid artery disease * myocardial ischemia * myocardial infarction * cardiomyopathy * Pulsus Paradoxus * Self-reported health conditions as identified in the Health Assessment Form (self-reported) * diabetes, * uncontrolled thyroid disease, * kidney disease / chronic renal impairment, * history of seizures (except childhood febrile seizures), * epilepsy, * history of unexplained syncope, * recent history of frequent migraine headaches, * recent head injury * cancer / chemotherapy * Subjects with known clotting disorders (self-reported) * history of bleeding disorders or personal history of prolonged bleeding from injury * history of blood clots * hemophilia * current use of blood thinner: prescription or daily use of aspirin * Subjects with severe contact allergies to standard adhesives, latex or other materials found in pulse oximetry sensors, ECG electrodes, respiration monitor electrodes or other medical sensors (self-reported) * Subjects with a contact allergy to ultrasound gel. * Subjects with prior or known allergies to iodine or lidocaine (or similar pharmacological agents, e.g. Novocaine) * Failure of the Perfusion Index Ulnar/Ulnar+Radial Ratio test * Subject is intoxicated during the time of the visit, or was intoxicated within 24 hours prior to study visit, as reported by the subject, or per study staff judgment. * Other known health condition, should be considered upon disclosure in health assessment form **Gender Based:** True **Gender Description:** At least 30% of the subjects will be female and at least 30% will be male **Healthy Volunteers:** True **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Louisville **Country:** United States **Facility:** Clinimark Lab **State:** Colorado **Zip:** 80027 #### Overall Officials **Official 1:** **Name:** Arthur Ruiz Cabrera, M.D **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:** NCT01197079 **Brief Title:** Utilization of Human Papillomavirus (HPV) Vaccine Among Young Men Who Have Sex With Men (MSM) and Parents of Boys (Aged 9 to 18 Years) **Official Title:** Survey Study of the Awareness, Acceptance, and Barriers to Utilization of Human Papillomavirus (HPV) Vaccine Among Young Men Who Have Sex With Men (MSM) and Parents of Boys (Aged 9 to 18 Years) #### Organization Study ID Info **ID:** Merck IISP 37875 #### Organization **Class:** OTHER **Full Name:** Ann & Robert H Lurie Children's Hospital of Chicago ### Status Module #### Completion Date **Date:** 2011-08 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** RECRUITING #### Last Update Post Date **Date:** 2011-07-15 **Type:** ESTIMATED **Last Update Submit Date:** 2011-07-14 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2011-08 **Type:** ESTIMATED #### Start Date **Date:** 2010-08 **Status Verified Date:** 2011-07 #### Study First Post Date **Date:** 2010-09-09 **Type:** ESTIMATED **Study First Submit Date:** 2010-09-08 **Study First Submit QC Date:** 2010-09-08 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Ann & Robert H Lurie Children's Hospital of Chicago #### Responsible Party **Old Name Title:** Tina Q. Tan, M.D. **Old Organization:** Children's Memorial Hospital ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** The objectives of this study are: 1. to determine the degree of understanding and perceived risks for human papillomavirus (HPV) disease, to examine and assess attitudes for personal use of HPV vaccine and identify potential barriers to HPV vaccine access and utilization in a population of young men who have sex with men (MSM) (under 26 years of age)and in parents of boys aged 9 to 18 years 2. to determine HPV vaccine acceptance and predictors of acceptance in a population of young MSM and in patients of boys ages 9 to 18 years 3. to develop strategies to overcome potential barriers to vaccination and improve vaccine access and utilization via development of targeted educational initiatives. ### Conditions Module **Conditions:** - Human Papillomavirus (HPV) **Keywords:** - HPV - Vaccine - Vaccine utilization - Disease awareness ### Design Module #### Design Info **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 800 **Type:** ESTIMATED **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Young men (under 26 years of age) who have sex with men **Intervention Names:** - Other: Survey **Label:** MSM #### Arm Group 2 **Description:** Parents of Boys aged 9 to 18 years **Intervention Names:** - Other: Survey **Label:** Parents ### Interventions #### Intervention 1 **Arm Group Labels:** - MSM - Parents **Description:** Self administered anonymous survey **Name:** Survey **Type:** OTHER ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * MSM group - under age 26 years * Parent group - parent of boy(s) ages 9 to 18 years Exclusion Criteria: * MSM group - previous receipt of HPV vaccine * Parent group - previous receipt of HPV vaccine by male child **Healthy Volunteers:** True **Maximum Age:** 26 Years **Minimum Age:** 9 Years **Sampling Method:** PROBABILITY_SAMPLE **Sex:** MALE **Standard Ages:** - CHILD - ADULT **Study Population:** Young men who have sex with men (MSM) that obtain medical care from a Gay/Lesbian/Bisexual/Transgender community health clinic Parents of boys aged 9 to 18 years who obtain their medical care from several public health clinics or who obtain their medical care from private pediatrician offices in Chicago ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Tina Q Tan, MD **Phone:** 773-880-4187 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Melvin V Gerbie, MD **Phone:** 312-951-0687 **Role:** CONTACT #### Locations **Location 1:** **City:** Chicago **Contacts:** ***Contact 1:*** - **Name:** Aleta Clark, MD - **Phone:** 312-943-6964 - **Role:** CONTACT ***Contact 2:*** - **Name:** Aleta Clark, MD - **Role:** SUB_INVESTIGATOR **Country:** United States **Facility:** Pediatric Private practice **State:** Illinois **Status:** NOT_YET_RECRUITING **Zip:** 60610 **Location 2:** **City:** Chicago **Contacts:** ***Contact 1:*** - **Name:** Marc Weissluth, MD - **Phone:** 312-642-5515 - **Role:** CONTACT ***Contact 2:*** - **Name:** Marc Weissbluth, MD - **Role:** SUB_INVESTIGATOR **Country:** United States **Facility:** Pediatric Private Practice **State:** Illinois **Status:** NOT_YET_RECRUITING **Zip:** 60610 **Location 3:** **City:** Chicago **Contacts:** ***Contact 1:*** - **Name:** Barbara Bayldon, MD - **Phone:** 773-561-6649 - **Role:** CONTACT ***Contact 2:*** - **Name:** Barbara Bayldon, MD - **Role:** SUB_INVESTIGATOR **Country:** United States **Facility:** Children's Memorial Hospital Uptown Clinic **State:** Illinois **Status:** NOT_YET_RECRUITING **Zip:** 60640 **Location 4:** **City:** Chicago **Contacts:** ***Contact 1:*** - **Name:** Bennett Kaye, MD - **Phone:** 773-348-8300 - **Role:** CONTACT ***Contact 2:*** - **Name:** Bennett Kaye, MD - **Role:** SUB_INVESTIGATOR **Country:** United States **Facility:** Pediatric Private Practice **State:** Illinois **Status:** RECRUITING **Zip:** 60657 **Location 5:** **City:** Chicago **Contacts:** ***Contact 1:*** - **Name:** Kate Laslo, MD - **Phone:** 312-666-5867 - **Role:** CONTACT ***Contact 2:*** - **Name:** Kate Laslo, MD - **Role:** SUB_INVESTIGATOR **Country:** United States **Facility:** Erie Family Health Clinic **State:** Illinois **Status:** NOT_YET_RECRUITING **Location 6:** **City:** Chicago **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Robert Garofalo, MD - **Phone:** 773-388-8898 - **Role:** CONTACT ***Contact 2:*** - **Email:** [email protected] - **Name:** Jennifer Leininger - **Phone:** 773-388-8898 - **Role:** CONTACT ***Contact 3:*** - **Name:** Robert Garofalo, MD - **Role:** SUB_INVESTIGATOR **Country:** United States **Facility:** Howard Brown Health Center **State:** Illinois **Status:** RECRUITING **Location 7:** **City:** Evanston **Contacts:** ***Contact 1:*** - **Name:** Irwin Benuck, MD - **Phone:** 847-869-4300 - **Role:** CONTACT ***Contact 2:*** - **Name:** Irwin Benuck, MD - **Role:** SUB_INVESTIGATOR **Country:** United States **Facility:** Private pediatric practice **State:** Illinois **Status:** RECRUITING **Zip:** 60202 **Location 8:** **City:** Evanston **Contacts:** ***Contact 1:*** - **Name:** Ira Salafsky, MD - **Phone:** 847-869-1070 - **Role:** CONTACT ***Contact 2:*** - **Name:** Ira Salafsky, MD - **Role:** SUB_INVESTIGATOR **Country:** United States **Facility:** Pediatric Private practice **State:** Illinois **Status:** NOT_YET_RECRUITING ## Derived Section ### 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:** NCT00310479 **Brief Title:** Clinico-pathologic Correlative Study of 3T Magnetic Resonance Spectroscopy in the Localization of Prostate Cancer **Official Title:** Clinico-pathologic Correlative Study of 3T Magnetic Resonance Spectroscopy in the Localization of Prostate Cancer #### Organization Study ID Info **ID:** GU-6-0062 / 22281 #### Organization **Class:** OTHER **Full Name:** AHS Cancer Control Alberta ### Status Module #### Completion Date **Date:** 2008-03 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2016-02-25 **Type:** ESTIMATED **Last Update Submit Date:** 2016-02-24 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2008-03 **Type:** ACTUAL #### Start Date **Date:** 2006-06 **Status Verified Date:** 2012-03 #### Study First Post Date **Date:** 2006-04-04 **Type:** ESTIMATED **Study First Submit Date:** 2006-04-03 **Study First Submit QC Date:** 2006-04-03 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** Cross Cancer Institute #### Lead Sponsor **Class:** OTHER **Name:** AHS Cancer Control Alberta #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** We seek to develop an advanced imaging approach to identifying and localizing prostate cancer. We believe that high field MRI (magnetic resonance imaging) has the potential to do this and we will endeavor to prove this by having patients with prostate cancer pre-operatively undergo a technique called magnetic resonance spectroscopy. After surgery, the microscopic locations of cancer will be compared with the pre-operative images to assess how well the imaging technique succeeds. **Detailed Description:** The proposed research is enormously relevant to the clinical understanding of early prostate cancer. We propose to test to see whether characteristic patterns of invivo 3T MRSI associated metabolites can be identified in correlation with clinically active tumor reserved on histopathologic analysis of resected specimens. We also plan to demonstrate that 3T MR spectra of prostate cancer will allow for more detailed metabolic assessment with higher sensitivity, specificity and accuracy and publish results established from MR spectra using 1.5T MR units. Functional imaging (eg. molecular imaging such as this) is felt to be the clinical wave of the future for cancer imaging, and if successful, will assume a very major role in the detection, assessment, treatment planning and delivery of drugs, radiation, heat and novel therapeutics in the fight against prostate cancer. ### Conditions Module **Conditions:** - Prostate Cancer **Keywords:** - Magnetic Resonance Imaging - prostate cancer imaging - 3T MRS - functional imaging ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** DIAGNOSTIC #### Enrollment Info **Count:** 16 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module ### Interventions #### Intervention 1 **Name:** Magnetic Resonance Spectroscopy (3Tesla) **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Measure:** characteristic metabolic pattern of prostate cancer at 3Tesla #### Secondary Outcomes **Measure:** specificity, accuracy, NPV **Measure:** PPV of MRS in the detection of prostate cancer ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Histologically verified prostate cancer * Patient has opted for surgery * Low risk prostate cancer PSA \<1 0, Gleason \< 7, Stage \< T2b * No contraindication to MR scanning * No prior history of malignancy * Fit for surgery Exclusion Criteria: * Nonbiopsied lesion * Intermediate or high risk prostate cancer * Unfit for surgery * Contraindication to MR scanning (i.e. pacemaker, aneurysm clips, claustrophobia) **Minimum Age:** 40 Years **Sex:** MALE **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Edmonton **Country:** Canada **Facility:** Cross Cancer Institute **State:** Alberta **Zip:** T6G 1Z2 #### Overall Officials **Official 1:** **Affiliation:** AHS Cancer Control Alberta **Name:** Matthew Parliament, MD **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000005834 - Term: Genital Neoplasms, Male - ID: D000014565 - Term: Urogenital Neoplasms - ID: D000009371 - Term: Neoplasms by Site - ID: D000009369 - Term: Neoplasms - ID: D000005832 - Term: Genital Diseases, Male - ID: D000091662 - Term: Genital Diseases - ID: D000091642 - Term: Urogenital Diseases - ID: D000011469 - Term: Prostatic 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 - Abbrev: BC14 - Name: Heart and Blood Diseases ### Condition Browse Module - Browse Leaves - ID: M14335 - Name: Prostatic Neoplasms - Relevance: HIGH - As Found: Prostate Cancer - ID: M11910 - Name: Mitral Valve Insufficiency - Relevance: LOW - As Found: Unknown - ID: M8946 - Name: Genital Neoplasms, Male - Relevance: LOW - As Found: Unknown - ID: M17315 - Name: Urogenital Neoplasms - Relevance: LOW - As Found: Unknown - ID: M2876 - Name: Genital Diseases - Relevance: LOW - As Found: Unknown - ID: M8944 - Name: Genital Diseases, Male - Relevance: LOW - As Found: Unknown - ID: M2875 - Name: Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M14333 - Name: Prostatic Diseases - Relevance: LOW - As Found: Unknown - ID: M27095 - Name: Male Urogenital Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000011471 - Term: Prostatic Neoplasms ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05630079 **Brief Title:** Variation of Atelectasis Score After High-frequency Percussions in Severe Acquired Brain Injury **Official Title:** Short-term Variation of Atelectasis Score After High-frequency Percussions in Patients With Severe Acquired Brain Injury: a Retrospective Cohort Study. #### Organization Study ID Info **ID:** FDG_05_17/02/2021 #### Organization **Class:** OTHER **Full Name:** Fondazione Don Carlo Gnocchi Onlus ### Status Module #### Completion Date **Date:** 2022-02-22 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2022-11-29 **Type:** ACTUAL **Last Update Submit Date:** 2022-11-17 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2021-07-31 **Type:** ACTUAL #### Start Date **Date:** 2021-02-22 **Type:** ACTUAL **Status Verified Date:** 2022-11 #### Study First Post Date **Date:** 2022-11-29 **Type:** ACTUAL **Study First Submit Date:** 2022-09-26 **Study First Submit QC Date:** 2022-11-17 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Fondazione Don Carlo Gnocchi Onlus #### Responsible Party **Investigator Affiliation:** Fondazione Don Carlo Gnocchi Onlus **Investigator Full Name:** Paolo Banfi **Investigator Title:** Head of Pneumological Rehabilitation **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** True **Is FDA Regulated Drug:** False **Is US Export:** False ### Description Module **Brief Summary:** Investigators conduced in the Neurological Rehabilitation Unit of the IRCCS "S.Maria Nascente - Fondazione Don Gnocchi", (Milan) a retrospective study on 19 patients hospitalized between September 2018 and February 2021, with the aim of comparing the efficacy of the two devices, MetaNeb® and Intrapulmonary Percussion Ventilation (IPV®). The efficacy was evaluated considering the change of various measures after two weeks of treatment. The main outcome considered is the atelectasis score, assigned by two radiologists who blindly and retrospectively evaluated it on high-resolution computed tomography (HRTC) images **Detailed Description:** Patients with severe acquired brain injury (sABI) frequently exhibit pulmonary complications, with atelectasis and/or consolidation of the lower lobes. The atelectasis in critically ill patients is a risk factor for pneumonia and increase the possibility to develop dysventilation syndrome with consequent negative impacts on gas exchanges. To the best of our knowledge, there is no study investigating the use of the two devices for the treatment of atelectasis in the specific population of non-cooperative tracheostomized patients with sABI who had been spontaneously breathing with no mechanical ventilation support. ### Conditions Module **Conditions:** - Atelectasis - Acquired Brain Injury - Respiratory Rehabilitation ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** RETROSPECTIVE #### Enrollment Info **Count:** 15 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Patients admitted for severe acquired brain injury (sABI) in Neurological Rehabilitation Unit of IRCCS "Santa Maria Nascente - Fondazione Don Gnocchi" received the MetaNeb® system treatment. It consist of simultaneous combination of positive pressure, continuous high frequency oscillations and aerosol delivery **Intervention Names:** - Device: Treatment with Metaneb® **Label:** Metaneb® #### Arm Group 2 **Description:** Patients with severe acquired brain injury from Neurological Rehabilitation Unit of IRCCS Fondazione Don Gnocchi, S.M. Nascente received the IPV® treatment. The principle of IPV® is to open collapsed airways and mobilize intrabronchial secretions through the delivery of small tidal volume at high frequency. IPV® adjusts the percussions to the changes in the mechanical properties of the patient's respiratory system: in case of high resistance, it produces small tidal volume at high pressure and low frequency; vice versa in case of low resistance, it produces large tidal volume at low pressure and high frequency **Intervention Names:** - Device: Treatment with IPV® **Label:** IPV® ### Interventions #### Intervention 1 **Arm Group Labels:** - Metaneb® **Description:** Every patient of this group receive 3 daily treatments of 20 minutes each, performed at approximately 4-hour intervals. Each treatment with MetaNeb system consists of four cycles: : 5 minutes of Continuous Positive Expiratory Pressure (CPEP) for lung re-expansion (Cycle I), 5 minutes of Chest High Frequency Oscillation (CHFO) for secretion clearance (Cycle II), 5 min of CPEP (Cycle III), 5 minutes of CHFO (Cycle IV). Treatments are performed by respiratory physiotherapists and the pressure setted was the highest tolerated by the patient. It's associated with the administration of aerosols with 10 ml of saline solution 0.9% and are carried out by connecting the tracheostomy cannula cuffed to the catheter mount. **Name:** Treatment with Metaneb® **Type:** DEVICE #### Intervention 2 **Arm Group Labels:** - IPV® **Description:** Each treatment with IPV provides 3 daily treatments of 20 minutes with the high percussion frequency tolerated by the patient. and I/E ratio: 1/1.2. Treatments are performed by respiratory physiotherapists and the pressure setted was the highest tolerated by the patient. It is associated with the administration of aerosols with 10 ml of saline solution 0.9% \[-\] and are carried out by connecting the tracheostomy cannula cuffed to the catheter mount. **Name:** Treatment with IPV® **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Description:** The aim is to compare the effect of the two devices, IPV® and MetaNeb® in the treatment of atelectasis. The atelectasis score is assigned by two radiologists who blindly and retrospectively evaluated it on high-resolution computed tomography (HRTC) images **Measure:** Variation of atelectasis score after treatment **Time Frame:** 15 days **Description:** Comparing the atelectasis score using an automatic score generated by Siemens (syngo.via CT Pneumonia Analysis), in case of discrepancy between all radiologists **Measure:** Automatic score by Siemens **Time Frame:** 15 days #### Secondary Outcomes **Description:** Changes of respiratory parameters in terms of normalization of oxyemia (Arterial Pressure of oxygen 80-100 mmHg) and normalization of capnia (Arterial Pressure of carbon dioxide 35-45 mmHg), assessed by blood gas analysis **Measure:** Blood Gas Analysis **Time Frame:** 15 days **Description:** Average SpO2, Lowest SpO2, \<90% (lenght of time SpO2 dropped below 90%), Average Heart Rate **Measure:** Peripheral Oxygen Saturation (SpO2) at night **Time Frame:** 15 days ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Spontaneous breathing 24h/24h * Presence of tracheostomy cannula * Presence of atelectasis diagnosed through High Resolution Computed Tomography * Levels of Cognitive Functioning (LCF) ≤ 5 * No pneumothorax * Consent signed Exclusion Criteria: * Age under 18 years old **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Patients admitted for severe acquired brain injury (sABI) in Neurological Rehabilitation Unit of IRCCS "Santa Maria Nascente - Fondazione Don Gnocchi" from September 2018 to February 2021 ### Contacts Locations Module #### Locations **Location 1:** **City:** Milano **Country:** Italy **Facility:** IRCCS Santa Maria Nascente, Fondazione Don Gnocchi **Zip:** 20148 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000001927 - Term: Brain Diseases - ID: D000002493 - Term: Central Nervous System Diseases - ID: D000009422 - Term: Nervous System Diseases - ID: D000006259 - Term: Craniocerebral Trauma - ID: D000020196 - Term: Trauma, Nervous System - ID: D000008171 - Term: Lung Diseases - ID: D000012140 - Term: Respiratory Tract Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: BC26 - Name: Wounds and Injuries - Abbrev: All - Name: All Conditions - Abbrev: BC08 - Name: Respiratory Tract (Lung and Bronchial) Diseases ### Condition Browse Module - Browse Leaves - ID: M5207 - Name: Brain Injuries - Relevance: HIGH - As Found: Brain Injury - ID: M4567 - Name: Pulmonary Atelectasis - Relevance: HIGH - As Found: Atelectasis - ID: M17685 - Name: Wounds and Injuries - Relevance: HIGH - As Found: Injury - ID: M5204 - Name: Brain Diseases - Relevance: LOW - As Found: Unknown - ID: M5742 - Name: Central Nervous System Diseases - Relevance: LOW - As Found: Unknown - ID: M9349 - Name: Craniocerebral Trauma - Relevance: LOW - As Found: Unknown - ID: M22023 - Name: Trauma, Nervous System - 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: D000001261 - Term: Pulmonary Atelectasis - ID: D000001930 - Term: Brain Injuries - ID: D000014947 - Term: Wounds and Injuries ### Intervention Browse Module - Browse Branches - Abbrev: PhSol - Name: Pharmaceutical Solutions - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Resp - Name: Respiratory System Agents ### Intervention Browse Module - Browse Leaves - ID: M21860 - Name: Pharmaceutical Solutions - Relevance: LOW - As Found: Unknown - ID: M21137 - Name: Respiratory System Agents - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05774379 **Acronym:** VRfatigue **Brief Title:** Virtual Reality and Fatigue Education **Official Title:** The Effect of Virtual Reality and Fatigue Education on Fatigue and Anxiety Levels in Children With Cancer #### Organization Study ID Info **ID:** 5776GOA #### Organization **Class:** OTHER **Full Name:** Dokuz Eylul University ### Status Module #### Completion Date **Date:** 2023-02-10 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2023-03-17 **Type:** ACTUAL **Last Update Submit Date:** 2023-03-07 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2023-02-01 **Type:** ACTUAL #### Start Date **Date:** 2022-04-01 **Type:** ACTUAL **Status Verified Date:** 2023-03 #### Study First Post Date **Date:** 2023-03-17 **Type:** ACTUAL **Study First Submit Date:** 2023-03-07 **Study First Submit QC Date:** 2023-03-07 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Dokuz Eylul University #### Responsible Party **Investigator Affiliation:** Dokuz Eylul University **Investigator Full Name:** Gülçin Özalp Gerçeker **Investigator Title:** pHD, Assoc. Prof. **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** It was planned to evaluate the effect of distraction intervention with virtual reality and fatigue education on the level of fatigue and anxiety in children with cancer. **Detailed Description:** H1: The fatigue scores of the patients who received distraction intervention with virtual reality and were given fatigue training were lower than the group that was given only fatigue training. H2: The anxiety scores of the patients who received distraction intervention with virtual reality and were given fatigue training were lower than the group that was given only fatigue training. Data collection After the child and his family are informed about the study, their written informed consent will be obtained. All children included in the study on the day (day 0) prior to the start of chemotherapy treatment will be given training on fatigue. In order to determine how he felt and his level of fatigue on the day of the training, it was planned to apply the Child Anxiety Scale-State (CAS-D), Child Fatigue Scale-24 Hours and Visual Fatigue Scale at 16.00 (pretest). After randomization is achieved, a distraction intervention will be applied once a day for 10-15 minutes with virtual glasses on the 1st, 2nd and 3rd days of the chemotherapy treatment of the children in the study group. This intervention is planned to take place between 14.00-15.00 in the afternoon. ### Conditions Module **Conditions:** - Fatigue - Anxiety **Keywords:** - virtual reality ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** SINGLE **Who Masked:** - INVESTIGATOR **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 41 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** watching the application by wearing virtual glasses for 3 days and Providing training on fatigue to all children (1 session, average 45 minutes) (using role-play, exercise, games, coloring books and activity materials) **Intervention Names:** - Device: virtual reality and fatigue education **Label:** virtual reality and fatigue education **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Providing training on fatigue to all children (1 session, average 45 minutes) (using role-play, exercise, games, coloring books and activity materials) **Intervention Names:** - Behavioral: fatigue education **Label:** fatigue education **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - virtual reality and fatigue education **Description:** virtual reality distraction for 3 days and fatigue education for children **Name:** virtual reality and fatigue education **Type:** DEVICE #### Intervention 2 **Arm Group Labels:** - fatigue education **Description:** fatigue education for children **Name:** fatigue education **Type:** BEHAVIORAL ### Outcomes Module #### Primary Outcomes **Description:** Child Fatigue Scale-24 Hours: It consists of 10 items related to the perception of fatigue in children with cancer. The items in the scale contain statements that will show the child's experience of fatigue-related symptoms in the last 24 hours. The items were arranged according to likert scoring between 'never (1)' and 'a lot (5)'. **Measure:** fatigue **Time Frame:** pretest, 1., 2. and 3. days of chemotheraphy **Description:** The Children's Anxiety Meter (CAM-S). The Children's Anxiety Meter assesses children's anxiety and uses before medical procedures. This scale is drawn like a thermometer with a bulb at the bottom and also includes horizontal lines at intervals going up to the top (0-10). This scale ranges from 0 to 10. Higher values represent higher anxiety **Measure:** anxiety **Time Frame:** pretest, 1., 2. and 3. days of chemotheraphy ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Be between 7-18 years old * Inpatient chemotherapy treatment for more than three days * 4 weeks over the time of diagnosis (not in the induction phase) * Having a hemoglobin level above the criteria for transfusion of blood products (8 mg/dl for hematological malignancies, below 7 mg/dl for oncological malignancies). * The child voluntarily agrees to participate in the study and consent is obtained from the child and parent Exclusion Criteria: * Being in terminal period * undergoing a surgical operation * Unwillingness to participate in the study **Maximum Age:** 18 Years **Minimum Age:** 7 Years **Sex:** ALL **Standard Ages:** - CHILD - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** İzmir **Country:** Turkey **Facility:** Gülçin Özalp Gerçeker **Zip:** 35100 #### Overall Officials **Official 1:** **Affiliation:** Dokuz Eylul University **Name:** Gülçin Özalp Gerçeker, pHD, RN **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Browse Branches - Abbrev: BXM - Name: Behaviors and Mental Disorders - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology ### Condition Browse Module - Browse Leaves - ID: M4324 - Name: Anxiety Disorders - Relevance: LOW - As Found: Unknown - ID: M8364 - Name: Fatigue - Relevance: HIGH - As Found: Fatigue ### Condition Browse Module - Meshes - ID: D000005221 - Term: Fatigue ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03174379 **Brief Title:** A Study to Analyze the Effect of Acupuncture on Mobility And Quality of Life in Multiple Sclerosis **Official Title:** A Pilot Study to Analyze the Effect of Acupuncture on Mobility And Quality of Life in Multiple Sclerosis #### Organization Study ID Info **ID:** 15-00440 #### Organization **Class:** OTHER **Full Name:** NYU Langone Health ### Status Module #### Completion Date **Date:** 2019-06-06 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2022-03-21 **Type:** ACTUAL **Last Update Submit Date:** 2022-03-07 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2019-06-06 **Type:** ACTUAL #### Start Date **Date:** 2017-06-05 **Type:** ACTUAL **Status Verified Date:** 2022-03 #### Study First Post Date **Date:** 2017-06-02 **Type:** ACTUAL **Study First Submit Date:** 2017-05-31 **Study First Submit QC Date:** 2017-06-01 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** NYU Langone Health #### 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 two-center study is to examine the effectiveness of acupuncture treatments in addressing mobility deficits, sensorimotor impairment, and quality of life (QOL) limitations in persons with Multiple Sclerosis (MS). It is hypothesized that acupuncture will result in an improvement in these limitations. **Detailed Description:** This research study will examine the effects of acupuncture on various symptoms experienced by persons with MS. Persons with MS often use acupuncture as a way of controlling the symptoms of the disease. However, there is little research on whether or not acupuncture has any effect on MS symptoms related to movement. This study intends to look at the effects of acupuncture treatment on walking, balance, and mood in persons with MS. ### Conditions Module **Conditions:** - Multiple Sclerosis ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** SINGLE **Who Masked:** - PARTICIPANT **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 13 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Standard of Care (SOC) treatment will be based upon Traditional Chinese Medicine (TCM) interpretation of 4 phases of MS. **Intervention Names:** - Procedure: Standard of Care with no acupuncture **Label:** Control Group **Type:** PLACEBO_COMPARATOR #### Arm Group 2 **Description:** 60-minute treatment session twice a week for three weeks **Intervention Names:** - Procedure: Acupuncture **Label:** Treatment Group **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Control Group **Description:** The control group will lie on a treatment table in the acupuncturist's office for the same amount of time that the treatment group did, but receive no acupuncture **Name:** Standard of Care with no acupuncture **Type:** PROCEDURE #### Intervention 2 **Arm Group Labels:** - Treatment Group **Description:** The first set consists of core point selection, used in an MS Standard of Care (SOC). The second set of points will be individualized to the patient's needs as determined by the acupuncturist. SOC treatment will be based upon Traditional Chinese Medicine (TCM) interpretation of 4 phases of MS. **Name:** Acupuncture **Type:** PROCEDURE ### Outcomes Module #### Primary Outcomes **Description:** The Fatigue Severity Scale (FSS) is a method of evaluating the impact of fatigue. The FSS is a short questionnaire that requires patient to rate level of fatigue. **Measure:** fatigue severity scale **Time Frame:** 14 Weeks **Description:** The MOS covers pain severity in terms of intensity, frequency, and duration while recording the impact on behaviours and moods. MOS contains twelve self report items on the severity of pain over the past four weeks and its effect on mood and behaviours **Measure:** Medical Outcomes Study Pain Effects Scale **Time Frame:** 14 Weeks **Description:** Assesses distance walked over 6 minutes as a sub-maximal test of aerobic capacity/endurance **Measure:** Gait measured by 6-minute walk test **Time Frame:** 14 Weeks **Description:** The T25-FW is a quantitative mobility and leg function performance test based on a timed 25-walk. **Measure:** Balance measured by 25-foot walk test **Time Frame:** 14 Weeks ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * diagnosis of MS * ability to walk unaided for 6 minutes with or without assistive device Exclusion Criteria: * bleeding precautions * trypanophobia * inability to lie still for 30 minutes * active cancer, current exacerbation, and history of previous acupuncture treatment **Maximum Age:** 65 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** New York **Country:** United States **Facility:** New York University School of Medicine **State:** New York **Zip:** 10016 #### Overall Officials **Official 1:** **Affiliation:** NYU Langone Health **Name:** Barbara Siminovich-blok **Role:** PRINCIPAL_INVESTIGATOR ## 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: BXM - Name: Behaviors and Mental Disorders ### 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 - ID: T6034 - Name: Quality of Life - Relevance: HIGH - As Found: Quality of Life ### 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:** NCT04261179 **Acronym:** SENTINELSEEK **Brief Title:** Study Comparing Lymphoseek® vs. Albumin Nanocolloid in Head and Neck, Melanoma and Breast Cancer **Official Title:** An Exploratory Prospective, Open-label, Unicentric Study With Cross-over Design, Comparing Lymphoseek® vs. Albumin Nanocolloid for Image- Guided Sentinel Lymph Node Mapping in Head and Neck, Melanoma and Breast Cancer. #### Organization Study ID Info **ID:** 2019-003825-56 #### Organization **Class:** OTHER **Full Name:** Fundacion Clinic per a la Recerca Biomédica ### Status Module #### Completion Date **Date:** 2021-08 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** NOT_YET_RECRUITING #### Last Update Post Date **Date:** 2020-02-20 **Type:** ACTUAL **Last Update Submit Date:** 2020-02-18 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2021-02 **Type:** ESTIMATED #### Start Date **Date:** 2020-03 **Type:** ESTIMATED **Status Verified Date:** 2020-02 #### Study First Post Date **Date:** 2020-02-07 **Type:** ACTUAL **Study First Submit Date:** 2020-02-05 **Study First Submit QC Date:** 2020-02-06 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Anna Cruceta #### Responsible Party **Investigator Affiliation:** Fundacion Clinic per a la Recerca Biomédica **Investigator Full Name:** Anna Cruceta **Investigator Title:** Project Manager **Type:** SPONSOR_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** Comparison of the concordance of albumin nanocolloid and Lymphoseek® in the detection of lymph nodes of primary and secondary stage drainage by performing two lymphogammagrams ### Conditions Module **Conditions:** - Head Cancer - Neck Cancer - Melanoma - Breast Cancer ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** DIAGNOSTIC #### Enrollment Info **Count:** 30 **Type:** ESTIMATED **Phases:** - PHASE4 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Comparison of the concordance of albumin nanocolloid and Lymphoseek® in the detection of lymph nodes of primary and secondary stage drainage by performing two lymphogammagrams **Intervention Names:** - Drug: Lymphoseek - Drug: Nanocoll **Label:** Lymphoseek + Nanocoll **Type:** OTHER ### Interventions #### Intervention 1 **Arm Group Labels:** - Lymphoseek + Nanocoll **Description:** 50 μg microgram(s), timepoint: 30-60 minutes **Name:** Lymphoseek **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Lymphoseek + Nanocoll **Description:** 500 μg microgram(s), timepoint: 30-60 minutes **Name:** Nanocoll **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** number and diameter in millimeters of nodes affected identified by 99mTc-tilmanocept vs nanocolloidal **Measure:** Nodal Concordance: proportion of lymph nodes identified by 99mTc-tilmanocept vs nanocolloidal human serum albumin by lymphoscintigraphies **Time Frame:** for at least 48 consecutive hours #### Secondary Outcomes **Measure:** Time frame to ascertain the sentinel nodes **Time Frame:** 1 week **Measure:** Concordance among early and delayed images obtained withLymphoseek® or with albumianocolloid and the SPECT/CT images. **Time Frame:** 1 week **Measure:** Number of sentinel nodes and secondary nodes depicted **Time Frame:** 1 week **Measure:** Tracer retention in injection site **Time Frame:** 1 week **Description:** Number of participants with treatment-related adverse events as assessed by Lymphoseek® or with albuminanocolloid **Measure:** Safety and tolerability of 99mTctilmanocept (Lymphoseek®) **Time Frame:** 1 week ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Written informed consent * Histologically confirmed diagnosis of melanoma, breast cancer or head and neck cancer and candidate for surgical resection with lymph node mapping being a part of the surgical plan. * At least 18 years of age at the time of consent. * The subject is clinically node negative (cN0) at the time of screening. * In Melanoma Patients * Diagnosis of primary melanoma with sentinel node indication ( \>0.8 mm Breslow thickness; clinically negative lymph nodes) * In Breast Cancer Patients * T1-T2 N0 breast cancer. * Patients with pure ductal carcinoma in situ (DCIS) if lymph node biopsy is part of the surgical plan. * In Oral cavity tumors patients * T1-T2 N0 oral cavity squamous cell carcinoma Exclusion Criteria: * Pregnancy or lactation * Clinical or radiological evidence of metastatic cancer including palpably abnormal or enlarged lymph nodes * Patients that have had preoperative chemotherapy, immunotherapy or radiation therapy * Patients who have undergone node basin surgery of any type or radiation to the nodal basin(s) potentially draining the primary tumor * Patients who have undergone a wide excision for their tumor or complex reconstruction (rotation, free flap or skin graft of any type). **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Barcelona **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Anna Cruceta Arboles, MD - **Role:** CONTACT **Country:** Spain **Facility:** Hospital Clínico y provincial de Barcelona **Zip:** 08036 ### 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: D000018358 - Term: Neuroendocrine Tumors - ID: D000017599 - Term: Neuroectodermal Tumors - ID: D000009373 - Term: Neoplasms, Germ Cell and Embryonal - ID: D000009370 - Term: Neoplasms by Histologic Type - ID: D000009380 - Term: Neoplasms, Nerve Tissue - ID: D000018326 - Term: Nevi and Melanomas - ID: D000012878 - Term: Skin Neoplasms ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC17 - Name: Skin and Connective Tissue Diseases - Abbrev: All - Name: All Conditions - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M5220 - Name: Breast Neoplasms - Relevance: HIGH - As Found: Breast Cancer - ID: M11528 - Name: Melanoma - Relevance: HIGH - As Found: Melanoma - ID: M9348 - Name: Head and Neck Neoplasms - Relevance: HIGH - As Found: Head Cancer - ID: M5218 - Name: Breast Diseases - Relevance: LOW - As Found: Unknown - ID: M15674 - Name: Skin Diseases - Relevance: LOW - As Found: Unknown - ID: M20495 - Name: Neuroendocrine Tumors - Relevance: LOW - As Found: Unknown - ID: M19845 - Name: Neuroectodermal Tumors - Relevance: LOW - As Found: Unknown - ID: M20388 - Name: Neuroectodermal Tumors, Primitive - Relevance: LOW - As Found: Unknown - ID: M12318 - Name: Neoplasms, Germ Cell and Embryonal - Relevance: LOW - As Found: Unknown - ID: M12315 - Name: Neoplasms by Histologic Type - Relevance: LOW - As Found: Unknown - ID: M12325 - Name: Neoplasms, Nerve Tissue - Relevance: LOW - As Found: Unknown - ID: M12448 - Name: Nevus, Pigmented - Relevance: LOW - As Found: Unknown - ID: M12446 - Name: Nevus - Relevance: LOW - As Found: Unknown - ID: M20470 - Name: Nevi and Melanomas - Relevance: LOW - As Found: Unknown - ID: M15681 - Name: Skin Neoplasms - Relevance: LOW - As Found: Unknown - ID: T4202 - Name: Oculocerebral Syndrome With Hypopigmentation - Relevance: LOW - As Found: Unknown - ID: T4091 - Name: Neuroendocrine Tumor - Relevance: LOW - As Found: Unknown - ID: T4092 - Name: Neuroepithelioma - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000001943 - Term: Breast Neoplasms - ID: D000008545 - Term: Melanoma - ID: D000006258 - Term: Head and Neck Neoplasms ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03612479 **Brief Title:** Response of the Gut Microbiome and Circulating Metabolome to Diet in Children: Ancillary Study to KIDFIT (NCT03405246) **Official Title:** Response of the Gut Microbiome and Circulating Metabolome to Diet Intervention in Young Children: Ancillary Study to the Keeping Ideal Cardiovascular Health Family Intervention Trial (KIDFIT) #### Organization Study ID Info **ID:** STU00207041 #### Organization **Class:** OTHER **Full Name:** Northwestern University ### Status Module #### Completion Date **Date:** 2020-11-16 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2022-06-29 **Type:** ACTUAL **Last Update Submit Date:** 2022-06-23 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2020-11-09 **Type:** ACTUAL #### Start Date **Date:** 2018-07-10 **Type:** ACTUAL **Status Verified Date:** 2022-06 #### Study First Post Date **Date:** 2018-08-02 **Type:** ACTUAL **Study First Submit Date:** 2018-07-27 **Study First Submit QC Date:** 2018-08-01 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** American Heart Association **Class:** NIH **Name:** National Heart, Lung, and Blood Institute (NHLBI) #### Lead Sponsor **Class:** OTHER **Name:** Northwestern University #### Responsible Party **Investigator Affiliation:** Northwestern University **Investigator Full Name:** Amanda Marma **Investigator Title:** Assistant Professor in Pediatrics-Cardiology and Preventive Medicine **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** This is an ancillary study to KIDFIT (NCT03405246). KIDFIT tests whether preschool-age children, born to overweight or obese mothers, respond to a healthy DASH diet intervention with better cardiovascular health. This ancillary study to KIDFIT investigates how the children's gut microbiomes (bacteria in the intestines) and blood metabolomes (small molecules in the blood) are affected by the DASH diet intervention, and how the microbiome and metabolome relate to the children's cardiovascular health over time. The investigators hypothesize that (1) the DASH diet will modify the gut microbiome and blood metabolome, (2) the gut microbiome and blood metabolome will be related to each other, and (3) the microbiome and metabolome will be associated with the children's cardiovascular health profiles (things like weight, body fat, blood pressure, and cholesterol). **Detailed Description:** The majority of deaths from cardiovascular disease (CVD) in US adults ages 25-54 years are associated with suboptimal diet. While diet is an important target of CVD prevention efforts in adults, intervention on the childhood diet may be more effective. Animal data suggest that early-life diet has the unique potential to modulate biological systems and durably program a child's biology for long-term health or disease. The objective of this study is to define the molecular effects of a dietary pattern intervention on the gut microbiome and circulating metabolome in young children. This objective will be attained through an ancillary study to KIDFIT, a clinical trial that tests the effects of a 12-month Dietary Approaches to Stop Hypertension (DASH) diet intervention on adiposity and other cardiovascular health (CVH) metrics (e.g., blood pressure, lipids) in 3- to 5-year old children. Using additional participant samples, deep phenotyping and advanced bioinformatics, the ancillary study will address three specific aims. First, it will test the effect of the DASH diet intervention on the gut microbiome, including abundances of microbial taxa, communities, and metabolism-related genes and transcripts. Second, it will define the associations of diet and the gut microbiome with the circulating metabolome. Using targeted and nontargeted metabolomics approaches, blood metabolites, metabolite networks, and metabolic pathways will be evaluated. Finally, in an exploratory fashion, it will probe pathways linking the diet intervention with subsequent adiposity and CVH metrics, through the gut microbiome and serum metabolome. The expected outcome is a preliminary model of how the DASH diet alters the gut microbiome and circulating metabolome in young children, and how these alterations relate to short-term CVH outcomes. ### Conditions Module **Conditions:** - Gastrointestinal Microbiome - Metabolome - Pediatric Obesity - Dietary Approaches to Stop Hypertension ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** SINGLE **Who Masked:** - OUTCOMES_ASSESSOR **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 46 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Intervention Names:** - Behavioral: KIDFIT Healthy **Label:** KIDFIT Healthy **Type:** EXPERIMENTAL #### Arm Group 2 **Intervention Names:** - Behavioral: KIDFIT Safe **Label:** KIDFIT Safe **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - KIDFIT Healthy **Description:** The KIDFIT Healthy intervention promotes the DASH diet, physical activity, limited screen time, and adequate sleep, through a combination of traditional in-person and electronic participant contacts. See NCT03405246 for details. **Name:** KIDFIT Healthy **Other Names:** - Intervention Group **Type:** BEHAVIORAL #### Intervention 2 **Arm Group Labels:** - KIDFIT Safe **Description:** The KIDFIT Safe active control provides electronic material about safe home environments and activities (e.g., sun screen, choking hazards, pet safety) for children. See NCT03405246 for details. **Name:** KIDFIT Safe **Other Names:** - Control Group **Type:** BEHAVIORAL ### Outcomes Module #### Primary Outcomes **Description:** abundances of gut microbial taxa, communities, and metabolic pathways activity **Measure:** Gut microbiome **Time Frame:** changes from baseline to 12 months **Description:** abundances of blood metabolites, metabolic networks, and metabolic pathways activity **Measure:** Blood metabolome **Time Frame:** changes from baseline to 12 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: - participating in KIDFIT (NCT03405246) Exclusion Criteria: - none **Maximum Age:** 5 Years **Minimum Age:** 3 Years **Sex:** ALL **Standard Ages:** - CHILD ### Contacts Locations Module #### Locations **Location 1:** **City:** Chicago **Country:** United States **Facility:** Northwestern University Department of Preventive Medicine **State:** Illinois **Zip:** 60611 #### Overall Officials **Official 1:** **Affiliation:** Northwestern University Feinberg School of Medicine and Ann & Robert H. Lurie Children's Hospital of Chicago **Name:** Amanda Marma Perak, MD MS **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **Description:** In accordance with the NIH policy to share genomic data from supported studies, raw and processed data from microbiomes, metabolomes, and relevant associated data will be submitted to public data repositories. **IPD Sharing:** YES ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009765 - Term: Obesity - ID: D000050177 - Term: Overweight - ID: D000044343 - Term: Overnutrition - ID: D000009748 - Term: Nutrition Disorders - ID: D000001835 - Term: Body Weight ### Condition Browse Module - Browse Branches - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC18 - Name: Nutritional and Metabolic Diseases - Abbrev: BC23 - Name: Symptoms and General Pathology ### Condition Browse Module - Browse Leaves - ID: M10024 - Name: Hypertension - Relevance: LOW - As Found: Unknown - ID: M12701 - Name: Obesity - Relevance: LOW - As Found: Unknown - ID: M30155 - Name: Pediatric Obesity - Relevance: HIGH - As Found: Pediatric 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: D000063766 - Term: Pediatric Obesity ### Intervention Browse Module - Browse Branches - Abbrev: Derm - Name: Dermatologic Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M16255 - Name: Sunscreening Agents - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04155879 **Brief Title:** Atrial Fibrillation Recurrence Following Cardioversion: the Role of Clinical Factors and Alpha Defensin Levels **Official Title:** Atrial Fibrillation Recurrence Following Cardioversion: the Role of Clinical Factors and Alpha Defensin Levels #### Organization Study ID Info **ID:** HYMC-19-0074 #### Organization **Class:** OTHER_GOV **Full Name:** Hillel Yaffe Medical Center ### Status Module #### Completion Date **Date:** 2022-11 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** NOT_YET_RECRUITING #### Last Update Post Date **Date:** 2019-11-07 **Type:** ACTUAL **Last Update Submit Date:** 2019-11-06 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2022-11 **Type:** ESTIMATED #### Start Date **Date:** 2019-11 **Type:** ESTIMATED **Status Verified Date:** 2019-11 #### Study First Post Date **Date:** 2019-11-07 **Type:** ACTUAL **Study First Submit Date:** 2019-09-11 **Study First Submit QC Date:** 2019-11-06 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER_GOV **Name:** Hillel Yaffe Medical Center #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** Atrial fibrillation and inflammation are strongly correlated. The aim of this study is to evaluate whether inflammation markers (alpha Defensin) predict maintenance of sinus rhythm following cardioversion. A secondary aim is to evaluate the role of Colchicine, an anti-inflammatory medication, in reducing the recurrence rate of atrial fibrillation. ### Conditions Module **Conditions:** - Atrial Fibrillation ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** DOUBLE **Masking Description:** Investigator and participants will be blinded regarding levels of anti-inflammatory markers **Who Masked:** - PARTICIPANT - INVESTIGATOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 300 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Cardioversion without treatment with Colchicine **Label:** Control Group **Type:** NO_INTERVENTION #### Arm Group 2 **Description:** This arm will undergo cardioversion followed by Colchicine (0.5 mg 2x per day) for six months **Intervention Names:** - Drug: Colchicine Tablets - Procedure: Cardioversion **Label:** Treatment group **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Treatment group **Description:** Administration of Colchicine at a dose of 0.5mg 2x a day for six months. **Name:** Colchicine Tablets **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Treatment group **Description:** Electrical or pharmacologic restoration of sinus rhythm **Name:** Cardioversion **Type:** PROCEDURE ### Outcomes Module #### Primary Outcomes **Description:** Atrial fibrillation recurrence rates over the next 12 months will be determined based on medical records and ECG documentation between treatment group (Colchicine) and control group. **Measure:** Recurrence of atrial fibrillation **Time Frame:** 12 months #### Secondary Outcomes **Description:** Alpha Defensin levels will be measured in patients with recurrence of atrial fibrillation and compared to levels in patients without recurrence. **Measure:** Alpha Defensin levels in patients with recurrence of atrial fibrillation **Time Frame:** 12 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Atrial fibrillation * Candidate for cardioversion Exclusion Criteria: * Colchicine allergy * Hepatic or renal failure **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Asaf Danon, MD, MSC **Phone:** 972-55-8867102 **Role:** CONTACT #### Locations **Location 1:** **City:** Hadera **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Asaf Danon, MD, MSC - **Phone:** 972-55-8867102 - **Role:** CONTACT **Country:** Israel **Facility:** Hillel Yaffe Medical Center **Zip:** 38100 ### IPD Sharing Statement Module **IPD Sharing:** NO ## 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 - ID: D000020969 - Term: Disease Attributes ### 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: M14850 - Name: Recurrence - Relevance: HIGH - As Found: Recurrence - ID: M4453 - Name: Arrhythmias, Cardiac - Relevance: LOW - As Found: Unknown - ID: M9419 - Name: Heart Diseases - Relevance: LOW - As Found: Unknown - ID: M22700 - Name: Disease Attributes - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000001281 - Term: Atrial Fibrillation - ID: D000012008 - Term: Recurrence ### Intervention Browse Module - Ancestors - ID: D000006074 - Term: Gout Suppressants - ID: D000018501 - Term: Antirheumatic Agents - ID: D000050257 - Term: Tubulin Modulators - ID: D000050256 - Term: Antimitotic Agents - ID: D000050258 - Term: Mitosis Modulators - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000000970 - Term: Antineoplastic Agents ### Intervention Browse Module - Browse Branches - Abbrev: ANeo - Name: Antineoplastic Agents - Abbrev: ARhu - Name: Antirheumatic Agents - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Infe - Name: Anti-Infective Agents ### Intervention Browse Module - Browse Leaves - ID: M6307 - Name: Colchicine - Relevance: HIGH - As Found: Positron - ID: M22859 - Name: Defensins - Relevance: LOW - As Found: Unknown - ID: M22861 - Name: alpha-Defensins - Relevance: LOW - As Found: Unknown - ID: M20604 - Name: Antirheumatic Agents - Relevance: LOW - As Found: Unknown - ID: M26197 - Name: Tubulin Modulators - Relevance: LOW - As Found: Unknown - ID: M26196 - Name: Antimitotic Agents - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000003078 - Term: Colchicine ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04934579 **Brief Title:** Rituximab,Methotrexate and Lenalidomide in Newly Diagnosed Primary Central Nervous System Lymphoma **Official Title:** Efficacy and Safety Study of Rituximab, Methotrexate and Lenalidomide Chemotherapy（R2-MTX） in Newly Diagnosed Primary Central Nervous System Lymphoma：a Single Arm, Multicenter, Phase 2 Study #### Organization Study ID Info **ID:** I2021001531 #### Organization **Class:** OTHER **Full Name:** Second Affiliated Hospital, School of Medicine, Zhejiang University ### Status Module #### Completion Date **Date:** 2022-11-15 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2022-11-23 **Type:** ACTUAL **Last Update Submit Date:** 2022-11-18 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2022-10-15 **Type:** ACTUAL #### Start Date **Date:** 2020-01-01 **Type:** ACTUAL **Status Verified Date:** 2022-11 #### Study First Post Date **Date:** 2021-06-22 **Type:** ACTUAL **Study First Submit Date:** 2021-06-14 **Study First Submit QC Date:** 2021-06-20 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Second Affiliated Hospital, School of Medicine, Zhejiang University #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Is US Export:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** It is a single arm, multicenter, phase 2 study to explore the efficacy and safety study of R2-MTX chemotherapy（Lenalidomide, Rituximab and Methotrexate）as first-line regimens in the treatment of newly diagnosed primary central nervous system lymphoma. Objective response rate is the primary endpoint. **Detailed Description:** This is a single arm, multicenter, phase 2 study designed to evaluate the efficacy and safety of rituximab, methotrexate and lenalidomide as first-line regimens in the treatment of newly primary central nervous system lymphoma. A total of 40 patients plan to participate in this study to receive a total 6 cycles of induction chemotherapy followed by 4 cycles of maintenance chemotherapy. Follow-ups should be taken up to the first 3 years. The primary endpoint is objective response rate (ORR) and secondary endpoint includes Progression free survival (PFS), overall survival (OS), and adverse events. ### Conditions Module **Conditions:** - Primary Central Nervous System Lymphoma ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 17 **Type:** ACTUAL **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Experimental arm will be treated with R2-MTX regimen(Lenalidomide plus Rituximab and Methotrexate) for 6 cycles as initiate induction.If the patients achieved complete remission（CR）or partial remission（PR）with additional whole-brain radiotherapy（WBRT）, they processed to R2 maintenance(Lenalidomide plus Rituximab) for 4 cycles. **Intervention Names:** - Drug: Rituximab - Drug: Lenalidomide - Drug: Methotrexate **Label:** R2-MTX **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - R2-MTX **Description:** 375mg/m2 intravenous infusion d1, every 3 weeks for 1 cycle, 6 cycles will be prescribed for induction therapy. 375mg/m2 intravenous infusion d1, every 8 weeks for 1 cycle, 4 cycles will be prescribed for maintenance therapy. **Name:** Rituximab **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - R2-MTX **Description:** 25mg orally d1-10 every 3 weeks for 1 cycle, 6 cycles will be prescribed for induction therapy. 25mg orally d1-14,d29-42 every 8 weeks for 1 cycle, 4 cycles will be prescribed for maintenance therapy. **Name:** Lenalidomide **Type:** DRUG #### Intervention 3 **Arm Group Labels:** - R2-MTX **Description:** 3.5g/m2 intravenous infusion for 4 hours in d1, every 21 days for 1 cycle, 6 cycles will be prescribed. **Name:** Methotrexate **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** The objective response rate is defined as the proportion of patients with a response of complete response(CR) or partial response(PR). **Measure:** Objective response rate(ORR) **Time Frame:** At the end of Cycle 6 chemotherapy (each cycle is 21 days), assessed up to 18 weeks. #### Secondary Outcomes **Description:** From date of patients sign informed consent until the date of progression or death or the date of last follow-up time, whichever came first, assessed up to 3 years **Measure:** Progression free survival **Time Frame:** 3 years **Description:** From date of patients sign informed consent until the date of death or the date of last follow-up time, whichever came first, assessed up to 3 years **Measure:** Overall survival **Time Frame:** 3 years **Description:** Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 **Measure:** Treatment-related adverse events **Time Frame:** 1 year ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Histologically confirmed Primary Central Nervous System (CNS) lymphoma 2. Age range 18-75 years old. 3. Eastern Cooperative Oncology Group performance status 0 to 3. 4. Previously untreated. Patients treated with steroid alone are eligible. 5. Patient's who are not planned to undergo consolidation with autologous hematopoietic stem cell transplantation（HSCT）. 6. Measurable disease was defined as at least ≥1.0cm in short-diameter by MRI. 7. Life expectancy of ≥ 3 months (in the opinion of the investigator). 8. Participants must be able to understand and be willing to sign a written informed consent document. 9. Women of reproductive potential must agree to use highly effective methods of birth control during the period of therapy and for 6 months after the last dose of the study drug. Men who are sexually active must agree to use highly effective contraception during the period of therapy and for 6 months after the last dose. 10. Women of childbearing potential must have a negative plasma pregnancy test upon study entry. 11. Adequate renal function: Estimated glomerular filtration rate (GFR) or estimated creatinine clearance (CrCl) ≥ 50 mL/min;Serum creatinine ≤ 2 times the upper limit of normal. 12. Adequate liver functions: Transaminase (AST/ALT) \< 3 X upper normal value \& Bilirubin \< 2 X upper normal value. 13. Adequate hematological function: hemoglobin ≥ 9 g/dL absolute neutrophil count (ANC) ≥ 1,500/μL and platelet count ≥ 75,000/μL. Exclusion Criteria: 1. Patient with systemic, non-CNS lymphoma metastatic to the CNS. 2. Patient is concurrently using other approved or investigational antineoplastic agents. 3. Presence of active hepatitis B virus(HBV) infection (HBsAg positive and HBV-DNA≥ 104), hepatitis C virus(HCV) infection, acquired and congenital immunodeficiency diseases include but not limited to HIV. 4. Patient is allergic to components of the study drug. 5. Patient has an active concurrent malignancy requiring active therapy. 6. Patient has significant abnormalities on screening electrocardiogram (EKG) and active and significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, uncontrolled congestive heart failure, uncontrolled hypertension, valvular disease, pericarditis, or myocardial infarction within 6 months of screening. 7. Patient is known to have an uncontrolled active systemic infection. 8. Patient has a life-threatening illness, medical condition, or organ system dysfunction that, in the opinion of the investigator, could compromise the subject's safety or put the study outcomes at undue risk. 9. Women who are pregnant or nursing (lactating), where pregnancy is defined as a state of a female after conception until the termination of gestation, confirmed by a positive plasma human chorionic gonadotropin(hCG) laboratory test of \> 5 mIU/mL. 10. The patient is unwell or unable to participate in all required study evaluations and procedures. 11. Drug abuse, medical, psychological or social conditions which may interfering with subjects' participation in the study or evaluation of the results. 12. Patients considered unsuitable to participate in the study by the researchers. **Maximum Age:** 75 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Hangzhou **Country:** China **Facility:** 2nd Affiliated Hospital, School of Medicine, Zhejiang University **State:** Zhejiang **Zip:** 310009 ### IPD Sharing Statement Module **IPD Sharing:** NO ## 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 ### 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: HIGH - As Found: Lymphoma - 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: T3543 - Name: Lymphosarcoma - Relevance: HIGH - As Found: Lymphoma - ID: T4686 - Name: Primary Central Nervous System Lymphoma - Relevance: HIGH - As Found: Primary Central Nervous System Lymphoma ### Condition Browse Module - Meshes - ID: D000008223 - Term: 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 - ID: D000000020 - Term: Abortifacient Agents, Nonsteroidal - ID: D000000019 - Term: Abortifacient Agents - ID: D000012102 - Term: Reproductive Control Agents - ID: D000000964 - Term: Antimetabolites, Antineoplastic - ID: D000000963 - Term: Antimetabolites - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000003879 - Term: Dermatologic Agents - ID: D000004791 - Term: Enzyme Inhibitors - ID: D000005493 - Term: Folic Acid Antagonists - ID: D000007166 - Term: Immunosuppressive Agents - ID: D000019384 - Term: Nucleic Acid Synthesis Inhibitors - ID: D000020533 - Term: Angiogenesis Inhibitors - ID: D000043924 - Term: Angiogenesis Modulating Agents - ID: D000006133 - Term: Growth Substances - ID: D000006131 - Term: Growth Inhibitors ### Intervention Browse Module - Browse Branches - Abbrev: ANeo - Name: Antineoplastic Agents - Abbrev: ARhu - Name: Antirheumatic Agents - Abbrev: Derm - Name: Dermatologic Agents - Abbrev: Repr - Name: Reproductive Control Agents - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Micro - Name: Micronutrients - Abbrev: Hemat - Name: Hematinics - Abbrev: Vi - Name: Vitamins ### Intervention Browse Module - Browse Leaves - ID: M11703 - Name: Methotrexate - Relevance: HIGH - As Found: Breast Cancer - ID: M373 - Name: Rituximab - Relevance: HIGH - As Found: Healthy - ID: M1725 - Name: Lenalidomide - Relevance: HIGH - As Found: Respiratory - 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 - ID: M4281 - Name: Antimetabolites - Relevance: LOW - As Found: Unknown - ID: M7074 - Name: Dermatologic Agents - Relevance: LOW - As Found: Unknown - ID: M7951 - Name: Enzyme Inhibitors - Relevance: LOW - As Found: Unknown - ID: M8618 - Name: Folic Acid - Relevance: LOW - As Found: Unknown - ID: M17546 - Name: Vitamin B Complex - Relevance: LOW - As Found: Unknown - ID: M8619 - Name: Folic Acid Antagonists - Relevance: LOW - As Found: Unknown - ID: M10212 - Name: Immunosuppressive Agents - Relevance: LOW - As Found: Unknown - ID: M22318 - Name: Angiogenesis Inhibitors - Relevance: LOW - As Found: Unknown - ID: M9231 - Name: Growth Inhibitors - Relevance: LOW - As Found: Unknown - ID: T447 - Name: Folinic Acid - 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: D000069283 - Term: Rituximab - ID: D000008727 - Term: Methotrexate - ID: D000077269 - Term: Lenalidomide ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00095979 **Brief Title:** Ixabepilone in Treating Patients With Recurrent or Persistent Endometrial Cancer **Official Title:** A Phase II Evaluation of Ixabepilone (BMS-247550) [NCI-Supplied Agent, NSC #710428]) in the Treatment of Recurrent or Persistent Endometrial Carcinoma #### Organization Study ID Info **ID:** NCI-2012-02628 #### Organization **Class:** NIH **Full Name:** National Cancer Institute (NCI) #### Secondary ID Infos **Domain:** CTRP (Clinical Trial Reporting Program) **ID:** NCI-2012-02628 **Type:** REGISTRY **ID:** CDR0000391849 **Domain:** Gynecologic Oncology Group **ID:** GOG-0129P **Type:** OTHER **Domain:** CTEP **ID:** GOG-0129P **Type:** OTHER **ID:** U10CA027469 **Link:** https://reporter.nih.gov/quickSearch/U10CA027469 **Type:** NIH ### Status Module #### Completion Date **Date:** 2009-07 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2019-07-24 **Type:** ACTUAL **Last Update Submit Date:** 2019-07-22 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2009-07 **Type:** ACTUAL #### Results First Post Date **Date:** 2015-05-21 **Type:** ESTIMATED **Results First Submit Date:** 2015-05-05 **Results First Submit QC Date:** 2015-05-05 #### Start Date **Date:** 2005-05 **Status Verified Date:** 2019-07 #### Study First Post Date **Date:** 2004-11-09 **Type:** ESTIMATED **Study First Submit Date:** 2004-11-09 **Study First Submit QC Date:** 2004-11-08 ### Sponsor Collaborators Module #### Collaborators **Class:** NETWORK **Name:** Gynecologic Oncology Group #### Lead Sponsor **Class:** NIH **Name:** National Cancer Institute (NCI) #### Responsible Party **Type:** SPONSOR ### Description Module **Brief Summary:** Drugs used in chemotherapy, such as ixabepilone, work in different ways to stop tumor cells from dividing so they stop growing or die. This phase II trial is studying how well ixabepilone works in treating patients with recurrent or persistent endometrial cancer. **Detailed Description:** PRIMARY OBJECTIVES: I. Determine the response rate in patients with recurrent or persistent endometrial adenocarcinoma treated with ixabepilone. II. Determine the nature and degree of toxicity of this drug in these patients. OUTLINE: This is a multicenter study. Patients receive ixabepilone IV over 3 hours on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months for 2 years and then every 6 months for 3 years. PROJECTED ACCRUAL: A total of 19-51 patients will be accrued for this study within 2.5 years. ### Conditions Module **Conditions:** - Endometrial Adenocarcinoma - Recurrent Endometrial Carcinoma - Stage IV Endometrial Carcinoma ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 52 **Type:** ACTUAL **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Patients receive ixabepilone IV over 3 hours on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. **Intervention Names:** - Drug: ixabepilone **Label:** Treatment (ixabepilone) **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Treatment (ixabepilone) **Description:** Given IV **Name:** ixabepilone **Other Names:** - BMS-247550 - epothilone B lactam - Ixempra **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** RECIST 1.0 defines complete response as the disappearance of all target lesions and non-target lesions and no evidence of new lesions documented by two disease assessments at least 4 weeks apart. Partial response is defined as at least a 30% decrease in the sum of longest dimensions (LD) of all target measurable lesions taking as reference the baseline sum of LD. There can be no unequivocal progression of non-target lesions and no new lesions. Documentation by two disease assessments at least 4 weeks apart is required. In the case where the ONLY target lesion is a solitary pelvic mass measured by physical exam, which is not radiographically measurable, a 50% decrease in the LD is required. These patients will have their response classified according to the definitions stated above. Complete and partial responses are included in the objective tumor response rate. **Measure:** Tumor Response **Time Frame:** Every other cycle for first 6 months; then every six months thereafter until completion of study treatment; and at any other time if clinically indicated based on symptoms or physical signs suggestive of progressive disease **Measure:** Frequency and Severity of Observed Adverse Effects Associated With Protocol Therapy (CTCAE Version 3) **Time Frame:** Every cycle until completion of study treatment up to 30 days after stopping study treatment (average length of data collection = 4 months) #### Secondary Outcomes **Description:** Progression is defined according to RECIST v1.0 as at least a 20% increase in the sum of LD target lesions taking as reference the smallest sum LD recorded since study entry, the appearance of one or more new lesions, death due to disease without prior objective documentation of progression, global deterioration in health status attributable to the disease requiring a change in therapy without objective evidence of progression, or unequivocal progression of existing non-target lesions. **Measure:** Progression-free Survival **Time Frame:** From study entry to disease progression, death or date of last contact, whichever occurs first, up to 5 years of follow-up. **Description:** Overall survival is defined as the duration of time from study entry to time of death or the date of last contact. **Measure:** Overall Survival **Time Frame:** From study entry to death or last contact, up to 5 years of follow-up. ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Histologically confirmed endometrial adenocarcinoma * Recurrent or persistent disease * Histologic confirmation of the original primary tumor is required * Not amenable to management with any of the following: * Surgery * Radiotherapy * Higher priority or standard chemotherapy * Measurable disease * At least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques (e.g., palpation, plain x-ray, CT scan, or MRI) OR ≥ 10 mm by spiral CT scan * At least 1 target lesion * Tumors within a previously irradiated field are designated as non-target lesions * Disease in an irradiated field as the only site of measurable disease is acceptable as a target lesion only if there has been clear progression of the lesion at least 90 days after completion of radiotherapy * Received 1, and only 1, prior chemotherapy regimen (e.g., high-dose therapy, consolidation, or extended therapy administered after surgery or non-surgical assessment) for management of endometrial adenocarcinoma * Ineligible for a higher priority Gynecologic Oncology Group (GOG) protocol (e.g., any active GOG phase III study for the same patient population) * Performance status - GOG 0-2 * Absolute neutrophil count ≥ 1,500/mm\^3 * Platelet count ≥ 100,000/mm\^3 * Bilirubin ≤ 1.5 times upper limit of normal (ULN) * AST (aspartate aminotransferase) ≤ 2.5 times ULN * Alkaline phosphatase ≤ 2.5 times ULN * Creatinine ≤ 1.5 times ULN * Sensory or motor neuropathy ≤ grade 1 * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No active infection requiring antibiotics * No other invasive malignancies within the past 5 years except non-melanoma skin cancer * At least 3 weeks since prior biologic or immunologic agents directed at the malignant tumor * One prior non-cytotoxic\* (biologic or cytostatic) regimen for management of recurrent or persistent disease allowed * See Disease Characteristics * Prior paclitaxel or docetaxel allowed * Recovered from prior chemotherapy * No more than 1 prior cytotoxic chemotherapy regimen (either single or combination drug therapy) * No prior ixabepilone * At least 1 week since prior hormonal therapy directed at the malignant tumor * Continuation of hormone replacement therapy allowed * See Disease Characteristics * Recovered from prior radiotherapy * Recovered from prior surgery * At least 3 weeks since other prior therapy directed at the malignant tumor * No prior cancer treatment that contraindicates study therapy **Sex:** FEMALE **Standard Ages:** - CHILD - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Philadelphia **Country:** United States **Facility:** Gynecologic Oncology Group **State:** Pennsylvania **Zip:** 19103 #### Overall Officials **Official 1:** **Affiliation:** Gynecologic Oncology Group **Name:** Don Dizon **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: D000020969 - Term: Disease Attributes - ID: D000010335 - Term: Pathologic Processes - ID: D000014594 - Term: Uterine Neoplasms - ID: D000005833 - Term: Genital Neoplasms, Female - ID: D000014565 - Term: Urogenital Neoplasms - ID: D000009371 - Term: Neoplasms by Site - ID: D000014591 - Term: Uterine Diseases - 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: BC04 - Name: Neoplasms - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: BXS - Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions ### Condition Browse Module - Browse Leaves - ID: M5534 - Name: Carcinoma - Relevance: HIGH - As Found: Carcinoma - ID: M3585 - Name: Adenocarcinoma - Relevance: LOW - As Found: Unknown - ID: M14850 - Name: Recurrence - Relevance: HIGH - As Found: Recurrent - ID: M19235 - Name: Endometrial Neoplasms - Relevance: HIGH - As Found: Endometrial Carcinoma - 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: M22700 - Name: Disease Attributes - Relevance: LOW - As Found: Unknown - ID: M17342 - Name: Uterine Neoplasms - Relevance: LOW - As Found: Unknown - ID: M8945 - Name: Genital Neoplasms, Female - Relevance: LOW - As Found: Unknown - ID: M17315 - Name: Urogenital Neoplasms - Relevance: LOW - As Found: Unknown - ID: M17339 - Name: Uterine Diseases - 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 ### Condition Browse Module - Meshes - ID: D000002277 - Term: Carcinoma - ID: D000016889 - Term: Endometrial Neoplasms - ID: D000012008 - Term: Recurrence ### Intervention Browse Module - Ancestors - ID: D000050257 - Term: Tubulin Modulators - ID: D000050256 - Term: Antimitotic Agents - ID: D000050258 - Term: Mitosis Modulators - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000000970 - Term: Antineoplastic Agents ### Intervention Browse Module - Browse Branches - Abbrev: Infe - Name: Anti-Infective Agents - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: ANeo - Name: Antineoplastic Agents ### Intervention Browse Module - Browse Leaves - ID: M10789 - Name: Lactams - Relevance: LOW - As Found: Unknown - ID: M24405 - Name: Epothilones - Relevance: HIGH - As Found: Breakthrough - ID: M209799 - Name: Epothilone B - Relevance: HIGH - As Found: Annuloplasty - ID: M26197 - Name: Tubulin Modulators - Relevance: LOW - As Found: Unknown - ID: M26196 - Name: Antimitotic Agents - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000034261 - Term: Epothilones - ID: C000093788 - Term: Epothilone B ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module #### Event Groups **Group ID:** EG000 **Title:** Ixabepilone **Description:** Ixabepilone 40 mg/m2 administered as 3-hour infusion on day 1 of a 21-day cycle until disease progression or adverse effects prohibit further treatment **ID:** EG000 **Other Num Affected:** 50 **Other Num at Risk:** 50 **Serious Number Affected:** 25 **Serious Number At Risk:** 50 **Title:** Ixabepilone **Frequency Threshold:** 0 #### Other Events **Term:** Allergic Reaction/Hypersensitivity **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Immune system disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Rhinitis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Immune system disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Hearing (Without Monitoring Program) **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Ear and labyrinth disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Tinnitus **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Ear and labyrinth disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Neutrophils **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Platelets **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Leukocytes **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Lymphopenia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Hemoglobin **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Supraventricular Tachycardia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Ventricular Arrhythmia - Pvcs **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Hypertension **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Hypotension **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Inr **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Sweating **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Patient Odor **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Fever **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Weight Loss **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Rigors/Chills **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Fatigue **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Insomnia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Nail Changes **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Hair Loss/Alopecia (Scalp Or Body) **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Bruising **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Rash **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Dry Skin **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Pruritus **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Flushing **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Hyperpigmentation **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Ulceration **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Hot Flashes **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Endocrine disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Diabetes **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Endocrine disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Hypoparathyroidism **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Endocrine disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Hyperthyroidism **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Endocrine disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Hypothyroidism **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Endocrine disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Esophagitis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Heartburn **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Ascites **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Leak, Gi - Rectum **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Ileus **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Dysphagia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Taste Alteration **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Dry Mouth **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Mucositis (Functional/Sympt) - Oral Cavity **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Obstruction, Gi - Small Bowel Nos **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Mucositis (Clinical Exam) - Oral Cavity **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Mucositis (Clinical Exam) - Esophagus **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Vomiting **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Anorexia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Dehydration **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Constipation **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Nausea **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Diarrhea **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Hemorrhage, Gu - Urinary Nos **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Hemorrhage, Gu - Vagina **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Hemorrhage, Gi - Rectum **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Hemorrhage, Gi - Upper Gi Nos **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Hemorrhage/Pulmonary - Nose **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Hemorrhage, Gu - Bladder **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Inf W/Gr 3 Or 4 Anc: Blood **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** CTCAE (3.0) **Term:** Inf W/Gr 3 Or 4 Anc: Middle Ear **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** CTCAE (3.0) **Term:** Inf W/Nml Or Gr 1 Or 2 Anc: Upper Airway Nos **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** CTCAE (3.0) **Term:** Inf W/Nml Or Gr 1 Or 2 Anc: Oral Cavity-Gums **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** CTCAE (3.0) **Term:** Inf W/Nml Or Gr 1 Or 2 Anc: Catheter-Related **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** CTCAE (3.0) **Term:** Febrile Neutropenia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** CTCAE (3.0) **Term:** Inf W/Nml Or Gr 1 Or 2 Anc: Urinary Tract Nos **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** CTCAE (3.0) **Term:** Infection - Other **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** CTCAE (3.0) **Term:** Inf W/Nml Or Gr 1 Or 2 Anc: Conjunctiva **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** CTCAE (3.0) **Term:** Inf W/Nml Or Gr 1 Or 2 Anc: Bronchus **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** CTCAE (3.0) **Term:** Inf Unknown Anc: Urinary Tract Nos **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** CTCAE (3.0) **Term:** Inf Unknown Anc: Bladder (Urinary) **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** CTCAE (3.0) **Term:** Inf Unknown Anc: Lip/Perioral **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** CTCAE (3.0) **Term:** Inf W/Gr 3 Or 4 Anc: Upper Airway Nos **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** CTCAE (3.0) **Term:** Inf W/Nml Or Gr 1 Or 2 Anc: Bladder **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** CTCAE (3.0) **Term:** Inf W/Gr 3 Or 4 Anc: Urinary Tract Nos **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** CTCAE (3.0) **Term:** Edema: Limb **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Ast **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Gfr **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Proteinuria **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Hemoglobinuria **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Creatinine **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Hypoalbuminemia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Alt **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Alkaline Phosphatase **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Bilirubin **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Hyponatremia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Hypernatremia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Hypocalcemia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Hyperkalemia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Hyperglycemia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Hypokalemia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Hypoglycemia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Hypomagnesemia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Joint-Function **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Arthritis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Muscle Weakness - Whole Body/Generalized **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Muscle Weakness - Left-Sided **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Muscle Weakness - Extremity-Lower **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Mood Alteration - Depression **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Mood Alteration - Anxiety **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Ataxia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Confusion **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Memory Impairment **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Dizziness **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Neuropathy-Sensory **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Neuropathy-Motor **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Ocular/Visual - Other **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Eye disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Uveitis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Eye disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Watery Eye **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Eye disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Dry Eye **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Eye disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Flashing Lights/Floaters **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Eye disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Blurred Vision **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Eye disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Eyelid Dysfunction **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Eye disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Pain: Pelvis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Pain: Breast **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Pain: Vagina **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Pain: Chest /Thorax Nos **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Pain: Chest Wall **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Pain: Eye **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Pain: Head/Headache **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Pain: Extremity-Limb **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Pain: Back **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Pain: Joint **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Pain: Bone **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Pain: Kidney **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Pain: Bladder **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Pain: Pain Nos **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Pain: Stomach **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Pain: Oral Cavity **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Pain: Abdominal Pain Nos **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Pain: Middle Ear **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Pain: Tumor **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Pain: Muscle **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Pain: Neuralgia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Voice Changes **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Hypoxia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Hiccoughs **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Cough **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Pneumonitis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Pleural Effusion **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Dyspnea **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Leak, Gu - Vagina **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Cystitis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Urinary Retention **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Obstruction, Gu - Ureter **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Incontinence, Urinary **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Bladder Spasm **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Urinary Frequency **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Vaginal Discharge **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Reproductive system and breast disorders **Source Vocabulary:** CTCAE (3.0) **Term:** Thrombosis/Thrombus/Embolism **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** CTCAE (3.0) #### Serious Events **Term:** Neutrophils **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** CTCAE (3.0) ##### Stats **Group ID:** EG000 **Num Affected:** 4 **Num At Risk:** 50 **Term:** Hemoglobin **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** CTCAE (3.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 50 **Term:** S/N Arrhythmia: Atrial Fibrillation **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** CTCAE (3.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 50 **Term:** Fatigue **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (3.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 50 **Term:** Death No Ctcae Term - Disease Progression Nos **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (3.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 50 **Term:** Vomiting **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (3.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 50 **Term:** Anorexia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (3.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 50 **Term:** Nausea **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (3.0) ##### Stats **Group ID:** EG000 **Num Affected:** 3 **Num At Risk:** 50 **Term:** Inf W/Gr 3 Or 4 Anc: Blood **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** CTCAE (3.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 50 **Term:** Febrile Neutropenia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** CTCAE (3.0) ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 50 **Term:** Creatinine **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** CTCAE (3.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 50 **Term:** Hypoalbuminemia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** CTCAE (3.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 50 **Term:** Hyponatremia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** CTCAE (3.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 50 **Term:** Syncope **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** CTCAE (3.0) ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 50 **Term:** Mood Alteration - Depression **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** CTCAE (3.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 50 **Term:** Memory Impairment **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** CTCAE (3.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 50 **Term:** Dizziness **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** CTCAE (3.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 50 **Term:** Pain: Abdominal Pain Nos **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (3.0) ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 50 **Term:** Pain: Tumor **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (3.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 50 **Term:** Hypoxia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** CTCAE (3.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 50 **Term:** Thrombosis/Thrombus/Embolism **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** CTCAE (3.0) ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 50 **Time Frame:** All Adverse Events (AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. Average length of data collection = 4 months. ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 50 **Units:** Participants ### Group **ID:** BG000 **Title:** Ixabepilone **Description:** Ixabepilone 40 mg/m2 administered as 3-hour infusion on day 1 of a 21-day cycle until disease progression or adverse effects prohibit further treatment ### Measure #### Measurement **Group ID:** BG000 **Spread:** 9.4 **Value:** 64.8 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 0 **Class Title:** 20-29 years #### Measurement **Group ID:** BG000 **Value:** 0 **Class Title:** 30-39 years #### Measurement **Group ID:** BG000 **Value:** 2 **Class Title:** 40-49 years #### Measurement **Group ID:** BG000 **Value:** 11 **Class Title:** 50-59 years #### Measurement **Group ID:** BG000 **Value:** 19 **Class Title:** 60-69 years #### Measurement **Group ID:** BG000 **Value:** 16 **Class Title:** 70-79 years #### Measurement **Group ID:** BG000 **Value:** 2 **Class Title:** 80-89 years ### Measure #### Measurement **Group ID:** BG000 **Value:** 50 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 0 **Category Title:** Male **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 50 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 1 **Class Title:** Adenocarcinoma, Unspecified #### Measurement **Group ID:** BG000 **Value:** 1 **Class Title:** Clear Cell Carcinoma #### Measurement **Group ID:** BG000 **Value:** 22 **Class Title:** Endometrioid Adenocarcinoma #### Measurement **Group ID:** BG000 **Value:** 4 **Class Title:** Mixed Epithelial Carcinoma #### Measurement **Group ID:** BG000 **Value:** 21 **Class Title:** Serous Adenocarcinoma #### Measurement **Group ID:** BG000 **Value:** 1 **Class Title:** Carcinosarcoma-homologous **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:** 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:** International Federation of Gynecology and Obstetrics (FIGO) Stage Recurrent/Persistent **Unit of Measure:** participants ### Measure 5 **Parameter Type:** NUMBER **Title:** Histologic Type **Unit of Measure:** participants **Population Description:** Eligible and treated patients ## Results Section - More Information Module ### Certain Agreement **Restriction Type:** LTE60 **Restrictive Agreement:** True ### Point of Contact **Email:** [email protected] **Organization:** NRG Oncology Statistics and Data Management Center - Buffalo **Phone:** 716-845-7733 **Title:** Angela M. Kuras, Associate Director of Data Management ## Results Section - Outcome Measures Module ### Outcome Measure 1 ### Outcome Measure 2 ### Outcome Measure 3 ### Outcome Measure 4 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 7 - **Spread:** - **Upper Limit:** 100 - **Value:** 12 **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 9 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 14 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 17 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 7 - **Comment:** - **Group ID:** OG004 - **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:** 7 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 14 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 12 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **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:** 29 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 6 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **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:** 4 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **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:** 0 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG004 - **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:** 2 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG004 - **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 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG004 - **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 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 15 - **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:** 1 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **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:** 21 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **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 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 12 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG004 - **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:** 0 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG004 - **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:** 0 - **Comment:** - **Group ID:** OG004 - **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:** 2 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 8 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG004 - **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:** 2 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **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 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG004 - **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 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 19 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 7 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **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 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG004 - **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:** 3 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **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 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **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:** 4 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG004 - **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:** 23 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG004 - **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 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** #### Outcome Measure 3 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 2.8 - **Spread:** - **Upper Limit:** 4.2 - **Value:** 3.1 **Title:** #### Outcome Measure 4 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 6.3 - **Spread:** - **Upper Limit:** 11.9 - **Value:** 8.8 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** RECIST 1.0 defines complete response as the disappearance of all target lesions and non-target lesions and no evidence of new lesions documented by two disease assessments at least 4 weeks apart. Partial response is defined as at least a 30% decrease in the sum of longest dimensions (LD) of all target measurable lesions taking as reference the baseline sum of LD. There can be no unequivocal progression of non-target lesions and no new lesions. Documentation by two disease assessments at least 4 weeks apart is required. In the case where the ONLY target lesion is a solitary pelvic mass measured by physical exam, which is not radiographically measurable, a 50% decrease in the LD is required. These patients will have their response classified according to the definitions stated above. Complete and partial responses are included in the objective tumor response rate. **Dispersion Type:** 90% Confidence Interval **Parameter Type:** NUMBER **Population Description:** Eligible and Treated Patients **Reporting Status:** POSTED **Time Frame:** Every other cycle for first 6 months; then every six months thereafter until completion of study treatment; and at any other time if clinically indicated based on symptoms or physical signs suggestive of progressive disease **Title:** Tumor Response **Type:** PRIMARY **Unit of Measure:** percentage of participants ##### Group **Description:** Ixabepilone 40 mg/m2 administered as 3-hour infusion on day 1 of a 21-day cycle until disease progression or adverse effects prohibit further treatment **ID:** OG000 **Title:** Ixabepilone #### Outcome Measure 2 **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Eligible and treated patients **Reporting Status:** POSTED **Time Frame:** Every cycle until completion of study treatment up to 30 days after stopping study treatment (average length of data collection = 4 months) **Title:** Frequency and Severity of Observed Adverse Effects Associated With Protocol Therapy (CTCAE Version 3) **Type:** PRIMARY **Unit of Measure:** Participants ##### Group **Description:** Number of patients who experienced a grade 1 event using Common Terminology Criteria for Adverse Events (CTCAE version 3). **ID:** OG000 **Title:** Grade 1 ##### Group **Description:** Number of patients who experienced a grade 2 event using Common Terminology Criteria for Adverse Events (CTCAE version 3). **ID:** OG001 **Title:** Grade 2 ##### Group **Description:** Number of patients who experienced a grade 3 event using Common Terminology Criteria for Adverse Events (CTCAE version 3). **ID:** OG002 **Title:** Grade 3 ##### Group **Description:** Number of patients who experienced a grade 4 event using Common Terminology Criteria for Adverse Events (CTCAE version 3). **ID:** OG003 **Title:** Grade 4 ##### Group **Description:** Number of patients who experienced a grade 5 event using Common Terminology Criteria for Adverse Events (CTCAE version 3). **ID:** OG004 **Title:** Grade 5 #### Outcome Measure 3 **Description:** Progression is defined according to RECIST v1.0 as at least a 20% increase in the sum of LD target lesions taking as reference the smallest sum LD recorded since study entry, the appearance of one or more new lesions, death due to disease without prior objective documentation of progression, global deterioration in health status attributable to the disease requiring a change in therapy without objective evidence of progression, or unequivocal progression of existing non-target lesions. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEDIAN **Population Description:** Eligible and Treated Patients **Reporting Status:** POSTED **Time Frame:** From study entry to disease progression, death or date of last contact, whichever occurs first, up to 5 years of follow-up. **Title:** Progression-free Survival **Type:** SECONDARY **Unit of Measure:** months ##### Group **Description:** Ixabepilone 40 mg/m2 administered as 3-hour infusion on day 1 of a 21-day cycle until disease progression or adverse effects prohibit further treatment **ID:** OG000 **Title:** Ixabepilone #### Outcome Measure 4 **Description:** Overall survival is defined as the duration of time from study entry to time of death or the date of last contact. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEDIAN **Population Description:** Eligible and treated patients **Reporting Status:** POSTED **Time Frame:** From study entry to death or last contact, up to 5 years of follow-up. **Title:** Overall Survival **Type:** SECONDARY **Unit of Measure:** months ##### Group **Description:** Ixabepilone 40 mg/m2 administered as 3-hour infusion on day 1 of a 21-day cycle until disease progression or adverse effects prohibit further treatment **ID:** OG000 **Title:** Ixabepilone ### Participant Flow Module #### Group **Description:** Ixabepilone 40 mg/m2 administered as 3-hour infusion on day 1 of a 21-day cycle until disease progression or adverse effects prohibit further treatment **ID:** FG000 **Title:** Ixabepilone #### Period **Title:** Overall Study ##### Withdraw **Type:** Ineligible: Second primary cancer site ###### Reason **Group ID:** FG000 **Number of Subjects:** 2 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 52 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 50 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 2 **Recruitment Details:** The study was activated on 5/2/2005 and closed to accrual on 1/3/2008 (suspended from 4/3/2006 to 4/1/2007). **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT05438979 **Brief Title:** Joint Health Study **Official Title:** Auburn University Joint Health Study #### Organization Study ID Info **ID:** 22-151 CFB #### Organization **Class:** OTHER **Full Name:** Auburn University ### Status Module #### Completion Date **Date:** 2024-12-31 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2023-08-16 **Type:** ACTUAL **Last Update Submit Date:** 2023-08-15 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2024-06-30 **Type:** ESTIMATED #### Start Date **Date:** 2022-07-01 **Type:** ACTUAL **Status Verified Date:** 2023-08 #### Study First Post Date **Date:** 2022-06-30 **Type:** ACTUAL **Study First Submit Date:** 2022-06-01 **Study First Submit QC Date:** 2022-06-28 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Auburn University #### Responsible Party **Investigator Affiliation:** Auburn University **Investigator Full Name:** Jennifer L. Robinson, Ph.D. **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:** Natural dietary health supplements that may improve quality of life by relieving joint discomfort have been of increasing interest. Recent studies have demonstrated promising effects of one such supplement - calcium fructoborate (CFB). Preliminary evidence suggests that CFB may reduce joint discomfort, however, few well-powered studies have been conducted to assess the true effects of this supplement. In this study, conducted virtually, we will examine changes in joint discomfort over a 90 day period. Participants will be randomized to receive either 216mg CFB or placebo (i.e., 216mg microcellulose) to take every day for the study period. **Detailed Description:** There has been increasing interest in natural dietary supplements other than glucosamine and/or chondroitin that may support healthy joints. Recent studies have demonstrated promising effects of calcium fructoborate (CFB), a generally-recognized-as-safe (GRAS) material and a key active ingredient in several commercially popular joint supplements, due to its potential to acutely as well as chronically improve symptoms of joint discomfort, possibly due to its anti-inflammatory properties. Clinical trials have demonstrated converging evidence that CFB improves joint health outcomes, but inadequate sample size has been a limiting factor of most studies to date, especially in terms of sub-domain and/or sub-group analyses within common joint pain/health inventories such as the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) and McGill Pain Questionnaire assessment tools. Here, we propose a higher N (N \> 300) study to examine the long-term effects of a daily 216mg morning dose of CFB on measures of pain, discomfort, and quality of life. CFB has been marketed and consumed at this dosage for over 17 years with over 5 billion servings having been provided to people with no reported adverse events. Most recently, the European Food Safety Authority has deemed CFB safe for the adult population (excluding pregnant and lactating women due to lack of data) at levels up to 220mg/day (3.14mg/kg bodyweight per day). Participants will be randomized to receive either 216mg CFB or placebo (i.e., 216mg microcellulose) to take every day for 90 days. On the first, 5th, 14th, 21st, 28th, 60th, and 90th days, participants will take a check-in questionnaire via Qualtrics. The survey will be composed of questionnaires that broadly cover joint pain, activities of daily living, sleep, and general well-being. Compliance checks will be administered daily via the participant's smartphone using the application MetricWire. This study will be conducted in a double-blind fashion, such that the experimental team and the participants are unaware of group assignment (216mg CFB vs. placebo). Blinding information will be held by the study sponsor, VDF FutureCeuticals, Inc. Group assignment will be determined by stratified permuted block (a form of covariate-adaptive randomization) to equal group sizes, and equal distribution of males/females in each group ### Conditions Module **Conditions:** - Effect of Drug **Keywords:** - calcium fructoborate - virtual study - joint pain - knee pain - internet - joint health ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** Participants will be randomly assigned to one of two groups - calcium fructoborate (CFB) or placebo. ##### Masking Info **Masking:** DOUBLE **Masking Description:** Blinding information will be held by the study sponsor, VDF FutureCeuticals, Inc. The study will be conducted in a double-blind fashion such that both the investigators and the participants are unaware of their assignment. Unblinding will only occur once the study has been completed. **Who Masked:** - PARTICIPANT - INVESTIGATOR **Primary Purpose:** OTHER #### Enrollment Info **Count:** 300 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** The placebo will be a simple microcellulose, which is generally-recognized-as-safe (GRAS) and commonly used in food products. **Intervention Names:** - Dietary Supplement: Placebo **Label:** Placebo **Type:** PLACEBO_COMPARATOR #### Arm Group 2 **Description:** Calcium Fructoborate (CFB), is a proprietary, safe generally-recognized-as-safe (GRAS) supplement. The only content of the supplement is CFB - there are no excipients, binders, or flow agents, nor are there any other materials. 216mg of CFB will be administered daily for 90 days. **Intervention Names:** - Dietary Supplement: Calcium Fructoborate **Label:** Calcium Fructoborate **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Placebo **Description:** Placebo for comparison to CFB **Name:** Placebo **Type:** DIETARY_SUPPLEMENT #### Intervention 2 **Arm Group Labels:** - Calcium Fructoborate **Description:** 216mg CFB **Name:** Calcium Fructoborate **Other Names:** - CFB **Type:** DIETARY_SUPPLEMENT ### Outcomes Module #### Other Outcomes **Description:** The investigators will assess compliance via daily questionnaires delivered to the participant's smartphone. Compliance will be determined by affirmative responses to daily questions as to whether participants have taken their study materials. To calculate compliance, we will add all affirmative responses (out of 90) and divide by 90 (scale is from 0 (not compliant) to 1 (100% compliant)). **Measure:** Compliance **Time Frame:** Daily for the duration of the study (approximately 90 days) #### Primary Outcomes **Description:** We will be administering the Western Ontario and McMaster Universities Osteoarthritis (WOMAC; scored 0-240 with higher scores indicating more discomfort) throughout the course of the study. We expect that WOMAC scores will change in as little as 5 days in the CFB group compared to the Placebo group. Furthermore, we hypothesize that these changes will persist throughout the entire 90 days for the CFB group. **Measure:** WOMAC Assessment **Time Frame:** The WOMAC is administered at baseline, and at days 5, 14, 21, 28, 60, and 90. **Description:** We will be administering the McGill Pain Questionnaire (scored 0-220, with higher scores indicating more discomfort) throughout the course of the study. We expect that McGill Pain Questionnaire scores will change in as little as 5 days in the CFB group compared to the Placebo group. Furthermore, we hypothesize that these changes will persist throughout the entire 90 days for the CFB group. **Measure:** McGill Pain Questionnaire **Time Frame:** The McGill Pain Questionnaire is administered at baseline, and at days 5, 14, 21, 28, 60, and 90. #### Secondary Outcomes **Description:** The investigators will assess changes in self-reported pain a participant had on a daily basis for the entire duration of the study via a daily question asked using a smartphone application. This assessment will be based on a scale of 0-9 with higher scores indicating greater pain. **Measure:** Daily Self-Reported Pain **Time Frame:** The daily pain question will be administered every day for the duration of the study (approximately 90 days) **Description:** The investigators will assess changes in the amount of sleep a participant had on a daily basis for the entire duration of the study via a single daily question asking about the number of hours of sleep the participant had the night before. **Measure:** Daily Self-Reported Sleep **Time Frame:** The question will be administered daily for the duration of the study (approximately 90 days) ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Between 40-65 years of age; 2. Self-reported or medically diagnosed knee joint pain for \> 3 months (chronic); 3. Diagnosis of osteoarthritis of the knee; 4. No diagnosed psychiatric or neurological condition; 5. Not taking antibiotics; 6. Not taking any other joint health supplement 7. Not taking prescription medications for OA or joint discomfort for the last 3 months 8. No use of NSAIDS or other pain relievers for two (2) weeks prior to enrollment in the study and who are willing to make best efforts to refrain from use of same throughout the study 9. Has reliable internet service; 10. Some computer literacy; 11. Has a smartphone; and 12. Has a laptop, desktop computer, or iPad. Exclusion Criteria: 1. \<40 or \>65 years of age; 2. Does not have osteoarthritis of the knee; 3. Diabetes or other metabolic disorders; 4. Inflammatory and/or infectious health conditions; 6) Participants medically diagnosed with rheumatoid arthritis; 7) Participants with cardiovascular diseases; 8) Participants with liver and/or kidney problems; 9) Participants who are pregnant; 10) Health conditions that would prevent the participant from successfully completing the study (i.e., motor control conditions such as Parkinson's; psychiatric conditions such as ADHD); 11) Use of antibiotics 1 month prior to the enrollment in the study; 12) Physician prescribed use of pharmaceutical medications for OA or joint discomfort within 3 months prior to enrollment in this study; 13) Any joint injury in the 6-months prior to the enrollment in the clinical trial; 14) Unreliable or no internet access/service; 15) Unable to use a smartphone or lacking the computer literacy needed to complete the study 16) No laptop, desktop, or iPad that would allow for the completion of the study tasks. **Healthy Volunteers:** True **Maximum Age:** 65 Years **Minimum Age:** 40 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Jennifer L Robinson, Ph.D. **Phone:** 3345212177 **Role:** CONTACT #### Locations **Location 1:** **City:** Auburn **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Jennifer L Robinson, Ph.D. - **Phone:** 334-521-2177 - **Role:** CONTACT **Country:** United States **Facility:** Auburn University **State:** Alabama **Status:** RECRUITING **Zip:** 36849 ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Mogosanu GD, Bita A, Bejenaru LE, Bejenaru C, Croitoru O, Rau G, Rogoveanu OC, Florescu DN, Neamtu J, Scorei ID, Scorei RI. Calcium Fructoborate for Bone and Cardiovascular Health. Biol Trace Elem Res. 2016 Aug;172(2):277-281. doi: 10.1007/s12011-015-0590-2. Epub 2015 Dec 21. **PMID:** 26686846 **Citation:** Pietrzkowski Z, Phelan MJ, Keller R, Shu C, Argumedo R, Reyes-Izquierdo T. Short-term efficacy of calcium fructoborate on subjects with knee discomfort: a comparative, double-blind, placebo-controlled clinical study. Clin Interv Aging. 2014 Jun 5;9:895-9. doi: 10.2147/CIA.S64590. eCollection 2014. Erratum In: Clin Interv Aging. 2021 Feb 02;16:203. **PMID:** 24940052 **Citation:** Price AK, de Godoy MRC, Harper TA, Knap KE, Joslyn S, Pietrzkowski Z, Cross BK, Detweiler KB, Swanson KS. Effects of dietary calcium fructoborate supplementation on joint comfort and flexibility and serum inflammatory markers in dogs with osteoarthritis. J Anim Sci. 2017 Jul;95(7):2907-2916. doi: 10.2527/jas.2017.1588. **PMID:** 28727103 **Citation:** Scorei ID, Scorei RI. Calcium fructoborate helps control inflammation associated with diminished bone health. Biol Trace Elem Res. 2013 Dec;155(3):315-21. doi: 10.1007/s12011-013-9800-y. Epub 2013 Aug 28. **PMID:** 23982445 **Citation:** Scorei R, Cimpoiasu VM, Iordachescu D. In vitro evaluation of the antioxidant activity of calcium fructoborate. Biol Trace Elem Res. 2005 Nov;107(2):127-34. doi: 10.1385/BTER:107:2:127. **PMID:** 16217137 **Citation:** Scorei RI, Ciofrangeanu C, Ion R, Cimpean A, Galateanu B, Mitran V, Iordachescu D. In vitro effects of calcium fructoborate upon production of inflammatory mediators by LPS-stimulated RAW 264.7 macrophages. Biol Trace Elem Res. 2010 Jun;135(1-3):334-44. doi: 10.1007/s12011-009-8488-5. Epub 2009 Aug 11. **PMID:** 19669712 **Citation:** Scorei RI, Rotaru P. Calcium fructoborate--potential anti-inflammatory agent. Biol Trace Elem Res. 2011 Dec;143(3):1223-38. doi: 10.1007/s12011-011-8972-6. Epub 2011 Jan 28. **PMID:** 21274653 **Citation:** Scorei R, Mitrut P, Petrisor I, Scorei I. A double-blind, placebo-controlled pilot study to evaluate the effect of calcium fructoborate on systemic inflammation and dyslipidemia markers for middle-aged people with primary osteoarthritis. Biol Trace Elem Res. 2011 Dec;144(1-3):253-63. doi: 10.1007/s12011-011-9083-0. Epub 2011 May 24. **PMID:** 21607703 **Citation:** EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA); Turck D, Castenmiller J, De Henauw S, Hirsch-Ernst KI, Kearney J, Maciuk A, Mangelsdorf I, McArdle HJ, Naska A, Pelaez C, Pentieva K, Siani A, Thies F, Tsabouri S, Vinceti M, Cubadda F, Frenzel T, Heinonen M, Marchelli R, Neuhauser-Berthold M, Poulsen M, Maradona MP, Schlatter JR, van Loveren H, Rossi A, Knutsen HK. Safety of calcium fructoborate as a novel food pursuant to Regulation (EU) 2015/2283. EFSA J. 2021 Jul 5;19(7):e06661. doi: 10.2903/j.efsa.2021.6661. eCollection 2021 Jul. **PMID:** 34257728 **Citation:** Bellamy N, Buchanan WW, Goldsmith CH, Campbell J, Stitt LW. Validation study of WOMAC: a health status instrument for measuring clinically important patient relevant outcomes to antirheumatic drug therapy in patients with osteoarthritis of the hip or knee. J Rheumatol. 1988 Dec;15(12):1833-40. **PMID:** 3068365 **Citation:** Melzack R. The McGill Pain Questionnaire: major properties and scoring methods. Pain. 1975 Sep;1(3):277-299. doi: 10.1016/0304-3959(75)90044-5. **PMID:** 1235985 **Citation:** Dworkin RH, Turk DC, Revicki DA, Harding G, Coyne KS, Peirce-Sandner S, Bhagwat D, Everton D, Burke LB, Cowan P, Farrar JT, Hertz S, Max MB, Rappaport BA, Melzack R. Development and initial validation of an expanded and revised version of the Short-form McGill Pain Questionnaire (SF-MPQ-2). Pain. 2009 Jul;144(1-2):35-42. doi: 10.1016/j.pain.2009.02.007. Epub 2009 Apr 7. **PMID:** 19356853 ## Derived Section ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC05 - Name: Musculoskeletal Diseases ### Condition Browse Module - Browse Leaves - ID: M13066 - Name: Pain - Relevance: LOW - As Found: Unknown - ID: M20833 - Name: Arthralgia - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Ancestors - ID: D000077264 - Term: Calcium-Regulating Hormones and Agents - ID: D000045505 - Term: Physiological Effects of Drugs ### Intervention Browse Module - Browse Branches - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: BDCA - Name: Bone Density Conservation Agents ### Intervention Browse Module - Browse Leaves - ID: M5381 - Name: Calcium - Relevance: HIGH - As Found: Radiation - ID: M5398 - Name: Calcium, Dietary - Relevance: LOW - As Found: Unknown - ID: M9789 - Name: Hormones - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000002118 - Term: Calcium ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT02108379 **Brief Title:** Compliance and Usability Study Evaluating RHINIX™ Nasal Filters **Official Title:** An Open-label Outpatient In-season Study Assessing Compliance and Usability of Rhinix™ Nasal Filters #### Organization Study ID Info **ID:** 00002 #### Organization **Class:** OTHER **Full Name:** University of Aarhus ### Status Module #### Completion Date **Date:** 2014-07 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2014-11-11 **Type:** ESTIMATED **Last Update Submit Date:** 2014-11-10 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2014-07 **Type:** ACTUAL #### Start Date **Date:** 2014-05 **Status Verified Date:** 2014-03 #### Study First Post Date **Date:** 2014-04-09 **Type:** ESTIMATED **Study First Submit Date:** 2014-03-18 **Study First Submit QC Date:** 2014-04-04 ### Sponsor Collaborators Module #### Collaborators **Class:** UNKNOWN **Name:** Rhinix ApS **Class:** UNKNOWN **Name:** Astma-Allergi Danmark #### Lead Sponsor **Class:** OTHER **Name:** University of Aarhus #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** This study will investigate usability and compliance related to rhinix nasal filters for the treatment of seasonal allergic rhinitis (hay fever) during the natural grass pollen season in Denmark. ### Conditions Module **Conditions:** - Seasonal Allergic Rhinitis ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 1073 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** All included will receive rhinix nasal filters **Intervention Names:** - Device: Rhinix Nasal Filters **Label:** Rhinix Nasal Filters **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Rhinix Nasal Filters **Name:** Rhinix Nasal Filters **Type:** DEVICE ### Outcomes Module #### Other Outcomes **Description:** In week 1: To assess the correlation between symptom severity at screening and likelihood of answering that they will definitely/likely continue using the product. **Measure:** Week 1: Correlation of use and allergy severiy **Time Frame:** One assessment at the end of the 1st week of use **Description:** Week 2: To assess the correlation between symptom severity at screening and likelihood of answering that they will definitely/likely continue using the product. **Measure:** Week 2: Correlation between use and allergy severity **Time Frame:** One assessment at the end of the 2nd week of use **Description:** In week 1: To assess whether use of RHINIX has led to a perceived decrease in use of medication. **Measure:** Week 1: Perceived decrease in medication **Time Frame:** One assessment after the 1st week of use **Description:** Week 2: To assess whether use of RHINIX has led to a perceived decrease in use of medication. **Measure:** Week 2: Perceived decrease in medication **Time Frame:** One assessment after 2nd week of use #### Primary Outcomes **Description:** In week 1: The proportion of subjects that rate that they will definitely or are likely to continue using RHINIX after the study is over given that they have stated that they have tried the device. **Measure:** Week 1 likelihood of continued use of RHINIX after study end. **Time Frame:** 1 assessment at the end of the 1st week of use. **Description:** In week 2: The proportion of subjects that rate that they will definitely or are likely to continue using RHINIX after the study is over given that they have stated that they have tried the device. **Measure:** Week 2 likelihood of continued use of RHINIX after study end. **Time Frame:** 1 assessment at the end of the 2nd week of use. #### Secondary Outcomes **Description:** In week 1: The proportion of subjects who are completely or somewhat satisfied with RHINIX given that they have used the product. **Measure:** Week 1 Satisfaction with RHINIX **Time Frame:** 1 assessment at the end of the 1st week **Description:** In week 2: The proportion of subjects who are completely or somewhat satisfied with RHINIX given that they have used the product. **Measure:** Week 2 satisfaction with RHINIX **Time Frame:** One assessment at the end of the 2nd week **Description:** In week 1: The proportion of subjects who state that RHINIX has helped "to a very high degree" or "to a high degree" in controlling their hay fever symptoms given that they have used the product **Measure:** Week 1: RHINIX Control **Time Frame:** One assessment at the end of the 1st week of use **Description:** In week 2: The proportion of subjects who state that RHINIX has helped "to a very high degree" or "to a high degree" in controlling their hay fever symptoms given that they have used the product **Measure:** Week 2: RHINIX Control **Time Frame:** One assessment at the end of the 2nd week of use. ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Motivated to try a different treatment approach to seasonal allergic rhinitis (documented by answering the call-out by Astma-Allergi Danmark) * Indicates having seasonal allergic rhinitis to grass via online questionnaire * Informed consent (by email acceptance after having received information on the trial) * Assess to internet and email Exclusion Criteria: * Improper fit of the Rhinix™ device **Maximum Age:** 65 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Aarhus **Country:** Denmark **Facility:** Aarhus University, School of Public Health, Department of Environmental & Occupational Medicine **Zip:** 8000 #### Overall Officials **Official 1:** **Affiliation:** Aarhus University, School of Public Health, Dept. of Environmental & Occupational Medicine **Name:** Torben Sigsgaard, Prof MD **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### References **Citation:** Kenney P, Hilberg O, Sigsgaard T. Clinical Application of Nasal Filters: An Observational Study on the Usability of Nasal Filters in Managing Seasonal Allergic Rhinitis. J Allergy Clin Immunol Pract. 2016 May-Jun;4(3):445-452.e4. doi: 10.1016/j.jaip.2016.01.003. Epub 2016 Feb 18. **PMID:** 26897304 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000012141 - Term: Respiratory Tract Infections - ID: D000007239 - Term: Infections - ID: D000009668 - Term: Nose Diseases - ID: D000012140 - Term: Respiratory Tract Diseases - ID: D000010038 - Term: Otorhinolaryngologic Diseases - ID: D000012130 - Term: Respiratory Hypersensitivity - ID: D000006969 - Term: Hypersensitivity, Immediate - ID: D000006967 - Term: Hypersensitivity - ID: D000007154 - Term: Immune System Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC01 - Name: Infections - Abbrev: BC08 - Name: Respiratory Tract (Lung and Bronchial) Diseases - Abbrev: BC09 - Name: Ear, Nose, and Throat Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC20 - Name: Immune System Diseases - Abbrev: BC23 - Name: Symptoms and General Pathology ### Condition Browse Module - Browse Leaves - ID: M15049 - Name: Rhinitis - Relevance: HIGH - As Found: Rhinitis - ID: M30545 - Name: Rhinitis, Allergic - Relevance: HIGH - As Found: Allergic Rhinitis - ID: M9345 - Name: Rhinitis, Allergic, Seasonal - Relevance: HIGH - As Found: Seasonal Allergic Rhinitis - 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: M12604 - Name: Nose 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 - ID: M10018 - Name: Hypersensitivity - Relevance: LOW - As Found: Unknown - ID: M14967 - Name: Respiratory Hypersensitivity - Relevance: LOW - As Found: Unknown - ID: M10020 - Name: Hypersensitivity, Immediate - Relevance: LOW - As Found: Unknown - ID: M10200 - Name: Immune System Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000012220 - Term: Rhinitis - ID: D000065631 - Term: Rhinitis, Allergic - ID: D000006255 - Term: Rhinitis, Allergic, Seasonal ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00839579 **Brief Title:** Cardiovascular Treatment **Official Title:** How Little Pain for Cardiac Gain? A Pilot Study #### Organization Study ID Info **ID:** 1x4min interval #### Organization **Class:** OTHER **Full Name:** Norwegian University of Science and Technology ### Status Module #### Completion Date **Date:** 2010-06 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2014-03-07 **Type:** ESTIMATED **Last Update Submit Date:** 2014-03-06 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2009-12 **Type:** ACTUAL #### Start Date **Date:** 2009-01 **Status Verified Date:** 2014-03 #### Study First Post Date **Date:** 2009-02-09 **Type:** ESTIMATED **Study First Submit Date:** 2009-02-06 **Study First Submit QC Date:** 2009-02-06 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Norwegian University of Science and Technology #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** Exercise training is proved to protect against premature cardiovascular mortality. Additionally there is evidence that relatively high exercise intensity may be an important factor for improving aerobic capacity and endothelial function in patients with post-infarction heart failure, metabolic syndrome, coronary artery disease, as well as in overweight and obese individuals. The aim of this study is to investigate the amount of high-intensity exercise needed to improve aerobic capacity and endothelial function. ### Conditions Module **Conditions:** - Obesity **Keywords:** - slightly overweight - males 35-45 years ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 26 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** 4x4minutes interval group **Intervention Names:** - Other: 1x4 min interval **Label:** 4x4min **Type:** EXPERIMENTAL #### Arm Group 2 **Intervention Names:** - Other: 1x4 min interval **Label:** 1x4min **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - 1x4min - 4x4min **Description:** Aerobic interval training **Name:** 1x4 min interval **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Measure:** Maximal oxygen consumption and endothelial function **Time Frame:** baseline and 12 weeks followup ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * BMI: 25-30 * Males, 35-45 years * Healthy **Healthy Volunteers:** True **Maximum Age:** 45 Years **Minimum Age:** 35 Years **Sex:** MALE **Standard Ages:** - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Trondheim **Country:** Norway **Facility:** Norwegian University of Science and Technology **Zip:** 7489 #### Overall Officials **Official 1:** **Affiliation:** Norwegian University of Science and Technology **Name:** Arnt E Tjønna, PhD **Role:** STUDY_CHAIR **Official 2:** **Affiliation:** Norwegian University of Science and Technology **Name:** Ulrik Wisløff, PhD **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### References **Citation:** Tjonna AE, Leinan IM, Bartnes AT, Jenssen BM, Gibala MJ, Winett RA, Wisloff U. Low- and high-volume of intensive endurance training significantly improves maximal oxygen uptake after 10-weeks of training in healthy men. PLoS One. 2013 May 29;8(5):e65382. doi: 10.1371/journal.pone.0065382. Print 2013. **PMID:** 23734250 ## Derived Section ### 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: LOW - As Found: Unknown - ID: M26186 - Name: Overweight - Relevance: LOW - As Found: Unknown - ID: M13066 - Name: Pain - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05487079 **Acronym:** DOP **Brief Title:** Identification and Characterization of Diabetes in Low-resource Populations **Official Title:** Identification and Characterization of Diabetes in Low-resource Populations #### Organization Study ID Info **ID:** RGMN210808 #### Organization **Class:** OTHER **Full Name:** MRC/UVRI and LSHTM Uganda Research Unit ### Status Module #### Completion Date **Date:** 2023-05-31 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2022-10-19 **Type:** ACTUAL **Last Update Submit Date:** 2022-10-17 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2023-05-31 **Type:** ESTIMATED #### Start Date **Date:** 2022-01-17 **Type:** ACTUAL **Status Verified Date:** 2022-10 #### Study First Post Date **Date:** 2022-08-04 **Type:** ACTUAL **Study First Submit Date:** 2022-08-03 **Study First Submit QC Date:** 2022-08-03 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** University of Exeter **Class:** OTHER_GOV **Name:** British Medical Research Council **Class:** OTHER_GOV **Name:** Department for International Development, United Kingdom #### Lead Sponsor **Class:** OTHER **Name:** MRC/UVRI and LSHTM Uganda Research Unit #### 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 true burden of diabetes in sub-Saharan Africa (SSA) is unknown as most of the countries do not have good quality data. As such, the overall estimate of diabetes prevalence is largely based on modelled estimates, which may not be accurate. Additionally, there is lack of clear guidance on which method and thresholds to use in the diagnosis of diabetes in African populations unlike in high income countries (HIC) where such guidance is clear. The limited data available shows that diabetes in Africa manifests differently for example occurring at younger age and in relatively lean individuals. Moreover, where the oral glucose tolerance test (OGTT) has been used to screen for diabetes, a significant proportion of individuals have isolated postprandial hyperglycaemia (IPH): The reasons for this differential manifestation are unclear and the diabetes progression of these unique phenotypes (for example in terms of risk of complications is unknown or response to treatment is unknown). Therefore, the overall aim of this research is to undertake a large study to determine the true prevalence of diabetes and identify/characterize the different phenotypes; 2) establish a cohort patients with diabetes to understand the natural course of these different phenotypes, including how they respond to treatment (i.e. do the IPH or thin diabetics progress at the same rate as obese, and are the currently used intervention/therapeutic approaches equally effective in the different phenotypes?). The collected data is likely to be directly relevant to an improved understanding of the cause and progression of diabetes, diagnostic test performance, and diabetes care in SSA, ultimately leading to better patient outcomes and well-being, as well as enhanced productivity. **Detailed Description:** The specific objectives will be to; (1) To determine the true prevalence of diabetes and prediabetes in a population-based cohort (2) To identify and characterize the different phenotypes of type 2 diabetes (3) To establish a base-line cohort of well-characterised people with diabetes to understand disease progression of the different phenotypes, including uptake and response to treatment. (4) To identify and recruit a cohort of non-diabetic volunteers (including prediabetes i.e., at high risk of developing diabetes) for longitudinal follow-up. Study setting: This will be a population-based survey nested within the General Population Cohort (GPC). The GPC is a rural population-based cohort study of people living within the 25 villages of Kyamulibwa sub-county of Kalungu District in rural southwest Uganda. The primary study will be conducted in Uganda. The study shall recruit from 2 sites (rural and urban areas) across the greater Masaka region in southwest Uganda in order to explore the differences in lifestyle, and how these influence prevalence of diabetes and its outcomes; General Population Cohort (GPC) in Kyamulibwa will provide the rural population, and the town of Lukaya the urban population. Both rural and urban sites are established research areas. The entire adult population of the GPC will be eligible for this survey. Data from the most recent Census (2020-2021) in the GPC shows that there are 8,864 adults (aged 18+) of the total population of 20,751 in Kyamulibwa. Eligibility: All adults aged 18 years and above will be invited to take part in the study. We will recruit all adults who are able to provide written informed consent and are residents at a household (i.e. not a temporary member with intent to leave) in either of the study areas. Individuals will be excluded from the study based on the following criteria: pregnant women (can participate six months after childbirth), live outside the geographical sampling frame for the relevant site or are unable to give informed consent, living outside the relevant site's catchment area. Sampling method: This study is powered to estimate the prevalence of diabetes and other primary outcomes like prediabetes Impaired fasting glycaemia (IFG), isolated postprandial hyperglycaemia (IPH), isolated-IFG and isolated-Impaired Glucose Tolerance) with sufficient precision. We have conservatively based our assumptions on results from the 2014 Ugandan nation-wide cross-sectional survey suggesting that the prevalence of IFG and diabetes in Uganda is 2% (95% CI: 1.5-2.5%) and 1.4% (95% CI: 0.9 - 1.9%) respectively.3 That survey detected dysglycaemia using fasting blood glucose alone, rather than OGTT. Applying a rule of thumb that the margin of error should not exceed 0.25 of the prevalence and based on the following assumptions: A margin of error of 0.5% (a margin of error of 0.5% to 1% would be acceptable for low prevalent conditions) and Diabetes prevalence of 5% (assuming OGTT would detect more cases of diabetes thus doubling the prevalence) and estimated 5% level of significance (z-value = 1.96). We aim to screen a minimum of 11700 adults across all sites; a minimum of 5,850 from each site. All the adults in Kyamulibwa- the rural site (8, 864) will be invited to take part in our survey. For Lukaya-the urban site; initially, 3 of the 5 cells will be randomly selected and all the adults in the selected cells (approximate total adult population of 6000) invited to take part in the survey. Recruitment will be restricted to individuals who reside within defined areas (villages). Enrollment: This study will consist of overlapping phases as described below: Phase One: Main baseline survey. This phase comprises the selection and training of survey team, community sensitisation, obtaining the consent of the study participants, and conducting the baseline survey. All consented individuals will be interviewed using a structured pre-tested questionnaire (Data Collection Form) by trained study staff to collect relevant information including; demographic, socioeconomic and lifestyle in the language understood by the patient. Thereafter, participants will undergo biophysical measurements (weight, height, waist and hip circumferences, Mid-upper arm circumference (MUAC) ) and blood pressure after which they will be invited to come to the research hub in the next days for blood sample collection after an overnight fast. Participants are required to have fasted for at least 8 hours and those who have not will be asked to come back another day in a fasting state. Blood sample collection will be done using standardised procedures. Venous whole blood will be used for HbA1C, complete blood count, genetics and malaria. Serum will be used for biochemistry and HIV. NaF blood tube will be used for fasting plasma glucose. hCG urine testing will be carried out on the urine samples collected. NB: Those with already clinically diagnosed diabetes and on treatment will come in fasted and baseline fasting samples taken off. They will not undergo OGTTT. Phase Two: This phase involves assessment of the reproducibility of diagnostic approaches, and comparing their general performance. From Phase I of the study, all those with dysglycaemia (diabetes; prediabetes; i-IFG and i-IGT) and age and sex-matched non-diabetic subjects (1:1) will be invited back to the research hub for further assessment. In Phase 2, the aim will be 1) to assess the reproducibility of the diagnostic tests, notably the OGTT; 2) to assess the burden of glycaemia through continuous glucose monitoring; 3) to identify participants for Phase 3 studies. Phase Three: This is aimed at assessing and describing any dysglycaemia clusters or phenotypes by comparing baseline characteristics and evaluating the distribution of various measures. Further tests may be done in the future to better understand the differences between the phenotypes. This phase involves utilisation of data generated from phases 1 and 2 to characterise individuals with dysglycaemia further: This is aimed at assessing and describing any dysglycaemia clusters or phenotypes by comparing baseline characteristics and evaluating the distribution of various measures inclusive of biochemical parameters (e.g., fasting and stimulated C-peptide), adiposity and anthropometric indices, continuous glucose measures in daily living. Further tests may be done at this level including vascular complications assessment, endogenous insulin secretion measurement, and exploration of the inflammatory and immune biomarker (including islet autoantibodies) profiles to better understand the differences between the phenotypes including Lean versus Non-lean, IPH vs IFG. Phase Four: Aimed at the creation of well-characterised diabetic and non-diabetic long-term cohorts. The newly diagnosed diabetes participants will be referred to the local diabetes clinics where they will be managed according to the Uganda Ministry of health guidelines. These patients will be followed up in clinics (supported by the research team) to study natural course, including response to treatment, and disease progression. The non-diabetic participants will be followed in a longitudinal study nested in the GPC to determine the incidence of diabetes. Data collected from the different clinical sites using the data collection form will be entered into a centralized data management tool (REDCap). All data will be anonymised before being stored in the data management system. Ethical consideration: All participants will be required to provide written informed consent before participating in the study. Refusal to participate will not affect the quality of care of the participants at the clinical sites. The study has received ethical clearance from the Uganda Virus Research Institute (GC/127/21/09/858) ### Conditions Module **Conditions:** - Diabetes **Keywords:** - Diabetes - Diabetes Complications - Pre-Diabetes - OGTT (Oral Glucose Tolerance Test) - Dysglycaemia - LMIC (Low Middle Income Countries) - Disease Progression - Treatment Outcomes ### Design Module #### Bio Spec **Description:** Urine Plasma Serum Whole Blood **Retention:** SAMPLES_WITH_DNA #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 11700 **Type:** ESTIMATED **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Diabetes will be defined as below (any or combination): 1. 2h-OGTT: ≥ 11.1 mmol/L 2. FPG (fasting plasma glucose): ≥ 7.0 mmol/L 3. HbA1c; ≥ 48 mmol/mol (6.5%) **Label:** Diabetic #### Arm Group 2 **Description:** Prediabetes will be defined as as below (any or combination) 1. 2h-OGTT is between 140 and 199 mg/dL (7.8-11.0 mmol/L) 2. FPG values is between 100 and 125 mg/dL (5.6-6.9 mmol/L) 3. HbA1c is between 42 and 47 mmol/mol (6.0 - 6.4%) **Label:** Pre-Diabetic #### Arm Group 3 **Description:** Normal glucose tolerance (NGT) 1. 2h-OGTT; \< 140 mg/dL (7.8 mmol/L). 2. FPG; \< 100 mg/dL (5.6 mmol/L) and 3. HbA1c; \< 42 mmol/mol **Label:** Non-Diabetics ### Outcomes Module #### Primary Outcomes **Description:** To determine the prevalence of diabetes defined by HbA1c, FPG and OGTT glucose To assess the reproducibility of the different diagnostic tests. **Measure:** Number of participants with diabetes and prediabetes **Time Frame:** 2 years **Description:** Identification and characterization of the different phenotypes of type 2 diabetes **Measure:** Number of distinct phenotypes of type 2 diabetes within this population **Time Frame:** 2 years #### Secondary Outcomes **Measure:** Number of individuals with diabetes that develop vascular complications **Time Frame:** 2 years **Measure:** Rate of progression of vascular disease within this population **Time Frame:** 2 years ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Age ≥ 18 years Signed informed consent * Willing to provide written informed consent Exclusion Criteria: * Pregnant women - can participate six months after childbirth * Living outside the geographical sampling frame for the relevant site * Unable to give informed consent **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Study participants are all Individuals aged 18 years or older, residing within the 25 villages of Kyamulibwa sub-county of Kalungu District and Lukaya town and willing to give informed consent. ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Isaac Sekitoleko, MSc **Phone:** 256701755373 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Viola M Mugamba, MBChB **Phone:** 256754676321 **Role:** CONTACT #### Locations **Location 1:** **City:** Entebbe **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Esther Nkiinzi, MPH - **Phone:** 256701951667 - **Role:** CONTACT **Country:** Uganda **Facility:** MRC/UVRI and LSHTM Uganda Research Unit **Status:** RECRUITING #### Overall Officials **Official 1:** **Affiliation:** MRC/UVRI AND LSHTM UGANDA and London School of Hygiene and Tropical Medicine **Name:** Moffat Nyirenda, PhD **Role:** PRINCIPAL_INVESTIGATOR **Official 2:** **Affiliation:** MRC/UVRI AND LSHTM UGANDA **Name:** Anxious J Niwaha, MSc **Role:** PRINCIPAL_INVESTIGATOR ## 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 - Abbrev: BC23 - Name: Symptoms and General Pathology ### Condition Browse Module - Browse Leaves - ID: M7115 - Name: Diabetes Mellitus - Relevance: HIGH - As Found: Diabetes - ID: M14117 - Name: Prediabetic State - Relevance: LOW - As Found: Unknown - ID: M20559 - Name: Disease Progression - Relevance: LOW - As Found: Unknown - ID: M20295 - Name: Glucose Intolerance - Relevance: LOW - As Found: Unknown - ID: M26004 - Name: Diabetes Complications - Relevance: LOW - As Found: Unknown - 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 ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04315779 **Brief Title:** Comparison of Two Different Approaches in the Surgical Treatment of Tubal Ectopic Pregnancy **Official Title:** Comparison of Conventional Laparoscopy and Natural Orifice Transluminal Endoscopic Surgery in the Surgical Treatment of Tubal Ectopic Pregnancy #### Organization Study ID Info **ID:** 20-2.1T/40 #### Organization **Class:** OTHER **Full Name:** Ege University ### Status Module #### Completion Date **Date:** 2021-05-19 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** RECRUITING #### Last Update Post Date **Date:** 2020-03-20 **Type:** ACTUAL **Last Update Submit Date:** 2020-03-18 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2021-02-19 **Type:** ESTIMATED #### Start Date **Date:** 2020-02-19 **Type:** ACTUAL **Status Verified Date:** 2020-03 #### Study First Post Date **Date:** 2020-03-20 **Type:** ACTUAL **Study First Submit Date:** 2020-03-17 **Study First Submit QC Date:** 2020-03-18 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Ege University #### Responsible Party **Investigator Affiliation:** Ege University **Investigator Full Name:** Gokay Ozceltik **Investigator Title:** MD **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False ### Description Module **Brief Summary:** In this study we aim to compare conventional laparoscopy and natural orifice transluminal endoscopic surgery in the surgical treatment of ectopic pregnancy. All the patients, with an indication of surgery for ectopic pregnancy, will be asked to participate in this clinical trial. Indication of surgery will be based on clinical findings, ultrasound scans and serum hcg levels. There will be no exclusion criteria. Duration of surgery, successful completion of the operation, intraoperative data and postoperative data will be collected. All the patients will be asked to fill out quality of recovery-40 (QoR-40) questionnaire and 36-item short form health survey (SF-36) before surgery. QoR-40 questionnaire will be repeated 24 hours after surgery and repeated every 24 hours until discharge. SF-36 will be repeated at 1-month follow-up visit. Patients will be also evaluated at postoperative 3-months, and female sexual function index will be asked to be filled-out. ### Conditions Module **Conditions:** - Ectopic Pregnancy **Keywords:** - natural orifice transluminal endoscopic surgery - laparoscopy - ectopic pregnancy - minimally invasive surgery - quality of life - sexual function ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 40 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** In this arm, patients will be treated via conventional laparoscopy **Intervention Names:** - Procedure: Salpingectomy **Label:** Conventional laparoscopy **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** In this arm, patients will be treated via transvaginal natural orifice transluminal endoscopic surgery **Intervention Names:** - Procedure: Salpingectomy **Label:** Transvaginal natural orifice transluminal endoscopic surgery **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Conventional laparoscopy - Transvaginal natural orifice transluminal endoscopic surgery **Description:** Patients will undergo removal of the affected tube **Name:** Salpingectomy **Type:** PROCEDURE ### Outcomes Module #### Primary Outcomes **Description:** The completion of the surgery with the route planned without having to change the surgical route **Measure:** Successful completion of surgery as intended **Time Frame:** Intraoperative, from the beginning to the end of surgical intervention **Measure:** Operating time **Time Frame:** Intraoperative **Measure:** Reoperation rate **Time Frame:** During follow-up, after surgery until hcg level drops below 5 U/L, up to 1 month **Measure:** Complication rate **Time Frame:** During follow-up, after surgery until hcg level drops below 5 U/L, up to 1 month #### Secondary Outcomes **Description:** The Quality of Recovery 40 questionnaire will be self-administered by patients at different time points **Measure:** Quality of Recovery-40 questionnaire **Time Frame:** Preoperatively and Postoperative every 24 hours until discharge, expected to be up to 3 days following surgery **Description:** Short form 36 item health survery (SF-36) questionnaire will be self-administered by patients at different time points **Measure:** Quality of life change **Time Frame:** Preoperative, Postoperative 1-month **Description:** Postoperative pain will be assessed on a 10-cm visual analog scale at different time points **Measure:** Postoperative pain scores **Time Frame:** Postoperative 2 hours, 6 hours, 12 hours, 24 hours, and every 24 hours until discharge (if the patient stays longer than 1 day at the hospital), , expected to be up to 3 days following surgery **Description:** Female sexual function index (FSFI) questionnaire will be self-administered by patients at postoperative 3-months **Measure:** Sexual function **Time Frame:** Postoperative 3 months **Description:** Patients will be routinely administered pethidine hydrochloride 3x50 mg parenteral on the day of surgery. Starting from postoperative day 1 patients will be administered paracetamol 500 mg oral upon their request. In case of inadequate pain relief and the need for additional analgesic use will ve recorded. **Measure:** The need for additional analgesic use **Time Frame:** Postoperative period until discharge, expected to be up to 3 days following surgery ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Adults over 18 years of age, * Diagnosis of tubal ectopic pregnancy * Patient's preference to undergo salpingectomy Exclusion Criteria: * Patients with contraindication to endoscopic surgery * Refusal to sign informed consent. **Minimum Age:** 18 Years **Sex:** FEMALE **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Gokay Ozceltik **Phone:** +905330922020 **Role:** CONTACT #### Locations **Location 1:** **City:** Bornova **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Gokay Ozceltik - **Phone:** +905330922020 - **Role:** CONTACT **Country:** Turkey **Facility:** Ege University University Hospital, Department of Obstetrics and Gynecology **State:** Izmir **Status:** RECRUITING **Zip:** 35100 ### IPD Sharing Statement Module **IPD Sharing:** UNDECIDED ## Derived Section ### Condition Browse Module - Ancestors - ID: D000001145 - Term: Arrhythmias, Cardiac - ID: D000006331 - Term: Heart Diseases - ID: D000002318 - Term: Cardiovascular Diseases - ID: D000075224 - Term: Cardiac Conduction System Disease - ID: D000010335 - Term: Pathologic Processes - ID: D000011248 - Term: Pregnancy Complications - ID: D000005261 - Term: Female Urogenital Diseases and Pregnancy Complications - ID: D000091642 - Term: Urogenital Diseases ### Condition Browse Module - Browse Branches - Abbrev: BXS - Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions - Abbrev: All - Name: All Conditions - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: BXM - Name: Behaviors and Mental Disorders - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M14147 - Name: Pregnancy, Ectopic - Relevance: HIGH - As Found: Ectopic Pregnancy - ID: M14150 - Name: Pregnancy, Tubal - Relevance: HIGH - As Found: Tubal Ectopic Pregnancy - ID: M8260 - Name: Cardiac Complexes, Premature - Relevance: HIGH - As Found: Ectopic - ID: M25869 - Name: Premature Birth - Relevance: LOW - As Found: Unknown - ID: M4453 - Name: Arrhythmias, Cardiac - Relevance: LOW - As Found: Unknown - ID: M9419 - Name: Heart Diseases - Relevance: LOW - As Found: Unknown - ID: M1472 - Name: Cardiac Conduction System Disease - 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: T6034 - Name: Quality of Life - Relevance: LOW - As Found: Unknown - ID: T2035 - Name: Ectopic Pregnancy - Relevance: HIGH - As Found: Ectopic Pregnancy ### Condition Browse Module - Meshes - ID: D000011271 - Term: Pregnancy, Ectopic - ID: D000011274 - Term: Pregnancy, Tubal - ID: D000005117 - Term: Cardiac Complexes, Premature ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT01815879 **Acronym:** MORE **Brief Title:** Metastatic Colorectal Cancer Liver Metastases Outcomes After Resin 90Y Microsphere Radioembolization in the USA Evaluation Project **Official Title:** Metastatic Colorectal Cancer Liver Metastases Outcomes After Resin 90Y Microsphere Radioembolization in the USA Evaluation Project #### Organization Study ID Info **ID:** MORE #### Organization **Class:** INDUSTRY **Full Name:** Sarah Cannon ### Status Module #### Expanded Access Info **Last Known Status:** ACTIVE_NOT_RECRUITING #### Last Update Post Date **Date:** 2013-03-21 **Type:** ESTIMATED **Last Update Submit Date:** 2013-03-20 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2013-06 **Type:** ESTIMATED #### Start Date **Date:** 2012-12 **Status Verified Date:** 2013-03 #### Study First Post Date **Date:** 2013-03-21 **Type:** ESTIMATED **Study First Submit Date:** 2012-12-18 **Study First Submit QC Date:** 2013-03-20 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** Sirtex Medical #### Lead Sponsor **Class:** INDUSTRY **Name:** Andrew Kennedy #### Responsible Party **Investigator Affiliation:** Sarah Cannon **Investigator Full Name:** Andrew Kennedy **Investigator Title:** Principal Investigator and Sponsor-Investigator **Type:** SPONSOR_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** Investigator initiated multi-institutional retrospective review of clinical and radiographic outcomes after 90Y resin microsphere radioembolization for metastatic colorectal liver metastases in the USA. The target is for at least 1,000 evaluable patients with 12+ weeks follow up. **Detailed Description:** Investigator initiated multi-institutional retrospective review of clinical and radiographic outcomes after 90Y resin microsphere radioembolization for metastatic colorectal liver metastases in the USA. The target is for at least 1,000 evaluable patients with 12+ weeks follow up. Objectives: Independent data collection and reporting of pre treatment and 12 week post treatment clinical, radiographic and radiation parameters and outcomes in patients treated in the USA from 2002-2010. Data beyond 12 weeks will be collected and highly desirable, however as a minimum all patients will have 12 week follow up. ### Conditions Module **Conditions:** - Colorectal Cancer - Liver Metastases **Keywords:** - metastatic colorectal cancer - liver metastases - 90Y resin microsphere radioembolization - retrospective data analysis ### Design Module #### Design Info **Observational Model:** CASE_ONLY **Time Perspective:** RETROSPECTIVE #### Enrollment Info **Count:** 1000 **Type:** ESTIMATED **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Retrospective review of clinical data on at least 1,000 evaluable US patients with 12+weeks follow up that were treated with 90Y resin microsphere radioembolization for metastatic colorectal liver metastases **Label:** Control Group ### Outcomes Module #### Primary Outcomes **Description:** Multiple systems monitored for side effects possibly related to liver radiotherapy. **Measure:** Adverse events at day 0-90 post 90Y therapy using CTCae 3.0 criteria. **Time Frame:** 3 months #### Secondary Outcomes **Description:** Pretreatment planning scans (-45 to -1 day) compared to post radiotherapy scans of the liver, PET/CT not recommended, prefer MRI with Gd or CT with contrast, 3 phase, with rescanning in similar fashion at day 90 post treatment. **Measure:** Radiographic response rate at 90 days (+/- 45 days) from treatment day, compared to pretreatment scans. **Time Frame:** 3 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Patients who received 90Y resin microsphere radioembolization for metastatic colorectal cancer with liver metastases between November 2010 and March 2011 in the USA. Patients must have at least 12 weeks of follow up. Exclusion Criteria: * Patients who received glass 90Y microsphere radioembolization for metastatic colorectal liver metastases. **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Patients with colorectal liver metastases in the USA treated with 90Y resin microsphere radioembolization ### Contacts Locations Module #### Locations **Location 1:** **City:** Nashville **Country:** United States **Facility:** Contact Sarah Cannon **State:** Tennessee **Zip:** 37203 #### Overall Officials **Official 1:** **Affiliation:** SCRI Development Innovations, LLC **Name:** Andrew S Kennedy, MD, FACRO **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000007414 - Term: Intestinal Neoplasms - ID: D000005770 - Term: Gastrointestinal Neoplasms - ID: D000004067 - Term: Digestive System Neoplasms - ID: D000009371 - Term: Neoplasms by Site - ID: D000009369 - Term: Neoplasms - ID: D000004066 - Term: Digestive System Diseases - ID: D000005767 - Term: Gastrointestinal Diseases - ID: D000003108 - Term: Colonic Diseases - ID: D000007410 - Term: Intestinal Diseases - ID: D000012002 - Term: Rectal Diseases - ID: D000009385 - Term: Neoplastic Processes - ID: D000010335 - Term: Pathologic Processes - ID: D000008107 - Term: Liver Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC06 - Name: Digestive System Diseases ### Condition Browse Module - Browse Leaves - ID: M12307 - Name: Neoplasm Metastasis - Relevance: HIGH - As Found: Metastases - ID: M17890 - Name: Colorectal Neoplasms - Relevance: HIGH - As Found: Colorectal Cancer - ID: M11113 - Name: Liver Neoplasms - Relevance: HIGH - As Found: Liver Metastases - ID: M10448 - Name: Intestinal 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: M6336 - Name: Colonic Diseases - Relevance: LOW - As Found: Unknown - ID: M10444 - Name: Intestinal Diseases - Relevance: LOW - As Found: Unknown - ID: M14844 - Name: Rectal Diseases - Relevance: LOW - As Found: Unknown - ID: M12330 - Name: Neoplastic Processes - Relevance: LOW - As Found: Unknown - ID: M11107 - Name: Liver Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000015179 - Term: Colorectal Neoplasms - ID: D000009362 - Term: Neoplasm Metastasis - ID: D000008113 - Term: Liver Neoplasms ### Intervention Browse Module - Browse Branches - Abbrev: Hemat - Name: Hematinics - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M11110 - Name: Liver Extracts - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00922779 **Brief Title:** A Study of Ribavirin in Combination With PEGASYS (Peginterferon Alfa-2a (40KD))in Patients With Chronic Hepatitis C **Official Title:** Safety and Tolerability of Ribavirin (RO 20-9963) in Combination With Peginterferon Alfa-2a (40 kD)in Patients With Chronic Hepatitis C #### Organization Study ID Info **ID:** ML16709 #### Organization **Class:** INDUSTRY **Full Name:** Hoffmann-La Roche ### Status Module #### Completion Date **Date:** 2012-06 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2016-01-20 **Type:** ESTIMATED **Last Update Submit Date:** 2015-12-11 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2012-06 **Type:** ACTUAL #### Results First Post Date **Date:** 2016-01-20 **Type:** ESTIMATED **Results First Submit Date:** 2015-12-11 **Results First Submit QC Date:** 2015-12-11 #### Start Date **Date:** 2002-06 **Status Verified Date:** 2015-12 #### Study First Post Date **Date:** 2009-06-17 **Type:** ESTIMATED **Study First Submit Date:** 2009-06-16 **Study First Submit QC Date:** 2009-06-16 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Hoffmann-La Roche #### Responsible Party **Type:** SPONSOR ### Description Module **Brief Summary:** This single arm study will evaluate the safety and tolerability of ribavirin in combination with PEGASYS in patients with chronic hepatitis C. Patients will receive ribavirin 800mg, or 1000-1200mg po daily, according to HCV genotype and body weight (\< and \>75kg)in combination with PEGASYS 180micrograms sc weekly. The anticipated time on study treatment is 3-12 months, and the target sample size is \>500 individuals. ### Conditions Module **Conditions:** - Hepatitis C, Chronic ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 6661 **Type:** ACTUAL **Phases:** - PHASE4 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Intervention Names:** - Drug: peginterferon alfa-2a [Pegasys] - Drug: ribavirin **Label:** 1 **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - 1 **Description:** 180micrograms sc weekly for 12-48 weeks **Name:** peginterferon alfa-2a [Pegasys] **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - 1 **Description:** 800mg, or 1000-1200mg, po daily (dependent on HCV genotype and body weight) **Name:** ribavirin **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** An AE was any untoward medical occurrence in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Number of participants with non-serious AEs were exclusive of serious AEs. **Measure:** Number of Participants With Non-Serious Adverse Events (AEs) And Serious Adverse Events (SAEs) **Time Frame:** From signing of informed consent up to end of study (up to Week 72) #### Secondary Outcomes **Description:** SVR at 24 weeks after end of therapy was defined as a negative result of HCV Ribonucleic Acid (HCV RNA) qualitative assay 24 weeks after end of therapy. Percentage of participants with SVR was calculated as \[number of participants with negative results of HCV RNA qualitative assay 24 weeks after end of therapy divided by the total number of participants analyzed\] multiplied by 100. The participants who failed to undergo tests at 24 weeks after completion of therapy were considered not amenable to therapy. **Measure:** Percentage of Participants With Sustained Virological Response (SVR) at 24 Weeks After End of Therapy **Time Frame:** 24 weeks after end of therapy (Week 72) **Description:** HCV RNA levels of \< 50 International Units per milliliter (IU/mL) were defined as undetectable HCV RNA. The percentage of participants with undetectable HCV RNA was calculated as \[number of participants with undetectable HCV RNA divided by the total number of participants analyzed\] multiplied by 100 for Weeks 12, 24 and 48. **Measure:** Percentage of Participants With Undetectable HCV RNA at Weeks 12, 24 and 48 After Therapy Initiation **Time Frame:** Weeks 12,24 and 48 After Therapy Initiation **Description:** Change in hemoglobin level (compared to baseline) was reported as "significant decrease", "Normal" (no change), "Increase", "Decrease", and "Missing". Significant decrease was defined as per Investigator's discretion. **Measure:** Percentage of Participants With Change in Hemoglobin Level **Time Frame:** Baseline, Weeks 2, 4, 8, 12, 24, 36, 48 and follow-up Weeks 4 (Week 52), 12 (Week 60), and 24 (Week 72) ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * adult patients, \>=18 years of age; * serological evidence of chronic hepatitis C; * detectable serum HCV-RNA; * liver biopsy findings consistent with a diagnosis of chronic hepatitis C. Exclusion Criteria: * history or other evidence of a medical condition associated with chronic liver disease other than HCV; * co-infection with active hepatitis A or B; * hepatocellular carcinoma; * patients with severe cardiovascular disease whose condition may worsen due to acute anemia. **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Arkhangelsk **Country:** Russian Federation **Zip:** 163000 **Location 2:** **City:** Barnaul **Country:** Russian Federation **Zip:** 656010 **Location 3:** **City:** Barnaul **Country:** Russian Federation **Zip:** 656045 **Location 4:** **City:** Blagoveshchensk **Country:** Russian Federation **Zip:** 675007 **Location 5:** **City:** Cheboksary **Country:** Russian Federation **Zip:** 428016 **Location 6:** **City:** Chelyabinsk **Country:** Russian Federation **Zip:** 454048 **Location 7:** **City:** Chelyabinsk **Country:** Russian Federation **Zip:** 454052 **Location 8:** **City:** Chelyabinsk **Country:** Russian Federation **Zip:** 454071 **Location 9:** **City:** Cherepovets **Country:** Russian Federation **Zip:** 162600 **Location 10:** **City:** Chita **Country:** Russian Federation **Zip:** 672090 **Location 11:** **City:** Ekaterinburg **Country:** Russian Federation **Zip:** 620020 **Location 12:** **City:** Ekaterinburg **Country:** Russian Federation **Zip:** 620042 **Location 13:** **City:** Ekaterinburg **Country:** Russian Federation **Zip:** 620102 **Location 14:** **City:** Irkutsk **Country:** Russian Federation **Zip:** 664043 **Location 15:** **City:** Irkutsk **Country:** Russian Federation **Zip:** 664047 **Location 16:** **City:** Irkutsk **Country:** Russian Federation **Zip:** 664079 **Location 17:** **City:** Izhevsk **Country:** Russian Federation **Zip:** 426067 **Location 18:** **City:** Kazan **Country:** Russian Federation **Zip:** 420097 **Location 19:** **City:** Kemerovo **Country:** Russian Federation **Zip:** 650000 **Location 20:** **City:** Kemerovo **Country:** Russian Federation **Zip:** 650036 **Location 21:** **City:** Kemerovo **Country:** Russian Federation **Zip:** 650099 **Location 22:** **City:** Khabarovsk **Country:** Russian Federation **Zip:** 680009 **Location 23:** **City:** Khabarovsk **Country:** Russian Federation **Zip:** 680022 **Location 24:** **City:** Khabarovsk **Country:** Russian Federation **Zip:** 680031 **Location 25:** **City:** Kirov **Country:** Russian Federation **Zip:** 610000 **Location 26:** **City:** Krasnodar **Country:** Russian Federation **Zip:** 350012 **Location 27:** **City:** Krasnodar **Country:** Russian Federation **Zip:** 350015 **Location 28:** **City:** Krasnodar **Country:** Russian Federation **Zip:** 350086 **Location 29:** **City:** Krasnoyarsk **Country:** Russian Federation **Zip:** 660022 **Location 30:** **City:** Krasnoyarsk **Country:** Russian Federation **Zip:** 660049 **Location 31:** **City:** Lipetsk **Country:** Russian Federation **Zip:** 398043 **Location 32:** **City:** Makhachkala **Country:** Russian Federation **Zip:** 367008 **Location 33:** **City:** Moscow **Country:** Russian Federation **Zip:** 103875 **Location 34:** **City:** Moscow **Country:** Russian Federation **Zip:** 105203 **Location 35:** **City:** Moscow **Country:** Russian Federation **Zip:** 109325 **Location 36:** **City:** Moscow **Country:** Russian Federation **Zip:** 111020 **Location 37:** **City:** Moscow **Country:** Russian Federation **Zip:** 111123 **Location 38:** **City:** Moscow **Country:** Russian Federation **Zip:** 115201 **Location 39:** **City:** Moscow **Country:** Russian Federation **Zip:** 115446 **Location 40:** **City:** Moscow **Country:** Russian Federation **Zip:** 115516 **Location 41:** **City:** Moscow **Country:** Russian Federation **Zip:** 115682 **Location 42:** **City:** Moscow **Country:** Russian Federation **Zip:** 119002 **Location 43:** **City:** Moscow **Country:** Russian Federation **Zip:** 119881 **Location 44:** **City:** Moscow **Country:** Russian Federation **Zip:** 121293 **Location 45:** **City:** Moscow **Country:** Russian Federation **Zip:** 123098 **Location 46:** **City:** Moscow **Country:** Russian Federation **Zip:** 123367 **Location 47:** **City:** Moscow **Country:** Russian Federation **Zip:** 125101 **Location 48:** **City:** Moscow **Country:** Russian Federation **Zip:** 125367 **Location 49:** **City:** Moscow **Country:** Russian Federation **Zip:** 127247 **Location 50:** **City:** Moscow **Country:** Russian Federation **Zip:** 129110 **Location 51:** **City:** Moscow **Country:** Russian Federation **Zip:** 143420 **Location 52:** **City:** Moscow **Country:** Russian Federation **Location 53:** **City:** Nizhny Novgorod **Country:** Russian Federation **Zip:** 603022 **Location 54:** **City:** Novokuznetsk **Country:** Russian Federation **Zip:** 654018 **Location 55:** **City:** Novokuznetsk **Country:** Russian Federation **Zip:** 654029 **Location 56:** **City:** Novosibirsk **Country:** Russian Federation **Zip:** 630016 **Location 57:** **City:** Novouralsk **Country:** Russian Federation **Zip:** 624130 **Location 58:** **City:** Omsk **Country:** Russian Federation **Zip:** 644010 **Location 59:** **City:** Orenburg **Country:** Russian Federation **Zip:** 460035 **Location 60:** **City:** Petropavlovsk-Kamchatskiy **Country:** Russian Federation **Zip:** 683003 **Location 61:** **City:** Rostov-na-donu **Country:** Russian Federation **Zip:** 344022 **Location 62:** **City:** Salekhard **Country:** Russian Federation **Zip:** 629001 **Location 63:** **City:** Samara **Country:** Russian Federation **Zip:** 443011 **Location 64:** **City:** Samara **Country:** Russian Federation **Zip:** 443021 **Location 65:** **City:** Saratov **Country:** Russian Federation **Zip:** 410026 **Location 66:** **City:** Saratov **Country:** Russian Federation **Zip:** 410028 **Location 67:** **City:** Saratov **Country:** Russian Federation **Zip:** 410040 **Location 68:** **City:** Soshi **Country:** Russian Federation **Zip:** 354057 **Location 69:** **City:** St Petersburg **Country:** Russian Federation **Zip:** 194044 **Location 70:** **City:** St Petersburg **Country:** Russian Federation **Zip:** 194291 **Location 71:** **City:** St Petersburg **Country:** Russian Federation **Zip:** 195067 **Location 72:** **City:** St Petersburg **Country:** Russian Federation **Zip:** 195275 **Location 73:** **City:** St Petersburg **Country:** Russian Federation **Zip:** 197022 **Location 74:** **City:** St Petersburg **Country:** Russian Federation **Zip:** 198103 **Location 75:** **City:** St Petersburg **Country:** Russian Federation **Zip:** 199034 **Location 76:** **City:** St. Petersburg **Country:** Russian Federation **Zip:** 191167 **Location 77:** **City:** Stavropol **Country:** Russian Federation **Zip:** 355017 **Location 78:** **City:** Surgut **Country:** Russian Federation **Zip:** 628400 **Location 79:** **City:** Tjumen **Country:** Russian Federation **Zip:** 629806 **Location 80:** **City:** Tomsk **Country:** Russian Federation **Zip:** 634050 **Location 81:** **City:** Tumen **Country:** Russian Federation **Zip:** 625002 **Location 82:** **City:** Tumen **Country:** Russian Federation **Zip:** 625017 **Location 83:** **City:** Tumen **Country:** Russian Federation **Zip:** 625026 **Location 84:** **City:** UFA **Country:** Russian Federation **Zip:** 450000 **Location 85:** **City:** UFA **Country:** Russian Federation **Zip:** 450005 **Location 86:** **City:** Ulan-ude **Country:** Russian Federation **Zip:** 670042 **Location 87:** **City:** Vladivostok **Country:** Russian Federation **Zip:** 690011 **Location 88:** **City:** Vladivostok **Country:** Russian Federation **Zip:** 690065 **Location 89:** **City:** Volgograd **Country:** Russian Federation **Zip:** 400040 **Location 90:** **City:** Volgograd **Country:** Russian Federation **Zip:** 400138 **Location 91:** **City:** Yakutsk **Country:** Russian Federation **Zip:** 677000 **Location 92:** **City:** Yujno-sakhalinsk **Country:** Russian Federation **Zip:** 690000 **Location 93:** **City:** Yujno-sakhalinsk **Country:** Russian Federation **Zip:** 693000 #### Overall Officials **Official 1:** **Affiliation:** Hoffmann-La Roche **Name:** Clinical Trials **Role:** STUDY_DIRECTOR ## 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: D000006521 - Term: Hepatitis, Chronic - ID: D000002908 - Term: Chronic Disease - ID: D000020969 - Term: Disease Attributes - ID: D000010335 - Term: Pathologic Processes ### Condition Browse Module - Browse Branches - Abbrev: BC01 - Name: Infections - Abbrev: BC06 - Name: Digestive 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: M9592 - Name: Hepatitis A - Relevance: HIGH - As Found: Hepatitis - ID: M9591 - Name: Hepatitis - Relevance: HIGH - As Found: Hepatitis - ID: M9607 - Name: Hepatitis, Chronic - Relevance: LOW - As Found: Unknown - ID: M9611 - Name: Hepatitis C - Relevance: HIGH - As Found: Hepatitis C - ID: M21613 - Name: Hepatitis C, Chronic - Relevance: HIGH - As Found: Hepatitis C, Chronic - 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: M17522 - Name: Virus Diseases - 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: 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: D000006506 - Term: Hepatitis A - ID: D000006526 - Term: Hepatitis C - ID: D000019698 - Term: Hepatitis C, Chronic - ID: D000006505 - Term: Hepatitis ### Intervention Browse Module - Ancestors - ID: D000000963 - Term: Antimetabolites - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - 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: M15083 - Name: Ribavirin - Relevance: HIGH - As Found: Bevacizumab - ID: M247369 - Name: Peginterferon alfa-2a - Relevance: HIGH - As Found: Longitudinal - ID: M4281 - Name: Antimetabolites - Relevance: LOW - As Found: Unknown - 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: D000012254 - Term: Ribavirin - ID: C000100416 - Term: Peginterferon alfa-2a ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module #### Event Groups **Group ID:** EG000 **Title:** Ribavirin + Peginterferon Alfa-2a **Description:** Participants with genotype 1 received ribavirin oral tablets daily depending on the body weight. Participants with body weight of less than 75 kg received dose of 400 mg (2 tablets of 200 mg) in morning and 600 mg (3 tablets of 200 mg) in evening, and participants with body weight of 75 kg or more, received dose of 600 mg (3 tablets of 200 mg) in the morning and evening along with PEG-INF Alfa-2a 180 µg/mL SC injection once weekly for 12 to 48 weeks. Participants with other genotypes received ribavirin dose of 400 mg (2 tablets of 200 mg) in morning and evening along with PEG-INF Alfa-2a 180 µg/mL SC injection once weekly for 12 to 24 weeks. **ID:** EG000 **Other Num Affected:** 1674 **Other Num at Risk:** 6661 **Serious Number Affected:** 67 **Serious Number At Risk:** 6661 **Title:** Ribavirin + Peginterferon Alfa-2a **Frequency Threshold:** 5 #### Other Events **Term:** Asthenia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 15.0 **Term:** Influenza like illness **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 15.0 **Term:** Pyrexia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 15.0 **Term:** Anaemia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA 15.0 **Term:** Weight loss poor **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 15.0 #### Serious Events **Term:** Pyelonephritis acute **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 15.0 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 6661 **Term:** Acute tonsillitis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 15.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 6661 **Term:** Appendicitis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 15.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 6661 **Term:** Chronic hepatitis C **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 15.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 6661 **Term:** Enteritis infectious **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 15.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 6661 **Term:** Furuncle **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 15.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 6661 **Term:** Hepatitis G **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 15.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 6661 **Term:** Pneumonia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 15.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 6661 **Term:** Urinary tract infection **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 15.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 6661 **Term:** Cholecystitis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA 15.0 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 6661 **Term:** Cholelithiasis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA 15.0 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 6661 **Term:** Hepatic cirrhosis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA 15.0 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 6661 **Term:** Hepatic failure **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA 15.0 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 6661 **Term:** Cholecystitis acute **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA 15.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 6661 **Term:** Hyperbilirubinaemia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA 15.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 6661 **Term:** Myocardial infarction **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 15.0 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 6661 **Term:** Cardiovascular insufficiency **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 15.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 6661 **Term:** Coronary artery disease **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 15.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 6661 **Term:** Tachycardia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 15.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 6661 **Term:** Ventricular extrasystoles **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 15.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 6661 **Term:** Completed suicide **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA 15.0 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 6661 **Term:** Depression **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA 15.0 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 6661 **Term:** Delusional disorder, persecutory type **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA 15.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 6661 **Term:** Schizophrenia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA 15.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 6661 **Term:** Food poisoning **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 15.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 6661 **Term:** Gastric ulcer haemorrhage **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 15.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 6661 **Term:** Gastrointestinal haemorrhage **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 15.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 6661 **Term:** Pancreatitis acute **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 15.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 6661 **Term:** Asthenia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 15.0 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 6661 **Term:** Death **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 15.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 6661 **Term:** Pyrexia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 15.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 6661 **Term:** Autonomic nervous system imbalance **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 15.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 6661 **Term:** Cranial nerve disorder **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 15.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 6661 **Term:** IIIrd nerve disorder **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 15.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 6661 **Term:** Intracranial pressure increased **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 15.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 6661 **Term:** Vascular encephalopathy **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 15.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 6661 **Term:** Toxic skin eruption **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA 15.0 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 6661 **Term:** Angioedema **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA 15.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 6661 **Term:** Dermatitis allergic **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA 15.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 6661 **Term:** Deep vein thrombosis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA 15.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 6661 **Term:** Thrombophlebitis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA 15.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 6661 **Term:** Vasculitis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA 15.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 6661 **Term:** Pancytopenia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA 15.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 6661 **Term:** Thrombocytopenia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA 15.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 6661 **Term:** Autoimmune thyroiditis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Endocrine disorders **Source Vocabulary:** MedDRA 15.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 6661 **Term:** Hyperthyroidism **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Endocrine disorders **Source Vocabulary:** MedDRA 15.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 6661 **Term:** Hypothyroidism **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Endocrine disorders **Source Vocabulary:** MedDRA 15.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 6661 **Term:** Injury **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 15.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 6661 **Term:** Spinal compression fracture **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 15.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 6661 **Term:** Diabetes mellitus **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 15.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 6661 **Term:** Hyperglycaemia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 15.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 6661 **Term:** Type 1 diabetes mellitus **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 15.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 6661 **Term:** Mixed connective tissue disease **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 15.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 6661 **Term:** Rheumatoid arthritis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 15.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 6661 **Term:** Brain neoplasm **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA 15.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 6661 **Term:** Breast cancer **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA 15.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 6661 **Term:** Asthma **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 15.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 6661 **Term:** Bronchial obstruction **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 15.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 6661 **Term:** Von Willebrand's disease **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Congenital, familial and genetic disorders **Source Vocabulary:** MedDRA 15.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 6661 **Term:** Sudden hearing loss **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Ear and labyrinth disorders **Source Vocabulary:** MedDRA 15.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 6661 **Term:** Macular oedema **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Eye disorders **Source Vocabulary:** MedDRA 15.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 6661 **Term:** Sarcoidosis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Immune system disorders **Source Vocabulary:** MedDRA 15.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 6661 **Term:** Renal impairment **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA 15.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 6661 **Term:** Metrorrhagia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Reproductive system and breast disorders **Source Vocabulary:** MedDRA 15.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 6661 **Term:** Chronic tonsillitis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 15.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 6661 **Time Frame:** From signing of informed consent up to end of study (up to Week 72) ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 6661 **Units:** Participants ### Group **ID:** BG000 **Title:** Ribavirin + Peginterferon Alfa-2a **Description:** Participants with genotype 1 received ribavirin oral tablets daily depending on the body weight. Participants with body weight of less than 75 kg received dose of 400 mg (2 tablets of 200 mg) in morning and 600 mg (3 tablets of 200 mg) in evening, and participants with body weight of 75 kg or more, received dose of 600 mg (3 tablets of 200 mg) in the morning and evening along with PEG-INF Alfa-2a 180 µg/mL SC injection once weekly for 12 to 48 weeks. Participants with other genotypes received ribavirin dose of 400 mg (2 tablets of 200 mg) in morning and evening along with PEG-INF Alfa-2a 180 µg/mL SC injection once weekly for 12 to 24 weeks. ### Measure #### Measurement **Group ID:** BG000 **Spread:** 9.81 **Value:** 34.21 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 4396 **Class Title:** Male #### Measurement **Group ID:** BG000 **Value:** 2250 **Class Title:** Female #### Measurement **Group ID:** BG000 **Value:** 15 **Class Title:** Missing **Denomination Units Selected:** ## Results Section - Baseline Characteristics Module ### Measure 1 **Description:** Here, number of participants analyzed for baseline measure "age" was 6622. **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** Age, Continuous **Unit of Measure:** Years ### Measure 2 **Parameter Type:** NUMBER **Title:** Sex/Gender, Customized **Unit of Measure:** Participants **Population Description:** Baseline population included all enrolled participants. ## Results Section - More Information Module ### Certain Agreement **Other Details:** The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights. **Restriction Type:** OTHER **Restrictive Agreement:** True ### Point of Contact **Email:** [email protected] **Organization:** Hoffmann-LaRoche **Phone:** 800-821-8590 **Title:** Medical Communications ## Results Section - Outcome Measures Module ### Outcome Measure 1 ### Outcome Measure 2 ### Outcome Measure 3 ### Outcome Measure 4 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2058 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 67 **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 50.9 **Title:** #### Outcome Measure 3 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 58.8 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 69.7 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 24.8 **Title:** #### Outcome Measure 4 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 13.5 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 32.4 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 11.7 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 32.3 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 10.0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 27.9 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 21.0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 6.9 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 35.1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 9.1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 35.4 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 15.3 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 5.1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 31.5 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 12.8 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 38.9 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 15.2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4.7 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 30.1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 11.1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 34.9 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 13.6 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4.6 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 25.4 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 21.5 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 16.2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4.1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1.7 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 9.1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 69.0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 13.7 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3.8 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1.7 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 7.7 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 73.1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 11.5 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 18.5 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 6.8 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 19.6 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 43.7 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 5.8 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 23.0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 10.2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 16.1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 44.8 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4.7 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 27.5 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 12.2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 15.5 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 40.2 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** An AE was any untoward medical occurrence in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Number of participants with non-serious AEs were exclusive of serious AEs. **Parameter Type:** NUMBER **Population Description:** Safety analysis population included all participants who received at least one therapeutic dose of ribavirin. **Reporting Status:** POSTED **Time Frame:** From signing of informed consent up to end of study (up to Week 72) **Title:** Number of Participants With Non-Serious Adverse Events (AEs) And Serious Adverse Events (SAEs) **Type:** PRIMARY **Unit of Measure:** Participants ##### Group **Description:** Participants with genotype 1 received ribavirin oral tablets daily depending on the body weight. Participants with body weight of less than 75 kg received dose of 400 mg (2 tablets of 200 mg) in morning and 600 mg (3 tablets of 200 mg) in evening, and participants with body weight of 75 kg or more, received dose of 600 mg (3 tablets of 200 mg) in the morning and evening along with PEG-INF Alfa-2a 180 µg/mL SC injection once weekly for 12 to 48 weeks. Participants with other genotypes received ribavirin dose of 400 mg (2 tablets of 200 mg) in morning and evening along with PEG-INF Alfa-2a 180 µg/mL SC injection once weekly for 12 to 24 weeks. **ID:** OG000 **Title:** Ribavirin + Peginterferon Alfa-2a #### Outcome Measure 2 **Description:** SVR at 24 weeks after end of therapy was defined as a negative result of HCV Ribonucleic Acid (HCV RNA) qualitative assay 24 weeks after end of therapy. Percentage of participants with SVR was calculated as \[number of participants with negative results of HCV RNA qualitative assay 24 weeks after end of therapy divided by the total number of participants analyzed\] multiplied by 100. The participants who failed to undergo tests at 24 weeks after completion of therapy were considered not amenable to therapy. **Parameter Type:** NUMBER **Population Description:** Intent-to-treat (ITT) population included all participants who received at least one therapeutic dose of ribavirin. **Reporting Status:** POSTED **Time Frame:** 24 weeks after end of therapy (Week 72) **Title:** Percentage of Participants With Sustained Virological Response (SVR) at 24 Weeks After End of Therapy **Type:** SECONDARY **Unit of Measure:** Percentage of Participants ##### Group **Description:** Participants with genotype 1 received ribavirin oral tablets daily depending on the body weight. Participants with body weight of less than 75 kg received dose of 400 mg (2 tablets of 200 mg) in morning and 600 mg (3 tablets of 200 mg) in evening, and participants with body weight of 75 kg or more, received dose of 600 mg (3 tablets of 200 mg) in the morning and evening along with PEG-INF Alfa-2a 180 µg/mL SC injection once weekly for 12 to 48 weeks. Participants with other genotypes received ribavirin dose of 400 mg (2 tablets of 200 mg) in morning and evening along with PEG-INF Alfa-2a 180 µg/mL SC injection once weekly for 12 to 24 weeks. **ID:** OG000 **Title:** Ribavirin + Peginterferon Alfa-2a #### Outcome Measure 3 **Description:** HCV RNA levels of \< 50 International Units per milliliter (IU/mL) were defined as undetectable HCV RNA. The percentage of participants with undetectable HCV RNA was calculated as \[number of participants with undetectable HCV RNA divided by the total number of participants analyzed\] multiplied by 100 for Weeks 12, 24 and 48. **Parameter Type:** NUMBER **Population Description:** ITT Population. **Reporting Status:** POSTED **Time Frame:** Weeks 12,24 and 48 After Therapy Initiation **Title:** Percentage of Participants With Undetectable HCV RNA at Weeks 12, 24 and 48 After Therapy Initiation **Type:** SECONDARY **Unit of Measure:** Percentage of Participants ##### Group **Description:** Participants with genotype 1 received ribavirin oral tablets daily depending on the body weight. Participants with body weight of less than 75 kg received dose of 400 mg (2 tablets of 200 mg) in morning and 600 mg (3 tablets of 200 mg) in evening, and participants with body weight of 75 kg or more, received dose of 600 mg (3 tablets of 200 mg) in the morning and evening along with PEG-INF Alfa-2a 180 µg/mL SC injection once weekly for 12 to 48 weeks. Participants with other genotypes received ribavirin dose of 400 mg (2 tablets of 200 mg) in morning and evening along with PEG-INF Alfa-2a 180 µg/mL SC injection once weekly for 12 to 24 weeks. **ID:** OG000 **Title:** Ribavirin + Peginterferon Alfa-2a #### Outcome Measure 4 **Description:** Change in hemoglobin level (compared to baseline) was reported as "significant decrease", "Normal" (no change), "Increase", "Decrease", and "Missing". Significant decrease was defined as per Investigator's discretion. **Parameter Type:** NUMBER **Population Description:** ITT Population. **Reporting Status:** POSTED **Time Frame:** Baseline, Weeks 2, 4, 8, 12, 24, 36, 48 and follow-up Weeks 4 (Week 52), 12 (Week 60), and 24 (Week 72) **Title:** Percentage of Participants With Change in Hemoglobin Level **Type:** SECONDARY **Unit of Measure:** Percentage of Participants ##### Group **Description:** Participants with genotype 1 received ribavirin oral tablets daily depending on the body weight. Participants with body weight of less than 75 kg received dose of 400 mg (2 tablets of 200 mg) in morning and 600 mg (3 tablets of 200 mg) in evening, and participants with body weight of 75 kg or more, received dose of 600 mg (3 tablets of 200 mg) in the morning and evening along with PEG-INF Alfa-2a 180 µg/mL SC injection once weekly for 12 to 48 weeks. Participants with other genotypes received ribavirin dose of 400 mg (2 tablets of 200 mg) in morning and evening along with PEG-INF Alfa-2a 180 µg/mL SC injection once weekly for 12 to 24 weeks. **ID:** OG000 **Title:** Ribavirin + Peginterferon Alfa-2a ### Participant Flow Module #### Group **Description:** Participants with genotype 1 received ribavirin oral tablets daily depending on the body weight. Participants with body weight of less than 75 kilograms (kg) received dose of 400 milligrams (mg) (2 tablets of 200 mg) in morning and 600 mg (3 tablets of 200 mg) in evening, and participants with body weight of 75 kg or more, received dose of 600 mg (3 tablets of 200 mg) in the morning and evening along with Peginterferon (PEG-INF) Alfa-2a 180 micrograms per milliliter (µg/mL) subcutaneous (SC) injection once weekly for 12 to 48 weeks. Participants with other genotypes received ribavirin dose of 400 mg (2 tablets of 200 mg) in morning and evening along with PEG-INF Alfa-2a 180 µg/mL SC injection once weekly for 12 to 24 weeks. **ID:** FG000 **Title:** Ribavirin + Peginterferon Alfa-2a #### Period **Title:** Overall Study ##### Withdraw **Type:** Adverse Event ###### Reason **Group ID:** FG000 **Number of Subjects:** 67 ##### Withdraw **Type:** Pregnancy ###### Reason **Group ID:** FG000 **Number of Subjects:** 7 ##### Withdraw **Type:** Withdrawal by Subject ###### Reason **Group ID:** FG000 **Number of Subjects:** 308 ##### Withdraw **Type:** Lost to Follow-up ###### Reason **Group ID:** FG000 **Number of Subjects:** 44 ##### Withdraw **Type:** Other ###### Reason **Group ID:** FG000 **Number of Subjects:** 27 ##### Withdraw **Type:** Missing ###### Reason **Group ID:** FG000 **Number of Subjects:** 1874 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 6661 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 4334 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 2327 **Recruitment Details:** A total of 7799 participants were screened, of which 6661 participants were included in the study. **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT02935179 **Brief Title:** The Effect of White Sweet Potato Meal Replacement on Weight Control of the Obesity **Official Title:** Office of Human Research, Taipei Medical University #### Organization Study ID Info **ID:** N201604045 #### Organization **Class:** OTHER **Full Name:** Taipei Medical University ### Status Module #### Completion Date **Date:** 2017-05 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2019-04-30 **Type:** ACTUAL **Last Update Submit Date:** 2019-04-17 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2016-12 **Type:** ACTUAL #### Results First Post Date **Date:** 2019-04-17 **Type:** ACTUAL **Results First Submit Date:** 2018-01-25 **Results First Submit QC Date:** 2019-04-15 #### Start Date **Date:** 2016-07 **Status Verified Date:** 2016-06 #### Study First Post Date **Date:** 2016-10-17 **Type:** ESTIMATED **Study First Submit Date:** 2016-10-14 **Study First Submit QC Date:** 2016-10-14 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Taipei Medical University #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** The purpose of this project is to use white-skinned sweet potato as the main material for weight control for overweight and obesity, the non-communicable diseases (cardiovascular diseases, cancers, chronic respiratory diseases and diabetes) are also included. All high quality sweet potato are provided by CAES in Taiwan to produce special nutrient food and health food that to do functional study in Shih Chien University and Taipei Medical University. In this study, the investigators will recruit overweight and obesity subjects that divide into white sweet potato group (experimental group) and no intervention group (control group) by using randomized, parallel and open clinical study in sixty days. **Detailed Description:** All subjects will be evaluated the body weight and clinical nutrition assessment such as postural measurement, urine test and blood biomarker examination. ### Conditions Module **Conditions:** - Overweight ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 60 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Normal diet with 1500\~2000 kcal **Intervention Names:** - Dietary Supplement: White sweet potato diet **Label:** Control Group **Type:** PLACEBO_COMPARATOR #### Arm Group 2 **Description:** White sweet potato diet with 1500\~2000 kcal **Intervention Names:** - Dietary Supplement: White sweet potato diet **Label:** Treatment Group **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Control Group - Treatment Group **Description:** The diet were supplied 516 kcal daily **Name:** White sweet potato diet **Type:** DIETARY_SUPPLEMENT ### Outcomes Module #### Primary Outcomes **Description:** Body weight change after 60 days intervention **Measure:** Body Weight After Intervention **Time Frame:** 60 days #### Secondary Outcomes **Description:** Body fat change after 60 days intervention **Measure:** Body Fat After Intervention **Time Frame:** 60 days ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * 24≦ BMI≦30 Exclusion Criteria: * Pregnant and lactating women * Patients within six months after surgery * Mental illness or depression * Suffering from cancer, ulcers, acute respiratory infections, dialysis, acute hepatitis and other diseases * Those who have taken "additional nutritional supplements" habit **Maximum Age:** 50 Years **Minimum Age:** 20 Years **Sex:** ALL **Standard Ages:** - ADULT ### Contacts Locations Module #### Overall Officials **Official 1:** **Affiliation:** Office of Human Research, Taipei Medical University **Name:** Chih-Han Lin, MS **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## 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: LOW - As Found: Unknown - 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: D000050177 - Term: Overweight ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module **Description:** No adverse event. #### Event Groups **Group ID:** EG000 **Title:** Control Group **Deaths Num At Risk:** 29 **Description:** Normal diet White sweet potato meal replacement: The formula were supplied 516 kcal daily **ID:** EG000 **Other Num at Risk:** 29 **Serious Number At Risk:** 29 **Title:** Control Group **Group ID:** EG001 **Title:** Treatment Group **Deaths Num At Risk:** 29 **Description:** Normal diet plus white sweet potato formula White sweet potato meal replacement: The formula were supplied 516 kcal daily **ID:** EG001 **Other Num at Risk:** 29 **Serious Number At Risk:** 29 **Title:** Treatment Group **Frequency Threshold:** 0 **Time Frame:** The adverse event data were collected from the participants during intervention and assessed after 24 weeks. ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 29 **Group ID:** BG001 **Value:** 29 **Group ID:** BG002 **Value:** 58 **Units:** Participants ### Group **ID:** BG000 **Title:** Control Group **Description:** Normal diet White sweet potato meal replacement: The formula were supplied 516 kcal daily ### Group **ID:** BG001 **Title:** Treatment Group **Description:** Normal diet plus white sweet potato formula White sweet potato meal replacement: The formula were supplied 516 kcal daily ### Group **ID:** BG002 **Title:** Total **Description:** Total of all reporting groups ### Measure #### Measurement **Group ID:** BG000 **Spread:** 5.51 **Value:** 37.33 #### Measurement **Group ID:** BG001 **Spread:** 6.24 **Value:** 38.76 #### Measurement **Group ID:** BG002 **Spread:** 5.89 **Value:** 38.07 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 14 #### Measurement **Group ID:** BG001 **Value:** 14 #### Measurement **Group ID:** BG002 **Value:** 28 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 15 #### Measurement **Group ID:** BG001 **Value:** 15 #### Measurement **Group ID:** BG002 **Value:** 30 **Category Title:** Male **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 ## Results Section - More Information Module ### Certain Agreement ### Limitations and Caveats **Description:** Small sample size and trial duration that may cause impose an obstacle in the detection of significant changes of the study measure. ### Point of Contact **Email:** [email protected] **Organization:** Taipei Medical University **Phone:** 886-2-27361661 **Phone Extension:** 6560 **Title:** Dr. Sing-Chung Li ## 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:** 1.7 - **Upper Limit:** - **Value:** -2.11 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 2.24 - **Upper Limit:** - **Value:** -3.7 **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 2.21 - **Upper Limit:** - **Value:** -0.95 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 2.09 - **Upper Limit:** - **Value:** -2.26 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** Body weight change after 60 days intervention **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Reporting Status:** POSTED **Time Frame:** 60 days **Title:** Body Weight After Intervention **Type:** PRIMARY **Unit of Measure:** Kg ##### Group **Description:** Normal diet White sweet potato meal replacement: The formula were supplied 516 kcal daily **ID:** OG000 **Title:** Control Group ##### Group **Description:** Normal diet plus white sweet potato formula White sweet potato meal replacement: The formula were supplied 516 kcal daily **ID:** OG001 **Title:** Treatment Group #### Outcome Measure 2 **Description:** Body fat change after 60 days intervention **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Reporting Status:** POSTED **Time Frame:** 60 days **Title:** Body Fat After Intervention **Type:** SECONDARY **Unit of Measure:** percentage of body fat ##### Group **Description:** Normal diet White sweet potato meal replacement: The formula were supplied 516 kcal daily **ID:** OG000 **Title:** Control Group ##### Group **Description:** Normal diet plus white sweet potato formula White sweet potato meal replacement: The formula were supplied 516 kcal daily **ID:** OG001 **Title:** Treatment Group ### Participant Flow Module #### Group **Description:** Normal diet White sweet potato meal replacement: The formula were supplied 516 kcal daily **ID:** FG000 **Title:** Control Group #### Group **Description:** Normal diet plus white sweet potato formula White sweet potato meal replacement: The formula were supplied 516 kcal daily **ID:** FG001 **Title:** Treatment Group #### Period **Title:** Overall Study ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 30 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 30 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 29 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 29 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 1 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 1 **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT05475379 **Brief Title:** Non-inferiority Trial of Locally Manufactured Typhoid Conjugate Vaccine 'Typhocon' in Bangladesh **Official Title:** A Randomized Control, Double Blinded, Non-inferiority Trial to Evaluate the Immunogenicity and Safety of Typhoid Vi Conjugate Vaccine 'Typhocon' in Bangladeshi Healthy Population #### Organization Study ID Info **ID:** PR-22013 #### Organization **Class:** OTHER **Full Name:** International Centre for Diarrhoeal Disease Research, Bangladesh ### Status Module #### Completion Date **Date:** 2023-04-30 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2022-08-30 **Type:** ACTUAL **Last Update Submit Date:** 2022-08-28 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2023-01-31 **Type:** ESTIMATED #### Start Date **Date:** 2022-07-01 **Type:** ACTUAL **Status Verified Date:** 2022-07 #### Study First Post Date **Date:** 2022-07-26 **Type:** ACTUAL **Study First Submit Date:** 2022-06-11 **Study First Submit QC Date:** 2022-07-25 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** International Centre for Diarrhoeal Disease Research, Bangladesh #### 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 double blinded, randomized-controlled, non-inferiority trial of a typhoid conjugate vaccine, Typhocon (Vi- polysaccharide conjugated to diphtheria toxoid, Vi-DT), manufactured by a local company, Incepta Vaccine Limited. The vaccine will be tested among individuals from 6 months to 60 years of age residing in Mirpur area of Dhaka city. The Typbar-TCV (Vi-polysaccharide conjugated to tetanus toxoid, Vi-TT), manufactured by Bharat Biotech International Limited will be used as a reference vaccine in this study. In Phase I the Typhocon vaccine will be tested in 30 adults. Safety and immunogenicity data of the vaccine for 30 adults will be submitted to the Data Safety Monitoring Board (DSMB), IRB and Directorate General of Drug Administration (DGDA). Upon receiving approval letter, the investigators will initiate the Phase II study including 600 individuals. The Phase II study will be conducted in age de-escalation manner (6-23 months, 2-5 years, 6-17 years and 18-60 years). Equal number of participants of all age groups will be enrolled for vaccination. Blood specimens will also be collected for carrying out the clinical chemistry (complete blood count with differential for white blood count, hemoglobin, absolute neutrophil count, platelet count, serum alanine transaminase, serum creatinine) on day -7 to day -2 for screening of participants before vaccination and on day 28, postvaccination. Based on blood reports of clinical chemistry, 600 participants will be randomized in a 1:1 ratio to allocate Typhocon or Typbar-TCV vaccine. Memory aid will be used to collect solicited adverse events following vaccination (AEFI) data up to day 7. Data on unsolicited AEFI and serious adverse events (SAEs) will be collected up to 28 days after vaccination. All study update including adverse events and serious adverse events will be reported to the DSMB. Blood specimen will be obtained on day 0 before vaccination, and day 28 for carrying out Enzyme-linked Immunosorbent Assay (ELISA) to determine anti-Vi-IgG antibody. **Detailed Description:** A double blinded, randomized-controlled, non-inferiority trial of a typhoid conjugate vaccine, Typhocon (Vi- polysaccharide conjugated to diphtheria toxoid, Vi-DT), manufactured by a local company, Incepta Vaccine Limited will be conducted. The vaccine will be tested among individuals from 6 months to 60 years of age residing in Mirpur area of Dhaka city. The Typbar-TCV (Vi-polysaccharide conjugated to tetanus toxoid, Vi-TT), manufactured by Bharat Biotech International Limited will be used as a reference vaccine in this study. Hypothesis: Locally produced typhoid conjugate vaccine 'Typhocon' is non-inferior in terms of safety and immunogenicity among healthy Bangladeshi population as compared to 'Typbar-TCV'. Objectives: 1. To evaluate and compare the safety of locally produced 'Typhocon' with 'Typbar- TCV'. 2. To evaluate and compare the immunogenicity of 'Typhocon' with 'Typbar-TCV' in healthy population in Bangladesh. Number of participants for enrollment: Age group Test vaccine Reference vaccine 18-60 Years 75 75 6-17 Years 75 75 2-5 Years 75 75 6-23 Months 75 75 Total 300 300 Study activities: Screening and eligibility assessment: Study field staff will visit different households in Mirpur area and brief apparently healthy and eligible participants about the study. They will invite them to Mirpur field clinic to be included as participants in the study. If agreed, written consent will be obtained from the participants at the field clinic. Blood specimens will be collected for carrying out clinical chemistry (complete blood count with differential for white blood count, hemoglobin, absolute neutrophil count, platelet count, serum alanine transaminase, serum creatinine). Participants with abnormalities in screening hematological and biochemical tests will be excluded for vaccination. After screening, the eligible participant will be enrolled for vaccination after matching with inclusion and exclusion criteria. A study ID will be provided to each participant once informed written consent has been obtained. Informed consent: The participants/parent/guardian must personally sign and date the latest approved version of the Informed Consent form before any trial specific procedures are performed. Assent will also be sought from children 11-17 years of age or older, to participate in the trial. Consent will be documented by signature or thumbprint on consent forms. Participants will read the informed consent or that will be read out to the ones who are not literate, and they will be encouraged to ask questions regarding the study. Informed consent will be obtained from participants who agree to take vaccine and give blood at two time points during the study period. Signature (or thumbprint, if illiterate) of each of the participants will be obtained before their enrollment in the study and prior to any study-related activity. A witness and the study personnel who obtains the consent must sign and date in the informed consent form. The participant will be provided with a copy of the signed consent form for their retention. If new information is obtained which is not covered in the proposal on the study product but becomes available later on and is relevant to the participants' willingness to continue in the study, the investigator will inform that in a timely manner to the IRB and use a revised written informed consent form. The proposal will be revised and resubmitted to RRC and ERC for the amendment which will then be used for obtaining permission. The clinical trial will be monitored by the sponsor. Randomisation: The randomization for this study will be generated using the statistical software. Each participant will be assigned with unique participant ID. The study agents (Typhocon or Typbar-TCV) will be labelled by Incepta Vaccine Limited as per the randomization list and the list will be provided by them. Randomization sheet will contain sequential treatment numbers unique to each participant. Blinding and Code Breaking Procedures: This is a randomized double-blind study. Study investigators along with study staff involved in safety evaluation and laboratory analysis will be blinded regarding the assigned treatment of the participant. The vaccine administration team will be un-blinded to the treatment assignment list. The vaccine administrator team members will not be involved in the evaluation of vaccine safety and laboratory analysis. The DSMB will be responsible for un-blinding the randomization number codes in the event of severe putative vaccine reactions. Otherwise, the codes will not be revealed until the end of the trial and until the computerized dataset has been frozen. If the intervention assignment is un-blinded, all study collaborators will be notified immediately. If deemed necessary, the DSMBs will recommend unblinding to the IRB and contact the study statistician responsible for providing information on the vaccine received by the individual in question. Vaccination of participants: Potential participants will attend the vaccination site. Upon arrival, inclusion/exclusion criteria will be assessed, and written informed consent/assent will be formally obtained with the participants/parent/ guardian of the participant. The participant will then be vaccinated, and a blood sample will be taken for immunological assay before vaccination. All details will be recorded in the CRF. Based on the randomization, the appropriate vaccine will be administered by a trained member of the study team. The site of vaccination (right or left arm or thigh) will be recorded. Investigational Product: Test vaccine: Typhocon (Incepta Vaccine Limited) Reference vaccine: Typbar-TCV (Bharat Biotech International Limited) Dosage and administration: For children and adults, the same dose (0.5 ml) of vaccine in prefilled syringe will be administered via intramuscular route on day 0 will be given. Visit 1: Day -7 to -2 Screening: The following procedures will be followed after obtaining the informed consent from the participants to determine the eligibility for participating in the study. At the screening visit(s), the designated study staff will provide a detailed description of the study objectives to the participant and also describe study participation requirements, potential health risks and benefits associated with study participation. 1. Written informed consent will be obtained and any remaining questions that the participant may have will be solicited/discussed. 2. A participant ID number will be assigned once the study specific consent form has been signed. 3. Demographic information will be obtained. 4. Vital signs (Blood pressure, pulse rate, respiratory rate and temperature) will be recorded. 5. Medical history will be obtained and a thorough physical examination will be performed by a physician. In addition, medical history will be taken thoroughly by study physician from the woman of childbearing age to completely exclude the probability of pregnancy during screening and prior to vaccination. Women who are married and living with a partner must agree to use a reliable contraceptive method to prevent pregnancy until final follow-up following vaccination. However abstinence is also acceptable. 6. Inclusion/exclusion criteria are reviewed to determine qualification for enrollment, including medications used in the past 30 days. 7. Females with child bearing potential, a urine dipstick pregnancy test will be performed and verified as negative prior to phlebotomy. 8. Blood samples (3-10ml) will be collected for Complete Blood Count (CBC) with differential for white blood count (WBC), hemoglobin (Hg) , Absolute Neutrophil Count (ANC), platelet count, Serum Alanine Transaminase (ALT), Serum Creatinine for screening of participants to enroll in the study. Plasma/serum will be separated from blood to determine anti-Vi-IgG antibody response for vaccinees. Visit-2: Day: 0 Enrollment and vaccination: 1. Clinical evaluation and eligibility criteria will be reviewed by study physician to determine qualification for enrollment, including medications. Vital signs (Blood pressure, pulse rate, respiratory rate and temperature) will be recorded. 2. Females with child bearing potential, a urine dipstick pregnancy test will be performed and verified as negative prior to vaccination. 3. The study agent (Typhocon or Typbar-TCV) will be given to the participant intramuscularly according to the randomization. 4. The participants will be observed for 30 minutes for solicited reactogenicity symptoms. 5. Vital signs (Blood pressure, pulse rate, respiratory rate and temperature) will be checked at least 30 minutes post-dose. 6. Each participant will be provided with a memory aid to record solicited symptoms on a daily basis through Day 7. Participants will be trained to record temperature and any symptoms on the memory aid. 7. Study staff will instruct the participant regarding continued assessment of his/her health and need to contact study staff (a) for follow-up of specific AEs, (b) if systemic symptoms worsen or do not resolve, and (c) if other AEs occur. 8. Participants will be instructed to bring the memory aid to the next scheduled clinic visit. 9. The next visit for Day 7 will be instructed. The vaccine will be administered by a trained study nurse. During vaccination, a team of trained doctors, nurses and medical technologists will be available at the vaccination sites to deal with all emergency situation including anaphylaxis. To deal with anaphylaxis first-line and second-line equipment will be available whenever a vaccine is administered at the vaccination sites. These will be physically separated into two separate boxes. Both boxes will be clearly labeled and kept together. The essential first-line equipment is to be used by any staff member trained in anaphylaxis and basic life support. It includes the following: * Adrenaline: at least 2 x 1ml vials of 1:1000 (1mg/mL) * Filter needles * 1ml syringes * Needles for IM injection: 25mm (23G) is appropriate * Cotton wool/gauze * Pocket masks (facemasks) for BLS * Paediatric and adult sizes * Copy of treatment algorithm * Copy of adrenaline dosage table * List of emergency contact numbers The essential second-line equipment is only to be used by trained medical personnel, such as doctors. It includes the following: * Self-inflating resuscitation bag (as part of a bag-valve-mask system) * 500ml for infants up to around 2 years * 1600ml - 2000ml for older children * Masks compatible with bag * Include 3 to 4 sizes, suitable sizes for infants to adults * Chlorphenamine: solution for injection, minimum of 10mg * For example 1 x 1ml vial of 10mg/ml solution * Hydrocortisone: solution for injection, minimum of 200For example 2 x 1ml vials of 100mg/ml solution * Salbutamol: dry powder inhaler, 100microgram per dose * Spacer for use with inhaler * Filter needles * 1ml syringes * 5ml syringes * Needles for IM injection: 25mm is appropriate * Cotton wool/gauze * Copy of advanced (second-line) treatment algorithm * Copy of drug dosage tables * List of emergency contact numbers Visit-3: Day: 7 (+3) Memory aid collection: The investigators will collect parent/guardian-reported information on adverse events following immunization (AEFIs). The investigators will encourage the parents/guardians to visit field clinic if any adverse event happens other than the schedule visit. Visit-4: Day: 28 (+7) Follow-up: 1. Participants will visit field clinic for clinical evaluation. 2. Blood samples (3-10ml) will be collected for Complete Blood Count (CBC) with differential for white blood count (WBC), hemoglobin (Hg) , Absolute Neutrophil Count (ANC), platelet count, Serum Alanine Transaminase (ALT), Serum Creatinine for clinical chemistry. Plasma/serum will be separated from blood to determine anti-Vi-IgG antibody response for vaccinees. Visit-5: Day: 90 (±7) Follow-up: The participant will come to Mirpur Field clinic and physical examination with vital sign (blood pressure, respiratory rate, pulse rate and temperature) will be performed. Laboratory assay: Blood samples will be transported to the laboratory to processed and stored by trained study staff, in accordance with standard operating procedures (SOP). The plasma/serum will be stored and used to measure the induced immune response in the vaccinees. The primary laboratory technique performed will be anti-Vi antibody ELISA performed on the extracted plasma sample, using a commercially available assay (VaccZyme, The Binding Site). This assay will be performed according to the manufacturer's instructions. Investigational Medicinal Product (IMP): IMP description Test vaccine Typhoid Vi polysaccharide-diphtheria toxoid conjugate vaccine (Vi-DT). Trade name: Typhocon®, Incepta Vaccine Ltd. Each 0.5ml vaccine dose contains: * Purified Typhoid Conjugate Bulk: 25 µg * Sodium Chloride: 8.7 mg * Disodium Hydrogen Phosphate Heptahydrate: 2.34 mg * Sodium Dihydrogen Phosphate Monohydrate: 0.23 mg Reference vaccine Vi polysaccharide-tetanus toxoid conjugate vaccine (Vi-TCV). Trade name: Typbar-TCV®, Bharat-Biotech International Limited. Each 0.5ml vaccine dose contains: * Purified Vi-Capsular Polysaccharide of S. Typhi Ty2 conjugated to Tetanus Toxoid 25µg * Sodium chloride 4.5 mg * Water for Injection q.s. to 0.5ml The vaccine is packaged as a pre-filled syringe and the Strength is 25 µg/0.5 ml. It will be administered as an intramuscular injection in the antero-lateral thigh for younger children, or the upper arm for older children, according to local protocols. Supply: Both test (Typhocon) and reference (Typbar-TCV) vaccines will be provided by Incepta vaccine limited. Storage: The vaccines will be stored at 2o to 8o C (35 o to 46 o F) in a temperature monitored cold room at the icddr,b, when not in use for the daily activities. The vaccines will be stored in temperature monitored refrigerators or cool boxes, when in use for the day's activities. Each vial will be labelled with a "vaccine vial monitor"; a temperature-sensitive dot that provides an indication of the cumulative heat to which the vial has been exposed. It warns the end user when exposure to heat is likely to have degraded the vaccine beyond an acceptable level and should not be used. Accountability of the trial treatment: The vaccines will be shipped to a central storage facility in the icddr,b. They will then be transported and distributed to the vaccine site whilst maintaining the cold-chain (aiming for temperature between 2-8oC). The number of doses of study vaccines that are received, used and wasted will be documented daily during the trial and checked weekly. Procedures for recording adverse events From vaccination through day 7: All adverse events related to vaccination, as judged by a medically qualified investigator, occurring during the first 7 days post vaccination that are observed by the study team/investigator or reported by the participants' parent/guardian, will be recorded on the CRF. The information will be collected both passively and actively. Parents of participants not in this subset will be encouraged to go to the 'Adverse Event Monitoring Cell' at the Mirpur Field Clinic which will have a medical doctor on-call 24 hours a day for adverse event monitoring throughout the whole vaccination period + 7 days. The following information will be recorded: description, date of onset and end date, severity, assessment of relatedness to trial medication, and action taken. Follow-up information should be provided as necessary. The severity of events will be assessed on the following scale: 1 = mild, 2 = moderate, 3 = severe. All Serious Adverse Events (SAEs) observed by the Investigator, members of the study team or reported by the parent/guardian will be recorded on the CRF. The following information will be recorded: description, date of onset and end date, severity, assessment of relatedness to trial medication, other suspect drug or device and action taken. Follow-up information should be provided as necessary. Throughout the study period: Serious Adverse Events (SAEs), as judged by a medically qualified investigator, observed by the Investigator, members of the study team or reported by the parent/guardian, will be recorded on the CRF. The following information will be recorded: description, date of onset and end date, severity, assessment of relatedness to trial medication, and action taken. Follow-up information should be provided as necessary. All mortality occurring during the duration of the trial will be recorded in the CRF, and investigated by medically qualified trial staff. All SAEs recorded in the CRFs, for the duration of the study, from first vaccination until trial completion, will be followed by a medically qualified investigator either until resolution, or until the event is considered stable. Reporting procedures for serious adverse events: For this study, forms will be used for reporting all SAEs occurring during this study. All SAEs occurring within the first 30 days, post vaccine administration, and then only SARs occurring until the end of the trial, will be reported to the Data Safety Monitoring Board (DSMB), Directorate General of Drug Administration (DGDA), the PI and the other study Investigators within 24 hours of the Site Study Team becoming aware of the event. A more detailed report form will be completed during medical follow-up, and sent within the shortest period possible of the initial report, to all parties mentioned above. Additional and further requested information (follow-up or corrections to the original case) will be detailed in subsequent safety report forms. All SAEs must be reported to the trial sponsor within 7 days. Summary reports will be submitted to the icddr,b IRB, and DGDA at the end of the study. SAEs will also be reported to the sponsor. Sample size calculation and outcome: Primary outcome of this study is the seroconversion rate (4-fold rise of anti-Vi plasma/serum immunoglobulin G (IgG) enzyme-linked immunosorbent assay titers over baseline). For the sample size calculation, the investigators are assuming 85% seroconversion rates for both reference (Typbar-TCV) and test (Typhocon) vaccines at day 28 after vaccination. The difference of seroconversion rates as large as 10% in favor of Typhocon vaccine would still allow to be non-inferior at 10% margin (delta = 0.10). To confirm non-inferiority with 90% study power and a one-sided confidence level of 97.5%, the investigators will need at least 270 study participants for each arm (total 540). Anticipating 10% attrition rate, the investigators will enroll total 600 participants. ### Conditions Module **Conditions:** - Typhoid **Keywords:** - Conjugate vaccine - Immunogenicity - Safety - Typhoid fever ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** SEQUENTIAL ##### Masking Info **Masking:** QUADRUPLE **Masking Description:** This is a randomized double-blind study. Study investigators along with study staff involved in safety evaluation and laboratory analysis will be blinded regarding the assigned treatment of the participant. The vaccine administration team will be un-blinded to the treatment assignment list. The vaccine administrator team members will not be involved in the evaluation of vaccine safety and laboratory analysis. The DSMB will be responsible for un-blinding the randomization number codes in the event of severe putative vaccine reactions. Otherwise, the codes will not be revealed until the end of the trial and until the computerized dataset has been frozen. If the intervention assignment is un-blinded, all study collaborators will be notified immediately. If deemed necessary, the DSMBs will recommend unblinding to the IRB and contact the study statistician responsible for providing information on the vaccine received by the individual in question. **Who Masked:** - PARTICIPANT - CARE_PROVIDER - INVESTIGATOR - OUTCOMES_ASSESSOR **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 630 **Type:** ESTIMATED **Phases:** - PHASE1 - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** 300 participants will receive Typhoid Vi polysaccharide-diphtheria toxoid conjugate vaccine (Vi-DT) Trade name: Typhocon®, Incepta Vaccine Ltd. **Intervention Names:** - Biological: Typhoid Vi polysaccharide-diphtheria toxoid conjugate vaccine (Vi-DT) **Label:** Test vaccine group **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** 300 participants will receive Vi polysaccharide-tetanus toxoid conjugate vaccine (Vi-TCV) Trade name: Typbar-TCV®, Bharat-Biotech International Limited. **Intervention Names:** - Biological: Typhoid Vi polysaccharide-diphtheria toxoid conjugate vaccine (Vi-DT) **Label:** Reference vaccine group **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Reference vaccine group - Test vaccine group **Description:** Typhoid Vi-polysaccharide-diphtheria toxoid conjugate vaccine (Vi-DT) "Typhocon" will be manufactured by Incepta Vaccine Limited **Name:** Typhoid Vi polysaccharide-diphtheria toxoid conjugate vaccine (Vi-DT) **Other Names:** - Vi polysaccharide-tetanus toxoid conjugate vaccine (Vi-TCV) **Type:** BIOLOGICAL ### Outcomes Module #### Primary Outcomes **Description:** Proportion of participants developing adverse events following immunization (AEFI) and serious adverse events (SAE). To estimate the proportion of safety data, the investigators will use memory aid, and AEFI and SAE forms to collect the data. **Measure:** Proportion of participants developing adverse events and serious adverse events **Time Frame:** 28 days #### Secondary Outcomes **Description:** To measure the immune response induced in vaccinees, blood specimens will be collected. Plasma/serum will be separated from blood specimens and anti Vi-IgG antibody responses will be measured using the commercially available kit. **Measure:** Immune response induced in vaccinees **Time Frame:** 6 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Provide informed written consent from participants or if minor from their parent/legal guardian 2. Healthy participants aged 6 months to 60 years 3. Family does not have any plan to move from the study area during study period. Exclusion Criteria: 1. History of hypersensitivity reaction to any component of the study vaccines. 2. History of typhoid vaccination within the last three years. 3. Fever of any origin or infections of more than 3 days within the past month. 4. Subjects with febrile illness (temperature \>37.9 C) at the time of enrollment. 5. History of any vaccination within the past 30 days. 6. Clinically significant systemic disorder such as cardiovascular, respiratory, neurologic, gastrointestinal, hepatic, renal, endocrine, hematological or immunological disorder. 7. Participants with abnormalities in screening hematological and biochemical tests will be excluded for vaccination 8. Subjects with confirmed or suspected immunosuppressive or immunodeficiency disorder; or subjects on any immunosuppressive or immunostimulant therapy. 9. Known case of thrombocytopenia or any coagulation disorder, or subjects on anticoagulation therapy. 10. Subjects administered blood, blood containing products or immunoglobulins within the last 3 months or planned administration during the study. 11. Urine dipstick pregnancy test verified as positive 12. Pregnant\* and lactating women \& female subjects not using acceptable contraceptive measures (double barrier methods, oral or injectable hormonal contraceptives or surgical sterilization). * Urine pregnancy test (UPT) will be performed in all married females prior to vaccination **Healthy Volunteers:** True **Maximum Age:** 60 Years **Minimum Age:** 6 Months **Sex:** ALL **Standard Ages:** - CHILD - ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Farhana Khanam, MPhil,PhD **Phone:** +8801755532548 **Role:** CONTACT #### Locations **Location 1:** **City:** Dhaka **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Md Anisur Rahman, MSS - **Phone:** 01325166414 - **Role:** CONTACT ***Contact 2:*** - **Name:** Farhana Khanam, Mphil,PhD - **Role:** PRINCIPAL_INVESTIGATOR **Country:** Bangladesh **Facility:** International Centre for Diarrhoeal Disease Research, Bangladesh **Status:** RECRUITING **Zip:** 1212 #### Overall Officials **Official 1:** **Affiliation:** International Centre for Diarrhoeal Disease Research, Bangladesh **Name:** Farhana Khanam, MPhil, PhD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Crump JA, Luby SP, Mintz ED. The global burden of typhoid fever. Bull World Health Organ. 2004 May;82(5):346-53. **PMID:** 15298225 **Citation:** Antillon M, Warren JL, Crawford FW, Weinberger DM, Kurum E, Pak GD, Marks F, Pitzer VE. The burden of typhoid fever in low- and middle-income countries: A meta-regression approach. PLoS Negl Trop Dis. 2017 Feb 27;11(2):e0005376. doi: 10.1371/journal.pntd.0005376. eCollection 2017 Feb. **PMID:** 28241011 **Citation:** Meiring JE, Shakya M, Khanam F, Voysey M, Phillips MT, Tonks S, Thindwa D, Darton TC, Dongol S, Karkey A, Zaman K, Baker S, Dolecek C, Dunstan SJ, Dougan G, Holt KE, Heyderman RS, Qadri F, Pitzer VE, Basnyat B, Gordon MA, Clemens J, Pollard AJ; STRATAA Study Group. Burden of enteric fever at three urban sites in Africa and Asia: a multicentre population-based study. Lancet Glob Health. 2021 Dec;9(12):e1688-e1696. doi: 10.1016/S2214-109X(21)00370-3. **PMID:** 34798028 **Citation:** World Health Organization. Typhoid vaccines: WHO position paper, March 2018 - Recommendations. Vaccine. 2019 Jan 7;37(2):214-216. doi: 10.1016/j.vaccine.2018.04.022. Epub 2018 Apr 13. **PMID:** 29661581 **Citation:** Qamar FN, Yousafzai MT, Khaliq A, Karim S, Memon H, Junejo A, Baig I, Rahman N, Bhurgry S, Afroz H, Sami U. Adverse events following immunization with typhoid conjugate vaccine in an outbreak setting in Hyderabad, Pakistan. Vaccine. 2020 Apr 23;38(19):3518-3523. doi: 10.1016/j.vaccine.2020.03.028. Epub 2020 Mar 20. **PMID:** 32201138 **Citation:** Mohan VK, Varanasi V, Singh A, Pasetti MF, Levine MM, Venkatesan R, Ella KM. Safety and immunogenicity of a Vi polysaccharide-tetanus toxoid conjugate vaccine (Typbar-TCV) in healthy infants, children, and adults in typhoid endemic areas: a multicenter, 2-cohort, open-label, double-blind, randomized controlled phase 3 study. Clin Infect Dis. 2015 Aug 1;61(3):393-402. doi: 10.1093/cid/civ295. Epub 2015 Apr 13. **PMID:** 25870324 **Citation:** Qadri F, Khanam F, Liu X, Theiss-Nyland K, Biswas PK, Bhuiyan AI, Ahmmed F, Colin-Jones R, Smith N, Tonks S, Voysey M, Mujadidi YF, Mazur O, Rajib NH, Hossen MI, Ahmed SU, Khan A, Rahman N, Babu G, Greenland M, Kelly S, Ireen M, Islam K, O'Reilly P, Scherrer KS, Pitzer VE, Neuzil KM, Zaman K, Pollard AJ, Clemens JD. Protection by vaccination of children against typhoid fever with a Vi-tetanus toxoid conjugate vaccine in urban Bangladesh: a cluster-randomised trial. Lancet. 2021 Aug 21;398(10301):675-684. doi: 10.1016/S0140-6736(21)01124-7. Epub 2021 Aug 9. **PMID:** 34384540 **Citation:** Theiss-Nyland K, Shakya M, Colin-Jones R, Voysey M, Smith N, Karkey A, Dongol S, Pant D, Farooq YG, Neuzil KM, Shrestha S, Basnyat B, Pollard AJ. Assessing the Impact of a Vi-polysaccharide Conjugate Vaccine in Preventing Typhoid Infections Among Nepalese Children: A Protocol for a Phase III, Randomized Control Trial. Clin Infect Dis. 2019 Mar 7;68(Suppl 2):S67-S73. doi: 10.1093/cid/ciy1106. Erratum In: Clin Infect Dis. 2021 Nov 16;73(10):1950. **PMID:** 30845329 **Citation:** Patel PD, Patel P, Liang Y, Meiring JE, Misiri T, Mwakiseghile F, Tracy JK, Masesa C, Msuku H, Banda D, Mbewe M, Henrion M, Adetunji F, Simiyu K, Rotrosen E, Birkhold M, Nampota N, Nyirenda OM, Kotloff K, Gmeiner M, Dube Q, Kawalazira G, Laurens MB, Heyderman RS, Gordon MA, Neuzil KM; TyVAC Malawi Team. Safety and Efficacy of a Typhoid Conjugate Vaccine in Malawian Children. N Engl J Med. 2021 Sep 16;385(12):1104-1115. doi: 10.1056/NEJMoa2035916. **PMID:** 34525285 **Citation:** Mond JJ, Lees A, Snapper CM. T cell-independent antigens type 2. Annu Rev Immunol. 1995;13:655-92. doi: 10.1146/annurev.iy.13.040195.003255. **PMID:** 7612238 **Citation:** Weintraub A. Immunology of bacterial polysaccharide antigens. Carbohydr Res. 2003 Nov 14;338(23):2539-47. doi: 10.1016/j.carres.2003.07.008. **PMID:** 14670715 **Citation:** Acharya IL, Lowe CU, Thapa R, Gurubacharya VL, Shrestha MB, Cadoz M, Schulz D, Armand J, Bryla DA, Trollfors B, et al. Prevention of typhoid fever in Nepal with the Vi capsular polysaccharide of Salmonella typhi. A preliminary report. N Engl J Med. 1987 Oct 29;317(18):1101-4. doi: 10.1056/NEJM198710293171801. **PMID:** 3657877 **Citation:** Klugman KP, Gilbertson IT, Koornhof HJ, Robbins JB, Schneerson R, Schulz D, Cadoz M, Armand J. Protective activity of Vi capsular polysaccharide vaccine against typhoid fever. Lancet. 1987 Nov 21;2(8569):1165-9. doi: 10.1016/s0140-6736(87)91316-x. **PMID:** 2890805 **Citation:** Yang HH, Wu CG, Xie GZ, Gu QW, Wang BR, Wang LY, Wang HF, Ding ZS, Yang Y, Tan WS, Wang WY, Wang XC, Qin M, Wang JH, Tang HA, Jiang XM, Li YH, Wang ML, Zhang SL, Li GL. Efficacy trial of Vi polysaccharide vaccine against typhoid fever in south-western China. Bull World Health Organ. 2001;79(7):625-31. **PMID:** 11477965 **Citation:** Froeschle JE, Decker MD. Duration of Vi antibodies in participants vaccinated with Typhim Vi (Typhoid Vi polysaccharide vaccine) in an area not endemic for typhoid fever. Vaccine. 2010 Feb 10;28(6):1451-3. doi: 10.1016/j.vaccine.2009.11.051. Epub 2009 Dec 8. **PMID:** 20003920 **Citation:** Michel R, Garnotel E, Spiegel A, Morillon M, Saliou P, Boutin JP. Outbreak of typhoid fever in vaccinated members of the French Armed Forces in the Ivory Coast. Eur J Epidemiol. 2005;20(7):635-42. doi: 10.1007/s10654-005-7454-6. **PMID:** 16119438 **Citation:** Pasetti MF, Simon JK, Sztein MB, Levine MM. Immunology of gut mucosal vaccines. Immunol Rev. 2011 Jan;239(1):125-48. doi: 10.1111/j.1600-065X.2010.00970.x. **PMID:** 21198669 **Citation:** Cryz SJ Jr, Vanprapar N, Thisyakorn U, Olanratmanee T, Losonsky G, Levine MM, Chearskul S. Safety and immunogenicity of Salmonella typhi Ty21a vaccine in young Thai children. Infect Immun. 1993 Mar;61(3):1149-51. doi: 10.1128/iai.61.3.1149-1151.1993. **PMID:** 8432597 **Citation:** Simanjuntak CH, Paleologo FP, Punjabi NH, Darmowigoto R, Soeprawoto, Totosudirjo H, Haryanto P, Suprijanto E, Witham ND, Hoffman SL. Oral immunisation against typhoid fever in Indonesia with Ty21a vaccine. Lancet. 1991 Oct 26;338(8774):1055-9. doi: 10.1016/0140-6736(91)91910-m. **PMID:** 1681365 **Citation:** Levine MM, Ferreccio C, Black RE, Germanier R. Large-scale field trial of Ty21a live oral typhoid vaccine in enteric-coated capsule formulation. Lancet. 1987 May 9;1(8541):1049-52. doi: 10.1016/s0140-6736(87)90480-6. **PMID:** 2883393 **Citation:** Olanratmanee T, Levine M, Losonsky G, Thisyakorn V, Cryz SJ Jr. Safety and immunogenicity of Salmonella typhi Ty21a liquid formulation vaccine in 4- to 6-year-old Thai children. J Infect Dis. 1992 Aug;166(2):451-2. doi: 10.1093/infdis/166.2.451. No abstract available. **PMID:** 1634818 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000012480 - Term: Salmonella Infections - ID: D000004756 - Term: Enterobacteriaceae Infections - ID: D000016905 - Term: Gram-Negative Bacterial Infections - ID: D000001424 - Term: Bacterial Infections - ID: D000001423 - Term: Bacterial Infections and Mycoses - ID: D000007239 - Term: Infections ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: BC26 - Name: Wounds and Injuries - Abbrev: All - Name: All Conditions - Abbrev: BC01 - Name: Infections - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M2454 - Name: Hyperthermia - Relevance: LOW - As Found: Unknown - ID: M8464 - Name: Fever - Relevance: LOW - As Found: Unknown - ID: M17185 - Name: Typhoid Fever - Relevance: HIGH - As Found: Typhoid - ID: M10283 - Name: Infections - Relevance: LOW - As Found: Unknown - ID: M6368 - Name: Communicable Diseases - Relevance: LOW - As Found: Unknown - ID: M15299 - Name: Salmonella Infections - Relevance: LOW - As Found: Unknown - ID: M7918 - Name: Enterobacteriaceae Infections - Relevance: LOW - As Found: Unknown - ID: M4722 - Name: Bacterial Infections - Relevance: LOW - As Found: Unknown - ID: M19249 - Name: Gram-Negative Bacterial Infections - Relevance: LOW - As Found: Unknown - ID: M12136 - Name: Mycoses - Relevance: LOW - As Found: Unknown - ID: M4721 - Name: Bacterial Infections and Mycoses - Relevance: LOW - As Found: Unknown - ID: T5771 - Name: Typhoid Fever - Relevance: HIGH - As Found: Typhoid ### Condition Browse Module - Meshes - ID: D000014435 - Term: Typhoid Fever ### Intervention Browse Module - Ancestors - 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: M17360 - Name: Vaccines - Relevance: HIGH - As Found: Other - ID: M10201 - Name: Immunologic Factors - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000014612 - Term: Vaccines ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05791279 **Brief Title:** Electrocardiography-based Estimation of Heart Age to Improve Blood Pressure - a Pilot Study **Official Title:** The Use of Electrocardiography-based Estimation of Heart Age to Improve Blood Pressure in a Primary Care Setting - a Pilot Study #### Organization Study ID Info **ID:** Kronoberg_HA #### Organization **Class:** OTHER_GOV **Full Name:** Kronoberg County Council ### Status Module #### Completion Date **Date:** 2024-09-01 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2023-10-11 **Type:** ACTUAL **Last Update Submit Date:** 2023-10-09 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2024-09-01 **Type:** ESTIMATED #### Start Date **Date:** 2023-05-01 **Type:** ACTUAL **Status Verified Date:** 2023-10 #### Study First Post Date **Date:** 2023-03-30 **Type:** ACTUAL **Study First Submit Date:** 2023-02-20 **Study First Submit QC Date:** 2023-03-17 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** Lund University **Class:** OTHER **Name:** University of Sydney #### Lead Sponsor **Class:** OTHER_GOV **Name:** Kronoberg County Council #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Successfully communicating cardiovascular risk to patients is essential for achieving compliance to medication and lifestyle changes. An intuitive way to translate cardiovascular risk is to present a Heart Age; an ECG-based age-estimation from ECG changes which can be contrasted to a patient's chronological age. In this pilot study, the feasibility of a randomized controlled study (RCT) in which hypertensive patients in primary care will receive information about their ECG-based Heart Age in addition to standard care, or standard care alone, will be assessed, in preparation for a larger RCT. **Detailed Description:** Cardiovascular disease processes begin early and progress silently for many years. Fortunately, several risk-factors are modifiable, and cardiovascular risk can therefore be reduced for example by smoking cessation, dietary changes, increased physical activity in sedentary people and adherence to pharmacological risk factor reduction. To accomplish this, the patient must understand that he or she is at risk. One way to do this could be to present the risk as a "Heart Age", which can be contrasted to the patient's chronological age. In a previous study, an accurate Heart Age could be obtained using conventional, 10-second ECG recordings. The ECG analysis included conventional and basic ECG measurements such as heart rate and waveform amplitudes and durations, but also combinations of advanced ECG measures from 12-lead-ECG-derived vectorcardiography and waveform complexity. However, it is not known whether the use of Heart Age can improve outcomes if applied in clinical care. To address this issue, a study in which patients, in addition to standard care, are randomized to either being presented with their Heart Age or not should be performed. In order to check the feasibility of such a randomized controlled study (RCT), a pilot study is necessary. This study will evaluate the feasibility of randomizing patients with hypertension to either being presented with their Heart Age or not, in addition to standard care, by describing the recruitment dropout rate, the quality of the recorded ECG and the tolerability of the intervention (participant experience). At the baseline visit a standardized resting blood pressure, height, weight and waist circumference will be measured. Baseline characteristics (age, sex, hypercholesterolemia, diabetes, ischemic heart disease, cerebrovascular disease, renal failure, heart failure, medications) will be recorded from the patient records. Unless a recent (\<1 month) ECG is available, a new resting ECG recording will be performed, and blood sampling will be done (total cholesterol, high-density lipoprotein \[HDL\], low-density lipoprotein \[LDL\] mmol/l, triglyceride mmol/mol, Hba1c (IFCC) mmol/mL, P-Creatinine (µmol/L). The participant will also receive a questionnaire for background information and information about tobacco and alcohol use, level of physical activity, dietary habits, medication adherence, quality of life and self-estimated health including estimating one's own risk of cardiovascular morbidity. ECG-based Heart Age will be estimated for all participants but presented only to patients in the intervention arm. A follow-up visit will be performed 6 months after the baseline visit. At follow-up, the same measurements including the same questionnaires will be obtained. Participants in the intervention arm will also receive a questionnaire on their experience of receiving information about their Heart Age (tolerability). ### Conditions Module **Conditions:** - Cardiovascular Diseases - Hypertension ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 60 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** The participants in the intervention group will receive information about their ECG-based Heart-Age and the Heart Age. The estimated Heart Age and Heart Age Gap will be presented in writing to the participants in the experimental arm within 2 weeks after the baseline visit. The presentation will include a brief and easy-to-understand description on how the Heart Age has been estimated. In addition, patients will receive information about general advice on how to improve blood pressure levels and reduce the risk of future cardiovascular disease by adopting a healthy lifestyle and adhering to the prescribed medication. This information will be the same for participants in the two study arms, and is based on recommendations from the European Society of Cardiology. For patients in the intervention group the ordinary primary care physicians will also be informed about the ECG-based Heart-Age. **Intervention Names:** - Other: Heart age **Label:** Interventional arm **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** The control group will receive standard care according to routine care at the individual primary health care center, and receive the same general advice, on how to improve blood pressure levels and/or to reduce risks of future cardiovascular disease, as the participants in the intervention group. **Label:** Control arm **Type:** NO_INTERVENTION ### Interventions #### Intervention 1 **Arm Group Labels:** - Interventional arm **Description:** information about their ECG-based Heart-Age and the Heart Age gap, i.e. the difference between chronological and ECG-based Heart Age. **Name:** Heart age **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** Number of patients being recruited within the specified time frame **Measure:** Recruitment rate **Time Frame:** 6 months **Description:** Number of patients who do not complete follow-up **Measure:** Dropout rate **Time Frame:** 6 months **Description:** Number of Heart Age estimations with adequate ECG signal quality **Measure:** Quality **Time Frame:** 6 months **Description:** Tolerability of the intervention assessed through questionnaires. **Measure:** Tolerability of the intervention **Time Frame:** 6 months #### Secondary Outcomes **Description:** Change in blood pressure **Measure:** Blood pressure (systolic and diastolic) **Time Frame:** 6 months **Description:** Change in HbA1c **Measure:** HbA1c **Time Frame:** 6 months **Description:** Change in physical activity assessed through questionnaires. **Measure:** Physical activity **Time Frame:** 6 months **Description:** Change in dietary habits assessed through questionnaires. **Measure:** Dietary habits **Time Frame:** 6 months **Description:** Change in tobacco use assessed through questionnaires. **Measure:** Tobacco **Time Frame:** 6 months **Description:** Change in alcohol use assessed through questionnaires. **Measure:** Alcohol **Time Frame:** 6 months **Description:** Change in medication adherence assessed through questionnaires. **Measure:** Medication adherence **Time Frame:** 6 months **Description:** Change in risk perception assessed through questionnaires. **Measure:** Risk perception **Time Frame:** 6 months **Description:** Change in BMI **Measure:** Body-mass index (BMI) **Time Frame:** 6 months **Description:** Change in Heart Age **Measure:** Heart Age **Time Frame:** 6 months ### Eligibility Module **Eligibility Criteria:** Eligibility: Patients with hypertension and systolic blood pressure \>140 mm Hg (measured during the inclusion period by doctor or nurse at the primary health care center) Inclusion Criteria: * Informed consent * Diagnosed hypertension (International classification of disease (ICD-10), I10.9) * 40 - 75 years Exclusion Criteria: * ECG findings that are incompatible with or may significantly distort the Heart Age estimation (left/right bundle branch block, atrial fibrillation/flutter, tachycardia (≥100/min), abundant ventricular ectopic beats, misplaced ECG electrodes, missing leads, excessive signal noise/baseline) * Short life expectancy (\<1 year) * Pregnancy, known secondary hypertension * Predicted inability to give informed consent due to either language difficulties, cognitive impairment or other. * Systolic blood pressure \<120 mmHg at the baseline visit **Maximum Age:** 75 Years **Minimum Age:** 40 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Thomas Lindow, MD, PhD **Phone:** +46470588000 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Karin Svensson Söderberg, MD **Role:** CONTACT #### Locations **Location 1:** **City:** Ryd **Contacts:** ***Contact 1:*** - **Name:** Karin Svensson Soderberg, MD - **Role:** CONTACT **Country:** Sweden **Facility:** Ryd Vardcentral **Status:** RECRUITING **Location 2:** **City:** Tingsryd **Contacts:** ***Contact 1:*** - **Name:** Karin Svensson Soderberg, MD - **Role:** CONTACT **Country:** Sweden **Facility:** Tingsryd Vardcentral **Status:** RECRUITING #### Overall Officials **Official 1:** **Affiliation:** Region Kronoberg, Sweden; Lund University, Lund, Sweden **Name:** Thomas Lindow, MD, PhD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Lindow T, Palencia-Lamela I, Schlegel TT, Ugander M. Heart age estimated using explainable advanced electrocardiography. Sci Rep. 2022 Jun 14;12(1):9840. doi: 10.1038/s41598-022-13912-9. **PMID:** 35701514 ## Derived Section ### Condition Browse Module - Browse Branches - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M10024 - Name: Hypertension - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000002318 - Term: Cardiovascular Diseases ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT01164579 **Brief Title:** Effects of Tofacitinib (CP-690,550) on Magnetic Resonance Imaging (MRI)- Assessed Joint Structure In Early Rheumatoid Arthritis (RA) **Official Title:** An Exploratory Phase 2, Randomized, Double-blind, Multicenter Study To Assess The Effects Of Tofacitinib (Cp-690,550) On Magnetic Resonance Imaging Endpoints, In Methotrexate Naive Subjects With Early Active Rheumatoid Arthritis #### Organization Study ID Info **ID:** A3921068 #### Organization **Class:** INDUSTRY **Full Name:** Pfizer #### Secondary ID Infos **ID:** 2010-020890-18 **Type:** EUDRACT_NUMBER ### Status Module #### Completion Date **Date:** 2013-11 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2015-04-22 **Type:** ESTIMATED **Last Update Submit Date:** 2015-04-21 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2013-11 **Type:** ACTUAL #### Results First Post Date **Date:** 2015-04-22 **Type:** ESTIMATED **Results First Submit Date:** 2014-11-05 **Results First Submit QC Date:** 2015-04-21 #### Start Date **Date:** 2010-10 **Status Verified Date:** 2015-04 #### Study First Post Date **Date:** 2010-07-16 **Type:** ESTIMATED **Study First Submit Date:** 2010-07-15 **Study First Submit QC Date:** 2010-07-15 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Pfizer #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** Evaluation of efficacy and safety of tofacitinib (CP-690,550) for the treatment of early rheumatoid arthritis in adult patients with moderate to severe disease who are methotrexate naïve. The efficacy will be evaluated by exploring the effects on joint structure assessed by magnetic resonance imaging, x-rays and by standard clinical assessment. ### Conditions Module **Conditions:** - Rheumatoid Arthritis **Keywords:** - Early Rheumatoid Arthritis - Joint Structure - Magnetic Resonance Imaging - Janus Kinase (JAK) Inhibitor - Tasocitinib - Tofacitinib ### 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:** 109 **Type:** ACTUAL **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Intervention Names:** - Drug: Tasocitinib plus Methotrexate **Label:** Tofacitinib (CP 690,550) 10 mg BID plus MTX **Type:** EXPERIMENTAL #### Arm Group 2 **Intervention Names:** - Drug: Tofacitinib plus placebo methotrexate **Label:** Tofacitinib (CP-690,550) 10 mg BID, tablet plus placebo MTX **Type:** EXPERIMENTAL #### Arm Group 3 **Intervention Names:** - Drug: Placebo tofacitinib plus Methotrexate **Label:** Placebo tofacitinib (CP-690,55) plus MTX 10 mg/wk to 20 mg/wk **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Tofacitinib (CP 690,550) 10 mg BID plus MTX **Description:** Tofacitinib (CP 690,550) 10 mg BID, tablets + methotrexate (MTX) 10 mg/wk to 20 mg/wk, titrated over 2 months **Name:** Tasocitinib plus Methotrexate **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Tofacitinib (CP-690,550) 10 mg BID, tablet plus placebo MTX **Description:** Tofacitinib (CP-90,550) 10 mg BID, tablets. Placebo to match methotrexate (MTX) capsules titrated as in Treatment Arm 1. **Name:** Tofacitinib plus placebo methotrexate **Type:** DRUG #### Intervention 3 **Arm Group Labels:** - Placebo tofacitinib (CP-690,55) plus MTX 10 mg/wk to 20 mg/wk **Description:** Methotrexate (MTX) 10 mg/wk to 20 mg/wk, capsules, titrated over 2 months. Placebo in tablets to match tofacitinib **Name:** Placebo tofacitinib plus Methotrexate **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Synovitis is defined as an area in the synovial compartment that shows above normal postgadolinium enhancement of a thickness greater than the width of the normal synovium. T1-weighted images were acquired before and after the administration of intravenous contrast agent containing gadolinium. Intravenous contrast was required to demonstrate enhancing synovitis. Synovitis was scored 0 to 3 in 3 wrist regions and in each of the first through fifth MCP joints. A score of 0 is normal, with no enhancement or enhancement up to the thickness of normal synovium, while scores of 1 to 3 (mild, moderate, severe) refer to increments of one-third of the presumed maximum volume of enhancing tissue in the synovial compartment. Total synovitis score ranges from a minimum of 0 to a maximum of 24. A negative value in synovitis change from Baseline score indicates an improvement. **Measure:** Change From Baseline to Month 3 in Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Imaging Score (RAMRIS) Wrist and Metacarpophalangeal (MCP) Synovitis **Time Frame:** Month 3 **Description:** Bone edema was assessed at 25 anatomic locations: 15 in 1 wrist and 10 in attached hand. Bone edema was defined as a lesion within the trabecular bone, with ill-defined margins and signal characteristics consistent with increased water content. Each bone was scored separately; the scale was 0-3 based on the proportion of bone with edema, as follows 0: no edema; 1: 1-33% of bone edematous; 2: 34-66% of bone edematous; 3: 67-100%. OMERACT RAMRIS total bone edema score for hands/wrists was sum of the individual scores for each location. Thus the maximum score per hand/wrist was 75 (range 0-75). Increasing score=greater severity. **Measure:** Change From Baseline to Month 6 in OMERACT RAMRIS Wrist and MCP Bone Marrow Edema **Time Frame:** Month 6 #### Secondary Outcomes **Description:** Synovitis is defined as an area in the synovial compartment that shows above normal postgadolinium enhancement of a thickness greater than the width of the normal synovium. T1-weighted images were acquired before and after the administration of intravenous contrast agent containing gadolinium. Intravenous contrast was required to demonstrate enhancing synovitis. Synovitis was scored 0 to 3 in 3 wrist regions and in each of the first through fifth MCP joints. A score of 0 is normal, with no enhancement or enhancement up to the thickness of normal synovium, while scores of 1 to 3 (mild, moderate, severe) refer to increments of one-third of the presumed maximum volume of enhancing tissue in the synovial compartment. Total synovitis score ranges from a minimum of 0 to a maximum of 24. A negative value in synovitis change from Baseline score indicates an improvement. **Measure:** Change From Baseline to Months 1, 6, and 12 in OMERACT RAMRIS Wrist and MCP Synovitis **Time Frame:** Months 1, 6, and 12 **Description:** Bone edema was assessed at 25 anatomic locations: 15 in 1 wrist and 10 in attached hand. Bone edema was defined as a lesion within the trabecular bone, with ill-defined margins and signal characteristics consistent with increased water content. Each bone was scored separately; the scale was 0â€"3 based on the proportion of bone with edema, as follows 0: no edema; 1: 1â€"33% of bone edematous; 2: 34â€"66% of bone edematous; 3: 67â€"100%. OMERACT RAMRIS total bone edema score for hands/wrists was sum of the individual scores for each location. Thus the maximum score per hand/wrist was 75 (range 0-75). Increasing score=greater severity. **Measure:** Change From Baseline to Months 1, 3, and 12 in OMERACT RAMRIS Bone Marrow Edema in Wrist and MCP **Time Frame:** Months 1, 3, and 12 **Description:** Bone erosion assessed at 25 anatomic locations: 15 in 1 wrist and 10 in attached hand. Each site was scored in 1.0 increments from 0 (no damage) to 10 (severe damage), indicating erosion (each unit=10% bone loss) of original articular bone. OMERACT RAMRIS total erosion score for hands/wrists was sum of the individual scores for each location. Thus the maximum score per hand/wrist is 250 (range 0-250). Increasing score=greater severity. **Measure:** Change From Baseline to Months 1, 3, 6, and 12 in OMERACT RAMRIS Wrist and MCP Erosions **Time Frame:** Months 1, 3, 6, and 12 **Description:** Modified TSS is a measure of change in joint health. TSS is defined as joint space narrowing score (range 0 \[no narrowing\] to 168 \[high narrowing\]) plus (+) erosion score (range is from 0 \[no erosion\] to 280 \[high erosion\]). The modified TSS range is from 0 (no damage) to 448 (bad joint status). Increase from baseline represents disease progression and / or joint worsening; no change represents halting of disease progression; a decrease represents improvement. **Measure:** Modified Total Sharp Score (mTSS) at Months 6 and 12 **Time Frame:** Months 6 and 12 **Description:** Modified TSS is a measure of change in joint health. TSS is defined as joint space narrowing score (range 0 \[no narrowing\] to 168 \[high narrowing\]) + erosion score (range is from 0 \[no erosion\] to 280 \[high erosion\]). The modified TSS range is from 0 (no damage) to 448 (bad joint status). Increase from baseline represents disease progression and / or joint worsening; no change represents halting of disease progression; a decrease represents improvement. **Measure:** Change From Baseline to Months 6 and 12 in mTSS **Time Frame:** Months 6 and 12 **Description:** JSN score (a component of the modified TSS) is a measure of change in joint health. JSN score range is 0 (no narrowing) to 168 (high narrowing). Increase from baseline represents disease progression and / or joint worsening; no change represents halting of disease progression; a decrease represents improvement. **Measure:** Joint Space Narrowing (JSN) Scores at Months 6 and 12 **Time Frame:** Months 6 and 12 **Description:** JSN score (a component of the modified TSS) is a measure of change in joint health. JSN score range is 0 (no narrowing) to 168 (high narrowing). Increase from baseline represents disease progression and / or joint worsening; no change represents halting of disease progression; a decrease represents improvement. **Measure:** Change From Baseline to Months 6 and 12 in JSN Scores **Time Frame:** Months 6 and 12 **Description:** Erosion score (a component of the modified TSS) is a measure of change in joint health. Erosion score range is from 0 (no erosion) to 280 (high erosion). Increase from baseline represents disease progression and / or joint worsening; no change represents halting of disease progression; a decrease represents improvement. **Measure:** Erosion Scores at Months 6 and 12 **Time Frame:** Months 6 and 12 **Description:** Erosion score (a component of the modified TSS) is a measure of change in joint health. Erosion score range is from 0 (no erosion) to 280 (high erosion). Increase from baseline represents disease progression and / or joint worsening; no change represents halting of disease progression; a decrease represents improvement. **Measure:** Change From Baseline to Months 6 and 12 in Erosion Score **Time Frame:** Months 6 and 12 **Description:** ACR20 response: greater than or equal to (≥)20% improvement in tender joint count; ≥20% improvement in swollen joint count; and ≥20% improvement in at least 3 of 5 remaining ACR core measures: Participant's Assessment of Pain; Participant's Global Assessment of Disease Activity; Physician Global Assessment of Disease Activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and C-Reactive Protein (CRP). **Measure:** Percentage of Participants With an American College of Rheumatology (ACR) 20 Percent (%) Improvement (ACR20) Response **Time Frame:** Months 1, 2, 3, 6, 9, and 12 **Description:** ACR50 response: ≥ 50% improvement in tender or swollen joint counts and 50% improvement in 3 of the following 5 criteria: 1) Physician's Global Assessment of Disease Activity, 2) Participant's Assessment of disease activity, 3) Paricipant's Assessment of Pain, 4) Participant's assessment of functional disability via a HAQ, and 5) CRP at each visit. **Measure:** Percentage of Participants With an ACR 50% Improvement (ACR50) Response **Time Frame:** Months 1, 2, 3, 6, 9, and 12 **Description:** ACR70 response: ≥70% improvement in tender or swollen joint counts and 70% improvement in 3 of the following 5 criteria: 1) Physician's Global Assessment of Disease Activity, 2) Participant's Assessment of Disease Activity, 3) Participant's Assessment of Pain, 4) Participant's Assessment of Functional Disability via a HAQ, and 5) CRP at each visit. **Measure:** Percentage of Participants With an ACR 70% Improvement (ACR70) Response **Time Frame:** Months 1, 2, 3, 6, 9, and 12 **Description:** DAS28-3 (CRP) was calculated from the swollen joint count and tender joint count using the 28 joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-3 (CRP) less than or equal to (≤)3.2 implied low disease activity and greater than (\>)3.2 to 5.1 implied moderate to high disease activity, and DAS28-3 (CRP) less than (\<)2.6 = remission. **Measure:** Disease Activity Score Based on 28-Joint Count and CRP (DAS28-3 [CRP]) **Time Frame:** Baseline and Months 1, 2, 3, 6, 9, and 12 **Description:** DAS28-3 (CRP) was calculated from the swollen joint count and tender joint count using the 28 joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. **Measure:** Change From Baseline in DAS28-3 (CRP) **Time Frame:** Months 1, 2, 3, 6, 9, and 12 **Description:** DAS28-4 (ESR) was calculated from swollen joint count and tender joint count using 28 joints count, ESR (millimeters per hour \[mm/hour\]) and Participant Global Assessment of disease activity (participant rated arthritis activity assessment). Total score range: 0 to 9.4; higher score=more disease activity. DAS28-4 (ESR) ≤3.2 implied low disease activity and \>3.2 to 5.1 implied moderate to high disease activity, and DAS28-4 (ESR) \<2.6 = remission. **Measure:** Disease Activity Score Based on 28-Joint Count and Erythrocyte Sedimentation Rate (DAS28-4 [ESR]) **Time Frame:** Baseline and Months 1, 2, 3, 6, 9, and 12 **Description:** DAS28-4 (ESR) was calculated from swollen joint count and tender joint count using 28 joints count, ESR (millimeters per hour \[mm/hour\]) and Participant Global Assessment of disease activity (participant rated arthritis activity assessment). Total score range: 0 to 9.4; higher score=more disease activity. **Measure:** Change From Baseline in DAS28-4 (ESR) **Time Frame:** Months 1, 2, 3, 6, 9, and 12 **Description:** DAS28-3(CRP) was calculated from the swollen joint count and tender joint count using 28-joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28 categorical responses define a good (absolute: \<3.2 or \>1.2 improvement from baseline \[BL\]), moderate (absolute: 3.2-5.1 or 0.6-1.2 change from BL), or no response (absolute: \>5.1 or \<0.6 change from BL). **Measure:** Percentage of Participants With DAS28-3 (CRP) Response (Good or Moderate Improvement) **Time Frame:** Months 1, 2, 3, 6, 9, and 12 **Description:** DAS28-3(CRP) was calculated from the swollen joint count and tender joint count using 28-joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-3(CRP) ≤3.2 implied low disease activity. **Measure:** Percentage of Participants With DAS28-3 (CRP) Score ≤3.2 **Time Frame:** Months 1, 2, 3, 6, 9, and 12 **Description:** DAS28-3(CRP) was calculated from the swollen joint count and tender joint count using 28-joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-3(CRP) \<2.6 implied remission. **Measure:** Percentage of Participants With DAS28-3 (CRP) Score <2.6 **Time Frame:** Months 1, 2, 3, 6, 9, and 12 **Description:** DAS28-4(ESR) was calculated from swollen joint count and tender joint count using 28 joints count, ESR (mm/hour) and Participant's Global Assessment of Disease Activity (participant rated arthritis activity assessment). Total score range: 0 to 9.4, higher score=more disease activity. DAS28 categorical responses define a good (absolute: \<3.2 or \>1.2 improvement from BL), moderate (absolute: 3.2-5.1 or 0.6-1.2 change from BL), or no response (absolute: \>5.1 or \<0.6 change from BL). **Measure:** Percentage of Participants With DAS28-4 (ESR) Response (Good or Moderate Improvement) **Time Frame:** Months 1, 2, 3, 6, 9, and 12 **Description:** DAS28-4(ESR) was calculated from swollen joint count and tender joint count using 28 joints count, ESR (mm/hour) and Participant's Global Assessment of Disease Activity (participant rated arthritis activity assessment). Total score range: 0 to 9.4, higher score=more disease activity. DAS28-4(ESR) ≤3.2 implied low disease activity. **Measure:** Percentage of Participants With DAS28-4 (ESR) ≤3.2 **Time Frame:** Months 1, 2, 3, 6, 9, and 12 **Description:** DAS28-4(ESR) was calculated from swollen joint count and tender joint count using 28 joints count, ESR (mm/hour) and Participant's Global Assessment of Disease Activity (participant rated arthritis activity assessment). Total score range: 0 to 9.4, higher score=more disease activity. DAS28-4(ESR) \<2.6 implied remission. **Measure:** Percentage of Participants With DAS28-4 (ESR) <2.6 **Time Frame:** Months 1, 2, 3, 6, 9, and 12 ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Adult patients with moderate to severe early rheumatoid arthritis (\< 2 years) who are methotrexate and biologic disease modifying antirheumatic drug naive. Exclusion Criteria: * Pregnant or lactating patients; * Patients with renal or hepatic impairment or other severe or progressing disease; * Patients with contraindication to magnetic resonance imaging with gadolinium contrast. **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Gilbert **Country:** United States **Facility:** ArthroCare, Arthritis Care & Research, PC **State:** Arizona **Zip:** 85234 **Location 2:** **City:** Huntington Beach **Country:** United States **Facility:** Talbert Medical Group **State:** California **Zip:** 92646 **Location 3:** **City:** Upland **Country:** United States **Facility:** Inland Rheumatology Clinical Trials, Inc. **State:** California **Zip:** 91786 **Location 4:** **City:** Ormond Beach **Country:** United States **Facility:** Millennium Research **State:** Florida **Zip:** 32174 **Location 5:** **City:** Pinellas Park **Country:** United States **Facility:** DMI Research, Inc. **State:** Florida **Zip:** 33782 **Location 6:** **City:** St. Petersburg **Country:** United States **Facility:** St. Petersburg Arthritis Center **State:** Florida **Zip:** 33710 **Location 7:** **City:** Oklahoma City **Country:** United States **Facility:** Oklahoma Medical Research Foundation **State:** Oklahoma **Zip:** 73104 5005 **Location 8:** **City:** Allen **Country:** United States **Facility:** Office of John P. Lavery, MD, PA **State:** Texas **Zip:** 75013 **Location 9:** **City:** Buenos Aires **Country:** Argentina **Facility:** OMI - Organización Médica de Investigación **Zip:** C1015ABO **Location 10:** **City:** Buenos Aires **Country:** Argentina **Facility:** Saint Dennis Medical Group S.A. **Zip:** C1034ACO **Location 11:** **City:** Buenos Aires **Country:** Argentina **Facility:** Consultorios Reumatologicos Pampa **Zip:** C1428DZF **Location 12:** **City:** Valdivia **Country:** Chile **Facility:** Hospital Base Valdivia **State:** Region XIV **Zip:** 5090145 **Location 13:** **City:** Osorno **Country:** Chile **Facility:** Consulta Privada Dr. Juan Ignacio Vargas **State:** X Region **Zip:** 5311089 **Location 14:** **City:** Split **Country:** Croatia **Facility:** University Hospital Centre Split,Department for Internal Medicine, Division of Clinical Rheumatology **Zip:** 21000 **Location 15:** **City:** Zagreb **Country:** Croatia **Facility:** General Hospital Sveti Duh **Zip:** 10000 **Location 16:** **City:** Hostivice **Country:** Czech Republic **Facility:** ARTMEDI UPD s r.o. **Zip:** 253 01 **Location 17:** **City:** Praha 11 - Chodov **Country:** Czech Republic **Facility:** DC Mediscan **Zip:** 148 00 **Location 18:** **City:** Praha 1 **Country:** Czech Republic **Facility:** Nemocnice na Frantisku s poliklinikou **Zip:** 110 00 **Location 19:** **City:** Praha 1 **Country:** Czech Republic **Facility:** Nemocnice na Frantisku **Zip:** 110 00 **Location 20:** **City:** Praha 2 **Country:** Czech Republic **Facility:** Revmatologicky ustav **Zip:** 128 50 **Location 21:** **City:** Uherske Hradiste **Country:** Czech Republic **Facility:** Uherskohradistska nemocnice, a.s. **Zip:** 686 68 **Location 22:** **City:** Zlin **Country:** Czech Republic **Facility:** Nemocnice Atlas, a.s. **Zip:** 760 01 **Location 23:** **City:** Zlin **Country:** Czech Republic **Facility:** PV-Medical s.r.o. **Zip:** 760 01 **Location 24:** **City:** Balatonfured **Country:** Hungary **Facility:** Drug Research Center Kft. **Zip:** 8230 **Location 25:** **City:** Budapest **Country:** Hungary **Facility:** Orszagos Reumatologiai es Fizioterapias Intezet **Zip:** 1023 **Location 26:** **City:** Budapest **Country:** Hungary **Facility:** Synexus Magyarorszag Kft. **Zip:** 1036 **Location 27:** **City:** Debrecen **Country:** Hungary **Facility:** Debreceni Egyetem Orvos- es Egeszsegtudomanyi Centrum, Reumatologiai Tanszek **Zip:** 4032 **Location 28:** **City:** Gyor **Country:** Hungary **Facility:** Petz Aladar Megyei Oktato Korhaz/Reumatologiai es Mozgasszervi Rehabilitacios Centrum **Zip:** 9027 **Location 29:** **City:** Mexico **Country:** Mexico **Facility:** Centro de Investigacion y Tratamiento Reumatologico S.C. **State:** D. F. **Zip:** 11850 **Location 30:** **City:** Mexico **Country:** Mexico **Facility:** Hospital Angeles Mocel **State:** D.f. **Zip:** 11850 **Location 31:** **City:** Mexico **Country:** Mexico **Facility:** Centro de Investigacion y Tratamiento Reumatologico SC **State:** Distrito Federal **Zip:** 11850 **Location 32:** **City:** Chapultepec **Country:** Mexico **Facility:** Hospital Angeles Mocel **Zip:** 11850 **Location 33:** **City:** Chihuahua **Country:** Mexico **Facility:** Investigacion y Biomedicina de Chihuahua S.C **Zip:** 31000 **Location 34:** **City:** Mexico D.F. **Country:** Mexico **Facility:** Hospital Angeles Mocel **Zip:** 11850 **Location 35:** **City:** San Luis Potosi **Country:** Mexico **Facility:** Centro de Alta Especialidad en Reumatologia e Investigacion del Potosi S.C. **Zip:** 78200 **Location 36:** **City:** Bialystok **Country:** Poland **Facility:** Niepubliczny Zaklad Opieki Zdrowotnej Centrum Osteoporozy i Chorob Kostno-Stawowych J. **Zip:** 15-879 **Location 37:** **City:** Poznan **Country:** Poland **Facility:** Prywatna Praktyka Lekarska Prof. UM dr hab. med. Pawel Hrycaj **Zip:** 61-397 **Location 38:** **City:** Torun **Country:** Poland **Facility:** Nzoz "Nasz Lekarz" **Zip:** 87-100 **Location 39:** **City:** San Juan **Country:** Puerto Rico **Facility:** Mindful Medical Research **Zip:** 00918 **Location 40:** **City:** San Juan **Country:** Puerto Rico **Facility:** San Juan Arthritis & Research Center **Zip:** 00918 #### Overall Officials **Official 1:** **Affiliation:** Pfizer **Name:** Pfizer CT.gov Call Center **Role:** STUDY_DIRECTOR ### References Module #### References **Citation:** Winthrop KL, Curtis JR, Yamaoka K, Lee EB, Hirose T, Rivas JL, Kwok K, Burmester GR. Clinical Management of Herpes Zoster in Patients With Rheumatoid Arthritis or Psoriatic Arthritis Receiving Tofacitinib Treatment. Rheumatol Ther. 2022 Feb;9(1):243-263. doi: 10.1007/s40744-021-00390-0. Epub 2021 Dec 6. **PMID:** 34870800 **Citation:** Cohen SB, Tanaka Y, Mariette X, Curtis JR, Lee EB, Nash P, Winthrop KL, Charles-Schoeman C, Wang L, Chen C, Kwok K, Biswas P, Shapiro A, Madsen A, Wollenhaupt J. Long-term safety of tofacitinib up to 9.5 years: a comprehensive integrated analysis of the rheumatoid arthritis clinical development programme. RMD Open. 2020 Oct;6(3):e001395. doi: 10.1136/rmdopen-2020-001395. **PMID:** 33127856 **Citation:** van der Heijde D, Landewe RBM, Wollenhaupt J, Strengholt S, Terry K, Kwok K, Wang L, Cohen S. Assessment of radiographic progression in patients with rheumatoid arthritis treated with tofacitinib in long-term studies. Rheumatology (Oxford). 2021 Apr 6;60(4):1708-1716. doi: 10.1093/rheumatology/keaa476. **PMID:** 33057725 **Citation:** Panaccione R, Isaacs JD, Chen LA, Wang W, Marren A, Kwok K, Wang L, Chan G, Su C. Characterization of Creatine Kinase Levels in Tofacitinib-Treated Patients with Ulcerative Colitis: Results from Clinical Trials. Dig Dis Sci. 2021 Aug;66(8):2732-2743. doi: 10.1007/s10620-020-06560-4. Epub 2020 Aug 20. Erratum In: Dig Dis Sci. 2020 Oct 10;: **PMID:** 32816215 **Citation:** Conaghan PG, Ostergaard M, Troum O, Bowes MA, Guillard G, Wilkinson B, Xie Z, Andrews J, Stein A, Chapman D, Koenig A. Very early MRI responses to therapy as a predictor of later radiographic progression in early rheumatoid arthritis. Arthritis Res Ther. 2019 Oct 21;21(1):214. doi: 10.1186/s13075-019-2000-1. **PMID:** 31639034 **Citation:** Cohen SB, Tanaka Y, Mariette X, Curtis JR, Lee EB, Nash P, Winthrop KL, Charles-Schoeman C, Thirunavukkarasu K, DeMasi R, Geier J, Kwok K, Wang L, Riese R, Wollenhaupt J. Long-term safety of tofacitinib for the treatment of rheumatoid arthritis up to 8.5 years: integrated analysis of data from the global clinical trials. Ann Rheum Dis. 2017 Jul;76(7):1253-1262. doi: 10.1136/annrheumdis-2016-210457. Epub 2017 Jan 31. **PMID:** 28143815 **Citation:** Conaghan PG, Ostergaard M, Bowes MA, Wu C, Fuerst T, van der Heijde D, Irazoque-Palazuelos F, Soto-Raices O, Hrycaj P, Xie Z, Zhang R, Wyman BT, Bradley JD, Soma K, Wilkinson B. Comparing the effects of tofacitinib, methotrexate and the combination, on bone marrow oedema, synovitis and bone erosion in methotrexate-naive, early active rheumatoid arthritis: results of an exploratory randomised MRI study incorporating semiquantitative and quantitative techniques. Ann Rheum Dis. 2016 Jun;75(6):1024-33. doi: 10.1136/annrheumdis-2015-208267. Epub 2016 Jan 25. **PMID:** 27002108 **Citation:** Cohen S, Radominski SC, Gomez-Reino JJ, Wang L, Krishnaswami S, Wood SP, Soma K, Nduaka CI, Kwok K, Valdez H, Benda B, Riese R. Analysis of infections and all-cause mortality in phase II, phase III, and long-term extension studies of tofacitinib in patients with rheumatoid arthritis. Arthritis Rheumatol. 2014 Nov;66(11):2924-37. doi: 10.1002/art.38779. **PMID:** 25047021 #### See Also Links **Label:** To obtain contact information for a study center near you, click here. **URL:** https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=A3921068&StudyName=Effects%20of%20Tofacitinib%20%28CP-690%2C550%29%20on%20Magnetic%20Resonance%20Imaging%20%28MRI%29-%20Assessed%20Joint%20Structure%20In%20Early%20Rheumatoid%20Arthritis%20%28R ## 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 ### Condition Browse Module - Browse Branches - Abbrev: BC05 - Name: Musculoskeletal Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC17 - Name: Skin and Connective Tissue Diseases - Abbrev: BC20 - Name: Immune System Diseases ### Condition Browse Module - Browse Leaves - 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 ### Condition Browse Module - Meshes - ID: D000001168 - Term: Arthritis - ID: D000001172 - Term: Arthritis, Rheumatoid ### 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: D000000964 - Term: Antimetabolites, Antineoplastic - ID: D000000963 - Term: Antimetabolites - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000000970 - Term: Antineoplastic Agents - ID: D000003879 - Term: Dermatologic Agents - ID: D000004791 - Term: Enzyme Inhibitors - ID: D000005493 - Term: Folic Acid Antagonists - ID: D000007166 - Term: Immunosuppressive Agents - ID: D000007155 - Term: Immunologic Factors - ID: D000018501 - Term: Antirheumatic Agents - ID: D000019384 - Term: Nucleic Acid Synthesis Inhibitors - ID: D000075242 - Term: Janus Kinase Inhibitors - ID: D000047428 - Term: Protein Kinase Inhibitors ### Intervention Browse Module - Browse Branches - Abbrev: ANeo - Name: Antineoplastic Agents - Abbrev: ARhu - Name: Antirheumatic Agents - Abbrev: Derm - Name: Dermatologic Agents - Abbrev: Repr - Name: Reproductive Control Agents - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Micro - Name: Micronutrients - Abbrev: Hemat - Name: Hematinics - Abbrev: Vi - Name: Vitamins ### Intervention Browse Module - Browse Leaves - ID: M11703 - Name: Methotrexate - Relevance: HIGH - As Found: Breast Cancer - ID: M258018 - Name: Tofacitinib - Relevance: HIGH - As Found: Voice - ID: M4281 - Name: Antimetabolites - Relevance: LOW - As Found: Unknown - ID: M7074 - Name: Dermatologic Agents - Relevance: LOW - As Found: Unknown - ID: M7951 - Name: Enzyme Inhibitors - Relevance: LOW - As Found: Unknown - ID: M8618 - Name: Folic Acid - Relevance: LOW - As Found: Unknown - ID: M17546 - Name: Vitamin B Complex - Relevance: LOW - As Found: Unknown - ID: M8619 - Name: Folic Acid Antagonists - 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: M20604 - Name: Antirheumatic Agents - Relevance: LOW - As Found: Unknown - ID: M1474 - Name: Janus Kinase Inhibitors - Relevance: LOW - As Found: Unknown - ID: M25820 - Name: Protein Kinase Inhibitors - Relevance: LOW - As Found: Unknown - ID: T447 - Name: Folinic Acid - 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: D000008727 - Term: Methotrexate - ID: C000479163 - Term: Tofacitinib ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module **Description:** The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study. #### Event Groups **Group ID:** EG000 **Title:** Tofacitinib (CP-690,550) Plus MTX **Description:** Participants received CP-690,550 10 mg, tablets, PO, BID, and MTX 10 mg/week to 20 mg/week, capsules, PO, for a maximum of 12 months. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** EG000 **Other Num Affected:** 24 **Other Num at Risk:** 36 **Serious Number Affected:** 2 **Serious Number At Risk:** 36 **Title:** Tofacitinib (CP-690,550) Plus MTX **Group ID:** EG001 **Title:** Tofacitinib (CP-690,550) **Description:** Participants received CP-690,550 10 mg tablets, PO, BID and matching placebo MTX capsules, PO, once weekly for a maximum of 12 months. To maintain the blind, matching placebo MTX was titrated as follows: 4 capsules once weekly for 4 weeks; if well tolerated, at Month 1 titrate up to 6 capsules once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 8 capsules once weekly for the duration of the study. A single dose reduction of MTX placebo to 2 capsules was allowed because of lack of tolerance, as long as the participant remained on a dose of at least 4 MTX placebo capsules weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** EG001 **Other Num Affected:** 31 **Other Num at Risk:** 36 **Serious Number Affected:** 1 **Serious Number At Risk:** 36 **Title:** Tofacitinib (CP-690,550) **Group ID:** EG002 **Title:** Methotrexate **Description:** Participants received MTX 10 mg/week to 20 mg/week, capsules, PO, and matching placebo CP-690,550 tablets, PO, BID. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** EG002 **Other Num Affected:** 29 **Other Num at Risk:** 37 **Serious Number Affected:** 2 **Serious Number At Risk:** 37 **Title:** Methotrexate **Frequency Threshold:** 2 #### Other Events **Term:** Anaemia **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Leukopenia **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Lymph node pain **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Lymphadenopathy **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Lymphopenia **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Macrocytosis **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Neutropenia **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Neutrophilia **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Normochromic normocytic anaemia **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Thrombocytosis **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Angina pectoris **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Myocardial ischaemia **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Palpitations **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Ear pruritus **Organ System:** Ear and labyrinth disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Vertigo **Organ System:** Ear and labyrinth disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Hypothyroidism **Organ System:** Endocrine disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Eye disorder **Organ System:** Eye disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Lacrimation increased **Organ System:** Eye disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Scleritis **Organ System:** Eye disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Visual acuity reduced **Organ System:** Eye disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Xerophthalmia **Organ System:** Eye disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Abdominal distension **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Abdominal pain **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Abdominal pain lower **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Abdominal pain upper **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Abdominal tenderness **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Aphthous stomatitis **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Constipation **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Diarrhoea **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Dry mouth **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Dyspepsia **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Food poisoning **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Gastric disorder **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Gastritis **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Gastrooesophageal reflux disease **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Hyperchlorhydria **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Irritable bowel syndrome **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Nausea **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Stomatitis **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Chest pain **Organ System:** General disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Local swelling **Organ System:** General disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Malaise **Organ System:** General disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Non-cardiac chest pain **Organ System:** General disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Pyrexia **Organ System:** General disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Cholelithiasis **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Hepatic steatosis **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Hypertransaminasaemia **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Acute tonsillitis **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA v16.1 **Term:** Anal abscess **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA v16.1 **Term:** Bronchitis **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA v16.1 **Term:** Folliculitis **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA v16.1 **Term:** Fungal skin infection **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA v16.1 **Term:** Furuncle **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA v16.1 **Term:** Gastroenteritis **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA v16.1 **Term:** Influenza **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA v16.1 **Term:** Nasopharyngitis **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA v16.1 **Term:** Oral fungal infection **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA v16.1 **Term:** Oral herpes **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA v16.1 **Term:** Pharyngitis **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA v16.1 **Term:** Pharyngotonsillitis **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA v16.1 **Term:** Pneumonia **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA v16.1 **Term:** Respiratory tract infection **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA v16.1 **Term:** Rhinitis **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA v16.1 **Term:** Sinusitis **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA v16.1 **Term:** Tonsillitis **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA v16.1 **Term:** Tooth abscess **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA v16.1 **Term:** Tooth infection **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA v16.1 **Term:** Upper respiratory tract infection **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA v16.1 **Term:** Urinary tract infection **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA v16.1 **Term:** Viral upper respiratory tract infection **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA v16.1 **Term:** Vulvovaginitis **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA v16.1 **Term:** Toxicity to various agents **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA v16.1 **Term:** Alanine aminotransferase increased **Organ System:** Investigations **Source Vocabulary:** MedDRA v16.1 **Term:** Aspartate aminotransferase increased **Organ System:** Investigations **Source Vocabulary:** MedDRA v16.1 **Term:** Blood bicarbonate decreased **Organ System:** Investigations **Source Vocabulary:** MedDRA v16.1 **Term:** Blood cholesterol increased **Organ System:** Investigations **Source Vocabulary:** MedDRA v16.1 **Term:** Blood creatine phosphokinase increased **Organ System:** Investigations **Source Vocabulary:** MedDRA v16.1 **Term:** Blood glucose increased **Organ System:** Investigations **Source Vocabulary:** MedDRA v16.1 **Term:** Gamma-glutamyltransferase increased **Organ System:** Investigations **Source Vocabulary:** MedDRA v16.1 **Term:** Haemoglobin decreased **Organ System:** Investigations **Source Vocabulary:** MedDRA v16.1 **Term:** Hepatic enzyme increased **Organ System:** Investigations **Source Vocabulary:** MedDRA v16.1 **Term:** Liver function test abnormal **Organ System:** Investigations **Source Vocabulary:** MedDRA v16.1 **Term:** Red blood cell count decreased **Organ System:** Investigations **Source Vocabulary:** MedDRA v16.1 **Term:** Transaminases increased **Organ System:** Investigations **Source Vocabulary:** MedDRA v16.1 **Term:** Weight increased **Organ System:** Investigations **Source Vocabulary:** MedDRA v16.1 **Term:** Hypercholesterolaemia **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Hypertriglyceridaemia **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Hypoglycaemia **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Increased appetite **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Type 2 diabetes mellitus **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Arthralgia **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Back pain **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Joint swelling **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Musculoskeletal stiffness **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Myalgia **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Pain in extremity **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Rheumatoid arthritis **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Rheumatoid nodule **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Tendonitis **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Dizziness **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Headache **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Hypoaesthesia **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Sciatica **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Tension headache **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Depression **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Insomnia **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Dysuria **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Urinary incontinence **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Breast tenderness **Organ System:** Reproductive system and breast disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Menorrhagia **Organ System:** Reproductive system and breast disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Sexual dysfunction **Organ System:** Reproductive system and breast disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Uterine fibrosis **Organ System:** Reproductive system and breast disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Vaginal discharge **Organ System:** Reproductive system and breast disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Cough **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Epistaxis **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Nasal congestion **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Oropharyngeal pain **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Pharyngeal inflammation **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Rhinitis allergic **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Upper respiratory tract inflammation **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Acne **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Alopecia **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Diffuse alopecia **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Ecchymosis **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Ingrowing nail **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Night sweats **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Pruritus **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Rash **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Rosacea **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA v16.1 **Term:** Hypertension **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA v16.1 #### Serious Events **Term:** Angina pectoris **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA v16.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 36 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 36 **Group ID:** EG002 **Num At Risk:** 37 **Term:** Hematochezia **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA v16.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 36 **Group ID:** EG001 **Num At Risk:** 36 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 37 **Term:** Cholelithiasis **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA v16.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 36 **Group ID:** EG001 **Num At Risk:** 36 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 37 **Term:** Anal abscess **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA v16.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 36 **Group ID:** EG001 **Num At Risk:** 36 **Group ID:** EG002 **Num At Risk:** 37 **Term:** Foot deformity **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA v16.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 36 **Group ID:** EG001 **Num At Risk:** 36 **Group ID:** EG002 **Num At Risk:** 37 **Time Frame:** Adverse events were collected up to 28 calendar days after the last administration of investigational product. ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 36 **Group ID:** BG001 **Value:** 36 **Group ID:** BG002 **Value:** 37 **Group ID:** BG003 **Value:** 109 **Units:** Participants ### Group **ID:** BG000 **Title:** Tofacitinib (CP-690,550) Plus MTX **Description:** Participants received CP-690,550 10 mg, tablets, PO, BID, and MTX 10 mg/week to 20 mg/week, capsules, PO, for a maximum of 12 months. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. ### Group **ID:** BG001 **Title:** Tofacitinib (CP-690,550) **Description:** Participants received CP-690,550 10 mg tablets, PO, BID and matching placebo MTX capsules, PO, once weekly for a maximum of 12 months. To maintain the blind, matching placebo MTX was titrated as follows: 4 capsules once weekly for 4 weeks; if well tolerated, at Month 1 titrate up to 6 capsules once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 8 capsules once weekly for the duration of the study. A single dose reduction of MTX placebo to 2 capsules was allowed because of lack of tolerance, as long as the participant remained on a dose of at least 4 MTX placebo capsules weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. ### Group **ID:** BG002 **Title:** Methotrexate **Description:** Participants received MTX 10 mg/week to 20 mg/week, capsules, PO, and matching placebo CP-690,550 tablets, PO, BID. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. ### Group **ID:** BG003 **Title:** Total **Description:** Total of all reporting groups ### Measure #### Measurement **Group ID:** BG000 **Spread:** 12.3 **Value:** 47.8 #### Measurement **Group ID:** BG001 **Spread:** 12.8 **Value:** 50.8 #### Measurement **Group ID:** BG002 **Spread:** 11.6 **Value:** 47.8 #### Measurement **Group ID:** BG003 **Spread:** 12.2 **Value:** 48.8 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 31 #### Measurement **Group ID:** BG001 **Value:** 30 #### Measurement **Group ID:** BG002 **Value:** 29 #### Measurement **Group ID:** BG003 **Value:** 90 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 5 #### Measurement **Group ID:** BG001 **Value:** 6 #### Measurement **Group ID:** BG002 **Value:** 8 #### Measurement **Group ID:** BG003 **Value:** 19 **Category Title:** Male **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 **Population Description:** Full Analysis Set (FAS): all participants who were randomized to study medication and received at least 1 dose of randomized study medication. ## Results Section - More Information Module ### Certain Agreement ### Point of Contact **Email:** [email protected] **Organization:** Pfizer, Inc. **Phone:** 1-800-718-1021 **Title:** Pfizer ClinicalTrials.gov Call Center ## Results Section - Outcome Measures Module ### Outcome Measure 1 #### Analysis **CI Lower Limit:** -1.58 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 0.31 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.57 **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.2696 **P-Value Comment:** 2-sided p-value; alpha equals (=) 0.10 **Parameter Type:** Difference in least squares (LS) Mean **Parameter Value:** -0.63 **Statistical Comment:** **Statistical Method:** mixed model repeated measures analysis **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -1.46 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 0.41 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.57 **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.3561 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Difference in LS Mean **Parameter Value:** -0.52 **Statistical Comment:** **Statistical Method:** mixed model repeated measures analysis **Tested Non-Inferiority:** False ### Outcome Measure 2 #### Analysis **CI Lower Limit:** -2.52 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** -0.58 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.59 **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0089 **P-Value Comment:** 2-sided p-value; alpha= 0.10 **Parameter Type:** Difference in LS Means **Parameter Value:** -1.55 **Statistical Comment:** **Statistical Method:** mixed model repeated measures analysis **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -2.72 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** -0.76 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.59 **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0038 **P-Value Comment:** 2-sided p-value; alpha= 0.10 **Parameter Type:** Difference in LS Means **Parameter Value:** -1.74 **Statistical Comment:** **Statistical Method:** mixed model repeated measures analysis **Tested Non-Inferiority:** False ### Outcome Measure 3 #### Analysis **CI Lower Limit:** -1.19 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 0.69 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.57 **Estimate Comment:** **Group Description:** Month 1 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.6576 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Difference in LS Means **Parameter Value:** -0.25 **Statistical Comment:** **Statistical Method:** mixed model repeated measures analysis **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -1.09 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 0.74 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.55 **Estimate Comment:** **Group Description:** Month 1 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.7565 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Difference in LS Means **Parameter Value:** -0.17 **Statistical Comment:** **Statistical Method:** mixed model repeated measures analysis **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -1.89 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 0.01 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.58 **Estimate Comment:** **Group Description:** Month 6 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.1038 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Difference in LS Means **Parameter Value:** -0.94 **Statistical Comment:** **Statistical Method:** mixed model repeated measures analysis **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -1.98 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** -0.04 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.59 **Estimate Comment:** **Group Description:** Month 6 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0868 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Difference in LS Means **Parameter Value:** -1.01 **Statistical Comment:** **Statistical Method:** mixed model repeated measures analysis **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -2.62 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** -0.58 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.62 **Estimate Comment:** **Group Description:** Month 12 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0103 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Difference in LS Means **Parameter Value:** -1.60 **Statistical Comment:** **Statistical Method:** mixed model repeated measures analysis **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -1.53 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 0.55 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.63 **Estimate Comment:** **Group Description:** Month 12 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.4350 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Difference in LS Means **Parameter Value:** -0.49 **Statistical Comment:** **Statistical Method:** mixed model repeated measures analysis **Tested Non-Inferiority:** False ### Outcome Measure 4 #### Analysis **CI Lower Limit:** -1.36 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 0.56 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.58 **Estimate Comment:** **Group Description:** Month 1 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.4890 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Difference in LS Means **Parameter Value:** -0.40 **Statistical Comment:** **Statistical Method:** mixed model repeated measures analysis **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -0.85 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 1.02 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.57 **Estimate Comment:** **Group Description:** Month 1 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.8817 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Difference in LS Means **Parameter Value:** 0.08 **Statistical Comment:** **Statistical Method:** mixed model repeated measures analysis **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -2.21 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** -0.27 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.59 **Estimate Comment:** **Group Description:** Month 3 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0351 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Difference in LS Means **Parameter Value:** -1.24 **Statistical Comment:** **Statistical Method:** mixed model repeated measures analysis **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -2.28 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** -0.37 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.58 **Estimate Comment:** **Group Description:** Month 3 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0231 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Difference in LS Means **Parameter Value:** -1.32 **Statistical Comment:** **Statistical Method:** mixed model repeated measures analysis **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -3.13 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** -1.08 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.62 **Estimate Comment:** **Group Description:** Month 12 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0008 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Difference in LS Means **Parameter Value:** -2.10 **Statistical Comment:** **Statistical Method:** mixed model repeated measures analysis **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -3.32 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** -1.25 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.63 **Estimate Comment:** **Group Description:** Month 12 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0003 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Difference in LS Means **Parameter Value:** -2.29 **Statistical Comment:** **Statistical Method:** mixed model repeated measures analysis **Tested Non-Inferiority:** False ### Outcome Measure 5 #### Analysis **CI Lower Limit:** -0.96 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 0.19 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.35 **Estimate Comment:** **Group Description:** Month 1 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.2689 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Difference in LS Means **Parameter Value:** -0.39 **Statistical Comment:** **Statistical Method:** mixed model repeated measures analysis **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -0.58 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 0.57 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.35 **Estimate Comment:** **Group Description:** Month 1 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.9935 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Difference in LS Means **Parameter Value:** 0 **Statistical Comment:** **Statistical Method:** mixed model repeated measures analysis **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -1.15 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 0.01 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.35 **Estimate Comment:** **Group Description:** Month 3 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.1086 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Difference in LS Means **Parameter Value:** -0.57 **Statistical Comment:** **Statistical Method:** mixed model repeated measures analysis **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -0.66 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 0.49 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.35 **Estimate Comment:** **Group Description:** Month 3 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.8092 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Difference in LS Means **Parameter Value:** -0.08 **Statistical Comment:** **Statistical Method:** mixed model repeated measures analysis **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -1.29 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** -0.12 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.35 **Estimate Comment:** **Group Description:** Month 6 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0463 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Difference in LS Means **Parameter Value:** -0.71 **Statistical Comment:** **Statistical Method:** mixed model repeated measures analysis **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -1.25 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** -0.08 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.35 **Estimate Comment:** **Group Description:** Month 6 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0624 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Difference in LS Means **Parameter Value:** -0.67 **Statistical Comment:** **Statistical Method:** mixed model repeated measures analysis **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -1.90 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** -0.69 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.37 **Estimate Comment:** **Group Description:** Month 12 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0005 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Difference in LS Means **Parameter Value:** -1.29 **Statistical Comment:** **Statistical Method:** mixed model repeated measures analysis **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -1.87 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** -0.65 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.37 **Estimate Comment:** **Group Description:** Month 12 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0008 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Difference in LS Means **Parameter Value:** -1.26 **Statistical Comment:** **Statistical Method:** mixed model repeated measures analysis **Tested Non-Inferiority:** False ### Outcome Measure 6 #### Analysis **CI Lower Limit:** -1.68 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 0.71 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.72 **Estimate Comment:** **Group Description:** Month 6 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.5019 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Difference in LS Means **Parameter Value:** -0.48 **Statistical Comment:** **Statistical Method:** mixed model repeated measures analysis **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -2.28 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 0.14 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.73 **Estimate Comment:** **Group Description:** Month 6 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.1462 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Difference in LS Means **Parameter Value:** -1.07 **Statistical Comment:** **Statistical Method:** mixed model repeated measures analysis **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -1.74 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 0.72 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.74 **Estimate Comment:** **Group Description:** Month 12 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.4900 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Difference in LS Means **Parameter Value:** -0.51 **Statistical Comment:** **Statistical Method:** mixed model repeated measures analysis **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -2.76 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** -0.27 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.75 **Estimate Comment:** **Group Description:** Month 12 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0459 **P-Value Comment:** **Parameter Type:** Difference in LS Means **Parameter Value:** -1.51 **Statistical Comment:** **Statistical Method:** mixed model repeated measures analysis **Tested Non-Inferiority:** False ### Outcome Measure 7 #### Analysis **CI Lower Limit:** -1.68 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 0.71 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.72 **Estimate Comment:** **Group Description:** Month 6 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.5019 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Difference in LS Means **Parameter Value:** -0.48 **Statistical Comment:** **Statistical Method:** mixed model repeated measures analysis **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -2.28 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 0.14 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.73 **Estimate Comment:** **Group Description:** Month 6 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.1462 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Difference in LS Means **Parameter Value:** -1.07 **Statistical Comment:** **Statistical Method:** mixed model repeated measures analysis **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -1.74 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 0.72 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.74 **Estimate Comment:** **Group Description:** Month 12 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.4900 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Difference in LS Means **Parameter Value:** -0.51 **Statistical Comment:** **Statistical Method:** mixed model repeated measures analysis **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -2.76 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** -0.27 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.75 **Estimate Comment:** **Group Description:** Month 12 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0459 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Difference in LS Means **Parameter Value:** -1.51 **Statistical Comment:** **Statistical Method:** mixed model repeated measures analysis **Tested Non-Inferiority:** False ### Outcome Measure 8 #### Analysis **CI Lower Limit:** -0.89 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 0.76 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.50 **Estimate Comment:** **Group Description:** Month 6 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.8959 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Difference in LS Means **Parameter Value:** -0.07 **Statistical Comment:** **Statistical Method:** mixed model repeated measures analysis **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -1.25 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 0.43 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.50 **Estimate Comment:** **Group Description:** Month 6 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.4193 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Difference in LS Means **Parameter Value:** -0.41 **Statistical Comment:** **Statistical Method:** mixed model repeated measures analysis **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -1.13 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 0.56 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.51 **Estimate Comment:** **Group Description:** Month 12 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.5764 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Difference in LS Means **Parameter Value:** -0.29 **Statistical Comment:** **Statistical Method:** mixed model repeated measures analysis **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -1.69 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 0.02 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.52 **Estimate Comment:** **Group Description:** Month 12 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.1101 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Difference in LS Means **Parameter Value:** -0.83 **Statistical Comment:** **Statistical Method:** mixed model repeated measures analysis **Tested Non-Inferiority:** False ### Outcome Measure 9 #### Analysis **CI Lower Limit:** -0.89 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 0.76 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.50 **Estimate Comment:** **Group Description:** Month 6 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.8959 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Difference in LS Means **Parameter Value:** -0.07 **Statistical Comment:** **Statistical Method:** mixed model repeated measures analysis **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -1.25 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 0.43 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.50 **Estimate Comment:** **Group Description:** Month 6 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.4193 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Difference in LS Means **Parameter Value:** -0.41 **Statistical Comment:** **Statistical Method:** mixed model repeated measures analysis **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -1.13 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 0.56 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.51 **Estimate Comment:** **Group Description:** Month 12 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.5764 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Difference in LS Means **Parameter Value:** -0.29 **Statistical Comment:** **Statistical Method:** mixed model repeated measures analysis **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -1.69 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 0.02 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.52 **Estimate Comment:** **Group Description:** Month 12 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.1101 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Difference in LS Means **Parameter Value:** -0.83 **Statistical Comment:** **Statistical Method:** mixed model repeated measures analysis **Tested Non-Inferiority:** False ### Outcome Measure 10 #### Analysis **CI Lower Limit:** -1.00 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 0.16 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.35 **Estimate Comment:** **Group Description:** Month 6 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.2351 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Difference in LS Means **Parameter Value:** -0.42 **Statistical Comment:** **Statistical Method:** mixed model repeated measures analysis **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -1.27 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** -0.08 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.36 **Estimate Comment:** **Group Description:** Month 6 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0631 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Difference in LS Means **Parameter Value:** -0.67 **Statistical Comment:** **Statistical Method:** mixed model repeated measures analysis **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -0.83 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 0.38 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.36 **Estimate Comment:** **Group Description:** Month 12 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.5369 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Difference in LS Means **Parameter Value:** -0.23 **Statistical Comment:** **Statistical Method:** mixed model repeated measures analysis **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -1.31 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** -0.08 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.37 **Estimate Comment:** **Group Description:** Month 12 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0620 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Difference in LS Means **Parameter Value:** -0.69 **Statistical Comment:** **Statistical Method:** mixed model repeated measures analysis **Tested Non-Inferiority:** False ### Outcome Measure 11 #### Analysis **CI Lower Limit:** -1.00 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 0.16 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.35 **Estimate Comment:** **Group Description:** Month 6 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.2351 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Difference in LS Means **Parameter Value:** -0.42 **Statistical Comment:** **Statistical Method:** mixed model repeated measures analysis **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -1.27 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** -0.08 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.36 **Estimate Comment:** **Group Description:** Month 6 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0631 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Difference in LS Means **Parameter Value:** -0.67 **Statistical Comment:** **Statistical Method:** mixed model repeated measures analysis **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -0.83 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 0.38 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.36 **Estimate Comment:** **Group Description:** Month 12 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.5369 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Difference in LS Means **Parameter Value:** -0.23 **Statistical Comment:** **Statistical Method:** mixed model repeated measures analysis **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -1.31 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** -0.08 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.37 **Estimate Comment:** **Group Description:** Month 12 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0620 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Difference in LS Means **Parameter Value:** -0.69 **Statistical Comment:** **Statistical Method:** mixed model repeated measures analysis **Tested Non-Inferiority:** False ### Outcome Measure 12 #### Analysis **CI Lower Limit:** -5.36 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 31.62 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 11.24 **Estimate Comment:** **Group Description:** Month 1 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.2430 **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 13.12 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** 8.91 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 45.90 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 11.24 **Estimate Comment:** **Group Description:** Month 1 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0147 **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 27.41 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** 9.51 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 46.54 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 11.25 **Estimate Comment:** **Group Description:** Month 2 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0127 **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 28.03 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** 1.73 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 39.41 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 11.45 **Estimate Comment:** **Group Description:** Month 2 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0724 **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 20.57 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** 10.63 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 46.35 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 10.85 **Estimate Comment:** **Group Description:** Month 3 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0086 **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 28.49 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -6.54 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 31.47 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 11.55 **Estimate Comment:** **Group Description:** Month 3 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.2808 **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 12.46 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** 9.81 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 46.55 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 11.16 **Estimate Comment:** **Group Description:** Month 9 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0115 **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 28.18 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -3.94 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 34.12 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 11.56 **Estimate Comment:** **Group Description:** Month 9 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.1921 **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 15.09 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** 9.81 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 46.55 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 11.16 **Estimate Comment:** **Group Description:** Month 12 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0115 **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 28.18 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -1.05 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 36.79 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 11.50 **Estimate Comment:** **Group Description:** Month 12 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.1203 **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 17.86 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False ### Outcome Measure 13 #### Analysis **CI Lower Limit:** 7.68 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 32.62 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 7.58 **Estimate Comment:** **Group Description:** Month 1 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0078 **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 20.15 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** 7.68 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 32.62 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 7.58 **Estimate Comment:** **Group Description:** Month 1 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0078 **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 20.15 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** 12.43 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 46.56 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 10.37 **Estimate Comment:** **Group Description:** Month 2 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0044 **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 29.49 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** 0.79 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 33.43 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 9.92 **Estimate Comment:** **Group Description:** Month 2 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0845 **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 17.11 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** 6.14 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 42.35 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 11.00 **Estimate Comment:** **Group Description:** Month 3 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0275 **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 24.24 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** 7.71 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 43.63 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 10.91 **Estimate Comment:** **Group Description:** Month 3 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0186 **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 25.67 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** 17.82 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 53.22 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 10.75 **Estimate Comment:** **Group Description:** Month 6 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0009 **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 35.52 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** 7.95 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 43.24 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 10.72 **Estimate Comment:** **Group Description:** Month 6 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0169 **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 25.60 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** 8.91 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 45.90 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 11.24 **Estimate Comment:** **Group Description:** Month 9 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0147 **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 27.41 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -3.68 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 33.11 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 11.18 **Estimate Comment:** **Group Description:** Month 9 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.1882 **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 14.71 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** 8.91 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 45.90 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 11.24 **Estimate Comment:** **Group Description:** Month 12 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0147 **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 27.41 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -3.68 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 33.11 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 11.18 **Estimate Comment:** **Group Description:** Month 12 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.1882 **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 14.71 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False ### Outcome Measure 14 #### Analysis **CI Lower Limit:** 0.78 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 16.35 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 4.73 **Estimate Comment:** **Group Description:** Month 1 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0700 **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 8.57 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -1.77 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 7.48 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 2.81 **Estimate Comment:** **Group Description:** Month 1 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.3102 **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 2.85 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** 11.73 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 40.30 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 8.68 **Estimate Comment:** **Group Description:** Month 2 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0027 **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 26.02 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** 3.88 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 29.75 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 7.86 **Estimate Comment:** **Group Description:** Month 2 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0324 **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 16.81 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** 0.13 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 29.67 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 8.97 **Estimate Comment:** **Group Description:** Month 3 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0969 **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 14.90 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** 2.09 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 31.84 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 9.04 **Estimate Comment:** **Group Description:** Month 3 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0606 **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 16.96 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -4.60 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 29.93 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 10.49 **Estimate Comment:** **Group Description:** Month 6 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.2276 **P-Value Comment:** **Parameter Type:** Mean Difference (Net) **Parameter Value:** 12.66 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -7.90 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 25.76 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 10.23 **Estimate Comment:** **Group Description:** Month 6 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.3827 **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 8.93 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -4.18 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 29.20 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 10.15 **Estimate Comment:** **Group Description:** Month 9 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.2177 **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 12.50 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -2.29 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 31.12 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 10.15 **Estimate Comment:** **Group Description:** Month 9 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.1558 **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 14.41 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -14.89 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 17.36 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 9.80 **Estimate Comment:** **Group Description:** Month 12 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.8997 **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 1.23 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -5.34 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 28.76 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 10.36 **Estimate Comment:** **Group Description:** Month 12 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.2587 **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 11.71 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False ### Outcome Measure 15 #### Analysis **CI Lower Limit:** -0.56 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 0.13 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Baseline **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:** -0.22 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -0.19 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 0.43 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Baseline **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:** 0.12 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -1.38 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** -0.50 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Month 1 **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:** -0.94 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -1.01 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** -0.22 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Month 1 **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:** -0.62 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -1.73 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** -0.70 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Month 2 **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:** -1.21 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -1.20 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** -0.18 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Month 2 **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:** -0.69 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -1.33 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** -0.29 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Month 3 **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:** -0.81 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -0.94 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 0.12 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Month 3 **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:** -0.41 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -1.75 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** -0.61 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Month 6 **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:** -1.18 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -1.73 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** -0.63 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Month 6 **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:** -1.18 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -1.81 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** -0.61 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Month 9 **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:** -1.21 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -1.33 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** -0.13 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Month 9 **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:** -0.73 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -1.69 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** -0.51 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Month 12 **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:** -1.10 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -1.51 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** -0.29 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Month 12 **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:** -0.90 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** False ### Outcome Measure 16 #### Analysis **CI Lower Limit:** -1.31 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** -0.45 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.26 **Estimate Comment:** **Group Description:** Month 1 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0010 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Difference in LS Means **Parameter Value:** -0.88 **Statistical Comment:** **Statistical Method:** mixed model repeated measures analysis **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -1.10 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** -0.24 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.26 **Estimate Comment:** **Group Description:** Month 1 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0102 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Difference in LS Means **Parameter Value:** -0.67 **Statistical Comment:** **Statistical Method:** mixed model repeated measures analysis **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -1.52 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** -0.64 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.27 **Estimate Comment:** **Group Description:** Month 2 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** <0.0001 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Difference in LS Means **Parameter Value:** -1.08 **Statistical Comment:** **Statistical Method:** mixed model repeated measures analysis **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -1.08 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** -0.20 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.27 **Estimate Comment:** **Group Description:** Month 2 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0175 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Difference in LS Means **Parameter Value:** -0.64 **Statistical Comment:** **Statistical Method:** mixed model repeated measures analysis **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -1.13 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** -0.23 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.27 **Estimate Comment:** **Group Description:** Month 3 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0125 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Difference in LS Means **Parameter Value:** -0.68 **Statistical Comment:** **Statistical Method:** mixed model repeated measures analysis **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -0.84 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 0.05 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.27 **Estimate Comment:** **Group Description:** Month 3 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.1457 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Difference in LS Means **Parameter Value:** -0.39 **Statistical Comment:** **Statistical Method:** mixed model repeated measures analysis **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -1.48 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** -0.57 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.28 **Estimate Comment:** **Group Description:** Month 6 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0003 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Difference in LS Means **Parameter Value:** -1.02 **Statistical Comment:** **Statistical Method:** mixed model repeated measures analysis **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -1.49 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** -0.58 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.28 **Estimate Comment:** **Group Description:** Month 6 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0002 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Difference in LS Means **Parameter Value:** -1.03 **Statistical Comment:** **Statistical Method:** mixed model repeated measures analysis **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -1.63 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** -0.69 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.28 **Estimate Comment:** **Group Description:** Month 9 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** <0.0001 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Difference in LS Means **Parameter Value:** -1.16 **Statistical Comment:** **Statistical Method:** mixed model repeated measures analysis **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -1.14 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** -0.20 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.28 **Estimate Comment:** **Group Description:** Month 9 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0196 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Difference in LS Means **Parameter Value:** -0.67 **Statistical Comment:** **Statistical Method:** mixed model repeated measures analysis **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -1.50 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** -0.52 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.30 **Estimate Comment:** **Group Description:** Month 12 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0007 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Difference in LS Means **Parameter Value:** -1.01 **Statistical Comment:** **Statistical Method:** mixed model repeated measures analysis **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -1.32 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** -0.35 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.30 **Estimate Comment:** **Group Description:** Month 12 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0049 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Difference in LS Means **Parameter Value:** -0.84 **Statistical Comment:** **Statistical Method:** mixed model repeated measures analysis **Tested Non-Inferiority:** False ### Outcome Measure 17 #### Analysis **CI Lower Limit:** -0.53 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 0.15 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Baseline **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:** -0.19 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -0.24 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 0.36 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Baseline **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:** 0.06 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -1.40 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** -0.42 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Month 1 **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:** -0.91 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -1.01 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** -0.14 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Month 1 **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:** -0.58 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -1.82 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** -0.73 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Month 2 **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:** -1.28 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -1.25 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** -0.13 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Month 2 **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:** -0.69 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -1.55 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** -0.38 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Month 3 **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:** -0.96 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -1.12 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 0.11 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Month 3 **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:** -0.51 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -2.13 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** -0.72 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Month 6 **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:** -1.43 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -1.91 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** -0.57 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Month 6 **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:** -1.24 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -1.84 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** -0.39 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Month 9 **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:** -1.11 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -1.30 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 0.13 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Month 9 **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:** -0.59 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -1.84 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** -0.39 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Month 12 **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:** -1.11 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -1.43 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 0.11 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Month 12 **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:** -0.66 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** False ### Outcome Measure 18 #### Analysis **CI Lower Limit:** -1.32 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** -0.35 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.29 **Estimate Comment:** **Group Description:** Month 1 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0046 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Difference in LS Means **Parameter Value:** -0.84 **Statistical Comment:** **Statistical Method:** mixed model repeated measures analysis **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -1.11 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** -0.15 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.29 **Estimate Comment:** **Group Description:** Month 1 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0303 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Difference in LS Means **Parameter Value:** -0.63 **Statistical Comment:** **Statistical Method:** mixed model repeated measures analysis **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -1.69 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** -0.68 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.30 **Estimate Comment:** **Group Description:** Month 2 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0001 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Difference in LS Means **Parameter Value:** -1.18 **Statistical Comment:** **Statistical Method:** mixed model repeated measures analysis **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -1.17 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** -0.18 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.30 **Estimate Comment:** **Group Description:** Month 2 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0255 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Difference in LS Means **Parameter Value:** -0.67 **Statistical Comment:** **Statistical Method:** mixed model repeated measures analysis **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -1.39 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** -0.39 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.30 **Estimate Comment:** **Group Description:** Month 3 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0035 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Difference in LS Means **Parameter Value:** -0.89 **Statistical Comment:** **Statistical Method:** mixed model repeated measures analysis **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -1.05 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** -0.05 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.30 **Estimate Comment:** **Group Description:** Month 3 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0683 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Difference in LS Means **Parameter Value:** -0.55 **Statistical Comment:** **Statistical Method:** mixed model repeated measures analysis **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -1.81 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** -0.78 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.31 **Estimate Comment:** **Group Description:** Month 6 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** <0.0001 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Difference in LS Means **Parameter Value:** -1.29 **Statistical Comment:** **Statistical Method:** mixed model repeated measures analysis **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -1.59 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** -0.56 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.31 **Estimate Comment:** **Group Description:** Month 6 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0006 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Difference in LS Means **Parameter Value:** -1.08 **Statistical Comment:** **Statistical Method:** mixed model repeated measures analysis **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -1.67 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** -0.62 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.32 **Estimate Comment:** **Group Description:** Month 9 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0004 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Difference in LS Means **Parameter Value:** -1.15 **Statistical Comment:** **Statistical Method:** mixed model repeated measures analysis **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -1.10 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** -0.05 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.32 **Estimate Comment:** **Group Description:** Month 9 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0706 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Difference in LS Means **Parameter Value:** -0.58 **Statistical Comment:** **Statistical Method:** mixed model repeated measures analysis **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -1.67 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** -0.58 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.33 **Estimate Comment:** **Group Description:** Month 12 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0008 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Difference in LS Means **Parameter Value:** -1.13 **Statistical Comment:** **Statistical Method:** mixed model repeated measures analysis **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -1.21 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** -0.12 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.33 **Estimate Comment:** **Group Description:** Month 12 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0466 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Difference in LS Means **Parameter Value:** -0.66 **Statistical Comment:** **Statistical Method:** mixed model repeated measures analysis **Tested Non-Inferiority:** False ### Outcome Measure 19 #### Analysis **CI Lower Limit:** 14.34 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 50.68 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 11.04 **Estimate Comment:** **Group Description:** Month 1 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0032 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 32.51 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** 9.81 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 46.55 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 11.16 **Estimate Comment:** **Group Description:** Month 1 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0115 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 28.18 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** 18.81 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 50.02 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 9.48 **Estimate Comment:** **Group Description:** Month 2 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0002 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 34.41 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** 6.55 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 41.03 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 10.48 **Estimate Comment:** **Group Description:** Month 2 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0231 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 23.79 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** 18.81 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 50.02 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 9.48 **Estimate Comment:** **Group Description:** Month 3 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0002 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 34.41 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** 3.43 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 38.61 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 10.69 **Estimate Comment:** **Group Description:** Month 3 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0493 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 21.02 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** 17.92 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 50.43 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 9.88 **Estimate Comment:** **Group Description:** Month 6 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0005 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 34.18 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** 6.07 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 41.37 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 10.73 **Estimate Comment:** **Group Description:** Month 6 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0270 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 23.72 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** 15.80 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 51.12 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 10.73 **Estimate Comment:** **Group Description:** Month 9 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0018 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 33.46 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** 5.02 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 41.96 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 11.22 **Estimate Comment:** **Group Description:** Month 9 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0363 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 23.49 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** 19.16 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 53.64 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 10.48 **Estimate Comment:** **Group Description:** Month 12 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0005 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 36.40 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** 8.04 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 44.50 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 11.08 **Estimate Comment:** **Group Description:** Month 12 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0177 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 26.27 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False ### Outcome Measure 20 #### Analysis **CI Lower Limit:** 6.62 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 38.42 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 9.66 **Estimate Comment:** **Group Description:** Month 1 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0197 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 22.52 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -7.09 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 19.76 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 8.16 **Estimate Comment:** **Group Description:** Month 1 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.4379 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 6.33 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** 10.40 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 46.34 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 10.92 **Estimate Comment:** **Group Description:** Month 2 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0093 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 28.37 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -2.75 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 31.73 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 10.48 **Estimate Comment:** **Group Description:** Month 2 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.1669 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 14.48 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** 10.40 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 46.34 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 10.92 **Estimate Comment:** **Group Description:** Month 3 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0093 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 28.37 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** 2.53 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 37.55 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 10.64 **Estimate Comment:** **Group Description:** Month 3 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0596 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 20.04 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** 16.51 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 52.96 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 11.07 **Estimate Comment:** **Group Description:** Month 6 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0017 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 34.73 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** 10.36 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 46.69 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 11.04 **Estimate Comment:** **Group Description:** Month 6 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0097 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 28.52 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** 16.68 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 53.26 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 11.11 **Estimate Comment:** **Group Description:** Month 9 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0016 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 34.97 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** 10.28 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 46.91 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 11.13 **Estimate Comment:** **Group Description:** Month 9 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0102 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 28.60 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** 16.51 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 52.96 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 11.07 **Estimate Comment:** **Group Description:** Month 12 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0017 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 34.73 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** 4.74 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 41.19 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 11.07 **Estimate Comment:** **Group Description:** Month 12 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0381 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 22.97 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False ### Outcome Measure 21 #### Analysis **CI Lower Limit:** 0.15 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 25.40 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 7.67 **Estimate Comment:** **Group Description:** Month 1 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0959 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 12.77 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -8.58 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 9.19 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 5.40 **Estimate Comment:** **Group Description:** Month 1 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.9544 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 0.30 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** 11.81 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 42.55 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 9.34 **Estimate Comment:** **Group Description:** Month 2 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0036 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 27.18 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -4.04 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 21.16 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 7.66 **Estimate Comment:** **Group Description:** Month 2 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.2640 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 8.55 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** 2.72 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 34.95 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 9.79 **Estimate Comment:** **Group Description:** Month 3 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0544 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 18.83 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -5.96 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 23.38 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 8.92 **Estimate Comment:** **Group Description:** Month 3 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.3290 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 8.70 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** 13.59 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 48.09 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 10.48 **Estimate Comment:** **Group Description:** Month 6 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0032 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 30.84 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** 0.79 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 33.43 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 9.92 **Estimate Comment:** **Group Description:** Month 6 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0845 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 17.11 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** 13.44 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 48.72 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 10.72 **Estimate Comment:** **Group Description:** Month 9 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0037 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 31.08 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** 2.91 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 37.02 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 10.36 **Estimate Comment:** **Group Description:** Month 9 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0540 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 19.96 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** 16.70 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 50.39 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 10.24 **Estimate Comment:** **Group Description:** Month 12 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0010 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 33.54 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** 3.92 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 35.71 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 9.66 **Estimate Comment:** **Group Description:** Month 12 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0401 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 19.81 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False ### Outcome Measure 22 #### Analysis **CI Lower Limit:** 19.83 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 55.99 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 10.99 **Estimate Comment:** **Group Description:** Month 1 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0005 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 37.91 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** 14.87 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 51.38 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 11.09 **Estimate Comment:** **Group Description:** Month 1 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0028 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 33.12 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** 9.21 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 42.45 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 10.10 **Estimate Comment:** **Group Description:** Month 2 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0105 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 25.83 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -8.33 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 28.30 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 11.13 **Estimate Comment:** **Group Description:** Month 2 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.3700 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 9.98 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** 24.11 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 55.53 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 9.54 **Estimate Comment:** **Group Description:** Month 3 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** <0.0001 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 39.82 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -0.40 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 36.59 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 11.24 **Estimate Comment:** **Group Description:** Month 3 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.1076 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 18.09 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** 17.13 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 50.75 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 10.21 **Estimate Comment:** **Group Description:** Month 6 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0008 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 33.94 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** 8.74 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 44.10 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 10.74 **Estimate Comment:** **Group Description:** Month 6 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0139 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 26.42 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** 19.16 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 53.64 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 10.48 **Estimate Comment:** **Group Description:** Month 9 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0005 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 36.40 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** 8.04 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 44.50 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 11.08 **Estimate Comment:** **Group Description:** Month 9 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0177 **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 26.27 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** 15.80 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 51.12 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 10.73 **Estimate Comment:** **Group Description:** Month 12 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0018 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 33.46 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** 5.02 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 41.96 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 11.22 **Estimate Comment:** **Group Description:** Month 12 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0363 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 23.49 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False ### Outcome Measure 23 #### Analysis **CI Lower Limit:** 5.66 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 30.10 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 7.42 **Estimate Comment:** **Group Description:** Month 1 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0160 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 17.88 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -3.06 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 14.80 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 5.43 **Estimate Comment:** **Group Description:** Month 1 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.2798 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 5.86 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** 11.81 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 42.55 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 9.34 **Estimate Comment:** **Group Description:** Month 2 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0036 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 27.18 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -6.23 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 17.79 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 7.30 **Estimate Comment:** **Group Description:** Month 2 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.4287 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 5.78 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** 2.72 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 34.95 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 9.79 **Estimate Comment:** **Group Description:** Month 3 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0544 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 18.83 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** 1.39 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 32.69 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 9.51 **Estimate Comment:** **Group Description:** Month 3 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0732 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 17.04 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** 4.79 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 39.72 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 10.61 **Estimate Comment:** **Group Description:** Month 6 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0360 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 22.25 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -7.35 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 25.07 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 9.85 **Estimate Comment:** **Group Description:** Month 6 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.3688 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 8.85 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** 7.63 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 42.76 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 10.67 **Estimate Comment:** **Group Description:** Month 9 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0182 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 25.19 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -2.29 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 31.12 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 10.15 **Estimate Comment:** **Group Description:** Month 9 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.1558 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 14.41 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** 16.51 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 51.05 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 10.49 **Estimate Comment:** **Group Description:** Month 12 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0012 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 33.78 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -1.74 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 30.42 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 9.78 **Estimate Comment:** **Group Description:** Month 12 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.1426 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Mean Difference (Net) **Parameter Value:** 14.33 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False ### Outcome Measure 24 #### Analysis **CI Lower Limit:** -0.75 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 12.52 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 4.03 **Estimate Comment:** **Group Description:** Month 1 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.1449 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 5.88 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -1.77 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 7.48 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 2.81 **Estimate Comment:** **Group Description:** Month 1 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.3102 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 2.85 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** 3.32 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 26.55 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 7.06 **Estimate Comment:** **Group Description:** Month 2 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0342 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 14.94 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -4.80 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 10.51 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 4.65 **Estimate Comment:** **Group Description:** Month 2 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.5400 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 2.85 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -5.10 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 25.13 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 9.19 **Estimate Comment:** **Group Description:** Month 3 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.2759 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 10.01 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -21.02 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** -0.45 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 6.25 **Estimate Comment:** **Group Description:** Month 3 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0859 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** -10.73 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** 0.06 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 31.73 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 9.62 **Estimate Comment:** **Group Description:** Month 6 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0985 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 15.89 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -12.86 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 13.61 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 8.05 **Estimate Comment:** **Group Description:** Month 6 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.9628 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 0.37 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** 2.31 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 35.84 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 10.19 **Estimate Comment:** **Group Description:** Month 9 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0612 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 19.07 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -16.08 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 11.43 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 8.36 **Estimate Comment:** **Group Description:** Month 9 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.7807 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** -2.32 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** 2.72 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 34.95 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 9.79 **Estimate Comment:** **Group Description:** Month 12 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0544 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 18.83 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** -8.32 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 90 **CI Upper Limit:** 20.18 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 8.66 **Estimate Comment:** **Group Description:** Month 12 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.4937 **P-Value Comment:** 2-sided p-value; alpha=0.10 **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 5.93 **Statistical Comment:** **Statistical Method:** Normal approximation to the binomial **Tested Non-Inferiority:** False ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.41 - **Upper Limit:** - **Value:** -0.80 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.40 - **Upper Limit:** - **Value:** -0.69 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 0.40 - **Upper Limit:** - **Value:** -0.17 **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.41 - **Upper Limit:** - **Value:** -1.26 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.42 - **Upper Limit:** - **Value:** -1.45 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 0.42 - **Upper Limit:** - **Value:** 0.29 **Title:** #### Outcome Measure 3 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.42 - **Upper Limit:** - **Value:** -0.42 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.40 - **Upper Limit:** - **Value:** -0.34 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 0.38 - **Upper Limit:** - **Value:** -0.17 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.40 - **Upper Limit:** - **Value:** -1.22 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.41 - **Upper Limit:** - **Value:** -1.29 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 0.42 - **Upper Limit:** - **Value:** -0.28 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.41 - **Upper Limit:** - **Value:** -2.26 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.43 - **Upper Limit:** - **Value:** -1.16 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 0.46 - **Upper Limit:** - **Value:** -0.66 **Title:** #### Outcome Measure 4 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.43 - **Upper Limit:** - **Value:** -0.29 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.41 - **Upper Limit:** - **Value:** 0.19 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 0.39 - **Upper Limit:** - **Value:** 0.11 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.42 - **Upper Limit:** - **Value:** -0.77 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.41 - **Upper Limit:** - **Value:** -0.86 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 0.41 - **Upper Limit:** - **Value:** 0.47 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.42 - **Upper Limit:** - **Value:** -1.52 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.43 - **Upper Limit:** - **Value:** -1.70 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 0.46 - **Upper Limit:** - **Value:** 0.59 **Title:** #### Outcome Measure 5 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.25 - **Upper Limit:** - **Value:** -0.12 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.25 - **Upper Limit:** - **Value:** 0.27 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 0.24 - **Upper Limit:** - **Value:** 0.27 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.25 - **Upper Limit:** - **Value:** -0.12 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.24 - **Upper Limit:** - **Value:** 0.36 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 0.25 - **Upper Limit:** - **Value:** 0.44 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.25 - **Upper Limit:** - **Value:** -0.06 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.25 - **Upper Limit:** - **Value:** -0.02 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 0.25 - **Upper Limit:** - **Value:** 0.65 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.25 - **Upper Limit:** - **Value:** -0.11 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.25 - **Upper Limit:** - **Value:** -0.08 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 0.26 - **Upper Limit:** - **Value:** 1.18 **Title:** #### Outcome Measure 6 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.50 - **Upper Limit:** - **Value:** 11.28 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.51 - **Upper Limit:** - **Value:** 10.70 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 0.52 - **Upper Limit:** - **Value:** 11.77 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.51 - **Upper Limit:** - **Value:** 11.70 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.52 - **Upper Limit:** - **Value:** 10.69 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 0.54 - **Upper Limit:** - **Value:** 12.21 **Title:** #### Outcome Measure 7 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.50 - **Upper Limit:** - **Value:** 0.44 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.51 - **Upper Limit:** - **Value:** -0.14 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 0.52 - **Upper Limit:** - **Value:** 0.93 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.51 - **Upper Limit:** - **Value:** 0.85 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.52 - **Upper Limit:** - **Value:** -0.15 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 0.54 - **Upper Limit:** - **Value:** 1.36 **Title:** #### Outcome Measure 8 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.34 - **Upper Limit:** - **Value:** 5.45 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.35 - **Upper Limit:** - **Value:** 5.11 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 0.36 - **Upper Limit:** - **Value:** 5.52 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.35 - **Upper Limit:** - **Value:** 5.59 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.36 - **Upper Limit:** - **Value:** 5.05 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 0.37 - **Upper Limit:** - **Value:** 5.88 **Title:** #### Outcome Measure 9 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.34 - **Upper Limit:** - **Value:** 0.29 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.35 - **Upper Limit:** - **Value:** -0.06 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 0.36 - **Upper Limit:** - **Value:** 0.35 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.35 - **Upper Limit:** - **Value:** 0.43 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.36 - **Upper Limit:** - **Value:** -0.12 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 0.37 - **Upper Limit:** - **Value:** 0.71 **Title:** #### Outcome Measure 10 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.24 - **Upper Limit:** - **Value:** 5.84 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.25 - **Upper Limit:** - **Value:** 5.59 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 0.25 - **Upper Limit:** - **Value:** 6.26 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.25 - **Upper Limit:** - **Value:** 6.10 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.26 - **Upper Limit:** - **Value:** 5.64 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 0.27 - **Upper Limit:** - **Value:** 6.33 **Title:** #### Outcome Measure 11 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.24 - **Upper Limit:** - **Value:** 0.16 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.25 - **Upper Limit:** - **Value:** -0.10 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 0.25 - **Upper Limit:** - **Value:** 0.58 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.25 - **Upper Limit:** - **Value:** 0.42 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.26 - **Upper Limit:** - **Value:** -0.05 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 0.27 - **Upper Limit:** - **Value:** 0.65 **Title:** #### Outcome Measure 12 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 42.86 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 57.14 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 29.73 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 68.57 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 61.11 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 40.54 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 77.14 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 61.11 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 48.65 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 74.29 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 66.67 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 45.95 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 71.43 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 58.33 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 43.24 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 71.43 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 61.11 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 43.24 **Title:** #### Outcome Measure 13 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 22.86 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 22.86 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2.70 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 45.71 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 33.33 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 16.22 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 48.57 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 50.00 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 24.32 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 57.14 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 47.22 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 21.62 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 57.14 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 44.44 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 29.73 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 57.14 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 44.44 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 29.73 **Title:** #### Outcome Measure 14 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 8.57 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2.86 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0.00 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 31.43 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 22.22 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 5.41 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 25.71 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 27.78 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 10.81 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 34.29 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 30.56 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 21.62 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 31.43 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 33.33 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 18.92 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 22.86 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 33.33 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 21.62 **Title:** #### Outcome Measure 15 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.96 - **Upper Limit:** - **Value:** 5.14 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.78 - **Upper Limit:** - **Value:** 5.48 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 0.80 - **Upper Limit:** - **Value:** 5.36 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.15 - **Upper Limit:** - **Value:** 3.71 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.91 - **Upper Limit:** - **Value:** 4.03 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 1.07 - **Upper Limit:** - **Value:** 4.65 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.17 - **Upper Limit:** - **Value:** 2.99 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.15 - **Upper Limit:** - **Value:** 3.52 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 1.31 - **Upper Limit:** - **Value:** 4.21 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.02 - **Upper Limit:** - **Value:** 3.06 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.09 - **Upper Limit:** - **Value:** 3.46 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 1.43 - **Upper Limit:** - **Value:** 3.87 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.15 - **Upper Limit:** - **Value:** 2.74 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.95 - **Upper Limit:** - **Value:** 2.75 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 1.49 - **Upper Limit:** - **Value:** 3.92 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.98 - **Upper Limit:** - **Value:** 2.37 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.90 - **Upper Limit:** - **Value:** 2.85 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 1.63 - **Upper Limit:** - **Value:** 3.58 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.02 - **Upper Limit:** - **Value:** 2.49 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.05 - **Upper Limit:** - **Value:** 2.68 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 1.40 - **Upper Limit:** - **Value:** 3.58 **Title:** #### Outcome Measure 16 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.19 - **Upper Limit:** - **Value:** -1.61 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.18 - **Upper Limit:** - **Value:** -1.40 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 0.18 - **Upper Limit:** - **Value:** -0.73 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.19 - **Upper Limit:** - **Value:** -2.32 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.19 - **Upper Limit:** - **Value:** -1.88 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 0.19 - **Upper Limit:** - **Value:** -1.24 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.19 - **Upper Limit:** - **Value:** -2.25 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.19 - **Upper Limit:** - **Value:** -1.96 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 0.19 - **Upper Limit:** - **Value:** -1.57 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.19 - **Upper Limit:** - **Value:** -2.54 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.20 - **Upper Limit:** - **Value:** -2.55 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 0.19 - **Upper Limit:** - **Value:** -1.52 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.20 - **Upper Limit:** - **Value:** -2.92 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.20 - **Upper Limit:** - **Value:** -2.43 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 0.21 - **Upper Limit:** - **Value:** -1.76 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.20 - **Upper Limit:** - **Value:** -2.78 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.20 - **Upper Limit:** - **Value:** -2.61 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 0.22 - **Upper Limit:** - **Value:** -1.77 **Title:** #### Outcome Measure 17 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.94 - **Upper Limit:** - **Value:** 6.25 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.75 - **Upper Limit:** - **Value:** 6.50 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 0.78 - **Upper Limit:** - **Value:** 6.44 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.37 - **Upper Limit:** - **Value:** 4.60 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.12 - **Upper Limit:** - **Value:** 4.93 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 1.09 - **Upper Limit:** - **Value:** 5.51 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.34 - **Upper Limit:** - **Value:** 3.77 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.40 - **Upper Limit:** - **Value:** 4.36 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 1.26 - **Upper Limit:** - **Value:** 5.05 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.16 - **Upper Limit:** - **Value:** 3.66 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.31 - **Upper Limit:** - **Value:** 4.12 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 1.63 - **Upper Limit:** - **Value:** 4.63 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.45 - **Upper Limit:** - **Value:** 3.32 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.20 - **Upper Limit:** - **Value:** 3.51 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 1.76 - **Upper Limit:** - **Value:** 4.75 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.27 - **Upper Limit:** - **Value:** 3.06 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.10 - **Upper Limit:** - **Value:** 3.58 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 1.91 - **Upper Limit:** - **Value:** 4.17 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.22 - **Upper Limit:** - **Value:** 3.02 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.36 - **Upper Limit:** - **Value:** 3.47 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 1.76 - **Upper Limit:** - **Value:** 4.13 **Title:** #### Outcome Measure 18 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.21 - **Upper Limit:** - **Value:** -1.77 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.21 - **Upper Limit:** - **Value:** -1.57 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 0.20 - **Upper Limit:** - **Value:** -0.94 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.22 - **Upper Limit:** - **Value:** -2.59 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.21 - **Upper Limit:** - **Value:** -2.08 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 0.21 - **Upper Limit:** - **Value:** -1.41 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.21 - **Upper Limit:** - **Value:** -2.69 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.21 - **Upper Limit:** - **Value:** -2.35 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 0.21 - **Upper Limit:** - **Value:** -1.80 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.22 - **Upper Limit:** - **Value:** -3.02 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.22 - **Upper Limit:** - **Value:** -2.81 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 0.22 - **Upper Limit:** - **Value:** -1.73 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.22 - **Upper Limit:** - **Value:** -3.29 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.22 - **Upper Limit:** - **Value:** -2.72 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 0.23 - **Upper Limit:** - **Value:** -2.14 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.22 - **Upper Limit:** - **Value:** -3.31 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.22 - **Upper Limit:** - **Value:** -2.84 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 0.24 - **Upper Limit:** - **Value:** -2.18 **Title:** #### Outcome Measure 19 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 75.76 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 71.43 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 43.24 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 91.18 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 80.56 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 56.76 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 91.18 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 77.78 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 56.76 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 88.24 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 77.78 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 54.05 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 79.41 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 69.44 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 45.95 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 82.35 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 72.22 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 45.95 **Title:** #### Outcome Measure 20 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 33.33 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 17.14 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 10.81 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 50.00 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 36.11 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 21.62 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 50.00 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 41.67 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 21.62 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 61.76 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 55.56 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 27.03 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 64.71 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 58.33 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 29.33 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 61.76 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 50.00 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 27.03 **Title:** #### Outcome Measure 21 **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:** 5.71 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 5.41 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 35.29 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 16.67 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 8.11 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 32.35 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 22.22 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 13.51 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 47.06 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 33.33 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 16.22 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 50.00 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 38.89 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 18.92 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 47.06 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 33.33 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 13.51 **Title:** #### Outcome Measure 22 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 67.65 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 62.86 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 29.73 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 85.29 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 69.44 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 59.46 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 91.18 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 69.44 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 51.35 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 85.29 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 77.78 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 51.35 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 82.35 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 72.22 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 45.95 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 79.41 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 69.44 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 45.95 **Title:** #### Outcome Measure 23 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 20.59 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 8.57 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2.70 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 35.29 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 13.89 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 8.11 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 32.35 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 30.56 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 13.51 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 41.18 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 27.78 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 18.92 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 44.12 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 33.33 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 18.92 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 50.00 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 30.56 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 16.22 **Title:** #### Outcome Measure 24 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 5.88 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2.86 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0.00 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 17.65 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 5.56 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2.70 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 23.53 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2.78 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 13.51 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 29.41 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 13.89 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 13.51 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 35.29 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 13.89 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 16.22 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 32.35 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 19.44 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 13.51 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** Synovitis is defined as an area in the synovial compartment that shows above normal postgadolinium enhancement of a thickness greater than the width of the normal synovium. T1-weighted images were acquired before and after the administration of intravenous contrast agent containing gadolinium. Intravenous contrast was required to demonstrate enhancing synovitis. Synovitis was scored 0 to 3 in 3 wrist regions and in each of the first through fifth MCP joints. A score of 0 is normal, with no enhancement or enhancement up to the thickness of normal synovium, while scores of 1 to 3 (mild, moderate, severe) refer to increments of one-third of the presumed maximum volume of enhancing tissue in the synovial compartment. Total synovitis score ranges from a minimum of 0 to a maximum of 24. A negative value in synovitis change from Baseline score indicates an improvement. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** Evaluable Set: all randomized participants who received at least 1 dose of the randomized investigational drug and for whom a variable is nonmissing at both baseline and the specified timepoint. **Reporting Status:** POSTED **Time Frame:** Month 3 **Title:** Change From Baseline to Month 3 in Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Imaging Score (RAMRIS) Wrist and Metacarpophalangeal (MCP) Synovitis **Type:** PRIMARY **Unit of Measure:** score on a scale ##### Group **Description:** Participants received CP-690,550 10 mg, tablets, PO, BID, and MTX 10 mg/week to 20 mg/week, capsules, PO, for a maximum of 12 months. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** OG000 **Title:** Tofacitinib (CP-690,550) Plus MTX ##### Group **Description:** Participants received CP-690,550 10 mg tablets, PO, BID and matching placebo MTX capsules, PO, once weekly for a maximum of 12 months. To maintain the blind, matching placebo MTX was titrated as follows: 4 capsules once weekly for 4 weeks; if well tolerated, at Month 1 titrate up to 6 capsules once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 8 capsules once weekly for the duration of the study. A single dose reduction of MTX placebo to 2 capsules was allowed because of lack of tolerance, as long as the participant remained on a dose of at least 4 MTX placebo capsules weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** OG001 **Title:** Tofacitinib (CP-690,550) ##### Group **Description:** Participants received MTX 10 mg/week to 20 mg/week, capsules, PO, and matching placebo CP-690,550 tablets, PO, BID. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** OG002 **Title:** Methotrexate #### Outcome Measure 2 **Description:** Bone edema was assessed at 25 anatomic locations: 15 in 1 wrist and 10 in attached hand. Bone edema was defined as a lesion within the trabecular bone, with ill-defined margins and signal characteristics consistent with increased water content. Each bone was scored separately; the scale was 0-3 based on the proportion of bone with edema, as follows 0: no edema; 1: 1-33% of bone edematous; 2: 34-66% of bone edematous; 3: 67-100%. OMERACT RAMRIS total bone edema score for hands/wrists was sum of the individual scores for each location. Thus the maximum score per hand/wrist was 75 (range 0-75). Increasing score=greater severity. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** Evaluable Set **Reporting Status:** POSTED **Time Frame:** Month 6 **Title:** Change From Baseline to Month 6 in OMERACT RAMRIS Wrist and MCP Bone Marrow Edema **Type:** PRIMARY **Unit of Measure:** score on a scale ##### Group **Description:** Participants received CP-690,550 10 mg, tablets, PO, BID, and MTX 10 mg/week to 20 mg/week, capsules, PO, for a maximum of 12 months. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** OG000 **Title:** Tofacitinib (CP-690,550) Plus MTX ##### Group **Description:** Participants received CP-690,550 10 mg tablets, PO, BID and matching placebo MTX capsules, PO, once weekly for a maximum of 12 months. To maintain the blind, matching placebo MTX was titrated as follows: 4 capsules once weekly for 4 weeks; if well tolerated, at Month 1 titrate up to 6 capsules once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 8 capsules once weekly for the duration of the study. A single dose reduction of MTX placebo to 2 capsules was allowed because of lack of tolerance, as long as the participant remained on a dose of at least 4 MTX placebo capsules weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** OG001 **Title:** Tofacitinib (CP-690,550) ##### Group **Description:** Participants received MTX 10 mg/week to 20 mg/week, capsules, PO, and matching placebo CP-690,550 tablets, PO, BID. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** OG002 **Title:** Methotrexate #### Outcome Measure 3 **Description:** Synovitis is defined as an area in the synovial compartment that shows above normal postgadolinium enhancement of a thickness greater than the width of the normal synovium. T1-weighted images were acquired before and after the administration of intravenous contrast agent containing gadolinium. Intravenous contrast was required to demonstrate enhancing synovitis. Synovitis was scored 0 to 3 in 3 wrist regions and in each of the first through fifth MCP joints. A score of 0 is normal, with no enhancement or enhancement up to the thickness of normal synovium, while scores of 1 to 3 (mild, moderate, severe) refer to increments of one-third of the presumed maximum volume of enhancing tissue in the synovial compartment. Total synovitis score ranges from a minimum of 0 to a maximum of 24. A negative value in synovitis change from Baseline score indicates an improvement. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** Evaluable Set **Reporting Status:** POSTED **Time Frame:** Months 1, 6, and 12 **Title:** Change From Baseline to Months 1, 6, and 12 in OMERACT RAMRIS Wrist and MCP Synovitis **Type:** SECONDARY **Unit of Measure:** score on a scale ##### Group **Description:** Participants received CP-690,550 10 mg, tablets, PO, BID, and MTX 10 mg/week to 20 mg/week, capsules, PO, for a maximum of 12 months. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** OG000 **Title:** Tofacitinib (CP-690,550) Plus MTX ##### Group **Description:** Participants received CP-690,550 10 mg tablets, PO, BID and matching placebo MTX capsules, PO, once weekly for a maximum of 12 months. To maintain the blind, matching placebo MTX was titrated as follows: 4 capsules once weekly for 4 weeks; if well tolerated, at Month 1 titrate up to 6 capsules once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 8 capsules once weekly for the duration of the study. A single dose reduction of MTX placebo to 2 capsules was allowed because of lack of tolerance, as long as the participant remained on a dose of at least 4 MTX placebo capsules weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** OG001 **Title:** Tofacitinib (CP-690,550) ##### Group **Description:** Participants received MTX 10 mg/week to 20 mg/week, capsules, PO, and matching placebo CP-690,550 tablets, PO, BID. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** OG002 **Title:** Methotrexate #### Outcome Measure 4 **Description:** Bone edema was assessed at 25 anatomic locations: 15 in 1 wrist and 10 in attached hand. Bone edema was defined as a lesion within the trabecular bone, with ill-defined margins and signal characteristics consistent with increased water content. Each bone was scored separately; the scale was 0â€"3 based on the proportion of bone with edema, as follows 0: no edema; 1: 1â€"33% of bone edematous; 2: 34â€"66% of bone edematous; 3: 67â€"100%. OMERACT RAMRIS total bone edema score for hands/wrists was sum of the individual scores for each location. Thus the maximum score per hand/wrist was 75 (range 0-75). Increasing score=greater severity. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** Evaluable Set; n=number of participants assessed for the specified parameter at a given visit. **Reporting Status:** POSTED **Time Frame:** Months 1, 3, and 12 **Title:** Change From Baseline to Months 1, 3, and 12 in OMERACT RAMRIS Bone Marrow Edema in Wrist and MCP **Type:** SECONDARY **Unit of Measure:** score on a scale ##### Group **Description:** Participants received CP-690,550 10 mg, tablets, PO, BID, and MTX 10 mg/week to 20 mg/week, capsules, PO, for a maximum of 12 months. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** OG000 **Title:** Tofacitinib (CP-690,550) Plus MTX ##### Group **Description:** Participants received CP-690,550 10 mg tablets, PO, BID and matching placebo MTX capsules, PO, once weekly for a maximum of 12 months. To maintain the blind, matching placebo MTX was titrated as follows: 4 capsules once weekly for 4 weeks; if well tolerated, at Month 1 titrate up to 6 capsules once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 8 capsules once weekly for the duration of the study. A single dose reduction of MTX placebo to 2 capsules was allowed because of lack of tolerance, as long as the participant remained on a dose of at least 4 MTX placebo capsules weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** OG001 **Title:** Tofacitinib (CP-690,550) ##### Group **Description:** Participants received MTX 10 mg/week to 20 mg/week, capsules, PO, and matching placebo CP-690,550 tablets, PO, BID. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** OG002 **Title:** Methotrexate #### Outcome Measure 5 **Description:** Bone erosion assessed at 25 anatomic locations: 15 in 1 wrist and 10 in attached hand. Each site was scored in 1.0 increments from 0 (no damage) to 10 (severe damage), indicating erosion (each unit=10% bone loss) of original articular bone. OMERACT RAMRIS total erosion score for hands/wrists was sum of the individual scores for each location. Thus the maximum score per hand/wrist is 250 (range 0-250). Increasing score=greater severity. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** Evaluable Set **Reporting Status:** POSTED **Time Frame:** Months 1, 3, 6, and 12 **Title:** Change From Baseline to Months 1, 3, 6, and 12 in OMERACT RAMRIS Wrist and MCP Erosions **Type:** SECONDARY **Unit of Measure:** score on a scale ##### Group **Description:** Participants received CP-690,550 10 mg, tablets, PO, BID, and MTX 10 mg/week to 20 mg/week, capsules, PO, for a maximum of 12 months. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** OG000 **Title:** Tofacitinib (CP-690,550) Plus MTX ##### Group **Description:** Participants received CP-690,550 10 mg tablets, PO, BID and matching placebo MTX capsules, PO, once weekly for a maximum of 12 months. To maintain the blind, matching placebo MTX was titrated as follows: 4 capsules once weekly for 4 weeks; if well tolerated, at Month 1 titrate up to 6 capsules once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 8 capsules once weekly for the duration of the study. A single dose reduction of MTX placebo to 2 capsules was allowed because of lack of tolerance, as long as the participant remained on a dose of at least 4 MTX placebo capsules weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** OG001 **Title:** Tofacitinib (CP-690,550) ##### Group **Description:** Participants received MTX 10 mg/week to 20 mg/week, capsules, PO, and matching placebo CP-690,550 tablets, PO, BID. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** OG002 **Title:** Methotrexate #### Outcome Measure 6 **Description:** Modified TSS is a measure of change in joint health. TSS is defined as joint space narrowing score (range 0 \[no narrowing\] to 168 \[high narrowing\]) plus (+) erosion score (range is from 0 \[no erosion\] to 280 \[high erosion\]). The modified TSS range is from 0 (no damage) to 448 (bad joint status). Increase from baseline represents disease progression and / or joint worsening; no change represents halting of disease progression; a decrease represents improvement. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** Evaluable Set; n=number of participants assessed for the specified parameter at a given visit. **Reporting Status:** POSTED **Time Frame:** Months 6 and 12 **Title:** Modified Total Sharp Score (mTSS) at Months 6 and 12 **Type:** SECONDARY **Unit of Measure:** score on a scale ##### Group **Description:** Participants received CP-690,550 10 mg, tablets, PO, BID, and MTX 10 mg/week to 20 mg/week, capsules, PO, for a maximum of 12 months. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** OG000 **Title:** Tofacitinib (CP-690,550) Plus MTX ##### Group **Description:** Participants received CP-690,550 10 mg tablets, PO, BID and matching placebo MTX capsules, PO, once weekly for a maximum of 12 months. To maintain the blind, matching placebo MTX was titrated as follows: 4 capsules once weekly for 4 weeks; if well tolerated, at Month 1 titrate up to 6 capsules once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 8 capsules once weekly for the duration of the study. A single dose reduction of MTX placebo to 2 capsules was allowed because of lack of tolerance, as long as the participant remained on a dose of at least 4 MTX placebo capsules weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** OG001 **Title:** Tofacitinib (CP-690,550) ##### Group **Description:** Participants received MTX 10 mg/week to 20 mg/week, capsules, PO, and matching placebo CP-690,550 tablets, PO, BID. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** OG002 **Title:** Methotrexate #### Outcome Measure 7 **Description:** Modified TSS is a measure of change in joint health. TSS is defined as joint space narrowing score (range 0 \[no narrowing\] to 168 \[high narrowing\]) + erosion score (range is from 0 \[no erosion\] to 280 \[high erosion\]). The modified TSS range is from 0 (no damage) to 448 (bad joint status). Increase from baseline represents disease progression and / or joint worsening; no change represents halting of disease progression; a decrease represents improvement. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** Evaluable Set; n=number of participants assessed for the specified parameter at a given visit. **Reporting Status:** POSTED **Time Frame:** Months 6 and 12 **Title:** Change From Baseline to Months 6 and 12 in mTSS **Type:** SECONDARY **Unit of Measure:** scores on a scale ##### Group **Description:** Participants received CP-690,550 10 mg, tablets, PO, BID, and MTX 10 mg/week to 20 mg/week, capsules, PO, for a maximum of 12 months. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** OG000 **Title:** Tofacitinib (CP-690,550) Plus MTX ##### Group **Description:** Participants received CP-690,550 10 mg tablets, PO, BID and matching placebo MTX capsules, PO, once weekly for a maximum of 12 months. To maintain the blind, matching placebo MTX was titrated as follows: 4 capsules once weekly for 4 weeks; if well tolerated, at Month 1 titrate up to 6 capsules once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 8 capsules once weekly for the duration of the study. A single dose reduction of MTX placebo to 2 capsules was allowed because of lack of tolerance, as long as the participant remained on a dose of at least 4 MTX placebo capsules weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** OG001 **Title:** Tofacitinib (CP-690,550) ##### Group **Description:** Participants received MTX 10 mg/week to 20 mg/week, capsules, PO, and matching placebo CP-690,550 tablets, PO, BID. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** OG002 **Title:** Methotrexate #### Outcome Measure 8 **Description:** JSN score (a component of the modified TSS) is a measure of change in joint health. JSN score range is 0 (no narrowing) to 168 (high narrowing). Increase from baseline represents disease progression and / or joint worsening; no change represents halting of disease progression; a decrease represents improvement. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** Evaluable Set; n=number of participants assessed for the specified parameter at a given visit. **Reporting Status:** POSTED **Time Frame:** Months 6 and 12 **Title:** Joint Space Narrowing (JSN) Scores at Months 6 and 12 **Type:** SECONDARY **Unit of Measure:** score on a scale ##### Group **Description:** Participants received CP-690,550 10 mg, tablets, PO, BID, and MTX 10 mg/week to 20 mg/week, capsules, PO, for a maximum of 12 months. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** OG000 **Title:** Tofacitinib (CP-690,550) Plus MTX ##### Group **Description:** Participants received CP-690,550 10 mg tablets, PO, BID and matching placebo MTX capsules, PO, once weekly for a maximum of 12 months. To maintain the blind, matching placebo MTX was titrated as follows: 4 capsules once weekly for 4 weeks; if well tolerated, at Month 1 titrate up to 6 capsules once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 8 capsules once weekly for the duration of the study. A single dose reduction of MTX placebo to 2 capsules was allowed because of lack of tolerance, as long as the participant remained on a dose of at least 4 MTX placebo capsules weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** OG001 **Title:** Tofacitinib (CP-690,550) ##### Group **Description:** Participants received MTX 10 mg/week to 20 mg/week, capsules, PO, and matching placebo CP-690,550 tablets, PO, BID. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** OG002 **Title:** Methotrexate #### Outcome Measure 9 **Description:** JSN score (a component of the modified TSS) is a measure of change in joint health. JSN score range is 0 (no narrowing) to 168 (high narrowing). Increase from baseline represents disease progression and / or joint worsening; no change represents halting of disease progression; a decrease represents improvement. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** Evaluable Set; n=number of participants assessed for the specified parameter at a given visit. **Reporting Status:** POSTED **Time Frame:** Months 6 and 12 **Title:** Change From Baseline to Months 6 and 12 in JSN Scores **Type:** SECONDARY **Unit of Measure:** scores on a scale ##### Group **Description:** Participants received CP-690,550 10 mg, tablets, PO, BID, and MTX 10 mg/week to 20 mg/week, capsules, PO, for a maximum of 12 months. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** OG000 **Title:** Tofacitinib (CP-690,550) Plus MTX ##### Group **Description:** Participants received CP-690,550 10 mg tablets, PO, BID and matching placebo MTX capsules, PO, once weekly for a maximum of 12 months. To maintain the blind, matching placebo MTX was titrated as follows: 4 capsules once weekly for 4 weeks; if well tolerated, at Month 1 titrate up to 6 capsules once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 8 capsules once weekly for the duration of the study. A single dose reduction of MTX placebo to 2 capsules was allowed because of lack of tolerance, as long as the participant remained on a dose of at least 4 MTX placebo capsules weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** OG001 **Title:** Tofacitinib (CP-690,550) ##### Group **Description:** Participants received MTX 10 mg/week to 20 mg/week, capsules, PO, and matching placebo CP-690,550 tablets, PO, BID. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** OG002 **Title:** Methotrexate #### Outcome Measure 10 **Description:** Erosion score (a component of the modified TSS) is a measure of change in joint health. Erosion score range is from 0 (no erosion) to 280 (high erosion). Increase from baseline represents disease progression and / or joint worsening; no change represents halting of disease progression; a decrease represents improvement. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** Evaluable Set; n=number of participants assessed for the specified parameter at a given visit. **Reporting Status:** POSTED **Time Frame:** Months 6 and 12 **Title:** Erosion Scores at Months 6 and 12 **Type:** SECONDARY **Unit of Measure:** scores on a scale ##### Group **Description:** Participants received CP-690,550 10 mg, tablets, PO, BID, and MTX 10 mg/week to 20 mg/week, capsules, PO, for a maximum of 12 months. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** OG000 **Title:** Tofacitinib (CP-690,550) Plus MTX ##### Group **Description:** Participants received CP-690,550 10 mg tablets, PO, BID and matching placebo MTX capsules, PO, once weekly for a maximum of 12 months. To maintain the blind, matching placebo MTX was titrated as follows: 4 capsules once weekly for 4 weeks; if well tolerated, at Month 1 titrate up to 6 capsules once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 8 capsules once weekly for the duration of the study. A single dose reduction of MTX placebo to 2 capsules was allowed because of lack of tolerance, as long as the participant remained on a dose of at least 4 MTX placebo capsules weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** OG001 **Title:** Tofacitinib (CP-690,550) ##### Group **Description:** Participants received MTX 10 mg/week to 20 mg/week, capsules, PO, and matching placebo CP-690,550 tablets, PO, BID. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** OG002 **Title:** Methotrexate #### Outcome Measure 11 **Description:** Erosion score (a component of the modified TSS) is a measure of change in joint health. Erosion score range is from 0 (no erosion) to 280 (high erosion). Increase from baseline represents disease progression and / or joint worsening; no change represents halting of disease progression; a decrease represents improvement. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** Evaluable Set; n=number of participants assessed for the specified parameter at a given visit. **Reporting Status:** POSTED **Time Frame:** Months 6 and 12 **Title:** Change From Baseline to Months 6 and 12 in Erosion Score **Type:** SECONDARY **Unit of Measure:** scores on a scale ##### Group **Description:** Participants received CP-690,550 10 mg, tablets, PO, BID, and MTX 10 mg/week to 20 mg/week, capsules, PO, for a maximum of 12 months. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** OG000 **Title:** Tofacitinib (CP-690,550) Plus MTX ##### Group **Description:** Participants received CP-690,550 10 mg tablets, PO, BID and matching placebo MTX capsules, PO, once weekly for a maximum of 12 months. To maintain the blind, matching placebo MTX was titrated as follows: 4 capsules once weekly for 4 weeks; if well tolerated, at Month 1 titrate up to 6 capsules once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 8 capsules once weekly for the duration of the study. A single dose reduction of MTX placebo to 2 capsules was allowed because of lack of tolerance, as long as the participant remained on a dose of at least 4 MTX placebo capsules weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** OG001 **Title:** Tofacitinib (CP-690,550) ##### Group **Description:** Participants received MTX 10 mg/week to 20 mg/week, capsules, PO, and matching placebo CP-690,550 tablets, PO, BID. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** OG002 **Title:** Methotrexate #### Outcome Measure 12 **Description:** ACR20 response: greater than or equal to (≥)20% improvement in tender joint count; ≥20% improvement in swollen joint count; and ≥20% improvement in at least 3 of 5 remaining ACR core measures: Participant's Assessment of Pain; Participant's Global Assessment of Disease Activity; Physician Global Assessment of Disease Activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and C-Reactive Protein (CRP). **Parameter Type:** NUMBER **Population Description:** FAS Non-Responder Imputation (NRI) method: participants with missing values were considered to be non-responders. n=number of participants assessed for the specified parameter at a given visit. **Reporting Status:** POSTED **Time Frame:** Months 1, 2, 3, 6, 9, and 12 **Title:** Percentage of Participants With an American College of Rheumatology (ACR) 20 Percent (%) Improvement (ACR20) Response **Type:** SECONDARY **Unit of Measure:** percentage of participants ##### Group **Description:** Participants received CP-690,550 10 mg, tablets, PO, BID, and MTX 10 mg/week to 20 mg/week, capsules, PO, for a maximum of 12 months. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** OG000 **Title:** Tofacitinib (CP-690,550) Plus MTX ##### Group **Description:** Participants received CP-690,550 10 mg tablets, PO, BID and matching placebo MTX capsules, PO, once weekly for a maximum of 12 months. To maintain the blind, matching placebo MTX was titrated as follows: 4 capsules once weekly for 4 weeks; if well tolerated, at Month 1 titrate up to 6 capsules once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 8 capsules once weekly for the duration of the study. A single dose reduction of MTX placebo to 2 capsules was allowed because of lack of tolerance, as long as the participant remained on a dose of at least 4 MTX placebo capsules weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** OG001 **Title:** Tofacitinib (CP-690,550) ##### Group **Description:** Participants received MTX 10 mg/week to 20 mg/week, capsules, PO, and matching placebo CP-690,550 tablets, PO, BID. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** OG002 **Title:** Methotrexate #### Outcome Measure 13 **Description:** ACR50 response: ≥ 50% improvement in tender or swollen joint counts and 50% improvement in 3 of the following 5 criteria: 1) Physician's Global Assessment of Disease Activity, 2) Participant's Assessment of disease activity, 3) Paricipant's Assessment of Pain, 4) Participant's assessment of functional disability via a HAQ, and 5) CRP at each visit. **Parameter Type:** NUMBER **Population Description:** FAS NRI; n=number of participants assess for the specified parameter at a given visit. **Reporting Status:** POSTED **Time Frame:** Months 1, 2, 3, 6, 9, and 12 **Title:** Percentage of Participants With an ACR 50% Improvement (ACR50) Response **Type:** SECONDARY **Unit of Measure:** percentage of participants ##### Group **Description:** Participants received CP-690,550 10 mg, tablets, PO, BID, and MTX 10 mg/week to 20 mg/week, capsules, PO, for a maximum of 12 months. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** OG000 **Title:** Tofacitinib (CP-690,550) Plus MTX ##### Group **Description:** Participants received CP-690,550 10 mg tablets, PO, BID and matching placebo MTX capsules, PO, once weekly for a maximum of 12 months. To maintain the blind, matching placebo MTX was titrated as follows: 4 capsules once weekly for 4 weeks; if well tolerated, at Month 1 titrate up to 6 capsules once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 8 capsules once weekly for the duration of the study. A single dose reduction of MTX placebo to 2 capsules was allowed because of lack of tolerance, as long as the participant remained on a dose of at least 4 MTX placebo capsules weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** OG001 **Title:** Tofacitinib (CP-690,550) ##### Group **Description:** Participants received MTX 10 mg/week to 20 mg/week, capsules, PO, and matching placebo CP-690,550 tablets, PO, BID. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** OG002 **Title:** Methotrexate #### Outcome Measure 14 **Description:** ACR70 response: ≥70% improvement in tender or swollen joint counts and 70% improvement in 3 of the following 5 criteria: 1) Physician's Global Assessment of Disease Activity, 2) Participant's Assessment of Disease Activity, 3) Participant's Assessment of Pain, 4) Participant's Assessment of Functional Disability via a HAQ, and 5) CRP at each visit. **Parameter Type:** NUMBER **Population Description:** FAS NRI; n=number of participants assessed for the specified parameter at a given visit. **Reporting Status:** POSTED **Time Frame:** Months 1, 2, 3, 6, 9, and 12 **Title:** Percentage of Participants With an ACR 70% Improvement (ACR70) Response **Type:** SECONDARY **Unit of Measure:** percentage of participants ##### Group **Description:** Participants received CP-690,550 10 mg, tablets, PO, BID, and MTX 10 mg/week to 20 mg/week, capsules, PO, for a maximum of 12 months. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** OG000 **Title:** Tofacitinib (CP-690,550) Plus MTX ##### Group **Description:** Participants received CP-690,550 10 mg tablets, PO, BID and matching placebo MTX capsules, PO, once weekly for a maximum of 12 months. To maintain the blind, matching placebo MTX was titrated as follows: 4 capsules once weekly for 4 weeks; if well tolerated, at Month 1 titrate up to 6 capsules once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 8 capsules once weekly for the duration of the study. A single dose reduction of MTX placebo to 2 capsules was allowed because of lack of tolerance, as long as the participant remained on a dose of at least 4 MTX placebo capsules weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** OG001 **Title:** Tofacitinib (CP-690,550) ##### Group **Description:** Participants received MTX 10 mg/week to 20 mg/week, capsules, PO, and matching placebo CP-690,550 tablets, PO, BID. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** OG002 **Title:** Methotrexate #### Outcome Measure 15 **Description:** DAS28-3 (CRP) was calculated from the swollen joint count and tender joint count using the 28 joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-3 (CRP) less than or equal to (≤)3.2 implied low disease activity and greater than (\>)3.2 to 5.1 implied moderate to high disease activity, and DAS28-3 (CRP) less than (\<)2.6 = remission. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** FAS; n=number of participants assess for the specified parameter at a given visit. **Reporting Status:** POSTED **Time Frame:** Baseline and Months 1, 2, 3, 6, 9, and 12 **Title:** Disease Activity Score Based on 28-Joint Count and CRP (DAS28-3 [CRP]) **Type:** SECONDARY **Unit of Measure:** score on a scale ##### Group **Description:** Participants received CP-690,550 10 mg, tablets, PO, BID, and MTX 10 mg/week to 20 mg/week, capsules, PO, for a maximum of 12 months. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** OG000 **Title:** Tofacitinib (CP-690,550) Plus MTX ##### Group **Description:** Participants received CP-690,550 10 mg tablets, PO, BID and matching placebo MTX capsules, PO, once weekly for a maximum of 12 months. To maintain the blind, matching placebo MTX was titrated as follows: 4 capsules once weekly for 4 weeks; if well tolerated, at Month 1 titrate up to 6 capsules once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 8 capsules once weekly for the duration of the study. A single dose reduction of MTX placebo to 2 capsules was allowed because of lack of tolerance, as long as the participant remained on a dose of at least 4 MTX placebo capsules weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** OG001 **Title:** Tofacitinib (CP-690,550) ##### Group **Description:** Participants received MTX 10 mg/week to 20 mg/week, capsules, PO, and matching placebo CP-690,550 tablets, PO, BID. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** OG002 **Title:** Methotrexate #### Outcome Measure 16 **Description:** DAS28-3 (CRP) was calculated from the swollen joint count and tender joint count using the 28 joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** FAS; n=number of participants assessed for the specified parameter at a given visit. **Reporting Status:** POSTED **Time Frame:** Months 1, 2, 3, 6, 9, and 12 **Title:** Change From Baseline in DAS28-3 (CRP) **Type:** SECONDARY **Unit of Measure:** scores on a scale ##### Group **Description:** Participants received CP-690,550 10 milligrams (mg), tablets, orally (PO), twice daily (BID), and MTX 10 mg per week (mg/week) to 20 mg/week, capsules, PO, for a maximum of 12 months. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** OG000 **Title:** Tofacitinib (CP-690,550) Plus MTX ##### Group **Description:** Participants received CP-690,550 10 mg tablets, PO, BID and matching placebo MTX capsules, PO, once weekly for a maximum of 12 months. To maintain the blind, matching placebo MTX was titrated as follows: 4 capsules once weekly for 4 weeks; if well tolerated, at Month 1 titrate up to 6 capsules once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 8 capsules once weekly for the duration of the study. A single dose reduction of MTX placebo to 2 capsules was allowed because of lack of tolerance, as long as the participant remained on a dose of at least 4 MTX placebo capsules weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** OG001 **Title:** Tofacitinib (CP-690,550) ##### Group **Description:** Participants received MTX 10 mg/week to 20 mg/week, capsules, PO, and matching placebo CP-690,550 tablets, PO, BID. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** OG002 **Title:** Methotrexate #### Outcome Measure 17 **Description:** DAS28-4 (ESR) was calculated from swollen joint count and tender joint count using 28 joints count, ESR (millimeters per hour \[mm/hour\]) and Participant Global Assessment of disease activity (participant rated arthritis activity assessment). Total score range: 0 to 9.4; higher score=more disease activity. DAS28-4 (ESR) ≤3.2 implied low disease activity and \>3.2 to 5.1 implied moderate to high disease activity, and DAS28-4 (ESR) \<2.6 = remission. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** FAS; n=number of participants assessed for the specified parameter at a given visit. **Reporting Status:** POSTED **Time Frame:** Baseline and Months 1, 2, 3, 6, 9, and 12 **Title:** Disease Activity Score Based on 28-Joint Count and Erythrocyte Sedimentation Rate (DAS28-4 [ESR]) **Type:** SECONDARY **Unit of Measure:** scores on a scale ##### Group **Description:** Participants received CP-690,550 10 mg, tablets, PO, BID, and MTX 10 mg/week to 20 mg/week, capsules, PO, for a maximum of 12 months. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** OG000 **Title:** Tofacitinib (CP-690,550) Plus MTX ##### Group **Description:** Participants received CP-690,550 10 mg tablets, PO, BID and matching placebo MTX capsules, PO, once weekly for a maximum of 12 months. To maintain the blind, matching placebo MTX was titrated as follows: 4 capsules once weekly for 4 weeks; if well tolerated, at Month 1 titrate up to 6 capsules once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 8 capsules once weekly for the duration of the study. A single dose reduction of MTX placebo to 2 capsules was allowed because of lack of tolerance, as long as the participant remained on a dose of at least 4 MTX placebo capsules weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** OG001 **Title:** Tofacitinib (CP-690,550) ##### Group **Description:** Participants received MTX 10 mg/week to 20 mg/week, capsules, PO, and matching placebo CP-690,550 tablets, PO, BID. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** OG002 **Title:** Methotrexate #### Outcome Measure 18 **Description:** DAS28-4 (ESR) was calculated from swollen joint count and tender joint count using 28 joints count, ESR (millimeters per hour \[mm/hour\]) and Participant Global Assessment of disease activity (participant rated arthritis activity assessment). Total score range: 0 to 9.4; higher score=more disease activity. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** FAS; n=number of participants assessed for the specified parameter at a given visit. **Reporting Status:** POSTED **Time Frame:** Months 1, 2, 3, 6, 9, and 12 **Title:** Change From Baseline in DAS28-4 (ESR) **Type:** SECONDARY **Unit of Measure:** scores on a scale ##### Group **Description:** Participants received CP-690,550 10 milligrams (mg), tablets, orally (PO), twice daily (BID), and MTX 10 mg per week (mg/week) to 20 mg/week, capsules, PO, for a maximum of 12 months. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** OG000 **Title:** Tofacitinib (CP-690,550) Plus MTX ##### Group **Description:** Participants received CP-690,550 10 mg tablets, PO, BID and matching placebo MTX capsules, PO, once weekly for a maximum of 12 months. To maintain the blind, matching placebo MTX was titrated as follows: 4 capsules once weekly for 4 weeks; if well tolerated, at Month 1 titrate up to 6 capsules once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 8 capsules once weekly for the duration of the study. A single dose reduction of MTX placebo to 2 capsules was allowed because of lack of tolerance, as long as the participant remained on a dose of at least 4 MTX placebo capsules weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** OG001 **Title:** Tofacitinib (CP-690,550) ##### Group **Description:** Participants received MTX 10 mg/week to 20 mg/week, capsules, PO, and matching placebo CP-690,550 tablets, PO, BID. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** OG002 **Title:** Methotrexate #### Outcome Measure 19 **Description:** DAS28-3(CRP) was calculated from the swollen joint count and tender joint count using 28-joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28 categorical responses define a good (absolute: \<3.2 or \>1.2 improvement from baseline \[BL\]), moderate (absolute: 3.2-5.1 or 0.6-1.2 change from BL), or no response (absolute: \>5.1 or \<0.6 change from BL). **Parameter Type:** NUMBER **Population Description:** FAS NRI; n=number of participants assessed for the specified parameter at a given visit. **Reporting Status:** POSTED **Time Frame:** Months 1, 2, 3, 6, 9, and 12 **Title:** Percentage of Participants With DAS28-3 (CRP) Response (Good or Moderate Improvement) **Type:** SECONDARY **Unit of Measure:** percentage of participants ##### Group **Description:** Participants received CP-690,550 10 mg, tablets, PO, BID, and MTX 10 mg/week to 20 mg/week, capsules, PO, for a maximum of 12 months. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** OG000 **Title:** Tofacitinib (CP-690,550) Plus MTX ##### Group **Description:** Participants received CP-690,550 10 mg tablets, PO, BID and matching placebo MTX capsules, PO, once weekly for a maximum of 12 months. To maintain the blind, matching placebo MTX was titrated as follows: 4 capsules once weekly for 4 weeks; if well tolerated, at Month 1 titrate up to 6 capsules once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 8 capsules once weekly for the duration of the study. A single dose reduction of MTX placebo to 2 capsules was allowed because of lack of tolerance, as long as the participant remained on a dose of at least 4 MTX placebo capsules weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** OG001 **Title:** Tofacitinib (CP-690,550) ##### Group **Description:** Participants received MTX 10 mg/week to 20 mg/week, capsules, PO, and matching placebo CP-690,550 tablets, PO, BID. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** OG002 **Title:** Methotrexate #### Outcome Measure 20 **Description:** DAS28-3(CRP) was calculated from the swollen joint count and tender joint count using 28-joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-3(CRP) ≤3.2 implied low disease activity. **Parameter Type:** NUMBER **Population Description:** FAS NRI; n=number of participants assessed for the specified parameter at a given visit. **Reporting Status:** POSTED **Time Frame:** Months 1, 2, 3, 6, 9, and 12 **Title:** Percentage of Participants With DAS28-3 (CRP) Score ≤3.2 **Type:** SECONDARY **Unit of Measure:** percentage of participants ##### Group **Description:** Participants received CP-690,550 10 mg, tablets, PO, BID, and MTX 10 mg/week to 20 mg/week, capsules, PO, for a maximum of 12 months. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** OG000 **Title:** Tofacitinib (CP-690,550) Plus MTX ##### Group **Description:** Participants received CP-690,550 10 mg tablets, PO, BID and matching placebo MTX capsules, PO, once weekly for a maximum of 12 months. To maintain the blind, matching placebo MTX was titrated as follows: 4 capsules once weekly for 4 weeks; if well tolerated, at Month 1 titrate up to 6 capsules once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 8 capsules once weekly for the duration of the study. A single dose reduction of MTX placebo to 2 capsules was allowed because of lack of tolerance, as long as the participant remained on a dose of at least 4 MTX placebo capsules weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** OG001 **Title:** Tofacitinib (CP-690,550) ##### Group **Description:** Participants received MTX 10 mg/week to 20 mg/week, capsules, PO, and matching placebo CP-690,550 tablets, PO, BID. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** OG002 **Title:** Methotrexate #### Outcome Measure 21 **Description:** DAS28-3(CRP) was calculated from the swollen joint count and tender joint count using 28-joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-3(CRP) \<2.6 implied remission. **Parameter Type:** NUMBER **Population Description:** FAS NRI; n=number of participants assessed for the specified parameter at a given visit. **Reporting Status:** POSTED **Time Frame:** Months 1, 2, 3, 6, 9, and 12 **Title:** Percentage of Participants With DAS28-3 (CRP) Score <2.6 **Type:** SECONDARY **Unit of Measure:** percentage of participants ##### Group **Description:** Participants received CP-690,550 10 mg, tablets, PO, BID, and MTX 10 mg/week to 20 mg/week, capsules, PO, for a maximum of 12 months. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** OG000 **Title:** Tofacitinib (CP-690,550) Plus MTX ##### Group **Description:** Participants received CP-690,550 10 mg tablets, PO, BID and matching placebo MTX capsules, PO, once weekly for a maximum of 12 months. To maintain the blind, matching placebo MTX was titrated as follows: 4 capsules once weekly for 4 weeks; if well tolerated, at Month 1 titrate up to 6 capsules once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 8 capsules once weekly for the duration of the study. A single dose reduction of MTX placebo to 2 capsules was allowed because of lack of tolerance, as long as the participant remained on a dose of at least 4 MTX placebo capsules weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** OG001 **Title:** Tofacitinib (CP-690,550) ##### Group **Description:** Participants received MTX 10 mg/week to 20 mg/week, capsules, PO, and matching placebo CP-690,550 tablets, PO, BID. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** OG002 **Title:** Methotrexate #### Outcome Measure 22 **Description:** DAS28-4(ESR) was calculated from swollen joint count and tender joint count using 28 joints count, ESR (mm/hour) and Participant's Global Assessment of Disease Activity (participant rated arthritis activity assessment). Total score range: 0 to 9.4, higher score=more disease activity. DAS28 categorical responses define a good (absolute: \<3.2 or \>1.2 improvement from BL), moderate (absolute: 3.2-5.1 or 0.6-1.2 change from BL), or no response (absolute: \>5.1 or \<0.6 change from BL). **Parameter Type:** NUMBER **Population Description:** FAS NRI; n=number of participants assessed for the specified parameter at a given visit. **Reporting Status:** POSTED **Time Frame:** Months 1, 2, 3, 6, 9, and 12 **Title:** Percentage of Participants With DAS28-4 (ESR) Response (Good or Moderate Improvement) **Type:** SECONDARY **Unit of Measure:** percentage of participants ##### Group **Description:** Participants received CP-690,550 10 mg, tablets, PO, BID, and MTX 10 mg/week to 20 mg/week, capsules, PO, for a maximum of 12 months. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** OG000 **Title:** Tofacitinib (CP-690,550) Plus MTX ##### Group **Description:** Participants received CP-690,550 10 mg tablets, PO, BID and matching placebo MTX capsules, PO, once weekly for a maximum of 12 months. To maintain the blind, matching placebo MTX was titrated as follows: 4 capsules once weekly for 4 weeks; if well tolerated, at Month 1 titrate up to 6 capsules once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 8 capsules once weekly for the duration of the study. A single dose reduction of MTX placebo to 2 capsules was allowed because of lack of tolerance, as long as the participant remained on a dose of at least 4 MTX placebo capsules weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** OG001 **Title:** Tofacitinib (CP-690,550) ##### Group **Description:** Participants received MTX 10 mg/week to 20 mg/week, capsules, PO, and matching placebo CP-690,550 tablets, PO, BID. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** OG002 **Title:** Methotrexate #### Outcome Measure 23 **Description:** DAS28-4(ESR) was calculated from swollen joint count and tender joint count using 28 joints count, ESR (mm/hour) and Participant's Global Assessment of Disease Activity (participant rated arthritis activity assessment). Total score range: 0 to 9.4, higher score=more disease activity. DAS28-4(ESR) ≤3.2 implied low disease activity. **Parameter Type:** NUMBER **Population Description:** FAS NRI; n=number of participants assessed for the specified parameter at a given visit. **Reporting Status:** POSTED **Time Frame:** Months 1, 2, 3, 6, 9, and 12 **Title:** Percentage of Participants With DAS28-4 (ESR) ≤3.2 **Type:** SECONDARY **Unit of Measure:** percentage of participants ##### Group **Description:** Participants received CP-690,550 10 mg, tablets, PO, BID, and MTX 10 mg/week to 20 mg/week, capsules, PO, for a maximum of 12 months. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** OG000 **Title:** Tofacitinib (CP-690,550) Plus MTX ##### Group **Description:** Participants received CP-690,550 10 mg tablets, PO, BID and matching placebo MTX capsules, PO, once weekly for a maximum of 12 months. To maintain the blind, matching placebo MTX was titrated as follows: 4 capsules once weekly for 4 weeks; if well tolerated, at Month 1 titrate up to 6 capsules once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 8 capsules once weekly for the duration of the study. A single dose reduction of MTX placebo to 2 capsules was allowed because of lack of tolerance, as long as the participant remained on a dose of at least 4 MTX placebo capsules weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** OG001 **Title:** Tofacitinib (CP-690,550) ##### Group **Description:** Participants received MTX 10 mg/week to 20 mg/week, capsules, PO, and matching placebo CP-690,550 tablets, PO, BID. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** OG002 **Title:** Methotrexate #### Outcome Measure 24 **Description:** DAS28-4(ESR) was calculated from swollen joint count and tender joint count using 28 joints count, ESR (mm/hour) and Participant's Global Assessment of Disease Activity (participant rated arthritis activity assessment). Total score range: 0 to 9.4, higher score=more disease activity. DAS28-4(ESR) \<2.6 implied remission. **Parameter Type:** NUMBER **Population Description:** FAS NRI; n=number of participants assessed for the specified parameter at a given visit. **Reporting Status:** POSTED **Time Frame:** Months 1, 2, 3, 6, 9, and 12 **Title:** Percentage of Participants With DAS28-4 (ESR) <2.6 **Type:** SECONDARY **Unit of Measure:** percentage of participants ##### Group **Description:** Participants received CP-690,550 10 mg, tablets, PO, BID, and MTX 10 mg/week to 20 mg/week, capsules, PO, for a maximum of 12 months. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** OG000 **Title:** Tofacitinib (CP-690,550) Plus MTX ##### Group **Description:** Participants received CP-690,550 10 mg tablets, PO, BID and matching placebo MTX capsules, PO, once weekly for a maximum of 12 months. To maintain the blind, matching placebo MTX was titrated as follows: 4 capsules once weekly for 4 weeks; if well tolerated, at Month 1 titrate up to 6 capsules once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 8 capsules once weekly for the duration of the study. A single dose reduction of MTX placebo to 2 capsules was allowed because of lack of tolerance, as long as the participant remained on a dose of at least 4 MTX placebo capsules weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** OG001 **Title:** Tofacitinib (CP-690,550) ##### Group **Description:** Participants received MTX 10 mg/week to 20 mg/week, capsules, PO, and matching placebo CP-690,550 tablets, PO, BID. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** OG002 **Title:** Methotrexate ### Participant Flow Module #### Group **Description:** Participants received CP-690,550 10 milligrams (mg), tablets, orally (PO), twice daily (BID), and MTX 10 mg per week (mg/week) to 20 mg/week, capsules, PO, for a maximum of 12 months. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** FG000 **Title:** Tofacitinib (CP-690,550) Plus Methotrexate (MTX) #### Group **Description:** Participants received CP-690,550 10 mg tablets, PO, BID and matching placebo MTX capsules, PO, once weekly for a maximum of 12 months. To maintain the blind, matching placebo MTX was titrated as follows: 4 capsules once weekly for 4 weeks; if well tolerated, at Month 1 titrate up to 6 capsules once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 8 capsules once weekly for the duration of the study. A single dose reduction of MTX placebo to 2 capsules was allowed because of lack of tolerance, as long as the participant remained on a dose of at least 4 MTX placebo capsules weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** FG001 **Title:** Tofacitinib (CP-690,550) #### Group **Description:** Participants received MTX 10 mg/week to 20 mg/week, capsules, PO, and matching placebo CP-690,550 tablets, PO, BID. MTX dose was titrated as follows: 10 mg once weekly for 4 weeks; if well tolerated, then at Month 1 titrate up to 15 mg once weekly for 4 weeks; if well tolerated, then at Month 2 titrate up to 20 mg once weekly for the duration of the study. A single dose reduction of MTX 5 mg was allowed because of lack of tolerance, as long as the participant remained on a dose of at least MTX 10 mg weekly. Participants also received folate supplementation according to local MTX label guidelines and standard of care. **ID:** FG002 **Title:** Methotrexate #### Period **Title:** Overall Study ##### Withdraw **Type:** Lack of Efficacy ###### Reason **Group ID:** FG000 **Number of Subjects:** 0 ###### Reason **Group ID:** FG001 **Number of Subjects:** 0 ###### Reason **Group ID:** FG002 **Number of Subjects:** 6 ##### Withdraw **Type:** Lost to Follow-up ###### Reason **Group ID:** FG000 **Number of Subjects:** 1 ###### Reason **Group ID:** FG001 **Number of Subjects:** 1 ###### Reason **Group ID:** FG002 **Number of Subjects:** 0 ##### Withdraw **Type:** Withdrawal by Subject ###### Reason **Group ID:** FG000 **Number of Subjects:** 2 ###### Reason **Group ID:** FG001 **Number of Subjects:** 5 ###### Reason **Group ID:** FG002 **Number of Subjects:** 3 ##### Withdraw **Type:** Protocol Violation ###### Reason **Group ID:** FG000 **Number of Subjects:** 0 ###### Reason **Group ID:** FG001 **Number of Subjects:** 1 ###### Reason **Group ID:** FG002 **Number of Subjects:** 2 ##### Withdraw **Type:** Adverse Event ###### Reason **Group ID:** FG000 **Number of Subjects:** 4 ###### Reason **Group ID:** FG001 **Number of Subjects:** 2 ###### Reason **Group ID:** FG002 **Number of Subjects:** 5 ##### Withdraw **Type:** Reason not specified ###### Reason **Group ID:** FG000 **Number of Subjects:** 1 ###### Reason **Group ID:** FG001 **Number of Subjects:** 0 ###### Reason **Group ID:** FG002 **Number of Subjects:** 0 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 36 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 36 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 37 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 28 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 27 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 21 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 8 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 9 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 16 **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT02802579 **Brief Title:** ECG Triggered Dual Source CT for Non-invasive Pre-operative Cardiac Imaging in Morbid Obese Patients **Official Title:** ECG Triggered Dual Source CT for Non-invasive Pre-operative Cardiac Imaging in Morbid Obese Patients #### Organization Study ID Info **ID:** RAD0701 #### Organization **Class:** OTHER **Full Name:** Cantonal Hospital of St. Gallen ### Status Module #### Completion Date **Date:** 2015-12 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2016-06-17 **Type:** ESTIMATED **Last Update Submit Date:** 2016-06-16 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2015-12 **Type:** ACTUAL #### Start Date **Date:** 2007-12 **Status Verified Date:** 2016-06 #### Study First Post Date **Date:** 2016-06-16 **Type:** ESTIMATED **Study First Submit Date:** 2016-06-14 **Study First Submit QC Date:** 2016-06-14 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Cantonal Hospital of St. Gallen #### Responsible Party **Investigator Affiliation:** Cantonal Hospital of St. Gallen **Investigator Full Name:** Sebastian Leschka, MD **Investigator Title:** Attending Physician **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** Coronary arterial disease is a risk factor for bariatric surgery and might be a predictor for later major adverse coronary events. Diagnosis of coronary arterial disease would thus be desirable for obese patients, however percutaneous angiography is an invasive procedure and associated with a certain morbidity in obese patients. In this study the investigators would like to assess whether dual source CT angiography can be used for diagnosis of coronary arterial disease in severely obese patients and which settings yield the best image quality. **Detailed Description:** Obesity is a major health problem in many countries and a major risk factor for cardiovascular disease. Extreme obesity can be treated with surgery, however these procedures are associated with a certain surgery-related morbidity which increases with comorbidities, in particular coronary diseases. Thus, preoperative cardiac risk assessment would be desirable, however percutaneous coronary angiography is an invasive procedure with problems and complications in obese patients. A non-invasive alternative would be coronary dual-.source CT angiography (CCTA), however little experience exists in the application of CCTA in morbid obese patients. This study would like to address the following issues: 1. Comparison of image quality of coronary CT angiography using a dual source CT from obese patients using a special protocol (140 kV, 350 mAs) with images from historical controls from normal weight patients with a standard protocol (120 kV, 330 mAs). 2. Prediction of major adverse coronary events. Patients with a coronary stenosis in CCTA will be followed for any major adverse coronary events (details see Outcomes) 3. Is it possible to detect myocardial fat by a reduced CT density. Images from obese patients will be compared to historical controls from normal patients. Furthermore, is the myocardial CT density correlated with the BMI of obese patients? 4. Optimisation of scan protocol. Increasing the scanning angle beyond the standard 90° will reduce the signal noise at the cost of temporal resolution. Various scanning angles with be tested for an optimal combination of signal noise and temporal resolution. 5. Does the long QT-syndrome improve after bariatric surgery? It is assumed that the long QT-syndrome is a consequence of fattening of the myocardia. Is it possible to see a reduction of myocardial fattening and thus an improvement of the long QT-syndrome with CT during the follow-up after bariatric surgery? ### Conditions Module **Conditions:** - Obesity, Morbid **Keywords:** - obesity - dual source CT - coronary CT angiography - prognosis - bariatric surgery - gastric bypass surgery - coronary arterial disease - major adverse coronary event ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** TRIPLE **Who Masked:** - PARTICIPANT - CARE_PROVIDER - OUTCOMES_ASSESSOR **Primary Purpose:** DIAGNOSTIC #### Enrollment Info **Count:** 70 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Standard dual-source computed tomography coronary angiography protocol **Intervention Names:** - Radiation: standard protocol **Label:** A: standard protocol **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** enhanced dual-source computed tomography coronary angiography protocol **Intervention Names:** - Radiation: enhanced protocol **Label:** B: enhanced protocol **Type:** EXPERIMENTAL #### Arm Group 3 **Description:** enhanced obesity-mode dual-source computed tomography coronary angiography protocol **Intervention Names:** - Radiation: enhanced obesity protocol **Label:** C: enhanced obesity protocol **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - A: standard protocol **Description:** tube voltage: 120 kV current time product: 350 mAs/rotation rotation: 90° (with two detectors in a 90° angle) **Name:** standard protocol **Other Names:** - dual source computed tomography coronary angiography **Type:** RADIATION #### Intervention 2 **Arm Group Labels:** - B: enhanced protocol **Description:** tube voltage: 140 kV current time product: 350 mAs/rotation rotation: 90° (with two detectors in a 90° angle) **Name:** enhanced protocol **Other Names:** - dual source computed tomography coronary angiography **Type:** RADIATION #### Intervention 3 **Arm Group Labels:** - C: enhanced obesity protocol **Description:** tube voltage: 140 kV current time product: 350 mAs/rotation rotation: 180° (with two detectors in a 90° angle) **Name:** enhanced obesity protocol **Other Names:** - dual source computed tomography coronary angiography **Type:** RADIATION ### Outcomes Module #### Primary Outcomes **Description:** Coronary arteries (with at least 1 mm diameter at their origin) were segmented according to the 15-segment model of the American Heart Association (Austen 1975). Subjective image quality was judged for each coronary artery segment on a 4-point scale (Leschka 2007) : 1. = excellent; 2. = good, minor artifacts; 3. = fair, moderate artifacts but still diagnostic; 4. = non-diagnostic **Measure:** Image quality **Time Frame:** 7 days **Description:** Significant coronary artery stenosis was defined as more than 50% narrowing of luminal diameter. Stenosis assessment was performed by a radiologist not involved in image quality assessment. **Measure:** coronary artery stenosis **Time Frame:** 7 days #### Secondary Outcomes **Description:** Image noise was determined as the standard deviation of the attenuation value in a region of 1 sq cm that was placed in the ascending aorta. The average of the attenuation in the left and right coronary artery were used for further calculations. **Measure:** Image noise **Time Frame:** 7 days **Description:** SNR was determined by dividing mean attenuation by image noise **Measure:** Signal-to-noise ratio (SNR) **Time Frame:** 7 days **Description:** Vessel contrast was calculated as the difference in the mean attenuation (in Hounsfield units) between the contrast-enhanced vessel lumen and the mean attenuation in the adjacent perivascular tissue. Attenuations were measured in a region in the proximal segment of the right coronary artery and in the left main artery, and were defined as large as possible, whereas avoiding calcifications and plaques. CNR was calculated as vessel contrast divided by image noise (Husmann 2006, Lembcke 2004). **Measure:** contrast-to-noise ratio (CNR) **Time Frame:** 7 days **Description:** Any of the following events: * death * non fatal myocardial infarction * late revascularization with percutaneous coronary intervention * coronary artery bypass grafting **Measure:** Major adverse cardiovascular events (MACE) **Time Frame:** 7 years ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * morbid obesity (BMI \>35 kg/m²) * intention to undergo bariatric surgery * increased risk for coronary artery disease (based on PROCAM score) Exclusion Criteria: * kidney insufficiency (serum creatinine \>100 µmol/l, creatinine clearance \<50 ml/min) * allergy to iodine containing contrast agents * hyperthyroidism * metformin medication * pregnancy **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** St. Gallen **Country:** Switzerland **Facility:** Cantonal Hospital St Gallen **Zip:** 9007 #### Overall Officials **Official 1:** **Affiliation:** Cantonal Hospital St. Gallen **Name:** Sebastian Leschka, MD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Austen WG, Edwards JE, Frye RL, Gensini GG, Gott VL, Griffith LS, McGoon DC, Murphy ML, Roe BB. A reporting system on patients evaluated for coronary artery disease. Report of the Ad Hoc Committee for Grading of Coronary Artery Disease, Council on Cardiovascular Surgery, American Heart Association. Circulation. 1975 Apr;51(4 Suppl):5-40. doi: 10.1161/01.cir.51.4.5. No abstract available. **PMID:** 1116248 **Citation:** Leschka S, Scheffel H, Desbiolles L, Plass A, Gaemperli O, Valenta I, Husmann L, Flohr TG, Genoni M, Marincek B, Kaufmann PA, Alkadhi H. Image quality and reconstruction intervals of dual-source CT coronary angiography: recommendations for ECG-pulsing windowing. Invest Radiol. 2007 Aug;42(8):543-9. doi: 10.1097/RLI.0b013e31803b93cf. **PMID:** 17620936 **Citation:** Husmann L, Alkadhi H, Boehm T, Leschka S, Schepis T, Koepfli P, Desbiolles L, Marincek B, Kaufmann PA, Wildermuth S. Influence of cardiac hemodynamic parameters on coronary artery opacification with 64-slice computed tomography. Eur Radiol. 2006 May;16(5):1111-6. doi: 10.1007/s00330-005-0110-4. Epub 2006 Jan 28. **PMID:** 16607499 **Citation:** Lembcke A, Wiese TH, Schnorr J, Wagner S, Mews J, Kroencke TJ, Enzweiler CN, Hamm B, Taupitz M. Image quality of noninvasive coronary angiography using multislice spiral computed tomography and electron-beam computed tomography: intraindividual comparison in an animal model. Invest Radiol. 2004 Jun;39(6):357-64. doi: 10.1097/01.rli.0000123316.10765.6c. **PMID:** 15167102 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009765 - Term: Obesity - 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: LOW - As Found: Unknown - ID: M12702 - Name: Obesity, Morbid - Relevance: HIGH - As Found: Obesity, Morbid - 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: D000009767 - Term: Obesity, Morbid ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT01421979 **Brief Title:** Clinical Trial on the Effects of Caffeine and Taurine From Energy Drinks (EDs) to Parameters of the Cardiovascular System in Humans #### Organization Study ID Info **ID:** ED2011 #### Organization **Class:** OTHER **Full Name:** University of Hohenheim ### Status Module #### Completion Date **Date:** 2013-08 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2015-02-05 **Type:** ESTIMATED **Last Update Submit Date:** 2015-02-04 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2013-08 **Type:** ACTUAL #### Start Date **Date:** 2011-04 **Status Verified Date:** 2015-02 #### Study First Post Date **Date:** 2011-08-23 **Type:** ESTIMATED **Study First Submit Date:** 2011-08-22 **Study First Submit QC Date:** 2011-08-22 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** University of Hohenheim #### Responsible Party **Type:** SPONSOR ### Description Module **Brief Summary:** The aim of this study is to examine the safety and the effects of EDs at high doses, either alone or in combination with other risk factors such as alcohol intake, physical exercise and sleep deprivation, on cardiovascular markers and subjective health. ### Conditions Module **Conditions:** - Cardiovascular Risk ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** CROSSOVER ##### Masking Info **Masking:** QUADRUPLE **Who Masked:** - PARTICIPANT - CARE_PROVIDER - INVESTIGATOR - OUTCOMES_ASSESSOR **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 38 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Examination of the effects of EDs in combination with alcohol consumption and sleep deprivation. **Intervention Names:** - Dietary Supplement: Energy Drink, Taurine, Caffeine **Label:** exposure under sleep deprivation **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Examination of the effects of EDs in combination with alcohol consumption and exercise. **Intervention Names:** - Dietary Supplement: Energy Drink, Taurine, Caffeine **Label:** Exercise after consumption **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Exercise after consumption - exposure under sleep deprivation **Name:** Energy Drink, Taurine, Caffeine **Type:** DIETARY_SUPPLEMENT ### Outcomes Module #### Primary Outcomes **Measure:** Heart-rate-variability (HRV) **Time Frame:** during 24 hours ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * written informed consent * healthy (no acute or chronic desease) * BMI 20,0 - 25,9 kg/m2 * moderate and non-regular consumption of alcohol, EDs and coffee Exclusion Criteria: * pregnancy * regular medication (oral contraceptives permitted) * hypertension and other deseases of the cardiovascular system * liver-deseases * psychiatric deseases * epilepsy * other relevant deseases * (former) alcoholics * non-compliance to the study-protocol * simultaneous participation in another clinical trial * retraction of the written informed consent **Healthy Volunteers:** True **Maximum Age:** 25 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Stuttgart **Country:** Germany **Facility:** University of Hohenheim **State:** Baden-Württemberg **Zip:** 70593 ### References Module #### References **Citation:** Basrai M, Schweinlin A, Menzel J, Mielke H, Weikert C, Dusemund B, Putze K, Watzl B, Lampen A, Bischoff SC. Energy Drinks Induce Acute Cardiovascular and Metabolic Changes Pointing to Potential Risks for Young Adults: A Randomized Controlled Trial. J Nutr. 2019 Mar 1;149(3):441-450. doi: 10.1093/jn/nxy303. **PMID:** 30805607 ## Derived Section ### Intervention Browse Module - Ancestors - ID: D000000697 - Term: Central Nervous System Stimulants - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000010726 - Term: Phosphodiesterase Inhibitors - ID: D000004791 - Term: Enzyme Inhibitors - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000058915 - Term: Purinergic P1 Receptor Antagonists - ID: D000058914 - Term: Purinergic Antagonists - ID: D000058905 - Term: Purinergic Agents - ID: D000018377 - Term: Neurotransmitter Agents ### Intervention Browse Module - Browse Branches - Abbrev: CNSSti - Name: Central Nervous System Stimulants - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Infe - Name: Anti-Infective Agents - Abbrev: CNSDep - Name: Central Nervous System Depressants - Abbrev: Ot - Name: Other Dietary Supplements - Abbrev: AA - Name: Amino Acids ### Intervention Browse Module - Browse Leaves - ID: M5373 - Name: Caffeine - Relevance: HIGH - As Found: Sterile - ID: M3777 - Name: Ethanol - Relevance: LOW - As Found: Unknown - ID: M4029 - Name: Central Nervous System Stimulants - Relevance: LOW - As Found: Unknown - ID: M13629 - Name: Phosphodiesterase Inhibitors - Relevance: LOW - As Found: Unknown - ID: M7951 - Name: Enzyme Inhibitors - Relevance: LOW - As Found: Unknown - ID: M20504 - Name: Neurotransmitter Agents - Relevance: LOW - As Found: Unknown - ID: T370 - Name: Caffeine - Relevance: HIGH - As Found: Sterile - ID: T19 - Name: Taurine - Relevance: HIGH - As Found: Sciatic nerve block ### Intervention Browse Module - Meshes - ID: D000002110 - Term: Caffeine ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT02251379 **Acronym:** ECATCh **Brief Title:** Environmental Control as Add-on Therapy in Childhood Asthma **Official Title:** Environmental Control as Add-on Therapy in Childhood Asthma #### Organization Study ID Info **ID:** NA_00093323 #### Organization **Class:** OTHER **Full Name:** Johns Hopkins University ### Status Module #### Completion Date **Date:** 2018-11 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2019-11-20 **Type:** ACTUAL **Last Update Submit Date:** 2019-11-08 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2018-11 **Type:** ACTUAL #### Results First Post Date **Date:** 2019-11-04 **Type:** ACTUAL **Results First Submit Date:** 2019-10-15 **Results First Submit QC Date:** 2019-10-15 #### Start Date **Date:** 2014-10-01 **Type:** ACTUAL **Status Verified Date:** 2019-11 #### Study First Post Date **Date:** 2014-09-29 **Type:** ESTIMATED **Study First Submit Date:** 2014-09-22 **Study First Submit QC Date:** 2014-09-25 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Johns Hopkins University #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** This study evaluates the effects of adding on an environmental home intervention to standard asthma medication management on controller medication requirements among children and adolescents with asthma. The investigators hypothesize that the addition of an individually-tailored, multi-faceted Environmental Control Strategy (ECS) to guidelines-based controller medication will result in less controller medication requirement and allergic inflammation than controller medication alone among urban asthmatic children. **Detailed Description:** The study is a parallel arm study of an individually tailored, multi-faceted ECS plus controller medication titration versus controller medication titration alone. After a 4-week run-in period to stabilize the asthma, the investigators will randomize 200 Baltimore children with persistent asthma and a recent exacerbation in a 1:1 ratio to the two arms and follow the children for six months. There will be five clinic visits and three home visits over this time period for clinical and home assessments, respectively. There will be up to four environmental intervention visits for participants randomized to the environmental control plus controller medication group. The environmental modules include mouse, cockroach, furry pets, dust mites, and smoking. Air purifiers and laundered bedding are also included in this arm. Participants randomized to the controller medication group have the option of having one home visit after completing the study at which the participants will receive home intervention services that the environmental control plus controller medication group received. Participants will have repeated assessment of: controller medication requirements; secondary clinical, physiologic, and inflammatory outcomes; and particulate matter (PM), air nicotine, and allergen levels. ### Conditions Module **Conditions:** - Asthma ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 155 **Type:** ACTUAL **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** The Environmental Control Strategy ("Home Environmental Intervention") plus inhaled corticosteroids or inhaled corticosteroids plus long-acting beta agonist. (Flovent Diskus or Advair diskus) **Intervention Names:** - Drug: Flovent Diskus - Other: Home Environmental Intervention - Drug: Advair Diskus **Label:** ECS + Medication Group **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** inhaled corticosteroids or inhaled corticosteroids plus long-acting beta agonist. (Flovent Diskus or Advair diskus) **Intervention Names:** - Drug: Flovent Diskus - Drug: Advair Diskus **Label:** Medication Group Alone **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - ECS + Medication Group - Medication Group Alone **Description:** Inhaled corticosteroids **Name:** Flovent Diskus **Other Names:** - Flovent Diskus, 50 mcg, 100mcg, 250 mcg **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - ECS + Medication Group **Description:** Mouse, Cockroach, Furry pets, Dust mites, Smoking, air purifiers, laundered bedding **Name:** Home Environmental Intervention **Type:** OTHER #### Intervention 3 **Arm Group Labels:** - ECS + Medication Group - Medication Group Alone **Description:** inhaled corticosteroids + long-acting beta agonist **Name:** Advair Diskus **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** The controller medication treatment step that was assigned at the visit, which is based on the current controller medication treatment step and the current level of asthma control. The range is from 0-6, with 0 indicating no controller medication and 6 indicating high dose inhaled corticosteroids plus long-acting beta agonist. **Measure:** The Medication Treatment Step Assigned **Time Frame:** 6 month clinic visit #### Secondary Outcomes **Description:** micrograms of inhaled corticosteroids (daily) **Measure:** Daily Inhaled Corticosteroid Dose **Time Frame:** 6 months **Description:** Exhaled nitric oxide in parts per billion. **Measure:** Exhaled Nitric Oxide **Time Frame:** 6 months **Description:** Number of asthma symptom days in the past two weeks will be a measure of asthma control. **Measure:** Number of Asthma Symptom Days **Time Frame:** 6 months **Description:** Asthma exacerbations will be assessed by number of acute visits to the emergency department (ED), hospitalizations and urgent doctor visits. **Measure:** Number of Asthma Exacerbations **Time Frame:** 6 months **Description:** Forced expiratory volume at one second/forced vital capacity (FEV1/FVC) will be evaluated as a continuous variable. This is a ratio without any units. **Measure:** FEV1/FVC **Time Frame:** 6 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Have physician-diagnosed asthma at least 1 year prior to the baseline visit, or asthma symptoms for at least 1 year * Meet criteria for current persistent asthma defined as either: 1. On a long-term controller medication for asthma, or 2. Meet National Asthma Education and Prevention Program (NAEPP) guideline requirements for persistent disease:(46) * Asthma symptoms 3 or more days per week over the past 2 weeks or * Nocturnal asthma symptoms at least 3 times in the past month * Have evidence of uncontrolled disease as defined by at least one of the following: 1. One asthma-related unscheduled visit to an emergency department (ED), clinic or urgent care facility in the previous 12 mo 2. One asthma-related overnight hospitalization in the previous 12 mo 3. One or more bursts of oral corticosteroids in the previous 12 mo * Reside within a geographic area of the study site so that home visits are feasible. * Have no plans to move within the upcoming 6 months * Have insurance to cover prescription medications. * Have a positive skin test (net wheal ≥2mm) to cat, dog, mouse, cockroach, or dust mites or have a positive cat, dog, mouse, German cockroach, or D. farinae-specific immunoglobulin E (IgE) test, as quantified using the ImmunoCAP system (≥0.35 kU/L) Exclusion Criteria: * Lung disease, other than asthma, that requires daily medication * Cardiovascular disease that requires daily medication, excluding hypertension * Taking a beta-blocker * Allergy to dairy * On Xolair \< 5 months * On immunotherapy and has not reached maintenance dose * Sleeping in another home 4 or more nights/week * Active smoker defined as a positive urine screen for high levels of urine cotinine * Unable to access areas of home necessary to conduct extermination **Maximum Age:** 17 Years **Minimum Age:** 5 Years **Sex:** ALL **Standard Ages:** - CHILD ### Contacts Locations Module #### Locations **Location 1:** **City:** Baltimore **Country:** United States **Facility:** Johns Hopkins University **State:** Maryland **Zip:** 21287 #### Overall Officials **Official 1:** **Affiliation:** Johns Hopkins University **Name:** Elizabeth C Matsui, MD MHS **Role:** STUDY_CHAIR **Official 2:** **Affiliation:** Johns Hopkins University **Name:** Meredith McCormack, MD MHS **Role:** PRINCIPAL_INVESTIGATOR **Official 3:** **Affiliation:** Johns Hopkins University **Name:** Corinne Keet, MD PHD **Role:** PRINCIPAL_INVESTIGATOR ## Document Section ### Large Document Module #### Large Docs - Date: 2016-10-03 - Filename: Prot_SAP_000.pdf - Has ICF: False - Has Protocol: True - Has SAP: True - Label: Study Protocol and Statistical Analysis Plan - Size: 1248763 - Type Abbrev: Prot_SAP - Upload Date: 2019-10-14T10:42 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000001982 - Term: Bronchial Diseases - ID: D000012140 - Term: Respiratory Tract Diseases - ID: D000008173 - Term: Lung Diseases, Obstructive - ID: D000008171 - Term: Lung Diseases - ID: D000012130 - Term: Respiratory Hypersensitivity - ID: D000006969 - Term: Hypersensitivity, Immediate - ID: D000006967 - Term: Hypersensitivity - ID: D000007154 - Term: Immune System Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC08 - Name: Respiratory Tract (Lung and Bronchial) Diseases - Abbrev: BC20 - Name: Immune System Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M4556 - Name: Asthma - Relevance: HIGH - As Found: Asthma - ID: M5258 - Name: Bronchial Diseases - Relevance: LOW - As Found: Unknown - ID: M14977 - Name: Respiratory Tract Diseases - Relevance: LOW - As Found: Unknown - ID: M11168 - Name: Lung Diseases - Relevance: LOW - As Found: Unknown - ID: M11170 - Name: Lung Diseases, Obstructive - Relevance: LOW - As Found: Unknown - ID: M10018 - Name: Hypersensitivity - Relevance: LOW - As Found: Unknown - ID: M14967 - Name: Respiratory Hypersensitivity - Relevance: LOW - As Found: Unknown - ID: M10020 - Name: Hypersensitivity, Immediate - Relevance: LOW - As Found: Unknown - ID: M10200 - Name: Immune System Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000001249 - Term: Asthma ### Intervention Browse Module - Ancestors - ID: D000001993 - Term: Bronchodilator Agents - ID: D000001337 - Term: Autonomic Agents - ID: D000018373 - Term: Peripheral Nervous System Agents - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000018927 - Term: Anti-Asthmatic Agents - ID: D000019141 - Term: Respiratory System Agents - ID: D000005938 - Term: Glucocorticoids - ID: D000006728 - Term: Hormones - ID: D000006730 - Term: Hormones, Hormone Substitutes, and Hormone Antagonists - ID: D000013566 - Term: Sympathomimetics - ID: D000000893 - Term: Anti-Inflammatory Agents - ID: D000003879 - Term: Dermatologic Agents - ID: D000018926 - Term: Anti-Allergic Agents ### Intervention Browse Module - Browse Branches - Abbrev: AAll - Name: Anti-Allergic Agents - Abbrev: Infl - Name: Anti-Inflammatory Agents - Abbrev: Derm - Name: Dermatologic Agents - Abbrev: Resp - Name: Respiratory System Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M250 - Name: Fluticasone - Relevance: HIGH - As Found: Coronary Revascularization - ID: M353494 - Name: Xhance - Relevance: HIGH - As Found: Coronary Revascularization - ID: M249 - Name: Fluticasone-Salmeterol Drug Combination - Relevance: HIGH - As Found: E. coli - ID: M251 - Name: Salmeterol Xinafoate - Relevance: LOW - As Found: Unknown - ID: M5269 - Name: Bronchodilator Agents - Relevance: LOW - As Found: Unknown - ID: M20963 - Name: Anti-Asthmatic Agents - Relevance: LOW - As Found: Unknown - ID: M21137 - Name: Respiratory System Agents - Relevance: LOW - As Found: Unknown - ID: M9047 - Name: Glucocorticoids - 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: M16345 - Name: Sympathomimetics - Relevance: LOW - As Found: Unknown - ID: M4217 - Name: Anti-Inflammatory Agents - Relevance: LOW - As Found: Unknown - ID: M7074 - Name: Dermatologic Agents - Relevance: LOW - As Found: Unknown - ID: M20962 - Name: Anti-Allergic Agents - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000068298 - Term: Fluticasone - ID: C000716389 - Term: Xhance - ID: D000068297 - Term: Fluticasone-Salmeterol Drug Combination ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module **Description:** Hospitalizations, including asthma-related hospitalizations, were considered serious adverse events. Participants were asked at each clinic visit about adverse events. #### Event Groups **Group ID:** EG000 **Title:** ECS + Medication Group **Deaths Num At Risk:** 77 **Description:** The Environmental Control Strategy ("Home Environmental Intervention") plus inhaled corticosteroids or inhaled corticosteroids plus long-acting beta agonist. (Flovent Diskus or Advair diskus) Flovent Diskus: Inhaled corticosteroids Home Environmental Intervention: Mouse, Cockroach, Furry pets, Dust mites, Smoking, air purifiers, laundered bedding Advair Diskus: inhaled corticosteroids + long-acting beta agonist **ID:** EG000 **Other Num at Risk:** 77 **Serious Number Affected:** 2 **Serious Number At Risk:** 77 **Title:** ECS + Medication Group **Group ID:** EG001 **Title:** Medication Group Alone **Deaths Num At Risk:** 78 **Description:** inhaled corticosteroids or inhaled corticosteroids plus long-acting beta agonist. (Flovent Diskus or Advair diskus) Flovent Diskus: Inhaled corticosteroids Advair Diskus: inhaled corticosteroids + long-acting beta agonist **ID:** EG001 **Other Num at Risk:** 78 **Serious Number Affected:** 10 **Serious Number At Risk:** 78 **Title:** Medication Group Alone **Frequency Threshold:** 5 #### Serious Events **Term:** asthma hospitalization **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 77 **Num Events:** 2 **Group ID:** EG001 **Num Affected:** 8 **Num At Risk:** 78 **Num Events:** 11 **Term:** hospitalization **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders ##### Stats **Group ID:** EG000 **Num At Risk:** 77 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 78 **Num Events:** 1 **Term:** hospitalization **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders ##### Stats **Group ID:** EG000 **Num At Risk:** 77 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 78 **Num Events:** 1 **Time Frame:** During the enrollment period, approximately 7 months ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 77 **Group ID:** BG001 **Value:** 78 **Group ID:** BG002 **Value:** 155 **Units:** Participants ### Group **ID:** BG000 **Title:** ECS + Medication Group **Description:** The Environmental Control Strategy ("Home Environmental Intervention") plus inhaled corticosteroids or inhaled corticosteroids plus long-acting beta agonist. (Flovent Diskus or Advair diskus) Flovent Diskus: Inhaled corticosteroids Home Environmental Intervention: Mouse, Cockroach, Furry pets, Dust mites, Smoking, air purifiers, laundered bedding Advair Diskus: inhaled corticosteroids + long-acting beta agonist ### Group **ID:** BG001 **Title:** Medication Group Alone **Description:** inhaled corticosteroids or inhaled corticosteroids plus long-acting beta agonist. (Flovent Diskus or Advair diskus) Flovent Diskus: Inhaled corticosteroids Advair Diskus: inhaled corticosteroids + long-acting beta agonist ### Group **ID:** BG002 **Title:** Total **Description:** Total of all reporting groups ### Measure #### Measurement **Group ID:** BG000 **Spread:** 3.3 **Value:** 10.1 #### Measurement **Group ID:** BG001 **Spread:** 3.3 **Value:** 10.1 #### Measurement **Group ID:** BG002 **Spread:** 3.3 **Value:** 10.1 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 31 #### Measurement **Group ID:** BG001 **Value:** 30 #### Measurement **Group ID:** BG002 **Value:** 61 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 46 #### Measurement **Group ID:** BG001 **Value:** 48 #### Measurement **Group ID:** BG002 **Value:** 94 **Category Title:** Male **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 2 #### Measurement **Group ID:** BG001 **Value:** 2 #### Measurement **Group ID:** BG002 **Value:** 4 **Category Title:** Hispanic or Latino #### Measurement **Group ID:** BG000 **Value:** 75 #### Measurement **Group ID:** BG001 **Value:** 76 #### Measurement **Group ID:** BG002 **Value:** 151 **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:** 72 #### Measurement **Group ID:** BG001 **Value:** 67 #### Measurement **Group ID:** BG002 **Value:** 139 **Category Title:** Black or African American #### Measurement **Group ID:** BG000 **Value:** 1 #### Measurement **Group ID:** BG001 **Value:** 3 #### Measurement **Group ID:** BG002 **Value:** 4 **Category Title:** White #### Measurement **Group ID:** BG000 **Value:** 4 #### Measurement **Group ID:** BG001 **Value:** 8 #### Measurement **Group ID:** BG002 **Value:** 12 **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:** 77 #### Measurement **Group ID:** BG001 **Value:** 78 #### Measurement **Group ID:** BG002 **Value:** 155 **Class Title:** United States ### Measure #### Measurement **Group ID:** BG000 **Spread:** 1.56 **Value:** 4.34 #### Measurement **Group ID:** BG001 **Spread:** 1.57 **Value:** 4.56 #### Measurement **Group ID:** BG002 **Spread:** 1.56 **Value:** 4.45 **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 **Description:** The controller medication treatment step that was assigned at the visit, which is based on the current controller medication treatment step and the current level of asthma control. The range is from 0-6, with 0 indicating no controller medication and 6 indicating high dose inhaled corticosteroids plus long-acting beta agonist. **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** The treatment step assigned **Unit of Measure:** score on a scale ## Results Section - More Information Module ### Certain Agreement **PI Sponsor Employee:** True ### Point of Contact **Email:** [email protected] **Organization:** Johns Hopkins University **Phone:** 410-955-5883 **Title:** Corinne Keet ## 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:** 1.91 - **Upper Limit:** - **Value:** 4.03 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.87 - **Upper Limit:** - **Value:** 4.05 **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 347.8 - **Upper Limit:** - **Value:** 557.5 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 401.7 - **Upper Limit:** - **Value:** 527.7 **Title:** #### Outcome Measure 3 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 10 - **Spread:** - **Upper Limit:** 38 - **Value:** 20 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 8 - **Spread:** - **Upper Limit:** 52 - **Value:** 20 **Title:** #### Outcome Measure 4 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 3.2 - **Upper Limit:** - **Value:** 2.5 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 3.6 - **Upper Limit:** - **Value:** 2.7 **Title:** #### Outcome Measure 5 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 35 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 53 **Title:** #### Outcome Measure 6 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 8.1 - **Upper Limit:** - **Value:** 79.3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 8.8 - **Upper Limit:** - **Value:** 80.8 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** The controller medication treatment step that was assigned at the visit, which is based on the current controller medication treatment step and the current level of asthma control. The range is from 0-6, with 0 indicating no controller medication and 6 indicating high dose inhaled corticosteroids plus long-acting beta agonist. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** participants completing the final 6 month follow-up visit **Reporting Status:** POSTED **Time Frame:** 6 month clinic visit **Title:** The Medication Treatment Step Assigned **Type:** PRIMARY **Unit of Measure:** score on a scale ##### Group **Description:** The Environmental Control Strategy ("Home Environmental Intervention") plus inhaled corticosteroids or inhaled corticosteroids plus long-acting beta agonist. (Flovent Diskus or Advair diskus) Flovent Diskus: Inhaled corticosteroids Home Environmental Intervention: Mouse, Cockroach, Furry pets, Dust mites, Smoking, air purifiers, laundered bedding Advair Diskus: inhaled corticosteroids + long-acting beta agonist **ID:** OG000 **Title:** ECS + Medication Group ##### Group **Description:** inhaled corticosteroids or inhaled corticosteroids plus long-acting beta agonist. (Flovent Diskus or Advair diskus) Flovent Diskus: Inhaled corticosteroids Advair Diskus: inhaled corticosteroids + long-acting beta agonist **ID:** OG001 **Title:** Medication Group Alone #### Outcome Measure 2 **Description:** micrograms of inhaled corticosteroids (daily) **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** participants who completed the final follow-up visit at 6 months **Reporting Status:** POSTED **Time Frame:** 6 months **Title:** Daily Inhaled Corticosteroid Dose **Type:** SECONDARY **Unit of Measure:** micrograms/day ##### Group **Description:** The Environmental Control Strategy ("Home Environmental Intervention") plus inhaled corticosteroids or inhaled corticosteroids plus long-acting beta agonist. (Flovent Diskus or Advair diskus) Flovent Diskus: Inhaled corticosteroids Home Environmental Intervention: Mouse, Cockroach, Furry pets, Dust mites, Smoking, air purifiers, laundered bedding Advair Diskus: inhaled corticosteroids + long-acting beta agonist **ID:** OG000 **Title:** ECS + Medication Group ##### Group **Description:** inhaled corticosteroids or inhaled corticosteroids plus long-acting beta agonist. (Flovent Diskus or Advair diskus) Flovent Diskus: Inhaled corticosteroids Advair Diskus: inhaled corticosteroids + long-acting beta agonist **ID:** OG001 **Title:** Medication Group Alone #### Outcome Measure 3 **Description:** Exhaled nitric oxide in parts per billion. **Dispersion Type:** Inter-Quartile Range **Parameter Type:** MEDIAN **Population Description:** participants completing the final follow-up visit at 6 months with valid exhaled nitric oxide measurement. Not all participants had valid measures. **Reporting Status:** POSTED **Time Frame:** 6 months **Title:** Exhaled Nitric Oxide **Type:** SECONDARY **Unit of Measure:** parts per billion ##### Group **Description:** The Environmental Control Strategy ("Home Environmental Intervention") plus inhaled corticosteroids or inhaled corticosteroids plus long-acting beta agonist. (Flovent Diskus or Advair diskus) Flovent Diskus: Inhaled corticosteroids Home Environmental Intervention: Mouse, Cockroach, Furry pets, Dust mites, Smoking, air purifiers, laundered bedding Advair Diskus: inhaled corticosteroids + long-acting beta agonist **ID:** OG000 **Title:** ECS + Medication Group ##### Group **Description:** inhaled corticosteroids or inhaled corticosteroids plus long-acting beta agonist. (Flovent Diskus or Advair diskus) Flovent Diskus: Inhaled corticosteroids Advair Diskus: inhaled corticosteroids + long-acting beta agonist **ID:** OG001 **Title:** Medication Group Alone #### Outcome Measure 4 **Description:** Number of asthma symptom days in the past two weeks will be a measure of asthma control. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** participants who completed the final follow-up visit at 6 months. **Reporting Status:** POSTED **Time Frame:** 6 months **Title:** Number of Asthma Symptom Days **Type:** SECONDARY **Unit of Measure:** days ##### Group **Description:** The Environmental Control Strategy ("Home Environmental Intervention") plus inhaled corticosteroids or inhaled corticosteroids plus long-acting beta agonist. (Flovent Diskus or Advair diskus) Flovent Diskus: Inhaled corticosteroids Home Environmental Intervention: Mouse, Cockroach, Furry pets, Dust mites, Smoking, air purifiers, laundered bedding Advair Diskus: inhaled corticosteroids + long-acting beta agonist **ID:** OG000 **Title:** ECS + Medication Group ##### Group **Description:** inhaled corticosteroids or inhaled corticosteroids plus long-acting beta agonist. (Flovent Diskus or Advair diskus) Flovent Diskus: Inhaled corticosteroids Advair Diskus: inhaled corticosteroids + long-acting beta agonist **ID:** OG001 **Title:** Medication Group Alone #### Outcome Measure 5 **Description:** Asthma exacerbations will be assessed by number of acute visits to the emergency department (ED), hospitalizations and urgent doctor visits. **Parameter Type:** NUMBER **Population Description:** participants completing the 6 month follow-up visit **Reporting Status:** POSTED **Time Frame:** 6 months **Title:** Number of Asthma Exacerbations **Type:** SECONDARY **Unit of Measure:** acute visits ##### Group **Description:** The Environmental Control Strategy ("Home Environmental Intervention") plus inhaled corticosteroids or inhaled corticosteroids plus long-acting beta agonist. (Flovent Diskus or Advair diskus) Flovent Diskus: Inhaled corticosteroids Home Environmental Intervention: Mouse, Cockroach, Furry pets, Dust mites, Smoking, air purifiers, laundered bedding Advair Diskus: inhaled corticosteroids + long-acting beta agonist **ID:** OG000 **Title:** ECS + Medication Group ##### Group **Description:** inhaled corticosteroids or inhaled corticosteroids plus long-acting beta agonist. (Flovent Diskus or Advair diskus) Flovent Diskus: Inhaled corticosteroids Advair Diskus: inhaled corticosteroids + long-acting beta agonist **ID:** OG001 **Title:** Medication Group Alone #### Outcome Measure 6 **Description:** Forced expiratory volume at one second/forced vital capacity (FEV1/FVC) will be evaluated as a continuous variable. This is a ratio without any units. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** participants completing the 6 month follow-up visit **Reporting Status:** POSTED **Time Frame:** 6 months **Title:** FEV1/FVC **Type:** SECONDARY **Unit of Measure:** ratio ##### Group **Description:** The Environmental Control Strategy ("Home Environmental Intervention") plus inhaled corticosteroids or inhaled corticosteroids plus long-acting beta agonist. (Flovent Diskus or Advair diskus) Flovent Diskus: Inhaled corticosteroids Home Environmental Intervention: Mouse, Cockroach, Furry pets, Dust mites, Smoking, air purifiers, laundered bedding Advair Diskus: inhaled corticosteroids + long-acting beta agonist **ID:** OG000 **Title:** ECS + Medication Group ##### Group **Description:** inhaled corticosteroids or inhaled corticosteroids plus long-acting beta agonist. (Flovent Diskus or Advair diskus) Flovent Diskus: Inhaled corticosteroids Advair Diskus: inhaled corticosteroids + long-acting beta agonist **ID:** OG001 **Title:** Medication Group Alone ### Participant Flow Module #### Group **Description:** The Environmental Control Strategy ("Home Environmental Intervention") plus inhaled corticosteroids or inhaled corticosteroids plus long-acting beta agonist. (Flovent Diskus or Advair diskus) Flovent Diskus: Inhaled corticosteroids Home Environmental Intervention: Mouse, Cockroach, Furry pets, Dust mites, Smoking, air purifiers, laundered bedding Advair Diskus: inhaled corticosteroids + long-acting beta agonist **ID:** FG000 **Title:** ECS + Medication Group #### Group **Description:** inhaled corticosteroids or inhaled corticosteroids plus long-acting beta agonist. (Flovent Diskus or Advair diskus) Flovent Diskus: Inhaled corticosteroids Advair Diskus: inhaled corticosteroids + long-acting beta agonist **ID:** FG001 **Title:** Medication Group Alone #### Period **Title:** Overall Study ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 77 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 78 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 57 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 58 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 20 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 20 **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT05199779 **Brief Title:** Single Session Intervention for Building Self-Compassion Habits-RCT **Official Title:** A Single Session Intervention Leveraging an Ultra-Brief Exercise for Building Self-Compassion Habits-A Randomized Controlled Trial #### Organization Study ID Info **ID:** 2021-12-14924 #### Organization **Class:** OTHER **Full Name:** University of California, Berkeley ### Status Module #### Completion Date **Date:** 2022-04-29 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2022-05-17 **Type:** ACTUAL **Last Update Submit Date:** 2022-05-14 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2022-04-29 **Type:** ACTUAL #### Start Date **Date:** 2022-02-13 **Type:** ACTUAL **Status Verified Date:** 2022-05 #### Study First Post Date **Date:** 2022-01-20 **Type:** ACTUAL **Study First Submit Date:** 2022-01-05 **Study First Submit QC Date:** 2022-01-05 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** University of California, Berkeley #### Responsible Party **Investigator Affiliation:** University of California, Berkeley **Investigator Full Name:** Allison Harvey **Investigator Title:** Professor of Clinical Psychology **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** The study will test a single session self-compassion intervention that leverages an ultra-brief contemplative exercise. It will evaluate the effect of this intervention on psychopathology, stress, growth mindset, positive affect, self-compassion and the automaticity of self-compassion, as well as the relationships between these constructs and the automaticity of self-compassion. The participants will be undergraduate students at a large public university. **Detailed Description:** The broad aims of the proposed research is to examine the outcomes of a single session psychological intervention and to further understand processes and factors associated with habit formation. undergraduate students at a large university will be randomly assigned to a self-compassion intervention (SCI), or an active control (AC), and complete assessments at baseline (pre-treatment) and 4 weeks later (post-treatment). The investigators seek to examine the following: (A1) Determine whether the group who receives the SCI, relative to the AC, will experience increased self-compassion, growth mindset and positive affect, as well as reduced stress and psychopathology. (A2) Evaluate whether the SCI group shows greater increases in automaticity of self-compassion compared to the AC pre- to post-treatment. (A3) Assess whether greater pre- to post-treatment increases in automaticity of self-compassionate are associated with increased self-compassion, growth mindset, and positive affect, as well as reductions in stress and psychopathology. The investigators hypothesize the following: (H1) SCI will promote greater increases in self-compassion, growth mindset, and positive affect, as well as greater reductions in stress and psychopathology from pre- to post-treatment, relative to AC. (H2) The SCI group will show greater increases in the automaticity of self-compassion than AC from pre- to post-treatment. (H3) Greater increases in the automaticity of self-compassion from pre- to post-treatment will be predicted by greater increases in self-compassion, growth mindset, and positive affect, as well as greater decreases in psychopathology and stress, from pre- to post treatment. To further understand the results obtained, the investigators will evaluate participants' frequency, adherence, and impressions of using the intervention. ### Conditions Module **Conditions:** - Transdiagnostic Psychopathology **Keywords:** - Self-Compassion - Habits - Transdiagnostic - Intervention ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** Participants will be randomized to the SCI or AC control using the randomizer elements in Qualtrics. ##### Masking Info **Masking:** SINGLE **Masking Description:** To reduce bias in the assessments, none of the constructs of interest to this study (e.g., "stress", "self-compassion") will be included in the language used to describe the intervention or in any materials used to advertise the study. Study participants will be told they are participating in a study on "fostering emotional well-being". No further information about the intervention will be provided. **Who Masked:** - PARTICIPANT **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 135 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** First, participants will be taught to implement a 20-second self-compassion induction via video recording. Second, participants will be taught to choose a cue that will precede their daily use of the self-compassion induction. Participants will document the cue they chose, and will be emailed a record of their selected cue, along with the recording and transcript of the self-compassion induction that they can refer back to for reference. Third, participants will be asked to use the self-compassion induction as much as they can and at least once during their daily routine following exposure to their chosen cue. **Intervention Names:** - Behavioral: Single Session Intervention Leveraging an Ultra-Brief Self-Compassion Exercise **Label:** Self-Compassion Intervention (SCI) **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** The active control will receive the same procedures as described above, except for receiving a different video containing different instructions describing a finger-tapping exercise. The videos will be virtually identical in length, quality, instructor/their outfit, and lighting. **Intervention Names:** - Behavioral: Finger-Tapping Active Control **Label:** Finger-Tapping Active Control (AC) **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Self-Compassion Intervention (SCI) **Description:** This 20-second contemplative exercise includes draws from the science of habit formation and includes elements of self-soothing touch, somatic experiencing, and mindful self-compassion. **Name:** Single Session Intervention Leveraging an Ultra-Brief Self-Compassion Exercise **Type:** BEHAVIORAL #### Intervention 2 **Arm Group Labels:** - Finger-Tapping Active Control (AC) **Description:** This 20-second finger tapping exercise involves touching each finger to the thumb on one hand and repeating for twenty seconds. This intervention was designed to control for the potential effect of assessment on outcomes, the effect of having an activity to do for the duration of the intervention (4 weeks), regression to the mean, time, or other nonspecific factors. **Name:** Finger-Tapping Active Control **Type:** BEHAVIORAL ### Outcomes Module #### Other Outcomes **Description:** Number of times practiced self-compassion exercise per day. 1 item. **Measure:** Practice Frequency **Time Frame:** Assessed at Post-treatment (week 4) **Description:** Number of days in the past two months that did not practice the exercise at all. 1 item. **Measure:** Overall Practice Frequency **Time Frame:** Assessed at Post-treatment (week 4) **Description:** 1 item, number of days practiced exercise but for less than 10 seconds. **Measure:** Practice Duration **Time Frame:** Assessed at Post-treatment (week 4) **Description:** 10 items on a five-point scale, where 5 = never, 4 = rarely, 3 = sometimes, 2 = often and 1 = always. Scores for each item were summed to give a total score, with higher scores indicating higher levels of reported adherence. **Measure:** Adherence Report Scale **Time Frame:** Assessed at Post-treatment (week 4) **Description:** Exploratory qualitative assessment. **Measure:** General impressions of exercise **Time Frame:** Assessed at Post-treatment (week 4) #### Primary Outcomes **Description:** Sum of 20-item, 5-point response scale. Scores can range from 20 to 100 (Higher score means higher compassion for self). Sub-scale items included. **Measure:** Sussex-Oxford Compassion for the Self Scale (SOCS-S) **Time Frame:** Change from baseline to post-treatment (week 4) **Description:** 8 items. 6-point response scale (1 = strongly agree; 6 = strongly disagree) Higher scores indicate a more growth mindset. Lower scores indicate a more fixed mindset. Score is sum of all items, with Q3, Q5, Q7, and Q8 reverse-scored. The formula for reverse-scoring an item is: ((Number of scale points) + 1) - (Respondent's answer) **Measure:** Kind of Person' Implicit Theory Scale (KOPITS) **Time Frame:** Change from baseline to post-treatment (week 4) **Description:** 10 items with a 6 point response scale. Positive affect sub-scale only. Scoring: Positive Affect Score: Sum score of 1, 3, 5, 9, 10, 12, 14, 16, 17, and 19. Scores range from 10 - 50. Higher scores = higher levels of positive affect. Negative Affect Score: Sum score of 2, 4, 6, 7, 8, 11, 13, 15, 18, and 20. Scores range from 10 - 50. Lower scores = lower levels of negative affect. **Measure:** Positive and Negative Affect Schedule (PANAS) **Time Frame:** Change from baseline to post-treatment (week 4) **Description:** 10 items, 5 point response scale (from 0 = Never to 4 = Very Often) Scoring: Reverse score (e.g., 0 = 4, 1 = 3, 2 = 2, 3 = 1 \& 4 = 0) items 4, 5, 7, \& 8 and then summing across all scale items. **Measure:** 10-item Perceived-Stress Scale (PSS-10) **Time Frame:** Change from baseline to post-treatment (week 4) **Description:** 22 items (suicidality item Q11 removed). 5-point scale (0=none or not at all; 1=slight or rare, less than a day or two; 2=mild or several days; 3=moderate or more than half the days; and 4=severe or nearly every day). **Measure:** DSM-5 Cross-Cutting Measure (DSM-XC) **Time Frame:** Change from baseline to post-treatment (week 4) **Description:** 20 items. 1-9 scale. **Measure:** Self-Report Behavioral Automaticity Index for Self-Compassion **Time Frame:** Change from baseline to post-treatment (week 4) #### Secondary Outcomes **Description:** 9 items. 1-5 scale. Scores range from 9-45. Mindfulness, common humanity, and self-kindness sub-scales only. **Measure:** State Self-Compassion Scale Long Form (SSCS-L) **Time Frame:** Change from pre-induction to post-induction at baseline and at post-treatment (week 4). Change in pre to post-induction changes in state self-compassion from baseline to post-treatment (week 4) **Description:** 4 items. 1-9 scale. **Measure:** Self-Report Behavioral Automaticity Index for Exercise **Time Frame:** Change from baseline to post-treatment (week 4) **Description:** 1 item. 1-8 scale. **Measure:** Real Self Overlap Scale **Time Frame:** Change from baseline to post-treatment (week 4) ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * 18 years of age or older. * English language proficiency. * Able and willing to give informed consent. Exclusion Criteria: * Does not have email address or access to email. * Not able/willing to participate in and/or complete the pre-treatment assessments **Healthy Volunteers:** True **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Berkeley **Country:** United States **Facility:** University of California at Berkeley **State:** California **Zip:** 94720-1650 #### Overall Officials **Official 1:** **Affiliation:** University of California, Berkeley **Name:** Allison Harvey, PhD **Role:** PRINCIPAL_INVESTIGATOR **Official 2:** **Affiliation:** University of California, Berkeley **Name:** Eli S Susman, BA **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00749879 **Brief Title:** Crossover Study of the Safety and PK Properties of Proellex® **Official Title:** A Phase I, Open-Label, Randomized, Single-Center, Unblinded, Single-Dose, Five-Way Crossover Study of the Safety and PK Properties of Proellex® #### Organization Study ID Info **ID:** ZP-008 #### Organization **Class:** INDUSTRY **Full Name:** Repros Therapeutics Inc. ### Status Module #### Completion Date **Date:** 2008-10-23 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2019-04-29 **Type:** ACTUAL **Last Update Submit Date:** 2019-01-23 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2008-10-23 **Type:** ACTUAL #### Results First Post Date **Date:** 2019-04-29 **Type:** ACTUAL **Results First Submit Date:** 2014-07-03 **Results First Submit QC Date:** 2019-01-23 #### Start Date **Date:** 2008-08-11 **Type:** ACTUAL **Status Verified Date:** 2019-01 #### Study First Post Date **Date:** 2008-09-09 **Type:** ESTIMATED **Study First Submit Date:** 2008-09-05 **Study First Submit QC Date:** 2008-09-05 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Repros Therapeutics Inc. #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** Study to evaluate the PK of 25 mg and 50 mg of Proellex from 2 different suppliers in the fed and fasting states. **Detailed Description:** This study is intended to evaluate the pharmacokinetic properties of two doses (25 mg and 50 mg) of Proellex® formulated with microcrystalline cellulose (MCC) from 2 different suppliers in the fed and fasting states. ### Conditions Module **Conditions:** - Pharmacokinetics **Keywords:** - PK - Pharmacokinetics ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** CROSSOVER ##### Masking Info **Masking:** NONE **Primary Purpose:** BASIC_SCIENCE #### Enrollment Info **Count:** 17 **Type:** ACTUAL **Phases:** - PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** 25 mg Proellex capsule formulated with AMCC coarse microcrystalline cellulose Fed State **Intervention Names:** - Drug: Proellex **Label:** 25 mg AMCC fed **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** 25 mg Proellex capsule formulated with AMCC coarse microcrystalline cellulose Fasting State **Intervention Names:** - Drug: Proellex **Label:** 25 mg AMCC fasting **Type:** EXPERIMENTAL #### Arm Group 3 **Description:** 2, 25 mg Proellex capsules formulated with AMCC coarse microcrystalline cellulose Fed State **Intervention Names:** - Drug: Proellex **Label:** 50 mg AMCC fed **Type:** EXPERIMENTAL #### Arm Group 4 **Description:** 2, 25 mg Proellex capsules formulated with AMCC coarse microcrystalline cellulose Fasting State **Intervention Names:** - Drug: Proellex **Label:** 50 mg AMCC fasting **Type:** EXPERIMENTAL #### Arm Group 5 **Description:** 2, 25 mg Proellex capsules formulated with SMCC microcrystalline cellulose Fasting State **Intervention Names:** - Drug: Proellex **Label:** 50 mg SMCC fasting **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - 25 mg AMCC fasting - 25 mg AMCC fed - 50 mg AMCC fasting - 50 mg AMCC fed - 50 mg SMCC fasting **Description:** 25 mg capsule administered once orally after subjects have been fed; 25 mg capsule administered once orally while subjects are fasting; 2, 25 mg capsules administered once orally after subjects have been fed; 2, 25 mg capsules administered once orally while subjects are fasting; and 2, 25 mg capsules administered once orally while subjects are fasting **Name:** Proellex **Other Names:** - Telapristone acetate **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Maximum observed concentration of Proellex **Measure:** Cmax of Proellex **Time Frame:** Up to 72 hours post-dose **Description:** Area under the plasma concentration curve from time 0 to the last measurable plasma concentration time point, up to 72 hours. **Measure:** AUC0-last of Proellex **Time Frame:** Up to 72 hours post dose **Description:** Time to maximum plasma occurrence of Cmax **Measure:** Tmax of Proellex **Time Frame:** Up to 72 hours post dose **Description:** Area under the plasma concentration curve from time 0 to extrapolated to infinity, calculated by summing the area under the curve from time zero to the time of the last quantifiable concentration **Measure:** AUC0-infinity of Proellex **Time Frame:** Up to 72 hours post dose **Description:** Time to maximum plasma occurrence of T1/2, calculated as ln(2)/Elimination rate constant. **Measure:** Terminal Elimination Half-life (T1/2) of Proellex **Time Frame:** Up to 72 hours post dose ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Subject must be able to speak, read, and understand English and be willing and able to provide written informed consent in English on an Institutional Review Board (IRB) * Premenopausal women aged 18-34, inclusive, with body mass index between 18 and 35, inclusive * Women of child-bearing potential must be willing to use effective non-hormonal, double-barrier method contraception during the study period and for a minimum of 30 days after discontinuation of the study medication. Women who have had a hysterectomy will be allowed into the study * Must have a negative urine pregnancy test at screening * Able to swallow gelatin capsules * Medically normal subjects with no significant abnormal findings at the screening physical examination as evaluated by the Principal Investigator that would interfere with the subject participating this study * Must have agreed to not attempt to become pregnant at any time during study participation or for 30 days thereafter * Other inclusion criteria may apply Exclusion Criteria: * Symptomatic uterine fibroids or endometriosis * Past or present history of any significant cardiovascular, renal, or hepatic disease requiring ongoing medical therapy or clinical intervention * Past or present history of thrombophlebitis, thromboembolic disorders, or cerebrovascular accident * Abnormal screening visit vital signs or clinical laboratory evaluation considered clinically significant by the Principal Investigator * Significant organ abnormality or disease (based on the Principal Investigator's judgment) that would in the opinion of the Principal Investigator exclude the subject from participating * Other exclusion criteria may apply **Healthy Volunteers:** True **Maximum Age:** 34 Years **Minimum Age:** 18 Years **Sex:** FEMALE **Standard Ages:** - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** San Antonio **Country:** United States **Facility:** Healthcare Discoveries Inc. **State:** Texas **Zip:** 78229 #### Overall Officials **Official 1:** **Affiliation:** Allergan **Name:** Anna Chan **Role:** STUDY_DIRECTOR ## Derived Section ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module #### Event Groups **Group ID:** EG000 **Title:** 25 mg AMCC Fed **Description:** 25 mg Proellex capsule formulated with AMCC coarse microcrystalline cellulose Fed State **ID:** EG000 **Other Num Affected:** 1 **Other Num at Risk:** 12 **Serious Number At Risk:** 12 **Title:** 25 mg AMCC Fed **Group ID:** EG001 **Title:** 25 mg AMCC Fasting **Description:** 25 mg Proellex capsule formulated with AMCC coarse microcrystalline cellulose Fasting State **ID:** EG001 **Other Num Affected:** 2 **Other Num at Risk:** 12 **Serious Number At Risk:** 12 **Title:** 25 mg AMCC Fasting **Group ID:** EG002 **Title:** 50 mg AMCC Fed **Description:** Two, 25 mg Proellex capsules formulated with AMCC coarse microcrystalline cellulose Fed State **ID:** EG002 **Other Num Affected:** 4 **Other Num at Risk:** 12 **Serious Number At Risk:** 12 **Title:** 50 mg AMCC Fed **Group ID:** EG003 **Title:** 50 mg AMCC Fasting **Description:** Two, 25 mg Proellex capsules formulated with AMCC coarse microcrystalline cellulose Fasting State **ID:** EG003 **Other Num Affected:** 7 **Other Num at Risk:** 12 **Serious Number At Risk:** 12 **Title:** 50 mg AMCC Fasting **Group ID:** EG004 **Title:** 50 mg SMCC Fasting **Description:** Two, 25 mg Proellex capsules formulated with SMCC microcrystalline cellulose Fasting State **ID:** EG004 **Other Num Affected:** 5 **Other Num at Risk:** 12 **Serious Number At Risk:** 12 **Title:** 50 mg SMCC Fasting **Frequency Threshold:** 5 #### Other Events **Term:** Nausea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA (Unspecified) **Term:** Hyperkalemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA (Unspecified) **Term:** Presyncope **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA (Unspecified) **Term:** Rhinitis allergic **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA (Unspecified) **Term:** Palpitations **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA (Unspecified) **Term:** Tachycardia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA (Unspecified) **Term:** Dizziness **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA (Unspecified) **Term:** Headache **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA (Unspecified) **Term:** Pelvi pain NOS **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Reproductive system and breast disorders **Source Vocabulary:** MedDRA (Unspecified) **Term:** Abdominal pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA (Unspecified) **Term:** Nipple pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Reproductive system and breast disorders **Source Vocabulary:** MedDRA (Unspecified) **Term:** Oligomenorrhea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Reproductive system and breast disorders **Source Vocabulary:** MedDRA (Unspecified) ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 12 **Units:** Participants ### Group **ID:** BG000 **Title:** All Subjects **Description:** All subjects enrolled ### Measure #### Measurement **Group ID:** BG000 **Value:** 0 **Category Title:** <=18 years #### Measurement **Group ID:** BG000 **Value:** 12 **Category Title:** Between 18 and 65 years #### Measurement **Group ID:** BG000 **Value:** 0 **Category Title:** >=65 years **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 12 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 0 **Category Title:** Male **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 12 **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:** Region of Enrollment **Unit of Measure:** Participants **Population Description:** All subjects enrolled ## Results Section - More Information Module ### Certain Agreement **Other Details:** Prior to publication, Investigator shall submit to the Sponsor a copy of any proposed publication. Sponsor shall have sixty (60) days to review the proposed publication for possible disclosure of Sponsor's Confidential Information and, upon request of Sponsor, Investigator shall delete any of Sponsor's Confidential Information or withhold submission of such publication to allow Sponsor to protect its intellectual property rights **Restriction Type:** OTHER **Restrictive Agreement:** True ### Point of Contact **Email:** [email protected] **Organization:** Repros Therapeutics Inc, an Allergan Affiliate **Phone:** 714-246-4500 **Title:** Therapeutic Area Head ## 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:** 151.3 - **Upper Limit:** - **Value:** 485.6 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 201.9 - **Upper Limit:** - **Value:** 876.7 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 157.6 - **Upper Limit:** - **Value:** 912.9 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** 154.5 - **Upper Limit:** - **Value:** 1322.5 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** 148.5 - **Upper Limit:** - **Value:** 1346.7 **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 2845.9 - **Upper Limit:** - **Value:** 6142.1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 3036.6 - **Upper Limit:** - **Value:** 5765.7 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 4209.0 - **Upper Limit:** - **Value:** 11094.2 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** 4217.5 - **Upper Limit:** - **Value:** 9252.0 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** 4328.3 - **Upper Limit:** - **Value:** 9576.2 **Title:** #### Outcome Measure 3 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.6 - **Upper Limit:** - **Value:** 2.6 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.2 - **Upper Limit:** - **Value:** 0.8 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 1.0 - **Upper Limit:** - **Value:** 2.6 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** 0.4 - **Upper Limit:** - **Value:** 0.9 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** 0.2 - **Upper Limit:** - **Value:** 0.7 **Title:** #### Outcome Measure 4 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 3715.6 - **Upper Limit:** - **Value:** 7039.8 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 4440.7 - **Upper Limit:** - **Value:** 6897.0 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 6753.2 - **Upper Limit:** - **Value:** 13014.9 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** 6726.6 - **Upper Limit:** - **Value:** 11271.6 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** 7186.9 - **Upper Limit:** - **Value:** 11804.8 **Title:** #### Outcome Measure 5 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 8.2 - **Upper Limit:** - **Value:** 22.1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 10.4 - **Upper Limit:** - **Value:** 25.2 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 10.8 - **Upper Limit:** - **Value:** 23.8 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** 11.8 - **Upper Limit:** - **Value:** 26.7 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** 11.9 - **Upper Limit:** - **Value:** 27.5 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** Maximum observed concentration of Proellex **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** 12 subjects received all 5 treatments **Reporting Status:** POSTED **Time Frame:** Up to 72 hours post-dose **Title:** Cmax of Proellex **Type:** PRIMARY **Unit of Measure:** ng/mL ##### Group **Description:** 25 mg Proellex capsule formulated with AMCC coarse microcrystalline cellulose Fed State **ID:** OG000 **Title:** 25 mg AMCC Fed ##### Group **Description:** 25 mg Proellex capsule formulated with AMCC coarse microcrystalline cellulose Fasting State **ID:** OG001 **Title:** 25 mg AMCC Fasting ##### Group **Description:** Two, 25 mg Proellex capsules formulated with AMCC coarse microcrystalline cellulose Fed State **ID:** OG002 **Title:** 50 mg AMCC Fed ##### Group **Description:** Two, 25 mg Proellex capsules formulated with AMCC coarse microcrystalline cellulose Fasting State **ID:** OG003 **Title:** 50 mg AMCC Fasting ##### Group **Description:** Two, 25 mg Proellex capsules formulated with SMCC microcrystalline cellulose Fasting State **ID:** OG004 **Title:** 50 mg SMCC Fasting #### Outcome Measure 2 **Description:** Area under the plasma concentration curve from time 0 to the last measurable plasma concentration time point, up to 72 hours. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** All 12 subjects received each treatment **Reporting Status:** POSTED **Time Frame:** Up to 72 hours post dose **Title:** AUC0-last of Proellex **Type:** PRIMARY **Unit of Measure:** ng/mL*hour ##### Group **Description:** 25 mg Proellex capsule formulated with AMCC coarse microcrystalline cellulose Fed State **ID:** OG000 **Title:** 25 mg AMCC Fed ##### Group **Description:** 25 mg Proellex capsule formulated with AMCC coarse microcrystalline cellulose Fasting State **ID:** OG001 **Title:** 25 mg AMCC Fasting ##### Group **Description:** Two, 25 mg Proellex capsules formulated with AMCC coarse microcrystalline cellulose Fed State **ID:** OG002 **Title:** 50 mg AMCC Fed ##### Group **Description:** Two, 25 mg Proellex capsules formulated with AMCC coarse microcrystalline cellulose Fasting State **ID:** OG003 **Title:** 50 mg AMCC Fasting ##### Group **Description:** Two, 25 mg Proellex capsules formulated with SMCC microcrystalline cellulose Fasting State **ID:** OG004 **Title:** 50 mg SMCC Fasting #### Outcome Measure 3 **Description:** Time to maximum plasma occurrence of Cmax **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** All 12 subjects received each treatment **Reporting Status:** POSTED **Time Frame:** Up to 72 hours post dose **Title:** Tmax of Proellex **Type:** PRIMARY **Unit of Measure:** Hours ##### Group **Description:** 25 mg Proellex capsule formulated with AMCC coarse microcrystalline cellulose Fed State **ID:** OG000 **Title:** 25 mg AMCC Fed ##### Group **Description:** 25 mg Proellex capsule formulated with AMCC coarse microcrystalline cellulose Fasting State **ID:** OG001 **Title:** 25 mg AMCC Fasting ##### Group **Description:** Two, 25 mg Proellex capsules formulated with AMCC coarse microcrystalline cellulose Fed State **ID:** OG002 **Title:** 50 mg AMCC Fed ##### Group **Description:** Two, 25 mg Proellex capsules formulated with AMCC coarse microcrystalline cellulose Fasting State **ID:** OG003 **Title:** 50 mg AMCC Fasting ##### Group **Description:** Two, 25 mg Proellex capsules formulated with SMCC microcrystalline cellulose Fasting State **ID:** OG004 **Title:** 50 mg SMCC Fasting #### Outcome Measure 4 **Description:** Area under the plasma concentration curve from time 0 to extrapolated to infinity, calculated by summing the area under the curve from time zero to the time of the last quantifiable concentration **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** All 12 subjects received each treatment **Reporting Status:** POSTED **Time Frame:** Up to 72 hours post dose **Title:** AUC0-infinity of Proellex **Type:** PRIMARY **Unit of Measure:** ng/mL*hour ##### Group **Description:** 25 mg Proellex capsule formulated with AMCC coarse microcrystalline cellulose Fed State **ID:** OG000 **Title:** 25 mg AMCC Fed ##### Group **Description:** 25 mg Proellex capsule formulated with AMCC coarse microcrystalline cellulose Fasting State **ID:** OG001 **Title:** 25 mg AMCC Fasting ##### Group **Description:** Two, 25 mg Proellex capsules formulated with AMCC coarse microcrystalline cellulose Fed State **ID:** OG002 **Title:** 50 mg AMCC Fed ##### Group **Description:** Two, 25 mg Proellex capsules formulated with AMCC coarse microcrystalline cellulose Fasting State **ID:** OG003 **Title:** 50 mg AMCC Fasting ##### Group **Description:** Two, 25 mg Proellex capsules formulated with SMCC microcrystalline cellulose Fasting State **ID:** OG004 **Title:** 50 mg SMCC Fasting #### Outcome Measure 5 **Description:** Time to maximum plasma occurrence of T1/2, calculated as ln(2)/Elimination rate constant. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** All 12 subjects received each treatment **Reporting Status:** POSTED **Time Frame:** Up to 72 hours post dose **Title:** Terminal Elimination Half-life (T1/2) of Proellex **Type:** PRIMARY **Unit of Measure:** Hours ##### Group **Description:** 25 mg Proellex capsule formulated with AMCC coarse microcrystalline cellulose Fed State **ID:** OG000 **Title:** 25 mg AMCC Fed ##### Group **Description:** 25 mg Proellex capsule formulated with AMCC coarse microcrystalline cellulose Fasting State **ID:** OG001 **Title:** 25 mg AMCC Fasting ##### Group **Description:** Two, 25 mg Proellex capsules formulated with AMCC coarse microcrystalline cellulose Fed State **ID:** OG002 **Title:** 50 mg AMCC Fed ##### Group **Description:** Two, 25 mg Proellex capsules formulated with AMCC coarse microcrystalline cellulose Fasting State **ID:** OG003 **Title:** 50 mg AMCC Fasting ##### Group **Description:** Two, 25 mg Proellex capsules formulated with SMCC microcrystalline cellulose Fasting State **ID:** OG004 **Title:** 50 mg SMCC Fasting ### Participant Flow Module #### Group **Description:** in randomly assigned sequences, all study participants received 5 open-label treatments of Proellex: 25 mg Proellex capsule formulated with AMCC coarse microcrystalline cellulose Fed State Proellex; 25 mg capsule administered once orally after subjects have been fed; 25 mg capsule administered once orally while subjects are fasting; 2, 25 mg capsules administered once orally after subjects have been fed; 2, 25 mg capsules administered once orally while subjects are fasting; and 2, 25 mg capsules administered once orally while subjects are fasting **ID:** FG000 **Title:** Proellex #### Period **Title:** Overall Study ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 12 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 12 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 0 **Pre-Assignment Details:** Each of the 12 participants were randomly assigned a unique sequence of the following 5 following open-label treatments of Proellex * 25 mg formulated with AMCC (fed state) * 25 mg formulated with AMCC (fasting state) * 50 mg formulated with AMCC (fed state) * 50 mg formulated with AMCC (fasting state) * 50 mg formulated with SMCC (fasting state) **Recruitment Details:** Of the 17 participants, 4 did not meet inclusion/exclusion criteria, and 1 participant enrolled as a spare was not needed, resulting in their involvement in the study being terminated. The remaining 12 participants completed all five study treatments of Proellex. **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT05090579 **Brief Title:** Comparison Between Two Different Doses of Nulbuphine _bupivacaine in TAP Block in Cancer Abdominal Surgeries **Official Title:** Nalgesic Effect of Nulbuphine-bupivacaine Combination in Ultrasound Guided Transversus Abdominis Plane Block in Patients Undergoing Major Abdominal Cancer Surgeries . #### Organization Study ID Info **ID:** Q123 #### Organization **Class:** OTHER **Full Name:** Assiut University ### Status Module #### Completion Date **Date:** 2024-10-01 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2021-10-25 **Type:** ACTUAL **Last Update Submit Date:** 2021-10-11 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2024-10-01 **Type:** ESTIMATED #### Start Date **Date:** 2022-06-01 **Type:** ESTIMATED **Status Verified Date:** 2021-10 #### Study First Post Date **Date:** 2021-10-25 **Type:** ACTUAL **Study First Submit Date:** 2021-09-02 **Study First Submit QC Date:** 2021-10-11 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Assiut University #### Responsible Party **Investigator Affiliation:** Assiut University **Investigator Full Name:** Amira Muhammed Othman **Investigator Title:** Resident **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False ### Description Module **Brief Summary:** To compare the analgesic effect of two different doses of nulbuphine (10 mg and 20 mg) added to bupivacaine in bilateral subcostal single injection in ultrasound-guided TAP block for abdominal surgeries. **Detailed Description:** The ultrasound-guided TAP block will be performed before the induction of general anesthesia. Upon arrival at the operating room, the patients will be place in the supine position and an 18-gauge intravenous (IV) cannula will be inserted for IV fluid and drug administration. Basic monitoring probes (electrocardiography, non-invasive blood pressure, oxygen saturation, and temperature) will be applied, and their baseline vital signs will be recorded. Lactated Ringer's solution 10mL/ kg will be infused intravenously over 10 minutes before the initiation of the TAP block. The TAP block will be performed with the use of ultrasound, under complete aseptic technique. A broadband linear array probe will be used with an imaging depth of 4 - 6 cm. The ultrasound probe will be placed transversely to the abdomen (horizontal plane) in the midaxillary line between the costal margin and the iliac crest. Three muscle layers are clearly seen in the image. The needle (22-gauge x 80 mm SonoPlex stim cannula, Pajunk®, Geisingen, Germany) will be inserted in a sagittal plane approximately 3 - 4 cm medial to the ultrasound probe. The point of needle insertion will be closer to the probe. For optimal imaging of the needle, it will be held parallel to the long axis of the probe (in-line view). The needle tip will be directed into the plane below the internal oblique and above the transversus abdominis muscle. A small volume of local anesthetic (2 mL) was seen to open the plane between the 2 muscles and was followed by insertion of the full dose of local anesthetic. If the 2 mL dose appears to be within the muscle rather than between them, then needle adjustment will be required. The local anesthetic injected appeared hypoechoic (black compared to the muscle layers) on ultrasound image. The TAP block will be performed with the use of ultrasound under complete aseptic technique. A broadband linear array probe will be used with an imaging depth of 4 - 6 cm using a 22-gauge × 80 mm SonoPlex stim cannula (Pajunk®, Geisingen, Germany). Twenty minutes after the TAP block, the extent of sensory blockade will be evaluated by using the pin prick test (0 = no block, 1 = hyposthesia, and 2 = anesthesia) by another blinded attending anesthetist. Any patients with a failed block will be excluded from the studied groups. Anesthetic Technique: The anesthetic technique will be standardized in the 3 groups. No preoperative analgesics will be given. After a successful TAP block, ?? general anesthesia will be induced intravenously (propofol 1 - 2 mg/kg, lidocaine 1.5 mg/ kg) and fentanyl 1 μg/kg. Endotracheal intubation will be facilitated by neuromuscular blockade with cisatracurium 0.3 mg/kg. Anesthesia and muscle relaxation will be maintained with isoflurane in an air/oxygen mixture and cisatracurium 0.15 mg/kg. The patients will be mechanically ventilated in parameters that maintain the end-tidal CO2 (ETCO2) between 33 and 36 mmHg. The patients' heart rate, oxygen saturation, ETCO2, and systolic and diastolic blood pressures will be measured and recorded. Hypotension will be defined as a 15% decrease in systolic blood pressure from the base line, bradycardia as a heart rate slower than 50 beats per minute, and hypoxia as an oxygen saturation less than 90%. Hypotension will be treated with intravenous boluses of ephedrine 0.1 mg/kg, repeated as required. Bradycardia will be treated with intravenous atropine 0.01 mg/kg. At the end of surgery, muscle relaxation will be reversed by neostigmine 50 μg/kg and atropine 10 μg/ kg. The patients will be extubated and transferred to the post-anesthesia care unit (PACU), where they will be monitored for vital signs (heart rate, non-invasive blood pressure, respiratory rate, and O2 saturation) immediately postoperatively and at 2, 4, 6, 12, 18, and 24 hours postoperatively. The severity of pain and the presence of nausea, vomiting, and respiratory depression will be assessed postoperatively at 0, 2, 4, 6, 12, 18 and 24 hours. The severity of pain will be assessed using a 10 cm VAS at rest and coughing (0 = no pain and 10 = worst imaginable pain). Repiratory function : FVC, FEV and FEV1 /FVC ratio will be recorded postoperatively and 6,12,\&24 hr. Postoperatively. If a patient's VAS score was ≥ 3, morphine will be administered intravenously by a dose of 0.05 mg/kg at 15minute intervals until complete pain relief will be achieved. Morphine administration will be ceased when the VAS score at rest and coughing was \< 3 on assessment or when over-sedation or respiratory depression will occur (a respiratory rate of \< 10 bpm). Rescue antiemetic will be given in the form of ???metoclopramide 10 mg (Zofran 4mg) IV when patients complained of nausea or vomiting.???? (Our primary outcome measure will be total morphine consumption in the first 24 hours postoperatively; our secondary outcome measures will be the postoperative VAS scores, the time of the first request of rescue analgesia (calculated from the time of the TAP block application), spirometry lung function testing and the incidence of postoperative side effects) ### Conditions Module **Conditions:** - Pain, Postoperative ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** SINGLE **Who Masked:** - CARE_PROVIDER **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 30 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** patients will receive an ultrasound-guided TAP block with 20 mL of 0.25% bupivacaine , 1 mL of 10 mg of nulbuphine plus 4 mL of normal saline to reach 25 mL as total volume on each side of the abdominal wall. **Intervention Names:** - Procedure: Group I (BN10) **Label:** Group I (BN10) **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** patients will receive an ultrasound-guided TAP block with 20 mL of 0.25% bupivacaine ,2 mL of 20 mg of nulbuphine plus 3 mL of normal saline to reach 25 mL as total volume on each side of the abdominal wall. **Intervention Names:** - Procedure: Active Comparator:Group ll (BN20) **Label:** Group II (BN20) **Type:** ACTIVE_COMPARATOR #### Arm Group 3 **Description:** patients will receive 20 mL of 0.25%bupivacaine plus 5 mL of normal saline to reach 25 mL as total volume on each side of the abdominal wall. **Intervention Names:** - Procedure: Active Comparator:Group lll (B) **Label:** Group lll(B) **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Group I (BN10) **Description:** patients will receive an ultrasound-guided TAP block with 20 mL of 0.25% bupivacaine, 1 mL of 10 mg of nalbuphine plus 4 mL of normal saline to reach 25 mL as total volume on each side of the abdominal wall **Name:** Group I (BN10) **Type:** PROCEDURE #### Intervention 2 **Arm Group Labels:** - Group II (BN20) **Description:** patients will receive an ultrasound-guided TAP block with 20 mL of 0.25% bupivacaine, 2 mL of 20 mg of nalbuphine plus 3 mL of normal saline to reach 25 mL as total volume on each side of the abdominal wall **Name:** Active Comparator:Group ll (BN20) **Type:** PROCEDURE #### Intervention 3 **Arm Group Labels:** - Group lll(B) **Description:** patients will receive 20 mL of 0.25%bupivacaine plus 5 mL of normal saline to reach 25 mL as total volume on each side of the abdominal wall **Name:** Active Comparator:Group lll (B) **Type:** PROCEDURE ### Outcomes Module #### Primary Outcomes **Description:** VAS (Visual Analogue Scale, 0-100 mm; where 0 = no pain, and 100 = worst imaginable pain) will be assessed, at rest, per hour for 24 hours post operatively. Moreover, VAS will also be assessed at 12 and 24 hours post-operatively while abducting the ipsilateral arm. If the patient experiences a pain of \> 3, IV morphine will be given at a dose of 2.5-5 mg per dose, with a maximum dose of 10 mg, aiming for a pain score of ≤ 3. Time which will pass until the request of first analgesia shall be determined for each group and compared. **Measure:** time of request of first analgesia **Time Frame:** Time Frame: 24 hours post-operatively ] #### Secondary Outcomes **Description:** If a patient's VAS score was ≥ 3, morphine will be administered intravenously by a dose of 0.05 mg/kg at 15 minute intervals until complete pain relief will be achieved. Morphine administration will be ceased when the VAS score at rest and coughing was \< 3 on assessment or when over-sedation or respiratory depression will occur (a respiratory rate of \< 10 bpm). Rescue antiemetic will be given in the form of ondasteron 4 mg IV when patients complained of nausea or vomiting. **Measure:** total morphine consumption in the first 24 hours postoperatively **Time Frame:** Time Frame: 24 hours post-operatively ] ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria:- * ASA classification I-ll, * Aged \>18 years, * weight 50-85 kg, * Patients who will undergo abdominal cancer surgery. Exclusion Criteria:- * Patient's refusal, * patients with a history of allergies to studied drugs, * Patients with coagulation disorders, * Patients with opioid dependence, * Patients with morbid obesity (body mass index more than 40 kg/m2), * Patients with sepsis, * patients with psychiatric illnesses that will interfere with the perception and assessment of pain . **Healthy Volunteers:** True **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Amira M Othman, MD **Phone:** 01098784161 **Phone Ext:** +2 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Eman A Ismail, Professor **Phone:** 01060223755 **Phone Ext:** +1 **Role:** CONTACT #### Locations **Location 1:** **City:** Assiut **Country:** Egypt **Facility:** Amira Muhammed Othman #### Overall Officials **Official 1:** **Affiliation:** South Egypt cancer Institute, Assuit university hospitals **Name:** Rania M. Abdel -Emam **Role:** STUDY_DIRECTOR **Official 2:** **Affiliation:** South Egypt cancer Institute, Assuit university hospitals **Name:** Shreen M. Muhammed, A.professor **Role:** STUDY_DIRECTOR **Official 3:** **Affiliation:** Assiut University hospitals **Name:** Eman A. Ismail **Role:** STUDY_CHAIR ## 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: Pain, Postoperative - 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 - Browse Branches - Abbrev: CNSDep - Name: Central Nervous System Depressants - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Analg - Name: Analgesics ### Intervention Browse Module - Browse Leaves - ID: M5315 - Name: Bupivacaine - Relevance: LOW - As Found: Unknown - ID: M12217 - Name: Nalbuphine - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT06272279 **Brief Title:** Neuromodulation With Spinal Stimulation Methods **Official Title:** Neuromodulation With Spinal Stimulation Methods #### Organization Study ID Info **ID:** HS23666(B2020:015) #### Organization **Class:** OTHER **Full Name:** University of Manitoba ### Status Module #### Completion Date **Date:** 2025-02-01 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-02-22 **Type:** ACTUAL **Last Update Submit Date:** 2024-02-21 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2024-12-31 **Type:** ESTIMATED #### Start Date **Date:** 2024-03-01 **Type:** ESTIMATED **Status Verified Date:** 2024-02 #### Study First Post Date **Date:** 2024-02-22 **Type:** ACTUAL **Study First Submit Date:** 2021-03-09 **Study First Submit QC Date:** 2024-02-21 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** University of Manitoba #### 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 pilot research study to test the protocols needed for transcutaneous spinal electrical stimulation in persons living with spinal cord injury (SCI). Up to 24 participants will be enrolled. A variety of stimulation parameters and outcome measures will be assessed. **Detailed Description:** Purpose of this project Spinal cord stimulation has the potential to improve motor function recovery after spinal cord injury. Commonly used approaches include low-intensity, direct current (DC) stimulation applied across multiple segments, electrical transcutaneous (ETC) stimulation, and magnetic transcutaneous stimulation (MTC). Objective: to evaluate and compare the voluntary and reflexive motor performance in the same subjects, including people with and without spinal cord injury, after non-invasive spinal cord stimulation interventions. Comparing two different interventions applied in different experimental sessions and the respective sham stimulation is the goal of this study. corticospinal and spinal motor pathways in paraplegics and in non-injured humans will be tested. ### Conditions Module **Conditions:** - Spinal Cord Injuries - Spinal Cord Injury at C5-C7 Level - Paraplegia, Spinal - Paraplegia, Incomplete ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** CROSSOVER **Intervention Model Description:** Semi-blinded, randomized block entry design, crossover intervention study. ##### Masking Info **Masking:** DOUBLE **Masking Description:** The participant will be connected to the stimulation device(s) but will not know if it has been turned on during each trial. In addition, the person analyzing the outcome data will not be aware of the stimulation status of the participant. **Who Masked:** - PARTICIPANT - OUTCOMES_ASSESSOR **Primary Purpose:** BASIC_SCIENCE #### Enrollment Info **Count:** 24 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Spinal cord stimulation will be administered to participants for 15 min. **Intervention Names:** - Device: spinal stimulation-DCS - Other: spinal stimulation-EPS **Label:** Spinal cord stimulation **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Sham spinal cord stimulation will be administered to participants for 15 min. **Intervention Names:** - Other: spinal stimulation-sham DCS - Other: sham spinal stimulation-EPS **Label:** Shamspinal cord stimulation **Type:** SHAM_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Spinal cord stimulation **Description:** transcutaneous spinal stimulation by direct current stimulation **Name:** spinal stimulation-DCS **Type:** DEVICE #### Intervention 2 **Arm Group Labels:** - Shamspinal cord stimulation **Description:** sham transcutaneous spinal stimulation by direct current stimulation **Name:** spinal stimulation-sham DCS **Type:** OTHER #### Intervention 3 **Arm Group Labels:** - Spinal cord stimulation **Description:** transcutaneous spinal stimulation by electrical pulsed stimulation **Name:** spinal stimulation-EPS **Type:** OTHER #### Intervention 4 **Arm Group Labels:** - Shamspinal cord stimulation **Description:** sham transcutaneous spinal stimulation by electrical pulsed stimulation **Name:** sham spinal stimulation-EPS **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** H-reflex input output curve **Measure:** Motor response **Time Frame:** Immediately after stimulation (within 1-15 min) **Description:** MEP input-output curve **Measure:** Motor evoked potentials **Time Frame:** Immediately after stimulation (within 1-15 min) #### Secondary Outcomes **Description:** Perception of discomfort due to stimulation **Measure:** Blood pressure **Time Frame:** During procedure ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * spinal cord injury C4 to L4 * ability to understand and follow directions Exclusion Criteria: * history of seizures, head injury, concussion, unexplained loss of consciousness or if they lived with an implanted cochlear stimulator, brain/neurostimulator, cardiac pacemaker, medication infusion device or live with metal implants in their body or if they are pregnant. **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:** Katinka Stecina, PhD **Phone:** 204 789 3761 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Kristine Cowley, PhD **Phone:** 2047893305 **Role:** CONTACT #### Locations **Location 1:** **City:** Winnipeg **Country:** Canada **Facility:** University of Manitoba **State:** Manitoba **Status:** ENROLLING_BY_INVITATION **Zip:** R3E 0J9 **Location 2:** **City:** Winnipeg **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Katinka Stecina, Ph.D. - **Phone:** 2047893761 - **Role:** CONTACT ***Contact 2:*** - **Email:** [email protected] - **Name:** Kristine Cowley, Ph.D. - **Phone:** 2047893305 - **Role:** CONTACT **Country:** Canada **Facility:** University of Manitoba **State:** Manitoba **Status:** RECRUITING **Zip:** R3E 0J9 ### IPD Sharing Statement Module **Access Criteria:** Upon request **Description:** Upon request, we will consider making anonymized data available for analysis by other researchers **Info Types:** - STUDY_PROTOCOL - ICF - CSR **IPD Sharing:** YES **Time Frame:** After study completion (May 2022) for one year. ## Derived Section ### Condition Browse Module - Ancestors - ID: D000013118 - Term: Spinal Cord Diseases - ID: D000002493 - Term: Central Nervous System Diseases - ID: D000009422 - Term: Nervous System Diseases - ID: D000020196 - Term: Trauma, Nervous System - ID: D000010243 - Term: Paralysis - ID: D000009461 - Term: Neurologic Manifestations ### Condition Browse Module - Browse Branches - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: BC26 - Name: Wounds and Injuries - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M15916 - Name: Spinal Cord Injuries - Relevance: HIGH - As Found: Spinal Cord Injury - ID: M13177 - Name: Paraplegia - Relevance: HIGH - As Found: Paraplegia - ID: M17685 - Name: Wounds and Injuries - Relevance: HIGH - As Found: Injury - ID: M15915 - Name: Spinal Cord Diseases - Relevance: LOW - As Found: Unknown - ID: M5742 - Name: Central Nervous System Diseases - Relevance: LOW - As Found: Unknown - ID: M22023 - Name: Trauma, Nervous System - Relevance: LOW - As Found: Unknown - ID: M13157 - Name: Paralysis - Relevance: LOW - As Found: Unknown - ID: M12404 - Name: Neurologic Manifestations - Relevance: LOW - As Found: Unknown - ID: T4421 - Name: Paraplegia - Relevance: HIGH - As Found: Paraplegia ### Condition Browse Module - Meshes - ID: D000013119 - Term: Spinal Cord Injuries - ID: D000010264 - Term: Paraplegia - ID: D000014947 - Term: Wounds and Injuries ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00266279 **Brief Title:** Phase II (Treatment) Study of Oxaliplatin and Capecitabine in Advanced Head and Neck Malignancies **Official Title:** Phase II Study of Oxaliplatin and Capecitabine in Advanced Head and Neck Malignancies #### Organization Study ID Info **ID:** 153.05 #### Organization **Class:** OTHER **Full Name:** University of Louisville ### Status Module #### Completion Date **Date:** 2009-10 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2020-09-03 **Type:** ACTUAL **Last Update Submit Date:** 2020-08-28 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2009-10 **Type:** ACTUAL #### Results First Post Date **Date:** 2014-10-31 **Type:** ESTIMATED **Results First Submit Date:** 2013-05-03 **Results First Submit QC Date:** 2014-10-30 #### Start Date **Date:** 2005-04 **Status Verified Date:** 2020-08 #### Study First Post Date **Date:** 2005-12-16 **Type:** ESTIMATED **Study First Submit Date:** 2005-12-15 **Study First Submit QC Date:** 2005-12-15 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** James Graham Brown Cancer Center #### Lead Sponsor **Class:** OTHER **Name:** University of Louisville #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** This phase II study will test the response rate of combined oxaliplatin and capecitabine treatment when administered at a given dose and schedule, in patients with Head and Neck cancer for which there is no curative treatment. **Detailed Description:** The optimal dose and schedule for the combined treatment with oxaliplatin and capecitabine have not been defined. The aim of this Phase II study is to determine the response rate of combined oxaliplatin and capecitabine treatment at a given dose and schedule in patients with Head and Neck cancer for which there is no curative treatment. The study also aims to determine the qualitative and quantitative toxicity and reversibility of toxicity of the above combination and to evaluate any changes in performance status, quality of life, overall survival and progression-free survival. ### Conditions Module **Conditions:** - Head or Neck Cancer ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 17 **Type:** ACTUAL **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Treatment with combination of oxaliplatin and capecitabine using study dose and schedule. **Intervention Names:** - Drug: Oxaliplatin, Capecitabine **Label:** Treatment with Study Drugs **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Treatment with Study Drugs **Description:** Agent, DOSE AND SCHEDULE (28-days cycle): Oxaliplatin 85 mg/m2 IV on days 1 and 15 Capecitabine 1500 mg PO BID on days 1-7 and 15-21 **Name:** Oxaliplatin, Capecitabine **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Among the 15 patients treated, 2 (13%) achieved partial response (PR), and 5 (33%) achieved stable disease (SD), for a Overall Response Rate (ORR) of 46% measured by RECIST criteria. Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started. Overall Response Rate (ORR)=PR+CR. **Measure:** Overall Response Rate **Time Frame:** Every two 28 day treatment cycles until subject no longer on treatment due to disease progression #### Secondary Outcomes **Description:** Number of patients that developed common side effect of diarrhea. **Measure:** Qualitative and Quantitative Toxicity **Time Frame:** At study enrollment, Every two 28 day treatment cycles, and at end of treatment due to disease progression ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Patients must have histologically or cytologically confirmed squamous cell cancer of Head and Neck * Patients must have metastatic or locally recurrent disease * Patients must have disease not curable by surgery as estimated by one of the protocol investigators, and should not be eligible for reradiation protocol or have failed reradiation protocol. * Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as \>20 mm with conventional techniques or as \>10 mm with spiral CT scan * Age \>18 years of age * Life expectancy of greater than 12 weeks * ECOG performance status 0, 1 or 2 (Karnofsky \>50%; see Appendix B) * Patients must have adequate bone marrow function as defined below: * absolute neutrophil count \> 1,500 * platelets \> 100,000 * hemoglobin \> 8 g/dl * Patients must have adequate renal function as defined by a creatinine clearance \>30 mL/min (measured or estimated by the Cockroft and Gault equation) * Cockroft and Gault equation: * Creatinine clearance for males =(140-age\[yrs\])(body wt\[kg\])/72(serum creatinine\[mg/dL\]) * Creatinine clearance for females = 0.85 x male value * Patients must have adequate liver function as defined below: * total bilirubin 1.5x upper limit of normal * albumin \> 2.5 g/dl * AST(SGOT) and ALT(SGPT) and Alkaline Phosphatase must be \< 5 times upper limit of normal * Patients could have received 1 or 2 previous chemotherapy regimens prior to entering the study. Patients must have recovered from acute toxicities from chemotherapy or radiotherapy administered prior to entering this study. Alopecia may not be resolved and peripheral neuropathy (grade 1) may be present. * Patients with reproductive potential must use an adequate contraceptive method (e.g., abstinence, intrauterine device, oral contraceptives, barrier device with spermicide or surgical sterilization) during treatment and for three months after completing treatment. * Ability to understand and willingness to sign a written informed consent document Exclusion Criteria: * Prior unanticipated severe reaction to fluoropyrimidine therapy or known hypersensitivity to 5-fluorouracil or oxaliplatin * Patients who have had chemotherapy or radiotherapy within 4 weeks prior to first treatment in this study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier * Patients receiving any other investigational agent(s) * Patients with symptomatic brain metastases or actively receiving any therapy for brain metastasis (because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events) * Active second malignancy in the last 5 years except for non-melanoma skin cancer or carcinoma-in-situ * Clinically significant cardiac disease (e.g. congestive heart failure, New York Heart Association Class II or greater, symptomatic coronary artery disease and cardiac arrhythmias) or myocardial infarction within the last 12 months. * If patient is unable to swallow, xeloda may be crushed per hospital policy/procedure. See attached Appendix G. * Patients who have had an organ allograft. * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements. * Pregnancy * Known Hepatitis B , Hepatitis C, HIV Inclusion of Minorities: Members of all ethnic groups are eligible for this trial. **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Louisville **Country:** United States **Facility:** University of Louisville, James Graham Brown Cancer Center **State:** Kentucky **Zip:** 40202 #### Overall Officials **Official 1:** **Affiliation:** University of Louisville, James Graham Brown Cancer Center **Name:** Damian Laber, M.D. **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### References **Citation:** Rabinowits G, Bhupalam L, Miller DM, Kloecker GH, Laber DA. Fixed-dose every-other-week capecitabine and oxaliplatin for refractory squamous cell carcinoma of the head and neck. Am J Med Sci. 2010 Feb;339(2):148-51. doi: 10.1097/MAJ.0b013e3181c4bd91. **PMID:** 20087165 #### See Also Links **Label:** James Graham Brown Cancer Center website **URL:** http://browncancercenter.org ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009371 - Term: Neoplasms by Site ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M9348 - Name: Head and Neck Neoplasms - Relevance: HIGH - As Found: Neck Cancer ### Condition Browse Module - Meshes - ID: D000009369 - Term: Neoplasms - ID: D000006258 - Term: Head and Neck Neoplasms ### 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 ### Intervention Browse Module - Browse Leaves - ID: M377 - Name: Capecitabine - Relevance: HIGH - As Found: Function - ID: M1674 - Name: Oxaliplatin - Relevance: HIGH - As Found: Outcomes - ID: M4281 - Name: Antimetabolites - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000069287 - Term: Capecitabine - ID: D000077150 - Term: Oxaliplatin ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module #### Event Groups **Group ID:** EG000 **Title:** Treatment With Study Drugs **Description:** Treatment with combination of oxaliplatin and capecitabine using study dose and schedule. Oxaliplatin, Capecitabine : Agent, DOSE AND SCHEDULE (28-days cycle): Oxaliplatin 85 mg/m2 IV on days 1 and 15 Capecitabine 1500 mg PO BID on days 1-7 and 15-21 **ID:** EG000 **Other Num at Risk:** 15 **Serious Number Affected:** 4 **Serious Number At Risk:** 15 **Title:** Treatment With Study Drugs **Frequency Threshold:** 5 #### Serious Events **Term:** Pneumonia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Notes:** Two patients were hospitalized because of pneumonia. **Organ System:** Infections and infestations ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 15 **Num Events:** 2 **Term:** Dehydration **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Notes:** 1 subjects was hospitalized for dehydration. **Organ System:** General disorders ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 15 **Num Events:** 1 **Term:** Gastrointestinal Bleeding **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Notes:** 1 Subject experienced gastrointestinal bleeding. **Organ System:** Gastrointestinal disorders ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 15 **Num Events:** 1 ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 15 **Units:** Participants ### Group **ID:** BG000 **Title:** Treatment With Study Drugs **Description:** Treatment with combination of oxaliplatin and capecitabine using study dose and schedule. Oxaliplatin, Capecitabine : Agent, DOSE AND SCHEDULE (28-days cycle): Oxaliplatin 85 mg/m2 IV on days 1 and 15 Capecitabine 1500 mg PO BID on days 1-7 and 15-21 ### Measure #### Measurement **Group ID:** BG000 **Value:** 15 **Class Title:** >=18 years ### Measure #### Measurement **Group ID:** BG000 **Value:** 10 **Class Title:** Male #### Measurement **Group ID:** BG000 **Value:** 5 **Class Title:** Femal **Denomination Units Selected:** ## Results Section - Baseline Characteristics Module ### Measure 1 **Parameter Type:** NUMBER **Title:** Age, Customized **Unit of Measure:** Participants ### Measure 2 **Parameter Type:** NUMBER **Title:** Sex/Gender, Customized **Unit of Measure:** Participants ## Results Section - More Information Module ### Certain Agreement ### Limitations and Caveats **Description:** Results data not available, PI not longer at institution ### Point of Contact **Email:** [email protected] **Organization:** University of Louisville, James Graham Brown Cancer Center **Phone:** 502-562-3429 **Title:** University of Louisville, James Graham Brown Cancer Center Clinical Trials ## 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:** - **Upper Limit:** - **Value:** 2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 5 **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** Among the 15 patients treated, 2 (13%) achieved partial response (PR), and 5 (33%) achieved stable disease (SD), for a Overall Response Rate (ORR) of 46% measured by RECIST criteria. Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started. Overall Response Rate (ORR)=PR+CR. **Parameter Type:** NUMBER **Reporting Status:** POSTED **Time Frame:** Every two 28 day treatment cycles until subject no longer on treatment due to disease progression **Title:** Overall Response Rate **Type:** PRIMARY **Unit of Measure:** Participants ##### Group **Description:** Treatment with combination of oxaliplatin and capecitabine using study dose and schedule. Oxaliplatin, Capecitabine : Agent, DOSE AND SCHEDULE (28-days cycle): Oxaliplatin 85 mg/m2 IV on days 1 and 15 Capecitabine 1500 mg PO BID on days 1-7 and 15-21 **ID:** OG000 **Title:** Treatment With Study Drugs #### Outcome Measure 2 **Description:** Number of patients that developed common side effect of diarrhea. **Parameter Type:** NUMBER **Reporting Status:** POSTED **Time Frame:** At study enrollment, Every two 28 day treatment cycles, and at end of treatment due to disease progression **Title:** Qualitative and Quantitative Toxicity **Type:** SECONDARY **Unit of Measure:** participants ##### Group **Description:** Treatment with combination of oxaliplatin and capecitabine using study dose and schedule. Oxaliplatin, Capecitabine: Agent, DOSE AND SCHEDULE (28-days cycle): Oxaliplatin 85 mg/m2 IV on days 1 and 15 Capecitabine 1500 mg PO BID on days 1-7 and 15-21 **ID:** OG000 **Title:** Treatment With Study Drugs ### Participant Flow Module #### Group **Description:** Treatment with combination of oxaliplatin and capecitabine using study dose and schedule. Oxaliplatin, Capecitabine : Agent, DOSE AND SCHEDULE (28-days cycle): Oxaliplatin 85 mg/m2 IV on days 1 and 15 Capecitabine 1500 mg PO BID on days 1-7 and 15-21 **ID:** FG000 **Title:** Treatment With Study Drugs #### Period **Title:** Overall Study ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 17 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 15 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 2 **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT03044379 **Brief Title:** Dapivirine Gel Rectal Safety and PK Study **Official Title:** A Randomized, Double Blind, Placebo-Controlled, Phase 1 Safety and Pharmacokinetic Study of Dapivirine Gel (0.05%) Administered Rectally to HIV-1 Seronegative Adults #### Organization Study ID Info **ID:** MTN-026/ IPM 038 #### Organization **Class:** INDUSTRY **Full Name:** International Partnership for Microbicides, Inc. ### Status Module #### Completion Date **Date:** 2017-11 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2017-02-08 **Type:** ESTIMATED **Last Update Submit Date:** 2017-02-06 **Overall Status:** WITHDRAWN #### Primary Completion Date **Date:** 2017-09 **Type:** ESTIMATED #### Start Date **Date:** 2015-09-29 **Type:** ACTUAL **Status Verified Date:** 2016-10 #### Study First Post Date **Date:** 2017-02-07 **Type:** ESTIMATED **Study First Submit Date:** 2016-09-06 **Study First Submit QC Date:** 2017-02-02 **Why Stopped:** Current program is on hold, not for safety reason ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** International Partnership for Microbicides, Inc. #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** Dapivirine Gel Rectal Safety and PK Study **Detailed Description:** A Randomized, Double Blind, Placebo-Controlled Phase 1 Safety and Pharmacokinetic Study of Dapivirine Gel (0.05%) Administered Rectally to HIV-1 Seronegative Adults ### Conditions Module **Conditions:** - HIV 1 Infection ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** DOUBLE **Who Masked:** - PARTICIPANT - INVESTIGATOR **Primary Purpose:** OTHER #### Enrollment Info **Type:** ACTUAL **Phases:** - PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Participants will be randomized to receive a single dose of dapivirine gel rectally, followed by 7 daily doses of the same product to be administered under direct observation in the clinic. **Intervention Names:** - Drug: Dapivirine gel (0.05%) **Label:** Dapivirine Gel **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** Participants will be randomized to receive the universal HEC placebo gel rectally, followed by 7 daily doses of the same product to be administered under direct observation in the clinic. **Intervention Names:** - Other: Universal HEC placebo gel **Label:** Placebo Gel HEC **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Dapivirine Gel **Description:** MTN-026/IPM 038 will use the HTI pre-filled applicator, the same applicator that has been utilized in other rectal studies. **Name:** Dapivirine gel (0.05%) **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Placebo Gel HEC **Name:** Universal HEC placebo gel **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** To evaluate the safety of dapivirine gel formulation when applied rectally. **Measure:** Safety To characterize the systemic and compartmental pharmacokinetics of dapivirine gel following rectal application. **Time Frame:** 9-12 months #### Secondary Outcomes **Description:** To identify product attributes considered likely to challenge and facilitate future sustained use of rectally applied dapivirine gel. **Measure:** Acceptability **Time Frame:** 9-12 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Age of 18 - 45 years (inclusive), verified per site SOP * Able and willing to provide written informed consent * HIV-1/2 uninfected at Screening and Enrollment, per applicable algorithm in Appendix II and willing to receive HIV test results * Able and willing to provide adequate locator information, as defined in site SOP * Available to return for all study visits and willing to comply with study participation requirements * In general good health at Screening and Enrollment, as determined by the site IoR or designee * Per participant report, a history of consensual RAI at least once in the past calendar year * Willing to not take part in other research studies involving drugs, medical devices, genital products, or vaccines for the duration of study participation, including the time between Screening and Enrollment Exclusion Criteria: At Screening: * Hemoglobin Grade 1 or higher\* * Platelet count Grade 1 or higher\* * White blood count Grade 2 or higher\* * Serum creatinine 1.3 the site laboratory upper limit of normal (ULN) * International normalized ratio (INR) 1.5 the site laboratory ULN * Aspartate aminotransferase (AST) or alanine transaminase (ALT) Grade 1 or higher\* * Positive for hepatitis C antibody * Positive for hepatitis B surface antigen * History of inflammatory bowel disease by participant report **Healthy Volunteers:** True **Maximum Age:** 45 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Pittsburgh **Country:** United States **Facility:** University of Pittsburgh Medical Center **State:** Pennsylvania **Zip:** 15213 ### IPD Sharing Statement Module **IPD Sharing:** NO ## 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 - Ancestors - ID: D000019380 - Term: Anti-HIV Agents - ID: D000044966 - Term: Anti-Retroviral Agents - 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: M256068 - Name: Dapivirine - Relevance: HIGH - As Found: Adult acute lymphoblastic leukemia - ID: M21350 - Name: Anti-HIV Agents - Relevance: LOW - As Found: Unknown - ID: M25428 - Name: Anti-Retroviral Agents - Relevance: LOW - As Found: Unknown - 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: C000481671 - Term: Dapivirine ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT01475279 **Brief Title:** A Study to Evaluate the Effect of T89(Dantonic®)on Steady-State Pharmacodynamics of Warfarin **Official Title:** An Open-Label, Multiple-Dose, Single-Center, Sequential, Inpatient Study to Determine the Effect of T89 on Steady-State Pharmacodynamics of Warfarin in Healthy Subjects #### Organization Study ID Info **ID:** T89-04-US #### Organization **Class:** INDUSTRY **Full Name:** Tasly Pharmaceuticals, Inc. ### Status Module #### Completion Date **Date:** 2012-01 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2012-11-08 **Type:** ESTIMATED **Last Update Submit Date:** 2012-11-07 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2011-11 **Type:** ACTUAL #### Start Date **Date:** 2011-07 **Status Verified Date:** 2011-11 #### Study First Post Date **Date:** 2011-11-21 **Type:** ESTIMATED **Study First Submit Date:** 2011-11-14 **Study First Submit QC Date:** 2011-11-18 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Tasly Pharmaceuticals, Inc. #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** The purpose of this study is to evaluate the potential effect of Dantonic on the steady-state pharmacodynamics and pharmacokinetic of warfarin in healthy subjects and safety of the co-administration of Dantonic and warfarin. **Detailed Description:** Due to a large proportion of patients that could benefit from Dantonic treatment is likely to take warfarin concomitantly. And there is no systematic experience of warfarin drug-drug interaction between Dantonic and warfarin on humans. It is highly relevant to investigate the potential interaction of theses two drugs. Primary endpoint: •The change in INR with T89 (Day 25) compared with that without T89 (Day 18) Secondary endpoints: * The change in PK variables for R-warfarin and S-warfarin on Day 17 compared with those on Day 24 * Safety assessments across all time points ### Conditions Module **Conditions:** - Healthy **Keywords:** - Warfarin - Dantonic - Pharmacodynamics - Pharmacokinetics - Interaction ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE #### Enrollment Info **Count:** 24 **Type:** ACTUAL **Phases:** - PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module ### Interventions #### Intervention 1 **Description:** Individual warfarin dose during the study; 225mg Dantonic b.i.d for one week **Name:** Warfarin; Dantonic **Other Names:** - coumadin **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** The mean INR change with T89 (Day 25) and without T89 (Day 18) will be assessed by standard t test. **Measure:** The change in INR with T89 (Day 25) compared with that without T89 (Day 18) **Time Frame:** outcome measure will be assessed in two weeks and data will be presented up to eight weeks #### Secondary Outcomes **Description:** The S- and R-warfarin concentration time profiles will be listed and displayed graphically. And 90% CI of the geometric mean ratio for Cmax and AUClast of both R- and S-warfarin will be caculated. **Measure:** The change in PK variables for R-warfarin and S-warfarin on Day 17 compared with those on Day 24 **Time Frame:** outcome measure will be assessed in two weeks and data will be presented up to eight weeks ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Nonsmoking male or female with 18-50 years of age and a body mass index (BMI) from 19.0 to 30.0 kg/m2; 2. Healthy adult with no active medical problems or significant chronic diseases as determined by the study doctor based on medical history, physical examination and laboratory evaluations; 3. Taking no medications 2 weeks before Day 0 and during the study, including drugs of abuse, prescription and non prescription medications (including natural health products, Vitamins, and herbals) and did not receive vaccinations; 4. Agree to avoid eating Seville oranges, grapefruits (including grapefruit juice), broccoli, brussels sprouts, charcoal-grilled meats, alcoholic beverages, and caffeine- and theobromine-containing beverages and foods from the time of screening visit and the duration of the study; 5. Agree to maintain adequate birth control, independent from hormonal contraceptive use, from the time of the screening visit and during the study, at the discretion of the investigator; 6. Agree to abstain from alcoholic beverages, caffeinated beverages and orange juice from 6pm the night before a study day until completion of that study day; 7. A negative fecal occult blood test (FOBT) ; 8. Agree to avoid participation in contact sports and/or other activities with significant risk of trauma injury for 7 days after each study day; 9. Subject understands and is willing, able and likely to comply with all study procedures and restrictions; 10. Subject is able to give voluntary oral and written informed consent, at the discretion of the investigator. Exclusion Criteria: 1. Subjects with an elevated INR (INR\> 1.2) at screening visit; 2. No gastrointestinal bleeding history within 12 months prior to screening visit; 3. No history of endoscopically proven peptic ulcer disease; 4. Known hypersensitivity to warfarin; 5. Prosthetic heart valves, mitral stenosis, or other conditions such as recent (\<3 months) pulmonary embolism requiring anticoagulant therapy; 6. History or presence of renal and hepatic insufficiency; 7. History of hyperthyroidism; 8. History of any bleeding disorder or hypercoagulation state; 9. Surgical or medical condition liable to interfere with the absorption, metabolism or excretion of warfarin; 10. Regular intake of other medication affecting the process of coagulation or platelet aggregation (during the 2 weeks prior to screening and/or during the run-in and treatment periods); 11. Significant change in diet likely to interfere with the effects of warfarin in the 2 weeks prior to screening and/or during the run-in and treatment periods, at the discretion of the investigator; 12. History of conditions associated with hemorrhagic risk, surgery or head injury within 6 months prior to screening visit; 13. Hematological abnormalities (thrombocytopenia, clinically significant low granulocyte count, anemia, hypofibrinogenaemia, hemophilia, purpura, hemopathy with prolongation of bleeding time); 14. Blood loss/donation \>400 mL within 12 weeks prior to the screening visit and/or during the run-in and treatment periods; 15. Known to have serum hepatitis or who are carrier of the hepatitis B surface antigen (HBsAg), or hepatitis C antibody, or have a positive result to the test for HIV antigens and/or antibodies; 16. Pregnancy or lactation; 17. Participation in any other clinical trial or receipt of an investigational drug within 60 days prior to the time of the screening visit, or previous participation in this study; 18. Those subjects unable, in the opinion of the investigator, to comply fully with the trial requirements; 19. Subjects with a recent history (within 24 months prior to the screening visit) of alcoholism or known drug dependence, at the discretion of the investigator; 20. Subjects with positive urine cotinine, urine drug screen and/or alcohol breath test; 21. In the opinion of the investigator, patients with medical history or other factors which may interfere with enrollment or the study. **Healthy Volunteers:** True **Maximum Age:** 50 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** San Antonio **Country:** United States **Facility:** Healthcare Discoveries, LLC d/b/a ICON Development Solutions **State:** Texas **Zip:** 78209 ## Derived Section ### Intervention Browse Module - Ancestors - ID: D000000925 - Term: Anticoagulants ### Intervention Browse Module - Browse Branches - Abbrev: AnCoag - Name: Anticoagulants - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M17602 - Name: Warfarin - Relevance: HIGH - As Found: Department - ID: M4244 - Name: Anticoagulants - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000014859 - Term: Warfarin ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00995579 **Brief Title:** Assessment of Energy Expenditure by Indirect Calorimetry for a Daily 10,000 Steps Goal **Official Title:** Assessment of Energy Expenditure by Indirect Calorimetry for a Daily 10,000 Steps Goal #### Organization Study ID Info **ID:** 200809081R #### Organization **Class:** OTHER **Full Name:** National Taiwan University Hospital ### Status Module #### Completion Date **Date:** 2009-02 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2009-10-15 **Type:** ESTIMATED **Last Update Submit Date:** 2009-10-14 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2009-02 **Type:** ACTUAL #### Start Date **Date:** 2008-11 **Status Verified Date:** 2009-10 #### Study First Post Date **Date:** 2009-10-15 **Type:** ESTIMATED **Study First Submit Date:** 2009-10-13 **Study First Submit QC Date:** 2009-10-14 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** National Taiwan University Hospital #### Responsible Party **Old Name Title:** Liying Wang **Old Organization:** School and Graduate Institute of Physical Therapy, National Taiwan University ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** The purpose of this study was to measure the actual energy expenditure (EE) using indirect calorimetry for the 10,000 steps goal, and compared to the estimated EE using predictive equation. **Detailed Description:** Physical inactivity is considered a major risk factor for a number of adverse health outcomes such as obesity, hypertension, cardiovascular disease, diabetes mellitus, and all-cause mortality. Certain guidelines specifically recommend taking 10,000 steps per day for a goal. Some of pedometers have a function of energy expenditure estimation in addition to counting steps. However, the EE derived from pedometers is the indirect estimation calculated from metabolic calculations instead of direct measurement.The purpose of this study was to measure the actual energy expenditure (EE) using indirect calorimetry for the 10,000 steps goal, and compared to the estimated EE using predictive equation. Twenty healthy college volunteers were recruited. First, height and weight were measured from each subject. Body mass index (BMI) was calculated as the ratio of weight to height in meters squared. We used BioScan 920 to get all subjects' body composition data including fat mass and fat-free mass. Followed by measurements of basic characteristics, all subjects wore the pedometer and walked 10,000 steps on the treadmill. The walking speeds ranged from 3.0 to 4.0 miles per hour (mph) according to different gender. The speed of 4.0 mph was set for male and 3.0 mph was set for female. If the subject could'nt follow the pre-set speed, he/she could walk with self-comfortable speed but the speed should be in the range of 3.0 to 4.0 mph defined as moderate intensity of ACSM's recommendation. Subjects rested on the chair with back support for 3 minutes and then completed the 10,000 steps goal. After recovery for 3 minutes, the data collection was finished. The stopping criteria of the test were as follows: dizziness, nausea, dyspnea, or leg fatigue which leads subjects unable to continue. Expired gas was collected using the Cosmed K4b2 portable indirect calorimetry system, and EE was monitored breath-by-breath according to the following formula: EE (Kcal/min)= 3.781×VO2＋1.237×VCO2 where VO2 represents the standardized oxygen consumption per minute, and VCO2 is the carbon dioxide production per minute. Estimated EE was calculated by the predictive equation published by ACSM: VO2 (ml/kg/min)= 0.1×S (m/min)＋1.8×S×G (%)＋3.5 where S represents the walking speed, and G is the walking grade. The total walking duration and distance for taking 10,000 steps were also recorded. Pulmonary function tests were performed on the other day to get each subject's functional vital capacity (FVC). We used this parameter to estimate subject's predicted maximal minute ventilation (predicted max VE) according to the equation provided in the guidelines of American Thoracic Society (ATS) for cardiopulmonary exercise testing: VE (L/min)= 26.3×VC-34 where VC represents vital capacity. The ratio of averaged VE during walking and predicted maximal VE was calculated to determine the level of exercise intensity for taking 10,000 steps. ### Conditions Module **Conditions:** - Physical Activity - Energy Expenditure **Keywords:** - Physical Activity - Energy Expenditure ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** CROSS_SECTIONAL #### Enrollment Info **Count:** 20 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Label:** Healthy college volunteers ### Outcomes Module #### Primary Outcomes **Measure:** energy expenditure **Time Frame:** 3 months #### Secondary Outcomes **Measure:** Body composition: fat mass and fat-free mass **Time Frame:** 3 months **Measure:** Pulmonary function: FVC, FEV1, FEV1/FVC **Time Frame:** 3 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Aged 18-30 y/o Exclusion Criteria: * Unstable systemic disease, respiratory diseases, cardiac diseases or other clinical diagnosis which would affect outcome measure * Subjects who answered yes to any of the PAR-Q questions or who were not physically able to complete the test **Healthy Volunteers:** True **Maximum Age:** 30 Years **Minimum Age:** 18 Years **Sampling Method:** PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT **Study Population:** Healthy college volunteers ### Contacts Locations Module #### Locations **Location 1:** **City:** Taipei **Country:** Taiwan **Facility:** School and Graduate Institute of Physical Therapy, National Taiwan University #### Overall Officials **Official 1:** **Affiliation:** chool and Graduate Institute of Physical Therapy, National Taiwan University **Name:** Liying Wang, Ph.D. **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04833179 **Brief Title:** Fecal Transplant for Alopecia Areata **Official Title:** Fecal Transplant for Alopecia Areata #### Organization Study ID Info **ID:** 001320 #### Organization **Class:** OTHER_GOV **Full Name:** Tel-Aviv Sourasky Medical Center ### Status Module #### Completion Date **Date:** 2025-04 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2021-04-06 **Type:** ACTUAL **Last Update Submit Date:** 2021-04-03 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2024-04 **Type:** ESTIMATED #### Start Date **Date:** 2021-05 **Type:** ESTIMATED **Status Verified Date:** 2021-04 #### Study First Post Date **Date:** 2021-04-06 **Type:** ACTUAL **Study First Submit Date:** 2021-03-01 **Study First Submit QC Date:** 2021-04-03 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER_GOV **Name:** Tel-Aviv Sourasky Medical Center #### Responsible Party **Investigator Affiliation:** Tel-Aviv Sourasky Medical Center **Investigator Full Name:** Eli Sprecher, MD **Investigator Title:** Liat Samuelov MD. Vice Chair, Division of Dermatology, Tel Aviv Sourasky Medical Center **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False ### Description Module **Brief Summary:** the investigators intend to analyze the microbiome in the diseased areas, healthy skin and fecal samples. In addition, the investigators plan to evaluate how the fecal transplant can influence the severity of the disease and hair growth, all in hope that fecal transplant can help to treat or even cure AA. This may help dermatologists in the future and expand the treatment options for AA. **Detailed Description:** Alopecia areata (AA) is a common autoimmune disease that triggers non scarring hair loss in different severities. Usually the hair loss will be contained to the scalp and / or beard, but in some cases, there will be total hair loss from the entire scalp (alopecia totalis), or complete loss of all body, facial and scalp hair (alopecia universalis). AA is an autoimmune disease that produces an inflammation surrounding the hair follicles, this leads to temporary hair loss. In cases the disease become chronic, the immune system attack may lead to a permanent hair loss. This common hair disease has a significant impact on the patient's quality of life, it can cause impairment on the patient's confidence, self-esteem, lead to depression and more. Lately two patients with AA and clostridium difficile infection were treated with fecal transplantation for their infection (Rebello et al. 2017). After the transplant a significant improvement was notice in hair growth. These 2 cases raised the option that a fecal transplant may have an additional effect on the autoimmune reaction against the hair follicle in AA. the investigators intend to analyze the microbiome in the diseased areas, healthy skin and fecal samples. In addition, the investigators plan to evaluate how the fecal transplant can influence the severity of the disease and hair growth, all in hope that fecal transplant can help to treat or even cure AA. This may help dermatologists in the future and expand the treatment options for AA. ### Conditions Module **Conditions:** - Alopecia Areata **Keywords:** - Alopecia Areata - Fecal transplant - Microbiome ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** 110 patients with alopecia areata. Prior the beginning of the study all subjects will undergo: Complete physical examination Clinical image of involved locations will be taken Estimating the severity of the disease Microbiome samples Blood sample The patients with AA will undergo randomization into two groups. Group 1 - the subjects will receive a complete fecal transplant course. Group 2 - the subjects will receive placebo. ##### Masking Info **Masking:** TRIPLE **Who Masked:** - PARTICIPANT - CARE_PROVIDER - INVESTIGATOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 110 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Healthy donors will be selected by the fecal transplant unit, in Tel-Aviv medical center. The treatment will be given in the form of fecal capsule. Each capsule will contain a double capsule with 2 layers to ensure that the fecal material will be contained. The treatments will include 30 capsules for the first treatment, that will be taken in two consecutive days, each day 15 capsules. The second, third and fourth treatments will all include 15 fecal capsules. There will be 2 weeks intervals between each treatment. **Intervention Names:** - Biological: fecal transplant **Label:** fecal transplant **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Placebo capsule that can not be differentiate from the focal transplant capsule will be given in the same interval as the fecal transplant procedure written above. **Intervention Names:** - Other: placebo **Label:** placebo **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - fecal transplant **Description:** Healthy donors will be selected by the fecal transplant unit, in Tel-Aviv medical center. All donors will undergo a screening process that will include a detailed medical history, blood work and fecal tests. Only after passing the screening, the donor will be added to the groups of donors that will participant in this study. The treatment will be givenin the form of fecal capsule. Each capsule will contain a double capsule with 2 layers to ensure that the fecal material will be contained. The treatments will include 30 capsules for the first treatment, that will be taken in two consecutive days, each day 15 capsules. The second, third and fourth treatments will all include 15 fecal capsules. There will be 2 weeks intervals between each treatment. **Name:** fecal transplant **Type:** BIOLOGICAL #### Intervention 2 **Arm Group Labels:** - placebo **Description:** placebo **Name:** placebo **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** The SALT score I (Olsen, 2004) is a global severity score that captures percentage hair loss. The scalp area is divided into 4 quadrants - Left (L) Right (R) Back (B) Top (T). Photographs taken of the four views of the scalp. The percentage of hair loss in any one of the four views (areas) of the scalp = the percentage hair loss X percent surface area of the scalp in that area. 1. left side view = ALOPECIA% x 18% 2. right side view = ALOPECIA% x 18% 3. top of scalp = ALOPECIA% x 40% 4. back of scalp = ALOPECIA% x 24% The SUM of all equals the score. (possible score range: 0-100) **Measure:** Severity alopecia tool score - SALT score I **Time Frame:** up to1 year after fecal transplantation **Description:** formula for the total AAPI score (possible score range: 0-600). The scalp area is divided into 4 quadrants - Left (L) Right (R) Back (B) Top (T) using the Olsen/Canfield tool. The percent alopecic area (%AA) and score of hair loss activity (SL) is determined in each quadrant. The %AA is defined as the percentage of alopecic area in each compartment. SL is calculated as the sum of the results of hair pull tests (2 = positive, excessive, i.e. \>20% of grasped hairs; 1 = positive, not excessive, 10-20%; 0 = negative, \<10%) and the magnification findings associated with hair loss activity such as exclamation mark hairs, broken hairs and black dots (4 = ≥50%, 2 = \<50%, 0 = 0%) in each quadrant. The total AAPI score is calculated by the following formula: \[%AA(L) × SL(L) × 0.18\] + \[%AA(R) × SL(R) × 0.18\] + \[%AA(T) × SL(T) × 0.4\] + \[%AA(B) × SL(B) × 0.24\]. (possible score range: 0-600) **Measure:** Alopecia Areata Progression Index, AAPI **Time Frame:** up to1 year after fecal transplantation **Description:** 1. \<25% regrowth. 2. 25%\<x\<50% regrowth. 3. 50%\<x\<70%regrowth. 4. \>75% regrowth. 5. 100% regrowth. **Measure:** patient assessment. **Time Frame:** up to1 year after fecal transplantation ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: AA patients with: * Acute disease that appeared in the last 3 months. * Recurrence of AA in the last 3 months, in a patient who had remission for at least one year. * At least one patch of hair loss on the scalp and / or the beard, or with a widespread disease such as total loss of the hair over the entire scalp (alopecia totalis). * In case of a single alopetic patch, the patch must be equal or bigger than 2 cm in diameter. * All patients will be diagnosed by two separate dermatologist, or one dermatologist with the support of classical finding on skin biopsy. Exclusion Criteria: 1. Patients who were treated with systemic corticosteroids / corticosteroids injection one year prior the study. 2. Patients who were treated with topical corticosteroids two weeks prior the study. 3. Patients who were treated with immunosuppressing medications or biological treatments one year prior the study. 4. Patients who were treated with systemic antibiotics of any kind 3 months prior the study. 5. Patient who were treated with topical antibiotics one months prior the study. 6. Patients who were treated with probiotics one months prior the study. 7. Patients with alopecia universalis (total loss of all body, scalp and facial hair). 8. Patients with bowel disease or an active infection including clostridium difficile. 9. Pregnant and breastfeeding women. 10. Childrenbelow the age of 18. 11. Malignant disease in the past 5 years. 12. Patient with any infectious disease that require antibiotics during the study period. In any case a patient would like to withdraw from the study, for any reason, all samples will be destroyed immediately, and the patient will stop his participant in the study. **Maximum Age:** 90 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Efrat Bar-Ilan, MD **Phone:** +972-54-8186226 **Role:** CONTACT #### Overall Officials **Official 1:** **Affiliation:** Vice chair, Department of Dermatology Tel Aviv Sourasky Medical center, Israel **Name:** Liat Samueluv, MD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000007039 - Term: Hypotrichosis - ID: D000006201 - Term: Hair Diseases - ID: D000012871 - Term: Skin Diseases - ID: D000020763 - Term: Pathological Conditions, Anatomical ### Condition Browse Module - Browse Branches - Abbrev: BC17 - Name: Skin and Connective Tissue Diseases - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M3846 - Name: Alopecia - Relevance: HIGH - As Found: Alopecia - ID: M3847 - Name: Alopecia Areata - Relevance: HIGH - As Found: Alopecia Areata - ID: M10089 - Name: Hypotrichosis - Relevance: LOW - As Found: Unknown - ID: M9293 - Name: Hair Diseases - Relevance: LOW - As Found: Unknown - ID: M15674 - Name: Skin Diseases - Relevance: LOW - As Found: Unknown - ID: M22519 - Name: Pathological Conditions, Anatomical - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000000505 - Term: Alopecia - ID: D000000506 - Term: Alopecia Areata ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03769779 **Brief Title:** Evaluation of the Benefits of FloraGLO™ Lutein on Skin Health **Official Title:** A 12-Week, Randomized, Double-Blind, Placebo-Controlled Evaluation of the Benefits of FloraGLO™ Lutein on Skin Health #### Organization Study ID Info **ID:** 4251KM0918 #### Organization **Class:** INDUSTRY **Full Name:** Kemin Foods LC ### Status Module #### Completion Date **Date:** 2020-03-30 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2021-02-03 **Type:** ACTUAL **Last Update Submit Date:** 2021-02-02 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2019-12-30 **Type:** ACTUAL #### Start Date **Date:** 2019-03-06 **Type:** ACTUAL **Status Verified Date:** 2018-12 #### Study First Post Date **Date:** 2018-12-10 **Type:** ACTUAL **Study First Submit Date:** 2018-12-04 **Study First Submit QC Date:** 2018-12-05 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Kemin Foods LC #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Therefore, the present study is designed to contribute to the body of literature by investigating the effect of 12-weeks of lutein supplementation on multiple parameters of skin health and appearance in healthy women. **Detailed Description:** This is a randomized, double-blind, placebo-controlled, parallel twelve-week study of the performance of an oral test product to evaluate the effects of twelve weeks of lutein supplementation on skin health and appearance in healthy women. A seven-day washout period will precede the evaluation period. The subjects in each cohort will use consume one softgel of their assigned test product (treatment or placebo) daily in the morning with breakfast for 12 weeks. Changes in skin condition and appearance as well as blood chemistry will be assessed using results from expert visual grading, instrumental assessments, skin and blood assays and subjective questionnaire responses. Subjects will be recruited during the winter season to account for seasonal variations of skin parameters. Evaluation points will occur pre-application (Baseline; Week 0) and after 42 and 84 days of use (D42, D84; Week 6, Week 12). Data will be collected on the following outcomes: 1. Skin Hydration 2. Skin texture/smoothness 2. Reduction of facial fine lines and wrinkles 3. Skin elasticity and firmness 4. Sagging skin, dry skin, skin tone, appearance from expert clinical grading and subjective questionnaire responses. 6. Skin hydration 7. Skin collagen 8. Skin lipid content. 9. Skin Carotenoids ### Conditions Module **Conditions:** - Aging - Wrinkle - Skin Elasticity - Healthy - Hydration ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** Randomized, Double-Blind, Placebo-Controlled, Parallel Study ##### Masking Info **Masking:** QUADRUPLE **Masking Description:** Envelopes that contain information regarding the coding of treatment and placebo will be provided to Sponsor, Site, and PI and kept in a secure location. Envelopes will be readily available for the investigator or site to open in the event that it becomes necessary to know which product a participant is taking for the sake of the participant health care. The sponsor must be notified of any unblinding by the site within 24 hours. **Who Masked:** - PARTICIPANT - CARE_PROVIDER - INVESTIGATOR - OUTCOMES_ASSESSOR **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 60 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Lutein (FloraGLO™) in safflower oil **Intervention Names:** - Dietary Supplement: FloraGLO Lutein **Label:** Treatment **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** safflower oil **Intervention Names:** - Dietary Supplement: Safflower Oil **Label:** Placebo **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Treatment **Description:** Lutein (FloraGLO™) in safflower oil **Name:** FloraGLO Lutein **Type:** DIETARY_SUPPLEMENT #### Intervention 2 **Arm Group Labels:** - Placebo **Description:** Safflower Oil **Name:** Safflower Oil **Type:** DIETARY_SUPPLEMENT ### Outcomes Module #### Primary Outcomes **Description:** Corneometer Value **Measure:** Objective Skin Hydration **Time Frame:** ANOVA including weeks 6 and 12 **Description:** Subjective Questionnaire Visual Analog Scale **Measure:** Subjective Skin Hydration **Time Frame:** ANOVA including weeks 6 and 12 #### Secondary Outcomes **Description:** Expert clinical grading **Measure:** Objective Skin Texture **Time Frame:** ANOVA including weeks 6 and 12 **Description:** Subjective Questionnaire Visual Analog Scale **Measure:** Subjective Skin Texture **Time Frame:** ANOVA including weeks 6 and 12 **Description:** Expert clinical grading **Measure:** Objective Facial Lines and Wrinkles **Time Frame:** ANOVA including weeks 6 and 12 **Description:** Subjective Questionnaire Visual Analog Scale **Measure:** Subjective Facial Lines and Wrinkles **Time Frame:** ANOVA including weeks 6 and 12 **Description:** Expert clinical grading **Measure:** Objective Sagging skin, dry skin, skin tone, and overall appearance **Time Frame:** ANOVA including weeks 6 and 12 **Description:** Subjective Questionnaire Visual Analog Scale **Measure:** Subjective Sagging skin, dry skin, skin tone, and overall appearance **Time Frame:** ANOVA including weeks 6 and 12 **Description:** Expert clinical grading **Measure:** Objective Skin elasticity **Time Frame:** ANOVA including weeks 6 and 12 **Description:** Subjective Questionnaire Visual Analog Scale **Measure:** Subjective Skin elasticity **Time Frame:** ANOVA including weeks 6 and 12 **Description:** Ultrasound **Measure:** Skin Collagen Ultrasound **Time Frame:** ANOVA including weeks 6 and 12 **Description:** SIAsScope assessments **Measure:** Skin Collagen SIAsScope **Time Frame:** ANOVA including weeks 6 and 12 **Description:** HPLC of tape strips **Measure:** Skin Lipids **Time Frame:** ANOVA including weeks 6 and 12 **Description:** Total carotenoid concentration **Measure:** Skin Carotenoids **Time Frame:** ANOVA including weeks 6 and 12 ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Females in good health, and between the ages of 30 and 65 years old 2. Fitzpatrick Skin Type I-V 3. Mild to moderate loss of skin elasticity, wrinkles (global) and rough skin texture 4. Able to read, understand and sign an informed consent form 5. Willing and able to follow all study directions, attend study visits as scheduled and willing to accept the restrictions of the study 6. Willing and able to maintain regular diet, exercise, hydration, and sleep patterns throughout the study Exclusion Criteria: 1. Participating in any other clinical study 2. Acute or chronic disease or medical condition 3. Unreliable or unlikely to be available for the duration of the study 4. Routine use of tanning bed(s) 5. History of abnormal response to sunshine 6. Current usage of medications with contraindication of enhancing sun exposure, or medications for skin conditions. 7. History of allergic reactions, skin sensitization and/or known allergies to cosmetic ingredients, toiletries, sunscreens, etc. 8. Immunocompromised subjects 9. Subject has a history of unconventional sleep patterns 10. Started Hormone Replacement Therapy within the last three months 11. Using oral contraception for less than three months 12. Known to be pregnant, lactating or planning to become pregnant within six months 13. Unable to communicate or cooperate with the Principal Investigator due to language problems, poor mental development, or impaired cerebral function **Gender Based:** True **Healthy Volunteers:** True **Maximum Age:** 65 Years **Minimum Age:** 30 Years **Sex:** FEMALE **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Port Chester **Country:** United States **Facility:** International Research Services, Inc. **State:** New York **Zip:** 10573 ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Intervention Browse Module - Browse Branches - Abbrev: Ot - Name: Other Dietary Supplements - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: T407 - Name: Lutein - Relevance: HIGH - As Found: Neurostimulation ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03290079 **Brief Title:** Phase II Study of Pembrolizumab and Lenvatinib in Advanced Well-differentiated Neuroendocrine Tumors **Official Title:** Phase II Study of Pembrolizumab and Lenvatinib in Advanced Well-differentiated Neuroendocrine Tumors #### Organization Study ID Info **ID:** MCC-19207 #### Organization **Class:** OTHER **Full Name:** H. Lee Moffitt Cancer Center and Research Institute ### Status Module #### Completion Date **Date:** 2024-07 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-03-26 **Type:** ACTUAL **Last Update Submit Date:** 2024-02-26 **Overall Status:** ACTIVE_NOT_RECRUITING #### Primary Completion Date **Date:** 2023-01-10 **Type:** ACTUAL #### Results First Post Date **Date:** 2024-03-26 **Type:** ACTUAL **Results First Submit Date:** 2024-01-26 **Results First Submit QC Date:** 2024-02-26 #### Start Date **Date:** 2017-12-15 **Type:** ACTUAL **Status Verified Date:** 2024-02 #### Study First Post Date **Date:** 2017-09-21 **Type:** ACTUAL **Study First Submit Date:** 2017-09-19 **Study First Submit QC Date:** 2017-09-19 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** Merck Sharp & Dohme LLC #### Lead Sponsor **Class:** OTHER **Name:** H. Lee Moffitt Cancer Center and Research Institute #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** True **Is US Export:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** The purpose of this study is to: * Assess overall radiographic response rate (ORR) * Assess progression-free survival (PFS) * Test the safety and tolerability of Pembrolizumab in combination with lenvatinib ### Conditions Module **Conditions:** - Neuroendocrine Tumors - Neuroendocrine Carcinoma - Neuroendocrine Cancer **Keywords:** - well-differentiated neuroendocrine tumors ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP **Intervention Model Description:** Simon 2-stage design ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 20 **Type:** ACTUAL **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Pembrolizumab 200 mg will be administered as a 30 minute intravenous (IV) infusion every 3 weeks, in addition to 20 mg Lenvatinib by mouth every day of each 3 week cycle. Estimated average length of treatment per participant: 4 months. **Intervention Names:** - Drug: Pembrolizumab - Drug: Lenvatinib **Label:** Pembrolizumab & Lenvatinib treatment **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Pembrolizumab & Lenvatinib treatment **Description:** 200 mg Pembrolizumab by IV on Day 1 of each 3 week cycle. **Name:** Pembrolizumab **Other Names:** - Keytruda® **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Pembrolizumab & Lenvatinib treatment **Description:** 20 mg Lenvatinib by mouth every day of each 3 week cycle **Name:** Lenvatinib **Other Names:** - Lenvima® **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Response Evaluation Criteria in Solid Tumors (RECIST) based response rate. Complete Response (CR): Disappearance of all extranodal target lesions. All pathological lymph nodes must have decreased to \<10 mm in short axis. Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (SLD) of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): SLD increased by at least 20% from the smallest value on study (including baseline, if that is the smallest). The SLD must also demonstrate an absolute increase of at least 5mm. (Two lesions increasing from 2 mm to 3 mm, for example, does not qualify). Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. **Measure:** Objective Radiographic Response Rate (ORR) **Time Frame:** Up to 12 months #### Secondary Outcomes **Description:** DOR, defined as the time from first documented evidence of Complete Response (CR) or Partial Response (PR) until disease progression or death due to any cause, whichever occurs first. **Measure:** Duration of Response (DOR) **Time Frame:** Up to 12 months **Description:** PFS, defined as the time from initial treatment to the first documented disease progression according to RECIST 1.1, or death due to any cause, whichever occurs first. **Measure:** Progression Free Survival (PFS) **Time Frame:** Up to 12 months **Description:** OS defined as the time from initial treatment until death from any cause. **Measure:** Overall Survival (OS) **Time Frame:** At 12 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Diagnosis/Condition for entry into the trial: Metastatic well differentiated neuroendocrine tumors of primary lung, thymic, small bowel and colorectal origin (including unknown primary) * Evidence of radiographic disease progression with scan documenting progression occurring within 8 months of signing informed consent * At least two prior lines of systemic treatment. If the only prior line of treatment was adjuvant or neoadjuvant, patient must have completed treatment within 12 months. There is no limit to number of prior therapies. * Willing and able to provide written informed consent/assent for the trial. * ≥ 18 years of age on day of signing informed consent. * Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. * Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale. * Demonstrate adequate organ function and laboratory values. All screening labs should be performed within 14 days of treatment initiation. * Females of childbearing potential (FOCBP) should have a negative serum pregnancy within 72 hours prior to receiving the first dose of study medication. * FOCBP must agree to use adequate contraception as outlined in study documentation for the course of the through 120 days after the last dose of study medication. * Male participants of childbearing potential must agree to use an adequate method of contraception as outlined in study documentation, starting with the first dose of study therapy through 120 days after the last dose of study therapy. Exclusion Criteria: * Poorly differentiated neuroendocrine carcinoma * Pancreatic neuroendocrine tumor * 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. * 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. * Known history of active TB (Bacillus Tuberculosis) * Hypersensitivity to pembrolizumab or any of its excipients. * 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. * Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent. - Note: Potential participants with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study. Note: If have received major surgery within 3 weeks, must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy. Adequate wound healing after major surgery must be assessed clinically, independent of time elapsed for eligibility. * Serious non-healing wound, ulcer or bone fracture * Has pre-existing \>/= Grade 3 gastrointestinal (GI) or non-GI fistula * Has significant cardiovascular impairment within 12 months of the first dose of study drug * Known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer. * Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Potential participants with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four 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. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability. * Has active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy is not considered a form of systemic treatment. * History of (non-infectious) pneumonitis that required steroids, or current pneumonitis. * An active infection requiring systemic therapy. * 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. * Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. * 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. * Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent. * Has received prior therapy with a tyrosine kinase inhibitor (TKI) (e.g.; sunitinib, pazopanib, cabozantinib) * Known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies). * Known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA \[qualitative\] is detected). * Has received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed. * Uncontrolled hypertension defined as systolic blood pressure \>150 mmHg or diastolic pressure \>90 mmHg, despite optimal medical management * Thrombotic or embolic events such as a cerebrovascular accident including transient ischemic, attacks, DVT within the past 6 months * Bleeding or thrombotic disorders or use of anticoagulants, such as warfarin, or similar agents requiring therapeutic international normalized ration (INR) monitoring.(Treatment with low molecular weight heparin (LMWH) is allowed) * Marked baseline prolongation of QT/QTc interval (QTc interval ≥ 480 msec) using the Fridericia method (QTc = QT/RR0.33) for QTc analysis * Clinically significant bleeding within 4 weeks * Medical need for the continued use of potent inhibitors/inducers of CYP3A4 * Creatinine clearance \<30 mL/min * Any condition that impairs patient's ability to swallow whole pills or gastrointestinal malabsorption that, in the investigator's opinion, might affect absorption of lenvatinib **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Tampa **Country:** United States **Facility:** H. Lee Moffitt Cancer Center and Research Institute **State:** Florida **Zip:** 33612 #### Overall Officials **Official 1:** **Affiliation:** H. Lee Moffitt Cancer Center and Research Institute **Name:** Jonathan Strosberg, M.D. **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### See Also Links **Label:** Moffitt Cancer Center Clinical Trials website **URL:** https://moffitt.org/clinical-trials-research/ ## Document Section ### Large Document Module #### Large Docs - Date: 2018-12-10 - Filename: Prot_SAP_000.pdf - Has ICF: False - Has Protocol: True - Has SAP: True - Label: Study Protocol and Statistical Analysis Plan - Size: 843054 - Type Abbrev: Prot_SAP - Upload Date: 2024-01-24T09:38 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009369 - Term: Neoplasms - ID: D000017599 - Term: Neuroectodermal Tumors - ID: D000009373 - Term: Neoplasms, Germ Cell and Embryonal - ID: D000009370 - Term: Neoplasms by Histologic Type - ID: D000009380 - Term: Neoplasms, Nerve Tissue - ID: D000000230 - Term: Adenocarcinoma - ID: D000002277 - Term: Carcinoma - ID: D000009375 - Term: Neoplasms, Glandular and Epithelial ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: All - Name: All Conditions - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M5534 - Name: Carcinoma - Relevance: LOW - As Found: Unknown - ID: M20495 - Name: Neuroendocrine Tumors - Relevance: HIGH - As Found: Neuroendocrine Tumors - ID: M20423 - Name: Carcinoma, Neuroendocrine - Relevance: HIGH - As Found: Neuroendocrine Carcinoma - ID: M19845 - Name: Neuroectodermal Tumors - Relevance: LOW - As Found: Unknown - ID: M20388 - Name: Neuroectodermal Tumors, Primitive - Relevance: LOW - As Found: Unknown - ID: M12318 - Name: Neoplasms, Germ Cell and Embryonal - Relevance: LOW - As Found: Unknown - ID: M12315 - Name: Neoplasms by Histologic Type - Relevance: LOW - As Found: Unknown - ID: M12325 - Name: Neoplasms, Nerve Tissue - Relevance: LOW - As Found: Unknown - ID: M3585 - Name: Adenocarcinoma - Relevance: LOW - As Found: Unknown - ID: M12320 - Name: Neoplasms, Glandular and Epithelial - Relevance: LOW - As Found: Unknown - ID: T4091 - Name: Neuroendocrine Tumor - Relevance: HIGH - As Found: Neuroendocrine Tumors - ID: T4092 - Name: Neuroepithelioma - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000018358 - Term: Neuroendocrine Tumors - ID: D000018278 - Term: Carcinoma, Neuroendocrine ### 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 - ID: D000047428 - Term: Protein Kinase Inhibitors - 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: M349416 - Name: Pembrolizumab - Relevance: HIGH - As Found: Blind - ID: M353738 - Name: Lenvatinib - Relevance: HIGH - As Found: Fibrillation - ID: M1346 - Name: Antineoplastic Agents, Immunological - Relevance: LOW - As Found: Unknown - ID: M2342 - Name: Immune Checkpoint Inhibitors - 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 ### Intervention Browse Module - Meshes - ID: C000582435 - Term: Pembrolizumab - ID: C000531958 - Term: Lenvatinib ### Misc Info Module #### Submission Tracking ##### First MCP Info ###### Post Date - Date: 2024-02-20 - Type: ACTUAL - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module #### Event Groups **Group ID:** EG000 **Title:** Pembrolizumab & Lenvatinib Treatment **Deaths Num Affected:** 6 **Deaths Num At Risk:** 20 **Description:** Pembrolizumab 200 mg will be administered as a 30 minute intravenous (IV) infusion every 3 weeks, in addition to 20 mg Lenvatinib by mouth every day of each 3 week cycle. Estimated average length of treatment per participant: 4 months. Pembrolizumab: 200 mg Pembrolizumab by IV on Day 1 of each 3 week cycle. Lenvatinib: 20 mg Lenvatinib by mouth every day of each 3 week cycle **ID:** EG000 **Other Num Affected:** 20 **Other Num at Risk:** 20 **Serious Number Affected:** 12 **Serious Number At Risk:** 20 **Title:** Pembrolizumab & Lenvatinib Treatment **Frequency Threshold:** 0 #### Other Events **Term:** Abdominal Pain **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Diarrhea **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Constipation **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Nausea **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Vomiting **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Mucositis oral **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Gastrointestinal disorders - Other **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Notes:** mucus in stool **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Gastrointestinal disorders - Other **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Notes:** hernia **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Belching **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Bloating **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Dry mouth **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Dyspepsia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Gastritis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Gastroesophageal reflux disease **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Gastrointestinal pain **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Hemorrhoids **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Lip pain **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Lower gastrointestinal hemorrhage **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Oral hemorrhage **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Oral pain **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Rectal hemorrhage **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Toothache **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Fatigue **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Fever **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Pain **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Edema limbs **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Non-cardiac chest pain **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Chills **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Flu like symptoms **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Facial pain **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (5.0) **Term:** General disorders and administration site conditions - Other **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Headache **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Dizziness **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Dysgeusia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Lethargy **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Paresthesia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Presyncope **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Hypertension **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Hypotension **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Flushing **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Back pain **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Arthralgia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Flank pain **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Generalized muscle weakness **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Myalgia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Bone pain **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Muscle cramp **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Muscle weakness lower limb **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Sinus tachycardia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Pericardial effusion **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Sinus bradycardia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Palpitations **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Atrioventricular block complete **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Atrioventricular block first degree **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Cardiac disorders - Other **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Myocarditis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Weight loss **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** CTCAE (5.0) **Term:** Alanine aminotransferase increased **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** CTCAE (5.0) **Term:** Aspartate aminotransferase increased **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** CTCAE (5.0) **Term:** Thyroid stimulating hormone increased **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** CTCAE (5.0) **Term:** Electrocardiogram T wave abnormal **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** CTCAE (5.0) **Term:** Alkaline phosphatase increased **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** CTCAE (5.0) **Term:** Blood bilirubin increased **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** CTCAE (5.0) **Term:** Electrocardiogram QT corrected interval prolonged **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** CTCAE (5.0) **Term:** Investigations - Other **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** CTCAE (5.0) **Term:** Cough **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Dyspnea **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Epistaxis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Nasal congestion **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Hoarseness **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Sore throat **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Palmar-plantar erythrodysesthesia syndrome **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Rash maculo-papular **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Pruritus **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Pain of skin **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Skin and subcutaneous tissue disorders - Other **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Proteinuria **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Hematuria **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Urinary frequency **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Urinary incontinence **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Hypothyroidism **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Endocrine disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Endocrine disorders - Other **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Endocrine disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Hyperthyroidism **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Endocrine disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Urinary tract infection **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** CTCAE (5.0) **Term:** Infections and infestations - Other **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** CTCAE (5.0) **Term:** Kidney infection **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** CTCAE (5.0) **Term:** Otitis externa **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** CTCAE (5.0) **Term:** Papulopustular rash **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** CTCAE (5.0) **Term:** Prostate infection **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** CTCAE (5.0) **Term:** Upper respiratory infection **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** CTCAE (5.0) **Term:** Anorexia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Hyperglycemia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Dehydration **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Hyperkalemia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Hypoglycemia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Hypokalemia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Anxiety **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Confusion **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Depression **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Insomnia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Fall **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** CTCAE (5.0) **Term:** Bruising **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** CTCAE (5.0) **Term:** Fracture **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** CTCAE (5.0) **Term:** Injury, poisoning and procedural complications - Other **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** CTCAE (5.0) **Term:** Wound complication **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** CTCAE (5.0) **Term:** Eye disorders - Other **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Eye disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Eye pain **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Eye disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Watering eyes **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Eye disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Irregular menstruation **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Reproductive system and breast disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Reproductive system and breast disorders - Other **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Reproductive system and breast disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Eosinophilia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Lymph node pain **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Ear and labyrinth disorders - Other **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Ear and labyrinth disorders **Source Vocabulary:** CTCAE (5.0) **Term:** Vertigo **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Ear and labyrinth disorders **Source Vocabulary:** CTCAE (5.0) #### Serious Events **Term:** Kidney Infection **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** CTCAE (5.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 20 **Num Events:** 1 **Term:** Lower gastrointestinal hemorrhage **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (5.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 20 **Num Events:** 1 **Term:** Abdominal Pain **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (5.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 20 **Num Events:** 1 **Term:** Constipation **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** CTCAE (5.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 20 **Num Events:** 1 **Term:** Alanine aminotransferase increased **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** CTCAE (5.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 20 **Num Events:** 1 **Term:** Aspartate aminotransferase increased **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** CTCAE (5.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 20 **Num Events:** 1 **Term:** Disease Progression **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (5.0) ##### Stats **Group ID:** EG000 **Num Affected:** 3 **Num At Risk:** 20 **Num Events:** 3 **Term:** Fever **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (5.0) ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 20 **Num Events:** 2 **Term:** Rash maculo-papular **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** CTCAE (5.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 20 **Num Events:** 1 **Term:** Infections and infestations - Other **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Notes:** COVID-19 **Organ System:** Infections and infestations **Source Vocabulary:** CTCAE (5.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 20 **Num Events:** 1 **Term:** Infections and infestations - Other **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Notes:** human metapneumovirus **Organ System:** Infections and infestations **Source Vocabulary:** CTCAE (5.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 20 **Num Events:** 1 **Term:** Hypotension **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** CTCAE (5.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 20 **Num Events:** 1 **Term:** Urinary tract infection **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** CTCAE (5.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 20 **Num Events:** 1 **Term:** Death, NOS **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (5.0) ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 20 **Num Events:** 2 **Term:** Atrioventricular block complete **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** CTCAE (5.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 20 **Num Events:** 1 **Term:** Pericardial effusion **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** CTCAE (5.0) ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 20 **Num Events:** 2 **Term:** Sinus tachycardia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** CTCAE (5.0) ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 20 **Num Events:** 2 **Term:** Hip pain **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** CTCAE (5.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 20 **Num Events:** 1 **Term:** Hypoglycemia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** CTCAE (5.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 20 **Num Events:** 2 **Term:** Headache **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** CTCAE (5.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 20 **Num Events:** 1 **Term:** Dehydration **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** CTCAE (5.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 20 **Num Events:** 1 **Term:** Hypertension **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** CTCAE (5.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 20 **Num Events:** 1 **Time Frame:** Adverse events were collected from start of treatment to 30 days after cessation of treatment, an average of 8.5 months. Patients were followed for survival only for 12 months. ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 20 **Units:** Participants ### Group **ID:** BG000 **Title:** Pembrolizumab & Lenvatinib Treatment **Description:** Pembrolizumab 200 mg will be administered as a 30 minute intravenous (IV) infusion every 3 weeks, in addition to 20 mg Lenvatinib by mouth every day of each 3 week cycle. Estimated average length of treatment per participant: 4 months. Pembrolizumab: 200 mg Pembrolizumab by IV on Day 1 of each 3 week cycle. Lenvatinib: 20 mg Lenvatinib by mouth every day of each 3 week cycle ### 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:** 11 **Category Title:** >=65 years **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 8 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 12 **Category Title:** Male **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 4 **Category Title:** Hispanic or Latino #### Measurement **Group ID:** BG000 **Value:** 15 **Category Title:** Not Hispanic or Latino #### Measurement **Group ID:** BG000 **Value:** 1 **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:** 1 **Category Title:** Black or African American #### Measurement **Group ID:** BG000 **Value:** 18 **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:** 20 **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:** 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:** Moffitt Cancer Center **Phone:** 813-745-5553 **Title:** Jonathan Strosberg, MD ## Results Section - Outcome Measures Module ### Outcome Measure 1 ### Outcome Measure 2 ### Outcome Measure 3 ### Outcome Measure 4 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** .03 - **Spread:** - **Upper Limit:** .30 - **Value:** .1 **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 4.8 - **Spread:** - **Upper Limit:** 7.4 - **Value:** 6.5 **Title:** #### Outcome Measure 3 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 5.8 - **Spread:** - **Upper Limit:** 10.2 - **Value:** 8 **Title:** #### Outcome Measure 4 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 48.1 - **Spread:** - **Upper Limit:** 84.4 - **Value:** 70 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** Response Evaluation Criteria in Solid Tumors (RECIST) based response rate. Complete Response (CR): Disappearance of all extranodal target lesions. All pathological lymph nodes must have decreased to \<10 mm in short axis. Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (SLD) of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): SLD increased by at least 20% from the smallest value on study (including baseline, if that is the smallest). The SLD must also demonstrate an absolute increase of at least 5mm. (Two lesions increasing from 2 mm to 3 mm, for example, does not qualify). Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** NUMBER **Population Description:** Evaluable participants **Reporting Status:** POSTED **Time Frame:** Up to 12 months **Title:** Objective Radiographic Response Rate (ORR) **Type:** PRIMARY **Unit of Measure:** proportion of participants ##### Group **Description:** Pembrolizumab 200 mg will be administered as a 30 minute intravenous (IV) infusion every 3 weeks, in addition to 20 mg Lenvatinib by mouth every day of each 3 week cycle. Estimated average length of treatment per participant: 4 months. Pembrolizumab: 200 mg Pembrolizumab by IV on Day 1 of each 3 week cycle. Lenvatinib: 20 mg Lenvatinib by mouth every day of each 3 week cycle **ID:** OG000 **Title:** Pembrolizumab & Lenvatinib Treatment #### Outcome Measure 2 **Description:** DOR, defined as the time from first documented evidence of Complete Response (CR) or Partial Response (PR) until disease progression or death due to any cause, whichever occurs first. **Dispersion Type:** Full Range **Parameter Type:** MEAN **Population Description:** Evaluable participants **Reporting Status:** POSTED **Time Frame:** Up to 12 months **Title:** Duration of Response (DOR) **Type:** SECONDARY **Unit of Measure:** months ##### Group **Description:** Pembrolizumab 200 mg will be administered as a 30 minute intravenous (IV) infusion every 3 weeks, in addition to 20 mg Lenvatinib by mouth every day of each 3 week cycle. Estimated average length of treatment per participant: 4 months. Pembrolizumab: 200 mg Pembrolizumab by IV on Day 1 of each 3 week cycle. Lenvatinib: 20 mg Lenvatinib by mouth every day of each 3 week cycle **ID:** OG000 **Title:** Pembrolizumab & Lenvatinib Treatment #### Outcome Measure 3 **Description:** PFS, defined as the time from initial treatment to the first documented disease progression according to RECIST 1.1, or death due to any cause, whichever occurs first. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEDIAN **Reporting Status:** POSTED **Time Frame:** Up to 12 months **Title:** Progression Free Survival (PFS) **Type:** SECONDARY **Unit of Measure:** months ##### Group **Description:** Pembrolizumab 200 mg will be administered as a 30 minute intravenous (IV) infusion every 3 weeks, in addition to 20 mg Lenvatinib by mouth every day of each 3 week cycle. Estimated average length of treatment per participant: 4 months. Pembrolizumab: 200 mg Pembrolizumab by IV on Day 1 of each 3 week cycle. Lenvatinib: 20 mg Lenvatinib by mouth every day of each 3 week cycle **ID:** OG000 **Title:** Pembrolizumab & Lenvatinib Treatment #### Outcome Measure 4 **Description:** OS defined as the time from initial treatment until death from any cause. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** NUMBER **Reporting Status:** POSTED **Time Frame:** At 12 months **Title:** Overall Survival (OS) **Type:** SECONDARY **Unit of Measure:** percentage of participants ##### Group **Description:** Pembrolizumab 200 mg will be administered as a 30 minute intravenous (IV) infusion every 3 weeks, in addition to 20 mg Lenvatinib by mouth every day of each 3 week cycle. Estimated average length of treatment per participant: 4 months. Pembrolizumab: 200 mg Pembrolizumab by IV on Day 1 of each 3 week cycle. Lenvatinib: 20 mg Lenvatinib by mouth every day of each 3 week cycle **ID:** OG000 **Title:** Pembrolizumab & Lenvatinib Treatment ### Participant Flow Module #### Group **Description:** Pembrolizumab 200 mg will be administered as a 30 minute intravenous (IV) infusion every 3 weeks, in addition to 20 mg Lenvatinib by mouth every day of each 3 week cycle. Estimated average length of treatment per participant: 4 months. Pembrolizumab: 200 mg Pembrolizumab by IV on Day 1 of each 3 week cycle. Lenvatinib: 20 mg Lenvatinib by mouth every day of each 3 week cycle **ID:** FG000 **Title:** Pembrolizumab & Lenvatinib Treatment #### Period **Title:** Overall Study ##### Withdraw **Type:** Death ###### Reason **Group ID:** FG000 **Number of Subjects:** 2 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 20 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 18 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 2 **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT05555979 **Acronym:** ELECTRIC **Brief Title:** A Study to Assess Change in Patient Experience in Adult Participants With Chronic Lymphocytic Leukemia (CLL) Receiving Oral Venetoclax Tablets + Intravenous Rituximab or Bruton's Tyrosine Kinase Inhibitors Tablets in the United Kingdom **Official Title:** Qualitative, Cross-sectional Observational Study Exploring the Experience of Patients Prescribed Venetoclax+Rituximab or Bruton's Tyrosine Kinase Inhibitors for Chronic Lymphocytic Leukaemia in Clinical Practice in the UK #### Organization Study ID Info **ID:** P23-486 #### Organization **Class:** INDUSTRY **Full Name:** AbbVie ### Status Module #### Completion Date **Date:** 2024-04-10 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-17 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-16 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2024-04-10 **Type:** ACTUAL #### Start Date **Date:** 2022-12-14 **Type:** ACTUAL **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2022-09-27 **Type:** ACTUAL **Study First Submit Date:** 2022-09-23 **Study First Submit QC Date:** 2022-09-23 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** AbbVie #### 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:** Chronic lymphocytic leukemia (CLL), a form of Non-Hodgkin's Lymphoma, is the most common type of leukemia in adults, affecting approximately 3,800 people in the UK each year. This study will evaluate the patient experience of CLL in adult participants who are prescribed venetoclax+rituximab or Bruton's tyrosine kinase inhibitors in the United Kingdom (UK). Venetoclax+rituximab is a drug approved to treat CLL. Study participants will receive venetoclax+rituximab as prescribed by their study doctor in accordance with approved local label. Adult participants prescribed venetoclax+rituximab or Bruton's tyrosine kinase inhibitors will be enrolled. Around 140 participants will be enrolled in the study in approximately 10 sites in the UK. Participants will receive venetoclax tablets to be taken by mouth and rituximab intravenous (IV) injection according to the approved local label. There is expected to be no additional burden for participants in this trial. All study visits will occur during routine clinical practice. ### Conditions Module **Conditions:** - Chronic Lymphocytic Leukemia **Keywords:** - Chronic Lymphocytic Leukemia - Rituximab - Bruton's Tyrosine Kinase Inhibitor - Venetoclax - Venclexta - Venclyxto - ABT-199 - Cancer ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 100 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Participants treated with venetoclax+rituximab or bruton's tyrosine kinase inhibitors in accordance with approved local label. **Label:** Chronic Lymphocytic Leukemia (CLL) Participants ### Outcomes Module #### Primary Outcomes **Description:** Number of participants who report a change in CLL symptoms through qualitative interviews. **Measure:** Number of Participants with a Change in Chronic Lymphocytic Leukemia (CLL) Symptoms **Time Frame:** Day 1 ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Has a confirmed diagnosis of chronic lymphocytic leukemia (CLL) (as defined by 2008 Modified International Workshop for Chronic Lymphocytic Leukemia National Cancer Institute Working Group (IWCLL NCI-WG) Guidelines). * Has relapsed/refractory (R/R) disease having received only 1 prior line of treatment, which must have been a chemotherapy or chemoimmunotherapy treatment. * Has treatment experience with venetoclax+rituximab (Ven+R) or bruton's tyrosine kinase inhibitor (BTKi)s that meets the criteria for inclusion described in the protocol, for which recruitment targets have not yet been met. Exclusion Criteria: * Previously treated with a BTKi, a BCL-2 inhibitor or other investigational agents. * Has any other medical condition or disorder that, in the opinion of the site investigator or study director, could compromise participant's ability to give written informed consent and/or prevent or interfere with his or her ability to comply with study procedures and provide meaningful information about his or her CLL experience. **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Adult participants with second-line (2L) chronic lymphocytic leukemia (CLL) treated with venetoclax+rituximab or bruton's tyrosine kinase inhibitors per approved local label in the United Kingdom. ### Contacts Locations Module #### Locations **Location 1:** **City:** London **Country:** United Kingdom **Facility:** Barts Health NHS Trust /ID# 252717 **State:** London, City Of **Zip:** E1 2ES **Location 2:** **City:** Norwich **Country:** United Kingdom **Facility:** Norfolk and Norwich University Hospitals NHS Foundation Trust /ID# 252720 **State:** Norfolk **Zip:** NR4 7UY **Location 3:** **City:** Nottingham **Country:** United Kingdom **Facility:** Nottingham City Hospital /ID# 252716 **State:** Nottinghamshire **Zip:** NG5 1PB **Location 4:** **City:** Oxford **Country:** United Kingdom **Facility:** Oxford University Hospitals NHS Foundation Trust /ID# 252715 **State:** Oxfordshire **Zip:** OX3 9DU **Location 5:** **City:** Worthing **Country:** United Kingdom **Facility:** University Hospitals Sussex NHS Foundation Trust /ID# 252672 **State:** West Sussex **Zip:** BN11 2DH **Location 6:** **City:** Leicester **Country:** United Kingdom **Facility:** University Hospitals of Leicester NHS Trust /ID# 252719 **Zip:** LE1 5WW **Location 7:** **City:** London **Country:** United Kingdom **Facility:** The Royal Marsden NHS Foundation Trust /ID# 252655 **Zip:** SW3 6JJ **Location 8:** **City:** Portsmouth **Country:** United Kingdom **Facility:** Portsmouth Hospitals University NHS Trust /ID# 252722 **Zip:** PO6 3LY **Location 9:** **City:** Sunderland **Country:** United Kingdom **Facility:** Sunderland Royal Hospital /ID# 252495 **Zip:** SR4 7TN **Location 10:** **City:** Taunton **Country:** United Kingdom **Facility:** Taunton and Somerset NHS Foundation Trust /ID# 252721 **Zip:** TA1 5DA #### Overall Officials **Official 1:** **Affiliation:** AbbVie **Name:** ABBVIE INC. **Role:** STUDY_DIRECTOR ### IPD Sharing Statement Module **IPD Sharing:** UNDECIDED ### References Module #### See Also Links **Label:** Related Info. **URL:** https://www.rxabbvie.com/ ## 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 - ID: T4202 - Name: Oculocerebral Syndrome With Hypopigmentation - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000007938 - Term: Leukemia - ID: D000007945 - Term: Leukemia, Lymphoid - ID: D000015451 - Term: Leukemia, Lymphocytic, Chronic, B-Cell ### Intervention Browse Module - Browse Branches - Abbrev: ANeo - Name: Antineoplastic Agents - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: ARhu - Name: Antirheumatic Agents - Abbrev: AA - Name: Amino Acids ### Intervention Browse Module - Browse Leaves - ID: M249656 - Name: Venetoclax - Relevance: LOW - As Found: Unknown - ID: M373 - Name: Rituximab - Relevance: LOW - As Found: Unknown - ID: M2889 - Name: Tyrosine Kinase Inhibitors - Relevance: LOW - As Found: Unknown - ID: T22 - Name: Tyrosine - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05448079 **Brief Title:** The Effect of Sexual Counseling Given According to the PLISSIT Model on FSFI, MAS and SQOL-F of Postmenopausal Women **Official Title:** The Effect of Sexual Counseling Given According to the PLISSIT Model on Sexual Functions, Marital Adjustment and Quality of Sexual Life of Postmenopausal Women #### Organization Study ID Info **ID:** SuleymanDUAyşeAKBAYKISA-001 #### Organization **Class:** OTHER **Full Name:** Suleyman Demirel University ### Status Module #### Completion Date **Date:** 2021-02-26 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2022-07-07 **Type:** ACTUAL **Last Update Submit Date:** 2022-07-03 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2020-12-26 **Type:** ACTUAL #### Start Date **Date:** 2020-09-28 **Type:** ACTUAL **Status Verified Date:** 2022-07 #### Study First Post Date **Date:** 2022-07-07 **Type:** ACTUAL **Study First Submit Date:** 2022-05-24 **Study First Submit QC Date:** 2022-07-03 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Suleyman Demirel University #### Responsible Party **Investigator Affiliation:** Suleyman Demirel University **Investigator Full Name:** Ayşe Sevim AKBAY KISA **Investigator Title:** Principal Investigator **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False ### Description Module **Brief Summary:** This study was conducted as a randomized pretest-posttest study to examine the effect of sexual counseling based on the PLISSIT model on post-menopausal women's sexual functions, marital adjustment and quality of sexual life. Sixty women (Experimental=30, Control=30) that applied to the menopause policlinic of a Women Diseases Training and Research Hospital were included in the study. Two women dropped out later, so the study was completed with 58 (Experimental=29, Control=29) women. Firstly, women were separated into two groups according to the cut-point of (26,55) in The Female Sexual Function Index (FSFI) (those who score 26,6 and above or 26,5 and below) and then these two groups were divided into intervention and control groups randomly. Data were collected with Descriptive Questions Form, Menopause Symptom Evaluation Scale (MRS), FSFI, Marital adjustment Scale (MAS) and Sexual Quality of Life Questionnaire Scale - Female Version (SQOL-F) between September 07, 2020 and March 26, 2021. The intervention group was given sexual counselling, prepared in line with the PLISSIT model, for three weeks, once a week and lasting approximately one hour. The effect of the counseling was tested twelve weeks after counseling was completed. Women in the control group were also interviewed twice concurrent with the intervention group; once when the counseling began and once during the last assessment. Women in the control group filled some data forms. After the study was completed, the counseling was also given to women who wanted it, in the control group. Frequency and percentage values, descriptive statistics, Fisher's Exact Test, Pearson Chi Square, t tests, for non-normally distributed data Mann Whitney U test and the Wilcoxon test were used for data analysis. Keywords: Post-menopausal period, sexual counseling, PLISSIT model, nursing care **Detailed Description:** Akbay-Kısa, A. S., The effect of sexual counseling given according to the PLISSIT model on sexual functions, marital adjustment and quality of sexual life of postmenopausal women. Hacettepe University Graduate School Health Sciences, Obstetrics and Gynecological Nursing Programme, Doctorate Thesis, Ankara, 2021. This study was conducted as a randomized pretest-posttest study to examine the effect of sexual counseling based on the PLISSIT model on post-menopausal women's sexual functions, marital adjustment and quality of sexual life. Sixty women (Experimental=30, Control=30) that applied to the menopause policlinic of a Women Diseases Training and Research Hospital were included in the study. Two women dropped out later, so the study was completed with 58 (Experimental=29, Control=29) women. Firstly, women were separated into two groups according to the cut-point of (26,55) in The Female Sexual Function Index (those who score 26,6 and above or 26,5 and below) and then these two groups were divided into intervention and control groups randomly. Data were collected with Descriptive Questions Form, The Female Sexual Function Index, Marital adjustment Scale and Sexual Quality of Life Questionnaire Scale - Female Version between September 07, 2020 and March 26, 2021. Women were asked to fill the demographic questions form and survey forms based on their own self-evaluations while they were accompanied by the researcher. The intervention group was given sexual counselling, prepared in line with the PLISSIT model, for three weeks, once a week and lasting approximately one hour. The effect of the counseling was tested twelve weeks after counseling was completed. Women in the control group were also interviewed twice concurrent with the intervention group; once when the counseling began and once during the last assessment. During those interviews, women in the control group filled some data forms. After the study was completed, the counseling was also given to women who wanted it, in the control group. Frequency and percentage values, descriptive statistics, Fisher's Exact Test, Pearson Chi Square, t tests, for non-normally distributed data Mann Whitney U test and the Wilcoxon test were used for data analysis. Keywords: Post-menopausal period, sexual counseling, PLISSIT model, nursing care ### Conditions Module **Conditions:** - Postmenopause - Sexual Function - Marital Relationship ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** The sample was divided into intervention and control groups sexual counseling based on the PLISSIT model ##### Masking Info **Masking:** NONE **Primary Purpose:** SUPPORTIVE_CARE #### Enrollment Info **Count:** 58 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Sexual counseling according to the PLISSIT model, randomized pretest-posttest **Intervention Names:** - Other: Sexual counseling according to the PLISSIT model, randomized pretest-posttest **Label:** Sexual counseling intervention group according to the PLISSIT model **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Non-counseling group **Intervention Names:** - Other: Sexual counseling according to the PLISSIT model, randomized pretest-posttest **Label:** control **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Sexual counseling intervention group according to the PLISSIT model - control **Description:** experimental and control ,a randomized pretest-posttest study to examine **Name:** Sexual counseling according to the PLISSIT model, randomized pretest-posttest **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** Rosen et al \[2000\] developed this scale. It includes 19 items. Responses to some items range from 0 to 5 while others range from 1 to 5. The scores are summed up to create single Female Sexual Function Index score that ranges from 2 to 36. Higher scores mean better sexual functions. **Measure:** Female Sexual Function Index **Time Frame:** 28.09.2020- 02.04.2021. The research period for a participant takes approximately four months. **Description:** It was developed by Locke and Wallace (1959) and consists of 15 items. The validity and reliability for Turkish translation was conducted by Kışlak-Tutarel (1999). The response range for the items are as the following: Item 1 = 0-6 points, Item 2 to 9 = 0-5 points, Items 10, 12, and 14 = 0-2 points, Items 11 and 13 = 0-3 points, and Item 15 = 0-2 points. The scale minimum value is 0 and maximum value is 58. Higher scores mean better marital adjustment. **Measure:** Marital Adjustment Subscale **Time Frame:** 28.09.2020- 02.04.2021. The research period for a participant takes approximately four months. **Description:** It was developed by Symonds et al (2005) and consists of 18 items. Items are scored from 0 to 5. The scale minimum value is 0 and maximum value is 90. Higher scores mean better sexual quality in a women's life. **Measure:** The Sexual Quality Of Life-Female **Time Frame:** 28.09.2020- 02.04.2021. The research period for a participant takes approximately four months. **Description:** It was developed by Schneider et al (1992) The Turkish validity and reliability study was carried by Gürkan (2005). The scale has a minimum value of 0 and a maximum value of 44. Higher scores mean more symptoms in menopause. **Measure:** Menopause Rating Scale **Time Frame:** 28.09.2020- 02.04.2021. The research period for a participant takes approximately four months. ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Being in the first year of postmenopause, 2. Living with spouse/partner, 3. Having an active sex life, 4. Being able to speak, understand and read Turkish, 5. Entering menopause naturally, 6. Living within the borders of Ankara province, 7. Not having menopause at an early or late age (over 40 years and under 55 years old), 8. Not taking hormone replacement therapy, 9. Not using herbal treatment for menopause (containing estrogen), 10. Not having a type of cancer that may affect sexual function, 11. Not receiving chemotherapy / radiotherapy, 12. No health problems (Hypertension, Diabetes, Cardiovascular disease, Urinary incontinence), 13. Not having a mental illness and/or not using drugs (antipsychotic drugs, Spironolactone, etc.), 14. Not being diagnosed with COVID in the last month, 15. Not having a sexual dysfunction diagnosis / treatment history in himself or his partner, 16. Not getting sexual health counseling before. Exclusion Criteria: 1. Receiving sexual health counseling from another consultant during the working period, 2. Desiring to leave the research at any stage of the research, 3. Failure to attend at least one of the sexual health counseling sessions, 4. Not participating in the post-test, 5. Getting a diagnosis of COVID. **Gender Based:** True **Gender Description:** Postmenopause, female **Healthy Volunteers:** True **Maximum Age:** 55 Years **Minimum Age:** 42 Years **Sex:** FEMALE **Standard Ages:** - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Isparta **Country:** Turkey **Facility:** Suleyman Demirel University **Zip:** 32500 #### Overall Officials **Official 1:** **Affiliation:** Hacettepe University **Name:** Gülten HÜ Koç, asst. prof. **Role:** STUDY_DIRECTOR **Official 2:** **Affiliation:** Etlik Hastanesi **Name:** Berna EH Dilbaz, professor **Role:** STUDY_CHAIR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT01350479 **Brief Title:** Gown and Glove Use to Prevent the Spread of Infection in VA Community Living Centers **Official Title:** Gown and Glove Use to Prevent the Spread of Infection in VA Community Living Centers #### Organization Study ID Info **ID:** IIR 10-154 #### Organization **Class:** FED **Full Name:** VA Office of Research and Development ### Status Module #### Completion Date **Date:** 2016-11-01 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2017-10-05 **Type:** ACTUAL **Last Update Submit Date:** 2017-09-06 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2016-01-15 **Type:** ACTUAL #### Results First Post Date **Date:** 2017-03-15 **Type:** ACTUAL **Results First Submit Date:** 2016-11-16 **Results First Submit QC Date:** 2017-01-24 #### Start Date **Date:** 2012-10-01 **Type:** ACTUAL **Status Verified Date:** 2017-09 #### Study First Post Date **Date:** 2011-05-09 **Type:** ESTIMATED **Study First Submit Date:** 2011-05-06 **Study First Submit QC Date:** 2011-05-06 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** FED **Name:** VA Office of Research and Development #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** Methicillin-resistant S. aureus (MRSA) infections are a common cause of morbidity and mortality in nursing home residents. MRSA is predominantly spread from patient-to-patient by health care workers. The use of gowns, gloves and hand washing prevents this spread; however, their use detracts from a patient-centered, home-like environment which is an important priority for nursing homes. The goal of this project is to determine when it is most important for health care workers to wear gowns and to wash their hands when caring for MRSA colonized Veterans in community living centers. **Detailed Description:** Methicillin-resistant S. aureus (MRSA) infections are a common cause of morbidity and mortality in nursing home residents. MRSA is predominantly spread from patient-to-patient by health care workers. The use of gowns, gloves and hand washing prevents this spread; however, their use detracts from a patient-centered, home-like environment which is an important priority for nursing homes. The goal of this project is to determine when it is most important for health care workers to wear gowns and to wash their hands when caring for MRSA colonized Veterans in community living centers. To meet this goal, the investigators will enroll \~400 MRSA-colonized residents and health care workers from VA community living centers in four states and the District of Columbia. Additionally, the investigators will enroll some non-MRSA colonized residents as control subjects. Each enrolled resident will be followed for 6-25 episodes of care observations over 30 days. During each observation, the investigators will have health care workers wear disposable gowns and gloves during each care activity (e.g. wound dressing) that occurs during the study visit. At the end of each care activity, the investigators will swab the gown and gloves prior to disposing of them. Each swab will be tested for MRSA to determine if MRSA from the resident was transferred to the healthcare worker's gown or gloves during that episode of care. The results of the investigators' analysis will be used to develop new infection control guidelines which balance patient safety and a home-like, patient-centered environment. ### Conditions Module **Conditions:** - Methicillin-Resistant Staphylococcus Aureus **Keywords:** - Cross infection - Long term care ### Design Module #### Bio Spec **Description:** Swabs of the gowns and gloves of health care workers that interact with the participants will be tested for MRSA and other types of bacteria. Swabs from body sites (e.g. nose) of participants will be tested for MRSA and other types of bacteria. **Retention:** SAMPLES_WITHOUT_DNA #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 203 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Residents with history of MRSA in the past year **Label:** MRSA colonized #### Arm Group 2 **Description:** Residents without history of MRSA in the past year **Label:** Not MRSA colonized ### Outcomes Module #### Primary Outcomes **Description:** Presence of MRSA on gown or gloves worn by enrolled health care worker for research purposes while providing a specific type of care for enrolled resident **Measure:** MRSA Transmission **Time Frame:** Will be measured during 6-25 episodes of care interactions scheduled over the 30 days following resident enrollment ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: Resident: * Age 18 years * Reside in a participating LTCF for rehabilitation, skilled nursing or maintenance care * Expected length of stay of \>4 weeks from enrollment * Written informed consent from participant, or written informed consent from legally authorized representative (LAR) with assent from participant Health Care Worker: * Has direct interaction with participating residents at participating VA Long Term Care Facility (LTCF) * Verbal informed consent Exclusion Criteria: Residents: * None Health Care Worker: * Unable or unwilling to wear protective gown or gloves during healthcare workers (HCW)-resident interaction **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Veterans residing in a participating VA Long Term Care Facility ### Contacts Locations Module #### Locations **Location 1:** **City:** Washington, D.C. **Country:** United States **Facility:** Washington DC VA Medical Center, Washington, DC **State:** District of Columbia **Zip:** 20422 **Location 2:** **City:** Baltimore **Country:** United States **Facility:** Baltimore VA Medical Center VA Maryland Health Care System, Baltimore, MD **State:** Maryland **Zip:** 21201 **Location 3:** **City:** Baltimore **Country:** United States **Facility:** Rehabilitation R&D Service, Baltimore, MD **State:** Maryland **Zip:** 21202 **Location 4:** **City:** Perry Point **Country:** United States **Facility:** Perry Point VA Medical Center VA Maryland Health Care System, Perry Point, MD **State:** Maryland **Zip:** 21902 **Location 5:** **City:** Boston **Country:** United States **Facility:** VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA **State:** Massachusetts **Zip:** 02130 **Location 6:** **City:** Buffalo **Country:** United States **Facility:** VA Western New York Healthcare System, Buffalo, NY **State:** New York **Zip:** 14215 **Location 7:** **City:** San Antonio **Country:** United States **Facility:** South Texas Health Care System, San Antonio, TX **State:** Texas **Zip:** 78229 #### Overall Officials **Official 1:** **Affiliation:** Baltimore VA Medical Center VA Maryland Health Care System, Baltimore, MD **Name:** Mary-Claire Roghmann, MD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Pineles L, Morgan DJ, Lydecker A, Johnson JK, Sorkin JD, Langenberg P, Blanco N, Lesse A, Sellick J, Gupta K, Leykum L, Cadena J, Lepcha N, Roghmann MC. Transmission of methicillin-resistant Staphylococcus aureus to health care worker gowns and gloves during care of residents in Veterans Affairs nursing homes. Am J Infect Control. 2017 Sep 1;45(9):947-953. doi: 10.1016/j.ajic.2017.03.004. Epub 2017 Apr 18. **PMID:** 28431853 **Citation:** Jackson SS, Lydecker AD, Magder LS, Roghmann MC. Development and Validation of a Clinical Prediction Rule to Predict Transmission of Methicillin-Resistant Staphylococcus aureus in Nursing Homes. Am J Epidemiol. 2019 Jan 1;188(1):214-221. doi: 10.1093/aje/kwy220. **PMID:** 30351349 **Citation:** Roghmann MC, Andronescu LR, Stucke EM, Johnson JK. Clostridium difficile Colonization of Nursing Home Residents. Infect Control Hosp Epidemiol. 2017 Oct;38(10):1267-1268. doi: 10.1017/ice.2017.172. Epub 2017 Aug 22. No abstract available. **PMID:** 28826425 **Citation:** Blanco N, Pineles L, Lydecker AD, Johnson JK, Sorkin JD, Morgan DJ; VA Gown and Glove Investigators; Roghmann MC. Transmission of Resistant Gram-Negative Bacteria to Health Care Worker Gowns and Gloves during Care of Nursing Home Residents in Veterans Affairs Community Living Centers. Antimicrob Agents Chemother. 2017 Sep 22;61(10):e00790-17. doi: 10.1128/AAC.00790-17. Print 2017 Oct. **PMID:** 28717036 ## Derived Section ### Condition Browse Module - Browse Branches - Abbrev: BC01 - Name: Infections - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: Rare - Name: Rare 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: M6642 - Name: Cross Infection - Relevance: LOW - As Found: Unknown - ID: T4202 - Name: Oculocerebral Syndrome With Hypopigmentation - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000007239 - Term: Infections ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module **Description:** Only serious adverse events were collected. #### Event Groups **Group ID:** EG000 **Title:** MRSA Colonized **Description:** Residents colonized with MRSA by culture at study admission **ID:** EG000 **Serious Number Affected:** 9 **Serious Number At Risk:** 94 **Title:** MRSA Colonized **Group ID:** EG001 **Title:** Not MRSA Colonized **Description:** Residents not colonized with MRSA by culture at study admission **ID:** EG001 **Serious Number Affected:** 8 **Serious Number At Risk:** 106 **Title:** Not MRSA Colonized **Frequency Threshold:** 0 #### Serious Events **Term:** Hospitalization **Notes:** Residents transferred from nursing home to acute care hospital, unrelated to study **Organ System:** General disorders ##### Stats **Group ID:** EG000 **Num Affected:** 9 **Num At Risk:** 94 **Group ID:** EG001 **Num Affected:** 6 **Num At Risk:** 106 **Term:** Death **Notes:** Death of resident unrelated to study **Organ System:** General disorders ##### Stats **Group ID:** EG000 **Num At Risk:** 94 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 106 ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 94 **Group ID:** BG001 **Value:** 106 **Group ID:** BG002 **Value:** 200 **Units:** Participants ### Group **ID:** BG000 **Title:** MRSA Colonized **Description:** Residents colonized with MRSA by culture at study admission ### Group **ID:** BG001 **Title:** Not MRSA Colonized **Description:** Residents not colonized with MRSA by culture at study admission ### Group **ID:** BG002 **Title:** Total **Description:** Total of all reporting groups ### Measure #### Measurement **Group ID:** BG000 **Spread:** 13 **Value:** 73 #### Measurement **Group ID:** BG001 **Spread:** 13 **Value:** 70 #### Measurement **Group ID:** BG002 **Spread:** 13 **Value:** 71 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 2 #### Measurement **Group ID:** BG001 **Value:** 6 #### Measurement **Group ID:** BG002 **Value:** 8 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 92 #### Measurement **Group ID:** BG001 **Value:** 100 #### Measurement **Group ID:** BG002 **Value:** 192 **Category Title:** Male **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 94 #### Measurement **Group ID:** BG001 **Value:** 106 #### Measurement **Group ID:** BG002 **Value:** 200 **Class Title:** United States **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:** 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:** VA Maryland Healthcare System **Phone:** 410-706-0062 **Title:** Mary-Claire Roghmann ## 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:** 0.20 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0.02 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0.11 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0.01 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** Presence of MRSA on gown or gloves worn by enrolled health care worker for research purposes while providing a specific type of care for enrolled resident **Parameter Type:** NUMBER **Population Description:** We analyzed the number of gown and glove swabs from HCW interacting with MRSA and non-MRSA colonized residents. **Reporting Status:** POSTED **Time Frame:** Will be measured during 6-25 episodes of care interactions scheduled over the 30 days following resident enrollment **Title:** MRSA Transmission **Type:** PRIMARY **Type Units Analyzed:** swabs **Unit of Measure:** Proportion of swabs positive for MRSA ##### Group **Description:** Swabs collected from healthcare workers interacting with residents colonized with MRSA by culture on enrollment **ID:** OG000 **Title:** Swabs From Interactions With MRSA Colonized Residents ##### Group **Description:** Swabs collected from healthcare workers interacting with residents not colonized with MRSA by culture on enrollment **ID:** OG001 **Title:** Swabs From Interactions With Not MRSA Colonized Residents ### Participant Flow Module #### Group **Description:** Residents colonized with MRSA by culture at study admission **ID:** FG000 **Title:** MRSA Colonized #### Group **Description:** Residents not colonized with MRSA by culture at study admission **ID:** FG001 **Title:** Not MRSA Colonized #### Period **Title:** Overall Study ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 94 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 106 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 94 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 106 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 0 **Pre-Assignment Details:** Three participants withdrew from the study prior to cultures being obtained and were not assigned to a study group. **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT05080179 **Brief Title:** Impact of Nudges on Downloads of COVID-19 Exposure Notification Smartphone Apps: A Randomized Trial **Official Title:** The Interactive Effect of Social Norm and Self (vs. Others) Benefit Nudges on Downloads of COVID-19 Exposure Notification Smartphone Apps: A Randomized Trial #### Organization Study ID Info **ID:** 844564 #### Organization **Class:** OTHER **Full Name:** University of Pennsylvania ### Status Module #### Completion Date **Date:** 2021-01-28 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2023-08-28 **Type:** ACTUAL **Last Update Submit Date:** 2022-10-17 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2021-01-28 **Type:** ACTUAL #### Results First Post Date **Date:** 2023-08-28 **Type:** ACTUAL **Results First Submit Date:** 2022-02-02 **Results First Submit QC Date:** 2022-10-17 #### Start Date **Date:** 2020-12-11 **Type:** ACTUAL **Status Verified Date:** 2022-10 #### Study First Post Date **Date:** 2021-10-15 **Type:** ACTUAL **Study First Submit Date:** 2021-10-12 **Study First Submit QC Date:** 2021-10-13 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER_GOV **Name:** Pennsylvania Department of Health #### Lead Sponsor **Class:** OTHER **Name:** University of Pennsylvania #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Eligible participants who were active beneficiaries of a large insurer living in Pennsylvania were sent an email encouraging them to download the contact tracing app in Pennsylvania, COVID Alert PA. Participants will be randomly assigned to one of four conditions in a 2 (Self-benefit vs. Other-Benefit) x 2 (Social Norms Present vs. Social Norms absent) design. All participants received an email that said : "COVID Alert PA is the official Exposure Notification App from the Pennsylvania Department of Health. Join Penn Medicine in the fight against COVID-19 and download COVID Alert PA today!" ---Investigators manipulated the content here--- "The app uses Bluetooth to sense when one person is in close contact with another person with the app. If someone tests positive for COVID-19, and they decide to upload the information to the health department, people who have the app and who have been in contact with them will be alerted. If you are interested in downloading the app, please click COVID Alert PA. We appreciate you joining our efforts. Together we can beat COVID-19!" In the Other-Benefit condition, it said: "It can help you reduce your risk of unknowingly spreading the virus to your friends, family, and larger community." In the Self-Benefit condition, it said: "It can help you determine where and when to get testing, and how to get care if you need it." In the Social Norms Present condition, it said: "Over 650,000 Pennsylvanians have already downloaded the app!" In the Social Norms Absent condition, it said the statement about social norms above. Participants who do not open the initial email received a follow-up email. ### Conditions Module **Conditions:** - COVID-19 ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** FACTORIAL **Intervention Model Description:** This is a 2 (Self-Benefit vs. Other-Benefit) x 2 (Social Norm vs. No Social Norm) design. There are thus four conditions total. ##### Masking Info **Masking:** SINGLE **Masking Description:** Participants were unaware they were participating in a study, and were thus blinded to their treatment assignment. **Who Masked:** - PARTICIPANT **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 16903 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** As part of their email, they read, "It can help you determine where and when to get testing, and how to get care if you need it." and "Over 650,000 Pennsylvanians have already downloaded the app!" **Intervention Names:** - Behavioral: Self-Benefit/Social Norm **Label:** Self-Benefit/Social Norm **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** As part of their email, they read, "It can help you determine where and when to get testing, and how to get care if you need it." They did not read any information about the number of Pennsylvanians who downloaded the app. **Intervention Names:** - Behavioral: Self-Benefit/No Social Norm **Label:** Self-Benefit/No Social Norm **Type:** EXPERIMENTAL #### Arm Group 3 **Description:** As part of their email, they read, "It can help you reduce your risk of unknowingly spreading the virus to your friends, family, and larger community." and "Over 650,000 Pennsylvanians have already downloaded the app!" **Intervention Names:** - Behavioral: Other Benefit/Social Norm **Label:** Other Benefit/Social Norm **Type:** EXPERIMENTAL #### Arm Group 4 **Description:** As part of their email, they read, "It can help you reduce your risk of unknowingly spreading the virus to your friends, family, and larger community." They did not read any information about the number of Pennsylvanians who downloaded the app. **Intervention Names:** - Behavioral: Other Benefit/No Social Norm **Label:** Other Benefit/No Social Norm **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Self-Benefit/Social Norm **Description:** As part of their email, they will read, "It can help you determine where and when to get testing, and how to get care if you need it." and "Over 650,000 Pennsylvanians have already downloaded the app!" **Name:** Self-Benefit/Social Norm **Type:** BEHAVIORAL #### Intervention 2 **Arm Group Labels:** - Self-Benefit/No Social Norm **Description:** As part of their email, they will read, "It can help you determine where and when to get testing, and how to get care if you need it." They will not read any information about the number of Pennsylvanians who downloaded the app. **Name:** Self-Benefit/No Social Norm **Type:** BEHAVIORAL #### Intervention 3 **Arm Group Labels:** - Other Benefit/Social Norm **Description:** As part of their email, they will read, "It can help you reduce your risk of unknowingly spreading the virus to your friends, family, and larger community." and "Over 650,000 Pennsylvanians have already downloaded the app!" **Name:** Other Benefit/Social Norm **Type:** BEHAVIORAL #### Intervention 4 **Arm Group Labels:** - Other Benefit/No Social Norm **Description:** As part of their email, they will read, "It can help you reduce your risk of unknowingly spreading the virus to your friends, family, and larger community." They will not read any information about the number of Pennsylvanians who downloaded the app. **Name:** Other Benefit/No Social Norm **Type:** BEHAVIORAL ### Outcomes Module #### Primary Outcomes **Description:** The investigators measured choice to click on the link to download the COVID Alert PA app or not, conditional on opening the email. Because participants may not immediately open their e-mail, or may return to the e-mail to click the link, we allowed for a period of approximately 7 weeks or 48 days from date of initial e-mail for completion of outcome measure. **Measure:** Click on Link to Download COVID Alert PA App **Time Frame:** 48 days ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Eligible participants were active beneficiaries of a large insurer living in Pennsylvania. Exclusion Criteria: * Participants who did not subscribe to offers and promotions emails were excluded, as were Medigap beneficiaries. **Healthy Volunteers:** True **Sex:** ALL **Standard Ages:** - CHILD - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Philadelphia **Country:** United States **Facility:** Independence Blue Cross (IBX) **State:** Pennsylvania **Zip:** 19146 ### IPD Sharing Statement Module **IPD Sharing:** NO ## Document Section ### Large Document Module #### Large Docs - Date: 2020-11-23 - Filename: Prot_000.pdf - Has ICF: False - Has Protocol: True - Has SAP: False - Label: Study Protocol - Size: 338154 - Type Abbrev: Prot - Upload Date: 2022-02-02T13:49 - Date: 2020-12-11 - Filename: SAP_001.pdf - Has ICF: False - Has Protocol: False - Has SAP: True - Label: Statistical Analysis Plan - Size: 333176 - Type Abbrev: SAP - Upload Date: 2022-02-02T13:50 ## 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 ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module **Description:** No adverse events anticipated as study only involved sending e-mails and having people click links. #### Event Groups **Group ID:** EG000 **Title:** Self-Benefit/Social Norm **Deaths Num At Risk:** 4232 **Description:** As part of their email, they read, "It can help you determine where and when to get testing, and how to get care if you need it." and "Over 650,000 Pennsylvanians have already downloaded the app!" Self-Benefit/Social Norm: As part of their email, they will read, "It can help you determine where and when to get testing, and how to get care if you need it." and "Over 650,000 Pennsylvanians have already downloaded the app!" **ID:** EG000 **Other Num at Risk:** 4232 **Serious Number At Risk:** 4232 **Title:** Self-Benefit/Social Norm **Group ID:** EG001 **Title:** Self-Benefit/No Social Norm **Deaths Num At Risk:** 4246 **Description:** As part of their email, they read, "It can help you determine where and when to get testing, and how to get care if you need it." They did not read any information about the number of Pennsylvanians who downloaded the app. Self-Benefit/No Social Norm: As part of their email, they will read, "It can help you determine where and when to get testing, and how to get care if you need it." They will not read any information about the number of Pennsylvanians who downloaded the app. **ID:** EG001 **Other Num at Risk:** 4246 **Serious Number At Risk:** 4246 **Title:** Self-Benefit/No Social Norm **Group ID:** EG002 **Title:** Other Benefit/Social Norm **Deaths Num At Risk:** 4211 **Description:** As part of their email, they read, "It can help you reduce your risk of unknowingly spreading the virus to your friends, family, and larger community." and "Over 650,000 Pennsylvanians have already downloaded the app!" Other Benefit/Social Norm: As part of their email, they will read, "It can help you reduce your risk of unknowingly spreading the virus to your friends, family, and larger community." and "Over 650,000 Pennsylvanians have already downloaded the app!" **ID:** EG002 **Other Num at Risk:** 4211 **Serious Number At Risk:** 4211 **Title:** Other Benefit/Social Norm **Group ID:** EG003 **Title:** Other Benefit/No Social Norm **Deaths Num At Risk:** 4214 **Description:** As part of their email, they read, "It can help you reduce your risk of unknowingly spreading the virus to your friends, family, and larger community." They did not read any information about the number of Pennsylvanians who downloaded the app. Other Benefit/No Social Norm: As part of their email, they will read, "It can help you reduce your risk of unknowingly spreading the virus to your friends, family, and larger community." They will not read any information about the number of Pennsylvanians who downloaded the app. **ID:** EG003 **Other Num at Risk:** 4214 **Serious Number At Risk:** 4214 **Title:** Other Benefit/No Social Norm **Frequency Threshold:** 0 **Time Frame:** Study duration, 48 days ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 4232 **Group ID:** BG001 **Value:** 4246 **Group ID:** BG002 **Value:** 4211 **Group ID:** BG003 **Value:** 4214 **Group ID:** BG004 **Value:** 16903 **Units:** Participants ### Group **ID:** BG000 **Title:** Self-Benefit/Social Norm **Description:** As part of their email, they read, "It can help you determine where and when to get testing, and how to get care if you need it." and "Over 650,000 Pennsylvanians have already downloaded the app!" Self-Benefit/Social Norm: As part of their email, they will read, "It can help you determine where and when to get testing, and how to get care if you need it." and "Over 650,000 Pennsylvanians have already downloaded the app!" ### Group **ID:** BG001 **Title:** Self-Benefit/No Social Norm **Description:** As part of their email, they read, "It can help you determine where and when to get testing, and how to get care if you need it." They did not read any information about the number of Pennsylvanians who downloaded the app. Self-Benefit/No Social Norm: As part of their email, they will read, "It can help you determine where and when to get testing, and how to get care if you need it." They will not read any information about the number of Pennsylvanians who downloaded the app. ### Group **ID:** BG002 **Title:** Other Benefit/Social Norm **Description:** As part of their email, they read, "It can help you reduce your risk of unknowingly spreading the virus to your friends, family, and larger community." and "Over 650,000 Pennsylvanians have already downloaded the app!" Other Benefit/Social Norm: As part of their email, they will read, "It can help you reduce your risk of unknowingly spreading the virus to your friends, family, and larger community." and "Over 650,000 Pennsylvanians have already downloaded the app!" ### Group **ID:** BG003 **Title:** Other Benefit/No Social Norm **Description:** As part of their email, they read, "It can help you reduce your risk of unknowingly spreading the virus to your friends, family, and larger community." They did not read any information about the number of Pennsylvanians who downloaded the app. Other Benefit/No Social Norm: As part of their email, they will read, "It can help you reduce your risk of unknowingly spreading the virus to your friends, family, and larger community." They will not read any information about the number of Pennsylvanians who downloaded the app. ### Group **ID:** BG004 **Title:** Total **Description:** Total of all reporting groups ### Measure #### Measurement **Group ID:** BG000 **Spread:** 13.33 **Value:** 46.85 #### Measurement **Group ID:** BG001 **Spread:** 13.26 **Value:** 47.31 #### Measurement **Group ID:** BG002 **Spread:** 13.39 **Value:** 46.74 #### Measurement **Group ID:** BG003 **Spread:** 13.43 **Value:** 46.83 #### Measurement **Group ID:** BG004 **Spread:** 13.35 **Value:** 46.93 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 4232 **Group ID:** BG001 **Value:** 4246 **Group ID:** BG002 **Value:** 4211 **Group ID:** BG003 **Value:** 4214 **Group ID:** BG004 **Value:** 16903 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 1720 #### Measurement **Group ID:** BG001 **Value:** 1686 #### Measurement **Group ID:** BG002 **Value:** 1762 #### Measurement **Group ID:** BG003 **Value:** 1798 #### Measurement **Group ID:** BG004 **Value:** 6966 **Category Title:** Male #### Measurement **Group ID:** BG000 **Value:** 2512 #### Measurement **Group ID:** BG001 **Value:** 2560 #### Measurement **Group ID:** BG002 **Value:** 2449 #### Measurement **Group ID:** BG003 **Value:** 2416 #### Measurement **Group ID:** BG004 **Value:** 9937 **Category Title:** Female #### 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 **Category Title:** Unknown #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 4232 **Group ID:** BG001 **Value:** 4246 **Group ID:** BG002 **Value:** 4211 **Group ID:** BG003 **Value:** 4214 **Group ID:** BG004 **Value:** 16903 **Class Title:** ### Measure #### Measurement **Group ID:** BG004 **Value:** 0 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 0 **Group ID:** BG001 **Value:** 0 **Group ID:** BG002 **Value:** 0 **Group ID:** BG003 **Value:** 0 **Group ID:** BG004 **Value:** 0 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 4232 #### Measurement **Group ID:** BG001 **Value:** 4246 #### Measurement **Group ID:** BG002 **Value:** 4211 #### Measurement **Group ID:** BG003 **Value:** 4214 #### Measurement **Group ID:** BG004 **Value:** 16903 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 4232 **Group ID:** BG001 **Value:** 4246 **Group ID:** BG002 **Value:** 4211 **Group ID:** BG003 **Value:** 4214 **Group ID:** BG004 **Value:** 16903 **Class Title:** United States **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/Gender, Customized **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 **Population Description:** Pennsylvania members of a large private insurer. ## Results Section - More Information Module ### Certain Agreement ### Point of Contact **Email:** [email protected] **Organization:** University of Pennsylvania, Perelman School of Medicine **Phone:** 215-573-9987 **Title:** Dr. Erica Dixon ## 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:** 4232 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4246 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4211 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4214 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 353 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 380 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 355 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 744 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** The investigators measured choice to click on the link to download the COVID Alert PA app or not, conditional on opening the email. Because participants may not immediately open their e-mail, or may return to the e-mail to click the link, we allowed for a period of approximately 7 weeks or 48 days from date of initial e-mail for completion of outcome measure. **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Pennsylvania members of large private insurer. **Reporting Status:** POSTED **Time Frame:** 48 days **Title:** Click on Link to Download COVID Alert PA App **Type:** PRIMARY **Unit of Measure:** Participants ##### Group **Description:** As part of their email, they read, "It can help you determine where and when to get testing, and how to get care if you need it." and "Over 650,000 Pennsylvanians have already downloaded the app!" Self-Benefit/Social Norm: As part of their email, they will read, "It can help you determine where and when to get testing, and how to get care if you need it." and "Over 650,000 Pennsylvanians have already downloaded the app!" **ID:** OG000 **Title:** Self-Benefit/Social Norm ##### Group **Description:** As part of their email, they read, "It can help you determine where and when to get testing, and how to get care if you need it." They did not read any information about the number of Pennsylvanians who downloaded the app. Self-Benefit/No Social Norm: As part of their email, they will read, "It can help you determine where and when to get testing, and how to get care if you need it." They will not read any information about the number of Pennsylvanians who downloaded the app. **ID:** OG001 **Title:** Self-Benefit/No Social Norm ##### Group **Description:** As part of their email, they read, "It can help you reduce your risk of unknowingly spreading the virus to your friends, family, and larger community." and "Over 650,000 Pennsylvanians have already downloaded the app!" Other Benefit/Social Norm: As part of their email, they will read, "It can help you reduce your risk of unknowingly spreading the virus to your friends, family, and larger community." and "Over 650,000 Pennsylvanians have already downloaded the app!" **ID:** OG002 **Title:** Other Benefit/Social Norm ##### Group **Description:** As part of their email, they read, "It can help you reduce your risk of unknowingly spreading the virus to your friends, family, and larger community." They did not read any information about the number of Pennsylvanians who downloaded the app. Other Benefit/No Social Norm: As part of their email, they will read, "It can help you reduce your risk of unknowingly spreading the virus to your friends, family, and larger community." They will not read any information about the number of Pennsylvanians who downloaded the app. **ID:** OG003 **Title:** Other Benefit/No Social Norm ### Participant Flow Module #### Group **Description:** As part of their email, they read, "It can help you determine where and when to get testing, and how to get care if you need it." and "Over 650,000 Pennsylvanians have already downloaded the app!" Self-Benefit/Social Norm: As part of their email, they will read, "It can help you determine where and when to get testing, and how to get care if you need it." and "Over 650,000 Pennsylvanians have already downloaded the app!" **ID:** FG000 **Title:** Self-Benefit/Social Norm #### Group **Description:** As part of their email, they read, "It can help you determine where and when to get testing, and how to get care if you need it." They did not read any information about the number of Pennsylvanians who downloaded the app. Self-Benefit/No Social Norm: As part of their email, they will read, "It can help you determine where and when to get testing, and how to get care if you need it." They will not read any information about the number of Pennsylvanians who downloaded the app. **ID:** FG001 **Title:** Self-Benefit/No Social Norm #### Group **Description:** As part of their email, they read, "It can help you reduce your risk of unknowingly spreading the virus to your friends, family, and larger community." and "Over 650,000 Pennsylvanians have already downloaded the app!" Other Benefit/Social Norm: As part of their email, they will read, "It can help you reduce your risk of unknowingly spreading the virus to your friends, family, and larger community." and "Over 650,000 Pennsylvanians have already downloaded the app!" **ID:** FG002 **Title:** Other Benefit/Social Norm #### Group **Description:** As part of their email, they read, "It can help you reduce your risk of unknowingly spreading the virus to your friends, family, and larger community." They did not read any information about the number of Pennsylvanians who downloaded the app. Other Benefit/No Social Norm: As part of their email, they will read, "It can help you reduce your risk of unknowingly spreading the virus to your friends, family, and larger community." They will not read any information about the number of Pennsylvanians who downloaded the app. **ID:** FG003 **Title:** Other Benefit/No Social Norm #### Period **Title:** Overall Study ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 4232 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 4246 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 4211 ###### Achievement **Group ID:** FG003 **Number of Subjects:** 4214 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 353 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 380 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 355 ###### Achievement **Group ID:** FG003 **Number of Subjects:** 744 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 3879 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 3866 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 3856 ###### Achievement **Group ID:** FG003 **Number of Subjects:** 3470 **Pre-Assignment Details:** For this study, participants are considered enrolled once they open the e-mail that is sent to them by the large private insurer. **Recruitment Details:** 39,938 Pennsylvania members of a larger insurer were randomly assigned to receive one email in a 2 (Focus on Self vs. Focus on Others) x 2 (Social Norm vs. No Social Norm) design. 16,903 members opened the e-mail - this is considered enrollment for the purposes of our study. **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT01809379 **Brief Title:** Intraperitoneal Aerosol High-pressure Chemotherapy for Women With Recurrent Ovarian Cancer **Official Title:** Feasibility, Efficacy and Safety of Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) With Cisplatin and Doxorubicin in Women With Recurrent Ovarian Cancer: an Open-label, Single-arm Phase II Clinical Trial #### Organization Study ID Info **ID:** PIPAC-OV1 #### Organization **Class:** OTHER **Full Name:** Ruhr University of Bochum ### Status Module #### Completion Date **Date:** 2014-09 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2022-07-08 **Type:** ACTUAL **Last Update Submit Date:** 2022-07-07 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2014-03 **Type:** ACTUAL #### Start Date **Date:** 2013-02 **Status Verified Date:** 2022-07 #### Study First Post Date **Date:** 2013-03-12 **Type:** ESTIMATED **Study First Submit Date:** 2013-03-08 **Study First Submit QC Date:** 2013-03-08 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Ruhr University of Bochum #### Responsible Party **Investigator Affiliation:** Ruhr University of Bochum **Investigator Full Name:** Clemens Tempfer **Investigator Title:** Prof. Dr. med. Clemens Tempfer, MBA **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** This trial aims to assess efficacy and safety of an intraperitoneal, aerosol, high-pressure chemotherapy in women with recurrent ovarian cancer **Detailed Description:** This study aims to investigate the therapeutic efficacy of PIPAC using doxorubicin and cisplatin in women with recurrent ovarian cancer and disease progression with peritoneal carcinomatosis. The primary objective of this study is to determine the Clinical Benefit Rate (CBR) according to RECIST criteria after three cycles of PIPAC with cisplatin and doxorubicin. ### Conditions Module **Conditions:** - Recurrent Ovarian Cancer **Keywords:** - ovarian cancer, recurrent, chemotherapy, intraperitoneal ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 69 **Type:** ACTUAL **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Intraperitoneal chemotherapy with cisplatin at a dose of 7.5 mg/m2 body surface in a 150 ml NaCl 0.9% and doxorubicin at a dose of 1.5 mg/m2 body surface in a 50 ml NaCl 0.9% solution with a flow of 30 ml/min and a max upstream pressure of 200 psi. **Intervention Names:** - Drug: chemotherapy with doxorubicin and cisplatin **Label:** intraperitoneal chemotherapy **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - intraperitoneal chemotherapy **Description:** intraperitoneal chemotherapy applied as an aerosol and under pressure **Name:** chemotherapy with doxorubicin and cisplatin **Other Names:** - CISPLATIN Teva, Adrimedac **Type:** DRUG ### Outcomes Module #### Other Outcomes **Description:** various measures of response to therapy on the clinical, biochemical, and histological level **Measure:** tumor apoptosis assessment, videolaparoscopy assessment of response, CA 125 assessment of response **Time Frame:** 6 months #### Primary Outcomes **Description:** The clinical benefit rate comprises complete remission, partial remission, and stable disease according to RECIST criteria. **Measure:** Clinical Benefit Rate **Time Frame:** 6 months #### Secondary Outcomes **Description:** left heart ejection fraction, neurological status, laparoscopy complications intraoperative, laparoscopy complications postoperative until hospital discharge, re-admission to hospital, death **Measure:** safety **Time Frame:** 6 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * at least 2 lines of previous chemotherapy * recurrent ovarian cancer * patient is mobile * informed consent Exclusion Criteria: * ileus * necessity of parenteral nutrition **Maximum Age:** 80 Years **Minimum Age:** 18 Years **Sex:** FEMALE **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Bochum **Country:** Germany **Facility:** Ruhr University Bochum **State:** NRW **Zip:** 44623 #### Overall Officials **Official 1:** **Affiliation:** Runr University Bochum **Name:** Clemens Tempfer, MD **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### References **Citation:** Tempfer CB, Winnekendonk G, Solass W, Horvat R, Giger-Pabst U, Zieren J, Rezniczek GA, Reymond MA. Pressurized intraperitoneal aerosol chemotherapy in women with recurrent ovarian cancer: A phase 2 study. Gynecol Oncol. 2015 May;137(2):223-8. doi: 10.1016/j.ygyno.2015.02.009. Epub 2015 Feb 18. **PMID:** 25701703 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000020969 - Term: Disease Attributes - ID: D000010335 - Term: Pathologic Processes - ID: D000004701 - Term: Endocrine Gland Neoplasms - ID: D000009371 - Term: Neoplasms by Site - ID: D000009369 - Term: Neoplasms - ID: D000010049 - Term: Ovarian Diseases - ID: D000000291 - Term: Adnexal Diseases - 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: D000005833 - Term: Genital Neoplasms, Female - ID: D000014565 - Term: Urogenital Neoplasms - ID: D000091662 - Term: Genital Diseases - ID: D000004700 - Term: Endocrine System Diseases - ID: D000006058 - Term: Gonadal Disorders - ID: D000002277 - Term: Carcinoma - ID: D000009375 - Term: Neoplasms, Glandular and Epithelial - ID: D000009370 - Term: Neoplasms by Histologic Type ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC04 - Name: Neoplasms - Abbrev: BXS - Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions - Abbrev: BC19 - Name: Gland and Hormone Related Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M14850 - Name: Recurrence - Relevance: HIGH - As Found: Recurrent - ID: M12974 - Name: Ovarian Neoplasms - Relevance: HIGH - As Found: Ovarian Cancer - ID: M1704 - Name: Carcinoma, Ovarian Epithelial - Relevance: HIGH - As Found: Ovarian Cancer - ID: M5534 - Name: Carcinoma - Relevance: LOW - As Found: Unknown - ID: M22700 - Name: Disease Attributes - Relevance: LOW - As Found: Unknown - ID: M7863 - Name: Endocrine Gland Neoplasms - Relevance: LOW - As Found: Unknown - ID: M12972 - Name: Ovarian Diseases - Relevance: LOW - As Found: Unknown - ID: M3643 - Name: Adnexal Diseases - 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: M8945 - Name: Genital Neoplasms, Female - Relevance: LOW - As Found: Unknown - ID: M17315 - Name: Urogenital Neoplasms - Relevance: LOW - As Found: Unknown - ID: M7862 - Name: Endocrine System Diseases - Relevance: LOW - As Found: Unknown - ID: M9163 - Name: Gonadal Disorders - 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: T4352 - Name: Ovarian Cancer - Relevance: HIGH - As Found: Ovarian Cancer - ID: T4354 - Name: Ovarian Epithelial Cancer - Relevance: HIGH - As Found: Ovarian Cancer ### Condition Browse Module - Meshes - ID: D000010051 - Term: Ovarian Neoplasms - ID: D000077216 - Term: Carcinoma, Ovarian Epithelial - ID: D000012008 - Term: Recurrence ### Intervention Browse Module - Ancestors - ID: D000000970 - Term: Antineoplastic Agents - ID: D000000903 - Term: Antibiotics, Antineoplastic - ID: D000059005 - Term: Topoisomerase II Inhibitors - ID: D000059003 - Term: Topoisomerase Inhibitors - ID: D000004791 - Term: Enzyme 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 - Abbrev: PhSol - Name: Pharmaceutical Solutions - Abbrev: Infe - Name: Anti-Infective Agents ### Intervention Browse Module - Browse Leaves - ID: M7492 - Name: Doxorubicin - Relevance: HIGH - As Found: Women - ID: M227339 - Name: Liposomal doxorubicin - Relevance: LOW - As Found: Unknown - ID: M21860 - Name: Pharmaceutical Solutions - Relevance: LOW - As Found: Unknown - ID: M6182 - Name: Cisplatin - Relevance: HIGH - As Found: High - ID: M4222 - Name: Anti-Bacterial Agents - Relevance: LOW - As Found: Unknown - ID: M4224 - Name: Antibiotics, Antitubercular - Relevance: LOW - As Found: Unknown - ID: M7951 - Name: Enzyme Inhibitors - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000002945 - Term: Cisplatin - ID: D000004317 - Term: Doxorubicin ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT01446679 **Acronym:** ALWAYS **Brief Title:** Special Drug Use-Results Survey of Lipitor Tablets **Official Title:** Special Drug Use-Results Survey of Lipitor Tablets #### Organization Study ID Info **ID:** LIP003 #### Organization **Class:** INDUSTRY **Full Name:** Astellas Pharma Inc ### Status Module #### Completion Date **Date:** 2012-03 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2013-02-21 **Type:** ESTIMATED **Last Update Submit Date:** 2013-02-20 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2012-03 **Type:** ACTUAL #### Start Date **Date:** 2010-09 **Status Verified Date:** 2013-02 #### Study First Post Date **Date:** 2011-10-05 **Type:** ESTIMATED **Study First Submit Date:** 2011-09-22 **Study First Submit QC Date:** 2011-10-03 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Astellas Pharma Inc #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** This study is to evaluate the controlling effect of atrovastatin on plasma lipid to achieve the category-specific targeted lipid levels. **Detailed Description:** To confirm the low-density lipoprotein cholesterol (LDL-C)-lowering effect of 24 weeks of treatment with Lipitor®(Generic Name : atorvastatin calcium) Tablets and determine the rate of achievement of the category-specific target LDL-C level in patients with hypercholesterolemia; and to confirm the usefulness (efficacy and safety) of atorvastatin in patients who have not responded sufficiently to other statin therapies ### Conditions Module **Conditions:** - Hypercholesterolemia **Keywords:** - Lipitor - HMG-CoA reductase inhibitor ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 24050 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Who receive atrovastatin **Intervention Names:** - Drug: atrovastatin **Label:** atrovastatin group ### Interventions #### Intervention 1 **Arm Group Labels:** - atrovastatin group **Description:** oral **Name:** atrovastatin **Other Names:** - Lipitor **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Measure:** Changes in plasma LDL-C concentration **Time Frame:** 0, 4, 12 and 24 week **Measure:** Change in rate of achievement of the category-specific target LDL-C level **Time Frame:** 0, 4, 12 and 24 week #### Secondary Outcomes **Measure:** Change in plasma lipid values (LDL cholesterol, HDL cholesterol, triglycerides, total cholesterol, and malondialdehyde-modified LDL [MDL-LDL]) **Time Frame:** 0, 4, 12 and 24 week **Measure:** Changes in renal function test values (urinary albumin, urinary creatinine, urinary protein, and serum creatinine) **Time Frame:** 0, 4, 12 and 24 week ### Eligibility Module **Eligibility Criteria:** Patients with hypercholesterolemia who have not achieved the category-specific target lipid level **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - CHILD - ADULT - OLDER_ADULT **Study Population:** Patients with hypercholesterolemia who have not achieved the category-specific target lipid level in other statin therapies ### Contacts Locations Module #### Locations **Location 1:** **City:** Chubu **Country:** Japan **Location 2:** **City:** Chugoku **Country:** Japan **Location 3:** **City:** Hokkaido **Country:** Japan **Location 4:** **City:** Kansai **Country:** Japan **Location 5:** **City:** Kantou **Country:** Japan **Location 6:** **City:** Kyushu **Country:** Japan **Location 7:** **City:** Shikoku **Country:** Japan **Location 8:** **City:** Touhoku **Country:** Japan #### Overall Officials **Official 1:** **Affiliation:** Astellas Pharma Inc **Name:** Use Central Contract **Role:** STUDY_CHAIR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000006949 - Term: Hyperlipidemias - ID: D000050171 - Term: Dyslipidemias - ID: D000052439 - Term: Lipid Metabolism Disorders - 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: M9988 - Name: Hypercholesterolemia - Relevance: HIGH - As Found: Hypercholesterolemia - ID: M10000 - Name: Hyperlipidemias - Relevance: LOW - As Found: Unknown - ID: M10002 - Name: Hyperlipoproteinemias - Relevance: LOW - As Found: Unknown - ID: M26181 - Name: Dyslipidemias - Relevance: LOW - As Found: Unknown - ID: M11639 - Name: Metabolic Diseases - Relevance: LOW - As Found: Unknown - ID: M27029 - Name: Lipid Metabolism Disorders - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000006937 - Term: Hypercholesterolemia ### Intervention Browse Module - Ancestors - ID: D000000924 - Term: Anticholesteremic Agents - ID: D000000960 - Term: Hypolipidemic Agents - ID: D000000963 - Term: Antimetabolites - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000057847 - Term: Lipid Regulating Agents - ID: D000019161 - Term: Hydroxymethylglutaryl-CoA Reductase Inhibitors - ID: D000004791 - Term: Enzyme Inhibitors ### Intervention Browse Module - Browse Branches - Abbrev: Lipd - Name: Lipid Regulating Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M351 - Name: Atorvastatin - Relevance: HIGH - As Found: 1 year - ID: M21155 - Name: Hydroxymethylglutaryl-CoA Reductase Inhibitors - Relevance: LOW - As Found: Unknown - ID: M4243 - Name: Anticholesteremic Agents - Relevance: LOW - As Found: Unknown - ID: M4278 - Name: Hypolipidemic Agents - Relevance: LOW - As Found: Unknown - ID: M4281 - Name: Antimetabolites - Relevance: LOW - As Found: Unknown - ID: M28883 - Name: Lipid Regulating Agents - Relevance: LOW - As Found: Unknown - ID: M7951 - Name: Enzyme Inhibitors - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000069059 - Term: Atorvastatin ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00556179 **Brief Title:** Lactoserum (Dermacyd Femina®) and Prevention of Recurrence of Bacterial Vaginosis **Official Title:** Local, National (Brazil), Multicentric, Open, Non-Controlled, Phase IV, Study of Lactoserum (Dermacyd Femina®), in Women at Reproductive Age, to Prevent Recurrence of Bacterial Vaginosis, During Three Months, After Standard Treatment With Metronidazole. #### Organization Study ID Info **ID:** LACTO_L_02399 #### Organization **Class:** INDUSTRY **Full Name:** Sanofi ### Status Module #### Expanded Access Info #### Last Update Post Date **Date:** 2009-01-22 **Type:** ESTIMATED **Last Update Submit Date:** 2009-01-21 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2008-12 **Type:** ACTUAL #### Start Date **Date:** 2007-09 **Status Verified Date:** 2009-01 #### Study First Post Date **Date:** 2007-11-09 **Type:** ESTIMATED **Study First Submit Date:** 2007-11-08 **Study First Submit QC Date:** 2007-11-08 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Sanofi #### Responsible Party **Old Name Title:** Medical Affairs Study Director **Old Organization:** sanofi-aventis ### Description Module **Brief Summary:** The purpose of this study is to demonstrate if the use of Dermacyd can avoid the recurrence of bacterial vaginosis after three months of the standard treatment. ### Conditions Module **Conditions:** - Bacterial Vaginosis ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 122 **Type:** ACTUAL **Phases:** - PHASE4 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Intervention Names:** - Drug: Lactoserum (Dermacyd Femina®) **Label:** 1 **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - 1 **Description:** Once a day during three months **Name:** Lactoserum (Dermacyd Femina®) **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Measure:** Rate of recurrence of bacterial vaginosis after three months of treatment. **Time Frame:** Three months #### Secondary Outcomes **Measure:** Quality of life **Time Frame:** Three months **Measure:** Vaginal Candidiasis **Time Frame:** Three months **Measure:** AE, particularly genital irritation (tolerability use of dermacyd) **Time Frame:** During the study ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Women in reproductive age * Confirmed cure of bacterial vaginosis after treatment with oral metronidazole. * Vaginal bacterioscopic examination negative for candida and trichomonas. Exclusion Criteria: * Pregnant or breastfeeding women * Allergy to dermacyd The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial. **Maximum Age:** 50 Years **Minimum Age:** 18 Years **Sex:** FEMALE **Standard Ages:** - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** São Paulo **Country:** Brazil **Facility:** Sanofi-aventis #### Overall Officials **Official 1:** **Affiliation:** Sanofi-aventis administrative office Brazil **Name:** Jaderson Lima **Role:** STUDY_DIRECTOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000020969 - Term: Disease Attributes - ID: D000010335 - Term: Pathologic Processes - 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 - ID: D000001424 - Term: Bacterial Infections - ID: D000001423 - Term: Bacterial Infections and Mycoses - ID: D000007239 - Term: Infections - ID: D000014627 - Term: Vaginitis ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC01 - Name: Infections - Abbrev: BXS - Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions ### Condition Browse Module - Browse Leaves - ID: M14850 - Name: Recurrence - Relevance: HIGH - As Found: Recurrence - ID: M18971 - Name: Vaginosis, Bacterial - Relevance: HIGH - As Found: Bacterial Vaginosis - ID: M17371 - Name: Vaginal Diseases - Relevance: HIGH - As Found: Vaginosis - ID: M22700 - Name: Disease Attributes - 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: 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: M12136 - Name: Mycoses - Relevance: LOW - As Found: Unknown - ID: M4721 - Name: Bacterial Infections and Mycoses - Relevance: LOW - As Found: Unknown - ID: M17375 - Name: Vaginitis - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000016585 - Term: Vaginosis, Bacterial - ID: D000014623 - Term: Vaginal Diseases - ID: D000012008 - Term: Recurrence ### Intervention Browse Module - Browse Branches - Abbrev: Infe - Name: Anti-Infective Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M11767 - Name: Metronidazole - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00010179 **Brief Title:** Lurtotecan Liposome in Treating Patients With Advanced or Recurrent Ovarian Epithelial Cancer **Official Title:** Randomized Phase II Study Of NX 211 Given By Two Different Intravenous Schedules In Advanced And/Or Recurrent Epithelial Ovarian Cancer #### Organization Study ID Info **ID:** I138 #### Organization **Class:** NETWORK **Full Name:** Canadian Cancer Trials Group #### Secondary ID Infos **Domain:** PDQ **ID:** CAN-NCIC-IND138 **Type:** OTHER **Domain:** PDQ **ID:** CDR0000068453 **Type:** OTHER ### Status Module #### Completion Date **Date:** 2008-09-22 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2020-04-06 **Type:** ACTUAL **Last Update Submit Date:** 2020-04-02 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2002-10-22 **Type:** ACTUAL #### Start Date **Date:** 2000-10-31 **Type:** ACTUAL **Status Verified Date:** 2020-04 #### Study First Post Date **Date:** 2004-02-26 **Type:** ESTIMATED **Study First Submit Date:** 2001-02-02 **Study First Submit QC Date:** 2004-02-25 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** NETWORK **Name:** NCIC Clinical Trials Group #### 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: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing of die. PURPOSE: Randomized phase II trial to compare the effectiveness of two treatment regimens of lurtotecan liposome in patients who have advanced or recurrent ovarian epithelial cancer, primary fallopian tube cancer, or peritoneal cancer that has been previously treated with chemotherapy. **Detailed Description:** OBJECTIVES: I. Compare the anti-tumor efficacy of two treatment schedules of lurtotecan liposome, in terms of clinical/radiological response and CA125 tumor marker, in patients with previously treated advanced or recurrent ovarian epithelial cancer. II. Compare the safety, pharmacokinetics, and possible pharmacokinetic/pharmacodynamic relationships of these treatment schedules in these patients. III. Compare the time to progression in patients treated with these treatment schedules. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to time from last prior chemotherapy (less than 6 months vs 6 months or more) and number of prior chemotherapy regimens (1 vs 2). Patients are randomized to one of two treatment arms. Arm I: Patients receive lurtotecan liposome IV over 30 minutes on days 1-3. Arm II: Patients receive lurtotecan liposome IV over 30 minutes on days 1 and 8. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients achieving complete response (CR) receive 2 additional courses after documented CR. Patients achieving partial response (PR) receive 4 additional courses after documented PR or until disease progression at investigator's discretion. Patients with stable disease continue therapy for a maximum of 6 courses. Patients are followed at 4 weeks and then every 3 months until disease relapse or progression. PROJECTED ACCRUAL: A total of 40-74 patients (20-37 per treatment arm) will be accrued for this study within 10 months. ### Conditions Module **Conditions:** - Fallopian Tube Cancer - Ovarian Cancer - Peritoneal Cavity Cancer **Keywords:** - stage III ovarian epithelial cancer - stage IV ovarian epithelial cancer - recurrent ovarian epithelial cancer - fallopian tube cancer - peritoneal cavity cancer ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 81 **Type:** ACTUAL **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module ### Interventions #### Intervention 1 **Name:** lurtotecan liposome **Type:** DRUG ### Eligibility Module **Eligibility Criteria:** DISEASE CHARACTERISTICS: Histologically confirmed ovarian epithelial cancer Primary fallopian or peritoneal cancer allowed Clinically and/or radiologically documented advanced and/or recurrent disease At least one site of disease unidimensionally measurable: Minimum indicator lesion site as follows: At least 10 mm on spiral CT scan At least 20 mm on conventional CT scan At least 20 mm on chest x-ray or physical exam No recent prior radiotherapy to indicator lesion(s) Clear disease progression or new lesion within a previously irradiated field allowed Previously treated with one or two chemotherapy regimens At least one regimen must have contained cisplatin or carboplatin (changing from one prior platinum compound to another for disease progression or failure to respond is considered a second regimen) Use of same prior chemotherapy combination for first-line and second-line therapy is considered two regimens No borderline ovarian tumor No ascites as only disease presentation No abdominal adenocarcinoma of unknown origin No symptomatic brain metastasis that are potentially life-threatening or require active treatment PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 Life expectancy: At least 12 weeks Hematopoietic: Absolute granulocyte count at least 1,500/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin no greater than upper limit of normal (ULN) AST/ALT no greater than 2.5 times ULN Renal: Creatinine no greater than 1.5 times ULN Other: No other prior malignancy within the past 5 years unless definitively treated with no evidence of recurrence No known hypersensitivity to systemic liposomal formulations or drugs chemically related to study drug No other serious illness or medical condition that would preclude study No active uncontrolled infection No complete bowel obstruction No history of significant neurologic or psychiatric disorder that would preclude informed consent Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: See Disease Characteristics At least 4 weeks since prior chemotherapy (6 weeks for mitomycin or nitrosourea) and recovered No prior topotecan or other topoisomerase-I inhibitor No other concurrent cytotoxic therapy for ovarian cancer Endocrine therapy: No concurrent hormonal therapy for ovarian cancer Radiotherapy: See Disease Characteristics Recovered from prior radiotherapy At least 4 weeks since prior radiotherapy to area comprising at least 25% of bone marrow stores Surgery: At least 4 weeks since prior major surgery and recovered Other: At least 30 days since prior investigational agent or new anticancer therapy No other concurrent investigational therapy **Maximum Age:** 120 Years **Minimum Age:** 18 Years **Sex:** FEMALE **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Calgary **Country:** Canada **Facility:** Tom Baker Cancer Center - Calgary **State:** Alberta **Zip:** T2N 4N2 **Location 2:** **City:** Kelowna **Country:** Canada **Facility:** BCCC - Cancer Center for the Southern Interior **State:** British Columbia **Zip:** V1Y 5L3 **Location 3:** **City:** Vancouver **Country:** Canada **Facility:** British Columbia Cancer Agency **State:** British Columbia **Zip:** V5Z 4E6 **Location 4:** **City:** Winnipeg **Country:** Canada **Facility:** CancerCare Manitoba **State:** Manitoba **Zip:** R3E 0V9 **Location 5:** **City:** Halifax **Country:** Canada **Facility:** Nova Scotia Cancer Centre **State:** Nova Scotia **Zip:** B3H 1V7 **Location 6:** **City:** Kingston **Country:** Canada **Facility:** Queen's University **State:** Ontario **Zip:** K7L 3N6 **Location 7:** **City:** Montreal **Country:** Canada **Facility:** Royal Victoria Hospital - Montreal **State:** Quebec **Zip:** H3A 1A1 **Location 8:** **City:** Saskatoon **Country:** Canada **Facility:** Royal University Hospital **State:** Saskatchewan **Zip:** S7N 0XO **Location 9:** **City:** Birmingham **Country:** United Kingdom **Facility:** City Hospital NHS Trust **State:** England **Zip:** B18 7QH **Location 10:** **City:** London **Country:** United Kingdom **Facility:** Royal Marsden NHS Trust **State:** England **Zip:** SW3 6JJ **Location 11:** **City:** Manchester **Country:** United Kingdom **Facility:** Christie Hospital N.H.S. Trust **State:** England **Zip:** M20 4BX **Location 12:** **City:** Newcastle Upon Tyne **Country:** United Kingdom **Facility:** Newcastle General Hospital **State:** England **Zip:** NE4 6BE **Location 13:** **City:** Sheffield **Country:** United Kingdom **Facility:** Weston Park Hospital **State:** England **Zip:** S1O 2SJ **Location 14:** **City:** Glasgow **Country:** United Kingdom **Facility:** Beatson Oncology Centre **State:** Scotland **Zip:** G11 6NT #### Overall Officials **Official 1:** **Affiliation:** Nova Scotia Cancer Centre **Name:** Robert N. Grimshaw, MD **Role:** STUDY_CHAIR ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Dark GG, Calvert AH, Grimshaw R, Poole C, Swenerton K, Kaye S, Coleman R, Jayson G, Le T, Ellard S, Trudeau M, Vasey P, Hamilton M, Cameron T, Barrett E, Walsh W, McIntosh L, Eisenhauer EA. Randomized trial of two intravenous schedules of the topoisomerase I inhibitor liposomal lurtotecan in women with relapsed epithelial ovarian cancer: a trial of the national cancer institute of Canada clinical trials group. J Clin Oncol. 2005 Mar 20;23(9):1859-66. doi: 10.1200/JCO.2005.02.028. Epub 2005 Feb 7. **PMID:** 15699482 **Citation:** Calvert AH, Grimshaw R, Poole C, et al.: Randomized phase II trial of two intravenous schedules of the liposomal topoisomerase I inhibitor, NX211, in women with relapsed epithelial ovarian cancer (OVCA): an NCIC CTG study. [Abstract] Proceedings of the American Society of Clinical Oncology 21: A-830, 2002. **Citation:** Wolf J, Hamilton M, Eisenhauer E, et al.: Pharmacokinetics of NX211 (liposomal lurtotecan) using a limited sampling model in a phase II trial of patients with ovarian cancer. [Abstract] Proceedings of the American Society of Clinical Oncology 21: A-485, 2002. ## Derived Section ### Condition Browse Module - Ancestors - ID: D000004701 - Term: Endocrine Gland Neoplasms - ID: D000009371 - Term: Neoplasms by Site - ID: D000009369 - Term: Neoplasms - ID: D000010049 - Term: Ovarian Diseases - ID: D000000291 - Term: Adnexal Diseases - 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: D000005833 - Term: Genital Neoplasms, Female - ID: D000014565 - Term: Urogenital Neoplasms - ID: D000091662 - Term: Genital Diseases - ID: D000004700 - Term: Endocrine System Diseases - ID: D000006058 - Term: Gonadal Disorders - ID: D000002277 - Term: Carcinoma - ID: D000009375 - Term: Neoplasms, Glandular and Epithelial - ID: D000009370 - Term: Neoplasms by Histologic Type - ID: D000005184 - Term: Fallopian Tube Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC04 - Name: Neoplasms - Abbrev: BXS - Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions - Abbrev: BC19 - Name: Gland and Hormone Related Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M14850 - Name: Recurrence - Relevance: LOW - As Found: Unknown - ID: M12974 - Name: Ovarian Neoplasms - Relevance: HIGH - As Found: Ovarian Cancer - ID: M1704 - Name: Carcinoma, Ovarian Epithelial - Relevance: HIGH - As Found: Ovarian Cancer - ID: M5534 - Name: Carcinoma - Relevance: LOW - As Found: Unknown - ID: M8328 - Name: Fallopian Tube Neoplasms - Relevance: HIGH - As Found: Fallopian Tube Cancer - ID: M7863 - Name: Endocrine Gland Neoplasms - Relevance: LOW - As Found: Unknown - ID: M12972 - Name: Ovarian Diseases - Relevance: LOW - As Found: Unknown - ID: M3643 - Name: Adnexal Diseases - 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: M8945 - Name: Genital Neoplasms, Female - Relevance: LOW - As Found: Unknown - ID: M17315 - Name: Urogenital Neoplasms - Relevance: LOW - As Found: Unknown - ID: M7862 - Name: Endocrine System Diseases - Relevance: LOW - As Found: Unknown - ID: M9163 - Name: Gonadal Disorders - 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: M8327 - Name: Fallopian Tube Diseases - Relevance: LOW - As Found: Unknown - ID: T4352 - Name: Ovarian Cancer - Relevance: HIGH - As Found: Ovarian Cancer - ID: T2189 - Name: Fallopian Tube Cancer - Relevance: HIGH - As Found: Fallopian Tube Cancer - ID: T4354 - Name: Ovarian Epithelial Cancer - Relevance: HIGH - As Found: Ovarian epithelial cancer ### Condition Browse Module - Meshes - ID: D000010051 - Term: Ovarian Neoplasms - ID: D000077216 - Term: Carcinoma, Ovarian Epithelial - ID: D000005185 - Term: Fallopian Tube Neoplasms ### Intervention Browse Module - Ancestors - 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: M208503 - Name: Lurtotecan - Relevance: HIGH - As Found: Lu-DOTA-TATE ### Intervention Browse Module - Meshes - ID: C000091719 - Term: Lurtotecan ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT02972879 **Brief Title:** Effectiveness of Non-surgical Interventions for the Trigger Finger: a Randomized Clinical Trial **Official Title:** Effectiveness of Non-surgical Interventions for the Trigger Finger: a Randomized Clinical Trial #### Organization Study ID Info **ID:** BSCPedro #### Organization **Class:** OTHER **Full Name:** Federal University of São Paulo ### Status Module #### Completion Date **Date:** 2020-07 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** NOT_YET_RECRUITING #### Last Update Post Date **Date:** 2017-07-06 **Type:** ACTUAL **Last Update Submit Date:** 2017-07-05 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2019-12 **Type:** ESTIMATED #### Start Date **Date:** 2018-03-01 **Type:** ESTIMATED **Status Verified Date:** 2017-07 #### Study First Post Date **Date:** 2016-11-25 **Type:** ESTIMATED **Study First Submit Date:** 2016-11-07 **Study First Submit QC Date:** 2016-11-21 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** Federal University of São Paulo #### Lead Sponsor **Class:** OTHER **Name:** Beatriz Sernajoto Cristiani Pedro #### Responsible Party **Investigator Affiliation:** Federal University of São Paulo **Investigator Full Name:** Beatriz Sernajoto Cristiani Pedro **Investigator Title:** BSCPedro **Type:** SPONSOR_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** The aim of this study is to assess the effectiveness of therapeutic modalities (paraffin, ultrasound and orthotics) versus corticosteroid injection for trigger finger. **Detailed Description:** There are several forms of nonsurgical treatment for trigger finger, the most used are: * Oral nonsteroidal and steroidal antiinflammatory's drugs use to resolve the inflammatory process * Corticosteroids local injection: that proposes to control the inflammation, these injections have shown good effectiveness for trigger finger treatment. * Orthotic: with the aim of to immobilize the affected joint until the resolution of the inflammatory process. * Electrotherapeutic modalities: * Paraffin that increases cellular metabolism and promotes peripheral vasodilatation, favoring the transduction tissue fluid, lymph flow, hyperemia and consequent absorption of exsudato. * LASER -Lower Level Laser Therapy (LLLT): the absorption of light through the skin's photoreceptors stimulates mitochondrial chain reactions, promoting adenosine triphosphate (ATP) synthesis, acting on gene expression, which raises the level of growth factors and Tissue repair Although the non-surgical treatment is often used there is no evidence in the literature of which is the most effective conservative treatment for trigger finger. Thus, it is necessary use appropriate methodology to define the benefits and harms of each treatment modality and assess the effectiveness of these nonsurgical treatments, and may define which one has a higher resolution and lower rates of trigger finger recurrences in short, medium and long term. ### Conditions Module **Conditions:** - Trigger Finger **Keywords:** - trigger finger - Therapeutic Modalities - Corticosteroid Injection - non-surgical treatment - physical therapy ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** SINGLE **Who Masked:** - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 132 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** * Group 1: Metal orthotic, keeping 0º of the extension of the proximal interphalangeal joint, during all day, for 5 weeks, stopping the use only for bathing * Group 2: 10 LLLT sessions applications on the A1 pulley and lump formed on the flexor tendon of the the affected finger; Two sessions per week, five weeks of treatment. * Group 3: Paraffin bath 2 times a week for 20 minutes (total of 10 sessions). **Intervention Names:** - Procedure: Therapeutic modalities: Orthotic (Group 1) - Procedure: Therapeutic modalities: LLLT (Group 2) - Procedure: Therapeutic modalities: Paraffin (Group 3) **Label:** Therapeutic Modalities **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** Group 4: Corticosteroid injection in the A1 pulley, 1 application. **Intervention Names:** - Procedure: Corticosteroid injection (Group 4) **Label:** Corticosteroid injection **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Therapeutic Modalities **Description:** participants will be instructed to remove the orthosis only two hours in the morning, two hours in the afternoon and two hours at night to avoid joint stiffness **Name:** Therapeutic modalities: Orthotic (Group 1) **Other Names:** - Metal orthotic **Type:** PROCEDURE #### Intervention 2 **Arm Group Labels:** - Therapeutic Modalities **Description:** The LLLT parameters are: * LASER 904nm * P: 1.5W/cm² * 30mV/cm² * Area 2 cm² * 1 Joule por ponto ( in the A1 pulley) **Name:** Therapeutic modalities: LLLT (Group 2) **Other Names:** - Ibramed's LASERPULSED 904nm **Type:** PROCEDURE #### Intervention 3 **Arm Group Labels:** - Therapeutic Modalities **Description:** Paraffin will be heated and maintained at 50 ° C. Participants will immerse their affected hand 10 times in heated paraffin, then they will roll up their affected hand in a towel that they will bring, after 20 minutes timed by a trained professional, the subjects will remove the towel and "paraffin glove": **Name:** Therapeutic modalities: Paraffin (Group 3) **Other Names:** - Bath Paraffin Carci´s **Type:** PROCEDURE #### Intervention 4 **Arm Group Labels:** - Corticosteroid injection **Description:** The injection solution is composed of 1 ml of betamethasone and 1 ml of 2% lidocaine.This group may repeat the procedure in two weeks if they report that there was no improvement of the triggering or pain. **Name:** Corticosteroid injection (Group 4) **Other Names:** - Bethametasone **Type:** PROCEDURE ### Outcomes Module #### Primary Outcomes **Description:** The patient must extend and flex the affected finger 10 times to verify the presence or absence of the trigger finger and determine the degree of commitment. **Measure:** Changes in the Resolution/cure of the trigger finger until the six months of the treatment **Time Frame:** 1, 5, 12 weeks and 6 month #### Secondary Outcomes **Measure:** Changes in Visual Analogue Scale (VAS) **Time Frame:** 1, 5, 12 weeks and 6 month **Measure:** Changes in Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH) **Time Frame:** 1, 5, 12 weeks and 6 month **Measure:** Changes in SF-12 (quality of life) **Time Frame:** 1, 5, 12 weeks and 6 month **Measure:** Changes in the numbers of the Complications **Time Frame:** 1, 5, 12 weeks and 6 month **Measure:** Changes in the numbers of the Relapses **Time Frame:** 1, 5, 12 weeks and 6 month ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * 2-3 grade of trigger finger (Quinnell´s classification) * Signing the Terms of Consent. Exclusion Criteria: * Presence of finger trigger in children * Presence of traumatic finger trigger * Secondary causes (patients with tumor of the tendon sheath, synovitis tuberculosis, etc ...) **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Beatriz S C Pedro **Phone:** 05511998035668 **Role:** CONTACT ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Binder A, Hodge G, Greenwood AM, Hazleman BL, Page Thomas DP. Is therapeutic ultrasound effective in treating soft tissue lesions? Br Med J (Clin Res Ed). 1985 Feb 16;290(6467):512-4. doi: 10.1136/bmj.290.6467.512. **PMID:** 3918652 **Citation:** Colbourn J, Heath N, Manary S, Pacifico D. Effectiveness of splinting for the treatment of trigger finger. J Hand Ther. 2008 Oct-Dec;21(4):336-43. doi: 10.1197/j.jht.2008.05.001. Epub 2008 Aug 22. **PMID:** 19006759 **Citation:** Chen PT, Lin CJ, Jou IM, Chieh HF, Su FC, Kuo LC. One digit interruption: the altered force patterns during functionally cylindrical grasping tasks in patients with trigger digits. PLoS One. 2013 Dec 31;8(12):e83632. doi: 10.1371/journal.pone.0083632. eCollection 2013. **PMID:** 24391799 **Citation:** Tarbhai K, Hannah S, von Schroeder HP. Trigger finger treatment: a comparison of 2 splint designs. J Hand Surg Am. 2012 Feb;37(2):243-9, 249.e1. doi: 10.1016/j.jhsa.2011.10.038. Epub 2011 Dec 20. **PMID:** 22189188 **Citation:** Langer D, Luria S, Maeir A, Erez A. Occupation-based assessments and treatments of trigger finger: a survey of occupational therapists from Israel and the United States. Occup Ther Int. 2014 Dec;21(4):143-55. doi: 10.1002/oti.1372. Epub 2014 May 12. **PMID:** 24821018 **Citation:** Howitt S, Wong J, Zabukovec S. The conservative treatment of Trigger thumb using Graston Techniques and Active Release Techniques. J Can Chiropr Assoc. 2006 Dec;50(4):249-54. **PMID:** 17549185 **Citation:** Peters-Veluthamaningal C, van der Windt DA, Winters JC, Meyboom-de Jong B. Corticosteroid injection for trigger finger in adults. Cochrane Database Syst Rev. 2009 Jan 21;(1):CD005617. doi: 10.1002/14651858.CD005617.pub2. **PMID:** 19160256 **Citation:** Huisstede BM, Hoogvliet P, Coert JH, Friden J; European HANDGUIDE Group. Multidisciplinary consensus guideline for managing trigger finger: results from the European HANDGUIDE Study. Phys Ther. 2014 Oct;94(10):1421-33. doi: 10.2522/ptj.20130135. Epub 2014 May 8. **PMID:** 24810861 **Citation:** Renno AC, Toma RL, Feitosa SM, Fernandes K, Bossini PS, de Oliveira P, Parizotto N, Ribeiro DA. Comparative effects of low-intensity pulsed ultrasound and low-level laser therapy on injured skeletal muscle. Photomed Laser Surg. 2011 Jan;29(1):5-10. doi: 10.1089/pho.2009.2715. Epub 2010 Dec 18. **PMID:** 21166589 **Citation:** Salim N, Abdullah S, Sapuan J, Haflah NH. Outcome of corticosteroid injection versus physiotherapy in the treatment of mild trigger fingers. J Hand Surg Eur Vol. 2012 Jan;37(1):27-34. doi: 10.1177/1753193411415343. Epub 2011 Aug 4. **PMID:** 21816888 **Citation:** Quinnell RC. Conservative management of trigger finger. Practitioner. 1980 Feb;224(1340):187-90. No abstract available. **PMID:** 7367373 **Citation:** Valdes K. A retrospective review to determine the long-term efficacy of orthotic devices for trigger finger. J Hand Ther. 2012 Jan-Mar;25(1):89-95; quiz 96. doi: 10.1016/j.jht.2011.09.005. **PMID:** 22265444 **Citation:** Dingemanse R, Randsdorp M, Koes BW, Huisstede BM. Evidence for the effectiveness of electrophysical modalities for treatment of medial and lateral epicondylitis: a systematic review. Br J Sports Med. 2014 Jun;48(12):957-65. doi: 10.1136/bjsports-2012-091513. Epub 2013 Jan 18. **PMID:** 23335238 **Citation:** Dilek B, Gozum M, Sahin E, Baydar M, Ergor G, El O, Bircan C, Gulbahar S. Efficacy of paraffin bath therapy in hand osteoarthritis: a single-blinded randomized controlled trial. Arch Phys Med Rehabil. 2013 Apr;94(4):642-9. doi: 10.1016/j.apmr.2012.11.024. Epub 2012 Nov 24. **PMID:** 23187044 **Citation:** Sibtain F, Khan A, Shakil-Ur-Rehman S. Efficacy of Paraffin Wax Bath with and without Joint Mobilization Techniques in Rehabilitation of post-Traumatic stiff hand. Pak J Med Sci. 2013 Apr;29(2):647-50. **PMID:** 24353596 **Citation:** Beaton DE, Wright JG, Katz JN; Upper Extremity Collaborative Group. Development of the QuickDASH: comparison of three item-reduction approaches. J Bone Joint Surg Am. 2005 May;87(5):1038-46. doi: 10.2106/JBJS.D.02060. **PMID:** 15866967 **Citation:** Ware J Jr, Kosinski M, Keller SD. A 12-Item Short-Form Health Survey: construction of scales and preliminary tests of reliability and validity. Med Care. 1996 Mar;34(3):220-33. doi: 10.1097/00005650-199603000-00003. **PMID:** 8628042 #### See Also Links **Label:** World Association of Laser Therapy. Recommended antiinflammatory dosage for low level laser therapy. 2005. (accessed june 20, 2017). **URL:** http://www.walt.nu/dosage-recommendations.html ## Derived Section ### Condition Browse Module - Ancestors - ID: D000053682 - Term: Tendon Entrapment - ID: D000052256 - Term: Tendinopathy - 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: BC26 - Name: Wounds and Injuries - Abbrev: BC10 - Name: Nervous System Diseases ### Condition Browse Module - Browse Leaves - ID: M27045 - Name: Trigger Finger Disorder - Relevance: HIGH - As Found: Trigger Finger - ID: M27421 - Name: Tendon Entrapment - Relevance: LOW - As Found: Unknown - ID: M27013 - Name: Tendinopathy - Relevance: LOW - As Found: Unknown - ID: M12092 - Name: Muscular Diseases - Relevance: LOW - As Found: Unknown - ID: M12097 - Name: Musculoskeletal Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000052582 - Term: Trigger Finger Disorder ### Intervention Browse Module - Browse Branches - Abbrev: AnArAg - Name: Anti-Arrhythmia Agents - Abbrev: ChanBlk - Name: Channel Blockers - Abbrev: CNSDep - Name: Central Nervous System Depressants - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: PhSol - Name: Pharmaceutical Solutions - Abbrev: Infl - Name: Anti-Inflammatory Agents - Abbrev: Resp - Name: Respiratory System Agents ### Intervention Browse Module - Browse Leaves - ID: M11014 - Name: Lidocaine - Relevance: LOW - As Found: Unknown - ID: M16759 - Name: Tin Fluorides - Relevance: LOW - As Found: Unknown - ID: M21860 - Name: Pharmaceutical Solutions - Relevance: LOW - As Found: Unknown - ID: M4909 - Name: Betamethasone - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT01718379 **Brief Title:** Lenalidomide in Subject With Low and Intermediate-1 Risk MDS and Without Chromosome 5 Abnormality. **Official Title:** A Phase II Study Evaluating the Efficacy/Safety of Lenalidomide With or Without Epoetin Beta in Transfusion-dependent ESA-resistant Patients With IPSS Low- and Intermediate-1 Risk Myelodysplastic Syndromes Without Chromosome 5 Abnormality. #### Organization Study ID Info **ID:** GFM-Len-Epo-08 #### Organization **Class:** OTHER **Full Name:** Groupe Francophone des Myelodysplasies ### Status Module #### Completion Date **Date:** 2016-06 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2016-11-08 **Type:** ESTIMATED **Last Update Submit Date:** 2016-11-07 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2012-11 **Type:** ACTUAL #### Start Date **Date:** 2010-07 **Status Verified Date:** 2016-11 #### Study First Post Date **Date:** 2012-10-31 **Type:** ESTIMATED **Study First Submit Date:** 2012-10-23 **Study First Submit QC Date:** 2012-10-29 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** Celgene **Class:** INDUSTRY **Name:** Roche Pharma AG #### Lead Sponsor **Class:** OTHER **Name:** Groupe Francophone des Myelodysplasies #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** The goal of the present study is to assess, through a randomized phase II trial, the efficacy and safety of Lenalidomide with or without Epoetin beta in transfusion-dependent, ESA-resistant, IPSS low and intermediate-1 risk MDS patients without chromosome 5 abnormality. Patients will receive either Lenalidomide alone or Lenalidomide and Epoetin beta for 4 months. Responders will be eligible for maintenance treatment with cycles identical to the first cycles, until relapse occurs or until unacceptable toxicity. **Detailed Description:** This is a multi-center, open-label, randomized, Phase II study. Patients will be treated either with arm A or B * Arm A: Lenalidomide 10 mg/day for 21 days every 28 days for 4 courses. * Arm B: Lenalidomide 10 mg/day for 21 days every 28 days for 4 courses combined with weekly subcutaneous injections of Epoetin beta (60,000 Units/w). Evaluation of response at the end of 4 months according to IWG 2006 and IWG 2000 criteria. Maintenance: responders will continue to follow the corresponding treatment arm until relapse occurs; non responders at Evaluation of response at the end of 4 months according to IWG 2006 and IWG 2000 criteria. in arm A will be considered in failure of treatment and the introduction of Epoetin beta is at the discretion of the physician. The patients will be followed every 3 months for 12 months ### Conditions Module **Conditions:** - Myelodysplastic Syndromes **Keywords:** - Myelodysplasia ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 132 **Type:** ACTUAL **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Lenalidomide 10 mg/day for 21 days every 28 days for 4 courses. Evaluation of response at the end of 4 months according to IWG 2006 and IWG 2000 criteria. Maintenance: responders will continue to follow the corresponding treatment arm until relapse occurs; non responders at cycle 4 in arm A will be considered in failure of treatment and the introduction of Epoetin beta is at the discretion of the physician. The patients will be followed every 3 months for 12 months **Intervention Names:** - Drug: Lenalidomide **Label:** Arm A **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Lenalidomide 10 mg/day for 21 days every 28 days for 4 courses combined with weekly subcutaneous injections of Epoetin beta (60,000 Units/w). Evaluation of response at the end of 4 months according to IWG 2006 and IWG 2000 criteria. Maintenance: responders will continue to follow the corresponding treatment arm until relapse occurs; non responders at cycle 4 in arm A will be considered in failure of treatment and the introduction of Epoetin beta is at the discretion of the physician. The patients will be followed every 3 months for 12 months **Intervention Names:** - Drug: Epoetin beta **Label:** Arm B **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Arm A **Description:** Lenalidomide:10 mg per day during 21 days **Name:** Lenalidomide **Other Names:** - Revlimid **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Arm B **Description:** Epoetin beta: 60,000 Units/week. **Name:** Epoetin beta **Other Names:** - NEORECORMON **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Primary outcome is a complete or partial response defined by the IWG 2006 criteria observed after 4 months of treatment. Comparison in the rate of response between the two groups will be performed with Chi-square test or if necessary Fisher exact test. Same analyzes will be performed with the IWG 2000 response definition . **Measure:** Comparing the efficacy of Lenalidomide alone to Lenalidomide with Epoetin beta in transfusion-dependent ESA-resistant **Time Frame:** After 4 months of treatment #### Secondary Outcomes **Description:** * Safety of Lenalidomide and of its combination with Epoetin beta: adverse events (type, frequency, severity) and relationship of adverse events to study drug * % of major HI-E and minor HI-E after 4 courses according to IWG 2000 criteria * Erythroid response duration * Time to response * Time to progression according to IPSS * RBC transfusion independence * Prognostic factors of response * Survival * Quality of life **Measure:** will be to assess the safety of Lenalidomide and of its combination with Epoetin beta **Time Frame:** After 2 months of treatment ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: MDS defined as * Low or int-1 IPSS score * Documented absence of chromosome 5 abnormality (del(5q) or -5 karyotype) * De novo MDS, excluding therapy-related MDS AND * Transfusion dependance (requirement of at least 4 units of RBC transfusions every 8 weeks ) * Resistance or loss of response to a previous treatment with Epoetin alpha/beta (at least 60,000 Units/w) or Darbepoetin (at least 250 µg/w), for at least 12 weeks * Ineligibility for allogeneic stem cell transplantation or intensive chemotherapy during the next 12 months * ECOG performance status ≤ 2 * Age ≥ 18 years * Life expectancy ≥ 3 months * Adequate liver function (transaminases serum levels ≤ 3N) * Adequate renal function (calculate creatinine clearance \> 50 ml/min) * Female subjects of chilbearing potential\* must : Agree to use effective contraception without interruption throughout the study and for at least 4 weeks after the end of treatment • Men must: Agree to not conceive during the treatment and to use effective contraception during the treatment period (including periods of dose reduction or temporary suspension) and during one week after end of treatment if their partner is of childbearing potential. Exclusion Criteria: * Active serious infection not controlled by oral or intravenous antibiotics * Platelets less than 50 G/L * Prior history of deep vein thrombosis or pulmonary embolism * Previous treatment by Thalidomide * Treatment with any investigational antileukemic agent or chemotherapy at least 6 weeks prior to study entry and lack of full recovery from side effects due to prior therapy independent of when that therapy were given * Rapidely progressive disease with copromised organ function judged to be life-threatening by the Investigator * Pregnant or lactating female * Known human immunodeficiency virus (HIV) infection * Known active hepatitis B and/or C virus infection * Hypersensitivity or intolerance to Lenalidomide or any of the excipients * Hypersensitivity to Epoetin beta or any of the excipients * Uncontrolled arterial hypertension * Any history of malignancy (other than myelodysplastic syndrome) unless the patient has remained disease free for more than 5 years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** CHU Albert Michallon **Country:** France **Facility:** Hematology Dpt, Service d'Hématologie Clinique **State:** Grenoble **Zip:** 38043 **Location 2:** **City:** Le Kremlin-Bicêtre **Country:** France **Facility:** Hematology Dpt, CHU de Bicêtre **State:** Ile de France **Zip:** 94275 **Location 3:** **City:** Paris **Country:** France **Facility:** Hematology Dpt, CHU Cochin **State:** Ile de France **Zip:** 75679 **Location 4:** **City:** Amiens **Country:** France **Facility:** Chu Amiens **Zip:** 80054 **Location 5:** **City:** Angers **Country:** France **Facility:** CHU Angers **Zip:** 43033 **Location 6:** **City:** Avignon **Country:** France **Facility:** Hematology Dpt, CH d'Avignon-305 rue Follereau- **Zip:** 84000 **Location 7:** **City:** Bayonne **Country:** France **Facility:** CH de la Cote Basque **Zip:** 64 100 **Location 8:** **City:** Blois **Country:** France **Facility:** centre de Blois **Zip:** 41016 **Location 9:** **City:** Bobigny **Country:** France **Facility:** Hopital Avicenne **Zip:** 93009 **Location 10:** **City:** Bordeaux **Country:** France **Facility:** Hematology Dpt, CHU Haut-Lévèque **Zip:** 33604 **Location 11:** **City:** Boulogne Sur Mer **Country:** France **Facility:** Hôpital Boulogne Sur Mer **Zip:** 62321 **Location 12:** **City:** Brest **Country:** France **Facility:** hôpital Morvan **Zip:** 29609 **Location 13:** **City:** Caen **Country:** France **Facility:** CHU Clémenceau **Zip:** 14033 **Location 14:** **City:** Carcassonne **Country:** France **Facility:** CH de Carcassonne **Zip:** 11890 **Location 15:** **City:** Cergy-pontoise **Country:** France **Facility:** Hematology Dpt, CH René Dubos **Zip:** 95303 **Location 16:** **City:** Clermont-Ferrand **Country:** France **Facility:** CHU de Clermont-Ferrand **Zip:** 63058 **Location 17:** **City:** Compiègne **Country:** France **Facility:** CH de Compiègne **Zip:** 60321 **Location 18:** **City:** Corbeil-essonnes **Country:** France **Facility:** Hematology Dpt, Hôpital Sud Francilien **Zip:** 91100 **Location 19:** **City:** Créteil **Country:** France **Facility:** hopital Henri Mondor **Zip:** 94010 **Location 20:** **City:** Dijon **Country:** France **Facility:** CHU de Dijon **Zip:** 21034 **Location 21:** **City:** Le Chesnay **Country:** France **Facility:** Hematology Dpt, Hôpital Versailles **Zip:** 78157 **Location 22:** **City:** Le mans **Country:** France **Facility:** Hematology Dpt,CH Le mans **Zip:** 72037 **Location 23:** **City:** Lille **Country:** France **Facility:** CHRU Huriez **Zip:** 59037 **Location 24:** **City:** Lille **Country:** France **Facility:** Hopital Saint-Vincent de Paul **Zip:** 59160 **Location 25:** **City:** Limoges **Country:** France **Facility:** CHRU de Limoges **Zip:** 87046 **Location 26:** **City:** Lyon **Country:** France **Facility:** Hematology Dpt, Centre Hospitalier Lyon Sud **Zip:** 69495 **Location 27:** **City:** Mantes-la-jolie **Country:** France **Facility:** CH de Mantes-la-jolie **Zip:** 78201 **Location 28:** **City:** Marseille **Country:** France **Facility:** Institut Paoli Calmettes **Zip:** 13009 **Location 29:** **City:** Nancy **Country:** France **Facility:** Hematology Dpt, CHU Brabois **Zip:** 54511 **Location 30:** **City:** Nantes **Country:** France **Facility:** Hematology Dpt, CHU de nantes **Zip:** 44093 **Location 31:** **City:** Nice **Country:** France **Facility:** Hematology Dpt, CHU Archet **Zip:** 06202 **Location 32:** **City:** Nimes **Country:** France **Facility:** Hematology Dpt, CHU Caremeau **Zip:** 30029 **Location 33:** **City:** Orléans **Country:** France **Facility:** Hematology Dpt, CHR La Source orléans **Zip:** 45067 **Location 34:** **City:** Paris Saint Cloud **Country:** France **Facility:** centre René Huguenin **Zip:** 92210 **Location 35:** **City:** Paris **Country:** France **Facility:** Hematology Dpt, Hôpital la pitié-Salpétrière **Zip:** 75013 **Location 36:** **City:** Paris **Country:** France **Facility:** Hematology Dpt, Hopital Saint Louis **Zip:** 75475 **Location 37:** **City:** Paris **Country:** France **Facility:** Hopital Saint Antoine **Zip:** 75571 **Location 38:** **City:** Perpignan **Country:** France **Facility:** Hematology Dpt, Hôpital Maréchal Joffre **Zip:** 66046 **Location 39:** **City:** Poitiers **Country:** France **Facility:** Hôpital Jean Bernard **Zip:** 86021 **Location 40:** **City:** Pringy cedex **Country:** France **Facility:** Hematology Dpt, Centre Hospitalier de la région d'Annecy **Zip:** 74374 **Location 41:** **City:** Reims **Country:** France **Facility:** CHRU de Reims **Zip:** 51092 **Location 42:** **City:** Rennes **Country:** France **Facility:** CHU Pontchaillou **Zip:** 35033 **Location 43:** **City:** Rouen **Country:** France **Facility:** Centre Henri Becquerel **Zip:** 76038 **Location 44:** **City:** Sint Quentin **Country:** France **Facility:** CH de Saint Quentin **Zip:** 02321 **Location 45:** **City:** Strasbourg **Country:** France **Facility:** Chu Strasbourg **Zip:** 67098 **Location 46:** **City:** Toulouse **Country:** France **Facility:** Hematology Dpt, CHU PURPAN **Zip:** 31059 **Location 47:** **City:** Tours **Country:** France **Facility:** Hematology Dpt, CH CHU Bretoneau **Zip:** 37044 **Location 48:** **City:** Monaco **Country:** Monaco **Facility:** centre hopitalier princesse Grace **Zip:** 98012 #### Overall Officials **Official 1:** **Affiliation:** Groupe Francophone des Myelodysplasies **Name:** Andréa TOMA, MD **Role:** PRINCIPAL_INVESTIGATOR **Official 2:** **Affiliation:** Groupe Francophone des Myelodysplasies **Name:** François Dreyfus, MD **Role:** STUDY_DIRECTOR ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Chesnais V, Renneville A, Toma A, Lambert J, Passet M, Dumont F, Chevret S, Lejeune J, Raimbault A, Stamatoullas A, Rose C, Beyne-Rauzy O, Delaunay J, Solary E, Fenaux P, Dreyfus F, Preudhomme C, Kosmider O, Fontenay M; Groupe Francophone des Myelodysplasies. Effect of lenalidomide treatment on clonal architecture of myelodysplastic syndromes without 5q deletion. Blood. 2016 Feb 11;127(6):749-60. doi: 10.1182/blood-2015-04-640128. Epub 2015 Dec 1. **PMID:** 26626993 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000004194 - Term: Disease - ID: D000010335 - Term: Pathologic Processes - ID: D000001855 - Term: Bone Marrow Diseases - ID: D000006402 - Term: Hematologic Diseases - ID: D000011230 - Term: Precancerous Conditions - ID: D000009369 - Term: Neoplasms ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC16 - Name: Diseases and Abnormalities at or Before Birth - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC15 - Name: Blood and Lymph Conditions - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M16355 - Name: Syndrome - Relevance: HIGH - As Found: Syndrome - ID: M12 - Name: Congenital Abnormalities - Relevance: LOW - As Found: Unknown - ID: M14164 - Name: Preleukemia - Relevance: HIGH - As Found: Myelodysplastic Syndrome - ID: M12145 - Name: Myelodysplastic Syndromes - Relevance: HIGH - As Found: Myelodysplastic Syndrome - ID: M5134 - Name: Bone Marrow Diseases - Relevance: LOW - As Found: Unknown - ID: M9490 - Name: Hematologic Diseases - Relevance: LOW - As Found: Unknown - ID: M14111 - Name: Precancerous Conditions - Relevance: LOW - As Found: Unknown - ID: T3993 - Name: Myelodysplastic Syndromes - Relevance: HIGH - As Found: Myelodysplastic Syndrome ### Condition Browse Module - Meshes - ID: D000011289 - Term: Preleukemia - ID: D000009190 - Term: Myelodysplastic Syndromes - ID: D000013577 - Term: Syndrome ### Intervention Browse Module - Ancestors - ID: D000007155 - Term: Immunologic Factors - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000020533 - Term: Angiogenesis Inhibitors - ID: D000043924 - Term: Angiogenesis Modulating Agents - ID: D000006133 - Term: Growth Substances - ID: D000006131 - Term: Growth Inhibitors - ID: D000000970 - Term: Antineoplastic Agents ### Intervention Browse Module - Browse Branches - Abbrev: ANeo - Name: Antineoplastic Agents - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Hemat - Name: Hematinics ### Intervention Browse Module - Browse Leaves - ID: M1725 - Name: Lenalidomide - Relevance: HIGH - As Found: Respiratory - ID: M314 - Name: Epoetin Alfa - Relevance: LOW - As Found: Unknown - ID: M10201 - Name: Immunologic Factors - Relevance: LOW - As Found: Unknown - ID: M22318 - Name: Angiogenesis Inhibitors - Relevance: LOW - As Found: Unknown - ID: M9231 - Name: Growth Inhibitors - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000077269 - Term: Lenalidomide ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00333879 **Brief Title:** Virtual Reality Mobility Training System for Veterans With Vision Loss **Official Title:** Virtual Reality Mobility Training System for Veterans With Vision Loss #### Organization Study ID Info **ID:** C4188-R #### Organization **Class:** FED **Full Name:** VA Office of Research and Development ### Status Module #### Completion Date **Date:** 2009-04 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2013-12-16 **Type:** ESTIMATED **Last Update Submit Date:** 2013-11-20 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2009-03 **Type:** ACTUAL #### Results First Post Date **Date:** 2013-11-19 **Type:** ESTIMATED **Results First Submit Date:** 2013-09-16 **Results First Submit QC Date:** 2013-09-16 #### Start Date **Date:** 2009-03 **Status Verified Date:** 2013-11 #### Study First Post Date **Date:** 2006-06-06 **Type:** ESTIMATED **Study First Submit Date:** 2006-06-02 **Study First Submit QC Date:** 2006-06-02 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** FED **Name:** US Department of Veterans Affairs #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** This is a two-year proof-of-concept study to evaluate a new Virtual Reality (VR) "holographic" sound system for use as an audiological Orientation and Mobility (O\&M) training tool **Detailed Description:** This is a two-year proof-of-concept study to evaluate a new Virtual Reality (VR) "holographic" sound system for use as an audiological Orientation and Mobility (O\&M) training tool. This new system avoids the limitations of other technologies (i.e., binaural recordings and existing VR sound systems) that have been employed with limited success for audiological training. Four advancements in the state-of-the-art represented by this new holographic system provide new promise for audiological O\&M training. First, unlike binaural systems, the new system allows the person to move their head in a natural fashion to localize sounds. Second, a spherical microphone array is used to record sound environments so as to retain the direction from which each ambient sound originated. When these recorded sound environments are later presented through head-tracking headphones in a VR environment, real-time software maintains the directionality of the sound so that it remains true no matter how the person moves or turns their head. Third, this new system models the actual physical acoustic structure of each person's head and ears to present sounds as they would be heard by that particular person in the recorded setting. Fourth, this system uses software algorithms to isolate specific sounds (i.e., of a moving vehicle) so that during virtual playback, these sounds can be inserted into the virtual sound field at will and in a customizable fashion to create truly unique and flexible virtual sound presentations. There are two study hypotheses. First, when using sounds to negotiate traffic intersections, skills employed by experienced travelers in real environments will readily transfer to the proposed VR environment to the extent that audiological tasks performed in real environments are just as easily performed in the VR environment. Second, when the VR environment is enhanced to emphasize critical sound cues and eliminate distracting or confusing noises and sounds, performance by skilled travelers in the VR environment will be significantly better than in the actual environment. The objectives are to: (1) adapt the existing spherical microphone array and digital recording software algorithms to best suit the capture of critical intersection sounds used for intersection negotiations; (2) develop software algorithms to deconstruct intersection sounds, isolating each sound for the VR construction of specific environments of varying complexity; (3) determine the level of sound detail necessary for negotiating intersections successfully; (4) expand the existing system to obtain the desired level of detail; (5) develop software to provide the ability to control the relative emphasis of a variety of sound elements being presented so as to simplify the auditory task; and (6) employ study participants to compare performance in the VR environment with outdoor performance. Once validated, this system should be able to: (1) leverage instructor time by providing students with an effective means of practicing audiological skills on their own, (2) provide instructors with a means of introducing concepts in a graduated learning sequence that is not dependent on the happenstance availability of specific sounds and conditions found in real environments, and (3) provide audiological training for environments not located in the vicinity of the training site, but which do represent the veteran's home community. Research will be conducted in collaboration with investigators in the Perceptual Interfaces and Reality Laboratory (PIRL) at the University of Maryland who initially conceived and developed this holographic VR sound system. COMPARISONS: Outdoor O\&M training exclusively ### Conditions Module **Conditions:** - Blindness **Keywords:** - Rehabilitation - Sensory Aid ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE #### Enrollment Info **Count:** 4 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Efficacy of using a virtual sound system to simulate street crossing conditions. **Intervention Names:** - Device: Virtual Sound System **Label:** Virtual Sound System **Type:** OTHER ### Interventions #### Intervention 1 **Arm Group Labels:** - Virtual Sound System **Description:** Virtual Sound System is tested for efficacy in its ability to realistically simulate Street Crossings sounds in a safe indoor environment. If efficacious, Blind students will be able to practice crossing streets in safety indoors. **Name:** Virtual Sound System **Other Names:** - 3-D Sound Simulation System **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Description:** Standing at an intersection subject indicates when traffic is moving left to right and right to left in front of him, versus traffic moving to and away on the street parallel to his path. Subject can respond in only two ways: 1) traffic is moving on the street in front of me, or 2) traffic is moving on the street beside me. Each trial lasts 5 minutes with a 2 minute and 30 second break between trials. Traffic stops and starts 5 times over the 5 minutes, each time moving in one of two randomly selected directions: 1) left and right in front of the subject, or 2) forward and back along the street beside the subject. The participant must correctly state the direction of traffic at least 4 out of five times for the equipment under test to be counted as efficacious for presenting accurate 3D sound information to the participant. **Measure:** Accuracy in Judging Direction of Traffic at Traffic Intersection **Time Frame:** 4 trials over 30 minutes after 30 minutes of training #### Secondary Outcomes **Description:** Subject is able to state when it is safe to cross the street based on traffic on the street beside him accelerating into motion after traffic on the street in front of him coming to a stop. Subject must state is it safe to cross within 5 seconds of the cars on the street beside him accelerating into motion. The system under test will be considered efficacious if the subject is correct at least 4 out of 5 times. This counts as being efficacious for that one subject. **Measure:** Accuracy in Selecting Appropriate Time to Cross Street **Time Frame:** 4 trials over 30 minutes after 30 minutes of training ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Must have little or no light perception * OMCT (Orientation-Memory Concentration Test) of 10 or less * Must have been independently and regularly crossing busy intersections for at least 3 years * Ambulatory and able to walk for at least 10 minutes at a time without resting * Auditory function at 25 db HL Exclusion Criteria: * Imbalance between ears - HL difference of 20 db HL or more **Healthy Volunteers:** True **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Decatur **Country:** United States **Facility:** Atlanta VA Medical and Rehab Center, Decatur **State:** Georgia **Zip:** 30033 #### Overall Officials **Official 1:** **Affiliation:** Atlanta VA Medical and Rehab Center, Decatur **Name:** David A Ross, MSEE Med **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000014786 - Term: Vision Disorders - ID: D000012678 - Term: Sensation Disorders - ID: D000009461 - Term: Neurologic Manifestations - ID: D000009422 - Term: Nervous System Diseases - ID: D000005128 - Term: Eye Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: BC11 - Name: Eye Diseases - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M5047 - Name: Blindness - Relevance: HIGH - As Found: Blindness - ID: M17530 - Name: Vision Disorders - 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: M8271 - Name: Eye Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000001766 - Term: Blindness ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module #### Event Groups **Group ID:** EG000 **Title:** Virtual Sound System **Description:** Efficacy of using a virtual sound system to simulate street crossing conditions. **ID:** EG000 **Other Num at Risk:** 4 **Serious Number At Risk:** 4 **Title:** Virtual Sound System **Frequency Threshold:** 0 ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 4 **Units:** Participants ### Group **ID:** BG000 **Title:** Virtual Sound System **Description:** Efficacy of using a virtual sound system to simulate street crossing conditions. ### Measure #### Measurement **Group ID:** BG000 **Value:** 0 **Category Title:** <=18 years #### Measurement **Group ID:** BG000 **Value:** 4 **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:** 14.7 **Value:** 43 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 2 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 2 **Category Title:** Male **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 4 **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 ## Results Section - More Information Module ### Certain Agreement **PI Sponsor Employee:** True ### Limitations and Caveats **Description:** Early termination leading to small numbers of subjects analyzed. Technical problems with Virtual Sound System. None of the first 4 Subjects could distinguish between sounds in front versus sounds beside them. ### Point of Contact **Email:** [email protected] **Organization:** Atlanta VA Rehab R&D Center **Phone:** 404-321-6111 **Phone Extension:** 6817 **Title:** David Ross ## 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:** - **Upper Limit:** - **Value:** 0 **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** Standing at an intersection subject indicates when traffic is moving left to right and right to left in front of him, versus traffic moving to and away on the street parallel to his path. Subject can respond in only two ways: 1) traffic is moving on the street in front of me, or 2) traffic is moving on the street beside me. Each trial lasts 5 minutes with a 2 minute and 30 second break between trials. Traffic stops and starts 5 times over the 5 minutes, each time moving in one of two randomly selected directions: 1) left and right in front of the subject, or 2) forward and back along the street beside the subject. The participant must correctly state the direction of traffic at least 4 out of five times for the equipment under test to be counted as efficacious for presenting accurate 3D sound information to the participant. **Parameter Type:** NUMBER **Population Description:** Initial pilot study design called for 16 subjects to provide data of significance based on a power analysis. Study terminated at 4 subjects when none of the subjects could identify the location of traffic vehicles when using the intervention across multiple (4) trials. **Reporting Status:** POSTED **Time Frame:** 4 trials over 30 minutes after 30 minutes of training **Title:** Accuracy in Judging Direction of Traffic at Traffic Intersection **Type:** PRIMARY **Unit of Measure:** participants ##### Group **Description:** Efficacy of using a virtual sound system to simulate street crossing conditions. **ID:** OG000 **Title:** Virtual Sound System #### Outcome Measure 2 **Description:** Subject is able to state when it is safe to cross the street based on traffic on the street beside him accelerating into motion after traffic on the street in front of him coming to a stop. Subject must state is it safe to cross within 5 seconds of the cars on the street beside him accelerating into motion. The system under test will be considered efficacious if the subject is correct at least 4 out of 5 times. This counts as being efficacious for that one subject. **Parameter Type:** NUMBER **Reporting Status:** POSTED **Time Frame:** 4 trials over 30 minutes after 30 minutes of training **Title:** Accuracy in Selecting Appropriate Time to Cross Street **Type:** SECONDARY **Unit of Measure:** participants ##### Group **Description:** Efficacy of using a virtual sound system to simulate street crossing conditions. **ID:** OG000 **Title:** Virtual Sound System ### Participant Flow Module #### Group **Description:** Efficacy of using a virtual sound system to simulate street crossing conditions. **ID:** FG000 **Title:** Virtual Sound System #### Period **Title:** Overall Study ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 4 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 4 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 0 **Pre-Assignment Details:** All 4 subjects were accepted for the study. None were excluded. **Recruitment Details:** The 4 totally blind Participants were recruited over three months (April - June) 2009 from the Atlanta Center for Visual Impairment. **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT01220479 **Acronym:** Diabex **Brief Title:** Exercise Training Intervention in Children With Type 1 Diabetes **Official Title:** Impact of an Exercise Training Program on Bone Development and Cardiovascular Disease Risk Factors in Children With Type 1 Diabetes Mellitus #### Organization Study ID Info **ID:** snf n°63164 #### Organization **Class:** OTHER **Full Name:** University Hospital, Geneva ### Status Module #### Completion Date **Date:** 2009-06 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2010-10-14 **Type:** ESTIMATED **Last Update Submit Date:** 2010-10-13 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2008-12 **Type:** ACTUAL #### Start Date **Date:** 2001-09 **Status Verified Date:** 2010-10 #### Study First Post Date **Date:** 2010-10-14 **Type:** ESTIMATED **Study First Submit Date:** 2010-05-04 **Study First Submit QC Date:** 2010-10-13 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** Swiss National Science Foundation #### Lead Sponsor **Class:** OTHER **Name:** University Hospital, Geneva #### Responsible Party **Old Name Title:** Farpour-Lambert Nathalie **Old Organization:** University Hospital of Geneva ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** Type 1 diabetes mellitus (T1DM) is associated with multiple co-morbidities, such as hypertension, dyslipidemia, coronary heart disease and osteoporosis. The foundation of these conditions lays in childhood. Exercise is known to have a positive influence on bone mineral density (BMD) and some impact on cardiovascular disease risk factors in healthy children, but little is known about these associations in children with T1DM. The main purpose of this study is to assess the effects of a 9-month weight-bearing exercise training program on skeletal development in children with T1DM, compared to healthy subjects. The second aim is to evaluate whether the program influences also cardiovascular diseases risk factors. This is a randomized controlled study incorporating 30 children with T1DM and 30 healthy children. Both groups are randomly divided (1:1) in an exercise or a control group: 1) exercise diabetic, 2) controls diabetic, 3) exercise healthy, 4) controls healthy. Exercise groups participate to an identical weight-bearing exercise training program 2 x 90 minutes per week and controls are relatively inactive. Main measures include: total body, lumbar spine and hip BMD by DXA, body fat and fat-free mass, bone biomarkers levels, resting and ambulatory blood pressure and fasting blood lipids. ### Conditions Module **Conditions:** - Type 1 Diabetes Mellitus **Keywords:** - Type 1 Diabetes, Bone mineral density, Growth - Cardiovascular diseases, Exercise, Training, - Child, Adolescent ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** SINGLE **Who Masked:** - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 59 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Intervention Names:** - Behavioral: Exercise training program **Label:** Control Healthy **Type:** NO_INTERVENTION #### Arm Group 2 **Intervention Names:** - Behavioral: Exercise training program **Label:** Control Diabetic **Type:** NO_INTERVENTION #### Arm Group 3 **Intervention Names:** - Behavioral: Exercise training program **Label:** Exercise Diabetic **Type:** EXPERIMENTAL #### Arm Group 4 **Intervention Names:** - Behavioral: Exercise training program **Label:** Exercise Healthy **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Control Diabetic - Control Healthy - Exercise Diabetic - Exercise Healthy **Description:** Exercise Diabetic and Healthy groups perform a similar training program including two exercise sessions per week, of 90 minutes each, during 9 months (excluding holidays) under supervision by physical education teachers and pediatricians. Sessions comprise various weight-bearing activities: rope skipping, jumping, ball games and gymnastics. Control groups are relatively inactive. **Name:** Exercise training program **Type:** BEHAVIORAL ### Outcomes Module #### Primary Outcomes **Description:** Assessment of bone mineral density (BMD) and content (BMC) at the whole body, hip and lumbar spine using DXA. **Measure:** Bone mineral density and content **Time Frame:** Baseline **Description:** Assessment of bone mineral density (BMD) and content (BMC) at the whole body, hip and lumbar spine using DXA. **Measure:** Bone mineral density and content **Time Frame:** at 9 months #### Secondary Outcomes **Description:** Body weight, height, body mass index and pubertal stage **Measure:** Anthropometrics **Time Frame:** Baseline **Description:** Fasting total cholesterol, LDL-Cholesterol, HDL-Cholesterol, triglycerides, lipoprotein (a), apolipoproteins A-I and B levels. **Measure:** Blood lipids levels **Time Frame:** Baseline **Description:** Physical activity level by questionnaire and accelerometer **Measure:** Physical activity **Time Frame:** Baseline **Description:** Total energy, proteins, lipids, carbohydrates and calcium intakes using food records **Measure:** Nutrition **Time Frame:** Baseline **Description:** Serum levels of beta-CrossLaps (CTX), N-MID-Osteocalcin (OC), N-Terminal Propeptide of Type I Collagen (PINP) and 25-OH-vitamin D (25-OH-D) **Measure:** Circulating bone biomarkers levels **Time Frame:** Baseline **Description:** capillary HbA1c levels **Measure:** Glycated Haemoglobin **Time Frame:** Baseline **Description:** Resting and 24-hour ambulatory systemic blood pressure monitoring **Measure:** Systemic blood pressure **Time Frame:** Baseline **Description:** Assessment of whole body and abdominal fat mass, and total fat-free mass using DXA. **Measure:** Body composition **Time Frame:** Baseline **Description:** Body weight, height, body mass index and pubertal stage **Measure:** Anthropometrics **Time Frame:** at 9 months **Description:** Fasting total cholesterol, LDL-Cholesterol, HDL-Cholesterol, triglycerides, lipoprotein (a), apolipoproteins A-I and B levels. **Measure:** Blood lipids levels **Time Frame:** at 9 months **Description:** Physical activity level by questionnaire and accelerometer **Measure:** Physical activity **Time Frame:** at 9 months **Description:** Total energy, proteins, lipids, carbohydrates and calcium intakes using food records **Measure:** Nutrition **Time Frame:** at 9 months **Description:** Serum levels of beta-CrossLaps (CTX), N-MID-Osteocalcin (OC), N-Terminal Propeptide of Type I Collagen (PINP) and 25-OH-vitamin D (25-OH-D) **Measure:** Circulating bone biomarkers levels **Time Frame:** at 9 months **Description:** capillary HbA1c levels **Measure:** Glycated Haemoglobin **Time Frame:** at 3 months **Description:** capillary HbA1c levels **Measure:** Glycated Haemoglobin **Time Frame:** at 6 months **Description:** capillary HbA1c levels **Measure:** Glycated Haemoglobin **Time Frame:** at 9 months **Description:** Resting and 24-hour ambulatory systemic blood pressure monitoring **Measure:** Systemic blood pressure **Time Frame:** at 9 months **Description:** Assessment of whole body and abdominal fat mass, and total fat-free mass using DXA. **Measure:** Body composition **Time Frame:** at 9 months ### Eligibility Module **Eligibility Criteria:** List of inclusion criteria for Type 1 diabetes patients: 1) disease for at least 1 year. List of inclusion criteria for healthy subjects: 1) good general health and normal growth. List of exclusion Criteria for all subjects: 1. presence of other chronic disease, including thyroid disease; 2. medications, hormones other than insulin, or calcium preparations taken in the preceding 6 months; 3. presence of nephropathy; 4. systemic disease or hospitalization for more than 2 weeks in the preceding year; 5. less than 6 menstrual cycles in the past year for post-menarche girls; 6. participation in competitive sport. **Healthy Volunteers:** True **Maximum Age:** 16 Years **Minimum Age:** 8 Years **Sex:** ALL **Standard Ages:** - CHILD ### Contacts Locations Module #### Locations **Location 1:** **City:** Geneva **Country:** Switzerland **Facility:** University Hospital of Geneva **Zip:** 1205 #### Overall Officials **Official 1:** **Affiliation:** University Hospital, Geneva **Name:** Farpour-Lambert Nathalie, PD **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### References **Citation:** Maggio AB, Rizzoli RR, Marchand LM, Ferrari S, Beghetti M, Farpour-Lambert NJ. Physical activity increases bone mineral density in children with type 1 diabetes. Med Sci Sports Exerc. 2012 Jul;44(7):1206-11. doi: 10.1249/MSS.0b013e3182496a25. **PMID:** 22246217 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000044882 - Term: Glucose Metabolism Disorders - ID: D000008659 - Term: Metabolic Diseases - ID: D000004700 - Term: Endocrine System Diseases - ID: D000001327 - Term: Autoimmune Diseases - ID: D000007154 - Term: Immune 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 - Abbrev: BC20 - Name: Immune System Diseases ### Condition Browse Module - Browse Leaves - ID: M7115 - Name: Diabetes Mellitus - Relevance: HIGH - As Found: Diabetes Mellitus - ID: M7117 - Name: Diabetes Mellitus, Type 1 - Relevance: HIGH - As Found: Type 1 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 - ID: M4629 - Name: Autoimmune Diseases - Relevance: LOW - As Found: Unknown - ID: M10200 - Name: Immune System Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000003920 - Term: Diabetes Mellitus - ID: D000003922 - Term: Diabetes Mellitus, Type 1 ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04222179 **Brief Title:** One Brand-new Maneuver to Place Nasoenteric Tube **Official Title:** Tzu-chi General Hospital,Hualien County,Taiwan,ROC #### Organization Study ID Info **ID:** IRB106-10-A #### Organization **Class:** OTHER **Full Name:** Buddhist Tzu Chi General Hospital ### Status Module #### Completion Date **Date:** 2020-12-31 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** RECRUITING #### Last Update Post Date **Date:** 2020-07-10 **Type:** ACTUAL **Last Update Submit Date:** 2020-07-08 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2020-12-31 **Type:** ESTIMATED #### Start Date **Date:** 2019-01-01 **Type:** ACTUAL **Status Verified Date:** 2020-07 #### Study First Post Date **Date:** 2020-01-09 **Type:** ACTUAL **Study First Submit Date:** 2020-01-02 **Study First Submit QC Date:** 2020-01-07 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Buddhist Tzu Chi General Hospital #### Responsible Party **Investigator Affiliation:** Buddhist Tzu Chi General Hospital **Investigator Full Name:** Jen-Shung Lin **Investigator Title:** Prıncıpal ınvestıgator **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False ### Description Module **Brief Summary:** Naso-enteric tube feeding is necessary for certain patients. Many methods are used to place a naso-enteric tube, such as bed-side blind method, fluoroscopy method and guide-wire method. INvestigators aim to introduce a safe, non-expensive and fast method to insert a silicon naso-gastric (NG) tube into the small intestine. **Detailed Description:** Investigators tied a 1-cm surgical suture at the tip of a 16 French silicon NG tube (120 cm long, cost 5 US dollars). One conventional EGD (diameter 2.8 mm) biopsy forceps was inserted into the lumen as a strengthened stylet. Then investigators inserted a biopsy forceps (diameter 2.0 mm) and protruded a little out of the working channel of an ultrathin EGD scope (Fujinon EG 530 N, diameter 5.9 mm) to grasp the suture. The ultrathin EGD and NG tube were parallelly pushed into a selected nostril after adequate decongestive anesthesia (Epinephrine 0.3% + Lidocaine 5%) into the small intestine as deep as possible to the jejunum. Being placed to the small intestine as far as possible, the NG tube was released and the ultrathin EGD scope withdrew. When the scope was pulled backwards from the stomach, the shape/layout of a NG-tube could be simultaneously monitored and adjusted. At last, the EGD biopsy forceps (2.8 mm) inside the NG tube was removed. With this method, in real life, a plain film is not necessary to confirm the NG tube position. However, for study purpose, a KUB film was taken to check the NG tube position. ### Conditions Module **Conditions:** - Nutrient Intake Disorder ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 100 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** The participants needed nutrition from naso-enteric tube feeding are enrolled into this study. Double-blind was not needed here. **Intervention Names:** - Device: ultrathın esophagogastroduodenoscope **Label:** Naso-enteric tube placement **Type:** OTHER ### Interventions #### Intervention 1 **Arm Group Labels:** - Naso-enteric tube placement **Description:** Place the naso-enteric tube together with the ultrathin esophagogastroduodenoscope from the same nasal cavity **Name:** ultrathın esophagogastroduodenoscope **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Description:** The procedure times to place the tube are recorded **Measure:** procedure time **Time Frame:** wıthın 20 mınutes #### Secondary Outcomes **Description:** The tıme of the naso-enteric tube was recorded in day **Measure:** the tıme of naso-enterıc tube usage **Time Frame:** within 90 days ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Esophageal obstruction 2. Gastric outlet obstruction 3. Duodenal obstruction 4. Pancreatitis 5. Gastroparesis - Exclusion Criteria: * (1)Coagulopathy (2)Deviation of nasal septa (3)Conscious disturbance **Maximum Age:** 90 Years **Minimum Age:** 20 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Jen S Lin, VS **Phone:** 886-3-8561825 **Phone Ext:** 13224 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Chi T Hu, VS **Phone:** 886-3-8561825 **Phone Ext:** 13224 **Role:** CONTACT #### Locations **Location 1:** **City:** Hualien City **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Jen S Lin, VS - **Phone:** 886-3-8561825 - **Phone Ext:** 13224 - **Role:** CONTACT **Country:** Taiwan **Facility:** Tzu-chi Hospital **State:** Hua-lien County **Status:** RECRUITING **Zip:** 97002 #### Overall Officials **Official 1:** **Affiliation:** Buddhist Tzu Chi General Hospital **Name:** Jen S Lin, VS **Role:** STUDY_DIRECTOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00253279 **Brief Title:** Alterations in Protein Synthesis Rates of Burn Patients Measured Over Time Using PET Scans **Official Title:** A Quantitative Study of the Metabolic Alterations in Protein Synthesis Rate That Occur in Burn Patients Over the Time Course of Their Injury Using Positron Emission Tomography. #### Organization Study ID Info **ID:** 2005-P-001510 #### Organization **Class:** NIH **Full Name:** National Institute of General Medical Sciences (NIGMS) #### Secondary ID Infos **ID:** G P50 GM021700-28 ### Status Module #### Completion Date **Date:** 2010-01 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** NOT_YET_RECRUITING #### Last Update Post Date **Date:** 2009-08-13 **Type:** ESTIMATED **Last Update Submit Date:** 2009-08-12 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2010-01 **Type:** ESTIMATED #### Start Date **Date:** 2009-11 **Status Verified Date:** 2009-08 #### Study First Post Date **Date:** 2005-11-15 **Type:** ESTIMATED **Study First Submit Date:** 2005-11-11 **Study First Submit QC Date:** 2005-11-11 ### Sponsor Collaborators Module #### Collaborators **Class:** NIH **Name:** National Institute of General Medical Sciences (NIGMS) #### Lead Sponsor **Class:** OTHER **Name:** Massachusetts General Hospital #### Responsible Party **Old Name Title:** Ronald G. Tompkins, MD, ScD, Chief, Burn Service **Old Organization:** Massachusetts General Hospital ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** Our specific aim is to gain an understanding of protein synthesis rates in burn patients at various times during their injury and recovery by using PET scans. This will be compared with healthy volunteer controls. We hope this will help optimize nutrition and care regimens for future burn patients. **Detailed Description:** The purpose of this study is to understand how muscles are built up and broken down (metabolism) in both burn patients and healthy people.The studies will help us understand how muscle metabolism is different for burn patients and healthy subjects. We hope to find ways to help the body of a burn victim heal without losing too much muscle. Protein is an important part of our daily diet. Normally, the body breaks down the protein we eat into smaller pieces called amino acids. It uses the amino acids to make its own proteins. It uses these proteins to heal wounds, fight infections, and provide energy. After a burn injury, the body speeds up the pace of its life activities. It needs more energy just to stay alive and recover from the burn. The body often gets the extra energy it needs by breaking the protein in muscles down into amino acids. The amino acids are then made into new proteins. If too much muscle is broken down, it is harder for the body to function. This can make recovery slower or possibly lead to death. For Healthy Volunteers, this study will require no more than 6 hours of time in total. This time will be spread out over two visits, a Screening Visit and a Scan Visit. For Burn Patients, this study will require no more than 14 hours total. This time will be spread out over four visits-a screening visit and a maximum of 3 scan visits. A total of three PET scans will be done over a 2 year period. ### Conditions Module **Conditions:** - Burn **Keywords:** - Protein Synthesis Rate - Burn Injury - PET Scan ### Design Module #### Design Info **Observational Model:** CASE_CONTROL **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 64 **Type:** ESTIMATED **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** 16 healthy subjects will be studied. Each patient will undergo one PET Scan to measure muscle protein synthesis rate. **Intervention Names:** - Procedure: PET Scans **Label:** 1 #### Arm Group 2 **Description:** 48 burn patients will be studied. Each patient will have a maximum of 3 PET Scans, which will be done at different times during the first 24 months after injury. A maximum of 2 of these scans will be done while they are inpatient; one after discharge. **Intervention Names:** - Procedure: PET Scans **Label:** 2 ### Interventions #### Intervention 1 **Arm Group Labels:** - 1 - 2 **Description:** Healthy volunteers will undergo one PET Scan; bur patients will undergo a maximum of 3 PET scans over 2 years after injury; a maximum of 2 will be done while inpatient; one after d/c. **Name:** PET Scans **Other Names:** - PET Scan - Muscle Protein Metabolism **Type:** PROCEDURE ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: FOR HEALTHY VOLUNTEERS Healthy males and females 18-70 years of age. Laboratory results within MGH-accepted normal range. Within 20% of the ideal weight for their height. Supine and standing blood pressure within the range of 110/60 to 150/90 mm Hg Heart rate within the range of 46-90 beats/minute after 5 minutes of rest. Subjects \<40 years old with HCT \>=24, age 40-60 with HCT \>=27, age 60-70 with HCT \>=30. FOR BURN SUBJECTS: Inclusion Criteria: Burn Injury of \>=5 % TBSA from any cause. 18 -70 years of age Stable hemodynamic and cardiopulmonary states as judged by the attending surgeons in the burn unit. Patient who is capable of giving full informed consent. Exclusion Criteria: FOR HEALTHY SUBJECTS Clinical evidence of physical or mental disease. Clinically significant abnormality of the laboratory tests. Known drug or alcohol dependence. History of drug allergy Taking standard prescription drugs within two weeks or investigational drugs within four weeks prior to the PET scan Diabetes mellitus and other metabolic endocrine disorders Pregnant or lactating FOR BURN SUBJECTS: Pregnant or lactating females **Healthy Volunteers:** True **Maximum Age:** 70 Years **Minimum Age:** 18 Years **Sampling Method:** PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Healthy subjects and burn patients ### Contacts Locations Module #### Locations **Location 1:** **City:** Boston **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Mary-Liz c Bilodeau, MS - **Phone:** 617-726-8766 - **Role:** CONTACT ***Contact 2:*** - **Email:** [email protected] - **Name:** Yong-Ming Yu, MD, PhD - **Phone:** 617-724-7766 - **Role:** CONTACT ***Contact 3:*** - **Name:** Alan J Fischman, MD, PhD - **Role:** PRINCIPAL_INVESTIGATOR ***Contact 4:*** - **Name:** Colleen M Ryan, MD - **Role:** SUB_INVESTIGATOR ***Contact 5:*** - **Name:** Robert L Sheridan, MD - **Role:** SUB_INVESTIGATOR ***Contact 6:*** - **Name:** Shawn P Fagan, MD - **Role:** SUB_INVESTIGATOR **Country:** United States **Facility:** Massachusetts General Hospital **State:** Massachusetts **Zip:** 02114 #### Overall Officials **Official 1:** **Affiliation:** Massachusetts General Hospital, Shriners Burn Hospital- Boston **Name:** Ronald T Tompkins, MD, ScD **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### References **Citation:** Fischman AJ, Hsu H, Carter EA, Yu YM, Tompkins RG, Guerrero JL, Young VR, Alpert NM. Regional measurement of canine skeletal muscle blood flow by positron emission tomography with H2(15)O. J Appl Physiol (1985). 2002 Apr;92(4):1709-16. doi: 10.1152/japplphysiol.00445.2001. **PMID:** 11896041 **Citation:** Fischman AJ, Yu YM, Livni E, Babich JW, Young VR, Alpert NM, Tompkins RG. Muscle protein synthesis by positron-emission tomography with L-[methyl-11C]methionine in adult humans. Proc Natl Acad Sci U S A. 1998 Oct 27;95(22):12793-8. doi: 10.1073/pnas.95.22.12793. **PMID:** 9788993 **Citation:** Hsu H, Yu YM, Babich JW, Burke JF, Livni E, Tompkins RG, Young VR, Alpert NM, Fischman AJ. Measurement of muscle protein synthesis by positron emission tomography with L-[methyl-11C]methionine. Proc Natl Acad Sci U S A. 1996 Mar 5;93(5):1841-6. doi: 10.1073/pnas.93.5.1841. **PMID:** 8700846 **Citation:** Carter EA, Yu YM, Alpert NM, Bonab AA, Tompkins RG, Fischman AJ. Measurement of muscle protein synthesis by positron emission tomography with L-[methyl-11C]methionine: effects of transamination and transmethylation. J Trauma. 1999 Aug;47(2):341-5. doi: 10.1097/00005373-199908000-00021. **PMID:** 10452471 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000014947 - Term: Wounds and Injuries ### Condition Browse Module - Browse Branches - Abbrev: BC26 - Name: Wounds and Injuries - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M5326 - Name: Burns - Relevance: HIGH - As Found: Burn - ID: M17685 - Name: Wounds and Injuries - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000002056 - Term: Burns ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00859079 **Brief Title:** Efficacy of GLP-1 Infusion in Comparison to an Insulin Infusion Protocol to Reach Normoglycemia Type 2 Diabetic Patients **Official Title:** Efficacy of a Continuous GLP-1 Infusion in Comparison to a Structured Insulin Infusion Protocol to Reach Normoglycemia in Non-Fasted Type 2 Diabetic Patients #### Organization Study ID Info **ID:** TCW-GLP1-1 #### Organization **Class:** OTHER **Full Name:** Medical University of Graz ### Status Module #### Completion Date **Date:** 2007-01 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2009-03-10 **Type:** ESTIMATED **Last Update Submit Date:** 2009-03-09 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2006-12 **Type:** ACTUAL #### Start Date **Date:** 2006-06 **Status Verified Date:** 2009-03 #### Study First Post Date **Date:** 2009-03-10 **Type:** ESTIMATED **Study First Submit Date:** 2009-03-07 **Study First Submit QC Date:** 2009-03-09 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Medical University of Graz #### Responsible Party **Old Name Title:** Dr. Thomas Wascher **Old Organization:** Medical University of Graz ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** The aim of the investigators study was to compare for the first time efficacy and safety of intravenously administered GLP-1 with an established intravenous insulin regimen in hyperglycaemic type 2 diabetic patients. **Detailed Description:** Intervention studies in patients with acute myocardial infraction or cardiac surgery, using intravenously administered human insulin, suggest that normalization of hyperglycemia can reduce morbidity as well as mortality in these patients. Insulin-based regimens require frequent blood glucose measurements and adjustments of infusion rate to achieve normoglycemia. In addition, hypoglycaemia is a frequent and important side effect. Glucagon-Like-Peptide 1 (GLP-1) is an insulinotropic, glucagonostatic gastrointestinal hormone that lowers glucose in a glycemia-dependent manner and therefore does not cause hypoglycemia. The aim of our study was to compare for the first time efficacy and safety of intravenously administered GLP-1 with an established intravenous insulin regimen in hyperglycaemic type 2 diabetic patients. ### Conditions Module **Conditions:** - Diabetes Mellitus Type 2 - Hyperglycemia **Keywords:** - diabetes mellitus type 2, GLP-1, insulin infusion ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** CROSSOVER ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 8 **Type:** ACTUAL **Phases:** - PHASE4 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Intravenously administered GLP-1 **Intervention Names:** - Drug: GLP-1 **Label:** GLP-1 **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** Insulin intravenously according to the Munich registry **Intervention Names:** - Drug: Human regular insulin intravenously **Label:** Insulin intravenously **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - GLP-1 **Description:** Patients received GLP-1 intravenously at a dose of 1.2 pmol/kg/min for at maximum 8 hours. **Name:** GLP-1 **Other Names:** - GLP-1 infusion (CLINALFA, Laeufelingen, Switzerland) **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Insulin intravenously **Description:** Human regular insulin intravenously according to the Munich-registry. **Name:** Human regular insulin intravenously **Other Names:** - Insulin Actrapid, NovoNordisk, Denmark **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Measure:** time to reach a plasma glucose below 115 mg/dl **Time Frame:** 0,30,60,120,150,180,210,240,270,300,330,360,390,420,450,480,510 min #### Secondary Outcomes **Measure:** plasma glucose after 2 and 4 hours as well as maximum glycemia **Time Frame:** 0,30,60,120,150,180,210,240,270,300,330,360,390,420,450,480,510 min **Measure:** number of hypoglycaemic episodes **Time Frame:** 0,30,60,120,150,180,210,240,270,300,330,360,390,420,450,480,510 min ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Type 2 diabetes mellitus * Fasting glycemia above 150 mg/dl * Signed informed consent Exclusion Criteria: * Patients with heart failure \> NYHA II * Uncontrolled hypertension * Impaired kidney function (creatinine \> 3 mg/dl) * Acute infection **Maximum Age:** 70 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Graz **Country:** Austria **Facility:** Medical University of Graz, Department for Internal Medicine **Zip:** 8036 #### Overall Officials **Official 1:** **Affiliation:** Medical University of Graz, Dept. of Internal Medicine, Auenbruggerpl. 15, 8036 Graz, Austria **Name:** Thomas C Wascher, MD **Role:** PRINCIPAL_INVESTIGATOR ## 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 Mellitus - ID: M7119 - Name: Diabetes Mellitus, Type 2 - Relevance: HIGH - As Found: Diabetes Mellitus Type 2 - ID: M9994 - Name: Hyperglycemia - Relevance: HIGH - As Found: Hyperglycemia - 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: D000006943 - Term: Hyperglycemia - ID: D000003924 - Term: Diabetes Mellitus, Type 2 ### Intervention Browse Module - Ancestors - 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: Micro - Name: Micronutrients - Abbrev: Gast - Name: Gastrointestinal Agents ### Intervention Browse Module - Browse Leaves - ID: M10365 - Name: Insulin - Relevance: HIGH - As Found: Day 1 - ID: M173166 - Name: Insulin, Globin Zinc - Relevance: HIGH - As Found: Day 1 - ID: M26997 - Name: Glucagon-Like Peptide 1 - Relevance: HIGH - As Found: Expected - ID: M17768 - Name: Zinc - Relevance: LOW - As Found: Unknown - ID: M9043 - Name: Glucagon - 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: D000007328 - Term: Insulin - ID: C000557859 - Term: Insulin, Globin Zinc - ID: D000052216 - Term: Glucagon-Like Peptide 1 ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05119179 **Brief Title:** Pharmacogenetics of the Response to GLP-1 in Mexican-Americans With Prediabetes **Official Title:** Pharmacogenetics of the Response to GLP-1 in Mexican-Americans With Prediabetes #### Organization Study ID Info **ID:** HSC-MS-21-0297 #### Organization **Class:** OTHER **Full Name:** The University of Texas Health Science Center, Houston ### Status Module #### Completion Date **Date:** 2026-07 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2023-06-12 **Type:** ACTUAL **Last Update Submit Date:** 2023-06-08 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2025-11 **Type:** ESTIMATED #### Start Date **Date:** 2021-11-22 **Type:** ACTUAL **Status Verified Date:** 2023-06 #### Study First Post Date **Date:** 2021-11-15 **Type:** ACTUAL **Study First Submit Date:** 2021-08-05 **Study First Submit QC Date:** 2021-11-01 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** Vanderbilt University Medical Center #### 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:** Absalon D Gutierrez **Investigator Title:** Associate Professor of Medicine **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** True **Oversight Has DMC:** True ### Description Module **Brief Summary:** This project uses both transcriptomic- and genomic-level data to identify mechanisms of individual responses to glucagon-like peptide-1 (GLP-1) in Mexican-Americans with prediabetes. The GLP-1 hormone is essential for glucose reduction, weight loss, cardiovascular risk reduction, and renal protection. Newly discovered mechanisms will illuminate causal links between disease genotype and phenotype, which may ultimately guide personalized therapeutic approaches for type 2 diabetes, prediabetes, obesity, cardiovascular disease, renal disease, and other related diseases. **Detailed Description:** This clinical trial will uncover new mechanisms of inter-individual responses to endogenous and exogenous glucagon-like peptide-1 (GLP-1) in Hispanics/Latinos (H/Ls) with prediabetes. The results move the management of prediabetes, type 2 diabetes mellitus (T2DM), and relevant metabolic diseases to a more individualized approach in an understudied and at-risk population. Few options exist for prediabetes treatment, and the current pharmaceutical management of T2DM does not predict drug treatment failures, nor differences in individual treatment responses and adverse effects. A precise, genetics-based approach will provide superior therapeutic management for patients. GLP-1-based therapies reduce blood glucose, promote weight loss, decrease cardiovascular events, and improve renal function. Prior genetic studies, most done in Caucasians, identified associations between genetic variants and decreased GLP-1-induced insulin secretion, in an effort to guide individualized treatment. However, these associations do not provide a clear mechanistic relationship between genotype and phenotype. Transcriptomic analyses will uncover many of these mechanisms. Here, we propose to 1) test the association of single nucleotide polymorphisms (SNPs) that regulate expression (eQTLs) of 11 candidate genes in a range of relevant metabolic tissues with differential GLP-1 response, 2) perform RNA sequencing before and after treatment to identify eQTLs in blood that predict response to GLP-1 therapy and develop risk-based prediction models in H/Ls, and 3) determine the effects of genetic regulation of candidate genes and newly discovered eQTLs phenome-wide in a large existing biobank, BioVU. For aims 1 and 2, responses will be measured in 300 study subjects with prediabetes recruited from an established Mexican-American cohort via the oral minimal model method, before and after GLP-1 therapy, quantifying GLP-1 hormone efficacy and GLP-1-induced pancreatic beta cell insulin release and peripheral insulin sensitivity. Procedures include serial measurements of plasma glucose, insulin, C-peptide, and GLP-1, and peripheral blood collection for RNA sequencing. Our central hypotheses are: (1) metabolic tissue-based eQTLs of GLP-1-associated genes will be associated with physiological response to endogenous and exogenous GLP-1,(2) identification of eQTLs associated with GLP-1 treatment-induced changes in whole blood will identify new gene targets, and (3) this data will lead to the creation of eQTL-based prediction models for related diseases. The study is innovative because it uses a novel combination of eQTL analysis and oral minimal model to assess GLP-1 response, examines a population highly underrepresented in pharmacogenomic studies, and utilizes novel statistical methods and applications to study gene expression. The significance of this newly acquired mechanistic information will ultimately guide precision therapeutic regimens for diabetes prevention and treatment, weight loss, cardiovascular risk reduction, and related metabolic complications in an understudied population. ### Conditions Module **Conditions:** - PreDiabetes **Keywords:** - prediabetes - Mexican-American - GLP-1 - pharmacogenetics - expression quantitative trait loci ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP **Intervention Model Description:** Single center, before and after clinical trial ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 300 **Type:** ESTIMATED **Phases:** - PHASE4 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Semaglutide 0.25 mg subcutaneously weekly for 4 weeks, followed by semaglutide 0.5 mg subcutaneously weekly for 8 weeks. **Intervention Names:** - Drug: Semaglutide **Label:** Semaglutide **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Semaglutide **Description:** Glucagon-like Peptide 1 Receptor Agonist **Name:** Semaglutide **Other Names:** - Ozempic **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** A rate which measures the ability of beta cells to secrete insulin **Measure:** Mean change in beta cell responsivity **Time Frame:** 12 weeks **Description:** Measurement of the efficacy of insulin action at peripheral tissues **Measure:** Insulin Sensitivity **Time Frame:** 12 weeks **Description:** Product of beta cell responsivity and insulin sensitivity (see above) **Measure:** Disposition Index **Time Frame:** 12 weeks **Description:** Measurement of GLP-1 (glucagon-like peptide 1) hormonal efficacy in relationship to postprandial insulin secretion **Measure:** GLP-1-Induced Potentiation **Time Frame:** 12 weeks **Description:** Comparison of GLP-1 AUC measurements before and after drug intervention **Measure:** Mean change in GLP-1 Area Under the Curve (AUC) **Time Frame:** 12 weeks **Description:** eQTLs (expresion quantitative trait loci) are genes which affect the mRNA expression of another target gene. **Measure:** Gene expression changes for minor variants of eQTLs for TCF7L2 **Time Frame:** 12 weeks **Description:** eQTLs (expresion quantitative trait loci) are genes which affect the mRNA expression of another target gene. **Measure:** Gene expression changes for minor variants of eQTLs for KCNQ1 **Time Frame:** 12 weeks **Description:** eQTLs (expresion quantitative trait loci) are genes which affect the mRNA expression of another target gene. **Measure:** Gene expression changes for minor variants of eQTLs for WFS1 **Time Frame:** 12 weeks **Description:** eQTLs (expresion quantitative trait loci) are genes which affect the mRNA expression of another target gene. **Measure:** Gene expression changes for minor variants of eQTLs for THADA **Time Frame:** 12 weeks **Description:** eQTLs (expresion quantitative trait loci) are genes which affect the mRNA expression of another target gene. **Measure:** Gene expression changes for minor variants of eQTLs for CNR1 **Time Frame:** 12 weeks **Description:** eQTLs (expresion quantitative trait loci) are genes which affect the mRNA expression of another target gene. **Measure:** Gene expression changes for minor variants of eQTLs for CTRB1 **Time Frame:** 12 weeks **Description:** eQTLs (expresion quantitative trait loci) are genes which affect the mRNA expression of another target gene. **Measure:** Gene expression changes for minor variants of eQTLs for CTRB2 **Time Frame:** 12 weeks **Description:** eQTLs (expresion quantitative trait loci) are genes which affect the mRNA expression of another target gene. **Measure:** Gene expression changes for minor variants of eQTLs for GLP1R **Time Frame:** 12 weeks **Description:** eQTLs (expresion quantitative trait loci) are genes which affect the mRNA expression of another target gene. **Measure:** Gene expression changes for minor variants of eQTLs for CHST3 **Time Frame:** 12 weeks **Description:** eQTLs (expresion quantitative trait loci) are genes which affect the mRNA expression of another target gene. **Measure:** Gene expression changes for minor variants of eQTLs for MTNR1B **Time Frame:** 12 weeks **Description:** eQTLs (expresion quantitative trait loci) are genes which affect the mRNA expression of another target gene. **Measure:** Gene expression changes for minor variants of eQTLs for SORCS1 **Time Frame:** 12 weeks **Description:** Study has statistical power to detect previously unidentified eQTLs **Measure:** Previously unidentified cis-eQTLs associated with change in gene expression due to GLP-1 challenge **Time Frame:** 12 weeks #### Secondary Outcomes **Description:** Comparison of glucose AUC measurements before and after drug intervention **Measure:** Mean change in glucose Area Under the Curve (AUC) **Time Frame:** 12 weeks **Description:** Comparison of C-peptide AUC measurements before and after drug intervention **Measure:** Mean change in C-peptide Area Under the Curve (AUC) **Time Frame:** 12 weeks **Description:** Change in hemoglobin A1C (measured once on each study day) before and after intervention **Measure:** Change in hemoglobin A1C **Time Frame:** 12 weeks **Description:** Comparison of insulin AUC measurements before and after drug intervention **Measure:** Mean change in insulin Area Under the Curve (AUC) **Time Frame:** 12 weeks **Description:** Create and apply eQTL-based prediction models to investigate the clinical consequences of variable GLP-1- induced gene expression changes (identified as above) in large electronic health records (EHRs), and use these models to predict disease risk phenome-wide. **Measure:** Creation of eQTL-based disease prediction models **Time Frame:** 5 years **Description:** Creation of Polygenic prediction model using above data **Measure:** Polygenic prediction model for GLP-1 therapy-associated outcomes **Time Frame:** 5 years ### Eligibility Module **Eligibility Criteria:** Inclusion criteria: 1. Men and women, ages 18 years and older 2. Diagnosis of Prediabetes - defined as either impaired fasting glucose (fasting glucose of 100-125 mg/dL), impaired glucose tolerance (2-hour postprandial blood glucose of 140-199 mg/dL after 75-gram oral glucose challenge), and/or a hemoglobin A1C ranging from 5.7% to 6.4% 3. High risk for progression to diabetes: defined as having at least one of the two following additional factors: Obesity (BMI ≥ 30 kg/m2) and/or metabolically unhealthy status. "Metabolically unhealthy status" is defined as at least two of the following: elevated blood pressure (SBP ≥ 130 mmHg and/or DBP ≥ 85 mmHg), elevated triglycerides ≥ 150 mg/dL, low HDL cholesterol (males \< 40 mg/dL; females \< 50 mg/dL), and elevated fasting glucose ≥ 100 mg/dL (Wu S et al., 2017). 4. Women of childbearing age must agree to use an acceptable method of pregnancy prevention (barrier methods, abstinence, hormonal contraception, intrauterine contraception, or surgical sterilization) for the duration of the study. 5. Patients must have the following laboratory values: Hematocrit ≥ 34 vol%, estimated glomerular filtration rate ≥ 60 mL/min per 1.73 m2, AST (SGOT) \< 2.5 times ULN, ALT (SGPT) \< 2.5 times ULN, alkaline phosphatase \< 2.5 times ULN Exclusion Criteria: 1. History of Type 1 or Type 2 diabetes mellitus 2. Pregnant or breastfeeding women 3. Medications: metformin, DPP-4 inhibitors, GLP-1 receptor agonists, SGLT-2 inhibitors, thiazolidinediones, insulin, sulfonylureas, meglitinides, alpha-glucosidase inhibitors, and/or corticosteroids over the last 3 months. 4. Active malignancy 5. History of clinically significant cardiac, hepatic, pancreatic or renal disease. 6. History of any serious hypersensitivity reaction to the study medication (or any other incretin mimetic) 7. Prisoners or subjects who are involuntarily incarcerated 8. Prior history of pancreatitis, medullary thyroid cancer, or multiple endocrine neoplasia type 2 (MEN 2) 9. Family history of medullary thyroid cancer (a rare form of thyroid cancer) or MEN2. However, as many individuals may not be aware of the specific type of thyroid cancer, will also exclude any family history of thyroid cancer or MEN2. 