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## Protocol Section ### Identification Module **NCT ID:** NCT05886179 **Brief Title:** COVID-19 IN CHILDREN IN NIGER, 2020 **Official Title:** Factors Associated With COVID-19 in Children Aged 0-15 Years in Niger, 2020 #### Organization Study ID Info **ID:** CERMES #### Organization **Class:** OTHER **Full Name:** Centre de Recherche Médicale et Sanitaire ### Status Module #### Completion Date **Date:** 2021-01-15 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2023-06-02 **Type:** ACTUAL **Last Update Submit Date:** 2023-05-31 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2020-08-28 **Type:** ACTUAL #### Start Date **Date:** 2020-02-25 **Type:** ACTUAL **Status Verified Date:** 2023-05 #### Study First Post Date **Date:** 2023-06-02 **Type:** ACTUAL **Study First Submit Date:** 2023-05-31 **Study First Submit QC Date:** 2023-05-31 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Centre de Recherche Médicale et Sanitaire #### Responsible Party **Investigator Affiliation:** Centre de Recherche Médicale et Sanitaire **Investigator Full Name:** IDE AMADOU Habibatou **Investigator Title:** Doctor **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** On January 30, 2020, the WHO declared COVID-19 a global health emergency. Children were affected with less severe forms. Niger had implemented measures in a context where children are a source of contamination. The objective was to determine the factors associated with COVID-19 in children in Niger from February to August 2020 through an analysis of the national database. **Detailed Description:** We conducted an analytical cross-sectional study including all COVID-19 suspects in the database. We used Excel and Epi Info 7.2.4. software for data extraction and analysis. Frequencies and proportions were calculated, we estimated in a logistic regression the OR of association with their 95% confidence interval, the factors associated with COVID-19 at the threshold of p\<0.05. Results: Of 572 notified suspected COVID-19 cases in children aged 0-15 years, 11.36% were positive. The median age of infected children was 10 years \[IQR: 5- 13 years\]. The sex ratio of males to females was 2.1. Children aged 11-15 years were 49.2%, 61.5% resided in Niamey, 4.6% had comorbidities. The notion of travel was 12.3% and 40% had a notion of contact, 24.4% had a fever, 23.2% had a cough, 18% were hospitalized and the case fatality was 1.5%. In etiological analysis, the factors associated with COVID-19 were sex ORa= 0.51 \[0.28-0.93\] p=0.028, the presence of symptoms ORa= 2.29 \[1.23-4.25\] p=0.008 and the notion of contact ORa= 0.32 \[0.13-0.77\] p=0.011. exposed children were sensitive to COVID-19, all age groups were affected with a male predominance. We recommend barrier measures adapted to young people, early detection and management of infected children. ### Conditions Module **Conditions:** - to Contribute to a Better Control of COVID-19 in Children in Niger **Keywords:** - factors, COVID-19, children, database, Niger ### Design Module #### Design Info **Observational Model:** OTHER **Time Perspective:** RETROSPECTIVE #### Enrollment Info **Count:** 572 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module ### Interventions #### Intervention 1 **Description:** analytical cross-sectional study with retrospective collection of epidemiological surveillance data on COVID-19 in Niger. **Name:** cross-sectional study **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** The first step concerned the descriptive part where the frequencies, proportions, means and extreme values of the variables were calculated. Some of these variables were presented in the form of tables and graphs. **Measure:** data base analysis **Time Frame:** May 2021 ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Children aged 0-15 years suspected of having COVID-19 whose data were in the DSRE database were included Exclusion Criteria: * Children whose data is not complete **Maximum Age:** 15 Years **Minimum Age:** 0 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - CHILD **Study Population:** This was an analytical cross-sectional study with retrospective collection of epidemiological surveillance data on COVID-19 in Niger. The study period spanned six (6) months from February 25 to August 28, 2020. Children aged 0-15 years suspected of having COVID-19 whose data were in the DSRE database were included. We used the data extraction form that served as a secondary database containing only our variables of interest. ### Contacts Locations Module #### Locations **Location 1:** **City:** Niamey **Country:** Niger **Facility:** IDE AMADOU Habibatou **Zip:** BP: 10887, Niamey, Niger ### IPD Sharing Statement Module **Description:** What is IPD ? **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000011024 - Term: Pneumonia, Viral - ID: D000011014 - Term: Pneumonia - ID: D000012141 - Term: Respiratory Tract Infections - ID: D000007239 - Term: Infections - ID: D000014777 - Term: Virus Diseases - ID: D000018352 - Term: Coronavirus Infections - ID: D000003333 - Term: Coronaviridae Infections - ID: D000030341 - Term: Nidovirales Infections - ID: D000012327 - Term: RNA Virus Infections - ID: D000008171 - Term: Lung Diseases - ID: D000012140 - Term: Respiratory Tract Diseases ### 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

## Protocol Section ### Identification Module **NCT ID:** NCT05693779 **Acronym:** EXPECT-PH **Brief Title:** Exercise Therapy After Pulmonary Thromboendarterectomy or Balloon Pulmonary Angioplasty for Chronic Thromboembolic Pulmonary Hypertension **Official Title:** Exercise Therapy After Pulmonary Thromboendarterectomy or Balloon Pulmonary Angioplasty for Chronic Thromboembolic Pulmonary Hypertension: EXPECT-PH #### Organization Study ID Info **ID:** HUM00214495 #### Organization **Class:** OTHER **Full Name:** University of Michigan ### Status Module #### Completion Date **Date:** 2024-02 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2023-06-07 **Type:** ACTUAL **Last Update Submit Date:** 2023-06-05 **Overall Status:** WITHDRAWN #### Primary Completion Date **Date:** 2024-02 **Type:** ESTIMATED #### Start Date **Date:** 2023-05 **Type:** ESTIMATED **Status Verified Date:** 2023-06 #### Study First Post Date **Date:** 2023-01-23 **Type:** ACTUAL **Study First Submit Date:** 2023-01-11 **Study First Submit QC Date:** 2023-01-11 **Why Stopped:** Administrative Changes. ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** University of Michigan #### Responsible Party **Investigator Affiliation:** University of Michigan **Investigator Full Name:** Brahmajee K Nallamothu **Investigator Title:** Professor of Internal Medicine **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False ### Description Module **Brief Summary:** This study is being completed to determine the feasibility and acceptability of completing a home-based, structured, low-to-moderate intensity exercise training program in chronic thromboembolic pulmonary hypertension (CTEPH) patients following surgical or percutaneous intervention. Eligible participants will be enrolled and have a 12 week home based exercise training program. The study team hypothesizes that: The following percentage of participants successfully complete the ramp-up phase of the exercise program: * Greater or equal to 70% at end of week 7 * Greater or equal to 80% at end of week 10 * Greater or equal to 90% at end of week 12 * Greater or equal to 80% of participants will both complete ≥1 week of maintenance phase exercise and complete 12 weeks of the exercise intervention. * Patients will have no adverse events, defined as syncope, worsening World Health Organization (WHO) functional class, pulmonary hypertension (PH) related hospitalization, or death, caused by the exercise intervention. ### Conditions Module **Conditions:** - Chronic Thromboembolic Pulmonary Hypertension **Keywords:** - Exercise - Balloon pulmonary angioplasty - Pulmonary thromboendarterectomy - Smart watch - Treadmill exercise test ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Individualized exercise prescription will be provided based on the gathered cardiopulmonary exercise test data. **Intervention Names:** - Behavioral: Home exercise training **Label:** Home exercise training **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Home exercise training **Description:** Participants will complete an Exercise Treadmill Test at baseline. The 12 weeks exercise program that will be assigned to each patient will be based on these results. The exercise will be three 20-minute exercise sessions per week for 6 weeks. This will increase to four 60-minute exercise sessions per week at increased intensity progressively over the course of the exercise program. The exercise program will involve walking/jogging, elliptical training, or biking 3-4 times per week for up to an hour each session. If participants don't have access to a bike or elliptical, they will be asked to exercise by walking/jogging. Participants will also a phone call or video chat that takes about 15 minutes per week to discuss the exercise program and take 2 short surveys weekly on the MyDataHelps application and filling out a logbook recording exercise sessions. In addition, participants activity will be measured by using a smartwatch during the study. **Name:** Home exercise training **Type:** BEHAVIORAL ### Outcomes Module #### Primary Outcomes **Description:** Based on intervention weeks 1-7. Compliance data will be documented by participants in virtual exercise logs and reviewed weekly with the study team. **Measure:** Percentage of participants who complete the ramp-up phase of the exercise program at end of week 7 of the intervention **Time Frame:** Week 7 **Description:** Based on intervention weeks 1-10. Compliance data will be documented by participants in virtual exercise logs and reviewed weekly with the study team. **Measure:** Percentage of participants who complete the ramp-up phase of the exercise program at end of week 10 of the intervention **Time Frame:** Week 10 **Description:** Based on intervention weeks 1-12. Compliance data will be documented by participants in virtual exercise logs and reviewed weekly with the study team. **Measure:** Percentage of participants who complete the ramp-up phase of the exercise program at end of week 12 of the intervention **Time Frame:** Week 12 #### Secondary Outcomes **Description:** These will be defined as hospitalization due to CTEPH-specific decompensation, worsening World Health Organization (WHO) functional class, syncope, and death. **Measure:** Number of adverse events **Time Frame:** 12 weeks ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Chronic Thromboembolic Pulmonary Hypertension (CTEPH) patients post-Pulmonary Thromboendarterectomy (PTE) or Balloon Pulmonary Angioplasty (BPA) * Planned follow-up at Michigan Medicine for at least one year * Has access to an Android or iPhone with study supported operating software, is willing to install MyDataHelps application, and is willing to wear a smart watch while awake Exclusion Criteria: * Life expectancy under 1 year * Orthopedic, neurological, or psychiatric condition limiting ability to actively engage in exercise training session * Currently receiving palliative care and/or in hospice care * Persistent severe Right Ventricular (RV) dysfunction on echocardiography post BPA or PTE * Recently completed, current enrollment, or planned enrollment in pulmonary rehabilitation * Moderate or severe obstructive lung disease or restrictive lung disease * Arterial oxygen saturation (SpO2) \<88% during 6 minute walk test(6MWT) on baseline home oxygen prescription * Wrist too large to wear a smart watch comfortably. * Participant noted to wear smart watch for less than 8 hours per day prior to intervention. * Determined to be unsafe for participation in exercise therapy as assessed by the clinical team. * Those with mobility issues that are unable to complete 6MWT. * Participant has sex minute walk distance (6MWD) greater or equal to 90% predicted at visit 1. * Pregnancy or lactation * Non-English speaking **Maximum Age:** 75 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Overall Officials **Official 1:** **Affiliation:** University of Michigan **Name:** Vikas Aggarwal, MD **Role:** PRINCIPAL_INVESTIGATOR **Official 2:** **Affiliation:** University of Michigan **Name:** Bramajee Nallamothu, MD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000014652 - Term: Vascular Diseases - ID: D000002318 - Term: Cardiovascular Diseases - ID: D000008171 - Term: Lung Diseases - ID: D000012140 - Term: Respiratory Tract Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC08 - Name: Respiratory Tract (Lung and Bronchial) Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M10024 - Name: Hypertension - Relevance: HIGH - As Found: Hypertension - ID: M10027 - Name: Hypertension, Pulmonary - Relevance: HIGH - As Found: Pulmonary Hypertension - ID: M17400 - Name: Vascular Diseases - Relevance: LOW - As Found: Unknown - ID: M11168 - Name: Lung Diseases - Relevance: LOW - As Found: Unknown - ID: M14977 - Name: Respiratory Tract Diseases - Relevance: LOW - As Found: Unknown - ID: T1303 - Name: Chronic Graft Versus Host Disease - Relevance: LOW - As Found: Unknown - ID: T1316 - Name: Chronic Thromboembolic Pulmonary Hypertension - Relevance: HIGH - As Found: Chronic Thromboembolic Pulmonary Hypertension ### Condition Browse Module - Meshes - ID: D000006976 - Term: Hypertension, Pulmonary - ID: D000006973 - Term: Hypertension ### Misc Info Module #### Removed Countries - Country: United States - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04424979 **Brief Title:** Feasibility Tests for Various Prism Configurations for Visual Field Loss **Official Title:** Visual Field Expansion Through Innovative Multi-Periscopic Prism Design #### Organization Study ID Info **ID:** MPP_Feasibility1 #### Organization **Class:** OTHER **Full Name:** Massachusetts Eye and Ear Infirmary #### Secondary ID Infos **ID:** R01EY023385 **Link:** https://reporter.nih.gov/quickSearch/R01EY023385 **Type:** NIH ### Status Module #### Completion Date **Date:** 2024-08 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-03-13 **Type:** ACTUAL **Last Update Submit Date:** 2024-03-11 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2024-08 **Type:** ESTIMATED #### Start Date **Date:** 2020-11-06 **Type:** ACTUAL **Status Verified Date:** 2024-03 #### Study First Post Date **Date:** 2020-06-11 **Type:** ACTUAL **Study First Submit Date:** 2020-06-05 **Study First Submit QC Date:** 2020-06-08 ### Sponsor Collaborators Module #### Collaborators **Class:** NIH **Name:** National Eye Institute (NEI) #### Lead Sponsor **Class:** OTHER **Name:** Massachusetts Eye and Ear Infirmary #### Responsible Party **Investigator Affiliation:** Massachusetts Eye and Ear Infirmary **Investigator Full Name:** Eli Peli **Investigator Title:** Senior Scientist **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** True **Is FDA Regulated Drug:** False **Is US Export:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** The investigators will develop and test different configurations of high-power prisms to expand the field of vision of patients with visual field loss to assist them with obstacle detection when walking. The study will involve multiple visits (typically four) to Schepens Eye Research Institute for fitting and testing with the prism glasses. The overall objective is to determine best designs and fitting parameters for implementation in prism devices for future clinical trials. ### Conditions Module **Conditions:** - Hemianopia, Homonymous - Tunnel Vision - Visual Field Defect, Peripheral - Visual Field Constriction Bilateral - Visual Field Defect Homonymous Bilateral **Keywords:** - Visual field expansion - Prisms - Hemianopsia - Tunnel vision - Visual field loss ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** DEVICE_FEASIBILITY #### Enrollment Info **Count:** 20 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Various configurations of high power prisms will be developed for each individual and custom fit into spectacles lenses. **Intervention Names:** - Device: High power prisms **Label:** High power prisms **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - High power prisms **Description:** High power prisms designed to shift images from blind areas into portions of the wearer's remaining, seeing, field of vision **Name:** High power prisms **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Description:** Horizontal and vertical extent of the expansion (in degrees) of the field of view **Measure:** Field of view expansion **Time Frame:** Through study completion, an average of four months #### Secondary Outcomes **Description:** Proportion of pedestrians detected (in simulated walking or simulated driving) **Measure:** Pedestrian detection rate **Time Frame:** Through study completion, an average of four months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Visual field loss, either peripheral field loss or hemianopic field loss * Visual acuity of at least 20/50 in the better eye * In sufficiently good health to be able to complete sessions lasting 2-4 hours * Able to independently walk short distances * Able to give voluntary, informed consent * Able to speak English Exclusion Criteria: * Any physical or mental impairments, including cognitive dysfunction, balance problems or other deficits that could impair the ability to walk or use the prism spectacles * A history of seizures in the last 6 months * Hemispatial neglect (subjects with hemianopic field loss only) **Maximum Age:** 80 Years **Minimum Age:** 7 Years **Sex:** ALL **Standard Ages:** - CHILD - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Sailaja Manda **Phone:** 617 912 2522 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Alex Bowers, PhD **Phone:** 617 912 2512 **Role:** CONTACT #### Locations **Location 1:** **City:** Boston **Country:** United States **Facility:** Schepens Eye Research Institute **State:** Massachusetts **Status:** RECRUITING **Zip:** 02114 #### Overall Officials **Official 1:** **Affiliation:** Schepens Eye Research Institute of Massachusetts Eye and Ear **Name:** Eliezer Peli, MSc, OD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## 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: D000001766 - Term: Blindness - ID: D000005128 - Term: Eye 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: BC11 - Name: Eye Diseases ### Condition Browse Module - Browse Leaves - ID: M6475 - Name: Constriction, Pathologic - Relevance: LOW - As Found: Unknown - ID: M9509 - Name: Hemianopsia - Relevance: HIGH - As Found: Hemianopia, Homonymous - 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: M5047 - Name: Blindness - Relevance: LOW - As Found: Unknown - ID: M8271 - Name: Eye Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000006423 - Term: Hemianopsia ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT01589679 **Acronym:** Bunionectomy **Brief Title:** Contracture Reduction Following Bunionectomy: a Longitudinal, Controlled Trial **Official Title:** Contracture Reduction Following Bunionectomy: a Longitudinal, Controlled Trial #### Organization Study ID Info **ID:** DYN1-12-047 #### Organization **Class:** INDUSTRY **Full Name:** Dynasplint Systems, Inc. ### Status Module #### Expanded Access Info #### Last Update Post Date **Date:** 2013-08-12 **Type:** ESTIMATED **Last Update Submit Date:** 2013-08-08 **Overall Status:** TERMINATED #### Primary Completion Date **Date:** 2016-05 **Type:** ESTIMATED #### Start Date **Date:** 2012-04 **Status Verified Date:** 2013-08 #### Study First Post Date **Date:** 2012-05-02 **Type:** ESTIMATED **Study First Submit Date:** 2012-04-30 **Study First Submit QC Date:** 2012-04-30 **Why Stopped:** Unrelated to Trial ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Dynasplint Systems, Inc. #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** To determine the efficacy of Metatarsal Dynasplint Sytem (MTP) in reducing contracture of hallux limitus secondary to Bunionectomy, in a longitudinal, controlled trial. ### Conditions Module **Conditions:** - Hallux Limitus ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** CROSSOVER ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 40 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** ALL SUBJECTS WILL RECEIVE SHOE INSERTS AND HOME STRETCHING REGIME. Control subjects will be treated with the Standard of Care during the first 12 weeks, but after the 12 weeks patients will be fit with MTP, which delivers a low-load, prolonged-duration stretch after completion of this study. **Intervention Names:** - Other: standard of care **Label:** control/ standard of care **Type:** OTHER #### Arm Group 2 **Description:** ALL SUBJECTS WILL RECEIVE SHOE INSERTS AND HOME STRETCHING REGIME. Experimental subjects will be immediated treated with the Metatarsal Dynasplint, which delivers a low-load, prolonged-duration stretch for 60 minutes, three times per day. **Intervention Names:** - Device: Metarsal Dynasplint **Label:** Dynasplint **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - control/ standard of care **Description:** Dynamic Splinting utilizes the protocols of Low-Load, Prolonged-Duration Stretch (LLPS) with calibrated, adjustable tension to increase the Total End Range Time (TERT) to reduce contracture. This unit is work for 60 minutes three times per day. **Name:** standard of care **Type:** OTHER #### Intervention 2 **Arm Group Labels:** - Dynasplint **Description:** Dynamic Splinting utilizes the protocols of Low-Load, Prolonged-Duration Stretch (LLPS) with calibrated, adjustable tension to increase the Total End Range Time (TERT) to reduce contracture. This unit is work for 60 minutes three times per day. **Name:** Metarsal Dynasplint **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Description:** ANOVA will be performed to measure different in category, pain, duration to full restoration of active range of motion(AROM). **Measure:** A Repeated Measures Analysis of Variance (ANOVA) **Time Frame:** 12 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Diagnosis 1st MTJ Contracture following Bunionectomy Exclusion Criteria: * Current treatment with Botulinium Toxin-A (Botox), lower extremity * Current treatment Fluoroquinolones (antibiotic medication) * Current use of muscle relaxant medications * Fibromyalgia * Stroke, CVA, Brain Injury, Spinal Cord Injury, or any neural pathology causing plasticity or hypertonicity * Treatment with electrical stimulation assisting ambulation (i.e Bioness, WalkAide, Parastep, etc.) **Maximum Age:** 90 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Boston **Country:** United States **Facility:** Tufts Medical Center **State:** Massachusetts **Zip:** 02111 **Location 2:** **City:** Henderson **Country:** United States **Facility:** Brown Hand Center and Achilles Foot & Ankle Specialist **State:** Nevada **Zip:** 89052 **Location 3:** **City:** Houston **Country:** United States **Facility:** Advanced Diagnostic Foot and Ankle Specialist of Cy-Fair **State:** Texas **Zip:** 77095 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000007592 - Term: Joint Diseases - ID: D000009140 - Term: Musculoskeletal Diseases - ID: D000009135 - Term: Muscular Diseases - ID: D000005531 - Term: Foot Deformities, Acquired - ID: D000005530 - Term: Foot Deformities - ID: D000018409 - Term: Foot Injuries - ID: D000007869 - Term: Leg Injuries - ID: D000014947 - Term: Wounds and Injuries ### 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 - Abbrev: BC16 - Name: Diseases and Abnormalities at or Before Birth ### Condition Browse Module - Browse Leaves - ID: M6510 - Name: Contracture - Relevance: HIGH - As Found: Contracture - ID: M22606 - Name: Hallux Rigidus - Relevance: HIGH - As Found: Hallux Limitus - ID: M22604 - Name: Hallux Limitus - Relevance: HIGH - As Found: Hallux Limitus - ID: M10621 - Name: Joint Diseases - Relevance: LOW - As Found: Unknown - ID: M12097 - Name: Musculoskeletal Diseases - Relevance: LOW - As Found: Unknown - ID: M12092 - Name: Muscular Diseases - Relevance: LOW - As Found: Unknown - ID: M12 - Name: Congenital Abnormalities - Relevance: LOW - As Found: Unknown - ID: M8654 - Name: Foot Deformities - Relevance: LOW - As Found: Unknown - ID: M8656 - Name: Foot Deformities, Congenital - Relevance: LOW - As Found: Unknown - ID: M8655 - Name: Foot Deformities, Acquired - Relevance: LOW - As Found: Unknown - ID: M20528 - Name: Foot Injuries - Relevance: LOW - As Found: Unknown - ID: M10881 - Name: Leg Injuries - Relevance: LOW - As Found: Unknown - ID: M17685 - Name: Wounds and Injuries - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000003286 - Term: Contracture - ID: D000020857 - Term: Hallux Limitus - ID: D000020859 - Term: Hallux Rigidus ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03635879 **Brief Title:** Medical Food Formulation Pharmacokinetic (PK) Study in Medium Chain Triglycerides **Official Title:** A Phase 1, Single-Center, Pilot, Single-Dose, 6-Way Crossover Study to Compare Six Formulations of Medium Chain Triglycerides on the Pharmacokinetics of Ketone Body Production #### Organization Study ID Info **ID:** AX-18-018_PK #### Organization **Class:** INDUSTRY **Full Name:** Cerecin ### Status Module #### Completion Date **Date:** 2019-04-16 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2018-09-27 **Type:** ACTUAL **Last Update Submit Date:** 2018-09-25 **Overall Status:** WITHDRAWN #### Primary Completion Date **Date:** 2019-04-16 **Type:** ESTIMATED #### Start Date **Date:** 2019-02-13 **Type:** ESTIMATED **Status Verified Date:** 2018-09 #### Study First Post Date **Date:** 2018-08-17 **Type:** ACTUAL **Study First Submit Date:** 2018-08-16 **Study First Submit QC Date:** 2018-08-16 **Why Stopped:** Study redesign ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Cerecin #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** True **Is US Export:** True **Oversight Has DMC:** False ### Description Module **Brief Summary:** This is a Phase I, open label, randomized, 6-way crossover, pilot PK study **Detailed Description:** 12 healthy, male subjects enrolled, subject will be randomized to receive a single dose of one of six treatment, with a 2 day washout in between each dosing period. ### Conditions Module **Conditions:** - Alzheimer Disease ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** CROSSOVER ##### Masking Info **Masking:** NONE **Primary Purpose:** OTHER #### Enrollment Info **Type:** ACTUAL **Phases:** - PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Vitaflo MCTprocal, single dose (20 g MCT) **Intervention Names:** - Other: MCTprocal medical food **Label:** MCTprocal medical food **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** Lactose-free milk and tricaprilin oil, blended,single dose (20 g tricaprilin) **Intervention Names:** - Other: Milk/tricaprilin oil blend **Label:** Milk/tricaprilin oil blend **Type:** ACTIVE_COMPARATOR #### Arm Group 3 **Description:** AC-1207 liquid, single dose (20 g tricaprilin) **Intervention Names:** - Other: AC-1207 **Label:** AC-1207 **Type:** ACTIVE_COMPARATOR #### Arm Group 4 **Description:** AC-1205 liquid, single dose (20 g tricaprilin) **Intervention Names:** - Other: AC-1205 **Label:** AC-1205 **Type:** ACTIVE_COMPARATOR #### Arm Group 5 **Description:** AC-1206 liquid, single dose (20 g tricaprilin) **Intervention Names:** - Other: AC-1206 **Label:** AC-1206 **Type:** ACTIVE_COMPARATOR #### Arm Group 6 **Description:** AC-1206 liquid, single dose (20 g tricaprilin) **Intervention Names:** - Drug: AC-1202 **Label:** AC-1202 **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - MCTprocal medical food **Description:** 32 g MCTprocal (20 g MCT) mixed in 180 mL of water at Hour 0 Day 1 **Name:** MCTprocal medical food **Type:** OTHER #### Intervention 2 **Arm Group Labels:** - Milk/tricaprilin oil blend **Description:** 154 mL of lactose-free skim milk/21 mL of tricaprilin oil blended and then mixed in 180 mL of water at Hour 0 Day 1 **Name:** Milk/tricaprilin oil blend **Type:** OTHER #### Intervention 3 **Arm Group Labels:** - AC-1207 **Description:** AC-1207 (20 g MCT) mixed in 180 mL of water at Hour 0 Day 1 **Name:** AC-1207 **Type:** OTHER #### Intervention 4 **Arm Group Labels:** - AC-1205 **Description:** AC-1205 (20 g MCT) mixed in 180 mL of water at Hour 0 Day 1 **Name:** AC-1205 **Type:** OTHER #### Intervention 5 **Arm Group Labels:** - AC-1206 **Description:** AC-1206 (20 g MCT) mixed in 180 mL of water at Hour 0 Day 1 **Name:** AC-1206 **Type:** OTHER #### Intervention 6 **Arm Group Labels:** - AC-1202 **Description:** AC-1202 (20 g MCT) mixed in 240 mL of water at Hour 0 Day 1 **Name:** AC-1202 **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Area Under the Curve (AUC) AUC 0 - last **Measure:** Total ketones **Time Frame:** 1 day **Description:** AUC 0 - 4 **Measure:** Total ketones **Time Frame:** 1 day **Description:** AUC 0 - 6 **Measure:** Total ketones **Time Frame:** 1 day **Description:** AUC 0 - 8 **Measure:** Total ketones **Time Frame:** 1 day **Description:** Maximum Plasma Concentration (Cmax) **Measure:** Total ketones **Time Frame:** 1 day **Description:** AUC 0 - last **Measure:** B-hydroxybutyrate **Time Frame:** 1 day **Description:** AUC 0 - 4 **Measure:** B-hydroxybutyrate **Time Frame:** 1 day **Description:** AUC 0 - 6 **Measure:** B-hydroxybutyrate **Time Frame:** 1 day **Description:** AUC 0 - 8 **Measure:** B-hydroxybutyrate **Time Frame:** 1 day **Description:** Cmax **Measure:** B-hydroxybutyrate **Time Frame:** 1 day **Description:** AUC 0 - last **Measure:** Acetoacetate **Time Frame:** 1 day **Description:** AUC 0 - 4 **Measure:** Acetoacetate **Time Frame:** 1 day **Description:** AUC 0 - 6 **Measure:** Acetoacetate **Time Frame:** 1 day **Description:** AUC 0 - 8 **Measure:** Acetoacetate **Time Frame:** 1 day **Description:** Cmax **Measure:** Acetoacetate **Time Frame:** 1 day ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Healthy, adult, male 18 55 years of age, inclusive, at Screening. 2. Continuous non smoker who has not used nicotine containing products for at least 3 months prior to Day -1 of Period 1 and throughout the study based on self-reporting. 3. Body mass index (BMI) ≥ 18.0 and ≤ 32.0 kg/m2 at Screening. 4. Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs or ECGs, as deemed by the PI or designee. At screening, subjects must have alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) ≤ the upper limit of normal and triglyceride levels must be \< 250 mg/dL. 5. Hemoglobin levels ≥ the lower limit of normal at Screening and Day -1 of Period 1. 6. A non vasectomized subject must agree to use a condom with spermicide or abstain from sexual intercourse during the study. (No restrictions are required for a vasectomized male provided his vasectomy has been performed 4 months or more prior to Day -1 of Period 1. A subject who has been vasectomized less than 4 months prior to Day -1 of Period 1 must follow the same restrictions as a non vasectomized male). 7. Understands the study procedures in the informed consent form (ICF), and be willing and able to comply with the protocol. Exclusion Criteria: 1. Subject is mentally or legally incapacitated or has significant emotional problems at the time of the screening visit or expected during the conduct of the study. 2. History or presence of clinically significant medical or psychiatric condition or disease in the opinion of the PI or designee. 3. History of any illness that, in the opinion of the PI or designee, might confound the results of the study or poses an additional risk to the subject by their participation in the study. 4. History or presence of alcoholism or drug abuse within the past year prior to Day -1 of Period 1. 5. History or presence of galactosemia or hypersensitivity or idiosyncratic reaction to the study drugs, related compounds, milk, palm or coconut oil, or soy. 6. History or presence of symptomatic diverticular disease, uncontrolled gastroesophageal reflux disease, ulcers, inflammatory bowel disease, irritable bowel syndrome or recurrent diarrhea, or gout. 7. Positive urine drug results at Screening or Check-in. 8. Positive alcohol results at Screening or Check-in. One repeat assessment is permitted. 9. Positive results at Screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV). 10. Seated blood pressure is less than 90/40 mmHg or greater than 140/90 mmHg at Screening. One repeat assessment is permitted. 11. Seated heart rate is lower than 40 bpm or higher than 99 bpm at Screening. 12. QTcF interval is \>460 msec or subject has ECG findings deemed abnormal with clinical significance by the PI or designee at Screening. 13. Estimated creatinine clearance ≤ 80 mL/min at Screening. 14. Unable to refrain from or anticipates the use of any drug, including prescription and non-prescription medications, herbal remedies, or vitamin supplements beginning 14 days prior to Day -1 of Period 1 and throughout the study. Acetaminophen (up to 2 g per 24 hours) may be permitted during the study. 15. Has been on a diet incompatible with the on-study diet, in the opinion of the PI or designee, within the 28 days prior to Day -1 of Period 1 and throughout the study. 16. Has been following a ketogenic diet, in the opinion of the PI or designee, within 2 weeks prior to Day -1 of Period 1. 17. Is lactose intolerant. 18. Is unable to complete the standard breakfast prior to dosing on Day 1 of each Period. 19. Donation of blood or significant blood loss within 56 days prior to Day -1 of Period 1. 20. Plasma donation within 7 days prior to Day -1 of Period 1. 