10. Hospitalization for COVID-19 in last 3 months **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Norma Perez-Olazaran **Phone:** (956) 755-0695 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Rocio Uribe **Phone:** (956) 882-5165 **Role:** CONTACT #### Locations **Location 1:** **City:** Brownsville **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Norma Perez-Olazaran - **Phone:** 956-755-0695 - **Role:** CONTACT ***Contact 2:*** - **Email:** [email protected] - **Name:** Rocio Uribe - **Phone:** (956) 882-5165 - **Role:** CONTACT **Country:** United States **Facility:** UTHealth Clinical Research Unit (CRU) at UT Brownsville **State:** Texas **Status:** RECRUITING **Zip:** 78520 #### Overall Officials **Official 1:** **Affiliation:** The University of Texas Health Science Center, Houston **Name:** Absalon D Gutierrez, MD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000003920 - Term: Diabetes Mellitus - ID: D000044882 - Term: Glucose Metabolism Disorders - ID: D000008659 - Term: Metabolic Diseases - ID: D000004700 - Term: Endocrine System Diseases - ID: D000006943 - Term: Hyperglycemia ### 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: M14117 - Name: Prediabetic State - Relevance: HIGH - As Found: Prediabetes - ID: M20295 - Name: Glucose Intolerance - Relevance: HIGH - As Found: Prediabetes - ID: M7115 - Name: Diabetes Mellitus - Relevance: LOW - As Found: Unknown - 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: M9994 - Name: Hyperglycemia - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000011236 - Term: Prediabetic State - ID: D000018149 - Term: Glucose Intolerance ### 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 ### Intervention Browse Module - Browse Branches - Abbrev: Gast - Name: Gastrointestinal Agents - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Hypo - Name: Hypoglycemic Agents ### Intervention Browse Module - Browse Leaves - ID: M9043 - Name: Glucagon - Relevance: LOW - As Found: Unknown - ID: M353561 - Name: Semaglutide - Relevance: HIGH - As Found: Physical therapy - 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 ### Intervention Browse Module - Meshes - ID: C000591245 - Term: Semaglutide ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04720079 **Brief Title:** Paravertebral Block With Brachial Plexus Block for Upper Arm Arteriovenous Fistula Surgery **Official Title:** The Effectiveness of Thoracic Paravertebral Block in Improving the Anesthetic Effects of Regional Anesthesia for Upper Extremity Arteriovenous Fistula Surgery #### Organization Study ID Info **ID:** 20-2303 #### Organization **Class:** OTHER **Full Name:** University of North Carolina, Chapel Hill ### Status Module #### Completion Date **Date:** 2022-02-15 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2022-05-13 **Type:** ACTUAL **Last Update Submit Date:** 2022-05-11 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2022-02-15 **Type:** ACTUAL #### Start Date **Date:** 2020-11-15 **Type:** ACTUAL **Status Verified Date:** 2021-11 #### Study First Post Date **Date:** 2021-01-22 **Type:** ACTUAL **Study First Submit Date:** 2021-01-14 **Study First Submit QC Date:** 2021-01-21 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** University of North Carolina, Chapel Hill #### 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 primary goal of this quality improvement project is to find the optimal surgical conditions for patients undergoing upper arm arteriovenous graft surgery. Currently, there are two anesthetic techniques used in clinical practice. The goal is to standardize future practice and improve the care of patients postoperatively. The two techniques used in conjunction with a brachial plexus block are paravertebral nerve block and subcutaneous infiltration. **Detailed Description:** This study is designed to test the null hypothesis that paravertebral nerve block or subcutaneous infiltration provide similar operating conditions when combined with supraclavicular nerve block for upper arm arteriovenous fistula surgery. The results will help determine which approach to use and guide future research in this area. ### Conditions Module **Conditions:** - Regional Anesthesia Success ### Design Module #### Design Info **Allocation:** NON_RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 63 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Preoperative infiltration of intercostobrachial nerve with 10ml of ropivacaine 0.5% **Intervention Names:** - Procedure: Subcutaneous infiltration of intercostobrachial nerve **Label:** Intercostobrachial nerve Infiltration **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** Preoperative ultrasound guided T2 paravertebral nerve block with 10ml of ropivacaine 0.5% **Intervention Names:** - Procedure: T2 paravertebral nerve block **Label:** Ultrasound guided T2 paravertebral block **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Intercostobrachial nerve Infiltration **Description:** Preoperative subcutaneous infiltration of intercostobrachial nerve with 10ml of 0.5% ropivacaine **Name:** Subcutaneous infiltration of intercostobrachial nerve **Type:** PROCEDURE #### Intervention 2 **Arm Group Labels:** - Ultrasound guided T2 paravertebral block **Description:** Preoperative ultrasound guided T2 paravertebral nerve block with 10ml of 0.5% ropivacaine **Name:** T2 paravertebral nerve block **Type:** PROCEDURE ### Outcomes Module #### Primary Outcomes **Description:** Success is considered a regional anesthetic without rescue analgesic medications (including surgeon administered local anesthetic) or conversion to general anesthesia **Measure:** Number of Participants with Successful Regional Anesthesia **Time Frame:** By end of surgery ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Adult patients (\>18 years) undergoing upper limb arteriovenous fistula surgery at UNC Chapel Hill hospital Exclusion Criteria: * Contraindication to regional anesthesia * Significant peripheral neuropathy or neurological disorder of the upper extremity * Cognitive or psychiatric condition that will interfere with patient assessment **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Chapel Hill **Country:** United States **Facility:** University of North Carolina at Chapel Hill **State:** North Carolina **Zip:** 27599 #### Overall Officials **Official 1:** **Affiliation:** UNC Chapel Hill **Name:** Stuart A Grant **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **Access Criteria:** Approval from an IRB, IEC, or REB, as applicable, and an executed data use/sharing agreement with UNC **Description:** Deidentified individual data that supports the results will be shared beginning 9 to 36 months following publication provided the investigator who proposes to use the data has approval from an Institutional Review Board (IRB), Independent Ethics Committee (IEC), or Research Ethics Board (REB), as applicable, and executes a data use/sharing agreement with UNC. **Info Types:** - STUDY_PROTOCOL - SAP - CSR **IPD Sharing:** YES **Time Frame:** 9 to 36 months following publication ## Derived Section ### Condition Browse Module - Ancestors - ID: D000020763 - Term: Pathological Conditions, Anatomical - ID: D000001165 - Term: Arteriovenous Malformations - ID: D000054079 - Term: Vascular Malformations - ID: D000018376 - Term: Cardiovascular Abnormalities - ID: D000002318 - Term: Cardiovascular Diseases - ID: D000016157 - Term: Vascular Fistula - ID: D000014652 - Term: Vascular Diseases - ID: D000000013 - Term: Congenital Abnormalities ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: BC16 - Name: Diseases and Abnormalities at or Before Birth ### Condition Browse Module - Browse Leaves - ID: M8532 - Name: Fistula - Relevance: HIGH - As Found: Fistula - ID: M4472 - Name: Arteriovenous Fistula - Relevance: HIGH - As Found: Arteriovenous Fistula - ID: M22519 - Name: Pathological Conditions, Anatomical - Relevance: LOW - As Found: Unknown - ID: M12 - Name: Congenital Abnormalities - Relevance: LOW - As Found: Unknown - ID: M4473 - Name: Arteriovenous Malformations - Relevance: LOW - As Found: Unknown - ID: M27558 - Name: Vascular Malformations - Relevance: LOW - As Found: Unknown - ID: M20503 - Name: Cardiovascular Abnormalities - Relevance: LOW - As Found: Unknown - ID: M18619 - Name: Vascular Fistula - Relevance: LOW - As Found: Unknown - ID: M17400 - Name: Vascular Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000001164 - Term: Arteriovenous Fistula - ID: D000005402 - Term: Fistula ### 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 - ID: M4107 - Name: Anesthetics - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00368979 **Brief Title:** Dutasteride (GI198745) In Benign Prostatic Hyperplasia Subjects **Official Title:** Clinical Evaluation of Dutasteride in Benign Prostatic Hyperplasia: A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Comparative Study of GI198745 (Dutasteride) in Subjects With Benign Prostatic Hyperplasia. #### Organization Study ID Info **ID:** ARI105326 #### Organization **Class:** INDUSTRY **Full Name:** GlaxoSmithKline ### Status Module #### Completion Date **Date:** 2007-12-06 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2018-09-26 **Type:** ACTUAL **Last Update Submit Date:** 2018-08-30 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2007-12-01 **Type:** ACTUAL #### Results First Post Date **Date:** 2009-04-02 **Type:** ESTIMATED **Results First Submit Date:** 2008-12-05 **Results First Submit QC Date:** 2009-03-03 #### Start Date **Date:** 2006-02-17 **Status Verified Date:** 2018-08 #### Study First Post Date **Date:** 2006-08-29 **Type:** ESTIMATED **Study First Submit Date:** 2006-08-24 **Study First Submit QC Date:** 2006-08-24 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** GlaxoSmithKline #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** This study will assess the efficacy and safety of GI198745 0.5mg given once daily for 52 weeks to Benign Prostatic Hyperplasia (BPH) patients. ### Conditions Module **Conditions:** - Prostatic Hyperplasia **Keywords:** - Benign Prostatic Hyperplasia BPH dutasteride ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** DOUBLE **Who Masked:** - PARTICIPANT - INVESTIGATOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 378 **Type:** ACTUAL **Phases:** - PHASE3 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Intervention Names:** - Drug: Dutasteride **Label:** Dutasteride **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Intervention Names:** - Drug: Placebo **Label:** Placebo **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Dutasteride **Description:** once daily **Name:** Dutasteride **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Placebo **Description:** once daily **Name:** Placebo **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** The International Prostate Symptom Score (I-PSS) consists of 7 verified questions concerning urinary symptoms and one quality of life question scored from 0 to 5(0=Not at All, to 5=Almost Always). The total score can range from 0 to 35. Score of 1-7=Mild, 8-19=Moderate, 20-35=Severe. **Measure:** Change From Baseline in International Prostate Symptom Score (IPSS) at Week 52 **Time Frame:** Baseline and Week 52 #### Secondary Outcomes **Description:** Prostate volume measurements by transrectal ultrasound (TRUS). Average prostate volume (55cc). The Ultrasound scans the prostate in the transverse plane while moving in the cephalocaudal direction of the prostate. The height and width of the prostate section with the greatest surface area is recorded. **Measure:** Percent Change From Baseline in Prostate Volume at Week 52 **Time Frame:** Baseline and Week 52 **Description:** Improvement is defined as greater than or equal to a 2 point increase in participants total score on the I-PSS questionaire. **Measure:** Number of Participants With IPSS Improvement From Baseline at Week 52 **Time Frame:** Baseline and Week 52 **Description:** Maximum Urine Flow Rate (Qmax) is the peak flow in milliliters per second. **Measure:** Change From Baseline in Maximum Urine Flow Rate (Qmax) at Week 52 **Time Frame:** Baseline and Week 52 **Description:** Improvement was defined as an increase in Qmax by greater than or equal to 1 mL/sec **Measure:** Number of Participants With Qmax Improvement From Baseline at Week 52 **Time Frame:** Baseline and Week 52 ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: Only subjects who meet all the following criteria during the screening phase will be enrolled in the study. 1. Diagnosis: BPH 2. Age: ≥50 years 3. Gender: Male 4. Estimated prostate volume ≥30cc (by TRUS) 5. I-PSS Symptom Score (total of 7 items) ≥8 points 6. Maximum flow rate (Qmax) ≤15mL/sec (voided volume measured simultaneously ≤150mL)\*\[1\] 7. Patients who meet either of the following regarding tamsulosin HCl use: Patients with tamsulosin HCl use: Patients who have received tamsulosin HCl continuously for at least 4 weeks and who are likely to continue to take tamsulosin HCl without any change to the dosage and administration of the drug until the end of study treatment. Patients without tamsulosin HCl use: Patients who haven't received tamsulosin HCl in the past 4 weeks and who are unlikely to use tamsulosin HCl until the end of study treatment. 8. Outpatients 9. Patients who in person have given written consent Exclusion Criteria: Patients who apply to any of the following criteria during the screening phase will not be enrolled in the study. 1. Post void residual volume \>250mL (by suprapubic ultrasound). 2. History of AUR within the previous 12 weeks. 3. Evidence or history of prostate cancer. 4. PSA \>10ng/mL \[in patients with PSA \>4ng/mL, the presence of prostate cancer should be ruled out by the investigator/subinvestigator. DRE and free/total PSA ratio should be considered, and prostate biopsy be conducted if necessary\]. 5. Previous surgery (including balloon dilatation, thermotherapy and stent placement) or minimally invasive techniques for BPH. 6. Any causes other than BPH, which may in the judgment of the investigator/subinvestigator, affect evaluation of symptoms or urine flow (e.g., neurogenic bladder, bladder neck contracture, urethral stricture, bladder malignancy, acute/chronic prostatitis, acute/chronic urinary tract infection). 7. History of any unstable, serious co-existing medical condition(s) including, but not limited to, myocardial infarction, coronary bypass surgery, unstable angina, cardiac arrhythmias\*\[2\], congestive heart failure or cerebrovascular accident within the previous 6 months; or diabetes mellitus or peptic ulcer uncontrollable with medical treatment. 8. Liver function tests (AST, ALT, AL-P) \>2 times the upper limit of normal. 9. Serum cleatinine \>1.8mg/dL. 10. Use of any antiandrogen (e.g., chlormadinone acetate, allylesterenol) for BPH within the previous 12 months. 11. Use of a1-adrenoceptor blockers excluding tamsulosin HCl (e.g., prazosin HCl, urapidil slow-release capsule formulation, terazosin HCl, naftopidil), plant extract preparations for treatment of BPH (e.g., Eviprostat, cernitin pollen extract), herbal medicines (e.g., hachimi-jio-gan, gosha-jinki-gan), other drugs (e.g., Paraprost), and dietary or herbal supplements (e.g., saw palmetto) for relief of BPH symptoms within the previous 4 weeks. Use of a-adrenoceptor agonists (e.g., pseudoephedrine, phenyle * \[1\] Subjects with voided volume \<150 mL at Qmax measurement cannot be enrolled in the study and may undergo re-measurement of Qmax before the visit for Week 0 for study entry. * \[2\] Of "Degree II" according to "Grading of Side Effects (PMSB Notification No. 80 dated June 29, 1992) or equivalent (Appendix 4). **Minimum Age:** 50 Years **Sex:** MALE **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Chiba **Country:** Japan **Facility:** GSK Investigational Site **Zip:** 263-0043 **Location 2:** **City:** Chiba **Country:** Japan **Facility:** GSK Investigational Site **Zip:** 266-0031 **Location 3:** **City:** Chiba **Country:** Japan **Facility:** GSK Investigational Site **Zip:** 272-0107 **Location 4:** **City:** Fukuoka **Country:** Japan **Facility:** GSK Investigational Site **Zip:** 802-0077 **Location 5:** **City:** Fukuoka **Country:** Japan **Facility:** GSK Investigational Site **Zip:** 810-0001 **Location 6:** **City:** Fukuoka **Country:** Japan **Facility:** GSK Investigational Site **Zip:** 830-0027 **Location 7:** **City:** Hyogo **Country:** Japan **Facility:** GSK Investigational Site **Zip:** 660-0052 **Location 8:** **City:** Kanagawa **Country:** Japan **Facility:** GSK Investigational Site **Zip:** 215-0021 **Location 9:** **City:** Kanagawa **Country:** Japan **Facility:** GSK Investigational Site **Zip:** 226-0025 **Location 10:** **City:** Kanagawa **Country:** Japan **Facility:** GSK Investigational Site **Zip:** 229-1103 **Location 11:** **City:** Kanagawa **Country:** Japan **Facility:** GSK Investigational Site **Zip:** 245-0015 **Location 12:** **City:** Kanagawa **Country:** Japan **Facility:** GSK Investigational Site **Zip:** 252-0804 **Location 13:** **City:** Kanagawa **Country:** Japan **Facility:** GSK Investigational Site **Zip:** 259-1132 **Location 14:** **City:** Kyoto **Country:** Japan **Facility:** GSK Investigational Site **Zip:** 604-8436 **Location 15:** **City:** Oita **Country:** Japan **Facility:** GSK Investigational Site **Zip:** 871-0012 **Location 16:** **City:** Oita **Country:** Japan **Facility:** GSK Investigational Site **Zip:** 874-0937 **Location 17:** **City:** Osaka **Country:** Japan **Facility:** GSK Investigational Site **Zip:** 542-0073 **Location 18:** **City:** Osaka **Country:** Japan **Facility:** GSK Investigational Site **Zip:** 562-0036 **Location 19:** **City:** Osaka **Country:** Japan **Facility:** GSK Investigational Site **Zip:** 584-0074 **Location 20:** **City:** Tokyo **Country:** Japan **Facility:** GSK Investigational Site **Zip:** 130-0026 **Location 21:** **City:** Tokyo **Country:** Japan **Facility:** GSK Investigational Site **Zip:** 131-0032 **Location 22:** **City:** Tokyo **Country:** Japan **Facility:** GSK Investigational Site **Zip:** 150-0002 **Location 23:** **City:** Tokyo **Country:** Japan **Facility:** GSK Investigational Site **Zip:** 152-0001 **Location 24:** **City:** Tokyo **Country:** Japan **Facility:** GSK Investigational Site **Zip:** 153-0051 **Location 25:** **City:** Tokyo **Country:** Japan **Facility:** GSK Investigational Site **Zip:** 183-0044 **Location 26:** **City:** Tokyo **Country:** Japan **Facility:** GSK Investigational Site **Zip:** 186-0011 #### Overall Officials **Official 1:** **Affiliation:** GlaxoSmithKline **Name:** GSK Clinical Trials **Role:** STUDY_DIRECTOR ### References Module #### References **Citation:** Tsukamoto T, Endo Y, Narita M. Efficacy and safety of dutasteride in Japanese men with benign prostatic hyperplasia. Int J Urol. 2009 Sep;16(9):745-50. doi: 10.1111/j.1442-2042.2009.02357.x. Epub 2009 Aug 5. **PMID:** 19674165 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000010335 - Term: Pathologic Processes - ID: D000011469 - Term: Prostatic Diseases - ID: D000005832 - Term: Genital Diseases, Male - ID: D000091662 - Term: Genital Diseases - ID: D000091642 - Term: Urogenital Diseases - ID: D000052801 - Term: Male Urogenital Diseases ### 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 ### Condition Browse Module - Browse Leaves - ID: M14334 - Name: Prostatic Hyperplasia - Relevance: HIGH - As Found: Prostatic Hyperplasia - ID: M10016 - Name: Hyperplasia - Relevance: HIGH - As Found: Hyperplasia - ID: M14333 - Name: Prostatic Diseases - Relevance: LOW - As Found: Unknown - ID: M2876 - Name: Genital Diseases - Relevance: LOW - As Found: Unknown - ID: M8944 - Name: Genital Diseases, Male - Relevance: LOW - As Found: Unknown - ID: M2875 - Name: Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M27095 - Name: Male Urogenital Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000011470 - Term: Prostatic Hyperplasia - ID: D000006965 - Term: Hyperplasia ### Intervention Browse Module - Ancestors - ID: D000058891 - Term: 5-alpha Reductase Inhibitors - ID: D000065088 - Term: Steroid Synthesis Inhibitors - ID: D000004791 - Term: Enzyme Inhibitors - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000006727 - Term: Hormone Antagonists - ID: D000006730 - Term: Hormones, Hormone Substitutes, and Hormone Antagonists - 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: M270 - Name: Dutasteride - Relevance: HIGH - As Found: Cells/kg - ID: M29274 - Name: 5-alpha Reductase Inhibitors - Relevance: LOW - As Found: Unknown - ID: M7951 - Name: Enzyme Inhibitors - 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: D000068538 - Term: Dutasteride ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module **Description:** Serious adverse events (SAEs) and non-serious AEs were collected in all participants who received at least one dose of the investigational product. #### Event Groups **Group ID:** EG000 **Title:** Placebo **Description:** Subjects who took no study medication capsule once daily for 52 weeks followed by up to 16 weeks of post-dosing assessments. **ID:** EG000 **Other Num Affected:** 116 **Other Num at Risk:** 184 **Serious Number Affected:** 8 **Serious Number At Risk:** 184 **Title:** Placebo **Group ID:** EG001 **Title:** Dutasteride **Description:** Subjects who took dutasteride, study medication of 0.5 mg capsule once daily for 52 weeks followed by up to 16 weeks of post-dosing assessments. **ID:** EG001 **Other Num Affected:** 124 **Other Num at Risk:** 193 **Serious Number Affected:** 20 **Serious Number At Risk:** 193 **Title:** Dutasteride **Frequency Threshold:** 5 #### Other Events **Term:** Nasopharyngitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (9.0) **Term:** Diarrhoea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA (9.0) **Term:** Upper respiratory tract inflammation **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA (9.0) **Term:** Back pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA (9.0) **Term:** Constipation **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA (9.0) **Term:** Eczema **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA (9.0) **Term:** Headache **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA (9.0) **Term:** Arthralgia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA (9.0) **Term:** Gastritis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA (9.0) #### Serious Events **Term:** Colonic polyp **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA (9.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 184 **Group ID:** EG001 **Num Affected:** 3 **Num At Risk:** 193 **Term:** Inguinal hernia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA (9.0) ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 184 **Group ID:** EG001 **Num At Risk:** 193 **Term:** Enterocolitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA (9.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 184 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 193 **Term:** Haemorrhoids **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA (9.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 184 **Group ID:** EG001 **Num At Risk:** 193 **Term:** Intestinal obstruction **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA (9.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 184 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 193 **Term:** Gastric cancer **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA (9.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 184 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 193 **Term:** Bladder cancer **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA (9.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 184 **Group ID:** EG001 **Num At Risk:** 193 **Term:** Lymph node cancer metastatic **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA (9.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 184 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 193 **Term:** Meningioma **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA (9.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 184 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 193 **Term:** Pancreatic carcinoma **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA (9.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 184 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 193 **Term:** Cerebral infarction **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA (9.0) ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 184 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 193 **Term:** Dementia Alzheimer's type **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA (9.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 184 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 193 **Term:** Thrombotic stroke **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA (9.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 184 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 193 **Term:** Intervertebral disc protrusion **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA (9.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 184 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 193 **Term:** Lumbar spinal stenosis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA (9.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 184 **Group ID:** EG001 **Num At Risk:** 193 **Term:** Synovitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA (9.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 184 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 193 **Term:** Acute myocardial infarction **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA (9.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 184 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 193 **Term:** Coronary artery stenosis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA (9.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 184 **Group ID:** EG001 **Num At Risk:** 193 **Term:** Pneumonia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (9.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 184 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 193 **Term:** Urinary tract infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (9.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 184 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 193 **Term:** Aortic dissection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA (9.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 184 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 193 **Term:** Microscopic polyangiitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA (9.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 184 **Group ID:** EG001 **Num At Risk:** 193 **Term:** Macular degeneration **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Eye disorders **Source Vocabulary:** MedDRA (9.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 184 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 193 **Term:** Cholangitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA (9.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 184 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 193 ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 181 **Group ID:** BG001 **Value:** 184 **Group ID:** BG002 **Value:** 365 **Units:** Participants ### Group **ID:** BG000 **Title:** Placebo **Description:** Subjects who took no study medication capsule once daily for 52 weeks followed by up to 16 weeks of post-dosing assessments. ### Group **ID:** BG001 **Title:** Dutasteride **Description:** Subjects who took dutasteride, study medication of 0.5 mg capsule once daily for 52 weeks followed by up to 16 weeks of post-dosing assessments. ### Group **ID:** BG002 **Title:** Total **Description:** Total of all reporting groups ### Measure #### Measurement **Group ID:** BG000 **Spread:** 6.76 **Value:** 66.9 #### Measurement **Group ID:** BG001 **Spread:** 6.07 **Value:** 68.0 #### Measurement **Group ID:** BG002 **Spread:** 6.44 **Value:** 67.4 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 181 #### Measurement **Group ID:** BG001 **Value:** 184 #### Measurement **Group ID:** BG002 **Value:** 365 **Category Title:** Male **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 181 #### Measurement **Group ID:** BG001 **Value:** 184 #### Measurement **Group ID:** BG002 **Value:** 365 **Class Title:** Asian-Japanese **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:** -2.7 **CI Number of Sides:** **CI Percentage Value:** 95 **CI Upper Limit:** -0.5 **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:** 0.003 **P-Value Comment:** **Parameter Type:** Mean Difference (Net) **Parameter Value:** -1.6 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** ### 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:** 5.72 - **Upper Limit:** - **Value:** -3.6 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 5.94 - **Upper Limit:** - **Value:** -5.5 **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 18.76 - **Upper Limit:** - **Value:** -8.9 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 16.85 - **Upper Limit:** - **Value:** -31.5 **Title:** #### Outcome Measure 3 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 113 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 139 **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:** 128 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 82 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 115 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 75 - **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:** 62 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 82 **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:** 122 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 84 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 114 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 71 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 106 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 54 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 86 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 39 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 67 **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:** 17 **Title:** #### Outcome Measure 4 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 3.82 - **Upper Limit:** - **Value:** 0.6 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 4.89 - **Upper Limit:** - **Value:** 2.2 **Title:** #### Outcome Measure 5 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 79 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 103 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 56 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 86 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 45 - **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:** 44 - **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:** 29 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 53 **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:** 44 **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:** 11 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 41 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 63 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** The International Prostate Symptom Score (I-PSS) consists of 7 verified questions concerning urinary symptoms and one quality of life question scored from 0 to 5(0=Not at All, to 5=Almost Always). The total score can range from 0 to 35. Score of 1-7=Mild, 8-19=Moderate, 20-35=Severe. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** The Full Analysis Set (FAS) which consisted of all randomized participants with a history excluding those who received no dose of the investigational product and who had no baseline or post baseline IPSS data. Last Observation Carried Forward (LOCF) method for lost data. **Reporting Status:** POSTED **Time Frame:** Baseline and Week 52 **Title:** Change From Baseline in International Prostate Symptom Score (IPSS) at Week 52 **Type:** PRIMARY **Unit of Measure:** score on a scale ##### Group **Description:** Subjects who took no study medication capsule once daily for 52 weeks followed by up to 16 weeks of post-dosing assessments. **ID:** OG000 **Title:** Placebo ##### Group **Description:** Subjects who took dutasteride, study medication of 0.5 mg capsule once daily for 52 weeks followed by up to 16 weeks of post-dosing assessments. **ID:** OG001 **Title:** Dutasteride #### Outcome Measure 2 **Description:** Prostate volume measurements by transrectal ultrasound (TRUS). Average prostate volume (55cc). The Ultrasound scans the prostate in the transverse plane while moving in the cephalocaudal direction of the prostate. The height and width of the prostate section with the greatest surface area is recorded. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** The Full Analysis Set (FAS) which consisted of all randomized participants with a history excluding those who received no dose of the investigational product and who had no baseline or post baseline IPSS data. Last Observation Carried Forward (LOCF) method for lost data. **Reporting Status:** POSTED **Time Frame:** Baseline and Week 52 **Title:** Percent Change From Baseline in Prostate Volume at Week 52 **Type:** SECONDARY **Unit of Measure:** cubic centimeters (cc) ##### Group **Description:** Subjects who took no study medication capsule once daily for 52 weeks followed by up to 16 weeks of post-dosing assessments. **ID:** OG000 **Title:** Placebo ##### Group **Description:** Subjects who took dutasteride, study medication of 0.5 mg capsule once daily for 52 weeks followed by up to 16 weeks of post-dosing assessments. **ID:** OG001 **Title:** Dutasteride #### Outcome Measure 3 **Description:** Improvement is defined as greater than or equal to a 2 point increase in participants total score on the I-PSS questionaire. **Parameter Type:** NUMBER **Population Description:** The Full Analysis Set (FAS) which consisted of all randomized participants with a history excluding those who received no dose of the investigational product and who had no baseline or post baseline IPSS data. Last Observation Carried Forward (LOCF) method for lost data. **Reporting Status:** POSTED **Time Frame:** Baseline and Week 52 **Title:** Number of Participants With IPSS Improvement From Baseline at Week 52 **Type:** SECONDARY **Unit of Measure:** participants ##### Group **Description:** Subjects who took no study medication capsule once daily for 52 weeks followed by up to 16 weeks of post-dosing assessments. **ID:** OG000 **Title:** Placebo ##### Group **Description:** Subjects who took dutasteride, study medication of 0.5 mg capsule once daily for 52 weeks followed by up to 16 weeks of post-dosing assessments. **ID:** OG001 **Title:** Dutasteride #### Outcome Measure 4 **Description:** Maximum Urine Flow Rate (Qmax) is the peak flow in milliliters per second. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** The Full Analysis Set (FAS) which consisted of all randomized participants with a history excluding those who received no dose of the investigational product and who had no baseline or post baseline IPSS data. Last Observation Carried Forward (LOCF) method for lost data. **Reporting Status:** POSTED **Time Frame:** Baseline and Week 52 **Title:** Change From Baseline in Maximum Urine Flow Rate (Qmax) at Week 52 **Type:** SECONDARY **Unit of Measure:** milliliters per second (mL/sec) ##### Group **Description:** Subjects who took no study medication capsule once daily for 52 weeks followed by up to 16 weeks of post-dosing assessments. **ID:** OG000 **Title:** Placebo ##### Group **Description:** Subjects who took dutasteride, study medication of 0.5 mg capsule once daily for 52 weeks followed by up to 16 weeks of post-dosing assessments. **ID:** OG001 **Title:** Dutasteride #### Outcome Measure 5 **Description:** Improvement was defined as an increase in Qmax by greater than or equal to 1 mL/sec **Parameter Type:** NUMBER **Population Description:** The Full Analysis Set (FAS) which consisted of all randomized participants with a history excluding those who received no dose of the investigational product and who had no baseline or post baseline IPSS data. Last Observation Carried Forward (LOCF) method for lost data. **Reporting Status:** POSTED **Time Frame:** Baseline and Week 52 **Title:** Number of Participants With Qmax Improvement From Baseline at Week 52 **Type:** SECONDARY **Unit of Measure:** participants ##### Group **Description:** Subjects who took no study medication capsule once daily for 52 weeks followed by up to 16 weeks of post-dosing assessments. **ID:** OG000 **Title:** Placebo ##### Group **Description:** Subjects who took dutasteride, study medication of 0.5 mg capsule once daily for 52 weeks followed by up to 16 weeks of post-dosing assessments. **ID:** OG001 **Title:** Dutasteride ### Participant Flow Module #### Group **Description:** Subjects who took no study medication capsule once daily for 52 weeks followed by up to 16 weeks of post-dosing assessments. **ID:** FG000 **Title:** Placebo #### Group **Description:** Subjects who took dutasteride, study medication of 0.5 mg capsule once daily for 52 weeks followed by up to 16 weeks of post-dosing assessments. **ID:** FG001 **Title:** Dutasteride #### Period **Title:** Overall Study ##### Withdraw **Type:** Adverse Event ###### Reason **Group ID:** FG000 **Number of Subjects:** 9 ###### Reason **Group ID:** FG001 **Number of Subjects:** 16 ##### Withdraw **Type:** Lack of Efficacy ###### Reason **Group ID:** FG000 **Number of Subjects:** 5 ###### Reason **Group ID:** FG001 **Number of Subjects:** 3 ##### Withdraw **Type:** Other ###### Reason **Group ID:** FG000 **Number of Subjects:** 3 ###### Reason **Group ID:** FG001 **Number of Subjects:** 1 ##### Withdraw **Type:** Lost to Follow-up ###### Reason **Group ID:** FG000 **Number of Subjects:** 1 ###### Reason **Group ID:** FG001 **Number of Subjects:** 0 ##### Withdraw **Type:** Protocol Violation ###### Reason **Group ID:** FG000 **Number of Subjects:** 2 ###### Reason **Group ID:** FG001 **Number of Subjects:** 1 ##### Withdraw **Type:** Withdrawal by Subject ###### Reason **Group ID:** FG000 **Number of Subjects:** 5 ###### Reason **Group ID:** FG001 **Number of Subjects:** 9 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 185 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 193 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 160 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 163 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 25 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 30 **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT02923479 **Brief Title:** Robot-assisted Rehabilitation of Ankle Fractures: Efficacy and Comparison With Traditional Methods **Official Title:** Robot-assisted Ankle Rehabilitation Using the High-performance Robotic Device IIT-ARBOT: A Pilot Randomised Controlled Study #### Organization Study ID Info **ID:** CRMINAIL01 #### Organization **Class:** OTHER **Full Name:** Istituto Nazionale Assicurazione contro gli Infortuni sul Lavoro ### Status Module #### Completion Date **Date:** 2015-09 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2016-10-04 **Type:** ESTIMATED **Last Update Submit Date:** 2016-10-01 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2015-09 **Type:** ACTUAL #### Start Date **Date:** 2013-03 **Status Verified Date:** 2016-09 #### Study First Post Date **Date:** 2016-10-04 **Type:** ESTIMATED **Study First Submit Date:** 2016-09-28 **Study First Submit QC Date:** 2016-10-01 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** Istituto Italiano di Tecnologia #### Lead Sponsor **Class:** OTHER **Name:** Istituto Nazionale Assicurazione contro gli Infortuni sul Lavoro #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** The purpose of this trial is to determine the effectiveness, safety and tolerability of robot-assisted rehabilitation using ARBOT in patients with ankle dysfunction resulting from work related ankle fractures, compared with conventional rehabilitation programs. **Detailed Description:** INTRODUCTION: Robotic devices for lower-limb rehabilitation have been mainly tested in neurologically injured patients. Up to now, clinical studies using robotic training in orthopedic conditions are few. A pilot study was carried out at INAIL Physical Rehabilitation Center of Volterra using ARBOT, a prototypal robotic system for ankle rehabilitation. This device has been developed by IIT - Italian Institute of Technology and it consists of a two-degree-of-freedom electromechanical platform which is able to perform most of the exercises foreseen by the standard rehabilitation programs. By virtue of its innovative motion system and control architecture, ARBOT integrates multiple rehabilitation equipment functions, performing also special exercise programs such as elastic and fluid-dynamic resistance. ARBOT allows training according to programmed sequences, in order to promote range of movement, muscular function and proprioceptive recovery. Exercises can be performed with or without bearing weight. Moreover, ARBOT is a powerful evaluation instrument for physiotherapists in order to verify and record the results of rehabilitative intervention. The primary aim of this trial was to determine the effectiveness, safety and tolerability of robot-assisted rehabilitation using ARBOT in patients with ankle dysfunction resulting from work related ankle fractures, compared with conventional rehabilitation programs. Secondary objectives was to investigate correlations among physical and disability parameters, to collect data in order to define further study protocols and improve ARBOT's performance and ergonomics, and ultimately to evaluate patient satisfaction with respect to robot assisted rehabilitation programs. METHODS: Thirty-two patients with work related injuries resulting in ankle and/or hindfoot fractures and subsequent to the immobilization phase was enrolled in an open randomized controlled trial over a 30 month period. Each participant was randomly allocated to experimental or control group and received a 4-week rehabilitation program (20 sessions, for 5 days/week from admission to discharge in the Rehabilitation Centre) and weekly robotic and clinical assessments. Subjects in the experimental group were treated using ARBOT with passive, active and active assisted range-of-motion exercises, resistive exercises in isometric, isotonic, isokinetic, elastic and fluid-dynamic conditions, and proprioceptive training. Control subjects were assisted by a physiotherapist during range of motion recovery exercises and performed resistive and proprioceptive training using Biodex System 3 dynamometer and ProKin PK254 mobile electronic platform. The assessment sessions included measurements of dorsiflexion ROM, isometric and isokinetic plantar-flexion torque and proprioceptive performance with ARBOT and 2 minutes walking and timed stair climbing test, LEFS-Lower Extremity Functional Scale and AOFAS-Ankle-Hindfoot Scale. Site monitoring of the study has been conducted according to the standard ISO 14155. ### Conditions Module **Conditions:** - Ankle Fractures **Keywords:** - Rehabilitation - Robotics ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 32 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** The patients in the "ARBOT Group" underwent to following interventions: 1. General Rehabilitation 2. Specific ankle rehabilitation by ARBOT device **Intervention Names:** - Device: Specific ankle rehabilitation by ARBOT device - Other: General Rehabilitation **Label:** Experimental: ARBOT Group **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** The patients in the Control Group underwent to following interventions: 1. General Rehabilitation 2. Specific ankle rehabilitation performed by physiotherapist 3. Specific ankle rehabilitation by Biodex System 3 dynamometer 4. Specific ankle rehabilitation by ProKin PK254 platform. **Intervention Names:** - Other: General Rehabilitation - Other: Specific ankle rehabilitation performed by physiotherapist - Device: Specific ankle rehabilitation by Biodex System 3 dynamometer - Device: Specific ankle rehabilitation by ProKin PK254 platform **Label:** Control Group **Type:** OTHER ### Interventions #### Intervention 1 **Arm Group Labels:** - Experimental: ARBOT Group **Description:** ARBOT is a programmable robotic device consisting in a two-degree-of-freedom electromechanical platform developed by Italian Institute of Technology - Advanced Robotics and Rehab Technologies. It is composed of a fixed base, a central strut, a moving platform supporting patient's foot and three actuated limbs with a universal-prismatic-spherical kinematic chain. A six-axis force/torque sensor mounted between the moving platform and the footplate senses the human-robot interaction force and torque. The device is interfaced to a standard all-in-one touch screen Personal Computer with graphic applications to give patients visual feedback in real time. **Name:** Specific ankle rehabilitation by ARBOT device **Type:** DEVICE #### Intervention 2 **Arm Group Labels:** - Control Group - Experimental: ARBOT Group **Description:** All patients underwent general rehabilitation (gait training, aerobic conditioning), including - if necessary - an initial weight training phase before the functional full weight-bearing program. **Name:** General Rehabilitation **Type:** OTHER #### Intervention 3 **Arm Group Labels:** - Control Group **Description:** Subjects in the control group underwent manually assisted range of motion exercises. **Name:** Specific ankle rehabilitation performed by physiotherapist **Type:** OTHER #### Intervention 4 **Arm Group Labels:** - Control Group **Description:** Subjects in the control group performed non-robotic resistive training using a Biodex System 3 dynamometer **Name:** Specific ankle rehabilitation by Biodex System 3 dynamometer **Type:** DEVICE #### Intervention 5 **Arm Group Labels:** - Control Group **Description:** Subjects in the control group performed non-robotic proprioceptive training using a ProKin PK254 mobile electronic platform. **Name:** Specific ankle rehabilitation by ProKin PK254 platform **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Measure:** Change of Dorsiflexion Range of Motion **Time Frame:** At baseline and after 1, 2, 3 and 4 weeks intervention **Measure:** Change of Isometric peak torque at 0° and 10° of plantar flexion **Time Frame:** At baseline and after 2 and 4 weeks intervention **Measure:** Change of Isokinetic plantar-flexion torque at speed of 30°, 60°, 120°/sec **Time Frame:** At baseline and after 2 and 4 weeks intervention **Measure:** Change of 2 Minute Walk Test (2MWT) **Time Frame:** At baseline and after 2 and 4 weeks intervention **Measure:** Side Effects using ARBOT **Time Frame:** Through study completion, up to 4 weeks #### Secondary Outcomes **Measure:** Timed Stair Climbing Test (10 steps) **Time Frame:** At baseline and after 2 and 4 weeks intervention **Measure:** Proprioceptive tests (time taking and accuracy) **Time Frame:** At baseline and after after 2 and 4 weeks intervention **Measure:** Pain (VAS 0-10) **Time Frame:** At baseline and after 1, 2, 3 and 4 weeks intervention **Measure:** LEFS - The Lower Extremity Functional Scale **Time Frame:** At baseline and after after 4 weeks intervention **Measure:** AOFAS - Ankle-Hindfoot Scale **Time Frame:** At baseline and after 4 weeks intervention **Measure:** Patient Satisfaction (VAS 0-10) **Time Frame:** After 4 weeks intervention ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Functional limitation following work-related ankle injuries, including: * Malleolar and/or tibial shaft fractures, both surgically and conservatively treated; * Distal tibia and fibula fractures, both surgically and conservatively treated; * Hindfoot (Calcaneus and Talus) fractures, both surgically and conservatively treated. 2. Post-immobilization phase; 3. Time interval since fracture event of less than 12 months; 4. Signed informed consent acquisition. Exclusion Criteria: 1. Non-compliance with study requirements; 2. Pregnancy or breast feeding; 3. Current or prior history of malignancy; 4. Open skin at the level of the patient-device interface; 5. Sensory deficit at the level of the patient-device interface; 6. Ankle motor deficit secondary to peroneal or tibial neuropathy; 7. Acute inflammatory arthritis of the ankle; 8. Other pathological conditions inducing lower limb pain or disfunction. **Maximum Age:** 65 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Volterra **Country:** Italy **Facility:** INAIL - Centro di Riabilitazione Motoria di Volterra **State:** Pisa **Zip:** 56048 #### Overall Officials **Official 1:** **Affiliation:** INAIL - Centro di Riabilitazione Motoria di Volterra **Name:** Paolo Catitti, MD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Saglia JA, Tsagarakis NG, Dai JS, Caldwell DG. Control Strategies for Patient-Assisted Training Using the Ankle Rehabilitation Robot (ARBOT). IEEE ASME TRANSACTIONS ON MECHATRONICS 2013; PP (99): 1-10. **Citation:** Saglia JA, Tsagarakis NG, Dai JS, Caldwell DG. A high-performance redundantly actuated parallel mechanism for ankle rehabilitation. International Journal of Robotics Research 2009; 28 (9): 1216-1227. **Citation:** Saglia JA, Tsagarakis NG, Dai JS, Caldwell DG. Inverse-Kinematics-Based Control of a Redundantly Actuated Platform for Rehabilitation. Journal of Systems and Control Engineering, IMechE Proceedings 2009; 223 (1): 53-70. ## Derived Section ### Condition Browse Module - Ancestors - ID: D000050723 - Term: Fractures, Bone - ID: D000014947 - Term: Wounds and Injuries - ID: D000016512 - Term: Ankle Injuries - ID: D000007869 - Term: Leg Injuries ### Condition Browse Module - Browse Branches - Abbrev: BC26 - Name: Wounds and Injuries - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M26370 - Name: Fractures, Bone - Relevance: LOW - As Found: Unknown - ID: M30291 - Name: Ankle Fractures - Relevance: HIGH - As Found: Ankle Fractures - ID: M17685 - Name: Wounds and Injuries - Relevance: LOW - As Found: Unknown - ID: M18909 - Name: Ankle Injuries - Relevance: LOW - As Found: Unknown - ID: M10881 - Name: Leg Injuries - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000064386 - Term: Ankle Fractures ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00940979 **Acronym:** ITT **Brief Title:** Trial Using Integuseal as Microbial Sealant for Arterial Bypass Surgery on Lower Extremities **Official Title:** Prospective Randomised Trial Using Integuseal as Microbial Sealant for Arterial Bypass Surgery on Lower Extremities #### Organization Study ID Info **ID:** LTC 625-230609 #### Organization **Class:** OTHER **Full Name:** Rijnstate Hospital ### Status Module #### Completion Date **Date:** 2011-05 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2014-01-13 **Type:** ESTIMATED **Last Update Submit Date:** 2014-01-10 **Overall Status:** TERMINATED #### Primary Completion Date **Date:** 2011-04 **Type:** ACTUAL #### Start Date **Date:** 2010-01 **Status Verified Date:** 2014-01 #### Study First Post Date **Date:** 2009-07-17 **Type:** ESTIMATED **Study First Submit Date:** 2009-07-16 **Study First Submit QC Date:** 2009-07-16 **Why Stopped:** Interim analyses showed insufficient result. Termination for reasons of futility ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** Kimberly-Clark Corporation #### Lead Sponsor **Class:** OTHER **Name:** Rijnstate Hospital ### Description Module **Brief Summary:** The purpose of this study is to prove a reduction of postoperative wound infections after direct preoperative use of a microbial sealant in the form of Integuseal for vascular procedures on lower extremities. ### Conditions Module **Conditions:** - Arterial Obstructive Diseases **Keywords:** - Integuseal microbial sealant - Infection prophylaxis - Postoperative wound infection - Arterial bypass surgery ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** SINGLE **Who Masked:** - PARTICIPANT **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 450 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Label:** No use of integuseal **Type:** NO_INTERVENTION #### Arm Group 2 **Description:** Application of a layer of Integuseal (Cyanoacrylate) from a ready to use applicator preoperative before incision Polymerisation immobilise the bacteria that survived the conventional skin preparation This way there will be les contamination of the wound. **Intervention Names:** - Procedure: Application of Integuseal sealant **Label:** Use of Integuseal **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Use of Integuseal **Description:** Microbial sealant (integuseal) applied with a sponge applicator **Name:** Application of Integuseal sealant **Type:** PROCEDURE ### Outcomes Module #### Primary Outcomes **Measure:** Postoperative wound infections #### Secondary Outcomes **Measure:** Costs of the use of Integuseal **Measure:** Complications during hospital stay ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * planned supragenual of infragenual peripheral arterial bypass procedures with autologue or prosthetic graft Exclusion Criteria: * secondary procedures and suprainguinal procedures **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Arnhem **Country:** Netherlands **Facility:** Ziekenhuis Rijnstate **Zip:** 6800 TA **Location 2:** **City:** Doetinchem **Country:** Netherlands **Facility:** Ziekenhuis Slingland **Location 3:** **City:** Drachten **Country:** Netherlands **Facility:** Ziekenhuis Nij Smellinghe #### Overall Officials **Official 1:** **Affiliation:** Rijstate hospital Arnhem the Netherlands **Name:** Michel MPJ Reijnen, MD **Role:** STUDY_DIRECTOR **Official 2:** **Name:** J. Klinkenbijl, MD **Role:** STUDY_DIRECTOR **Official 3:** **Affiliation:** Rijnstate Hospital Arnhem the Netherlands **Name:** Sjoerd A de Beer, MD **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000014652 - Term: Vascular Diseases - ID: D000002318 - Term: Cardiovascular Diseases ### 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 - Abbrev: BC14 - Name: Heart and Blood 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: M17685 - Name: Wounds and Injuries - Relevance: LOW - As Found: Unknown - ID: M17684 - Name: Wound Infection - Relevance: LOW - As Found: Unknown - ID: M16310 - Name: Surgical Wound Infection - Relevance: LOW - As Found: Unknown - ID: M4465 - Name: Arterial Occlusive Diseases - Relevance: HIGH - As Found: Arterial Obstructive Disease - ID: M17400 - Name: Vascular Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000001157 - Term: Arterial Occlusive Diseases ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03124979 **Brief Title:** Accuracy of Noninvasive Pulse Oximeter Sensor (LNCS DBI) #### Organization Study ID Info **ID:** TR22194-TP16113 #### Organization **Class:** INDUSTRY **Full Name:** Masimo Corporation ### Status Module #### Completion Date **Date:** 2012-04-10 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2017-07-28 **Type:** ACTUAL **Last Update Submit Date:** 2017-06-28 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2012-04-10 **Type:** ACTUAL #### Results First Post Date **Date:** 2017-07-28 **Type:** ACTUAL **Results First Submit Date:** 2017-05-08 **Results First Submit QC Date:** 2017-06-28 #### Start Date **Date:** 2012-01-18 **Type:** ACTUAL **Status Verified Date:** 2017-06 #### Study First Post Date **Date:** 2017-04-24 **Type:** ACTUAL **Study First Submit Date:** 2017-04-14 **Study First Submit QC Date:** 2017-04-20 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Masimo Corporation #### 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:** In this study, the level of oxygen within the blood will be reduced in a controlled manner by reducing the percentage of oxygen the study volunteer breathes. The accuracy of a noninvasive pulse oximeter sensor will be assessed by comparison to the oxygen saturation measurements from a laboratory blood gas analyzer. ### Conditions Module **Conditions:** - Healthy ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** OTHER #### Enrollment Info **Count:** 13 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** All subjects are enrolled into the test group and all subjects received the LNCS DBI Sensor. **Intervention Names:** - Device: LNCS DBI Sensor **Label:** Test Subject **Type:** OTHER ### Interventions #### Intervention 1 **Arm Group Labels:** - Test Subject **Description:** Noninvasive Measurement of SpO2 **Name:** LNCS DBI Sensor **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Description:** Accuracy will be determined by comparing the noninvasive blood oxygen saturation measurement of the pulse oximeter to that obtained from a blood sample and calculating the arithmetic root mean square(Arms) error value. In order to obtain the Arms value, the blood oxygen saturation measurement is subtracted from the pulse oximeter oxygen saturation measurement for a number of samples, the average of this difference is computed as the bias. The standard deviation of these differences is computed as the precision. The square root of the sum of the squares of bias and precision is computed as the Arms Error value. **Measure:** Accuracy of Sensor by Arms Calculation **Time Frame:** 1-5 hours ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Competent non-smoking adults between the ages of 18 and 40 for each series of tests. * Subjects must understand and consent to be in the study. * American Society of Anesthesiology Class 1 (Healthy subjects without any systemic disease at all). Exclusion Criteria: * Subjects who have any systemic disease at all. * Subjects who do not understand the study and the risks. * Smokers. * Subjects who are pregnant. * Subjects having either signs or history of peripheral ischemia. * Others deemed ineligible by the clinical staff. **Healthy Volunteers:** True **Maximum Age:** 40 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Irvine **Country:** United States **Facility:** Masimo **State:** California **Zip:** 92618 ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module #### Event Groups **Group ID:** EG000 **Title:** Test Subject **Description:** All subjects are enrolled into the test group and all subjects received the LNCS DBI Sensor. **ID:** EG000 **Other Num at Risk:** 13 **Serious Number At Risk:** 13 **Title:** Test Subject **Frequency Threshold:** 0 ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 13 **Units:** Participants ### Group **ID:** BG000 **Title:** Test Subject **Description:** All subjects are enrolled into the test group and all subjects received the LNCS DBI Sensor. ### Measure #### Measurement **Group ID:** BG000 **Value:** 13 **Class Title:** 20-32 years ### Measure #### Measurement **Group ID:** BG000 **Value:** 2 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 11 **Category Title:** Male **Class Title:** **Denomination Units Selected:** ## Results Section - Baseline Characteristics Module ### Measure 1 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Age, Customized **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:** Masimo **Title:** Tala Harake ## 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:** 1.69 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** Accuracy will be determined by comparing the noninvasive blood oxygen saturation measurement of the pulse oximeter to that obtained from a blood sample and calculating the arithmetic root mean square(Arms) error value. In order to obtain the Arms value, the blood oxygen saturation measurement is subtracted from the pulse oximeter oxygen saturation measurement for a number of samples, the average of this difference is computed as the bias. The standard deviation of these differences is computed as the precision. The square root of the sum of the squares of bias and precision is computed as the Arms Error value. **Parameter Type:** NUMBER **Reporting Status:** POSTED **Time Frame:** 1-5 hours **Title:** Accuracy of Sensor by Arms Calculation **Type:** PRIMARY **Type Units Analyzed:** data points **Unit of Measure:** % of oxygen saturated hemoglobin ##### Group **Description:** All subjects are enrolled into the test group and all subjects received the LNCS DBI Sensor. **ID:** OG000 **Title:** Test Subject ### Participant Flow Module #### Group **Description:** All subjects are enrolled into the test group and all subjects received the LNCS DBI Sensor. **ID:** FG000 **Title:** Test Subject #### Period **Title:** Overall Study ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 13 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 13 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 0 **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT04796779 **Brief Title:** The Pediatric Artificial Pancreas (PEDAP) Trial of Control-IQ Technology in Young Children in Type 1 Diabetes **Official Title:** The Pediatric Artificial Pancreas (PEDAP) Trial: A Randomized Controlled Comparison of the Control-IQ Technology Versus Standard of Care in Young Children in Type 1 Diabetes #### Organization Study ID Info **ID:** 200433 #### Organization **Class:** OTHER **Full Name:** University of Virginia #### Secondary ID Infos **ID:** 1U01DK127551-01 **Link:** https://reporter.nih.gov/quickSearch/1U01DK127551-01 **Type:** NIH **Domain:** NIDDK **ID:** RFA-DK-19-036 **Type:** OTHER_GRANT ### Status Module #### Completion Date **Date:** 2022-07-31 **Type:** ACTUAL #### Last Update Post Date **Date:** 2023-06-28 **Type:** ACTUAL **Last Update Submit Date:** 2023-06-05 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2022-04-12 **Type:** ACTUAL #### Results First Post Date **Date:** 2023-06-28 **Type:** ACTUAL **Results First Submit Date:** 2023-04-10 **Results First Submit QC Date:** 2023-06-05 #### Start Date **Date:** 2021-04-21 **Type:** ACTUAL **Status Verified Date:** 2023-06 #### Study First Post Date **Date:** 2021-03-15 **Type:** ACTUAL **Study First Submit Date:** 2021-02-15 **Study First Submit QC Date:** 2021-03-10 ### Sponsor Collaborators Module #### Collaborators **Class:** NIH **Name:** National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) **Class:** OTHER **Name:** Jaeb Center for Health Research **Class:** INDUSTRY **Name:** Tandem Diabetes Care, Inc. #### Lead Sponsor **Class:** OTHER **Name:** Marc Breton #### Responsible Party **Investigator Affiliation:** University of Virginia **Investigator Full Name:** Marc Breton **Investigator Title:** Principal Investigator **Type:** SPONSOR_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** True **Is FDA Regulated Drug:** False **Is Unapproved Device:** True **Oversight Has DMC:** True ### Description Module **Brief Summary:** The purpose of this study is to learn whether an investigational automated insulin delivery system ("study system") for young children (2 yo to less than 6 yo) with type 1 diabetes can safely improve blood glucose (sometimes called blood sugar) control. **Detailed Description:** Participants will be randomized to closed loop control (CLC) system (t:slim X2 with Control-IQ Technology) or to standard of care where the children will continue to use his or her personal insulin pump or multiple daily injections. Both groups will use a continuous glucose monitor (CGM) throughout the study. The study system will also use a study insulin pump and a software algorithm to automatically give insulin and control blood glucose. This system is also sometimes called a "closed-loop" system. This study will take about 6-7 months for the child to complete. Study visits can be completed from home via videoconference (e.g. Zoom) without visiting the clinic or in-person at the clinic. A subset of participants will be asked to join an ancillary study with Meal Bolus and Exercise challenges during the extension phase. Data collected from the start of each of these challenges until the following morning will be excluded from the analysis of the extension phase. ### Conditions Module **Conditions:** - Type 1 Diabetes **Keywords:** - Control-IQ Technology - Insulin Pump - Closed Loop Control (CLC) - Continuous Glucose Monitor (CGM) - Multiple Daily Injections (MDI) ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 102 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Participants who skip or successfully complete the run-in will be randomly assigned 2:1 to the use of closed-loop control (CLC group) system using Tandem t:slim X2 with Control-IQ Technology vs Standard of Care (SC group) for 3 weeks. Participants randomized to the intervention group will use the Tandem t:slim X2 with Control-IQ Technology v1.0 during the first 13 weeks of the study (RCT phase, weeks 1-13) and then use Tandem t:slim X2 insulin pump with Control-IQ Technology v1.5 for the remaining 13 weeks of the study (extension phase, weeks 14-26). **Intervention Names:** - Device: Tandem t:slim X2 with Control-IQ Technology Pro - Device: Tandem t:slim X2 with Control-IQ Technology V1.5 **Label:** CLC Group **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Participants who skip or successfully complete the run-in will be randomly assigned 2:1 to the use of closed-loop control (CLC group) system using Tandem t:slim X2 with Control-IQ Technology vs Standard of Care (SC group) for 3 weeks. Participants randomized to the SC group will use their existing insulin therapy in conjunction with study Dexcom G6 CGM during the first 13 weeks of the study (RCT phase, weeks 1-13). The SC group will then transition to using the Tandem t:slim X2 insulin pump with Control-IQ Technology v1.5 and study Dexcom G6 CGM for the remaining 13 weeks of the study (weeks 14-26). **Intervention Names:** - Device: Standard Care (SC) - Device: Tandem t:slim X2 with Control-IQ Technology V1.5 **Label:** SC Group **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - CLC Group **Description:** The Tandem t:slim X2 with Control-IQ Technology Pro is an "artificial pancreas" (AP) application that uses advanced closed loop control algorithms to automatically manage blood glucose levels for people with Type 1 Diabetes. The system modulates insulin to keep blood glucose in a targeted range. The system components include the t:slim X2 with Control-IQ Technology and the Dexcom G6 CGM. The system is very similar to the commercially available t:sli X2 with Control-IQ but modified to accept the lower weight and Total Daily Insulin of the studied population. **Name:** Tandem t:slim X2 with Control-IQ Technology Pro **Type:** DEVICE #### Intervention 2 **Arm Group Labels:** - SC Group **Description:** Standard of Care consists in the participant existing insulin therapy (prior to enrollment) in conjunction with a study Dexcom G6 CGM. Existing insulin therapies are defined as multiple daily injections of insulin (MDI) or use of an insulin pump without hybrid closed-loop control capabilities (low-glucose suspend or predictive low-glucose suspend functionality is permitted). **Name:** Standard Care (SC) **Type:** DEVICE #### Intervention 3 **Arm Group Labels:** - CLC Group - SC Group **Description:** The Tandem t:slim X2 with Control-IQ Technology V1.5 is an "artificial pancreas" (AP) application that uses advanced closed loop control algorithms to automatically manage blood glucose levels for people with Type 1 Diabetes. The system modulates insulin to keep blood glucose in a targeted range. The system components include the t:slim X2 with Control-IQ Technology and the Dexcom G6 CGM. The system is derived from the commercially available t:slim X2 with Control-IQ, with additional features. **Name:** Tandem t:slim X2 with Control-IQ Technology V1.5 **Type:** DEVICE ### Outcomes Module #### Other Outcomes **Description:** percent above 180 mg/dL **Measure:** Percent Above 180 mg/dL **Time Frame:** 13 weeks **Description:** percent in range 70-140 mg/dL **Measure:** Percent in Range 70-140 mg/dL **Time Frame:** 13 weeks **Description:** glucose variability measured with the coefficient of variation (CV) **Measure:** Glucose Variability Measured With the Coefficient of Variation (CV) **Time Frame:** 13 weeks **Description:** glucose variability measured with the standard deviation (SD) **Measure:** Glucose Variability Measured With the Standard Deviation (SD) **Time Frame:** 13 weeks **Description:** CGM-measured percent \<60 mg/dL **Measure:** CGM-measured Percent <60 mg/dL **Time Frame:** 13 weeks **Description:** low blood glucose index (LBGI)\* **Measure:** Low Blood Glucose Index (LBGI)* **Time Frame:** 13 weeks **Description:** hypoglycemic events (defined as at least 15 consecutive minutes \<54 mg/dL) **Measure:** Hypoglycemic Events (Defined as at Least 15 Consecutive Minutes <54 mg/dL) **Time Frame:** 13 weeks **Description:** hyperglycemic events (defined as at least 90 consecutive minutes \>300 mg/dL) **Measure:** Hyperglycemic Events (Defined as at Least 90 Consecutive Minutes >300 mg/dL) **Time Frame:** 13 weeks **Description:** percent \>300 mg/dL **Measure:** Percent >300 mg/dL **Time Frame:** 13 weeks **Description:** high blood glucose index (HBGI)\* **Measure:** High Blood Glucose Index (HBGI)* **Time Frame:** 13 weeks **Description:** percent in range 70-180 mg/dL improvement from baseline to 13 weeks ≥5 percent **Measure:** Percent in Range 70-180 mg/dL Improvement From Baseline to 13 Weeks ≥5 Percent **Time Frame:** 13 weeks **Description:** percent in range 70-180 mg/dL improvement from baseline to 13 weeks ≥10 percent **Measure:** Percent in Range 70-180 mg/dL Improvement From Baseline to 13 Weeks ≥10 Percent **Time Frame:** 13 weeks **Description:** percent time in range 70-180 mg/dL \>70 percent and percent time \<70 mg/dL \<4 percent **Measure:** Percent Time in Range 70-180 mg/dL >70 Percent and Percent Time <70 mg/dL <4 Percent **Time Frame:** 13 weeks **Description:** HbA1c \<7.0 percent at 13 weeks **Measure:** HbA1c <7.0 Percent at 13 Weeks **Time Frame:** 13 weeks **Description:** HbA1c \<7.5 percent at 13 weeks **Measure:** HbA1c <7.5 Percent at 13 Weeks **Time Frame:** 13 weeks **Description:** HbA1c improvement from baseline to 13 weeks \>0.5 percent **Measure:** HbA1c Improvement From Baseline to 13 Weeks >0.5 Percent **Time Frame:** 13 weeks **Description:** HbA1c improvement from baseline to 13 weeks \>1.0 percent **Measure:** HbA1c Improvement From Baseline to 13 Weeks >1.0 Percent **Time Frame:** 13 weeks **Description:** HbA1c relative improvement from baseline to 13 weeks \>10 percent **Measure:** HbA1c Relative Improvement From Baseline to 13 Weeks >10 Percent **Time Frame:** 13 weeks **Description:** HbA1c absolute improvement from baseline to 13 weeks \>1.0 percent or HbA1c \<7.0 percent at 13 weeks **Measure:** HbA1c Absolute Improvement From Baseline to 13 Weeks >1.0 Percent or HbA1c <7.0 Percent at 13 Weeks **Time Frame:** 13 weeks **Description:** Number of SH events and SH event rate per 100 person-years **Measure:** Number of Severe Hypoglycemic (SH) Events and SH Event Rate Per 100 Person-years **Time Frame:** 13 weeks **Description:** Number of DKA events and DKA event rate per 100 person-years **Measure:** Number of Diabetic Ketoacidosis (DKA) Events and DKA Event Rate Per 100 Person-years **Time Frame:** 13 weeks **Description:** Number of other serious adverse events (SAEs other than SH events and DKA events) **Measure:** Number of Other Serious Adverse Events **Time Frame:** 13 weeks **Description:** Any adverse event rate **Measure:** Any Adverse Event Rate **Time Frame:** 13 weeks **Description:** Number of calendar days with any ketone level ≥1.0 mmol/L (if ≥5 total calendar days combined) **Measure:** Number of Calendar Days With Any Ketone Level ≥1.0 mmol/L (if ≥5 Total Calendar Days Combined) **Time Frame:** 13 weeks **Description:** Worsening of HbA1c from baseline to 13 weeks by \>0.5 percent **Measure:** Worsening of HbA1c From Baseline to 13 Weeks by >0.5 Percent **Time Frame:** 13 weeks **Description:** Adverse device effects (ADE) in intervention group only **Measure:** Adverse Device Effects (ADE) **Time Frame:** 13 weeks **Description:** Serious adverse device events (SADE) in intervention group only **Measure:** Serious Adverse Device Events (SADE) **Time Frame:** 13 weeks **Description:** Unanticipated adverse device effects (UADE) in intervention group only **Measure:** Unanticipated Adverse Device Effects (UADE) **Time Frame:** 13 weeks **Description:** Total daily insulin (units/kg) **Measure:** Total Daily Insulin (Units/kg) **Time Frame:** 13 weeks **Description:** Percentage of total insulin delivered via basal **Measure:** Percentage of Total Insulin Delivered Via Basal **Time Frame:** 13 weeks **Description:** Weight **Measure:** Weight **Time Frame:** 13 weeks **Description:** Body Mass Index (BMI) **Measure:** Body Mass Index (BMI) **Time Frame:** 13 weeks **Description:** PedsQL Diabetes Module - total score and 5 subscales: Diabetes, Treatment 1, Treatment 2, Worry, Communication **Measure:** PedsQL Diabetes Module - Total Score and 5 Subscales **Time Frame:** 13 weeks **Description:** Pediatric Inventory for Parents (PIP) 2 domains each with a total score and 4 subscales for (5x2=10 difference scores): Frequency (Total Score, Communication, Medical Care, Role Function, Emotional Functioning), Difficulty ( Same total + 4 subscales as above for frequency) **Measure:** Pediatric Inventory for Parents (PIP) 2 Domains Each With a Total Score and 4 Subscales for (5x2=10 Difference Scores) **Time Frame:** 13 weeks **Description:** INSPIRE (CLC arm only) 5-point Likert scale from strongly agree to strongly disagree, along with an N/A option. **Measure:** INSPIRE Survey (Insulin Delivery Systems: Perceptions, Ideas, Reflections and Expectations) (CLC Arm Only) **Time Frame:** 13 weeks **Description:** An abbreviated 9-question version of the Pittsburgh Sleep Quality Index (PSQI), a validated tool for assessing self-reported sleep quantity and quality, will be completed by parents. Seven component scores are derived, each scored 0 (no difficulty) to 3 (severe difficulty). The component scores are summed to produce a global score (range 0 to 21). Higher scores indicate worse sleep quality. **Measure:** Pittsburgh Sleep Quality Index (PSQI) Global Score **Time Frame:** 13 weeks **Description:** Fear of Hypoglycemia Survey for Parents (HFS-P) - total score, 2 subscales and 4 factor scores: Behavior (avoidance, Maintain high BG), Worry (Helplessness, Social consequences) **Measure:** Fear of Hypoglycemia Survey for Parents (HFS-P) - Total Score, 2 Subscales and 4 Factor Scores **Time Frame:** 13 weeks **Description:** Number of SH events during, immediately after and overnight from the study challenges **Measure:** Number of SH Events During, Immediately After and Overnight From the Study Challenges **Time Frame:** Up to 24 hour period **Description:** Number of adverse events during, immediately after and overnight from the study challenges **Measure:** Number of Adverse Events During, Immediately After and Overnight From the Study Challenges **Time Frame:** Up to 24 hour period **Description:** CGM-measured % \<54 mg/dL overnight (all challenge types) **Measure:** CGM-measured % <54 mg/dL Overnight (All Challenge Types) **Time Frame:** 8 hours **Description:** CGM-measured % \<70 mg/dL overnight (all challenge types) **Measure:** CGM-measured % <70 mg/dL Overnight (All Challenge Types) **Time Frame:** 8 hours **Description:** CGM-measured % \>180 mg/dL overnight (all challenge types) **Measure:** CGM-measured % >180 mg/dL Overnight (All Challenge Types) **Time Frame:** 8 hours **Description:** CGM-measured % \<54 mg/dL during the two hours immediately following the start of exercise for each exercise-related challenge **Measure:** CGM-measured % <54 mg/dL During the Two Hours Immediately Following the Start of Exercise for Each Exercise-related Challenge **Time Frame:** 2 hours **Description:** CGM-measured % \<70 mg/dL during the two hours immediately following the start of exercise for each exercise-related challenge **Measure:** CGM-measured % <70 mg/dL During the Two Hours Immediately Following the Start of Exercise for Each Exercise-related Challenge **Time Frame:** 2 hours **Description:** CGM-measured % \>180 mg/dL during the four hours following the announced meal, or until the next meal bolus is given, for the missed meal bolus challenge **Measure:** CGM-measured % >180 mg/dL During the Four Hours Following the Announced Meal, or Until the Next Meal Bolus is Given, for the Missed Meal Bolus Challenge **Time Frame:** 4 hours **Description:** CGM-measured % \>300 mg/dL during the four hours following the announced meal, or until the next meal bolus is given, for the missed meal bolus challenge **Measure:** CGM-measured % >300 mg/dL During the Four Hours Following the Announced Meal, or Until the Next Meal Bolus is Given, for the Missed Meal Bolus Challenge **Time Frame:** 4 hours #### Primary Outcomes **Description:** Time in range is the amount of time spent in the target glucose range-between 70 and 180 mg/dL-as measured by CGM **Measure:** Time in Range **Time Frame:** 13 weeks #### Secondary Outcomes **Description:** Percentage of time with a glucose above 250 mg/dL as measured by CGM **Measure:** CGM-measured Percent Above 250 mg/dL **Time Frame:** 13 weeks **Description:** Average glucose value measured by CGM **Measure:** CGM-measured Mean Glucose **Time Frame:** 13 weeks **Description:** HbA1c at 13 weeks **Measure:** HbA1c at 13 Weeks **Time Frame:** 13 weeks **Description:** Percentage of time with glucose below 70 mg/dL as measured by CGM **Measure:** CGM-measured Percent Below 70 mg/dL **Time Frame:** 13 weeks **Description:** Percentage of time with glucose below 54 mg/dL as measured by CGM **Measure:** CGM-measured Percent Below 54 mg/dL **Time Frame:** 13 weeks ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Clinical diagnosis, based on investigator assessment, of type 1 diabetes for at least 6 months and using insulin for at least 6 months 2. Familiarity and use of a carbohydrate ratio for meal boluses. 3. Age ≥2 and \<6 years old 4. Living with one or more parent/legal guardian knowledgeable about emergency procedures for severe hypoglycemia and able to contact emergency services and study staff. 5. Investigator has confidence that the parent can successfully operate all study devices and is capable of adhering to the protocol 6. Willingness to switch to lispro (Humalog) or aspart (Novolog) if not using already, and to use no other insulin besides lispro (Humalog) or aspart (Novolog) during the study for participants using a study-provided Tandem pump during the study. • Study will not be providing insulin; therefore, participants will need to have access to either lispro or aspart 7. Total daily insulin dose (TDD) at least 5 U/day 8. Body weight at least 20 lbs. 9. Willingness not to start any new non-insulin glucose-lowering agent during the course of the trial (see section 2.3) 10. Participant and parent(s)/guardian(s) willingness to participate in all training sessions as directed by study staff. 11. Parent/guardian proficient in reading and writing English. Exclusion Criteria: 1. Concurrent use of any non-insulin glucose-lowering agent (including Glucagon-like peptide-1 \[GLP-1\] agonists, Symlin, Dipeptidyl peptidase-4 \[DPP-4\] inhibitors, Sodium-glucose Cotransporter-2 (SGLT-2) inhibitors, sulfonylureas). 2. Hemophilia or any other bleeding disorder 3. History of \>1 severe hypoglycemic event with seizure or loss of consciousness in the last 3 months 4. History of \>1 DKA event in the last 6 months not related to illness, infusion set failure, or initial diagnosis 5. History of chronic renal disease or currently on hemodialysis 6. History of adrenal insufficiency 7. Hypothyroidism that is not adequately treated 8. Use of oral or injectable steroids within the last 8 weeks 9. Known, ongoing adhesive intolerance 10. Plans to receive blood transfusions or erythropoietin injections during the course of the study 11. A condition, which in the opinion of the investigator or designee, would put the participant or study at risk (specified in the study procedure manual) 12. Currently using any closed-loop system, or using an insulin pump that is incompatible with use of the study CGM 13. Participation in another pharmaceutical or device trial at the time of enrollment or during the study 14. Employed by, or having immediate family members employed by Tandem Diabetes Care, Inc., or having a direct supervisor at place of employment who is also directly involved in conducting the clinical trial (as a study investigator, coordinator, etc.); or having a first-degree relative who is directly involved in conducting the clinical trial **Maximum Age:** 71 Months **Minimum Age:** 24 Months **Sex:** ALL **Standard Ages:** - CHILD ### Contacts Locations Module #### Locations **Location 1:** **City:** Stanford **Country:** United States **Facility:** Stanford University **State:** California **Zip:** 94304 **Location 2:** **City:** Aurora **Country:** United States **Facility:** Barbara Davis Center, University of Colorado **State:** Colorado **Zip:** 80045 **Location 3:** **City:** Charlottesville **Country:** United States **Facility:** University of Virginia Center for Diabetes Technology **State:** Virginia **Zip:** 22903 #### Overall Officials **Official 1:** **Affiliation:** Jaeb Center for Health Research **Name:** John Lum, MS **Role:** STUDY_DIRECTOR ### IPD Sharing Statement Module **Description:** Will follow the NIH Data Sharing Policy and Implementation Guidance on sharing research resources for research purposes to qualified individuals within the scientific community. **Info Types:** - STUDY_PROTOCOL - SAP - ICF **IPD Sharing:** YES **Time Frame:** Generally, data will be made available after the primary publications of each study. ### References Module #### References **Citation:** Wadwa RP, Reed ZW, Buckingham BA, DeBoer MD, Ekhlaspour L, Forlenza GP, Schoelwer M, Lum J, Kollman C, Beck RW, Breton MD; PEDAP Trial Study Group. Trial of Hybrid Closed-Loop Control in Young Children with Type 1 Diabetes. N Engl J Med. 2023 Mar 16;388(11):991-1001. doi: 10.1056/NEJMoa2210834. **PMID:** 36920756 #### See Also Links **Label:** Study Results **URL:** https://pubmed.ncbi.nlm.nih.gov/36920756/ ## Document Section ### Large Document Module #### Large Docs - Date: 2021-12-03 - Filename: Prot_001.pdf - Has ICF: False - Has Protocol: True - Has SAP: False - Label: Study Protocol - Size: 1679569 - Type Abbrev: Prot - Upload Date: 2022-08-24T14:21 - Date: 2022-05-18 - Filename: SAP_003.pdf - Has ICF: False - Has Protocol: False - Has SAP: True - Label: Statistical Analysis Plan - Size: 773158 - Type Abbrev: SAP - Upload Date: 2022-10-06T21:33 - Date: 2021-07-22 - Filename: ICF_004.pdf - Has ICF: True - Has Protocol: False - Has SAP: False - Label: Informed Consent Form - Size: 282881 - Type Abbrev: ICF - Upload Date: 2023-05-04T11:21 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000044882 - Term: Glucose Metabolism Disorders - ID: D000008659 - Term: Metabolic Diseases - ID: D000004700 - Term: Endocrine System Diseases - ID: D000001327 - Term: Autoimmune Diseases - ID: D000007154 - Term: Immune 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 - Abbrev: BC20 - Name: Immune System Diseases ### Condition Browse Module - Browse Leaves - ID: M7115 - Name: Diabetes Mellitus - Relevance: HIGH - As Found: Diabetes - ID: M7117 - Name: Diabetes Mellitus, Type 1 - Relevance: HIGH - As Found: Type 1 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 - ID: M4629 - Name: Autoimmune Diseases - Relevance: LOW - As Found: Unknown - ID: M10200 - Name: Immune System Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000003920 - Term: Diabetes Mellitus - ID: D000003922 - Term: Diabetes Mellitus, Type 1 ### Intervention Browse Module - Ancestors - ID: D000014131 - Term: Trace Elements - ID: D000018977 - Term: Micronutrients - ID: D000045505 - Term: Physiological Effects of Drugs ### Intervention Browse Module - Browse Branches - Abbrev: Hypo - Name: Hypoglycemic Agents - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Gast - Name: Gastrointestinal Agents - Abbrev: Micro - Name: Micronutrients ### Intervention Browse Module - Browse Leaves - ID: M10365 - Name: Insulin - Relevance: LOW - As Found: Unknown - ID: M173166 - Name: Insulin, Globin Zinc - Relevance: LOW - As Found: Unknown - ID: M22554 - Name: Pancrelipase - Relevance: LOW - As Found: Unknown - ID: M13114 - Name: Pancreatin - Relevance: LOW - As Found: Unknown - ID: M225448 - Name: Ferrous fumarate - Relevance: HIGH - As Found: Blunt - ID: M21009 - Name: Micronutrients - Relevance: LOW - As Found: Unknown - ID: M16885 - Name: Trace Elements - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: C000031621 - Term: Ferrous fumarate ### Misc Info Module #### Submission Tracking ##### First MCP Info ###### Post Date - Date: 2023-05-06 - Type: ACTUAL - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module #### Event Groups **Group ID:** EG000 **Title:** CLC Group **Deaths Num At Risk:** 68 **Description:** Participants who skip or successfully complete the run-in will be randomly assigned 2:1 to the use of closed-loop control (CLC group) system using Tandem t:slim X2 with Control-IQ Technology vs Standard of Care (SC group) for 3 weeks. Participants randomized to the intervention group will use the Tandem t:slim X2 with Control-IQ Technology v1.0 during the first 13 weeks of the study (RCT phase, weeks 1-13) and then use Tandem t:slim X2 insulin pump with Control-IQ Technology v1.5 for the remaining 13 weeks of the study (extension phase, weeks 14-26). **ID:** EG000 **Other Num Affected:** 40 **Other Num at Risk:** 68 **Serious Number Affected:** 3 **Serious Number At Risk:** 68 **Title:** CLC Group **Group ID:** EG001 **Title:** SC Group **Deaths Num At Risk:** 34 **Description:** Participants who skip or successfully complete the run-in will be randomly assigned 2:1 to the use of closed-loop control (CLC group) system using Tandem t:slim X2 with Control-IQ Technology vs Standard of Care (SC group) for 3 weeks. Participants randomized to the SC group will use their existing insulin therapy in conjunction with study Dexcom G6 CGM during the first 13 weeks of the study (RCT phase, weeks 1-13). The SC group will then transition to using the Tandem t:slim X2 insulin pump with Control-IQ Technology v1.5 and study Dexcom G6 CGM for the remaining 13 weeks of the study (weeks 14-26). **ID:** EG001 **Other Num Affected:** 9 **Other Num at Risk:** 34 **Serious Number Affected:** 2 **Serious Number At Risk:** 34 **Title:** SC Group **Frequency Threshold:** 0 #### Other Events **Term:** Hyperglycemia with or without Ketosis Related to Study Device **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Endocrine disorders **Source Vocabulary:** **Term:** Hyperglycemia with or without Ketosis Not Related to Study Device **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Endocrine disorders **Source Vocabulary:** **Term:** Hypoglycemia (not severe) **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Endocrine disorders **Source Vocabulary:** **Term:** Burn **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** **Term:** COVID-19 **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:** Fractured Finger **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** **Term:** Gastroenteritis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** **Term:** Hematuria **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** **Term:** Medical Device Site Bleeding **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** **Term:** Skin Infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** **Term:** Streptococcal Sore Throat **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** **Term:** Upper Respiratory Infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** **Term:** Vomiting **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** #### Serious Events **Term:** Severe hypoglycemic event **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 68 **Num Events:** 2 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 34 **Num Events:** 1 **Term:** Diabetic ketoacidosis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 68 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 34 **Term:** Other serious adverse event **Assessment Type:** SYSTEMATIC_ASSESSMENT **Notes:** One participant in the SC group was hospitalized for an asthma flare **Organ System:** Respiratory, thoracic and mediastinal disorders ##### Stats **Group ID:** EG000 **Num At Risk:** 68 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 34 **Num Events:** 1 **Time Frame:** Baseline to Week 13 ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 68 **Group ID:** BG001 **Value:** 34 **Group ID:** BG002 **Value:** 102 **Units:** Participants ### Group **ID:** BG000 **Title:** CLC Group **Description:** Participants who skip or successfully complete the run-in will be randomly assigned 2:1 to the use of closed-loop control (CLC group) system using Tandem t:slim X2 with Control-IQ Technology vs Standard of Care (SC group) for 3 weeks. Participants randomized to the intervention group will use the Tandem t:slim X2 with Control-IQ Technology v1.0 during the first 13 weeks of the study (RCT phase, weeks 1-13) and then use Tandem t:slim X2 insulin pump with Control-IQ Technology v1.5 for the remaining 13 weeks of the study (extension phase, weeks 14-26). ### Group **ID:** BG001 **Title:** SC Group **Description:** Participants who skip or successfully complete the run-in will be randomly assigned 2:1 to the use of closed-loop control (CLC group) system using Tandem t:slim X2 with Control-IQ Technology vs Standard of Care (SC group) for 3 weeks. Participants randomized to the SC group will use their existing insulin therapy in conjunction with study Dexcom G6 CGM during the first 13 weeks of the study (RCT phase, weeks 1-13). The SC group will then transition to using the Tandem t:slim X2 insulin pump with Control-IQ Technology v1.5 and study Dexcom G6 CGM for the remaining 13 weeks of the study (weeks 14-26). ### Group **ID:** BG002 **Title:** Total **Description:** Total of all reporting groups ### Measure #### Measurement **Group ID:** BG000 **Spread:** 1.23 **Value:** 3.84 #### Measurement **Group ID:** BG001 **Spread:** 1.25 **Value:** 4.06 #### Measurement **Group ID:** BG002 **Spread:** 1.24 **Value:** 3.92 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 68 **Group ID:** BG001 **Value:** 34 **Group ID:** BG002 **Value:** 102 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 31 #### Measurement **Group ID:** BG001 **Value:** 16 #### Measurement **Group ID:** BG002 **Value:** 47 **Category Title:** 2 to <4 years #### Measurement **Group ID:** BG000 **Value:** 37 #### Measurement **Group ID:** BG001 **Value:** 18 #### Measurement **Group ID:** BG002 **Value:** 55 **Category Title:** 4 to <6 years #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 68 **Group ID:** BG001 **Value:** 34 **Group ID:** BG002 **Value:** 102 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 33 #### Measurement **Group ID:** BG001 **Value:** 19 #### Measurement **Group ID:** BG002 **Value:** 52 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 35 #### Measurement **Group ID:** BG001 **Value:** 15 #### Measurement **Group ID:** BG002 **Value:** 50 **Category Title:** Male #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 68 **Group ID:** BG001 **Value:** 34 **Group ID:** BG002 **Value:** 102 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 50 #### Measurement **Group ID:** BG001 **Value:** 25 #### Measurement **Group ID:** BG002 **Value:** 75 **Category Title:** White non-Hispanic #### Measurement **Group ID:** BG000 **Value:** 4 #### Measurement **Group ID:** BG001 **Value:** 2 #### Measurement **Group ID:** BG002 **Value:** 6 **Category Title:** Black/African American #### Measurement **Group ID:** BG000 **Value:** 11 #### Measurement **Group ID:** BG001 **Value:** 5 #### Measurement **Group ID:** BG002 **Value:** 16 **Category Title:** Hispanic or Latino #### Measurement **Group ID:** BG000 **Value:** 1 #### Measurement **Group ID:** BG001 **Value:** 1 #### Measurement **Group ID:** BG002 **Value:** 2 **Category Title:** Asian #### Measurement **Group ID:** BG000 **Value:** 2 #### Measurement **Group ID:** BG001 **Value:** 1 #### Measurement **Group ID:** BG002 **Value:** 3 **Category Title:** More than one race #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 68 **Group ID:** BG001 **Value:** 34 **Group ID:** BG002 **Value:** 102 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 68 #### Measurement **Group ID:** BG001 **Value:** 34 #### Measurement **Group ID:** BG002 **Value:** 102 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 68 **Group ID:** BG001 **Value:** 34 **Group ID:** BG002 **Value:** 102 **Class Title:** United States ### Measure #### Measurement **Group ID:** BG000 **Value:** 29 #### Measurement **Group ID:** BG001 **Value:** 10 #### Measurement **Group ID:** BG002 **Value:** 39 **Category Title:** 0.5 to <1 years #### Measurement **Group ID:** BG000 **Value:** 24 #### Measurement **Group ID:** BG001 **Value:** 15 #### Measurement **Group ID:** BG002 **Value:** 39 **Category Title:** 1 to <2 years #### Measurement **Group ID:** BG000 **Value:** 11 #### Measurement **Group ID:** BG001 **Value:** 7 #### Measurement **Group ID:** BG002 **Value:** 18 **Category Title:** 2 to <4 years #### Measurement **Group ID:** BG000 **Value:** 4 #### Measurement **Group ID:** BG001 **Value:** 2 #### Measurement **Group ID:** BG002 **Value:** 6 **Category Title:** ≥4 years #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 68 **Group ID:** BG001 **Value:** 34 **Group ID:** BG002 **Value:** 102 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Spread:** 1.2 **Value:** 7.5 #### Measurement **Group ID:** BG001 **Spread:** 0.9 **Value:** 7.7 #### Measurement **Group ID:** BG002 **Spread:** 1.1 **Value:** 7.6 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 64 **Group ID:** BG001 **Value:** 32 **Group ID:** BG002 **Value:** 96 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 42 #### Measurement **Group ID:** BG001 **Value:** 24 #### Measurement **Group ID:** BG002 **Value:** 66 **Category Title:** Insulin pump #### Measurement **Group ID:** BG000 **Value:** 26 #### Measurement **Group ID:** BG001 **Value:** 10 #### Measurement **Group ID:** BG002 **Value:** 36 **Category Title:** Multiple daily injections #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 68 **Group ID:** BG001 **Value:** 34 **Group ID:** BG002 **Value:** 102 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 2 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 2 **Category Title:** In past, but not current #### Measurement **Group ID:** BG000 **Value:** 66 #### Measurement **Group ID:** BG001 **Value:** 34 #### Measurement **Group ID:** BG002 **Value:** 100 **Category Title:** Current #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 68 **Group ID:** BG001 **Value:** 34 **Group ID:** BG002 **Value:** 102 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 2 #### Measurement **Group ID:** BG001 **Value:** 2 #### Measurement **Group ID:** BG002 **Value:** 4 **Category Title:** $25,000 - <$35,000 #### Measurement **Group ID:** BG000 **Value:** 6 #### Measurement **Group ID:** BG001 **Value:** 4 #### Measurement **Group ID:** BG002 **Value:** 10 **Category Title:** $35,000 - <$50,000 #### Measurement **Group ID:** BG000 **Value:** 8 #### Measurement **Group ID:** BG001 **Value:** 5 #### Measurement **Group ID:** BG002 **Value:** 13 **Category Title:** $50,000 - <$75,000 #### Measurement **Group ID:** BG000 **Value:** 11 #### Measurement **Group ID:** BG001 **Value:** 7 #### Measurement **Group ID:** BG002 **Value:** 18 **Category Title:** $75,000 - <$100,000 #### Measurement **Group ID:** BG000 **Value:** 22 #### Measurement **Group ID:** BG001 **Value:** 10 #### Measurement **Group ID:** BG002 **Value:** 32 **Category Title:** $100,000 - <$200,000 #### Measurement **Group ID:** BG000 **Value:** 15 #### Measurement **Group ID:** BG001 **Value:** 4 #### Measurement **Group ID:** BG002 **Value:** 19 **Category Title:** ≥ $200,000 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 64 **Group ID:** BG001 **Value:** 32 **Group ID:** BG002 **Value:** 96 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 6 #### Measurement **Group ID:** BG001 **Value:** 3 #### Measurement **Group ID:** BG002 **Value:** 9 **Category Title:** ≤High School Diploma #### Measurement **Group ID:** BG000 **Value:** 2 #### Measurement **Group ID:** BG001 **Value:** 1 #### Measurement **Group ID:** BG002 **Value:** 3 **Category Title:** Associates Degree or Some College but no Degree #### Measurement **Group ID:** BG000 **Value:** 6 #### Measurement **Group ID:** BG001 **Value:** 5 #### Measurement **Group ID:** BG002 **Value:** 11 **Category Title:** Bachelor's Degree #### Measurement **Group ID:** BG000 **Value:** 22 #### Measurement **Group ID:** BG001 **Value:** 13 #### Measurement **Group ID:** BG002 **Value:** 35 **Category Title:** Master's Degree #### Measurement **Group ID:** BG000 **Value:** 32 #### Measurement **Group ID:** BG001 **Value:** 12 #### Measurement **Group ID:** BG002 **Value:** 44 **Category Title:** Doctoral or Prof Degree #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 68 **Group ID:** BG001 **Value:** 34 **Group ID:** BG002 **Value:** 102 **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:** 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:** COUNT_OF_PARTICIPANTS **Title:** Race/Ethnicity, Customized **Unit of Measure:** Participants ### Measure 5 **Parameter Type:** NUMBER **Title:** Region of Enrollment **Unit of Measure:** participants ### Measure 6 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Diabetes Duration **Unit of Measure:** Participants ### Measure 7 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Population Description:** Missing data (CLC/SC): HbA1c 4/2 **Title:** Glycosylated Hemoglobin (HbA1c) at Randomization **Unit of Measure:** Percentage of glycosylated hemoglobin ### Measure 8 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Insulin Modality **Unit of Measure:** Participants ### Measure 9 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Prior Continuous Glucose Monitor (CGM) Use **Unit of Measure:** Participants ### Measure 10 **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Missing data (CLC/SC): annual household income 4/2 **Title:** Annual Household Income **Unit of Measure:** Participants ### Measure 11 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Parent Education **Unit of Measure:** Participants ## Results Section - More Information Module ### Certain Agreement ### Point of Contact **Email:** [email protected] **Organization:** University of Virginia **Phone:** 434-982-6484 **Title:** Marc Breton, PhD ## 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:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** <0.001 **P-Value Comment:** **Parameter Type:** **Parameter Value:** **Statistical Comment:** The model was adjusted for the baseline value of the metric, age, prior CGM and pump use, and site as a random effect. **Statistical Method:** Direct likelihood model **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:** <0.001 **P-Value Comment:** To preserve the overall type I error for the multiple secondary outcomes, a hierarchical gatekeeping approach was used. **Parameter Type:** **Parameter Value:** **Statistical Comment:** The model was adjusted for baseline value of the metric, age, prior CGM and pump use, and site as a fixed effect. **Statistical Method:** Robust regression using M-estimation **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:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** <0.001 **P-Value Comment:** To preserve the overall type I error for the multiple secondary outcomes, a hierarchical gatekeeping approach was used. **Parameter Type:** **Parameter Value:** **Statistical Comment:** The model was adjusted for the baseline value of the metric, age, prior CGM and pump use, and site as a random effect. **Statistical Method:** Direct likelihood model **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:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** <0.001 **P-Value Comment:** To preserve the overall type I error for the multiple secondary outcomes, a hierarchical gatekeeping approach was used. **Parameter Type:** **Parameter Value:** **Statistical Comment:** The model was adjusted for the baseline value of the metric, age, prior CGM and pump use, and site as a random effect. **Statistical Method:** Direct likelihood model **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 **Other Analysis Description:** **P-Value:** 0.57 **P-Value Comment:** To preserve the overall type I error for the multiple secondary outcomes, a hierarchical gatekeeping approach was used. **Parameter Type:** **Parameter Value:** **Statistical Comment:** The model was adjusted for the baseline value of the metric, age, prior CGM and pump use, and site as a fixed effect. **Statistical Method:** Robust regression using M-estimation **Tested Non-Inferiority:** ### 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 ### Outcome Measure 23 ### Outcome Measure 24 ### Outcome Measure 25 ### Outcome Measure 26 ### Outcome Measure 27 ### Outcome Measure 28 ### Outcome Measure 29 ### Outcome Measure 30 ### Outcome Measure 31 ### Outcome Measure 32 ### Outcome Measure 33 ### Outcome Measure 34 ### Outcome Measure 35 ### Outcome Measure 36 ### Outcome Measure 37 ### Outcome Measure 38 ### Outcome Measure 39 ### Outcome Measure 40 ### Outcome Measure 41 ### Outcome Measure 42 ### Outcome Measure 43 ### Outcome Measure 44 ### Outcome Measure 45 ### Outcome Measure 46 ### Outcome Measure 47 ### Outcome Measure 48 ### Outcome Measure 49 ### Outcome Measure 50 ### Outcome Measure 51 ### Outcome Measure 52 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 18.0 - **Upper Limit:** - **Value:** 56.7 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 14.7 - **Upper Limit:** - **Value:** 54.9 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 67 - **Group ID:** OG001 - **Value:** 34 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 11.1 - **Upper Limit:** - **Value:** 69.3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 12.6 - **Upper Limit:** - **Value:** 55.9 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 68 - **Group ID:** OG001 - **Value:** 34 **Units:** Participants #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 15.5 - **Upper Limit:** - **Value:** 14.8 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 13.9 - **Upper Limit:** - **Value:** 16.0 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 67 - **Group ID:** OG001 - **Value:** 34 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 7.2 - **Upper Limit:** - **Value:** 8.4 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 10.9 - **Upper Limit:** - **Value:** 15.0 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 68 - **Group ID:** OG001 - **Value:** 34 **Units:** Participants #### Outcome Measure 3 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 36 - **Upper Limit:** - **Value:** 173 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 26 - **Upper Limit:** - **Value:** 176 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 67 - **Group ID:** OG001 - **Value:** 34 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 20 - **Upper Limit:** - **Value:** 155 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 22 - **Upper Limit:** - **Value:** 174 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 68 - **Group ID:** OG001 - **Value:** 34 **Units:** Participants #### Outcome Measure 4 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.2 - **Upper Limit:** - **Value:** 7.5 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.9 - **Upper Limit:** - **Value:** 7.7 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 64 - **Group ID:** OG001 - **Value:** 32 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.8 - **Upper Limit:** - **Value:** 7.0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.9 - **Upper Limit:** - **Value:** 7.5 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 62 - **Group ID:** OG001 - **Value:** 33 **Units:** Participants #### Outcome Measure 5 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 2.2 - **Upper Limit:** - **Value:** 3.0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 2.0 - **Upper Limit:** - **Value:** 2.7 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 67 - **Group ID:** OG001 - **Value:** 34 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.8 - **Upper Limit:** - **Value:** 3.0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 2.2 - **Upper Limit:** - **Value:** 3.0 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 68 - **Group ID:** OG001 - **Value:** 34 **Units:** Participants #### Outcome Measure 6 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.7 - **Upper Limit:** - **Value:** 0.6 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.6 - **Upper Limit:** - **Value:** 0.5 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 67 - **Group ID:** OG001 - **Value:** 34 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.5 - **Upper Limit:** - **Value:** 0.6 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.5 - **Upper Limit:** - **Value:** 0.5 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 68 - **Group ID:** OG001 - **Value:** 34 **Units:** Participants #### 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 #### Outcome Measure 23 #### Outcome Measure 24 #### Outcome Measure 25 #### Outcome Measure 26 #### Outcome Measure 27 #### Outcome Measure 28 #### Outcome Measure 29 #### Outcome Measure 30 #### Outcome Measure 31 #### Outcome Measure 32 #### Outcome Measure 33 #### Outcome Measure 34 #### Outcome Measure 35 #### Outcome Measure 36 #### Outcome Measure 37 #### Outcome Measure 38 #### Outcome Measure 39 #### Outcome Measure 40 #### Outcome Measure 41 #### Outcome Measure 42 #### Outcome Measure 43 #### Outcome Measure 44 #### Outcome Measure 45 #### Outcome Measure 46 #### Outcome Measure 47 #### Outcome Measure 48 #### Outcome Measure 49 #### Outcome Measure 50 #### Outcome Measure 51 #### Outcome Measure 52 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** Time in range is the amount of time spent in the target glucose range-between 70 and 180 mg/dL-as measured by CGM **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** One participant in the CLC group was missing baseline CGM data. **Reporting Status:** POSTED **Time Frame:** 13 weeks **Title:** Time in Range **Type:** PRIMARY **Unit of Measure:** Percent of time ##### Group **Description:** Participants who skip or successfully complete the run-in will be randomly assigned 2:1 to the use of closed-loop control (CLC group) system using Tandem t:slim X2 with Control-IQ Technology vs Standard of Care (SC group) for 3 weeks. Participants randomized to the intervention group will use the Tandem t:slim X2 with Control-IQ Technology v1.0 during the first 13 weeks of the study (RCT phase, weeks 1-13) and then use Tandem t:slim X2 insulin pump with Control-IQ Technology v1.5 for the remaining 13 weeks of the study (extension phase, weeks 14-26). **ID:** OG000 **Title:** CLC Group ##### Group **Description:** Participants who skip or successfully complete the run-in will be randomly assigned 2:1 to the use of closed-loop control (CLC group) system using Tandem t:slim X2 with Control-IQ Technology vs Standard of Care (SC group) for 3 weeks. Participants randomized to the SC group will use their existing insulin therapy in conjunction with study Dexcom G6 CGM during the first 13 weeks of the study (RCT phase, weeks 1-13). The SC group will then transition to using the Tandem t:slim X2 insulin pump with Control-IQ Technology v1.5 and study Dexcom G6 CGM for the remaining 13 weeks of the study (weeks 14-26). **ID:** OG001 **Title:** SC Group #### Outcome Measure 2 **Description:** Percentage of time with a glucose above 250 mg/dL as measured by CGM **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** One participant in the CLC group was missing baseline CGM data. **Reporting Status:** POSTED **Time Frame:** 13 weeks **Title:** CGM-measured Percent Above 250 mg/dL **Type:** SECONDARY **Unit of Measure:** Percent of time ##### Group **Description:** Participants who skip or successfully complete the run-in will be randomly assigned 2:1 to the use of closed-loop control (CLC group) system using Tandem t:slim X2 with Control-IQ Technology vs Standard of Care (SC group) for 3 weeks. Participants randomized to the intervention group will use the Tandem t:slim X2 with Control-IQ Technology v1.0 during the first 13 weeks of the study (RCT phase, weeks 1-13) and then use Tandem t:slim X2 insulin pump with Control-IQ Technology v1.5 for the remaining 13 weeks of the study (extension phase, weeks 14-26). **ID:** OG000 **Title:** CLC Group ##### Group **Description:** Participants who skip or successfully complete the run-in will be randomly assigned 2:1 to the use of closed-loop control (CLC group) system using Tandem t:slim X2 with Control-IQ Technology vs Standard of Care (SC group) for 3 weeks. Participants randomized to the SC group will use their existing insulin therapy in conjunction with study Dexcom G6 CGM during the first 13 weeks of the study (RCT phase, weeks 1-13). The SC group will then transition to using the Tandem t:slim X2 insulin pump with Control-IQ Technology v1.5 and study Dexcom G6 CGM for the remaining 13 weeks of the study (weeks 14-26). **ID:** OG001 **Title:** SC Group #### Outcome Measure 3 **Description:** Average glucose value measured by CGM **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** One participant in the CLC group was missing baseline CGM data. **Reporting Status:** POSTED **Time Frame:** 13 weeks **Title:** CGM-measured Mean Glucose **Type:** SECONDARY **Unit of Measure:** mg/dL ##### Group **Description:** Participants who skip or successfully complete the run-in will be randomly assigned 2:1 to the use of closed-loop control (CLC group) system using Tandem t:slim X2 with Control-IQ Technology vs Standard of Care (SC group) for 3 weeks. Participants randomized to the intervention group will use the Tandem t:slim X2 with Control-IQ Technology v1.0 during the first 13 weeks of the study (RCT phase, weeks 1-13) and then use Tandem t:slim X2 insulin pump with Control-IQ Technology v1.5 for the remaining 13 weeks of the study (extension phase, weeks 14-26). **ID:** OG000 **Title:** CLC Group ##### Group **Description:** Participants who skip or successfully complete the run-in will be randomly assigned 2:1 to the use of closed-loop control (CLC group) system using Tandem t:slim X2 with Control-IQ Technology vs Standard of Care (SC group) for 3 weeks. Participants randomized to the SC group will use their existing insulin therapy in conjunction with study Dexcom G6 CGM during the first 13 weeks of the study (RCT phase, weeks 1-13). The SC group will then transition to using the Tandem t:slim X2 insulin pump with Control-IQ Technology v1.5 and study Dexcom G6 CGM for the remaining 13 weeks of the study (weeks 14-26). **ID:** OG001 **Title:** SC Group #### Outcome Measure 4 **Description:** HbA1c at 13 weeks **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Baseline HbA1c values were available for n=64/68 in the CLC group and n=32/34 in the SC group. At 13 Weeks, HbA1c data were available for n=62/68 in the CLC group and n=33/34 in the SC group. **Reporting Status:** POSTED **Time Frame:** 13 weeks **Title:** HbA1c at 13 Weeks **Type:** SECONDARY **Unit of Measure:** Percentage of glycosylated hemoglobin ##### Group **Description:** Participants who skip or successfully complete the run-in will be randomly assigned 2:1 to the use of closed-loop control (CLC group) system using Tandem t:slim X2 with Control-IQ Technology vs Standard of Care (SC group) for 3 weeks. Participants randomized to the intervention group will use the Tandem t:slim X2 with Control-IQ Technology v1.0 during the first 13 weeks of the study (RCT phase, weeks 1-13) and then use Tandem t:slim X2 insulin pump with Control-IQ Technology v1.5 for the remaining 13 weeks of the study (extension phase, weeks 14-26). **ID:** OG000 **Title:** CLC Group ##### Group **Description:** Participants who skip or successfully complete the run-in will be randomly assigned 2:1 to the use of closed-loop control (CLC group) system using Tandem t:slim X2 with Control-IQ Technology vs Standard of Care (SC group) for 3 weeks. Participants randomized to the SC group will use their existing insulin therapy in conjunction with study Dexcom G6 CGM during the first 13 weeks of the study (RCT phase, weeks 1-13). The SC group will then transition to using the Tandem t:slim X2 insulin pump with Control-IQ Technology v1.5 and study Dexcom G6 CGM for the remaining 13 weeks of the study (weeks 14-26). **ID:** OG001 **Title:** SC Group #### Outcome Measure 5 **Description:** Percentage of time with glucose below 70 mg/dL as measured by CGM **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** One participant in the CLC group was missing baseline CGM data. **Reporting Status:** POSTED **Time Frame:** 13 weeks **Title:** CGM-measured Percent Below 70 mg/dL **Type:** SECONDARY **Unit of Measure:** Percent of time ##### Group **Description:** Participants who skip or successfully complete the run-in will be randomly assigned 2:1 to the use of closed-loop control (CLC group) system using Tandem t:slim X2 with Control-IQ Technology vs Standard of Care (SC group) for 3 weeks. Participants randomized to the intervention group will use the Tandem t:slim X2 with Control-IQ Technology v1.0 during the first 13 weeks of the study (RCT phase, weeks 1-13) and then use Tandem t:slim X2 insulin pump with Control-IQ Technology v1.5 for the remaining 13 weeks of the study (extension phase, weeks 14-26). **ID:** OG000 **Title:** CLC Group ##### Group **Description:** Participants who skip or successfully complete the run-in will be randomly assigned 2:1 to the use of closed-loop control (CLC group) system using Tandem t:slim X2 with Control-IQ Technology vs Standard of Care (SC group) for 3 weeks. Participants randomized to the SC group will use their existing insulin therapy in conjunction with study Dexcom G6 CGM during the first 13 weeks of the study (RCT phase, weeks 1-13). The SC group will then transition to using the Tandem t:slim X2 insulin pump with Control-IQ Technology v1.5 and study Dexcom G6 CGM for the remaining 13 weeks of the study (weeks 14-26). **ID:** OG001 **Title:** SC Group #### Outcome Measure 6 **Description:** Percentage of time with glucose below 54 mg/dL as measured by CGM **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** One participant in the CLC group was missing baseline CGM data. **Reporting Status:** POSTED **Time Frame:** 13 weeks **Title:** CGM-measured Percent Below 54 mg/dL **Type:** SECONDARY **Unit of Measure:** Percent of time ##### Group **Description:** Participants who skip or successfully complete the run-in will be randomly assigned 2:1 to the use of closed-loop control (CLC group) system using Tandem t:slim X2 with Control-IQ Technology vs Standard of Care (SC group) for 3 weeks. Participants randomized to the intervention group will use the Tandem t:slim X2 with Control-IQ Technology v1.0 during the first 13 weeks of the study (RCT phase, weeks 1-13) and then use Tandem t:slim X2 insulin pump with Control-IQ Technology v1.5 for the remaining 13 weeks of the study (extension phase, weeks 14-26). **ID:** OG000 **Title:** CLC Group ##### Group **Description:** Participants who skip or successfully complete the run-in will be randomly assigned 2:1 to the use of closed-loop control (CLC group) system using Tandem t:slim X2 with Control-IQ Technology vs Standard of Care (SC group) for 3 weeks. Participants randomized to the SC group will use their existing insulin therapy in conjunction with study Dexcom G6 CGM during the first 13 weeks of the study (RCT phase, weeks 1-13). The SC group will then transition to using the Tandem t:slim X2 insulin pump with Control-IQ Technology v1.5 and study Dexcom G6 CGM for the remaining 13 weeks of the study (weeks 14-26). **ID:** OG001 **Title:** SC Group #### Outcome Measure 7 **Description:** percent above 180 mg/dL **Reporting Status:** NOT_POSTED **Time Frame:** 13 weeks **Title:** Percent Above 180 mg/dL **Type:** OTHER_PRE_SPECIFIED #### Outcome Measure 8 **Description:** percent in range 70-140 mg/dL **Reporting Status:** NOT_POSTED **Time Frame:** 13 weeks **Title:** Percent in Range 70-140 mg/dL **Type:** OTHER_PRE_SPECIFIED #### Outcome Measure 9 **Description:** glucose variability measured with the coefficient of variation (CV) **Reporting Status:** NOT_POSTED **Time Frame:** 13 weeks **Title:** Glucose Variability Measured With the Coefficient of Variation (CV) **Type:** OTHER_PRE_SPECIFIED #### Outcome Measure 10 **Description:** glucose variability measured with the standard deviation (SD) **Reporting Status:** NOT_POSTED **Time Frame:** 13 weeks **Title:** Glucose Variability Measured With the Standard Deviation (SD) **Type:** OTHER_PRE_SPECIFIED #### Outcome Measure 11 **Description:** CGM-measured percent \<60 mg/dL **Reporting Status:** NOT_POSTED **Time Frame:** 13 weeks **Title:** CGM-measured Percent <60 mg/dL **Type:** OTHER_PRE_SPECIFIED #### Outcome Measure 12 **Description:** low blood glucose index (LBGI)\* **Reporting Status:** NOT_POSTED **Time Frame:** 13 weeks **Title:** Low Blood Glucose Index (LBGI)* **Type:** OTHER_PRE_SPECIFIED #### Outcome Measure 13 **Description:** hypoglycemic events (defined as at least 15 consecutive minutes \<54 mg/dL) **Reporting Status:** NOT_POSTED **Time Frame:** 13 weeks **Title:** Hypoglycemic Events (Defined as at Least 15 Consecutive Minutes <54 mg/dL) **Type:** OTHER_PRE_SPECIFIED #### Outcome Measure 14 **Description:** hyperglycemic events (defined as at least 90 consecutive minutes \>300 mg/dL) **Reporting Status:** NOT_POSTED **Time Frame:** 13 weeks **Title:** Hyperglycemic Events (Defined as at Least 90 Consecutive Minutes >300 mg/dL) **Type:** OTHER_PRE_SPECIFIED #### Outcome Measure 15 **Description:** percent \>300 mg/dL **Reporting Status:** NOT_POSTED **Time Frame:** 13 weeks **Title:** Percent >300 mg/dL **Type:** OTHER_PRE_SPECIFIED #### Outcome Measure 16 **Description:** high blood glucose index (HBGI)\* **Reporting Status:** NOT_POSTED **Time Frame:** 13 weeks **Title:** High Blood Glucose Index (HBGI)* **Type:** OTHER_PRE_SPECIFIED #### Outcome Measure 17 **Description:** percent in range 70-180 mg/dL improvement from baseline to 13 weeks ≥5 percent **Reporting Status:** NOT_POSTED **Time Frame:** 13 weeks **Title:** Percent in Range 70-180 mg/dL Improvement From Baseline to 13 Weeks ≥5 Percent **Type:** OTHER_PRE_SPECIFIED #### Outcome Measure 18 **Description:** percent in range 70-180 mg/dL improvement from baseline to 13 weeks ≥10 percent **Reporting Status:** NOT_POSTED **Time Frame:** 13 weeks **Title:** Percent in Range 70-180 mg/dL Improvement From Baseline to 13 Weeks ≥10 Percent **Type:** OTHER_PRE_SPECIFIED #### Outcome Measure 19 **Description:** percent time in range 70-180 mg/dL \>70 percent and percent time \<70 mg/dL \<4 percent **Reporting Status:** NOT_POSTED **Time Frame:** 13 weeks **Title:** Percent Time in Range 70-180 mg/dL >70 Percent and Percent Time <70 mg/dL <4 Percent **Type:** OTHER_PRE_SPECIFIED #### Outcome Measure 20 **Description:** HbA1c \<7.0 percent at 13 weeks **Reporting Status:** NOT_POSTED **Time Frame:** 13 weeks **Title:** HbA1c <7.0 Percent at 13 Weeks **Type:** OTHER_PRE_SPECIFIED #### Outcome Measure 21 **Description:** HbA1c \<7.5 percent at 13 weeks **Reporting Status:** NOT_POSTED **Time Frame:** 13 weeks **Title:** HbA1c <7.5 Percent at 13 Weeks **Type:** OTHER_PRE_SPECIFIED #### Outcome Measure 22 **Description:** HbA1c improvement from baseline to 13 weeks \>0.5 percent **Reporting Status:** NOT_POSTED **Time Frame:** 13 weeks **Title:** HbA1c Improvement From Baseline to 13 Weeks >0.5 Percent **Type:** OTHER_PRE_SPECIFIED #### Outcome Measure 23 **Description:** HbA1c improvement from baseline to 13 weeks \>1.0 percent **Reporting Status:** NOT_POSTED **Time Frame:** 13 weeks **Title:** HbA1c Improvement From Baseline to 13 Weeks >1.0 Percent **Type:** OTHER_PRE_SPECIFIED #### Outcome Measure 24 **Description:** HbA1c relative improvement from baseline to 13 weeks \>10 percent **Reporting Status:** NOT_POSTED **Time Frame:** 13 weeks **Title:** HbA1c Relative Improvement From Baseline to 13 Weeks >10 Percent **Type:** OTHER_PRE_SPECIFIED #### Outcome Measure 25 **Description:** HbA1c absolute improvement from baseline to 13 weeks \>1.0 percent or HbA1c \<7.0 percent at 13 weeks **Reporting Status:** NOT_POSTED **Time Frame:** 13 weeks **Title:** HbA1c Absolute Improvement From Baseline to 13 Weeks >1.0 Percent or HbA1c <7.0 Percent at 13 Weeks **Type:** OTHER_PRE_SPECIFIED #### Outcome Measure 26 **Description:** Number of SH events and SH event rate per 100 person-years **Reporting Status:** NOT_POSTED **Time Frame:** 13 weeks **Title:** Number of Severe Hypoglycemic (SH) Events and SH Event Rate Per 100 Person-years **Type:** OTHER_PRE_SPECIFIED #### Outcome Measure 27 **Description:** Number of DKA events and DKA event rate per 100 person-years **Reporting Status:** NOT_POSTED **Time Frame:** 13 weeks **Title:** Number of Diabetic Ketoacidosis (DKA) Events and DKA Event Rate Per 100 Person-years **Type:** OTHER_PRE_SPECIFIED #### Outcome Measure 28 **Description:** Number of other serious adverse events (SAEs other than SH events and DKA events) **Reporting Status:** NOT_POSTED **Time Frame:** 13 weeks **Title:** Number of Other Serious Adverse Events **Type:** OTHER_PRE_SPECIFIED #### Outcome Measure 29 **Description:** Any adverse event rate **Reporting Status:** NOT_POSTED **Time Frame:** 13 weeks **Title:** Any Adverse Event Rate **Type:** OTHER_PRE_SPECIFIED #### Outcome Measure 30 **Description:** Number of calendar days with any ketone level ≥1.0 mmol/L (if ≥5 total calendar days combined) **Reporting Status:** NOT_POSTED **Time Frame:** 13 weeks **Title:** Number of Calendar Days With Any Ketone Level ≥1.0 mmol/L (if ≥5 Total Calendar Days Combined) **Type:** OTHER_PRE_SPECIFIED #### Outcome Measure 31 **Description:** Worsening of HbA1c from baseline to 13 weeks by \>0.5 percent **Reporting Status:** NOT_POSTED **Time Frame:** 13 weeks **Title:** Worsening of HbA1c From Baseline to 13 Weeks by >0.5 Percent **Type:** OTHER_PRE_SPECIFIED #### Outcome Measure 32 **Description:** Adverse device effects (ADE) in intervention group only **Reporting Status:** NOT_POSTED **Time Frame:** 13 weeks **Title:** Adverse Device Effects (ADE) **Type:** OTHER_PRE_SPECIFIED #### Outcome Measure 33 **Description:** Serious adverse device events (SADE) in intervention group only **Reporting Status:** NOT_POSTED **Time Frame:** 13 weeks **Title:** Serious Adverse Device Events (SADE) **Type:** OTHER_PRE_SPECIFIED #### Outcome Measure 34 **Description:** Unanticipated adverse device effects (UADE) in intervention group only **Reporting Status:** NOT_POSTED **Time Frame:** 13 weeks **Title:** Unanticipated Adverse Device Effects (UADE) **Type:** OTHER_PRE_SPECIFIED #### Outcome Measure 35 **Description:** Total daily insulin (units/kg) **Reporting Status:** NOT_POSTED **Time Frame:** 13 weeks **Title:** Total Daily Insulin (Units/kg) **Type:** OTHER_PRE_SPECIFIED #### Outcome Measure 36 **Description:** Percentage of total insulin delivered via basal **Reporting Status:** NOT_POSTED **Time Frame:** 13 weeks **Title:** Percentage of Total Insulin Delivered Via Basal **Type:** OTHER_PRE_SPECIFIED #### Outcome Measure 37 **Description:** Weight **Reporting Status:** NOT_POSTED **Time Frame:** 13 weeks **Title:** Weight **Type:** OTHER_PRE_SPECIFIED #### Outcome Measure 38 **Description:** Body Mass Index (BMI) **Reporting Status:** NOT_POSTED **Time Frame:** 13 weeks **Title:** Body Mass Index (BMI) **Type:** OTHER_PRE_SPECIFIED #### Outcome Measure 39 **Description:** PedsQL Diabetes Module - total score and 5 subscales: Diabetes, Treatment 1, Treatment 2, Worry, Communication **Reporting Status:** NOT_POSTED **Time Frame:** 13 weeks **Title:** PedsQL Diabetes Module - Total Score and 5 Subscales **Type:** OTHER_PRE_SPECIFIED #### Outcome Measure 40 **Description:** Pediatric Inventory for Parents (PIP) 2 domains each with a total score and 4 subscales for (5x2=10 difference scores): Frequency (Total Score, Communication, Medical Care, Role Function, Emotional Functioning), Difficulty ( Same total + 4 subscales as above for frequency) **Reporting Status:** NOT_POSTED **Time Frame:** 13 weeks **Title:** Pediatric Inventory for Parents (PIP) 2 Domains Each With a Total Score and 4 Subscales for (5x2=10 Difference Scores) **Type:** OTHER_PRE_SPECIFIED #### Outcome Measure 41 **Description:** INSPIRE (CLC arm only) 5-point Likert scale from strongly agree to strongly disagree, along with an N/A option. **Reporting Status:** NOT_POSTED **Time Frame:** 13 weeks **Title:** INSPIRE Survey (Insulin Delivery Systems: Perceptions, Ideas, Reflections and Expectations) (CLC Arm Only) **Type:** OTHER_PRE_SPECIFIED #### Outcome Measure 42 **Description:** An abbreviated 9-question version of the Pittsburgh Sleep Quality Index (PSQI), a validated tool for assessing self-reported sleep quantity and quality, will be completed by parents. Seven component scores are derived, each scored 0 (no difficulty) to 3 (severe difficulty). The component scores are summed to produce a global score (range 0 to 21). Higher scores indicate worse sleep quality. **Reporting Status:** NOT_POSTED **Time Frame:** 13 weeks **Title:** Pittsburgh Sleep Quality Index (PSQI) Global Score **Type:** OTHER_PRE_SPECIFIED #### Outcome Measure 43 **Description:** Fear of Hypoglycemia Survey for Parents (HFS-P) - total score, 2 subscales and 4 factor scores: Behavior (avoidance, Maintain high BG), Worry (Helplessness, Social consequences) **Reporting Status:** NOT_POSTED **Time Frame:** 13 weeks **Title:** Fear of Hypoglycemia Survey for Parents (HFS-P) - Total Score, 2 Subscales and 4 Factor Scores **Type:** OTHER_PRE_SPECIFIED #### Outcome Measure 44 **Description:** Number of SH events during, immediately after and overnight from the study challenges **Reporting Status:** NOT_POSTED **Time Frame:** Up to 24 hour period **Title:** Number of SH Events During, Immediately After and Overnight From the Study Challenges **Type:** OTHER_PRE_SPECIFIED #### Outcome Measure 45 **Description:** Number of adverse events during, immediately after and overnight from the study challenges **Reporting Status:** NOT_POSTED **Time Frame:** Up to 24 hour period **Title:** Number of Adverse Events During, Immediately After and Overnight From the Study Challenges **Type:** OTHER_PRE_SPECIFIED #### Outcome Measure 46 **Description:** CGM-measured % \<54 mg/dL overnight (all challenge types) **Reporting Status:** NOT_POSTED **Time Frame:** 8 hours **Title:** CGM-measured % <54 mg/dL Overnight (All Challenge Types) **Type:** OTHER_PRE_SPECIFIED #### Outcome Measure 47 **Description:** CGM-measured % \<70 mg/dL overnight (all challenge types) **Reporting Status:** NOT_POSTED **Time Frame:** 8 hours **Title:** CGM-measured % <70 mg/dL Overnight (All Challenge Types) **Type:** OTHER_PRE_SPECIFIED #### Outcome Measure 48 **Description:** CGM-measured % \>180 mg/dL overnight (all challenge types) **Reporting Status:** NOT_POSTED **Time Frame:** 8 hours **Title:** CGM-measured % >180 mg/dL Overnight (All Challenge Types) **Type:** OTHER_PRE_SPECIFIED #### Outcome Measure 49 **Description:** CGM-measured % \<54 mg/dL during the two hours immediately following the start of exercise for each exercise-related challenge **Reporting Status:** NOT_POSTED **Time Frame:** 2 hours **Title:** CGM-measured % <54 mg/dL During the Two Hours Immediately Following the Start of Exercise for Each Exercise-related Challenge **Type:** OTHER_PRE_SPECIFIED #### Outcome Measure 50 **Description:** CGM-measured % \<70 mg/dL during the two hours immediately following the start of exercise for each exercise-related challenge **Reporting Status:** NOT_POSTED **Time Frame:** 2 hours **Title:** CGM-measured % <70 mg/dL During the Two Hours Immediately Following the Start of Exercise for Each Exercise-related Challenge **Type:** OTHER_PRE_SPECIFIED #### Outcome Measure 51 **Description:** CGM-measured % \>180 mg/dL during the four hours following the announced meal, or until the next meal bolus is given, for the missed meal bolus challenge **Reporting Status:** NOT_POSTED **Time Frame:** 4 hours **Title:** CGM-measured % >180 mg/dL During the Four Hours Following the Announced Meal, or Until the Next Meal Bolus is Given, for the Missed Meal Bolus Challenge **Type:** OTHER_PRE_SPECIFIED #### Outcome Measure 52 **Description:** CGM-measured % \>300 mg/dL during the four hours following the announced meal, or until the next meal bolus is given, for the missed meal bolus challenge **Reporting Status:** NOT_POSTED **Time Frame:** 4 hours **Title:** CGM-measured % >300 mg/dL During the Four Hours Following the Announced Meal, or Until the Next Meal Bolus is Given, for the Missed Meal Bolus Challenge **Type:** OTHER_PRE_SPECIFIED ### Participant Flow Module #### Group **Description:** Participants who skip or successfully complete the run-in will be randomly assigned 2:1 to the use of closed-loop control (CLC group) system using Tandem t:slim X2 with Control-IQ Technology vs Standard of Care (SC group) for 3 weeks. Participants randomized to the intervention group will use the Tandem t:slim X2 with Control-IQ Technology v1.0 during the first 13 weeks of the study (RCT phase, weeks 1-13) and then use Tandem t:slim X2 insulin pump with Control-IQ Technology v1.5 for the remaining 13 weeks of the study (extension phase, weeks 14-26). **ID:** FG000 **Title:** CLC Group #### Group **Description:** Participants who skip or successfully complete the run-in will be randomly assigned 2:1 to the use of closed-loop control (CLC group) system using Tandem t:slim X2 with Control-IQ Technology vs Standard of Care (SC group) for 3 weeks. Participants randomized to the SC group will use their existing insulin therapy in conjunction with study Dexcom G6 CGM during the first 13 weeks of the study (RCT phase, weeks 1-13). The SC group will then transition to using the Tandem t:slim X2 insulin pump with Control-IQ Technology v1.5 and study Dexcom G6 CGM for the remaining 13 weeks of the study (weeks 14-26). **ID:** FG001 **Title:** SC Group #### Period **Title:** Overall Study ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 68 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 34 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 67 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 34 ##### 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:** NCT05554679 **Brief Title:** Maternal and Fetal Outcome With Metformin Therapy for Obese Pregnant Women . **Official Title:** Maternal and Fetal Outcome With Metformin Therapy for Obese Pregnant Women a Randomized Control Trial. #### Organization Study ID Info **ID:** Metformin in preganancy #### Organization **Class:** OTHER **Full Name:** Assiut University ### Status Module #### Completion Date **Date:** 2023-07-11 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2024-02-13 **Type:** ACTUAL **Last Update Submit Date:** 2024-02-10 **Overall Status:** TERMINATED #### Primary Completion Date **Date:** 2022-12-30 **Type:** ACTUAL #### Start Date **Date:** 2021-02-01 **Type:** ACTUAL **Status Verified Date:** 2024-02 #### Study First Post Date **Date:** 2022-09-26 **Type:** ACTUAL **Study First Submit Date:** 2020-03-20 **Study First Submit QC Date:** 2022-09-22 **Why Stopped:** financial issues ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Assiut University #### Responsible Party **Investigator Affiliation:** Assiut University **Investigator Full Name:** Andrew Ibram Samy **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:** To evaluate the role of metformin in pregnant women with obesity (BMI above 30) , on maternal and infant outcome. **Detailed Description:** Obesity is defined as having an excessive amount of body fat based on the BMI, Obesity can be classified based on the BMI to obese class I ,Class II ,and extreme obesity (class III) , Obesity can harm the fertility by inhibiting normal ovulation. Even in women who regularly ovulate, the greater the BMI, the longer it appears to take to become pregnant. Obesity can also affect the outcome of in vitro fertilization (IVF). (1) Being obese during pregnancy increases the risk of various pregnancy complications, including : Miscarriage ,stillbirth ,GD , preeclampsia , obstructive sleep apnea , difficult vaginal delivery ,need for C-section ,and complication of C-section ,Fetal macrosomia , and increasing the risk for metabolic syndrome and childhood obesity , it also make It may be hard for the participants health care provider to diagnose birth defects during pregnancy even prenatal tests like ultrasound(2),(3) . Normal weight gain during pregnancy for obese women having single pregnancy is between about (5-9) KG . Normal weight gain during pregnancy for obese women having Multiple pregnancy is between about (11-19) KG (4). For women who are extremely obese, gaining less than the recommended amount or losing weight during pregnancy might lower the risk of fetal and neonatal macrosomia . The fetus is regarded as suspected appropriate or gestational age (AGA) when the Sonographic Estimated Fetal Weight (SEFW) is at 10th to 90th percentile for gestational age (GA), and suspected LGA when the SEFW \> 90th percentile (5) . A baby diagnosed with fetal macrosomia has a birth weight of more than 8 pounds,(4,000 grams), regardless of his or her gestational age (6,7,8) . In this study the investigator will try to focus on diagnose undiagnosed diabetic using GTT (glucose tolerance test specially with women who has one or more risk factors A raised body mass index (BMI) over 30kg/m². A previous baby over 4kg or more ,Confirmed gestational diabetes in a previous pregnancy or have a first degree relative that has diabetes All pregnant women who have not already been diagnosed with diabetes should be screened for Diabetes with a fasting plasma glucose (FPG), an HbA1c, or an untimed random plasma glucose test at their first prenatal visit * Women who by 24 weeks' gestation have not yet been diagnosed with overt or gestational diabetes should, at between 24 and 28 weeks' gestation, undergo a 2-hour, 75-g OGTT for gestational diabetes * At 24-28 weeks' gestation, a result of 153-199 mg/dL for a 2-hour, 75-g OGTT indicates gestational diabetes, while a test result of 200 mg/dL or higher indicates overt diabetes(9),(10) ### Conditions Module **Conditions:** - Metformin for Obese Pregnant Women ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** metformin effect on prevention of macrosomia in obese pregnant women ##### Masking Info **Masking:** NONE **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 178 **Type:** ACTUAL **Phases:** - PHASE4 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** obese pregnant women who take metformin **Intervention Names:** - Drug: Metformin **Label:** group A **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** obese pregnant women who take no metformin **Label:** group B **Type:** NO_INTERVENTION ### Interventions #### Intervention 1 **Arm Group Labels:** - group A **Description:** Metformin is an oral insulin-sensitising medication that acts to decrease blood glucose concentrations. It inhibits pathways in the liver that stimulate glucose production and also acts to increase glucose uptake into skeletal muscle and fat cells . Metformin is commonly used in the treatment of type 2 diabetes mellitus and polycystic ovarian syndrome , and is being used increasingly in the treatment of gestational diabetes, having been shown to result in decreased rates of neonatal hypoglycaemia and no increased risk of adverse maternal outcomes when compared with insulin. **Name:** Metformin **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** The fetus is regarded as suspected appropriate for gestational age (AGA) when the Sonographic Estimated Fetal Weight (SEFW) is at 10th to 90th percentile for gestational age (GA), and suspected LGA when the SEFW \> 90th percentile ,A baby diagnosed with fetal macrosomia has a birth weight of more than 8 pounds,(4,000 grams), regardless of his or her gestational age. **Measure:** Neonatal birth weight **Time Frame:** Baseline #### Secondary Outcomes **Description:** Health care providers who care for pregnant women should determine a woman's body mass index at the initial prenatal visit and counsel her regarding the benefits of appropriate weight gain, nutrition and exercise, and, especially, the need to limit excessive weight gain to achieve best pregnancy outcome . for women of normal weight, 14.1-22.7 kg (31-50 lb) for overweight women, and 11.3-19.1 kg (25-42 lb) for obese women **Measure:** Maternal weight gain **Time Frame:** Baseline ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * pregnant women with BMI ≥ 30 kg/m2, and normal glucose tolerance test. Exclusion Criteria: * pregnant women who are diabetic, * had a history of previous GDM, * previous small baby, * PCO or * previous early pre-eclampsia, **Maximum Age:** 44 Years **Minimum Age:** 17 Years **Sex:** FEMALE **Standard Ages:** - CHILD - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Asyut **Country:** Egypt **Facility:** Assiut university **Zip:** 11117 #### Overall Officials **Official 1:** **Affiliation:** Assiut University **Name:** Ahmed Abuelhasan **Role:** STUDY_DIRECTOR ### References Module #### References **Citation:** Hyer S, Balani J, Shehata H. Metformin in Pregnancy: Mechanisms and Clinical Applications. Int J Mol Sci. 2018 Jul 4;19(7):1954. doi: 10.3390/ijms19071954. **PMID:** 29973490 ## 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: Obese - 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 ### Intervention Browse Module - Ancestors - ID: D000007004 - Term: Hypoglycemic Agents - ID: D000045505 - Term: Physiological Effects of Drugs ### Intervention Browse Module - Browse Branches - Abbrev: Hypo - Name: Hypoglycemic Agents - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Hemat - Name: Hematinics ### Intervention Browse Module - Browse Leaves - ID: M11667 - Name: Metformin - Relevance: HIGH - As Found: Assessment - ID: M10365 - Name: Insulin - Relevance: LOW - As Found: Unknown - ID: M173166 - Name: Insulin, Globin Zinc - Relevance: LOW - As Found: Unknown - ID: M11110 - Name: Liver Extracts - Relevance: LOW - As Found: Unknown - ID: M10054 - Name: Hypoglycemic Agents - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000008687 - Term: Metformin ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03052179 **Acronym:** CABRIO **Brief Title:** The Clinical and Biological Effects Of The Use Of Probiotic VSL#3 In Patients With Oral Lichen Planus **Official Title:** The Clinical and Biological Effects Of The Use Of Probiotic VSL#3 In Patients With Oral Lichen Planus : a Proof-of-concept Study #### Organization Study ID Info **ID:** 16/0622 #### Organization **Class:** OTHER **Full Name:** University College, London ### Status Module #### Completion Date **Date:** 2018-09-11 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2020-03-27 **Type:** ACTUAL **Last Update Submit Date:** 2020-03-25 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2018-09-11 **Type:** ACTUAL #### Start Date **Date:** 2017-08-24 **Type:** ACTUAL **Status Verified Date:** 2020-03 #### Study First Post Date **Date:** 2017-02-14 **Type:** ACTUAL **Study First Submit Date:** 2017-02-09 **Study First Submit QC Date:** 2017-02-09 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** University College, London #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** Oral Lichen Planus (OLP) is an inflammatory disease of mucosal and skin with unknown etiology. The prevalence rate in England is reported to be between 1-2.4%. OLP contributed to around 40% of all visits or 1,200 appointments in 2014 at the Eastman Dental Hospital. Pain, discomfort, long-standing use of medications, lesion recurrence and adverse side effects of therapy are commonly associated with OLP, eventually leading to a significant reduction in a patient quality of life. In addition, there is also increased risk of developing oral cancer in patients with OLP. The current gold standard treatment for OLP is corticosteroid, which can result in adverse side effects including increased risk of infections and skin cancer, reduced systemic immune system, and hepatotoxicity with long-term usage. Alternatively, a probiotic food supplement, VSL#3, has shown evidence of been able to induce and maintain remission in Inflammatory Bowel Disease (IBD), with no adverse effect a part than bloating, reported. Additionally, a preliminary report shown that probiotics treatment in Behcet's disease and Recurrent Aphthous Stomatitis (RAS) lesion resulted in reducing the number of oral ulcerations and subjective relief of oral discomfort. Investigator designed a clinical trial with 30 participants allocated to one of two interventions, VSL#3 or placebo. Individuals with biopsy-confirmed OLP who experience painful symptoms will be recruited from a single site research site (Eastman Dental Hospital (EDH)). Either the active VSL#3 or the placebo, provided by Ferring Pharmaceuticals Limited, will be consume twice a day over a 30 days period. Questionnaires that will determine pain levels, disease activity and quality of life will be completed before the study begins, on days 15, 30 and 30 days after the last supplement intake. In addition saliva and blood samples will be taken before therapy begin, at 30 days of therapy, and 30 days after the last supplement intake. The levels of pro-inflammatory cytokines and the oral microbiota will be investigated using these samples. A blinded clinician will assess the clinical effects between groups of active VSL #3 and placebo and the results will analyze by statistician. **Detailed Description:** Primary objective: • To investigate the effects of 30 days use of supplement therapy of probiotic VSL#3 on painful symptoms of OLP at the end of the therapy (30-days endpoint) and 30 days after the last dose (60-days endpoint). Secondary objective: 1. To investigate the effects of 30 days use of supplement therapy of probiotic VSL#3 on OLP disease activity. 2. To investigate the effect of 30 days use of supplement therapy of probiotic VSL#3 on quality of life. 3. To investigate acceptability of the intervention and potential adverse effects. and for the mechanistic study, whether : * The use of VSL#3 is associated with metagenomics changes in saliva. * The use of VSL#3 is associated with changes in the serum expression profile of pro-inflammatory cytokines. A randomized, double blinded, placebo-controlled trial study on individuals with OLP. Patients with painful ulcerative biopsy-confirmed OLP attending the Oral Medicine clinics of the UCLH ( University college of London hospital) Eastman Hospital and meeting the inclusion criteria of the study will be given information about the trial and invited to participate. 30 individuals who consent will be recruited and randomised in two groups: group A (15 participants) will receive the VSL#3 and group B (15 participants) will receive a placebo. A centralised computer-generated randomization list provided by an independent third party will be used to conceal allocation of patients to the treatments. The list will be sent to the drug manufacturer who will label the VSL#3 or placebo with relevant study participant code, which will come in the same identical plain-packages to ensure blinding (neither the participants nor the investigator will be aware of the sachets content). The study statistician will also be blinded to the allocation. Patients will be allowed to use best standard therapy during the study. To demonstrate the research hypotheses, Investigators will record oral painful symptoms, disease activity, and quality of life in participants before, at 15 and 30 days from treatment start, and 30 days (day 60) after the last VSL#3 supplement intake. 60 days + 15 days 21 months Single-site 30 participants Inclusion Criteria: 1. Biopsy-proven diagnosis of OLP as per WHO histological criteria\* with no evidence of epithelial dysplasia or malignancy. 2. Presence of painful oral symptoms associated to OLP, with minimum severity of pain being 3 or more, on a 0-10 numeric pain rating scale at screening and confirmed at recruitment/start of the intervention. 3. Age \>18 years and willing to participate into the study. 4. Receiving no therapy or receiving best standard topical therapy (typically topical corticosteroids or immunosuppressant) with the exclusion of systemic corticosteroids or systemic immunosuppressant. * I. R. H. Kramer, R. B. Lucas, J. J. Pindborg, and L. H. Sobin, "Definition of leukoplakia and related lesions: an aid to studies on oral precancer," Oral Surgery Oral Medicine and Oral Pathology, vol. 46, no. 4, pp. 518-539, 1978 Exclusion Criteria 1. The use of systemic antibiotics, retinoid, corticosteroids or immunosuppressant within four weeks prior to enrolment in the study. 2. Pregnancy\* or receiving IVF treatment. 3. Individuals with known history of systemic disorders affecting the immune system (e.g., connective tissue disorders, cancer, etc.) 4. Active cancer or cancer in remission undergoing maintenance with chemotherapy or immunomodulatory agents. 5. Evidence of oral epithelial dysplasia or malignancy on previous biopsy. * Evidence of negative pregnancy test at screening / randomization visit (strip urine test) in women of child-bearing age in which the possibility of being pregnant cannot be otherwise excluded. ### Conditions Module **Conditions:** - Oral Lichen Planus ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** Double blind, randomized, placebo-controlled ##### Masking Info **Masking:** DOUBLE **Masking Description:** Either participant or the investigator will be blinded. The key of randomisation will be held by the third statistician party, and the company which supply and labeled the product study. **Who Masked:** - PARTICIPANT - INVESTIGATOR **Primary Purpose:** SUPPORTIVE_CARE #### Enrollment Info **Count:** 30 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** VSL#3 poly-biotic 450 billion in sachet orally, two sachets in the morning and two sahcets in the evening for 30 days **Intervention Names:** - Dietary Supplement: Poly-biotic **Label:** VSL#3 **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** Maltose in sachet orally, two sachets in the morning and two sahcets in the evening for 30 days **Intervention Names:** - Dietary Supplement: Poly-biotic **Label:** Placebo **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Placebo - VSL#3 **Description:** Before-after treatment **Name:** Poly-biotic **Other Names:** - VSL#3 5015919450087 **Type:** DIETARY_SUPPLEMENT ### Outcomes Module #### Other Outcomes **Description:** To observed changing of bacterial composition before and after treatment **Measure:** Metagenomic changing in saliva **Time Frame:** 30 days **Description:** To observed changing in serum level cytokine before and after treatment **Measure:** Cytokine serum level **Time Frame:** 30 days #### Primary Outcomes **Description:** is a 10 point scale for participant self-reporting pain. Participant will asked to point out the scale from 0 = no pain and 10 = worse pain can imagine. **Measure:** pain - Numeric Rating Scale (NRS) **Time Frame:** 30 days #### Secondary Outcomes **Description:** Escudier's scoring system to measure disease activity based on size and number of lesion **Measure:** ESS **Time Frame:** 30 days **Description:** Validated questioner for chronic oral mucosal disease **Measure:** COMDQ **Time Frame:** 30 days ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Biopsy-proven diagnosis of OLP as per WHO histological criteria\* with no evidence of epithelial dysplasia or malignancy. 2. Presence of painful oral symptoms associated to OLP, with minimum severity of pain being 3 or more, on a 0-10 numeric pain rating scale at screening and confirmed at recruitment/start of the intervention. 3. Age \>18 years and willing to participate into the study. 4. Receiving no therapy or receiving best standard topical therapy (typically topical corticosteroids or immunosuppressant) with the exclusion of systemic corticosteroids or systemic immunosuppressant Exclusion Criteria: 1. Use of systemic antibiotics, retinoid, corticosteroids or immunosuppressant. 2. Pregnancy or receiving IVF treatment. 3. Individuals with systemic disorders affecting the immune system (e.g., HIV, connective tissue disorders, cancer, etc.) 4. Evidence of oral dysplasia or malignancy on previous biopsy. - **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** London **Country:** United Kingdom **Facility:** University College of London Hospital **Zip:** WC1E 6BT #### Overall Officials **Official 1:** **Affiliation:** University College, London **Name:** Andrew M Smith, Dr **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **Description:** the data will be kept anynomous. This data only accessible by the party mention in the protocols **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000017512 - Term: Lichenoid Eruptions - ID: D000017444 - Term: Skin Diseases, Papulosquamous - ID: D000012871 - Term: Skin Diseases - ID: D000009059 - Term: Mouth Diseases - ID: D000009057 - Term: Stomatognathic Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC07 - Name: Mouth and Tooth Diseases - Abbrev: BC17 - Name: Skin and Connective Tissue Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M19896 - Name: Lichen Planus, Oral - Relevance: HIGH - As Found: Oral Lichen Planus - ID: M11012 - Name: Lichen Planus - Relevance: HIGH - As Found: Lichen Planus - ID: M19775 - Name: Lichenoid Eruptions - Relevance: LOW - As Found: Unknown - ID: M8219 - Name: Exanthema - Relevance: LOW - As Found: Unknown - ID: M15674 - Name: Skin Diseases - Relevance: LOW - As Found: Unknown - ID: M19713 - Name: Skin Diseases, Papulosquamous - 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: D000017676 - Term: Lichen Planus, Oral - ID: D000008010 - Term: Lichen Planus ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00700479 **Brief Title:** Studies on Aldosterone and Vascular Function **Official Title:** Studies on Aldosterone and Vascular Function #### Organization Study ID Info **ID:** 602001143 #### Organization **Class:** OTHER **Full Name:** Yale University ### Status Module #### Completion Date **Date:** 2008-06 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2008-06-18 **Type:** ESTIMATED **Last Update Submit Date:** 2008-06-17 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2008-06 **Type:** ACTUAL #### Start Date **Date:** 2006-01 **Status Verified Date:** 2008-06 #### Study First Post Date **Date:** 2008-06-18 **Type:** ESTIMATED **Study First Submit Date:** 2007-12-25 **Study First Submit QC Date:** 2008-06-17 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** Pfizer #### Lead Sponsor **Class:** OTHER **Name:** Yale University #### Responsible Party **Old Name Title:** Stuart Katz **Old Organization:** Yale School of Medicine ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** A randomized crossover trial to determine the effects of sodium loading and aldosterone infusion on endothelial function in normal subjects. ### Conditions Module **Conditions:** - Inflammation **Keywords:** - vascular endothelium - nitric oxide - aldosterone - vascular biology ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** CROSSOVER ##### Masking Info **Masking:** QUADRUPLE **Who Masked:** - PARTICIPANT - CARE_PROVIDER - INVESTIGATOR - OUTCOMES_ASSESSOR **Primary Purpose:** DIAGNOSTIC #### Enrollment Info **Count:** 20 **Type:** ESTIMATED **Phases:** - PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Aldosterone plus low salt diet **Intervention Names:** - Drug: aldosterone - Dietary Supplement: low or high sodium diet **Label:** A **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Aldosterone plus high sodium diet **Intervention Names:** - Drug: aldosterone - Dietary Supplement: low or high sodium diet **Label:** B **Type:** EXPERIMENTAL #### Arm Group 3 **Description:** Placebo plus low sodium diet **Intervention Names:** - Dietary Supplement: low or high sodium diet - Drug: placebo **Label:** C **Type:** PLACEBO_COMPARATOR #### Arm Group 4 **Description:** placebo plus high sodium diet **Intervention Names:** - Dietary Supplement: low or high sodium diet - Drug: placebo **Label:** D **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - A - B **Description:** 4 hour infusion **Name:** aldosterone **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - A - B - C - D **Name:** low or high sodium diet **Type:** DIETARY_SUPPLEMENT #### Intervention 3 **Arm Group Labels:** - C - D **Description:** placebo **Name:** placebo **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Measure:** Flow mediated dilation brachial artery **Time Frame:** 0 and 4 hours ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Healthy subjects age \>18 years Exclusion Criteria: * Any chronic medical disease or chronic use of medications **Healthy Volunteers:** True **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** New Haven **Country:** United States **Facility:** Yale University School of Medicine **State:** Connecticut **Zip:** 06510 #### Overall Officials **Official 1:** **Affiliation:** Yale School of Medicine **Name:** Stuart Katz, MD **Role:** PRINCIPAL_INVESTIGATOR ## 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: M10293 - Name: Inflammation - Relevance: HIGH - As Found: Inflammation ### Condition Browse Module - Meshes - ID: D000007249 - Term: Inflammation ### Intervention Browse Module - Browse Branches - Abbrev: VaDiAg - Name: Vasodilator Agents - Abbrev: Resp - Name: Respiratory System Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M12507 - Name: Nitric Oxide - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00645879 **Brief Title:** Anaplerotic Therapy in Propionic Acidemia **Official Title:** Safety & Efficacy of Investigational Products: Ornithine Alpha-ketoglutarate, Glutamine, or Disodium Citrate on Hyperammonemia in Propionic Acidemia. #### Organization Study ID Info **ID:** 24806 #### Organization **Class:** OTHER **Full Name:** University of Utah #### Secondary ID Infos **ID:** 1R21DK077415-01A1 **Link:** https://reporter.nih.gov/quickSearch/1R21DK077415-01A1 **Type:** NIH **Domain:** University of Utah **ID:** ANA-PA-001 **Type:** OTHER ### Status Module #### Completion Date **Date:** 2010-02 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2015-01-21 **Type:** ESTIMATED **Last Update Submit Date:** 2015-01-17 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2009-08 **Type:** ACTUAL #### Start Date **Date:** 2008-07 **Status Verified Date:** 2015-01 #### Study First Post Date **Date:** 2008-03-28 **Type:** ESTIMATED **Study First Submit Date:** 2008-03-25 **Study First Submit QC Date:** 2008-03-27 ### Sponsor Collaborators Module #### Collaborators **Class:** NIH **Name:** National Institutes of Health (NIH) **Class:** NIH **Name:** National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) #### Lead Sponsor **Class:** OTHER **Name:** Nicola Longo #### Responsible Party **Investigator Affiliation:** University of Utah **Investigator Full Name:** Nicola Longo **Investigator Title:** MD, Professor, Biochemical Geneticist **Type:** SPONSOR_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** The objective of this project is to define whether nutritional supplements (ornithine alpha-ketoglutarate, glutamine, or citrate) capable of filling-up the citric acid cycle (anaplerotic therapy) can improve hyperammonemia, glutamine levels, and outcome in patients with propionic acidemia. Ornithine alpha-ketoglutarate, glutamine, and citrate are commonly used as nutritional supplements specially by athletes to increase muscle strength. They can be mixed with formula or other foods. **Detailed Description:** Propionic acidemia is caused by deficiency of propionyl CoA carboxylase that impairs the supply of succinyl CoA to the citric acid (Krebs) cycle. The Krebs cycle is responsible for obtaining energy from food in the form of ATP. ATP is essential for muscle contraction and correct functioning of all organs including the hearth, the kidney, and the pancreas. Patients with propionic acidemia develop hyperammonemia at birth that recurs during episodes of metabolic decompensation. We found that plasma levels of the amino acids glutamine/glutamate are reduced in patients with propionic acidemia and decrease, rather than increase (like in urea cycle defects or other types of hyperammonemia) with hyperammonemia. Since alpha-ketoglutarate is the main source of endogenous glutamate/glutamine synthesis, our hypothesis is that chronic hyperammonemia and progressive dysfunction of multiple organs in patients with propionic acidemia is due to a functional insufficiency of the citric acid (Krebs) cycle with defective production of alpha-ketoglutarate. The basic deficiency of intermediates of the Krebs cycle can decrease production of ATP and explain the low muscle tone, progressive organ dysfunction, and poor long-term outcome of patients with propionic acidemia. To test this hypothesis, we will test whether dietary supplementation with alpha ketoglutarate precursors (in the form of ornithine alpha ketoglutarate, glutamine or citrate) can improve plasma ammonia and overall outcome in patients with propionic acidemia. In this study, a limited number of patients (3) with propionic acidemia will be given the 3 different nutritional supplements and studied at regular intervals to see whether their glutamine/glutamate levels improve and if they have fewer episodes of hyperammonemia or acute decompensation. The supplement that produces the best increase in plasma glutamine levels will be tested for an additional 30 weeks. Children's development and motor skills will be tested before and after therapy to see if there is any improvement. The study will be conducted on outpatients at the University of Utah Clinical Research Center. If the initial trial is successful, we will try to launch a national trial involving multiple centers in the US and abroad to involve the largest number of patients possible. The current therapy of propionic acidemia is based on restriction of precursors of propionic acid (methionine, valine, isoleucine, threonine, odd chain fatty acids, cholesterol) and administration of carnitine to help remove toxic organic acids. This therapy is not effective in preventing the long-term complications of the disease, even in children identified at birth by newborn screening. This research will test a completely new way of treating patients with severe and disabling metabolic disorders using replacement of downstream products involved in the generation of energy (ATP). This approach, if effective, could be extended to a number of other diseases, including other organic acidemias and mitochondrial disorders. ### Conditions Module **Conditions:** - Propionic Acidemia **Keywords:** - Propionic Acidemia - hyperammonemia - hypotonia - glutamine - ornithine alpha ketoglutarate - citrate ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 3 **Type:** ACTUAL **Phases:** - PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Ornithine Alpha Ketoglutarate for 4 weeks, followed by 2 week washout period. 4 weeks Glutamine, followed by 2 week washout period. 4 weeks Disodium Citrate, followed by 2 to 12 week washout period. Then continue an additional 30 weeks on Disodium Citrate (drug producing the best increment in plasma glutamine levels). **Intervention Names:** - Drug: ornithine alpha ketoglutarate - Drug: glutamine - Drug: disodium citrate **Label:** OKG, Glutamine, and Disodium Citrate **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - OKG, Glutamine, and Disodium Citrate **Description:** A dose of 400 mg/kg up to 16 g per day was selected. Split into 2 doses taken for 4 weeks. If determined the drug with the best effect, drug will be taken for 30 weeks. **Name:** ornithine alpha ketoglutarate **Other Names:** - OKG **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - OKG, Glutamine, and Disodium Citrate **Description:** A dose of 400 mg/kg up to 16 g per day was selected. Split into 2 doses taken for 4 weeks. If determined the drug with the best effects, drug will be taken for 30 weeks. **Name:** glutamine **Other Names:** - Glutamic Acid **Type:** DRUG #### Intervention 3 **Arm Group Labels:** - OKG, Glutamine, and Disodium Citrate **Description:** Dose: 7.5 mEq/Kg or 658 mg/kg up to 16 g per day Split into 2 doses taken for 4 weeks. If determined the drug with the best effects, drug will be taken for 30 weeks. **Name:** disodium citrate **Other Names:** - Citric Acid Sodium Salt, Sodium Citrate **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Measure:** Define safety and efficacy of nutritional therapy with these investigational products: L-Ornithine alpha-ketoglutarate, Glutamine, or disodium citrate (anaplerotic therapy) on hyperammonemia and outcome in patients with propionic acidemia. **Time Frame:** end of study #### Secondary Outcomes **Measure:** Define the effect of citrate, alpha-ketoglutarate and glutamine on plasma amino acids, acylcarnitines, ammonia, lactic acid and urine organic acids in patients with propionic acidemia. **Time Frame:** end of study **Measure:** Evaluate the effect of investigational products on the developmental quotient and medical complications in patients with propionic acidemia. **Time Frame:** end of study ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Confirmed diagnosis of propionic acidemia (propionyl CoA carboxylase deficiency) Exclusion Criteria: * Severe illness with cardiac or hepatic compromise that could affect study results * Use of other investigative therapies * Inability to comply with study directions **Maximum Age:** 12 Years **Minimum Age:** 5 Years **Sex:** ALL **Standard Ages:** - CHILD ### Contacts Locations Module #### Locations **Location 1:** **City:** Salt Lake City **Country:** United States **Facility:** University of Utah, Department of Pediatrics **State:** Utah **Zip:** 84132 #### Overall Officials **Official 1:** **Affiliation:** University of Utah **Name:** Nicola Longo, MD, PhD **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### References **Citation:** Deodato F, Boenzi S, Santorelli FM, Dionisi-Vici C. Methylmalonic and propionic aciduria. Am J Med Genet C Semin Med Genet. 2006 May 15;142C(2):104-12. doi: 10.1002/ajmg.c.30090. **PMID:** 16602092 **Citation:** Dionisi-Vici C, Deodato F, Roschinger W, Rhead W, Wilcken B. 'Classical' organic acidurias, propionic aciduria, methylmalonic aciduria and isovaleric aciduria: long-term outcome and effects of expanded newborn screening using tandem mass spectrometry. J Inherit Metab Dis. 2006 Apr-Jun;29(2-3):383-9. doi: 10.1007/s10545-006-0278-z. **PMID:** 16763906 **Citation:** Mochel F, DeLonlay P, Touati G, Brunengraber H, Kinman RP, Rabier D, Roe CR, Saudubray JM. Pyruvate carboxylase deficiency: clinical and biochemical response to anaplerotic diet therapy. Mol Genet Metab. 2005 Apr;84(4):305-12. doi: 10.1016/j.ymgme.2004.09.007. **PMID:** 15781190 **Citation:** Roe CR, Sweetman L, Roe DS, David F, Brunengraber H. Treatment of cardiomyopathy and rhabdomyolysis in long-chain fat oxidation disorders using an anaplerotic odd-chain triglyceride. J Clin Invest. 2002 Jul;110(2):259-69. doi: 10.1172/JCI15311. **PMID:** 12122118 **Citation:** Filipowicz HR, Ernst SL, Ashurst CL, Pasquali M, Longo N. Metabolic changes associated with hyperammonemia in patients with propionic acidemia. Mol Genet Metab. 2006 Jun;88(2):123-30. doi: 10.1016/j.ymgme.2005.11.016. Epub 2006 Jan 10. **PMID:** 16406646 **Citation:** Longo N, Price LB, Gappmaier E, Cantor NL, Ernst SL, Bailey C, Pasquali M. Anaplerotic therapy in propionic acidemia. Mol Genet Metab. 2017 Sep;122(1-2):51-59. doi: 10.1016/j.ymgme.2017.07.003. Epub 2017 Jul 12. **PMID:** 28712602 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000000137 - Term: Acid-Base Imbalance - ID: D000008659 - Term: Metabolic Diseases - ID: D000010335 - Term: Pathologic Processes - ID: D000000592 - Term: Amino Acid Metabolism, Inborn Errors - ID: D000008661 - Term: Metabolism, Inborn Errors - ID: D000030342 - Term: Genetic Diseases, Inborn ### Condition Browse Module - Browse Branches - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC16 - Name: Diseases and Abnormalities at or Before Birth - Abbrev: BC18 - Name: Nutritional and Metabolic Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M12080 - Name: Muscle Hypotonia - Relevance: LOW - As Found: Unknown - ID: M22784 - Name: Hyperammonemia - Relevance: HIGH - As Found: Hyperammonemia - ID: M28553 - Name: Propionic Acidemia - Relevance: HIGH - As Found: Propionic Acidemia - ID: M3499 - Name: Acidosis - Relevance: HIGH - As Found: Acidemia - ID: M3498 - Name: Acid-Base Imbalance - Relevance: LOW - As Found: Unknown - ID: M11639 - Name: Metabolic Diseases - Relevance: LOW - As Found: Unknown - ID: M11641 - Name: Metabolism, Inborn Errors - Relevance: LOW - As Found: Unknown - ID: M3932 - Name: Amino Acid Metabolism, Inborn Errors - Relevance: LOW - As Found: Unknown - ID: M23686 - Name: Genetic Diseases, Inborn - Relevance: LOW - As Found: Unknown - ID: T4751 - Name: Propionic Acidemia - Relevance: HIGH - As Found: Propionic Acidemia - ID: T3036 - Name: Inborn Amino Acid Metabolism Disorder - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000056693 - Term: Propionic Acidemia - ID: D000000138 - Term: Acidosis - ID: D000022124 - Term: Hyperammonemia ### Intervention Browse Module - Ancestors - ID: D000000925 - Term: Anticoagulants - ID: D000065096 - Term: Calcium Chelating Agents - ID: D000002614 - Term: Chelating Agents - ID: D000064449 - Term: Sequestering Agents - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action ### Intervention Browse Module - Browse Branches - Abbrev: AnCoag - Name: Anticoagulants - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: BDCA - Name: Bone Density Conservation Agents - Abbrev: Ot - Name: Other Dietary Supplements - Abbrev: AA - Name: Amino Acids ### Intervention Browse Module - Browse Leaves - ID: M21320 - Name: Citric Acid - Relevance: HIGH - As Found: Free - ID: M1837 - Name: Sodium Citrate - Relevance: HIGH - As Found: Free - ID: M4244 - Name: Anticoagulants - Relevance: LOW - As Found: Unknown - ID: M5381 - Name: Calcium - Relevance: LOW - As Found: Unknown - ID: M5398 - Name: Calcium, Dietary - Relevance: LOW - As Found: Unknown - ID: M5860 - Name: Chelating Agents - Relevance: LOW - As Found: Unknown - ID: T382 - Name: Citrate - Relevance: HIGH - As Found: Free - ID: T6 - Name: Glutamine - Relevance: HIGH - As Found: Bladder Cancer - ID: T13 - Name: Ornithine - Relevance: HIGH - As Found: Colorectal Polyps - ID: T5 - Name: Glutamic Acid - Relevance: HIGH - As Found: Implantable Cardioverter Defibrillator ### Intervention Browse Module - Meshes - ID: D000019343 - Term: Citric Acid - ID: D000077559 - Term: Sodium Citrate ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03223779 **Brief Title:** Study of TAS-102 Plus Radiation Therapy for the Treatment of the Liver in Patients With Hepatic Metastases From Colorectal Cancer **Official Title:** Phase Ib/II Study of TAS-102 Plus Radiation Therapy for the Treatment of the Liver in Patients With Hepatic Metastases From Colorectal Cancer #### Organization Study ID Info **ID:** 17-231 #### Organization **Class:** OTHER **Full Name:** Massachusetts General Hospital ### Status Module #### Completion Date **Date:** 2025-01 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2022-09-08 **Type:** ACTUAL **Last Update Submit Date:** 2022-09-07 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2023-01 **Type:** ESTIMATED #### Start Date **Date:** 2017-10-13 **Type:** ACTUAL **Status Verified Date:** 2022-09 #### Study First Post Date **Date:** 2017-07-21 **Type:** ACTUAL **Study First Submit Date:** 2017-07-12 **Study First Submit QC Date:** 2017-07-14 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** Taiho Oncology, Inc. #### Lead Sponsor **Class:** OTHER **Name:** Massachusetts General Hospital #### Responsible Party **Investigator Affiliation:** Massachusetts General Hospital **Investigator Full Name:** Theodore Sunki Hong **Investigator Title:** Director, Gastrointestinal Service, Department of Radiation Oncology **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** True **Oversight Has DMC:** True ### Description Module **Brief Summary:** This research study is studying a drug in combination with radiation therapy as a possible treatment for hepatic metastases from colorectal cancer. The interventions involved in this study are: * Trifluridine (TAS-102) * Radiation Therapy **Detailed Description:** This is a Phase I/II clinical trial. Patients are being asked to participate in the Phase I portion of the study. A Phase I clinical trial tests the safety of an investigational intervention and also tries to define the appropriate dose of the investigational drug to use for further studies. "Investigational" means that the intervention is being studied. The FDA (the U.S. Food and Drug Administration) has approved Trifluridine as a treatment option for this disease. The FDA has not approved Trifluridine in combination with radiation therapy as a treatment option for this disease. In this research study, the investigators are determining the safest and most effective dose of Trifluridine in combination with radiation therapy in participants with hepatic metastases from colorectal cancer. Trifluridine stops DNA replication which may prevent the cancer cells from growing. Radiation may help to kill the cancer cells while protecting normal tissue cells. Studies have shown Trifluridine may make radiation more effective. ### Conditions Module **Conditions:** - Colorectal Cancer **Keywords:** - Colorectal Cancer ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 56 **Type:** ESTIMATED **Phases:** - PHASE1 - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** * Photon treatments will be performed on a linear accelerator * Photon SBRT will be given during TAS-102 dosing * TAS-102 dosing occurs on days 1 through 5 and 8 through 12 * TAS-102 tablets should be taken twice a day orally **Intervention Names:** - Drug: TAS-102 - Radiation: Photon SBRT **Label:** TAS-102 **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - TAS-102 **Description:** Trifluridine stops DNA replication which may prevent the cancer cells from growing **Name:** TAS-102 **Other Names:** - Lonsurf - Trifluridine **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - TAS-102 **Description:** SBRT stands for Stereotactic Body Radiation Therapy. Radiation may help to kill the cancer cells while protecting your normal tissue cells **Name:** Photon SBRT **Type:** RADIATION ### Outcomes Module #### Primary Outcomes **Description:** MTD will be determined using a 3 + 3 dose escalation. 3 participants enrolled at the starting dose of 20 mg/m2 BID (Bis in die, Latin for twice daily). Based on the number of dose limiting toxicities (DLT), the dose can be either be increased to 25 mg/m2 BID then 30 mg/m2 BID or it could be reduced to 15 mg/m2 BID. * If 0 out of 3 have DLT, enroll 3 participants at next dose level * If ≥ 2 DLT out of 3 or 6 participants in a dose cohort have DLT, this will be the MTD and 3 additional participants are enrolled at next lowest dose if only 3 were treated at that level so far. * If 1 out of 3 have DLT, 3 more enrolled at current dose level. If no DLT in those 3, move to next dose level. If ≥ 1 DLT, declare this the MTD and enroll 3 additional at next lowest dose if only 3 treated so far. * If ≤ 1 out of 6 DLT at highest dose level below maximally administered dose, MTD is generally the rerecorded phase 2 dose (RP2D). Dose level 3 is RP2D if MTD not reached. **Measure:** Maximum Tolerated Dose (MTD) **Time Frame:** From start of treatment until 4 weeks after the end of treatment **Description:** Local control is the absence of local failure defined as evidence of tumor growth/regrowth that meets Response Evaluation Criteria In Solid Tumors (RECIST) criteria for progressive disease in any direction beyond that present in pre-treatment imaging studies of the treated lesion(s). The duration of local control will be measured from the start date of protocol treatment until the date of local failure. * Marginal failure is defined as appearance of tumor growth at the margin of the target volume. * Nodal failure is defined as failure in regional lymph nodes (i.e. porta-hepatis, para-aortic, diaphragmatic). * Distant failure is defined as appearance of tumor at sites beyond marginal and regional nodal sites. * Intrahepatic recurrence is defined as any new lesion elsewhere in the liver and separate from local failure. **Measure:** The Duration of Local Control **Time Frame:** Baseline, 1 month post treatment, every 6 months for two years or until death #### Secondary Outcomes **Description:** Summary of the Adverse events experienced during treatment. Adverse events are assessed with Common Terminology Criteria for Adverse Events (CTCAE) 4.0. **Measure:** Toxicity associated with TAS-102 combined with SBRT **Time Frame:** From start of treatment until 4 weeks after the end of treatment **Description:** Progression-free survival (PFS) will be measured from the start date of protocol treatment (first TAS-102 dose and/or first SBRT fraction) to the earlier date of first failure at any pre-treatment or new site (defined in 'Duration of Local Control' section) or death. PFS will be censored at the date of last follow-up for participants still alive who have not failed. **Measure:** Progression Free Survival **Time Frame:** from the start of treatment until 2 years, or until time of progression/death **Description:** Overall survival (OS) will be measured from the start date of protocol treatment (first TAS-102 dose and/or first SBRT fraction) to the date of death. OS will be censored at the date of last follow-up for participants who are still alive. **Measure:** Overall Survival **Time Frame:** from the start of treatment until 2 years, or until time of death **Description:** Association between KRAS or BRAF mutation status with local control will be assessed using Gray's test with death as a competing risk in the absence of local failure. Local control is defined in the 'Duration of Local Control' description. **Measure:** Association between KRAS or BRAF mutation status with local control **Time Frame:** Baseline, 1 month post treatment, every 6 months for two years or until death **Description:** Serial ctDNA will be analyzed by descriptive methods to identify potential trends and correlations with synchronous radiologic endpoints (baseline, one month post-treatment). ctDNA level (detectable versus negative) at early (week 1, week 2) and post-treatment (one month) assessments will be analyzed for differences in local control **Measure:** Serial ctDNA **Time Frame:** Baseline, week 1, week 2, 1 month post treatment, at the time of progression ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Participants must have biopsy-proven diagnosis of a colorectal cancer with 1-4 liver metastases. There is no upper size limit and participants must have at least 800 mL of uninvolved liver. Liver metastases may be diagnosed by imaging alone, no liver biopsy is required. Extrahepatic disease is allowed if 1) it has been stable for 3 months prior to study entry, 2) the dominant disease burden is intrahepatic and 3) the patient is referred for definitive radiation therapy to the disease in the liver. * Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 10 mm with spiral CT scan. See Section 13 for the evaluation of measurable disease. * Participants may have had prior chemotherapy, targeted biological therapy (i.e. sorafenib), surgery, transarterial chemoembolization (TACE), radiofrequency ablation, or cryosurgery for their disease as long as the prior therapy occurred more than 3 weeks before the first radiation treatment. Patients may not have had prior liver directed radiation, including radioembolization. * Participants must be 18 years of age or older. * Because no dosing or adverse event data are currently available on the use of high dose liver radiation in participants \<18 years of age, children are excluded from this study. * Expected survival must be greater than three months. * ECOG Performance Status 0 or 1.. * Participants must have liver metastases deemed unresectable due to anatomy, medical fitness, or presence of extrahepatic disease. * Participants must have normal organ and marrow function as defined below. History of transfusion is acceptable and transfusions may be given to meet eligibility requirements. * Hgb ≥ 9g/dL * Absolute neutrophil count ≥ 1,500/mm3 * Platelets ≥ 75,000/mm3 * Total bilirubin ≤ 1.5 X institutional upper limit of normal * AST (SGOT) and ALT (SGPT) ≤ 1.5 X institutional upper limit of normal * Creatinine ≤ 1.5 mg/dl or creatinine clearance ≥ 60 mL/min/1.73 m2 (Calculated per Cockroft \& Gault formula) for subjects with creatinine levels above institutional normal. * If patient has underlying cirrhosis, only Child-Pugh classification Group A patients should be included in this study. Clinical assessment of ascites and encephalopathy is required. Child-Pugh classification must be determined for all study participants at the time of eligibility analysis. As albumin and PT/INR are required for Child-Pugh classification; these labs should be drawn with other labs required for eligibility analysis. See Appendix B for Child-Pugh classification table. * The effects of radiation on the developing human fetus are known to be teratogenic and the safety of TAS-102 in pregnant women and their fetuses has not been established. Therefore, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 6 months after stopping study treatment. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. * Ability to understand and the willingness to sign a written informed consent document. * Ability to take oral medications (i.e. no feeding tube and able to swallow whole) Exclusion Criteria: * Women who are pregnant or lactating. Patients must be either surgically sterile (via hysterectomy or bilateral tubal ligation), post menopausal or using acceptable methods of contraception if they are of child bearing potential. Female patients of child bearing potential must have a negative serum or urine pregnancy test within 7 days prior to starting drug. Because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with radiation, breastfeeding should be discontinued if the mother is treated with radiation. * Participants with gross ascites or encephalopathy * Participants with local conditions or systemic illnesses that would reduce the local tolerance to radiation treatment, such as serious local injuries, active collagen vascular disease, etc. * Participants who have had prior liver directed radiation treatment, including selective internal radiation (SIRspheres or Theraspheres) * Participants with a serious medical illness that may limit survival to less than 3 months * Participants who have had chemotherapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to starting study treatment or those who have not recovered from adverse events due to agents administered more than 3 weeks earlier. * Participants who are receiving any other investigational agents, or any other anti-cancer therapy during study treatment. * Participants with any uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or serious psychiatric illness/social situations that would limit compliance with study requirements. * Participants who have previously received TAS-102 **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Theodore S Hong, MD **Phone:** 617-724-8770 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Tarin Grillo **Phone:** 617-724-3661 **Role:** CONTACT #### Locations **Location 1:** **City:** Boston **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Theodore S. Hong, MD - **Phone:** 617-724-8770 - **Role:** CONTACT ***Contact 2:*** - **Name:** Theodore S. Hong, MD - **Role:** PRINCIPAL_INVESTIGATOR **Country:** United States **Facility:** Massachusetts General Hospital **State:** Massachusetts **Status:** RECRUITING **Zip:** 02215 #### Overall Officials **Official 1:** **Affiliation:** Massachusetts General Hospital **Name:** Theodore S. Hong, MD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000007414 - Term: Intestinal Neoplasms - ID: D000005770 - Term: Gastrointestinal Neoplasms - ID: D000004067 - Term: Digestive System Neoplasms - ID: D000009371 - Term: Neoplasms by Site - ID: D000009369 - Term: Neoplasms - ID: D000004066 - Term: Digestive System Diseases - ID: D000005767 - Term: Gastrointestinal Diseases - ID: D000003108 - Term: Colonic Diseases - ID: D000007410 - Term: Intestinal Diseases - ID: D000012002 - Term: Rectal Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC06 - Name: Digestive System Diseases ### Condition Browse Module - Browse Leaves - ID: M12307 - Name: Neoplasm Metastasis - Relevance: LOW - As Found: Unknown - ID: M17890 - Name: Colorectal Neoplasms - Relevance: HIGH - As Found: Colorectal Cancer - ID: M10448 - Name: Intestinal 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: M6336 - Name: Colonic Diseases - Relevance: LOW - As Found: Unknown - ID: M10444 - Name: Intestinal Diseases - Relevance: LOW - As Found: Unknown - ID: M14844 - Name: Rectal Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000015179 - Term: Colorectal Neoplasms ### Intervention Browse Module - Ancestors - ID: D000000963 - Term: Antimetabolites - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - 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 - Abbrev: Hemat - Name: Hematinics ### Intervention Browse Module - Browse Leaves - ID: M17023 - Name: Trifluridine - Relevance: HIGH - As Found: NAC - ID: M11110 - Name: Liver Extracts - Relevance: LOW - As Found: Unknown - ID: M4281 - Name: Antimetabolites - Relevance: LOW - As Found: Unknown - 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: D000014271 - Term: Trifluridine ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04389879 **Acronym:** Retention **Brief Title:** CAD/CAM Fixed Retainers vs. Conventional Multistranded Fixed Retainers in Orthodontic Patients. Comparison of Stability, Retainer Failure Rate, Adverse Effects, Cost-effectiveness, and Patient Satisfaction. A Randomized Controlled Clinical Trial **Official Title:** CAD/CAM Fixed Retainers vs. Conventional Multistranded Fixed Retainers in Orthodontic Patients. Comparison of Stability, Retainer Failure Rate, Adverse Effects, Cost-effectiveness, and Patient Satisfaction. A Randomized Controlled Clinical Trial. #### Organization Study ID Info **ID:** 01286 #### Organization **Class:** OTHER **Full Name:** University of Aarhus ### Status Module #### Completion Date **Date:** 2025-12 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2022-11-03 **Type:** ACTUAL **Last Update Submit Date:** 2022-11-02 **Overall Status:** ACTIVE_NOT_RECRUITING #### Primary Completion Date **Date:** 2025-11 **Type:** ESTIMATED #### Start Date **Date:** 2018-09-01 **Type:** ACTUAL **Status Verified Date:** 2022-11 #### Study First Post Date **Date:** 2020-05-15 **Type:** ACTUAL **Study First Submit Date:** 2020-04-16 **Study First Submit QC Date:** 2020-05-11 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** University of Oslo #### Lead Sponsor **Class:** OTHER **Name:** University of Aarhus #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** Introduction: Orthodontic retainers are used after the completion of orthodontic treatment to assure dental occlusal stability and to maintain the achieved end-result. However, without retention teeth could go back to their initial dental malposition or could even take a different unpredicted position resulting once again in dental malocclusion (a deviation from normal occlusion). There are different types of retainers, some are fixed (glued to the back of the front teeth), and others are removable (can be removed and replaced into the mouth by the patient). While there are various retainers used for retention (stability), there is no perfect method. Fixed retainers (FRs) are used worldwide. On the one hand, FRs focus on preventing relapse. On the other hand, there are sometimes some adverse effects of retainers; they could fail at a certain point (break/get loose), or cause unwanted tooth movements. Until now, the choice of a retention method is based solely on clinicians' experience as there is no substantial evidence regarding the best retention method or the duration of the retention period. Some clinicians prolong the retention period while others prefer to keep the retainers for an indefinite time. As the world is advancing, so is the orthodontic science. New FR fabricated by CAD/CAM (Computer-Aided Design/Computer-Aided Manufacturing), are assumed to have greater accuracy, better fit, and most importantly, might offer a passive positioning of the retainer. However, the evidence about CAD/CAM FRs is very limited. Purpose: To investigate and compare the clinical effectiveness of two types of FRs; CAD/CAM vs. multistranded wire, in terms of stability (primary outcome), failure rate, adverse effects, cost-effectiveness, and patient satisfaction (secondary outcomes), substantial up to 5 years after retainer placement. Hypotheses: Compared to traditional multistranded FRs, CAD/CAM FRs have: * Better long term stability, * Similar failure rate, * Fewer adverse effects, * Similar cost-effectiveness and patient satisfaction. **Detailed Description:** Material and Methods Setting: Section of Orthodontics, Department of Dentistry and Oral Health, Aarhus University, Denmark and Department of Orthodontics, Faculty of Dentistry, University of Oslo, Norway. Sample size: 126 participants are needed for this study. Randomization: After oral and written consent is obtained, allocation to groups, either conventional multistranded Stainless Steel fixed retainers, or CAD/CAM custom-cut Nickel Titanium fixed retainers, will take place at the last appointment before debonding. Subjects will be allocated 1:1 into one of the two groups. Intervention protocol: After completing a full active orthodontic treatment, at both centers. The achieved treatment end result has to be maintained in the long term in order to prevent relapse (movement of teeth to the initial malocclusion). One of either two different fixed retainers will be bonded (to the upper and lower anterior teeth) by one operator in each center. This study follows a standard retention protocol procedure carried at both centers and has a long term posttreatment follow-up of 5 years. Patients will be recalled for follow-up appointments after 1, 3, 6, 12, 24, 36 and 60 months. At follow-up visits, we will perform the following: at 1, and 3 months - a clinical examination. At 6, 12, 24, 36, and 60 months - a clinical examination, a digital impression of the teeth known as "an intraoral scan" (Trios 3, 3Shape, Copenhagen, Denmark) and intraoral photographs. In addition, at 1, 6, and 12 months patients will be asked to fill out a Visual Analogue Scale (VAS) form regarding patient satisfaction Furthermore, we will investigate stability by superimposition (Orthoanalyzer, 3Shape, Copenhagen, Denmark) together with recording of adverse effects (i.e. any changes in torque and/or rotations of the teeth). ### Conditions Module **Conditions:** - Relapse **Keywords:** - Orthodontic retainer - relapse - stability - CAD/CAM - fixed retainer ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** Two-center randomized controlled clinical trial. Consecutive patients who are about to finish their fixed appliance orthodontic treatment at the two orthodontic departments will be screened for eligibility criteria. Eligible subjects will be randomized to have one of either two different fixed retainers to be bonded (to the upper and lower anterior teeth) by one operator in each center. Subjects will be allocated 1:1 into one of the two groups. ##### Masking Info **Masking:** NONE **Masking Description:** The outcome assessor will be blinded only to the patient satisfaction and cost-effectiveness outcomes. **Primary Purpose:** OTHER #### Enrollment Info **Count:** 126 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** CAD/CAM custom-cut Nickel Titanium (NiTi) FR **Intervention Names:** - Other: Bonding of either CAD/CAM or conventional multistranded stainless steel fixed retainer **Label:** CAD/CAM **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Conventional multistranded Stainless Steel (SS) FR **Intervention Names:** - Other: Bonding of either CAD/CAM or conventional multistranded stainless steel fixed retainer **Label:** Conventional multistranded **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - CAD/CAM - Conventional multistranded **Description:** Investigate and compare the clinical effectiveness of two types of fixed retainers; CAD/CAM vs. multistranded wire. **Name:** Bonding of either CAD/CAM or conventional multistranded stainless steel fixed retainer **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** Change in lower incisor crowding will be assessed using Little's Irregularity Index (LII). Change in overall occlusal stability will be assessed by the Peer Assessment Rating (PAR) index. In addition, changes in arch dimensions, occlusal relationships, and re-opening of extraction spaces will be recorded. **Measure:** Stability **Time Frame:** From debonding (T1), and after 6, 12, 24, 36 and 60 months in retention phase (T4, T5, T6, T7, and T8 respectively) #### Secondary Outcomes **Description:** Calculated from the first day of retainer's bonding to the day of the first failure episode **Measure:** Failure rate and survival time **Time Frame:** From the time of retainer bonding to the first failure episode: From debonding, and up to 60 months later **Description:** Screen for unexpected posttreatment changes in the mandibular anterior region associated with the use of both types of fixed retainers **Measure:** Adverse effects **Time Frame:** From debonding, and up to 60 months later **Description:** Unit costs in euros (€) will be used to value the resources included **Measure:** Cost-effectiveness **Time Frame:** From debonding, and up to 60 months later **Description:** Visual Analogue Scale (VAS) **Measure:** Patient satisfaction **Time Frame:** From debonding, and after 1, 6 and 12 months in retention phase ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Healthy patients. 2. Age: 12-25 years old (at time of debonding). 3. Presence of all maxillary and mandibular anterior teeth, with normal shape and size. 4. Completion of a course of fixed appliance therapy involving both dental arches. 5. Subjects willing to consent to the trial and comply with the trial regime. No restriction to presenting initial malocclusion, type of active orthodontic treatment undertaken provided that it included full fixed appliances (functional/removable appliances in combination with fixed appliances - extraction or non-extraction) Exclusion Criteria: 1. Patients with cleft lip or palate, or both or any other craniofacial syndrome. 2. Patients who had surgical correction of the jaws: Le fort I (2- or 3-piece maxilla) or SARPE (surgically assisted rapid palatal expansion). 3. Lingual appliance treatments. 4. Periodontal disease. 5. Hypoplasia of enamel. 6. Fluorosis. 7. Active caries, restorations or fractures in the anterior teeth. 8. Patients who have had separate debonding appointments for each jaw, with a difference of more than 2 months in between. 9. Re-treated patients. **Healthy Volunteers:** True **Maximum Age:** 25 Years **Minimum Age:** 12 Years **Sex:** ALL **Standard Ages:** - CHILD - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Aarhus **Country:** Denmark **Facility:** Marie Anne Michele Cornelis **Zip:** 8000 **Location 2:** **City:** Oslo **Country:** Norway **Facility:** University of Oslo **Zip:** 0455 #### Overall Officials **Official 1:** **Affiliation:** University of Aarhus **Name:** Marie A Cornelis **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Owman G, Bjerklin K, Kurol J. Mandibular incisor stability after orthodontic treatment in the upper arch. Eur J Orthod. 1989 Nov;11(4):341-50. doi: 10.1093/oxfordjournals.ejo.a036005. **PMID:** 2591482 **Citation:** Al Yami EA, Kuijpers-Jagtman AM, van 't Hof MA. Stability of orthodontic treatment outcome: follow-up until 10 years postretention. Am J Orthod Dentofacial Orthop. 1999 Mar;115(3):300-4. doi: 10.1016/s0889-5406(99)70333-1. **PMID:** 10066979 **Citation:** Littlewood SJ, Millett DT, Doubleday B, Bearn DR, Worthington HV. Retention procedures for stabilising tooth position after treatment with orthodontic braces. Cochrane Database Syst Rev. 2004;(1):CD002283. doi: 10.1002/14651858.CD002283.pub2. **PMID:** 14973985 **Citation:** Reitan K. Clinical and histologic observations on tooth movement during and after orthodontic treatment. Am J Orthod. 1967 Oct;53(10):721-45. doi: 10.1016/0002-9416(67)90118-2. No abstract available. **PMID:** 5233926 **Citation:** Little RM, Wallen TR, Riedel RA. Stability and relapse of mandibular anterior alignment-first premolar extraction cases treated by traditional edgewise orthodontics. Am J Orthod. 1981 Oct;80(4):349-65. doi: 10.1016/0002-9416(81)90171-8. **PMID:** 6945805 **Citation:** Littlewood SJ, Millett DT, Doubleday B, Bearn DR, Worthington HV. Orthodontic retention: a systematic review. J Orthod. 2006 Sep;33(3):205-12. doi: 10.1179/146531205225021624. **PMID:** 16926314 **Citation:** Gardner SD, Chaconas SJ. Posttreatment and postretention changes following orthodontic therapy. Angle Orthod. 1976 Apr;46(2):151-61. doi: 10.1043/0003-3219(1976)0462.0.CO;2. **PMID:** 1064343 **Citation:** Goldberg AI, Behrents RG, Oliver DR, Buschang PH. Facial divergence and mandibular crowding in treated subjects. Angle Orthod. 2013 May;83(3):381-8. doi: 10.2319/061912-505.1. Epub 2012 Oct 18. **PMID:** 23075061 **Citation:** Artun J, Spadafora AT, Shapiro PA. A 3-year follow-up study of various types of orthodontic canine-to-canine retainers. Eur J Orthod. 1997 Oct;19(5):501-9. doi: 10.1093/ejo/19.5.501. **PMID:** 9386336 **Citation:** Bolla E, Cozzani M, Doldo T, Fontana M. Failure evaluation after a 6-year retention period: a comparison between glass fiber-reinforced (GFR) and multistranded bonded retainers. Int Orthod. 2012 Mar;10(1):16-28. doi: 10.1016/j.ortho.2011.12.005. Epub 2012 Jan 11. English, French. **PMID:** 22240271 **Citation:** Rose E, Frucht S, Jonas IE. Clinical comparison of a multistranded wire and a direct-bonded polyethylene ribbon-reinforced resin composite used for lingual retention. Quintessence Int. 2002 Sep;33(8):579-83. **PMID:** 12238688 **Citation:** Salehi P, Zarif Najafi H, Roeinpeikar SM. Comparison of survival time between two types of orthodontic fixed retainer: a prospective randomized clinical trial. Prog Orthod. 2013 Sep 11;14:25. doi: 10.1186/2196-1042-14-25. **PMID:** 24326013 **Citation:** Saleh M, Hajeer MY, Muessig D. Acceptability comparison between Hawley retainers and vacuum-formed retainers in orthodontic adult patients: a single-centre, randomized controlled trial. Eur J Orthod. 2017 Aug 1;39(4):453-461. doi: 10.1093/ejo/cjx024. **PMID:** 28430890 **Citation:** Hichens L, Rowland H, Williams A, Hollinghurst S, Ewings P, Clark S, Ireland A, Sandy J. Cost-effectiveness and patient satisfaction: Hawley and vacuum-formed retainers. Eur J Orthod. 2007 Aug;29(4):372-8. doi: 10.1093/ejo/cjm039. **PMID:** 17702797 **Citation:** Tynelius GE, Lilja-Karlander E, Petren S. A cost-minimization analysis of an RCT of three retention methods. Eur J Orthod. 2014 Aug;36(4):436-41. doi: 10.1093/ejo/cjt070. Epub 2013 Oct 1. **PMID:** 24084630 **Citation:** Forde K, Storey M, Littlewood SJ, Scott P, Luther F, Kang J. Bonded versus vacuum-formed retainers: a randomized controlled trial. Part 1: stability, retainer survival, and patient satisfaction outcomes after 12 months. Eur J Orthod. 2018 Jul 27;40(4):387-398. doi: 10.1093/ejo/cjx058. **PMID:** 29059289 **Citation:** Wolf M, Schumacher P, Jager F, Wego J, Fritz U, Korbmacher-Steiner H, Jager A, Schauseil M. Novel lingual retainer created using CAD/CAM technology: evaluation of its positioning accuracy. J Orofac Orthop. 2015 Mar;76(2):164-74. doi: 10.1007/s00056-014-0279-8. English, German. **PMID:** 25744094 **Citation:** Jost-Brinkmann PG, Cacciafesta V, Miethke RR. Computer-aided fabrication of bonded lingual retainers. J Clin Orthod. 1996 Oct;30(10):559-63. No abstract available. **PMID:** 10356474 **Citation:** Artun J, Zachrisson B. Improving the handling properties of a composite resin for direct bonding. Am J Orthod. 1982 Apr;81(4):269-76. doi: 10.1016/0002-9416(82)90212-3. **PMID:** 6217753 **Citation:** Little RM. The irregularity index: a quantitative score of mandibular anterior alignment. Am J Orthod. 1975 Nov;68(5):554-63. doi: 10.1016/0002-9416(75)90086-x. **PMID:** 1059332 **Citation:** Bjering R, Sandvik L, Midtbo M, Vandevska-Radunovic V. Stability of anterior tooth alignment 10 years out of retention. J Orofac Orthop. 2017 Jul;78(4):275-283. doi: 10.1007/s00056-017-0084-2. Epub 2017 Apr 13. **PMID:** 28409195 **Citation:** Renkema AM, Renkema A, Bronkhorst E, Katsaros C. Long-term effectiveness of canine-to-canine bonded flexible spiral wire lingual retainers. Am J Orthod Dentofacial Orthop. 2011 May;139(5):614-21. doi: 10.1016/j.ajodo.2009.06.041. **PMID:** 21536204 **Citation:** Katsaros C, Livas C, Renkema AM. Unexpected complications of bonded mandibular lingual retainers. Am J Orthod Dentofacial Orthop. 2007 Dec;132(6):838-41. doi: 10.1016/j.ajodo.2007.07.011. **PMID:** 18068606 **Citation:** Pazera P, Fudalej P, Katsaros C. Severe complication of a bonded mandibular lingual retainer. Am J Orthod Dentofacial Orthop. 2012 Sep;142(3):406-9. doi: 10.1016/j.ajodo.2012.01.019. **PMID:** 22920708 **Citation:** Gera A, Pullisaar H, Cattaneo PM, Gera S, Vandevska-Radunovic V, Cornelis MA. Stability, survival, and patient satisfaction with CAD/CAM versus conventional multistranded fixed retainers in orthodontic patients: a 6-month follow-up of a two-centre randomized controlled clinical trial. Eur J Orthod. 