21. Participation in another clinical study within 28 days prior to Day -1 of Period 1. The 28-day window will be derived from the date of the last blood collection or dosing, whichever is later, in the previous study to Day -1 of Period 1 of the current study. **Healthy Volunteers:** True **Maximum Age:** 55 Years **Minimum Age:** 18 Years **Sex:** MALE **Standard Ages:** - ADULT ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000003704 - Term: Dementia - ID: D000001927 - Term: Brain Diseases - ID: D000002493 - Term: Central Nervous System Diseases - ID: D000009422 - Term: Nervous System Diseases - ID: D000024801 - Term: Tauopathies - ID: D000019636 - Term: Neurodegenerative Diseases - ID: D000019965 - Term: Neurocognitive Disorders - ID: D000001523 - Term: Mental Disorders ### Condition Browse Module - Browse Branches - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: BXM - Name: Behaviors and Mental Disorders - Abbrev: All - Name: All Conditions - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M3885 - Name: Alzheimer Disease - Relevance: HIGH - As Found: Alzheimer's Disease - ID: M6904 - Name: Dementia - 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: M23002 - Name: Tauopathies - Relevance: LOW - As Found: Unknown - ID: M21558 - Name: Neurodegenerative Diseases - Relevance: LOW - As Found: Unknown - ID: M21836 - Name: Neurocognitive Disorders - Relevance: LOW - As Found: Unknown - ID: M4815 - Name: Mental Disorders - Relevance: LOW - As Found: Unknown - ID: M14473 - Name: Psychotic Disorders - Relevance: LOW - As Found: Unknown - ID: T2192 - Name: Familial Alzheimer Disease - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000000544 - Term: Alzheimer Disease ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT02426879 **Acronym:** Node **Brief Title:** Esophagectomy for Patients With Esophageal Cancer and Cervical Lymph Node Metastases **Official Title:** Esophagectomy for Patients With Esophageal Cancer and Cervical Lymph Node Metastases Node Study #### Organization Study ID Info **ID:** NL48231.041.14 #### Organization **Class:** OTHER **Full Name:** UMC Utrecht ### Status Module #### Completion Date **Date:** 2021-01-25 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2021-09-30 **Type:** ACTUAL **Last Update Submit Date:** 2021-09-28 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2021-01-25 **Type:** ACTUAL #### Start Date **Date:** 2015-02-11 **Type:** ACTUAL **Status Verified Date:** 2021-09 #### Study First Post Date **Date:** 2015-04-27 **Type:** ESTIMATED **Study First Submit Date:** 2015-01-30 **Study First Submit QC Date:** 2015-04-21 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** UMC Utrecht #### Responsible Party **Investigator Affiliation:** UMC Utrecht **Investigator Full Name:** Richard van Hillegersberg **Investigator Title:** prof Dr **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** There is no world-wide consensus on the oncological benefit versus increased morbidity associated with three field lymphadenectomy in patients with esophageal cancer and cervical lymph node metastases. In Asian countries, esophagectomy is commonly combined with a three field lymphadenectomy, including resection of cervical, thoracic and abdominal lymph nodes. However, in Western countries patients with cervical lymph node metastases are generally precluded from curative treatment. **Detailed Description:** Objective: To assess the safety and feasibility of curative esophagectomy combined with three field lymphadenectomy after chemo-radiation in Western patients with resectable thoracic esophageal carcinoma and cervical lymph node metastases. Secondary objective is to determine the effect on survival and recurrence. Study design: Mono centre prospective phase II single-arm feasibility study. Study population: Western patients diagnosed with resectable (cT1-4a, N1-3) intra thoracic esophageal carcinoma with histological or cytological proven cervical lymph node metastases in level III and/ or IV. Intervention: Transthoracic esophageal resection combined with three field lymphadenectomy after neoadjuvant chemo-radiation. Main study parameters/ endpoints: Primary outcome is the percentage of overall surgical complications grade 3b and higher as stated by the Modified Clavien-Dindo classification. Secondary outcomes are mortality, operation related events and postoperative recovery, including quality of life, disease free survival, overall survival and if applicable the location of recurrent disease. ### Conditions Module **Conditions:** - Cancer - Squamous Cell Carcinoma - Adenocarcinoma - Malignancy **Keywords:** - three-field lymphadenectomy - cervical metastases - esophagectomy ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 20 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** esophagectomy with three-field lymphnode dissection **Intervention Names:** - Procedure: esophagectomy with three-field lymphnode dissection **Label:** surgery **Type:** OTHER ### Interventions #### Intervention 1 **Arm Group Labels:** - surgery **Description:** robot assisted thoraco-laparoscopic esophagectomy with three-field lymphnode dissection **Name:** esophagectomy with three-field lymphnode dissection **Type:** PROCEDURE ### Outcomes Module #### Other Outcomes **Description:** pTNM stage **Measure:** pathology results 1 **Time Frame:** 5 years **Description:** site of tumour **Measure:** pathology results 2 **Time Frame:** 5 years **Description:** length of tumour **Measure:** pathology results 3 **Time Frame:** 5 years **Description:** type of tumour **Measure:** pathology results 4 **Time Frame:** 5 years **Description:** gradation of tumour **Measure:** pathology results 5 **Time Frame:** 5 years **Description:** margins of resection (R0, R1, R2) **Measure:** pathology results 6 **Time Frame:** 5 years **Description:** mandard score **Measure:** pathology results 7 **Time Frame:** 5 years **Description:** lymphnode status **Measure:** pathology results 8 **Time Frame:** 5 years **Description:** vaso-invasion **Measure:** pathology results 9 **Time Frame:** 5 years **Description:** perineural growth **Measure:** pathology results 10 **Time Frame:** 5 years #### Primary Outcomes **Description:** Safety is measured by the percentage of overall postoperative complications grade 3b and higher as stated by the modified Clavien-Dindo classification (MCDC) **Measure:** Safety measured by the percentage of overall postoperative complications grade 3b and higher as stated by the modified Clavien-Dindo classification (MCDC) **Time Frame:** 5 years #### Secondary Outcomes **Description:** in-hospital mortality and 30- and 60 day mortality (absolute numbers/ percentages) **Measure:** mortality **Time Frame:** 5 years **Description:** 5 year overall- and disease free survival. **Measure:** survival **Time Frame:** 5 years **Description:** QoL is measured by questionnaires (EORTC-QLQ_C30 and EORTC-QLQ_Oes18) **Measure:** quality of life measured by questionnaires (EORTC-QLQ_C30 and EORTC-QLQ_Oes18) **Time Frame:** 10 years **Description:** duration of surgery (minutes) **Measure:** operation related events 1 **Time Frame:** 5 years **Description:** reason for prolongation of surgery if applicable **Measure:** operation related events 2 **Time Frame:** 5 years **Description:** unexpected events/ complications **Measure:** operation related events 3 **Time Frame:** 5 years **Description:** bloodloss (ml) reason for conversion if applicable. **Measure:** operation related events 4 **Time Frame:** 5 years **Description:** reason for conversion if applicable. **Measure:** operation related events 5 **Time Frame:** 5 years **Description:** duration of intubation (days), length of ICU/ MCU stay(days), length of hospital stay (days), **Measure:** postoperative recovery **Time Frame:** 5 years ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Histologically proven squamous cell carcinoma or adenocarcinoma of the esophagus. * Surgical resectable carcinoma (T1-4a, N1-3) (table 1) * Histologically/ cytologically proven resectable cervical lymph node metastases level III and/ or IV * Age ≥ 18 * European Clinical Oncology Group (ECOG) performance status 0,1 or 2 * Written informed consent Exclusion Criteria: * Distant metastases * Esophageal carcinoma \< 3 cm beneath UES * Carcinoma of the gastro-esophageal junction (GEJ) with major tumor in the gastric cardia (Siewert III) * Former radiotherapy or chemotherapy for esophageal carcinoma * Former radiotherapy precluding radiotherapy according the CROSS protocol * Inadequate pulmonary function disabling transthoracic resection * \>10% loss of weight in the last six months * Previous neck dissection * New York heart association class III/IV and no history of active angina. Patients with a history of significant ventricular arrhythmia requiring medication or congestive heart failure. History of 2nd or 3rd degree heart blocks **Maximum Age:** 99 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Utrecht **Country:** Netherlands **Facility:** UMC Utrecht **Zip:** 3584 CX #### Overall Officials **Official 1:** **Affiliation:** UMCU **Name:** Richard V Hillegersberg, Prof Dr **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009369 - Term: Neoplasms - ID: D000009385 - Term: Neoplastic Processes - ID: D000010335 - Term: Pathologic Processes - ID: D000005770 - Term: Gastrointestinal Neoplasms - ID: D000004067 - Term: Digestive System Neoplasms - ID: D000009371 - Term: Neoplasms by Site - ID: D000006258 - Term: Head and Neck Neoplasms - ID: D000004066 - Term: Digestive System Diseases - ID: D000004935 - Term: Esophageal Diseases - ID: D000005767 - Term: Gastrointestinal Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: All - Name: All Conditions - Abbrev: BC06 - Name: Digestive System Diseases - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M5534 - Name: Carcinoma - Relevance: LOW - As Found: Unknown - ID: M5550 - Name: Carcinoma, Squamous Cell - Relevance: LOW - As Found: Unknown - ID: M8088 - Name: Esophageal Neoplasms - Relevance: HIGH - As Found: Esophageal Cancer - ID: M12307 - Name: Neoplasm Metastasis - Relevance: HIGH - As Found: Metastases - ID: M3585 - Name: Adenocarcinoma - Relevance: LOW - As Found: Unknown - ID: M11204 - Name: Lymphatic Metastasis - Relevance: HIGH - As Found: Lymph Node Metastasis - ID: M12330 - Name: Neoplastic Processes - 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: M9348 - Name: Head and Neck 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: M8085 - Name: Esophageal Diseases - Relevance: LOW - As Found: Unknown - ID: T2141 - Name: Esophageal Cancer - Relevance: HIGH - As Found: Esophageal Cancer ### Condition Browse Module - Meshes - ID: D000009362 - Term: Neoplasm Metastasis - ID: D000004938 - Term: Esophageal Neoplasms - ID: D000008207 - Term: Lymphatic Metastasis ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT02195479 **Brief Title:** A Study of Combination of Daratumumab and Velcade (Bortezomib) Melphalan-Prednisone (DVMP) Compared to Velcade Melphalan-Prednisone (VMP) in Participants With Previously Untreated Multiple Myeloma **Official Title:** A Phase 3, Randomized, Controlled, Open-label Study of VELCADE (Bortezomib) Melphalan-Prednisone (VMP) Compared to Daratumumab in Combination With VMP (D-VMP), in Subjects With Previously Untreated Multiple Myeloma Who Are Ineligible for High-dose Therapy #### Organization Study ID Info **ID:** CR104761 #### Organization **Class:** INDUSTRY **Full Name:** Janssen Research & Development, LLC #### Secondary ID Infos **Domain:** Janssen Research and Development, LLC **ID:** 54767414MMY3007 **Type:** OTHER **ID:** 2014-002272-88 **Type:** EUDRACT_NUMBER ### Status Module #### Completion Date **Date:** 2024-06-30 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-23 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-21 **Overall Status:** ACTIVE_NOT_RECRUITING #### Primary Completion Date **Date:** 2017-11-21 **Type:** ACTUAL #### Results First Post Date **Date:** 2018-12-17 **Type:** ACTUAL **Results First Submit Date:** 2018-11-21 **Results First Submit QC Date:** 2018-11-21 #### Start Date **Date:** 2014-12-09 **Type:** ACTUAL **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2014-07-21 **Type:** ESTIMATED **Study First Submit Date:** 2014-07-18 **Study First Submit QC Date:** 2014-07-18 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Janssen Research & Development, LLC #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** The purpose of this study is to determine if the addition of daratumumab to velcade (bortezomib) melphalan-prednisone (VMP) will prolong progression-free survival (PFS) compared with VMP alone in participants with previously untreated multiple myeloma who are ineligible for high dose chemotherapy and autologous stem cell transplant (ASCT). **Detailed Description:** The study consists of 3 phases: Screening Phase (within 21 days prior to randomization), Treatment Phase (Cycle 1 Day 1 to discontinuation of all study treatment), and Follow-up Phase (from discontinuation of all study treatment up to death, lost to follow up, withdrawal of consent, or the study ends, whichever occurs first). Treatment phase will include 2 treatments (Treatment A: participants will receive Velcade MelphalanPrednisone (VMP) alone and Treatment B: participants will receive daratumumab in combination with VMP).Two interim analyses are planned. The first will be to evaluate safety after a total of approximately 100 participants have been treated for at least 2 cycles or discontinued the study treatment. The second will be to evaluate cumulative interim safety and efficacy data, and will be performed when approximately 216 PFS events have been accumulated. The final OS analysis will occur when approximately 382 deaths have occurred. Efficacy will be primarily measured by comparison of PFS between the two treatment arms. Participants' safety will be monitored throughout the study. ### Conditions Module **Conditions:** - Multiple Myeloma **Keywords:** - Multiple Myeloma - Bortezomib - Velcade - Melphalan - Prednisone - Daratumumab ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 706 **Type:** ACTUAL **Phases:** - PHASE3 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Participants will receive velcade (bortezomib) 1.3 milligram per square meter (mg/m\^2) as subcutaneous injection, twice weekly at Weeks 1, 2, 4 and 5 in Cycle 1 followed by once weekly at Weeks 1, 2, 4 and 5 in Cycles 2 to 9, melphalan 9 mg/m\^2 , orally, once daily (on Days 1-4) and prednisone 60 mg/m\^2, orally, once daily, on Days 1 to 4 of each cycle up to Cycle 9. **Intervention Names:** - Drug: Velcade - Drug: Melphalan - Drug: Prednisone **Label:** Treatment Arm A (VMP Alone) **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** Participants will receive velcade 1.3 mg/m\^2 as SC injection, twice weekly at Weeks 1, 2, 4 and 5 in Cycle 1 followed by once weekly at Weeks 1, 2, 4 and 5 in Cycles 2 to 9, melphalan 9 mg/m\^2, orally, once daily (on Days 1-4) and prednisone 60 mg/m\^2, orally, once daily, on Days 1 to 4 of each cycle up to Cycle 9. In addition participants will also receive daratumumab 16 mg/kg as IV infusion, once weekly, for 6 weeks in Cycle 1 and then every 3 weeks, in Cycle 2 to 9 and thereafter, once every 4 weeks until documented progression, unacceptable toxicity, or until the end of study. On days when daratumumab is given, dexamethasone 20 mg IV or PO is given 1 hour or less prior to daratumumab administration as pre medication and prednisone substitute, and prednisone 60 mg/m2 once daily will be given on Days 2-4. Following amendment 7, participants will have the option to switch to daratumumab subcutaneous (SC) on Day 1 of any cycle, at the discretion of the investigator. **Intervention Names:** - Drug: Velcade - Drug: Melphalan - Drug: Prednisone - Drug: Daratumumab IV - Drug: Dexamethasone - Drug: Daratumumab SC **Label:** Treatment Arm B (D-VMP) **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Treatment Arm A (VMP Alone) - Treatment Arm B (D-VMP) **Description:** Participants will receive velcade 1.3 mg/m\^2, as subcutaneous injection, twice weekly at Weeks 1, 2, 4 and 5 in Cycle 1 followed by once weekly at Weeks 1, 2, 4 and 5 in Cycles 2 to 9. **Name:** Velcade **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Treatment Arm A (VMP Alone) - Treatment Arm B (D-VMP) **Description:** Participants will receive melphalan 9 mg/m\^2, orally, once daily on Days 1 to 4 of each cycle up to Cycle 9. **Name:** Melphalan **Type:** DRUG #### Intervention 3 **Arm Group Labels:** - Treatment Arm A (VMP Alone) - Treatment Arm B (D-VMP) **Description:** Participants will receive prednisone 60 mg/m\^2, orally, once daily, on Days 1 to 4 of each cycle up to Cycle 9. **Name:** Prednisone **Type:** DRUG #### Intervention 4 **Arm Group Labels:** - Treatment Arm B (D-VMP) **Description:** Participants will receive daratumumab 16 mg/kg as intravenous infusion, once weekly, for 6 weeks in Cycle 1 and then once every 3 weeks, in Cycle 2 to 9 and thereafter, once every 4 weeks until documented progression, unacceptable toxicity, or until the end of study . **Name:** Daratumumab IV **Type:** DRUG #### Intervention 5 **Arm Group Labels:** - Treatment Arm B (D-VMP) **Description:** Participants administered with dexamethasone 20 mg IV or PO is given 1 hour or less prior to daratumumab administration as pre medication and prednisone substitute. **Name:** Dexamethasone **Type:** DRUG #### Intervention 6 **Arm Group Labels:** - Treatment Arm B (D-VMP) **Description:** Daratumumab SC will be administered by SC injection at a fixed dose of 1800 mg once every 4 weeks until documented progression, unacceptable toxicity, or until the end of study. Following amendment 7, participants can switch from daratumumab IV to daratumumab SC. **Name:** Daratumumab SC **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** PFS- duration from date of randomization to Progressive disease (PD)/death, whichever occurs first. PD per IMWG criteria-Increase of 25% from lowest response value in one of following: Serum and urine M-component (absolute increase \>=0.5 gram per deciliter \[g/dL\] and \>=200 milligram \[mg\]/24 hours respectively); Only participants without measurable serum and urine M-protein levels: difference between involved and uninvolved free light chain (FLC) levels (absolute increase\>10 mg/dL); Only participants without measurable serum and urine M-protein levels,without measurable disease by FLC levels,bone marrow Plasma cells (PC) %(absolute % \>=10%);Bone marrow PC%: absolute% \>10%; Definite development of new bone lesions/soft tissue plasmacytomas/definite increase in size of existing bone lesions/soft tissue plasmacytomas and Development of hypercalcemia (corrected serum calcium \>11.5 mg/dL) that can be attributed solely to the PC proliferative disorder. **Measure:** Progression Free Survival (PFS) **Time Frame:** From randomization to either disease progression or death whichever occurs first (up to 2.4 years) #### Secondary Outcomes **Description:** The Overall response rate was defined as the percentage of participants who achieved a partial response (PR) or better, according to the International Myeloma Working Group (IMWG) criteria, during the study or during follow up. IMWG criteria for PR: greater than or equal to (\>=) 50 percentage(%) reduction of serum M-protein and reduction in 24 hour urinary M-protein by \>=90% or to \<200 mg/24 hours, if the serum and urine M-protein are not measurable, a decrease of \>=50% in the difference between involved and uninvolved free light chain (FLC) levels is required in place of the M-protein criteria, If serum and urine M-protein are not measurable, and serum free light assay is also not measurable, \>=50% reduction in bone marrow plasma cells (PCs) is required in place of M-protein, provided baseline bone marrow plasma cell percentage was \>=30%, in addition to the above criteria, if present at baseline, a \>=50% reduction in the size of soft tissue plasmacytomas is also required. **Measure:** Overall Response Rate (ORR) **Time Frame:** From randomization to disease progression (up to 2.4 years) **Description:** VGPR or better rate was defined as the percentage of participants who achieved VGPR or complete response (CR) (including stringent complete response\[sCR\]) according to the IMWG criteria during or after the study treatment. VGPR: Serum and urine component detectable by immunofixation but not on electrophoresis, or \>= 90% reduction in serum M-protein plus urine M-protein level less than (\<) 100 milligram (mg) per 24 hour; CR: negative immunofixation on the serum and urine, Disappearance of any soft tissue plasmacytomas and \< 5% plasms cells (PCs) in bone marrow; sCR: CR in addition to having a normal FLC ratio and an absence of clonal cells in bone marrow by immunohistochemistry, immunofluorescence, 2-4 color flow cytometry. **Measure:** Percentage of Participants With Very Good Partial Response (VGPR) or Better **Time Frame:** From randomization to disease progression (up to 2.4 years) **Description:** CR or better rate was defined as the percentage of participants with a CR or better (i.e. CR and sCR) as per IMWG criteria. CR: as negative immunofixation on the serum and urine and disappearance of soft tissue plasmacytomas and less than (\<) 5 percent plasma cells in bone marrow; sCR: CR plus normal free light chain (FLC) ratio and absence of clonal PCs by immunohistochemistry, immunofluorescence or 2- to 4-color flow cytometry. **Measure:** Percentage of Participants With Complete Response (CR) or Better **Time Frame:** From randomization to disease progression (up to 2.4 years) **Description:** The Minimal Residual Disease negativity rate was defined as the percentage of participants who had negative MRD (detection of less than 1 malignant cell among 100,000 normal cells) assessment at any timepoint after the first dose of study drugs by evaluation of bone marrow aspirates or whole blood at 10\^-5 threshold. MRD was evaluated by using Deoxyribonucleic acid (DNA) sequencing of immunoglobulin genes. MRD was assessed in participants who achieved complete response or stringent complete response (CR/sCR). **Measure:** Percentage of Participants With Negative Minimal Residual Disease (MRD) **Time Frame:** From randomization to disease progression (up to 2.4 years) **Description:** Overall Survival (OS) was defined as the number of days the date of randomization to date of death. Median Overall Survival was estimated by using the Kaplan-Meier method. **Measure:** Overall Survival (OS) **Time Frame:** From randomization to death (up to approximately 2.4 years) **Description:** Progression-free survival after next-line therapy is defined as the time from randomization to progression on the next line of subsequent antimyeloma therapy or death due to any cause (prior to start of second line of antimyeloma therapy), whichever comes first. Disease progression on next line of treatment was based on investigator judgment. **Measure:** Progression Free Survival on Next Line of Therapy (PFS2) **Time Frame:** From randomization to either disease progression or death whichever occurs first (up to 2.4 years) **Description:** sCR as per IMWG criteria is CR plus normal free light chain (FLC) ratio and absence of clonal PCs by immunohistochemistry, immunofluorescence or 2- to 4-color flow cytometry. CR: Negative immunofixation on the serum and urine; Disappearance of any soft tissue plasmacytomas; \<5% plasma cells (PCs) in bone marrow. **Measure:** Percentage of Participants With Stringent Complete Response (sCR) **Time Frame:** From randomization to disease progression (up to 2.4 years) **Description:** TTP: Time from date of randomization to date of first documented evidence of PD or death due to PD, whichever occurs first. PD per IMWG criteria- Increase of 25 % from lowest response value in one of following: Serum and urine M-component (absolute increase \>=0.5 gram per deciliter \[g/dL\] and \>=200 mg/24 hours respectively); Only in participants without measurable serum and urine M-protein levels: difference between involved and uninvolved FLC levels (absolute increase \>10 milligram per deciliter \[mg/dL\]); Only in participants without measurable serum and urine M-protein levels and without measurable disease by FLC levels, bone marrow plasma cells (PC)% (absolute % \>=10%); Bone marrow PC %: absolute % \>10%; Definite development of new bone lesions/soft tissue plasmacytomas or definite increase in size of existing bone lesions/soft tissue plasmacytomas and Development of hypercalcemia (corrected serum calcium \>11.5 mg/dL) that can be attributed solely to the PC proliferative disorder. **Measure:** Time to Disease Progression (TTP) **Time Frame:** From randomization to either disease progression or death due to PD whichever occurs first (up to 2.4 years) **Description:** Time to response, defined as the time between the date of randomization and the first efficacy evaluation that the participant has met all criteria for PR or better. PR: \>=50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by \>=90% or to \<200 mg/24 hours; If the serum and urine M-protein are not measurable, a decrease of \>=50% in the difference between involved and uninvolved FLC levels is required in place of the M-protein criteria; If serum and urine M-protein are not measurable, and serum free light assay is also not measurable, \>=50% reduction in bone marrow PCs is required in place of M-protein, provided baseline bone marrow plasma cell percentage was \>=30%. **Measure:** Time to Response **Time Frame:** From randomization to first documented PR or better (up to 2.4 years) **Description:** DOR: participants with a confirmed response (PR or better) as time between first documentation of response and disease progression, IMWG response criteria, or death due to PD, whichever occurs first. PD: Increase of 25% from lowest response value in any one of following: Serum M-component (absolute increase\>=0.5 g/dL); Urine M-component (absolute increase\>=200 mg/24 hours); Only participants without measurable serum and urine M-protein levels: difference between involved and uninvolved FLC levels (absolute increase \>10 mg/dL); Only participants without measurable serum and urine M-protein levels and without measurable disease by FLC levels, bone marrow PC%(absolute%\>=10%); Bone marrow PC's %: absolute%\>10%; Definite development of new bone lesions/soft tissue plasmacytomas/definite increase in the size of existing bone lesions or soft tissue plasmacytomas and Development of hypercalcemia (corrected serum calcium \>11.5 mg/dL) that can be attributed solely to PC proliferative disorder. **Measure:** Duration of Response (DOR) **Time Frame:** Up to 2.4 years **Description:** Time to next treatment is defined as the time from randomization to the start of the next-line treatment. **Measure:** Time to Next Treatment (TNT) **Time Frame:** Approximately up to 2.4 years **Description:** Percentage of participants with Best M- protein response of 100% reduction and \>=90% to \< 100% reduction were assessed. Best M-protein response was defined as the maximal percent reduction or the lowest percent increase from baseline in serum M-protein for participants with measurable heavy chain at baseline or urine M-protein for participants without measurable heavy chain, but with measurable light chain disease at baseline. For participants without measurable heavy chain and light chain disease at baseline, best response in serum free light chain (FLC) was defined as the maximal percent reduction or the lowest percent increase from baseline in the difference between involved and uninvolved serum FLC level (dFLC). **Measure:** Percentage of Participants With Best M-protein Response **Time Frame:** Approximately up to 2.4 years **Description:** The EORTC QLQ-C30 is a 30 items self-reporting questionnaire, with a 1 week recall period, resulting in 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 1 Global Health Status (GHS) scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single symptom items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The questionnaire includes 28 items with 4-point Likert type responses from "1-not at all" to "4-very much" to assess functioning and symptoms; 2 items with 7-point Likert scales (1= poor and 7= excellent) for global health and overall QoL. Scores are transformed to a 0 to 100 scale, with higher scores representing better GHS, better functioning, and more symptoms. Negative change from baseline values indicate deterioration in quality of life or functioning and positive values indicate improvement. **Measure:** Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-C30: Emotional Functioning Score **Time Frame:** Baseline, Months 3, 6, 9, 12 and 18 **Description:** EQ-5D-5L is a standardized, participant-rated questionnaire to assess health-related quality of life. The EQ-5D-5L includes 2 components: the EQ-5D-5L health state profile (descriptive system) and the EQ-5D-5L Visual Analog Scale. The Visual Analogue Scale is designed to rate the participant's current health state on a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state. **Measure:** Change From Baseline in EuroQol-5 Dimensions-5 Levels (EQ-5D-5L): Visual Analogue Scale (VAS) **Time Frame:** Baseline, Months 3, 6, 9, 12 and 18 **Description:** EQ-5D-5L is a standardized, participant-rated questionnaire to assess health-related quality of life. The EQ-5D-5L includes 2 components: the EQ-5D-5L health state profile (descriptive system) and the EQ-5D-5L Visual Analog Scale. The EQ-5D-5L descriptive system provides a profile of the participant's health state 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 response options (no problems, slight problems, moderate problems, severe problems and extreme problems) that reflect increasing levels of difficulty. The participant was asked to indicate his/her current health state by selecting the most appropriate level in each of the 5 dimensions. Responses to the 5 dimension scores were combined and converted into a single preference-weighted health utility index score 0 (0.0- worst health state) to 1 (1.0- better health state) representing the general health status of the individual based on the UK scoring algorithm. **Measure:** Change From Baseline in EuroQol 5 Dimensions-5 Level (EQ-5D-5L) Utility Score **Time Frame:** Baseline, Months 3, 6, 9, 12 and 18 ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Participant must have documented multiple myeloma satisfying the calcium elevation, renal insufficiency, anemia, and bone abnormalities (CRAB) diagnostic criteria, monoclonal plasma cells in the bone marrow greater than or equal to 10 percent (%) or presence of a biopsy proven plasmacytoma, and measurable secretory disease, as assessed by the central laboratory, and defined in protocol * Participants who are newly diagnosed and not considered candidate for high-dose chemotherapy with stem cell transplantation (SCT) due to: being age \>=65 years, or in participants \<65 years: presence of important comorbid conditions likely to have a negative impact on tolerability of high dose chemotherapy with stem cell transplantation * Participant must have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2 * Meet the clinical laboratory criteria as specified in the protocol * A woman of childbearing potential must have a negative serum pregnancy test at screening within 14 days prior to randomization * Women of childbearing potential must commit to either abstain continuously from heterosexual sexual intercourse or to use 2 methods of reliable birth control simultaneously. This includes one highly effective form of contraception (tubal ligation, intrauterine device, hormonal \[birth control pills, injections, hormonal patches, vaginal rings or implants\] or partner's vasectomy) and one additional effective contraceptive method (male latex or synthetic condom, diaphragm, or cervical cap). Contraception must begin prior to dosing. Reliable contraception is indicated even where there has been a history of infertility, unless due to hysterectomy or bilateral oophorectomy Exclusion Criteria: * Participant has a diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance, or smoldering multiple myeloma * Participant has a diagnosis of Waldenstrom's disease, or other conditions in which IgM M-protein is present in the absence of a clonal plasma cell infiltration with lytic bone lesions * Participant has prior or current systemic therapy or SCT for multiple myeloma, with the exception of an emergency use of a short course (equivalent of dexamethasone 40 mg/day for 4 days) of corticosteroids before treatment * Participant has peripheral neuropathy or neuropathic pain Grade 2 or higher, as defined by the national cancer institute common terminology criteria for adverse events (NCI CTCAE) Version 4 * Participant has a history of malignancy (other than multiple myeloma) within 3 years before the date of randomization (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy that in the opinion of the investigator, with concurrence with the sponsor's medical monitor, is considered cured with minimal risk of recurrence within 3 years) * Participant has had radiation therapy within 14 days of randomization * Participant has had plasmapheresis within 28 days of randomization * Participant has known chronic obstructive pulmonary disease (COPD) (defined as a forced expiratory volume in 1 second \[FEV1\] \<50% of predicted normal), known moderate or severe persistent asthma within the last 2 years or currently has uncontrolled asthma of any classification (controlled intermittent asthma or controlled mild persistent asthma is allowed) * Participants with known or suspected COPD must have a FEV1 test during screening * Participant is known to be seropositive for human immunodeficiency virus (HIV), known to have hepatitis B surface antigen positivity, or history of to have a history of hepatitis C * Participant has any concurrent medical or psychiatric condition or disease (example active systemic infection, uncontrolled diabetes, acute diffuse infiltrative pulmonary disease) that is likely to interfere with the study procedures or results, or that in the opinion of the investigator, would constitute a hazard for participating in this study **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** California City **Country:** United States **State:** California **Location 2:** **City:** Corona **Country:** United States **State:** California **Location 3:** **City:** Fountain Valley **Country:** United States **State:** California **Location 4:** **City:** Los Angeles **Country:** United States **State:** California **Location 5:** **City:** Hialeah **Country:** United States **State:** Florida **Location 6:** **City:** Orange Park **Country:** United States **State:** Florida **Location 7:** **City:** Chicago **Country:** United States **State:** Illinois **Location 8:** **City:** Springfield **Country:** United States **State:** Missouri **Location 9:** **City:** Cleveland **Country:** United States **State:** Ohio **Location 10:** **City:** Fredericksburg **Country:** United States **State:** Virginia **Location 11:** **City:** Buenos Aires **Country:** Argentina **Location 12:** **City:** Ciudad Autonoma Buenos Aires **Country:** Argentina **Location 13:** **City:** Córdoba **Country:** Argentina **Location 14:** **City:** Santa Fe **Country:** Argentina **Location 15:** **City:** Adelaide **Country:** Australia **Location 16:** **City:** Bendigo **Country:** Australia **Location 17:** **City:** Camperdown N/a **Country:** Australia **Location 18:** **City:** Geelong **Country:** Australia **Location 19:** **City:** Gosford **Country:** Australia **Location 20:** **City:** Greenslopes **Country:** Australia **Location 21:** **City:** Hobart **Country:** Australia **Location 22:** **City:** North Adelaide **Country:** Australia **Location 23:** **City:** Parkville **Country:** Australia **Location 24:** **City:** Antwerpen **Country:** Belgium **Location 25:** **City:** Antwerp **Country:** Belgium **Location 26:** **City:** Brussel **Country:** Belgium **Location 27:** **City:** Charleroi **Country:** Belgium **Location 28:** **City:** Gent **Country:** Belgium **Location 29:** **City:** Kortrijk **Country:** Belgium **Location 30:** **City:** Roeselare **Country:** Belgium **Location 31:** **City:** Turnhout **Country:** Belgium **Location 32:** **City:** Yvoir **Country:** Belgium **Location 33:** **City:** Barretos **Country:** Brazil **Location 34:** **City:** Cuiaba - Mount **Country:** Brazil **Location 35:** **City:** Fortaleza **Country:** Brazil **Location 36:** **City:** Goiania **Country:** Brazil **Location 37:** **City:** Natal **Country:** Brazil **Location 38:** **City:** Porto Alegre **Country:** Brazil **Location 39:** **City:** Ribeirao Preto **Country:** Brazil **Location 40:** **City:** Rio de Janeiro **Country:** Brazil **Location 41:** **City:** Sao Paulo **Country:** Brazil **Location 42:** **City:** São Paulo **Country:** Brazil **Location 43:** **City:** Pleven **Country:** Bulgaria **Location 44:** **City:** Plovdiv **Country:** Bulgaria **Location 45:** **City:** Sofia **Country:** Bulgaria **Location 46:** **City:** Varna **Country:** Bulgaria **Location 