2023 Feb 10;45(1):58-67. doi: 10.1093/ejo/cjac042. **PMID:** 35964235 ## 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 ### Condition Browse Module - Browse Leaves - ID: M14850 - Name: Recurrence - Relevance: HIGH - As Found: Relapse - ID: M22700 - Name: Disease Attributes - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000012008 - Term: Recurrence ### Intervention Browse Module - Browse Branches - Abbrev: Micro - Name: Micronutrients - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M12472 - Name: Nickel - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05398679 **Acronym:** OraPAT-IEGAMES **Brief Title:** Oral Antimicrobial Treatment vs. Outpatient Parenteral for Infective Endocarditis **Official Title:** Oral Antimicrobial Treatment vs. Outpatient Parenteral for Infective Endocarditis #### Organization Study ID Info **ID:** OraPAT-IE GAMES #### Organization **Class:** OTHER **Full Name:** Fundacion Clinic per a la Recerca Biomédica ### Status Module #### Completion Date **Date:** 2024-12-30 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2022-06-01 **Type:** ACTUAL **Last Update Submit Date:** 2022-05-26 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2024-06-30 **Type:** ESTIMATED #### Start Date **Date:** 2022-06-01 **Type:** ESTIMATED **Status Verified Date:** 2022-05 #### Study First Post Date **Date:** 2022-06-01 **Type:** ACTUAL **Study First Submit Date:** 2022-05-04 **Study First Submit QC Date:** 2022-05-26 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Fundacion Clinic per a la Recerca Biomédica #### Responsible Party **Investigator Affiliation:** Fundacion Clinic per a la Recerca Biomédica **Investigator Full Name:** Anna Cruceta **Investigator Title:** Project Manager Clinical Trial Unit **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Non-inferiority trial to determine whether partial oral treatment is non-inferior to OPAT(Outpatient parenteral therapy) in patients diagnosed with infective endocarditis **Detailed Description:** The trial will include patients diagnosed with left-side Infective Endocarditis according to the modified Duke criteria, with ≥10 days of appropriate parenteral antibiotic treatment overall and at least one week of appropriate parenteral treatment after valve surgery The patients will be randomized in two arms, one with oral antibiotic therapy and the other one with outpatient parenteral therapy This trial aims to demonstrate the non-inferiority of outpatient oral antibiotic therapy in comparison with outpatient parenteral antibiotic treatment (OPAT), to improve the quality of life of infective endocarditis (IE) patients, and to reduce the cost of the intervention without increasing morbidity and mortality rates ### Conditions Module **Conditions:** - Endocarditis Infective ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** National multi-center study, open, controlled, and randomized ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 360 **Type:** ESTIMATED **Phases:** - PHASE4 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Patients with infective endocarditis diagnostic, who have completed at least 10 days of intravenous therapy, and/ or seven days in the case of cardiac valvular surgery, and shown good clinical evolution and no clinical or echocardiographic signs of potential bad prognosis will be randomized. If assigned to this arm the patient will recieve parenteral antibiotics until the end of treatment. **Intervention Names:** - Drug: Cefaclor - Drug: Ciprofloxacin Injection - Drug: Clindamycin Injection - Drug: Dicloxacillin - Drug: Fusidic Acid Only Product in Parenteral Dose Form - Drug: Levofloxacin Injection - Drug: Linezolid Injectable Product - Drug: Moxifloxacin Injectable Product - Drug: Rifampicin Only Product in Parenteral Dose Form - Drug: Sulfamethoxazole / Trimethoprim Injectable Product - Drug: Tedizolid Injection - Drug: Amoxicillin **Label:** OPAT **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** Patients with infective endocarditis diagnostic, who have completed at least 10 days of intravenous therapy, and/ or seven days in the case of cardiac valvular surgery, and shown good clinical evolution and no clinical or echocardiographic signs of potential bad prognosis will be randomized. If assigned to this arm the patient will recieve oral antibiotics until the end of treatment. **Intervention Names:** - Drug: Ciprofloxacin Tablets - Drug: Clindamycin Oral Capsule - Drug: Dicloxacillin Oral Capsule - Drug: Fusidic Acid Only Product in Oral Dose Form - Drug: Levofloxacin Oral Tablet - Drug: Linezolid Oral Tablet - Drug: Moxifloxacin tablet - Drug: Rifampicin Only Product in Oral Dose Form - Drug: Sulfamethoxazole / Trimethoprim Oral Tablet [Bactrim] - Drug: Tedizolid Oral Tablet - Drug: Amoxicillin Capsules - Drug: Cefaclor Capsules **Label:** Oral Therapy **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - OPAT **Description:** cefaclor intravenous 2 gr/day **Name:** Cefaclor **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Oral Therapy **Description:** 500-750 mg/12 hrs (maximum 3g x day) **Name:** Ciprofloxacin Tablets **Type:** DRUG #### Intervention 3 **Arm Group Labels:** - OPAT **Description:** 1200 mg/day maximum dose IV **Name:** Ciprofloxacin Injection **Type:** DRUG #### Intervention 4 **Arm Group Labels:** - Oral Therapy **Description:** 600 mg/8 hours (maximum 1.800 mg x day) **Name:** Clindamycin Oral Capsule **Type:** DRUG #### Intervention 5 **Arm Group Labels:** - OPAT **Description:** 600 mg/8 hours (maximum 1.800 mg x day) IV **Name:** Clindamycin Injection **Type:** DRUG #### Intervention 6 **Arm Group Labels:** - Oral Therapy **Description:** 1g/8 hours (maximum 4 gr day) **Name:** Dicloxacillin Oral Capsule **Type:** DRUG #### Intervention 7 **Arm Group Labels:** - OPAT **Description:** 1g/8 hours (maximum 4 g x day) IV **Name:** Dicloxacillin **Type:** DRUG #### Intervention 8 **Arm Group Labels:** - Oral Therapy **Description:** 0,750g/12 hours (maximum 1,5 g x day) **Name:** Fusidic Acid Only Product in Oral Dose Form **Type:** DRUG #### Intervention 9 **Arm Group Labels:** - OPAT **Description:** 0,75 g/12 hours (maximum 1,5 g x day) **Name:** Fusidic Acid Only Product in Parenteral Dose Form **Type:** DRUG #### Intervention 10 **Arm Group Labels:** - Oral Therapy **Description:** 0.5g/12-24hours (maximum 1 g x day) **Name:** Levofloxacin Oral Tablet **Type:** DRUG #### Intervention 11 **Arm Group Labels:** - OPAT **Description:** 0.5g/12-24hours (maximum 1 g x day) **Name:** Levofloxacin Injection **Type:** DRUG #### Intervention 12 **Arm Group Labels:** - Oral Therapy **Description:** 0,6 g/12 hours (maximum 1200 mg x day) **Name:** Linezolid Oral Tablet **Type:** DRUG #### Intervention 13 **Arm Group Labels:** - OPAT **Description:** 0,6 g/12 hours (maximum 1200 mg x day) **Name:** Linezolid Injectable Product **Type:** DRUG #### Intervention 14 **Arm Group Labels:** - Oral Therapy **Description:** 0,4 g/day (maximum 400 mg x day) **Name:** Moxifloxacin tablet **Type:** DRUG #### Intervention 15 **Arm Group Labels:** - OPAT **Description:** 0,4 g/day (maximum 400 mg x day) **Name:** Moxifloxacin Injectable Product **Type:** DRUG #### Intervention 16 **Arm Group Labels:** - Oral Therapy **Description:** 0,3-0,5 g/12 hours (maximum 1200 mg x day) **Name:** Rifampicin Only Product in Oral Dose Form **Type:** DRUG #### Intervention 17 **Arm Group Labels:** - OPAT **Description:** 0,3-0,6 g/12 hours (maximum 1200 mg x day) **Name:** Rifampicin Only Product in Parenteral Dose Form **Type:** DRUG #### Intervention 18 **Arm Group Labels:** - Oral Therapy **Description:** sulfamethoxazole 1600 mg/trimethoprin 320 mg (maximum x day) **Name:** Sulfamethoxazole / Trimethoprim Oral Tablet [Bactrim] **Type:** DRUG #### Intervention 19 **Arm Group Labels:** - OPAT **Description:** sulfamethoxazole 1600 mg/trimethoprin 320 mg (maximum x day) **Name:** Sulfamethoxazole / Trimethoprim Injectable Product **Type:** DRUG #### Intervention 20 **Arm Group Labels:** - Oral Therapy **Description:** 200 mg tedizolid (maximum x day) **Name:** Tedizolid Oral Tablet **Type:** DRUG #### Intervention 21 **Arm Group Labels:** - OPAT **Description:** 200 mg (maximum x day) **Name:** Tedizolid Injection **Type:** DRUG #### Intervention 22 **Arm Group Labels:** - Oral Therapy **Description:** 1 gr/6 hours (4 g x day) **Name:** Amoxicillin Capsules **Type:** DRUG #### Intervention 23 **Arm Group Labels:** - OPAT **Description:** 1 gr/6 hours (4 g x day) Intravenous **Name:** Amoxicillin **Type:** DRUG #### Intervention 24 **Arm Group Labels:** - Oral Therapy **Description:** 2 gr/day **Name:** Cefaclor Capsules **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Measure:** Non-inferiority of outpatient oral vs parenteral antibiotic therapy measured by the number of unplanned hospitalizations **Time Frame:** At any time during the study duration (up to 24 months) **Measure:** Non-inferiority of outpatient oral vs parenteral antibiotic therapy measured by the number of all-cause mortality **Time Frame:** At any time during the study duration (up to 24 months) **Measure:** Non-inferiority of outpatient oral vs parenteral antibiotic therapy measured by the number of relapses of Infective Endocarditis **Time Frame:** within 6 months from diagnosis of Infective Endocarditis **Measure:** Non-inferiority of outpatient oral vs parenteral antibiotic therapy measured by the number of patients requiring cardiac surgery **Time Frame:** At any time during the study duration (up to 24 months) #### Secondary Outcomes **Measure:** Quality of life and patient satisfaction of infective endocarditis patients. It will be measured through the standardized Saillen questionnaire of antibiotic treatment satisfaction **Time Frame:** At any time during the study duration (up to 24 months) **Description:** through a pharmacoeconomic analysis **Measure:** Costs of both interventions, measured through a pharmaco-economic sub-study including direct and indirect costs, following the methodology described by Lacroix A et al Med Mal Infect. 2014 **Time Frame:** At any time during the study duration (up to 24 months) **Description:** such as antibiotic or catheter-related adverse events e.g.,phlebitis and line-related bloodstream infections, and superinfections **Measure:** The complications related to parenteral and oral administration of antibiotics will be measured through the number of antibiotic adverse reactions, catheter-related adverse events, and number of superinfections **Time Frame:** At any time during the study duration (up to 24 months) ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Left-sided native or prosthetic infective endocarditis based on the modified Duke criteria infected with one of the following nonresistant microorganisms: Non-resistant streptococci and other gram positive cocci,e.g., Granulicatella and Abiotrophia; Enterococcus faecalis; Staphylococcus aureus;coagulase-negative staphylococci and HACEK group. * Male or female 18 years old or older. * 10 days or more of appropriate parenteral antibiotic treatment overall and at least one week of appropriate parenteral treatment after value surgery. * Temperature inferior to 38ºC for more than two days. 5. C-reactive protein dropped to \<25% of peak value or \<20 mg/l, and white blood cell count \<15x10\^9/l during antibiotic treatment * Transthoracic / transesophageal echocardiography performed within 48 hours of randomization Exclusion Criteria: * Body mass index \>40 * Concomitant infection requiring intravenous antibiotic therapy * Inability to give informed consent to participation * Suspicion of reduced absorption of oral treatment due to abdominal disorder * Microorganisms with no oral combinations for treatment (two active antibiotics of different families) * Any immunosuppressive disease or any medical condition at the discretion of the investigator that may preclude oral or OPAT therapy * No family or appropriate home support * Reduced compliance * Women of childbearing potential with a positive pregnancy test, or participants (male or female) who wish to plan a pregnancy during the trial period * Women in lactancy period **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Anna Cruceta **Phone:** +34 932275400 **Phone Ext:** 4380 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Laura Burunat **Phone:** +34 932275400 **Phone Ext:** 4198 **Role:** CONTACT #### Locations **Location 1:** **City:** Barcelona **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Anna Cruceta, MD - **Phone:** +34 932275400 - **Phone Ext:** 4380 - **Role:** CONTACT ***Contact 2:*** - **Email:** [email protected] - **Name:** Laura Burunat - **Phone:** +34 932275400 - **Phone Ext:** 4198 - **Role:** CONTACT ***Contact 3:*** - **Name:** Juan Ambrosioni, MD - **Role:** PRINCIPAL_INVESTIGATOR **Country:** Spain **Facility:** Hospital Clinic i Provincial de Barcelona **Zip:** 08036 ### IPD Sharing Statement Module **IPD Sharing:** UNDECIDED ## Derived Section ### Condition Browse Module - Ancestors - ID: D000006331 - Term: Heart Diseases - ID: D000002318 - Term: Cardiovascular Diseases - ID: D000001424 - Term: Bacterial Infections - ID: D000001423 - Term: Bacterial Infections and Mycoses - ID: D000007239 - Term: Infections - ID: D000053821 - Term: Cardiovascular Infections ### Condition Browse Module - Browse Branches - Abbrev: BC01 - Name: Infections - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M7859 - Name: Endocarditis, Bacterial - Relevance: HIGH - As Found: Infective Endocarditis - ID: M7858 - Name: Endocarditis - Relevance: HIGH - As Found: Endocarditis - ID: M9419 - Name: Heart Diseases - 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: M4722 - Name: Bacterial Infections - Relevance: LOW - As Found: Unknown - ID: M12136 - Name: Mycoses - Relevance: LOW - As Found: Unknown - ID: M4721 - Name: Bacterial Infections and Mycoses - Relevance: LOW - As Found: Unknown - ID: M27489 - Name: Cardiovascular Infections - Relevance: LOW - As Found: Unknown - ID: T3065 - Name: Infective Endocarditis - Relevance: HIGH - As Found: Infective Endocarditis ### Condition Browse Module - Meshes - ID: D000004697 - Term: Endocarditis, Bacterial - ID: D000004696 - Term: Endocarditis ### Intervention Browse Module - Ancestors - ID: D000000900 - Term: Anti-Bacterial Agents - ID: D000000890 - Term: Anti-Infective Agents - ID: D000059005 - Term: Topoisomerase II Inhibitors - ID: D000059003 - Term: Topoisomerase Inhibitors - ID: D000004791 - Term: Enzyme Inhibitors - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000000970 - Term: Antineoplastic Agents - ID: D000080066 - Term: Contraceptive Agents, Hormonal - ID: D000003270 - Term: Contraceptive Agents - ID: D000012102 - Term: Reproductive Control Agents - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000003277 - Term: Contraceptives, Oral, Combined - ID: D000003276 - Term: Contraceptives, Oral - ID: D000003271 - Term: Contraceptive Agents, Female - ID: D000000892 - Term: Anti-Infective Agents, Urinary - ID: D000065609 - Term: Cytochrome P-450 CYP1A2 Inhibitors - ID: D000065607 - Term: Cytochrome P-450 Enzyme Inhibitors - ID: D000000904 - Term: Antibiotics, Antitubercular - ID: D000000995 - Term: Antitubercular Agents - ID: D000007917 - Term: Leprostatic Agents - ID: D000019384 - Term: Nucleic Acid Synthesis Inhibitors - ID: D000065695 - Term: Cytochrome P-450 CYP2B6 Inducers - ID: D000065693 - Term: Cytochrome P-450 Enzyme Inducers - ID: D000065696 - Term: Cytochrome P-450 CYP2C8 Inducers - ID: D000065697 - Term: Cytochrome P-450 CYP2C19 Inducers - ID: D000065698 - Term: Cytochrome P-450 CYP2C9 Inducers - ID: D000065701 - Term: Cytochrome P-450 CYP3A Inducers - ID: D000011500 - Term: Protein Synthesis Inhibitors - ID: D000000962 - Term: Antimalarials - ID: D000000981 - Term: Antiprotozoal Agents - ID: D000000977 - Term: Antiparasitic Agents - ID: D000005493 - Term: Folic Acid Antagonists - ID: D000018726 - Term: Anti-Dyskinesia Agents - ID: D000065687 - Term: Cytochrome P-450 CYP2C8 Inhibitors ### Intervention Browse Module - Browse Branches - Abbrev: Infe - Name: Anti-Infective Agents - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: ANeo - Name: Antineoplastic Agents - Abbrev: AnDyAg - Name: Anti-Dyskinesia Agents - Abbrev: Repr - Name: Reproductive Control Agents - Abbrev: Micro - Name: Micronutrients - Abbrev: Hemat - Name: Hematinics - Abbrev: Vi - Name: Vitamins ### Intervention Browse Module - Browse Leaves - ID: M3995 - Name: Amoxicillin - Relevance: HIGH - As Found: Pembrolizumab - ID: M6176 - Name: Ciprofloxacin - Relevance: HIGH - As Found: Endothelial - ID: M4222 - Name: Anti-Bacterial Agents - Relevance: LOW - As Found: Unknown - ID: M6214 - Name: Clindamycin - Relevance: HIGH - As Found: Six months - ID: M220697 - Name: Clindamycin palmitate - Relevance: HIGH - As Found: Six months - ID: M231711 - Name: Clindamycin phosphate - Relevance: HIGH - As Found: Six months - ID: M4214 - Name: Anti-Infective Agents - Relevance: LOW - As Found: Unknown - ID: M30370 - Name: Levofloxacin - Relevance: HIGH - As Found: Sodium chloride - ID: M17946 - Name: Ofloxacin - Relevance: HIGH - As Found: Sodium chloride - ID: M1722 - Name: Moxifloxacin - Relevance: HIGH - As Found: Range - ID: M5683 - Name: Cefaclor - Relevance: HIGH - As Found: Phase II/III Trial - ID: M4224 - Name: Antibiotics, Antitubercular - Relevance: LOW - As Found: Unknown - ID: M15118 - Name: Rifampin - Relevance: HIGH - As Found: Intrathecal - ID: M400 - Name: Linezolid - Relevance: HIGH - As Found: Silicone - ID: M18253 - Name: Trimethoprim, Sulfamethoxazole Drug Combination - Relevance: HIGH - As Found: Bone Tumors - ID: M17047 - Name: Trimethoprim - Relevance: HIGH - As Found: Decision aid - ID: M16206 - Name: Sulfamethoxazole - Relevance: HIGH - As Found: Epidermal - ID: M266292 - Name: Norgestimate, ethinyl estradiol drug combination - Relevance: HIGH - As Found: Range - ID: M8791 - Name: Fusidic Acid - Relevance: HIGH - As Found: Epistaxis - ID: M7198 - Name: Dicloxacillin - Relevance: HIGH - As Found: Electronic monitoring - ID: M266543 - Name: Tedizolid - Relevance: HIGH - As Found: PONV - ID: M22872 - Name: Oxazolidinones - Relevance: HIGH - As Found: PONV - ID: M8145 - Name: Ethinyl Estradiol - Relevance: LOW - As Found: Unknown - ID: M266279 - Name: Estradiol 17 beta-cypionate - Relevance: LOW - As Found: Unknown - ID: M266280 - Name: Estradiol 3-benzoate - Relevance: LOW - As Found: Unknown - ID: M8108 - Name: Estradiol - Relevance: LOW - As Found: Unknown - ID: M234941 - Name: Polyestradiol phosphate - Relevance: LOW - As Found: Unknown - ID: M230936 - Name: Norgestimate - Relevance: LOW - As Found: Unknown - ID: M7951 - Name: Enzyme Inhibitors - Relevance: LOW - As Found: Unknown - ID: M6494 - Name: Contraceptive Agents - Relevance: LOW - As Found: Unknown - ID: M2116 - Name: Contraceptive Agents, Hormonal - Relevance: LOW - As Found: Unknown - ID: M6500 - Name: Contraceptives, Oral - Relevance: LOW - As Found: Unknown - ID: M6501 - Name: Contraceptives, Oral, Combined - Relevance: LOW - As Found: Unknown - ID: M6495 - Name: Contraceptive Agents, Female - Relevance: LOW - As Found: Unknown - ID: M30537 - Name: Cytochrome P-450 Enzyme Inhibitors - Relevance: LOW - As Found: Unknown - ID: M4311 - Name: Antitubercular Agents - 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: M8618 - Name: Folic Acid - Relevance: LOW - As Found: Unknown - ID: M17546 - Name: Vitamin B Complex - Relevance: LOW - As Found: Unknown - ID: M8619 - Name: Folic Acid Antagonists - Relevance: LOW - As Found: Unknown - ID: T447 - Name: Folinic Acid - 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: D000000658 - Term: Amoxicillin - ID: D000077266 - Term: Moxifloxacin - ID: D000064704 - Term: Levofloxacin - ID: D000015242 - Term: Ofloxacin - ID: D000002939 - Term: Ciprofloxacin - ID: D000012293 - Term: Rifampin - ID: D000002981 - Term: Clindamycin - ID: C000000489 - Term: Clindamycin palmitate - ID: C000007084 - Term: Clindamycin phosphate - ID: D000069349 - Term: Linezolid - ID: D000015662 - Term: Trimethoprim, Sulfamethoxazole Drug Combination - ID: C000546016 - Term: Tedizolid - ID: D000005672 - Term: Fusidic Acid - ID: D000004009 - Term: Dicloxacillin - ID: D000002433 - Term: Cefaclor - ID: D000014295 - Term: Trimethoprim - ID: D000013420 - Term: Sulfamethoxazole - ID: D000023303 - Term: Oxazolidinones - ID: C000109079 - Term: Norgestimate, ethinyl estradiol drug combination ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05227079 **Brief Title:** Assessing the Histological Quality of Biopsy Samples Obtained With Multibite Forceps **Official Title:** Comparison of the Histological Quality of Endoscopic Biopsy Samples Obtained With Novel Multiple-bite Forceps Versus Conventional Double Bite Forceps #### Organization Study ID Info **ID:** DMED-2634-21 #### Organization **Class:** OTHER **Full Name:** Queen's University ### Status Module #### Completion Date **Date:** 2023-07-30 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2024-04-03 **Type:** ACTUAL **Last Update Submit Date:** 2024-04-02 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2022-12-21 **Type:** ACTUAL #### Start Date **Date:** 2022-05-01 **Type:** ACTUAL **Status Verified Date:** 2024-04 #### Study First Post Date **Date:** 2022-02-07 **Type:** ACTUAL **Study First Submit Date:** 2022-01-27 **Study First Submit QC Date:** 2022-01-27 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Lawrence Charles Hookey #### Responsible Party **Investigator Affiliation:** Queen's University **Investigator Full Name:** Lawrence Charles Hookey **Investigator Title:** Professor **Type:** SPONSOR_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Biopsies are routinely taken during endoscopy and colonoscopy in order to facilitate histological analysis of various disease processes. The current practice of obtaining biopsies involves taking a maximum of two biopsies at a single time (ie. with a single pass). When investigating certain diseases, such as celiac disease, there is a need to obtain several biopsies (sometimes greater than 6) and the current practice of taking one to two biopsies at a time can lengthen endoscopy time. This study investigates a new approved multiple bite forceps that has the ability to retrieve six biopsies during a single pass which could reduce endoscopy time and improve diagnostic yield. This study will assess the histological quality of multiple biopsies when taken with the multiple bite forceps compared to the standard double bite forceps. This multiple bite forcep is approved for clinical use in Canada. **Detailed Description:** This will be a prospective randomized noninferiority study that will take place at Hotel Dieu Hospital. Based on a statistical power calculation, a total of 100 patients are required for enrollment. Enrollment will take place at the outpatient endoscopy suite at Hotel Dieu Hospital. Patients will be reviewed for eligibility as per the inclusion and exclusion criteria and those deemed eligible will consent for participation. Members of the research time will attempt to contact patients two to three weeks prior to their schedule endoscopy for consent. If unable to reach them after two attempts, they will then be consented for their participation during the day of their endoscopy at Hotel Dieu Hospital. Once enrolled in the study, each patient will be randomly allocated to one of two groups (group A and group B) using a computer randomizer generator. The aim is to have equal numbers in both groups (ie. 50 patients in each group). Participants in group A will have their biopsies during endoscopy taken with the conventional double bite forceps. On the other hand, participants in group B will have their biopsies taken with the multiple bite forceps. Each patient in both groups will have at least six biopsies taken. In both groups, biopsies will be taken for assessment of H. pylori and/or celiac disease. Patients recruited will be those who would require these biopsies to be taken regardless of this study. The samples will be sent to pathology where two independent expert gastrointestinal pathologists will examine the slides and grade each specimen using a five-point scale. The overall histological score given to samples will then be assessed to compare those retrieved with the multiple bite forceps and conventional forceps. ### Conditions Module **Conditions:** - Helicobacter Pylori Infection - Celiac Disease **Keywords:** - Biopsy - Histological quality - Endoscopy - Forceps ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** Participants will be randomized to one of two groups (group A and group B). Group A will include patients who will have their biopsies taken with the conventional double bite forceps during endoscopy. Group B will include patients who will have their biopsies taken with the multiple bite forceps. Each patient in both groups will have the same number of biopsies taken from the same anatomical areas; the only difference will be the number of biopsies that are taken consecutively. ##### Masking Info **Masking:** DOUBLE **Masking Description:** The participant will be blinded as to which forceps (ie. conventional double bite or multiple bite forceps) are used for sampling during endoscopy. The pathologists assessing the histological quality of biopsy specimens will also be blinded to which forceps were used to obtain the samples. **Who Masked:** - PARTICIPANT - INVESTIGATOR **Primary Purpose:** DIAGNOSTIC #### Enrollment Info **Count:** 100 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Participants in group A will proceed to have their biopsies during endoscopy taken with the conventional double bite forceps. Meaning, they will have two biopsies taken each time the forcep is passed through the endoscope. To obtain a total of six biopsies, the forceps will be passed through the endoscope a total of three times. **Intervention Names:** - Device: Conventional double bite forcep **Label:** Group A (double bite forceps) **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** Participants in group B will have their biopsies during endoscopy retrieved with the multiple bite forceps. Meaning, they will have six consecutive biopsies taken with each pass through the endoscope. **Intervention Names:** - Device: MultCROC multibite forcep **Label:** Group B (multiple bite forceps) **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Group B (multiple bite forceps) **Description:** Alligator style 2.4 mm diameter jaws that can hold up to six samples in one pass through endoscope. **Name:** MultCROC multibite forcep **Type:** DEVICE #### Intervention 2 **Arm Group Labels:** - Group A (double bite forceps) **Description:** Use of conventional double bite forceps that can store up to two specimens in one pass through endoscope **Name:** Conventional double bite forcep **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Description:** Comparison of the histological quality of specimens retrieved with multiple bite forceps compared to double bite forceps **Measure:** Histological quality **Time Frame:** Duration of endoscopy and pathological assessment of specimens #### Secondary Outcomes **Description:** Total time taken to retrieve six biopsies with the multiple bite forceps compared to time taken to retrieve six biopsies using double bite forceps **Measure:** Time duration **Time Frame:** Duration of endoscopy ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Patients who were referred for outpatient upper endoscopy at Hotel Dieu Hospital requiring biopsies to investigate for celiac disease or H. Pylori infection. Exclusion Criteria: * Patients with clinical or endoscopic evidence of gastric mucosal atrophy. **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Kingston **Country:** Canada **Facility:** Hotel Dieu Hospital **State:** Ontario **Zip:** K7L 5G2 #### Overall Officials **Official 1:** **Affiliation:** Queen's University **Name:** Lawrence C Hookey, MD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Lebwohl B, Kapel RC, Neugut AI, Green PH, Genta RM. Adherence to biopsy guidelines increases celiac disease diagnosis. Gastrointest Endosc. 2011 Jul;74(1):103-9. doi: 10.1016/j.gie.2011.03.1236. Epub 2011 May 20. **PMID:** 21601201 **Citation:** Rostom A, Murray JA, Kagnoff MF. American Gastroenterological Association (AGA) Institute technical review on the diagnosis and management of celiac disease. Gastroenterology. 2006 Dec;131(6):1981-2002. doi: 10.1053/j.gastro.2006.10.004. No abstract available. **PMID:** 17087937 **Citation:** Rubio-Tapia A, Hill ID, Kelly CP, Calderwood AH, Murray JA; American College of Gastroenterology. ACG clinical guidelines: diagnosis and management of celiac disease. Am J Gastroenterol. 2013 May;108(5):656-76; quiz 677. doi: 10.1038/ajg.2013.79. Epub 2013 Apr 23. **PMID:** 23609613 **Citation:** Zaidman JS, Frederick WG, Furth EE, Su CG, Ginsberg GG. Comparison of Pelican single-use multibite biopsy forceps and traditional double-bite forceps: evaluation in a porcine model. Gastrointest Endosc. 2006 Oct;64(4):582-8. doi: 10.1016/j.gie.2006.06.060. **PMID:** 16996354 **Citation:** Fantin AC, Neuweiler J, Binek JS, Suter WR, Meyenberger C. Diagnostic quality of biopsy specimens: comparison between a conventional biopsy forceps and multibite forceps. Gastrointest Endosc. 2001 Nov;54(5):600-4. doi: 10.1067/mge.2001.118945. **PMID:** 11677476 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000008286 - Term: Malabsorption Syndromes - ID: D000007410 - Term: Intestinal Diseases - ID: D000005767 - Term: Gastrointestinal Diseases - ID: D000004066 - Term: Digestive System Diseases - ID: D000008659 - Term: Metabolic Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC01 - Name: Infections - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: BC06 - Name: Digestive System Diseases - Abbrev: BC18 - Name: Nutritional and Metabolic 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: M5696 - Name: Celiac Disease - Relevance: HIGH - As Found: Celiac Disease - ID: M16355 - Name: Syndrome - 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: M11639 - Name: Metabolic Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000002446 - Term: Celiac Disease ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04644679 **Brief Title:** Monitoring Strategies for the Detection of Atrial Fibrillation in Patients With Cryptogenic Stroke **Official Title:** 48-hour Versus 7-day Monitoring for the Detection of Atrial Fibrillation in Patients With Cryptogenic Stroke #### Organization Study ID Info **ID:** 5767 #### Organization **Class:** OTHER **Full Name:** Hospital Italiano de Buenos Aires ### Status Module #### Completion Date **Date:** 2021-10-07 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2022-09-01 **Type:** ACTUAL **Last Update Submit Date:** 2022-08-29 **Overall Status:** TERMINATED #### Primary Completion Date **Date:** 2021-09-30 **Type:** ACTUAL #### Start Date **Date:** 2020-11-02 **Type:** ACTUAL **Status Verified Date:** 2020-11 #### Study First Post Date **Date:** 2020-11-25 **Type:** ACTUAL **Study First Submit Date:** 2020-09-30 **Study First Submit QC Date:** 2020-11-19 **Why Stopped:** Poor enrollment rate ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Hospital Italiano de Buenos Aires #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Is US Export:** True **Oversight Has DMC:** True ### Description Module **Brief Summary:** Randomized clinical trial comparing two monitoring strategies, the use of a 48-hour Holter (routine care branch) and an event recorder for 7 days (intervention branch). Patients admitted for cryptogenic stroke will be included. Enrollment and randomization of patients will be carried out during the index case hospitalization, while follow-up will be done on an outpatient basis until day 7. **Detailed Description:** Once the diagnose of cryptogenic stroke have been carried out, informed consent will be taken and participants will be randomized to 48-hour monitoring arm or 7-day monitoring arm, followed by discharge from hospital. ### Conditions Module **Conditions:** - Stroke - Atrial Fibrillation ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** DIAGNOSTIC #### Enrollment Info **Count:** 49 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** 48-hr electrocardiographic monitoring **Intervention Names:** - Diagnostic Test: 48-hr electrocardiographic monitoring **Label:** 48-hr **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** 7-day electrocardiographic monitoring **Intervention Names:** - Diagnostic Test: 7-day electrocardiographic monitoring **Label:** 7-day **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - 7-day **Description:** 7-day external electrocardiographic monitoring **Name:** 7-day electrocardiographic monitoring **Type:** DIAGNOSTIC_TEST #### Intervention 2 **Arm Group Labels:** - 48-hr **Description:** 48-hr external electrocardiographic monitoring **Name:** 48-hr electrocardiographic monitoring **Type:** DIAGNOSTIC_TEST ### Outcomes Module #### Primary Outcomes **Description:** Detection of one episode of atrial fibrillation or atrial flutter \>30 seconds up to 7 days **Measure:** Atrial fibrillation **Time Frame:** 7 days #### Secondary Outcomes **Description:** Count of beats per day of non-sustained irregular atrial tachyarrhythmia or supraventricular extrasystoles up to 7 days **Measure:** Supraventricular arrhythmia **Time Frame:** 7 days ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * All patients who have studies that classify stroke or TIA as cryptogenic and who can carry out monitoring for 48 hours or 7 days will be included. * Age ≥ 18 years Exclusion criteria * History of atrial fibrillation (or atrial flutter) documented. * Patients who already have an event recorder in place, permanent pacemaker, or implantable cardioverter-defibrillator * Evidence of lacunar infarction. * Hemorrhagic stroke * Patient for palliative care **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Buenos Aires **Country:** Argentina **Facility:** Hospital Italiano de Buenos Aires **State:** C.a.b.a **Zip:** C1199 #### Overall Officials **Official 1:** **Affiliation:** Hospital Italiano de Buenos Aires **Name:** Gustavo Maid, MD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000002561 - Term: Cerebrovascular Disorders - ID: D000001927 - Term: Brain Diseases - ID: D000002493 - Term: Central Nervous System Diseases - ID: D000009422 - Term: Nervous System Diseases - ID: D000014652 - Term: Vascular Diseases - ID: D000002318 - Term: Cardiovascular Diseases - ID: D000001145 - Term: Arrhythmias, Cardiac - ID: D000006331 - Term: Heart Diseases - ID: D000010335 - Term: Pathologic Processes ### Condition Browse Module - Browse Branches - Abbrev: BC10 - Name: Nervous System Diseases - 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: M22306 - Name: Stroke - Relevance: HIGH - As Found: Stroke - ID: M4586 - Name: Atrial Fibrillation - Relevance: HIGH - As Found: Atrial Fibrillation - ID: M10543 - Name: Ischemia - Relevance: LOW - As Found: Unknown - ID: M2400 - Name: Ischemic Stroke - Relevance: HIGH - As Found: Cryptogenic Stroke - ID: M5810 - Name: Cerebrovascular Disorders - 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: M17400 - Name: Vascular Diseases - Relevance: LOW - As Found: Unknown - 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: D000020521 - Term: Stroke - ID: D000083242 - Term: Ischemic Stroke - ID: D000001281 - Term: Atrial Fibrillation ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05034679 **Acronym:** Israel **Brief Title:** Impact of Corona Vaccination on AMH- Anti Mullerian Hormone **Official Title:** Wether Corona Vaccination Has Negative Impact on AMH- Anti Mullerian Hormone Which Express Ovarin Function #### Organization Study ID Info **ID:** 0013-21-WOMC #### Organization **Class:** OTHER_GOV **Full Name:** Wolfson Medical Center ### Status Module #### Completion Date **Date:** 2022-10-15 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** RECRUITING #### Last Update Post Date **Date:** 2021-09-05 **Type:** ACTUAL **Last Update Submit Date:** 2021-08-29 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2022-08-15 **Type:** ESTIMATED #### Start Date **Date:** 2021-07-15 **Type:** ACTUAL **Status Verified Date:** 2021-08 #### Study First Post Date **Date:** 2021-09-05 **Type:** ACTUAL **Study First Submit Date:** 2021-08-29 **Study First Submit QC Date:** 2021-08-29 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER_GOV **Name:** Wolfson Medical Center #### Responsible Party **Investigator Affiliation:** Wolfson Medical Center **Investigator Full Name:** Eran Horowitz M.D. **Investigator Title:** Senior Physician **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False ### Description Module **Brief Summary:** Since December 2020 Nationwide anti-COVID-19 vaccination began in Israel using the Pfizer - BioNtech vaccine (BNT162b2 mRNA). The vaccination campaign has been associated with concerns regarding potential detrimental effects on future fertility. The aim of the study is to determine the impact of COVID-19 vaccination on n AMH- Anti Mullerian Hormone which express ovarin function. disease and/or immunization on human follicular function, by comparing follicular steroidogenesis, response to the LH/hCG trigger, and oocyte quality biomarker (HSPG2), in the aspirated follicular fluid of patients undergoing ovum pick-up. **Detailed Description:** Our assumption is that there is no effect of the vaccination on the AMH level. We plan to recruit 90 patients who are divided to three groups First group patients who vaccinated and measure the AMH before and up to 9 months after vaccination. Second group patients who were infected by Covid-19 ant therefor were not vaccinated to compare the AMH level before and after the infectious. The third group patients who were not infected and not vaccinated. ### Conditions Module **Conditions:** - Patient Participation ### Design Module #### Bio Spec **Description:** Blood samples evaluated for Anti Mullarin Hormone (AMH) **Retention:** SAMPLES_WITHOUT_DNA #### Design Info **Observational Model:** CASE_CONTROL **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 90 **Type:** ESTIMATED **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** First group patients who vaccinated and measure the AMH before and up to 9 months after vaccination. **Intervention Names:** - Biological: Vcinated **Label:** Vaciinated #### Arm Group 2 **Description:** Second group patients who were infected by Covid-19 ant therefor were not vaccinated **Label:** Infected patients by covid-19 and not vacinated #### Arm Group 3 **Description:** Ptients who who were not infected nor vacinated by Covid-19. **Label:** Not infected nor vacinated ### Interventions #### Intervention 1 **Arm Group Labels:** - Vaciinated **Description:** Patients who were vacinated. **Name:** Vcinated **Type:** BIOLOGICAL ### Outcomes Module #### Primary Outcomes **Description:** Before and after vacination **Measure:** Amh levels **Time Frame:** 9 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Age 18-44 Exclusion Criteria: Age over 45 **Gender Based:** True **Gender Description:** Women in reproductive age. **Healthy Volunteers:** True **Maximum Age:** 44 Years **Minimum Age:** 18 Years **Sampling Method:** PROBABILITY_SAMPLE **Sex:** FEMALE **Standard Ages:** - ADULT **Study Population:** Women who are going through IVF treatments. ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Eran Horowitz, M.D **Phone:** +972-54-4991919 **Role:** CONTACT #### Locations **Location 1:** **City:** Holon **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Eran Horowitz, M.D - **Phone:** 972-3-5028105 - **Role:** CONTACT ***Contact 2:*** - **Name:** Eran Horowitz, M.D - **Role:** SUB_INVESTIGATOR **Country:** Israel **Facility:** Wolfson medical center **Status:** RECRUITING **Zip:** 58100 ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Intervention Browse Module - Browse Branches - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M9789 - Name: Hormones - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05211479 **Brief Title:** Tele Nursing Application For Type 1 Diabetes Mellitus Adolescents **Official Title:** The Effect Of Tele-Nursing Application On Metabolic Control, Self-Efficacy, Quality Of Life And Anxiety Level Of Adolescents With Type 1 Diabetes #### Organization Study ID Info **ID:** 2020-14 #### Organization **Class:** OTHER **Full Name:** University of Yalova ### Status Module #### Completion Date **Date:** 2022-08-31 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2022-11-01 **Type:** ACTUAL **Last Update Submit Date:** 2022-10-31 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2022-03-15 **Type:** ACTUAL #### Start Date **Date:** 2021-12-20 **Type:** ACTUAL **Status Verified Date:** 2022-10 #### Study First Post Date **Date:** 2022-01-27 **Type:** ACTUAL **Study First Submit Date:** 2021-11-25 **Study First Submit QC Date:** 2022-01-26 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** University of Yalova #### Responsible Party **Investigator Affiliation:** University of Yalova **Investigator Full Name:** Emel AVÇİN **Investigator Title:** Lecturer **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** Studies have shown that tele-nursing practice is effective in children with Type 1 Diabetes Mellitus, but the number of studies conducted is very few. No study examining the concepts of metabolic control, self-efficacy, quality of life and anxiety together was found in the literature review. With this study, it is aimed that diabetes education given by tele-nursing has an effect on metabolic control, self-efficacy, quality of life and anxiety level of adolescents with type 1 diabetes, and that diabetic adolescents can easily obtain the information they need about nursing care when they cannot come to the clinic. ### Conditions Module **Conditions:** - Telenursing - Adolescent - Type 1 Diabetes Mellitus **Keywords:** - Telenursing - Type 1 Diabetes Mellitus - Metabolic Control - Self Efficacy - Quality of Life - Anxiety ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** Randomized controlled and quasi-experimental research ##### Masking Info **Masking:** NONE **Primary Purpose:** SUPPORTIVE_CARE #### Enrollment Info **Count:** 67 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Tele-nursing will be applied to adolescents in this group for 24 weeks. Weekly meeting and blood glucose monitoring will be done. The HbA1c value will be checked and the scales will be filled by meeting 3 times in total with 3 months intervals. **Intervention Names:** - Behavioral: educational intervention **Label:** intervention group **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** This group will be given face-to-face training only in the first encounter. During the research, no interviews will be provided through tele nursing. Only at the 3rd and 6th months will be interviewed to measure the HbA1c value and to fill the scales. **Label:** Control Group **Type:** NO_INTERVENTION ### Interventions #### Intervention 1 **Arm Group Labels:** - intervention group **Description:** In the light of up-to-date information, "Type I Diabetes Education Guide" was created. With this guide, both face-to-face and tele-nursing training will be provided. Both working groups will receive training before starting research. The intervention group will continue their weekly training throughout the study. **Name:** educational intervention **Type:** BEHAVIORAL ### Outcomes Module #### Primary Outcomes **Description:** HbA1c values were recorded before starting the study to determine the level of metabolic control. The HbA1c values will be followed up in the 3rd and 6th months of the research. When the adolescents go to the hospital for a routine control every 3 months, the HbA1c value will be checked from the blood values and the researcher will obtain it from the records. **Measure:** Evaluation of Metabolic control level of adolescents with type 1 diabetes **Time Frame:** Baseline, 12 weeks and 24 weeks after randomization **Description:** "Diabetes Self-Efficacy Scale in Adolescents with Type 1 Diabetes" was used to measure self-efficacy in diabetes management in adolescents aged 12-18 years with Type 1 Diabetes. Scale; medical treatment and nutrition, nutrition and insulin dose adjustment, being able to tell about diabetes, being honest with oneself and others (Ozturk, Ayar \& Bektas, 2016). Participants will be asked to fill in the "Diabetes Self-Efficacy Scale in Adolescents with Type 1 Diabetes" scale to determine their self-efficacy levels in the 3rd and 6th months of the research. **Measure:** Evaluation of the level of self-efficacy of adolescents with type 1 diabetes **Time Frame:** Baseline, 12 weeks and 24 weeks after randomization **Description:** "Quality of Life Scale for Children Adolescent Form (Kiddo-KINDL)" was used to determine the level of quality of life of adolescents. The scale form consists of 30 items and dimensions of physical well-being, mental well-being, self-esteem, family, friends, school, and illness (Eser et al., 2004). In the 3rd and 6th months of the study, participants will be asked to fill in the "Quality of Life Scale for Children Adolescent Form" scale to determine their quality of life. **Measure:** Evaluation of the level of quality of life of adolescents with type 1 diabetes **Time Frame:** Baseline, 12 weeks and 24 weeks after randomization **Description:** The scale is a self-report scale used in the evaluation of childhood anxiety disorders. The scale consists of 41 items and sub-dimensions of Panic Disorder/Somatic Disorder, Generalized Anxiety Disorder, Separation Anxiety, Social Anxiety, and School Fear. A cut-off value of 25 and above is accepted as a warning for anxiety disorder. An increase in the total score obtained from the scale means that the level of anxiety also increases (Cakmakcı, 2004). Participants will be asked to fill in the "Childhood Anxiety Screening Scale" scale to determine their anxiety levels in the 3rd and 6th months of the study. **Measure:** Evaluation of the anxiety level of adolescents with type 1 diabetes **Time Frame:** Baseline, 12 weeks and 24 weeks after randomization ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: Inclusion Criteria: * The child is between the ages of 12-18, * After the information, the adolescent agrees to participate in the study, and the parent gives written consent, * The child can understand and speak Turkish, * Parent's ability to understand and speak Turkish, * Having a smart phone and having access to the internet, * Having been diagnosed with T1DM at least 1 year ago, * Being on insulin therapy by the subcutaneous route, * Coming to the outpatient clinic at least once every 3 months. Exclusion Criteria: Exclusion Criteria: * Age younger than 12 or older than 18, * Having another chronic disease, * Using an insulin pump * Having vision and hearing problems, * Using the Continuous Glucose Tracking System, * Having a physical or mental disability. **Maximum Age:** 18 Years **Minimum Age:** 12 Years **Sex:** ALL **Standard Ages:** - CHILD - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Yalova **Country:** Turkey **Facility:** Yalova University **Zip:** 77200 #### Overall Officials **Official 1:** **Affiliation:** University of Yalova **Name:** Emel AVÇİN, Doctorate **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000044882 - Term: Glucose Metabolism Disorders - ID: D000008659 - Term: Metabolic Diseases - ID: D000004700 - Term: Endocrine System Diseases - ID: D000001327 - Term: Autoimmune Diseases - ID: D000007154 - Term: Immune 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 - Abbrev: BC20 - Name: Immune System Diseases - Abbrev: BXM - Name: Behaviors and Mental Disorders ### Condition Browse Module - Browse Leaves - ID: M7115 - Name: Diabetes Mellitus - Relevance: HIGH - As Found: Diabetes Mellitus - ID: M7117 - Name: Diabetes Mellitus, Type 1 - Relevance: HIGH - As Found: Type 1 Diabetes Mellitus - ID: M4324 - Name: Anxiety Disorders - Relevance: LOW - As Found: Unknown - 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: M4629 - Name: Autoimmune Diseases - Relevance: LOW - As Found: Unknown - ID: M10200 - Name: Immune System Diseases - Relevance: LOW - As Found: Unknown - ID: T6034 - Name: Quality of Life - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000003920 - Term: Diabetes Mellitus - ID: D000003922 - Term: Diabetes Mellitus, Type 1 ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00671879 **Brief Title:** Study to Evaluate Two Formulations of Carisoprodol in Subjects With Musculoskeletal Spasm of the Lower Back **Official Title:** Randomized, Double-Blind, Double-Dummy Trial of Two Sustained Release Formulations of Carisoprodol Compared to Placebo in Subjects With Acute, Painful, Musculoskeletal Spasm of the Lower Back #### Organization Study ID Info **ID:** MP511 #### Organization **Class:** INDUSTRY **Full Name:** Meda Pharmaceuticals ### Status Module #### Completion Date **Date:** 2009-03 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2012-11-21 **Type:** ESTIMATED **Last Update Submit Date:** 2012-10-22 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2009-03 **Type:** ACTUAL #### Results First Post Date **Date:** 2012-11-21 **Type:** ESTIMATED **Results First Submit Date:** 2011-07-13 **Results First Submit QC Date:** 2012-10-22 #### Start Date **Date:** 2008-04 **Status Verified Date:** 2012-10 #### Study First Post Date **Date:** 2008-05-05 **Type:** ESTIMATED **Study First Submit Date:** 2008-05-01 **Study First Submit QC Date:** 2008-05-02 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Meda Pharmaceuticals #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** The purpose of this study is to determine if two sustained released formulations of carisoprodol are more effective than placebo. **Detailed Description:** Methodology: This will be a randomized, double-blind, double-dummy, placebo-controlled, parallel-group study in subjects 18-70 years of age with acute, painful, muscle spasm of the lower back. The study consists of a baseline screening (Study Day 1), during which subjects will be evaluated for inclusion/exclusion criteria, and a 7-day double-blind treatment period (Study Day 1 through Study Day 7). Subjects will be randomly assigned to be dosed twice daily with one of the following double-blind treatments: SR carisoprodol 500-mg tablets, SR carisoprodol 700-mg tablets, or placebo. Subjects will be evaluated in the clinic on Study Days 1, 3 and 7. Subjects who remain symptomatic on Study Day 7 will be allowed to continue in the study for a 7-day, double-blind extension period at the discretion of the Investigator. Subjects will be contacted by telephone for a safety follow-up 7 days after the last dose of study medication. A pharmacokinetic (PK) substudy will be conducted at selected sites. These sites will obtain blood samples for PK analysis at the end of the 7-day treatment period and the 14-day treatment period, if applicable. ### Conditions Module **Conditions:** - Lower Back 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:** 830 **Type:** ACTUAL **Phases:** - PHASE3 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Carisoprodol 700 mg twice daily **Intervention Names:** - Drug: Carisoprodol SR 700 mg **Label:** Carisprodol SR 700 mg **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Carisoprodol SR 500 mg twice daily **Intervention Names:** - Drug: Carisoprodol SR 500 mg **Label:** Carisoprodol SR 500mg **Type:** EXPERIMENTAL #### Arm Group 3 **Description:** Placebo **Intervention Names:** - Drug: Placebo **Label:** Placebo **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Carisprodol SR 700 mg **Description:** 700 mg twice daily tablet **Name:** Carisoprodol SR 700 mg **Other Names:** - no other name **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Carisoprodol SR 500mg **Description:** carisoprodol SR 500 mg tablet **Name:** Carisoprodol SR 500 mg **Other Names:** - no other name **Type:** DRUG #### Intervention 3 **Arm Group Labels:** - Placebo **Description:** placebo tablet **Name:** Placebo **Other Names:** - no other name **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** on a visual analog scale of 0 to 100 millimeters(mm) with 0 being no pain and 100 being maximum pain By measuring the amount of pain before and during treatment done at each visit and recording the difference in mm.During treatment scores were averaged and this average was compared to the baseline value. **Measure:** Subject Rated Change Relief From Starting Backache of Pain on a 100-point Visual Analog Scale **Time Frame:** baseline to 14 days #### Secondary Outcomes **Description:** Subject functional assessment based on the Roland-Morris Disability Questionnaire (RMDQ)at day 14.Subjects were asked to read a list of 24 sentences that people have used to describe themselves when they had back pain, and were asked to mark those statements that described their condition that day. The number of marked statements was added. A decrease in the number of marked statements from baseline represented improvement on the RMDQ. **Measure:** Subject Functional Assessment Based on the Roland-Morris Disability Questionnaire (RMDQ) **Time Frame:** baseline and day +14 ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Onset of pain is within 3 days of first visit * Subject rating of pain must be 40 mm or greater on VAS * Ability to discontinue all analgesics, NSAIDs, and other muscle relaxants * Willingness to provide written informed consent * Must be in generally good health Exclusion Criteria: * Presence of sciatic pain * History of clinically significant spine pathology such as herniated nucleus pulpous, spondylolisthesis, spinal stenosis * Presence of underlying chronic back pain * Neurological signs and symptoms such as numbness, tingling, foot drop, paresthesia, unexplained constipation, urinary retention or urinary incontinence * Myocardial infarction within one year of study * Cancer not in remission or in remission less than one year * HIV or other immunodeficiency syndromes * History of osteoporosis or at high risk for vertebral fracture * Underlying rheumatologic disease such as rheumatoid arthritis, ankylosing spondylitis, etc. * Presence of active influenza or other viral syndromes * Morbid obesity (BMI \>39) * Evidence of infection, such as low grade fever or neutrophilia * Existence of any medical/surgical condition that could interfere with the evaluation of the study medication * Known history of alcohol or drug abuse * Injury involving high potential for litigation, including worker's compensation or automobile accidents * Pregnancy or breast feeding * Women of child-bearing potential not abstinent or not practicing a medically acceptable method of contraception * Vertebral body or spinous process, percussive tenderness on physical exam * Any abnormalities in the following tests of both lower extremities: ankle dorsiflexion strength, great toe dorsiflexion strength, absent or hyperreflexic Achilles or patellar tendor reflexes, abnormal sensory exam in the medial, dorsal or lateral aspect of the foot and positive straight leg raise test * Urgent medical conditions on comprehensive exam that might indicate a more serious condition should be treated urgently **Maximum Age:** 70 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Birmingham **Country:** United States **Facility:** Brookwood Internists, P.C. **State:** Alabama **Zip:** 35209 **Location 2:** **City:** Gulf Shores **Country:** United States **Facility:** Gulf Shores General Practice Center **State:** Alabama **Zip:** 36547 **Location 3:** **City:** Hueytown **Country:** United States **Facility:** Simon Williamson Clinic, PC **State:** Alabama **Zip:** 35023 **Location 4:** **City:** Montgomery **Country:** United States **Facility:** Vaugh H Mancha Jr., PC Family Practice **State:** Alabama **Zip:** 36117 **Location 5:** **City:** Phoenix **Country:** United States **Facility:** NextCare Institute for Clinical Research **State:** Arizona **Zip:** 85016 **Location 6:** **City:** Phoenix **Country:** United States **Facility:** HOPE Research Institute **State:** Arizona **Zip:** 85050 **Location 7:** **City:** Tempe **Country:** United States **Facility:** Fiel Family and Sports Medicine **State:** Arizona **Zip:** 85283 **Location 8:** **City:** Little Rock **Country:** United States **Facility:** Lynn Institute of the Ozarks **State:** Arkansas **Zip:** 72205 **Location 9:** **City:** Anaheim **Country:** United States **Facility:** Quality of life Medical, LLC **State:** California **Zip:** 92801 **Location 10:** **City:** Beverly Hills **Country:** United States **Facility:** ICT - Beverly Hills **State:** California **Zip:** 90211 **Location 11:** **City:** Burbank **Country:** United States **Facility:** Lovelace Scientific Resources, Inc. **State:** California **Zip:** 91506 **Location 12:** **City:** Inglewood **Country:** United States **Facility:** Chrishard Medical Group **State:** California **Zip:** 90301 **Location 13:** **City:** Los Angeles **Country:** United States **Facility:** Impact Clinical Trials and Powerplay **State:** California **Zip:** 90036 **Location 14:** **City:** Newport Beach **Country:** United States **Facility:** Newport Beach Clinical Research Associates, Inc. **State:** California **Zip:** 92660 **Location 15:** **City:** San Diego **Country:** United States **Facility:** San Diego Managed Care Group **State:** California **Zip:** 92128 **Location 16:** **City:** Santa Ana **Country:** United States **Facility:** Crest Clinical Trials, Inc. **State:** California **Zip:** 92701 **Location 17:** **City:** Santa Barbara **Country:** United States **Facility:** Santa Barbara Clinical Research Inc. **State:** California **Zip:** 93108 **Location 18:** **City:** Colorado Springs **Country:** United States **Facility:** Clinicos, LLC **State:** Colorado **Zip:** 80904 **Location 19:** **City:** Denver **Country:** United States **Facility:** Horizons Clinical Research Center, LLC **State:** Colorado **Zip:** 80220 **Location 20:** **City:** Clearwater **Country:** United States **Facility:** Tampa Bay Medical Research **State:** Florida **Zip:** 33761 **Location 21:** **City:** Daytona Beach **Country:** United States **Facility:** Atlantic Institute of Clinical Research **State:** Florida **Zip:** 32114 **Location 22:** **City:** Gainesville **Country:** United States **Facility:** Florida Research Network, LLC **State:** Florida **Zip:** 32605 **Location 23:** **City:** Hollywood **Country:** United States **Facility:** Orthopaedic Assoc. of S. Broward, P.A. **State:** Florida **Zip:** 33021 **Location 24:** **City:** Kissimmee **Country:** United States **Facility:** FPA Clinical Research **State:** Florida **Zip:** 34741 **Location 25:** **City:** Lakeland **Country:** United States **Facility:** Jay Care Medical Center **State:** Florida **Zip:** 33805 **Location 26:** **City:** Largo **Country:** United States **Facility:** Innovative Research of West FL, Inc. **State:** Florida **Zip:** 33770 **Location 27:** **City:** Melbourne **Country:** United States **Facility:** Oslar Medical, Inc./ Osler Clinical Research **State:** Florida **Zip:** 32901 **Location 28:** **City:** Naranja **Country:** United States **Facility:** Homestead Clinical Research **State:** Florida **Zip:** 33032 **Location 29:** **City:** Pembroke Pines **Country:** United States **Facility:** Andres Patron, DO, PA **State:** Florida **Zip:** 33026 **Location 30:** **City:** St. Cloud **Country:** United States **Facility:** Wilker/Powers Center for Clinical Studies **State:** Florida **Zip:** 34769 **Location 31:** **City:** Tampa **Country:** United States **Facility:** Orlando Rangel, M.D., P.A. **State:** Florida **Zip:** 33607 **Location 32:** **City:** Tampa **Country:** United States **Facility:** West Wind'r Research & Development, LLC **State:** Florida **Zip:** 33607 **Location 33:** **City:** West Palm Beach **Country:** United States **Facility:** Palm Beach Research center **State:** Florida **Zip:** 33409 **Location 34:** **City:** Atlanta **Country:** United States **Facility:** PMI Health Research Group **State:** Georgia **Zip:** 30312 **Location 35:** **City:** Atlanta **Country:** United States **Facility:** Perimeter Institute for Clinical Research, Inc. **State:** Georgia **Zip:** 30338 **Location 36:** **City:** Decatur **Country:** United States **Facility:** Best Clinical Research **State:** Georgia **Zip:** 30034 **Location 37:** **City:** Naperville **Country:** United States **Facility:** Dupage Family Medicine **State:** Illinois **Zip:** 60564 **Location 38:** **City:** Wichita **Country:** United States **Facility:** Heartland Research Associates, LLC **State:** Kansas **Zip:** 67205 **Location 39:** **City:** Lexington **Country:** United States **Facility:** Bluegrass Orthopaedics & Hand Care Research **State:** Kentucky **Zip:** 40509 **Location 40:** **City:** Lexington **Country:** United States **Facility:** Central Kentucky Research Associates, Inc. **State:** Kentucky **Zip:** 40509 **Location 41:** **City:** New Orleans **Country:** United States **Facility:** Clinical Research Institute **State:** Louisiana **Zip:** 70128 **Location 42:** **City:** Shreveport **Country:** United States **Facility:** Highland Clinic, APMC **State:** Louisiana **Zip:** 71105 **Location 43:** **City:** Waterford **Country:** United States **Facility:** Waterford Medical Associates **State:** Michigan **Zip:** 48328 **Location 44:** **City:** Jackson **Country:** United States **Facility:** CRC of Jackson **State:** Mississippi **Zip:** 39202 **Location 45:** **City:** Omaha **Country:** United States **Facility:** Quality Clinical Research, Inc. **State:** Nebraska **Zip:** 68114 **Location 46:** **City:** Omaha **Country:** United States **Facility:** Dr. Meera Dewan PC **State:** Nebraska **Zip:** 68144 **Location 47:** **City:** Las Vegas **Country:** United States **Facility:** Association of International Professionals **State:** Nevada **Zip:** 89101 **Location 48:** **City:** Las Vegas **Country:** United States **Facility:** ICT - Las Vegas **State:** Nevada **Zip:** 89106 **Location 49:** **City:** Bloomfield **Country:** United States **Facility:** Immedicenter **State:** New Jersey **Zip:** 07003 **Location 50:** **City:** West Caldwell **Country:** United States **Facility:** Land Clinical Studies **State:** New Jersey **Zip:** 07006 **Location 51:** **City:** New York **Country:** United States **Facility:** Research Across America **State:** New York **Zip:** 10022 **Location 52:** **City:** Fargo **Country:** United States **Facility:** Odyssey Research **State:** North Dakota **Zip:** 58104 **Location 53:** **City:** Columbus **Country:** United States **Facility:** Parsons Avenue Medical Clinic **State:** Ohio **Zip:** 43207 **Location 54:** **City:** Dayton **Country:** United States **Facility:** Dayton Clinical Research **State:** Ohio **Zip:** 45406 **Location 55:** **City:** Oklahoma City **Country:** United States **Facility:** Hillcrest Clinical Research **State:** Oklahoma **Zip:** 73119 **Location 56:** **City:** Harleysville **Country:** United States **Facility:** Harleysville Medical Associates **State:** Pennsylvania **Zip:** 19438 **Location 57:** **City:** Warminster **Country:** United States **Facility:** Warminster Medical Association **State:** Pennsylvania **Zip:** 18974 **Location 58:** **City:** Greer **Country:** United States **Facility:** DeGarmo Institute of Medical Research **State:** South Carolina **Zip:** 29651 **Location 59:** **City:** Pelzer **Country:** United States **Facility:** Palmetto Family Medicine Center **State:** South Carolina **Zip:** 29669 **Location 60:** **City:** Kingsport **Country:** United States **Facility:** Holston Medical Group, P.C. **State:** Tennessee **Zip:** 37660 **Location 61:** **City:** Arlington **Country:** United States **Facility:** Medical Clinic of North Texas **State:** Texas **Zip:** 76012 **Location 62:** **City:** Austin **Country:** United States **Facility:** Central Texas Clinical Research **State:** Texas **Zip:** 78705 **Location 63:** **City:** Bryan **Country:** United States **Facility:** DiscoveResearch, Inc. **State:** Texas **Zip:** 77802 **Location 64:** **City:** Colleyville **Country:** United States **Facility:** Texas Family Care Clinical Research **State:** Texas **Zip:** 76034 **Location 65:** **City:** Dallas **Country:** United States **Facility:** Research Across America **State:** Texas **Zip:** 75234 **Location 66:** **City:** Georgetown **Country:** United States **Facility:** Georgetown Medical Clinic **State:** Texas **Zip:** 78626 **Location 67:** **City:** Houston **Country:** United States **Facility:** F. Adam Kawley, MD PA **State:** Texas **Zip:** 77024 **Location 68:** **City:** New Braunfels **Country:** United States **Facility:** Central Texas Health Research **State:** Texas **Zip:** 78130 **Location 69:** **City:** San Antonio **Country:** United States **Facility:** GSA Research **State:** Texas **Zip:** 78213 **Location 70:** **City:** San Antonio **Country:** United States **Facility:** Sun Research Institute **State:** Texas **Zip:** 78215 **Location 71:** **City:** San Antonio **Country:** United States **Facility:** Sylvana Research Associates **State:** Texas **Zip:** 78229 **Location 72:** **City:** Sugar Land **Country:** United States **Facility:** Clinical Health Research, LLC **State:** Texas **Zip:** 77479 **Location 73:** **City:** Weber City **Country:** United States **Facility:** Holston Medical Group, P.C. **State:** Virginia **Zip:** 24290 #### Overall Officials **Official 1:** **Affiliation:** Meda Pharmaceuticals **Name:** Lewis M. Fredane, MD **Role:** STUDY_DIRECTOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000001416 - Term: Back Pain - 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: BC05 - Name: Musculoskeletal Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M4714 - Name: Back Pain - Relevance: LOW - As Found: Unknown - ID: M19433 - Name: Low Back Pain - Relevance: HIGH - As Found: Lower Back Pain - ID: M13066 - Name: Pain - Relevance: LOW - As Found: Unknown - ID: M15837 - Name: Spasm - Relevance: LOW - As Found: Unknown - ID: M12077 - Name: Muscle Cramp - 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: D000017116 - Term: Low Back Pain ### Intervention Browse Module - Ancestors - 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 ### Intervention Browse Module - Browse Branches - Abbrev: MuRelCen - Name: Muscle Relaxants, Central - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M5583 - Name: Carisoprodol - Relevance: HIGH - As Found: Cognitive Fatigue ### Intervention Browse Module - Meshes - ID: D000002328 - Term: Carisoprodol ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module #### Event Groups **Group ID:** EG000 **Title:** Carisprodol SR 700 mg **Description:** Carisoprodol 700 mg twice daily **ID:** EG000 **Other Num Affected:** 98 **Other Num at Risk:** 281 **Serious Number At Risk:** 281 **Title:** Carisprodol SR 700 mg **Group ID:** EG001 **Title:** Carisoprodol SR 500mg **Description:** Carisoprodol SR 500 mg twice daily **ID:** EG001 **Other Num Affected:** 94 **Other Num at Risk:** 275 **Serious Number Affected:** 3 **Serious Number At Risk:** 275 **Title:** Carisoprodol SR 500mg **Group ID:** EG002 **Title:** Placebo **Description:** Placebo treatment arm **ID:** EG002 **Other Num Affected:** 49 **Other Num at Risk:** 274 **Serious Number At Risk:** 274 **Title:** Placebo **Frequency Threshold:** 0.4 #### Other Events **Term:** somnolence **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA **Term:** headache **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA (10.0) **Term:** dizziness **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA (10.0) **Term:** nausea **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA **Term:** fatigue **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA **Term:** increased blood CPK **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA **Term:** insomnia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA **Term:** constipation **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA **Term:** diarrhea **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA **Term:** dry mouth **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA **Term:** vomiting **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA **Term:** Lasegues Test Positive **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA **Term:** anxiety **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA **Term:** clumsiness **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA **Term:** pain in extremity **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA #### Serious Events **Term:** atypical pneumonitis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (11.1) ##### Stats **Group ID:** EG000 **Num At Risk:** 281 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 275 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 274 **Term:** stroke **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA (11.1) ##### Stats **Group ID:** EG000 **Num At Risk:** 281 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 275 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 274 **Term:** severe influenza **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (11.1) ##### Stats **Group ID:** EG000 **Num At Risk:** 281 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 275 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 274 ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 281 **Group ID:** BG001 **Value:** 279 **Group ID:** BG002 **Value:** 280 **Group ID:** BG003 **Value:** 840 **Units:** Participants ### Group **ID:** BG000 **Title:** Carisprodol SR 700 mg **Description:** Carisoprodol 700 mg twice daily ### Group **ID:** BG001 **Title:** Carisoprodol SR 500mg **Description:** Carisoprodol SR 500 mg twice daily ### Group **ID:** BG002 **Title:** Placebo **Description:** Placebo treatment arm ### Group **ID:** BG003 **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 #### Measurement **Group ID:** BG003 **Value:** 0 **Category Title:** <=18 years #### Measurement **Group ID:** BG000 **Value:** 279 #### Measurement **Group ID:** BG001 **Value:** 279 #### Measurement **Group ID:** BG002 **Value:** 280 #### Measurement **Group ID:** BG003 **Value:** 838 **Category Title:** Between 18 and 65 years #### Measurement **Group ID:** BG000 **Value:** 2 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 #### Measurement **Group ID:** BG003 **Value:** 2 **Category Title:** >=65 years **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Spread:** 12.35 **Value:** 41.5 #### Measurement **Group ID:** BG001 **Spread:** 11.79 **Value:** 41.6 #### Measurement **Group ID:** BG002 **Spread:** 11.86 **Value:** 41.4 #### Measurement **Group ID:** BG003 **Spread:** 12.0 **Value:** 41.5 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 149 #### Measurement **Group ID:** BG001 **Value:** 145 #### Measurement **Group ID:** BG002 **Value:** 144 #### Measurement **Group ID:** BG003 **Value:** 438 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 132 #### Measurement **Group ID:** BG001 **Value:** 134 #### Measurement **Group ID:** BG002 **Value:** 136 #### Measurement **Group ID:** BG003 **Value:** 402 **Category Title:** Male **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 281 #### Measurement **Group ID:** BG001 **Value:** 279 #### Measurement **Group ID:** BG002 **Value:** 280 #### Measurement **Group ID:** BG003 **Value:** 840 **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 ## Results Section - More Information Module ### Certain Agreement ### Point of Contact **Email:** [email protected] **Organization:** Meda Pharma US **Phone:** 732 564 2347 **Title:** David Ginsberg, DO Sr Dir Medical Scientific Affairs ## 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:** 1.30 - **Upper Limit:** - **Value:** 16.4 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.34 - **Upper Limit:** - **Value:** 15.5 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 1.32 - **Upper Limit:** - **Value:** 15.2 **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.64 - **Upper Limit:** - **Value:** 4.2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.64 - **Upper Limit:** - **Value:** 5.0 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 0.65 - **Upper Limit:** - **Value:** 4.3 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** on a visual analog scale of 0 to 100 millimeters(mm) with 0 being no pain and 100 being maximum pain By measuring the amount of pain before and during treatment done at each visit and recording the difference in mm.During treatment scores were averaged and this average was compared to the baseline value. **Dispersion Type:** Standard Deviation **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** intent to treat(ITT) population least square mean(LSMEAN, LSMEAN) diff vs Placebo **Reporting Status:** POSTED **Time Frame:** baseline to 14 days **Title:** Subject Rated Change Relief From Starting Backache of Pain on a 100-point Visual Analog Scale **Type:** PRIMARY **Unit of Measure:** mm ##### Group **Description:** Carisoprodol SR 700 mg twice daily **ID:** OG000 **Title:** Carisprodol SR 700 mg ##### Group **Description:** Carisoprodol SR 500 mg twice daily **ID:** OG001 **Title:** Carisoprodol SR 500mg ##### Group **Description:** Placebo treatment arm **ID:** OG002 **Title:** Placebo #### Outcome Measure 2 **Description:** Subject functional assessment based on the Roland-Morris Disability Questionnaire (RMDQ)at day 14.Subjects were asked to read a list of 24 sentences that people have used to describe themselves when they had back pain, and were asked to mark those statements that described their condition that day. The number of marked statements was added. A decrease in the number of marked statements from baseline represented improvement on the RMDQ. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** Intent to Treat(ITT) population **Reporting Status:** POSTED **Time Frame:** baseline and day +14 **Title:** Subject Functional Assessment Based on the Roland-Morris Disability Questionnaire (RMDQ) **Type:** SECONDARY **Unit of Measure:** marked statements ##### Group **Description:** Carisoprodol 700 mg twice daily **ID:** OG000 **Title:** Carisprodol SR 700 mg ##### Group **Description:** Carisoprodol SR 500 mg twice daily **ID:** OG001 **Title:** Carisoprodol SR 500mg ##### Group **Description:** Placebo treatment arm **ID:** OG002 **Title:** Placebo ### Participant Flow Module #### Group **Description:** Carisoprodol 700 mg twice daily **ID:** FG000 **Title:** Carisprodol SR 700 mg #### Group **Description:** Carisoprodol SR 500 mg twice daily **ID:** FG001 **Title:** Carisoprodol SR 500mg #### Group **Description:** Placebo treatment arm **ID:** FG002 **Title:** Placebo #### Period **Title:** Overall Study ##### Withdraw **Type:** Withdrawal by Subject ###### Reason **Group ID:** FG000 **Number of Subjects:** 0 ###### Reason **Group ID:** FG001 **Number of Subjects:** 4 ###### Reason **Group ID:** FG002 **Number of Subjects:** 6 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 281 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 279 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 280 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 281 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 275 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 274 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 4 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 6 **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT00877279 **Brief Title:** Multicenter Study of the Safety and Efficacy of Dermal Filler, Belotero® Soft **Official Title:** A Randomized,Blinded,Controlled,Multicenter Study of the Safety and Effectiveness of Dermal Filler, Belotero® Soft, After Superficial to Mid Dermal Implantation for Correction of Mild Facial Wrinkles Over 4 Weeks. #### Organization Study ID Info **ID:** MUS 90028-0717/1 #### Organization **Class:** INDUSTRY **Full Name:** Merz North America, Inc. ### Status Module #### Completion Date **Date:** 2008-03 **Type:** ACTUAL #### Disp First Post Date **Date:** 2011-10-21 **Type:** ESTIMATED **Disp First Submit Date:** 2011-10-12 **Disp First Submit QC Date:** 2011-10-12 #### Expanded Access Info #### Last Update Post Date **Date:** 2013-11-15 **Type:** ESTIMATED **Last Update Submit Date:** 2013-10-23 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2008-03 **Type:** ACTUAL #### Start Date **Date:** 2007-11 **Status Verified Date:** 2013-10 #### Study First Post Date **Date:** 2009-04-07 **Type:** ESTIMATED **Study First Submit Date:** 2009-04-03 **Study First Submit QC Date:** 2009-04-06 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Merz North America, Inc. #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** This study is to determine the safety and effectiveness of Belotero® Soft compared to active comparator in the correction of mild facial wrinkles, such as nasolabial folds. **Detailed Description:** The purpose of the study is to see if Belotero® Soft is safe and effective for correction of mild facial wrinkles, such as nasolabial folds. The second objective of the study is to see if Belotero® Soft works better than the active comparator. Subjects will receive Belotero® Soft injection to one side of the face and the active comparator to the other side of the face. ### Conditions Module **Conditions:** - Facial Wrinkles **Keywords:** - Facial wrinkles - Nasolabial folds ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** DOUBLE **Who Masked:** - PARTICIPANT - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 64 **Type:** ACTUAL **Phases:** - PHASE3 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Comparator will be given into the opposite side of the face that Belotero® Soft was administered for facial wrinkles, such as nasolabial folds. **Intervention Names:** - Device: Belotero Soft **Label:** Belotero® Soft **Type:** EXPERIMENTAL #### Arm Group 2 **Intervention Names:** - Device: CosmoDerm1 **Label:** CosmoDerm1 **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - CosmoDerm1 **Description:** CosmoDerm1 is a single use syringe, injected into the mid dermal layer. **Name:** CosmoDerm1 **Type:** DEVICE #### Intervention 2 **Arm Group Labels:** - Belotero® Soft **Description:** Dermal Filler **Name:** Belotero Soft **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Measure:** The severity of the facial wrinkle **Time Frame:** 2 weeks and 4 weeks #### Secondary Outcomes **Measure:** Investigator and subject assessments **Time Frame:** 2 weeks and 4 weeks ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Subjects must have bilateral facial wrinkles, such as nasolabial folds Exclusion Criteria: * Other nasolabial fold correction within 6 months prior to study entry. **Healthy Volunteers:** True **Maximum Age:** 75 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:** Skin Care & Laser Physicians of Beverly Hills **State:** California **Zip:** 90069 **Location 2:** **City:** San Francisco **Country:** United States **Facility:** Maas Clinic **State:** California **Zip:** 94115 **Location 3:** **City:** New Haven **Country:** United States **Facility:** Savin Dermatology Center **State:** Connecticut **Zip:** 06511 **Location 4:** **City:** Metairie **Country:** United States **Facility:** William Coleman, III, MD **State:** Louisiana **Zip:** 70006 **Location 5:** **City:** White Plains **Country:** United States **Facility:** Dermatology Surgery and Laser Center **State:** New York **Zip:** 10604 #### Overall Officials **Official 1:** **Affiliation:** Dermatology Surgery and Laser Center **Name:** Rhoda Narins, MD **Role:** PRINCIPAL_INVESTIGATOR ## 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 ### Condition Browse Module - Browse Leaves - ID: M21089 - Name: Facies - Relevance: HIGH - As Found: Facial - ID: M22700 - Name: Disease Attributes - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000019066 - Term: Facies ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00411879 **Brief Title:** Combined Vasopressin, Methylprednisolone, and Epinephrine for Inhospital Cardiac Arrest **Official Title:** Phase 2, Single-Center, Placebo-Controlled Study of the Effects of Combined Administration of Vasopressin, Methylprednisolone, and Epinephrine During Cardiopulmonary Resuscitation on Survival After Cardiac Arrest #### Organization Study ID Info **ID:** 10531-VMA #### Organization **Class:** OTHER **Full Name:** University of Athens ### Status Module #### Completion Date **Date:** 2007-04 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2016-01-12 **Type:** ESTIMATED **Last Update Submit Date:** 2016-01-08 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2007-04 **Type:** ACTUAL #### Start Date **Date:** 2006-06 **Status Verified Date:** 2016-01 #### Study First Post Date **Date:** 2006-12-15 **Type:** ESTIMATED **Study First Submit Date:** 2006-12-14 **Study First Submit QC Date:** 2006-12-14 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** University of Athens #### Responsible Party **Investigator Affiliation:** University of Athens **Investigator Full Name:** Spyros D. Mentzelopoulos **Investigator Title:** Lecturer in Intensive Care Medicine **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** A randomized controlled trial did not show benefit of vasopressin versus epinephrine in inhospital cardiac arrest. Preceding laboratory data suggest that combined vasopressin and epinephrine ensure long-term survival and neurologic recovery. Also, postresuscitation abnormalities mimic severe sepsis. The investigators hypothesized that combined vasopressin and epinephrine during cardiopulmonary resuscitation (CPR), and steroid supplementation during and after (when required) CPR may improve survival in cardiac arrest. **Detailed Description:** Inhospital cardiac arrest still constitutes an important clinical problem with survival to discharge ranging within 0-42% (most common range = 15-20%). Survival after witnessed, pulseless ventricular fibrillation/tachycardia(VF/VT) that is responsive to one or two direct current countershock(s) may exceed 30%. However, survival after inhospital asystole, pulseless electrical activity, or refractory VF/VT (defined as not responsive to two countershocks) may be substantially lower (\< 5-10%). As in nonsurvivors, both endogenous vasopressin and adrenocorticotrophin are reduced compared to survivors, we hypothesized that the addition of exogenous vasopressin and steroids to the standard CPR protocol may increase the rates of both the return of spontaneous circulation (ROSC) and of post-arrest survival. The mechanistic basis of this hypothesis comprises the simultaneous activation of adrenergic and vasopressin receptors, in conjunction with a potential steroid-mediated enhancement of the vascular reactivity to epinephrine. Adult in-patients with cardiac arrest not responsive to two direct current countershocks (when applicable) or asystole or pulseless electrical activity are randomized to receive either arginine vasopressin (Pitressin, 20 IU/CPR cycle for the first 5 CPR-cycles in non-VF/VT and from the second to sixth CPR-cycle in VF/VT) plus epinephrine (1 mg/CPR-cycle) plus methylprednisolone (single dose = 40 mg during the first and second CPR-cycle in non-VF/VT and VF/VT, respectively) or normal saline-placebo plus epinephrine (1 mg/CPR-cycle) plus normal saline-placebo during the first 5 or second to sixth CPR-cycles. Further CPR-vasopressor treatment includes epinephrine (1 mg/CPR-cycle) for both groups. Apart from the initial, combined drug administration in the study group, CPR is conducted in full concordance with the 2005 European Resuscitation Council Guidelines. Following ROSC and in the presence of postresuscitation shock (defined as inability to maintain mean arterial pressure \> 70 mm Hg without using exogenous catecholamines at infusion rates conferring vasopressor and/or inotropic activity), study group patients receive stress dose hydrocortisone (300 mg/day for a maximum of 7 days and then gradual taper), whereas controls receive saline placebo. Following ROSC, control group patients may receive stress dose steroid treatment if prescribed by the attending physician for indications such as septic shock or known adrenocortical insufficiency. This holds also for study group patients during the follow-up period. Any steroid prescription by attending physicians cancels any concomitant investigational interventions regarding steroid supplementation. The investigators involved in CPR drug administration are blinded to the use (or no-use) of vasopressin and methylprednisolone, and do not coordinate the CPR procedures. For the study group, steroid treatment is determined by the director of the pharmacy of Evaggelismos hospital, who also performs the computer-based patient randomization and encoding, and supervises the preparation of study drugs for CPR. Patient follow-up and data recording is being conducted by four associates who are unaware of the CPR interventions. Daily follow-up to day 28 post-arrest includes physiological variables, medication and other treatment interventions, results of laboratory and diagnostic studies (including serum interleukins), and determination of the sequential organ dysfunction assessment (SOFA) score. Physiological variables include hemodynamics (arterial and central venous pressure, and heart rate), gas exchange and respiratory mechanics, body temperature, urinary output and fluid balance. Patient neurological status is being assessed with the Glasgow Coma Score. Following successful weaning from mechanical ventilation, cerebral performance is being assessed with the cerebral performance scale. Additional follow-up data include hospital/intensive care unit (ICU)-related morbidity, length of ICU/hospital stay, and cerebral performance/residual disabilities at hospital discharge. Primary end-points are ROSC for ≥ 15 min, and survival to discharge either to home or to a rehabilitation facility. Secondary end-points include arterial pressure during CPR and at 15-20 min following ROSC, the intensity of the post-arrest systemic inflammatory response, the number of organ failure-free days during follow-up, and neurological status and cerebral performance during follow up and at discharge from the hospital. In patients who survived for more than 28 days after the occurrence of the cardiac arrest, it has been ultimately feasible to collect full data on organ failure free days and medication until 60 days following randomization. Consequently, the analysis of the data during April and May 2007, actually enabled the calculation of the organ failure free days, the comparison of the length of the use of various drugs between the two groups, and the construction of survival curves and conduct of Kaplan-Meier analysis and Cox regression analysis until day 60 following randomization. As in previous cardiac arrest trials, the requirement of informed consent before the administration of the drug combination during CPR has been waived. Informed consent was actually obtained for corticosteroid treatment of postresuscitation shock and for the blood sampling required for determination of plasma cytokine concentration after ROSC. ### Conditions Module **Conditions:** - Heart Arrest **Keywords:** - Heart Arrest - Cardiopulmonary Resuscitation - Epinephrine - Vasopressin - Adrenal Cortex Hormones ### 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:** 100 **Type:** ACTUAL **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Patients with refractory cardiac arrest (as defined in methods) treated according to the latest guidelines for resuscitation and receiving placebo instead of vasopressin and corticosteroids **Intervention Names:** - Drug: Placebo, Epinephrine, Placebo **Label:** Control Group **Type:** PLACEBO_COMPARATOR #### Arm Group 2 **Description:** Patients with refractory cardiac arrest treated with combined vasopressin, epinephrine, and methylprednisolone during resuscitation. Patients receive stress-dose hydrocortisone for postresuscitation shock **Intervention Names:** - Drug: Vasopressin, Epinephrine, and Steroids **Label:** Study Group **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Study Group **Description:** During resuscitation, study group patients receive vasopresssin \[20 IU IV maximum dose = 100 IU\] and methylprednisolone (40 mg IV). Epinephrine is given to both groups according to guidelines for resuscitation 2005. In the study group, postresuscitation shock is treated with stress-dose hydrocortisone. **Name:** Vasopressin, Epinephrine, and Steroids **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Control Group **Description:** Epinephrine is given to both groups according to guidelines for resuscitation 2005. Control group patients receive placebo instead of vasopressin and steroids. **Name:** Placebo, Epinephrine, Placebo **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Measure:** 1) Return of Spontaneous Circulation for > 15 min and 2) Survival to discharge either to home or to a rehabilitation facility. **Time Frame:** 60 days (actual) #### Secondary Outcomes **Measure:** Sequential Organ Dysfunction Assessment Score during follow-up. Organ failure free days. **Time Frame:** 60 days (actual) **Measure:** Neurological status during follow-up. **Time Frame:** 60 days (actual) **Measure:** Cerebral performance during follow-up and at discharge. **Time Frame:** 60 days (actual) **Measure:** Peri-arrest arterial pressure **Time Frame:** 30 minutes (actual) **Measure:** Plasma cytokine concentration **Time Frame:** 7 days (actual) ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Adult in-patients with cardiac arrest requiring epinephrine according to current guidelines. Exclusion Criteria: * Age \< 18 years. * Documented terminal illness (life expectancy \< 6 weeks). * Do not resuscitate status. * Cardiac arrest before arrival at hospital. * Prior enrollment into the study (i.e. second or third inhospital arrest etc.). * Corticosteroid treatment before the cardiac arrest. * Any inaccurate documentation of CPR data such as medication, number of countershocks etc. **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Athens **Country:** Greece **Facility:** Evaggelismos General Hospital **State:** Attica **Zip:** 106 75 #### Overall Officials **Official 1:** **Affiliation:** First Department of Intensive Care Medicine, Univerisy of Athens Medical School **Name:** Spyros D Mentzelopoulos, Lecturer **Role:** PRINCIPAL_INVESTIGATOR **Official 2:** **Affiliation:** First Department of Intensive Care Medicine, Univerisy of Athens Medical School **Name:** Charis Roussos, Professor **Role:** STUDY_CHAIR **Official 3:** **Affiliation:** First Department of Intensive Care Medicine, Univerisy of Athens Medical School **Name:** Spyros G Zakynthinos, As Professor **Role:** STUDY_DIRECTOR ### References Module #### References **Citation:** Wenzel V, Krismer AC, Arntz HR, Sitter H, Stadlbauer KH, Lindner KH; European Resuscitation Council Vasopressor during Cardiopulmonary Resuscitation Study Group. A comparison of vasopressin and epinephrine for out-of-hospital cardiopulmonary resuscitation. N Engl J Med. 2004 Jan 8;350(2):105-13. doi: 10.1056/NEJMoa025431. **PMID:** 14711909 **Citation:** Stiell IG, Hebert PC, Wells GA, Vandemheen KL, Tang AS, Higginson LA, Dreyer JF, Clement C, Battram E, Watpool I, Mason S, Klassen T, Weitzman BN. Vasopressin versus epinephrine for inhospital cardiac arrest: a randomised controlled trial. Lancet. 2001 Jul 14;358(9276):105-9. doi: 10.1016/S0140-6736(01)05328-4. **PMID:** 11463411 **Citation:** Holmberg MJ, Granfeldt A, Mentzelopoulos SD, Andersen LW. Vasopressin and glucocorticoids for in-hospital cardiac arrest: A systematic review and meta-analysis of individual participant data. Resuscitation. 2022 Feb;171:48-56. doi: 10.1016/j.resuscitation.2021.12.030. Epub 2022 Jan 3. Erratum In: Resuscitation. 2023 Sep;190:109929. **PMID:** 34990764 **Citation:** Mentzelopoulos SD, Zakynthinos SG, Tzoufi M, Katsios N, Papastylianou A, Gkisioti S, Stathopoulos A, Kollintza A, Stamataki E, Roussos C. Vasopressin, epinephrine, and corticosteroids for in-hospital cardiac arrest. Arch Intern Med. 2009 Jan 12;169(1):15-24. doi: 10.1001/archinternmed.2008.509. **PMID:** 19139319 ## 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: M9411 - Name: Heart Arrest - Relevance: HIGH - As Found: Heart Arrest - ID: M9419 - Name: Heart Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000006323 - Term: Heart Arrest ### Intervention Browse Module - Ancestors - ID: D000000316 - Term: Adrenergic alpha-Agonists - ID: D000000322 - Term: Adrenergic Agonists - ID: D000018663 - Term: Adrenergic Agents - ID: D000018377 - Term: Neurotransmitter Agents - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000000318 - Term: Adrenergic beta-Agonists - ID: D000001993 - Term: Bronchodilator Agents - ID: D000001337 - Term: Autonomic Agents - ID: D000018373 - Term: Peripheral Nervous System Agents - ID: D000018927 - Term: Anti-Asthmatic Agents - ID: D000019141 - Term: Respiratory System Agents - ID: D000009184 - Term: Mydriatics - ID: D000013566 - Term: Sympathomimetics - ID: D000014662 - Term: Vasoconstrictor Agents - ID: D000006490 - Term: Hemostatics - ID: D000003029 - Term: Coagulants - ID: D000050034 - Term: Antidiuretic Agents - ID: D000045283 - Term: Natriuretic Agents ### Intervention Browse Module - Browse Branches - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: NaAg - Name: Natriuretic Agents - Abbrev: VaCoAg - Name: Vasoconstrictor Agents - Abbrev: Coag - Name: Coagulants - Abbrev: Infl - Name: Anti-Inflammatory Agents - Abbrev: ANeo - Name: Antineoplastic Agents - Abbrev: Resp - Name: Respiratory System Agents - Abbrev: AnEm - Name: Antiemetics - Abbrev: NeuroAg - Name: Neuroprotective Agents - Abbrev: Gast - Name: Gastrointestinal Agents - Abbrev: AA - Name: Amino Acids ### Intervention Browse Module - Browse Leaves - ID: M9789 - Name: Hormones - Relevance: LOW - As Found: Unknown - ID: M17414 - Name: Vasopressins - Relevance: HIGH - As Found: Anti-VEGF - ID: M4437 - Name: Arginine Vasopressin - Relevance: HIGH - As Found: Anti-VEGF - ID: M14120 - Name: Prednisolone - Relevance: LOW - As Found: Unknown - ID: M7992 - Name: Epinephrine - Relevance: HIGH - As Found: Growth - ID: M9912 - Name: Hydrocortisone - Relevance: LOW - As Found: Unknown - ID: M11749 - Name: Methylprednisolone - 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: M1833 - Name: Methylprednisolone Acetate - Relevance: LOW - As Found: Unknown - ID: M11750 - Name: Methylprednisolone Hemisuccinate - Relevance: LOW - As Found: Unknown - ID: M229449 - Name: Prednisolone acetate - Relevance: LOW - As Found: Unknown - ID: M211887 - Name: Prednisolone hemisuccinate - Relevance: LOW - As Found: Unknown - ID: M248881 - Name: Prednisolone phosphate - Relevance: LOW - As Found: Unknown - ID: M30371 - Name: Racepinephrine - Relevance: HIGH - As Found: Growth - ID: M211043 - Name: Epinephryl borate - Relevance: HIGH - As Found: Growth - ID: M20746 - Name: Adrenergic Agents - Relevance: LOW - As Found: Unknown - ID: M3668 - Name: Adrenergic alpha-Agonists - Relevance: LOW - As Found: Unknown - ID: M3673 - Name: Adrenergic Agonists - Relevance: LOW - As Found: Unknown - ID: M20504 - Name: Neurotransmitter Agents - Relevance: LOW - As Found: Unknown - ID: M3670 - Name: Adrenergic beta-Agonists - Relevance: LOW - As Found: Unknown - ID: M5269 - Name: Bronchodilator Agents - Relevance: LOW - As Found: Unknown - ID: M20963 - Name: Anti-Asthmatic Agents - Relevance: LOW - As Found: Unknown - ID: M21137 - Name: Respiratory System Agents - Relevance: LOW - As Found: Unknown - ID: M12139 - Name: Mydriatics - Relevance: LOW - As Found: Unknown - ID: M16345 - Name: Sympathomimetics - Relevance: LOW - As Found: Unknown - ID: M17409 - Name: Vasoconstrictor Agents - Relevance: LOW - As Found: Unknown - ID: M9576 - Name: Hemostatics - Relevance: LOW - As Found: Unknown - ID: M6259 - Name: Coagulants - Relevance: LOW - As Found: Unknown - ID: T1 - Name: Arginine - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000014667 - Term: Vasopressins - ID: D000001127 - Term: Arginine Vasopressin - ID: D000004837 - Term: Epinephrine - ID: D000064705 - Term: Racepinephrine - ID: C000018285 - Term: Epinephryl borate ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04413279 **Brief Title:** Lipiflow Treatment Alone vs. Lipiflow + Dextenza Treatment for Dry Eye Disease **Official Title:** Intracanalicular Dexamethasone Used in Conjunction With LipiFlow for the Treatment of Meibomian Gland Dysfunction in Patients With Evaporative Dry Eye Disease and Evidence of Clinically Significant Inflammation #### Organization Study ID Info **ID:** The DIERKER Study #### Organization **Class:** NETWORK **Full Name:** Eye Surgeons of Indiana ### Status Module #### Completion Date **Date:** 2021-07-01 **Type:** ACTUAL #### Last Update Post Date **Date:** 2022-04-18 **Type:** ACTUAL **Last Update Submit Date:** 2022-04-11 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2021-07-01 **Type:** ACTUAL #### Start Date **Date:** 2020-08-01 **Type:** ACTUAL **Status Verified Date:** 2022-04 #### Study First Post Date **Date:** 2020-06-02 **Type:** ACTUAL **Study First Submit Date:** 2020-05-28 **Study First Submit QC Date:** 2020-05-28 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** Ocular Therapeutix, Inc. #### Lead Sponsor **Class:** NETWORK **Name:** Eye Surgeons of Indiana #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** True **Oversight Has DMC:** False ### Description Module **Brief Summary:** To evaluate the benefit of treatment with a physician administered intracanalicular dexamethasone insert in evaporative dry eye disease (DED) patients with meibomian gland disfunction (MGD) and underlying inflammation undergoing LipiFlow Thermal Pulsation. **Detailed Description:** This prospective, open-label, single-center, non-randomized, investigator-sponsored clinical study seeks to investigate the benefit of managing patients with DED secondary to MGD with a sustained release intracanalicular dexamethasone (0.4 mg) insert in addition to LipiFlow Thermal Pulsation compared to LipiFlow Thermal Pulsation alone. In addition, this study will evaluate the ease of Dextenza insertion and the patient preference for therapy. After screening a given patient for inclusion and exclusion criteria, and gaining informed consent, each eye will undergo LipiFlow Thermal Pulsation on the same day. The most symptomatic eye will be selected to receive DEXTENZA® insertion on the day of the procedure (study eye), while the other eye will be assigned to a receive a sham punctum dilation (control eye). If there is no obvious symptomatic difference, the right eye will receive the intracanalicular insert. Per patient, the study period will last for approximately 12 weeks after the LipiFlow procedure, consisting of one screening visit, one treatment v4isit and 3 post-procedure follow-up visits (week 1, week 4 and week 12). At week 1, week 4 and week 12, primary and secondary endpoints will be assessed alongside standard-of-care procedures. Adjusting for enrollment period, the study will last a total of approximately 4 months. ### Conditions Module **Conditions:** - Dry Eye Syndromes ### Design Module #### Design Info **Allocation:** NON_RANDOMIZED **Intervention Model:** CROSSOVER ##### Masking Info **Masking:** SINGLE **Who Masked:** - PARTICIPANT **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 20 **Type:** ACTUAL **Phases:** - PHASE4 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Patients with dry eye disease Lipiflow only **Intervention Names:** - Procedure: LipiFlow Thermal Pulsation **Label:** Lipiflow Only Group **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** Patients with dry eye disease Lipiflow + Dextenza **Intervention Names:** - Drug: Dexamethasone Intracanalicular Insert, 0.4mg with LipiFlow Thermal Pulsation **Label:** Lipiflow + Dextenza Group **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Lipiflow Only Group **Description:** To manage patients with dry eye disease secondary to MGD **Name:** LipiFlow Thermal Pulsation **Type:** PROCEDURE #### Intervention 2 **Arm Group Labels:** - Lipiflow + Dextenza Group **Description:** to investigate the benefit of managing patients with DED secondary to MGD with a sustained release intracanalicular dexamethasone (0.4 mg) insert in addition to LipiFlow Thermal Pulsation **Name:** Dexamethasone Intracanalicular Insert, 0.4mg with LipiFlow Thermal Pulsation **Other Names:** - Dextenza **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** As measured on a grading scale 1 to 4 and graded by the physician **Measure:** Change from baseline in meibomian gland scores (expressibility and quality) **Time Frame:** Assessed at Baseline, Week 1, Week 4 and Week 12 **Description:** As measured by COMTOL Survey **Measure:** Patient preference for **Time Frame:** Assessed at Week 12 #### Secondary Outcomes **Description:** As measured by InflammaDry **Measure:** Mean change in MMP-9 **Time Frame:** Assessed at Baseline, Week 1, Week 4 and Week 12 Visit **Description:** As measured by sodium fluorescein and lissamine green **Measure:** Mean change in ocular surface staining **Time Frame:** Assessed at Baseline, Week 1, Week 4 and Week 12 Visit **Description:** As measured by TBUT testing **Measure:** Mean change in tear break-up time (TBUT) **Time Frame:** Assessed at Baseline, Week 1, Week 4 and Week 12 Visit **Description:** As measured by TearLab **Measure:** Mean change in tear osmolarity **Time Frame:** Assessed at Baseline, Week 1, Week 4 and Week 12 Visit **Description:** As measured by DEQ-5 Questionnaire (Dry Eye Questionnaire. The DEQ-5 is comprised of 5 items: frequency of watery eyes, discomfort, and dryness (0-4 scale) and late day discomfort and dryness intensity (0-5 scale). Higher numbers indicate more severe symptoms. **Measure:** Mean change in DEQ-5 **Time Frame:** Assessed at Baseline, Week 1, Week 4 and Week 12 Visit **Description:** As measured by ETDRS chart **Measure:** Mean change in Best-corrected Visual Acuity (BCVA) **Time Frame:** Assessed at Baseline, Week 1, Week 4 and Week 12 Visit ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: A patient's study eye must meet the following criteria to be eligible for inclusion in the study: * 18 years of age or older * Evaporative DED with MGD and clinically significant inflammation * Willing and able to comply with clinic visits and study related procedures * Willing and able to sign the informed consent form Exclusion Criteria: A patient who meets any of the following criteria will be excluded from the study: * Patients under the age of 18. * Pregnancy (must be ruled out in women of child-bearing age with pregnancy test) * Active infectious systemic disease * Active infectious ocular or extraocular disease * Altered nasolacrimal flow of either acquired, induced, or congenital origin * Hypersensitivity to dexamethasone * Patient being treated with either topical, oral, or intravenous steroids * Patients with severe disease that warrants critical attention, deemed unsafe for the study by the investigator **Sex:** ALL **Standard Ages:** - CHILD - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Indianapolis **Country:** United States **Facility:** Eye Surgeons of Indiana **State:** Indiana **Zip:** 46040 #### Overall Officials **Official 1:** **Affiliation:** Eye Surgeons of Indiana **Name:** Damon Dierker, OD, FAAO **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000007766 - Term: Lacrimal Apparatus Diseases - ID: D000007637 - Term: Keratoconjunctivitis - ID: D000003231 - Term: Conjunctivitis - ID: D000003229 - Term: Conjunctival Diseases - ID: D000007634 - Term: Keratitis - ID: D000003316 - Term: Corneal Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC11 - Name: Eye Diseases ### Condition Browse Module - Browse Leaves - ID: M10293 - Name: Inflammation - Relevance: LOW - As Found: Unknown - ID: M16355 - Name: Syndrome - Relevance: LOW - As Found: Unknown - ID: M18040 - Name: Dry Eye Syndromes - Relevance: HIGH - As Found: Dry Eye - ID: M10664 - Name: Keratoconjunctivitis Sicca - Relevance: HIGH - As Found: Dry Eye - ID: M8271 - Name: Eye Diseases - Relevance: HIGH - As Found: Eye Disease - ID: M2143 - Name: Meibomian Gland Dysfunction - Relevance: LOW - As Found: Unknown - ID: M10663 - Name: Keratoconjunctivitis - Relevance: LOW - As Found: Unknown - ID: M10786 - Name: Lacrimal Apparatus Diseases - Relevance: LOW - As Found: Unknown - ID: M6455 - Name: Conjunctivitis - Relevance: LOW - As Found: Unknown - ID: M6453 - Name: Conjunctival Diseases - Relevance: LOW - As Found: Unknown - ID: M10660 - Name: Keratitis - Relevance: LOW - As Found: Unknown - ID: M6539 - Name: Corneal Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000015352 - Term: Dry Eye Syndromes - ID: D000007638 - Term: Keratoconjunctivitis Sicca - ID: D000005128 - Term: Eye Diseases ### Intervention Browse Module - Ancestors - ID: D000000893 - Term: Anti-Inflammatory Agents - ID: D000000932 - Term: Antiemetics - ID: D000001337 - Term: Autonomic Agents - ID: D000018373 - Term: Peripheral Nervous System Agents - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000005765 - Term: Gastrointestinal Agents - ID: D000005938 - Term: Glucocorticoids - ID: D000006728 - Term: Hormones - ID: D000006730 - Term: Hormones, Hormone Substitutes, and Hormone Antagonists - ID: D000018931 - Term: Antineoplastic Agents, Hormonal - ID: D000000970 - Term: Antineoplastic Agents ### Intervention Browse Module - Browse Branches - Abbrev: Infl - Name: Anti-Inflammatory Agents - Abbrev: ANeo - Name: Antineoplastic Agents - Abbrev: AnEm - Name: Antiemetics - Abbrev: Gast - Name: Gastrointestinal Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M7102 - Name: Dexamethasone - Relevance: HIGH - As Found: Children - ID: M235549 - Name: Dexamethasone acetate - Relevance: LOW - As Found: Unknown - ID: M199152 - Name: BB 1101 - Relevance: LOW - As Found: Unknown - ID: M4217 - Name: Anti-Inflammatory Agents - Relevance: LOW - As Found: Unknown - ID: M4251 - Name: Antiemetics - Relevance: LOW - As Found: Unknown - ID: M8881 - Name: Gastrointestinal Agents - Relevance: LOW - As Found: Unknown - ID: M9047 - Name: Glucocorticoids - 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: M20966 - Name: Antineoplastic Agents, Hormonal - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000003907 - Term: Dexamethasone ### Misc Info Module #### Submission Tracking - Estimated Results First Submit Date: 2023-10-04 ##### Submission Infos - MCP Release N: 3 - Release Date: 2023-10-04 - Reset Date: 2023-10-27 - Unrelease Date: Unknown - Unrelease Date Unknown: Unknown - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00756379 **Acronym:** Century **Brief Title:** Century Trial, a Randomized Lifestyle Modification Study for Management of Stable Coronary Artery Disease **Official Title:** Randomized Trial of Comprehensive Lifestyle Modifications, Optimal Pharmacological Treatment and PET Imaging for Detection and Management of Stable Coronary Artery Disease #### Organization Study ID Info **ID:** HSC-MS-08-0312 #### Organization **Class:** OTHER **Full Name:** The University of Texas Health Science Center, Houston ### Status Module #### Completion Date **Date:** 2027-05-31 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2023-09-22 **Type:** ACTUAL **Last Update Submit Date:** 2023-09-21 **Overall Status:** ACTIVE_NOT_RECRUITING #### Primary Completion Date **Date:** 2027-05-31 **Type:** ESTIMATED #### Start Date **Date:** 2009-03-11 **Type:** ACTUAL **Status Verified Date:** 2023-09 #### Study First Post Date **Date:** 2008-09-22 **Type:** ESTIMATED **Study First Submit Date:** 2008-09-18 **Study First Submit QC Date:** 2008-09-19 ### 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:** K.Lance Gould **Investigator Title:** Professor, Internal Medicine, Cardiology **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** The Century Trial is a single center Phase III randomized study sponsored by the Albert Weatherhead III Foundation and conducted by Dr. K. Lance Gould. The study hypothesis is that a combined image-treatment regimen of PET + comprehensive program of lifestyle modification and lipid lowering drugs to target lipid level will result in an improved cardiovascular risk score when compared to current standard optimal medical therapy, potentially resulting in a lower rate of death, non-fatal myocardial infarction (MI) and revascularization procedures during long term follow-up when compared with current standard of care. If our hypothesis is correct, we will not only improve our ability to prevent and treat CAD but we will also illustrate that, even with the expenses of behavioral interventions and imaging techniques, we can be very cost effective. This information may help patients at risk or with known CAD to obtain insurance coverage to prevent the disease as well as providing a more effective way of treating it. **Detailed Description:** Advances in diagnostic imaging with expensive technologies and reimbursement policies that favor illness intervention rather than primary and secondary prevention have resulted in rising costs of health care and more people being deprived of its benefits (Sultz 2004, Bodenheimer 2002). In the field of coronary artery disease (CAD) are several non-invasive imaging techniques for diagnostic and risk stratification purposes such as echocardiography, perfusion imaging (cardiac stress SPECT - single photon emission computed tomography - and stress PET - positron emission tomography), non-invasive cardiac computed tomography angiography (CTA) and combined perfusion-anatomy (PET-CT) studies. There are an estimated 40 million noninvasive cardiac tests performed each year (Mark DB 2003). For echocardiography and SPECT imaging, reimbursement from Medicare encompasses approximately 30% of all payments, totaling over $1 billion in the year 2000 (ACC 2003). There are, however, basic questions about cardiovascular imaging techniques that need to be addressed: how does technology benefit the patient? It is worth the cost? Is treatment plan enhanced? Is outcome better? Data are necessary for addressing these questions and if appropriate for acceptance among practicing physicians, patients and third party insurers. The relevance of the proposed study, the CENTURY trial, lies in its original design, testing the impact of stress perfusion imaging by PET coupled with two different intensities of clinical management strategies (standard or comprehensive respectively). This study will examine post-test resource utilization and reduction of cardiovascular risk in patients with known disease or at high risk for CAD. There will be a total of 1300 men and women enrolled with approximately 650 subjects randomized to one of two treatment arms. Eligible patients must have clinical indications for stress perfusion testing. Following confirmation of eligibility and provision of signed informed consent, patients will be randomized to one of the two possible treatment strategies. At time of randomization patients will be assigned to "PET guided + comprehensive" versus "standard medical treatment." Patients of both groups will have a baseline myocardial PET perfusion study to quantify the blood flow to the heart muscle, an electrocardiogram, an exercise treadmill stress test to assess exercise tolerance (fitness), a thorough review of the quality of their diet and a complete blood work covering individual lipid profiles. These tests and assessments will be repeated at 2 years and at 5 years. In addition, subjects assigned to the standard medical management arm will be managed by current standard care provided by their primary referring physician and will be asked to come for clinic study visits annually for 5 years to document their medical and lifestyle management. The PET scan results will be blinded until the end of the study to the standard of care management group. Subjects enrolled in the comprehensive medical management arm will have the support of a team of professionals focusing on atherosclerotic risk factor modification that involves recommended treatment to target lipid levels, blood pressure and diabetes control, smoking cessation, very low fat diet and aerobic exercise program. This is in addition to standard current medical therapy as provided by the primary referring physician. No experimental medication or procedures will be used. Clinic visits for subject's education and consulting in the comprehensive program will be performed five times during the first year and semiannually thereafter. At the end of the first 5 years, patients in the "comprehensive" medical management arm will be offered an additional 5-year follow-up at the current study location once a year. The extended follow-up on cardiovascular or other adverse events for the "current standard of care" group will be based on yearly telephone or mail follow-up. Both groups will have a full consultation visit, exercise treadmill and dipyridamole PET scan at the end of the total 10 years follow-up, replicating the current initial 5-year follow-up visit protocol. ### Conditions Module **Conditions:** - Cardiovascular Disease - Atherosclerosis - Coronary Artery Disease - Coronary Stenosis **Keywords:** - Cardiovascular disease - Atherosclerosis - Coronary artery disease - Coronary perfusion defect - Absolute coronary flow - Lifestyle management - Cardiovascular rehabilitation - Cardiovascular dietary guidelines ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** Study Intervention: PET diagnostic imaging offered in addition to current standard of care for the detection of coronary atherosclerosis. Comprehensive program of atherosclerotic risk factor modification, involving treatment to target lipid levels, blood pressure and diabetes control, smoking cessation, very low fat diet and aerobic exercise program. This is addition to standard current medical therapy as provided by primary referring physician. No experimental medication or procedure will be used. Clinic visits for patients education and consulting in the comprehensive program will be performed five times during the first year and semiannually thereafter. ##### Masking Info **Masking:** SINGLE **Who Masked:** - OUTCOMES_ASSESSOR **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 1085 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** P.E.T. guided comprehensive therapy program. The study intervention is Comprehensive therapy program for risk factor modification. The Comprehensive program of atherosclerotic risk factor modification involves treatment to target lipid levels, blood pressure and diabetes control, smoking cessation, very low fat diet and aerobic exercise program. This is in addition to standard current medical therapy as provided by primary physician. No experimental medications or procedures will be used. **Intervention Names:** - Other: Comprehensive therapy program for risk factor modification **Label:** Intensive lifestyle modification **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Current standard of care medical management as provided by primary physician. **Label:** Current standard of care **Type:** NO_INTERVENTION ### Interventions #### Intervention 1 **Arm Group Labels:** - Intensive lifestyle modification **Description:** Patients enrolled in the comprehensive therapy arm will have a baseline myocardial perfusion PET and the support of a team of professionals aiming to modify and minimize all the known CAD risk factors. During the 5 year follow-up they will be educated and guided toward a healthy lifestyle by a dietician, an exercise physiologist/cardiovascular physician specialist. **Name:** Comprehensive therapy program for risk factor modification **Other Names:** - Coronary artery disease - Lifestyle management - Atherosclerosis - Cardiovascular disease management - Cardiovascular disease reversal **Type:** OTHER ### Outcomes Module #### Other Outcomes **Description:** Will compare total cost and health outcomes of treating patients at risk or with established CAD **Measure:** Comprehensive economic analysis **Time Frame:** 2 years, 5 years and 10 years #### Primary Outcomes **Description:** Average Risk Score modification during 5 year follow-up and major cardiovascular clinical events of death and non-fatal myocardial infarction. **Measure:** 1.Clinical Endpoints- **Time Frame:** 2 years, 5 years and 10 years #### Secondary Outcomes **Description:** These measures are major events consisting of death, non-fatal MI, stroke, and revascularization procedures. **Measure:** 2. Secondary outcome **Time Frame:** 2 years, 5 years and 10 years ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Subjects must be competent to provide written informed consent. * Subjects must sign an Institutional Review Board (IRB) approved Informed Consent Form (ICF) and HIPAA Authorization prior to the initiation of any study procedures. * Men and women age ≥40 _ Indication for stress perfusion testing * Appropriate Indications for stress perfusion testing: * Suspected CAD: * Men with any chest pain syndrome and two other risk factors * Women \>50 years old with any chest pain syndrome and two other risk factors * Asymptomatic men and women \>50 years with at least three other risk factors\* or Coronary Calcium Agatston score \>400. * Diabetic men and women and two other risk factors * Documented known CAD: * Men and women asymptomatic or stable symptoms and known CAD by abnormal catheterization or prior SPECT without revascularization after \>2 years to evaluate worsening disease or * Men and women with worsening symptoms and known CAD by abnormal catheterization or prior SPECT/PET without revascularization * Men and women with chest pain syndrome and previous revascularization * Asymptomatic men and women \>5 years after coronary artery bypass graft surgery (CABG) or \>2 years after PCI * Risk factors: Diabetes, Current or recent cigarette smoking (within the last 12 months), LDL\>130, low HDL \<50 women, HDL \<45 men, history of metabolic syndrome, hypertension (SPB\>140), family history of premature (\<60 year) CAD, Atherosclerotic carotid artery disease OR atherosclerotic peripheral vascular disease (APVD) as defined by ankle-brachial index below 0.9 and/or by abnormal duplex ultrasound, CT angiography, magnetic resonance angiography (MRA) or conventional invasive angiogram or previous revascularization procedure. * Framingham's high risk criteria refers to presence of diabetes mellitus with the limitation described above (c) or 10 year absolute Coronary Heart Disease(CHD)risk of \>or= 20% (see tables Appendix A). * Chest pain is defined as Typical Angina if Exertional + Retrosternal + relieved with rest or sublingual nitroglycerin (NTG) , Atypical angina if only two of the above criteria are present and Non-anginal if one or none of the above are present. Exclusion Criteria: * Age \<40 * Low pretest likelihood of CAD (= not meeting the above criteria) * Unstable angina high risk (dynamic ST-Twave ECG changes and/or elevated troponin) * Recent MI (\<4 weeks) * Recent stroke (\<4 weeks) * CABG or percutaneous coronary intervention (PCI) within the last 6 months * Severe renal dysfunction as defined by creatinine \> 2.0 mg/dl * Active liver disease or hepatic dysfunction, AST or ALT \> x 2 the upper limit of normal (ULN) * Concomitant valvular heart disease * Left ventricular ejection fraction (LVEF) \<30% * Severe systemic hypertension defined as systolic blood pressure (SBP) \> 200 mmHg * Symptomatic sustained or non-sustained ventricular tachycardia * Morbid Obesity defined by Body Mass Index \> 35 * Sever disability to prevent therapeutic exercise not expected to resolve within 6 months * Major non-cardiac co-morbidity limiting survival or social situation/condition that in the opinion of the investigator will preclude the patient from participation in the study follow-up. * Concurrent or prior (within last 30 days) participation in other research studies using investigational drugs or devices. **Minimum Age:** 40 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Houston **Country:** United States **Facility:** Weatherhead PET Center, Memorial Hermann Hospital TMC **State:** Texas **Zip:** 77030 #### Overall Officials **Official 1:** **Affiliation:** University of Texas Medical Health Science Center at Houston **Name:** K. Lance Gould, MD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Kitkungvan D, Johnson NP, Kirkeeide R, Haynie M, Carter C, Patel MB, Bui L, Madjid M, Mendoza P, Roby AE, Hood S, Zhu H, Lai D, Sdringola S, Gould KL. Design and rationale of the randomized trial of comprehensive lifestyle modification, optimal pharmacological treatment and utilizing PET imaging for quantifying and managing stable coronary artery disease (the CENTURY study). Am Heart J. 2021 Jul;237:135-146. doi: 10.1016/j.ahj.2021.03.012. Epub 2021 Mar 21. **PMID:** 33762179 #### See Also Links **Label:** For more information about cardiac PET imaging **URL:** http://www.uth.tmc.edu/pet/ ## Derived Section ### Condition Browse Module - Ancestors - ID: D000006331 - Term: Heart 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: HIGH - As Found: Coronary Artery Disease - ID: M6546 - Name: Coronary Artery Disease - Relevance: HIGH - As Found: Coronary Artery Disease - ID: M19506 - Name: Myocardial Ischemia - Relevance: HIGH - As Found: Coronary Artery Disease - ID: M26188 - Name: Atherosclerosis - Relevance: HIGH - As Found: Atherosclerosis - ID: M6475 - Name: Constriction, Pathologic - Relevance: LOW - As Found: Unknown - ID: M22913 - Name: Coronary Stenosis - Relevance: HIGH - As Found: Coronary Stenosis - 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: D000002318 - Term: Cardiovascular Diseases - ID: D000003324 - Term: Coronary Artery Disease - ID: D000017202 - Term: Myocardial Ischemia - ID: D000003327 - Term: Coronary Disease - ID: D000050197 - Term: Atherosclerosis - ID: D000023921 - Term: Coronary Stenosis ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT01587079 **Brief Title:** Glycopyrrolate/Formoterol Fumarate MDI Compared With Spiriva® as An Active Control in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease **Official Title:** A Randomized, Double Blind, (Test Products), Chronic Dosing (7 Days), Four Period, Eight Treatment , Incomplete Block, Cross Over, Multi Center Study to Assess Efficacy and Safety of Five Doses of PT003, One Dose of PT001 and One Dose of PT005 in Patients With Moderate to Severe COPD, Compared With Spiriva® Handihaler® (Tiotropium Bromide 18 µg, Open Label) as Active Control #### Organization Study ID Info **ID:** PT003005 #### Organization **Class:** INDUSTRY **Full Name:** Pearl Therapeutics, Inc. ### Status Module #### Completion Date **Date:** 2012-10 **Type:** ACTUAL #### Disp First Post Date **Date:** 2013-11-14 **Type:** ESTIMATED **Disp First Submit Date:** 2013-10-22 **Disp First Submit QC Date:** 2013-10-22 #### Expanded Access Info #### Last Update Post Date **Date:** 2016-06-30 **Type:** ESTIMATED **Last Update Submit Date:** 2016-05-23 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2012-09 **Type:** ACTUAL #### Results First Post Date **Date:** 2016-06-30 **Type:** ESTIMATED **Results First Submit Date:** 2016-05-23 **Results First Submit QC Date:** 2016-05-23 #### Start Date **Date:** 2012-04 **Status Verified Date:** 2016-05 #### Study First Post Date **Date:** 2012-04-27 **Type:** ESTIMATED **Study First Submit Date:** 2012-04-25 **Study First Submit QC Date:** 2012-04-26 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Pearl Therapeutics, Inc. #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** The primary objective of this study is to assess the efficacy of Glycopyrrolate/Formoterol Fumarate MDI relative to individual components (GP MDI and FF MDI) in subjects with moderate to severe COPD ### Conditions Module **Conditions:** - Chronic Obstructive Pulmonary Disease **Keywords:** - COPD ### 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:** 159 **Type:** ACTUAL **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** PT003 MDI Dose 1 **Intervention Names:** - Drug: PT003 **Label:** PT003 (Dose 1) **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** PT003 MDI Dose 2 **Intervention Names:** - Drug: PT003 **Label:** PT003 (Dose 2) **Type:** EXPERIMENTAL #### Arm Group 3 **Description:** PT003 MDI Dose 3 **Intervention Names:** - Drug: PT003 **Label:** PT003 (Dose 3) **Type:** EXPERIMENTAL #### Arm Group 4 **Description:** PT003 MDI Dose 4 **Intervention Names:** - Drug: PT003 **Label:** PT003 (Dose 4) **Type:** EXPERIMENTAL #### Arm Group 5 **Description:** PT003 MDI Dose 5 **Intervention Names:** - Drug: PT003 **Label:** PT003 (Dose 5) **Type:** EXPERIMENTAL #### Arm Group 6 **Description:** PT001 MDI **Intervention Names:** - Drug: PT001 **Label:** PT001 **Type:** EXPERIMENTAL #### Arm Group 7 **Description:** PT005 MDI **Intervention Names:** - Drug: PT005 **Label:** PT005 **Type:** EXPERIMENTAL #### Arm Group 8 **Description:** Tiotropium Bromide **Intervention Names:** - Drug: Tiotropium inhalation powder **Label:** Spiriva® Handihaler® **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - PT003 (Dose 1) - PT003 (Dose 2) - PT003 (Dose 3) - PT003 (Dose 4) - PT003 (Dose 5) **Description:** PT003 MDI administered as two puffs BID for 7 days **Name:** PT003 **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - PT001 **Description:** PT001 MDI administered as two puffs BID for 7 days **Name:** PT001 **Type:** DRUG #### Intervention 3 **Arm Group Labels:** - PT005 **Description:** PT005 MDI administered as two puffs BID for 7 days **Name:** PT005 **Type:** DRUG #### Intervention 4 **Arm Group Labels:** - Spiriva® Handihaler® **Description:** Taken as 1 capsule containing 18 µg of Tiotropium via the Handihaler DPI for 7 days **Name:** Tiotropium inhalation powder **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** FEV1 AUC 0-12 **Measure:** FEV1 AUC 0-12 on Day 7 **Time Frame:** Day 7 #### Secondary Outcomes **Description:** Peak change from Baseline in FEV1 on Treatment **Measure:** Peak Change From Baseline in FEV1 on Treatment Day 1 **Time Frame:** Day 1 **Description:** Time to onset of action (\>10% improvement in FEV1) **Measure:** Time to Onset of Action (>10% Improvement in FEV1) on Day 1 **Time Frame:** Day 1 **Description:** Proportion of subjects achieving \>=12% improvement in FEV1 **Measure:** Proportion of Subjects Achieving >=12% Improvement in FEV1 on Day 1 **Time Frame:** Day 1 **Description:** Peak change from baseline in Inspiratory Capacity **Measure:** Peak Change From Baseline in Inspiratory Capacity on Day 1 **Time Frame:** Day 1 **Description:** Change from baseline in morning pre-dose trough FEV1 **Measure:** Change From Baseline in Morning Pre-dose Trough FEV1 on Day 7 **Time Frame:** Day 7 **Description:** Peak change from baseline in FEV1 Day 7 **Measure:** Peak Change From Baseline in FEV1 on Day 7 **Time Frame:** Day 7 **Description:** Change from baseline in morning pre-dose trough IC **Measure:** Change From Baseline in Morning Pre-dose Trough IC on Day 7 **Time Frame:** Day 7 **Description:** Peak change from baseline IC **Measure:** Peak Change From Baseline IC on Day 7 **Time Frame:** Day 7 **Description:** Change from baseline at evening 12-hour post-dose trough FEV1 **Measure:** Change From Baseline at Evening 12-hour Post-dose Trough FEV1 on Day 7 **Time Frame:** Day 7 **Description:** Change from baseline in mean morning pre-dose daily peak flow readings **Measure:** Change From Baseline in Mean Morning Pre-dose Daily Peak Flow Readings on Day 7 **Time Frame:** Day 7 **Description:** Change from baseline in mean morning post-dose daily peak flow readings on **Measure:** Change From Baseline in Mean Morning Post-dose Daily Peak Flow Readings on Day 7 **Time Frame:** Day 7 **Description:** Change from baseline in mean evening pre-dose daily peak flow readings (BID treatments only) **Measure:** Change From Baseline in Mean Evening Pre-dose Daily Peak Flow Readings on Day 7 **Time Frame:** Day 7 **Description:** Change from baseline in mean evening post-dose daily peak flow readings (12 Hours post-dose for Spiriva) **Measure:** Change From Baseline in Mean Evening Post-dose Daily Peak Flow Readings on Day 7 **Time Frame:** Day 7 ### Eligibility Module **Eligibility Criteria:** Key Inclusion Criteria: * Signed written informed consent * 40 - 80 years of age * Clinical history of COPD with airflow limitation that is not fully reversible * Females of non-child bearing potential or females of child bearing potential with negative pregnancy test and acceptable contraceptive methods * Current/former smokers with at least a 10 pack-year history of cigarette smoking * A measured post-bronchodilator FEV1/FVC ratio of \< or = 0.70 * A measured post-bronchodilator FEV1 \> or = 750ml or 30% predicted and \< or = 80% of predicted normal values * Able to change COPD treatment as required by protocol Key Exclusion Criteria: * Women who are pregnant or lactating * Primary diagnosis of asthma * Alpha-1 antitrypsin deficiency as the cause of COPD * Active pulmonary diseases * Prior lung volume reduction surgery * Abnormal chest X-ray not due to the presence of COPD * Hospitalized due to poorly controlled COPD within 3 months of Screening * Clinically significant medical conditions that preclude participation in the study (e.g. clinically significant abnormal ECG, uncontrolled hypertension, glaucoma, symptomatic prostatic hypertrophy) * Cancer that has not been in complete remission for at least 5 years * Treatment with investigational study drug or participation in another clinical trial or study within the last 30 days or 5 half lives Other inclusion/exclusion criteria as defined in the protocol **Maximum Age:** 80 Years **Minimum Age:** 40 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Glendale **Country:** United States **Facility:** Pearl Investigative Site **State:** Arizona **Location 2:** **City:** Rancho Mirage **Country:** United States **Facility:** Pearl Investigative Site **State:** California **Location 3:** **City:** Waterbury **Country:** United States **Facility:** Pearl Investigative Site **State:** Connecticut **Location 4:** **City:** Clearwater **Country:** United States **Facility:** Pearl Investigative Site **State:** Florida **Zip:** 33765 **Location 5:** **City:** Clearwater **Country:** United States **Facility:** Pearl Investigative Site **State:** Florida **Location 6:** **City:** Pensacola **Country:** United States **Facility:** Pearl Investigative Site **State:** Florida **Location 7:** **City:** Winter Park **Country:** United States **Facility:** Pearl Investigative Site **State:** Florida **Zip:** 32789 **Location 8:** **City:** Lafayette **Country:** United States **Facility:** Pearl Investigative Site **State:** Louisiana **Location 9:** **City:** North Dartmouth **Country:** United States **Facility:** Pearl Investigative Site **State:** Massachusetts **Location 10:** **City:** Fridley **Country:** United States **Facility:** Pearl Investigative Site **State:** Minnesota **Location 11:** **City:** St. Louis **Country:** United States **Facility:** Pearl Investigative Site **State:** Missouri **Location 12:** **City:** Summit **Country:** United States **Facility:** Pearl Investigative Site **State:** New Jersey **Location 13:** **City:** Cincinnati **Country:** United States **Facility:** Pearl Investigative Site **State:** Ohio **Location 14:** **City:** Medford **Country:** United States **Facility:** Pearl Investigative Site **State:** Oregon **Zip:** 97504 **Location 15:** **City:** Medford **Country:** United States **Facility:** Pearl Investigative Site **State:** Oregon **Location 16:** **City:** Rock Hill **Country:** United States **Facility:** Pearl Investigative Site **State:** South Carolina **Location 17:** **City:** Spartanburg **Country:** United States **Facility:** Pearl Investigative Site **State:** South Carolina **Zip:** 29303 **Location 18:** **City:** San Antonio **Country:** United States **Facility:** Pearl Investigative Site **State:** Texas **Location 19:** **City:** Morgantown **Country:** United States **Facility:** Pearl Investigative Site **State:** West Virginia #### Overall Officials **Official 1:** **Affiliation:** Pearl Therapeutics, Inc. **Name:** Colin Reisner, MD **Role:** STUDY_DIRECTOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000012140 - Term: Respiratory Tract Diseases - ID: D000002908 - Term: Chronic Disease - ID: D000020969 - Term: Disease Attributes - ID: D000010335 - Term: Pathologic Processes ### 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: HIGH - As Found: Pulmonary Disease - ID: M11170 - Name: Lung Diseases, Obstructive - Relevance: HIGH - As Found: Obstructive Pulmonary Disease - ID: M23449 - Name: Pulmonary Disease, Chronic Obstructive - Relevance: HIGH - As Found: Chronic Obstructive Pulmonary Disease - ID: M14977 - Name: Respiratory Tract Diseases - 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 - ID: T4202 - Name: Oculocerebral Syndrome With Hypopigmentation - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000008171 - Term: Lung Diseases - ID: D000008173 - Term: Lung Diseases, Obstructive - ID: D000029424 - Term: Pulmonary Disease, Chronic Obstructive ### Intervention Browse Module - Ancestors - ID: D000001993 - Term: Bronchodilator Agents - ID: D000001337 - Term: Autonomic Agents - ID: D000018373 - Term: Peripheral Nervous System Agents - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000018927 - Term: Anti-Asthmatic Agents - ID: D000019141 - Term: Respiratory System Agents - ID: D000010276 - Term: Parasympatholytics - ID: D000018680 - Term: Cholinergic Antagonists - ID: D000018678 - Term: Cholinergic Agents - ID: D000018377 - Term: Neurotransmitter Agents - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action ### Intervention Browse Module - Browse Branches - Abbrev: AntiConv - Name: Anticonvulsants - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: AdjAn - Name: Adjuvants, Anesthesia - Abbrev: Resp - Name: Respiratory System Agents ### Intervention Browse Module - Browse Leaves - ID: M5241 - Name: Bromides - Relevance: LOW - As Found: Unknown - ID: M9130 - Name: Glycopyrrolate - Relevance: LOW - As Found: Unknown - ID: M304 - Name: Formoterol Fumarate - Relevance: LOW - As Found: Unknown - ID: M416 - Name: Tiotropium Bromide - Relevance: HIGH - As Found: Melanoma - ID: M5269 - Name: Bronchodilator Agents - Relevance: LOW - As Found: Unknown - ID: M20963 - Name: Anti-Asthmatic Agents - Relevance: LOW - As Found: Unknown - ID: M21137 - Name: Respiratory System Agents - Relevance: LOW - As Found: Unknown - ID: M13189 - Name: Parasympatholytics - Relevance: LOW - As Found: Unknown - ID: M20760 - Name: Cholinergic Antagonists - Relevance: LOW - As Found: Unknown - ID: M20758 - Name: Cholinergic Agents - Relevance: LOW - As Found: Unknown - ID: M20504 - Name: Neurotransmitter Agents - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000069447 - Term: Tiotropium Bromide ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module **Description:** Safety Population - All subjects who were randomized, received at least 1 dose of a study treatment, and had a post-baseline safety assessment for that treatment. #### Event Groups **Group ID:** EG000 **Title:** GP MDI 18 μg (PT001) **Description:** 18 μg **ID:** EG000 **Other Num Affected:** 8 **Other Num at Risk:** 66 **Serious Number Affected:** 1 **Serious Number At Risk:** 66 **Title:** GP MDI 18 μg (PT001) **Group ID:** EG001 **Title:** GFF MDI 18/9.6 μg (PT003) **Description:** 18/9.6 μg **ID:** EG001 **Other Num Affected:** 2 **Other Num at Risk:** 71 **Serious Number Affected:** 1 **Serious Number At Risk:** 71 **Title:** GFF MDI 18/9.6 μg (PT003) **Group ID:** EG002 **Title:** GFF MDI 9/9.6 μg (PT003) **Description:** 9/9.6 μg **ID:** EG002 **Other Num Affected:** 8 **Other Num at Risk:** 70 **Serious Number At Risk:** 70 **Title:** GFF MDI 9/9.6 μg (PT003) **Group ID:** EG003 **Title:** GFF MDI 4.6/9.6 μg (PT003) **Description:** 4.6/9.6 μg **ID:** EG003 **Other Num Affected:** 5 **Other Num at Risk:** 67 **Serious Number At Risk:** 67 **Title:** GFF MDI 4.6/9.6 μg (PT003) **Group ID:** EG004 **Title:** GFF MDI 2.4/9.6 μg (PT003) **Description:** 2.4/9.6 μg **ID:** EG004 **Other Num Affected:** 9 **Other Num at Risk:** 71 **Serious Number Affected:** 1 **Serious Number At Risk:** 71 **Title:** GFF MDI 2.4/9.6 μg (PT003) **Group ID:** EG005 **Title:** GFF MDI 1.2/9.6 μg (PT003) **Description:** 1.2/9.6 μg **ID:** EG005 **Other Num Affected:** 2 **Other Num at Risk:** 68 **Serious Number Affected:** 2 **Serious Number At Risk:** 68 **Title:** GFF MDI 1.2/9.6 μg (PT003) **Group ID:** EG006 **Title:** FF MDI 9.6 μg (PT005) **Description:** 9.6 μg **ID:** EG006 **Other Num Affected:** 8 **Other Num at Risk:** 73 **Serious Number Affected:** 1 **Serious Number At Risk:** 73 **Title:** FF MDI 9.6 μg (PT005) **Group ID:** EG007 **Title:** Spiriva **Description:** 18 μg **ID:** EG007 **Other Num Affected:** 6 **Other Num at Risk:** 71 **Serious Number At Risk:** 71 **Title:** Spiriva **Frequency Threshold:** 5 #### Other Events **Term:** Dry Mouth **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA **Term:** Tremor **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA #### Serious Events **Term:** Cardio-Respiratory arrest **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA ##### Stats **Group ID:** EG000 **Num At Risk:** 66 **Group ID:** EG001 **Num At Risk:** 71 **Group ID:** EG002 **Num At Risk:** 70 **Group ID:** EG003 **Num At Risk:** 67 **Group ID:** EG004 **Num At Risk:** 71 **Group ID:** EG005 **Num Affected:** 1 **Num At Risk:** 68 **Num Events:** 1 **Group ID:** EG006 **Num At Risk:** 73 **Group ID:** EG007 **Num At Risk:** 71 **Term:** Tachycardia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA ##### Stats **Group ID:** EG000 **Num At Risk:** 66 **Group ID:** EG001 **Num At Risk:** 71 **Group ID:** EG002 **Num At Risk:** 70 **Group ID:** EG003 **Num At Risk:** 67 **Group ID:** EG004 **Num At Risk:** 71 **Group ID:** EG005 **Num Affected:** 1 **Num At Risk:** 68 **Num Events:** 1 **Group ID:** EG006 **Num At Risk:** 73 **Group ID:** EG007 **Num At Risk:** 71 **Term:** Sudden Death **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA ##### Stats **Group ID:** EG000 **Num At Risk:** 66 **Group ID:** EG001 **Num At Risk:** 71 **Group ID:** EG002 **Num At Risk:** 70 **Group ID:** EG003 **Num At Risk:** 67 **Group ID:** EG004 **Num At Risk:** 71 **Group ID:** EG005 **Num At Risk:** 68 **Group ID:** EG006 **Num Affected:** 1 **Num At Risk:** 73 **Num Events:** 1 **Group ID:** EG007 **Num At Risk:** 71 **Term:** Spinal Compression fracture **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA ##### Stats **Group ID:** EG000 **Num At Risk:** 66 **Group ID:** EG001 **Num At Risk:** 71 **Group ID:** EG002 **Num At Risk:** 70 **Group ID:** EG003 **Num At Risk:** 67 **Group ID:** EG004 **Num Affected:** 1 **Num At Risk:** 71 **Num Events:** 1 **Group ID:** EG005 **Num At Risk:** 68 **Group ID:** EG006 **Num At Risk:** 73 **Group ID:** EG007 **Num At Risk:** 71 **Term:** Transient Ischaemic attack **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA ##### Stats **Group ID:** EG000 **Num At Risk:** 66 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 71 **Num Events:** 1 **Group ID:** EG002 **Num At Risk:** 70 **Group ID:** EG003 **Num At Risk:** 67 **Group ID:** EG004 **Num At Risk:** 71 **Group ID:** EG005 **Num At Risk:** 68 **Group ID:** EG006 **Num At Risk:** 73 **Group ID:** EG007 **Num At Risk:** 71 **Term:** Pneumothorax **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 66 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 71 **Group ID:** EG002 **Num At Risk:** 70 **Group ID:** EG003 **Num At Risk:** 67 **Group ID:** EG004 **Num At Risk:** 71 **Group ID:** EG005 **Num At Risk:** 68 **Group ID:** EG006 **Num At Risk:** 73 **Group ID:** EG007 **Num At Risk:** 71 **Time Frame:** SAEs and AEs were collected throughout study participation and up to 14 days following the last dose of study drug. ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 159 **Units:** Participants ### Group **ID:** BG000 **Title:** All Subjects Screened ### Measure #### Measurement **Group ID:** BG000 **Spread:** 8.6 **Value:** 62.8 **Class Title:** Age, years ### Measure #### Measurement **Group ID:** BG000 **Spread:** 47.8 **Value:** 76 **Category Title:** Female #### Measurement **Group ID:** BG000 **Spread:** 52.2 **Value:** 83 **Category Title:** Male **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 **Population Description:** ITT/Safety Population ## Results Section - More Information Module ### Certain Agreement **Other Details:** Drafts of any and all publications or presentations of this study must be submitted at least 30 days prior to submission for publication or presentation to Pearl Therapeutics for review, approval, and to ensure consistency. Pearl Therapeutics has the right to request appropriate modification to correct facts and to represent its opinions, or the opinions of the publication committee, if these differ with the proposed publication. **Restriction Type:** OTHER **Restrictive Agreement:** True ### Point of Contact **Email:** [email protected] **Organization:** Pearl Therapeutics, Inc **Phone:** 973-975-0320 **Title:** Colin Resiner, MD, FCCP, FAAAAI ## 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 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 1.415 - **Spread:** - **Upper Limit:** 1.489 - **Value:** 1.452 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 1.554 - **Spread:** - **Upper Limit:** 1.628 - **Value:** 1.591 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** 1.509 - **Spread:** - **Upper Limit:** 1.585 - **Value:** 1.547 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** 1.502 - **Spread:** - **Upper Limit:** 1.575 - **Value:** 1.539 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** 1.502 - **Spread:** - **Upper Limit:** 1.575 - **Value:** 1.538 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** 1.472 - **Spread:** - **Upper Limit:** 1.545 - **Value:** 1.508 - **Comment:** - **Group ID:** OG006 - **Lower Limit:** 1.430 - **Spread:** - **Upper Limit:** 1.505 - **Value:** 1.467 - **Comment:** - **Group ID:** OG007 - **Lower Limit:** 1.453 - **Spread:** - **Upper Limit:** 1.525 - **Value:** 1.489 **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 172 - **Spread:** - **Upper Limit:** 246 - **Value:** 209 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 302 - **Spread:** - **Upper Limit:** 376 - **Value:** 339 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** 292 - **Spread:** - **Upper Limit:** 367 - **Value:** 329 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** 311 - **Spread:** - **Upper Limit:** 386 - **Value:** 348 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** 296 - **Spread:** - **Upper Limit:** 370 - **Value:** 333 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** 275 - **Spread:** - **Upper Limit:** 349 - **Value:** 312 - **Comment:** - **Group ID:** OG006 - **Lower Limit:** 280 - **Spread:** - **Upper Limit:** 355 - **Value:** 317 - **Comment:** - **Group ID:** OG007 - **Lower Limit:** 201 - **Spread:** - **Upper Limit:** 274 - **Value:** 238 **Title:** #### Outcome Measure 3 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 27 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 65 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 51 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 62 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 65 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 66 - **Comment:** - **Group ID:** OG006 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 60 - **Comment:** - **Group ID:** OG007 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 37 **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:** 18 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 13 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 10 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 10 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 9 - **Comment:** - **Group ID:** OG006 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 - **Comment:** - **Group ID:** OG007 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 21 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 15 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 6 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 11 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 12 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 12 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 5 - **Comment:** - **Group ID:** OG006 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 12 - **Comment:** - **Group ID:** OG007 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 11 **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:** 5 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 7 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 5 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 9 - **Comment:** - **Group ID:** OG006 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 - **Comment:** - **Group ID:** OG007 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 5 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 40 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 6 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 18 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 10 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 12 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 11 - **Comment:** - **Group ID:** OG006 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 22 - **Comment:** - **Group ID:** OG007 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 26 **Title:** #### Outcome Measure 4 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 56 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 93 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 85 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 84 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 86 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 83 - **Comment:** - **Group ID:** OG006 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 80 - **Comment:** - **Group ID:** OG007 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 72 **Title:** #### Outcome Measure 5 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 131 - **Spread:** - **Upper Limit:** 278 - **Value:** 204 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 320 - **Spread:** - **Upper Limit:** 467 - **Value:** 393 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** 244 - **Spread:** - **Upper Limit:** 397 - **Value:** 320 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** 313 - **Spread:** - **Upper Limit:** 461 - **Value:** 387 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** 274 - **Spread:** - **Upper Limit:** 421 - **Value:** 347 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** 276 - **Spread:** - **Upper Limit:** 420 - **Value:** 348 - **Comment:** - **Group ID:** OG006 - **Lower Limit:** 261 - **Spread:** - **Upper Limit:** 409 - **Value:** 335 - **Comment:** - **Group ID:** OG007 - **Lower Limit:** 160 - **Spread:** - **Upper Limit:** 305 - **Value:** 233 **Title:** #### Outcome Measure 6 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 87 - **Spread:** - **Upper Limit:** 152 - **Value:** 120 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 151 - **Spread:** - **Upper Limit:** 216 - **Value:** 183 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** 117 - **Spread:** - **Upper Limit:** 184 - **Value:** 150 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** 121 - **Spread:** - **Upper Limit:** 186 - **Value:** 154 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** 130 - **Spread:** - **Upper Limit:** 195 - **Value:** 163 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** 98 - **Spread:** - **Upper Limit:** 162 - **Value:** 130 - **Comment:** - **Group ID:** OG006 - **Lower Limit:** 71 - **Spread:** - **Upper Limit:** 137 - **Value:** 104 - **Comment:** - **Group ID:** OG007 - **Lower Limit:** 90 - **Spread:** - **Upper Limit:** 155 - **Value:** 122 **Title:** #### Outcome Measure 7 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 257 - **Spread:** - **Upper Limit:** 342 - **Value:** 300 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 402 - **Spread:** - **Upper Limit:** 487 - **Value:** 444 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** 370 - **Spread:** - **Upper Limit:** 458 - **Value:** 414 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** 361 - **Spread:** - **Upper Limit:** 446 - **Value:** 403 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** 345 - **Spread:** - **Upper Limit:** 430 - **Value:** 388 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** 321 - **Spread:** - **Upper Limit:** 404 - **Value:** 363 - **Comment:** - **Group ID:** OG006 - **Lower Limit:** 289 - **Spread:** - **Upper Limit:** 375 - **Value:** 332 - **Comment:** - **Group ID:** OG007 - **Lower Limit:** 267 - **Spread:** - **Upper Limit:** 351 - **Value:** 309 **Title:** #### Outcome Measure 8 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 46 - **Spread:** - **Upper Limit:** 171 - **Value:** 109 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 123 - **Spread:** - **Upper Limit:** 246 - **Value:** 185 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** 119 - **Spread:** - **Upper Limit:** 247 - **Value:** 183 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** 153 - **Spread:** - **Upper Limit:** 278 - **Value:** 215 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** 141 - **Spread:** - **Upper Limit:** 265 - **Value:** 203 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** 89 - **Spread:** - **Upper Limit:** 212 - **Value:** 151 - **Comment:** - **Group ID:** OG006 - **Lower Limit:** 67 - **Spread:** - **Upper Limit:** 191 - **Value:** 129 - **Comment:** - **Group ID:** OG007 - **Lower Limit:** 45 - **Spread:** - **Upper Limit:** 168 - **Value:** 106 **Title:** #### Outcome Measure 9 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 149 - **Spread:** - **Upper Limit:** 297 - **Value:** 223 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 357 - **Spread:** - **Upper Limit:** 503 - **Value:** 430 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** 366 - **Spread:** - **Upper Limit:** 516 - **Value:** 441 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** 335 - **Spread:** - **Upper Limit:** 484 - **Value:** 409 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** 294 - **Spread:** - **Upper Limit:** 441 - **Value:** 368 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** 298 - **Spread:** - **Upper Limit:** 444 - **Value:** 371 - **Comment:** - **Group ID:** OG006 - **Lower Limit:** 303 - **Spread:** - **Upper Limit:** 452 - **Value:** 377 - **Comment:** - **Group ID:** OG007 - **Lower Limit:** 168 - **Spread:** - **Upper Limit:** 314 - **Value:** 241 **Title:** #### Outcome Measure 10 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 53 - **Spread:** - **Upper Limit:** 145 - **Value:** 99 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 151 - **Spread:** - **Upper Limit:** 241 - **Value:** 196 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** 115 - **Spread:** - **Upper Limit:** 209 - **Value:** 162 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** 73 - **Spread:** - **Upper Limit:** 163 - **Value:** 118 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** 87 - **Spread:** - **Upper Limit:** 179 - **Value:** 133 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** 65 - **Spread:** - **Upper Limit:** 155 - **Value:** 110 - **Comment:** - **Group ID:** OG006 - **Lower Limit:** 28 - **Spread:** - **Upper Limit:** 119 - **Value:** 73 - **Comment:** - **Group ID:** OG007 - **Lower Limit:** 85 - **Spread:** - **Upper Limit:** 174 - **Value:** 130 **Title:** #### Outcome Measure 11 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0.5 - **Spread:** - **Upper Limit:** 14.8 - **Value:** 7.6 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 18.1 - **Spread:** - **Upper Limit:** 32.4 - **Value:** 25.2 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** 9.4 - **Spread:** - **Upper Limit:** 23.9 - **Value:** 16.6 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** 5.2 - **Spread:** - **Upper Limit:** 19.5 - **Value:** 12.4 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** 10.9 - **Spread:** - **Upper Limit:** 25.1 - **Value:** 18.0 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** 6.7 - **Spread:** - **Upper Limit:** 20.8 - **Value:** 13.8 - **Comment:** - **Group ID:** OG006 - **Lower Limit:** 1.5 - **Spread:** - **Upper Limit:** 15.7 - **Value:** 8.6 - **Comment:** - **Group ID:** OG007 - **Lower Limit:** 4.5 - **Spread:** - **Upper Limit:** 18.7 - **Value:** 11.6 **Title:** #### Outcome Measure 12 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 23.0 - **Spread:** - **Upper Limit:** 39.0 - **Value:** 31.0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 50.9 - **Spread:** - **Upper Limit:** 66.7 - **Value:** 58.8 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** 46.9 - **Spread:** - **Upper Limit:** 63.1 - **Value:** 55.0 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** 38.8 - **Spread:** - **Upper Limit:** 54.6 - **Value:** 46.7 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** 44.1 - **Spread:** - **Upper Limit:** 60.0 - **Value:** 52.1 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** 41.7 - **Spread:** - **Upper Limit:** 57.4 - **Value:** 49.6 - **Comment:** - **Group ID:** OG006 - **Lower Limit:** 35.3 - **Spread:** - **Upper Limit:** 51.1 - **Value:** 43.2 - **Comment:** - **Group ID:** OG007 - **Lower Limit:** 30.0 - **Spread:** - **Upper Limit:** 45.8 - **Value:** 37.9 **Title:** #### Outcome Measure 13 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 4.6 - **Spread:** - **Upper Limit:** 18.7 - **Value:** 11.7 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 25.4 - **Spread:** - **Upper Limit:** 39.5 - **Value:** 32.5 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** 18.0 - **Spread:** - **Upper Limit:** 32.1 - **Value:** 25.0 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** 12.0 - **Spread:** - **Upper Limit:** 26.0 - **Value:** 19.0 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** 18.7 - **Spread:** - **Upper Limit:** 32.5 - **Value:** 25.6 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** 13.0 - **Spread:** - **Upper Limit:** 26.8 - **Value:** 19.9 - **Comment:** - **Group ID:** OG006 - **Lower Limit:** 9.6 - **Spread:** - **Upper Limit:** 23.4 - **Value:** 16.5 **Title:** #### Outcome Measure 14 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 26.8 - **Spread:** - **Upper Limit:** 43.2 - **Value:** 35.0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 53.1 - **Spread:** - **Upper Limit:** 69.8 - **Value:** 61.5 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** 47.8 - **Spread:** - **Upper Limit:** 64.3 - **Value:** 56.1 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** 43.3 - **Spread:** - **Upper Limit:** 59.7 - **Value:** 51.5 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** 45.6 - **Spread:** - **Upper Limit:** 61.7 - **Value:** 53.7 - **Comment:** - **Group ID:** OG005 - **Lower Limit:** 45.8 - **Spread:** - **Upper Limit:** 61.8 - **Value:** 53.8 - **Comment:** - **Group ID:** OG006 - **Lower Limit:** 40.3 - **Spread:** - **Upper Limit:** 56.4 - **Value:** 48.3 - **Comment:** - **Group ID:** OG007 - **Lower Limit:** 22.2 - **Spread:** - **Upper Limit:** 38.4 - **Value:** 30.3 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** FEV1 AUC 0-12 **Dispersion Type:** 95% Confidence Interval **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** MITT **Reporting Status:** POSTED **Time Frame:** Day 7 **Title:** FEV1 AUC 0-12 on Day 7 **Type:** PRIMARY **Unit of Measure:** Liters ##### Group **Description:** 18 μg **ID:** OG000 **Title:** GP MDI 18 μg (PT001) ##### Group **Description:** 18/9.6 μg **ID:** OG001 **Title:** GFF MDI 18/9.6 μg (PT003) ##### Group **Description:** 9/9.6 μg **ID:** OG002 **Title:** GFF/MDI 9/9.6 μg ##### Group **Description:** 4.6/9.6 μg **ID:** OG003 **Title:** GFF MDI BID 4.6/9.6 μg ##### Group **Description:** 2.4/9.6 μg **ID:** OG004 **Title:** GFF MDI 2.4/9.6 μg (PT003) ##### Group **Description:** 1.2/9.6 μg **ID:** OG005 **Title:** GFF MDI 1.2/9.6 μg (PT003) ##### Group **Description:** 9.6 μg **ID:** OG006 **Title:** FF MDI 9.6 μg ##### Group **Description:** 18 μg QD **ID:** OG007 **Title:** Spiriva 18 μg QD #### Outcome Measure 2 **Description:** Peak change from Baseline in FEV1 on Treatment **Dispersion Type:** 95% Confidence Interval **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** MITT **Reporting Status:** POSTED **Time Frame:** Day 1 **Title:** Peak Change From Baseline in FEV1 on Treatment Day 1 **Type:** SECONDARY **Unit of Measure:** Milliliters ##### Group **Description:** BID 18 μg **ID:** OG000 **Title:** GP MDI BID 18 μg ##### Group **Description:** BID 18/9.6 μg **ID:** OG001 **Title:** GFF MDI BID 18/9.6 μg ##### Group **Description:** BID 9/9.6 μg **ID:** OG002 **Title:** GFF/MDI BID 9/9.6 μg ##### Group **Description:** 4.6/9.6 μg **ID:** OG003 **Title:** GFF MDI BID 4.6/9.6 μg ##### Group **Description:** BID 2.4/9.6 μg **ID:** OG004 **Title:** GFF MDI BID 2.4/9.6 μg ##### Group **Description:** BID 1.2/9.6 μg **ID:** OG005 **Title:** GFF MDI BID 1.2/9.6 μg ##### Group **Description:** BID 9.6 μg **ID:** OG006 **Title:** FF MDI BID 9.6 μg ##### Group **Description:** 18 μg QD **ID:** OG007 **Title:** Spiriva 18 μg QD #### Outcome Measure 3 **Description:** Time to onset of action (\>10% improvement in FEV1) **Parameter Type:** NUMBER **Population Description:** MITT **Reporting Status:** POSTED **Time Frame:** Day 1 **Title:** Time to Onset of Action (>10% Improvement in FEV1) on Day 1 **Type:** SECONDARY **Unit of Measure:** Percentage ##### Group **Description:** BID 18 μg **ID:** OG000 **Title:** GP MDI BID 18 μg ##### Group **Description:** BID 18/9.6 μg **ID:** OG001 **Title:** GFF MDI BID 18/9.6 μg ##### Group **Description:** BID 9/9.6 μg **ID:** OG002 **Title:** GFF/MDI BID 9/9.6 μg ##### Group **Description:** 4.6/9.6 μg **ID:** OG003 **Title:** GFF MDI BID 4.6/9.6 μg ##### Group **Description:** BID 2.4/9.6 μg **ID:** OG004 **Title:** GFF MDI BID 2.4/9.6 μg ##### Group **Description:** BID 1.2/9.6 μg **ID:** OG005 **Title:** GFF MDI BID 1.2/9.6 μg ##### Group **Description:** BID 9.6 μg **ID:** OG006 **Title:** FF MDI BID 9.6 μg ##### Group **Description:** 18 μg QD **ID:** OG007 **Title:** Spiriva 18 μg QD #### Outcome Measure 4 **Description:** Proportion of subjects achieving \>=12% improvement in FEV1 **Parameter Type:** NUMBER **Population Description:** MITT **Reporting Status:** POSTED **Time Frame:** Day 1 **Title:** Proportion of Subjects Achieving >=12% Improvement in FEV1 on Day 1 **Type:** SECONDARY **Unit of Measure:** Percentage ##### Group **Description:** BID 18 μg **ID:** OG000 **Title:** GP MDI BID 18 μg ##### Group **Description:** BID 18/9.6 μg **ID:** OG001 **Title:** GFF MDI BID 18/9.6 μg ##### Group **Description:** BID 9/9.6 μg **ID:** OG002 **Title:** GFF/MDI BID 9/9.6 μg ##### Group **Description:** 4.6/9.6 μg **ID:** OG003 **Title:** GFF MDI BID 4.6/9.6 μg ##### Group **Description:** BID 2.4/9.6 μg **ID:** OG004 **Title:** GFF MDI BID 2.4/9.6 μg ##### Group **Description:** BID 1.2/9.6 μg **ID:** OG005 **Title:** GFF MDI BID 1.2/9.6 μg ##### Group **Description:** BID 9.6 μg **ID:** OG006 **Title:** FF MDI BID 9.6 μg ##### Group **Description:** 18 μg **ID:** OG007 **Title:** GP MDI 18 μg (PT001) #### Outcome Measure 5 **Description:** Peak change from baseline in Inspiratory Capacity **Dispersion Type:** 95% Confidence Interval **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** MITT **Reporting Status:** POSTED **Time Frame:** Day 1 **Title:** Peak Change From Baseline in Inspiratory Capacity on Day 1 **Type:** SECONDARY **Unit of Measure:** Milliliters ##### Group **Description:** BID 18 μg **ID:** OG000 **Title:** GP MDI BID 18 μg ##### Group **Description:** BID 18/9.6 μg **ID:** OG001 **Title:** GFF MDI BID 18/9.6 μg ##### Group **Description:** BID 9/9.6 μg **ID:** OG002 **Title:** GFF/MDI BID 9/9.6 μg ##### Group **Description:** 4.6/9.6 μg **ID:** OG003 **Title:** GFF MDI BID 4.6/9.6 μg ##### Group **Description:** BID 2.4/9.6 μg **ID:** OG004 **Title:** GFF MDI BID 2.4/9.6 μg ##### Group **Description:** BID 1.2/9.6 μg **ID:** OG005 **Title:** GFF MDI BID 1.2/9.6 μg ##### Group **Description:** BID 9.6 μg **ID:** OG006 **Title:** FF MDI BID 9.6 μg ##### Group **Description:** 18 μg QD **ID:** OG007 **Title:** Spiriva 18 μg QD #### Outcome Measure 6 **Description:** Change from baseline in morning pre-dose trough FEV1 **Dispersion Type:** 95% Confidence Interval **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** MITT **Reporting Status:** POSTED **Time Frame:** Day 7 **Title:** Change From Baseline in Morning Pre-dose Trough FEV1 on Day 7 **Type:** SECONDARY **Unit of Measure:** Milliliters ##### Group **Description:** BID 18 μg **ID:** OG000 **Title:** GP MDI BID 18 μg ##### Group **Description:** BID 18/9.6 μg **ID:** OG001 **Title:** GFF MDI BID 18/9.6 μg ##### Group **Description:** BID 9/9.6 μg **ID:** OG002 **Title:** GFF/MDI BID 9/9.6 μg ##### Group **Description:** 4.6/9.6 μg **ID:** OG003 **Title:** GFF MDI BID 4.6/9.6 μg ##### Group **Description:** BID 2.4/9.6 μg **ID:** OG004 **Title:** GFF MDI BID 2.4/9.6 μg ##### Group **Description:** BID 1.2/9.6 μg **ID:** OG005 **Title:** GFF MDI BID 1.2/9.6 μg ##### Group **Description:** BID 9.6 μg **ID:** OG006 **Title:** FF MDI BID 9.6 μg ##### Group **Description:** 18 μg QD **ID:** OG007 **Title:** Spiriva 18 μg QD #### Outcome Measure 7 **Description:** Peak change from baseline in FEV1 Day 7 **Dispersion Type:** 95% Confidence Interval **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** MITT **Reporting Status:** POSTED **Time Frame:** Day 7 **Title:** Peak Change From Baseline in FEV1 on Day 7 **Type:** SECONDARY **Unit of Measure:** Millliters ##### Group **Description:** BID 18 μg **ID:** OG000 **Title:** GP MDI BID 18 μg ##### Group **Description:** BID 18/9.6 μg **ID:** OG001 **Title:** GFF MDI BID 18/9.6 μg ##### Group **Description:** BID 9/9.6 μg **ID:** OG002 **Title:** GFF/MDI BID 9/9.6 μg ##### Group **Description:** 4.6/9.6 μg **ID:** OG003 **Title:** GFF MDI BID 4.6/9.6 μg ##### Group **Description:** BID 2.4/9.6 μg **ID:** OG004 **Title:** GFF MDI BID 2.4/9.6 μg ##### Group **Description:** BID 1.2/9.6 μg **ID:** OG005 **Title:** GFF MDI BID 1.2/9.6 μg ##### Group **Description:** BID 9.6 μg **ID:** OG006 **Title:** FF MDI BID 9.6 μg ##### Group **Description:** 18 μg QD **ID:** OG007 **Title:** Spiriva 18 μg QD #### Outcome Measure 8 **Description:** Change from baseline in morning pre-dose trough IC **Dispersion Type:** 95% Confidence Interval **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** MITT **Reporting Status:** POSTED **Time Frame:** Day 7 **Title:** Change From Baseline in Morning Pre-dose Trough IC on Day 7 **Type:** SECONDARY **Unit of Measure:** Millliters ##### Group **Description:** BID 18 μg **ID:** OG000 **Title:** GP MDI BID 18 μg ##### Group **Description:** BID 18/9.6 μg **ID:** OG001 **Title:** GFF MDI BID 18/9.6 μg ##### Group **Description:** BID 9/9.6 μg **ID:** OG002 **Title:** GFF/MDI BID 9/9.6 μg ##### Group **Description:** 4.6/9.6 μg **ID:** OG003 **Title:** GFF MDI BID 4.6/9.6 μg ##### Group **Description:** BID 2.4/9.6 μg **ID:** OG004 **Title:** GFF MDI BID 2.4/9.6 μg ##### Group **Description:** BID 1.2/9.6 μg **ID:** OG005 **Title:** GFF MDI BID 1.2/9.6 μg ##### Group **Description:** BID 9.6 μg **ID:** OG006 **Title:** FF MDI BID 9.6 μg ##### Group **Description:** 18 μg QD **ID:** OG007 **Title:** Spiriva 18 μg QD #### Outcome Measure 9 **Description:** Peak change from baseline IC **Dispersion Type:** 95% Confidence Interval **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** MITT **Reporting Status:** POSTED **Time Frame:** Day 7 **Title:** Peak Change From Baseline IC on Day 7 **Type:** SECONDARY **Unit of Measure:** Millliters ##### Group **Description:** BID 18 μg **ID:** OG000 **Title:** GP MDI BID 18 μg ##### Group **Description:** BID 18/9.6 μg **ID:** OG001 **Title:** GFF MDI BID 18/9.6 μg ##### Group **Description:** BID 9/9.6 μg **ID:** OG002 **Title:** GFF/MDI BID 9/9.6 μg ##### Group **Description:** 4.6/9.6 μg **ID:** OG003 **Title:** GFF MDI BID 4.6/9.6 μg ##### Group **Description:** BID 2.4/9.6 μg **ID:** OG004 **Title:** GFF MDI BID 2.4/9.6 μg ##### Group **Description:** BID 1.2/9.6 μg **ID:** OG005 **Title:** GFF MDI BID 1.2/9.6 μg ##### Group **Description:** BID 9.6 μg **ID:** OG006 **Title:** FF MDI BID 9.6 μg ##### Group **Description:** 18 μg QD **ID:** OG007 **Title:** Spiriva 18 μg QD #### Outcome Measure 10 **Description:** Change from baseline at evening 12-hour post-dose trough FEV1 **Dispersion Type:** 95% Confidence Interval **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** MITT **Reporting Status:** POSTED **Time Frame:** Day 7 **Title:** Change From Baseline at Evening 12-hour Post-dose Trough FEV1 on Day 7 **Type:** SECONDARY **Unit of Measure:** Millliters ##### Group **Description:** BID 18 μg **ID:** OG000 **Title:** GP MDI BID 18 μg ##### Group **Description:** BID 18/9.6 μg **ID:** OG001 **Title:** GFF MDI BID 18/9.6 μg ##### Group **Description:** BID 9/9.6 μg **ID:** OG002 **Title:** GFF/MDI BID 9/9.6 μg ##### Group **Description:** 4.6/9.6 μg **ID:** OG003 **Title:** GFF MDI BID 4.6/9.6 μg ##### Group **Description:** BID 2.4/9.6 μg **ID:** OG004 **Title:** GFF MDI BID 2.4/9.6 μg ##### Group **Description:** BID 1.2/9.6 μg **ID:** OG005 **Title:** GFF MDI BID 1.2/9.6 μg ##### Group **Description:** BID 9.6 μg **ID:** OG006 **Title:** FF MDI BID 9.6 μg ##### Group **Description:** 18 μg QD **ID:** OG007 **Title:** Spiriva 18 μg QD #### Outcome Measure 11 **Description:** Change from baseline in mean morning pre-dose daily peak flow readings **Dispersion Type:** 95% Confidence Interval **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** MITT **Reporting Status:** POSTED **Time Frame:** Day 7 **Title:** Change From Baseline in Mean Morning Pre-dose Daily Peak Flow Readings on Day 7 **Type:** SECONDARY **Unit of Measure:** L/min ##### Group **Description:** 18 μg BID **ID:** OG000 **Title:** GP MDI 18 μg BID ##### Group **Description:** 18/9.6 μg BID **ID:** OG001 **Title:** GFF MDI 18/9.6 μg BID ##### Group **Description:** 9/9.6 μg BID **ID:** OG002 **Title:** GFF/MDI 9/9.6 μg BID ##### Group **Description:** 4.6/9.6 μg **ID:** OG003 **Title:** GFF MDI BID 4.6/9.6 μg ##### Group **Description:** 2.4/9.6 μg BID **ID:** OG004 **Title:** GFF MDI 2.4/9.6 μg BID ##### Group **Description:** 1.2/9.6 μg BID **ID:** OG005 **Title:** GFF MDI 1.2/9.6 μg BID ##### Group **Description:** 9.6 μg BID **ID:** OG006 **Title:** FF MDI 9.6 μg BID ##### Group **Description:** 18 μg QD **ID:** OG007 **Title:** Spiriva 18 μg QD #### Outcome Measure 12 **Description:** Change from baseline in mean morning post-dose daily peak flow readings on **Dispersion Type:** 95% Confidence Interval **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** MITT **Reporting Status:** POSTED **Time Frame:** Day 7 **Title:** Change From Baseline in Mean Morning Post-dose Daily Peak Flow Readings on Day 7 **Type:** SECONDARY **Unit of Measure:** L/min ##### Group **Description:** 18 μg BID **ID:** OG000 **Title:** GP MDI 18 μg BID ##### Group **Description:** BID 18/9.6 μg **ID:** OG001 **Title:** GFF MDI BID 18/9.6 μg ##### Group **Description:** BID 9/9.6 μg **ID:** OG002 **Title:** GFF/MDI BID 9/9.6 μg ##### Group **Description:** 4.6/9.6 μg **ID:** OG003 **Title:** GFF MDI BID 4.6/9.6 μg ##### Group **Description:** BID 2.4/9.6 μg **ID:** OG004 **Title:** GFF MDI BID 2.4/9.6 μg ##### Group **Description:** 1.2/9.6 μg BID **ID:** OG005 **Title:** GFF MDI 1.2/9.6 μg BID ##### Group **Description:** 9.6 μg BID **ID:** OG006 **Title:** FF MDI 9.6 μg BID ##### Group **Description:** 18 μg QD **ID:** OG007 **Title:** Spiriva 18 μg QD #### Outcome Measure 13 **Description:** Change from baseline in mean evening pre-dose daily peak flow readings (BID treatments only) **Dispersion Type:** 95% Confidence Interval **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** MITT **Reporting Status:** POSTED **Time Frame:** Day 7 **Title:** Change From Baseline in Mean Evening Pre-dose Daily Peak Flow Readings on Day 7 **Type:** SECONDARY **Unit of Measure:** L/min ##### Group **Description:** 18 μg BID **ID:** OG000 **Title:** GP MDI 18 μg BID ##### Group **Description:** 18/9.6 μg BID **ID:** OG001 **Title:** GFF MDI 18/9.6 μg BID ##### Group **Description:** 9/9.6 μg BID **ID:** OG002 **Title:** GFF/MDI 9/9.6 μg BID ##### Group **Description:** 4.6/9.6 μg BID **ID:** OG003 **Title:** GFF MDI 4.6/9.6 μg BID ##### Group **Description:** 2.4/9.6 μg BID **ID:** OG004 **Title:** GFF MDI 2.4/9.6 μg BID ##### Group **Description:** 1.2/9.6 μg BID **ID:** OG005 **Title:** GFF MDI 1.2/9.6 μg BID ##### Group **Description:** 9.6 μg BID **ID:** OG006 **Title:** FF MDI 9.6 μg BID ##### Group **Description:** 18 μg QD **ID:** OG007 **Title:** Spiriva18 μg QD #### Outcome Measure 14 **Description:** Change from baseline in mean evening post-dose daily peak flow readings (12 Hours post-dose for Spiriva) **Dispersion Type:** 95% Confidence Interval **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** MITT **Reporting Status:** POSTED **Time Frame:** Day 7 **Title:** Change From Baseline in Mean Evening Post-dose Daily Peak Flow Readings on Day 7 **Type:** SECONDARY **Unit of Measure:** L/min ##### Group **Description:** 18 μg BID **ID:** OG000 **Title:** GP MDI 18 μg BID ##### Group **Description:** 18/9.6 μg BID **ID:** OG001 **Title:** GFF MDI 18/9.6 μg BID ##### Group **Description:** 9/9.6 μg BID **ID:** OG002 **Title:** GFF/MDI 9/9.6 μg BID ##### Group **Description:** 4.6/9.6 μg BID **ID:** OG003 **Title:** GFF MDI BID 4.6/9.6 μg BID ##### Group **Description:** 2.4/9.6 μg BID **ID:** OG004 **Title:** GFF MDI 2.4/9.6 μg BID ##### Group **Description:** 1.2/9.6 μg BID **ID:** OG005 **Title:** GFF MDI 1.2/9.6 μg BID ##### Group **Description:** 9.6 μg BID **ID:** OG006 **Title:** FF MDI 9.6 μg BID ##### Group **Description:** 18 μg QD **ID:** OG007 **Title:** Spiriva 18 μg QD ### Participant Flow Module #### Group **ID:** FG000 **Title:** All Subjects #### Period **Title:** Overall Study ##### Withdraw **Type:** Protocol-specified criteria ###### Reason **Group ID:** FG000 **Number of Subjects:** 9 ##### Withdraw **Type:** Protocol Violation ###### Reason **Group ID:** FG000 **Number of Subjects:** 5 ##### Withdraw **Type:** Lost to Follow-up ###### Reason **Group ID:** FG000 **Number of Subjects:** 2 ##### Withdraw **Type:** Physician Decision ###### Reason **Group ID:** FG000 **Number of Subjects:** 2 ##### Withdraw **Type:** Withdrawal by Subject ###### Reason **Group ID:** FG000 **Number of Subjects:** 7 ##### Withdraw **Type:** Adverse Event ###### Reason **Group ID:** FG000 **Number of Subjects:** 14 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 159 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 120 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 39 **Pre-Assignment Details:** Study was a chronic dosing (7 days), 4-period, 8-treatment, Incomplete Block, Cross-Over. **Recruitment Details:** The study was conducted at 20 sites in the US from May 2012 until September 2012. The entire study was scheduled to take a maximum of 19 weeks for each individual subject. **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT02276079 **Brief Title:** The Effect of Exercise on Neurorecovery Following Mild Traumatic Brain Injury **Official Title:** The Effect of Exercise on Neurorecovery Following Mild Traumatic Brain Injury #### Organization Study ID Info **ID:** IRB201400882 #### Organization **Class:** OTHER **Full Name:** University of Florida ### Status Module #### Completion Date **Date:** 2016-12-22 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2018-12-04 **Type:** ACTUAL **Last Update Submit Date:** 2018-11-30 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2016-12-22 **Type:** ACTUAL #### Start Date **Date:** 2015-02-17 **Type:** ACTUAL **Status Verified Date:** 2018-11 #### Study First Post Date **Date:** 2014-10-27 **Type:** ESTIMATED **Study First Submit Date:** 2014-10-23 **Study First Submit QC Date:** 2014-10-23 ### Sponsor Collaborators Module #### Collaborators **Class:** UNKNOWN **Name:** Clinical & Translational Science Institute **Class:** OTHER **Name:** American Psychological Foundation **Class:** OTHER **Name:** American Psychological Association (APA) #### Lead Sponsor **Class:** OTHER **Name:** University of Florida #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** The study is a "proof-of-principle" project to examine the safety and feasibility of implementing a 1-week aerobic exercise program in the post-acute phase after mild traumatic brain injury (mTBI). The study will define the extent to which the exercise program improves recovery from mTBI in terms of relevant functional outcomes (cognition, mood, and physical status) and biomarkers (peripheral brain-derived neurotrophic factor \[BDNF\] concentration). **Detailed Description:** This is a "proof-of-principle" project for human subjects to examine the safety and feasibility of implementing a 1-week aerobic exercise program in the post-acute phase after mild traumatic brain injury (mTBI). This study will define the extent to which the exercise program improves recovery from mTBI in terms of relevant functional outcomes (cognition, mood, and physical status) and biomarkers (peripheral brain-derived neurotrophic factor \[BDNF\] concentration). This project will also lay the foundation for understanding the relationship between exercise and BDNF in the area of mTBI neurorecovery, thereby allowing future studies to develop best-practice methods for implementing exercise interventions as a treatment option for brain injuries. ### Conditions Module **Conditions:** - Brain Concussion **Keywords:** - Mild Traumatic Brain Injury - Aerobic Exercise - Brain-Derived Neurotrophic Factor ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** SINGLE **Who Masked:** - PARTICIPANT **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 39 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Participants are two-three weeks post-mild traumatic brain injury are randomized to receive a daily aerobic exercise intervention lasting 1-week. **Intervention Names:** - Behavioral: Aerobic Exercise **Label:** mTBI Aerobic Exercise Group **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Participants are two-three weeks post-mild traumatic brain injury are randomized to receive a daily non-aerobic exercise intervention lasting 1-week. **Intervention Names:** - Behavioral: Non-Aerobic Exercise **Label:** mTBI Non-Aerobic Exercise Group **Type:** EXPERIMENTAL #### Arm Group 3 **Description:** Non-injured, healthy participants will serve as a reference group for functional outcome measures. **Label:** Non-injured Reference Group **Type:** NO_INTERVENTION ### Interventions #### Intervention 1 **Arm Group Labels:** - mTBI Aerobic Exercise Group **Description:** Aerobic exercise will consist of riding a stationary bicycle at moderate intensity for 2 consecutive, 20-minute periods with a 5-minute break in between. Moderate intensity is defined as maintaining 65-75% of estimated maximum heart rate based on the calculation (HRmax = 208 - 0.7 × age). **Name:** Aerobic Exercise **Type:** BEHAVIORAL #### Intervention 2 **Arm Group Labels:** - mTBI Non-Aerobic Exercise Group **Description:** Non-Aerobic exercise will consist of very low-intensity movements including static stretching and toning exercises.Participants will complete 2 consecutive, 20-minute periods with a 5-minute break in between, mirroring the aerobic exercise condition. Heart rate will be monitored by research staff to ensure that it remains below 50% of estimated maximum heart rate. **Name:** Non-Aerobic Exercise **Type:** BEHAVIORAL ### Outcomes Module #### Other Outcomes **Description:** Measured by the 3-Minute Step Test, which provides an estimate of aerobic fitness. Participants step up and down continuously on a 12-inch step for 3 minutes and the time it takes for their heart rate to return to baseline is recorded. **Measure:** Change in aerobic fitness **Time Frame:** Baseline and up to day 8 **Description:** Body weight measured in kilograms. **Measure:** Change in body weight **Time Frame:** Baseline and up to day 8 **Description:** Average number of minutes the participant spent engaging in physical activity outside of the exercise sessions during the one-week exercise program. This will be measured by a digital fitness monitor that will be worn 24 hours per day during the 7 day exercise program. **Measure:** Minutes of physical activity outside of exercise program **Time Frame:** Day 7 of exercise program #### Primary Outcomes **Description:** Obtained from the 22-item symptom evaluation included in the Sport Concussion Assessment Tool (SCAT3). The participant's present experience of each symptom is rated on a likert scale from 0 (none) to 6 (severe). The symptom score represents how many symptoms the participant endorses experiencing at a level greater than 0 (maximum 22 points). **Measure:** Change in Symptom Score on the Sport Concussion Assessment Tool (SCAT3) **Time Frame:** Baseline and up to day 8 **Description:** Symptom evaluation included in the Sport Concussion Assessment Tool (SCAT3). The participant's present experience of each symptom is rated on a likert scale from 0 (none) to 6 (severe). The symptom severity represents the total summed severity ratings for all symptoms (maximum 132 points). **Measure:** Change in Symptom Severity on the Sport Concussion Assessment Tool (SCAT3) **Time Frame:** Baseline and up to day 8 **Description:** Obtained from the Medical Outcomes Sleep Scale (MOS). This measure has 12 items and asks the participant to rate different aspects of their sleep experiences and sleep quality. The first two questions inquire about sleep times and the remaining questions utilize a likert scale ranging from 1 (all of the time) to 6 (none of the time). Some items are reverse scored and the scale yields several subscale measures, so scoring rules depend on the specific subscale. **Measure:** Change in sleep quality **Time Frame:** Baseline and up to day 8 **Description:** The Balance Error Scoring System (BESS) will be used to measure postural stability, which is sensitive to deficits in balance following mild head injury. A modified version of (SCAT3) will be used. It includes three different stances, double leg, single leg, and tandem stance. A point is added for committing an error during the test interval and if the participant is unable to maintain his or her balance for more than 5 seconds, the trial is discontinued and maximum points are awarded. The total score ranges from 0 (better postural stability) to 30 (worse postural stability). **Measure:** Change in postural stability **Time Frame:** Baseline and up to day 8 **Description:** Measured by the California Verbal Learning Test, 2nd Edition (CVLT-II). This test measures word recall and assesses the following skills: immediate recall, short delay free recall, short delay cued recall, long delay free recall, long delay cued recall, and long delay recognition. **Measure:** Change in verbal learning and memory **Time Frame:** Baseline and up to day 8 **Description:** Measured by the Wechsler Memory Scale, 3rd Edition (WMS-III), Logical Memory subtests. Two stories are read to participants and then they are asked to freely recall items after a short and a long delay. A recognition trial is administered following the long delay. **Measure:** Change in auditory-linguistic memory **Time Frame:** Baseline and up to day 8 **Description:** Measured by the Controlled Oral Word Association (COWA). Participants are asked to say as many words beginning with a specified letter as they can in a one minute time period. Three trials with different letters are administered. **Measure:** Change in word-fluency **Time Frame:** Baseline and up to day 8 **Description:** Measured by the Verbal Fluency Test - Categories. Participants are asked to say as many items belonging to a specified semantic category as they can in a one minute time period. **Measure:** Change in semantic fluency **Time Frame:** Baseline and up to day 8 **Description:** Measured by the Delis-Kaplan Executive Functioning System (D-KEFS), Trail Making Test. The test consists of five different conditions where participants are asked to draw trails according to specified rules. **Measure:** Change in psychomotor/executive functioning **Time Frame:** Baseline and up to day 8 **Description:** Measured by the Wisconsin Card Sorting Test (WCST). Initially, a number of stimulus cards are presented to the participant. The participant is told to match the cards, but not how to match; however, he or she is told whether a particular match is right or wrong. A total of 128 cards are played. **Measure:** Change in problem solving and abstract reasoning **Time Frame:** Baseline and up to day 8 **Description:** Measured by the Wechsler Adult Intelligence Scale, 3rd Edition (WAIS-III), Digit Span subtest. Participants are asked to repeat digit strings that are verbally administered exactly as they hear them (digits forward) or to repeat them backwards (digits backward). **Measure:** Change in attention **Time Frame:** Baseline and up to day 8 **Description:** Measured by the Wechsler Adult Intelligence Scale, 3rd Edition (WAIS-III), Digit Symbol-Coding subtest. Participants are given three minutes to draw symbols as quickly and as accurately as possible according to a key code. **Measure:** Change in processing speed **Time Frame:** Baseline and up to day 8 **Description:** Measured by the Wechsler Memory Scale, 3rd Edition (WMS-III), Visual Reproduction subtest. Participants are asked to draw abstract figures from memory at different time intervals. The subtest assesses the following visual memory skills: immediate free recall, long delayed free recall and a long delayed recognition. **Measure:** Change in visual memory **Time Frame:** Baseline and up to day 8 **Description:** Measured by the Ruff 2 \& 7 Selective Attention Test. The test consists of a series of 20 trials of a visual search and cancellation task. The participant detects and marks through all occurrences of the two target digits: "2" and "7." In the 10 Automatic Detection trials, the target digits are embedded among alphabetical letters that serve as distractors. In the 10 Controlled Search trials, the target digits are embedded among other numbers that serve as distractors. Correct hits and errors are counted for each trial and serve as the basis for scoring the test. **Measure:** Change in sustained and selective attention **Time Frame:** Baseline and up to day 8 **Description:** Measured by the Paced Auditory Serial Addition Test (PASAT). Participants are read a series of numbers at specified time intervals. The participants are instructed to add the number to the preceding number and continue adding them together until the end of the trial. Four trials with 50 items each are administered with a 30 second break in between. **Measure:** Change in working memory and attention **Time Frame:** Baseline and up to day 8 **Description:** Measured by the Beck Depression Inventory, 2nd Edition (BDI-II), which is a self-report questionnaire with 21 multiple choice items. The total score ranges from 0 to 63 with higher numbers indicating greater severity of depression symptoms. **Measure:** Change in depression symptoms **Time Frame:** Baseline and up to day 8 **Description:** Measured by the State Trait Anxiety Inventory (STAI), which is a self-report questionnaire with 40 questions on a 4-point likert scale. The STAI measures two types of anxiety - state and trait scores. Higher scores are positively correlated with higher levels of anxiety. **Measure:** Change in anxiety symptoms **Time Frame:** Baseline and up to day 8 #### Secondary Outcomes **Description:** Functional resting state sequences will be performed on the Phillips 3 tesla magnetic resonance (MR) research scanner. **Measure:** Change in functional neuroimaging activation **Time Frame:** Baseline and up to day 8 **Description:** Obtained from the 22-item symptom evaluation included in the Sport Concussion Assessment Tool (SCAT3). The participant's present experience of each symptom is rated on a likert scale from 0 (none) to 6 (severe). The symptom score represents how many symptoms the participant endorses experiencing at a level greater than 0 (maximum 22 points). **Measure:** Change in Symptom Score on the Sport Concussion Assessment Tool (SCAT3) **Time Frame:** Baseline and up to day 70 **Description:** Symptom evaluation included in the Sport Concussion Assessment Tool (SCAT3). The participant's present experience of each symptom is rated on a likert scale from 0 (none) to 6 (severe). The symptom severity represents the total summed severity ratings for all symptoms (maximum 132 points). **Measure:** Change in Symptom Severity on the Sport Concussion Assessment Tool (SCAT3) **Time Frame:** Baseline and up to day 70 **Description:** Obtained from the Medical Outcomes Sleep Scale (MOS). This measure has 12 items and asks the participant to rate different aspects of their sleep experiences and sleep quality. The first two questions inquire about sleep times and the remaining questions utilize a likert scale ranging from 1 (all of the time) to 6 (none of the time). **Measure:** Change in sleep quality **Time Frame:** Baseline and up to day 70 **Description:** The Balance Error Scoring System (BESS) will be used to measure postural stability, which is sensitive to deficits in balance following mild head injury. A modified version of (SCAT3) will be used. It includes three different stances, double leg, single leg, and tandem stance. A point is added for committing an error during the test interval and if the participant is unable to maintain his or her balance for more than 5 seconds, the trial is discontinued and maximum points are awarded. The total score ranges from 0 (better postural stability) to 30 (worse postural stability). **Measure:** Change in postural stability **Time Frame:** Baseline and up to day 70 **Description:** Measured by the Beck Depression Inventory, 2nd Edition (BDI-II), which is a self-report questionnaire with 21 multiple choice items. The total score ranges from 0 to 63 with higher numbers indicating greater severity of depression symptoms. **Measure:** Change in depression symptoms **Time Frame:** Baseline and up to day 70 **Description:** Measured by the State Trait Anxiety Inventory (STAI), which is a self-report questionnaire with 40 questions on a 4-point likert scale. The STAI measures two types of anxiety - state and trait scores. Higher scores are positively correlated with higher levels of anxiety. **Measure:** Change in anxiety symptoms **Time Frame:** Baseline and up to day 70 ### Eligibility Module **Eligibility Criteria:** Mild traumatic brain injury (mTBI) group: Inclusion Criteria: * Meet criteria for mTBI as set forth by the American Congress of Rehabilitation Medicine * mTBI was sustained 14-25 days before beginning the exercise intervention Exclusion Criteria: * comorbid orthopaedic injury that inhibits movement * history of serious psychiatric disturbance with hospitalization, * prior history of neurologic disease, * current or past history of substance abuse disorder, * diabetes * previous history of moderate or severe head injury, * neurological disorder unrelated to TBI (e.g., seizure disorder) * physician recommendations against exercise * non-English speakers Non-injured Group: Inclusion Criteria: - Gainesville, Florida community member Exclusion Criteria: * History of mTBI or other brain injury in the past year * comorbid orthopaedic injury that inhibits movement * history of serious psychiatric disturbance with hospitalization, * prior history of neurologic disease, * current or past history of substance abuse disorder, * diabetes * previous history of moderate or severe head injury, * neurological disorder unrelated to TBI (e.g., seizure disorder) * physician recommendations against exercise * non-English speakers **Healthy Volunteers:** True **Maximum Age:** 40 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Gainesville **Country:** United States **Facility:** University of Florida Health Science Center **State:** Florida **Zip:** 32610 #### Overall Officials **Official 1:** **Affiliation:** University of Florida **Name:** Russell M. Bauer, Ph.D. **Role:** PRINCIPAL_INVESTIGATOR **Official 2:** **Affiliation:** University of Florida **Name:** Aliyah R. Snyder, M.S. **Role:** STUDY_DIRECTOR ### References Module #### References **Citation:** Cassidy JD, Carroll LJ, Peloso PM, Borg J, von Holst H, Holm L, Kraus J, Coronado VG; WHO Collaborating Centre Task Force on Mild Traumatic Brain Injury. Incidence, risk factors and prevention of mild traumatic brain injury: results of the WHO Collaborating Centre Task Force on Mild Traumatic Brain Injury. J Rehabil Med. 2004 Feb;(43 Suppl):28-60. doi: 10.1080/16501960410023732. **PMID:** 15083870 **Citation:** Barkhoudarian G, Hovda DA, Giza CC. The molecular pathophysiology of concussive brain injury. Clin Sports Med. 2011 Jan;30(1):33-48, vii-iii. doi: 10.1016/j.csm.2010.09.001. **PMID:** 21074080 **Citation:** Prins ML, Alexander D, Giza CC, Hovda DA. Repeated mild traumatic brain injury: mechanisms of cerebral vulnerability. J Neurotrauma. 2013 Jan 1;30(1):30-8. doi: 10.1089/neu.2012.2399. **PMID:** 23025820 **Citation:** Griesbach GS, Gomez-Pinilla F, Hovda DA. Time window for voluntary exercise-induced increases in hippocampal neuroplasticity molecules after traumatic brain injury is severity dependent. J Neurotrauma. 2007 Jul;24(7):1161-71. doi: 10.1089/neu.2006.0255. **PMID:** 17610355 **Citation:** Bigler ED. Neuropsychology and clinical neuroscience of persistent post-concussive syndrome. J Int Neuropsychol Soc. 2008 Jan;14(1):1-22. doi: 10.1017/S135561770808017X. **PMID:** 18078527 **Citation:** Griesbach GS, Hovda DA, Gomez-Pinilla F. Exercise-induced improvement in cognitive performance after traumatic brain injury in rats is dependent on BDNF activation. Brain Res. 2009 Sep 8;1288:105-15. doi: 10.1016/j.brainres.2009.06.045. Epub 2009 Jun 23. **PMID:** 19555673 **Citation:** Coelho FG, Gobbi S, Andreatto CA, Corazza DI, Pedroso RV, Santos-Galduroz RF. Physical exercise modulates peripheral levels of brain-derived neurotrophic factor (BDNF): a systematic review of experimental studies in the elderly. Arch Gerontol Geriatr. 2013 Jan-Feb;56(1):10-5. doi: 10.1016/j.archger.2012.06.003. Epub 2012 Jun 29. **PMID:** 22749404 **Citation:** Tanaka H, Monahan KD, Seals DR. Age-predicted maximal heart rate revisited. J Am Coll Cardiol. 2001 Jan;37(1):153-6. doi: 10.1016/s0735-1097(00)01054-8. **PMID:** 11153730 **Citation:** Dunn AL, Trivedi MH, Kampert JB, Clark CG, Chambliss HO. The DOSE study: a clinical trial to examine efficacy and dose response of exercise as treatment for depression. Control Clin Trials. 2002 Oct;23(5):584-603. doi: 10.1016/s0197-2456(02)00226-x. **PMID:** 12392873 **Citation:** Efird J. Blocked randomization with randomly selected block sizes. Int J Environ Res Public Health. 2011 Jan;8(1):15-20. doi: 10.3390/ijerph8010015. Epub 2010 Dec 23. **PMID:** 21318011 **Citation:** Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)--a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009 Apr;42(2):377-81. doi: 10.1016/j.jbi.2008.08.010. Epub 2008 Sep 30. **PMID:** 18929686 **Citation:** Riemann BL, Guskiewicz KM. Effects of mild head injury on postural stability as measured through clinical balance testing. J Athl Train. 2000 Jan;35(1):19-25. **PMID:** 16558603 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000001927 - Term: Brain Diseases - ID: D000002493 - Term: Central Nervous System Diseases - ID: D000009422 - Term: Nervous System Diseases - ID: D000006259 - Term: Craniocerebral Trauma - ID: D000020196 - Term: Trauma, Nervous System - ID: D000014947 - Term: Wounds and Injuries - ID: D000016489 - Term: Head Injuries, Closed - ID: D000014949 - Term: Wounds, Nonpenetrating ### Condition Browse Module - Browse Branches - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: BC26 - Name: Wounds and Injuries - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M5207 - Name: Brain Injuries - Relevance: HIGH - As Found: Brain Injury - ID: M628 - Name: Brain Injuries, Traumatic - Relevance: HIGH - As Found: Traumatic Brain Injury - ID: M5201 - Name: Brain Concussion - Relevance: HIGH - As Found: Mild Traumatic Brain Injury - ID: M5204 - Name: Brain Diseases - Relevance: LOW - As Found: Unknown - ID: M5742 - Name: Central Nervous System Diseases - Relevance: LOW - As Found: Unknown - ID: M17685 - Name: Wounds and Injuries - Relevance: LOW - As Found: Unknown - ID: M9349 - Name: Craniocerebral Trauma - Relevance: LOW - As Found: Unknown - ID: M22023 - Name: Trauma, Nervous System - Relevance: LOW - As Found: Unknown - ID: M18892 - Name: Head Injuries, Closed - Relevance: LOW - As Found: Unknown - ID: M17687 - Name: Wounds, Nonpenetrating - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000001930 - Term: Brain Injuries - ID: D000070642 - Term: Brain Injuries, Traumatic - ID: D000001924 - Term: Brain Concussion ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05956379 **Brief Title:** Chronic Hepatitis B Patients With Concurrent MAFLD: Cohort Study and Exercise Intervention. **Official Title:** Chronic Hepatitis B Patients With Concurrent MAFLD: Cohort Study and Exercise Intervention. #### Organization Study ID Info **ID:** 202212084RINC #### Organization **Class:** OTHER **Full Name:** National Taiwan University Hospital ### Status Module #### Completion Date **Date:** 2027-07-31 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2023-07-21 **Type:** ACTUAL **Last Update Submit Date:** 2023-07-13 **Overall Status:** ENROLLING_BY_INVITATION #### Primary Completion Date **Date:** 2027-07-31 **Type:** ESTIMATED #### Start Date **Date:** 2023-08-01 **Type:** ESTIMATED **Status Verified Date:** 2023-06 #### Study First Post Date **Date:** 2023-07-21 **Type:** ACTUAL **Study First Submit Date:** 2023-06-13 **Study First Submit QC Date:** 2023-07-13 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** National Taiwan University 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:** In Taiwan, HBV infection is endemic in the adult population. With the westernization of eating habit and lifestyle, metabolic syndrome and related non-alcoholic fatty liver diseases (NAFLD, newly proposed as metabolic dysfunction associated fatty liver diseases, MAFLD) has become another important health issue. It is therefore common to encounter subjects with concurrent MAFLD and HBV infection in HBV endemic countries. This project will study the clinical data of patients with concurrent MAFLD and HBV, and aim to explore the impact of exercise intervention on the hepatic fatty infiltration, alteration of gut microbiota and HBV replication status in this group of patients. The research strategies will include (1) improving fatty liver and metabolic syndrome in subjects with concurrent MAFLD and HBV; and (2) exploring the changes of HBV replication and intestinal microflora in patients with concurrent HBV and MAFLD after exercise intervention. **Detailed Description:** The investigators will first collect and analyze clinical data of patients with concurrent MAFLD and HBV in a retrospective cohort in NTUH. The investigators aim to clarify the interactions of MAFLD and HBV based on different HBV-related liver disease stage and different metabolic derangement. Second, using the well-established platform for the detection and staging of fatty liver at NTUH, the investigators plan to enroll 100 patients with concurrent HBV and MAFLD. The investigators will collect all basic information including intrahepatic fat and fibrosis severity, and randomize them to the exercise intervention group (n = 50) and the observation group (n = 50) after conditional screening. After 6-month of exercise intervention, the investigators will analyze the effect of exercise on intrahepatic fat (main parameter: 10% reduction in intrahepatic fat; 30% achieved in the exercise intervention group; 5% achieved in the control group) and analyze the influence of co-existing HBV on the change of hepatic steatosis. Description of the prospective randomized exercise intervention studies 1. Enrolment of 100 patients with concurrent chronic HBV infection and MAFLD 2. Collection of baseline data: Clinical parameters, virologic parameters, metabolic and MAFLD parameters, nutritional and exercise fitness data, and liver steatosis/fibrosis data 3. Randomization: Randomization into exercise (Group I) versus non-exercise group (Group II) will be conducted with the help of random number table. 4. 24-week exercise intervention 5. 