47:** **City:** Vratsa **Country:** Bulgaria **Location 48:** **City:** Zadar **Country:** Croatia **Location 49:** **City:** Zagreb **Country:** Croatia **Location 50:** **City:** Brno **Country:** Czechia **Location 51:** **City:** Hradec Kralove **Country:** Czechia **Location 52:** **City:** Olomouc **Country:** Czechia **Location 53:** **City:** Ostrava-Poruba **Country:** Czechia **Location 54:** **City:** Praha 10 **Country:** Czechia **Location 55:** **City:** Praha 2 **Country:** Czechia **Location 56:** **City:** Tbilisi **Country:** Georgia **Location 57:** **City:** Berlin **Country:** Germany **Location 58:** **City:** Dortmund **Country:** Germany **Location 59:** **City:** Karlsruhe **Country:** Germany **Location 60:** **City:** Potsdam **Country:** Germany **Location 61:** **City:** Saarbrücken **Country:** Germany **Location 62:** **City:** Stuttgart **Country:** Germany **Location 63:** **City:** Würzburg **Country:** Germany **Location 64:** **City:** Athens Attica **Country:** Greece **Location 65:** **City:** Athens **Country:** Greece **Location 66:** **City:** Patra **Country:** Greece **Location 67:** **City:** Thessaloniki **Country:** Greece **Location 68:** **City:** Budapest **Country:** Hungary **Location 69:** **City:** Debrecen **Country:** Hungary **Location 70:** **City:** Kaposvar **Country:** Hungary **Location 71:** **City:** Pecs N/a **Country:** Hungary **Location 72:** **City:** Chiba **Country:** Japan **Location 73:** **City:** Hitachi **Country:** Japan **Location 74:** **City:** Kanazawa **Country:** Japan **Location 75:** **City:** Kawasaki **Country:** Japan **Location 76:** **City:** Kobe **Country:** Japan **Location 77:** **City:** Kurume **Country:** Japan **Location 78:** **City:** Matsuyama **Country:** Japan **Location 79:** **City:** Nagoya **Country:** Japan **Location 80:** **City:** Narita **Country:** Japan **Location 81:** **City:** Ohgaki **Country:** Japan **Location 82:** **City:** Okayama **Country:** Japan **Location 83:** **City:** Osaka **Country:** Japan **Location 84:** **City:** Sendai-shi **Country:** Japan **Location 85:** **City:** Shibukawa **Country:** Japan **Location 86:** **City:** Shibuya **Country:** Japan **Location 87:** **City:** Tachikawa **Country:** Japan **Location 88:** **City:** Toyohashi **Country:** Japan **Location 89:** **City:** Busan **Country:** Korea, Republic of **Location 90:** **City:** Gyeonggi-do **Country:** Korea, Republic of **Location 91:** **City:** Hwasun **Country:** Korea, Republic of **Location 92:** **City:** Incheon **Country:** Korea, Republic of **Location 93:** **City:** Seongnam **Country:** Korea, Republic of **Location 94:** **City:** Seoul **Country:** Korea, Republic of **Location 95:** **City:** Skopje **Country:** North Macedonia **Location 96:** **City:** Bialystok **Country:** Poland **Location 97:** **City:** Bydgoszcz **Country:** Poland **Location 98:** **City:** Chorzow **Country:** Poland **Location 99:** **City:** Gdansk **Country:** Poland **Location 100:** **City:** Legnica **Country:** Poland **Location 101:** **City:** Lublin **Country:** Poland **Location 102:** **City:** Opole **Country:** Poland **Location 103:** **City:** Slupsk **Country:** Poland **Location 104:** **City:** Warszawa Ul **Country:** Poland **Location 105:** **City:** Warszawa **Country:** Poland **Location 106:** **City:** Wroclaw **Country:** Poland **Location 107:** **City:** Lisboa **Country:** Portugal **Location 108:** **City:** Lisbon **Country:** Portugal **Location 109:** **City:** Porto **Country:** Portugal **Location 110:** **City:** Brasov **Country:** Romania **Location 111:** **City:** Bucharest **Country:** Romania **Location 112:** **City:** Iasi **Country:** Romania **Location 113:** **City:** Arkhangelsk **Country:** Russian Federation **Location 114:** **City:** Dzerzhinsk **Country:** Russian Federation **Location 115:** **City:** Ekaterinbourg **Country:** Russian Federation **Location 116:** **City:** Nizhny Novgorod **Country:** Russian Federation **Location 117:** **City:** Ryazan **Country:** Russian Federation **Location 118:** **City:** Saint-Petersburg **Country:** Russian Federation **Location 119:** **City:** Saratov **Country:** Russian Federation **Location 120:** **City:** Sochi **Country:** Russian Federation **Location 121:** **City:** St Petersburg **Country:** Russian Federation **Location 122:** **City:** Volgograd **Country:** Russian Federation **Location 123:** **City:** Belgrade **Country:** Serbia **Location 124:** **City:** Nis **Country:** Serbia **Location 125:** **City:** Novi Sad **Country:** Serbia **Location 126:** **City:** Sremska Kamenica **Country:** Serbia **Location 127:** **City:** Zemun **Country:** Serbia **Location 128:** **City:** Andalucía **Country:** Spain **Location 129:** **City:** Badalona **Country:** Spain **Location 130:** **City:** Barcelona **Country:** Spain **Location 131:** **City:** Córdoba **Country:** Spain **Location 132:** **City:** Girona **Country:** Spain **Location 133:** **City:** La Laguna **Country:** Spain **Location 134:** **City:** Madrid **Country:** Spain **Location 135:** **City:** Maranon **Country:** Spain **Location 136:** **City:** Murcia N/a **Country:** Spain **Location 137:** **City:** Ourense **Country:** Spain **Location 138:** **City:** Pamplona **Country:** Spain **Location 139:** **City:** Salamanca **Country:** Spain **Location 140:** **City:** Sevilla **Country:** Spain **Location 141:** **City:** Toledo **Country:** Spain **Location 142:** **City:** Valencia **Country:** Spain **Location 143:** **City:** Zaragoza **Country:** Spain **Location 144:** **City:** Altindag **Country:** Turkey **Location 145:** **City:** Ankara **Country:** Turkey **Location 146:** **City:** Aydin **Country:** Turkey **Location 147:** **City:** Izmir **Country:** Turkey **Location 148:** **City:** Kayseri **Country:** Turkey **Location 149:** **City:** Samsun **Country:** Turkey **Location 150:** **City:** Tekirdag **Country:** Turkey **Location 151:** **City:** Cherkassy **Country:** Ukraine **Location 152:** **City:** Dnepropetrovsk **Country:** Ukraine **Location 153:** **City:** Ivano-Frankivsk **Country:** Ukraine **Location 154:** **City:** Kharkov **Country:** Ukraine **Location 155:** **City:** Khmelnitskiy **Country:** Ukraine **Location 156:** **City:** Lviv **Country:** Ukraine **Location 157:** **City:** Zaporizhzhia **Country:** Ukraine **Location 158:** **City:** Birmingham **Country:** United Kingdom **Location 159:** **City:** Cambridge **Country:** United Kingdom **Location 160:** **City:** Colchester **Country:** United Kingdom **Location 161:** **City:** Harlow **Country:** United Kingdom **Location 162:** **City:** Leicester **Country:** United Kingdom **Location 163:** **City:** London **Country:** United Kingdom **Location 164:** **City:** Manchester **Country:** United Kingdom **Location 165:** **City:** Woolwich **Country:** United Kingdom #### Overall Officials **Official 1:** **Affiliation:** Janssen Research & Development, LLC **Name:** Janssen Research & Development, LLC Clinical Trial **Role:** STUDY_DIRECTOR ### References Module #### References **Citation:** Mateos MV, Dimopoulos MA, Cavo M, Suzuki K, Knop S, Doyen C, Lucio P, Nagy Z, Pour L, Grosicki S, Crepaldi A, Liberati AM, Campbell P, Yoon SS, Iosava G, Fujisaki T, Garg M, Iida S, Blade J, Ukropec J, Pei H, Van Rampelbergh R, Kudva A, Qi M, San-Miguel J. Daratumumab Plus Bortezomib, Melphalan, and Prednisone Versus Bortezomib, Melphalan, and Prednisone in Transplant-Ineligible Newly Diagnosed Multiple Myeloma: Frailty Subgroup Analysis of ALCYONE. Clin Lymphoma Myeloma Leuk. 2021 Nov;21(11):785-798. doi: 10.1016/j.clml.2021.06.005. Epub 2021 Jun 18. **PMID:** 34344638 **Citation:** Cavo M, San-Miguel J, Usmani SZ, Weisel K, Dimopoulos MA, Avet-Loiseau H, Paiva B, Bahlis NJ, Plesner T, Hungria V, Moreau P, Mateos MV, Perrot A, Iida S, Facon T, Kumar S, van de Donk NWCJ, Sonneveld P, Spencer A, Krevvata M, Heuck C, Wang J, Ukropec J, Kobos R, Sun S, Qi M, Munshi N. Prognostic value of minimal residual disease negativity in myeloma: combined analysis of POLLUX, CASTOR, ALCYONE, and MAIA. Blood. 2022 Feb 10;139(6):835-844. doi: 10.1182/blood.2021011101. **PMID:** 34289038 **Citation:** San-Miguel J, Avet-Loiseau H, Paiva B, Kumar S, Dimopoulos MA, Facon T, Mateos MV, Touzeau C, Jakubowiak A, Usmani SZ, Cook G, Cavo M, Quach H, Ukropec J, Ramaswami P, Pei H, Qi M, Sun S, Wang J, Krevvata M, DeAngelis N, Heuck C, Van Rampelbergh R, Kudva A, Kobos R, Qi M, Bahlis NJ. Sustained minimal residual disease negativity in newly diagnosed multiple myeloma and the impact of daratumumab in MAIA and ALCYONE. Blood. 2022 Jan 27;139(4):492-501. doi: 10.1182/blood.2020010439. **PMID:** 34269818 **Citation:** Knop S, Mateos MV, Dimopoulos MA, Suzuki K, Jakubowiak A, Doyen C, Lucio P, Nagy Z, Usenko G, Pour L, Cook M, Grosicki S, Crepaldi A, Liberati AM, Campbell P, Shelekhova T, Yoon SS, Losava G, Fujisaki T, Garg M, Wang J, Wroblewski S, Kudva A, Gries KS, Fastenau J, San-Miguel J, Cavo M. Health-related quality of life in patients with newly diagnosed multiple myeloma ineligible for stem cell transplantation: results from the randomized phase III ALCYONE trial. BMC Cancer. 2021 Jun 2;21(1):659. doi: 10.1186/s12885-021-08325-2. **PMID:** 34078314 **Citation:** Mateos MV, Cavo M, Blade J, Dimopoulos MA, Suzuki K, Jakubowiak A, Knop S, Doyen C, Lucio P, Nagy Z, Pour L, Cook M, Grosicki S, Crepaldi A, Liberati AM, Campbell P, Shelekhova T, Yoon SS, Iosava G, Fujisaki T, Garg M, Krevvata M, Chen Y, Wang J, Kudva A, Ukropec J, Wroblewski S, Qi M, Kobos R, San-Miguel J. Overall survival with daratumumab, bortezomib, melphalan, and prednisone in newly diagnosed multiple myeloma (ALCYONE): a randomised, open-label, phase 3 trial. Lancet. 2020 Jan 11;395(10218):132-141. doi: 10.1016/S0140-6736(19)32956-3. Epub 2019 Dec 10. **PMID:** 31836199 **Citation:** Mateos MV, Dimopoulos MA, Cavo M, Suzuki K, Jakubowiak A, Knop S, Doyen C, Lucio P, Nagy Z, Kaplan P, Pour L, Cook M, Grosicki S, Crepaldi A, Liberati AM, Campbell P, Shelekhova T, Yoon SS, Iosava G, Fujisaki T, Garg M, Chiu C, Wang J, Carson R, Crist W, Deraedt W, Nguyen H, Qi M, San-Miguel J; ALCYONE Trial Investigators. Daratumumab plus Bortezomib, Melphalan, and Prednisone for Untreated Myeloma. N Engl J Med. 2018 Feb 8;378(6):518-528. doi: 10.1056/NEJMoa1714678. Epub 2017 Dec 12. **PMID:** 29231133 ## Document Section ### Large Document Module #### Large Docs - Date: 2018-02-14 - Filename: Prot_000.pdf - Has ICF: False - Has Protocol: True - Has SAP: False - Label: Study Protocol - Size: 2416702 - Type Abbrev: Prot - Upload Date: 2018-11-21T07:08 - Date: 2017-07-19 - Filename: SAP_001.pdf - Has ICF: False - Has Protocol: False - Has SAP: True - Label: Statistical Analysis Plan - Size: 860873 - Type Abbrev: SAP - Upload Date: 2018-11-21T07:08 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009370 - Term: Neoplasms by Histologic Type - ID: D000009369 - Term: Neoplasms - ID: D000020141 - Term: Hemostatic Disorders - ID: D000014652 - Term: Vascular Diseases - ID: D000002318 - Term: Cardiovascular Diseases - ID: D000010265 - Term: Paraproteinemias - ID: D000001796 - Term: Blood Protein Disorders - ID: D000006402 - Term: Hematologic Diseases - ID: D000006474 - Term: Hemorrhagic Disorders - ID: D000008232 - Term: Lymphoproliferative Disorders - ID: D000007160 - Term: Immunoproliferative Disorders - ID: D000007154 - Term: Immune System Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC14 - Name: Heart and Blood Diseases - 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: M12058 - Name: Multiple Myeloma - Relevance: HIGH - As Found: Multiple Myeloma - ID: M27588 - Name: Neoplasms, Plasma Cell - Relevance: HIGH - As Found: Multiple Myeloma - ID: M12315 - Name: Neoplasms by Histologic Type - Relevance: LOW - As Found: Unknown - ID: M21977 - Name: Hemostatic Disorders - Relevance: LOW - As Found: Unknown - ID: M5059 - Name: Blood Coagulation Disorders - Relevance: LOW - As Found: Unknown - ID: M17400 - Name: Vascular Diseases - Relevance: LOW - As Found: Unknown - ID: M13178 - Name: Paraproteinemias - Relevance: LOW - As Found: Unknown - ID: M5077 - Name: Blood Protein Disorders - Relevance: LOW - As Found: Unknown - ID: M9490 - Name: Hematologic Diseases - Relevance: LOW - As Found: Unknown - ID: M9560 - Name: Hemorrhagic Disorders - Relevance: LOW - As Found: Unknown - ID: M11225 - Name: Lymphoproliferative Disorders - 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: T3947 - Name: Multiple Myeloma - Relevance: HIGH - As Found: Multiple Myeloma ### Condition Browse Module - Meshes - ID: D000009101 - Term: Multiple Myeloma - ID: D000054219 - Term: Neoplasms, Plasma Cell ### 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 - ID: D000018906 - Term: Antineoplastic Agents, Alkylating - ID: D000000477 - Term: Alkylating Agents - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000019653 - Term: Myeloablative Agonists - ID: D000007166 - Term: Immunosuppressive Agents - ID: D000007155 - Term: Immunologic Factors ### 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: M14121 - Name: Prednisone - Relevance: HIGH - As Found: Min - ID: M11541 - Name: Melphalan - Relevance: HIGH - As Found: Modified - ID: M376 - Name: Bortezomib - Relevance: HIGH - As Found: Old - ID: M272211 - Name: Daratumumab - Relevance: HIGH - As Found: National - ID: M235549 - Name: Dexamethasone acetate - Relevance: LOW - As Found: Unknown - ID: M4225 - Name: Antibodies - Relevance: LOW - As Found: Unknown - ID: M4230 - Name: Antibodies, Monoclonal - Relevance: HIGH - As Found: National - ID: M10184 - Name: Immunoglobulins - 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 - ID: M20942 - Name: Antineoplastic Agents, Alkylating - Relevance: LOW - As Found: Unknown - ID: M3820 - Name: Alkylating Agents - Relevance: LOW - As Found: Unknown - ID: M10212 - Name: Immunosuppressive Agents - Relevance: LOW - As Found: Unknown - ID: M10201 - Name: Immunologic Factors - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000003907 - Term: Dexamethasone - ID: D000011241 - Term: Prednisone - ID: D000008558 - Term: Melphalan - ID: D000069286 - Term: Bortezomib - ID: C000556306 - Term: Daratumumab - ID: D000000911 - Term: Antibodies, Monoclonal ### Misc Info Module #### Removed Countries - Country: Czech Republic - Country: Macedonia, The Former Yugoslav Republic of - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module **Description:** Safety population defined as participants who have received at least 1 administration of any study drug. #### Event Groups **Group ID:** EG000 **Title:** Velcade, Melphalan and Prednisone (VMP) **Deaths Num Affected:** 48 **Deaths Num At Risk:** 354 **Description:** Participants received Velcade (bortezomib) 1.3 milligram per square meter (mg/m\^2) as subcutaneous (SC) injection, twice weekly at Weeks 1, 2, 4 and 5 in Cycle 1 followed by once weekly at Weeks 1, 2, 4 and 5 in Cycles 2 to 9, melphalan 9 mg/m\^2 orally once daily on Days 1 to 4 and prednisone 60 mg/m\^2 orally once daily on Days 1 to 4 of each cycle up to Cycle 9. **ID:** EG000 **Other Num Affected:** 331 **Other Num at Risk:** 354 **Serious Number Affected:** 115 **Serious Number At Risk:** 354 **Title:** Velcade, Melphalan and Prednisone (VMP) **Group ID:** EG001 **Title:** Daratumumab, Velcade, Melphalan and Prednisone (D-VMP) **Deaths Num Affected:** 45 **Deaths Num At Risk:** 346 **Description:** Participants received velcade 1.3 mg/m\^2 as SC injection, twice weekly at Weeks 1, 2, 4 and 5 in Cycle 1 followed by once weekly at weeks 1, 2, 4 and 5 in Cycles 2 to 9, melphalan 9 mg/m\^2, orally once daily on Days 1 to 4 and prednisone 60 mg/m\^2, orally once daily on Days 2 to 4 of each cycle up to Cycle 9. In addition, participants also received daratumumab 16 milligram per kilogram (mg/kg) as intravenous (IV) infusion once weekly for 6 weeks in Cycle 1 and then every 3 weeks, in Cycle 2 to 9 and thereafter, once every 4 weeks until documented progression, unacceptable toxicity, or study end. On Day 1 of each cycle, dexamethasone 20 mg IV or per oral (PO) was given 1 hour or less prior to daratumumab infusion as pre medication and prednisone substitute. **ID:** EG001 **Other Num Affected:** 324 **Other Num at Risk:** 346 **Serious Number Affected:** 144 **Serious Number At Risk:** 346 **Title:** Daratumumab, Velcade, Melphalan and Prednisone (D-VMP) **Frequency Threshold:** 5 #### Other Events **Term:** Anaemia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA Version 20.0 **Term:** Leukopenia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA Version 20.0 **Term:** Lymphopenia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA Version 20.0 **Term:** Neutropenia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA Version 20.0 **Term:** Thrombocytopenia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA Version 20.0 **Term:** Abdominal Pain **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA Version 20.0 **Term:** Constipation **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA Version 20.0 **Term:** Diarrhoea **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA Version 20.0 **Term:** Dyspepsia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA Version 20.0 **Term:** Nausea **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA Version 20.0 **Term:** Vomiting **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA Version 20.0 **Term:** Asthenia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA Version 20.0 **Term:** Chills **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA Version 20.0 **Term:** Fatigue **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA Version 20.0 **Term:** Injection Site Erythema **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA Version 20.0 **Term:** Oedema Peripheral **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA Version 20.0 **Term:** Pyrexia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA Version 20.0 **Term:** Bronchitis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 20.0 **Term:** Nasopharyngitis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 20.0 **Term:** Pneumonia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 20.0 **Term:** Upper Respiratory Tract Infection **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 20.0 **Term:** Urinary Tract Infection **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 20.0 **Term:** Decreased Appetite **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA Version 20.0 **Term:** Hyperglycaemia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA Version 20.0 **Term:** Hypocalcaemia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA Version 20.0 **Term:** Hypokalaemia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA Version 20.0 **Term:** Arthralgia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA Version 20.0 **Term:** Back Pain **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA Version 20.0 **Term:** Bone Pain **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA Version 20.0 **Term:** Pain in Extremity **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA Version 20.0 **Term:** Dizziness **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA Version 20.0 **Term:** Headache **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA Version 20.0 **Term:** Neuralgia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA Version 20.0 **Term:** Paraesthesia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA Version 20.0 **Term:** Peripheral Sensory Neuropathy **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA Version 20.0 **Term:** Insomnia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA Version 20.0 **Term:** Cough **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA Version 20.0 **Term:** Dyspnoea **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA Version 20.0 **Term:** Pruritus **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA Version 20.0 **Term:** Rash **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA Version 20.0 **Term:** Hypertension **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA Version 20.0 **Term:** Hypotension **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA Version 20.0 #### Serious Events **Term:** Anaemia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 9 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 6 **Num At Risk:** 346 **Term:** Febrile Neutropenia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 7 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 346 **Term:** Leukopenia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num At Risk:** 346 **Term:** Neutropenia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 4 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 3 **Num At Risk:** 346 **Term:** Thrombocytopenia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 4 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 5 **Num At Risk:** 346 **Term:** Acute Coronary Syndrome **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Acute Myocardial Infarction **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 346 **Term:** Angina Unstable **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num At Risk:** 346 **Term:** Atrial Fibrillation **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 6 **Num At Risk:** 346 **Term:** Cardiac Arrest **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Cardiac Failure **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 7 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Cardiac Failure Acute **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Cardiac Failure Chronic **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Cardiac Failure Congestive **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Cardio-Respiratory Arrest **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num At Risk:** 346 **Term:** Cardiovascular Insufficiency **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Sinus Bradycardia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 346 **Term:** Stress Cardiomyopathy **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Supraventricular Tachycardia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Tachycardia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Conjunctival Haemorrhage **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Eye disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Retinal Detachment **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Eye disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Abdominal Adhesions **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Abdominal Pain **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Abdominal Pain Upper **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num At Risk:** 346 **Term:** Anal Haemorrhage **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Colitis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num At Risk:** 346 **Term:** Constipation **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num At Risk:** 346 **Term:** Diarrhoea **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 346 **Term:** Diverticular Perforation **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num At Risk:** 346 **Term:** Enterocolitis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Gastric Haemorrhage **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num At Risk:** 346 **Term:** Gastritis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num At Risk:** 346 **Term:** Gastrointestinal Disorder **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num At Risk:** 346 **Term:** Gastrointestinal Haemorrhage **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 346 **Term:** Haematemesis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 354 **Group ID:** EG001 **Num At Risk:** 346 **Term:** Haemorrhoidal Haemorrhage **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Ileus **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num At Risk:** 346 **Term:** Ileus Paralytic **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Inguinal Hernia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Large Intestine Perforation **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Nausea **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num At Risk:** 346 **Term:** Oesophageal Rupture **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num At Risk:** 346 **Term:** Oesophagitis Haemorrhagic **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num At Risk:** 346 **Term:** Rectal Haemorrhage **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Vomiting **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 6 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 346 **Term:** Asthenia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 346 **Term:** Chest Pain **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Death **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 346 **Term:** Fatigue **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Generalised Oedema **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Hyperthermia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Malaise **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num At Risk:** 346 **Term:** Multiple Organ Dysfunction Syndrome **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num At Risk:** 346 **Term:** Non-Cardiac Chest Pain **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Pain **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Pyrexia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 5 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 5 **Num At Risk:** 346 **Term:** Cholelithiasis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num At Risk:** 346 **Term:** Abdominal Abscess **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num At Risk:** 346 **Term:** Bacteraemia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 346 **Term:** Bronchitis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 8 **Num At Risk:** 346 **Term:** Candida Sepsis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num At Risk:** 346 **Term:** Cellulitis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num At Risk:** 346 **Term:** Clostridium Colitis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Clostridium Difficile Colitis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num At Risk:** 346 **Term:** Clostridium Difficile Infection **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 354 **Group ID:** EG001 **Num At Risk:** 346 **Term:** Cytomegalovirus Infection **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 346 **Term:** Device Related Infection **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num At Risk:** 346 **Term:** Diverticulitis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Enterococcal Bacteraemia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num At Risk:** 346 **Term:** Epiglottitis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Gastroenteritis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** H1n1 Influenza **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Herpes Zoster **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num At Risk:** 346 **Term:** Herpes Zoster Disseminated **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Infection **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 3 **Num At Risk:** 346 **Term:** Infective Exacerbation of Chronic Obstructive Airways Disease **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num At Risk:** 346 **Term:** Infective Myositis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Influenza **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 3 **Num At Risk:** 346 **Term:** Lower Respiratory Tract Infection **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 3 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 8 **Num At Risk:** 346 **Term:** Lower Respiratory Tract Infection Bacterial **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Lung Infection **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Meningitis Pneumococcal **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Neutropenic Infection **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Pelvic Infection **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num At Risk:** 346 **Term:** Peritonitis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Pharyngitis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Pneumococcal Sepsis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Pneumonia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 11 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 35 **Num At Risk:** 346 **Term:** Pneumonia Bacterial **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num At Risk:** 346 **Term:** Pneumonia Pneumococcal **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 346 **Term:** Pneumonia Streptococcal **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num At Risk:** 346 **Term:** Pneumonia Viral **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Pseudomembranous Colitis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Pulmonary Sepsis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num At Risk:** 346 **Term:** Respiratory Syncytial Virus Infection **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Respiratory Tract Infection **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 346 **Term:** Sepsis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 5 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 5 **Num At Risk:** 346 **Term:** Septic Shock **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Staphylococcal Infection **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num At Risk:** 346 **Term:** Tuberculosis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Tuberculous Pleurisy **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num At Risk:** 346 **Term:** Upper Respiratory Tract Infection **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 3 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 7 **Num At Risk:** 346 **Term:** Urinary Tract Infection **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 4 **Num At Risk:** 346 **Term:** Urinary Tract Infection Bacterial **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Urosepsis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Wound Infection **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Chest Injury **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Femoral Neck Fracture **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num At Risk:** 346 **Term:** Femur Fracture **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 4 **Num At Risk:** 346 **Term:** Foot Fracture **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Humerus Fracture **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 354 **Group ID:** EG001 **Num At Risk:** 346 **Term:** Infusion Related Reaction **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Skeletal Injury **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num At Risk:** 346 **Term:** Spinal Compression Fracture **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 4 **Num At Risk:** 346 **Term:** Subarachnoid Haemorrhage **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Toxicity to Various Agents **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Traumatic Shock **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num At Risk:** 346 **Term:** Upper Limb Fracture **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Wrist Fracture **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num At Risk:** 346 **Term:** Alanine Aminotransferase Increased **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num At Risk:** 346 **Term:** Aspartate Aminotransferase Increased **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 354 **Group ID:** EG001 **Num At Risk:** 346 **Term:** Blood Creatinine Increased **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** C-Reactive Protein Increased **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Oxygen Saturation Decreased **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 346 **Term:** Troponin Increased **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num At Risk:** 346 **Term:** Decreased Appetite **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Dehydration **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 346 **Term:** Hyperkalaemia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num At Risk:** 346 **Term:** Hypophagia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Tumour Lysis Syndrome **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Arthralgia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Back Pain **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 3 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 6 **Num At Risk:** 346 **Term:** Bone Pain **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 346 **Term:** Dactylitis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Neck Pain **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Osteonecrosis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num At Risk:** 346 **Term:** Spinal Column Stenosis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Acute Myeloid Leukaemia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num At Risk:** 346 **Term:** Adenocarcinoma of Colon **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num At Risk:** 346 **Term:** Bile Duct Cancer **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Breast Cancer **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num At Risk:** 346 **Term:** Meningioma **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num At Risk:** 346 **Term:** Oesophageal Adenocarcinoma **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Plasmacytoma **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Rectal Adenocarcinoma **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num At Risk:** 346 **Term:** Renal Cell Carcinoma **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Autonomic Nervous System Imbalance **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num At Risk:** 346 **Term:** Cerebral Infarction **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num At Risk:** 346 **Term:** Cerebral Ischaemia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num At Risk:** 346 **Term:** Cerebrovascular Accident **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Dizziness **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num At Risk:** 346 **Term:** Epilepsy **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Haemorrhage Intracranial **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Headache **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 354 **Group ID:** EG001 **Num At Risk:** 346 **Term:** Ischaemic Stroke **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 346 **Term:** Neuralgia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Neurotoxicity **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num At Risk:** 346 **Term:** Paraesthesia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Paraparesis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Parkinson's Disease **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Peripheral Motor Neuropathy **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Peripheral Sensorimotor Neuropathy **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Peripheral Sensory Neuropathy **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 346 **Term:** Sciatica **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Somnolence **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Spinal Cord Compression **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Syncope **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Agitation **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Delirium **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num At Risk:** 346 **Term:** Depression **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Psychotic Disorder **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num At Risk:** 346 **Term:** Acute Kidney Injury **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 5 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 3 **Num At Risk:** 346 **Term:** Anuria **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num At Risk:** 346 **Term:** Chronic Kidney Disease **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num At Risk:** 346 **Term:** Haematuria **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Prerenal Failure **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num At Risk:** 346 **Term:** Renal Failure **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Urinary Retention **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num At Risk:** 346 **Term:** Acute Respiratory Distress Syndrome **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Acute Respiratory Failure **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 346 **Term:** Bronchiectasis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Bronchospasm **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 346 **Term:** Chronic Obstructive Pulmonary Disease **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Cough **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Dyspnoea **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 4 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 6 **Num At Risk:** 346 **Term:** Haemoptysis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num At Risk:** 346 **Term:** Hypoxia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 346 **Term:** Interstitial Lung Disease **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Laryngeal Oedema **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num At Risk:** 346 **Term:** Obstructive Airways Disorder **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num At Risk:** 346 **Term:** Pneumonitis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Pneumothorax Spontaneous **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num At Risk:** 346 **Term:** Pulmonary Embolism **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 4 **Num At Risk:** 354 **Group ID:** EG001 **Num At Risk:** 346 **Term:** Pulmonary Oedema **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 6 **Num At Risk:** 346 **Term:** Tachypnoea **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Wheezing **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Decubitus Ulcer **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Erythema Multiforme **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 354 **Group ID:** EG001 **Num At Risk:** 346 **Term:** Rash Erythematous **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Rash Vesicular **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num At Risk:** 346 **Term:** Hypertension **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 346 **Term:** Hypotension **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Hypovolaemic Shock **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Orthostatic Hypotension **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 354 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 346 **Term:** Thrombophlebitis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA Version 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 354 **Group ID:** EG001 **Num At Risk:** 346 **Time Frame:** Up to 2.4 years ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 356 **Group ID:** BG001 **Value:** 350 **Group ID:** BG002 **Value:** 706 **Units:** Participants ### Group **ID:** BG000 **Title:** Velcade, Melphalan and Prednisone (VMP) **Description:** Participants received Velcade (bortezomib) 1.3 milligram per square meter (mg/m\^2) as subcutaneous (SC) injection, twice weekly at Weeks 1, 2, 4 and 5 in Cycle 1 followed by once weekly at Weeks 1, 2, 4 and 5 in Cycles 2 to 9, melphalan 9 mg/m\^2 orally once daily on Days 1 to 4 and prednisone 60 mg/m\^2 orally once daily on Days 1 to 4 of each cycle up to Cycle 9. ### Group **ID:** BG001 **Title:** Daratumumab, Velcade, Melphalan and Prednisone (D-VMP) **Description:** Participants received velcade 1.3 mg/m\^2 as SC injection, twice weekly at Weeks 1, 2, 4 and 5 in Cycle 1 followed by once weekly at weeks 1, 2, 4 and 5 in Cycles 2 to 9, melphalan 9 mg/m\^2, orally once daily on Days 1 to 4 and prednisone 60 mg/m\^2, orally once daily on Days 2 to 4 of each cycle up to Cycle 9. In addition, participants also received daratumumab 16 milligram per kilogram (mg/kg) as intravenous (IV) infusion once weekly for 6 weeks in Cycle 1 and then every 3 weeks, in Cycle 2 to 9 and thereafter, once every 4 weeks until documented progression, unacceptable toxicity, or study end. On Day 1 of each cycle, dexamethasone 20 mg IV or per oral (PO) was given 1 hour or less prior to daratumumab infusion as pre medication and prednisone substitute. ### Group **ID:** BG002 **Title:** Total **Description:** Total of all reporting groups ### Measure #### Measurement **Group ID:** BG000 **Spread:** 5.82 **Value:** 71.5 #### Measurement **Group ID:** BG001 **Spread:** 6.66 **Value:** 71.3 #### Measurement **Group ID:** BG002 **Spread:** 6.25 **Value:** 71.4 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 356 **Group ID:** BG001 **Value:** 350 **Group ID:** BG002 **Value:** 706 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 189 #### Measurement **Group ID:** BG001 **Value:** 190 #### Measurement **Group ID:** BG002 **Value:** 379 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 167 #### Measurement **Group ID:** BG001 **Value:** 160 #### Measurement **Group ID:** BG002 **Value:** 327 **Category Title:** Male #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 356 **Group ID:** BG001 **Value:** 350 **Group ID:** BG002 **Value:** 706 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 16 #### Measurement **Group ID:** BG001 **Value:** 24 #### Measurement **Group ID:** BG002 **Value:** 40 **Category Title:** Hispanic or Latino #### Measurement **Group ID:** BG000 **Value:** 332 #### Measurement **Group ID:** BG001 **Value:** 320 #### Measurement **Group ID:** BG002 **Value:** 652 **Category Title:** Not Hispanic or Latino #### Measurement **Group ID:** BG000 **Value:** 8 #### Measurement **Group ID:** BG001 **Value:** 6 #### Measurement **Group ID:** BG002 **Value:** 14 **Category Title:** Unknown or Not Reported #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 356 **Group ID:** BG001 **Value:** 350 **Group ID:** BG002 **Value:** 706 **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:** 45 #### Measurement **Group ID:** BG001 **Value:** 47 #### Measurement **Group ID:** BG002 **Value:** 92 **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:** 3 #### Measurement **Group ID:** BG001 **Value:** 3 #### Measurement **Group ID:** BG002 **Value:** 6 **Category Title:** Black or African American #### Measurement **Group ID:** BG000 **Value:** 304 #### Measurement **Group ID:** BG001 **Value:** 297 #### Measurement **Group ID:** BG002 **Value:** 601 **Category Title:** White #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** More than one race #### Measurement **Group ID:** BG000 **Value:** 4 #### Measurement **Group ID:** BG001 **Value:** 3 #### Measurement **Group ID:** BG002 **Value:** 7 **Category Title:** Unknown or Not Reported #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 356 **Group ID:** BG001 **Value:** 350 **Group ID:** BG002 **Value:** 706 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 2 #### Measurement **Group ID:** BG001 **Value:** 2 #### Measurement **Group ID:** BG002 **Value:** 4 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 356 **Group ID:** BG001 **Value:** 350 **Group ID:** BG002 **Value:** 706 **Class Title:** Argentina #### Measurement **Group ID:** BG000 **Value:** 10 #### Measurement **Group ID:** BG001 **Value:** 5 #### Measurement **Group ID:** BG002 **Value:** 15 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 356 **Group ID:** BG001 **Value:** 350 **Group ID:** BG002 **Value:** 706 **Class Title:** Australia #### Measurement **Group ID:** BG000 **Value:** 8 #### Measurement **Group ID:** BG001 **Value:** 6 #### Measurement **Group ID:** BG002 **Value:** 14 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 356 **Group ID:** BG001 **Value:** 350 **Group ID:** BG002 **Value:** 706 **Class Title:** Belgium #### Measurement **Group ID:** BG000 **Value:** 2 #### Measurement **Group ID:** BG001 **Value:** 4 #### Measurement **Group ID:** BG002 **Value:** 6 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 356 **Group ID:** BG001 **Value:** 350 **Group ID:** BG002 **Value:** 706 **Class Title:** Brazil #### Measurement **Group ID:** BG000 **Value:** 15 #### Measurement **Group ID:** BG001 **Value:** 8 #### Measurement **Group ID:** BG002 **Value:** 23 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 356 **Group ID:** BG001 **Value:** 350 **Group ID:** BG002 **Value:** 706 **Class Title:** Bulgaria #### Measurement **Group ID:** BG000 **Value:** 2 #### Measurement **Group ID:** BG001 **Value:** 2 #### Measurement **Group ID:** BG002 **Value:** 4 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 356 **Group ID:** BG001 **Value:** 350 **Group ID:** BG002 **Value:** 706 **Class Title:** Croatia #### Measurement **Group ID:** BG000 **Value:** 29 #### Measurement **Group ID:** BG001 **Value:** 21 #### Measurement **Group ID:** BG002 **Value:** 50 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 356 **Group ID:** BG001 **Value:** 350 **Group ID:** BG002 **Value:** 706 **Class Title:** Czech Republic #### Measurement **Group ID:** BG000 **Value:** 11 #### Measurement **Group ID:** BG001 **Value:** 11 #### Measurement **Group ID:** BG002 **Value:** 22 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 356 **Group ID:** BG001 **Value:** 350 **Group ID:** BG002 **Value:** 706 **Class Title:** Georgia #### Measurement **Group ID:** BG000 **Value:** 2 #### Measurement **Group ID:** BG001 **Value:** 5 #### Measurement **Group ID:** BG002 **Value:** 7 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 356 **Group ID:** BG001 **Value:** 350 **Group ID:** BG002 **Value:** 706 **Class Title:** Germany #### Measurement **Group ID:** BG000 **Value:** 15 #### Measurement **Group ID:** BG001 **Value:** 14 #### Measurement **Group ID:** BG002 **Value:** 29 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 356 **Group ID:** BG001 **Value:** 350 **Group ID:** BG002 **Value:** 706 **Class Title:** Greece #### Measurement **Group ID:** BG000 **Value:** 12 #### Measurement **Group ID:** BG001 **Value:** 14 #### Measurement **Group ID:** BG002 **Value:** 26 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 356 **Group ID:** BG001 **Value:** 350 **Group ID:** BG002 **Value:** 706 **Class Title:** Hungary #### Measurement **Group ID:** BG000 **Value:** 26 #### Measurement **Group ID:** BG001 **Value:** 28 #### Measurement **Group ID:** BG002 **Value:** 54 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 356 **Group ID:** BG001 **Value:** 350 **Group ID:** BG002 **Value:** 706 **Class Title:** Italy #### Measurement **Group ID:** BG000 **Value:** 26 #### Measurement **Group ID:** BG001 **Value:** 24 #### Measurement **Group ID:** BG002 **Value:** 50 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 356 **Group ID:** BG001 **Value:** 350 **Group ID:** BG002 **Value:** 706 **Class Title:** Japan #### Measurement **Group ID:** BG000 **Value:** 27 #### Measurement **Group ID:** BG001 **Value:** 39 #### Measurement **Group ID:** BG002 **Value:** 66 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 356 **Group ID:** BG001 **Value:** 350 **Group ID:** BG002 **Value:** 706 **Class Title:** Poland #### Measurement **Group ID:** BG000 **Value:** 4 #### Measurement **Group ID:** BG001 **Value:** 3 #### Measurement **Group ID:** BG002 **Value:** 7 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 356 **Group ID:** BG001 **Value:** 350 **Group ID:** BG002 **Value:** 706 **Class Title:** Portugal #### Measurement **Group ID:** BG000 **Value:** 10 #### Measurement **Group ID:** BG001 **Value:** 1 #### Measurement **Group ID:** BG002 **Value:** 11 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 356 **Group ID:** BG001 **Value:** 350 **Group ID:** BG002 **Value:** 706 **Class Title:** Macedonia #### Measurement **Group ID:** BG000 **Value:** 18 #### Measurement **Group ID:** BG001 **Value:** 10 #### Measurement **Group ID:** BG002 **Value:** 28 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 356 **Group ID:** BG001 **Value:** 350 **Group ID:** BG002 **Value:** 706 **Class Title:** Romania #### Measurement **Group ID:** BG000 **Value:** 21 #### Measurement **Group ID:** BG001 **Value:** 22 #### Measurement **Group ID:** BG002 **Value:** 43 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 356 **Group ID:** BG001 **Value:** 350 **Group ID:** BG002 **Value:** 706 **Class Title:** Russia #### Measurement **Group ID:** BG000 **Value:** 3 #### Measurement **Group ID:** BG001 **Value:** 7 #### Measurement **Group ID:** BG002 **Value:** 10 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 356 **Group ID:** BG001 **Value:** 350 **Group ID:** BG002 **Value:** 706 **Class Title:** Serbia #### Measurement **Group ID:** BG000 **Value:** 18 #### Measurement **Group ID:** BG001 **Value:** 23 #### Measurement **Group ID:** BG002 **Value:** 41 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 356 **Group ID:** BG001 **Value:** 350 **Group ID:** BG002 **Value:** 706 **Class Title:** Korea, Democratic People'S Republic Of #### Measurement **Group ID:** BG000 **Value:** 47 #### Measurement **Group ID:** BG001 **Value:** 56 #### Measurement **Group ID:** BG002 **Value:** 103 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 356 **Group ID:** BG001 **Value:** 350 **Group ID:** BG002 **Value:** 706 **Class Title:** Spain #### Measurement **Group ID:** BG000 **Value:** 10 #### Measurement **Group ID:** BG001 **Value:** 5 #### Measurement **Group ID:** BG002 **Value:** 15 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 356 **Group ID:** BG001 **Value:** 350 **Group ID:** BG002 **Value:** 706 **Class Title:** Turkey #### Measurement **Group ID:** BG000 **Value:** 20 #### Measurement **Group ID:** BG001 **Value:** 28 #### Measurement **Group ID:** BG002 **Value:** 48 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 356 **Group ID:** BG001 **Value:** 350 **Group ID:** BG002 **Value:** 706 **Class Title:** Ukraine #### Measurement **Group ID:** BG000 **Value:** 15 #### Measurement **Group ID:** BG001 **Value:** 9 #### Measurement **Group ID:** BG002 **Value:** 24 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 356 **Group ID:** BG001 **Value:** 350 **Group ID:** BG002 **Value:** 706 **Class Title:** United Kingdom #### Measurement **Group ID:** BG000 **Value:** 3 #### Measurement **Group ID:** BG001 **Value:** 3 #### Measurement **Group ID:** BG002 **Value:** 6 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 356 **Group ID:** BG001 **Value:** 350 **Group ID:** BG002 **Value:** 706 **Class Title:** United States ### Measure #### Measurement **Group ID:** BG000 **Value:** 38 #### Measurement **Group ID:** BG001 **Value:** 47 #### Measurement **Group ID:** BG002 **Value:** 85 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 331 **Group ID:** BG001 **Value:** 333 **Group ID:** BG002 **Value:** 664 **Class Title:** I #### Measurement **Group ID:** BG000 **Value:** 247 #### Measurement **Group ID:** BG001 **Value:** 226 #### Measurement **Group ID:** BG002 **Value:** 473 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 331 **Group ID:** BG001 **Value:** 333 **Group ID:** BG002 **Value:** 664 **Class Title:** II #### Measurement **Group ID:** BG000 **Value:** 46 #### Measurement **Group ID:** BG001 **Value:** 60 #### Measurement **Group ID:** BG002 **Value:** 106 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 331 **Group ID:** BG001 **Value:** 333 **Group ID:** BG002 **Value:** 664 **Class Title:** III ### Measure #### Measurement **Group ID:** BG000 **Spread:** 1.737 **Value:** 1.27 #### Measurement **Group ID:** BG001 **Spread:** 1.056 **Value:** 1.09 #### Measurement **Group ID:** BG002 **Spread:** 1.442 **Value:** 1.18 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 356 **Group ID:** BG001 **Value:** 350 **Group ID:** BG002 **Value:** 706 **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 International Staging System (ISS) consists of following 3 stages - Stage I: serum beta2-microglobulin less than (\<)3.5 milligram per liter (mg/L) and albumin greater than or equal to (\>=) 3.5 gram per 100 Milliliter (g/100 mL); Stage II: neither stage I nor stage III and Stage III: serum beta2-microglobulin \>= 5.5 mg/L. **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Here, 'N' (number of participants analyzed) signifies number of participants who were evaluable for this study specific characteristic. **Title:** Stage of Disease (ISS) **Unit of Measure:** Participants ### Measure 7 **Description:** Time from multiple myeloma (MM) diagnosis is the time from diagnosis of multiple myeloma to randomization in each treatment group. **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** Time from multiple myeloma (MM) diagnosis **Unit of Measure:** Months ## Results Section - More Information Module ### Certain Agreement **Other Details:** A copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested in writing, such publication will be withheld for up to an additional 60 days. **Restriction Type:** OTHER **Restrictive Agreement:** True ### Point of Contact **Email:** [email protected] **Organization:** Janssen Research and Development, LLC **Phone:** 844-434-4210 **Title:** Executive Medical Director ## Results Section - Outcome Measures Module ### Outcome Measure 1 ### Outcome Measure 2 ### Outcome Measure 3 ### Outcome Measure 4 ### Outcome Measure 5 ### Outcome Measure 6 ### Outcome Measure 7 ### Outcome Measure 8 ### Outcome Measure 9 ### Outcome Measure 10 ### Outcome Measure 11 ### Outcome Measure 12 ### Outcome Measure 13 ### Outcome Measure 14 ### Outcome Measure 15 ### Outcome Measure 16 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 16.53 - **Spread:** - **Upper Limit:** 19.91 - **Value:** 18.14 - **Comment:** Median and 95% confidence interval (CI) was not estimable due to insufficient number of events. - **Group ID:** OG001 - **Lower Limit:** NA - **Spread:** - **Upper Limit:** NA - **Value:** NA **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 73.9 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 90.9 **Title:** #### Outcome Measure 3 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 49.7 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 71.1 **Title:** #### Outcome Measure 4 **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:** 42.6 **Title:** #### Outcome Measure 5 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 6.2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 22.3 **Title:** #### Outcome Measure 6 **Class:** ##### Category **Measurements:** - **Comment:** Median and 95% CI was not estimable due to insufficient number of events. - **Group ID:** OG000 - **Lower Limit:** NA - **Spread:** - **Upper Limit:** NA - **Value:** NA - **Comment:** Median and 95% CI was not estimable due to insufficient number of events. - **Group ID:** OG001 - **Lower Limit:** NA - **Spread:** - **Upper Limit:** NA - **Value:** NA **Title:** #### Outcome Measure 7 **Class:** ##### Category **Measurements:** - **Comment:** Median and 95% CI was not estimable due to insufficient number of events. - **Group ID:** OG000 - **Lower Limit:** NA - **Spread:** - **Upper Limit:** NA - **Value:** NA - **Comment:** Median and 95% CI was not estimable due to insufficient number of events. - **Group ID:** OG001 - **Lower Limit:** NA - **Spread:** - **Upper Limit:** NA - **Value:** NA **Title:** #### Outcome Measure 8 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 9.3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 20.3 **Title:** #### Outcome Measure 9 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 17.38 - **Spread:** - **Upper Limit:** 22.67 - **Value:** 19.35 - **Comment:** Median and 95% CI was not estimable due to insufficient number of events. - **Group ID:** OG001 - **Lower Limit:** NA - **Spread:** - **Upper Limit:** NA - **Value:** NA **Title:** #### Outcome Measure 10 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0.7 - **Spread:** - **Upper Limit:** 12.6 - **Value:** 0.82 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 0.4 - **Spread:** - **Upper Limit:** 15.5 - **Value:** 0.79 **Title:** #### Outcome Measure 11 **Class:** ##### Category **Measurements:** - **Comment:** Upper limit of 95% CI was not estimable due to insufficient number of events. - **Group ID:** OG000 - **Lower Limit:** 18.4 - **Spread:** - **Upper Limit:** NA - **Value:** 21.3 - **Comment:** Median and 95% CI was not estimable due to insufficient number of events. - **Group ID:** OG001 - **Lower Limit:** NA - **Spread:** - **Upper Limit:** NA - **Value:** NA **Title:** #### Outcome Measure 12 **Class:** ##### Category **Measurements:** - **Comment:** Median and upper limit of 95% CI was not estimable due to insufficient number of events. - **Group ID:** OG000 - **Lower Limit:** 21.4 - **Spread:** - **Upper Limit:** NA - **Value:** NA - **Comment:** Median and 95% CI was not estimable due to insufficient number of events. - **Group ID:** OG001 - **Lower Limit:** NA - **Spread:** - **Upper Limit:** NA - **Value:** NA **Title:** #### Outcome Measure 13 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 38.7 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 58.5 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 287 - **Group ID:** OG001 - **Value:** 277 **Units:** Participants **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:** 15.2 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 287 - **Group ID:** OG001 - **Value:** 277 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 69.4 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 90.5 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 36 - **Group ID:** OG001 - **Value:** 42 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 13.9 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 7.1 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 36 - **Group ID:** OG001 - **Value:** 42 **Units:** Participants **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:** **Denomination:** - **Group ID:** OG000 - **Value:** 18 - **Group ID:** OG001 - **Value:** 18 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 77.8 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 100.0 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 18 - **Group ID:** OG001 - **Value:** 18 **Units:** Participants #### Outcome Measure 14 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 7.1 - **Spread:** - **Upper Limit:** 11.7 - **Value:** 9.4 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 6.6 - **Spread:** - **Upper Limit:** 11.1 - **Value:** 8.8 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 244 - **Group ID:** OG001 - **Value:** 261 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 8.1 - **Spread:** - **Upper Limit:** 12.9 - **Value:** 10.5 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 8.3 - **Spread:** - **Upper Limit:** 12.9 - **Value:** 10.6 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 212 - **Group ID:** OG001 - **Value:** 233 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 9.4 - **Spread:** - **Upper Limit:** 14.4 - **Value:** 11.9 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 8.8 - **Spread:** - **Upper Limit:** 13.5 - **Value:** 11.1 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 189 - **Group ID:** OG001 - **Value:** 226 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 8.4 - **Spread:** - **Upper Limit:** 13.6 - **Value:** 11 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 10.2 - **Spread:** - **Upper Limit:** 14.9 - **Value:** 12.6 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 179 - **Group ID:** OG001 - **Value:** 220 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 8.5 - **Spread:** - **Upper Limit:** 16.9 - **Value:** 12.7 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 7.9 - **Spread:** - **Upper Limit:** 14.9 - **Value:** 11.4 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 52 - **Group ID:** OG001 - **Value:** 78 **Units:** Participants #### Outcome Measure 15 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 20.610 - **Upper Limit:** - **Value:** 60.33 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 20.190 - **Upper Limit:** - **Value:** 57.90 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 325 - **Group ID:** OG001 - **Value:** 315 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 18.417 - **Upper Limit:** - **Value:** 4.20 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 20.195 - **Upper Limit:** - **Value:** 9.28 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 241 - **Group ID:** OG001 - **Value:** 258 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 18.002 - **Upper Limit:** - **Value:** 7.40 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 20.123 - **Upper Limit:** - **Value:** 10.83 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 209 - **Group ID:** OG001 - **Value:** 229 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 19.516 - **Upper Limit:** - **Value:** 9.89 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 20.616 - **Upper Limit:** - **Value:** 12.50 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 186 - **Group ID:** OG001 - **Value:** 225 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 19.386 - **Upper Limit:** - **Value:** 10.80 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 20.271 - **Upper Limit:** - **Value:** 10.79 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 179 - **Group ID:** OG001 - **Value:** 216 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 19.284 - **Upper Limit:** - **Value:** 7.65 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 20.126 - **Upper Limit:** - **Value:** 12.04 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 51 - **Group ID:** OG001 - **Value:** 77 **Units:** Participants #### Outcome Measure 16 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.301 - **Upper Limit:** - **Value:** 0.59 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.292 - **Upper Limit:** - **Value:** 0.57 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 325 - **Group ID:** OG001 - **Value:** 315 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.312 - **Upper Limit:** - **Value:** 0.09 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.265 - **Upper Limit:** - **Value:** 0.12 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 241 - **Group ID:** OG001 - **Value:** 258 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.270 - **Upper Limit:** - **Value:** 0.12 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.271 - **Upper Limit:** - **Value:** 0.13 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 209 - **Group ID:** OG001 - **Value:** 229 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.270 - **Upper Limit:** - **Value:** 0.16 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.270 - **Upper Limit:** - **Value:** 0.16 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 186 - **Group ID:** OG001 - **Value:** 225 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.278 - **Upper Limit:** - **Value:** 0.15 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.287 - **Upper Limit:** - **Value:** 0.17 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 179 - **Group ID:** OG001 - **Value:** 216 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.247 - **Upper Limit:** - **Value:** 0.13 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.314 - **Upper Limit:** - **Value:** 0.13 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 51 - **Group ID:** OG001 - **Value:** 77 **Units:** Participants ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** PFS- duration from date of randomization to Progressive disease (PD)/death, whichever occurs first. PD per IMWG criteria-Increase of 25% from lowest response value in one of following: Serum and urine M-component (absolute increase \>=0.5 gram per deciliter \[g/dL\] and \>=200 milligram \[mg\]/24 hours respectively); Only participants without measurable serum and urine M-protein levels: difference between involved and uninvolved free light chain (FLC) levels (absolute increase\>10 mg/dL); Only participants without measurable serum and urine M-protein levels,without measurable disease by FLC levels,bone marrow Plasma cells (PC) %(absolute % \>=10%);Bone marrow PC%: absolute% \>10%; Definite development of new bone lesions/soft tissue plasmacytomas/definite increase in size of existing bone lesions/soft tissue plasmacytomas and Development of hypercalcemia (corrected serum calcium \>11.5 mg/dL) that can be attributed solely to the PC proliferative disorder. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEDIAN **Population Description:** Intent-to-treat (ITT) population included all participants randomized into the study; classified according to assigned treatment group, regardless of the actual treatment received. **Reporting Status:** POSTED **Time Frame:** From randomization to either disease progression or death whichever occurs first (up to 2.4 years) **Title:** Progression Free Survival (PFS) **Type:** PRIMARY **Unit of Measure:** Months ##### Group **Description:** Participants received Velcade (bortezomib) 1.3 milligram per square meter (mg/m\^2) as subcutaneous (SC) injection, twice weekly at Weeks 1, 2, 4 and 5 in Cycle 1 followed by once weekly at Weeks 1, 2, 4 and 5 in Cycles 2 to 9, melphalan 9 mg/m\^2 orally once daily on Days 1 to 4 and prednisone 60 mg/m\^2 orally once daily on Days 1 to 4 of each cycle up to Cycle 9. **ID:** OG000 **Title:** Velcade, Melphalan and Prednisone (VMP) ##### Group **Description:** Participants received velcade 1.3 mg/m\^2 as SC injection, twice weekly at Weeks 1, 2, 4 and 5 in Cycle 1 followed by once weekly at weeks 1, 2, 4 and 5 in Cycles 2 to 9, melphalan 9 mg/m\^2, orally once daily on Days 1 to 4 and prednisone 60 mg/m\^2, orally once daily on Days 2 to 4 of each cycle up to Cycle 9. In addition, participants also received daratumumab 16 milligram per kilogram (mg/kg) as intravenous (IV) infusion once weekly for 6 weeks in Cycle 1 and then every 3 weeks, in Cycle 2 to 9 and thereafter, once every 4 weeks until documented progression, unacceptable toxicity, or study end. On Day 1 of each cycle, dexamethasone 20 mg IV or per oral (PO) was given 1 hour or less prior to daratumumab infusion as pre medication and prednisone substitute. **ID:** OG001 **Title:** Daratumumab, Velcade, Melphalan and Prednisone (D-VMP) #### Outcome Measure 2 **Description:** The Overall response rate was defined as the percentage of participants who achieved a partial response (PR) or better, according to the International Myeloma Working Group (IMWG) criteria, during the study or during follow up. IMWG criteria for PR: greater than or equal to (\>=) 50 percentage(%) reduction of serum M-protein and reduction in 24 hour urinary M-protein by \>=90% or to \<200 mg/24 hours, if the serum and urine M-protein are not measurable, a decrease of \>=50% in the difference between involved and uninvolved free light chain (FLC) levels is required in place of the M-protein criteria, If serum and urine M-protein are not measurable, and serum free light assay is also not measurable, \>=50% reduction in bone marrow plasma cells (PCs) is required in place of M-protein, provided baseline bone marrow plasma cell percentage was \>=30%, in addition to the above criteria, if present at baseline, a \>=50% reduction in the size of soft tissue plasmacytomas is also required. **Parameter Type:** NUMBER **Population Description:** ITT population included all participants randomized into the study; classified according to assigned treatment group, regardless of the actual treatment received. **Reporting Status:** POSTED **Time Frame:** From randomization to disease progression (up to 2.4 years) **Title:** Overall Response Rate (ORR) **Type:** SECONDARY **Unit of Measure:** Percentage of participants ##### Group **Description:** Participants received Velcade (bortezomib) 1.3 milligram per square meter (mg/m\^2) as subcutaneous (SC) injection, twice weekly at Weeks 1, 2, 4 and 5 in Cycle 1 followed by once weekly at Weeks 1, 2, 4 and 5 in Cycles 2 to 9, melphalan 9 mg/m\^2 orally once daily on Days 1 to 4 and prednisone 60 mg/m\^2 orally once daily on Days 1 to 4 of each cycle up to Cycle 9. **ID:** OG000 **Title:** Velcade, Melphalan and Prednisone (VMP) ##### Group **Description:** Participants received velcade 1.3 mg/m\^2 as SC injection, twice weekly at Weeks 1, 2, 4 and 5 in Cycle 1 followed by once weekly at weeks 1, 2, 4 and 5 in Cycles 2 to 9, melphalan 9 mg/m\^2, orally once daily on Days 1 to 4 and prednisone 60 mg/m\^2, orally once daily on Days 2 to 4 of each cycle up to Cycle 9. In addition, participants also received daratumumab 16 milligram per kilogram (mg/kg) as intravenous (IV) infusion once weekly for 6 weeks in Cycle 1 and then every 3 weeks, in Cycle 2 to 9 and thereafter, once every 4 weeks until documented progression, unacceptable toxicity, or study end. On Day 1 of each cycle, dexamethasone 20 mg IV or per oral (PO) was given 1 hour or less prior to daratumumab infusion as pre medication and prednisone substitute. **ID:** OG001 **Title:** Daratumumab, Velcade, Melphalan and Prednisone (D-VMP) #### Outcome Measure 3 **Description:** VGPR or better rate was defined as the percentage of participants who achieved VGPR or complete response (CR) (including stringent complete response\[sCR\]) according to the IMWG criteria during or after the study treatment. VGPR: Serum and urine component detectable by immunofixation but not on electrophoresis, or \>= 90% reduction in serum M-protein plus urine M-protein level less than (\<) 100 milligram (mg) per 24 hour; CR: negative immunofixation on the serum and urine, Disappearance of any soft tissue plasmacytomas and \< 5% plasms cells (PCs) in bone marrow; sCR: CR in addition to having a normal FLC ratio and an absence of clonal cells in bone marrow by immunohistochemistry, immunofluorescence, 2-4 color flow cytometry. **Parameter Type:** NUMBER **Population Description:** ITT population included all participants randomized into the study; classified according to assigned treatment group, regardless of the actual treatment received. **Reporting Status:** POSTED **Time Frame:** From randomization to disease progression (up to 2.4 years) **Title:** Percentage of Participants With Very Good Partial Response (VGPR) or Better **Type:** SECONDARY **Unit of Measure:** Percentage of participants ##### Group **Description:** Participants received Velcade (bortezomib) 1.3 milligram per square meter (mg/m\^2) as subcutaneous (SC) injection, twice weekly at Weeks 1, 2, 4 and 5 in Cycle 1 followed by once weekly at Weeks 1, 2, 4 and 5 in Cycles 2 to 9, melphalan 