12-week post-exercise follow-up period 6. Collection of final data, statistical analyses and paper preparation II-1: Enrolment of subjects: Patients from NTUH with the diagnosis of chronic HBV infection will be screened for the presence of MAFLD at the out-patient clinics. Treatment naïve patients found to have co-existing MAFLD and willing to join the active exercise program will be invited to join the study by the clinical physicians after thorough evaluation. Patients with age less than 18 years, concurrent HCV or HIV co-infection will be excluded. CHB patients fulfilling reimbursement criteria for the treatment of HBAg-positive or -negative CHB, or advanced fibrosis/cirrhosis will not be enrolled since the virologic profiles under NUC therapy would not likely to be affected by the change of hepatic steatosis through exercise intervention. Assessment of HBV replication status and liver disease severity: The clinical phenotype of HBV infection will be determined by liver function test (serum ALT level) and platelet count number, abdominal ultrasonography, FibroScan™, along with serum HBeAg and HBV DNA level. At enrolment, the patients will be categorized into HBeAg positive chronic HBV infection (immune tolerance phase), HBeAg positive chronic hepatitis B (immune clearance phase), HBeAg negative chronic HBV infection (low replication phase), and HBeAg negative chronic hepatitis B (reactivation phase). The stage of liver fibrosis will determined by FIB-4, FibroScan™and MR elastography (MRE). Diagnosis and assessment of MAFLD: The diagnosis of MAFLD will be made if the patient has evidence of hepatic steatosis by both abdominal ultrasonography and FibroScan™, along with one of the three criteria, namely overweight/obesity, presence of type 2 diabetes mellitus (DM), and at least two metabolic risk abnormalities. Then the degree of hepatic steatosis and fibrosis will be semi-quantitatively assessed by FibroScan™. In this proposal, the investigators will for the first time adopt MR PDFF and MR elastography (MRE) to accurately assess the degree of steatosis and the stage of fibrosis in each enrolled subject before and after the intervention. ### Conditions Module **Conditions:** - Chronic Hepatitis B - Non-alcoholic Fatty Liver Disease **Keywords:** - Metabolic syndrome - Exercise intervention - Fatty liver - Chronic Hepatitis B - Gut microbiota ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 100 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Physical therapists will provide personalized aerobic exercise program prescriptions in the preparatory period based on the results of exercise-related assessments, and the training intensity is based on the results of the maximum exercise test, with moderate intensity for 24 weeks, \>=3 cardio workouts per week. **Intervention Names:** - Other: exercise **Label:** Exercise group **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** No change in exercise habits and maintaining baseline physical activity. **Label:** Control group **Type:** NO_INTERVENTION ### Interventions #### Intervention 1 **Arm Group Labels:** - Exercise group **Description:** Physical therapists will provide personalized aerobic exercise program prescriptions in the preparatory period based on the results of exercise-related assessments, and the training intensity is based on the results of the maximum exercise test, with moderate intensity for 24 weeks, \>=3 cardio workouts per week. The form of aerobic exercise can be carried out in the form of treadmill walking, walking, jogging, cycling, aerobic dance, ball games, swimming, rope skipping, stepping exercises, etc. When the exercise reaches the target intensity, we will adjust the training intensity process according to personal ability. The physical therapist will again adjust the content of the aerobic exercise program at week 12 based on the reassessment of the exercise capacity. **Name:** exercise **Type:** OTHER ### Outcomes Module #### Other Outcomes **Description:** 1. Dynamics of HBV profiles after exercise 2. Impact of diminishing hepatic steatosis on the evolution of liver fibrosis 3. Impact of diminishing hepatic steatosis on the profiles of HBV replication **Measure:** Exploratory outcomes **Time Frame:** 24 weeks #### Primary Outcomes **Description:** We will measure change of hepatic steatosis at week 24 in comparison to baseline steatosis by MRI-PDFF. Reduction of hepatic steatosis by \>=10% will be defined as responder. **Measure:** Change of hepatic steatosis after 6-month exercise intervention by MRI-PDFF **Time Frame:** 24 weeks ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Age \>18 years of age * Either gender * HBV treatment naïve * Capable of taking exercise * HBsAg positivity for \>6 months * Evidence of fatty liver in both abdominal ultrasonography and Fibroscan™(CAP\>215) Exclusion Criteria: * Age \>70 years of age * Evidence of liver cirrhosis * Patients fulfilling reimbursement criteria for HBV treatment * Evidence of severe cardiopulmonary diseases * Evidence of serious hip or knee problems, incapable of taking exercise * Evidence of liver decompensation * Evidence of active HCV (positive for serum HCV RNA) or HIV infection (positive for anti-HCV) * Clinical diagnosis of Alzheimer's Disease * Thyroid disease **Maximum Age:** 70 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Taipei **Country:** Taiwan **Facility:** National Taiwan University Hospital **State:** Zhongzheng Dist. **Zip:** 100229 #### Overall Officials **Official 1:** **Affiliation:** National Taiwan University Hospital **Name:** Chun-Jen Liu, Professor **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - 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: D000018347 - Term: Hepadnaviridae Infections - ID: D000004266 - Term: DNA Virus Infections - ID: D000002908 - Term: Chronic Disease - 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: BC01 - Name: Infections - 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: M9592 - Name: Hepatitis A - Relevance: HIGH - As Found: Hepatitis - ID: M9595 - Name: Hepatitis B - Relevance: HIGH - As Found: Hepatitis B - ID: M21609 - Name: Hepatitis B, Chronic - Relevance: HIGH - As Found: Chronic Hepatitis B - ID: M9591 - Name: Hepatitis - Relevance: HIGH - As Found: Hepatitis - ID: M9607 - Name: Hepatitis, Chronic - Relevance: HIGH - As Found: Chronic Hepatitis - ID: M11107 - Name: Liver Diseases - Relevance: HIGH - As Found: Liver Disease - ID: M23005 - Name: Metabolic Syndrome - Relevance: LOW - As Found: Unknown - ID: M8375 - Name: Fatty Liver - Relevance: HIGH - As Found: Fatty Liver - ID: M30540 - Name: Non-alcoholic Fatty Liver Disease - Relevance: HIGH - As Found: Non-alcoholic Fatty Liver Disease - 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: M17522 - Name: Virus Diseases - 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: M20487 - Name: Hepadnaviridae Infections - Relevance: LOW - As Found: Unknown - ID: M7442 - Name: DNA Virus Infections - 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 - ID: T5868 - Name: Visceral Steatosis - Relevance: HIGH - As Found: Fatty Liver ### Condition Browse Module - Meshes - ID: D000006506 - Term: Hepatitis A - ID: D000006509 - Term: Hepatitis B - ID: D000019694 - Term: Hepatitis B, Chronic - ID: D000006505 - Term: Hepatitis - ID: D000006521 - Term: Hepatitis, Chronic - ID: D000008107 - Term: Liver Diseases - ID: D000005234 - Term: Fatty Liver - ID: D000065626 - Term: Non-alcoholic Fatty Liver Disease ### Intervention Browse Module - Browse Branches - Abbrev: Hemat - Name: Hematinics - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M11110 - Name: Liver Extracts - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03080779 **Brief Title:** Long Term Outcomes After Accidental Dural Puncture ADP Study **Official Title:** The Incidence of Chronic Headache and Low Back Pain After Accidental Dural Puncture (ADP) With a Tuohy Needle and Epidural Blood Patch in the Obstetric Population: A Prospective 2-group Cohort Multicentre Study #### Organization Study ID Info **ID:** UHLeicester #### Organization **Class:** OTHER **Full Name:** University Hospitals, Leicester ### Status Module #### Completion Date **Date:** 2020-06-27 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2020-08-13 **Type:** ACTUAL **Last Update Submit Date:** 2020-08-12 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2020-04-27 **Type:** ACTUAL #### Start Date **Date:** 2017-02-03 **Type:** ACTUAL **Status Verified Date:** 2020-08 #### Study First Post Date **Date:** 2017-03-15 **Type:** ACTUAL **Study First Submit Date:** 2016-12-20 **Study First Submit QC Date:** 2017-03-08 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** University Hospitals, Leicester #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** Post Dural Puncture Headache (PDPH) causes significant short-term disability, prevents mobilisation, affects childcare activities and results in prolonged hospital stay. Initial treatment involves painkillers and if patient fails to respond, an Epidural Blood Patch (EBP). EBP involves taking patient's blood and injecting into the epidural space. It is generally agreed that PDPH is a self-limiting condition and resolves in two weeks. However there is emerging evidence that patients with PDPH could be at an increased risk of developing longstanding (chronic) headaches. Retrospective case studies show that between 28 - 34% of patients who developed PDPH had longstanding headaches at 18 months after the insertion of the epidural. There is also recent evidence of new onset low back pain developing in patients who have received an epidural blood patch that was performed to treat PDPH. Nearly two thirds of patients from a hospital in UK had new onset low back pain after they had received epidural blood patch treatment. Presently, there is no prospective clinical study evaluating the development of longstanding headaches and new onset low back pain after the development of PDPH. Aim of the present study is to evaluate the incidence of longstanding headache after accidental dural (ADP) puncture and the incidence of new onset low back pain after epidural blood patch treatment. **Detailed Description:** Headache can be a complication after insertion of an epidural needle for pain relief during labour. The headache is called Post Dural Puncture Headache (PDPH). PDPH causes significant short-term disability, prevents mobilisation, affects childcare activities and results in prolonged hospital stay. Initial treatment involves painkillers and if patient fails to respond, an Epidural Blood Patch (EBP). EBP involves taking patient's blood and injecting into the epidural space. It is generally agreed that PDPH is a self-limiting condition and resolves in two weeks. However there is emerging evidence that patients with PDPH could be at an increased risk of developing longstanding (chronic) headaches. Retrospective case studies show that between 28 - 34% of patients who developed PDPH had longstanding headaches at 18 months after the insertion of the epidural. There is also recent evidence of new onset low back pain developing in patients who have received an epidural blood patch that was performed to treat PDPH. Nearly two thirds of patients from a hospital in UK had new onset low back pain after they had received epidural blood patch treatment. Presently, there is no prospective clinical study evaluating the development of longstanding headaches and new onset low back pain after the development of PDPH. Aim of the present study is to evaluate the incidence of longstanding headache after accidental dural (ADP) puncture and the incidence of new onset low back pain after epidural blood patch treatment. Methods: The proposed study is a prospective, cohort study that will be conducted at six centres (Leicester, Derby, Bradford, Colchester, Bedford and Cambridge) over 36 months. Index participants who suffer ADP will be matched with control participants who have received an uneventful epidural insertion. The index and control participants will be matched for age, body weight, parity and the type of delivery. Mothers who have longstanding headache or low back pain will be excluded form the study. After providing written consent, the participants will be provided with a questionnaire pack containing three sets of two questionnaires to be completed at 6, 12 and 18 months after developing the headache as well as stamped envelopes to return the questionnaires to the research team. A research team member will perform telephone follow up 6, 12 and 18 months to encourage completion of the questionnaires. Participation in the study will end at 18 months after completion of the study questionnaires. ### Conditions Module **Conditions:** - Post-Dural Puncture Headache - Chronic Headache - Chronic Low Back Pain ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 270 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Index group includes participants who have suffered an accidental dural puncture with a 16 gauge Tuohy needle **Label:** ADP Group #### Arm Group 2 **Description:** Control group includes participants who received an uneventful epidural analgesia with a 16 gauge Tuohy needle **Label:** Non-ADP group ### Outcomes Module #### Primary Outcomes **Description:** Questionnaire **Measure:** The incidence of chronic headache at 18 months in the ADP group when compared to the control non-ADP group **Time Frame:** 18 months #### Secondary Outcomes **Description:** Questionnaire **Measure:** The incidence of chronic low back pain at 18 months in the ADP group when compared to the control non-ADP group. **Time Frame:** 18 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Index: Participants aged over 18 years who have sustained accidental dural puncture with 16-gauge Tuohy needle * Control: Participants aged over 18 years who have received uneventful epidural insertion with 16-gauge Tuohy needle Exclusion Criteria: * Lack of consent including from those participants who lack mental capacity to give informed consent * Pre-existing chronic headache (the patients suffer from 15 or more headache days every month) * Pre-existing chronic low back pain (the patients suffer from 7 or more low back pain days every month) **Maximum Age:** 50 Years **Minimum Age:** 18 Years **Sampling Method:** PROBABILITY_SAMPLE **Sex:** FEMALE **Standard Ages:** - ADULT **Study Population:** Obstetric ### Contacts Locations Module #### Locations **Location 1:** **City:** Leicester **Country:** United Kingdom **Facility:** University Hospitals of Leicester NHS Trust **State:** Leicestershire **Zip:** LE54PW **Location 2:** **City:** Bedford **Country:** United Kingdom **Facility:** Bedford Hospitals NHS Trust **Location 3:** **City:** Derby **Country:** United Kingdom **Facility:** Royal Derby Hospitals #### Overall Officials **Official 1:** **Affiliation:** University Hospitals, Leicester **Name:** N Gopinath **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Niraj G, Mushambi M, Gauthama P, Patil A, Kelkar A, Hart E, Nurmikko T; Accidental Dural Puncture Outcome Study Collaborative Group. Persistent headache and low back pain after accidental dural puncture in the obstetric population: a prospective, observational, multicentre cohort study. Anaesthesia. 2021 Aug;76(8):1068-1076. doi: 10.1111/anae.15491. Epub 2021 Apr 23. **PMID:** 33891312 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000010146 - Term: Pain - ID: D000009461 - Term: Neurologic Manifestations - ID: D000051271 - Term: Headache Disorders, Secondary - ID: D000001927 - Term: Brain Diseases - ID: D000002493 - Term: Central Nervous System Diseases - ID: D000009422 - Term: Nervous 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: BC04 - Name: Neoplasms - Abbrev: Rare - Name: Rare 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: M9351 - Name: Headache - Relevance: HIGH - As Found: Headache - ID: M26670 - Name: Post-Dural Puncture Headache - Relevance: HIGH - As Found: Post-Dural Puncture Headache - ID: M22529 - Name: Headache Disorders - Relevance: HIGH - As Found: Chronic Headache - ID: M12404 - Name: Neurologic Manifestations - Relevance: LOW - As Found: Unknown - ID: M12307 - Name: Neoplasm Metastasis - Relevance: LOW - As Found: Unknown - ID: M26658 - Name: Headache Disorders, Secondary - 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: T1303 - Name: Chronic Graft Versus Host Disease - Relevance: HIGH - As Found: Chronic ### Condition Browse Module - Meshes - ID: D000051299 - Term: Post-Dural Puncture Headache - ID: D000020773 - Term: Headache Disorders - ID: D000001416 - Term: Back Pain - ID: D000017116 - Term: Low Back Pain - ID: D000006261 - Term: Headache ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03794479 **Brief Title:** Intestinal Microbiota and Antimicrobial Resistance in Hong Kong Residents After Travel **Official Title:** Changes in Intestinal Microbiota and Acquisition of Antimicrobial Resistance in Hong Kong Residents After Travel #### Organization Study ID Info **ID:** travellers_version 2_20180724 #### Organization **Class:** OTHER **Full Name:** Chinese University of Hong Kong ### Status Module #### Completion Date **Date:** 2023-06-06 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2023-08-30 **Type:** ACTUAL **Last Update Submit Date:** 2023-08-28 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2023-06-06 **Type:** ACTUAL #### Start Date **Date:** 2018-11-05 **Type:** ACTUAL **Status Verified Date:** 2023-08 #### Study First Post Date **Date:** 2019-01-07 **Type:** ACTUAL **Study First Submit Date:** 2019-01-03 **Study First Submit QC Date:** 2019-01-03 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Chinese University of Hong Kong #### Responsible Party **Investigator Affiliation:** Chinese University of Hong Kong **Investigator Full Name:** Grace Lui **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:** International travel is well reported to be associated with acquisition of multidrug-resistant organisms, however, the impact of colonization of these multidrug-resistant organisms is currently uncertain. As colonization of multidrug-resistant organisms had been demonstrated to be associated with distinct intestinal microbiota composition and travellers constitute a generally healthy population with minimal antibiotics exposure; by evaluating serial stool samples before and after travel, the investigators can delineate a potential causal relationship between host intestinal microbiota and subsequent risk of acquisition of multidrug-resistant organisms. ### Conditions Module **Conditions:** - Antimicrobial Resistance **Keywords:** - Intestinal microbiota - Antimicrobial resistance ### Design Module #### Bio Spec **Description:** Stool sample retained. **Retention:** SAMPLES_WITHOUT_DNA #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 125 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Adults planning for travel **Label:** Travellers ### Outcomes Module #### Primary Outcomes **Description:** Intestinal colonization of ESBL-producing Enterobacteriaceae is defined as the presence of ESBL in Enterobacteriaceae identified in the post-travel stool samples, in patients without these organisms detected in their stool samples before travel. **Measure:** Proportion of patients acquiring intestinal colonization of ESBL-producing Enterobacteriaceae **Time Frame:** 1 year #### Secondary Outcomes **Description:** Intestinal colonization of carbapenem-resistant Enterobacteriaceae is defined as the presence of carbapenem-resistant Enterobacteriaceae identified in the stool samples, in patients without these organisms detected in their stool samples before travel. **Measure:** Proportion of patients acquiring intestinal colonization of carbapenem-resistant Enterobacteriaceae **Time Frame:** 1 year ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Adults aged 18 years or above * Chinese ethnicity * Planning to visit any places outside of Hong Kong within the next three months * Able to provide informed consent Exclusion Criteria: * Use of antibiotics within 4 weeks prior to the time of recruitment (Except for antimalarial prophylaxis) * Hospitalization within 3 months * Underlying gastrointestinal diseases, including gastrointestinal malignancy, inflammatory bowel disease, resection of small or large bowel * Pregnancy **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Adults planning for travel ### Contacts Locations Module #### Locations **Location 1:** **City:** Sha Tin **Country:** Hong Kong **Facility:** Prince of Wales Hospital ### IPD Sharing Statement Module **IPD Sharing:** UNDECIDED ## 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: M4222 - Name: Anti-Bacterial Agents - Relevance: LOW - As Found: Unknown - ID: M4214 - Name: Anti-Infective Agents - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05451979 **Brief Title:** HIIT in Pediatric Heart Transplant Recipients (MedBIKE™) **Official Title:** High Intensity Interval Training in Pediatric Heart Transplant Recipients: Evaluating a Novel Telemedicine Video Game-Linked Exercise Platform (MedBIKE™) #### Organization Study ID Info **ID:** Pro00109855 #### Organization **Class:** OTHER **Full Name:** University of Alberta ### Status Module #### Completion Date **Date:** 2025-12-31 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2023-07-11 **Type:** ACTUAL **Last Update Submit Date:** 2023-07-07 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2024-12-31 **Type:** ESTIMATED #### Start Date **Date:** 2022-02-22 **Type:** ACTUAL **Status Verified Date:** 2023-07 #### Study First Post Date **Date:** 2022-07-11 **Type:** ACTUAL **Study First Submit Date:** 2021-11-08 **Study First Submit QC Date:** 2022-07-06 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** Women and Children's Health Research Institute, Canada **Class:** UNKNOWN **Name:** Canadian Donation and Transplantation Research Program #### Lead Sponsor **Class:** OTHER **Name:** University of Alberta #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** Heart transplantation is the long-term treatment for children and adults with advanced heart failure. Post-transplant outcomes have improved over time, such that 50% of pediatric heart transplant recipients (HTR) remain alive with a need for re-transplantation 17-years following the initial transplant. With improved short- and medium-term outcomes, focus has shifted towards optimizing long-term survival and reducing transplant-associated morbidities. This includes strategies aimed at optimizing cardiorespiratory fitness and physical activity levels. Pediatric and adult HTRs have reduced exercise capacity compared with the general population. Previous groups have shown gradual improvements in heart rate response to exercise and exercise capacity in pediatric HTRs. However, after an initial improvement, exercise capacity appears to plateau, or even decline in pediatric HTRs, and remains sub-optimal compared with the general population. Most exercise interventions in HTRs to date have focused on moderate-intensity continuous exercise (MICE), with some resistance components incorporated. More recently, high-intensity interval training (HIIT), consisting of short, intense bursts of exercise with rest periods, has been explored in the adult HTR population, with findings to date suggesting that it may yield greater improvements in cardiorespiratory fitness compared with MICE. Exercise interventions, particularly HIIT interventions, have consistently shown clinically important improvements in exercise capacity in adult HTRs that are linked with improved long-term post-transplant outcomes and well-being. Unfortunately, trials of exercise interventions in pediatric HTRs remain lacking. This study team is proposing an assessment of the feasibility of a home-based HIIT exercise program using a novel telemedicine-enable video game linked customizable cycle ergometer (MedBIKE™). **Detailed Description:** Purpose: To determine the feasibility of MedBIKE™ in a 12-week home-based high intensity interval training program in pediatric heart transplant recipients (HTRs). Hypothesis: The MedBIKE™ intervention will be feasible, with adequate enrolment of eligible participants (\>60%), high session compliance (\>80%), and low-drop out rate (\~10%), with no adverse events directly related to the intervention. The investigators further hypothesize that the MedBIKE™ HIIT intervention will result in immediate and sustained improvements in exercise capacity, physical activity, self-efficacy towards physical activity, and HRQoL. Justification: Clinical trials of exercise interventions in pediatric HTRs remains significantly lacking. This lack of literature to date has been identified as a significant knowledge gap in the Canadian Society of Transplantation/CAN-RESTORE recent joint statement. While the findings to date indicate that exercise interventions in pediatric HTRs may show improvements in exercise capacity, numerous knowledge gaps remain. For example, despite promising findings in adult HTRs, HIIT has not yet been studied in pediatric HTRs. Moreover, the effect of exercise interventions on physical activity, HRQoL, and self-efficacy towards physical activity have not been well studied. It is important to evaluate whether a supervised exercise intervention at near-maximal intensity can promote improvements in physical activity self-efficacy that may in turn yield sustained improvements in physical activity. One of the limiting factors for regular participation in post-transplant exercise programs is the necessary time commitment that is intensified in a program with demographics such as ours in Western Canada with many post-transplant children living far from the transplant center and with limited access to exercise facilities. A supervised home-based training program could optimize the time-efficiency and accommodate the patient's routine schedules. Thus, the investigators are proposing an assessment of the feasibility of a home-based HIIT exercise program using a novel telemedicine-enabled video game-linked customizable cycle ergometer (MedBIKE™). Objectives: (Primary) Evaluate the feasibility of a 12-week, home-based HIIT MedBIKE™ intervention in pediatric HTRs. (Secondary) Evaluate the impact of the MedBIKE™ HIIT intervention on 1) exercise capacity; 2) physical activity; 3) self-efficacy towards physical activity; 4) HRQoL and 5) sustained changes in all secondary outcomes at 6- and 12-months post-intervention. Research Method: Single-center, randomized crossover feasibility trial with a multi-method approach. Potential participants and families will be approached first by a clinical team member. Participants and parents expressing interest will meet with a research coordinator who, along with one of the investigators and the clinical team will screen for eligibility. Written consent and assent (if applicable) will be obtained from participants who are deemed eligible. Following recruitment, participants will be administered the PedsQL and CSAPPA questionnaires, an accelerometer will be provided for seven days, and a baseline CPET will be performed or scheduled to occur following completion of the accelerometer assessment. Participants will then be randomized via a 1:1 allocation ratio with permuted blocks of randomly varied sizes either to the immediate MedBIKE™ arm or the immediate control arm (usual care) for 12-weeks, followed by a repeat assessment. Participants in the control arm will then cross-over and complete the 12-week MedBIKE™ HIIT program, followed by a repeat assessment at the completion of the intervention. All post-intervention assessments will occur 3-7 days post-MedBIKE™ intervention (to allow adequate recovery) and accelerometers will be programmed to commence counts 24 hours post-assessment to avoid bias from fatigue from the CPET. Participants will then return for final assessments at 6- and 12-months post-MedBIKE™ intervention. Whenever possible, follow-up assessments will be coordinated with clinical appointments (pediatric HTRs are typically clinically assessed every 3-4 months or more frequently). The MedBIKE™ program is a first-person interactive videogame in which the participant is 'biking' around a safari collecting animals and will enter a wormhole when completing the high-intensity exercise portion. The participant and clinician applications are Windows WPF applications that run on windows 10 PCs. The participant application also includes a companion app that runs on an Android table. The MedBIKE™ service application is a platform-independent Python application that is run on a a secure Ubuntu Linux instance operated by the University of Alberta's Faculty of Medicine and Dentistry IT department. A follow-up assessment, identical to that of the baseline (questionnaires, CPET, interviews and a 7-day week wear of an accelerometer) will occur 3-14 days post-intervention. These assessments will be repeated at 6- and 12-months post-intervention. Plan for Data Analysis: The WHCRI biostatistics group will provide statistical and data analysis support. Continuous data will be summarized as median with first and third quartiles and changes in pre- and post-intervention measures will be evaluated using the Mann-Whitney test. Categorical data will be presented by absolute and relative frequencies (n and %). All statistical analyses will be performed by SAS 9.4 or later (SAS Institute Inc., Cary, NC, USA). ### Conditions Module **Conditions:** - Pediatric ALL - Transplant; Failure, Heart **Keywords:** - Cardiac rehabilitation - High Intensity Interval Training - Telemedicine ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** CROSSOVER **Intervention Model Description:** Randomized crossover study design. ##### Masking Info **Masking:** NONE **Primary Purpose:** DEVICE_FEASIBILITY #### Enrollment Info **Count:** 10 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Participants will complete the baseline assessments and begin the MedBIKE HIIT Exercise Program intervention within 2-weeks. After the completion of the 12-week program, participants will return for follow-up assessments which will be repeated at 6- and 12-months post intervention. **Intervention Names:** - Device: MedBIKE HIIT **Label:** MedBIKE HIIT **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Participants will complete the baseline assessments and continue with standard of care (no intervention) for 12-weeks then return for a repeat assessment. Participants will then crossover into the MedBIKE HIIT Exercise Program intervention group for 12-weeks. A post-intervention assessment will be completed and follow-up assessments at 6- and 12-months post intervention. **Label:** Standard of Care **Type:** NO_INTERVENTION ### Interventions #### Intervention 1 **Arm Group Labels:** - MedBIKE HIIT **Description:** Participants will complete a high intensity interval training exercise program 3 times a week for 12 weeks (36 sessions total) **Name:** MedBIKE HIIT **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Description:** Pediatric heart transplant participants will be provided with a MedBIKE™ system to complete a video game linked 12-week high intensity interval training program equipped with telemedicine capabilities. Feasibility will be defined as adequate recruitment of eligible participants (greater than 60 percent), high session compliance (greater than 80 percent), low drop-out rate (less than 10 percent) and safety in terms of no severe adverse events related to the intervention. **Measure:** Evaluate the feasibility of a 12-week, home-based HIIT MedBIKE™ intervention in pediatric heart transplant recipients. **Time Frame:** 12 weeks #### Secondary Outcomes **Description:** CPET (Exercise Stress Test with Spirometry) will be done to measure the VO2peak (mL/kg/min) output of participants. A comparison will be done pre- and post-MedBIKE intervention, as well as 6 and 12-months post, to determine the change in overall VO2peak of participants. **Measure:** Exercise capacity through the change in VO2peak (mL/kg/min) measured using CPET testing. **Time Frame:** 13 months **Description:** Participants will be provided with an accelerometer to wear for 7-days prior to the start of the MedBIKE intervention program and again for 7-days post intervention and again at 6 and 12-months post intervention. The accelerometer will measure the time spent in moderate to vigorous physical activity (MVPA) and the sedentary time. A comparison will be done pre- and post-MedBIKE intervention to determine changes in the physical activity levels. The 6-month and 12-month time points will be used for a comparison on the sustained changes of the intervention. **Measure:** Changes in physical activity, defined as time spent in moderate to vigorous physical activity (MVPA) and sedentary time, measured by wearing an accelerometer for 7-days prior and 7-days post MedBIKE intervention **Time Frame:** 13 months **Description:** Participants will be asked to complete the PedsQL Cardiac Module questionnaire. This questionnaire is a validated multidimensional instrument to assess cardiac specific health-related quality of life in youth. This questionnaire is scored on a scale of 0-100, where a higher score indicates a better quality of life. These scores will be compared pre- and post-MedBIKE intervention to determine changes in health-related quality of life. The 6-month and 12-month time points will be used for a comparison on the sustained changes of the intervention. **Measure:** Changes in cardiac specific health-related quality of life will be measured using the PedsQL Cardiac Module questionnaire. **Time Frame:** 13 months **Description:** Participants will be asked to complete the Children's Self-Perceptions of Adequacy in and Predilection for Physical Activity (CSAPPA) scale. This questionnaire consists of 19 questions and is a validated tool designed to assess self-perceptions of adequacy and predilection towards physical activity in youth on a scale of low, moderate and high in terms of attitudes towards physical activity. The overall score of this questionnaire will be compared pre- and post-MedBIKE intervention and again at 6 and 12-months post-intervention to evaluate sustained changes. **Measure:** Changes in self efficacy towards physical activity measured on the Children's Self-Perceptions of Adequacy in and Predilection for Physical Activity (CSAPPA) scale. **Time Frame:** 13 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Pediatric heart transplant recipients, at least 6-months post heart transplantation * Aged 10-18 years Exclusion Criteria: * Non-English speaking (thus limiting communication during the MedBIKE™ sessions) * Home environment cannot accommodate the MedBIKE™ system (for example, space limitations) * History of multiorgan transplant * Adult unavailable to supervise the home-based exercise sessions * Episode of clinical antibody- or cellular-mediated rejection within 3-months of the baseline assessment * Previous involvement in a cardiac rehabilitation or exercise intervention program * Primary cardiologist has exercise restricted the participant or counsels against participation * Previous exercise stress test demonstrating sustained arrhythmias, ST segment elevation or depression greater than 3mm, an inappropriate rise in blood pressure (BP) (\<20 mmHg) or a systolic BP \>200 mmHg, or symptoms of chest pain or syncope * Resting arterial saturation \<85% or oxygen requirements * Moderate ventricular systolic dysfunction (or worse) at the most recent echocardiogram * History of chest pain on exertion * Unrepaired/unpalliated CHD * Arrhythmias in the last year (including supraventricular tachycardia, ventricular tachycardia, atrioventricular block (Mobitz II or worse)) * New York Heart Association class II or worse symptoms * Active medical inter-current illness limiting ability to participate * Cognitive impairment limiting the communication needed for the HIIT program * Extracardiac or congenital abnormality limiting the participant's functional ability to exercise **Maximum Age:** 18 Years **Minimum Age:** 10 Years **Sex:** ALL **Standard Ages:** - CHILD - ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Rae Foshaug **Phone:** 7804077499 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Michael Khoury, MD **Phone:** 7804920103 **Role:** CONTACT #### Locations **Location 1:** **City:** Edmonton **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Rae Foshaug - **Phone:** 7804077499 - **Role:** CONTACT ***Contact 2:*** - **Email:** [email protected] - **Name:** Michael Khoury, MD - **Phone:** 7804920103 - **Role:** CONTACT ***Contact 3:*** - **Name:** Michael Khoury, MD - **Role:** PRINCIPAL_INVESTIGATOR **Country:** Canada **Facility:** University of Alberta **State:** Alberta **Status:** RECRUITING **Zip:** T6G 2B7 #### Overall Officials **Official 1:** **Affiliation:** University of Alberta **Name:** Michael Khoury, MD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **Description:** Individual participant data will not be shared with other researchers. All data will be de-identified prior to analysis and publication. **IPD Sharing:** NO ### References Module #### References **Citation:** Khoury M, Phillips DB, Wood PW, Mott WR, Stickland MK, Boulanger P, Rempel GR, Conway J, Mackie AS, Khoo NS. Cardiac rehabilitation in the paediatric Fontan population: development of a home-based high-intensity interval training programme. Cardiol Young. 2020 Oct;30(10):1409-1416. doi: 10.1017/S1047951120002097. Epub 2020 Jul 27. **PMID:** 32716280 ## Derived Section ### Condition Browse Module - Browse Branches - Abbrev: Rare - Name: Rare Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: T1134 - Name: Childhood Acute Lymphoblastic Leukemia - Relevance: HIGH - As Found: Pediatric ALL ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05247879 **Brief Title:** Clinical Effectiveness and Safety of a Novel Oral Rehydration Solution **Official Title:** Clinical Effectiveness and Safety of a Novel Oral Rehydration Solution in Children Ages 1-5 Years Presenting to Hospital With Mild or Moderate Dehydration Gastroenteritis: Randomized, Open-label, Controlled Trial #### Organization Study ID Info **ID:** 5003 #### Organization **Class:** INDUSTRY **Full Name:** Mead Johnson Nutrition ### Status Module #### Completion Date **Date:** 2024-01-18 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2024-03-25 **Type:** ACTUAL **Last Update Submit Date:** 2024-03-22 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2023-09-20 **Type:** ACTUAL #### Start Date **Date:** 2022-06-30 **Type:** ACTUAL **Status Verified Date:** 2024-03 #### Study First Post Date **Date:** 2022-02-21 **Type:** ACTUAL **Study First Submit Date:** 2022-01-07 **Study First Submit QC Date:** 2022-02-17 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Mead Johnson Nutrition #### 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 randomised, controlled, open-label study to determine the clinical effectiveness and safety of a novel ORS compared with a commercial ORS in children 1 to 5 years of age attending emergency departments with gastroenteritis. ### Conditions Module **Conditions:** - Gastroenteritis Acute ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** SUPPORTIVE_CARE #### Enrollment Info **Count:** 60 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Intervention Names:** - Dietary Supplement: Glucose containing Oral Rehydration Solution (ORS) **Label:** Commercial reduced-osmolarity oral rehydration solution (ORS **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Intervention Names:** - Dietary Supplement: Sugar free - amino acid and electrolyte ORS **Label:** VS011, new children's ORS, a sugar-free blend of amino acids and electrolytes **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Commercial reduced-osmolarity oral rehydration solution (ORS **Description:** Oral rehydration solution **Name:** Glucose containing Oral Rehydration Solution (ORS) **Type:** DIETARY_SUPPLEMENT #### Intervention 2 **Arm Group Labels:** - VS011, new children's ORS, a sugar-free blend of amino acids and electrolytes **Description:** Glucose free oral rehydration solution **Name:** Sugar free - amino acid and electrolyte ORS **Type:** DIETARY_SUPPLEMENT ### Outcomes Module #### Primary Outcomes **Description:** Assess change in clinical hydration status from presenting baseline status **Measure:** Clinically assessed adequate rehydration based on clinical judgement of change in or absence of presenting symptoms from baseline (i.e. heart rate, urine output, etc.) **Time Frame:** every 4 hours up to 24 hours or hospital discharge, whichever occurs first #### Secondary Outcomes **Description:** 5 point scale, 1(no discomfort) minimum, 5 (severe discomfort) maximum **Measure:** Clinical Assessment of patient's hydration status based on presenting symptoms (i.e. heart rate, urine output, etc.) **Time Frame:** Baseline **Measure:** Study ORS intake (units) **Time Frame:** Every 4 hours up to 24 hours or hospital discharge, whichever occurs first **Measure:** Use of IV fluids **Time Frame:** up to 24 hours or hospital discharge, whichever occurs first **Description:** kg **Measure:** Weight **Time Frame:** Every 4 hours up to 24 h or at hospital discharge, whichever occurs first **Measure:** Participant comfort questionaire **Time Frame:** baseline and 24 hours or hospital discharge, whichever occurs first **Measure:** Parent satisfaction questionnaire **Time Frame:** baseline and 24 hours or hospital discharge, whichever occurs first **Measure:** Frequency of vomiting **Time Frame:** every 4 hours up to 24 hours or hospital discharge, whichever occurs first **Measure:** Frequency episodes of urination **Time Frame:** every 4 hours up to 24 hours or hospital discharge, whichever occurs first **Measure:** Frequency of liquid/watery stool **Time Frame:** every 4 hours up to 24 hours or hospital discharge, whichever occurs first **Measure:** Time to resolution of liquid/water stool **Time Frame:** up to 24 hours or hospital discharge, whichever comes first **Measure:** Stool for bacterial pathogen culture and viral antigens **Time Frame:** up to 24 hours or hospital discharge, whichever comes first **Measure:** Time ready for discharge **Time Frame:** At discharge or 48 hours whichever occurs first **Measure:** Medically confirmed adverse events collected throughout the study period **Time Frame:** 0 hours through 7 days post discharge **Measure:** Record patient use of antibiotics during hospitalization **Time Frame:** up to 24 hours or hospital discharge, whichever comes first ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * 1 to 5 years of age, inclusive at randomization * Hospitalized with mild to moderate dehydration due to ongoing diarrhea * Signed informed consent obtained for child's participation in the study Exclusion Criteria: * Severe dehydration and/or use of IV fluids for current hospitalization * Experiencing bloody diarrhea or diarrhea due to Cholera, Dysentery, persistent/chronic diarrhea, diarrhea with severe malnutrition, diarrhea associated with recent antibiotic use * In the opinion of the Investigator, not suitable for treatment with ORS * Have any underlying disease or disorder that may, in the opinion of the Investigator, affect the results of the study if they were enrolled (includes, but is not limited to, gastrointestinal disorders such as Crohn's disease or other inflammatory bowel disease or congenital malabsorption disorders) * Cause of the dehydration is something other than diarrhea * Known to be allergic to any of the components of the Investigational ORS **Maximum Age:** 5 Years **Minimum Age:** 1 Year **Sex:** ALL **Standard Ages:** - CHILD ### Contacts Locations Module #### Locations **Location 1:** **City:** Bangkok **Country:** Thailand **Facility:** Ramathibodi Hospital **Location 2:** **City:** Bangkok **Country:** Thailand **Facility:** Siriraj Hospital **Location 3:** **City:** Chiang Mai **Country:** Thailand **Facility:** Maharaj Nakorn Chiang Mai Hospital **Location 4:** **City:** Phitsanulok **Country:** Thailand **Facility:** Naresuan University Hospital ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000005767 - Term: Gastrointestinal Diseases - ID: D000004066 - Term: Digestive System 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: BC06 - Name: Digestive System Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M6883 - Name: Dehydration - Relevance: LOW - As Found: Unknown - ID: M8875 - Name: Gastroenteritis - Relevance: HIGH - As Found: Gastroenteritis - ID: M7255 - Name: Digestive System Diseases - Relevance: LOW - As Found: Unknown - ID: M8883 - Name: Gastrointestinal Diseases - Relevance: LOW - As Found: Unknown - ID: T170 - Name: Acute Graft Versus Host Disease - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000005759 - Term: Gastroenteritis ### 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 ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03063879 **Acronym:** SD-CRF **Brief Title:** Treating Hepatitis C in CRF Using Sofosbuvir and Daclatasvir **Official Title:** Efficacy and Safety of Sofosbuvir and Daclatasvir in Treating Patients With Hepatitis C and Renal Failure. #### Organization Study ID Info **ID:** 96-04-37-37348 #### Organization **Class:** OTHER **Full Name:** Tehran University of Medical Sciences ### Status Module #### Completion Date **Date:** 2019-02-01 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2019-09-30 **Type:** ACTUAL **Last Update Submit Date:** 2019-09-27 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2018-09-01 **Type:** ACTUAL #### Start Date **Date:** 2017-04-01 **Type:** ACTUAL **Status Verified Date:** 2018-02 #### Study First Post Date **Date:** 2017-02-24 **Type:** ACTUAL **Study First Submit Date:** 2017-02-21 **Study First Submit QC Date:** 2017-02-23 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** Ahvaz Jundishapur University of Medical Sciences **Class:** OTHER **Name:** Shiraz University of Medical Sciences **Class:** OTHER **Name:** Hamadan University of Medical Science #### Lead Sponsor **Class:** OTHER **Name:** Tehran University of Medical Sciences #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Sofosbuvir is the base of most treatment regimens for hepatitis C. In patients with renal failure the blood level of one of its metabolites (GS-331007) rises up to 20 folds. Although no particular adverse event has been linked to this metabolite sofosbuvir is not recommended for patients with renal failure mainly because of lack of data. Nevertheless there are anecdotal reports and small studies proving the safety of sofosbuvir in renal failure. This study addresses this lack of information by evaluating the safety and efficacy of sofosbuvir and daclatasvir in treating hepatitis C in 100 patients with renal failure. ### Conditions Module **Conditions:** - Hepatitis C, Chronic - Chronic Renal Failure **Keywords:** - hepatitis C - renal failure - sofosbuvir - daclatasvir ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 95 **Type:** ACTUAL **Phases:** - PHASE4 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Sofosbuvir 400 mg and daclatasvir 60 mg **Intervention Names:** - Drug: Sofosbuvir 400 mg and daclatasvir 60 mg **Label:** Sovodak **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Sovodak **Description:** Daily fixed dose combination pill (Sovodak) containing 400 mg sofosbuvir and 60 mg daclatasvir for 12 weeks if not cirrhotic (liver stiffness \< 12 KPa) or 24 weeks if cirrhotic **Name:** Sofosbuvir 400 mg and daclatasvir 60 mg **Other Names:** - Sovodak **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Lack of detectable hepatitis C virus in blood 12 weeks after end of treatment **Measure:** Sustained Viral Response (SVR12) **Time Frame:** 12 weeks after end of treatment #### Secondary Outcomes **Description:** Adverse drug events recorded by direct questioning **Measure:** Safety as assessed by adverse drug events **Time Frame:** From start of treatment to 12 weeks after end of treatment ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Positive qualitative hepatitis C virus RNA test on two occasions at least 6 months apart * Renal failure (eGFR \< 30 cc/min) or under hemodialysis Exclusion Criteria: * Model for End-stage Liver Disease (MELD) score \> 20, * Child's C (CTP score \> 12), * Heart rate \< 50/min, * Taking amiodarone **Maximum Age:** 75 Years **Minimum Age:** 16 Years **Sex:** ALL **Standard Ages:** - CHILD - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Tehran **Country:** Iran, Islamic Republic of **Facility:** Shariati Hospital **Zip:** 14117 #### Overall Officials **Official 1:** **Affiliation:** Tehran University of Medical Sciences **Name:** Shahin Merat, MD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Poustchi H, Majd Jabbari S, Merat S, Sharifi AH, Shayesteh AA, Shayesteh E, Minakari M, Fattahi MR, Moini M, Roozbeh F, Mansour-Ghanaei F, Afshar B, Mokhtare M, Amiriani T, Sofian M, Somi MH, Agah S, Maleki I, Latifnia M, Fattahi Abdizadeh M, Hormati A, Khoshnia M, Sohrabi M, Malekzadeh Z, Merat D, Malekzadeh R. The combination of sofosbuvir and daclatasvir is effective and safe in treating patients with hepatitis C and severe renal impairment. J Gastroenterol Hepatol. 2020 Sep;35(9):1590-1594. doi: 10.1111/jgh.14994. Epub 2020 Feb 5. **PMID:** 31994788 ## 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: 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: D000091642 - Term: Urogenital Diseases - ID: D000052801 - Term: Male Urogenital Diseases - ID: D000051436 - Term: Renal Insufficiency, Chronic - ID: D000002908 - Term: Chronic Disease - ID: D000020969 - Term: Disease Attributes - ID: D000010335 - Term: Pathologic Processes - ID: D000006521 - Term: Hepatitis, Chronic ### Condition Browse Module - Browse Branches - Abbrev: BC01 - Name: Infections - Abbrev: BC06 - Name: Digestive System Diseases - Abbrev: All - Name: All Conditions - Abbrev: BXS - Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: Rare - Name: Rare Diseases ### 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: M10699 - Name: Kidney Failure, Chronic - Relevance: HIGH - As Found: Chronic Renal Failure - ID: M9611 - Name: Hepatitis C - Relevance: HIGH - As Found: Hepatitis C - ID: M26718 - Name: Renal Insufficiency - Relevance: HIGH - As Found: Renal Failure - ID: M21613 - Name: Hepatitis C, Chronic - Relevance: HIGH - As Found: Hepatitis C, Chronic - 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: M17522 - Name: Virus Diseases - 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: M10698 - Name: Kidney Diseases - Relevance: LOW - As Found: Unknown - ID: M17319 - Name: Urologic 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: M27095 - Name: Male Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M26717 - Name: Renal Insufficiency, Chronic - 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: M9607 - Name: Hepatitis, Chronic - Relevance: LOW - As Found: Unknown - ID: T1303 - Name: Chronic Graft Versus Host Disease - Relevance: HIGH - As Found: Chronic ### Condition Browse Module - Meshes - ID: D000006506 - Term: Hepatitis A - ID: D000006526 - Term: Hepatitis C - ID: D000019698 - Term: Hepatitis C, Chronic - ID: D000006505 - Term: Hepatitis - ID: D000051437 - Term: Renal Insufficiency - ID: D000007676 - Term: Kidney Failure, Chronic ### Intervention Browse Module - Ancestors - ID: D000000998 - Term: Antiviral Agents - ID: D000000890 - Term: Anti-Infective Agents ### Intervention Browse Module - Browse Branches - Abbrev: Hemat - Name: Hematinics - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Infe - Name: Anti-Infective Agents ### Intervention Browse Module - Browse Leaves - ID: M11110 - Name: Liver Extracts - Relevance: LOW - As Found: Unknown - ID: M443 - Name: Sofosbuvir - Relevance: HIGH - As Found: Chronic Pain - 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 ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT02207179 **Brief Title:** Breast Cancer Margin Delineation Using Polarization Subtraction Imaging Technology **Official Title:** Breast Cancer Margin Delineation Using Polarization Subtraction Imaging Technology: An Ex-vivo Pilot Study of Real-time Breast Margin Imaging in Women Undergoing Breast Conservation Surgery for Early Stage Breast Cancer #### Organization Study ID Info **ID:** LM010 #### Organization **Class:** INDUSTRY **Full Name:** LumaMed ### Status Module #### Completion Date **Date:** 2015-11 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** RECRUITING #### Last Update Post Date **Date:** 2015-03-31 **Type:** ESTIMATED **Last Update Submit Date:** 2015-03-30 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2015-09 **Type:** ESTIMATED #### Start Date **Date:** 2014-01 **Status Verified Date:** 2015-03 #### Study First Post Date **Date:** 2014-08-04 **Type:** ESTIMATED **Study First Submit Date:** 2014-03-25 **Study First Submit QC Date:** 2014-08-01 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** University of Wisconsin, Madison #### Lead Sponsor **Class:** INDUSTRY **Name:** LumaMed #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** This study will evaluate LumaScan, an innovative polarization microscope for real time, intraoperative imaging and evaluation of the surface of excised tissue excised during Breast Conservation Surgery (BCS) for non invasive and invasive breast cancer. The investigators hypothesis is that LumaScan will be comparable for cancer detection to conventional histopathologic evaluation of the same areas of breast tissue. The real time, intraoperative images provided by LumaScan will help improve BCS and lessen the need for BCS re-excision surgeries which can lead to higher cost, poor cosmetic outcomes, reduced survival rates, and loss of confidence in the tissue conservation surgery procedure. **Detailed Description:** LumaScan is an innovative polarization microscope that uses Polarization Subtraction Imaging (PSI) technology to provide real time, intra operative, digital images of the surface of tissue removed during BCS for breast cancer. PSI uses polarized visible light for optical sectioning and geometric imaging of the superficial layers of the surgically removed tissue while rejecting surface scatter and light from deeper layers. By rejecting light from deeper tissues PSI is able to exclusively focus on the superficial tissue layers. This also results in higher resolution images than are possible with standard optical imaging. PSI is used in both reflectance and fluorescence modes. Reflectance detects morphologic abnormalities that occur in tumor progression such as increased nuclear density, angiogenesis, cellular infiltration and crowding while fluorescence detects early biochemical changes. To enhance the contrast of tumor at the margins the investigators will use Methylene blue (MB), a dye that has been commonly used in breast surgery for mapping sentinel lymph nodes. MB can be administered peritumorally and is quickly taken up by cells in only a few minutes of exposure and its presence does not interfere with or preclude later histopathology on the same tissue specimen. A tumor specimen may also be dipped in MB post-excision to achieve tumor margin contrast enhancement and not interfere with pathologic assessment. Previous research using PSI technology has demonstrated the value of PSI in mapping tumor boundaries of breast cancer in excised tissue specimens and in non-melanoma skin cancers and these boundaries in side by side comparisons correlate well with those marked by a pathologist on representative sections prepared using standard H\&E staining procedures. ### Conditions Module **Conditions:** - Breast Cancer **Keywords:** - Intraoperative - Cancer margin - Spectroscopy - Polarization ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 40 **Type:** ESTIMATED **Phases:** - EARLY_PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** LumaScan Image Guided Surgery **Intervention Names:** - Device: LumaScan Image Guided Surgery **Label:** Single Arm **Type:** NO_INTERVENTION ### Interventions #### Intervention 1 **Arm Group Labels:** - Single Arm **Name:** LumaScan Image Guided Surgery **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Description:** Quantitative metrics (e.g. size or area of tumor found between the two images) will be used to to compare en-face pathology and corresponding LumaScan images from excised breast tissue margins. **Measure:** Tumor areas shown on LumaScan images are the same as those shown on subsequent en-face pathology images. **Time Frame:** From day of surgery until receipt of pathology results (upto 2 weeks) #### Secondary Outcomes **Description:** The Pathologists will be asked to interpret LumaScan images and corresponding histopathology images. The images will be randomly presented to the Pathologist in order to be blinded to each. **Measure:** Pathologist interpretation of LumaScan images (blinded) are similar to those of histopathology images. **Time Frame:** From day of surgery until receipt of pathology results (upto 2 weeks) **Description:** To correlate and determine the surgeons blinded interpretation of the LumaScan images, digital photographs vs. the final pathologic outcomes (post image acquisition) **Measure:** Surgeons interpretation of LumaScan images (blinded) are similar to those of histopathology images. **Time Frame:** From day of surgery until receipt of pathology results (upto 2 weeks) **Measure:** Time for each margin and bi-valved image acquisition in the operating room **Time Frame:** Duration of surgery (upto 3 hours) ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Women referred for breast conservation surgery following a diagnosis of invasive or in situ carcinoma of the breast by histopathology or women referred for lumpectomy due to a benign (fibroadenoma or papilloma) or high risk breast lesion(Atypical ductal hyperplasia, atypical lobular hyperplasia, lobular carcinoma in-situ, atypical papilloma). 2. 18 years of age or older. 3. Able to read or understand and give informed consent. Exclusion Criteria: 1. Patients undergoing neo-adjuvant systemic therapy. 2. Previous breast cancer and /or radiation in the operated breast. 3. Implants in the operated breast. 4. Pregnant or Lactating. 5. History of photosensitizing disease (porphyria, lupus etc.) or of allergy to methylene blue dye. 6. Recent use of photosensitizing agents such as fluoroquinolones and retinoids or patients undergoing phototherapy. 7. Participation in any other intraoperative margin assessment protocol that would affect data acquisition. 8. Subareolar location (cancer is directly and completely under the nipple/areolar complex) of breast abnormality. 9. Patients for whom English is not their native language **Maximum Age:** 70 Years **Minimum Age:** 18 Years **Sex:** FEMALE **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Shabbir B Bambot, PhD **Phone:** 678-907-4711 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Mark Samuels, MS **Phone:** 404-376-6726 **Role:** CONTACT #### Locations **Location 1:** **City:** Madison **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Jennifer Mirrielees, MS - **Phone:** 608-265-1113 - **Role:** CONTACT **Country:** United States **Facility:** University of Wisconsin **State:** Wisconsin **Status:** RECRUITING **Zip:** 53792 #### Overall Officials **Official 1:** **Affiliation:** University of Wisconsin, Madison **Name:** Lee G Wilke, MD **Role:** PRINCIPAL_INVESTIGATOR ## 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: 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 ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03291379 **Acronym:** VEROnA **Brief Title:** Vandetanib-eluting Radiopaque Embolic Beads in Patients With Resectable Liver Malignancies **Official Title:** VEROnA: A Window of Opportunity Study of Vandetanib-eluting Radiopaque Embolic Beads (BTG-002814) in Patients With Resectable Liver Malignancies #### Organization Study ID Info **ID:** BTG-002814-01 #### Organization **Class:** INDUSTRY **Full Name:** Boston Scientific Corporation ### Status Module #### Completion Date **Date:** 2019-08-03 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2021-07-19 **Type:** ACTUAL **Last Update Submit Date:** 2021-07-15 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2019-08-03 **Type:** ACTUAL #### Results First Post Date **Date:** 2021-02-03 **Type:** ACTUAL **Results First Submit Date:** 2020-10-05 **Results First Submit QC Date:** 2021-01-14 #### Start Date **Date:** 2017-05-17 **Type:** ACTUAL **Status Verified Date:** 2021-07 #### Study First Post Date **Date:** 2017-09-25 **Type:** ACTUAL **Study First Submit Date:** 2017-05-17 **Study First Submit QC Date:** 2017-09-21 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** Biocompatibles UK Ltd #### Lead Sponsor **Class:** INDUSTRY **Name:** Boston Scientific Corporation #### 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 pilot, open label single arm phase 0 window of opportunity study of vandetanib-eluting radiopaque beads in patients with resectable liver malignancies. **Detailed Description:** A pilot open-label single arm multicenter phase 0 window of opportunity study of BTG-002814 given up to 3 weeks prior to surgery in up to 12 patients with resectable Hepatocellular carcinoma (HCC) or Colorectal cancer (CRC) with liver metastases. ### Conditions Module **Conditions:** - Carcinoma, Hepatocellular - Metastatic Colorectal Cancer **Keywords:** - mCRC, HCC, radiopaque beads, vandetanib ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP **Intervention Model Description:** 1 mL BTG-002814 containing 100 mg vandetanib ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 8 **Type:** ACTUAL **Phases:** - EARLY_PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Single arm: BTG-002814 (vandetanib-eluting radiopaque beads) **Intervention Names:** - Drug: BTG-002814 **Label:** BTG-002814 **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - BTG-002814 **Description:** BTG-002814 containing 100 mg vandetanib **Name:** BTG-002814 **Other Names:** - vandetanib-eluting radiopaque beads **Type:** DRUG ### Outcomes Module #### Other Outcomes **Description:** The following serum biomarkers were measured at Baseline, pre-treatment, 1 day after treatment, Up to 3 days prior to surgical resection, end of study ; cytokines, chemokines and growth factors relevant to cancer and inflammation. **Measure:** Study Blood Biomarkers With the Potential to Identify Patients Likely to Respond to Treatment With BTG-002814 **Time Frame:** Baseline, pre-treatment, 1 day after treatment, Up to 3 days prior to surgical resection, end of study (28-32 days post-surgery). **Description:** The following tissue biomarkers were measured at Baseline, pre-treatment, Up to 3 days prior to surgical resection; Levels of serum alpha-fetoprotein (AFP) in patients with HCC. Levels of serum Carcinoembryonic Antigen (CEA), Cancer Antigen (CA)19-9 and CA-125 in patients with metastatic colorectal cancer (mCRC). **Measure:** Study Tissue Biomarkers to Explore Key Immune, Inflammatory and Drug Related Mechanisms **Time Frame:** Baseline, pre-treatment, Up to 3 days prior to surgical resection. #### Primary Outcomes **Description:** Adverse events (AEs) related to treatment with BTG-002814 using the National Cancer Institute- Common Terminology Criteria for Adverse Events- Version 4.0 (NCI-CTCAE v4.0) **Measure:** To Assess the Safety and Tolerability of Treatment With BTG-002814 **Time Frame:** Continuously throughout the study totalling 9 weeks **Description:** Pharmacokinetic (PK) analysis of participants plasma samples by liquid chromatography with tandem mass spectrometry at the following timepoints: pre-treatment, post treatment (2 hours, 4 hours, 24 hours), prior to surgery, and end of study to derive Cmax. **Measure:** Maximum Concentration (Cmax) of Vandetanib and N-desmethyl Vandetanib in Plasma Following Treatment With BTG-002814 **Time Frame:** pre-treatment, 2 hours post-treatment, 4 hours post treatment, 24 hours post treatment, prior to surgery, and end of study (28-32 days post-surgery) **Description:** PK analysis of participants resected liver tissue samples by liquid chromatography with tandem mass spectrometry to determine vandetanib concentrations at the centre, middle, and edge of the tumour, as well as in the normal tissue surrounding the tumour (1cm away). **Measure:** Concentration of Vandetanib in Resected Liver Tissue Following Treatment With BTG-002814 **Time Frame:** Following surgical resection of tumour **Description:** PK analysis of participants plasma samples by liquid chromatography with tandem mass spectrometry at the following timepoints: pre-treatment, post treatment (2 hours, 4 hours, 24 hours), prior to surgery, and end of study to derive Tmax **Measure:** Time Taken to Reach the Maximum Concentration (Tmax) of Vandetanib and N-desmethyl Vandetanib in Plasma Following Treatment With BTG-002814 **Time Frame:** pre-treatment, 2 hours post-treatment, 4 hours post treatment, 24 hours post treatment, prior to surgery, and end of study (28-32 days post-surgery) **Description:** PK analysis of participants plasma samples by liquid chromatography with tandem mass spectrometry at the following timepoints: pre-treatment, post treatment (2 hours, 4 hours, 24 hours), prior to surgery, and end of study to derive AUCEoS (area under the curve at end of study). **Measure:** Concentration of Vandetanib and N-desmethyl Vandetanib in Plasma Over Time Until End of Study Following Treatment With BTG-002814 **Time Frame:** pre-treatment, 2 hours post-treatment, 4 hours post treatment, 24 hours post treatment, prior to surgery, and end of study (28-32 days post-surgery) **Description:** PK analysis of participants resected liver tissue samples by liquid chromatography with tandem mass spectrometry to determine N-desmethyl vandetanib concentrations at the centre, middle, and edge of the tumour, as well as in the normal tissue surrounding the tumour (1cm away). **Measure:** Concentration of N-desmethyl Vandetanib in Resected Liver Tissue Following Treatment With BTG-002814 **Time Frame:** Following surgical resection of tumour #### Secondary Outcomes **Description:** An automated thresholding and filtering algorithm was designed to allow the volume of delivered beads to be quantitatively determined for regions of interest (liver, registered sample, tumour, tumour dilated 1cm, tumour dilated 2cm) from the pre-surgical non-contrast CT scan and the PET/CT of the explanted liver samples following surgery. **Measure:** Evaluate the Anatomical Distribution of BTG-002814 on Non-contrast Enhanced Imaging Using 4D CT **Time Frame:** 1 day after treatment **Description:** An evaluation of histopathological features in both malignant and non-malignant liver tissue from the surgical specimen was performed by microscopic examination. Sections of resected liver tissue was paraffin-embedded and Hematoxylin and Eosin (H\&E) slides were produced. The H\&E slides were scanned to produce 3D pathology models of tumour volume and compared to the 3D models generated from clinical imaging. This allowed the extent of tumour necrosis and viable tumour to be determined. **Measure:** Evaluation of Histopathological Features in the Surgical Specimen (Malignant and Non-malignant Liver Tissue) by Analysing Percentage of Tumour Necrosis and Viability **Time Frame:** Post-surgery (tumour resection) **Description:** An evaluation of histopathological features in both malignant and non-malignant liver tissue from the surgical specimen was performed by microscopic examination. Sections of resected liver tissue was paraffin-embedded and Hematoxylin and Eosin (H\&E) slides were produced. The H\&E slides were scanned to produce 3D pathology models of tumour volume and compared to the 3D models generated from clinical imaging. This allowed any vascular changes to be determined. **Measure:** Evaluation of Histopathological Features in the Surgical Specimen (Malignant and Non-malignant Liver Tissue) by Assessing Number of Participants With Any Vascular Changes. **Time Frame:** Post-surgery (tumour resection) **Description:** After acquisition of DCE-MRI liver sequences, tumour signal intensity curves were used to calculate tissue parameters describing tumour perfusion, blood flow and vascularity, before and following treatment with BTG 002814. Bland Altman analysis showed the variability between baseline and pre-treatment readings to be too high, so an interpretation of the changes in blood flow prior to surgery is unreliable. **Measure:** Assessment of Changes in Blood Flow on Dynamic Contrast-Enhanced (DCE) MRI Following Treatment With BTG-002814. The Following Parameters Will be Derived From DCE-MRI Images: Ktrans, Kep and Ve. **Time Frame:** Baseline, pre-treatment, up to 3 days prior to surgical resection of tumour ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Male or female adults (≥ 18 years old) 2. Patient with resectable HCC (Child Pugh A, International Normalized Ratio (INR) ≤1.5) or resectable liver metastases from CRC and a candidate for liver surgery 3. Patients with low risk for surgical morbidity and mortality from liver surgery according to the investigators judgement 4. World Health Organization (WHO) performance status 0, 1 or 2 5. Adequate haematological function with Hb \>90 g/L, absolute neutrophil count \>1.5 x 10\^9/L, Plt \>100 x 10\^9/L 6. Adequate liver function with serum bilirubin \<1.5 x upper limit of normal (ULN), alanine aminotransferase (ALT) (or aspartate aminotransferase (AST) if ALT not available) ≤5 x ULN, alkaline phosphatase (ALP) \<5 x ULN 7. Adequate renal function with serum creatinine ≤1.5 x ULN and calculated creatinine clearance (GFR) ≥50 mL/min estimated using a validated creatinine clearance calculation (e.g., Cockcroft-Gault or Wright formula). 8. Patient is willing to provide blood samples, and tissue samples at surgical resection, for research purposes 9. Patient is willing and able to provide written informed consent Exclusion Criteria: 1. Any systemic chemotherapy within 3 months of the screening visit or any plan to administer systemic chemotherapy prior to surgery 2. Previous treatment with transarterial embolisation (with or without chemotherapy) of the liver, prior radiotherapy or ablation therapy to the liver or prior yttrium-90 microsphere therapy 3. Any contraindication to vandetanib according to its local label including: * Hypersensitivity to the active substance * Congenital long corrected QT interval (QTc) syndrome * Patients known to have a QTc interval over 480 milliseconds * Concomitant use of medicinal products known to also prolong the QTc interval and/or induce Torsades de pointes 4. Any contraindication to hepatic artery catheterisation or hepatic embolisation procedures (e.g. portal venous thrombosis, severely reduced portal venous flow or hepatofugal blood flow, untreated varices at high risk of bleeding) 5. Women of childbearing potential not using effective contraception or women who are breast feeding 6. Confirmed allergy to iodine-based intravenous contrast media 7. Patients who cannot have CT, MRI or dynamic contrast-enhanced (DCE) MRI Imaging (according to site policy) 8. Active uncontrolled cardiovascular disease 9. Any co-morbid disease or condition or event that, in the investigator's judgment, would place the patient at undue risk and would preclude the safe use of BTG-002814 10. Levels of potassium, calcium, magnesium or thyroid stimulating hormone (TSH) outside the normal ranges, and that in the investigator's judgement are clinically significant, or other laboratory findings that in the view of the investigator makes it undesirable for the patient to participate in the study 11. Patients who have participated in another clinical trial with an investigational product within 4 weeks prior to the screening visit **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Bloomsbury **Country:** United Kingdom **Facility:** University College London Hospital **State:** London **Zip:** NW1 2BU #### Overall Officials **Official 1:** **Affiliation:** University College, London **Name:** Professor Ricky Sharma **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** UNDECIDED ### References Module #### References **Citation:** Beaton L, Tregidgo HFJ, Znati SA, Forsyth S, Clarkson MJ, Bandula S, Chouhan M, Lowe HL, Zaw Thin M, Hague J, Sharma D, Pollok JM, Davidson BR, Raja J, Munneke G, Stuckey DJ, Bascal ZA, Wilde PE, Cooper S, Ryan S, Czuczman P, Boucher E, Hartley JA, Lewis AL, Jansen M, Meyer T, Sharma RA. VEROnA Protocol: A Pilot, Open-Label, Single-Arm, Phase 0, Window-of-Opportunity Study of Vandetanib-Eluting Radiopaque Embolic Beads (BTG-002814) in Patients With Resectable Liver Malignancies. JMIR Res Protoc. 2019 Oct 2;8(10):e13696. doi: 10.2196/13696. **PMID:** 31579027 ## Document Section ### Large Document Module #### Large Docs - Date: 2018-12-03 - Filename: Prot_001.pdf - Has ICF: False - Has Protocol: True - Has SAP: False - Label: Study Protocol - Size: 1984491 - Type Abbrev: Prot - Upload Date: 2020-08-20T05:30 - Date: 2019-05-16 - Filename: SAP_000.pdf - Has ICF: False - Has Protocol: False - Has SAP: True - Label: Statistical Analysis Plan - Size: 725837 - Type Abbrev: SAP - Upload Date: 2020-08-19T12:59 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000004067 - Term: Digestive System Neoplasms - ID: D000009371 - Term: Neoplasms by Site - ID: D000009369 - Term: Neoplasms - ID: D000004066 - Term: Digestive System Diseases - ID: D000000230 - Term: Adenocarcinoma - ID: D000002277 - Term: Carcinoma - ID: D000009375 - Term: Neoplasms, Glandular and Epithelial - ID: D000009370 - Term: Neoplasms by Histologic Type - ID: D000008113 - Term: Liver Neoplasms - ID: D000008107 - Term: Liver Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: All - Name: All Conditions - Abbrev: BC06 - Name: Digestive System Diseases ### Condition Browse Module - Browse Leaves - ID: M5534 - Name: Carcinoma - Relevance: LOW - As Found: Unknown - ID: M9613 - Name: Carcinoma, Hepatocellular - Relevance: HIGH - As Found: Carcinoma, Hepatocellular - 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: M3585 - Name: Adenocarcinoma - 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: M11113 - Name: Liver Neoplasms - Relevance: LOW - As Found: Unknown - ID: M11107 - Name: Liver Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000006528 - Term: Carcinoma, Hepatocellular ### Intervention Browse Module - Browse Branches - Abbrev: Hemat - Name: Hematinics - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M11110 - Name: Liver Extracts - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module #### Event Groups **Group ID:** EG000 **Title:** BTG-002814 **Deaths Num Affected:** 1 **Deaths Num At Risk:** 8 **Description:** Single arm: BTG-002814 (vandetanib-eluting radiopaque beads) BTG-002814 (vandetanib-eluting radiopaque beads): BTG-002814 containing 100 mg vandetanib **ID:** EG000 **Other Num Affected:** 8 **Other Num at Risk:** 8 **Serious Number Affected:** 4 **Serious Number At Risk:** 8 **Title:** BTG-002814 **Frequency Threshold:** 0 #### Other Events **Term:** Bradycardia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA (21.0) **Term:** Cardiac signs and symptoms NEC **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA (21.0) **Term:** Sinus bradycardia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA (21.0) **Term:** Tinnitus **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Ear and labyrinth disorders **Source Vocabulary:** MedDRA (21.0) **Term:** Abdominal distension **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA (21.0) **Term:** Abdominal pain **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA (21.0) **Term:** Constipation **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA (21.0) **Term:** Diarrhoea **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA (21.0) **Term:** Dry mouth **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA (21.0) **Term:** Dyspepsia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA (21.0) **Term:** Gastritis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA (21.0) **Term:** Gastrooesophageal reflux disease **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA (21.0) **Term:** Nausea **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA (21.0) **Term:** Vomiting **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA (21.0) **Term:** Fatigue **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA (21.0) **Term:** Influenza like illness **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA (21.0) **Term:** Non-cardiac chest pain **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA (21.0) **Term:** Pain **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA (21.0) **Term:** Pyrexia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA (21.0) **Term:** Lung infection **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (21.0) **Term:** Postoperative wound infection **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (21.0) **Term:** Alanine aminotransferase **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA (21.0) **Term:** Aspartate aminotransferase **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA (21.0) **Term:** Blood albumin **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA (21.0) **Term:** Blood alkaline phosphatase **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA (21.0) **Term:** Blood bilirubin **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA (21.0) **Term:** Blood calcium **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA (21.0) **Term:** Blood creatinine **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA (21.0) **Term:** Blood glucose **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA (21.0) **Term:** Blood lactic acid **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA (21.0) **Term:** Blood magnesium **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA (21.0) **Term:** Blood sodium **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA (21.0) **Term:** Blood thyroid stimulating hormone **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA (21.0) **Term:** Blood urea **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA (21.0) **Term:** Blood uric acid **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA (21.0) **Term:** C-reactive protein **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA (21.0) **Term:** Electrocardiogram QT prolonged **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA (21.0) **Term:** Gamma-glutamyl transferase **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA (21.0) **Term:** Glomerular filtration rate **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA (21.0) **Term:** Haemoglobin **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA (21.0) **Term:** International normalized ratio **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA (21.0) **Term:** Neutrophil count **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA (21.0) **Term:** Neutrophil count decreased **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA (21.0) **Term:** Platelet count **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA (21.0) **Term:** Weight decreased **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA (21.0) **Term:** White blood cell count **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA (21.0) **Term:** Decreased appetite **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA (21.0) **Term:** Dehydration **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA (21.0) **Term:** Arthralgia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA (21.0) **Term:** Back pain **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA (21.0) **Term:** Groin pain **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA (21.0) **Term:** Myalgia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA (21.0) **Term:** Paraesthesia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA (21.0) **Term:** Delirium **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA (21.0) **Term:** Insomnia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA (21.0) **Term:** Cough **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA (21.0) **Term:** Dysphonia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA (21.0) **Term:** Dyspnoea **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA (21.0) **Term:** Hiccups **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA (21.0) **Term:** Laryngeal inflammation **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA (21.0) **Term:** Oropharyngeal pain **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA (21.0) **Term:** Dermatitis acneiform **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA (21.0) **Term:** Pruritus **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA (21.0) **Term:** Rash **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA (21.0) **Term:** Haematoma **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA (21.0) **Term:** Hypertension **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA (21.0) **Term:** Hypotension **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA (21.0) #### Serious Events **Term:** Ileus **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA (21.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 8 **Num Events:** 1 **Term:** Upper gastrointestinal hemorrhage **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA (21.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 8 **Num Events:** 1 **Term:** Ascites **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA (21.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 8 **Num Events:** 1 **Term:** Post procedural bile leak **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA (21.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 8 **Num Events:** 1 **Term:** Lung infection **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (21.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 8 **Num Events:** 1 **Term:** Postoperative wound infection **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (21.0) ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 8 **Num Events:** 2 **Term:** Sepsis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (21.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 8 **Num Events:** 1 **Term:** Abdominal wound dehiscence **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA (21.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 8 **Num Events:** 1 **Term:** Renal failure acute **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA (21.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 8 **Num Events:** 1 **Time Frame:** From date participant signed Informed Consent until the patient's last visit (up to 9 weeks) (or after this date if the site Investigator feels the event is related to study treatment) ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 8 **Units:** Participants ### Group **ID:** BG000 **Title:** BTG-002814 **Description:** Single arm: BTG-002814 (vandetanib-eluting radiopaque beads) BTG-002814 (vandetanib-eluting radiopaque beads): BTG-002814 containing 100 mg vandetanib ### Measure #### Measurement **Group ID:** BG000 **Lower Limit:** 50 **Upper Limit:** 69 **Value:** 62.5 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 1 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 7 **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:** 0 **Category Title:** Black or African American #### Measurement **Group ID:** BG000 **Value:** 7 **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:** 8 **Class Title:** United Kingdom ### Measure #### Measurement **Group ID:** BG000 **Value:** 8 **Class Title:** Grade 0 (asymptomatic) #### Measurement **Group ID:** BG000 **Value:** 0 **Class Title:** Grade 1 (Symptomatic, but ambulatory) #### Measurement **Group ID:** BG000 **Value:** 0 **Class Title:** Grade 2 (Symptomatic, <50% in bed) ### Measure #### Measurement **Group ID:** BG000 **Value:** 2 **Class Title:** Hepatocellular carcinoma (HCC) #### Measurement **Group ID:** BG000 **Value:** 6 **Class Title:** Metastatic colorectal cancer (mCRC) ### Measure #### Measurement **Group ID:** BG000 **Spread:** 1.4 **Value:** 1.6 **Class Title:** **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:** Race (NIH/OMB) **Unit of Measure:** Participants ### Measure 4 **Parameter Type:** NUMBER **Title:** Region of Enrollment **Unit of Measure:** participants ### Measure 5 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** World Health Organisation (WHO) Performance Status **Unit of Measure:** Participants ### Measure 6 **Description:** Participants must have resectable Hepatocellular carcinoma (HCC) (Child Pugh A, international normalized ratio (INR) ≤1.5) or resectable liver metastases from colorectal cancer (CRC) and be a candidate for liver surgery **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Tumour type **Unit of Measure:** Participants ### Measure 7 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** Number of liver lesions **Unit of Measure:** Count ## Results Section - More Information Module ### Certain Agreement **Restriction Type:** LTE60 **Restrictive Agreement:** True ### Point of Contact **Email:** [email protected] **Organization:** Biocompatibles UK Ltd **Phone:** 07805354224 **Title:** Sarah Cooper ## 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 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **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:** 4 **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 13.94 - **Upper Limit:** - **Value:** 24.3 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.82 - **Upper Limit:** - **Value:** 0.6 **Title:** #### Outcome Measure 3 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 404000 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 394000 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 327000 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 10800 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 8510 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 11000 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 18800 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 9120 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 7340 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 7550 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 12500 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 7090 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 160000 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 151000 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 11100 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1480 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4570 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 531 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 441 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2760 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1140 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 93500 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 6180 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1240 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1440 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2840 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2710 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 29100 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 5350 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 6010 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants #### Outcome Measure 4 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 67.08 - **Upper Limit:** - **Value:** 26.0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.04 - **Upper Limit:** - **Value:** 0.8 **Title:** #### Outcome Measure 5 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 3188.21 - **Upper Limit:** - **Value:** 6979.3 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 169.40 - **Upper Limit:** - **Value:** 81.1 **Title:** #### Outcome Measure 6 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4620 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4740 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3680 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 280 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 69.6 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 59.8 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 69.2 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 831 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 421 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 418 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 469 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 544 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 113 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 93.9 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 11.4 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 55.6 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 21 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 15.7 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 28.7 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 84 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 39.3 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 208 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 80.2 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 57.1 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 101 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 145 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 171 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 389 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 342 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 405 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants #### Outcome Measure 7 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 928.83 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 399.27 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 361.14 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 393.79 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 479.28 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 764.69 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 596.78 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 617.72 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 649.97 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 594.79 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 116.54 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0.32 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 36.26 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 108.85 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 852.03 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 849.29 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 751.62 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 15.26 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 86.28 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 202.56 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 148.09 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 51.14 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 115.39 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 166.80 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 720.78 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 103.82 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4.32 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 75.43 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 133.26 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 693.73 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 422.37 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 21.87 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 264.90 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 378.15 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 1 **Units:** Participants #### Outcome Measure 8 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 5 - **Spread:** - **Upper Limit:** 100 - **Value:** 92.5 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 95 - **Value:** 7.5 **Title:** #### Outcome Measure 9 **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:** 0 **Title:** #### Outcome Measure 10 #### Outcome Measure 11 #### Outcome Measure 12 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** Adverse events (AEs) related to treatment with BTG-002814 using the National Cancer Institute- Common Terminology Criteria for Adverse Events- Version 4.0 (NCI-CTCAE v4.0) **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Safety population - all participants treated with BTG-002814 **Reporting Status:** POSTED **Time Frame:** Continuously throughout the study totalling 9 weeks **Title:** To Assess the Safety and Tolerability of Treatment With BTG-002814 **Type:** PRIMARY **Unit of Measure:** Participants ##### Group **Description:** Single arm: BTG-002814 (vandetanib-eluting radiopaque beads) BTG-002814 (vandetanib-eluting radiopaque beads): BTG-002814 containing 100 mg vandetanib **ID:** OG000 **Title:** BTG-002814 #### Outcome Measure 2 **Description:** Pharmacokinetic (PK) analysis of participants plasma samples by liquid chromatography with tandem mass spectrometry at the following timepoints: pre-treatment, post treatment (2 hours, 4 hours, 24 hours), prior to surgery, and end of study to derive Cmax. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** all participants treated with BTG-002814 **Reporting Status:** POSTED **Time Frame:** pre-treatment, 2 hours post-treatment, 4 hours post treatment, 24 hours post treatment, prior to surgery, and end of study (28-32 days post-surgery) **Title:** Maximum Concentration (Cmax) of Vandetanib and N-desmethyl Vandetanib in Plasma Following Treatment With BTG-002814 **Type:** PRIMARY **Unit of Measure:** ng/mL ##### Group **Description:** Single arm: BTG-002814 (vandetanib-eluting radiopaque beads) BTG-002814 (vandetanib-eluting radiopaque beads): BTG-002814 containing 100 mg vandetanib **ID:** OG000 **Title:** BTG-002814 #### Outcome Measure 3 **Description:** PK analysis of participants resected liver tissue samples by liquid chromatography with tandem mass spectrometry to determine vandetanib concentrations at the centre, middle, and edge of the tumour, as well as in the normal tissue surrounding the tumour (1cm away). **Parameter Type:** NUMBER **Population Description:** Results were not available for 2 patients where sample was incorrectly prepared, or no sample was received. For patients with multiple tumours, only the treated tumours were sampled and analysed. The results for this outcome measure are reported by individual subject (where data was available) by each sample location (centre, middle, edge of the tumour or 1cm away from tumour) per row. **Reporting Status:** POSTED **Time Frame:** Following surgical resection of tumour **Title:** Concentration of Vandetanib in Resected Liver Tissue Following Treatment With BTG-002814 **Type:** PRIMARY **Unit of Measure:** ng/mL ##### Group **Description:** Single arm: BTG-002814 (vandetanib-eluting radiopaque beads) BTG-002814 (vandetanib-eluting radiopaque beads): BTG-002814 containing 100 mg vandetanib **ID:** OG000 **Title:** BTG-002814 #### Outcome Measure 4 **Description:** PK analysis of participants plasma samples by liquid chromatography with tandem mass spectrometry at the following timepoints: pre-treatment, post treatment (2 hours, 4 hours, 24 hours), prior to surgery, and end of study to derive Tmax **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** all participants treated with BTG-002814 **Reporting Status:** POSTED **Time Frame:** pre-treatment, 2 hours post-treatment, 4 hours post treatment, 24 hours post treatment, prior to surgery, and end of study (28-32 days post-surgery) **Title:** Time Taken to Reach the Maximum Concentration (Tmax) of Vandetanib and N-desmethyl Vandetanib in Plasma Following Treatment With BTG-002814 **Type:** PRIMARY **Unit of Measure:** hours ##### Group **Description:** Single arm: BTG-002814 (vandetanib-eluting radiopaque beads) BTG-002814: BTG-002814 containing 100 mg vandetanib **ID:** OG000 **Title:** BTG-002814 #### Outcome Measure 5 **Description:** PK analysis of participants plasma samples by liquid chromatography with tandem mass spectrometry at the following timepoints: pre-treatment, post treatment (2 hours, 4 hours, 24 hours), prior to surgery, and end of study to derive AUCEoS (area under the curve at end of study). **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** all participants treated with BTG-002814 **Reporting Status:** POSTED **Time Frame:** pre-treatment, 2 hours post-treatment, 4 hours post treatment, 24 hours post treatment, prior to surgery, and end of study (28-32 days post-surgery) **Title:** Concentration of Vandetanib and N-desmethyl Vandetanib in Plasma Over Time Until End of Study Following Treatment With BTG-002814 **Type:** PRIMARY **Unit of Measure:** ng*h/mL ##### Group **Description:** Single arm: BTG-002814 (vandetanib-eluting radiopaque beads) BTG-002814 (vandetanib-eluting radiopaque beads): BTG-002814 containing 100 mg vandetanib **ID:** OG000 **Title:** BTG-002814 #### Outcome Measure 6 **Description:** PK analysis of participants resected liver tissue samples by liquid chromatography with tandem mass spectrometry to determine N-desmethyl vandetanib concentrations at the centre, middle, and edge of the tumour, as well as in the normal tissue surrounding the tumour (1cm away). **Parameter Type:** NUMBER **Population Description:** Results were not available for 2 patients where sample was incorrectly prepared, or no sample was received. For patients with multiple tumours, only the treated tumours were sampled and analysed. The results for this outcome measure are reported by individual subject (where data was available), by each sample location (centre, middle, edge of the tumour, 1cm away from tumour) per row. **Reporting Status:** POSTED **Time Frame:** Following surgical resection of tumour **Title:** Concentration of N-desmethyl Vandetanib in Resected Liver Tissue Following Treatment With BTG-002814 **Type:** PRIMARY **Unit of Measure:** ng/mL ##### Group **Description:** Single arm: BTG-002814 (vandetanib-eluting radiopaque beads) BTG-002814 (vandetanib-eluting radiopaque beads): BTG-002814 containing 100 mg vandetanib **ID:** OG000 **Title:** BTG-002814 #### Outcome Measure 7 **Description:** An automated thresholding and filtering algorithm was designed to allow the volume of delivered beads to be quantitatively determined for regions of interest (liver, registered sample, tumour, tumour dilated 1cm, tumour dilated 2cm) from the pre-surgical non-contrast CT scan and the PET/CT of the explanted liver samples following surgery. **Parameter Type:** NUMBER **Population Description:** All 8 subjects treated with BTG-002814 were analysed, however, not all subjects have sampling of all regions (liver, registered sample, tumour, tumour dilated 1cm, tumour dilated 2cm) due to some samples not being able to be accurately processed and registered. The data for this outcome measure is reported by individual subject, for each sample region (where data is available) per row. **Reporting Status:** POSTED **Time Frame:** 1 day after treatment **Title:** Evaluate the Anatomical Distribution of BTG-002814 on Non-contrast Enhanced Imaging Using 4D CT **Type:** SECONDARY **Unit of Measure:** µL ##### Group **Description:** Single arm: BTG-002814 (vandetanib-eluting radiopaque beads) BTG-002814 (vandetanib-eluting radiopaque beads): BTG-002814 containing 100 mg vandetanib **ID:** OG000 **Title:** BTG-002814 #### Outcome Measure 8 **Description:** An evaluation of histopathological features in both malignant and non-malignant liver tissue from the surgical specimen was performed by microscopic examination. Sections of resected liver tissue was paraffin-embedded and Hematoxylin and Eosin (H\&E) slides were produced. The H\&E slides were scanned to produce 3D pathology models of tumour volume and compared to the 3D models generated from clinical imaging. This allowed the extent of tumour necrosis and viable tumour to be determined. **Dispersion Type:** Full Range **Parameter Type:** MEDIAN **Population Description:** all participants treated with BTG-002814 **Reporting Status:** POSTED **Time Frame:** Post-surgery (tumour resection) **Title:** Evaluation of Histopathological Features in the Surgical Specimen (Malignant and Non-malignant Liver Tissue) by Analysing Percentage of Tumour Necrosis and Viability **Type:** SECONDARY **Unit of Measure:** percentage of surgical specimen ##### Group **Description:** Single arm: BTG-002814 (vandetanib-eluting radiopaque beads) BTG-002814 (vandetanib-eluting radiopaque beads): BTG-002814 containing 100 mg vandetanib **ID:** OG000 **Title:** BTG-002814 #### Outcome Measure 9 **Description:** An evaluation of histopathological features in both malignant and non-malignant liver tissue from the surgical specimen was performed by microscopic examination. Sections of resected liver tissue was paraffin-embedded and Hematoxylin and Eosin (H\&E) slides were produced. The H\&E slides were scanned to produce 3D pathology models of tumour volume and compared to the 3D models generated from clinical imaging. This allowed any vascular changes to be determined. **Parameter Type:** NUMBER **Reporting Status:** POSTED **Time Frame:** Post-surgery (tumour resection) **Title:** Evaluation of Histopathological Features in the Surgical Specimen (Malignant and Non-malignant Liver Tissue) by Assessing Number of Participants With Any Vascular Changes. **Type:** SECONDARY **Unit of Measure:** Count of Participants ##### Group **Description:** Single arm: BTG-002814 (vandetanib-eluting radiopaque beads) BTG-002814 (vandetanib-eluting radiopaque beads): BTG-002814 containing 100 mg vandetanib **ID:** OG000 **Title:** BTG-002814 #### Outcome Measure 10 **Description:** After acquisition of DCE-MRI liver sequences, tumour signal intensity curves were used to calculate tissue parameters describing tumour perfusion, blood flow and vascularity, before and following treatment with BTG 002814. Bland Altman analysis showed the variability between baseline and pre-treatment readings to be too high, so an interpretation of the changes in blood flow prior to surgery is unreliable. **Reporting Status:** NOT_POSTED **Time Frame:** Baseline, pre-treatment, up to 3 days prior to surgical resection of tumour **Title:** Assessment of Changes in Blood Flow on Dynamic Contrast-Enhanced (DCE) MRI Following Treatment With BTG-002814. The Following Parameters Will be Derived From DCE-MRI Images: Ktrans, Kep and Ve. **Type:** SECONDARY #### Outcome Measure 11 **Description:** The following serum biomarkers were measured at Baseline, pre-treatment, 1 day after treatment, Up to 3 days prior to surgical resection, end of study ; cytokines, chemokines and growth factors relevant to cancer and inflammation. **Reporting Status:** NOT_POSTED **Time Frame:** Baseline, pre-treatment, 1 day after treatment, Up to 3 days prior to surgical resection, end of study (28-32 days post-surgery). **Title:** Study Blood Biomarkers With the Potential to Identify Patients Likely to Respond to Treatment With BTG-002814 **Type:** OTHER_PRE_SPECIFIED #### Outcome Measure 12 **Description:** The following tissue biomarkers were measured at Baseline, pre-treatment, Up to 3 days prior to surgical resection; Levels of serum alpha-fetoprotein (AFP) in patients with HCC. Levels of serum Carcinoembryonic Antigen (CEA), Cancer Antigen (CA)19-9 and CA-125 in patients with metastatic colorectal cancer (mCRC). **Reporting Status:** NOT_POSTED **Time Frame:** Baseline, pre-treatment, Up to 3 days prior to surgical resection. **Title:** Study Tissue Biomarkers to Explore Key Immune, Inflammatory and Drug Related Mechanisms **Type:** OTHER_PRE_SPECIFIED ### Participant Flow Module #### Group **Description:** Single arm: BTG-002814 (vandetanib-eluting radiopaque beads) BTG-002814 (vandetanib-eluting radiopaque beads): BTG-002814 containing 100 mg vandetanib **ID:** FG000 **Title:** BTG-002814 #### Period **Title:** Overall Study ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 8 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 8 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 0 **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT02666079 **Brief Title:** The LightPath® Breast Cancer Study **Official Title:** A Multi-centre Clinical Study to Evaluate the LightPath® Imaging System in Wide Local Excision (WLE) for Breast Cancer #### Organization Study ID Info **ID:** LPM-007 #### Organization **Class:** INDUSTRY **Full Name:** Lightpoint Medical Limited ### Status Module #### Completion Date **Date:** 2018-12 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** RECRUITING #### Last Update Post Date **Date:** 2018-06-20 **Type:** ACTUAL **Last Update Submit Date:** 2018-06-19 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2018-11 **Type:** ESTIMATED #### Start Date **Date:** 2017-05-01 **Type:** ACTUAL **Status Verified Date:** 2018-06 #### Study First Post Date **Date:** 2016-01-28 **Type:** ESTIMATED **Study First Submit Date:** 2016-01-25 **Study First Submit QC Date:** 2016-01-25 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** European Commission #### Lead Sponsor **Class:** INDUSTRY **Name:** Lightpoint Medical Limited #### 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 is a prospective, single arm, multi-centre study to evaluate the intra-operative use of the LightPath® Imaging System for the assessment of tumour margin status compared to hospital standard of care histopathology in wide local excision (WLE) for breast cancer The intraoperative 18F-fluorodeoxyglucose (18F-FDG) LightPath® Images will be used to inform the surgeons about detectable residual cancer, in an attempt to achieve better guided cancer surgery and complete tumour excision with clear WLE resection margins. Study sites will use the local criteria considered standard of care to guide decisions to act on positive margins. In the LightPath® arm the resection margin status of the WLE specimen, cavity shavings (if any) and the metastatic status of axillary (sentinel) lymph nodes as measured with the LightPath® Imaging System will be compared with histopathology results. **Detailed Description:** Female subjects with a diagnosis of invasive breast cancer scheduled to have wide local excision (WLE) +/- sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND) will be screened and receive 18F-FDG plus LightPath® Image. Subjects will have standard of care WLE. Extra cavity shaving due to positive 18F-FDG LightPath® Images is at the discretion of the surgeon. Subjects will receive an intravenous injection of up to 5 MBq/kg, to a maximum 300 MegaBecquerel (MBq) of 18F-FDG prior to surgery. Following resection, the WLE specimen will be examined using the LightPath® Imaging System. If the surgeons detect a positive signal they may perform cavity shavings of the resection cavity area corresponding to the positive signal area (up to a maximum thickness of 10mm). Axillary SLNB will be performed according to local practice. At sites where 99mTc is used: In the 18F-FDG + LightPath® a higher dose of up to 150 MBq technetium-99m (99mTc) nanocolloid is necessary to avoid 18F-FDG masking the signal from 99mTc. Blue dye will be used according to local practice at sites where it is considered standard of care. Sentinel lymph nodes (SLNs) will be examined using the LightPath® Imaging System. Where clinically indicated, ALND will be performed as per standard of care. At the time this protocol was finalised, LightPath® data involved lymph nodes sufficient to support recommendations were not available. For this reason, LightPath® Image results will not be used to direct ALND. All LightPath® Images will be performed between 60 and 180 minutes post injection of 18F-FDG. The WLE specimen, cavity shavings (where performed) and SLNs (where performed) will then undergo standard of care histopathological analysis. Lymph nodes will also be examined according to standard of care histopathological analysis. The results of the histopathological analysis will then be correlated with the LightPath® Images. All staff in the operating room will wear badge dosimeters. Staff handling surgical specimens in theatre will also wear ring dosimeters. Histopathology analyses should be delayed to allow for radioactive decay of tissue samples to suitably low levels. Subjects will be evaluated at screening and enrolment into the study. Data will be collected until the decision by the study site's MDT to recommend re-excision or mastectomy because of a positive margin on histopathological analysis (approx. 1-6 weeks post surgery) ### Conditions Module **Conditions:** - Breast Cancer **Keywords:** - Wide local excision (WLE) for breast cancer ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** DIAGNOSTIC #### Enrollment Info **Count:** 170 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Wide local excision (WLE) for breast cancer with intra-operative use of the LightPath® Imaging System. **Intervention Names:** - Device: LightPath® Imaging System. **Label:** Treatment arm **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Treatment arm **Description:** Intra-operative use of the LightPath® Imaging System. **Name:** LightPath® Imaging System. **Type:** DEVICE ### Outcomes Module #### Other Outcomes **Description:** Proportion of lymph nodes that agree metastatic status **Measure:** Agreement between LightPath® Image for lymph nodes status and histology **Time Frame:** Initial surgery **Description:** ER/PR/HER2 will each be defined as positive or negative in accordance with local practice **Measure:** Biomarkers ER/PR/HER2 status **Time Frame:** Screening #### Primary Outcomes **Description:** The diagnostic performance of tumour margin assessment with the LightPath® Imaging System compared to hospital histopathology. **Measure:** Diagnostic performance of the LightPath® Imaging System **Time Frame:** Initial surgery #### Secondary Outcomes **Description:** MDT recommendation for the subject to undergo re-excision or mastectomy because of a positive margin on histopathological analysis. **Measure:** The recommendation by the study site's multidisciplinary team (MDT) to re-operate at the index location (breast) within 1 to 6 weeks post-initial surgery according to local practice. **Time Frame:** 1-6 weeks post initial surgery **Description:** The number of subjects undergoing re-operation at the index location because of a positive margin on histopathological analysis, compared to published data on re-operation rates. **Measure:** Rate of re-operation at the index location **Time Frame:** 1 to 6 weeks post initial surgery **Description:** Weight (g) of all fresh pieces of tissue removed **Measure:** Volume of tissue excised **Time Frame:** Initial surgery **Description:** Dosimetry readings will be summarised by staff member and procedure **Measure:** Radiation dosimetry **Time Frame:** Initial surgery **Description:** Any untoward medical occurrence, unintended disease or injury, or untoward clinical signs (including abnormal laboratory findings) in subjects, users or other persons, whether r not related to the device **Measure:** Safety - adverse events (related to breast surgery) **Time Frame:** Initial surgery ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Subjects who have signed an informed consent form prior to any study related activity * Subjects who are able to give voluntary, written informed consent to participate in this study. * Subjects who are able to understand this study and are willing to complete all the study assessments * Female participants ≥18 years of age with a diagnosis of invasive breast cancer * Subjects who have disease in one quadrant of the breast, not including the nipple * Subjects scheduled for WLE for breast cancer +/- SLNB or ALND. * Females of childbearing age must have a negative pregnancy test (by Beta human chorionic gonadotropin (HCG) qualitative analysis), or must have had a history of a surgical sterilisation, or must give history of no menses in the past twelve months Exclusion Criteria: * Subjects with pure DCIS or with pleomorphic LCIS * Subjects who have had surgery in the ipsilateral breast in the past 12 months * Subjects who have had radiotherapy in the ipsilateral breast * Subjects who have had neoadjuvant systemic therapy * Subjects who have had systemic chemotherapy in the past two years * Subjects with a non-palpable lesion scheduled to have radio guided occult lesion localisation (ROLL) * Subjects who have known hypersensitivity to 18F-FDG * Subjects who are pregnant or lactating * Subjects who have an existing medical condition that would compromise their participation in the study * Subjects who have participated in a clinical study in the last 2 months * Subjects with a current or active history of other known cancer **Minimum Age:** 18 Years **Sex:** FEMALE **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Qamar B Akbar **Phone:** +44 (0) 1494 917 697 **Role:** CONTACT #### Locations **Location 1:** **City:** Gliwice **Contacts:** ***Contact 1:*** - **Name:** Maria Turska-d'Amico, MD - **Role:** CONTACT **Country:** Poland **Facility:** Klinika Chirurgii Onkologicznej i Rekonstrukcyjnej Centrum Onkologii- Instytut oddział w Gliwicach, ul. Wybrzeże Armii Krajowej 15, **Status:** RECRUITING **Zip:** 44-101 **Location 2:** **City:** Kraków **Contacts:** ***Contact 1:*** - **Name:** Anna Sowa-Staszczak, MD, PhD - **Role:** CONTACT **Country:** Poland **Facility:** Szpital Uniwersytecki w Krakowie, Oddział Kliniczny Endokrynologii, ul. Mikołaja Kopernika 17, **Status:** RECRUITING **Zip:** 31-501 **Location 3:** **City:** Warszawa **Contacts:** ***Contact 1:*** - **Name:** Prof. Zbigniew Nowecki, MD, PhD - **Role:** CONTACT **Country:** Poland **Facility:** Centrum Onkologii - Instytut, im Marii Skłodowskiej-Curie, Klinika Nowotworów Piersi i Chirurgii Rekonstrukcyjnej ul. Roetgena 5 **Status:** RECRUITING **Zip:** 02-781 **Location 4:** **City:** Liverpool **Country:** United Kingdom **Facility:** Royal Liverpool Hospital **Status:** TERMINATED **Zip:** L7 8XP **Location 5:** **City:** Llandough **Country:** United Kingdom **Facility:** Cardiff Breast Centre, LLandough Hospital **Status:** ACTIVE_NOT_RECRUITING **Zip:** CF64 2XX #### Overall Officials **Official 1:** **Affiliation:** Clinical Project Manager **Name:** Qamar B Akbar, MSc **Role:** STUDY_DIRECTOR ### IPD Sharing Statement Module **IPD Sharing:** UNDECIDED ### References Module #### References **Citation:** Jurrius PAGT, Grootendorst MR, Krotewicz M, Cariati M, Kothari A, Patani N, Karcz P, Nagadowska M, Vyas KN, Purushotham A, Turska-d'Amico M. Intraoperative [18F]FDG flexible autoradiography for tumour margin assessment in breast-conserving surgery: a first-in-human multicentre feasibility study. EJNMMI Res. 2021 Mar 18;11(1):28. doi: 10.1186/s13550-021-00759-w. **PMID:** 33738563 #### See Also Links **Label:** Company website with description of the technology and Conformité Européenne (CE) marked medical device **URL:** http://www.lightpointmedical.com/ **Label:** ISRCTN17778965 **URL:** http://www.isrctn.com/ISRCTN17778965 ## 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: 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 ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT02380079 **Brief Title:** Dose-Escalation Study of SCD-101 in Sickle Cell Disease **Official Title:** Part A: Phase IB, Single Site, Dose-Escalation of SCD-101 and Part B: Randomized, Double-Blind, Placebo-Controlled Crossover of SCD-101 in Adults With Homozygous Sickle Cell Disease or S/Beta 0 Thalassemia. #### Organization Study ID Info **ID:** INVX-SCD-101-11 #### Organization **Class:** INDUSTRY **Full Name:** Invenux, LLC ### Status Module #### Completion Date **Date:** 2023-12 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2023-03-21 **Type:** ACTUAL **Last Update Submit Date:** 2023-03-20 **Overall Status:** ACTIVE_NOT_RECRUITING #### Primary Completion Date **Date:** 2023-11 **Type:** ESTIMATED #### Start Date **Date:** 2015-02 **Type:** ACTUAL **Status Verified Date:** 2023-03 #### Study First Post Date **Date:** 2015-03-05 **Type:** ESTIMATED **Study First Submit Date:** 2015-02-23 **Study First Submit QC Date:** 2015-03-04 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** State University of New York - Downstate Medical Center #### Lead Sponsor **Class:** INDUSTRY **Name:** Invenux, LLC #### 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 purpose of this study is to determine the safety and clinical effects of SCD-101 when given to adults with sickle cell disease. **Detailed Description:** This is single site, dose- escalation study of SCD-101 in participants with homozygous sickle cell disease (S/S) or S/beta 0 Thalassemia. All participants will be monitored for safety, tolerability, and dose-limiting toxicities. The study is divided into two parts. Part A is an open-label, non-randomized, non-placebo-controlled dose escalation study with a 28-day treatment phase and 14-day follow-up phase with five cohorts . Part B is a randomized, placebo-controlled, confirmatory 2x2 crossover cohort with a 28 day washout between periods, and a 28-day follow-up phase. ### Conditions Module **Conditions:** - Sickle Cell Disease - Sickle-Beta Zero Thalassemia **Keywords:** - Homozygous Sickle Cell Disease S/Beta 0 Thalassemia ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** CROSSOVER **Intervention Model Description:** 2x2 crossover ##### Masking Info **Masking:** QUADRUPLE **Who Masked:** - PARTICIPANT - CARE_PROVIDER - INVESTIGATOR - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 60 **Type:** ESTIMATED **Phases:** - PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** SCD-101 dosed TID for 28-days **Intervention Names:** - Drug: SCD-101 **Label:** SCD-101 **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Placebo dosed TID for 28-days **Intervention Names:** - Drug: SCD-101 **Label:** Placebo **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Placebo - SCD-101 **Description:** Administered as gelatin capsules **Name:** SCD-101 **Type:** DRUG ### Outcomes Module #### Other Outcomes **Measure:** Part B: Exploratory Outcome Measure the mean change from baseline in sleep interference as measured by the PROMIS sleep interference questionnaire **Time Frame:** From the time the participant is accessed at baseline through the final follow-up (18 weeks) **Measure:** Part B: Exploratory Outcome Measure the mean change from baseline in pain interference as measured by the PROMIS pain interference questionnaire **Time Frame:** From the time the participant is accessed at baseline through the final follow-up (18 weeks) **Measure:** Part B: Exploratory Outcome Measure the mean change from baseline in patient reported daily pain as measured by a Numeric Rating Scale (NRS 0-10) **Time Frame:** From the time the participant is accessed at baseline through the final follow-up (18 weeks) **Measure:** Part B: Exploratory Outcome Measure the mean change from baseline in analgesic usage as measured by patient medication diary **Time Frame:** From the time the participant is accessed at baseline through the final follow-up (18 weeks) **Measure:** Part B: Exploratory Outcome Measure the mean:change from baseline in exercise and sleep activity as measured by wrist actigraphy **Time Frame:** From the time the participant is accessed at baseline through the final follow-up (18 weeks) **Measure:** Part B: Exploratory Outcome Measure the mean:change from baseline in plasma inflammatory cytokines as measured by ELISA **Time Frame:** From the time the participant is accessed at baseline through the final follow-up (18 weeks) #### Primary Outcomes **Measure:** Determine the safety, tolerability, and dose limiting toxicities of escalating doses of SCD-101, assessed by frequency and severity of adverse events (AEs), and changes in vital signs, 12-lead ECGs and laboratory assessments as compared to baseline **Time Frame:** From the time the participant is administered the first dose through the final follow-up (18 weeks) #### Secondary Outcomes **Measure:** Determine the effect of escalating doses of SCD-101 on the mean change in hemoglobin form base line **Time Frame:** From the time the participant is accessed at baseline through the final follow-up (18 weeks) **Measure:** Determine the effect of escalating doses of SCD-101 on the mean change in percent reticulocytes from baseline **Time Frame:** From the time the participant is accessed at baseline through the final follow-up (18 weeks) **Measure:** Determine the effect of escalating doses of SCD-101 on the mean change from baseline in red blood cell hemolysis as measured by lactate dehydrogenase (LDH) and indirect bilirubin. **Time Frame:** From the time the participant is accessed at baseline through the final follow-up (18 weeks) **Measure:** Determine the effect of escalating doses of SCD-101 on the mean change from baseline in fatigue as measured by the PROMIS fatigue questionnaire **Time Frame:** From the time the participant is accessed at baseline through the final follow-up (18 weeks) **Measure:** Determine the effect of escalating doses of SCD-101 on the mean change from baseline in the percent of venous circulating sickle red blood cells **Time Frame:** From the time the participant is accessed at baseline through the final follow-up (18 weeks) **Measure:** Determine the effect of escalating doses of SCD-101 on the mean change from baseline in functional capacity as measured by the 6-Minute Walk Test **Time Frame:** From the time the participant is accessed at baseline through the final follow-up (18 weeks) ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Male or female, 18-55 years of age 2. Homozygous sickle cell disease or S/beta 0 thalassemia 3. Hemoglobin F ≤10% 4. Hemoglobin ≥ 6.0 g/dL and ≤ 9.5 g/dL 5. Female participants of child bearing potential and male participants whose partner is a female of child bearing potential must be willing to use approved contraception during the trial and for 3 months following the end of treatment. Only barrier methods or complete abstinence are acceptable for this study. Participants using hormonal contraception (including morning-after-pill) and IUD are excluded unless willing/able to change to an acceptable form of contraception. 6. Ability to adhere to the study visit schedule and other protocol requirements 7. Ability to understand and the willingness to sign an informed consent document Exclusion Criteria: 1. Red blood cell transfusion within 3 months of enrollment 2. Hydroxyurea treatment within 6 months of enrollment 3. Painful or other acute sickle cell event that required a hospitalization within 4-weeks of enrollment 4. AST and/or ALT \>3x upper limit of normal and/or creatinine \>2x upper limit of normal or any other significant renal or hepatic impairment 5. Estimated creatinine clearance (CrCl) \< 60 mL/min (Cockcroft- Gault formula) at screening. 6. QTc interval of \>470 msec at trial entry and participant with congenital long QT syndrome. 7. No other significant sickle cell or non-sickle cell illness that would confound the results of the trial 8. Any condition that, in the view of the investigator, places the participant at risk because of participation in the trial, or may influence the result of the trial or the participant's ability to participate in the trial 9. Participant pregnant or nursing an infant or planning pregnancy during the course of the trial 10. History of allergic reactions attributed to sorghum or compounds of similar chemical or biologic composition (such as Nicosan, Niprisan, Jobelyn or Xickle). 11. Other investigational drug use within 3 months of enrollment 12. PROMIS Fatigue Questionnaire 8a T-score ˂ 44.3 **Maximum Age:** 55 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Brooklyn **Country:** United States **Facility:** King's County Hospital **State:** New York **Zip:** 11203 #### Overall Officials **Official 1:** **Affiliation:** King's County Hospital **Name:** John Muthu, MD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Wambebe C, Khamofu H, Momoh JA, Ekpeyong M, Audu BS, Njoku OS, Bamgboye EA, Nasipuri RN, Kunle OO, Okogun JI, Enwerem MN, Audam JG, Gamaniel KS, Obodozie OO, Samuel B, Fojule G, Ogunyale O. Double-blind, placebo-controlled, randomised cross-over clinical trial of NIPRISAN in patients with Sickle Cell Disorder. Phytomedicine. 2001 Jul;8(4):252-61. doi: 10.1078/0944-7113-00040. **PMID:** 11515714 **Citation:** Iyamu EW, Turner EA, Asakura T. In vitro effects of NIPRISAN (Nix-0699): a naturally occurring, potent antisickling agent. Br J Haematol. 2002 Jul;118(1):337-43. doi: 10.1046/j.1365-2141.2002.03593.x. **PMID:** 12100171 **Citation:** Iyamu EW, Turner EA, Asakura T. Niprisan (Nix-0699) improves the survival rates of transgenic sickle cell mice under acute severe hypoxic conditions. Br J Haematol. 2003 Sep;122(6):1001-8. doi: 10.1046/j.1365-2141.2003.04536.x. **PMID:** 12956772 **Citation:** Swift, RA, Nathan, S, Tripathi, P, Chen, Q, Asakura,T (2009, September). Research Preview on Improving Nicosan™/Xickle™: A Phyto-Medicine for the Treatment of Sickle Cell Disease. Paper presented at the meeting of the Sickle Cell Disease Association of America, Orlando, FL. **Citation:** Li Q, Henry ER, Hofrichter J, Smith JF, Cellmer T, Dunkelberger EB, Metaferia BB, Jones-Straehle S, Boutom S, Christoph GW, Wakefield TH, Link ME, Staton D, Vass ER, Miller JL, Hsieh MM, Tisdale JF, Eaton WA. Kinetic assay shows that increasing red cell volume could be a treatment for sickle cell disease. Proc Natl Acad Sci U S A. 2017 Jan 31;114(5):E689-E696. doi: 10.1073/pnas.1619054114. Epub 2017 Jan 17. **PMID:** 28096387 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000000745 - Term: Anemia, Hemolytic, Congenital - ID: D000000743 - Term: Anemia, Hemolytic - ID: D000000740 - Term: Anemia - ID: D000006402 - Term: Hematologic Diseases - ID: D000006453 - Term: Hemoglobinopathies - ID: D000030342 - Term: Genetic Diseases, Inborn ### Condition Browse Module - Browse Branches - Abbrev: BC15 - Name: Blood and Lymph Conditions - Abbrev: BC16 - Name: Diseases and Abnormalities at or Before Birth - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M16557 - Name: Thalassemia - Relevance: HIGH - As Found: Thalassemia - ID: M4085 - Name: Anemia, Sickle Cell - Relevance: HIGH - As Found: Sickle Cell Disease - ID: M4070 - Name: Anemia - Relevance: LOW - As Found: Unknown - ID: M9547 - Name: Hemolysis - Relevance: LOW - As Found: Unknown - ID: M4073 - Name: Anemia, Hemolytic - Relevance: LOW - As Found: Unknown - ID: M4075 - Name: Anemia, Hemolytic, Congenital - Relevance: LOW - As Found: Unknown - ID: M9490 - Name: Hematologic Diseases - Relevance: LOW - As Found: Unknown - ID: M9539 - Name: Hemoglobinopathies - Relevance: LOW - As Found: Unknown - ID: M23686 - Name: Genetic Diseases, Inborn - Relevance: LOW - As Found: Unknown - ID: T5622 - Name: Thalassemia - Relevance: HIGH - As Found: Thalassemia - ID: T5229 - Name: Sickle Cell Anemia - Relevance: HIGH - As Found: Sickle Cell Disease ### Condition Browse Module - Meshes - ID: D000000755 - Term: Anemia, Sickle Cell - ID: D000013789 - Term: Thalassemia ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT01598779 **Brief Title:** Human Papillomavirus (HPV) Types Present in External Genital Warts (EGW) in the Argentinean Population **Official Title:** Human Papillomavirus (HPV) Types Present in External Genital Warts (EGW) in the Argentinean Population #### Organization Study ID Info **ID:** Genital Warts #### Organization **Class:** OTHER **Full Name:** University of Buenos Aires ### Status Module #### Completion Date **Date:** 2014-08 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2015-12-21 **Type:** ESTIMATED **Last Update Submit Date:** 2015-12-18 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2014-08 **Type:** ACTUAL #### Results First Post Date **Date:** 2015-12-21 **Type:** ESTIMATED **Results First Submit Date:** 2014-12-09 **Results First Submit QC Date:** 2015-12-18 #### Start Date **Date:** 2012-06 **Status Verified Date:** 2015-12 #### Study First Post Date **Date:** 2012-05-15 **Type:** ESTIMATED **Study First Submit Date:** 2012-05-11 **Study First Submit QC Date:** 2012-05-11 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** Merck Sharp & Dohme LLC #### Lead Sponsor **Class:** OTHER **Name:** University of Buenos Aires #### Responsible Party **Investigator Affiliation:** University of Buenos Aires **Investigator Full Name:** Laura Alicia Fleider **Investigator Title:** Physician **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** The summary of this study is to know which HPV types are present in genital warts in Argentinean population. **Detailed Description:** This is a prospective study. Patients will be evaluated for the presence of external anogenital warts in our clinic. Biopsy will be performed if patients have genital lesions consistent with genital warts of the external genitalia or perianal area. All patients will be provided with an informed consent for the excision biopsy procedure, before performing the biopsy of the lesion. Biopsy specimens will be held in a formol 10% solution and will be sent to the pathologist. A portion of each sample will be processed for histological analysis, which will be performed by one pathologist. The remainder of each specimen will be saved to extract DNA for PCR analysis. All biopsies will be analyzed by the same pathologist who will confirm the histology of the lesion. A part of the specimen will be kept frozen and if the biopsy confirm genital warts by histology; then the specimen will be analyzed by PCR for the presence of DNA HPV 6 and 11. The PCR analysis will be done by microarrays. Detection is performed in a subtype of array platform system which detects the different types of virus. The reports will be as undetectable / detectable and type. The study will be conducted in the Institute of Gynecology and Fertility (Institute affiliated with the School of Medicine - University of Buenos Aires). Chronogram of activities: all activities will be done in a maximum of 60 days 1. st visit: detect external genital warts and firm informed consent and take the biopsy 2. nd visit: inform the result ### Conditions Module **Conditions:** - Condylomata Acuminata **Keywords:** - genital warts - HPV types - Sexually Transmitted Diseases - Skin Diseases, Viral - Tumor Virus Infections - Skin Diseases, Infectious - Skin Diseases - Papillomavirus Infections - DNA Virus Infections - Virus Diseases - Sexually Transmitted Diseases, Viral ### Design Module #### Bio Spec **Description:** Biopsy specimens will be held in a formol 10% solution and will be sent to the pathologist. A portion of each sample will be processed for histological analysis, which will be performed by one pathologist. The remainder of each specimen will be saved to extract DNA for PCR analysis **Retention:** SAMPLES_WITH_DNA #### Design Info **Observational Model:** CASE_ONLY **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 150 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Outcomes Module #### Primary Outcomes **Description:** 150 biopsies with histological diagnosis of genital warts were analyzed by PCR to detect HPV type **Measure:** Human Papillomavirus (HPV) Types in External Genital Warts (EGW) **Time Frame:** 4 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * women between 15 and 45 years old, with External Genital Warts Exclusion Criteria: * women taking corticoid therapy, having an immunosuppressed disease, pregnancy, cancer related to HPV, VIN confirmed by histology, other sexually transmitted infection, HIV+ known **Healthy Volunteers:** True **Maximum Age:** 45 Years **Minimum Age:** 15 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** FEMALE **Standard Ages:** - CHILD - ADULT **Study Population:** Women with genital warts ### Contacts Locations Module #### Locations **Location 1:** **City:** Buenos Aires **Country:** Argentina **Facility:** IFER **Zip:** 1425 #### Overall Officials **Official 1:** **Affiliation:** University of Buenos Aires **Name:** Laura A Fleider, MD **Role:** PRINCIPAL_INVESTIGATOR **Official 2:** **Affiliation:** Institute of Gynecology and Fertility **Name:** Laura A Fleider, MD **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000015229 - Term: Sexually Transmitted Diseases, Viral - ID: D000012749 - Term: Sexually Transmitted Diseases - ID: D000003141 - Term: Communicable Diseases - ID: D000007239 - Term: Infections - ID: D000014860 - Term: Warts - ID: D000030361 - Term: Papillomavirus Infections - ID: D000004266 - Term: DNA Virus Infections - ID: D000014777 - Term: Virus Diseases - ID: D000017193 - Term: Skin Diseases, Viral - ID: D000014412 - Term: Tumor Virus Infections - ID: D000091662 - Term: Genital Diseases - ID: D000091642 - Term: Urogenital Diseases - ID: D000012874 - Term: Skin Diseases, Infectious - ID: D000012871 - Term: Skin 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: BC17 - Name: Skin and Connective Tissue 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: M17522 - Name: Virus Diseases - Relevance: LOW - As Found: Unknown - ID: M23687 - Name: Papillomavirus Infections - Relevance: LOW - As Found: Unknown - ID: M15558 - Name: Sexually Transmitted Diseases - Relevance: LOW - As Found: Unknown - ID: M15674 - Name: Skin Diseases - Relevance: LOW - As Found: Unknown - ID: M17603 - Name: Warts - Relevance: LOW - As Found: Unknown - ID: M6443 - Name: Condylomata Acuminata - Relevance: HIGH - As Found: Genital Warts - ID: M15677 - Name: Skin Diseases, Infectious - Relevance: LOW - As Found: Unknown - ID: M17933 - Name: Sexually Transmitted Diseases, Viral - Relevance: LOW - As Found: Unknown - ID: M7442 - Name: DNA Virus Infections - Relevance: LOW - As Found: Unknown - ID: M17162 - Name: Tumor Virus Infections - Relevance: LOW - As Found: Unknown - ID: M19501 - Name: Skin Diseases, Viral - 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 ### Condition Browse Module - Meshes - ID: D000003218 - Term: Condylomata Acuminata ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module #### Event Groups **Group ID:** EG000 **Title:** Patients Having External Genital Warts **Description:** Patients were examined by experienced ginecologists in their first visit to evaluate the presence of lesions suspicious of condilomata acuminate, If they had lesions suspicious of gential warts, they were invited to participate and given an informed consent. Biopsied from genital warts were taken with an excisional procedure under local anesthesia. Biopsied sample was splinted in order to obtain two pieces, one of them was kept in formol solution (10%) and sent to the pathology laboratory for hematoxiline - eosine paint and lecture. All biopsies were analyzed by expert pathologists in order to confirm the histological diagnosis of genital warts. The other piece was sent to the laboratory to investigate the presence of HPV 6 and 11. In this first visit, the chronogram of activities included the detection of external genital warts, review of the criteria for inclusion and exclusion, firm informed consent, complete the questionnaire and take the biopsy, on a 2nd visit we informed the **ID:** EG000 **Other Num at Risk:** 150 **Serious Number At Risk:** 150 **Title:** Patients Having External Genital Warts **Frequency Threshold:** 0 ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 150 **Units:** Participants ### Group **ID:** BG000 **Title:** Patients Having External Genital Warts **Description:** Patients were examined by experienced ginecologists in their first visit to evaluate the presence of lesions suspicious of condilomata acuminate, If they had lesions suspicious of gential warts, they were invited to participate and given an informed consent. Biopsied from genital warts were taken with an excisional procedure under local anesthesia. Biopsied sample was splinted in order to obtain two pieces, one of them was kept in formol solution (10%) and sent to the pathology laboratory for hematoxiline - eosine paint and lecture. All biopsies were analyzed by expert pathologists in order to confirm the histological diagnosis of genital warts. The other piece was sent to the laboratory to investigate the presence of HPV 6 and 11. In this first visit, the chronogram of activities included the detection of external genital warts, review of the criteria for inclusion and exclusion, firm informed consent, complete the questionnaire and take the biopsy, on a 2nd visit we informed the ### Measure #### Measurement **Group ID:** BG000 **Lower Limit:** 15 **Upper Limit:** 45 **Value:** 28.48 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 150 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 0 **Category Title:** Male **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 150 **Class Title:** Argentina **Denomination Units Selected:** ## Results Section - Baseline Characteristics Module ### Measure 1 **Description:** Women age 15-45 years, with a lesion suspected of being HPV related were eligible to enter in the study. **Dispersion Type:** FULL_RANGE **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:** Region of Enrollment **Unit of Measure:** participants **Population Description:** Women age 15-45 attending an outpatient consultation at clinics of the investigators or at University of Buenos Aires, with a lesion suspected of being HPV related. ## Results Section - More Information Module ### Certain Agreement ### Point of Contact **Email:** [email protected] **Organization:** University of Buenos Aires **Phone:** 541159508000 **Phone Extension:** 8582 **Title:** Dr. Laura Fleider ## 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:** 80 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 12.66 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0.66 **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:** 0.66 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** 150 biopsies with histological diagnosis of genital warts were analyzed by PCR to detect HPV type **Parameter Type:** NUMBER **Population Description:** Biopsied from genital warts were taken with an excisional procedure under local anesthesia. Biopsied sample was splinted in order to obtain two pieces, All biopsies were analyzed to confirm the histological diagnosis of genital warts. The other piece was sent to the laboratory to investigate the presence of HPV 6 and 11. **Reporting Status:** POSTED **Time Frame:** 4 months **Title:** Human Papillomavirus (HPV) Types in External Genital Warts (EGW) **Type:** PRIMARY **Unit of Measure:** percentage of participants ##### Group **Description:** Women age 15-45 attending an outpatient consultation at clinics of the investigators or at University of Buenos Aires, with a lesion suspected of being HPV related were eligible to enter in the study. The main manifestations of genital warts include cauliflower-like condylomata acuminata lesions, keratotic and smooth papular warts, subclinical "flat" warts, Patients previously vaccinated with commercially available vaccines (Gardasil™ or Cervarix™) were not invited to participate. Inclusion criteria: women between 15 and 45 years old, with External Genital Warts. We will exclude women under treatment corticosteroids, having an immunosuppressive disease, pregnancy, cancer related to HPV, VIN confirmed by histology, other sexually transmitted infection, HIV+ known **ID:** OG000 **Title:** Women With External Genital Warts ### Participant Flow Module #### Group **Description:** Patients were examined by experienced ginecologists in their first visit to evaluate the presence of lesions suspicious of condilomata acuminate, If they had lesions suspicious of gential warts, they were invited to participate and given an informed consent. Biopsied from genital warts were taken with an excisional procedure under local anesthesia. Biopsied sample was splinted in order to obtain two pieces, one of them was kept in formol solution (10%) and sent to the pathology laboratory for hematoxiline - eosine paint and lecture. All biopsies were analyzed by expert pathologists in order to confirm the histological diagnosis of genital warts. The other piece was sent to the laboratory to investigate the presence of HPV 6 and 11. In this first visit, the chronogram of activities included the detection of external genital warts, review of the criteria for inclusion and exclusion, firm informed consent, complete the questionnaire and take the biopsy, on a 2nd visit we informed the **ID:** FG000 **Title:** Patients Having External Genital Warts #### Period **Title:** Overall Study ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 150 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 150 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 0 **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT04461379 **Brief Title:** Prevention, Efficacy and Safety of BCG Vaccine in COVID-19 Among Healthcare Workers **Official Title:** Prevention, Efficacy and Safety of BCG Vaccine in COVID-19- Randomized Clinical Trial #### Organization Study ID Info **ID:** EN20-00011 #### Organization **Class:** OTHER **Full Name:** Hospital Universitario Dr. Jose E. Gonzalez ### Status Module #### Completion Date **Date:** 2021-01-01 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** ACTIVE_NOT_RECRUITING #### Last Update Post Date **Date:** 2020-11-13 **Type:** ACTUAL **Last Update Submit Date:** 2020-11-12 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2021-01-01 **Type:** ESTIMATED #### Start Date **Date:** 2020-07-21 **Type:** ACTUAL **Status Verified Date:** 2020-11 #### Study First Post Date **Date:** 2020-07-08 **Type:** ACTUAL **Study First Submit Date:** 2020-07-02 **Study First Submit QC Date:** 2020-07-07 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Hospital Universitario Dr. Jose E. Gonzalez #### Responsible Party **Investigator Affiliation:** Hospital Universitario Dr. Jose E. Gonzalez **Investigator Full Name:** René Rodríguez-Gutiérrez **Investigator Title:** Professor Endocrinology Division, Facultad de Medicina **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** In Mexico the total number of confirmed cases of COVID-19 is 232, 000 and 28,510 deaths. Health workers are at high risk of COVID-19 infection. Their absence from work dramatically limits the ability to contain the disease. There is currently no vaccine to prevent the disease. Since the introduction to the vaccination schedule of the Bacillus Calmette-Guerin (BCG) live attenuated vaccine directed towards tuberculosis prevention, a decrease in infant mortality has been reported, not related only to tuberculosis. BCG vaccine has been hypothesized to have a non-specific role towards other unrelated pathogens such as viruses that cause airway disease, with reduced morbidity and mortality. In murine as well as in human models it has been shown to decrease the incidence of acute respiratory influenza infections. Likewise, in countries with a high endemicity for tuberculosis, the BCG vaccine reduces the incidence of respiratory infections by up to 80% . In healthy subjects, the BCG vaccine increases the production of proinflammatory cytokines in monocytes. Likewise, it increases the epigenetic response, causing an increase in the transcription of genes important in the antimicrobial response, as well as an improvement in cellular function. This is the first national clinical trial to evaluate prospectively the effect that the BCG vaccine offers towards the prevention and reduction of severity in cases of COVID-19. **Detailed Description:** The study design is a randomized, double-blinded, placebo-controlled clinical trial. Age stratified randomization (\<45 years and\> 45 years) was performed using permuted blocks with allocation concealment. The sample size is 908 patients. 454 patients in each stratum (227 with placebo and 227 with BCG vaccine). Eligible participants will be healthcare professionals over 18 years of age who are in contact with patients with COVID-19, with negative IgG and IgM antibodies results for SARS-CoV-2 prior to their inclusion and sign the informed consent. After signing the informed consent, the participants will be randomized 1:1 to the intervention group (BCG vaccine) or control (placebo), a medical history will be performed, and a blood plasma sample will be obtained to determine specific antibodies against SARS-CoV-2. The patients will be followed up for 6 months after the application of the vaccine, they will be contacted by phone every two weeks in order to identify the adverse effects of the vaccine (30 days after the application) as well as to identify symptoms of COVID-19, in addition, follow-up visits will be carried out at the third and sixth months, in each of these visits a blood plasma sample will be obtained and IgG and IgM antibodies will be measured. Statistical Analysis Type: By intention to treatment ### Conditions Module **Conditions:** - BCG - COVID-19 - SARS-CoV2 - Corona Virus Infection **Keywords:** - Healthcare workers ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** A randomized double-blinded clinical trial, using computer software, participants will be allocated between two groups: Intervention: BCG vaccine intradermally 0.1 ml, equivalent to 0.075 mg of attenuated Mycobacterium bovis. (Tokio 172 strain). The application technique is based on the National Vaccination Manual version 2017. Comparator: Placebo, intradermally 0.1 ml of NaCl 0.9% ##### Masking Info **Masking:** TRIPLE **Masking Description:** Participants, researchers (including members of the research team that will assess outcomes), and treating physicians or health personnel (should the patient require in-hospital management) will be blinded to the treatment group to which the patients were randomized. Only the personnel who apply the vaccine will not be blinded to the treatment group to which the patients were randomized (this personnel will not have any further contact with the patients or provide any other type of patient care). **Who Masked:** - PARTICIPANT - CARE_PROVIDER - OUTCOMES_ASSESSOR **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 908 **Type:** ESTIMATED **Phases:** - PHASE3 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** A single dose BCG vaccine intradermally 0.1 ml. **Intervention Names:** - Biological: BCG vaccine **Label:** BCG Vaccine **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** A single dose intradermally 0.1 ml of NaCl 0.9% solution **Intervention Names:** - Other: Placebo **Label:** Placebo **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - BCG Vaccine **Description:** A single dose BCG vaccine intradermally (deltoid region of the right arm) 0.1 ml, equivalent to 0.075 mg of attenuated Mycobacterium bovis . (Tokio 172 strain) **Name:** BCG vaccine **Other Names:** - Calmette-Guerin Bacillus vaccine **Type:** BIOLOGICAL #### Intervention 2 **Arm Group Labels:** - Placebo **Description:** A single dose intradermally ((deltoid region of the right arm) 0.1 ml of NaCl 0.9% solution **Name:** Placebo **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** Cumulative incidence of infection in 6 months: disease defined as positive SARS-Cov-2 test (serology), plus fever (using self-reported questionnaire), or at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure (using self-reported questionnaire) **Measure:** Demonstrate COVID- 19 disease incidence among Health care workers: **Time Frame:** During the 6 months study period **Description:** Cumulative incidence of hospitalization for COVID-19 **Measure:** Demonstrate cumulative incidence of hospitalization for COVID-19 among Health care workers: **Time Frame:** During the 6 months study period **Description:** Incidence of specific Antibodies (IgG and IgM) against SARS-CoV-2 will be measured at 3 and 6 months **Measure:** Demonstrate the Incidence of specific Antibodies against SARS-CoV-2 at 3 and 6 months in health care workers **Time Frame:** During the 6 months study period **Description:** Number of participants who needed hospitalization **Measure:** Hospitalization of severe disease COVID-19 **Time Frame:** During the 6 months study period **Description:** Number of participants who Need for oxygen supplementation (nasal cannulas, masks, high flow oxygen) in hospitalized patients **Measure:** Oxygen supplementation in severe disease COVID-19 **Time Frame:** During the 6 months study period **Description:** Number of participants who Need for intubation or non-invasive ventilation in hospitalized patients **Measure:** Need for intubation or non-invasive ventilation for the patient. **Time Frame:** During the 6 months study period **Description:** Number of participants in Critical care admission with SARS-CoV2 in hospitalized patients **Measure:** Critical care admission with SARS-CoV2 **Time Frame:** During the 6 months study period **Description:** Mortality associated to progressive pulmonary disease in hospitalized patients **Measure:** Mortality associated to progressive pulmonary disease **Time Frame:** During the 6 months study period #### Secondary Outcomes **Measure:** Evaluate the safety of the vaccine by measuring the incidence rates of local and systemic adverse effects that occur after one month its application. **Time Frame:** 1 month after vaccine/placebo application **Measure:** Calculate the incidence of COVID-19 complications **Time Frame:** During the 6 months study period **Measure:** Determine the mean days of hospitalization and days in intensive care unit by COIVD-19 **Time Frame:** During the 6 months study period **Measure:** Calculate the cost associated with in-hospital medical care **Time Frame:** During the 6 months study period **Description:** SOFA score: PaO2/FIO2 (mm Hg), SaO2/FIO2, Platelets (×10³/µL), Bilirubin (mg/dL), Hypotension, Glasgow Coma Score and Creatinine (mg/dL) or urine output (mL/d). **Measure:** Determine the scores of the Clinical Prediction Rules associated with mortality using Sequential Organ Failure Assessment (SOFA score) at the patient's hospital admission: **Time Frame:** During the 6 months study period **Description:** APACHE: History of severe organ failure or immunocompromise Heart Failure Class IV, cirrhosis, chronic lung disease, or dialysis-dependent, Age, Temperature (C°), Mean arterial pressure (mmHg), pH, Sodium (mEq/L), Potassium (mEq/L), Creatinine (mg/dL), Hematocrit (%), WBC (x 109/L) **Measure:** Determine the scores of the Clinical Prediction Rules associated with mortality using Acute Physiology and Chronic Health disease Classification System (APACHE) at the patient's hospital admission: **Time Frame:** During the 6 months study period **Description:** CPR, ESR, Ferritin, D-dimer, LDH,Troponins, Procalcitonin, Interleukin-6, Hemoglobin, Hematocrit, Erythrocytes, Leukocytes, MCV, HCM, MCHC, Lymphocytes, Monocytes, Eosinophils, Basophils, Platelets, Glucose, Urea, Creatinine, BUN, Sodium, Potassium, Chlorine, Calcium, Serum albumin, Direct bilirubin, Indirect bilirubin, Alkaline phosphatase, AST, ALT, bleeding time, Prothrombin Time, Activated partial thromboplastin time, Arterial / Venous Blood Gasometry, pH, pCO2, HCO3, pO2, SaO2%, Lactate. **Measure:** Evaluate and determine the alteration profile in laboratory studies at the patient's hospital admission **Time Frame:** During the 6 months study period **Measure:** Registration of chronic medications **Time Frame:** During the 6 months study period **Measure:** Need for vasopressors **Time Frame:** During the 6 months study period ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Health workers who are working onsite in patients' areas with COVID-19 * Age \> 18 years * Negative specific IgG and IgM antibodies test result for SARS CoV-2 before the enrollment. * Provide a signed and dated informed consent form Exclusion Criteria: * Age \<18 years * Positive test for specific antibodies IgG and IgM antibodies result for SARS Cov-2 * Primary or secondary immunosuppression * Use of immunosuppression drugs, use of hydroxychloroquine, cloroquine, Azithromycin, Lopinavir/ritonavir, Ivermectin or any other drug used to treat patients COVID-19 before the enrollment. * Chemotherapy treatment * Presence of antibodies IgA, IgM, IgG against SARS-CoV-2 * Pregnancy or breastfeeding * Missing informed consent form * Fever \> 38° in the previous 24 hours * Any BCG vaccine contraindication * History of previous allergy to the components of the vaccine * Already part of any other trial * Previous or active tuberculosis (TB) disease * Another vaccine administrated 4 months before the start of the trial. * Any underlying history of malignancy or lymphoma. * Actual treatment with steroids * Absence of more than 1 month from the hospital, from the study period. **Healthy Volunteers:** True **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Monterrey **Country:** Mexico **Facility:** Hospital Universitario "José E. González" **State:** Nuevo León **Zip:** 64460 ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### See Also Links **Label:** Related Info **URL:** https://www.who.int/emergencies/diseases/novel-coronavirus-2019 **Label:** Related Info **URL:** http://www.nature.com/articles/s41585-020-0325-9 **Label:** Related Info **URL:** http://www.ncbi.nlm.nih.gov/pubmed/32393823 **Label:** Related Info **URL:** https://www.gob.mx/salud%7Ccensia/documentos/manual-de-vacunacion-edicion-2017 ## 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: 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: M10283 - Name: Infections - Relevance: LOW - As Found: Unknown - ID: M6368 - Name: Communicable Diseases - Relevance: LOW - As Found: Unknown - ID: M17522 - Name: Virus Diseases - Relevance: LOW - As Found: Unknown - ID: M20490 - Name: Coronavirus Infections - Relevance: HIGH - As Found: Corona Virus Infection - ID: M13904 - Name: Pneumonia - Relevance: LOW - As Found: Unknown - ID: M13914 - Name: Pneumonia, Viral - Relevance: LOW - As Found: Unknown - ID: M14978 - Name: Respiratory Tract 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 - ID: D000018352 - Term: Coronavirus Infections ### Intervention Browse Module - Ancestors - ID: D000007155 - Term: Immunologic Factors - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000000276 - Term: Adjuvants, Immunologic ### Intervention Browse Module - Browse Branches - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: PhSol - Name: Pharmaceutical Solutions ### Intervention Browse Module - Browse Leaves - ID: M17360 - Name: Vaccines - Relevance: HIGH - As Found: Other - ID: M21860 - Name: Pharmaceutical Solutions - Relevance: LOW - As Found: Unknown - ID: M4793 - Name: BCG Vaccine - Relevance: HIGH - As Found: Right and left - ID: M10201 - Name: Immunologic Factors - Relevance: LOW - As Found: Unknown - ID: M3628 - Name: Adjuvants, Immunologic - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000014612 - Term: Vaccines - ID: D000001500 - Term: BCG Vaccine ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04202679 **Brief Title:** Study of Dupilumab for the Treatment of Patients With Prurigo Nodularis, Inadequately Controlled on Topical Prescription Therapies or When Those Therapies Are Not Advisable (PRIME2) **Official Title:** A Randomized, Double Blind, Placebo-controlled, Multi-center, Parallel Group Study to Evaluate the Efficacy and Safety of Dupilumab in Patients With Prurigo Nodularis Who Are Inadequately Controlled on Topical Prescription Therapies or When Those Therapies Are Not Advisable #### Organization Study ID Info **ID:** EFC16460 #### Organization **Class:** INDUSTRY **Full Name:** Sanofi #### Secondary ID Infos **ID:** 2019-003801-90 **Domain:** UTN **ID:** U1111-1241-8174 **Type:** OTHER ### Status Module #### Completion Date **Date:** 2021-11-22 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2022-12-21 **Type:** ACTUAL **Last Update Submit Date:** 2022-11-21 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2021-08-30 **Type:** ACTUAL #### Results First Post Date **Date:** 2022-09-28 **Type:** ACTUAL **Results First Submit Date:** 2022-08-29 **Results First Submit QC Date:** 2022-08-29 #### Start Date **Date:** 2020-01-16 **Type:** ACTUAL **Status Verified Date:** 2022-11 #### Study First Post Date **Date:** 2019-12-17 **Type:** ACTUAL **Study First Submit Date:** 2019-12-16 **Study First Submit QC Date:** 2019-12-16 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** Regeneron Pharmaceuticals #### Lead Sponsor **Class:** INDUSTRY **Name:** Sanofi #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** True **Oversight Has DMC:** False ### Description Module **Brief Summary:** Primary Objective: To demonstrate the efficacy of dupilumab on itch response in participants with prurigo nodularis (PN), inadequately controlled on topical prescription therapy or when those therapies are not advisable. Secondary Objectives: To demonstrate the efficacy of dupilumab on additional itch endpoints in participants with PN, inadequately controlled on topical prescription therapy or when those therapies are not advisable. To demonstrate efficacy of dupilumab on skin lesions of PN. To demonstrate the improvement in health-related quality of life. To evaluate safety outcome measures. To evaluate immunogenicity of dupilumab. **Detailed Description:** The duration of study for each participant included 2-4 weeks of screening period, 24 weeks of treatment period and 12 weeks of post treatment period. ### Conditions Module **Conditions:** - Neurodermatitis ### 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:** 160 **Type:** ACTUAL **Phases:** - PHASE3 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Participants received placebo matched to dupilumab 600 milligrams (mg) (loading dose), subcutaneously (SC) on Day 1 followed by placebo matched to dupilumab 300 mg once every 2 weeks (q2w) for 24 weeks added to background therapy of topical corticosteroids/topical calcineurin inhibitors (TCS/TCI) at stable dose. **Intervention Names:** - Drug: Placebo - Drug: Moisturizers - Drug: Low to medium potent topical corticosteroids - Drug: Topical calcineurin inhibitors **Label:** Placebo **Type:** PLACEBO_COMPARATOR #### Arm Group 2 **Description:** Participants received dupilumab at a loading dose of 600 mg, SC on Day 1 followed by dupilumab 300 mg q2w for 24 weeks added to background therapy of TCS/TCI at stable dose. **Intervention Names:** - Drug: Dupilumab SAR231893 - Drug: Moisturizers - Drug: Low to medium potent topical corticosteroids - Drug: Topical calcineurin inhibitors **Label:** Dupilumab 300 mg Q2W **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Dupilumab 300 mg Q2W **Description:** Pharmaceutical form:Injection solution Route of administration: Subcutaneous **Name:** Dupilumab SAR231893 **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Placebo **Description:** Pharmaceutical form:Injection solution Route of administration: Subcutaneous **Name:** Placebo **Type:** DRUG #### Intervention 3 **Arm Group Labels:** - Dupilumab 300 mg Q2W - Placebo **Description:** Pharmaceutical form: Route of administration: Topical **Name:** Moisturizers **Type:** DRUG #### Intervention 4 **Arm Group Labels:** - Dupilumab 300 mg Q2W - Placebo **Description:** Pharmaceutical form: Route of administration: Topical **Name:** Low to medium potent topical corticosteroids **Type:** DRUG #### Intervention 5 **Arm Group Labels:** - Dupilumab 300 mg Q2W - Placebo **Description:** Pharmaceutical form: Route of administration: Topical **Name:** Topical calcineurin inhibitors **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** WI-NRS is a validated measure of itch severity. Participants were asked daily to rate the intensity of their worst pruritus (itch) over the past 24 hours, using a 11-point scale ranging from 0 (no itch) to 10 (worst imaginable itch). Higher scores indicated more severity. Percentage of participants with \>=4 points improvement (reduction) from baseline in WI-NRS scores at Week 12 is reported in this outcome measure. **Measure:** Percentage of Participants With Greater Than or Equal to (>=) 4 Points Improvement (Reduction) From Baseline in Worst-Itch Numeric Rating Scale (WI-NRS) Scores at Week 12 **Time Frame:** Baseline, Week 12 #### Secondary Outcomes **Description:** WI-NRS is a validated measure of itch severity. Participants were asked daily to rate the intensity of their worst pruritus (itch) over the past 24 hours, using a 11-point scale ranging from 0 (no itch) to 10 (worst imaginable itch). Higher scores indicated more severity. Percentage of participants with \>=4 points improvement (reduction) from baseline in WI-NRS scores at Week 24 is reported in this outcome measure. **Measure:** Percentage of Participants With >=4 Points Improvement (Reduction) From Baseline in WI-NRS Scores at Week 24 **Time Frame:** Baseline, Week 24 **Description:** IGA PN-S is an instrument used to assess the overall number and thickness of PN lesions at a given time point, as determined by the investigator. It consists of a 5-point scale ranging from 0 to 4 where 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate and 4 = severe. Higher scores indicate severe prurigo nodularis. In this outcome measure, percentage of participants with IGA PN-S score of either 0 (clear) or 1 (almost clear) has been reported. **Measure:** Percentage of Participants With Investigator's Global Assessment For Prurigo Nodularis-Stage (IGA PN-S) Scores of 0 or 1 at Week 24 **Time Frame:** At Week 24 **Description:** WI-NRS is a validated measure of itch severity. Participants were asked daily to rate the intensity of their worst pruritus (itch) over the past 24 hours, using a 11-point scale ranging from 0 (no itch) to 10 (worst imaginable itch), higher scores indicated more severity. IGA PN-S assess the overall number and thickness of PN lesions at a given time point, as determined by the investigator. It consists of a 5-point scale ranging from 0 to 4 where 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate and 4 = severe. Higher scores indicated greater severity. Percentage of participants with both an improvement (reduction) in WI-NRS by \>=4 Points (from Baseline) and an IGA PN-S score of 0 or 1 were reported in this outcome measure. **Measure:** Percentage of Participants With Both an Improvement (Reduction) in WI-NRS by >=4 Points and an IGA PN-S Score of 0 or 1 From Baseline at Week 24 **Time Frame:** Baseline, Week 24 **Description:** IGA PN-S is an instrument used to assess the overall number and thickness of PN lesions at a given time point, as determined by the investigator. It consists of a 5-point scale ranging from 0 to 4 where 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate and 4 = severe. Higher scores indicate severe prurigo nodularis. In this outcome measure, percentage of participants with IGA PN-S score of either 0 (clear) or 1 (almost clear) has been reported. **Measure:** Percentage of Participants With IGA PN-S Scores of 0 or 1 at Week 12 **Time Frame:** At Week 12 **Description:** WI-NRS is a validated measure of itch severity. Participants were asked daily to rate the intensity of their worst pruritus (itch) over the past 24 hours, using a 11-point scale ranging from 0 (no itch) to 10 (worst imaginable itch). Higher scores indicated more severity. Least squares (LS) means and standard error (SE) were obtained from Analysis of covariance (ANCOVA) model. **Measure:** Percent Change From Baseline in WI-NRS Scores at Week 24 **Time Frame:** Baseline, Week 24 **Description:** DLQI is developed to measure dermatology specific HRQoL in adult participants. It comprises of set of 10 questions assessing the impact of skin disease on participants' HRQoL over the previous week. Responses to each question were assessed on a 4-point Likert scale ranged from 0 (not at all) to 3 (very much). Scores from all 10 questions added up to give total DLQI scores ranged from 0 (not at all) to 30 (very much), higher scores indicated more impact on quality of life. LS means and SE were obtained from ANCOVA model. **Measure:** Change From Baseline in Health-related Quality of Life (HRQoL) as Measured by Dermatology Life Quality Index (DLQI) at Week 24 **Time Frame:** Baseline, Week 24 **Description:** Skin Pain-NRS was used to measure skin pain intensity. Participants were asked daily to rate the intensity of their worst skin pain over the past 24 hours, using a 11-point scale ranging from 0 ("No pain") to 10 ("Worst possible pain"). Higher scores indicated more severity. LS means and SE were obtained from ANCOVA model. **Measure:** Change From Baseline in Skin Pain-NRS at Week 24 **Time Frame:** Baseline, Week 24 **Description:** Sleep-NRS was used to measure sleep intensity. Participants were asked to rate their sleep quality on their past night upon awakening, using a 11-point NRS ranging from 0 to 10, where 0 = worst possible sleep and 10 = best possible sleep. Higher scores indicated less severity. LS means and SE were obtained from ANCOVA model. **Measure:** Change From Baseline in Sleep-NRS at Week 24 **Time Frame:** Baseline, Week 24 **Description:** HADS is a 14-item self-administered questionnaire that consists of 2 scales, one measuring anxiety (HADS-A), and the other measuring depression (HADS-D). Each subscale comprised of 7 items with a scoring range from 0 (less severity of anxiety and depression) to 21 (greater severity of anxiety and depression symptoms) for each subscale. The total HADS score ranges from 0 (less severity) to 42 (more severity), with a high score indicative of a severe anxiety and/or depression level. LS means and SE were obtained from ANCOVA model. **Measure:** Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Total Score at Week 24 **Time Frame:** Baseline, Week 24 **Description:** WI-NRS is a validated measure of itch severity. Participants were asked daily to rate the intensity of their worst pruritus (itch) over the past 24 hours, using a 11-point scale ranging from 0 (no itch) to 10 (worst imaginable itch). Higher scores indicated more severity. Probability of participants with an improvement (reduction) in WI-NRS at Week 24 was based on Kaplan-Meier estimates and was reported in this outcome measure. **Measure:** Probability of Participants With an Improvement (Reduction) in WI-NRS by >=4 From Baseline at Week 24 **Time Frame:** Baseline, Week 24 **Description:** WI-NRS is a validated measure of itch severity. Participants were asked daily to rate the intensity of their worst pruritus (itch) over the past 24 hours, using a 11-point scale ranging from 0 (no itch) to 10 (worst imaginable itch). Higher scores indicated more severity. LS means and SE were obtained from ANCOVA model. **Measure:** Change From Baseline in WI-NRS Scores at Weeks 12 and 24 **Time Frame:** Baseline, Weeks 12 and 24 **Description:** WI-NRS is a validated measure of itch severity. Participants were asked daily to rate the intensity of their worst pruritus (itch) over the past 24 hours, using a 11-point scale ranging from 0 (no itch) to 10 (worst imaginable itch). Higher scores indicated more severity. LS means and SE were obtained from ANCOVA model. **Measure:** Percent Change From Baseline in WI-NRS Scores at Weeks 2, 4 and 12 **Time Frame:** Baseline, Weeks 2, 4 and 12 **Description:** WI-NRS is a validated measure of itch severity. Participants were asked daily to rate the intensity of their worst pruritus (itch) over the past 24 hours, using a 11-point scale ranging from 0 (no itch) to 10 (worst imaginable itch). Higher scores indicated more severity. LS means and SE were obtained from ANCOVA model. **Measure:** Percent Change From Baseline in WI-NRS Scores at Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, and 24 **Time Frame:** Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, and 24 **Description:** WI-NRS is a validated measure of itch severity. Participants were asked daily to rate the intensity of their worst pruritus (itch) over the past 24 hours, using a 11-point scale ranging from 0 (no itch) to 10 (worst imaginable itch). Higher scores indicated more severity. Percentage of participants with improvement (Reduction) in WI-NRS scale by \>=4 Points at Week 4 is reported in this outcome measure. **Measure:** Percentage of Participants With Improvement (Reduction) in WI-NRS >=4 Points From Baseline at Week 4 **Time Frame:** Baseline, Week 4 **Description:** WI-NRS is a validated measure of itch severity. Participants were asked daily to rate the intensity of their worst pruritus (itch) over the past 24 hours, using a 11-point scale ranging from 0 (no itch) to 10 (worst imaginable itch). Higher scores indicated more severity. Percentage of participants achieving \>=4 points improvement (reduction) from Baseline in WI-NRS scores at Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 and 24 is reported in this outcome measure. **Measure:** Percentage of Participants Achieving >=4 Points Improvement (Reduction) From Baseline in WI-NRS Scores at Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, and 24 **Time Frame:** Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 and 24 **Description:** Onset of action was defined as the first p\<0.05 difference from placebo in the weekly average WI-NRS that remained significant at subsequent measurements. WI-NRS is a validated measure of itch severity. Participants were asked daily to rate the intensity of their worst pruritus (itch) over the past 24 hours, using a 11-point scale ranging from 0 (no itch) to 10 (worst imaginable itch). Higher scores indicated greater severity. **Measure:** Onset of Action Based on Change From Baseline in WI-NRS at Week 4 **Time Frame:** Baseline, Week 4 **Description:** IGA PN-S is an instrument used to assess the overall number and thickness of PN lesions at a given time point, as determined by the investigator. It consists of a 5-point scale ranging from 0 to 4: where 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate and 4 = severe. Higher scores indicate severe prurigo nodularis. In this outcome measure, percentage of participants with IGA PN-S score of either 0 (clear) or 1 (almost clear) has been reported. **Measure:** Percentage of Participants With Investigator's Global Assessment for PN-Stage (IGA PN-S) Score of 0 or 1 at Weeks 4 and 8 **Time Frame:** At Weeks 4 and 8 **Description:** IGA PN-S is an instrument used to assess the overall number and thickness of PN lesions at a given time point, as determined by the investigator. It consists of a 5-point scale ranging from 0 to 4: where 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate and 4 = severe. Higher scores indicate severe prurigo nodularis. LS means and SE were obtained from ANCOVA model. **Measure:** Change From Baseline in IGA PN-S Scores at Weeks 4, 8, 12, and 24 **Time Frame:** Baseline, Weeks 4, 8, 12, and 24 **Description:** The IGA PN-A is an instrument used to assess the overall activity of PN lesions at a given time point, as determined by the investigator. It consists of a 5-point scale ranging from 0 to 4: where 0 = clear (0% nodules showing excoriations/crusts), 1 = almost clear (up to 10% nodules showing excoriations/crusts), 2 = mild (11-25% nodules showing excoriations/crusts), 3 = moderate (26-75% nodules showing excoriations/crusts) and 4 = severe (76-100% of nodules showing excoriations/crusts). Higher scores indicate severe prurigo nodularis. In this outcome measure, percentage of participants with IGA PN-A score of either 0 (clear) or 1 (almost clear) has been reported. **Measure:** Percentage of Participants With Investigator's Global Assessment for PN-Activity (IGA PN-A) Score of 0 or 1 at Weeks 4, 8, 12 and 24 **Time Frame:** At Weeks 4, 8, 12 and 24 **Description:** DLQI is developed to measure dermatology specific HRQoL in adult participants. It comprises of set of 10 questions assessing the impact of skin disease on participants' HRQoL over the previous week. Responses to each question were assessed on a 4-point Likert scale ranged from 0 (not at all) to 3 (very much). Scores from all 10 questions added up to give total DLQI scores ranged from 0 (not at all) to 30 (very much), higher scores indicated more impact on quality of life. LS means and SE were obtained from ANCOVA model. **Measure:** Change From Baseline in HRQoL, as Measured by DLQI at Week 12 **Time Frame:** Baseline, Week 12 **Description:** An adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily have to have a causal relationship with the treatment. Serious adverse events (SAEs) was defined as any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. TEAEs were defined as AEs that developed, worsened or became serious during the treatment-emergent (TE) period (time from the first investigational medicinal product \[IMP\] administration to the last IMP administration + 14 weeks). **Measure:** Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) **Time Frame:** From the first IMP administration to the last IMP administration + 14 weeks (i.e., up to 36 weeks) **Description:** ADA response was categorized as: Treatment emergent and Treatment-boosted. Treatment emergent ADAs were defined as a participant with no positive assay response at baseline but with a positive assay response during the entire TEAE period. Treatment boosted ADAs: defined as participants with a positive ADA assay response at baseline and with at least a 4-fold increase in titer compared to baseline during the TE period (time from the first IMP administration to the last IMP administration + 14 weeks). Titer values were defined as low titer (\< 1,000); moderate (1,000 \<= titer \<= 10,000) and high titer (\> 10,000). **Measure:** Number of Participants With Treatment-emergent and Treatment Boosted Antidrug Antibodies (ADA) **Time Frame:** From the first IMP administration to the last IMP administration + 14 weeks (i.e., up to 36 weeks) ### Eligibility Module **Eligibility Criteria:** Inclusion criteria : Must be 18 to 80 years of age, at the time of signing the informed consent. With a clinical diagnosis of PN defined by all of the following: * Diagnosed by a dermatologist for at least 3 months before the Screening visit. * On the Worst Itch Numeric Rating Scale (WI-NRS) ranging from 0 to 10, participants must have an average worst itch score of \>=7 in the 7 days prior to Day1. * Participants must have a minimum of 20 PN lesions in total on both legs, and/or both arms and/or trunk, at Screening visit and Day 1 * History of failing a 2-week course of medium-to-superpotent topical corticosteroids (TCS) or when TCS are not medically advisable * Have applied a stable dose of topical emollient (moisturizer) once or twice daily for at least 5 out of the 7 consecutive days immediately before Day 1. Must be willing and able to complete a daily symptom eDiary for the duration of the study. Exclusion criteria: Participants were excluded from the study if any of the following criteria apply: * Presence of skin morbidities other than PN and mild atopic dermatitis that may interfere with the assessment of the study outcomes. * PN secondary to medications. * PN secondary to medical conditions such as neuropathy or psychiatric disease. * Within 6 months before the screening visit, or documented diagnosis of moderate to severe atopic dermatitis from screening visit to randomization visit. * Severe concomitant illness(es) under poor control that, in the investigator's judgment, would adversely affect the participant's participation in the study. * Severe renal conditions (eg, participants with uremia and/or on dialysis). * Participants with uncontrolled thyroid disease. * Active tuberculosis or non-tuberculous mycobacterial infection, or a history of incompletely treated tuberculosis unless documented adequately treated. * Diagnosed active endoparasitic infections; suspected or high risk of endoparasitic infection, unless clinical and (if necessary) laboratory assessment have ruled out active infection before randomization. * Active chronic or acute infection (except HIV) requiring treatment with systemic antibiotics, antivirals, antiprotozoals, or antifungals within 2 weeks before the screening visit and during the screening period. * Known or suspected immunodeficiency. * Active malignancy or history of malignancy within 5 years before the Baseline visit, except completely treated in situ carcinoma of the cervix, completely treated and resolved non-metastatic squamous or basal cell carcinoma of the skin. The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial. **Maximum Age:** 80 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Fort Smith **Country:** United States **Facility:** Investigational Site Number :8400054 **State:** Arkansas **Zip:** 72916 **Location 2:** **City:** Sacramento **Country:** United States **Facility:** Investigational Site Number :8400008 **State:** California **Zip:** 95816 **Location 3:** **City:** Pembroke Pines **Country:** United States **Facility:** Investigational Site Number :8400005 **State:** Florida **Zip:** 33028 **Location 4:** **City:** Plainfield **Country:** United States **Facility:** Investigational Site Number :8400002 **State:** Indiana **Zip:** 46168 **Location 5:** **City:** Baltimore **Country:** United States **Facility:** Investigational Site Number :8400003 **State:** Maryland **Zip:** 21205 **Location 6:** **City:** East Windsor **Country:** United States **Facility:** Investigational Site Number :8400006 **State:** New Jersey **Zip:** 08520 **Location 7:** **City:** Sugar Land **Country:** United States **Facility:** Investigational Site Number :8400001 **State:** Texas **Zip:** 77479 **Location 8:** **City:** Calgary **Country:** Canada **Facility:** Investigational Site Number :1240002 **State:** Alberta **Zip:** T2G 1B1 **Location 9:** **City:** Surrey **Country:** Canada **Facility:** Investigational Site Number :1240006 **State:** British Columbia **Zip:** V3R 6A7 **Location 10:** **City:** Markham **Country:** Canada **Facility:** Investigational Site Number :1240007 **State:** Ontario **Zip:** L3P 1X3 **Location 11:** **City:** Newmarket **Country:** Canada **Facility:** Investigational Site Number :1240008 **State:** Ontario **Zip:** L3Y 5G8 **Location 12:** **City:** Toronto **Country:** Canada **Facility:** Investigational Site Number :1240001 **State:** Ontario **Zip:** M5A 3R6 **Location 13:** **City:** Saskatoon **Country:** Canada **Facility:** Investigational Site Number :1240009 **State:** Saskatchewan **Zip:** S7K 0H6 **Location 14:** **City:** Valdivia **Country:** Chile **Facility:** Investigational Site Number :1520005 **State:** Los Ríos **Zip:** 5110683 **Location 15:** **City:** Osorno **Country:** Chile **Facility:** Investigational Site Number :1520006 **State:** Reg Metropolitana De Santiago **Zip:** 5311523 **Location 16:** **City:** Santiago **Country:** Chile **Facility:** Investigational Site Number :1520003 **State:** Reg Metropolitana De Santiago **Zip:** 7580206 **Location 17:** **City:** Santiago **Country:** Chile **Facility:** Investigational Site Number :1520001 **State:** Reg Metropolitana De Santiago **Zip:** 7640881 **Location 18:** **City:** Santiago **Country:** Chile **Facility:** Investigational Site Number :1520004 **State:** Reg Metropolitana De Santiago **Zip:** 80004005 **Location 19:** **City:** Santiago **Country:** Chile **Facility:** Investigational Site Number :1520002 **Location 20:** **City:** Bordeaux **Country:** France **Facility:** Investigational Site Number :2500007 **Zip:** 33075 **Location 21:** **City:** Brest **Country:** France **Facility:** Investigational Site Number :2500001 **Zip:** 29200 **Location 22:** **City:** Le Mans **Country:** France **Facility:** Investigational Site Number :2500008 **Zip:** 72037 **Location 23:** **City:** Lille **Country:** France **Facility:** Investigational Site Number :2500002 **Zip:** 59037 **Location 24:** **City:** Lyon **Country:** France **Facility:** Investigational Site Number :2500006 **Zip:** 69003 **Location 25:** **City:** Paris **Country:** France **Facility:** Investigational Site Number :2500004 **Zip:** 75010 **Location 26:** **City:** Reims **Country:** France **Facility:** Investigational Site Number :2500005 **Zip:** 51100 **Location 27:** **City:** Toulouse **Country:** France **Facility:** Investigational Site Number :2500003 **Zip:** 31059 **Location 28:** **City:** Debrecen **Country:** Hungary **Facility:** Investigational Site Number :3480004 **Zip:** 4032 **Location 29:** **City:** Orosháza **Country:** Hungary **Facility:** Investigational Site Number :3480002 **Zip:** 5900 **Location 30:** **City:** Pécs **Country:** Hungary **Facility:** Investigational Site Number :3480005 **Zip:** 7632 **Location 31:** **City:** Szeged **Country:** Hungary **Facility:** Investigational Site Number :3480003 **Zip:** 6720 **Location 32:** **City:** Rozzano **Country:** Italy **Facility:** Investigational Site Number :3800001 **State:** Milano **Zip:** 20089 **Location 33:** **City:** Ancona **Country:** Italy **Facility:** Investigational Site Number :3800004 **Zip:** 60032 **Location 34:** **City:** Catanzaro **Country:** Italy **Facility:** Investigational Site Number :3800003 **Zip:** 88100 **Location 35:** **City:** Milano **Country:** Italy **Facility:** Investigational Site Number :3800002 **Zip:** 20122 **Location 36:** **City:** Busan **Country:** Korea, Republic of **Facility:** Investigational Site Number :4100002 **State:** Busan-gwangyeoksi **Zip:** 49241 **Location 37:** **City:** Bucheon-si **Country:** Korea, Republic of **Facility:** Investigational Site Number :4100003 **State:** Gyeonggi-do **Zip:** 14584 **Location 38:** **City:** Incheon **Country:** Korea, Republic of **Facility:** Investigational Site Number :4100007 **State:** Incheon-gwangyeoksi **Zip:** 21431 **Location 39:** **City:** Seoul **Country:** Korea, Republic of **Facility:** Investigational Site Number :4100005 **State:** Seoul-teukbyeolsi **Zip:** 03722 **Location 40:** **City:** Seoul **Country:** Korea, Republic of **Facility:** Investigational Site Number :4100001 **State:** Seoul-teukbyeolsi **Zip:** 06973 **Location 41:** **City:** Seoul **Country:** Korea, Republic of **Facility:** Investigational Site Number :4100006 **State:** Seoul-teukbyeolsi **Zip:** 07441 **Location 42:** **City:** Coimbra **Country:** Portugal **Facility:** Investigational Site Number :6200001 **Zip:** 3000-075 **Location 43:** **City:** Lisboa **Country:** Portugal **Facility:** Investigational Site Number :6200002 **Zip:** 1998-018 **Location 44:** **City:** Porto **Country:** Portugal **Facility:** Investigational Site Number :6200003 **Zip:** 4099-001 **Location 45:** **City:** Santullano **Country:** Spain **Facility:** Investigational Site Number :7240008 **State:** Asturias **Zip:** 33619 **Location 46:** **City:** Badalona **Country:** Spain **Facility:** Investigational Site Number :7240009 **State:** Barcelona [Barcelona] **Zip:** 08916 **Location 47:** **City:** Pontevedra **Country:** Spain **Facility:** Investigational Site Number :7240001 **State:** Galicia [Galicia] **Zip:** 36071 **Location 48:** **City:** Córdoba **Country:** Spain **Facility:** Investigational Site Number :7240004 **Zip:** 14004 **Location 49:** **City:** Madrid **Country:** Spain **Facility:** Investigational Site Number :7240007 **Zip:** 28034 **Location 50:** **City:** Valencia **Country:** Spain **Facility:** Investigational Site Number :7240003 **Zip:** 46026 **Location 51:** **City:** Zaragoza **Country:** Spain **Facility:** Investigational Site Number :7240002 **Zip:** 50009 **Location 52:** **City:** Hsinchu City **Country:** Taiwan **Facility:** Investigational Site Number :1580005 **Zip:** 30059 **Location 53:** **City:** Kaohsiung **Country:** Taiwan **Facility:** Investigational Site Number :1580006 **Zip:** 833 **Location 54:** **City:** Taichung **Country:** Taiwan **Facility:** Investigational Site Number :1580008 **Location 55:** **City:** Taipei **Country:** Taiwan **Facility:** Investigational Site Number :1580001 **Zip:** 10002 **Location 56:** **City:** Taipei **Country:** Taiwan **Facility:** Investigational Site Number :1580002 **Zip:** 10449 **Location 57:** **City:** Redhill **Country:** United Kingdom **Facility:** Investigational Site Number :8260001 **State:** Surrey **Zip:** RH1 5RH #### Overall Officials **Official 1:** **Affiliation:** Sanofi **Name:** Clinical Sciences & Operations **Role:** STUDY_DIRECTOR ### IPD Sharing Statement Module **Description:** Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org **IPD Sharing:** YES ## Document Section ### Large Document Module #### Large Docs - Date: 2020-05-20 - Filename: Prot_000.pdf - Has ICF: False - Has Protocol: True - Has SAP: False - Label: Study Protocol - Size: 1478945 - Type Abbrev: Prot - Upload Date: 2022-08-23T15:51 - Date: 2021-08-08 - Filename: SAP_001.pdf - Has ICF: False - Has Protocol: False - Has SAP: True - Label: Statistical Analysis Plan - Size: 801691 - Type Abbrev: SAP - Upload Date: 2022-08-23T15:53 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000012871 - Term: Skin Diseases - ID: D000003872 - Term: Dermatitis - ID: D000017443 - Term: Skin Diseases, Eczematous ### Condition Browse Module - Browse Branches - Abbrev: BC17 - Name: Skin and Connective Tissue Diseases - Abbrev: All - Name: All Conditions - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M14395 - Name: Prurigo - Relevance: HIGH - As Found: Prurigo - ID: M12394 - Name: Neurodermatitis - Relevance: HIGH - As Found: Neurodermatitis - ID: M15674 - Name: Skin Diseases - Relevance: LOW - As Found: Unknown - ID: M7067 - Name: Dermatitis - Relevance: LOW - As Found: Unknown - ID: M19712 - Name: Skin Diseases, Eczematous - Relevance: LOW - As Found: Unknown - ID: T4769 - Name: Prurigo Nodularis - Relevance: HIGH - As Found: Prurigo Nodularis ### Condition Browse Module - Meshes - ID: D000011536 - Term: Prurigo - ID: D000009450 - Term: Neurodermatitis ### Intervention Browse Module - Ancestors - ID: D000004791 - Term: Enzyme Inhibitors - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action ### 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: M30452 - Name: Calcineurin Inhibitors - Relevance: HIGH - As Found: PMR - ID: M7951 - Name: Enzyme Inhibitors - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000065095 - Term: Calcineurin Inhibitors ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module **Description:** Reported AEs were TEAEs that developed/worsened in grade or became serious during TE period (defined as the time from the first IMP administration to the last IMP administration + 14 weeks). Analysis was performed on safety population. #### Event Groups **Group ID:** EG000 **Title:** Placebo **Deaths Num At Risk:** 82 **Description:** Participants received placebo matched to dupilumab 600 mg (loading dose), SC on Day 1 followed by placebo matched to dupilumab 300 mg q2w for 24 weeks added to background therapy of TCS/TCI at stable dose. **ID:** EG000 **Other Num Affected:** 10 **Other Num at Risk:** 82 **Serious Number Affected:** 4 **Serious Number At Risk:** 82 **Title:** Placebo **Group ID:** EG001 **Title:** Dupilumab 300 mg Q2W **Deaths Num At Risk:** 77 **Description:** Participants received dupilumab at a loading dose of 600 mg, SC on Day 1 followed by dupilumab 300 mg q2w for 24 weeks added to background therapy of TCS/TCI at stable dose. **ID:** EG001 **Other Num Affected:** 11 **Other Num at Risk:** 77 **Serious Number Affected:** 2 **Serious Number At Risk:** 77 **Title:** Dupilumab 300 mg Q2W **Frequency Threshold:** 5 #### Other Events **Term:** Nasopharyngitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.1 **Term:** Headache **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 24.1 **Term:** Accidental Overdose **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 24.1 #### Serious Events **Term:** Pelvic Inflammatory Disease **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 82 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 77 **Num Events:** 1 **Term:** Pyelonephritis Acute **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 82 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 77 **Num Events:** 1 **Term:** Cutaneous T-Cell Lymphoma **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 82 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 77 **Term:** Large Granular Lymphocytosis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 82 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 77 **Term:** Lipoma **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 82 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 77 **Num Events:** 1 **Term:** Uterine Leiomyoma **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 82 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 77 **Num Events:** 1 **Term:** Cauda Equina Syndrome **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 82 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 77 **Term:** Cholecystitis Acute **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 82 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 77 **Term:** Rotator Cuff Syndrome **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 24.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 82 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 77 **Time Frame:** From the first IMP administration to the last IMP administration + 14 weeks (i.e., up to 36 weeks) ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 82 **Group ID:** BG001 **Value:** 78 **Group ID:** BG002 **Value:** 160 **Units:** Participants ### Group **ID:** BG000 **Title:** Placebo **Description:** Participants received placebo matched to dupilumab 600 mg (loading dose), SC on Day 1 followed by placebo matched to dupilumab 300 mg q2w for 24 weeks added to background therapy TCS/TCI at stable dose. ### Group **ID:** BG001 **Title:** Dupilumab 300 mg Q2W **Description:** Participants received dupilumab at a loading dose of 600 mg, SC on Day 1 followed by dupilumab 300 mg q2w for 24 weeks added to background therapy of TCS/TCI at stable dose. ### Group **ID:** BG002 **Title:** Total **Description:** Total of all reporting groups ### Measure #### Measurement **Group ID:** BG000 **Spread:** 15.2 **Value:** 46.7 #### Measurement **Group ID:** BG001 **Spread:** 15.8 **Value:** 51.0 #### Measurement **Group ID:** BG002 **Spread:** 15.6 **Value:** 48.8 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 51 #### Measurement **Group ID:** BG001 **Value:** 52 #### Measurement **Group ID:** BG002 **Value:** 103 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 31 #### Measurement **Group ID:** BG001 **Value:** 26 #### Measurement **Group ID:** BG002 **Value:** 57 **Category Title:** Male **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 1 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 1 **Category Title:** American Indian or Alaska Native #### Measurement **Group ID:** BG000 **Value:** 27 #### Measurement **Group ID:** BG001 **Value:** 25 #### Measurement **Group ID:** BG002 **Value:** 52 **Category Title:** Asian #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 1 #### Measurement **Group ID:** BG002 **Value:** 1 **Category Title:** Native Hawaiian or Other Pacific Islander #### Measurement **Group ID:** BG000 **Value:** 5 #### Measurement **Group ID:** BG001 **Value:** 3 #### Measurement **Group ID:** BG002 **Value:** 8 **Category Title:** Black or African American #### Measurement **Group ID:** BG000 **Value:** 48 #### Measurement **Group ID:** BG001 **Value:** 48 #### Measurement **Group ID:** BG002 **Value:** 96 **Category Title:** White #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 1 #### Measurement **Group ID:** BG002 **Value:** 1 **Category Title:** More than one race #### Measurement **Group ID:** BG000 **Value:** 1 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 1 **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:** Analysis was performed on randomized population. ## Results Section - More Information Module ### Certain Agreement **Other Details:** The Sponsor supports publication of clinical trial results but may request that investigators temporarily delay or alter publications in order to protect proprietary information. The Sponsor may also require that the results of multicenter studies be published only in their entirety and not as individual site data. **Restriction Type:** OTHER **Restrictive Agreement:** True ### Point of Contact **Email:** [email protected] **Organization:** Sanofi aventis recherche & développement **Phone:** 800-633-1610 **Phone Extension:** 6# **Title:** Trial Transparency Team ## Results Section - Outcome Measures Module ### Outcome Measure 1 #### Analysis **CI Lower Limit:** 1.08 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 5.00 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** Dupilumab 300 mg q2w versus Placebo **Group Description:** A hierarchical testing procedure was used to control the overall type I error. Testing was then performed sequentially in order the outcome measures were reported and continued when primary outcome measure was statistically significant at two-sided 0.05. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.0216 **P-Value Comment:** Threshold of significance at 0.05 level. **Parameter Type:** Odds Ratio (OR) **Parameter Value:** 2.3 **Statistical Comment:** **Statistical Method:** Cochran-Mantel-Haenszel **Tested Non-Inferiority:** ### Outcome Measure 2 #### Analysis **CI Lower Limit:** 3.56 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 22.66 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** Dupilumab 300 mg q2w versus Placebo **Group Description:** A hierarchical testing procedure was used to control the overall type I error. Testing was then performed sequentially in order the outcome measures were reported and continued when previous outcome measure was statistically significant at two-sided 0.05. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** <0.0001 **P-Value Comment:** Threshold of significance at 0.05 level. **Parameter Type:** Odds Ratio (OR) **Parameter Value:** 9.0 **Statistical Comment:** **Statistical Method:** Cochran-Mantel-Haenszel **Tested Non-Inferiority:** ### Outcome Measure 3 #### Analysis **CI Lower Limit:** 2.02 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 9.55 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** Dupilumab 300 mg q2w versus Placebo **Group Description:** A hierarchical testing procedure was used to control the overall type I error. Testing was then performed sequentially in order the outcome measures were reported and continued when previous outcome measure was statistically significant at two-sided 0.05. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** <0.0001 **P-Value Comment:** Threshold of significance at 0.05 level. **Parameter Type:** Odds Ratio (OR) **Parameter Value:** 4.4 **Statistical Comment:** **Statistical Method:** Cochran-Mantel-Haenszel **Tested Non-Inferiority:** ### Outcome Measure 4 #### Analysis **CI Lower Limit:** 2.03 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 18.11 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** Dupilumab 300 mg q2w versus Placebo **Group Description:** A hierarchical testing procedure was used to control the overall type I error. Testing was then performed sequentially in order the outcome measures were reported and continued when previous outcome measure was statistically significant at two-sided 0.05 **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.0001 **P-Value Comment:** Threshold of significance at 0.05 level. **Parameter Type:** Odds Ratio (OR) **Parameter Value:** 6.1 **Statistical Comment:** **Statistical Method:** Cochran-Mantel-Haenszel **Tested Non-Inferiority:** ### Outcome Measure 5 #### Analysis **CI Lower Limit:** 1.13 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 7.52 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** Dupilumab 300 mg q2w versus Placebo **Group Description:** A hierarchical testing procedure was used to control the overall type I error. Testing was then performed sequentially in order the outcome measures were reported and continued when previous outcome measure was statistically significant at two-sided 0.05. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.0194 **P-Value Comment:** Threshold of significance at 0.05 level. **Parameter Type:** Odds Ratio (OR) **Parameter Value:** 2.9 **Statistical Comment:** **Statistical Method:** Cochran-Mantel-Haenszel **Tested Non-Inferiority:** ### Outcome Measure 6 #### Analysis **CI Lower Limit:** -33.81 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -12.51 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** Dupilumab 300 mg q2w versus Placebo **Group Description:** A hierarchical testing procedure was used to control the overall type I error. Testing was then performed sequentially in order the outcome measures were reported and continued when previous outcome measure was statistically significant at two-sided 0.05. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** <0.0001 **P-Value Comment:** Threshold of significance at 0.05 level. **Parameter Type:** LS mean difference **Parameter Value:** -23.16 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** ### Outcome Measure 7 #### Analysis **CI Lower Limit:** -8.42 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -4.36 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** Dupilumab 300 mg q2w versus Placebo **Group Description:** A hierarchical testing procedure was used to control the overall type I error. Testing was then performed sequentially in order the outcome measures were reported and continued when previous outcome measure was statistically significant at two-sided 0.05. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** <0.0001 **P-Value Comment:** Threshold of significance at 0.05 level. **Parameter Type:** LS mean difference **Parameter Value:** -6.39 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** ### Outcome Measure 8 #### Analysis **CI Lower Limit:** -2.49 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -0.73 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** Dupilumab 300 mg q2w versus Placebo **Group Description:** A hierarchical testing procedure was used to control the overall type I error. Testing was then performed sequentially in order the outcome measures were reported and continued when previous outcome measure was statistically significant at two-sided 0.05. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.0003 **P-Value Comment:** Threshold of significance at 0.05 level. **Parameter Type:** LS mean difference **Parameter Value:** -1.61 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** ### Outcome Measure 9 #### Analysis **CI Lower Limit:** -0.22 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 1.30 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** Dupilumab 300 mg q2w versus Placebo **Group Description:** A hierarchical testing procedure was used to control the overall type I error. Testing was then performed sequentially in order the outcome measures were reported and continued when previous outcome measure was statistically significant at two-sided 0.05. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.1658 **P-Value Comment:** Threshold of significance at 0.05 level. **Parameter Type:** LS mean difference **Parameter Value:** 0.54 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** ### Outcome Measure 10 ### Outcome Measure 11 ### Outcome Measure 12 ### Outcome Measure 13 ### Outcome Measure 14 ### Outcome Measure 15 ### Outcome Measure 16 ### Outcome Measure 17 #### Analysis **CI Lower Limit:** -1.18 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -0.04 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** Dupilumab 300 mg q2w versus Placebo **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.0370 **P-Value Comment:** Threshold of significance was \<0.05. **Parameter Type:** LS mean difference **Parameter Value:** -0.61 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** ### Outcome Measure 18 ### Outcome Measure 19 ### Outcome Measure 20 ### Outcome Measure 21 ### Outcome Measure 22 ### Outcome Measure 23 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 22.0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 37.2 **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 19.5 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 57.7 **Title:** #### Outcome Measure 3 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 15.9 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 44.9 **Title:** #### Outcome Measure 4 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 8.5 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 32.1 **Title:** #### Outcome Measure 5 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 12.2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 25.6 **Title:** #### Outcome Measure 6 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 6.21 - **Upper Limit:** - **Value:** -36.18 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 6.39 - **Upper Limit:** - **Value:** -59.34 **Title:** #### Outcome Measure 7 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.18 - **Upper Limit:** - **Value:** -6.77 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.21 - **Upper Limit:** - **Value:** -13.16 **Title:** #### Outcome Measure 8 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.51 - **Upper Limit:** - **Value:** -2.74 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.53 - **Upper Limit:** - **Value:** -4.35 **Title:** #### Outcome Measure 9 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.45 - **Upper Limit:** - **Value:** 0.76 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.46 - **Upper Limit:** - **Value:** 1.30 **Title:** #### Outcome Measure 10 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.03 - **Upper Limit:** - **Value:** -2.59 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.06 - **Upper Limit:** - **Value:** -5.55 **Title:** #### Outcome Measure 11 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0.250 - **Spread:** - **Upper Limit:** 0.457 - **Value:** 0.353 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 0.552 - **Spread:** - **Upper Limit:** 0.764 - **Value:** 0.670 **Title:** #### Outcome Measure 12 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.46 - **Upper Limit:** - **Value:** -3.04 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.47 - **Upper Limit:** - **Value:** -4.11 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 79 - **Group ID:** OG001 - **Value:** 77 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.53 - **Upper Limit:** - **Value:** -3.10 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.54 - **Upper Limit:** - **Value:** -5.05 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 74 - **Group ID:** OG001 - **Value:** 76 **Units:** Participants #### Outcome Measure 13 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 3.06 - **Upper Limit:** - **Value:** -15.61 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 3.15 - **Upper Limit:** - **Value:** -17.41 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 81 - **Group ID:** OG001 - **Value:** 77 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 4.00 - **Upper Limit:** - **Value:** -22.61 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 4.12 - **Upper Limit:** - **Value:** -30.09 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 81 - **Group ID:** OG001 - **Value:** 77 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 5.42 - **Upper Limit:** - **Value:** -35.83 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 5.59 - **Upper Limit:** - **Value:** -48.86 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 79 - **Group ID:** OG001 - **Value:** 77 **Units:** Participants #### Outcome Measure 14 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 2.12 - **Upper Limit:** - **Value:** -9.49 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 2.18 - **Upper Limit:** - **Value:** -8.66 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 82 - **Group ID:** OG001 - **Value:** 78 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 3.06 - **Upper Limit:** - **Value:** -15.61 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 3.15 - **Upper Limit:** - **Value:** -17.41 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 81 - **Group ID:** OG001 - **Value:** 77 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 3.66 - **Upper Limit:** - **Value:** -20.44 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 3.77 - **Upper Limit:** - **Value:** -25.26 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 81 - **Group ID:** OG001 - **Value:** 77 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 4.00 - **Upper Limit:** - **Value:** -22.61 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 4.12 - **Upper Limit:** - **Value:** -30.09 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 81 - **Group ID:** OG001 - **Value:** 77 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 4.21 - **Upper Limit:** - **Value:** -25.21 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 4.33 - **Upper Limit:** - **Value:** -34.41 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 81 - **Group ID:** OG001 - **Value:** 77 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 4.33 - **Upper Limit:** - **Value:** -27.87 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 4.46 - **Upper Limit:** - **Value:** -36.98 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 80 - **Group ID:** OG001 - **Value:** 77 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 4.69 - **Upper Limit:** - **Value:** -28.99 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 4.84 - **Upper Limit:** - **Value:** -39.30 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 78 - **Group ID:** OG001 - **Value:** 76 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 4.56 - **Upper Limit:** - **Value:** -30.45 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 4.70 - **Upper Limit:** - **Value:** -41.32 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 79 - **Group ID:** OG001 - **Value:** 77 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 4.89 - **Upper Limit:** - **Value:** -34.86 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 5.04 - **Upper Limit:** - **Value:** -47.08 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 79 - **Group ID:** OG001 - **Value:** 77 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 5.04 - **Upper Limit:** - **Value:** -32.90 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 5.20 - **Upper Limit:** - **Value:** -44.65 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 78 - **Group ID:** OG001 - **Value:** 76 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 5.25 - **Upper Limit:** - **Value:** -34.64 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 5.41 - **Upper Limit:** - **Value:** -45.98 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 79 - **Group ID:** OG001 - **Value:** 77 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 5.42 - **Upper Limit:** - **Value:** -35.83 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 5.59 - **Upper Limit:** - **Value:** -48.86 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 79 - **Group ID:** OG001 - **Value:** 77 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 5.69 - **Upper Limit:** - **Value:** -34.49 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 5.86 - **Upper Limit:** - **Value:** -48.32 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 79 - **Group ID:** OG001 - **Value:** 77 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 5.71 - **Upper Limit:** - **Value:** -36.60 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 5.88 - **Upper Limit:** - **Value:** -50.67 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 79 - **Group ID:** OG001 - **Value:** 77 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 5.74 - **Upper Limit:** - **Value:** -35.96 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 5.91 - **Upper Limit:** - **Value:** -51.89 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 79 - **Group ID:** OG001 - **Value:** 77 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 5.74 - **Upper Limit:** - **Value:** -37.80 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 5.91 - **Upper Limit:** - **Value:** -54.36 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 77 - **Group ID:** OG001 - **Value:** 77 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 5.98 - **Upper Limit:** - **Value:** -39.15 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 6.15 - **Upper Limit:** - **Value:** -55.95 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 77 - **Group ID:** OG001 - **Value:** 77 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 6.15 - **Upper Limit:** - **Value:** -40.38 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 6.32 - **Upper Limit:** - **Value:** -56.80 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 77 - **Group ID:** OG001 - **Value:** 77 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 6.05 - **Upper Limit:** - **Value:** -40.03 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 6.23 - **Upper Limit:** - **Value:** -57.75 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 76 - **Group ID:** OG001 - **Value:** 77 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 5.94 - **Upper Limit:** - **Value:** -36.12 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 6.10 - **Upper Limit:** - **Value:** -56.80 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 74 - **Group ID:** OG001 - **Value:** 77 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 6.16 - **Upper Limit:** - **Value:** -36.43 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 6.34 - **Upper Limit:** - **Value:** -56.91 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 74 - **Group ID:** OG001 - **Value:** 76 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 6.19 - **Upper Limit:** - **Value:** -37.34 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 6.33 - **Upper Limit:** - **Value:** -58.78 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 74 - **Group ID:** OG001 - **Value:** 76 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 6.19 - **Upper Limit:** - **Value:** -36.87 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 6.32 - **Upper Limit:** - **Value:** -59.43 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 73 - **Group ID:** OG001 - **Value:** 75 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 6.21 - **Upper Limit:** - **Value:** -36.18 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 6.39 - **Upper Limit:** - **Value:** -59.34 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 74 - **Group ID:** OG001 - **Value:** 76 **Units:** Participants #### Outcome Measure 15 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 7.3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 16.7 **Title:** #### Outcome Measure 16 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1.2 - **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:** 1.2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 5.1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 6.1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 12.8 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 7.3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 16.7 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4.9 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 17.9 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 13.4 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 23.1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 15.9 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 24.4 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 14.6 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 28.2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 24.4 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 32.1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 18.3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 32.1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 17.1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 33.3 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 22.0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 37.2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 19.5 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 39.7 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 22.0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 39.7 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 20.7 - **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:** 19.5 - **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:** 23.2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 47.4 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 24.4 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 48.7 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 23.2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 51.3 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 20.7 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 51.3 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 20.7 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 48.7 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 22.0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 50.0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 20.7 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 55.1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 19.5 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 57.7 **Title:** #### Outcome Measure 17 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.33 - **Upper Limit:** - **Value:** -1.94 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.34 - **Upper Limit:** - **Value:** -2.55 **Title:** #### Outcome Measure 18 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 6.1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 7.7 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 9.8 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 15.4 **Title:** #### Outcome Measure 19 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.13 - **Upper Limit:** - **Value:** -0.54 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.13 - **Upper Limit:** - **Value:** -0.69 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 80 - **Group ID:** OG001 - **Value:** 77 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.17 - **Upper Limit:** - **Value:** -0.79 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.17 - **Upper Limit:** - **Value:** -1.19 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 76 - **Group ID:** OG001 - **Value:** 76 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.18 - **Upper Limit:** - **Value:** -0.86 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.18 - **Upper Limit:** - **Value:** -1.47 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 78 - **Group ID:** OG001 - **Value:** 77 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.20 - **Upper Limit:** - **Value:** -1.07 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.20 - **Upper Limit:** - **Value:** -2.03 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 74 - **Group ID:** OG001 - **Value:** 77 **Units:** Participants #### Outcome Measure 20 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4.9 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 14.1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 15.9 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 23.1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 19.5 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 42.3 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 18.3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 51.3 **Title:** #### Outcome Measure 21 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.12 - **Upper Limit:** - **Value:** -7.05 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.16 - **Upper Limit:** - **Value:** -12.07 **Title:** #### Outcome Measure 22 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 47 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 47 **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:** 2 **Title:** #### Outcome Measure 23 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **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:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** WI-NRS is a validated measure of itch severity. Participants were asked daily to rate the intensity of their worst pruritus (itch) over the past 24 hours, using a 11-point scale ranging from 0 (no itch) to 10 (worst imaginable itch). Higher scores indicated more severity. Percentage of participants with \>=4 points improvement (reduction) from baseline in WI-NRS scores at Week 12 is reported in this outcome measure. **Parameter Type:** NUMBER **Population Description:** Analysis was performed on intent-to-treat (ITT) population which included all participants with a treatment kit number allocated and recorded in the IRT database analyzed according to the treatment group allocated by randomization regardless of if treatment kit was used or not. **Reporting Status:** POSTED **Time Frame:** Baseline, Week 12 **Title:** Percentage of Participants With Greater Than or Equal to (>=) 4 Points Improvement (Reduction) From Baseline in Worst-Itch Numeric Rating Scale (WI-NRS) Scores at Week 12 **Type:** PRIMARY **Unit of Measure:** percentage of participants ##### Group **Description:** Participants received placebo matched to dupilumab 600 mg (loading dose), SC on Day 1 followed by placebo matched to dupilumab 300 mg q2w for 24 weeks added to background therapy of TCS/TCI at stable dose. **ID:** OG000 **Title:** Placebo ##### Group **Description:** Participants received dupilumab at a loading dose of 600 mg, SC on Day 1 followed by dupilumab 300 mg q2w for 24 weeks added to background therapy of TCS/TCI at stable dose. **ID:** OG001 **Title:** Dupilumab 300 mg Q2W #### Outcome Measure 2 **Description:** WI-NRS is a validated measure of itch severity. Participants were asked daily to rate the intensity of their worst pruritus (itch) over the past 24 hours, using a 11-point scale ranging from 0 (no itch) to 10 (worst imaginable itch). Higher scores indicated more severity. Percentage of participants with \>=4 points improvement (reduction) from baseline in WI-NRS scores at Week 24 is reported in this outcome measure. **Parameter Type:** NUMBER **Population Description:** Analysis was performed on ITT population. **Reporting Status:** POSTED **Time Frame:** Baseline, Week 24 **Title:** Percentage of Participants With >=4 Points Improvement (Reduction) From Baseline in WI-NRS Scores at Week 24 **Type:** SECONDARY **Unit of Measure:** percentage of participants ##### Group **Description:** Participants received placebo matched to dupilumab 600 mg (loading dose), SC on Day 1 followed by placebo matched to dupilumab 300 mg q2w for 24 weeks added to background therapy of TCS/TCI at stable dose. **ID:** OG000 **Title:** Placebo ##### Group **Description:** Participants received dupilumab at a loading dose of 600 mg, SC on Day 1 followed by dupilumab 300 mg q2w for 24 weeks added to background therapy of TCS/TCI at stable dose. **ID:** OG001 **Title:** Dupilumab 300 mg Q2W #### Outcome Measure 3 **Description:** IGA PN-S is an instrument used to assess the overall number and thickness of PN lesions at a given time point, as determined by the investigator. It consists of a 5-point scale ranging from 0 to 4 where 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate and 4 = severe. Higher scores indicate severe prurigo nodularis. In this outcome measure, percentage of participants with IGA PN-S score of either 0 (clear) or 1 (almost clear) has been reported. **Parameter Type:** NUMBER **Population Description:** Analysis was performed on ITT population. **Reporting Status:** POSTED **Time Frame:** At Week 24 **Title:** Percentage of Participants With Investigator's Global Assessment For Prurigo Nodularis-Stage (IGA PN-S) Scores of 0 or 1 at Week 24 **Type:** SECONDARY **Unit of Measure:** percentage of participants ##### Group **Description:** Participants received placebo matched to dupilumab 600 mg (loading dose), SC on Day 1 followed by placebo matched to dupilumab 300 mg q2w for 24 weeks added to background therapy of TCS/TCI at stable dose. **ID:** OG000 **Title:** Placebo ##### Group **Description:** Participants received dupilumab at a loading dose of 600 mg, SC on Day 1 followed by dupilumab 300 mg q2w for 24 weeks added to background therapy of TCS/TCI at stable dose. **ID:** OG001 **Title:** Dupilumab 300 mg Q2W #### Outcome Measure 4 **Description:** WI-NRS is a validated measure of itch severity. Participants were asked daily to rate the intensity of their worst pruritus (itch) over the past 24 hours, using a 11-point scale ranging from 0 (no itch) to 10 (worst imaginable itch), higher scores indicated more severity. IGA PN-S assess the overall number and thickness of PN lesions at a given time point, as determined by the investigator. It consists of a 5-point scale ranging from 0 to 4 where 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate and 4 = severe. Higher scores indicated greater severity. Percentage of participants with both an improvement (reduction) in WI-NRS by \>=4 Points (from Baseline) and an IGA PN-S score of 0 or 1 were reported in this outcome measure. **Parameter Type:** NUMBER **Population Description:** Analysis was performed on ITT population. **Reporting Status:** POSTED **Time Frame:** Baseline, Week 24 **Title:** Percentage of Participants With Both an Improvement (Reduction) in WI-NRS by >=4 Points and an IGA PN-S Score of 0 or 1 From Baseline at Week 24 **Type:** SECONDARY **Unit of Measure:** percentage of participants ##### Group **Description:** Participants received placebo matched to dupilumab 600 mg (loading dose), SC on Day 1 followed by placebo matched to dupilumab 300 mg q2w for 24 weeks added to background therapy of TCS/TCI at stable dose. **ID:** OG000 **Title:** Placebo ##### Group **Description:** Participants received dupilumab at a loading dose of 600 mg, SC on Day 1 followed by dupilumab 300 mg q2w for 24 weeks added to background therapy of TCS/TCI at stable dose. **ID:** OG001 **Title:** Dupilumab 300 mg Q2W #### Outcome Measure 5 **Description:** IGA PN-S is an instrument used to assess the overall number and thickness of PN lesions at a given time point, as determined by the investigator. It consists of a 5-point scale ranging from 0 to 4 where 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate and 4 = severe. Higher scores indicate severe prurigo nodularis. In this outcome measure, percentage of participants with IGA PN-S score of either 0 (clear) or 1 (almost clear) has been reported. **Parameter Type:** NUMBER **Population Description:** Analysis was performed on ITT population. **Reporting Status:** POSTED **Time Frame:** At Week 12 **Title:** Percentage of Participants With IGA PN-S Scores of 0 or 1 at Week 12 **Type:** SECONDARY **Unit of Measure:** percentage of participants ##### Group **Description:** Participants received placebo matched to dupilumab 600 mg (loading dose), SC on Day 1 followed by placebo matched to dupilumab 300 mg q2w for 24 weeks added to background therapy of TCS/TCI at stable dose. **ID:** OG000 **Title:** Placebo ##### Group **Description:** Participants received dupilumab at a loading dose of 600 mg, SC on Day 1 followed by dupilumab 300 mg q2w for 24 weeks added to background therapy of TCS/TCI at stable dose. **ID:** OG001 **Title:** Dupilumab 300 mg Q2W #### Outcome Measure 6 **Description:** WI-NRS is a validated measure of itch severity. Participants were asked daily to rate the intensity of their worst pruritus (itch) over the past 24 hours, using a 11-point scale ranging from 0 (no itch) to 10 (worst imaginable itch). Higher scores indicated more severity. Least squares (LS) means and standard error (SE) were obtained from Analysis of covariance (ANCOVA) model. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** Analysis was performed on ITT population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure. **Reporting Status:** POSTED **Time Frame:** Baseline, Week 24 **Title:** Percent Change From Baseline in WI-NRS Scores at Week 24 **Type:** SECONDARY **Unit of Measure:** percent change ##### Group **Description:** Participants received placebo matched to dupilumab 600 mg (loading dose), SC on Day 1 followed by placebo matched to dupilumab 300 mg q2w for 24 weeks added to background therapy of TCS/TCI at stable dose. **ID:** OG000 **Title:** Placebo ##### Group **Description:** Participants received dupilumab at a loading dose of 600 mg, SC on Day 1 followed by dupilumab 300 mg q2w for 24 weeks added to background therapy of TCS/TCI at stable dose. **ID:** OG001 **Title:** Dupilumab 300 mg Q2W #### Outcome Measure 7 **Description:** DLQI is developed to measure dermatology specific HRQoL in adult participants. It comprises of set of 10 questions assessing the impact of skin disease on participants' HRQoL over the previous week. Responses to each question were assessed on a 4-point Likert scale ranged from 0 (not at all) to 3 (very much). Scores from all 10 questions added up to give total DLQI scores ranged from 0 (not at all) to 30 (very much), higher scores indicated more impact on quality of life. LS means and SE were obtained from ANCOVA model. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** Analysis was performed on ITT population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure. **Reporting Status:** POSTED **Time Frame:** Baseline, Week 24 **Title:** Change From Baseline in Health-related Quality of Life (HRQoL) as Measured by Dermatology Life Quality Index (DLQI) at Week 24 **Type:** SECONDARY **Unit of Measure:** score on a scale ##### Group **Description:** Participants received placebo matched to dupilumab 600 mg (loading dose), SC on Day 1 followed by placebo matched to dupilumab 300 mg q2w for 24 weeks added to background therapy of TCS/TCI at stable dose. **ID:** OG000 **Title:** Placebo ##### Group **Description:** Participants received dupilumab at a loading dose of 600 mg, SC on Day 1 followed by dupilumab 300 mg q2w for 24 weeks added to background therapy of TCS/TCI at stable dose. **ID:** OG001 **Title:** Dupilumab 300 mg Q2W #### Outcome Measure 8 **Description:** Skin Pain-NRS was used to measure skin pain intensity. Participants were asked daily to rate the intensity of their worst skin pain over the past 24 hours, using a 11-point scale ranging from 0 ("No pain") to 10 ("Worst possible pain"). Higher scores indicated more severity. LS means and SE were obtained from ANCOVA model. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** Analysis was performed on ITT population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure. **Reporting Status:** POSTED **Time Frame:** Baseline, Week 24 **Title:** Change From Baseline in Skin Pain-NRS at Week 24 **Type:** SECONDARY **Unit of Measure:** score on a scale ##### Group **Description:** Participants received placebo matched to dupilumab 600 mg (loading dose), SC on Day 1 followed by placebo matched to dupilumab 300 mg q2w for 24 weeks added to background therapy of TCS/TCI at stable dose. **ID:** OG000 **Title:** Placebo ##### Group **Description:** Participants received dupilumab at a loading dose of 600 mg, SC on Day 1 followed by dupilumab 300 mg q2w for 24 weeks added to background therapy of TCS/TCI at stable dose. **ID:** OG001 **Title:** Dupilumab 300 mg Q2W #### Outcome Measure 9 **Description:** Sleep-NRS was used to measure sleep intensity. Participants were asked to rate their sleep quality on their past night upon awakening, using a 11-point NRS ranging from 0 to 10, where 0 = worst possible sleep and 10 = best possible sleep. Higher scores indicated less severity. LS means and SE were obtained from ANCOVA model. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** Analysis was performed on ITT population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure. **Reporting Status:** POSTED **Time Frame:** Baseline, Week 24 **Title:** Change From Baseline in Sleep-NRS at Week 24 **Type:** SECONDARY **Unit of Measure:** score on a scale ##### Group **Description:** Participants received placebo matched to dupilumab 600 mg (loading dose), SC on Day 1 followed by placebo matched to dupilumab 300 mg q2w for 24 weeks added to background therapy TCS/TCI at stable dose. **ID:** OG000 **Title:** Placebo ##### Group **Description:** Participants received dupilumab at a loading dose of 600 mg, SC on Day 1 followed by dupilumab 300 mg q2w for 24 weeks added to background therapy of TCS/TCI at stable dose. **ID:** OG001 **Title:** Dupilumab 300 mg Q2W #### Outcome Measure 10 **Description:** HADS is a 14-item self-administered questionnaire that consists of 2 scales, one measuring anxiety (HADS-A), and the other measuring depression (HADS-D). Each subscale comprised of 7 items with a scoring range from 0 (less severity of anxiety and depression) to 21 (greater severity of anxiety and depression symptoms) for each subscale. The total HADS score ranges from 0 (less severity) to 42 (more severity), with a high score indicative of a severe anxiety and/or depression level. LS means and SE were obtained from ANCOVA model. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** Analysis was performed on ITT population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure. **Reporting Status:** POSTED **Time Frame:** Baseline, Week 24 **Title:** Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Total Score at Week 24 **Type:** SECONDARY **Unit of Measure:** score on a scale ##### Group **Description:** Participants received placebo matched to dupilumab 600 mg (loading dose), SC on Day 1 followed by placebo matched to dupilumab 300 mg q2w for 24 weeks added to background therapy TCS/TCI at stable dose. **ID:** OG000 **Title:** Placebo ##### Group **Description:** Participants received dupilumab at a loading dose of 600 mg, SC on Day 1 followed by dupilumab 300 mg q2w for 24 weeks added to background therapy of TCS/TCI at stable dose. **ID:** OG001 **Title:** Dupilumab 300 mg Q2W #### Outcome Measure 11 **Description:** WI-NRS is a validated measure of itch severity. Participants were asked daily to rate the intensity of their worst pruritus (itch) over the past 24 hours, using a 11-point scale ranging from 0 (no itch) to 10 (worst imaginable itch). Higher scores indicated more severity. Probability of participants with an improvement (reduction) in WI-NRS at Week 24 was based on Kaplan-Meier estimates and was reported in this outcome measure. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** NUMBER **Population Description:** Analysis was performed on ITT population. **Reporting Status:** POSTED **Time Frame:** Baseline, Week 24 **Title:** Probability of Participants With an Improvement (Reduction) in WI-NRS by >=4 From Baseline at Week 24 **Type:** SECONDARY **Unit of Measure:** probability of participants ##### Group **Description:** Participants received placebo matched to dupilumab 600 mg (loading dose), SC on Day 1 followed by placebo matched to dupilumab 300 mg q2w for 24 weeks added to background therapy of TCS/TCI at stable dose. **ID:** OG000 **Title:** Placebo ##### Group **Description:** Participants received dupilumab at a loading dose of 600 mg, SC on Day 1 followed by dupilumab 300 mg q2w for 24 weeks added to background therapy of TCS/TCI at stable dose. **ID:** OG001 **Title:** Dupilumab 300 mg Q2W #### Outcome Measure 12 **Description:** WI-NRS is a validated measure of itch severity. Participants were asked daily to rate the intensity of their worst pruritus (itch) over the past 24 hours, using a 11-point scale ranging from 0 (no itch) to 10 (worst imaginable itch). Higher scores indicated more severity. LS means and SE were obtained from ANCOVA model. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** Analysis was performed on ITT population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure and 'number analyzed' = participants with available data for each specified category. **Reporting Status:** POSTED **Time Frame:** Baseline, Weeks 12 and 24 **Title:** Change From Baseline in WI-NRS Scores at Weeks 12 and 24 **Type:** SECONDARY **Unit of Measure:** score on a scale ##### Group **Description:** Participants received placebo matched to dupilumab 600 mg (loading dose), SC on Day 1 followed by placebo matched to dupilumab 300 mg q2w for 24 weeks added to background therapy of TCS/TCI at stable dose. **ID:** OG000 **Title:** Placebo ##### Group **Description:** Participants received dupilumab at a loading dose of 600 mg, SC on Day 1 followed by dupilumab 300 mg q2w for 24 weeks added to background therapy of TCS/TCI at stable dose. **ID:** OG001 **Title:** Dupilumab 300 mg Q2W #### Outcome Measure 13 **Description:** WI-NRS is a validated measure of itch severity. Participants were asked daily to rate the intensity of their worst pruritus (itch) over the past 24 hours, using a 11-point scale ranging from 0 (no itch) to 10 (worst imaginable itch). Higher scores indicated more severity. LS means and SE were obtained from ANCOVA model. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** Analysis was performed on ITT population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure and 'number analyzed' = participants with available data for each specified category. **Reporting Status:** POSTED **Time Frame:** Baseline, Weeks 2, 4 and 12 **Title:** Percent Change From Baseline in WI-NRS Scores at Weeks 2, 4 and 12 **Type:** SECONDARY **Unit of Measure:** percent change ##### Group **Description:** Participants received placebo matched to dupilumab 600 mg (loading dose), SC on Day 1 followed by placebo matched to dupilumab 300 mg q2w for 24 weeks added to background therapy of TCS/TCI at stable dose. **ID:** OG000 **Title:** Placebo ##### Group **Description:** Participants received dupilumab at a loading dose of 600 mg, SC on Day 1 followed by dupilumab 300 mg q2w for 24 weeks added to background therapy of TCS/TCI at stable dose. **ID:** OG001 **Title:** Dupilumab 300 mg Q2W #### Outcome Measure 14 **Description:** WI-NRS is a validated measure of itch severity. Participants were asked daily to rate the intensity of their worst pruritus (itch) over the past 24 hours, using a 11-point scale ranging from 0 (no itch) to 10 (worst imaginable itch). Higher scores indicated more severity. LS means and SE were obtained from ANCOVA model. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** Analysis was performed on ITT population. Here, 'number analyzed' = participants with available data for each specified category. **Reporting Status:** POSTED **Time Frame:** Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, and 24 **Title:** Percent Change From Baseline in WI-NRS Scores at Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, and 24 **Type:** SECONDARY **Unit of Measure:** percent change ##### Group **Description:** Participants received placebo matched to dupilumab 600 mg (loading dose), SC on Day 1 followed by placebo matched to dupilumab 300 mg q2w for 24 weeks added to background therapy of TCS/TCI at stable dose. **ID:** OG000 **Title:** Placebo ##### Group **Description:** Participants received dupilumab at a loading dose of 600 mg, SC on Day 1 followed by dupilumab 300 mg q2w for 24 weeks added to background therapy of TCS/TCI at stable dose. **ID:** OG001 **Title:** Dupilumab 300 mg Q2W #### Outcome Measure 15 **Description:** WI-NRS is a validated measure of itch severity. Participants were asked daily to rate the intensity of their worst pruritus (itch) over the past 24 hours, using a 11-point scale ranging from 0 (no itch) to 10 (worst imaginable itch). Higher scores indicated more severity. Percentage of participants with improvement (Reduction) in WI-NRS scale by \>=4 Points at Week 4 is reported in this outcome measure. **Parameter Type:** NUMBER **Population Description:** Analysis was performed on ITT population. **Reporting Status:** POSTED **Time Frame:** Baseline, Week 4 **Title:** Percentage of Participants With Improvement (Reduction) in WI-NRS >=4 Points From Baseline at Week 4 **Type:** SECONDARY **Unit of Measure:** percentage of participants ##### Group **Description:** Participants received placebo matched to dupilumab 600 mg (loading dose), SC on Day 1 followed by placebo matched to dupilumab 300 mg q2w for 24 weeks added to background therapy of TCS/TCI at stable dose. **ID:** OG000 **Title:** Placebo ##### Group **Description:** Participants received dupilumab at a loading dose of 600 mg, SC on Day 1 followed by dupilumab 300 mg q2w for 24 weeks added to background therapy of TCS/TCI at stable dose. **ID:** OG001 **Title:** Dupilumab 300 mg Q2W #### Outcome Measure 16 **Description:** WI-NRS is a validated measure of itch severity. Participants were asked daily to rate the intensity of their worst pruritus (itch) over the past 24 hours, using a 11-point scale ranging from 0 (no itch) to 10 (worst imaginable itch). Higher scores indicated more severity. Percentage of participants achieving \>=4 points improvement (reduction) from Baseline in WI-NRS scores at Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 and 24 is reported in this outcome measure. **Parameter Type:** NUMBER **Population Description:** Analysis was performed on ITT population. **Reporting Status:** POSTED **Time Frame:** Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 and 24 **Title:** Percentage of Participants Achieving >=4 Points Improvement (Reduction) From Baseline in WI-NRS Scores at Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, and 24 **Type:** SECONDARY **Unit of Measure:** percentage of participants ##### Group **Description:** Participants received placebo matched to dupilumab 600 mg (loading dose), SC on Day 1 followed by placebo matched to dupilumab 300 mg q2w for 24 weeks added to background therapy of TCS/TCI at stable dose. **ID:** OG000 **Title:** Placebo ##### Group **Description:** Participants received dupilumab at a loading dose of 600 mg, SC on Day 1 followed by dupilumab 300 mg q2w for 24 weeks added to background therapy of TCS/TCI at stable dose. **ID:** OG001 **Title:** Dupilumab 300 mg Q2W #### Outcome Measure 17 **Description:** Onset of action was defined as the first p\<0.05 difference from placebo in the weekly average WI-NRS that remained significant at subsequent measurements. WI-NRS is a validated measure of itch severity. Participants were asked daily to rate the intensity of their worst pruritus (itch) over the past 24 hours, using a 11-point scale ranging from 0 (no itch) to 10 (worst imaginable itch). Higher scores indicated greater severity. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** Analysis was performed on ITT population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure. **Reporting Status:** POSTED **Time Frame:** Baseline, Week 4 **Title:** Onset of Action Based on Change From Baseline in WI-NRS at Week 4 **Type:** SECONDARY **Unit of Measure:** score on a scale ##### Group **Description:** Participants received placebo matched to dupilumab 600 mg (loading dose), SC on Day 1 followed by placebo matched to dupilumab 300 mg q2w for 24 weeks added to background therapy of TCS/TCI at stable dose. **ID:** OG000 **Title:** Placebo ##### Group **Description:** Participants received dupilumab at a loading dose of 600 mg, SC on Day 1 followed by dupilumab 300 mg q2w for 24 weeks added to background therapy of TCS/TCI at stable dose. **ID:** OG001 **Title:** Dupilumab 300 mg Q2W #### Outcome Measure 18 **Description:** IGA PN-S is an instrument used to assess the overall number and thickness of PN lesions at a given time point, as determined by the investigator. It consists of a 5-point scale ranging from 0 to 4: where 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate and 4 = severe. Higher scores indicate severe prurigo nodularis. In this outcome measure, percentage of participants with IGA PN-S score of either 0 (clear) or 1 (almost clear) has been reported. **Parameter Type:** NUMBER **Population Description:** Analysis was performed on ITT population. **Reporting Status:** POSTED **Time Frame:** At Weeks 4 and 8 **Title:** Percentage of Participants With Investigator's Global Assessment for PN-Stage (IGA PN-S) Score of 0 or 1 at Weeks 4 and 8 **Type:** SECONDARY **Unit of Measure:** percentage of participants ##### Group **Description:** Participants received placebo matched to dupilumab 600 mg (loading dose), SC on Day 1 followed by placebo matched to dupilumab 300 mg q2w for 24 weeks added to background therapy of TCS/TCI at stable dose. **ID:** OG000 **Title:** Placebo ##### Group **Description:** Participants received dupilumab at a loading dose of 600 mg, SC on Day 1 followed by dupilumab 300 mg q2w for 24 weeks added to background therapy of TCS/TCI at stable dose. **ID:** OG001 **Title:** Dupilumab 300 mg Q2W #### Outcome Measure 19 **Description:** IGA PN-S is an instrument used to assess the overall number and thickness of PN lesions at a given time point, as determined by the investigator. It consists of a 5-point scale ranging from 0 to 4: where 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate and 4 = severe. Higher scores indicate severe prurigo nodularis. LS means and SE were obtained from ANCOVA model. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** Analysis was performed on ITT population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure and 'number analyzed' = participants with available data for each specified category. **Reporting Status:** POSTED **Time Frame:** Baseline, Weeks 4, 8, 12, and 24 **Title:** Change From Baseline in IGA PN-S Scores at Weeks 4, 8, 12, and 24 **Type:** SECONDARY **Unit of Measure:** score on a scale ##### Group **Description:** Participants received placebo matched to dupilumab 600 mg (loading dose), SC on Day 1 followed by placebo matched to dupilumab 300 mg q2w for 24 weeks added to background therapy of TCS/TCI at stable dose. **ID:** OG000 **Title:** Placebo ##### Group **Description:** Participants received dupilumab at a loading dose of 600 mg, SC on Day 1 followed by dupilumab 300 mg q2w for 24 weeks added to background therapy of TCS/TCI at stable dose. **ID:** OG001 **Title:** Dupilumab 300 mg Q2W #### Outcome Measure 20 **Description:** The IGA PN-A is an instrument used to assess the overall activity of PN lesions at a given time point, as determined by the investigator. It consists of a 5-point scale ranging from 0 to 4: where 0 = clear (0% nodules showing excoriations/crusts), 1 = almost clear (up to 10% nodules showing excoriations/crusts), 2 = mild (11-25% nodules showing excoriations/crusts), 3 = moderate (26-75% nodules showing excoriations/crusts) and 4 = severe (76-100% of nodules showing excoriations/crusts). Higher scores indicate severe prurigo nodularis. In this outcome measure, percentage of participants with IGA PN-A score of either 0 (clear) or 1 (almost clear) has been reported. **Parameter Type:** NUMBER **Population Description:** Analysis was performed on ITT population. **Reporting Status:** POSTED **Time Frame:** At Weeks 4, 8, 12 and 24 **Title:** Percentage of Participants With Investigator's Global Assessment for PN-Activity (IGA PN-A) Score of 0 or 1 at Weeks 4, 8, 12 and 24 **Type:** SECONDARY **Unit of Measure:** percentage of participants ##### Group **Description:** Participants received placebo matched to dupilumab 600 mg (loading dose), SC on Day 1 followed by placebo matched to dupilumab 300 mg q2w for 24 weeks added to background therapy TCS/TCI at stable dose. **ID:** OG000 **Title:** Placebo ##### Group **Description:** Participants received dupilumab at a loading dose of 600 mg, SC on Day 1 followed by dupilumab 300 mg q2w for 24 weeks added to background therapy of TCS/TCI at stable dose. **ID:** OG001 **Title:** Dupilumab 300 mg Q2W #### Outcome Measure 21 **Description:** DLQI is developed to measure dermatology specific HRQoL in adult participants. It comprises of set of 10 questions assessing the impact of skin disease on participants' HRQoL over the previous week. Responses to each question were assessed on a 4-point Likert scale ranged from 0 (not at all) to 3 (very much). Scores from all 10 questions added up to give total DLQI scores ranged from 0 (not at all) to 30 (very much), higher scores indicated more impact on quality of life. LS means and SE were obtained from ANCOVA model. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** Analysis was performed on ITT population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure. **Reporting Status:** POSTED **Time Frame:** Baseline, Week 12 **Title:** Change From Baseline in HRQoL, as Measured by DLQI at Week 12 **Type:** SECONDARY **Unit of Measure:** score on a scale ##### Group **Description:** Participants received placebo matched to dupilumab 600 mg (loading dose), SC on Day 1 followed by placebo matched to dupilumab 300 mg q2w for 24 weeks added to background therapy of TCS/TCI at stable dose. **ID:** OG000 **Title:** Placebo ##### Group **Description:** Participants received dupilumab at a loading dose of 600 mg, SC on Day 1 followed by dupilumab 300 mg q2w for 24 weeks added to background therapy of TCS/TCI at stable dose. **ID:** OG001 **Title:** Dupilumab 300 mg Q2W #### Outcome Measure 22 **Description:** An adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily have to have a causal relationship with the treatment. Serious adverse events (SAEs) was defined as any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. TEAEs were defined as AEs that developed, worsened or became serious during the treatment-emergent (TE) period (time from the first investigational medicinal product \[IMP\] administration to the last IMP administration + 14 weeks). **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Analysis was performed on safety population which included all participants who received at least 1 dose of study intervention analyzed according to the intervention actually received. **Reporting Status:** POSTED **Time Frame:** From the first IMP administration to the last IMP administration + 14 weeks (i.e., up to 36 weeks) **Title:** Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) **Type:** SECONDARY **Unit of Measure:** Participants ##### Group **Description:** Participants received placebo matched to dupilumab 600 mg (loading dose), SC on Day 1 followed by placebo matched to dupilumab 300 mg q2w for 24 weeks added to background therapy of TCS/TCI at stable dose. **ID:** OG000 **Title:** Placebo ##### Group **Description:** Participants received dupilumab at a loading dose of 600 mg, SC on Day 1 followed by dupilumab 300 mg q2w for 24 weeks added to background therapy of TCS/TCI at stable dose. **ID:** OG001 **Title:** Dupilumab 300 mg Q2W #### Outcome Measure 23 **Description:** ADA response was categorized as: Treatment emergent and Treatment-boosted. Treatment emergent ADAs were defined as a participant with no positive assay response at baseline but with a positive assay response during the entire TEAE period. Treatment boosted ADAs: defined as participants with a positive ADA assay response at baseline and with at least a 4-fold increase in titer compared to baseline during the TE period (time from the first IMP administration to the last IMP administration + 14 weeks). Titer values were defined as low titer (\< 1,000); moderate (1,000 \<= titer \<= 10,000) and high titer (\> 10,000). **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Analysis was performed on ADA population which included all participants who received at least one dose of the study drug and had at least one non-missing ADA result after first dose of study drug. Participants were analyzed according to the intervention actually received. **Reporting Status:** POSTED **Time Frame:** From the first IMP administration to the last IMP administration + 14 weeks (i.e., up to 36 weeks) **Title:** Number of Participants With Treatment-emergent and Treatment Boosted Antidrug Antibodies (ADA) **Type:** SECONDARY **Unit of Measure:** Participants ##### Group **Description:** Participants received placebo matched to dupilumab 600 mg (loading dose), SC on Day 1 followed by placebo matched to dupilumab 300 mg q2w for 24 weeks added to background therapy of TCS/TCI at stable dose. **ID:** OG000 **Title:** Placebo ##### Group **Description:** Participants received dupilumab at a loading dose of 600 mg, SC on Day 1 followed by dupilumab 300 mg q2w for 24 weeks added to background therapy of TCS/TCI at stable dose. **ID:** OG001 **Title:** Dupilumab 300 mg Q2W ### Participant Flow Module #### Group **Description:** Participants received placebo matched to dupilumab 600 milligrams (mg) (loading dose), subcutaneously (SC) on Day 1 followed by placebo matched to dupilumab 300 mg once every 2 weeks (q2w) for 24 weeks added to background therapy of topical corticosteroids/topical calcineurin inhibitors (TCS/TCI) at stable dose. **ID:** FG000 **Title:** Placebo #### Group **Description:** Participants received dupilumab at a loading dose of 600 mg, SC on Day 1 followed by dupilumab 300 mg q2w for 24 weeks added to background therapy of TCS/TCI at stable dose. **ID:** FG001 **Title:** Dupilumab 300 mg Q2W #### Period **Title:** Overall Study ##### Withdraw **Type:** Adverse Event ###### Reason **Group ID:** FG000 **Number of Subjects:** 2 ###### Reason **Group ID:** FG001 **Number of Subjects:** 0 ##### Withdraw **Type:** Poor compliance to protocol ###### 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:** 23 ###### Reason **Group ID:** FG001 **Number of Subjects:** 6 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 82 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 78 ##### Milestone **Type:** Treated ###### Achievement **Group ID:** FG000 **Number of Subjects:** 82 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 77 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 56 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 72 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 26 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 6 **Pre-Assignment Details:** A total of 160 participants were randomized in 1:1 ratio to receive study interventions (placebo or dupilumab) by interactive response technology (IRT). **Recruitment Details:** This study was conducted at 57 sites in 11 countries. A total of 221 participants were screened from 16 January 2020 to 24 February 2021, out of which 61 were screen failures. Screen failures were mainly due to not meeting eligibility criteria. **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT04950179 **Brief Title:** PDRI Rates Among CAPD Patients at a Tertiary University Hospital: A 5-Year Retrospective Study **Official Title:** Peritoneal Dialysis-Related Infection Rates and Outcomes of Antibiotic Treatments Among Continuous Ambulatory Peritoneal Dialysis Patients at a Tertiary University Hospital: A 5-Year Retrospective Study #### Organization Study ID Info **ID:** PDRI-2020 #### Organization **Class:** OTHER **Full Name:** Phramongkutklao College of Medicine and Hospital ### Status Module #### Completion Date **Date:** 2021-04-14 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2021-07-12 **Type:** ACTUAL **Last Update Submit Date:** 2021-07-06 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2021-03-11 **Type:** ACTUAL #### Start Date **Date:** 2021-02-24 **Type:** ACTUAL **Status Verified Date:** 2021-07 #### Study First Post Date **Date:** 2021-07-06 **Type:** ACTUAL **Study First Submit Date:** 2021-06-25 **Study First Submit QC Date:** 2021-06-25 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** Silpakorn University #### Lead Sponsor **Class:** OTHER **Name:** Phramongkutklao College of Medicine and 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:** Peritoneal dialysis-related infection is a complication that leads to peritoneal dialysis catheter removal or patient death. The present study aimed to investigate peritoneal dialysis-related infection rates, causative pathogens, appropriation of antibiotic use, treatment outcomes and trend in antimicrobial resistance of causative pathogens. ### Conditions Module **Conditions:** - Peritoneal Dialysis-related Infection **Keywords:** - Peritoneal dialysis-related infection - Infectious peritonitis - Exit-site infection - Tunnel infection - Infection rate ### Design Module #### Design Info **Observational Model:** CASE_ONLY **Time Perspective:** RETROSPECTIVE #### Enrollment Info **Count:** 135 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module ### Interventions #### Intervention 1 **Description:** The study was conducted by retrospective data collection from medical records of 135 continuous ambulatory peritoneal dialysis (CAPD) patients at Phramongkutklao Hospital from January 1, 2016 to December 31, 2020. **Name:** PDRI patients **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** Retrospective data collection from patients' medical records **Measure:** Rate of peritoneal dialysis-related infection **Time Frame:** January 1, 2016 to December 31, 2020 **Description:** Retrospective data collection from patients' medical records **Measure:** Treatment outcomes of peritoneal dialysis-related infection **Time Frame:** January 1, 2016 to December 31, 2020 #### Secondary Outcomes **Description:** Retrospective data collection from patients' medical records **Measure:** Causative pathogens of peritoneal dialysis-related infection **Time Frame:** January 1, 2016 to December 31, 2020 **Description:** Retrospective data collection from patients' medical records **Measure:** Appropriation of antibiotic use in the treatments of peritoneal dialysis-related infection **Time Frame:** January 1, 2016 to December 31, 2020 ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Patients who were at least 18 years old. 2. Patients who were diagnosed with stage 5 chronic kidney disease (eGFR \< 15 ml/min/1.73m\^2). 3. Patients who were undergoing Continuous Ambulatory Peritoneal Dialysis (CAPD) at CAPD clinic, Phramongkutklao Hospital during January 1, 2016 to December 31, 2020. Exclusion Criteria: 1. Patients with incomplete data records that invalid to include in the process of data analysis 2. Patients who were not treated and started their first CAPD at CAPD clinic, Phramongkutklao Hospital. **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Patients who were undergoing Continuous Ambulatory Peritoneal Dialysis (CAPD) at CAPD clinic, Phramongkutklao Hospital. ### Contacts Locations Module #### Locations **Location 1:** **City:** Ratchathewi **Country:** Thailand **Facility:** Phramongkutklao Hospital **State:** Bangkok **Zip:** 10400 #### Overall Officials **Official 1:** **Affiliation:** Phramongkutklao Hospital and College of Medicine **Name:** Pamila Tasanavipas, MD **Role:** STUDY_CHAIR **Official 2:** **Affiliation:** Faculty of Pharmacy, Silpakorn University **Name:** Daraporn Rungprai, BCP **Role:** STUDY_DIRECTOR **Official 3:** **Affiliation:** Faculty of Pharmacy, Silpakorn University **Name:** Vorada Pengsong **Role:** PRINCIPAL_INVESTIGATOR **Official 4:** **Affiliation:** Faculty of Pharmacy, Silpakorn University **Name:** Vattanai Dhamnimitchok **Role:** PRINCIPAL_INVESTIGATOR **Official 5:** **Affiliation:** Faculty of Pharmacy, Silpakorn University **Name:** Vilai Wisuthip **Role:** PRINCIPAL_INVESTIGATOR **Official 6:** **Affiliation:** Faculty of Pharmacy, Silpakorn University **Name:** Supichaya Hluangbumroong **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Luvira V, Satirapoj B, Supasyndh O, Chaiprasert A, Ruangkanchanasetr P, Nata N, Kanjanakul I, Supaporn T, Choovichian P, Bijaphala S, Luvira U, Phiboonbanakit D. A single-centre experience: peritoneal dialysis-related infections in patients on long-term dialysis. J Med Assoc Thai. 2011 Sep;94 Suppl 4:S30-6. **PMID:** 22043564 **Citation:** Kanjanabuch T, Chancharoenthana W, Katavetin P, Sritippayawan S, Praditpornsilpa K, Ariyapitipan S, Eiam-Ong S, Dhanakijcharoen P, Lumlertgul D. The incidence of peritoneal dialysis-related infection in Thailand: a nationwide survey. J Med Assoc Thai. 2011 Sep;94 Suppl 4:S7-12. **PMID:** 22043560 **Citation:** Perl J, Fuller DS, Bieber BA, Boudville N, Kanjanabuch T, Ito Y, Nessim SJ, Piraino BM, Pisoni RL, Robinson BM, Schaubel DE, Schreiber MJ, Teitelbaum I, Woodrow G, Zhao J, Johnson DW. Peritoneal Dialysis-Related Infection Rates and Outcomes: Results From the Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS). Am J Kidney Dis. 2020 Jul;76(1):42-53. doi: 10.1053/j.ajkd.2019.09.016. Epub 2020 Jan 10. **PMID:** 31932094 **Citation:** Wang HH, Huang CH, Kuo MC, Lin SY, Hsu CH, Lee CY, Chiu YW, Chen YH, Lu PL. Microbiology of peritoneal dialysis-related infection and factors of refractory peritoneal dialysis related peritonitis: A ten-year single-center study in Taiwan. J Microbiol Immunol Infect. 2019 Oct;52(5):752-759. doi: 10.1016/j.jmii.2018.10.013. Epub 2019 Jan 8. **PMID:** 30665844 **Citation:** Chen HC, Shieh CC, Sung JM. Increasing Staphylococcus Species Resistance in Peritoneal Dialysis-Related Peritonitis over a 10-Year Period in a Single Taiwanese Center. Perit Dial Int. 2018 Jul-Aug;38(4):266-270. doi: 10.3747/pdi.2017.00226. **PMID:** 29987065 **Citation:** Li PK, Szeto CC, Piraino B, Bernardini J, Figueiredo AE, Gupta A, Johnson DW, Kuijper EJ, Lye WC, Salzer W, Schaefer F, Struijk DG; International Society for Peritoneal Dialysis. Peritoneal dialysis-related infections recommendations: 2010 update. Perit Dial Int. 2010 Jul-Aug;30(4):393-423. doi: 10.3747/pdi.2010.00049. No abstract available. Erratum In: Perit Dial Int. 2011 Sep-Oct;31(5):512. **PMID:** 20628102 **Citation:** Szeto CC, Li PK, Johnson DW, Bernardini J, Dong J, Figueiredo AE, Ito Y, Kazancioglu R, Moraes T, Van Esch S, Brown EA. ISPD Catheter-Related Infection Recommendations: 2017 Update. Perit Dial Int. 2017 Mar-Apr;37(2):141-154. doi: 10.3747/pdi.2016.00120. No abstract available. **PMID:** 28360365 **Citation:** Li PK, Szeto CC, Piraino B, de Arteaga J, Fan S, Figueiredo AE, Fish DN, Goffin E, Kim YL, Salzer W, Struijk DG, Teitelbaum I, Johnson DW. ISPD Peritonitis Recommendations: 2016 Update on Prevention and Treatment. Perit Dial Int. 2016 Sep 10;36(5):481-508. doi: 10.3747/pdi.2016.00078. Epub 2016 Jun 9. No abstract available. Erratum In: Perit Dial Int. 2018 Jul-Aug;38(4):313. **PMID:** 27282851 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000020969 - Term: Disease Attributes - ID: D000010335 - Term: Pathologic Processes ### Condition Browse Module - Browse Branches - Abbrev: BC01 - Name: Infections - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: BC06 - Name: Digestive System Diseases ### 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: M13447 - Name: Peritonitis - Relevance: LOW - As Found: Unknown - ID: M22700 - Name: Disease Attributes - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000007239 - Term: Infections - ID: D000003141 - Term: Communicable Diseases ### 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 - ID: M4224 - Name: Antibiotics, Antitubercular - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00314379 **Brief Title:** Endothelial Function in a Sample Group of Patients From the ICARE Study **Official Title:** Vitamin E Treatment and Endothelial Function in Type 2 Diabetic Patients With Hp 2-2 Phenotype From the I CARE Study (EFI) #### Organization Study ID Info **ID:** HP1980 #### Organization **Class:** OTHER **Full Name:** Technion, Israel Institute of Technology ### Status Module #### Completion Date **Date:** 2007-12 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2009-01-22 **Type:** ESTIMATED **Last Update Submit Date:** 2009-01-20 **Overall Status:** COMPLETED #### Start Date **Date:** 2006-04 **Status Verified Date:** 2009-01 #### Study First Post Date **Date:** 2006-04-13 **Type:** ESTIMATED **Study First Submit Date:** 2006-04-10 **Study First Submit QC Date:** 2006-04-12 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** Clalit Health Services **Class:** OTHER **Name:** Rambam Health Care Campus #### Lead Sponsor **Class:** OTHER **Name:** Technion, Israel Institute of Technology ### Description Module **Brief Summary:** The ICARE study, clinicaltrials.gov ID number: NCT00220831 and protocol number KL-2004, is recruiting diabetic patients with haptoglobin phenotype 2-2, which are randomised to either Vitamin E 400IU per day or placebo. Patients will be followed for 4 years for the major cardiovascular complications of diabetes, acute myocardial infarction (MI), stroke and cardiovascular mortality (see ICARE protocol). The EFI study, Endothelial Function in ICARE will recruit a sample group of 50 patients from the ICARE cohort. These patients will complete all requirements by ICARE protocol and in addition will be tested for endothelial function by a non-invasive method of flow mediated dilatation (FMD). **Detailed Description:** Fifty patients will be randomly sampled from the ICARE untreated cohort (registry) of diabetic patients with Hp2-2 phenotype which were not randomised to treatment under ICARE study. Patients will be randomised to either vitamin E 400 IU/d or Placebo upon sampling for EFI study. The patients will be tested for endothelial function by a method of Post Ischemic Flow mediated Dilatation. all patients will undergo a baseline Endothelial Function test and then start taking the study drug for 2 months. at the end of two months of therapy the patients will undergo a second endothelial function test, then therapy will be stopped for 2 weeks and a cross over will be performed for an additional 2 months of therapy which in the end the third and final endothelial function test will be done. An interim Results analysis is set to be done once the first 20 patients completed the protocol. In case of significant differences between the groups, study principal investigators will decide about study completion. ### Conditions Module **Conditions:** - Cardiovascular Diseases **Keywords:** - Diabetes - Endothelial Function - Haptoglobin ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** DOUBLE **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 50 **Type:** ESTIMATED **Phases:** - PHASE2 - PHASE3 **Study Type:** INTERVENTIONAL ### Arms Interventions Module ### Interventions #### Intervention 1 **Name:** Vitamin E 400IU/day **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Measure:** Endothelial function by a non-invasive method of FMD #### Secondary Outcomes **Measure:** Predefined in the protocol submitted to the EC approved prior to study beginning and the Inform Consent Form signed by all study participants prior to study related procedures, serum was preserved for the analysis of oxidative and inflammatory markers. ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Diabetic patients aged 55 and above Exclusion Criteria: * Patient who takes antioxidant treatment will be asked to stop, or cannot be included in the study. * Patients who had a cardiovascular disease (CVD) incident (myocardial infarction \[MI\], stroke, transient ischemic attack \[TIA\]), unstable angina pectoris, uncontrolled hypertension (HTN), will have to wait a month after stabilization to be included in the study. * Allergy to vitamin E. **Minimum Age:** 55 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Haifa **Country:** Israel **Facility:** Rambam Medical Center #### Overall Officials **Official 1:** **Affiliation:** Technion, Israel Institute of Technology **Name:** Shany Blum, M.D. M.Sc. **Role:** PRINCIPAL_INVESTIGATOR **Official 2:** **Affiliation:** Clalit Health Services **Name:** Uzi Milman, M.D. **Role:** PRINCIPAL_INVESTIGATOR **Official 3:** **Affiliation:** Clalit Health Services **Name:** Chen Shapira, M.D. **Role:** PRINCIPAL_INVESTIGATOR **Official 4:** **Affiliation:** Rambam Health Care Campus **Name:** Giris Jacob, M.D. Ph.D. **Role:** PRINCIPAL_INVESTIGATOR **Official 5:** **Affiliation:** Rambam Health Care Campus **Name:** Lior Dayan, M.D. M.Sc. **Role:** PRINCIPAL_INVESTIGATOR **Official 6:** **Affiliation:** Technion, Israel Institute of Technology **Name:** Andrew P Levy, M.D. Ph.D. **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### References **Citation:** Asleh R, Blum S, Kalet-Litman S, Alshiek J, Miller-Lotan R, Asaf R, Rock W, Aviram M, Milman U, Shapira C, Abassi Z, Levy AP. Correction of HDL dysfunction in individuals with diabetes and the haptoglobin 2-2 genotype. Diabetes. 2008 Oct;57(10):2794-800. doi: 10.2337/db08-0450. Epub 2008 Jul 3. **PMID:** 18599520 ## Derived Section ### 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: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M7115 - Name: Diabetes Mellitus - Relevance: LOW - As Found: Unknown - ID: T4694 - Name: Primary Hyperoxaluria Type 2 - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000002318 - Term: Cardiovascular Diseases ### Intervention Browse Module - Ancestors - ID: D000014815 - Term: Vitamins - ID: D000018977 - Term: Micronutrients - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000000975 - Term: Antioxidants - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000020011 - Term: Protective Agents ### Intervention Browse Module - Browse Branches - Abbrev: Micro - Name: Micronutrients - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Vi - Name: Vitamins ### Intervention Browse Module - Browse Leaves - ID: M22972 - Name: Tocopherols - Relevance: LOW - As Found: Unknown - ID: M17553 - Name: Vitamin E - Relevance: HIGH - As Found: Untreated - ID: M22975 - Name: Tocotrienols - Relevance: LOW - As Found: Unknown - ID: M22969 - Name: alpha-Tocopherol - Relevance: LOW - As Found: Unknown - ID: M17558 - Name: Vitamins - 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: M4292 - Name: Antioxidants - Relevance: LOW - As Found: Unknown - ID: M21869 - Name: Protective Agents - Relevance: LOW - As Found: Unknown - ID: T466 - Name: Tocopherol - Relevance: LOW - As Found: Unknown - ID: T467 - Name: Tocotrienol - Relevance: LOW - As Found: Unknown - ID: T480 - Name: Vitamin E - Relevance: HIGH - As Found: Untreated ### Intervention Browse Module - Meshes - ID: D000014810 - Term: Vitamin E ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT01389479 **Brief Title:** Study to Evaluate the Safety, Tolerance and Immunogenicity of Fluviral™ in Healthy Adults **Official Title:** Active-control Study to Evaluate the Safety, Tolerance and Immunogenicity of Fluviral™ S/F Influenza Vaccine in Healthy Adults Aged 18-64 Years of Age #### Organization Study ID Info **ID:** IDB-707-105 #### Organization **Class:** INDUSTRY **Full Name:** GlaxoSmithKline ### Status Module #### Completion Date **Date:** 2005-05 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2017-06-08 **Type:** ACTUAL **Last Update Submit Date:** 2017-06-07 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2005-05 **Type:** ACTUAL #### Start Date **Date:** 2005-01 **Status Verified Date:** 2017-05 #### Study First Post Date **Date:** 2011-07-08 **Type:** ESTIMATED **Study First Submit Date:** 2011-07-04 **Study First Submit QC Date:** 2011-07-06 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** ID Biomedical Corporation, Quebec #### Lead Sponsor **Class:** INDUSTRY **Name:** GlaxoSmithKline #### Responsible Party **Type:** SPONSOR ### Description Module **Brief Summary:** The purpose of the study is to evaluate the safety, tolerance and immunogenicity of Fluviral™ in healthy adults aged 18-64 years. **Detailed Description:** This study was conducted by ID BioMedical which has been taken over by GlaxoSmithKline. At the time of conduct of this study, Fluviral was produced by ID BioMedical. ### Conditions Module **Conditions:** - Influenza ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** DOUBLE **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 1000 **Type:** ACTUAL **Phases:** - PHASE3 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Intervention Names:** - Biological: Fluviral™ **Label:** Fluviral Group **Type:** EXPERIMENTAL #### Arm Group 2 **Intervention Names:** - Biological: Fluzone® **Label:** Fluzone Group **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Fluviral Group **Description:** Intramuscular, single dose **Name:** Fluviral™ **Type:** BIOLOGICAL #### Intervention 2 **Arm Group Labels:** - Fluzone Group **Description:** Intramuscular, single dose **Name:** Fluzone® **Type:** BIOLOGICAL ### Outcomes Module #### Primary Outcomes **Measure:** Number of subjects with solicited local and systemic reactogenicity symptoms **Time Frame:** First three days after vaccination **Measure:** Number of subjects reporting spontaneous adverse events **Time Frame:** Throughout the entire study period (Day 0-42) **Measure:** Immune response in terms of number of seroconverted subjects **Time Frame:** Before (Day 0) and after (Day 21) vaccination **Measure:** Immune response in terms of number of seroprotected subjects **Time Frame:** Before (Day 0) and after (Day 21) vaccination #### Secondary Outcomes **Description:** Titres calculated as geometric mean **Measure:** Immunogenicity with respect to components of the study vaccine in terms of number of subjects with titres above the pre-defined cut-off **Time Frame:** At Day 21 after vaccination **Measure:** Immune response to components of the study vaccine in terms of mean Geometric increase **Time Frame:** At Day 21 after vaccination ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Male or female. * Adults 18-64 years of age, inclusive. * Satisfactory baseline medical assessment by history, physical examination, and clinical laboratory testing. * Capable of informed consent. * Able, willing and likely to fully comply with study procedures and restrictions. Exclusion Criteria: * Acute illness at the time of enrollment. * Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus infection and/or chronic use of immunosuppressants of other immune-modifying drugs within 6 months of administration of the study vaccine. * Presence of an unstable chronic illness. * Complicated diabetes mellitus. * Active neurological disorder. * History of any demyelinating disease including Guillain-Barré syndrome. * Any clinical laboratory abnormality. * Any disorder of coagulation or treatment with coumadin derivatives or heparin. * Vital sign abnormalities at screening. * Acute or chronic liver, renal or inflammatory bowel disease or collagen vascular disease. * Cancer, or treatment for cancer, within three years. * History of significant alcohol or drug abuse within one year prior to the screening visit. * Positive urine drug screen at screening within 3 months prior to the screening visit or hard drugs. Products such as ativan, tylenol with codeine should be stopped sufficiently ahead of the screening visit in order to avoid a positive urine drug screen. * Positive testing for hepatitis B, hepatitis C or human immunodeficiency virus at screening. * Receipt of an influenza vaccine within 9 months prior to dosing. * Planned administration of any other vaccines 30 days before study immunization or during the course of the study. Immunization on an emergency basis, such as Tetanus and Diphtheria Toxoids Adsorbed for adult use, will be allowed provided the vaccine is not administered within two weeks prior to study immunization. * Use of any investigational or non-registered drug or vaccine or participation in an investigational study within 30 days prior to administration of study vaccine, or planned use during the study period. * Receipt of any immunoglobulins and/or any blood products within three months of screening or planned administration of any of these products during the study period. * Receipt of a depot injection or an implant of any drug within 3 months prior to administration of study vaccine. * Any known or suspected allergy to any constituent of Fluviral™ S/F or Fluzone®. * A history of severe adverse reaction to a previous dose of any influenza vaccine. * History of anaphylactic type reactions to consumption of eggs. * Any other condition or social circumstance that, in the opinion of the Principal Investigator, would make the subject unsuitable for or unable to complete the study. * Breast-feeding subject. * Positive urine pregnancy test at screening. * Female subjects having sexual intercourse with any non-sterile male partner within 14 days prior to vaccine administration and without a history of acceptable contraception. **Healthy Volunteers:** True **Maximum Age:** 64 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT ### Contacts Locations Module #### Overall Officials **Official 1:** **Affiliation:** GlaxoSmithKline **Name:** GSK Clinical Trials **Role:** STUDY_DIRECTOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000012141 - Term: Respiratory Tract Infections - ID: D000007239 - Term: Infections - ID: D000009976 - Term: Orthomyxoviridae Infections - ID: D000012327 - Term: RNA Virus Infections - ID: D000014777 - Term: Virus 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: M10295 - Name: Influenza, Human - Relevance: HIGH - As Found: Influenza - 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: M12902 - Name: Orthomyxoviridae Infections - Relevance: LOW - As Found: Unknown - ID: M17522 - Name: Virus Diseases - Relevance: LOW - As Found: Unknown - ID: M15149 - Name: RNA Virus Infections - Relevance: LOW - As Found: Unknown - ID: M14977 - Name: Respiratory Tract Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000007251 - Term: Influenza, Human ### 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:** NCT02047279 **Acronym:** ALARM-vs-AF **Brief Title:** Ablation and Left Atrium Reduction During Mitral Valve Surgery for Atrial Fibrillation **Official Title:** Left Atrium Reduction Versus no Left Atrium Reduction for Patients With Enlarged Left Atria and Persistent or Long Standing Persistent Atrial Fibrillation Undergoing Mitral Valve Surgery #### Organization Study ID Info **ID:** 14-04-31491 #### Organization **Class:** NETWORK **Full Name:** Meshalkin Research Institute of Pathology of Circulation ### Status Module #### Completion Date **Date:** 2017-09 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2017-09-11 **Type:** ACTUAL **Last Update Submit Date:** 2017-09-07 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2017-09 **Type:** ACTUAL #### Start Date **Date:** 2014-09 **Type:** ACTUAL **Status Verified Date:** 2017-09 #### Study First Post Date **Date:** 2014-01-28 **Type:** ESTIMATED **Study First Submit Date:** 2014-01-24 **Study First Submit QC Date:** 2014-01-24 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** NETWORK **Name:** Meshalkin Research Institute of Pathology of Circulation #### Responsible Party **Investigator Affiliation:** Meshalkin Research Institute of Pathology of Circulation **Investigator Full Name:** Alexander Bogachev-Prokophiev **Investigator Title:** PhD **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** The purpose of this study is to estimate left atrial volume reduction surgery concomitant with the maze procedure and mitral valve repair/replacement in patients with atrial fibrillation with an enlarged left atria. **Detailed Description:** The Cox-Maze procedure has been a gold standard for the treatment of atrial fibrillation. Success of the modified maze procedure after valvular operation with an enlarged left atria and persistent and longstanding persistent atrial fibrillation remains suboptimal. The question addressed was: In adults undergoing a maze procedure for atrial fibrillation does left atrial size reduction compared to maze surgery alone improve maze surgery success? ### Conditions Module **Conditions:** - Atrial Fibrillation **Keywords:** - Atrial fibrillation - Mitral valve ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** SINGLE **Who Masked:** - PARTICIPANT **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 120 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Procedure: Maze procedure, mitral valve surgery The scheme of lesion pattern: "box" lesion + line to mitral valve + line from "box" to left atrial appendage. The ablation procedure was performed by using a dry bipolar radiofrequency ablation clamp. The left atrial appendage was excluded in all cases. For mitral regurgitation or stenosis, the procedures will be a valve repair in the majority of cases. For valves that are not amenable to repair, a valve replacement will be performed. **Intervention Names:** - Procedure: maze procedure - Procedure: mitral valve surgery **Label:** MVS + maze **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** Procedure: maze procedure, mitral valve surgery, left atrial reduction The scheme of lesion pattern: "box" lesion + line to mitral valve + line from "box" to left atrial appendage. The ablation procedure was performed by using a dry bipolar radiofrequency ablation clamp. The left atrial appendage was excluded in all cases. For mitral regurgitation or stenosis, the procedures will be a valve repair in the majority of cases. For valves that are not amenable to repair, a valve replacement will be performed. The enlarged left atria are plicated (suture technique) between the left and right pulmonary vein down to the inferior end of left atrial incision on the half-moon shape. **Intervention Names:** - Procedure: maze procedure - Procedure: mitral valve surgery - Procedure: left atrial reduction **Label:** MVS + maze + LA reduction **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - MVS + maze - MVS + maze + LA reduction **Description:** The scheme of lesion pattern: "box" lesion + line to mitral valve + line from "box" to left atrial appendage. The ablation procedure was performed by using a dry bipolar radiofrequency ablation clamp. The left atrial appendage was excluded in all cases. **Name:** maze procedure **Other Names:** - surgical ablation - radiofrequency ablation **Type:** PROCEDURE #### Intervention 2 **Arm Group Labels:** - MVS + maze - MVS + maze + LA reduction **Description:** For mitral regurgitation or stenosis, the procedures will be a valve repair in the majority of cases. For valves that are not amenable to repair, a valve replacement will be performed. **Name:** mitral valve surgery **Other Names:** - mitral valve repair - mitral velve replacement **Type:** PROCEDURE #### Intervention 3 **Arm Group Labels:** - MVS + maze + LA reduction **Description:** The enlarged left atria are plicated (suture technique) between the left and right pulmonary vein down to the inferior end of left atrial incision on the half-moon shape. **Name:** left atrial reduction **Other Names:** - left atrial volume reduction **Type:** PROCEDURE ### Outcomes Module #### Primary Outcomes **Measure:** Freedom from atrial fibrillation **Time Frame:** 12 months #### Secondary Outcomes **Measure:** Rate of significant adverse events **Time Frame:** 12 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Able to sign Informed Consent and Release of Medical Information forms * Age ≥ 18 years * Clinical indications for mitral valve surgery for organic mitral valve disease Note: May include need for surgical management of functional tricuspid regurgitation or patent foramen ovale. Surgical intervention may be performed via sternotomy or minimally invasive procedure. * a) Persistent atrial fibrillation (AF) within 6 months prior to randomization, defined as non self-terminating AF lasting greater than 7 days but no more than one year, or lasting less than 7 days but necessitating pharmacologic or electrical cardioversion. Duration of AF must be documented by medical history and Presence of AF must be documented by a direct electrocardiographic assessment within 6 months prior to randomization. b) Longstanding persistent AF is defined as continuous AF of greater than one year duration. Duration of AF must be documented by medical history and Presence of AF must be documented by a direct electrocardiographic assessment upon arrival in the OR. * left atrial diameter \> 65mm * Able to use heart rhythm monitor Exclusion Criteria: * AF is paroxysmal * AF without indication for mitral valve surgery * Concomitant coronary artery bypass grafting (CABG), aortic arch or aortic valve procedure * Previous catheter ablation for AF * Redo cardiac surgery * Left ventricle ejection fraction (LV EF) \< 35% * Life expectancy of less than one year * Mental impairment or other conditions that may not allow subject to understand the nature, significance, and scope of study **Maximum Age:** 65 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Novosibirsk **Country:** Russian Federation **Facility:** Novosibirsk State Research Institute of Circulation Pathology **Zip:** 630055 #### Overall Officials **Official 1:** **Affiliation:** Meshalkin Research Institute of Pathology of Circulation **Name:** Alexander V Bogachev-Prokophiev, PhD **Role:** PRINCIPAL_INVESTIGATOR ## 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:** NCT05128279 **Acronym:** AIS **Brief Title:** Adolescent and Young Adulte Scoliosis **Official Title:** Analysis of Corrections of Adolescent and Young Adulte Scoliosis by Posterior Instrumentation #### Organization Study ID Info **ID:** 7961 #### Organization **Class:** OTHER **Full Name:** University Hospital, Strasbourg, France ### Status Module #### Completion Date **Date:** 2023-03-18 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** RECRUITING #### Last Update Post Date **Date:** 2021-11-30 **Type:** ACTUAL **Last Update Submit Date:** 2021-11-23 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2023-03 **Type:** ESTIMATED #### Start Date **Date:** 2020-10-28 **Type:** ACTUAL **Status Verified Date:** 2021-10 #### Study First Post Date **Date:** 2021-11-19 **Type:** ACTUAL **Study First Submit Date:** 2021-10-20 **Study First Submit QC Date:** 2021-11-17 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** University Hospital, Strasbourg, France #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Thoracic hypocyphosis and greater lumbar lordosis after correction of idiopathic scoliosis in adolescents and young adults may adversely affect overall sagittal alignment and increase the risk of proximal junctional kyphosis. The objective of this study is to analyze surgical corrections and maintenance of correction over time using modern posterior instrumentation strategies by comparing technical developments. ### Conditions Module **Conditions:** - Idiopathic Scoliosis **Keywords:** - Idiopathic scoliosis - Thoracic hyperkyphosis - Cyphosis ### Design Module #### Design Info **Observational Model:** CASE_CONTROL **Time Perspective:** RETROSPECTIVE #### Enrollment Info **Count:** 150 **Type:** ESTIMATED **Study Type:** OBSERVATIONAL ### Outcomes Module #### Primary Outcomes **Measure:** Study of corrections of adolescent and young adult scoliosis by posterior instrumentation **Time Frame:** Files analysed retrospectively from January 01, 2010 to December 31, 2020 will be examined] ### Eligibility Module **Eligibility Criteria:** Inclusion criteria: * Major subjects\> 18 years old * Subject with a surgical indication for arthrodesis and surgical correction of adolescent or young adult scoliosis * Subject not having expressed his opposition, after information, to the reuse of his data for the purposes of this research. Exclusion criteria: * Subject having expressed opposition to participating in the study * Subject under guardianship or guardianship * Subject under safeguard of justice **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Major subjects with a surgical indication for arthrodesis and surgical correction of adolescent or young adult scoliosis ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Yann Philippe CHARLES, MD, PhD **Phone:** 33 3 68 76 52 68 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Saïd CHAYER, PhD, HDR **Role:** CONTACT #### Locations **Location 1:** **City:** Strasbourg **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Yann Philippe CHARLES, MD, PhD - **Phone:** 33 3 68 76 52 68 - **Role:** CONTACT ***Contact 2:*** - **Name:** Saïd CHAYER, PhD, HDR - **Role:** CONTACT ***Contact 3:*** - **Name:** Yann Philippe CHARLES, MD, PhD - **Role:** PRINCIPAL_INVESTIGATOR ***Contact 4:*** - **Name:** Nicolas TUZIN, Statistician - **Role:** SUB_INVESTIGATOR **Country:** France **Facility:** Service de Chirurgie du Rachis - Hôpitaux Universitaires de Strasbourg **Status:** RECRUITING **Zip:** 67091 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000013121 - Term: Spinal Curvatures - ID: D000013122 - Term: Spinal Diseases - ID: D000001847 - Term: Bone Diseases - ID: D000009140 - Term: Musculoskeletal Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC05 - Name: Musculoskeletal Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M15417 - Name: Scoliosis - Relevance: HIGH - As Found: Scoliosis - ID: M10758 - Name: Kyphosis - Relevance: LOW - As Found: Unknown - ID: M15918 - Name: Spinal Curvatures - 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: D000012600 - Term: Scoliosis ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT06062979 **Acronym:** CREATE **Brief Title:** Clinical Effectiveness-Implementation Hybrid Type 2 Study on Home-Delivered Cabenuva for People Living With HIV Who Are Not Retained in Care **Official Title:** Clinical Effectiveness-Implementation Hybrid Type 2 Study on Home-Delivered Cabenuva for People Living With HIV Who Are Not Retained in Care #### Organization Study ID Info **ID:** ViiV-219548 #### Organization **Class:** OTHER_GOV **Full Name:** Whitman-Walker Institute ### Status Module #### Completion Date **Date:** 2025-06-30 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-04-25 **Type:** ACTUAL **Last Update Submit Date:** 2024-04-23 **Overall Status:** ENROLLING_BY_INVITATION #### Primary Completion Date **Date:** 2025-06-30 **Type:** ESTIMATED #### Start Date **Date:** 2023-11-01 **Type:** ACTUAL **Status Verified Date:** 2024-04 #### Study First Post Date **Date:** 2023-10-02 **Type:** ACTUAL **Study First Submit Date:** 2023-09-25 **Study First Submit QC Date:** 2023-09-25 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** ViiV Healthcare #### Lead Sponsor **Class:** OTHER_GOV **Name:** Whitman-Walker Institute #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** True **Is US Export:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** The purpose of this study is to assess adherence to home-delivered long-acting injectable rilpivirine/cabotegravir (Cabenuva) among people living with HIV enrolled in the Mobile Outreach Retention and Engagement (MORE) program at Whitman-Walker Health due to significant barriers to being retained in care; the MORE program provides supportive services including dedicated care navigation, transportation assistance, and mobile/home-delivered care. The investigators will examine the equivalence of treatment outcomes among patients receiving injectable treatment within the MORE program as compared to those of patients receiving Cabenuva in standard care at Whitman-Walker Health. **Detailed Description:** Advances in HIV treatment could promote better health and racial equity to address the gaps seen across the HIV care continuum nationally and locally. In Washington DC, HIV viral load suppression among People Living With HIV (PLWH) lies at 66%. Whitman-Walker Clinic, Inc., d/b/a Whitman-Walker Health (WWH), is a Federally Qualified Health Center ("FQHC") affiliated with Whitman-Walker Institute, Inc. ("Institute"). Institute is uniquely capable of addressing gaps with Cabenuva through WWH's existing MORE program, which includes supportive navigation and wrap-around services paired with home-based HIV care. However, there are many implementation knowledge gaps to identify with implementing Cabenuva injection protocols for PLWH who face significant barriers to retention in care and who may significantly benefit from integrating Cabenuva within the context of the MORE program. The investigators propose a home-delivered Cabenuva HIV care program in Washington, D.C. to address the local HIV care continuum gaps. The investigative team has over five years of experience and lessons learned from our Mobile Outreach, Retention and Engagement (MORE) home-based HIV care program and plan to integrate Cabenuva therapy. MORE utilizes NP/PA providers and an HIV care navigator to deliver care to over 130 HIV-infected clients, who have a history of having fallen out of care, in their homes. The investigators envision that the inclusion of injectable treatment can expand the current program by geographic reach and the number of PWLH served by coupling Cabenuva with our ability to deliver patient-centered care outside of the traditional clinic. This proposal is critical to gathering early insights in Cabenuva implementation in Washington, D.C. and other EHE territories in FQHC clinic and affiliated non-clinic settings. Moreover, the data collected will demonstrate the extent to which a population experiencing significant barriers to retention in care-for whom Cabenuva would otherwise likely be counterindicated-can be supported via the MORE program to achieve comparable adherence and outcomes to typical patients receiving standard of care Cabenuva. WWH is currently providing Cabenuva treatment as a treatment option for eligible patients. The purpose of the proposed study is to further investigate the delivery of Cabenuva among two subpopulations of WWH patients. Cabenuva within standard clinical care at WWH: The majority of WWH patients receiving HIV treatment are offered and receive Cabenuva within the standard clinical setting. Among these patients, the proposed study will gather EMR-based data to characterize retention and HIV outcomes and to compare these and other relevant implementation factors with the MORE group. Medical providers identify eligible patients for Cabenvua based on a WWH protocol devised by medical leadership and a Cabenuva workgroup. Eligibility is viral load \< 100,000 copies, no medication contraindications, no co-existing Hepatitis B infection, and no RAMs for rilpivirine or cabotegravir. Medical providers explain the risk and benefits and if the patient desires Cabeuva, the prescription is sent to the WWH onsite pharmacy at WWH sites MRC or 1525. The patient's case is sent via the EHR to the Cabenuva injection clinic admin lead at WWH. Patient appointment reminders and medication attainment are coordinated through SMS and phone call communication with patients. Cabenuva within MORE-based clinical care at WWH: To address the unique structural and psychosocial factors that create significant barriers to engagement and retention in care for a subset of patients with a history of non-retention, the MORE program was developed. MORE's primary features include home-based care delivery, dedicated care navigation, transportation support, and wrap-around supportive services. WWH is currently expanding the MORE program to provide injectable Cabenuva to these patients for whom, without the intensive support of the MORE program, treatment with Cabenuva would likely be counterindicated. More follows a stepped-care approach to support that includes a customized combination of its services to each patient based on need and preferences. ### Conditions Module **Conditions:** - HIV ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 180 **Type:** ESTIMATED **Patient Registry:** True **Study Type:** OBSERVATIONAL **Target Duration:** 12 Months ### Arms Interventions Module #### Arm Group 1 **Description:** Study participants in this condition will be those engaged in clinical care as part of the MORE program, receiving supportive, wrap-around, and home-based HIV care services; all participants will be offered injectable Cabenuva and studied with regard to uptake and outcomes. Participants in this group will receive quantitative health survey assessments as per standard of care at Whitman-Walker Health. Participants will be offered quantitative and qualitative assessments regarding their experiences related to Cabenuva. **Intervention Names:** - Drug: rilpivirine/cabotegravir **Label:** Enhanced (MORE) implementation (i.e., MORE group) #### Arm Group 2 **Description:** Study participants in this comparison condition will be those engaged in clinical care receiving Cabenuva per standard of care at Whitman-Walker Health. Participants in this group will contribute ongoing electronic health record data under the auspices of an IRB-granted waiver of informed consent and waiver of HIPAA authorization. **Intervention Names:** - Drug: rilpivirine/cabotegravir **Label:** Standard-of-care implementation (i.e., comparison group) ### Interventions #### Intervention 1 **Arm Group Labels:** - Enhanced (MORE) implementation (i.e., MORE group) - Standard-of-care implementation (i.e., comparison group) **Description:** WWH is currently providing Cabenuva treatment as a treatment option for eligible patients. The purpose of the proposed study is to use an observational, prospective cohort design to further investigate the delivery of Cabenuva among two subpopulations of WWH patients. **Name:** rilpivirine/cabotegravir **Type:** DRUG ### Outcomes Module #### Other Outcomes **Description:** Participants will be asked, "How easy was it to receive Cabenuva injections at home?" **Measure:** Implementation Feasibility (qualitative) **Time Frame:** 6 months **Description:** Participants will be asked, "How do you like receiving an injection at home?" **Measure:** Implementation Acceptability (qualitative) **Time Frame:** 6 months **Description:** # of providers who referred their patients to receive home-delivered Cabenuva among total number of providers **Measure:** Adoption Rate **Time Frame:** 12 months #### Primary Outcomes **Description:** % of patients initiated who received each injection in the +/- 7 day window period for 4 months **Measure:** 4-month adherence rate **Time Frame:** 4 months #### Secondary Outcomes **Description:** % of patients who received each injection in the +/- 7 day window period for 10 months **Measure:** 10-month adherence rate **Time Frame:** 10 months **Description:** % of patients with virologic suppression (measured twice within 4 weeks and both values \<200 copies/mL) **Measure:** Virologic suppression (200 copies/mL) **Time Frame:** 1 through 12 months following first injection **Description:** % of patients with virologic suppression (measured twice within 4 weeks and both values \<50 copies/mL) **Measure:** Virologic suppression (50 copies/mL) **Time Frame:** 1 through 12 months following first injection **Description:** % of patients with detection of resistance associated mutations **Measure:** Resistance associated viral mutations **Time Frame:** 1 through 12 months following first injection ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * HIV-infected individuals, aged 18 years or older, who are eligible to receive Cabenuva as standard of care at Whitman-Walker Health * For those participants who will be prospectively enrolled via informed consent and offered survey and qualitative interviews, participants will be those receiving HIV-related treatment via the MORE program Exclusion Criteria: * HIV-uninfected individuals **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** This study will be conducted among people living with HIV who are 18 years or older receiving HIV treatment at Whitman-Walker Health ### Contacts Locations Module #### Locations **Location 1:** **City:** Washington **Country:** United States **Facility:** Whitman-Walker 1525 Clinic **State:** District of Columbia **Zip:** 20009 **Location 2:** **City:** Washington **Country:** United States **Facility:** Whitman-Walker Max Robinson Center **State:** District of Columbia **Zip:** 20032 #### Overall Officials **Official 1:** **Affiliation:** Whitman-Walker Institute **Name:** Megan Dieterich, PA **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Browse Branches - Abbrev: BC01 - Name: Infections - Abbrev: BXS - Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions - Abbrev: BC20 - Name: Immune System Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M3522 - Name: Acquired Immunodeficiency Syndrome - Relevance: LOW - As Found: Unknown - ID: M18250 - Name: HIV Infections - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Ancestors - ID: D000018894 - Term: Reverse Transcriptase Inhibitors - ID: D000019384 - Term: Nucleic Acid Synthesis Inhibitors - ID: D000004791 - Term: Enzyme Inhibitors - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000000998 - Term: Antiviral Agents - ID: D000000890 - Term: Anti-Infective Agents - ID: D000019380 - Term: Anti-HIV Agents - ID: D000044966 - Term: Anti-Retroviral Agents - ID: D000019428 - Term: HIV Integrase Inhibitors - ID: D000019429 - Term: Integrase Inhibitors ### Intervention Browse Module - Browse Branches - Abbrev: Infe - Name: Anti-Infective Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M295 - Name: Rilpivirine - Relevance: HIGH - As Found: Mailed - ID: M254021 - Name: Cabotegravir - Relevance: HIGH - As Found: Rubber - ID: M20935 - Name: Reverse Transcriptase Inhibitors - Relevance: LOW - As Found: Unknown - ID: M7951 - Name: Enzyme Inhibitors - Relevance: LOW - As Found: Unknown - ID: M4314 - Name: Antiviral Agents - Relevance: LOW - As Found: Unknown - ID: M4214 - Name: Anti-Infective Agents - Relevance: LOW - As Found: Unknown - ID: M21350 - Name: Anti-HIV Agents - Relevance: LOW - As Found: Unknown - ID: M25428 - Name: Anti-Retroviral Agents - Relevance: LOW - As Found: Unknown - ID: M21386 - Name: Integrase Inhibitors - Relevance: LOW - As Found: Unknown - ID: M21385 - Name: HIV Integrase Inhibitors - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000068696 - Term: Rilpivirine - ID: C000584914 - Term: Cabotegravir ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT01874379 **Acronym:** M•TIJRP **Brief Title:** 'M'-Technique, Guided Imagery, or Standard of Care on Anxiety and Pain Pre- & Post-operatively in Elective Joint Replacement Patients **Official Title:** Investigating the Effect of the 'M'-Technique, Guided Imagery, or Standard of Care on Anxiety and Pain Pre- & Post-operatively in Elective Joint Replacement Patients. #### Organization Study ID Info **ID:** M•TIJRP #### Organization **Class:** OTHER **Full Name:** Saint Clare's Health System #### Secondary ID Infos **Domain:** Western Institutional Review Board **ID:** WIRB #: 20121832 **Type:** OTHER ### Status Module #### Expanded Access Info **Last Known Status:** RECRUITING #### Last Update Post Date **Date:** 2013-06-11 **Type:** ESTIMATED **Last Update Submit Date:** 2013-06-06 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2014-06 **Type:** ESTIMATED #### Start Date **Date:** 2012-12 **Status Verified Date:** 2013-06 #### Study First Post Date **Date:** 2013-06-11 **Type:** ESTIMATED **Study First Submit Date:** 2013-04-22 **Study First Submit QC Date:** 2013-06-06 ### Sponsor Collaborators Module #### Collaborators **Class:** UNKNOWN **Name:** Saint Clare's Foundation #### Lead Sponsor **Class:** OTHER **Name:** Saint Clare's Health System #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** In the M-TIJRP protocol the investigators will utilize two Integrative Medicine modalities in a randomized, controlled study using either the 'M'-Technique® developed by Jane Buckle, PhD or Diane L. Tusek's Guided Imagery for Pre-Procedure/Surgery™ with nature sounds to determine their effects on a specific group of pre- and post-operative patients, compared to no integrative medicine intervention - considered Standard of Care. A total of 225 patients undergoing surgical hip or knee replacement will participate; one third of the patient population will receive the 'M'-Technique touch intervention, one third will receive Tusek's Guided Imagery intervention delivered by headsets monitored by therapists from our Center for Complementary Medicine (CCM) and one third will comprise the control group, consisting of routine preoperative \& postoperative care without integrated intervention. Patients will be asked to complete Pain and Anxiety scales at four different timepoints throughout their hospital stay. These will occur at Same Day Surgery (pre-operatively), and Post Operatively Day 0, Day 1 \& Day 2. Rationale: Patients are often at their most vulnerable just prior to surgery when their stress and anticipation are high and again immediately afterward when their energy is lower and their bodies are trying to accommodate after an invasive procedure. In addition, the patient and his or her family sense a lack of control and feel a rise in anxiety over the possible outcomes. This stress, anxiety, and pain associated with surgery and recovery can increase complication rates and slow recovery times resulting in longer hospital stays. ### Conditions Module **Conditions:** - Hip or Knee Replacement **Keywords:** - Joint Replacement - Hip Replacement - Knee Replacement - Complementary Medicine Intervention ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 225 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** The therapist will instruct the patient on the Guided Imagery protocol and will provide the patient with headphones and an MP-3 player to use for the guided imagery intervention. The patient will listen to the Guided Imagery for 18min 30 sec. **Intervention Names:** - Other: Guided Imagery **Label:** Guided Imagery **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** This group will serve as the control arm **Intervention Names:** - Other: Standard of Care **Label:** Standard of Care **Type:** ACTIVE_COMPARATOR #### Arm Group 3 **Description:** The 'M'-Technique will be administered to the patient's hands and feet for a total of 18-20 minutes, to be equally divided between extremities used according to limitations as outlined. Any hand or foot that is accessed by an IV will be avoided. **Intervention Names:** - Other: 'M'-Technique® **Label:** 'M'-Technique® **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - 'M'-Technique® **Description:** 'M'-Technique is a series of gentle stroking movements performed in a set sequence, with a set pressure of 3 on a scale of 0-10. **Name:** 'M'-Technique® **Other Names:** - Light Structured Touch **Type:** OTHER #### Intervention 2 **Arm Group Labels:** - Guided Imagery **Description:** Diane L. Tusek's Guided Imagery for Pre-Procedure/Surgery™ will be used. **Name:** Guided Imagery **Type:** OTHER #### Intervention 3 **Arm Group Labels:** - Standard of Care **Description:** Normal Procedures, no complementary medicine intervention. **Name:** Standard of Care **Other Names:** - Control - No Intervention **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** Measurement with Visual Analogue Scale **Measure:** Symptomatic pain relief expressed in Visual Analogue Scales from no pain 0-10 worst possible pain **Time Frame:** 18 months **Description:** Visual Analogue Scale **Measure:** Symptomatic anxiety relief expressed in Visual Analogue Scales from no anxiety 0-10 worst possible anxiety **Time Frame:** 18 months **Measure:** Change from Baseline in Hamilton Anxiety Scale at Post Op Day 2 **Time Frame:** 18 Months #### Secondary Outcomes **Description:** Protocol specific questionnaire **Measure:** Patient Satisfaction Measure **Time Frame:** 18 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Age \> 18 years old 2. Be receiving an initial or subsequent elective hip or knee replacement surgery Exclusion Criteria: 1. Patients with an active infection or open wound in the location of the extremities where the 'M'-Technique will be performed 2. Patients with touch aversion 3. Non-English speaking patients - due to guided imagery recording availability in English only 4. Patients who demonstrate insufficient auditory discrimination as determined by their ability to engage in normal conversation 5. Patients who lack the sensation of being touched on the hands and/or feet **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Denville **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Serena A Schmitz, BS, CCRC - **Phone:** 973-625-6377 - **Role:** CONTACT ***Contact 2:*** - **Name:** J. Brent Forward, MD, FACP - **Role:** PRINCIPAL_INVESTIGATOR ***Contact 3:*** - **Name:** Nancy Greuter, RN, NCTMB - **Role:** SUB_INVESTIGATOR **Country:** United States **Facility:** Saint Clare's Health System **State:** New Jersey **Status:** RECRUITING **Zip:** 07834 #### Overall Officials **Official 1:** **Affiliation:** Saint Clare's Health System **Name:** J. Brent Forward, MD, FACP **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Browse Branches - Abbrev: BXM - Name: Behaviors and Mental Disorders - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology ### Condition Browse Module - Browse Leaves - ID: M4324 - Name: Anxiety Disorders - Relevance: LOW - As Found: Unknown - ID: M13066 - Name: Pain - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Browse Branches - Abbrev: ANeo - Name: Antineoplastic Agents - Abbrev: Repr - Name: Reproductive Control Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M19653 - Name: Cyproterone Acetate - Relevance: LOW - As Found: Unknown - ID: M6739 - Name: Cyproterone - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT01948479 **Brief Title:** Insole Optimisation for Ulcer Prevention: a Feasibility Trial **Official Title:** Prevention of Foot Ulcer Recurrence in People With Diabetes Using an In-shoe Pressure Measurement Technology: A Randomised Control Trial Feasibility Study #### Organization Study ID Info **ID:** PatonRCT02 #### Organization **Class:** OTHER **Full Name:** University of Plymouth ### Status Module #### Completion Date **Date:** 2015-01 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** NOT_YET_RECRUITING #### Last Update Post Date **Date:** 2013-09-26 **Type:** ESTIMATED **Last Update Submit Date:** 2013-09-25 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2015-01 **Type:** ESTIMATED #### Start Date **Date:** 2014-01 **Status Verified Date:** 2013-09 #### Study First Post Date **Date:** 2013-09-23 **Type:** ESTIMATED **Study First Submit Date:** 2013-09-18 **Study First Submit QC Date:** 2013-09-20 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** University Hospital Plymouth NHS Trust #### Lead Sponsor **Class:** OTHER **Name:** University of Plymouth #### Responsible Party **Investigator Affiliation:** University of Plymouth **Investigator Full Name:** Joanne Paton **Investigator Title:** NIHR Clinical Research Fellow **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** Insoles are designed to reduce increased loads and re-ulceration risk in patients with diabetes. The investigators previous research findings suggest that an instant insole solution may benefit some, but effectiveness is difficult to predict. The investigators propose a feasibility study using in-shoe pressure analysis to optimise the protective effect of insoles and footwear with the aim of reducing re-ulceration rates. Early indications from exploratory case studies within the real world clinical setting suggest that by implementing the investigators previous published research findings the investigators can optimise effectiveness and reduce outcome variability of protective footwear and insoles provided to patients at risk of re-ulceration. However a further randomised control trial is necessary to evaluate the effectiveness of in-shoe pressure analysis in reducing re-ulceration rates within the NHS setting. The proposed feasibility study will recruit 20 participants from the multidisaplinary diabetic foot clinic Derriford Hospital and allocate them to either 1) Routine insoles and footwear provision or 2) Routine insole and footwear provision, and temporary insole provision with optimisation. The findings from the feasibility study will inform protocol development for a larger clinical trial. The results of the feasibility study will be used to strengthen a protocol for a grant application to conduct the main RCT. A secondary output from the pilot study will be the dissemination of findings in a peer reviewed journal and at conference. ### Conditions Module **Conditions:** - Diabetic - Neuropathic - Past Ulceration ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 20 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Intervention Names:** - Device: Optimised instant offloading insole **Label:** Insole optimised with inshoe analysis **Type:** EXPERIMENTAL #### Arm Group 2 **Intervention Names:** - Device: Optimised instant offloading insole **Label:** Routine insole provision **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Insole optimised with inshoe analysis - Routine insole provision **Name:** Optimised instant offloading insole **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Measure:** ulcer recurrence rates **Time Frame:** 6 months #### Secondary Outcomes **Measure:** peak pressure reduction with the addition of the intervention **Time Frame:** Issue and 6 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Participant is willing and able to give informed consent for participation in the study. * Male or Female, aged 30 years or above * Diagnosed with Diabetes Mellitus * Recently healed/healing target ulcer on the weight-bearing surface of the foot * Neuropathic (Mild to moderate DPN defined as insensitivity of a 10 g monofilament at 1-3 sites in the following locations: hallux, 1st, 3rd, and 5th metatarsal heads (Boulton AJ, Armstrong DG, Albert SF, Frykberg RG, Hellman R, Kirkman MS, Lavery LA, Lemaster JW, Mills JL Sr, Mueller MJ, Sheehan P, Wukich DK: Comprehensive foot examination and risk assessment: a report of the task force of the foot care interest group of the American Diabetes Association, with endorsement by the American Association of Clinical Endocrinologists. Diabetes Care 2008;31:1679-1685) * Able (in the Investigators opinion) and willing to comply with all study requirements Exclusion Criteria: * The participant may not enter the study if ANY of the following apply: Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the study, or may influence the result of the study, or the participant's ability to participate in the study. * None healing foot ulcer at another site that requires targeted off-loading. * Unable to walk 5 metres with/without walking aid * Peripheral vascular disease (non-re-constructible vascular disease as determined by arterial duplex and clinically assessed by a vascular consultant) * Unwilling to wear therapeutic footwear * Where amputation has been part of the current episode of care and includes ulceration site. **Minimum Age:** 30 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Joanne Paton, PhD **Phone:** 01752 588845 **Role:** CONTACT #### Locations **Location 1:** **City:** Plymouth **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Graham Bruce - **Role:** CONTACT ***Contact 2:*** - **Name:** Graham Bruce - **Role:** SUB_INVESTIGATOR **Country:** United Kingdom **Facility:** Derriford Hospital **State:** Devon **Zip:** PL6 8BH ## Derived Section ### Condition Browse Module - Ancestors - ID: D000010335 - Term: Pathologic Processes ### 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: BC23 - Name: Symptoms and General Pathology - Abbrev: BC17 - Name: Skin and Connective Tissue Diseases ### Condition Browse Module - Browse Leaves - ID: M7115 - Name: Diabetes Mellitus - Relevance: LOW - As Found: Unknown - ID: M17206 - Name: Ulcer - Relevance: HIGH - As Found: Ulceration - ID: M14850 - Name: Recurrence - Relevance: LOW - As Found: Unknown - ID: M18919 - Name: Foot Ulcer - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000014456 - Term: Ulcer ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05709379 **Brief Title:** Effects of Interrupting Sedentary Behavior With High - or Low Intensity PA on CVD - and Cardiometabolic Riskfactors, and Cognitive Performance. **Official Title:** Effects of Interrupting Sedentary Behavior With High - or Low Intensity Physical Activity on Cardiovascular - and Cardiometabolic Riskfactors, and Cognitive Performance. #### Organization Study ID Info **ID:** GENSED#2 #### Organization **Class:** OTHER **Full Name:** Norwegian School of Sport Sciences ### Status Module #### Completion Date **Date:** 2024-08-31 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-02-14 **Type:** ACTUAL **Last Update Submit Date:** 2024-02-13 **Overall Status:** ENROLLING_BY_INVITATION #### Primary Completion Date **Date:** 2023-09-30 **Type:** ACTUAL #### Start Date **Date:** 2023-01-02 **Type:** ACTUAL **Status Verified Date:** 2024-02 #### Study First Post Date **Date:** 2023-02-02 **Type:** ACTUAL **Study First Submit Date:** 2023-01-06 **Study First Submit QC Date:** 2023-01-23 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** The Research Council of Norway #### Lead Sponsor **Class:** OTHER **Name:** Norwegian School of Sport Sciences #### Responsible Party **Investigator Affiliation:** Norwegian School of Sport Sciences **Investigator Full Name:** Jostein Steene-Johannessen **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 knowledge gap on sedentary behavior and sedentary breaks includes whether detrimental effects of sedentary behavior can be fully attenuated by 1.) sedentary breaks 2.) physical activity or 3.) both combined. Specifically, when breaking sedentary time which physical activity pattern- and intensity modifies the negative effects of sedentary behavior on glucose- and lipid metabolism? This lack of quantitative evidence calls for prospective experimental studies investigating the physiological and biological impacts of sedentary behavior, as well as the effectiveness of different strategies to reduce sedentary time. Thus, quantifying effects of the intensity, frequency, volume of sedentary breaks and/or physical activity on predefined outcomes is of importance. Aims: Our primary aims are to investigate the effects of breaking up sedentary time on glucose- and lipid metabolism and thus examine whether physical activity intensity breaks during sedentary breaks matter. Specifically, the aims of the PhD-project are to provide knowledge on the following questions: • How does high- or low physical activity intensity sedentary breaks acutely influence glucose- and lipid metabolism under iso-caloric conditions? **Detailed Description:** The participants will undergo 3 different trial conditions of which all are iso-caloric, but with different intensities when executing physical activity (PA) by treadmill walking corresponding to 25-30% or 80-85%, respectively, of their individual VO2max/peak values. PA intensities are estimated from the individual's pre-test. The trial-conditions are iso-caloric, and tailored to each individual's energy expenditure. This study has a is randomized cross-over design. If found eligible from step 1 and 2 in the inclusion process, participants will be invited to a final screening day in our lab. Eligible participants then consenting to joining the study will continue on to 3 trial days. Due to possible acute rise in insulin for up to 48 hours, a 5-14 day washout period between trials will be used to avoid carryover effects. In the washout periods between experimental conditions the participants will resume their habitual life activities and behaviors, i.e., diet and physical activity patterns. However, from visit 2, during washout the participants will wear accelerometers (ActiGraph GTX3+, Pensacola, FL) during waking hours to objectively measure sedentary time and physical activity for 7 consecutive days after each trial. Average sedentary time (hour/day) and time spent in , light-, moderate- and vigorous physical activity intensity (min/day) will be derived. During the main trial days, the participants may read or work on a personal computer during the sedentary time in the respective trial conditions. The sample size calculations with glucose as the primary outcome, are based on the study by Dunstan et al. (2012). They estimated that 19 paired observations were needed to secure a power of 0.90 in order to detect the smallest expected effect size between the interventions, when using a two-tailed test with a significance level of 5%. To account for the possibility of dropouts the sample size in the present project is set to recruit 30 participants, with 25 participants completing the trials, and thus planning for 80% power ### Conditions Module **Conditions:** - Sedentary Behavior - Physical Activity **Keywords:** - Sedentary behavior - Physical Activity - Cardiometabolic - Cardiovascular - Sitting ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** CROSSOVER **Intervention Model Description:** This study will be conducted as randomized controlled crossover trials involving 3 different trial conditions in each of the studies. Randomization will be stratified based on sex. The order of trials will be assigned randomly by a third party using a computer software. After pre-testing and familiarization (visit 1), the participants will undergo 3 different trial conditions of 7 hours. The trials are all iso-caloric, but with different intervals of sitting and executing moderate physical activity by treadmill walking/running corresponding to 25-30% or 80-85%, repectively of their individual VO2max values, estimated from the individual's pre-test. Blood samples will be taken and blood pressure measured every 30 minutes. The visits for main testing will be separated by a washout period of minimum 5 days, and women will be tested in the follicular phase. ##### Masking Info **Masking:** NONE **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 25 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Sitting from 8 am until 3pm. **Intervention Names:** - Behavioral: Sedentary behavior **Label:** Control trial **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Physical activity on 80-85% of individual VO2max every hour. Modality: Hill walking/jogging on treadmill. **Intervention Names:** - Behavioral: Sedentary behavior **Label:** High intensity sedentary breaks **Type:** EXPERIMENTAL #### Arm Group 3 **Description:** Physical activity on 25-30% of individual VO2max every hour. Modality: Hill walking on treadmill. **Intervention Names:** - Behavioral: Sedentary behavior **Label:** Low intensity sedentary breaks **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Control trial - High intensity sedentary breaks - Low intensity sedentary breaks **Description:** Interrupting sitting with walking/jogging at either high -or low physical activity intensity. **Name:** Sedentary behavior **Type:** BEHAVIORAL ### Outcomes Module #### Primary Outcomes **Description:** During each of the trial conditions blood samples will be taken in the fasted state in the morning and then every 30 minutes of the trials (total 420minutes) through a peripheral venous catheter. We will then calculate the iAUC for glucose for each of the trial condition and compare the different trial conditions with the control condition **Measure:** Total (tAUC)- and incremental areas under the curve (iAUC) for glucose **Time Frame:** The iAUC for glucose will be assessed during the procedure and consist of measures every 30 minute throughout the trial (420 minutes) #### Secondary Outcomes **Description:** During each of the trial conditions blood samples will be taken in the fasted state in the morning and then every 30 minutes of the trials (total 420minutes) through a peripheral venous catheter. We will then calculate the iAUC for glucose for each of the trial condition and compare the different trial conditions with the control condition **Measure:** tAUC and iAUC analyses for insulin **Time Frame:** The iAUC for the secondary outcomes will be assessed during the procedure and consist of measures every 30 minute throughout the trial (420 minutes) **Description:** During each of the trial conditions blood samples will be taken in the fasted state in the morning and then every 30 minutes of the trials (total 420minutes) through a peripheral venous catheter. We will then calculate the iAUC for glucose for each of the trial condition and compare the different trial conditions with the control condition **Measure:** tAUC and iAUC analyses for c-peptide **Time Frame:** The iAUC for the secondary outcomes will be assessed during the procedure and consist of measures every 30 minute throughout the trial (420 minutes) **Description:** During each of the trial conditions blood samples will be taken in the fasted state in the morning and then every 30 minutes of the trials (total 420minutes) through a peripheral venous catheter. We will then calculate the iAUC for glucose for each of the trial condition and compare the different trial conditions with the control condition **Measure:** tAUC and iAUC analyses for triglycerides **Time Frame:** The iAUC for the secondary outcomes will be assessed during the procedure and consist of measures every 30 minute throughout the trial (420 minutes) **Description:** During each of the trial conditions blood samples will be taken in the fasted state in the morning and then every 30 minutes of the trials (total 420minutes) through a peripheral venous catheter. We will then calculate the iAUC for glucose for each of the trial condition and compare the different trial conditions with the control condition **Measure:** tAUC and iAUC analyses for lipids **Time Frame:** The iAUC for the secondary outcomes will be assessed during the procedure and consist of measures every 30 minute throughout the trial (420 minutes) **Description:** Cognitive function tasks will be performed, and cognitive function will be assessed by Trail making test A and B, and Stroop-test. **Measure:** Cognitive function and performance **Time Frame:** The cognitive measures will be performed during the procedure (at approx 400 minutes) ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: Inclusion Criteria: * Predominantly sedentary occupation. * Physical activity: equal or less tham 150 minutes /week * Nonobese. Central adiposity: Waist circumference equal or less than 102 cm for men and equal or less than \< 88 cm for women. BMI \< 30 km·m2 Exclusion Criteria: * Shift-work * Smoking * Pregnancy * Current use of medication, except from hormonal contraceptives. * No presence of any co-morbidity (e.g. diabetes type 2, cardiovascular or cardiorespiratory disease, or other conditions known to affect carbohydrate and lipid metabolism - thyroid-, -liver or kidney). * Systolic /diastolic resting blood pressure: \> 140/90 mmHg * Fasting blood glucose concentration: \> 6.1 mmol/L * Abnormal total cholesterol, LDL, LDL or triglyceride concentrations (\> 50% above recommendations) **Healthy Volunteers:** True **Maximum Age:** 45 Years **Minimum Age:** 20 Years **Sex:** ALL **Standard Ages:** - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Oslo **Country:** Norway **Facility:** Norwegian School of Sports Sciences **Zip:** 0806 #### Overall Officials **Official 1:** **Affiliation:** Norwegian School of Sports Sciences **Name:** Jostein Steene-Johennessen, Professor **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:** NCT02568579 **Brief Title:** Infant Immunity Comparison of Breastfed and Bottlefed Infants **Official Title:** Effects of Breastfeeding in Immunologic Priming in Young Infants #### Organization Study ID Info **ID:** Pro00050219 #### Organization **Class:** OTHER **Full Name:** Duke University ### Status Module #### Completion Date **Date:** 2017-12 **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:** 2017-11 **Type:** ACTUAL #### Start Date **Date:** 2015-01 **Type:** ACTUAL **Status Verified Date:** 2017-06 #### Study First Post Date **Date:** 2015-10-06 **Type:** ESTIMATED **Study First Submit Date:** 2015-09-15 **Study First Submit QC Date:** 2015-10-02 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** University of South Florida **Class:** OTHER **Name:** Children's Hospital Los Angeles #### Lead Sponsor **Class:** OTHER **Name:** Duke University #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** This study will follow 40 healthy, vaginally delivered infants that are primarily (\>/- 75%) breast fed and 40 infants that are exclusively formula fed for at least the first 4 months of life from birth until 12 month age. Visits - Subjects will be consented prior to delivery, visit 1. Subject will be seen if possible after delivery for instruction on stool collection and distribution of supplies, visit 2. Subject will be seen at 6 months of age post immunization, visit 3. Subject will be seen prior to 12 month visit. Study staff will contact via phone/email to collect information about feeding changes. **Detailed Description:** Cord Blood will be collected at birth if possible and peripheral blood will be collected at 6 month of age (5 to 10 days after receiving their standard 6 month immunizations) and at 12 months of age prior to their 12 month immunization. Additionally, stool samples will be collected within the first week of live and once monthly through 12 months of age. Breastfeeding mothers will collect breast milk once monthly at the same time as the stool specimen during the period of breastfeeding. ### Conditions Module **Conditions:** - Infant Immunity Response and Immunoglobulin Diversity ### Design Module #### Bio Spec **Description:** Four 2.6 ml ACD tubes will be collected . All blood will be processed for pyrosequencing, TBNK, CBC and differential, platelets, sera plasman and PBMC's. Stool samples **Retention:** SAMPLES_WITH_DNA #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 85 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** collection of blood/stool/breast milk samples and information about feeding changes and introduction of solid foods. - Cord Blood sample, stool samples monthly and blood sample at 6 month and 12 months of age **Intervention Names:** - Procedure: blood sample/ stool sample **Label:** Breastfed #### Arm Group 2 **Description:** collection of blood/stool samples and information about feeding changes and introduction of solid foods. Coord blood sample, stool samples monthly and blood sample at 6 month and 12 month of age. **Intervention Names:** - Procedure: blood sample/ stool sample **Label:** Bottlefed ### Interventions #### Intervention 1 **Arm Group Labels:** - Bottlefed - Breastfed **Description:** blood sample to be done when possible with standard of care lab draw. Stool sample to be collected monthly at home. **Name:** blood sample/ stool sample **Type:** PROCEDURE ### Outcomes Module #### Primary Outcomes **Description:** B cell priming and immunoglobulin diversity following immunizations at 2 and 4 month of age by modulating the microbial colonization of infant gut by pyrosequencing by using isotype specific primers. **Measure:** Molecular profile of human IgG and IgA by pyrosequencing. **Time Frame:** 12 months #### Secondary Outcomes **Description:** post immunization antibody titers (via ELISA) to Hib, tetanus, diphtheria, pertussis and pneumococcal polysaccharide serotypes contained in the Prevnar 13 vaccine. **Measure:** Vaccine response **Time Frame:** 12 months **Description:** Functional activity of antibodies measured by opsonophagocytic activity to Pneumococcal and Hib vaccine **Measure:** Antibody activity **Time Frame:** 12 months **Description:** Degree of B cell differentiation and activation in B cell by BD bioscience Canto flow cytometry. **Measure:** Plasma level of B cell activating factor and/or a proliferation-inducing ligand **Time Frame:** 12 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Self-declared pregnant woman * Age 18 years or older at the time of consent * Willing and able to sign consent and follow study schedule * Planned vaginal delivery * Willing to primarily breastfed or formula feed for the first four months Exclusion Criteria: * Planned delivery by C-Section * Unwillingness to exclusively breast feed or formula feed their infant for at least the first 4 months * Unwillingness to receive standard immunizations on the schedule recommended by the American Academy of Pediatrics * Chronic maternal condition that may influence infant immunity including but not limited to: maternal HIV, immunodeficiency, use of immunosuppressive medications, malignancy or autoimmunity * Known fetal medical conditions such as congenital malformations * Use of immune modulating/immune suppressive medication and prophylactic antibiotics during pregnancy * Any condition that may prevent a mother who plans to breast feed from breast feeding * Any condition that in the opinion of the investigator would interfere with the conduct of the study **Healthy Volunteers:** True **Maximum Age:** 45 Years **Minimum Age:** 18 Years **Sampling Method:** PROBABILITY_SAMPLE **Sex:** FEMALE **Standard Ages:** - ADULT **Study Population:** * Pregnant women 18 years of age or older. * Vaginal delivery * Healthy, full-term babies. * Willing to primarily (\> 75%) breastfeed or exclusively formula feed for at least the first 4 months of life. * Willing to follow the American Academy of Pediatrics' Immunizations guidelines. ### Contacts Locations Module #### Locations **Location 1:** **City:** Los Angeles **Country:** United States **Facility:** Children's Hospital Los Angeles **State:** California **Zip:** 90027 **Location 2:** **City:** Chapel Hill **Country:** United States **Facility:** UNC Chapel Hill **State:** North Carolina **Zip:** 27514 **Location 3:** **City:** Durham **Country:** United States **Facility:** Duke University Medical Center **State:** North Carolina **Zip:** 27710 #### Overall Officials **Official 1:** **Affiliation:** Duke University **Name:** John Sleasman, MD **Role:** STUDY_DIRECTOR ## Derived Section ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00303979 **Acronym:** IMPROVE-HF **Brief Title:** IMPROVE HF: Registry to Improve the Use of Evidence-Based Heart Failure Therapies in the Outpatient Setting **Official Title:** Registry to Improve the Use of Evidence-Based Heart Failure Therapies in the Outpatient Setting #### Organization Study ID Info **ID:** 258 #### Organization **Class:** INDUSTRY **Full Name:** Medtronic Cardiac Rhythm and Heart Failure ### Status Module #### Completion Date **Date:** 2009-08 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2019-01-31 **Type:** ACTUAL **Last Update Submit Date:** 2019-01-29 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2009-08 **Type:** ACTUAL #### Results First Post Date **Date:** 2012-12-27 **Type:** ESTIMATED **Results First Submit Date:** 2012-11-21 **Results First Submit QC Date:** 2012-11-21 #### Start Date **Date:** 2005-05 **Status Verified Date:** 2019-01 #### Study First Post Date **Date:** 2006-03-17 **Type:** ESTIMATED **Study First Submit Date:** 2006-03-15 **Study First Submit QC Date:** 2006-03-15 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** Medtronic #### Lead Sponsor **Class:** INDUSTRY **Name:** Medtronic Cardiac Rhythm and Heart Failure #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** The purpose of this study is to characterize current management of patients with either heart failure or prior myocardial infarction and left ventricular dysfunction and to assess the effect of education, specific clinical guidelines, reminder systems, comprehensive disease state management tools, benchmarked quality reports, and academic detailing on the use of evidence-based heart failure therapies in cardiology practices. This study is a quality improvement initiative that is being conducted through review of patient records. **Detailed Description:** IMPROVE HF, the largest US outpatient HF patient registry, has substantially contributed to our knowledge of how systolic HF and post MI left ventricular systolic dysfunction (LVSD) patients are treated in the outpatient setting. The findings of IMPROVE HF clearly support this guideline and may help to establish a model framework for future performance improvement programs for outpatient cardiology practices. ### Conditions Module **Conditions:** - Heart Failure, Congestive - Myocardial Infarction - Ventricular Dysfunction, Left **Keywords:** - Systolic Heart Failure - Quality of Care - Outcomes - Evidence-based Guidelines - Recommended Therapies ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 34810 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Longitudinal Cohort: Approximately 15,000 patients followed at baseline, 12 months and 24 months **Label:** Cohort A (longitudinal) #### Arm Group 2 **Description:** 6 Month Cohort: Approximately 10,000 patients reviewed at single time point **Label:** Cohort B (6 Month) #### Arm Group 3 **Description:** 18 Month Cohort: Approximately 10,000 patients reviewed at single time point **Label:** Cohort C (18 Month) ### Outcomes Module #### Primary Outcomes **Description:** 7 performance measures: angiotensin converting enzyme inhibitor and/or angiotensin II receptor blockers (ACEI/ARB), beta-blokers, aldosterone receptor antagonists, anticoagulation for atrial fibrillation (AF), cardiac resynchronization therapy (CRT-P/CRT-D), cardioverter-defibrillator (ICD/CRT-D), heart failure (HF) education. We first calcuated % of patients who were eligible for a performance measure that were treated by it at baseline and 24 months. We then calculated the relative change as (% treated at 24 months - % treated at baseline)/% treated at baseline. The 95% confidence interval (CI) was calculated and the relative change of each performance measure was evaluated using a z-test for one-sample proportion. The number of performance measures with \>= 20% relative improvement was determined. The intervention was considered successful if a relative 20% or greater improvement in at least 2 of the 7 performance measures at 24 months compared with baseline was achieved. **Measure:** To Evaluate Over the Aggregate IMPROVE-HF Practice Sites the Relative Changes in 7 Performance Measures at 24 Months Compared With Baseline and Determine the Number of Performance Measures That Achieved a Relative 20% or Greater Positive Change. **Time Frame:** 24 Month #### Secondary Outcomes **Description:** The number of practices that achieved greater than or equal to 20% improvement in two or more of the 7 performance measures at 24 months as compared to baseline of cohort A is presented. **Measure:** Observe the Number of Sites That Demonstrate a Relative 20% or Greater Improvement in 2 or More of the 7 Performance Measures at 24 Months as Compared to Baseline in Cohort A. **Time Frame:** 24 months **Description:** performance measure improvement for each performance measure was analyzed at a practice level from baseline to 24 months. Performance measure adherence was calculated at the individual practice level and then combined and summarized. Mean, standard deviation, and 95% confidence intervals for performance measure adherence, composite score and relative change (24 months compared with baseline) are reported. The Composite Score is based on the ratio of the sum of the numerators of all individual performance measures to the sum of the denominators of all individual performances measures. The numerator of a performance measure is the number of patients treated with that measure. The denomiator of a performance measure is the number of patients eligible for being treated with that measure. **Measure:** Observe the Change From Baseline to 24 Months in Each Performance Measure and Composite Score for the Aggregate Practices. **Time Frame:** 24 months **Description:** The relative changes between baseline of cohort A and 6 months of cohort B in performance measures and composite score for the aggregate practices were calculated using mean, standard deviation and 95% CI. **Measure:** Observe the Relative Change Between Baseline of Cohort A and 6 Months of Cohort B in Performance Measures and Composite Score for the Aggregate Practices. **Time Frame:** Baseline and 6 Months **Description:** The relative changes between baseline of cohort A and 18 months of cohort C in performance measures and composite score for the aggregate practices were calculated using mean, standard deviation and 95% CI. **Measure:** Observe the Relative Change Between Baseline of Cohort A and 18 Months of Cohort C in Performance Measures and Composite Score for the Aggregate Practices. **Time Frame:** baseline and 18 Months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * 18 years of age or older * Primary or secondary diagnosis of heart failure or prior myocardial infarction (heart attack) * Moderate-to-severe left ventricular dysfunction (LVD) as demonstrated by an ejection fraction \< or = 35% and/or a qualitative assessment of LVD of moderate-to-severe or severe LVD * Patient has been seen at the clinic at least twice in the past 2 years * Patient received care from the physician participating in the study Exclusion Criteria: * Patient has died * Patient is not expected to survive for 12 months due to medical conditions other than heart failure * Patient has undergone heart transplant surgery **Minimum Age:** 18 Years **Sampling Method:** PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Heart failure patients in outpatient cardiology practices ### Contacts Locations Module #### Locations **Location 1:** **City:** Birmingham **Country:** United States **Facility:** Cardiovascular Associates of Montclair **State:** Alabama **Zip:** 36608 **Location 2:** **City:** Mobile **Country:** United States **Facility:** Cardiology Associates **State:** Alabama **Zip:** 36608 **Location 3:** **City:** Mesa **Country:** United States **Facility:** Cardiovascular Associates of Mesa **State:** Arizona **Zip:** 85205 **Location 4:** **City:** Scottsdale **Country:** United States **Facility:** Heart Care, PC **State:** Arizona **Zip:** 85258 **Location 5:** **City:** Tucson **Country:** United States **Facility:** Southern Arizona VA Health Care System **State:** Arizona **Zip:** 85723 **Location 6:** **City:** Hot Springs **Country:** United States **Facility:** Central Arkansas Cardiovascular Institute **State:** Arkansas **Zip:** 71913 **Location 7:** **City:** Little Rock **Country:** United States **Facility:** Arkansas Cardiology Clinic **State:** Arkansas **Zip:** 72202 **Location 8:** **City:** Fullerton **Country:** United States **Facility:** St. Jude Heritage Medical Group **State:** California **Zip:** 92835 **Location 9:** **City:** La Jolla **Country:** United States **Facility:** Scripps Clinic Green Hospital **State:** California **Zip:** 92037 **Location 10:** **City:** Los Angeles **Country:** United States **Facility:** Veterans Administration Hospital **State:** California **Zip:** 92357 **Location 11:** **City:** Los Angeles **Country:** United States **Facility:** University Cardiovascular Medical Group **State:** California **Zip:** 94115 **Location 12:** **City:** Monterey **Country:** United States **Facility:** Cardio-Pulmonary Associates **State:** California **Zip:** 93940 **Location 13:** **City:** Murrieta **Country:** United States **Facility:** Temecula Valley Cardiology **State:** California **Zip:** 92562 **Location 14:** **City:** San Francisco **Country:** United States **Facility:** California Pacific Cardiovascular Medical **State:** California **Zip:** 94115 **Location 15:** **City:** San Pablo **Country:** United States **Facility:** East Bay Cardiology **State:** California **Zip:** 94803 **Location 16:** **City:** Tarzana **Country:** United States **Facility:** Cardiology Consultants Medical Group **State:** California **Zip:** 91335 **Location 17:** **City:** Fort Collins **Country:** United States **Facility:** Medical Center of the Rockies **State:** Colorado **Zip:** 80521 **Location 18:** **City:** Bridgeport **Country:** United States **Facility:** Connecticut Heart & Vascular Center **State:** Connecticut **Zip:** 06606 **Location 19:** **City:** Newark **Country:** United States **Facility:** Cardiology Consultants, PA **State:** Delaware **Zip:** 19702 **Location 20:** **City:** Bradenton **Country:** United States **Facility:** Heart and Vascular Center of Bradenton **State:** Florida **Zip:** 34209 **Location 21:** **City:** Clearwater **Country:** United States **Facility:** Clearwater Cardiovascular & Intervention **State:** Florida **Zip:** 33756 **Location 22:** **City:** Clearwater **Country:** United States **Facility:** Mahesh Amin, MD PA **State:** Florida **Zip:** 33756 **Location 23:** **City:** Hudson **Country:** United States **Facility:** Pasco Cardiology **State:** Florida **Zip:** 34667 **Location 24:** **City:** Kissimmee **Country:** United States **Facility:** Cardiovascular Associates **State:** Florida **Zip:** 34741 **Location 25:** **City:** Lakeland **Country:** United States **Facility:** Clark and Daughtrey Medical Group **State:** Florida **Zip:** 33803 **Location 26:** **City:** Melbourne **Country:** United States **Facility:** OMNI **State:** Florida **Zip:** 32901 **Location 27:** **City:** Miami **Country:** United States **Facility:** Miami Cardiology Group **State:** Florida **Zip:** 33176 **Location 28:** **City:** Orlando **Country:** United States **Facility:** Florida Heart Group **State:** Florida **Zip:** 32803 **Location 29:** **City:** Port Charlotte **Country:** United States **Facility:** Cardiology Associates **State:** Florida **Zip:** 33952 **Location 30:** **City:** Tamarac **Country:** United States **Facility:** Cardiovascular Consultants, **State:** Florida **Zip:** 33309 **Location 31:** **City:** Vero Beach **Country:** United States **Facility:** Indian River Cardiovascular Associate **State:** Florida **Zip:** 32960 **Location 32:** **City:** Zephyrhills **Country:** United States **Facility:** Florida Medical Clinic **State:** Florida **Zip:** 33542 **Location 33:** **City:** Atlanta **Country:** United States **Facility:** Cardiology of Atlanta **State:** Georgia **Zip:** 30342 **Location 34:** **City:** Atlanta **Country:** United States **Facility:** Northside Cardiology **State:** Georgia **Zip:** 30342 **Location 35:** **City:** Gainesville **Country:** United States **Facility:** Northeast Georgia Heart Center **State:** Georgia **Zip:** 30501 **Location 36:** **City:** Savannah **Country:** United States **Facility:** Southcoast Cardiology **State:** Georgia **Zip:** 31406 **Location 37:** **City:** Honolulu **Country:** United States **Facility:** Pacific Cardiology **State:** Hawaii **Zip:** 96817 **Location 38:** **City:** Boise **Country:** United States **Facility:** St. Luke's Idaho Cardiology Associates **State:** Idaho **Zip:** 83702 **Location 39:** **City:** Blue Island **Country:** United States **Facility:** Heart Care Center of Illinois **State:** Illinois **Zip:** 60406 **Location 40:** **City:** Frankfort **Country:** United States **Facility:** MidAmerica Cardiovascular Consultants **State:** Illinois **Zip:** 60453 **Location 41:** **City:** Glenview **Country:** United States **Facility:** Cardiovascular Associates of Glenbrook and Evanston, LLC **State:** Illinois **Zip:** 60026 **Location 42:** **City:** Indianapolis **Country:** United States **Facility:** St. Vincent's Hospital **State:** Indiana **Zip:** 46201 **Location 43:** **City:** Indianapolis **Country:** United States **Facility:** Methodist Hospital **State:** Indiana **Zip:** 46202 **Location 44:** **City:** Indianapolis **Country:** United States **Facility:** St. Vincent's Hospital Indianapolis **State:** Indiana **Zip:** 46278 **Location 45:** **City:** Indianapolis **Country:** United States **Facility:** St. Vincent's Hospital, **State:** Indiana **Zip:** 46278 **Location 46:** **City:** West Des Moines **Country:** United States **Facility:** Iowa Heart Center PC, **State:** Iowa **Zip:** 50266 **Location 47:** **City:** Kansas City **Country:** United States **Facility:** Mid America Cardiology **State:** Kansas **Zip:** 66102 **Location 48:** **City:** Topeka **Country:** United States **Facility:** Cardiology Consultants **State:** Kansas **Zip:** 66102 **Location 49:** **City:** Wichita **Country:** United States **Facility:** Cardiovascular Consultants of Kansas **State:** Kansas **Zip:** 67226 **Location 50:** **City:** Louisville **Country:** United States **Facility:** Louisville Cardiology Medical Group P.S **State:** Kentucky **Zip:** 40026 **Location 51:** **City:** Louisville **Country:** United States **Facility:** Medical Center Cardiologists P.S.C **State:** Kentucky **Zip:** 40201 **Location 52:** **City:** Louisville **Country:** United States **Facility:** Louisville Cardiology Medical Group P.S **State:** Kentucky **Zip:** 40207 **Location 53:** **City:** Owensboro **Country:** United States **Facility:** Owensboro Heart and Vascular **State:** Kentucky **Zip:** 42303 **Location 54:** **City:** Covington **Country:** United States **Facility:** Tchefuncte Cardiovascular Associates, **State:** Louisiana **Zip:** 70433 **Location 55:** **City:** Marrero **Country:** United States **Facility:** Heart Clinic of Louisiana **State:** Louisiana **Zip:** 70072 **Location 56:** **City:** Bethesda **Country:** United States **Facility:** Maryland Heart, PC **State:** Maryland **Zip:** 20817 **Location 57:** **City:** Clinton **Country:** United States **Facility:** Heart Center of Southern Maryland **State:** Maryland **Zip:** 20735 **Location 58:** **City:** Glen Burnie **Country:** United States **Facility:** Arundel Heart Associates **State:** Maryland **Zip:** 21061 **Location 59:** **City:** Salisbury **Country:** United States **Facility:** Peninsula Cardiology **State:** Maryland **Zip:** 21804 **Location 60:** **City:** Ayer **Country:** United States **Facility:** Primary Care Specialists Inc **State:** Massachusetts **Zip:** 01432 **Location 61:** **City:** Chelmsford **Country:** United States **Facility:** Merrimack Valley Cardiology **State:** Massachusetts **Zip:** 01824 **Location 62:** **City:** Weymouth **Country:** United States **Facility:** Harbor Medical AssociatesSo Weymouth **State:** Massachusetts **Zip:** 02190 **Location 63:** **City:** Farmington Hills **Country:** United States **Facility:** Consultants in Cardiology **State:** Michigan **Zip:** 48331 **Location 64:** **City:** Rochester **Country:** United States **Facility:** Cardiovascular Consultants PC **State:** Michigan **Zip:** 48312 **Location 65:** **City:** Roseville **Country:** United States **Facility:** Eastside Cardiology, Roseville **State:** Michigan **Zip:** 48066 **Location 66:** **City:** Saint Paul **Country:** United States **Facility:** St. Paul Cardiology **State:** Minnesota **Zip:** 55102 **Location 67:** **City:** Jackson **Country:** United States **Facility:** University of Mississippi Medical Center **State:** Mississippi **Zip:** 39216 **Location 68:** **City:** Columbia **Country:** United States **Facility:** Missouri Cardiovascular Specialists **State:** Missouri **Zip:** 65201 **Location 69:** **City:** Columbia **Country:** United States **Facility:** University Hospital Healthcare **State:** Missouri **Zip:** 65210 **Location 70:** **City:** Joplin **Country:** United States **Facility:** Freeman Heart Institute **State:** Missouri **Zip:** 64804 **Location 71:** **City:** Saint Louis **Country:** United States **Facility:** Mercy Cardiology **State:** Missouri **Zip:** 63101 **Location 72:** **City:** Saint Louis **Country:** United States **Facility:** Cardiology Diagnostics, Ltd, **State:** Missouri **Zip:** 63131 **Location 73:** **City:** Concord **Country:** United States **Facility:** Cardiac Associates of New Hampshire **State:** New Hampshire **Zip:** 03303 **Location 74:** **City:** Lebanon **Country:** United States **Facility:** Dartmouth-Hitchcock Medical Center **State:** New Hampshire **Zip:** 03756 **Location 75:** **City:** Lebanon **Country:** United States **Facility:** Dartmouth-Hitchcock Medical Center **State:** New Hampshire **Zip:** 03766 **Location 76:** **City:** Bridgewater **Country:** United States **Facility:** Medicor **State:** New Jersey **Zip:** 08807 **Location 77:** **City:** Edgewater **Country:** United States **Facility:** Cross County Cardiology **State:** New Jersey **Zip:** 07020 **Location 78:** **City:** Hawthorne **Country:** United States **Facility:** Heart-Lung Center **State:** New Jersey **Zip:** 07506-1919 **Location 79:** **City:** Voorhees **Country:** United States **Facility:** Southern New Jersey Cardiac Specialists **State:** New Jersey **Zip:** 08043 **Location 80:** **City:** West Orange **Country:** United States **Facility:** Diagnostic and Clinical Cardiologists **State:** New Jersey **Zip:** 07052 **Location 81:** **City:** Westwood **Country:** United States **Facility:** Westwood Cardiology **State:** New Jersey **Zip:** 07675 **Location 82:** **City:** Albany **Country:** United States **Facility:** Albany Associates in Cardiology, **State:** New York **Zip:** 12205 **Location 83:** **City:** Brooklyn **Country:** United States **Facility:** SUNY Downstate Medical Center **State:** New York **Zip:** 11203 **Location 84:** **City:** Brooklyn **Country:** United States **Facility:** Cardiology Associates of Brooklyn **State:** New York **Zip:** 11219 **Location 85:** **City:** Brooklyn **Country:** United States **Facility:** United Medical Associates **State:** New York **Zip:** 11219 **Location 86:** **City:** Manhattan **Country:** United States **Facility:** Concorde Medical Group/NYU Hospital **State:** New York **Zip:** 10001 **Location 87:** **City:** Mineola **Country:** United States **Facility:** Island Cardiac Specialists **State:** New York **Zip:** 11501 **Location 88:** **City:** Mineola **Country:** United States **Facility:** Island Cardiac Specialist **State:** New York **Zip:** 11501 **Location 89:** **City:** New York **Country:** United States **Facility:** Gotham Cardiovascular Research **State:** New York **Zip:** 10001 **Location 90:** **City:** Scarsdale **Country:** United States **Facility:** Westchester Medical Group **State:** New York **Zip:** 10583 **Location 91:** **City:** Staten Island **Country:** United States **Facility:** Vazzana and Bogin Cardiology Associates **State:** New York **Zip:** 10305 **Location 92:** **City:** Syracuse **Country:** United States **Facility:** Cardiology PC **State:** New York **Zip:** 13210 **Location 93:** **City:** West Islip **Country:** United States **Facility:** Southbay Cardiology **State:** New York **Zip:** 11795 **Location 94:** **City:** Asheville **Country:** United States **Facility:** Asheville Cardiology Associates **State:** North Carolina **Zip:** 28803 **Location 95:** **City:** Charlotte **Country:** United States **Facility:** Sanger Clinic **State:** North Carolina **Zip:** 28202 **Location 96:** **City:** Gastonia **Country:** United States **Facility:** Carolina Heart Specialists **State:** North Carolina **Zip:** 28054 **Location 97:** **City:** Greensboro **Country:** United States **Facility:** Southeastern Heart and Vascular **State:** North Carolina **Zip:** 27403 **Location 98:** **City:** Hickory **Country:** United States **Facility:** Hickory Cardiology **State:** North Carolina **Zip:** 28602 **Location 99:** **City:** High Point **Country:** United States **Facility:** Carolina Cardiology Associates **State:** North Carolina **Zip:** 27262 **Location 100:** **City:** New Bern **Country:** United States **Facility:** Heart Center of Eastern Carolina, **State:** North Carolina **Zip:** 28562 **Location 101:** **City:** New Bern **Country:** United States **Facility:** Heart Center of Eastern Carolina **State:** North Carolina **Zip:** 28562 **Location 102:** **City:** Pinehurst **Country:** United States **Facility:** Pinehurst Cardiology Consultants **State:** North Carolina **Zip:** 28370 **Location 103:** **City:** Pinehurst **Country:** United States **Facility:** Pinehurst Cardiology Consultants **State:** North Carolina **Zip:** 28374 **Location 104:** **City:** Raleigh **Country:** United States **Facility:** Raleigh Cardiology **State:** North Carolina **Zip:** 27610 **Location 105:** **City:** Fargo **Country:** United States **Facility:** Meritcare Medical Center **State:** North Dakota **Zip:** 58122 **Location 106:** **City:** Akron **Country:** United States **Facility:** Northeast Ohio Cardiovascular Specialists **State:** Ohio **Zip:** 44301 **Location 107:** **City:** Cleveland **Country:** United States **Facility:** Muhammed H. Zahra **State:** Ohio **Zip:** 44125 **Location 108:** **City:** Cleveland **Country:** United States **Facility:** Cleveland Clinic Foundation **State:** Ohio **Zip:** 44195 **Location 109:** **City:** Columbus **Country:** United States **Facility:** Doctors Hospital Heart Failure Clinic **State:** Ohio **Zip:** 43228 **Location 110:** **City:** Kettering **Country:** United States **Facility:** Schuster Cardiology Associates **State:** Ohio **Zip:** 45336 **Location 111:** **City:** Lima **Country:** United States **Facility:** The Heart Institute of Northwest Ohio **State:** Ohio **Zip:** 45801 **Location 112:** **City:** Newark **Country:** United States **Facility:** Bryce Morrice MD and Debra Heldman MD Inc **State:** Ohio **Zip:** 43055 **Location 113:** **City:** Parma **Country:** United States **Facility:** Cardiovascular Clinic, Inc. **State:** Ohio **Zip:** 44129 **Location 114:** **City:** Toledo **Country:** United States **Facility:** North West Ohio Cardiology Consultants **State:** Ohio **Zip:** 43615 **Location 115:** **City:** Abington **Country:** United States **Facility:** Abington Medical Specialists **State:** Pennsylvania **Zip:** 19001 **Location 116:** **City:** Danville **Country:** United States **Facility:** Geisinger Medical Center **State:** Pennsylvania **Zip:** 17822 **Location 117:** **City:** Doylestown **Country:** United States **Facility:** Central Bucks Specialists, Ltd., **State:** Pennsylvania **Zip:** 18901 **Location 118:** **City:** Harrisburg **Country:** United States **Facility:** Associated Cardiologists **State:** Pennsylvania **Zip:** 17103 **Location 119:** **City:** Lancaster **Country:** United States **Facility:** The Heart Group, Ltd **State:** Pennsylvania **Zip:** 17603 **Location 120:** **City:** Philadelphia **Country:** United States **Facility:** Drexel University College of Medicine **State:** Pennsylvania **Zip:** 19129 **Location 121:** **City:** Wynnewood **Country:** United States **Facility:** Cardiology Associates of Southeastern PA **State:** Pennsylvania **Zip:** 19064 **Location 122:** **City:** York **Country:** United States **Facility:** York Hospital **State:** Pennsylvania **Zip:** 17403 **Location 123:** **City:** Pawtucket **Country:** United States **Facility:** Blackstone Cardiology Associates **State:** Rhode Island **Zip:** 02860 **Location 124:** **City:** Charleston **Country:** United States **Facility:** Medical University of South **State:** South Carolina **Zip:** 29406 **Location 125:** **City:** Greenville **Country:** United States **Facility:** Upstate Cardiology **State:** South Carolina **Zip:** 29605 **Location 126:** **City:** Myrtle Beach **Country:** United States **Facility:** Cardiology Associates **State:** South Carolina **Zip:** 29572 **Location 127:** **City:** Spartanburg **Country:** United States **Facility:** Cardiology Consultants, PA **State:** South Carolina **Zip:** 29301 **Location 128:** **City:** Sumter **Country:** United States **Facility:** Sumter Medical Consultants **State:** South Carolina **Zip:** 29150 **Location 129:** **City:** West Columbia **Country:** United States **Facility:** Columbia Cardiology Consultants **State:** South Carolina **Zip:** 29204 **Location 130:** **City:** Germantown **Country:** United States **Facility:** Sutherland Clinic **State:** Tennessee **Zip:** 38119 **Location 131:** **City:** Lexington **Country:** United States **Facility:** Dela Clinic **State:** Tennessee **Zip:** 38351 **Location 132:** **City:** Arlington **Country:** United States **Facility:** Heart Place North Arlington **State:** Texas **Zip:** 75284 **Location 133:** **City:** Dallas **Country:** United States **Facility:** University of Texas South Western Medical Center at Dallas **State:** Texas **Zip:** 75201 **Location 134:** **City:** Houston **Country:** United States **Facility:** Comprehensive Heart Care, PA **State:** Texas **Zip:** 77024 **Location 135:** **City:** Houston **Country:** United States **Facility:** Cardiology Consultants of Houston **State:** Texas **Zip:** 77030 **Location 136:** **City:** Plano **Country:** United States **Facility:** Legacy Heart Center **State:** Texas **Zip:** 75024 **Location 137:** **City:** San Antonio **Country:** United States **Facility:** Cardiology Clinic of San Antonio **State:** Texas **Zip:** 78229 **Location 138:** **City:** San Antonio **Country:** United States **Facility:** Wilford Hall Medical Center **State:** Texas **Zip:** 78229 **Location 139:** **City:** Tyler **Country:** United States **Facility:** Tyler Cardiovascular Consultants **State:** Texas **Zip:** 75701 **Location 140:** **City:** Burlington **Country:** United States **Facility:** University Associates in Cardiology **State:** Vermont **Zip:** 05401 **Location 141:** **City:** Fairfax **Country:** United States **Facility:** Cardiology Associates of Lakeview **State:** Virginia **Zip:** 05454 **Location 142:** **City:** Fairfax **Country:** United States **Facility:** The Cardiovascular Group **State:** Virginia **Zip:** 22031 **Location 143:** **City:** Hampton **Country:** United States **Facility:** Tidewater Heart Specialists, Inc., **State:** Virginia **Zip:** 23666 **Location 144:** **City:** Green Bay **Country:** United States **Facility:** Cardiology Associates of Green Bay **State:** Wisconsin **Zip:** 54301 #### Overall Officials **Official 1:** **Affiliation:** University of California at Los Angeles **Name:** Gregg Fonarow, MD **Role:** STUDY_CHAIR **Official 2:** **Affiliation:** UT Southwestern Medical Center at Dallas **Name:** Clyde Yancy, MD **Role:** STUDY_CHAIR ### References Module #### References **Citation:** Shukla A, Curtis AB, Mehra MR, Albert NM, Gheorghiade M, Heywood JT, Liu Y, O'Connor CM, Reynolds D, Walsh MN, Yancy CW, Fonarow GC. Factors associated with improvement in utilization of cardiac resynchronization therapy in eligible heart failure patients: findings from IMPROVE HF. Pacing Clin Electrophysiol. 2013 Apr;36(4):433-43. doi: 10.1111/pace.12090. Epub 2013 Feb 4. **PMID:** 23380000 **Citation:** Barkoudah E, Skali H, Uno H, Solomon SD, Pfeffer MA. Mortality rates in trials of subjects with type 2 diabetes. J Am Heart Assoc. 2012 Feb;1(1):8-15. doi: 10.1161/JAHA.111.000059. Epub 2012 Feb 20. **PMID:** 23130114 **Citation:** Reynolds D, Albert NM, Curtis AB, Gheorghiade M, Heywood JT, Mcbride ML, Inge PJ, Mehra MR, O'Connor CM, Walsh MN, Yancy CW, Fonarow GC. Race and improvements in the use of guideline-recommended therapies for patients with heart failure: findings from IMPROVE HF. J Natl Med Assoc. 2012 May-Jun;104(5-6):287-98. doi: 10.1016/s0027-9684(15)30156-5. **PMID:** 22973678 **Citation:** Fonarow GC, Albert NM, Curtis AB, Gheorghiade M, Heywood JT, Liu Y, Mehra MR, O'Connor CM, Reynolds D, Walsh MN, Yancy CW. Associations between outpatient heart failure process-of-care measures and mortality. Circulation. 2011 Apr 19;123(15):1601-10. doi: 10.1161/CIRCULATIONAHA.110.989632. Epub 2011 Apr 4. **PMID:** 21464053 **Citation:** Walsh MN, Yancy CW, Albert NM, Curtis AB, Gheorghiade M, Heywood JT, Inge PJ, McBride ML, Mehra MR, O'Connor CM, Reynolds D, Fonarow GC. Equitable improvement for women and men in the use of guideline-recommended therapies for heart failure: findings from IMPROVE HF. J Card Fail. 2010 Dec;16(12):940-9. doi: 10.1016/j.cardfail.2010.07.250. **PMID:** 21111983 **Citation:** Fonarow GC, Albert NM, Curtis AB, Stough WG, Gheorghiade M, Heywood JT, McBride ML, Inge PJ, Mehra MR, O'Connor CM, Reynolds D, Walsh MN, Yancy CW. Improving evidence-based care for heart failure in outpatient cardiology practices: primary results of the Registry to Improve the Use of Evidence-Based Heart Failure Therapies in the Outpatient Setting (IMPROVE HF). Circulation. 2010 Aug 10;122(6):585-96. doi: 10.1161/CIRCULATIONAHA.109.934471. Epub 2010 Jul 26. **PMID:** 20660805 **Citation:** Heywood JT, Fonarow GC, Yancy CW, Albert NM, Curtis AB, Gheorghiade M, Inge PJ, McBride ML, Mehra MR, O'Connor CM, Reynolds D, Walsh MN. Comparison of medical therapy dosing in outpatients cared for in cardiology practices with heart failure and reduced ejection fraction with and without device therapy: report from IMPROVE HF. Circ Heart Fail. 2010 Sep;3(5):596-605. doi: 10.1161/CIRCHEARTFAILURE.109.912683. Epub 2010 Jul 15. **PMID:** 20634483 **Citation:** Walsh MN, Yancy CW, Albert NM, Curtis AB, Stough WG, Gheorghiade M, Heywood JT, McBride ML, Mehra MR, O'Connor CM, Reynolds D, Fonarow GC. Electronic health records and quality of care for heart failure. Am Heart J. 2010 Apr;159(4):635-642.e1. doi: 10.1016/j.ahj.2010.01.006. **PMID:** 20362723 **Citation:** Mehra MR, Yancy CW, Albert NM, Curtis AB, Stough WG, Gheorghiade M, Heywood JT, McBride ML, O'Connor CM, Reynolds D, Walsh MN, Fonarow GC. Evidence of clinical practice heterogeneity in the use of implantable cardioverter-defibrillators in heart failure and post-myocardial infarction left ventricular dysfunction: Findings from IMPROVE HF. Heart Rhythm. 2009 Dec;6(12):1727-34. doi: 10.1016/j.hrthm.2009.08.022. Epub 2009 Aug 22. **PMID:** 19959119 **Citation:** Curtis AB, Yancy CW, Albert NM, Stough WG, Gheorghiade M, Heywood JT, McBride ML, Mehra MR, Oconnor CM, Reynolds D, Walsh MN, Fonarow GC. Cardiac resynchronization therapy utilization for heart failure: findings from IMPROVE HF. Am Heart J. 2009 Dec;158(6):956-64. doi: 10.1016/j.ahj.2009.10.011. **PMID:** 19958862 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000006331 - Term: Heart Diseases - ID: D000002318 - Term: Cardiovascular Diseases - ID: D000007511 - Term: Ischemia - ID: D000010335 - Term: Pathologic Processes - ID: D000009336 - Term: Necrosis - ID: D000017202 - Term: Myocardial Ischemia - 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: M9421 - Name: Heart Failure - Relevance: HIGH - As Found: Heart Failure - ID: M20591 - Name: Ventricular Dysfunction, Left - Relevance: HIGH - As Found: Ventricular Dysfunction, Left - ID: M27583 - Name: Systolic Murmurs - Relevance: LOW - As Found: Unknown - ID: M12155 - Name: Myocardial Infarction - Relevance: HIGH - As Found: Myocardial Infarction - ID: M10282 - Name: Infarction - Relevance: HIGH - As Found: Infarction - ID: M20824 - Name: Ventricular Dysfunction - Relevance: HIGH - As Found: Ventricular Dysfunction - ID: M27579 - Name: Heart Failure, Systolic - Relevance: LOW - As Found: Unknown - ID: M9419 - Name: Heart Diseases - Relevance: LOW - As Found: Unknown - ID: M10543 - Name: Ischemia - Relevance: LOW - As Found: Unknown - ID: M12284 - Name: Necrosis - Relevance: LOW - As Found: Unknown - ID: M6546 - Name: Coronary Artery Disease - Relevance: LOW - As Found: Unknown - ID: M19506 - Name: Myocardial Ischemia - Relevance: LOW - As Found: Unknown - ID: M17400 - Name: Vascular Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000006333 - Term: Heart Failure - ID: D000009203 - Term: Myocardial Infarction - ID: D000018754 - Term: Ventricular Dysfunction - ID: D000018487 - Term: Ventricular Dysfunction, Left - ID: D000007238 - Term: Infarction ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module **Description:** Adverse events were not collected for this study. #### Event Groups **Group ID:** EG000 **Title:** Cohort A (Baseline, 12 and 24 Months) **Description:** Cohort A: The charts of 15,177 patients were reviewed at baseline, 12 months and 24 months. The principal investigator and HF nurse of the study sites attended an educational workshop at baseline, 12 and 24 months as well where they were provided with tools meant to improve HF care at their practices. The tools included tip cards, worksheets, and patient education materials. Cohort A is a longitudinal cohort. **ID:** EG000 **Title:** Cohort A (Baseline, 12 and 24 Months) **Group ID:** EG001 **Title:** Cohort B (6 Months) **Description:** Cohort B: The charts of 9,992 patients were reviewed at 6 months. The principal investigator and HF nurse of the study sites attended an educational workshop at the same time where they were provided with tools meant to improve HF care at their practices. The tools included tip cards, worksheets, and patient education materials. Cohort B is a single time point cohort. **ID:** EG001 **Title:** Cohort B (6 Months) **Group ID:** EG002 **Title:** Cohort C (18 Months) **Description:** Cohort C: The charts of 9,641 patients were reviewed at 18 months. The principal investigator and HF nurse of the study sites attended an educational workshop at the same time where they were provided with tools meant to improve HF care at their practices. The tools included tip cards, worksheets, and patient education materials. Cohort C is a single time point cohort. **ID:** EG002 **Title:** Cohort C (18 Months) **Frequency Threshold:** 0 ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 15177 **Group ID:** BG001 **Value:** 9992 **Group ID:** BG002 **Value:** 9641 **Group ID:** BG003 **Value:** 34810 **Units:** Participants ### Group **ID:** BG000 **Title:** Cohort A (Baseline, 12 and 24 Months) **Description:** Cohort A: The charts of 15,177 patients were reviewed at baseline, 12 months and 24 months. The principal investigator and HF nurse of the study sites attended an educational workshop at baseline, 12 and 24 months as well where they were provided with tools meant to improve HF care at their practices. The tools included tip cards, worksheets, and patient education materials. Cohort A is a longitudinal cohort. ### Group **ID:** BG001 **Title:** Cohort B (6 Months) **Description:** Cohort B: The charts of 9,992 patients were reviewed at 6 months. The principal investigator and HF nurse of the study sites attended an educational workshop at the same time where they were provided with tools meant to improve HF care at their practices. The tools included tip cards, worksheets, and patient education materials. Cohort B is a single time point cohort. ### Group **ID:** BG002 **Title:** Cohort C (18 Months) **Description:** Cohort C: The charts of 9,641 patients were reviewed at 18 months. The principal investigator and HF nurse of the study sites attended an educational workshop at the same time where they were provided with tools meant to improve HF care at their practices. The tools included tip cards, worksheets, and patient education materials. Cohort C is a single time point cohort. ### Group **ID:** BG003 **Title:** Total **Description:** Total of all reporting groups ### Measure #### Measurement **Group ID:** BG000 **Spread:** 13.2 **Value:** 68.7 #### Measurement **Group ID:** BG001 **Spread:** 13.2 **Value:** 68.3 #### Measurement **Group ID:** BG002 **Spread:** 13.6 **Value:** 68.2 #### Measurement **Group ID:** BG003 **Spread:** 13.3 **Value:** 68.4 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 5274 #### Measurement **Group ID:** BG001 **Value:** 3606 #### Measurement **Group ID:** BG002 **Value:** 3539 #### Measurement **Group ID:** BG003 **Value:** 12419 **Class Title:** <=64 years #### Measurement **Group ID:** BG000 **Value:** 5127 #### Measurement **Group ID:** BG001 **Value:** 3344 #### Measurement **Group ID:** BG002 **Value:** 3089 #### Measurement **Group ID:** BG003 **Value:** 11560 **Class Title:** Between 64 and 76 years #### Measurement **Group ID:** BG000 **Value:** 4748 #### Measurement **Group ID:** BG001 **Value:** 3041 #### Measurement **Group ID:** BG002 **Value:** 3010 #### Measurement **Group ID:** BG003 **Value:** 10799 **Class Title:** >76 years #### Measurement **Group ID:** BG000 **Value:** 28 #### Measurement **Group ID:** BG001 **Value:** 1 #### Measurement **Group ID:** BG002 **Value:** 3 #### Measurement **Group ID:** BG003 **Value:** 32 **Class Title:** Missing ### Measure #### Measurement **Group ID:** BG000 **Value:** 4383 #### Measurement **Group ID:** BG001 **Value:** 2918 #### Measurement **Group ID:** BG002 **Value:** 2827 #### Measurement **Group ID:** BG003 **Value:** 10128 **Class Title:** Female #### Measurement **Group ID:** BG000 **Value:** 10787 #### Measurement **Group ID:** BG001 **Value:** 7069 #### Measurement **Group ID:** BG002 **Value:** 6814 #### Measurement **Group ID:** BG003 **Value:** 24670 **Class Title:** Male #### Measurement **Group ID:** BG000 **Value:** 7 #### Measurement **Group ID:** BG001 **Value:** 5 #### Measurement **Group ID:** BG002 **Value:** 0 #### Measurement **Group ID:** BG003 **Value:** 12 **Class Title:** Missing ### Measure #### Measurement **Group ID:** BG000 **Value:** 15177 #### Measurement **Group ID:** BG001 **Value:** 9992 #### Measurement **Group ID:** BG002 **Value:** 9641 #### Measurement **Group ID:** BG003 **Value:** 34810 **Class Title:** United States **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:** NUMBER **Title:** Age, Customized **Unit of Measure:** participants ### Measure 3 **Parameter Type:** NUMBER **Title:** Sex/Gender, Customized **Unit of Measure:** participants ### Measure 4 **Parameter Type:** NUMBER **Title:** Region of Enrollment **Unit of Measure:** participants ## Results Section - More Information Module ### Certain Agreement **Other Details:** In most cases, contracts allow investigators ("PI") to publish per the publication strategy/Clinical Investigation Plan following Medtronic's review for (a) disclosure of confidential information ("CI"), and (b) selection and order of publications by the publications committee. Any such CI is deleted prior to publication/presentation. Medtronic may not otherwise censor/interfere with the publication. PI's may not publish single-site data until the main multi-site publication has occurred. **Restriction Type:** OTHER **Restrictive Agreement:** True ### Point of Contact **Email:** [email protected] **Organization:** Medtronic Cardiac Rhythm Disease Management **Title:** IMPROVE HF, Clinical Research Specialist ## Results Section - Outcome Measures Module ### Outcome Measure 1 #### Analysis **CI Lower Limit:** 7.0 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 9.7 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Performance Measure #1: relative change in % of eligible patients treated with angiotensin converting enzyme inhibitor and/or angiotensin II receptor blockers (ACEU/ARB). **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** <0.001 **P-Value Comment:** **Parameter Type:** Relative Improvement (%) **Parameter Value:** 8.4 **Statistical Comment:** **Statistical Method:** a large sample test (z-test) **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 7.7 **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:** Performance Measure #2: relative change in % of eligible patients treated with beta-blockers. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** <0.001 **P-Value Comment:** **Parameter Type:** Relative improvement (%) **Parameter Value:** 8.6 **Statistical Comment:** **Statistical Method:** a large sample test (z-test) **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 70.5 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 89.0 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Performance Measure #3: relative change in % of eligible patients treated with aldosterone receptor antagonists. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** <0.001 **P-Value Comment:** **Parameter Type:** Relative improvement (%) **Parameter Value:** 79.7 **Statistical Comment:** **Statistical Method:** a large sample test (z-test) **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** -2.2 **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:** Performance Measure #4: relative change in % of eligible patients treated with anticoagulation for AF. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.546 **P-Value Comment:** **Parameter Type:** Relative Improvement (%) **Parameter Value:** 1.0 **Statistical Comment:** **Statistical Method:** a large sample test (z-test) **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 72.2 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 91.7 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Performance Measure #5: relative change in % of eligible patients treated with cardiac resynchronization therapy (CRT-P/CRT-D). **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** <0.001 **P-Value Comment:** **Parameter Type:** Relative Improvement (%) **Parameter Value:** 81.9 **Statistical Comment:** **Statistical Method:** a large sample test (z-test) **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 59.1 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 65.1 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Performance Measure #6: relative change in % of eligible patients treated with implantable cardioverter-defibrillator (ICD) or CRT-D. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** <0.001 **P-Value Comment:** **Parameter Type:** Relative Improvement (%) **Parameter Value:** 62.1 **Statistical Comment:** **Statistical Method:** a large sample test (z-test) **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 12.6 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 16.8 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Performance Measure #7: relative change in % of eligible patients with HF education. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** <0.001 **P-Value Comment:** **Parameter Type:** Relative Improvement (%) **Parameter Value:** 14.7 **Statistical Comment:** **Statistical Method:** a large sample test (z-test) **Tested Non-Inferiority:** ### Outcome Measure 2 ### Outcome Measure 3 #### Analysis **CI Lower Limit:** -1.1 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 39.8 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Performance Measure #1: Relative change at 24 months compared with baseline in ACEI/ARB for the aggregate practices. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.004 **P-Value Comment:** **Parameter Type:** Mean Relative Change (%) **Parameter Value:** 19.4 **Statistical Comment:** **Statistical Method:** t-test, 2 sided **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 5.1 **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:** Performance Measure #2: the relative change at 24 months compared with baseline in beta-blockers for the aggregate practices. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** <0.001 **P-Value Comment:** **Parameter Type:** Mean Relative Change (%) **Parameter Value:** 7.6 **Statistical Comment:** **Statistical Method:** t-test, 2 sided **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 24.6 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 35.5 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Performance Measure #3: the relative change at 24 months compared with baseline in aldosterone antagonist for the aggregate practices. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** <0.001 **P-Value Comment:** **Parameter Type:** Mean Relative Change (%) **Parameter Value:** 30.0 **Statistical Comment:** **Statistical Method:** t-test, 2 sided **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** -3.6 **CI Number of Sides:** **CI Percentage Value:** 95 **CI Upper Limit:** 5.5 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Performance Measure #4: the relative change at 24 months compared with baseline in anticoagulation for AF for the aggregate practices. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.513 **P-Value Comment:** **Parameter Type:** Mean Relative Change (%) **Parameter Value:** 1.0 **Statistical Comment:** **Statistical Method:** t-test, 2 sided **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 37.9 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 58.8 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Performance Measure #5: the relative change at 24 months compared with baseline in CRT-P/CRT-D for the aggregate practices. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** <0.001 **P-Value Comment:** **Parameter Type:** Mean Relative Change (%) **Parameter Value:** 48.4 **Statistical Comment:** **Statistical Method:** t-test, 2 sided **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 61.0 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 80.8 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Performance Measure #6: the relative change at 24 months compared with baseline in ICD/CRT-D for the aggregate practices. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** <0.001 **P-Value Comment:** **Parameter Type:** Mean Relative Change (%) **Parameter Value:** 70.9 **Statistical Comment:** **Statistical Method:** t-test, 2 sided **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 27.1 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 74.2 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Performance Measure #7: the relative change at 24 months compared with baseline in HF education for the aggregate practices. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** <0.001 **P-Value Comment:** **Parameter Type:** Mean Relative Change (%) **Parameter Value:** 50.6 **Statistical Comment:** **Statistical Method:** t-test, 2 sided **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 16.3 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 22.0 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Composite Score: The relative change at 24 months compared with baseline in composite score for the aggregate practices. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** <0.001 **P-Value Comment:** **Parameter Type:** Mean Relative Change (%) **Parameter Value:** 19.2 **Statistical Comment:** **Statistical Method:** t-test, 2 sided **Tested Non-Inferiority:** ### Outcome Measure 4 #### Analysis **CI Lower Limit:** -5.4 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 25.9 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Performance Measure #1: the relative change of Cohort B (6 months) compared with Cohort A at baseline in ACEI/ARB for the aggregate practices. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.197 **P-Value Comment:** **Parameter Type:** Mean Relative Change (%) **Parameter Value:** 10.3 **Statistical Comment:** **Statistical Method:** t-test, 2 sided **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** -0.5 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 21.7 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Performance Measure #2: the relative change of Cohort B (6 months) compared with Cohort A at baseline in beta-blockers for the aggregate practices. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.061 **P-Value Comment:** **Parameter Type:** Mean Relative Change (%) **Parameter Value:** 10.6 **Statistical Comment:** **Statistical Method:** t-test, 2 sided **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** -5.7 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 3.4 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Performance Measure #3: the relative change of Cohort B (6 months) compared with Cohort A at baseline in aldosterone antagonist for the aggregate practices. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.622 **P-Value Comment:** **Parameter Type:** Mean Relative Change (%) **Parameter Value:** -1.1 **Statistical Comment:** **Statistical Method:** t-test, 2 sided **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 0.0 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 12.4 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Performance Measure #4: the relative change of Cohort B (6 months) compared with Cohort A at baseline in anticoagulation for AF for the aggregate practices. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.05 **P-Value Comment:** **Parameter Type:** Mean Relative Change (%) **Parameter Value:** 6.2 **Statistical Comment:** **Statistical Method:** t-test, 2 sided **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** -11.2 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 7.7 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Performance Measure #5: the relative change of Cohort B (6 months) compared with Cohort A at baseline in CRT-P/CRT-D for the aggregate practices. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.711 **P-Value Comment:** **Parameter Type:** Mean Relative Change (%) **Parameter Value:** -1.8 **Statistical Comment:** **Statistical Method:** t-test, 2 sided **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 6.9 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 22.0 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Performance Measure #6: the relative change of Cohort B (6 months) compared with Cohort A at baseline in ICD/CRT-D for the aggregate practices. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** <0.001 **P-Value Comment:** **Parameter Type:** Mean Relative Change (%) **Parameter Value:** 14.4 **Statistical Comment:** **Statistical Method:** t-test, 2 sided **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 23.2 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 53.8 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Performance Measure #7: the relative change of Cohort B (6 months) compared with Cohort A at baseline in HF education for the aggregate practices. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** <0.001 **P-Value Comment:** **Parameter Type:** Mean Relative Change (%) **Parameter Value:** 38.5 **Statistical Comment:** **Statistical Method:** t-test, 2 sided **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 4.2 **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:** Composite Score: the relative change of Cohort B (6 months) compared with Cohort A at baseline in composite score for the aggregate practices. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** <0.001 **P-Value Comment:** **Parameter Type:** Mean Relative Change (%) **Parameter Value:** 6.6 **Statistical Comment:** **Statistical Method:** t-test, 2 sided **Tested Non-Inferiority:** ### Outcome Measure 5 #### Analysis **CI Lower Limit:** -5.3 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 26.3 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Performance Measure #1: the relative change of Cohort C (18 months) compared with Cohort A at baseline in ACEI/ARB for the aggregate practices. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.190 **P-Value Comment:** **Parameter Type:** Mean Relative Change (%) **Parameter Value:** 10.5 **Statistical Comment:** **Statistical Method:** t-test, 2 sided **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 0.1 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 28.4 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Performance Measure #2: the relative change of Cohort C (18 months) compared with Cohort A at baseline in beta-blockers for the aggregate practices. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.048 **P-Value Comment:** **Parameter Type:** Mean Relative Change (%) **Parameter Value:** 14.3 **Statistical Comment:** **Statistical Method:** t-test, 2 sided **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** -3.9 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 15.4 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Performance Measure #3: the relative change of Cohort C (18 months) compared with Cohort A at baseline in aldosterone antagonist for the aggregate practices. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.240 **P-Value Comment:** **Parameter Type:** Mean Relative Change (%) **Parameter Value:** 5.8 **Statistical Comment:** **Statistical Method:** t-test, 2 sided **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 0.5 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 13.0 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Performance Measure #4: the relative change of Cohort C (18 months) compared with Cohort A at baseline in anticoagulation for AF for the aggregate practices. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.033 **P-Value Comment:** **Parameter Type:** Mean Relative Change (%) **Parameter Value:** 6.7 **Statistical Comment:** **Statistical Method:** t-test, 2 sided **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** -1.3 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 19.8 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Performance Measure #5: the relative change of Cohort C (18 months) compared with Cohort A at baseline in CRT-P/CRT-D for the aggregate practices. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.085 **P-Value Comment:** **Parameter Type:** Mean Relative Change (%) **Parameter Value:** 9.3 **Statistical Comment:** **Statistical Method:** t-test, 2 sided **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 9.3 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 25.8 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Performance Measure #6: the relative change of Cohort C (18 months) compared with Cohort A at baseline in ICD/CRT-D for the aggregate practices. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** <0.001 **P-Value Comment:** **Parameter Type:** Mean Relative Change (%) **Parameter Value:** 17.6 **Statistical Comment:** **Statistical Method:** t-test, 2 sided **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 33.9 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 85.2 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Performance Measure #7: the relative change of Cohort C (18 months) compared with Cohort A at baseline in HF education for the aggregate practices. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** <0.001 **P-Value Comment:** **Parameter Type:** Mean Relative Change (%) **Parameter Value:** 59.5 **Statistical Comment:** **Statistical Method:** t-test, 2 sided **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 7.6 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 13.6 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Composite Score: the relative change of Cohort C (18 months) compared with Cohort A at baseline in composite score for the aggregate practices. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** <0.001 **P-Value Comment:** **Parameter Type:** Mean Relative Change (%) **Parameter Value:** 10.6 **Statistical Comment:** **Statistical Method:** t-test, 2 sided **Tested Non-Inferiority:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 79.2 - **Spread:** - **Upper Limit:** 80.5 - **Value:** 79.8 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 85.6 - **Spread:** - **Upper Limit:** 87.3 - **Value:** 86.5 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** 7.0 - **Spread:** - **Upper Limit:** 9.7 - **Value:** 8.4 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 85.6 - **Spread:** - **Upper Limit:** 86.8 - **Value:** 86.2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 93.0 - **Spread:** - **Upper Limit:** 94.2 - **Value:** 93.6 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** 7.7 - **Spread:** - **Upper Limit:** 9.6 - **Value:** 8.6 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 32.7 - **Spread:** - **Upper Limit:** 36.1 - **Value:** 34.4 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 59.2 - **Spread:** - **Upper Limit:** 64.5 - **Value:** 61.8 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** 70.5 - **Spread:** - **Upper Limit:** 89.0 - **Value:** 79.7 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 67.2 - **Spread:** - **Upper Limit:** 70.0 - **Value:** 68.6 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 67.5 - **Spread:** - **Upper Limit:** 71.0 - **Value:** 69.3 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** -2.2 - **Spread:** - **Upper Limit:** 4.2 - **Value:** 1.0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 35.2 - **Spread:** - **Upper Limit:** 40.1 - **Value:** 37.7 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 65.8 - **Spread:** - **Upper Limit:** 71.3 - **Value:** 68.5 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** 72.2 - **Spread:** - **Upper Limit:** 91.7 - **Value:** 81.9 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 47.8 - **Spread:** - **Upper Limit:** 49.8 - **Value:** 48.8 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 78.0 - **Spread:** - **Upper Limit:** 80.2 - **Value:** 79.1 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** 59.1 - **Spread:** - **Upper Limit:** 65.1 - **Value:** 62.1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 61.0 - **Spread:** - **Upper Limit:** 62.5 - **Value:** 61.8 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 69.8 - **Spread:** - **Upper Limit:** 71.9 - **Value:** 70.8 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** 12.6 - **Spread:** - **Upper Limit:** 16.8 - **Value:** 14.7 **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 15 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 9 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 82 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 14 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 83 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 114 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 59 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 123 **Title:** #### Outcome Measure 3 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 11.5 - **Upper Limit:** - **Value:** 78.3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 10.6 - **Upper Limit:** - **Value:** 85.1 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 128.9 - **Upper Limit:** - **Value:** 19.4 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 10.8 - **Upper Limit:** - **Value:** 86.0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 9.8 - **Upper Limit:** - **Value:** 92.2 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 16.1 - **Upper Limit:** - **Value:** 7.6 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 18.5 - **Upper Limit:** - **Value:** 34.5 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 25.9 - **Upper Limit:** - **Value:** 60.3 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 33.8 - **Upper Limit:** - **Value:** 30.0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 16.1 - **Upper Limit:** - **Value:** 68.0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 18.0 - **Upper Limit:** - **Value:** 67.8 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 28.5 - **Upper Limit:** - **Value:** 1.0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 30.5 - **Upper Limit:** - **Value:** 37.2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 29.0 - **Upper Limit:** - **Value:** 66.3 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 62.3 - **Upper Limit:** - **Value:** 48.4 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 17.5 - **Upper Limit:** - **Value:** 50.1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 16.8 - **Upper Limit:** - **Value:** 77.5 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 62.4 - **Upper Limit:** - **Value:** 70.9 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 23.7 - **Upper Limit:** - **Value:** 59.5 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 24.0 - **Upper Limit:** - **Value:** 72.1 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 147.7 - **Upper Limit:** - **Value:** 50.6 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 8.9 - **Upper Limit:** - **Value:** 67.1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 9.3 - **Upper Limit:** - **Value:** 79.0 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 18.1 - **Upper Limit:** - **Value:** 19.2 **Title:** #### Outcome Measure 4 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 11.3 - **Upper Limit:** - **Value:** 78.7 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 10.6 - **Upper Limit:** - **Value:** 80.2 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 97.1 - **Upper Limit:** - **Value:** 10.3 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 10.9 - **Upper Limit:** - **Value:** 85.9 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 7.2 - **Upper Limit:** - **Value:** 90.0 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 68.9 - **Upper Limit:** - **Value:** 10.6 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 18.7 - **Upper Limit:** - **Value:** 34.7 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 20.7 - **Upper Limit:** - **Value:** 33.4 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 27.4 - **Upper Limit:** - **Value:** -1.1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 15.8 - **Upper Limit:** - **Value:** 67.9 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 17.4 - **Upper Limit:** - **Value:** 68.9 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 38.2 - **Upper Limit:** - **Value:** 6.2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 30.7 - **Upper Limit:** - **Value:** 37.6 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 27.8 - **Upper Limit:** - **Value:** 34.9 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 53.7 - **Upper Limit:** - **Value:** -1.8 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 17.0 - **Upper Limit:** - **Value:** 49.9 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 17.4 - **Upper Limit:** - **Value:** 52.7 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 46.9 - **Upper Limit:** - **Value:** 14.4 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 23.6 - **Upper Limit:** - **Value:** 59.4 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 20.8 - **Upper Limit:** - **Value:** 67.5 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 94.8 - **Upper Limit:** - **Value:** 38.5 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 8.8 - **Upper Limit:** - **Value:** 67.1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 8.0 - **Upper Limit:** - **Value:** 70.7 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 15.1 - **Upper Limit:** - **Value:** 6.6 **Title:** #### Outcome Measure 5 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 11.3 - **Upper Limit:** - **Value:** 78.7 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 12.2 - **Upper Limit:** - **Value:** 80.3 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 97.9 - **Upper Limit:** - **Value:** 10.5 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 10.9 - **Upper Limit:** - **Value:** 85.9 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 7.0 - **Upper Limit:** - **Value:** 91.8 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 87.7 - **Upper Limit:** - **Value:** 14.3 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 18.7 - **Upper Limit:** - **Value:** 34.7 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 23.1 - **Upper Limit:** - **Value:** 36.6 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 58.3 - **Upper Limit:** - **Value:** 5.8 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 15.8 - **Upper Limit:** - **Value:** 67.9 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 17.1 - **Upper Limit:** - **Value:** 69.6 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 38.3 - **Upper Limit:** - **Value:** 6.7 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 30.7 - **Upper Limit:** - **Value:** 37.6 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 30.1 - **Upper Limit:** - **Value:** 43.5 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 59.7 - **Upper Limit:** - **Value:** 9.3 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 17.0 - **Upper Limit:** - **Value:** 49.9 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 17.2 - **Upper Limit:** - **Value:** 54.0 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 51.3 - **Upper Limit:** - **Value:** 17.6 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 23.6 - **Upper Limit:** - **Value:** 59.4 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 22.6 - **Upper Limit:** - **Value:** 75.0 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 158.5 - **Upper Limit:** - **Value:** 59.5 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 8.8 - **Upper Limit:** - **Value:** 67.1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 8.4 - **Upper Limit:** - **Value:** 73.2 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 18.5 - **Upper Limit:** - **Value:** 10.6 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** 7 performance measures: angiotensin converting enzyme inhibitor and/or angiotensin II receptor blockers (ACEI/ARB), beta-blokers, aldosterone receptor antagonists, anticoagulation for atrial fibrillation (AF), cardiac resynchronization therapy (CRT-P/CRT-D), cardioverter-defibrillator (ICD/CRT-D), heart failure (HF) education. We first calcuated % of patients who were eligible for a performance measure that were treated by it at baseline and 24 months. We then calculated the relative change as (% treated at 24 months - % treated at baseline)/% treated at baseline. The 95% confidence interval (CI) was calculated and the relative change of each performance measure was evaluated using a z-test for one-sample proportion. The number of performance measures with \>= 20% relative improvement was determined. The intervention was considered successful if a relative 20% or greater improvement in at least 2 of the 7 performance measures at 24 months compared with baseline was achieved. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** NUMBER **Population Description:** 167 practices contributed data to the baseline chart review. Twelve of the practices withdrew from the study prior to the next chart review milestone. 155 of those practices' data contributed to the follow up of the longitudinal cohort time points of 12 and 24 months post educational workshop. **Reporting Status:** POSTED **Time Frame:** 24 Month **Title:** To Evaluate Over the Aggregate IMPROVE-HF Practice Sites the Relative Changes in 7 Performance Measures at 24 Months Compared With Baseline and Determine the Number of Performance Measures That Achieved a Relative 20% or Greater Positive Change. **Type:** PRIMARY **Unit of Measure:** percentage of participants in aggregate ##### Group **Description:** For this longitudinal cohort, data are collected at baseline, 12 months and 24 months after the principle investigator and HF nurse attend an educational workshop. All longitudinal analyses will be performed on this cohort of patients. This arm includes all the atients at baseline. Percentage of patients who were eligible for a performance measure that were treated by it at baseline was calculated. **ID:** OG000 **Title:** Cohort A (at Baseline) ##### Group **Description:** For this longitudinal cohort, data are collected at baseline, 12 months and 24 months after the principle investigator and HF nurse attend an educational workshop. All longitudinal analyses will be performed on this cohort of patients. This arm includes the completers, i.e. patients who have a qualifying visit at both baseline and 24 months who were living at the 24 month chart review and are qualified for at least one performance measure at 24 months. Percentage of the patients who were eligible for a performance measure that were treated by it at the 24 months was calculated. **ID:** OG001 **Title:** Cohort A (at 24 Months) ##### Group **Description:** For this longitudinal cohort, data are collected at baseline, 12 months and 24 months after the principle investigator and HF nurse attend an educational workshop. All longitudinal analyses will be performed on this cohort of patients. This arm includes the completers, i.e. patients who have a qualifying visit at both baseline and 24 months who were living at the 24 month chart review and are qualified for at least one performance measure at 24 months. The relative changes in the percentages from 24 months to baseline were calculated for the 7 performance measures. **ID:** OG002 **Title:** Cohort A (Relative Change 24 Months vs. Baseline) #### Outcome Measure 2 **Description:** The number of practices that achieved greater than or equal to 20% improvement in two or more of the 7 performance measures at 24 months as compared to baseline of cohort A is presented. **Parameter Type:** NUMBER **Reporting Status:** POSTED **Time Frame:** 24 months **Title:** Observe the Number of Sites That Demonstrate a Relative 20% or Greater Improvement in 2 or More of the 7 Performance Measures at 24 Months as Compared to Baseline in Cohort A. **Type:** SECONDARY **Type Units Analyzed:** Sites **Unit of Measure:** Sites ##### Group **Description:** In this analysis, 167 practices contributed data to the baseline chart review of Cohort A. Of them, 12 practices withdrew from the study prior to the next chart review milestone. Therefore, 155 practices' data contributed to the follow up of the longitudinal cohort time points of 12 and 24 months post educational workshop. Correspondingly there were 7605 patients whose chart review was completed at both baseline and 24 months. **ID:** OG000 **Title:** Practice Sites in Cohort A #### Outcome Measure 3 **Description:** performance measure improvement for each performance measure was analyzed at a practice level from baseline to 24 months. Performance measure adherence was calculated at the individual practice level and then combined and summarized. Mean, standard deviation, and 95% confidence intervals for performance measure adherence, composite score and relative change (24 months compared with baseline) are reported. The Composite Score is based on the ratio of the sum of the numerators of all individual performance measures to the sum of the denominators of all individual performances measures. The numerator of a performance measure is the number of patients treated with that measure. The denomiator of a performance measure is the number of patients eligible for being treated with that measure. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Reporting Status:** POSTED **Time Frame:** 24 months **Title:** Observe the Change From Baseline to 24 Months in Each Performance Measure and Composite Score for the Aggregate Practices. **Type:** SECONDARY **Type Units Analyzed:** Sites **Unit of Measure:** percentage ##### Group **Description:** Cohort A at baseline included 15177 patients from 167 study sites (practices). **ID:** OG000 **Title:** Cohort A (at Baseline) ##### Group **Description:** Cohort A at 24 months included 7605 patients from 155 study sites (practices). **ID:** OG001 **Title:** Cohort A (at 24 Months) ##### Group **Description:** The ralative changes in performance measures and compsite score at 24 months compared to baseline were calculated based on 155 study sites that involved 7605 patients. **ID:** OG002 **Title:** Cohort A (Relative Change 24 Months vs. Baseline) #### Outcome Measure 4 **Description:** The relative changes between baseline of cohort A and 6 months of cohort B in performance measures and composite score for the aggregate practices were calculated using mean, standard deviation and 95% CI. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Reporting Status:** POSTED **Time Frame:** Baseline and 6 Months **Title:** Observe the Relative Change Between Baseline of Cohort A and 6 Months of Cohort B in Performance Measures and Composite Score for the Aggregate Practices. **Type:** SECONDARY **Type Units Analyzed:** Sites **Unit of Measure:** percentage of participants ##### Group **Description:** In this analysis, data of Cohort A at baseline were used. This included 15177 patients from 167 cardiology practices. **ID:** OG000 **Title:** Cohort A: Baseline ##### Group **Description:** In this analysis, data of Cohort B (i.e. 6 months single time point cohort) were used. This included 9992 patients from 154 cardiology practices. **ID:** OG001 **Title:** Cohort B: 6 Months ##### Group **Description:** The relative changes in performance measures and composite score of Cohort B (6 months) compared with those of Cohort A at baseline were calculated **ID:** OG002 **Title:** Cohort B 6 Months vs. Cohort A Baseline (Relative Change) #### Outcome Measure 5 **Description:** The relative changes between baseline of cohort A and 18 months of cohort C in performance measures and composite score for the aggregate practices were calculated using mean, standard deviation and 95% CI. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Reporting Status:** POSTED **Time Frame:** baseline and 18 Months **Title:** Observe the Relative Change Between Baseline of Cohort A and 18 Months of Cohort C in Performance Measures and Composite Score for the Aggregate Practices. **Type:** SECONDARY **Type Units Analyzed:** Sites **Unit of Measure:** percentage of participants ##### Group **Description:** In this analysis, data of Cohort A at baseline were used. This included 15177 patients from 167 cardiology practices. **ID:** OG000 **Title:** Cohort A: Baseline ##### Group **Description:** In this analysis, data of Cohort C (i.e. 18 months single time point cohort) were used. This included 9641 patients from 150 cardiology practices. **ID:** OG001 **Title:** Cohort C (18 Months) ##### Group **Description:** The relative changes in performance measures and composite score of Cohort C (18 months) compared with those of Cohort A at baseline were calculated. **ID:** OG002 **Title:** Cohort C 18 Months vs. Cohort A Baseline (Relative Change) ### Participant Flow Module #### Group **Description:** Cohort A: The charts of 15,177 patients were reviewed at baseline, 12 months and 24 months. The principal investigator and HF nurse of the study sites attended an educational workshop at baseline, 12 and 24 months as well where they were provided with tools meant to improve HF care at their practices. The tools included tip cards, worksheets, and patient education materials. Cohort A is a longitudinal cohort. **ID:** FG000 **Title:** Cohort A (Baseline, 12 and 24 Months) #### Group **Description:** Cohort B: The charts of 9,992 patients were reviewed at 6 months. The principal investigator and HF nurse of the study sites attended an educational workshop at the same time where they were provided with tools meant to improve HF care at their practices. The tools included tip cards, worksheets, and patient education materials. Cohort B is a single time point cohort. **ID:** FG001 **Title:** Cohort B (6 Months) #### Group **Description:** Cohort C: The charts of 9,641 patients were reviewed at 18 months. The principal investigator and HF nurse of the study sites attended an educational workshop at the same time where they were provided with tools meant to improve HF care at their practices. The tools included tip cards, worksheets, and patient education materials. Cohort C is a single time point cohort. **ID:** FG002 **Title:** Cohort C (18 Months) #### Period **Title:** Overall Study ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 15177 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 9992 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 9641 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 7605 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 9992 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 9641 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 7572 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 0 **Pre-Assignment Details:** The study included 3 mutually exclusive patient cohorts. Patients in cohort A were reviewed at baseline, 12 and 24 months. This is also called the longitudinal cohort. Patients in cohort B and C were reviewed at 6 and 18 months, respectively. These two cohorts are referred to as the single time point cohorts. **Recruitment Details:** The study sites included outpatient cardiology practices in the United States. Patients diagnosed with heart failure or prior myocardial infarction or developed moderate-severe left ventricular dysfunction were included. Each cardiology practice had five chart reviews and an educational workshop as a part of the process improvement intervention. **Has Results:** True