9 mg/m\^2 orally once daily on Days 1 to 4 and prednisone 60 mg/m\^2 orally once daily on Days 1 to 4 of each cycle up to Cycle 9. **ID:** OG000 **Title:** Velcade, Melphalan and Prednisone (VMP) ##### Group **Description:** Participants received velcade 1.3 mg/m\^2 as SC injection, twice weekly at Weeks 1, 2, 4 and 5 in Cycle 1 followed by once weekly at weeks 1, 2, 4 and 5 in Cycles 2 to 9, melphalan 9 mg/m\^2, orally once daily on Days 1 to 4 and prednisone 60 mg/m\^2, orally once daily on Days 2 to 4 of each cycle up to Cycle 9. In addition, participants also received daratumumab 16 milligram per kilogram (mg/kg) as intravenous (IV) infusion once weekly for 6 weeks in Cycle 1 and then every 3 weeks, in Cycle 2 to 9 and thereafter, once every 4 weeks until documented progression, unacceptable toxicity, or study end. On Day 1 of each cycle, dexamethasone 20 mg IV or per oral (PO) was given 1 hour or less prior to daratumumab infusion as pre medication and prednisone substitute. **ID:** OG001 **Title:** Daratumumab, Velcade, Melphalan and Prednisone (D-VMP) #### Outcome Measure 4 **Description:** CR or better rate was defined as the percentage of participants with a CR or better (i.e. CR and sCR) as per IMWG criteria. CR: as negative immunofixation on the serum and urine and disappearance of soft tissue plasmacytomas and less than (\<) 5 percent plasma cells in bone marrow; sCR: CR plus normal free light chain (FLC) ratio and absence of clonal PCs by immunohistochemistry, immunofluorescence or 2- to 4-color flow cytometry. **Parameter Type:** NUMBER **Population Description:** ITT population included all participants randomized into the study; classified according to assigned treatment group, regardless of the actual treatment received. **Reporting Status:** POSTED **Time Frame:** From randomization to disease progression (up to 2.4 years) **Title:** Percentage of Participants With Complete Response (CR) or Better **Type:** SECONDARY **Unit of Measure:** Percentage of participants ##### Group **Description:** Participants received Velcade (bortezomib) 1.3 milligram per square meter (mg/m\^2) as subcutaneous (SC) injection, twice weekly at Weeks 1, 2, 4 and 5 in Cycle 1 followed by once weekly at Weeks 1, 2, 4 and 5 in Cycles 2 to 9, melphalan 9 mg/m\^2 orally once daily on Days 1 to 4 and prednisone 60 mg/m\^2 orally once daily on Days 1 to 4 of each cycle up to Cycle 9. **ID:** OG000 **Title:** Velcade, Melphalan and Prednisone (VMP) ##### Group **Description:** Participants received velcade 1.3 mg/m\^2 as SC injection, twice weekly at Weeks 1, 2, 4 and 5 in Cycle 1 followed by once weekly at weeks 1, 2, 4 and 5 in Cycles 2 to 9, melphalan 9 mg/m\^2, orally once daily on Days 1 to 4 and prednisone 60 mg/m\^2, orally once daily on Days 2 to 4 of each cycle up to Cycle 9. In addition, participants also received daratumumab 16 milligram per kilogram (mg/kg) as intravenous (IV) infusion once weekly for 6 weeks in Cycle 1 and then every 3 weeks, in Cycle 2 to 9 and thereafter, once every 4 weeks until documented progression, unacceptable toxicity, or study end. On Day 1 of each cycle, dexamethasone 20 mg IV or per oral (PO) was given 1 hour or less prior to daratumumab infusion as pre medication and prednisone substitute. **ID:** OG001 **Title:** Daratumumab, Velcade, Melphalan and Prednisone (D-VMP) #### Outcome Measure 5 **Description:** The Minimal Residual Disease negativity rate was defined as the percentage of participants who had negative MRD (detection of less than 1 malignant cell among 100,000 normal cells) assessment at any timepoint after the first dose of study drugs by evaluation of bone marrow aspirates or whole blood at 10\^-5 threshold. MRD was evaluated by using Deoxyribonucleic acid (DNA) sequencing of immunoglobulin genes. MRD was assessed in participants who achieved complete response or stringent complete response (CR/sCR). **Parameter Type:** NUMBER **Population Description:** ITT population included all participants randomized into the study; classified according to assigned treatment group, regardless of the actual treatment received. **Reporting Status:** POSTED **Time Frame:** From randomization to disease progression (up to 2.4 years) **Title:** Percentage of Participants With Negative Minimal Residual Disease (MRD) **Type:** SECONDARY **Unit of Measure:** Percentage of participants ##### Group **Description:** Participants received Velcade (bortezomib) 1.3 milligram per square meter (mg/m\^2) as subcutaneous (SC) injection, twice weekly at Weeks 1, 2, 4 and 5 in Cycle 1 followed by once weekly at Weeks 1, 2, 4 and 5 in Cycles 2 to 9, melphalan 9 mg/m\^2 orally once daily on Days 1 to 4 and prednisone 60 mg/m\^2 orally once daily on Days 1 to 4 of each cycle up to Cycle 9. **ID:** OG000 **Title:** Velcade, Melphalan and Prednisone (VMP) ##### Group **Description:** Participants received velcade 1.3 mg/m\^2 as SC injection, twice weekly at Weeks 1, 2, 4 and 5 in Cycle 1 followed by once weekly at weeks 1, 2, 4 and 5 in Cycles 2 to 9, melphalan 9 mg/m\^2, orally once daily on Days 1 to 4 and prednisone 60 mg/m\^2, orally once daily on Days 2 to 4 of each cycle up to Cycle 9. In addition, participants also received daratumumab 16 milligram per kilogram (mg/kg) as intravenous (IV) infusion once weekly for 6 weeks in Cycle 1 and then every 3 weeks, in Cycle 2 to 9 and thereafter, once every 4 weeks until documented progression, unacceptable toxicity, or study end. On Day 1 of each cycle, dexamethasone 20 mg IV or per oral (PO) was given 1 hour or less prior to daratumumab infusion as pre medication and prednisone substitute. **ID:** OG001 **Title:** Daratumumab, Velcade, Melphalan and Prednisone (D-VMP) #### Outcome Measure 6 **Description:** Overall Survival (OS) was defined as the number of days the date of randomization to date of death. Median Overall Survival was estimated by using the Kaplan-Meier method. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEDIAN **Population Description:** ITT population included all participants randomized into the study; classified according to assigned treatment group, regardless of the actual treatment received. **Reporting Status:** POSTED **Time Frame:** From randomization to death (up to approximately 2.4 years) **Title:** Overall Survival (OS) **Type:** SECONDARY **Unit of Measure:** Months ##### Group **Description:** Participants received Velcade (bortezomib) 1.3 milligram per square meter (mg/m\^2) as subcutaneous (SC) injection, twice weekly at Weeks 1, 2, 4 and 5 in Cycle 1 followed by once weekly at Weeks 1, 2, 4 and 5 in Cycles 2 to 9, melphalan 9 mg/m\^2 orally once daily on Days 1 to 4 and prednisone 60 mg/m\^2 orally once daily on Days 1 to 4 of each cycle up to Cycle 9. **ID:** OG000 **Title:** Velcade, Melphalan and Prednisone (VMP) ##### Group **Description:** Participants received velcade 1.3 mg/m\^2 as SC injection, twice weekly at Weeks 1, 2, 4 and 5 in Cycle 1 followed by once weekly at weeks 1, 2, 4 and 5 in Cycles 2 to 9, melphalan 9 mg/m\^2, orally once daily on Days 1 to 4 and prednisone 60 mg/m\^2, orally once daily on Days 2 to 4 of each cycle up to Cycle 9. In addition, participants also received daratumumab 16 milligram per kilogram (mg/kg) as intravenous (IV) infusion once weekly for 6 weeks in Cycle 1 and then every 3 weeks, in Cycle 2 to 9 and thereafter, once every 4 weeks until documented progression, unacceptable toxicity, or study end. On Day 1 of each cycle, dexamethasone 20 mg IV or per oral (PO) was given 1 hour or less prior to daratumumab infusion as pre medication and prednisone substitute. **ID:** OG001 **Title:** Daratumumab, Velcade, Melphalan and Prednisone (D-VMP) #### Outcome Measure 7 **Description:** Progression-free survival after next-line therapy is defined as the time from randomization to progression on the next line of subsequent antimyeloma therapy or death due to any cause (prior to start of second line of antimyeloma therapy), whichever comes first. Disease progression on next line of treatment was based on investigator judgment. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEDIAN **Population Description:** ITT population included all participants randomized into the study; classified according to assigned treatment group, regardless of the actual treatment received. **Reporting Status:** POSTED **Time Frame:** From randomization to either disease progression or death whichever occurs first (up to 2.4 years) **Title:** Progression Free Survival on Next Line of Therapy (PFS2) **Type:** SECONDARY **Unit of Measure:** Months ##### Group **Description:** Participants received Velcade (bortezomib) 1.3 milligram per square meter (mg/m\^2) as subcutaneous (SC) injection, twice weekly at Weeks 1, 2, 4 and 5 in Cycle 1 followed by once weekly at Weeks 1, 2, 4 and 5 in Cycles 2 to 9, melphalan 9 mg/m\^2 orally once daily on Days 1 to 4 and prednisone 60 mg/m\^2 orally once daily on Days 1 to 4 of each cycle up to Cycle 9. **ID:** OG000 **Title:** Velcade, Melphalan and Prednisone (VMP) ##### Group **Description:** Participants received velcade 1.3 mg/m\^2 as SC injection, twice weekly at Weeks 1, 2, 4 and 5 in Cycle 1 followed by once weekly at weeks 1, 2, 4 and 5 in Cycles 2 to 9, melphalan 9 mg/m\^2, orally once daily on Days 1 to 4 and prednisone 60 mg/m\^2, orally once daily on Days 2 to 4 of each cycle up to Cycle 9. In addition, participants also received daratumumab 16 milligram per kilogram (mg/kg) as intravenous (IV) infusion once weekly for 6 weeks in Cycle 1 and then every 3 weeks, in Cycle 2 to 9 and thereafter, once every 4 weeks until documented progression, unacceptable toxicity, or study end. On Day 1 of each cycle, dexamethasone 20 mg IV or per oral (PO) was given 1 hour or less prior to daratumumab infusion as pre medication and prednisone substitute. **ID:** OG001 **Title:** Daratumumab, Velcade, Melphalan and Prednisone (D-VMP) #### Outcome Measure 8 **Description:** sCR as per IMWG criteria is CR plus normal free light chain (FLC) ratio and absence of clonal PCs by immunohistochemistry, immunofluorescence or 2- to 4-color flow cytometry. CR: Negative immunofixation on the serum and urine; Disappearance of any soft tissue plasmacytomas; \<5% plasma cells (PCs) in bone marrow. **Parameter Type:** NUMBER **Population Description:** ITT population included all participants randomized into the study; classified according to assigned treatment group, regardless of the actual treatment received. **Reporting Status:** POSTED **Time Frame:** From randomization to disease progression (up to 2.4 years) **Title:** Percentage of Participants With Stringent Complete Response (sCR) **Type:** SECONDARY **Unit of Measure:** Percentage of participants ##### Group **Description:** Participants received Velcade (bortezomib) 1.3 milligram per square meter (mg/m\^2) as subcutaneous (SC) injection, twice weekly at Weeks 1, 2, 4 and 5 in Cycle 1 followed by once weekly at Weeks 1, 2, 4 and 5 in Cycles 2 to 9, melphalan 9 mg/m\^2 orally once daily on Days 1 to 4 and prednisone 60 mg/m\^2 orally once daily on Days 1 to 4 of each cycle up to Cycle 9. **ID:** OG000 **Title:** Velcade, Melphalan and Prednisone (VMP) ##### Group **Description:** Participants received velcade 1.3 mg/m\^2 as SC injection, twice weekly at Weeks 1, 2, 4 and 5 in Cycle 1 followed by once weekly at weeks 1, 2, 4 and 5 in Cycles 2 to 9, melphalan 9 mg/m\^2, orally once daily on Days 1 to 4 and prednisone 60 mg/m\^2, orally once daily on Days 2 to 4 of each cycle up to Cycle 9. In addition, participants also received daratumumab 16 milligram per kilogram (mg/kg) as intravenous (IV) infusion once weekly for 6 weeks in Cycle 1 and then every 3 weeks, in Cycle 2 to 9 and thereafter, once every 4 weeks until documented progression, unacceptable toxicity, or study end. On Day 1 of each cycle, dexamethasone 20 mg IV or per oral (PO) was given 1 hour or less prior to daratumumab infusion as pre medication and prednisone substitute. **ID:** OG001 **Title:** Daratumumab, Velcade, Melphalan and Prednisone (D-VMP) #### Outcome Measure 9 **Description:** TTP: Time from date of randomization to date of first documented evidence of PD or death due to PD, whichever occurs first. PD per IMWG criteria- Increase of 25 % from lowest response value in one of following: Serum and urine M-component (absolute increase \>=0.5 gram per deciliter \[g/dL\] and \>=200 mg/24 hours respectively); Only in participants without measurable serum and urine M-protein levels: difference between involved and uninvolved FLC levels (absolute increase \>10 milligram per deciliter \[mg/dL\]); Only in participants without measurable serum and urine M-protein levels and without measurable disease by FLC levels, bone marrow plasma cells (PC)% (absolute % \>=10%); Bone marrow PC %: absolute % \>10%; Definite development of new bone lesions/soft tissue plasmacytomas or definite increase in size of existing bone lesions/soft tissue plasmacytomas and Development of hypercalcemia (corrected serum calcium \>11.5 mg/dL) that can be attributed solely to the PC proliferative disorder. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEDIAN **Population Description:** ITT population included all participants randomized into the study; classified according to assigned treatment group, regardless of the actual treatment received. **Reporting Status:** POSTED **Time Frame:** From randomization to either disease progression or death due to PD whichever occurs first (up to 2.4 years) **Title:** Time to Disease Progression (TTP) **Type:** SECONDARY **Unit of Measure:** Months ##### Group **Description:** Participants received Velcade (bortezomib) 1.3 milligram per square meter (mg/m\^2) as subcutaneous (SC) injection, twice weekly at Weeks 1, 2, 4 and 5 in Cycle 1 followed by once weekly at Weeks 1, 2, 4 and 5 in Cycles 2 to 9, melphalan 9 mg/m\^2 orally once daily on Days 1 to 4 and prednisone 60 mg/m\^2 orally once daily on Days 1 to 4 of each cycle up to Cycle 9. **ID:** OG000 **Title:** Velcade, Melphalan and Prednisone (VMP) ##### Group **Description:** Participants received velcade 1.3 mg/m\^2 as SC injection, twice weekly at Weeks 1, 2, 4 and 5 in Cycle 1 followed by once weekly at weeks 1, 2, 4 and 5 in Cycles 2 to 9, melphalan 9 mg/m\^2, orally once daily on Days 1 to 4 and prednisone 60 mg/m\^2, orally once daily on Days 2 to 4 of each cycle up to Cycle 9. In addition, participants also received daratumumab 16 milligram per kilogram (mg/kg) as intravenous (IV) infusion once weekly for 6 weeks in Cycle 1 and then every 3 weeks, in Cycle 2 to 9 and thereafter, once every 4 weeks until documented progression, unacceptable toxicity, or study end. On Day 1 of each cycle, dexamethasone 20 mg IV or per oral (PO) was given 1 hour or less prior to daratumumab infusion as pre medication and prednisone substitute. **ID:** OG001 **Title:** Daratumumab, Velcade, Melphalan and Prednisone (D-VMP) #### Outcome Measure 10 **Description:** Time to response, defined as the time between the date of randomization and the first efficacy evaluation that the participant has met all criteria for PR or better. PR: \>=50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by \>=90% or to \<200 mg/24 hours; If the serum and urine M-protein are not measurable, a decrease of \>=50% in the difference between involved and uninvolved FLC levels is required in place of the M-protein criteria; If serum and urine M-protein are not measurable, and serum free light assay is also not measurable, \>=50% reduction in bone marrow PCs is required in place of M-protein, provided baseline bone marrow plasma cell percentage was \>=30%. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEDIAN **Population Description:** Response-evaluable population: participants who have a confirmed diagnosis of MM and measurable disease at baseline or screening, must receive at least one component of study treatment and have adequate post-baseline disease assessments. "N" (number of participants analyzed) signifies number of participants evaluable for this endpoint. **Reporting Status:** POSTED **Time Frame:** From randomization to first documented PR or better (up to 2.4 years) **Title:** Time to Response **Type:** SECONDARY **Unit of Measure:** Months ##### Group **Description:** Participants received Velcade (bortezomib) 1.3 milligram per square meter (mg/m\^2) as subcutaneous (SC) injection, twice weekly at Weeks 1, 2, 4 and 5 in Cycle 1 followed by once weekly at Weeks 1, 2, 4 and 5 in Cycles 2 to 9, melphalan 9 mg/m\^2 orally once daily on Days 1 to 4 and prednisone 60 mg/m\^2 orally once daily on Days 1 to 4 of each cycle up to Cycle 9. **ID:** OG000 **Title:** Velcade, Melphalan and Prednisone (VMP) ##### Group **Description:** Participants received velcade 1.3 mg/m\^2 as SC injection, twice weekly at Weeks 1, 2, 4 and 5 in Cycle 1 followed by once weekly at weeks 1, 2, 4 and 5 in Cycles 2 to 9, melphalan 9 mg/m\^2, orally once daily on Days 1 to 4 and prednisone 60 mg/m\^2, orally once daily on Days 2 to 4 of each cycle up to Cycle 9. In addition, participants also received daratumumab 16 milligram per kilogram (mg/kg) as intravenous (IV) infusion once weekly for 6 weeks in Cycle 1 and then every 3 weeks, in Cycle 2 to 9 and thereafter, once every 4 weeks until documented progression, unacceptable toxicity, or study end. On Day 1 of each cycle, dexamethasone 20 mg IV or per oral (PO) was given 1 hour or less prior to daratumumab infusion as pre medication and prednisone substitute. **ID:** OG001 **Title:** Daratumumab, Velcade, Melphalan and Prednisone (D-VMP) #### Outcome Measure 11 **Description:** DOR: participants with a confirmed response (PR or better) as time between first documentation of response and disease progression, IMWG response criteria, or death due to PD, whichever occurs first. PD: Increase of 25% from lowest response value in any one of following: Serum M-component (absolute increase\>=0.5 g/dL); Urine M-component (absolute increase\>=200 mg/24 hours); Only participants without measurable serum and urine M-protein levels: difference between involved and uninvolved FLC levels (absolute increase \>10 mg/dL); Only participants without measurable serum and urine M-protein levels and without measurable disease by FLC levels, bone marrow PC%(absolute%\>=10%); Bone marrow PC's %: absolute%\>10%; Definite development of new bone lesions/soft tissue plasmacytomas/definite increase in the size of existing bone lesions or soft tissue plasmacytomas and Development of hypercalcemia (corrected serum calcium \>11.5 mg/dL) that can be attributed solely to PC proliferative disorder. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEDIAN **Population Description:** Response-evaluable set: participants who have a confirmed diagnosis of MM and measurable disease at baseline or screening. Participants must have received at least one component of study treatment and have adequate post-baseline disease assessments. "N"(number of participants analyzed) signifies number of participants evaluable for this endpoint. **Reporting Status:** POSTED **Time Frame:** Up to 2.4 years **Title:** Duration of Response (DOR) **Type:** SECONDARY **Unit of Measure:** Months ##### Group **Description:** Participants received Velcade (bortezomib) 1.3 milligram per square meter (mg/m\^2) as subcutaneous (SC) injection, twice weekly at Weeks 1, 2, 4 and 5 in Cycle 1 followed by once weekly at Weeks 1, 2, 4 and 5 in Cycles 2 to 9, melphalan 9 mg/m\^2 orally once daily on Days 1 to 4 and prednisone 60 mg/m\^2 orally once daily on Days 1 to 4 of each cycle up to Cycle 9. **ID:** OG000 **Title:** Velcade, Melphalan and Prednisone (VMP) ##### Group **Description:** Participants received velcade 1.3 mg/m\^2 as SC injection, twice weekly at Weeks 1, 2, 4 and 5 in Cycle 1 followed by once weekly at weeks 1, 2, 4 and 5 in Cycles 2 to 9, melphalan 9 mg/m\^2, orally once daily on Days 1 to 4 and prednisone 60 mg/m\^2, orally once daily on Days 2 to 4 of each cycle up to Cycle 9. In addition, participants also received daratumumab 16 milligram per kilogram (mg/kg) as intravenous (IV) infusion once weekly for 6 weeks in Cycle 1 and then every 3 weeks, in Cycle 2 to 9 and thereafter, once every 4 weeks until documented progression, unacceptable toxicity, or study end. On Day 1 of each cycle, dexamethasone 20 mg IV or per oral (PO) was given 1 hour or less prior to daratumumab infusion as pre medication and prednisone substitute. **ID:** OG001 **Title:** Daratumumab, Velcade, Melphalan and Prednisone (D-VMP) #### Outcome Measure 12 **Description:** Time to next treatment is defined as the time from randomization to the start of the next-line treatment. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** MEDIAN **Population Description:** ITT population included all participants randomized into the study; classified according to assigned treatment group, regardless of the actual treatment received. **Reporting Status:** POSTED **Time Frame:** Approximately up to 2.4 years **Title:** Time to Next Treatment (TNT) **Type:** SECONDARY **Unit of Measure:** Months ##### Group **Description:** Participants received Velcade (bortezomib) 1.3 milligram per square meter (mg/m\^2) as subcutaneous (SC) injection, twice weekly at Weeks 1, 2, 4 and 5 in Cycle 1 followed by once weekly at Weeks 1, 2, 4 and 5 in Cycles 2 to 9, melphalan 9 mg/m\^2 orally once daily on Days 1 to 4 and prednisone 60 mg/m\^2 orally once daily on Days 1 to 4 of each cycle up to Cycle 9. **ID:** OG000 **Title:** Velcade, Melphalan and Prednisone (VMP) ##### Group **Description:** Participants received velcade 1.3 mg/m\^2 as SC injection, twice weekly at Weeks 1, 2, 4 and 5 in Cycle 1 followed by once weekly at weeks 1, 2, 4 and 5 in Cycles 2 to 9, melphalan 9 mg/m\^2, orally once daily on Days 1 to 4 and prednisone 60 mg/m\^2, orally once daily on Days 2 to 4 of each cycle up to Cycle 9. In addition, participants also received daratumumab 16 milligram per kilogram (mg/kg) as intravenous (IV) infusion once weekly for 6 weeks in Cycle 1 and then every 3 weeks, in Cycle 2 to 9 and thereafter, once every 4 weeks until documented progression, unacceptable toxicity, or study end. On Day 1 of each cycle, dexamethasone 20 mg IV or per oral (PO) was given 1 hour or less prior to daratumumab infusion as pre medication and prednisone substitute. **ID:** OG001 **Title:** Daratumumab, Velcade, Melphalan and Prednisone (D-VMP) #### Outcome Measure 13 **Description:** Percentage of participants with Best M- protein response of 100% reduction and \>=90% to \< 100% reduction were assessed. Best M-protein response was defined as the maximal percent reduction or the lowest percent increase from baseline in serum M-protein for participants with measurable heavy chain at baseline or urine M-protein for participants without measurable heavy chain, but with measurable light chain disease at baseline. For participants without measurable heavy chain and light chain disease at baseline, best response in serum free light chain (FLC) was defined as the maximal percent reduction or the lowest percent increase from baseline in the difference between involved and uninvolved serum FLC level (dFLC). **Parameter Type:** NUMBER **Population Description:** Response-evaluable set: participants have confirmed diagnosis of MM and measurable disease at baseline or screening. Participants must receive at least one component of study treatment, have adequate post-baseline disease assessments. 'n' (number of participants analyzed) signifies number of participants analyzed for each specified category. **Reporting Status:** POSTED **Time Frame:** Approximately up to 2.4 years **Title:** Percentage of Participants With Best M-protein Response **Type:** SECONDARY **Unit of Measure:** Percentage of participants ##### Group **Description:** Participants received Velcade (bortezomib) 1.3 milligram per square meter (mg/m\^2) as subcutaneous (SC) injection, twice weekly at Weeks 1, 2, 4 and 5 in Cycle 1 followed by once weekly at Weeks 1, 2, 4 and 5 in Cycles 2 to 9, melphalan 9 mg/m\^2 orally once daily on Days 1 to 4 and prednisone 60 mg/m\^2 orally once daily on Days 1 to 4 of each cycle up to Cycle 9. **ID:** OG000 **Title:** Velcade, Melphalan and Prednisone (VMP) ##### Group **Description:** Participants received velcade 1.3 mg/m\^2 as SC injection, twice weekly at Weeks 1, 2, 4 and 5 in Cycle 1 followed by once weekly at weeks 1, 2, 4 and 5 in Cycles 2 to 9, melphalan 9 mg/m\^2, orally once daily on Days 1 to 4 and prednisone 60 mg/m\^2, orally once daily on Days 2 to 4 of each cycle up to Cycle 9. In addition, participants also received daratumumab 16 milligram per kilogram (mg/kg) as intravenous (IV) infusion once weekly for 6 weeks in Cycle 1 and then every 3 weeks, in Cycle 2 to 9 and thereafter, once every 4 weeks until documented progression, unacceptable toxicity, or study end. On Day 1 of each cycle, dexamethasone 20 mg IV or per oral (PO) was given 1 hour or less prior to daratumumab infusion as pre medication and prednisone substitute. **ID:** OG001 **Title:** Daratumumab, Velcade, Melphalan and Prednisone (D-VMP) #### Outcome Measure 14 **Description:** The EORTC QLQ-C30 is a 30 items self-reporting questionnaire, with a 1 week recall period, resulting in 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 1 Global Health Status (GHS) scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single symptom items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The questionnaire includes 28 items with 4-point Likert type responses from "1-not at all" to "4-very much" to assess functioning and symptoms; 2 items with 7-point Likert scales (1= poor and 7= excellent) for global health and overall QoL. Scores are transformed to a 0 to 100 scale, with higher scores representing better GHS, better functioning, and more symptoms. Negative change from baseline values indicate deterioration in quality of life or functioning and positive values indicate improvement. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** ITT population: participants randomized into the study; classified according to assigned treatment group,regardless actual treatment received. 'N' (number of participants analyzed) signifies participants evaluable for this endpoint and 'n' signifies number of participants who were analyzed at each specified timepoint, for each arm, respectively. **Reporting Status:** POSTED **Time Frame:** Baseline, Months 3, 6, 9, 12 and 18 **Title:** Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-C30: Emotional Functioning Score **Type:** SECONDARY **Unit of Measure:** Units on a scale ##### Group **Description:** Participants received Velcade (bortezomib) 1.3 milligram per square meter (mg/m\^2) as subcutaneous (SC) injection, twice weekly at Weeks 1, 2, 4 and 5 in Cycle 1 followed by once weekly at Weeks 1, 2, 4 and 5 in Cycles 2 to 9, melphalan 9 mg/m\^2 orally once daily on Days 1 to 4 and prednisone 60 mg/m\^2 orally once daily on Days 1 to 4 of each cycle up to Cycle 9. **ID:** OG000 **Title:** Velcade, Melphalan and Prednisone (VMP) ##### Group **Description:** Participants received velcade 1.3 mg/m\^2 as SC injection, twice weekly at Weeks 1, 2, 4 and 5 in Cycle 1 followed by once weekly at weeks 1, 2, 4 and 5 in Cycles 2 to 9, melphalan 9 mg/m\^2, orally once daily on Days 1 to 4 and prednisone 60 mg/m\^2, orally once daily on Days 2 to 4 of each cycle up to Cycle 9. In addition, participants also received daratumumab 16 milligram per kilogram (mg/kg) as intravenous (IV) infusion once weekly for 6 weeks in Cycle 1 and then every 3 weeks, in Cycle 2 to 9 and thereafter, once every 4 weeks until documented progression, unacceptable toxicity, or study end. On Day 1 of each cycle, dexamethasone 20 mg IV or per oral (PO) was given 1 hour or less prior to daratumumab infusion as pre medication and prednisone substitute. **ID:** OG001 **Title:** Daratumumab, Velcade, Melphalan and Prednisone (D-VMP) #### Outcome Measure 15 **Description:** EQ-5D-5L is a standardized, participant-rated questionnaire to assess health-related quality of life. The EQ-5D-5L includes 2 components: the EQ-5D-5L health state profile (descriptive system) and the EQ-5D-5L Visual Analog Scale. The Visual Analogue Scale is designed to rate the participant's current health state on a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** ITT population: participants randomized into the study; classified according to assigned treatment group,regardless actual treatment received. 'N' (number of participants analyzed) signifies participants evaluable for this endpoint and 'n' signifies number of participants who were analyzed at each specified timepoint, for each arm, respectively. **Reporting Status:** POSTED **Time Frame:** Baseline, Months 3, 6, 9, 12 and 18 **Title:** Change From Baseline in EuroQol-5 Dimensions-5 Levels (EQ-5D-5L): Visual Analogue Scale (VAS) **Type:** SECONDARY **Unit of Measure:** Units on a scale ##### Group **Description:** Participants received Velcade (bortezomib) 1.3 milligram per square meter (mg/m\^2) as subcutaneous (SC) injection, twice weekly at Weeks 1, 2, 4 and 5 in Cycle 1 followed by once weekly at Weeks 1, 2, 4 and 5 in Cycles 2 to 9, melphalan 9 mg/m\^2 orally once daily on Days 1 to 4 and prednisone 60 mg/m\^2 orally once daily on Days 1 to 4 of each cycle up to Cycle 9. **ID:** OG000 **Title:** Velcade, Melphalan and Prednisone (VMP) ##### Group **Description:** Participants received velcade 1.3 mg/m\^2 as SC injection, twice weekly at Weeks 1, 2, 4 and 5 in Cycle 1 followed by once weekly at weeks 1, 2, 4 and 5 in Cycles 2 to 9, melphalan 9 mg/m\^2, orally once daily on Days 1 to 4 and prednisone 60 mg/m\^2, orally once daily on Days 2 to 4 of each cycle up to Cycle 9. In addition, participants also received daratumumab 16 milligram per kilogram (mg/kg) as intravenous (IV) infusion once weekly for 6 weeks in Cycle 1 and then every 3 weeks, in Cycle 2 to 9 and thereafter, once every 4 weeks until documented progression, unacceptable toxicity, or study end. On Day 1 of each cycle, dexamethasone 20 mg IV or per oral (PO) was given 1 hour or less prior to daratumumab infusion as pre medication and prednisone substitute. **ID:** OG001 **Title:** Daratumumab, Velcade, Melphalan and Prednisone (D-VMP) #### Outcome Measure 16 **Description:** EQ-5D-5L is a standardized, participant-rated questionnaire to assess health-related quality of life. The EQ-5D-5L includes 2 components: the EQ-5D-5L health state profile (descriptive system) and the EQ-5D-5L Visual Analog Scale. The EQ-5D-5L descriptive system provides a profile of the participant's health state 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 response options (no problems, slight problems, moderate problems, severe problems and extreme problems) that reflect increasing levels of difficulty. The participant was asked to indicate his/her current health state by selecting the most appropriate level in each of the 5 dimensions. Responses to the 5 dimension scores were combined and converted into a single preference-weighted health utility index score 0 (0.0- worst health state) to 1 (1.0- better health state) representing the general health status of the individual based on the UK scoring algorithm. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** ITT population: participants randomized into the study; classified according to assigned treatment group,regardless actual treatment received. 'N' (number of participants analyzed) signifies participants evaluable for this endpoint and 'n' signifies number of participants who were analyzed at each specified timepoint, for each arm, respectively. **Reporting Status:** POSTED **Time Frame:** Baseline, Months 3, 6, 9, 12 and 18 **Title:** Change From Baseline in EuroQol 5 Dimensions-5 Level (EQ-5D-5L) Utility Score **Type:** SECONDARY **Unit of Measure:** Units on a scale ##### Group **Description:** Participants received Velcade (bortezomib) 1.3 milligram per square meter (mg/m\^2) as subcutaneous (SC) injection, twice weekly at Weeks 1, 2, 4 and 5 in Cycle 1 followed by once weekly at Weeks 1, 2, 4 and 5 in Cycles 2 to 9, melphalan 9 mg/m\^2 orally once daily on Days 1 to 4 and prednisone 60 mg/m\^2 orally once daily on Days 1 to 4 of each cycle up to Cycle 9. **ID:** OG000 **Title:** Velcade, Melphalan and Prednisone (VMP) ##### Group **Description:** Participants received velcade 1.3 mg/m\^2 as SC injection, twice weekly at Weeks 1, 2, 4 and 5 in Cycle 1 followed by once weekly at weeks 1, 2, 4 and 5 in Cycles 2 to 9, melphalan 9 mg/m\^2, orally once daily on Days 1 to 4 and prednisone 60 mg/m\^2, orally once daily on Days 2 to 4 of each cycle up to Cycle 9. In addition, participants also received daratumumab 16 milligram per kilogram (mg/kg) as intravenous (IV) infusion once weekly for 6 weeks in Cycle 1 and then every 3 weeks, in Cycle 2 to 9 and thereafter, once every 4 weeks until documented progression, unacceptable toxicity, or study end. On Day 1 of each cycle, dexamethasone 20 mg IV or per oral (PO) was given 1 hour or less prior to daratumumab infusion as pre medication and prednisone substitute. **ID:** OG001 **Title:** Daratumumab, Velcade, Melphalan and Prednisone (D-VMP) ### Participant Flow Module #### Group **Description:** Participants received Velcade (bortezomib) 1.3 milligram per square meter (mg/m\^2) as subcutaneous (SC) injection, twice weekly at Weeks 1, 2, 4 and 5 in Cycle 1 followed by once weekly at Weeks 1, 2, 4 and 5 in Cycles 2 to 9, melphalan 9 mg/m\^2 orally once daily on Days 1 to 4 and prednisone 60 mg/m\^2 orally once daily on Days 1 to 4 of each cycle up to Cycle 9. **ID:** FG000 **Title:** Velcade, Melphalan and Prednisone (VMP) #### Group **Description:** Participants received velcade 1.3 mg/m\^2 as SC injection, twice weekly at Weeks 1, 2, 4 and 5 in Cycle 1 followed by once weekly at weeks 1, 2, 4 and 5 in Cycles 2 to 9, melphalan 9 mg/m\^2, orally once daily on Days 1 to 4 and prednisone 60 mg/m\^2, orally once daily on Days 2 to 4 of each cycle up to Cycle 9. In addition, participants also received daratumumab 16 milligram per kilogram (mg/kg) as intravenous (IV) infusion once weekly for 6 weeks in Cycle 1 and then every 3 weeks, in Cycle 2 to 9 and thereafter, once every 4 weeks until documented progression, unacceptable toxicity, or study end. On Day 1 of each cycle, dexamethasone 20 mg IV or per oral (PO) was given 1 hour or less prior to daratumumab infusion as pre medication and prednisone substitute. **ID:** FG001 **Title:** Daratumumab, Velcade, Melphalan and Prednisone (D-VMP) #### Period **Title:** Overall Study ##### Withdraw **Type:** Lost to Follow-up ###### Reason **Group ID:** FG000 **Number of Subjects:** 3 ###### Reason **Group ID:** FG001 **Number of Subjects:** 0 ##### Withdraw **Type:** Death ###### Reason **Group ID:** FG000 **Number of Subjects:** 48 ###### Reason **Group ID:** FG001 **Number of Subjects:** 45 ##### Withdraw **Type:** Physician Decision ###### 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:** 11 ###### Reason **Group ID:** FG001 **Number of Subjects:** 6 ##### Withdraw **Type:** Other ###### Reason **Group ID:** FG000 **Number of Subjects:** 2 ###### Reason **Group ID:** FG001 **Number of Subjects:** 2 ##### Withdraw **Type:** Ongoing ###### Reason **Group ID:** FG000 **Number of Subjects:** 291 ###### Reason **Group ID:** FG001 **Number of Subjects:** 297 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 356 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 350 ##### Milestone **Type:** Treated ###### Achievement **Group ID:** FG000 **Number of Subjects:** 354 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 346 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 0 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 356 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 350 **Pre-Assignment Details:** Results are reported up to second interim analysis (up to 2.4 years). Complete data through 6.4 years will be reported within 1 year of end of study trial date when final data based on study completion date will be available. **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT02916979 **Acronym:** FluBuATG **Brief Title:** Myeloid-Derived Suppressor Cells and Checkpoint Immune Regulators' Expression in Allogeneic SCT Using FluBuATG **Official Title:** A Pilot Trial Examining Myeloid-Derived Suppressor Cells and Checkpoint Immune Regulators' Expression in Allogeneic Stem Cell Transplant Recipients Using Myeloablative Busulfan and Fludarabine #### Organization Study ID Info **ID:** D16127 #### Organization **Class:** OTHER **Full Name:** Dartmouth-Hitchcock Medical Center ### Status Module #### Completion Date **Date:** 2022-02-11 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2023-10-18 **Type:** ACTUAL **Last Update Submit Date:** 2023-10-17 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2019-06-07 **Type:** ACTUAL #### Start Date **Date:** 2016-09-06 **Type:** ACTUAL **Status Verified Date:** 2023-10 #### Study First Post Date **Date:** 2016-09-28 **Type:** ESTIMATED **Study First Submit Date:** 2016-08-15 **Study First Submit QC Date:** 2016-09-26 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Dartmouth-Hitchcock Medical Center #### Responsible Party **Investigator Affiliation:** Dartmouth-Hitchcock Medical Center **Investigator Full Name:** Kenneth Meehan **Investigator Title:** Director, Bone Marrow Transplant Program **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** This study is examining a chemotherapy regimen and immune suppressive medications in the setting of an allogeneic stem cell transplant. A pilot clinical trial to characterize the incidence, prevalence and function of myeloid-derived suppressor cells (MDSCs) and immune checkpoint regulators (V-domain Ig Suppressor of T-cell Activation \[VISTA\], cytotoxic T-lymphocyte- associated protein 4 \[CTLA-4\], programmed death-ligand 1 \[PD-L1\]) during early immune recovery following an allogeneic stem cell transplant. The site will use a myeloablative regimen of fludarabine with busulfan, adopted from CALGB 100801, to define clinical endpoints, including engraftment, 100 day survival and one year survival (Objective #1). The site will characterize the incidence, prevalence and function of MDSCs and immune checkpoint regulators in patients' blood and bone marrow following transplantation (Objective #2). The site will correlate these laboratory results with clinical outcomes and the incidence of graft-versus-host disease (GVHD). As an exploratory aim, in those patients experiencing GVHD and requiring treatment, the site will define the MDSCs frequency and checkpoint regulator expression and correlate these results with the patient's response to GVHD therapy. ### Conditions Module **Conditions:** - Leukemia, Lymphoid - Leukemia, Myeloid - Myelodysplastic Syndromes - Myelofibrosis - Lymphoma, Malignant - Multiple Myeloma - Waldenstrom Macroglobulinemia ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 20 **Type:** ACTUAL **Phases:** - PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Fludarabine, Busulfan, Rabbit ATG, Methotrexate **Intervention Names:** - Drug: Fludarabine - Drug: Busulfan - Biological: Rabbit ATG - Drug: Methotrexate **Label:** Conditioning Regimen **Type:** OTHER ### Interventions #### Intervention 1 **Arm Group Labels:** - Conditioning Regimen **Description:** Fludarabine: 30 mg/m2 daily for 5 days **Name:** Fludarabine **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Conditioning Regimen **Description:** Busulfan: 100 mg/m2 daily for 4 days **Name:** Busulfan **Type:** DRUG #### Intervention 3 **Arm Group Labels:** - Conditioning Regimen **Description:** Rabbit ATG: Related donors: 1.5 mg/kg daily x 2 days (on days -6 and -5) Unrelated donors: 1.5 mg/kg on day - 6 2 mg/kg on day -5 2.5 mg/kg on day -4 **Name:** Rabbit ATG **Type:** BIOLOGICAL #### Intervention 4 **Arm Group Labels:** - Conditioning Regimen **Description:** Methotrexate: Related donors: 5 mg/m2 on days 1, 3 and 6 Unrelated donors: 5 mg/m2 on days 1, 3, 6 and 11 **Name:** Methotrexate **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** 100-Day survival of patients **Measure:** Number of patients who are surviving at 100-Days post-transplant **Time Frame:** 100 Days #### Secondary Outcomes **Description:** Time to marrow engraftment (defined as absolute neutrophil count \> 500/mm3 and platelets \> 20,000/mcl for three consecutive days (count first day as engraftment) **Measure:** Time to marrow engraftment **Time Frame:** 100 Days **Description:** Response to treatment at 100 days using standard international response criteria, based on CIBMTR definitions. **Measure:** Assessing all subjects' response to treatment at 100 days post-transplant **Time Frame:** 100 Days **Description:** Response to treatment at one year using standard international response criteria, based on CIBMTR definitions. **Measure:** Assessing all subjects' response to treatment at 1 year post-transplant **Time Frame:** 365 Days **Description:** One year survival **Measure:** Assessing all subjects' survival at 1 year post-transplant **Time Frame:** 365 Days **Description:** Treatment-related mortality in the first 100 days **Measure:** Assessing the mortality rate of patients in the first 100 days post-transplant **Time Frame:** 100 Days **Description:** Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 **Measure:** Assessing the number of treatment-related adverse events **Time Frame:** 365 Days **Description:** Incidence of acute and chronic GVHD **Measure:** Collecting the incidents of GvHD experienced by patients post-transplant **Time Frame:** 365 Days **Description:** Donor-recipient chimerism following transplant at Days 30, 60 and 90. **Measure:** Assessing the donor-chimerism at 30, 60 and 90 days post-transplant **Time Frame:** 30, 60, and 90 Days ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Age less than or equal to 75 years 2. The patient must be approved for transplant by the treating transplant physician. This includes completion of their pretransplant workup, as directed by standard Dartmouth-Hitchcock Medical Center (DHMC) Standard Operating Procedures (SOPs). DHMC SOP for Pretransplant Evaluation of allogeneic recipient. 3. The patient must have a disease, listed below, with treatment responsiveness that the treating transplant physician believes will benefit from an allogeneic stem cell transplant. The diseases include: 1. Acute leukemia AML (Acute Myeloid Leukemia), ALL (Acute Lymphoid Leukemia) 2. Chronic leukemia CML (Chronic Myeloid Leukemia), CLL (Chronic Lymphoid Leukemia) 3. Myelodysplasia 4. Myelofibrosis 5. Lymphoma NHL (Non-Hodgkin's Lymphoma) and Hodgkin's disease 6. Plasma cell disorder, including myeloma, Waldenstrom's Macroglobulinemia 4. Donor availability- the patient must have an identified donor 1. Sibling Availability of a 6 out of 6 identical donor 2. Unrelated donor: Availability of a 6 out of 6 unrelated donor 5. No human immunodeficiency virus (HIV) infection or active hepatitis B or C 6. Easter Cooperative Oncology Group (ECOG) performance status 0, 1, or 2 7. Diffusing capacity of the lungs for carbon monoxide DLCO more than or equal to 40 percent predicted 8. Left ventricular ejection fraction more than or equal to 35 percent 9. Serum bilirubin less than 2x upper limit of normal transaminases less than 3x normal at the time of transplant 10. No active or uncontrollable infection 11. In female, a negative pregnancy test if experiencing menstrual periods 12. No major organ dysfunction precluding transplantation 13. No evidence of an active malignancy that would limit the patient's survival to less than 2 years. If there is any question, the principal investigator can make a decision. Exclusion Criteria: 1. Psychiatric disorder or a mental deficiency of the patient that is sufficiently severe to make compliance with the treatment unlikely, and making informed consent impossible. 2. Major anticipated illness or organ failure incompatible with survival from bone marrow transplant. 3. History of refractory systemic infection Donor eligibility 1. Human leukocyte antigen (HLA) 6 out of 6 matched related or unrelated donor. 2. The donor must be healthy and must be willing to serve as a donor, based on standard guidelines 3. The donor must have no significant comorbidities that would put the donor at marked increased risk 4. There is no age restriction for the donor 5. Informed consent must be signed by donor, if sibling donor, or by third party if unrelated donor. Donor Exclusion Criteria 6. The National Marrow Donor Program (NMDP) guidelines for exclusion criteria will be used. In addition, the following donors are NOT eligible: 7. Syngeneic donor 8. Pregnant or lactating donor 9. Human immunodeficiency virus (HIV) or active HepB or C in the donor 10. Donor unfit to receive Granulocyte-colony stimulating factor (GCSF) and undergo apheresis 11. A donor with a psychiatric disorder or mental deficiency that makes compliance with the procedure unlikely and informed consent impossible **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:** Lebanon **Country:** United States **Facility:** Dartmouth-Hitchcock Medical Center **State:** New Hampshire **Zip:** 03756 #### Overall Officials **Official 1:** **Affiliation:** Dartmouth-Hitchcock Medical Center **Name:** Kenneth Meehan, MD **Role:** PRINCIPAL_INVESTIGATOR ### 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: D000006402 - Term: Hematologic Diseases - ID: D000054219 - Term: Neoplasms, Plasma Cell - ID: D000020141 - Term: Hemostatic Disorders - ID: D000014652 - Term: Vascular Diseases - ID: D000002318 - Term: Cardiovascular Diseases - ID: D000010265 - Term: Paraproteinemias - ID: D000001796 - Term: Blood Protein Disorders - ID: D000006474 - Term: Hemorrhagic Disorders - ID: D000008232 - Term: Lymphoproliferative Disorders - ID: D000007160 - Term: Immunoproliferative Disorders - ID: D000007154 - Term: Immune System Diseases - ID: D000001855 - Term: Bone Marrow Diseases - ID: D000008206 - Term: Lymphatic Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: BC15 - Name: Blood and Lymph Conditions - Abbrev: BC20 - Name: Immune 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: M12058 - Name: Multiple Myeloma - Relevance: HIGH - As Found: Multiple Myeloma - ID: M27588 - Name: Neoplasms, Plasma Cell - Relevance: LOW - As Found: Unknown - ID: M10945 - Name: Leukemia - Relevance: HIGH - As Found: Leukemia - ID: M10955 - Name: Leukemia, Myeloid - Relevance: HIGH - As Found: Leukemia, Myeloid - ID: M10951 - Name: Leukemia, Lymphoid - Relevance: HIGH - As Found: Leukemia, Lymphoid - ID: M16355 - Name: Syndrome - Relevance: LOW - As Found: Unknown - ID: M11220 - Name: Lymphoma - Relevance: HIGH - As Found: Lymphoma, Malignant - ID: M14164 - Name: Preleukemia - Relevance: LOW - As Found: Unknown - ID: M12145 - Name: Myelodysplastic Syndromes - Relevance: HIGH - As Found: Myelodysplastic Syndrome - ID: M28312 - Name: Primary Myelofibrosis - Relevance: LOW - As Found: Unknown - ID: M11251 - Name: Waldenstrom Macroglobulinemia - Relevance: HIGH - As Found: Waldenstrom Macroglobulinemia - ID: M12315 - Name: Neoplasms by Histologic Type - Relevance: LOW - As Found: Unknown - ID: M9490 - Name: Hematologic Diseases - Relevance: LOW - As Found: Unknown - ID: M21977 - Name: Hemostatic Disorders - Relevance: LOW - As Found: Unknown - ID: M5059 - Name: Blood Coagulation Disorders - Relevance: LOW - As Found: Unknown - ID: M17400 - Name: Vascular Diseases - Relevance: LOW - As Found: Unknown - ID: M13178 - Name: Paraproteinemias - Relevance: LOW - As Found: Unknown - ID: M5077 - Name: Blood Protein Disorders - Relevance: LOW - As Found: Unknown - ID: M9560 - Name: Hemorrhagic Disorders - Relevance: LOW - As Found: Unknown - ID: M11225 - Name: Lymphoproliferative Disorders - 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: M5134 - Name: Bone Marrow Diseases - Relevance: LOW - As Found: Unknown - ID: M11203 - Name: Lymphatic Diseases - Relevance: LOW - As Found: Unknown - ID: T3947 - Name: Multiple Myeloma - Relevance: HIGH - As Found: Multiple Myeloma - ID: T3543 - Name: Lymphosarcoma - Relevance: HIGH - As Found: Lymphoma, Malignant - ID: T3993 - Name: Myelodysplastic Syndromes - Relevance: HIGH - As Found: Myelodysplastic Syndrome - ID: T4705 - Name: Primary Myelofibrosis - Relevance: LOW - As Found: Unknown - ID: T5887 - Name: Waldenstrom Macroglobulinemia - Relevance: HIGH - As Found: Waldenstrom Macroglobulinemia ### Condition Browse Module - Meshes - ID: D000007938 - Term: Leukemia - ID: D000009101 - Term: Multiple Myeloma - ID: D000008258 - Term: Waldenstrom Macroglobulinemia - ID: D000007951 - Term: Leukemia, Myeloid - ID: D000007945 - Term: Leukemia, Lymphoid - ID: D000008223 - Term: Lymphoma - ID: D000009190 - Term: Myelodysplastic Syndromes ### 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: D000000477 - Term: Alkylating Agents - ID: D000018906 - Term: Antineoplastic Agents, Alkylating - ID: D000019653 - Term: Myeloablative Agonists ### 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: M2853 - Name: Immunomodulating Agents - Relevance: LOW - As Found: Unknown - ID: M283230 - Name: Fludarabine - Relevance: HIGH - As Found: Comparison - ID: M255823 - Name: Thymoglobulin - Relevance: HIGH - As Found: Represent - ID: M5336 - Name: Busulfan - Relevance: HIGH - As Found: Full - ID: M225513 - Name: Fludarabine phosphate - 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: M10201 - Name: Immunologic Factors - Relevance: LOW - As Found: Unknown - ID: M20604 - Name: Antirheumatic Agents - Relevance: LOW - As Found: Unknown - ID: M3820 - Name: Alkylating Agents - Relevance: LOW - As Found: Unknown - ID: M20942 - Name: Antineoplastic Agents, Alkylating - 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: C000024352 - Term: Fludarabine - ID: D000002066 - Term: Busulfan - ID: C000512542 - Term: Thymoglobulin ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05223179 **Brief Title:** Intramuscular CodaVax-H1N1 in Healthy Adults **Official Title:** Randomised, Double-blind, Placebo-controlled, Dose-escalation Study of the Safety, Tolerability, and Immunogenicity of Intramuscular CodaVax-H1N1 in Healthy Adults #### Organization Study ID Info **ID:** CDX-FLU-103 #### Organization **Class:** INDUSTRY **Full Name:** Codagenix, Inc ### Status Module #### Completion Date **Date:** 2024-01 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2023-08-01 **Type:** ACTUAL **Last Update Submit Date:** 2023-07-31 **Overall Status:** ACTIVE_NOT_RECRUITING #### Primary Completion Date **Date:** 2024-01 **Type:** ESTIMATED #### Start Date **Date:** 2022-04-11 **Type:** ACTUAL **Status Verified Date:** 2023-07 #### Study First Post Date **Date:** 2022-02-03 **Type:** ACTUAL **Study First Submit Date:** 2022-01-24 **Study First Submit QC Date:** 2022-01-24 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Codagenix, Inc #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** True **Is US Export:** True **Oversight Has DMC:** False ### Description Module **Brief Summary:** This study is a Phase 1, 2-part, randomised, double-blind, controlled, clinical trial to evaluate the safety and immune response of CodaVax-H1N1 in healthy adults aged 18 to 49 years. Participants will be enrolled in autumn 2022 (southern hemisphere) and followed through the 2022 influenza season (Part A) or enrolled in autumn 2023 and followed through the 2023 influenza season (Part B). Participants will be screened within 28 days of randomization, and eligible participants in Part A will be enrolled into 1 of 3 sequential cohorts and randomised to receive a single dose of CodaVax-H1N1, placebo (normal saline), or licenced injectable seasonal influenza vaccine (Flucelvax Quad). Each subsequent cohort will include a higher dose of CodaVax H1N1 than the previous cohort, in addition to placebo and the licensed injectable seasonal influenza vaccine. In Part B, 24 eligible participants will be enrolled into 1 of 2 sequential cohorts and randomised to receive a single IM dose of CodaVax-H1N1 or placebo. **Detailed Description:** This study is a Phase 1, 2-part, randomised, double-blind, controlled, clinical trial to evaluate the safety and immune response of CodaVax-H1N1 in healthy adults aged 18 to 49 years. Participants will be enrolled in autumn 2022 (southern hemisphere) and followed through the 2022 influenza season (Part A) or enrolled in autumn 2023 and followed through the 2023 influenza season. Participants will be screened within 28 days of randomization, and eligible participants in Part A will be enrolled into 1 of 3 sequential cohorts and randomised to receive a single dose of CodaVax-H1N1, placebo (normal saline), or licensed injectable seasonal influenza vaccine (Flucelvax Quad). Each subsequent cohort will include a higher dose of CodaVax H1N1 than the previous cohort, in addition to placebo and the licensed injectable seasonal influenza vaccine. In Part B, 24 eligible participants will be enrolled into 1 of 2 additional sequential cohorts and randomised to receive a single IM dose of CodaVax-H1N1 or placebo. Participants will record reactogenicity events (local events, systemic events, and temperature) in a daily diary for 7 days after the dose. Each participant will be contacted by telephone on the day after dosing for safety assessment and review of the diary data. Participants will return to the clinic on Days 4, 8, 29, 91, and 181 for safety and immune response assessments. All adverse events and concomitant medications will be recorded from signing of the informed consent form (ICF) to 28 days postdose. After 28 days until the end of the study, only medically attended adverse events (MAAEs), new onset chronic illnesses (NCIs), serious adverse events (SAEs), immunosuppressive medications, blood products like transfusions or infusions, and vaccines will be recorded. A complete physical examination will be performed at Screening, and targeted and symptom-driven physical examinations will be performed predose on Day 1, 2 hours postdose, and at each postdose visit through Day 91. Vital signs will be measured at the same time points. An electrocardiogram (ECG) will be performed at Screening and on Day 29. A serum sample will be collected predose and on Days 29, 91, and 181 for measurement of immune response. A whole blood sample will be collected predose and on Day 8 and PBMCs isolated for measurement of T-cell response. If a participant experiences acute symptoms compatible with viral respiratory infection, nasopharyngeal swab samples will be collected for a rapid influenza diagnostic test and respiratory virus PCR assay panel (including SARS-CoV-2) as indicated for symptomatic respiratory infection and will perform the rapid influenza diagnostic test. The primary analysis of study data will be conducted after all participants complete the Day 29 visit. The final analysis will be conducted at the end of the study. ### Conditions Module **Conditions:** - Influenza, Human **Keywords:** - Influenza, Human - Viral Vaccines - Vaccines, Live Attenuated ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** QUADRUPLE **Who Masked:** - PARTICIPANT - CARE_PROVIDER - INVESTIGATOR - OUTCOMES_ASSESSOR **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 69 **Type:** ACTUAL **Phases:** - PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Live Attenuated Vaccine administered by Intramuscular Injection **Intervention Names:** - Biological: CODA-VAX H1N1 **Label:** CODA-VAX H1N1 **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Licensed Injectable Seasonal Influenza Vaccine **Intervention Names:** - Biological: Flucelvax Quad **Label:** Flucelvax Quad **Type:** ACTIVE_COMPARATOR #### Arm Group 3 **Description:** Normal Sterile Saline for Intramuscular Injection **Intervention Names:** - Other: Saline **Label:** Saline **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - CODA-VAX H1N1 **Description:** Intramuscular Live Attenuated Influenza H1N1 Vaccine **Name:** CODA-VAX H1N1 **Type:** BIOLOGICAL #### Intervention 2 **Arm Group Labels:** - Flucelvax Quad **Description:** Licensed Seasonal Injectable Influenza Vaccine **Name:** Flucelvax Quad **Type:** BIOLOGICAL #### Intervention 3 **Arm Group Labels:** - Saline **Description:** Saline **Name:** Saline **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** Percentage of participants with reactogenicity events **Measure:** Safety and Tolerability by Assessing Percentage of Participants with Reactogenicity Events **Time Frame:** Reactogenicity events from Day 1 to Day 7 **Description:** Percentage of participants with adverse events **Measure:** Safety and Tolerability by Assessing Percentage of Participants with Adverse Events **Time Frame:** Adverse events (AEs) from Day 1 to Day 29 **Description:** Percentage of participants with MAAEs, NCIs, and SAEs. **Measure:** Safety and Tolerability by Assessing Percentage of Participants with MAAEs, NCIs, and SAEs. **Time Frame:** MAAEs, NCIs, SAEs from Day 1 to Day 181 #### Secondary Outcomes **Description:** To assess the humoral immunogenicity elicited by CodaVax-H1N1 at nominal doses of 5×104, 5×105, and 5×106 PFU by IM injection **Measure:** Humoral Immunogenicity **Time Frame:** HAI assay titre against A/California/07/2009 and the current seasonal influenza vaccine H1N1 and H3N2 strains measured in samples collected on Days 1, 29, 91, and 181 ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Body mass index (BMI) ≥ 18 and ≤ 35 kg/m2 * In good health with no history, or current evidence, of clinically significant medical conditions * Negative SARS-CoV-2 test predose on Day 1 * For all women, negative pregnancy test * Agreement to comply with conditions to prevent the spread of genetically modified organisms (GMOs) Exclusion Criteria: * Pregnant or lactating women or women who plan to become pregnant through Day 29 * Inadequate venous access for repeated phlebotomy * History of severe reaction to vaccination * Receipt of any licenced or investigational influenza vaccine within 6 months before Day 1 * Receipt of any live vaccine within 30 days before Day 1 * Tattoo, skin reaction, or other condition at the injection site that would interfere with assessment of local reactogenicity **Healthy Volunteers:** True **Maximum Age:** 49 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Morayfield **Country:** Australia **Facility:** Lis Gilmour, Senior Project Manager **State:** Queensland **Zip:** QLD 4556 ### IPD Sharing Statement Module **IPD Sharing:** UNDECIDED ## 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, Human - 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:** NCT03851679 **Brief Title:** Pulmonary Echography and BNP Value Pre- and Post- Elective Cesarean Section in Spinal Anesthesia **Official Title:** Pulmonary Echography and BNP Value Pre- and Post- Elective Cesarean Section in Spinal Anesthesia #### Organization Study ID Info **ID:** BNP and pulmonary echography #### Organization **Class:** OTHER **Full Name:** University of Udine ### Status Module #### Completion Date **Date:** 2018-11 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2019-02-22 **Type:** ACTUAL **Last Update Submit Date:** 2019-02-20 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2018-08-08 **Type:** ACTUAL #### Start Date **Date:** 2016-12-17 **Type:** ACTUAL **Status Verified Date:** 2019-02 #### Study First Post Date **Date:** 2019-02-22 **Type:** ACTUAL **Study First Submit Date:** 2019-02-20 **Study First Submit QC Date:** 2019-02-20 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** University of Udine #### Responsible Party **Investigator Affiliation:** University of Udine **Investigator Full Name:** Bove **Investigator Title:** Professor **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False ### Description Module **Brief Summary:** Pregnancy is characterized by many biohumoral changes: circulation, respiratory mechanics, oncotic pressure, vascular permeability and many other systems are affected. Vascular permeability is controlled by endothelial glycocalyx. Several factors such as sepsis, ischemia / reperfusion, inflammatory mediators, trauma, surgery including the Cesarean Section and fluid overload can increase vascular permeability due to a glycocalyx damage. During Cesarean Section under subarachnoid anesthesia, hypotension may occur. It is a common side effect caused by reduced preload due to aortocaval compression by the uterus. Furthermore, subarachnoid anesthesia causes block of the sympathetic preganglionic fibers which is associated with vasodilation. These changes often require the use of vasopressors and fluids. A fluid overload associated with the physiological and pathological factors discussed earlier might cause an increased risk of pulmonary edema and acute respiratory failure (IRA) in women undergoing cesarean section under arachnoid anesthesia. IRA occurs in less than 0.2% of total pregnancies but it is one of the most common cause of admission to intensive care unit in pregnant women. Among the causes that can lead to IRA in the last trimester of pregnancy we find pneumopathies such as asthma, pulmonary embolism due to amniotic fluid and pulmonary edema related to severe preeclampsia. Diagnosis of pulmonary edema can be clinical or sub-clinical through laboratory tests such as BNP (b-type natriuretic peptide). It might also be necessary to execute instrumental examinations such as chest radiography (contraindicated in pregnancy) or trans-thoracic ultrasound. Hypothesis: correlation between subarachnoid anesthesia, fluidic therapy and BNP values and ultrasound pattern ### Conditions Module **Conditions:** - Pregnancy Related **Keywords:** - pulmonary echography - B-Type natriuretic peptide - Spinal anesthesia ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** RETROSPECTIVE #### Enrollment Info **Count:** 80 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** woman who are submitted to elective Cesarean Section in spinal anesthesia **Intervention Names:** - Diagnostic Test: B-Type natriuretic peptide (BNP) serum values - Device: Pulmonary echography - Other: urine collection **Label:** pregnancy woman ### Interventions #### Intervention 1 **Arm Group Labels:** - pregnancy woman **Description:** evaluation BNP serum values: * pre- Cesarean Section (30 minutes before surgery) * post- Cesarean Section (6 hour and 24 hour after surgery) **Name:** B-Type natriuretic peptide (BNP) serum values **Type:** DIAGNOSTIC_TEST #### Intervention 2 **Arm Group Labels:** - pregnancy woman **Description:** Pulmonary echography: * pre- Cesarean Section (30 minutes before surgery) * post- Cesarean Section (6 hour and 24 hour after surgery) **Name:** Pulmonary echography **Type:** DEVICE #### Intervention 3 **Arm Group Labels:** - pregnancy woman **Description:** 6 hour and 24 hour urine collection after Cesarean Section **Name:** urine collection **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** The main goal of our study is to evaluate, preoperatively, the incidence of ultrasound pulmonary variations in pregnant women attending elective Cesarean Section **Measure:** Ultrasound pulmonary variations **Time Frame:** pulmonary echography is made 30 minutes before Cesarean Section, 6 and 24 hours after surgery #### Secondary Outcomes **Description:** Evaluating the incidence of subclinical variations in ecographic lung characteristics at 6 and 24 hours after Cesarean Section **Measure:** subclinical pulmonary echography variation **Time Frame:** pulmonary echography is made 30 minutes before Cesarean Section, 6 and 24 hours after surgery **Description:** Finding if there is any correlation between preoperative b-type natriuretic peptide and ecographic lung characteristics in pregnants, before and 24 hours after Cesarean Section **Measure:** B-type natriuretic peptide serum value variation **Time Frame:** B-type natriuretic peptide serum level is sampled 30 minutes before Cesarean Section, 6 and 24 hours after surgery 30 minutes before Cesarean Section, 6 and 24 hours after surgery **Description:** Finding if there is any correlation between intraoperative fluids administered and ecographic lung characteristics **Measure:** fluid administration and pulmonary echography variation **Time Frame:** pulmonary echography is made 30 minutes before Cesarean Section, 6 and 24 hours after surgery ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: woman submit elective Cesarean Section: * age \> 18 years * American Society of Anesthesiologists (ASA) physical status classification system \> 2 * \> 37 gestational age * arterial pressure \>/ = 140/90 mmHg and proteinuria \< 300 mmHg during anesthesia pre-examination * no known cardiovascular/respiratory disease * pre-partum pulmonary echography Exclusion Criteria: * age \< 18 years * pulmonary echographic windows not satisfying * blood loss during Cesarean Section more than 1000 mL and/or necessity to administer colloid * postpartum hemorrhage within the first 24 hours following childbirth * pre-eclamptic sign/symptoms within the first 5 days following childbirth * twin pregnancy **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** FEMALE **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Patients' anthropometric data were collected, data related to the anesthetic technique, pharmacological and intraoperative fluid therapy, sensory level reached after subarachnoid anesthesia, sensory level and motor blockade at discharge from the operating room. We also collected BNP serum values and pulmonary ultrasound images at 6 and 24 h after the intervention. Diuresis collection at 6 and 24 h after the intervention was registered as well as water balance. ### References Module #### References **Citation:** Bamfo JE, Kametas NA, Nicolaides KH, Chambers JB. Maternal left ventricular diastolic and systolic long-axis function during normal pregnancy. Eur J Echocardiogr. 2007 Oct;8(5):360-8. doi: 10.1016/j.euje.2006.12.004. Epub 2007 Feb 23. **PMID:** 17321800 **Citation:** Campos O, Andrade JL, Bocanegra J, Ambrose JA, Carvalho AC, Harada K, Martinez EE. Physiologic multivalvular regurgitation during pregnancy: a longitudinal Doppler echocardiographic study. Int J Cardiol. 1993 Jul 15;40(3):265-72. doi: 10.1016/0167-5273(93)90010-e. **PMID:** 8225661 **Citation:** Lapinsky SE. Acute respiratory failure in pregnancy. Obstet Med. 2015 Sep;8(3):126-32. doi: 10.1177/1753495X15589223. Epub 2015 Jun 10. **PMID:** 27512467 **Citation:** Pereira A, Krieger BP. Pulmonary complications of pregnancy. Clin Chest Med. 2004 Jun;25(2):299-310. doi: 10.1016/j.ccm.2004.01.010. **PMID:** 15099890 **Citation:** Chappell D, Jacob M, Hofmann-Kiefer K, Conzen P, Rehm M. A rational approach to perioperative fluid management. Anesthesiology. 2008 Oct;109(4):723-40. doi: 10.1097/ALN.0b013e3181863117. **PMID:** 18813052 **Citation:** Resnik JL, Hong C, Resnik R, Kazanegra R, Beede J, Bhalla V, Maisel A. Evaluation of B-type natriuretic peptide (BNP) levels in normal and preeclamptic women. Am J Obstet Gynecol. 2005 Aug;193(2):450-4. doi: 10.1016/j.ajog.2004.12.006. **PMID:** 16098869 ## Derived Section ### Intervention Browse Module - Ancestors - ID: D000045283 - Term: Natriuretic Agents - ID: D000045505 - Term: Physiological Effects of Drugs ### Intervention Browse Module - Browse Branches - Abbrev: CNSDep - Name: Central Nervous System Depressants - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: NaAg - Name: Natriuretic Agents ### Intervention Browse Module - Browse Leaves - ID: M4107 - Name: Anesthetics - Relevance: LOW - As Found: Unknown - ID: M21935 - Name: Natriuretic Peptide, Brain - Relevance: HIGH - As Found: SHR-1316 ### Intervention Browse Module - Meshes - ID: D000020097 - Term: Natriuretic Peptide, Brain ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05839379 **Brief Title:** Targeted Pediatric High-Grade Glioma Therapy **Official Title:** Molecularly-Guided Phase II Umbrella Trial for Children, Adolescents, and Young Adults Newly Diagnosed With High-Grade Glioma, Including Diffuse Intrinsic Pontine Glioma #### Organization Study ID Info **ID:** TarGeT-SCR #### Organization **Class:** OTHER **Full Name:** Nationwide Children's Hospital ### Status Module #### Completion Date **Date:** 2034-05-30 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-05-14 **Type:** ACTUAL **Last Update Submit Date:** 2024-05-13 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2029-05-30 **Type:** ESTIMATED #### Start Date **Date:** 2024-05-30 **Type:** ESTIMATED **Status Verified Date:** 2024-05 #### Study First Post Date **Date:** 2023-05-03 **Type:** ACTUAL **Study First Submit Date:** 2023-04-20 **Study First Submit QC Date:** 2023-05-01 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Nationwide Children's Hospital #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** The goal of this study is to perform genetic sequencing on brain tumors from children, adolescents, and young adult patients who have been newly diagnosed with a high-grade glioma. This molecular profiling will decide if patients are eligible to participate in a subsequent treatment-based clinical trial based on the genetic alterations identified in their tumor. **Detailed Description:** A novel, molecularly-guided, multi-arm phase umbrella II trial is proposed in children, adolescents, and young adults with newly diagnosed HGG, including DIPG, in which we will (1) conduct comprehensive molecular screening of tumor tissue using a multi-omic approach (WES/WGS, gene fusion panels/RNASeq, DNA methylation microarray) across international CONNECT genomics cores with rapid return of clinical results, (2) stratify patients to biologically-targeted treatment arms, based on the tumor molecular profile and histopathology, and (3) perform longitudinal evaluation of peripheral blood, cerebrospinal fluid (CSF), and/or tumor tissue as well as advanced neuro-imaging to determine genomic, immune, and radiologic biomarkers predictive of response, recurrence, resistance, and toxicity. Based on results of the above tumor molecular profiling and pathology-based confirmation of HGG diagnosis, eligible patients will be assigned to one of several biologically guided treatment arms on a phase II trial. Approximately 400-450 patients will be enrolled on the screening protocol through which biospecimens (paired tumor DNA/RNA and normal comparator samples) will undergo extensive molecular profiling to assess eligibility to any of the therapeutic subprotocols of the phase II study. ### Conditions Module **Conditions:** - High Grade Glioma - Diffuse Intrinsic Pontine Glioma - Anaplastic Astrocytoma - Glioblastoma - Glioblastoma Multiforme - Diffuse Midline Glioma, H3 K27M-Mutant - Metastatic Brain Tumor - WHO Grade III Glioma - WHO Grade IV Glioma ### Design Module #### Bio Spec **Description:** Brain tumor samples with matched normal comparator (blood preferred alternatively, saliva or buccal swab) **Retention:** SAMPLES_WITH_DNA #### Design Info **Observational Model:** OTHER **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 450 **Type:** ESTIMATED **Study Type:** OBSERVATIONAL ### Outcomes Module #### Primary Outcomes **Description:** Utilize molecular, clinical, and histopathologic data to assess eligibility for specific biologically-guided treatment subprotocols among pediatric, adolescent and young adult patients with newly diagnosed HGG, including DIPG. **Measure:** Molecular profiling **Time Frame:** 4 years **Description:** Determine the percent of pediatric, adolescent, and young adult patients newly diagnosed with HGG, including DIPG, who undergo comprehensive molecular characterization across clinical molecular testing laboratories at CONNECT sites and begin treatment on a TarGeT treatment subprotocol within 10 calendar days of starting radiation therapy (RT) (if treatment involves an agent given concurrently with RT) or within 35 days of completion of RT (if treatment involves adjuvant maintenance therapy). **Measure:** Feasibility of molecular profiling and enrollment to a TarGeT treatment protocol **Time Frame:** 4 years #### Secondary Outcomes **Description:** Increase knowledge of the genomic and immunologic landscape of newly-diagnosed pediatric and young adult HGGs, including DIPG, through comprehensive molecular characterization. **Measure:** Genomic Research **Time Frame:** 6 years **Description:** Determine the frequency and spectrum of germline cancer susceptibility mutations in children and young adults with HGG and DIPG and assess the feasibility of return of those results. **Measure:** Germline susceptibility testing **Time Frame:** 4 years **Description:** Prospectively collect tumor tissue from diagnostic biopsy/resection as well as baseline peripheral blood and cerebrospinal fluid (CSF) samples for the CONNECT biorepository to be used in correlative research for the present trial as well as future studies. **Measure:** Biobanking **Time Frame:** 4 years ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Age: Patients must be ≥12 months and ≤30 years of age at the time of enrollment onto this screening protocol. 2. Diagnosis: Patients with newly diagnosed HGG, including DIPG are eligible. The diagnosis of HGG must have been confirmed by local pathology review. for the diagnosis of DIPG, patients must have a tumor with pontine epicenter and diffuse involvement of at least 2/3 of the pons, with histopathology consistent with diffuse WHO grade 2-4 glioma (eg, diffuse astrocytoma, anaplastic astrocytoma, glioblastoma, H3K27-altered diffuse midline glioma). For all other tumors, histologic grade must be WHO grade 3-4. 3. Disease Status: There are no disease status requirements for enrollment. * Measurable disease is not required. Patients without measurable disease are eligible. * Patients with metastatic/disseminated or multifocal disease or gliomatosis cerebri are eligible. * Patients with a primary spinal tumor are eligible. * Patients with secondary, radiation related HGG are eligible. 4. Prior Therapy for HGG: Surgery, radiation, and/or dexamethasone are permissible. Temozolomide concurrent with radiation is permissible, but not recommended. No other prior anticancer therapy for HGG will be allowed. Timing from surgery to start of RT: For patients who have started RT, radiation must have started within 31 days of definitive surgery or biopsy (if patient had two surgeries, radiation must have started within 31 days from second surgery). 5. Tumor Sample Availability OR results from previous molecular profiling/targeted sequencing * If a patient screens through OPTION #1, tumor sample in addition to normal comparator tissue (peripheral blood or saliva) must be submitted for comprehensive molecular screening at the time of screening enrollment. * If a patient screens through OPTIONS #2 or #3, results from previously performed molecular profiling must be submitted following enrollment. It is highly recommended that results be uploaded within 7 days of enrollment (if results are available at time of enrollment) or within 7 days of results becoming available (if pending at time of enrollment) to allow adequate time for central review. 6. Informed Consent: All patients and/or their parents or legally authorized representatives must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines. 7. Enrollment timeline: Patients are eligible to enroll on the TarGeT-SCR anytime between diagnosis and the following specific timepoints post completion of RT * Patients screening through OPTION #1 are eligible to enroll anytime between diagnosis and 10 days post RT. * Patients screening through OPTIONS #2 or #3 are eligible to enroll anytime between diagnosis and 21 days post RT. However, it is important to note the following: * For treatment protocols that include targeted therapy administered concurrently with RT, patients must start treatment within 10 calendar days of starting RT. * For treatment protocols that only include maintenance/adjuvant therapy (no systemic therapy given concurrently with radiation), patients must start treatment by 35 days post RT #SCREENING OPTIONS * OPTION1: Molecular screening through CONNECT TarGeT Clinical Testing Laboratories * OPTION2: Molecular screening through a national comprehensive tumor profiling program * OPTION3: Clinically validated targeted sequencing or focused profiling Exclusion Criteria: -Tumors that do not meet HGG and DIPG diagnoses specified above **Maximum Age:** 39 Years **Minimum Age:** 12 Months **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - CHILD - ADULT **Study Population:** Pediatric and young adult patients new diagnosed with High Grade Glioma including Diffuse Intrinsic Pontine Glioma (per 2021 WHO CNS tumor classification) ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Leonie Mikael, PhD **Phone:** 16147223284 **Role:** CONTACT #### Locations **Location 1:** **City:** Aurora **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Kathleen H Dorris, MD - **Phone:** 720-777-8314 - **Role:** CONTACT **Country:** United States **Facility:** Children's Hospital Colorado **State:** Colorado **Zip:** 80045 **Location 2:** **City:** Washington **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Eugene M Hwang, MD - **Phone:** 202-476-5046 - **Role:** CONTACT **Country:** United States **Facility:** Children's National Medical Center **State:** District of Columbia **Zip:** 20010 **Location 3:** **City:** Chicago **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Ashley O Plant, MD - **Phone:** 312-227-4090 - **Role:** CONTACT **Country:** United States **Facility:** Ann & Robert H. Lurie Children's Hospital of Chicago **State:** Illinois **Zip:** 60611 **Location 4:** **City:** Boston **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Susan C Chi, MD - **Phone:** 617-632-4386 - **Role:** CONTACT **Country:** United States **Facility:** Dana-Farber Cancer Institute **State:** Massachusetts **Zip:** 02215 **Location 5:** **City:** Durham **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** David H Ashley, MD - **Phone:** 919-681-3824 - **Role:** CONTACT **Country:** United States **Facility:** Duke University Health System **State:** North Carolina **Zip:** 27708 **Location 6:** **City:** Cincinnati **Country:** United States **Facility:** Cincinnati Children's Hospital Medical Center **State:** Ohio **Zip:** 45229 **Location 7:** **City:** Columbus **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Maryam Fouladi - **Phone:** 614-722-5758 - **Role:** CONTACT **Country:** United States **Facility:** Nationwide Children's Hospital **State:** Ohio **Zip:** 43205 **Location 8:** **City:** Philadelphia **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Michael J Fisher, MD - **Phone:** 215-590-5188 - **Role:** CONTACT **Country:** United States **Facility:** Children's Hospital of Philadelphia **State:** Pennsylvania **Zip:** 19104 **Location 9:** **City:** Houston **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Patricia Baxter, MD - **Phone:** 832-824-4681 - **Role:** CONTACT **Country:** United States **Facility:** Texas Children's Hospital **State:** Texas **Zip:** 77030 **Location 10:** **City:** Seattle **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Sarah Leary, MD - **Phone:** 206-987-2106 - **Role:** CONTACT **Country:** United States **Facility:** Seattle Children's Hospital **State:** Washington **Zip:** 98105 **Location 11:** **City:** Randwick **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** David Ziegler, MBBS - **Phone:** +61293821730 - **Role:** CONTACT **Country:** Australia **Facility:** Sydney Children's Hospital **State:** New South Wales **Zip:** 2031 **Location 12:** **City:** South Brisbane **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Tim Hassall, MBBS - **Phone:** +61730683593 - **Role:** CONTACT **Country:** Australia **Facility:** Queensland Children's Hospital **State:** Queensland **Zip:** 4101 **Location 13:** **City:** Perth **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Nick Gottardo, MBChB - **Phone:** +61864560241 - **Role:** CONTACT **Country:** Australia **Facility:** Perth Children's Hospital **State:** Western Australia **Zip:** 6000 **Location 14:** **City:** Toronto **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Eric Bouffet, MD - **Phone:** 4168137457 - **Role:** CONTACT **Country:** Canada **Facility:** The Hospital for Sick Children (SickKids) **State:** Ontario **Zip:** M5G1X8 **Location 15:** **City:** Montréal **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Genevieve Legault, MD - **Phone:** 5144124400 - **Phone Ext:** 60497 - **Role:** CONTACT **Country:** Canada **Facility:** Montreal Children's Hospital **State:** Quebec **Zip:** H4A3J1 **Location 16:** **City:** Heidelberg **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Olaf Witt, MD - **Phone:** 0496221423570 - **Role:** CONTACT **Country:** Germany **Facility:** Hopp Children's Cancer Center at NCT Heidelberg (KiTZ) **State:** Baden-Württemberg **Zip:** 69120 **Location 17:** **City:** Utrecht **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Jasper van der Lugt, MD, PhD - **Phone:** 31 6 18559694 - **Role:** CONTACT **Country:** Netherlands **Facility:** Princess Máxima Center **Zip:** 3720 **Location 18:** **City:** London **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Darren Hargrave, MD - **Phone:** 02078138525 - **Role:** CONTACT **Country:** United Kingdom **Facility:** Great Ormond Street Hospital **Zip:** WC1N 3JH #### Overall Officials **Official 1:** **Affiliation:** Nationwide Children's Hospital **Name:** Maryam Fouladi, MD **Role:** STUDY_CHAIR **Official 2:** **Affiliation:** Nationwide Children's Hospital **Name:** Margot Lazow, MD **Role:** STUDY_DIRECTOR ### IPD Sharing Statement Module **IPD Sharing:** UNDECIDED ## Derived Section ### Condition Browse Module - Ancestors - ID: D000018302 - Term: Neoplasms, Neuroepithelial - ID: D000017599 - Term: Neuroectodermal Tumors - ID: D000009373 - Term: Neoplasms, Germ Cell and Embryonal - ID: D000009370 - Term: Neoplasms by Histologic Type - ID: D000009369 - Term: Neoplasms - ID: D000009375 - Term: Neoplasms, Glandular and Epithelial - ID: D000009380 - Term: Neoplasms, Nerve Tissue - ID: D000001932 - Term: Brain Neoplasms - ID: D000016543 - Term: Central Nervous System Neoplasms - ID: D000009423 - Term: Nervous System Neoplasms - ID: D000009371 - Term: Neoplasms by Site - ID: D000001927 - Term: Brain Diseases - ID: D000002493 - Term: Central Nervous System Diseases - ID: D000009422 - Term: Nervous System Diseases - ID: D000020295 - Term: Brain Stem Neoplasms - ID: D000015192 - Term: Infratentorial Neoplasms ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: All - Name: All Conditions - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M9020 - Name: Glioma - Relevance: HIGH - As Found: Glioma - ID: M9019 - Name: Glioblastoma - Relevance: HIGH - As Found: Glioblastoma - ID: M5209 - Name: Brain Neoplasms - Relevance: LOW - As Found: Unknown - ID: M2159 - Name: Diffuse Intrinsic Pontine Glioma - Relevance: HIGH - As Found: Diffuse Intrinsic Pontine Glioma - ID: M4561 - Name: Astrocytoma - Relevance: HIGH - As Found: Anaplastic Astrocytoma - ID: M20446 - Name: Neoplasms, Neuroepithelial - 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: M12320 - Name: Neoplasms, Glandular and Epithelial - Relevance: LOW - As Found: Unknown - ID: M12325 - Name: Neoplasms, Nerve Tissue - Relevance: LOW - As Found: Unknown - ID: M18937 - Name: Central Nervous System Neoplasms - Relevance: LOW - As Found: Unknown - ID: M12367 - Name: Nervous System Neoplasms - Relevance: LOW - As Found: Unknown - ID: M5204 - Name: Brain Diseases - Relevance: LOW - As Found: Unknown - ID: M5742 - Name: Central Nervous System Diseases - Relevance: LOW - As Found: Unknown - ID: M22108 - Name: Brain Stem Neoplasms - Relevance: LOW - As Found: Unknown - ID: M17898 - Name: Infratentorial Neoplasms - Relevance: LOW - As Found: Unknown - ID: T2519 - Name: Glioma - Relevance: HIGH - As Found: Glioma - ID: T2518 - Name: Glioblastoma - Relevance: HIGH - As Found: Glioblastoma - ID: T1865 - Name: Diffuse Intrinsic Pontine Glioma - Relevance: HIGH - As Found: Diffuse Intrinsic Pontine Glioma - ID: T364 - Name: Anaplastic Astrocytoma - Relevance: HIGH - As Found: Anaplastic Astrocytoma - ID: T4092 - Name: Neuroepithelioma - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000005909 - Term: Glioblastoma - ID: D000005910 - Term: Glioma - ID: D000001254 - Term: Astrocytoma - ID: D000080443 - Term: Diffuse Intrinsic Pontine Glioma ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04744779 **Brief Title:** Office Based Vergence/Accommodative Therapy for the Treatment of Intermittent Exotropia **Official Title:** Effectiveness of Office Based Vergence/Accommodative Therapy for the Treatment of Intermittent Exotropia: A Randomized Clinical Trial #### Organization Study ID Info **ID:** XT4 #### Organization **Class:** OTHER **Full Name:** Sun Yat-sen University ### Status Module #### Completion Date **Date:** 2023-06 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** NOT_YET_RECRUITING #### Last Update Post Date **Date:** 2021-02-23 **Type:** ACTUAL **Last Update Submit Date:** 2021-02-21 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2023-06 **Type:** ESTIMATED #### Start Date **Date:** 2021-03 **Type:** ESTIMATED **Status Verified Date:** 2021-02 #### Study First Post Date **Date:** 2021-02-09 **Type:** ACTUAL **Study First Submit Date:** 2021-02-04 **Study First Submit QC Date:** 2021-02-04 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** Salus University #### Lead Sponsor **Class:** OTHER **Name:** Sun Yat-sen University #### Responsible Party **Investigator Affiliation:** Sun Yat-sen University **Investigator Full Name:** Ying Kang **Investigator Title:** Associate Professor of Ophthalmology **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Effectiveness of office based vergence/accommodative therapy for the treatment of intermittent exotropia is investigated through a randomized clinical trial **Detailed Description:** Purpose of study: i) To evaluate the short-term effectiveness of office based vergence/accommodative therapy (OBVAT) for improving control of intermittent exotropia compared to observation alone; ii) To evaluate the long-term effectiveness of OBVAT for improving control of intermittent exotropia compared to observation alone; iii) To determine the natural history of intermittent exotropia among patients aged 6 to \< 18 years who have baseline near stereoacuity of 400 arc sec or better using the Preschool Randot stereotest ### Conditions Module **Conditions:** - Intermittent Exotropia ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** SINGLE **Who Masked:** - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 40 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Observation only. **Label:** Observation **Type:** NO_INTERVENTION #### Arm Group 2 **Description:** Office-based accommodative/vergence therapy (60 minutes per visit, one time per week, 16 weeks) and home reinforcement (15 minutes each time, five times per week, 16 weeks) **Intervention Names:** - Behavioral: Office-based accommodative/vergence therapy and home reinforcement **Label:** Office-based accommodative/vergence therapy and home reinforcement **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Office-based accommodative/vergence therapy and home reinforcement **Description:** Office-based accommodative/vergence therapy (60 minutes per visit, one time per week, 16 weeks) and home reinforcement (15 minutes each time, five times per week, 16 weeks) **Name:** Office-based accommodative/vergence therapy and home reinforcement **Type:** BEHAVIORAL ### Outcomes Module #### Other Outcomes **Description:** Comparison of deterioration rate between 2 groups **Measure:** Comparison of deterioration rate between 2 groups **Time Frame:** 16 months #### Primary Outcomes **Description:** Comparison of the distant office control score between two groups at the primary outcome visit **Measure:** Comparison of the distant office control score between two groups at the primary outcome visit **Time Frame:** 16 months #### Secondary Outcomes **Description:** Comparison of percentage of patients showing ≥ 1 point change and ≥ 2 points change in office control score **Measure:** Comparison of percentage of patients showing ≥ 1 point change and ≥ 2 points change in office control score **Time Frame:** 16 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. 6 to \<18 years old 2. Distance exodeviation between 10 and 30 prism diopters (PD) measured by prism and alternate cover test (PACT) 3. Near deviation not exceeding the distance deviation by \>10PD by PACT (i.e., convergence insufficiency type intermittent exotropia excluded) 4. Control of deviation meeting all the following criteria based on the office control score scale: 4.1 Intermittent or constant exotropia at distance (mean of 3 baseline assessments of distance control ≥ Grade 2)# 4.2 Intermittent exotropia or exophoria at near (at least 1 of 3 assessments of near control at the baseline visit Grade 0-4) or orthophoria 5. Stereoacuity: near stereoacuity of 400 arcsec or better by the Preschool Randot stereotest 6. Cycloplegic subjective refraction spherical equivalent (SE) refractive error between -6.00 diopters (D)and +3.50 D inclusive in either eye 7. Must be wearing the updated refractive correction (spectacles) for at least 2 weeks if refractive error (based on cycloplegic subjective refraction performed within 6 months) meets any of the following: 7.1 Myopia \>-0.50 D spherical equivalent in either eye 7.2 Anisometropia \>1.00 D spherical equivalent 7.3 Astigmatism in either eye \>1.50 D 8. Refractive correction must meet the following guidelines: 8.1 Anisometropia spherical equivalent must be within 0.25 D of the full anisometropic difference 8.2 Astigmatism cylinder must be within 0.25 D of full correction and axis must be within 5 degree 8.3 For hyperopia and myopia, the spherical component can be reduced by investigator discretion provided reduction is symmetrical and results in residual (i.e., uncorrected) spherical equivalent refractive error that does not exceed +3.50 D spherical equivalent hyperopia or -0.50 D spherical equivalent myopia 9. Gestational age \>34 weeks 10. Birth weight \>1500 g 11. No previous surgical or nonsurgical treatment for intermittent exotropia other than single vision refractive correction (e.g. progressive addition lens, bifocals, patching, or deliberate over-minus with spectacles \>0.50 D) 12. No prior office-based vision therapy for any reason 13. No prior strabismus surgery or botulinum injection, intraocular surgery, or refractive surgery 14. No planned strabismus surgery 15. Visual acuity correctable to at least 20/25 or better at distance and near in each eye. * Inclusion criteria 4.1 may be changed to "Intermittent or constant exotropia at distance (mean of 3 baseline assessments of distance control ≥ Grade 1" if there is difficulty in patient recruitment. Exclusion Criteria: 1. Amblyopia, nystagmus, restrictive or paretic strabismus 2. Regular use of any ocular or systemic medications known to affect accommodation or vergence system, such as atropine, pirenzepine, and anti-epileptic medications, in the most recent 3 months 3. Developmental disability, attention-deficit/hyperactivity disorder (ADHD), or learning disability diagnosis in children that in the investigator's discretion would interfere with office-based treatment 4. Relocation anticipated within 2 year 5. Significant ocular or neurologic disorders (e.g. cerebral palsy) other than strabismus 6. Vertical deviation greater than 3 pd 7. Household member already in the study **Maximum Age:** 17 Years **Minimum Age:** 6 Years **Sex:** ALL **Standard Ages:** - CHILD ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000013285 - Term: Strabismus - ID: D000015835 - Term: Ocular Motility Disorders - ID: D000003389 - Term: Cranial Nerve Diseases - 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: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M8242 - Name: Exotropia - Relevance: HIGH - As Found: Exotropia - ID: M16075 - Name: Strabismus - Relevance: LOW - As Found: Unknown - ID: M18386 - Name: Ocular Motility Disorders - Relevance: LOW - As Found: Unknown - ID: M6605 - Name: Cranial Nerve Diseases - Relevance: LOW - As Found: Unknown - ID: M8271 - Name: Eye Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000005099 - Term: Exotropia ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03326479 **Brief Title:** POA Retrospective Repository **Official Title:** Caris Molecular Intelligence® and Caris Centers of Excellence for Precision Medicine NetworkTM Retrospective Outcomes-Associated Database #### Organization Study ID Info **ID:** COE-002-1116 #### Organization **Class:** INDUSTRY **Full Name:** Caris Science, Inc. ### Status Module #### Completion Date **Date:** 2023-01-01 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** ENROLLING_BY_INVITATION #### Last Update Post Date **Date:** 2017-10-31 **Type:** ACTUAL **Last Update Submit Date:** 2017-10-26 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2023-01-01 **Type:** ESTIMATED #### Start Date **Date:** 2016-11-30 **Type:** ACTUAL **Status Verified Date:** 2017-10 #### Study First Post Date **Date:** 2017-10-31 **Type:** ACTUAL **Study First Submit Date:** 2017-10-19 **Study First Submit QC Date:** 2017-10-26 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Caris Science, Inc. #### 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 repository is a multi-center, outcomes study designed to retrospectively collect data on the demographics, presentation, diagnosis, treatment, cost of associated care, quality of life, and outcomes of subjects utilizing Caris Molecular Intelligence® (CMI) Services for the treatment of cancer. Prior to enrolling a subject, the subject's physician will have made the independent decision whether or not to utilize the drug associations provided by CMI and made clinical treatment choices as appropriate. Thus, data captured and reported provides a "real world" perspective on diagnosis, treatment, cost, and outcomes. **Detailed Description:** This repository is a multi-center, outcomes study designed to retrospectively collect data on the demographics, presentation, diagnosis, treatment, cost of associated care, quality of life, and outcomes of subjects utilizing Caris Molecular Intelligence® (CMI) Services for the treatment of cancer. Prior to enrolling a subject, the subject's physician will have made the independent decision whether or not to utilize the drug associations provided by CMI and made clinical treatment choices as appropriate. Thus, data captured and reported provides a "real world" perspective on diagnosis, treatment, cost, and outcomes. Patients who have had CMI testing prior to the initial IRB submission date of November 11, 2016 for the respective site would be eligible to have their treatment and treatment response data entered into the study Database. All entered data would be de-identified. The patient's CMI biomarker results and treatment response data will be coupled together in order to allow the investigation of research questions concerning biomarker status and treatment response. ### Conditions Module **Conditions:** - Oncology - Solid Tumor, Adult **Keywords:** - Molecular Profiling - Biomarker Analysis - Outcomes Database ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** RETROSPECTIVE #### Enrollment Info **Count:** 10000 **Type:** ESTIMATED **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Subject who have previously had MI Profiling performed prior to 11/11/2016 are eligible for this study. No drug intervention is required for this study. **Intervention Names:** - Diagnostic Test: Caris Molecular Intelligence Profile **Label:** Retrospective ### Interventions #### Intervention 1 **Arm Group Labels:** - Retrospective **Description:** A comprehensive biomarker testing **Name:** Caris Molecular Intelligence Profile **Type:** DIAGNOSTIC_TEST ### Outcomes Module #### Primary Outcomes **Description:** Documentation of the frequency of specific clinical events in relation to diagnosis, treatments and outcomes provided **Measure:** Data Gathering **Time Frame:** 5 years per patient ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Subject' s age must be greater than or equal to 18 years and must have received CMI testing prior to the initial protocol IRB submission date of November 11, 2016. Exclusion Criteria: * Due to the complexity of state and federal requirements governing the participation of prisoners in research, prisoners-patients shall not be approached for participation. **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Subject's who have had CMI testing prior to 11/11/2016 at one of the participating POA sites. ### Contacts Locations Module #### Locations **Location 1:** **City:** Fayetteville **Country:** United States **Facility:** Highlands Oncology Group **State:** Arkansas **Zip:** 72703 **Location 2:** **City:** Omaha **Country:** United States **Facility:** Nebraska Cancer Specialists **State:** Nebraska **Zip:** 68130 **Location 3:** **City:** San Antonio **Country:** United States **Facility:** The University of Texas Health Science Center at San Antonio **State:** Texas **Zip:** 78229 ## Derived Section ### Condition Browse Module - Meshes - ID: D000009369 - Term: Neoplasms ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05606679 **Brief Title:** Maternal KIR and Fetal HLA Influence Reproductive Success in ART-oocyte Donor. **Official Title:** Maternal KIR and Fetal HLA Influence Reproductive Success in ART-oocyte Donor. #### Organization Study ID Info **ID:** 2207-MAD-098-DA #### Organization **Class:** OTHER **Full Name:** IVI Madrid ### Status Module #### Completion Date **Date:** 2025-12-31 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-01-11 **Type:** ACTUAL **Last Update Submit Date:** 2024-01-10 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2024-12-01 **Type:** ESTIMATED #### Start Date **Date:** 2022-11-01 **Type:** ACTUAL **Status Verified Date:** 2024-01 #### Study First Post Date **Date:** 2022-11-07 **Type:** ACTUAL **Study First Submit Date:** 2022-10-31 **Study First Submit QC Date:** 2022-10-31 ### Sponsor Collaborators Module #### Collaborators **Class:** UNKNOWN **Name:** Diana Alecsandru #### Lead Sponsor **Class:** OTHER **Name:** IVI Madrid #### 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 present project is an ambispective study designed to answer how HLA-F SNPs, as well as KIR-HLA-C compatibility, influence reproductive outcomes in oocyte donation cycles. On the one hand, healthy patients without history of RIF and RM and with indication of egg donation cycle as ART treatment will be genotype for KIR, HLA-C and HLA-F. HLA-C from male partners and egg donors will be also analyzed. No matching based on HLA-C genotypes would be performed and donors would be assigned to recipients following the routine clinical practices. After SET, patients will be followed up until delivery or until the end of treatment. On the other hand, access to data from patients who have equally undergone oocyte-donation cycles, who meet the inclusion criteria and who have been genotyped for KIR and HLA-C as a matter of routine practice, will be requested. For this study, only the first SET of oocyte-donation that patients undergo will be considered. LBR will be the primary endpoint of the study. In addition, secondary endpoints such as embryo development, sustained implantation, progesterone levels, implantation failure, miscarriage rate and unwanted events (preeclampsia, fetal grow restriction, premature birth, low birth weight...) will also be evaluated. **Detailed Description:** This is an ambispective study in which healthy patients without history of RIF and RM and with indication of egg donation cycle as ART treatment will be genotyped for KIR, HLA-C and HLA-F. Male partners and egg donors will also be studied for their HLA-C alleles. Patients would be assigned to donors, following routine clinical practice, without matching based on donor's HLA-C genotype. They would undergo SET and be followed up until delivery. In addition to this prospective part, we will request access to data from patients who have equally undergone oocyte donation cycles at the clinic, who meet the inclusion criteria and who have been genotyped for KIR and HLA-C as a matter of routine practice. Combinations of maternal KIR and HLA-C genotypes of the egg donor and fetus (based on the genotypes of the donor and male partner), as well as different HLA-F SNP genotypes of the recipients (form the prospective part of this proyect) will be correlated with reproductive outcomes. LBR will be the primary endpoint of the study. In addition, secondary endpoints such as embryo development, sustained implantation, progesterone leves, implantation failure and miscarriage rate will also be evaluated. Obstetrical complications such as preeclampsia, premature birth (\<34 weeks) and low birth weight will also be evaluated. ### Conditions Module **Conditions:** - Reproductive Issues ### Design Module #### Design Info **Observational Model:** OTHER **Time Perspective:** OTHER #### Enrollment Info **Count:** 400 **Type:** ESTIMATED **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Healthy patients with no history of RIF and RM which have undergone or are undergoing ART with oocyte donation and SET. **Intervention Names:** - Genetic: Analysis combinations of maternal KIR and HLA-C genotypes **Label:** Patients undergoing ART with oocyte donation ### Interventions #### Intervention 1 **Arm Group Labels:** - Patients undergoing ART with oocyte donation **Description:** Analysis of combinations of maternal KIR and HLA-C genotypes of the egg donor and fetus (based on the genotypes of the donor and male partner), as well as different HLA-F SNP genotypes of the recipients **Name:** Analysis combinations of maternal KIR and HLA-C genotypes **Type:** GENETIC ### Outcomes Module #### Primary Outcomes **Description:** Principally, to establish whether patients of KIR AA and KIR Bx (2DS1-) genotypes show better outcomes when receiving oocytes from HLA-C1C1 donors than from donors with at least one HLA-C2 allele. **Measure:** To determine if certain combinations of maternal KIR and oocyte donor HLA-C genotypes results in improved outcomes of live birth rate. **Time Frame:** 36 months #### Secondary Outcomes **Description:** To determine if certain combinations of maternal KIR and oocyte donor HLA-C genotypes results in improved outcomes of live birth rathe, in the same way as in the primary target, but taking into account the extra HLA-C2 alleles of the embryo with respect to the mother and the alternative division of the maternal genotypes into KIR AA, AB and BB. **Measure:** To determine if certain combinations of maternal KIR and oocyte donor HLA-C genotypes results in improved outcomes of live birth rate taking into account the extra HLA-C2 alleles of the embryo. **Time Frame:** 36 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Patients who have undergone or are undergoing their first egg donation cycle. * Between 18 and 45 years of age. * BMI between 19 and 25 kg/m2 * Signed written informed consent submitted. * No history of RIF, defined as implantation failure after 4 consecutive blastocysts are transferred. * No history of RM, defined as the presence of 2 or more clinical miscarriages. * Normal blood pressure and viral serology. Exclusion Criteria: * Male partner diagnosed with severe male factor * Patients who test positive for thrombophilic disorders (factor V Leiden, prothrombinG20210A mutation, positive antiphospholipid antibodies) * Participation in a different study or clinical trial with a research drug or device in the last three months prior to recruitment. * Known abnormal karyotype of subject or of her partner * Any known clinically significant systemic disease * Known inherited or acquired thrombophilia disease. * Any known endocrine or metabolic abnormalities with the exception of controlled thyroid function disease. * Severe psychiatric conditions. * Patients with uterine factor/abnormalities (eg. myomas, polyps, adenomyosis, etc), that determines an unsatisfactory ultrasound for their ART. * Patients with PCOS. * Patients diagnosed with autoimmune diseases (eg. Systemic Lupus erythematosus, multiple sclerosis, rheumatoid arthritis). * Patients with recent diagnosis (6 months) of chronic infectious disease (HPV, HBV, HCV, HIV, TBC). * Patients with current treatment of immunosuppressant (eg. corticosteroids, monoclonal antibodies...). **Maximum Age:** 45 Years **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT **Study Population:** The study population will consist of healthy patients with no history of RIF and RM which have undergone or are undergoing ART with oocyte donation and SET at IVI RMA Madrid, Valencia y Barcelona. Study subject candidates will be informed about the study once the inclusion criteria have been met. Data on reproductive outcomes, embryo development and perinatal and obstetric complications will be collected. ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Diana Alecsandru, PhD **Phone:** +34 91 180 29 00 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Juan Antonio Garcia Velasco, PhD **Phone:** +34 91 180 29 00 **Role:** CONTACT #### Locations **Location 1:** **City:** Madrid **Contacts:** ***Contact 1:*** - **Name:** Juan A Garcia-Velasco, MD - **Phone:** 341802900 - **Role:** CONTACT ***Contact 2:*** - **Name:** Juan A Garcia-Velasco, MD - **Role:** PRINCIPAL_INVESTIGATOR **Country:** Spain **Facility:** Instituto Valenciano de Infertilidad **Status:** RECRUITING **Zip:** 28035 #### Overall Officials **Official 1:** **Affiliation:** IVIRMA MADRID **Name:** Juan Antonio Garcia Velasco, PhD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05381779 **Brief Title:** Comparison the Effects of Inspiratory Muscle Training and Aerobic Exercise Training in Patients With Post COVID-19 **Official Title:** Comparison the Effects of Inspiratory Muscle Training and High Intensity Interval Aerobic Exercise Training in Patients With Post COVID-19 #### Organization Study ID Info **ID:** Gazi University4 #### Organization **Class:** OTHER **Full Name:** Gazi University ### Status Module #### Completion Date **Date:** 2024-08-05 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2023-07-25 **Type:** ACTUAL **Last Update Submit Date:** 2023-07-22 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2024-06-05 **Type:** ESTIMATED #### Start Date **Date:** 2022-06-05 **Type:** ACTUAL **Status Verified Date:** 2023-07 #### Study First Post Date **Date:** 2022-05-19 **Type:** ACTUAL **Study First Submit Date:** 2022-05-17 **Study First Submit QC Date:** 2022-05-17 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Gazi University #### Responsible Party **Investigator Affiliation:** Gazi University **Investigator Full Name:** Meral Boşnak Güçlü **Investigator Title:** Study director, PT, PhD, Prof.Dr. Faculty of Health Sciences, Department of Physiotherapy and Rehabilitation, Head of Cardiopulmonary Rehabilitation Clinic **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Coronavirus-2019 (COVID-19) is a new virus that emerged in December 2019 and spread quickly all over the world. Problems such as hypoxia, dyspnea, increased fatigue, decreased exercise capacity and respiratory muscle strength occur in COVID-19 patients.In addition, abnormalities in skeletal muscles due to systemic inflammation, mechanical ventilation, sedation and prolonged bed rest in hospital and intensive care patients cause decreased exercise capacity. **Detailed Description:** Dyspnea is one of the most common long-term symptoms in COVID-19 patients. It has been determined that dyspnea that persists three and six months after hospital discharge is associated with peak oxygen consumption in hospitalized and discharged COVID-19 patients, while peak oxygen consumption decreases in patients with dyspnea.The effects of inspiratory muscle training have been investigated in different lung diseases. In these studies, it was reported that inspiratory muscle training increased respiratory muscle strength and endurance, exercise capacity and quality of life, and decreased fatigue and dyspnea. In addition, it has been found that high-intensity interval aerobic exercise training increases exercise capacity in patients with lung disease and heart failure.In heart failure patients, it was found that high-intensity interval aerobic exercise training increased peak oxygen consumption more than moderate-intensity continuous aerobic exercise training.Patients need exercise training because symptoms such as lung involvement, decreased exercise capacity, dyspnea and fatigue continue after the disease in patients who have had COVID-19. The aim of this study is to comparison of the effects of inspiratory muscle training and high intensity interval aerobic exercise training in patients with COVID-19. Primary outcome measurement will be oxygen consumption (cardiopulmonary exercise test). Secondary outcome will be muscle oxygenation (Moxy device), physical activity level (multi sensor activity device), pulmonary function (spirometer), functional exercise capacity (six-minute walk test), respiratory (mouth pressure device) and peripheral muscle (hand-held dynamometer) strength, inspiratory muscle endurance (incremental threshold loading test), functional status (Post-COVID-19 Functional Status Scale), dyspnea (London Chest Daily Living Activity Scale), fatigue (Fatigue Severity Scale) and quality of life (Saint George Respiratory Questionnaire). ### Conditions Module **Conditions:** - COVID-19 - Aerobic Exercise - Inspiratory Muscle Training - Physical Activity - Oxygen Consumption ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** TRIPLE **Masking Description:** Triple (Participant, Investigator, Outcomes Assessor)Triple-blind study; the patients will not be informed about their groups (training group or the control group) and they will be evaluated and trained at different places and times. Evaluations and interventions will be performed different physiotherapist. In addition, before statistical analysis patients' groups will be coded. **Who Masked:** - PARTICIPANT - INVESTIGATOR - OUTCOMES_ASSESSOR **Primary Purpose:** SUPPORTIVE_CARE #### Enrollment Info **Count:** 60 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Patients in the training group will be performed inspiratory muscle training with the PowerBreathe® (inspiratory muscle training device) device at 50% of the maximal inspiratory pressure. **Intervention Names:** - Other: Inspiratory Muscle Training Group **Label:** Inspiratory Muscle Training Group **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Training group will receive high-intensity interval aerobic exercise training on treadmill accompanied by physiotherapist for 8 weeks. **Intervention Names:** - Other: High Intensity Interval Training Group **Label:** High Intensity Interval Training Group **Type:** EXPERIMENTAL #### Arm Group 3 **Description:** Breathing exercises will be given to control group as a home program for 8 weeks. **Intervention Names:** - Other: Control Group **Label:** Control Group **Type:** SHAM_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Inspiratory Muscle Training Group **Description:** Patients in the training group will receive inspiratory muscle training with the PowerBreathe® (inspiratory muscle training device) at 50% of the maximal inspiratory pressure. Patients in the training group inspiratory muscle training will be given 2 sets of 15 minutes a day for a total of 30 minutes/per day or a single session for 30 minutes/week, 7 days/week for a total of 8 weeks. Patients in the training group will be given respiratory muscle strength training with a home program 6 days a week under the supervision of a physiotherapist 1 day a week. **Name:** Inspiratory Muscle Training Group **Type:** OTHER #### Intervention 2 **Arm Group Labels:** - High Intensity Interval Training Group **Description:** High-intensity interval aerobic exercise training will be given to training group on treadmill 3 days in a week and 15-45 minutes in a day for 8 weeks with the assistance of a physiotherapist. The training workload of the active phase of high-intensity interval aerobic exercise training will be applied at 80-100% of peak oxygen consumption or 85-95% of peak heart rate or according to Borg scale dyspnea/fatigue 15-18 points. The training workload of the active recovery phase of high-intensity interval aerobic exercise training will be applied at 50-60% of peak oxygen consumption or 60-75% of peak heart rate or according to Borg scale dyspnea/fatigue 11-13 points. **Name:** High Intensity Interval Training Group **Type:** OTHER #### Intervention 3 **Arm Group Labels:** - Control Group **Description:** Breathing exercises will be given to the control group 120 times in a day and 7 days in a week for 8 weeks as a home program. The control group will be followed-up by telephone once a week. **Name:** Control Group **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** Maximal exercise capacity will be assessed with symptom limited cardiopulmonary exercise test on a treadmill at a progressively increasing speed and grade. Oxygen consumption will be measured during the test. **Measure:** Oxygen consumption **Time Frame:** First Day #### Secondary Outcomes **Description:** Muscle oxygenation will be measured with 'Moxy' muscle oxygenation device during cardiopulmonary exercise test and six-minute walk test. Measurements will be done over quadriceps femoris, locally. Local muscle oxygen saturation and total hemoglobin amount will be assessed during the both tests. **Measure:** Muscle Oxygenation **Time Frame:** First and second day **Description:** Physical activity level will be evaluated with multi sensor activity device. Patients will be asked to wear the device for five consecutive days on weekdays. **Measure:** Physical activity level **Time Frame:** Second day **Description:** Six-minute walk test will be used to evaluate functional exercise capacity. The test will be done according to American Thoracic Society and European Respiratory Society criteria. **Measure:** Functional exercise capacity **Time Frame:** Second day **Description:** Respiratory muscle strength will be assessed with mouth pressure device. Maximal inspiratory and expiratory pressure will be measured during the test. **Measure:** Respiratory muscle strength **Time Frame:** Second day **Description:** Quadriceps femoris and shoulder abduction muscle strength will be measured by using hand-held dynamometer. **Measure:** Peripheral muscle strength **Time Frame:** Second day **Description:** Inspiratory muscle endurance will be measured incremental threshold loading test, in which patients started an initial load of 30% of maximal inspiratory pressure and test load will be increased with among 10% of maximal inspiratory pressure every 2 minutes. **Measure:** Inspiratory muscle endurance **Time Frame:** Second day **Description:** Functional status of patients after COVID-19 will be evaluated with Post COVID-19 Functional Status Scale (PCFS), which was developed specifically for COVID patients. Limitation and improvement in the functional status of patients after COVID could be assessed with this scale. Functional status were graded from 0 (no functional limitations) to 4 (severe functional limitations) in the scale. **Measure:** Functional status **Time Frame:** First day **Description:** London Chest Activity of Daily Living scale (LCADL): LCADL evaluates the limitation to perform activities of daily living by dyspnea and looks at four domains: selfcare, domestic, physical and leisure. It is composed of 15 items, which are scored by the patient as follows: 0 (I do not perform this activity because I never had to do it or it is irrelevant), 1 (I do not feel any breathless when performing this activity), 2 (I feel moderate breathless when performing this activity), 3 (I feel a lot of breathless in doing this activity), 4 (I cannot perform this activity due to breathless and I have no one who can do the activity for me) or 5 (I cannot perform this activity anymore and I need someone to do it for me or help me because of breathless). **Measure:** Dyspnea **Time Frame:** First day **Description:** St. George Respiratory Questionnaire (Turkish version) (respiratory) - St. George Respiratory Questionnaire (SGRQ) is a self-reported questionnaire. SGRQ evaluates patients' respiratory disease associated quality of life. This questionnaire includes 2 part (part one is about symptoms (one subsection) and part two is about activity (seven subsection)) and 50 items. Some items scored as Likert scale and others scored as dichotomous (true/false). **Measure:** Respiratory Associated Quality of Life (respiratory) **Time Frame:** First Day ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Between the ages of 18-75 * Diagnosed with COVID-19 * COVID-19 Polymerase Chain Reaction (PCR) test result negative * Volunteer to participate in the study Exclusion Criteria: * Body mass index \>35 kg/m2 * Acute pulmonary exacerbation, acute upper or lower respiratory tract infection * Aortic stenosis, complex arrhythmia, aortic aneurysm * Serious neurological, neuromuscular, orthopedic, other systemic diseases or other diseases affecting physical functions * Cognitive impairment that causes difficulty in understanding and following exercise test instructions * Participated in a planned exercise program in the last three months * Bulla formation in the lung * Uncontrolled hypertension and/or diabetes mellitus, heart failure and cardiovascular disease * Contraindication for exercise testing and/or exercise training according to the American College of Sports Medicine **Maximum Age:** 75 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Meral BOŞNAK GÜÇLÜ, Prof.Dr. **Phone:** +903122162647 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Başak KAVALCI KOL, Pt. MSc. **Role:** CONTACT #### Locations **Location 1:** **City:** Ankara **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Meral Boşnak Güçlü, Prof. Dr. - **Phone:** +903122162647 - **Role:** CONTACT ***Contact 2:*** - **Name:** Başak Kavalcı Kol, Pt. MSc - **Role:** PRINCIPAL_INVESTIGATOR **Country:** Turkey **Facility:** Gazi University, Faculty of Health Sciences, Department of Physiotherapy and Rehabilitation, Cardiopulmonary Rehabilitation Clinic **Status:** RECRUITING **Zip:** 06560 #### Overall Officials **Official 1:** **Affiliation:** Gazi University **Name:** Başak KAVALCI KOL, Pt. MSc. **Role:** PRINCIPAL_INVESTIGATOR **Official 2:** **Affiliation:** Gazi University **Name:** Ece BAYTOK, Pt. MSc. **Role:** PRINCIPAL_INVESTIGATOR **Official 3:** **Affiliation:** Gazi University **Name:** Nilgün YILMAZ DEMİRCİ, Assoc. Prof. **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Debeaumont D, Boujibar F, Ferrand-Devouge E, Artaud-Macari E, Tamion F, Gravier FE, Smondack P, Cuvelier A, Muir JF, Alexandre K, Bonnevie T. Cardiopulmonary Exercise Testing to Assess Persistent Symptoms at 6 Months in People With COVID-19 Who Survived Hospitalization: A Pilot Study. Phys Ther. 2021 Jun 1;101(6):pzab099. doi: 10.1093/ptj/pzab099. **PMID:** 33735374 **Citation:** Abodonya AM, Abdelbasset WK, Awad EA, Elalfy IE, Salem HA, Elsayed SH. Inspiratory muscle training for recovered COVID-19 patients after weaning from mechanical ventilation: A pilot control clinical study. Medicine (Baltimore). 2021 Apr 2;100(13):e25339. doi: 10.1097/MD.0000000000025339. **PMID:** 33787632 **Citation:** Anastasio F, Barbuto S, Scarnecchia E, Cosma P, Fugagnoli A, Rossi G, Parravicini M, Parravicini P. Medium-term impact of COVID-19 on pulmonary function, functional capacity and quality of life. Eur Respir J. 2021 Sep 16;58(3):2004015. doi: 10.1183/13993003.04015-2020. Print 2021 Sep. **PMID:** 33574080 **Citation:** Carfi A, Bernabei R, Landi F; Gemelli Against COVID-19 Post-Acute Care Study Group. Persistent Symptoms in Patients After Acute COVID-19. JAMA. 2020 Aug 11;324(6):603-605. doi: 10.1001/jama.2020.12603. **PMID:** 32644129 **Citation:** Sawyer A, Cavalheri V, Hill K. Effects of high intensity interval training on exercise capacity in people with chronic pulmonary conditions: a narrative review. BMC Sports Sci Med Rehabil. 2020 Mar 30;12:22. doi: 10.1186/s13102-020-00167-y. eCollection 2020. **PMID:** 32257221 **Citation:** Donelli da Silveira A, Beust de Lima J, da Silva Piardi D, Dos Santos Macedo D, Zanini M, Nery R, Laukkanen JA, Stein R. High-intensity interval training is effective and superior to moderate continuous training in patients with heart failure with preserved ejection fraction: A randomized clinical trial. Eur J Prev Cardiol. 2020 Nov;27(16):1733-1743. doi: 10.1177/2047487319901206. Epub 2020 Jan 21. **PMID:** 31964186 **Citation:** Karadalli MN, Bosnak-Guclu M, Camcioglu B, Kokturk N, Turktas H. Effects of Inspiratory Muscle Training in Subjects With Sarcoidosis: A Randomized Controlled Clinical Trial. Respir Care. 2016 Apr;61(4):483-94. doi: 10.4187/respcare.04312. Epub 2015 Dec 29. **PMID:** 26715771 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000011024 - Term: Pneumonia, Viral - ID: D000011014 - Term: Pneumonia - ID: D000012141 - Term: Respiratory Tract Infections - ID: D000007239 - Term: Infections - ID: D000014777 - Term: Virus Diseases - ID: D000018352 - Term: Coronavirus Infections - ID: D000003333 - Term: Coronaviridae Infections - ID: D000030341 - Term: Nidovirales Infections - ID: D000012327 - Term: RNA Virus Infections - ID: D000008171 - Term: Lung Diseases - ID: D000012140 - Term: Respiratory Tract Diseases - ID: D000012120 - Term: Respiration Disorders - ID: D000010335 - Term: Pathologic Processes ### 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: M27137 - Name: Respiratory Aspiration - Relevance: HIGH - As Found: Inspiratory - ID: M13904 - Name: Pneumonia - Relevance: LOW - As Found: Unknown - ID: M13914 - Name: Pneumonia, Viral - Relevance: LOW - As Found: Unknown - ID: M10283 - Name: Infections - Relevance: LOW - As Found: Unknown - ID: M6368 - Name: Communicable Diseases - Relevance: LOW - As Found: Unknown - ID: M14978 - Name: Respiratory Tract Infections - Relevance: LOW - As Found: Unknown - ID: M17522 - Name: Virus Diseases - Relevance: LOW - As Found: Unknown - ID: M20490 - Name: Coronavirus Infections - Relevance: LOW - As Found: Unknown - ID: M6555 - Name: Coronaviridae Infections - Relevance: LOW - As Found: Unknown - ID: M23685 - Name: Nidovirales Infections - Relevance: LOW - As Found: Unknown - ID: M15149 - Name: RNA Virus Infections - Relevance: LOW - As Found: Unknown - ID: M11168 - Name: Lung Diseases - Relevance: LOW - As Found: Unknown - ID: M14977 - Name: Respiratory Tract Diseases - Relevance: LOW - As Found: Unknown - ID: M14957 - Name: Respiration Disorders - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000086382 - Term: COVID-19 - ID: D000053120 - Term: Respiratory Aspiration ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT02416479 **Acronym:** MAGIC **Brief Title:** SystemCHANGE: An Intervention for Medication Change in Adult Kidney Transplant Patients **Official Title:** SystemCHANGE: An Intervention for Medication Adherence in Transplant Recipients #### Organization Study ID Info **ID:** 0039040 #### Organization **Class:** OTHER **Full Name:** University of Missouri, Kansas City ### Status Module #### Completion Date **Date:** 2018-12 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** ACTIVE_NOT_RECRUITING #### Last Update Post Date **Date:** 2018-05-04 **Type:** ACTUAL **Last Update Submit Date:** 2018-05-03 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2018-12 **Type:** ESTIMATED #### Start Date **Date:** 2014-06 **Status Verified Date:** 2018-05 #### Study First Post Date **Date:** 2015-04-15 **Type:** ESTIMATED **Study First Submit Date:** 2015-04-04 **Study First Submit QC Date:** 2015-04-09 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** University of Tennessee **Class:** OTHER **Name:** University of Missouri-Columbia #### Lead Sponsor **Class:** OTHER **Name:** Cynthia Russell #### Responsible Party **Investigator Affiliation:** University of Missouri, Kansas City **Investigator Full Name:** Cynthia Russell **Investigator Title:** Professor **Type:** SPONSOR_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** With kidney transplant (KT) recipients as our exemplar population, our goal is to develop and test interventions that increase medication adherence (MA) in chronically ill adults. Among adult KT recipients, non-adherence to immunosuppressive medications (MNA) is the leading predictor of poor outcomes, including rejection, kidney loss, and death. An alarming one-third of KT patients experience MNA even though the problem is preventable. Adherence intervention studies have proven marginally effective for those with acute and chronic illnesses and ineffective for adult KT recipients. Using a randomized controlled trial design with an attention-control group, this R01 will test an innovative 6-month SystemCHANGE intervention to enhance immunosuppressive MA in adult non-adherent KT recipients. This intervention shows great promise for increasing MA with a large effect size of 1.4 in our pilot study. Grounded in the socio-ecological model, SystemCHANGE seeks to systematically improve MA behaviors by identifying and shaping routines, involving supportive others in routines, and using medication taking feedback through small patient-lead experiments to change and maintain behavior. The Medication Event Monitoring System cap, which contains microelectronics that record the date and time of the cap removal, will be used to measure MA. Persistence of the MA behavior change will be examined by evaluating the difference in MA between the two groups during the 6-month maintenance phase. Mediators and moderators of MA will be examined. Health outcomes will be compared and a cost-effectiveness analysis will be conducted. **Detailed Description:** SPECIFIC AIMS For adult kidney transplant (KT) patients, the leading predictor of rejection, kidney loss, death and their attendant costs is immunosuppressive medications nonadherence (MNA). An alarming one-third of KT recipients experience this preventable problem. According to meta-analysis, predictors of MNA are nonwhite ethnicity, poorer social support and poorer perceived health. Patients' most frequent barrier to adhering to immunosuppressive medication is forgetting. 9 Even minor deviations from adherence have shown negative effects, though the precise extent of poor outcomes stemming from nonadherence is not clear. Traditionally, intervention studies aimed at boosting adherence target cognition (knowledge, attitudes, beliefs) and behavioral skills. However, these have proven marginally effective for individuals with acute and chronic illnesses and ineffective for adult KT recipients. In a sample of KT recipients, we propose to test the innovative and successful SystemCHANGE intervention, which is grounded in the socio-ecological model. This approach is a paradigm shift in behavioral interventions because it seeks to redesign the system of the interpersonal environment and daily routines linked to health behavior, rather than to alter individuals' efforts to change their behavior. Using a four-pronged, patient-centered approach, we will (1) assess individual systems (including important others who shape medication taking), how they influence medication taking and their proposals for improving medication adherence, (2) implement the proposed individual systems solutions for improving adherence, (3) track adherence data, and (4) evaluate adherence data through small experiments. In our pilot study, this intervention yielded a large effect size of 1.4. This study's innovation lies in its use of a socio-ecological model known as SystemCHANGE, which differs greatly from previous cognitive and behavioral skills-focused interventions for improving medication adherence. This will be the first rigorous evaluation of SystemCHANGE with a diverse sample of KT recipients and long-term follow up. This study presents a unique opportunity to evaluate moderators and mediators of adherence and has potential, based upon pilot work, to have immediate "dose" impact. As such, it could hold great promise as an intervention that translates very well into practice settings. Our 6-month SystemCHANGE intervention (also referred to as "intervention") seeks to enhance adherence to immunosuppressive medication among adult KT recipients who are non-adherent. The study is a randomized controlled trial with an attention-control intervention (also referred to as "control") to determine persistence of medication adherence behavior change and differences in adherence between the two groups during the 6-month maintenance phase. Primary Aim (PA): PA: To determine whether the intervention is more effective than control in increasing medication adherence in adult KT recipients at the completion of the intervention and maintenance phases. Hypothesis: Adult KT recipients participating in the intervention will have higher immunosuppressive adherence rates than those participating in the control at the completion of intervention and maintenance phases. Secondary Aim (Sec): SA: To examine the patterns of medication adherence in adult KT recipients in both groups. Research question (RQ): When does the intervention become effective (e.g., what "dose" is needed)? RQ: What is the pattern of decay in adherence over time in both groups? Exploratory Aims (EA): EA1: To determine whether the intervention is more effective than the control in decreasing poor health outcomes (e.g. increasing creatinine/BUN, infection, acute/chronic rejection, graft loss, death, hospitalizations, length of hospital stay, and healthcare appointments). Hypothesis: At one year, there will be differential levels of poor outcomes, with the intervention demonstrating lower levels of poor outcomes than the control. EA2: To evaluate the role of potential mediators and moderators of medication adherence and health outcomes in adult KT recipients in the intervention and those in the control. Hypothesis: Incorporating potential mediators and moderators of the intervention (e.g., nonwhite ethnicity, perceived social support, perceived health status, personal systems behavior) will increase the medication adherence variance explained by the intervention. EA3: To determine if the intervention is cost-effective. Hypothesis: The cost-effectiveness ratio for the intervention will be less than for the control. Each year, 35.6 KT recipients per 100 are non-adherent with their medications, which is the primary cause of post-transplant morbidity. Thus, the need for effective interventions is compelling: Decreasing transplant complications from MNA will reduce costs and make additional kidneys available to those waiting for transplants by reducing the number of KT recipients who must rejoin the organ list. This project builds on our research team's previous adherence work, including a SystemCHANGE intervention pilot study that addresses Healthy People 2020 initiatives of reducing chronic kidney disease complications, disability, death, and costs by optimizing transplant medication adherence and increasing the number of patients who receive a transplant. ### Conditions Module **Conditions:** - Kidney Disease **Keywords:** - medication adherence - outcomes - intervention - randomized controlled trial ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** SINGLE **Who Masked:** - PARTICIPANT **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 84 **Type:** ACTUAL **Phases:** - PHASE3 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** SystemCHANGE supports patient-designed, interventionist-guided, small experiments to: 1) assess individual systems (including important others who shape medication taking) and the system's impact on medication taking and propose individual system solutions to improve MA, 2) implement the proposed individual systems' solutions to improve MA, 3) track MA data, and 4) evaluate MA data. **Intervention Names:** - Behavioral: SystemCHANGE **Label:** SystemCHANGE **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** The 6-month Patient education attention-control (AC) intervention includes 6 transplant educational materials, covering healthy post-transplant behavior, developed by the International Transplant Nurses Society. The RA calls Pps at 1, 2, 3, 4, 5 and 6 months to review the brochure information and answer any questions about it. **Intervention Names:** - Behavioral: Patient-education attention control **Label:** Patient-education attention-control **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - SystemCHANGE **Description:** SystemCHANGE self-management supports patient-designed, interventionist-guided, small experiments using Deming's Plan-Do-Check-Act cycle26 to: (1) assess individual systems (including important others who shape medication taking), how they influence medication taking and their proposals for improving medication adherence, (2) implement the proposed individual systems' solutions to improve adherence, (3) track adherence data, and (4) evaluate adherence data. **Name:** SystemCHANGE **Type:** BEHAVIORAL #### Intervention 2 **Arm Group Labels:** - Patient-education attention-control **Description:** The 6-month Patient education attention-control (AC) intervention includes 6 transplant educational materials, covering healthy post-transplant behavior, developed by the International Transplant Nurses Society. The RA calls Pps at 1, 2, 3, 4, 5 and 6 months to review the brochure information and answer any questions about it. **Name:** Patient-education attention control **Type:** BEHAVIORAL ### Outcomes Module #### Primary Outcomes **Description:** Medication adherence score of .85 or greater **Measure:** Medication Adherence Change from Baseline to 6 Months **Time Frame:** 6 months **Description:** Medication adherence score of .85 or greater **Measure:** Medication Adherence Change from 6 Months to 12 Months **Time Frame:** 12 months **Description:** Medication adherence score of .85 or greater **Measure:** Medication Adherence Change from Baseline to 12 Months **Time Frame:** 12 #### Secondary Outcomes **Description:** Creatinine blood level **Measure:** Creatinine **Time Frame:** 12 months **Description:** Blood, sputum, and/or urine culture positive for an abnormal organism **Measure:** Infection **Time Frame:** 12 months **Description:** Biposy proven **Measure:** Acute rejection **Time Frame:** 12 months **Description:** Biopsy proven **Measure:** Chronic rejection **Time Frame:** 12 months **Description:** BUN blood level **Measure:** BUN **Time Frame:** 12 months **Description:** 3-day dose of intravenous prednisone **Measure:** Kidney graph loss **Time Frame:** 12 months **Description:** Death documented by transplant team **Measure:** Death **Time Frame:** 12 months **Description:** Resource use costs of both Interventions **Measure:** Cost effectiveness **Time Frame:** 12 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. age 18 years or older, 2. prescribed at least 1 immunosuppressive medication taken twice a day, 3. functioning KT (not on dialysis), 4. has received a kidney-only transplant, 5. agreement from the transplant physician and nephrologist that individual is able to participate in the study, 6. able to speak, hear, and understand English as determined by the ability to participate and comprehend conversation about potential inclusion in the study, 7. able to open a MEMS cap as assessed by the Research Assistant (RA) asking if there is any problem with opening pill bottle caps, 8. able to administer immunosuppressive medications to self, 9. has a telephone or has access to a telephone, 10. has no cognitive impairment as determined by a score of 4 or greater on the 6-item Telephone Mental Status Screen Derived from the Mini-Mental Status Exam, 11. has no other diagnoses that may shorten life span, such as metastatic cancer, 12. is not currently hospitalized, 13. receives post-transplant care by the Missouri or Tennessee transplant programs. Exclusion Criteria: * None **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Kansas City **Country:** United States **Facility:** University of Missouri-Kansas City **State:** Missouri **Zip:** 64108 ### References Module #### References **Citation:** Mellon L, Doyle F, Hickey A, Ward KD, de Freitas DG, McCormick PA, O'Connell O, Conlon P. Interventions for increasing immunosuppressant medication adherence in solid organ transplant recipients. Cochrane Database Syst Rev. 2022 Sep 12;9(9):CD012854. doi: 10.1002/14651858.CD012854.pub2. **PMID:** 36094829 **Citation:** Russell CL, Hathaway D, Remy LM, Aholt D, Clark D, Miller C, Ashbaugh C, Wakefield M, Ye S, Staggs VS, Ellis RJ, Goggin K. Improving medication adherence and outcomes in adult kidney transplant patients using a personal systems approach: SystemCHANGE results of the MAGIC randomized clinical trial. Am J Transplant. 2020 Jan;20(1):125-136. doi: 10.1111/ajt.15528. Epub 2019 Aug 20. **PMID:** 31291507 **Citation:** Russell CL, Moore S, Hathaway D, Cheng AL, Chen G, Goggin K. MAGIC Study: Aims, Design and Methods using SystemCHANGE to Improve Immunosuppressive Medication Adherence in Adult Kidney Transplant Recipients. BMC Nephrol. 2016 Jul 16;17(1):84. doi: 10.1186/s12882-016-0285-8. **PMID:** 27421884 ## Derived Section ### Condition Browse Module - Ancestors - 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 ### Condition Browse Module - Browse Branches - Abbrev: BXS - Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M10698 - Name: Kidney Diseases - Relevance: HIGH - As Found: Kidney Disease - 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 ### Condition Browse Module - Meshes - ID: D000007674 - Term: Kidney Diseases ### 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:** NCT00779779 **Brief Title:** Evaluation of Reactogenicity and Safety of GSK Biologicals' Rotarix™ (Human Rotavirus Vaccine) in Infants **Official Title:** Reactogenicity and Safety of Two Doses of GSK Biologicals' Oral Live Attenuated Human Rotavirus Vaccine, Rotarix™ When Administered in Sri Lankan Infants Aged at Least 6 Weeks at the Time of First Vaccination. #### Organization Study ID Info **ID:** 111664 #### Organization **Class:** INDUSTRY **Full Name:** GlaxoSmithKline ### Status Module #### Completion Date **Date:** 2009-08-26 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2018-08-28 **Type:** ACTUAL **Last Update Submit Date:** 2018-07-02 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2009-05-25 **Type:** ACTUAL #### Results First Post Date **Date:** 2010-07-30 **Type:** ESTIMATED **Results First Submit Date:** 2010-06-29 **Results First Submit QC Date:** 2010-06-29 #### Start Date **Date:** 2008-11-22 **Status Verified Date:** 2011-02 #### Study First Post Date **Date:** 2008-10-24 **Type:** ESTIMATED **Study First Submit Date:** 2008-10-23 **Study First Submit QC Date:** 2008-10-23 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** GlaxoSmithKline #### Responsible Party **Type:** SPONSOR ### Description Module **Brief Summary:** This Post Marketing Surveillance (PMS) will collect reactogenicity and safety data on the use of human rotavirus vaccine in healthy infants aged from 6 weeks (first dose) to not more than 24 weeks (second dose). ### Conditions Module **Conditions:** - Infections, Rotavirus **Keywords:** - Gastroenteritis ### Design Module #### Enrollment Info **Count:** 522 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Subjects received 2 oral doses of Rotarix vaccine at an interval of at least 4 weeks between doses. The first dose was given from the age of 6 weeks and vaccination with both doses was to be completed by 24 weeks of age. **Intervention Names:** - Biological: Rotarix™ **Label:** Rotarix Group ### Interventions #### Intervention 1 **Arm Group Labels:** - Rotarix Group **Description:** Two oral doses, with at least 4 weeks interval in-between **Name:** Rotarix™ **Type:** BIOLOGICAL ### Outcomes Module #### Primary Outcomes **Description:** Grade 2 fever was defined as axillary temperature \> 38.0 to \<= 39.0 degrees Celsius and grade 3 fever as axillary temperature \> 39.0 degrees Celsius. Grade 2 vomiting was defined as 2 episodes of vomiting per day and grade 3 as 3 or more episodes of vomiting per day. Grade 2 diarrhoea was defined as 4-5 looser than normal stools per day and grade 3 as 6 or more looser than normal stools a day. **Measure:** Number of Subjects With at Least One >= Grade "2" Fever, Vomiting or Diarrhoea **Time Frame:** During the 8-day solicited follow-up period #### Secondary Outcomes **Description:** Solicited symptoms included cough, diarrhoea, irritability, loss of appetite, fever (degrees Celsius) and vomiting. **Measure:** Number of Subjects Reporting Each Type of Solicited General Symptoms **Time Frame:** During the 8-day follow-up period **Description:** Unsolicited AEs cover any AE reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. **Measure:** Number of Subjects Reporting Unsolicited Adverse Events (AEs) **Time Frame:** During the 31-day follow-up period **Description:** SAEs assessed include medical occurrences that result in death, is life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject **Measure:** Number of Subjects Reporting Serious Adverse Events (SAEs) **Time Frame:** Throughout the study period (Day 0 to Month 3 or 4) ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Subjects who the investigator believes that their parents/guardians can and will comply with the requirements of the protocol . * A male or female at least 6 weeks of age at the time of the first vaccination. * Written informed consent obtained from the parent or guardian of the subject. Exclusion Criteria: * History of allergic disease or reactions likely to be exacerbated by any component of the vaccine. * Acute disease at the time of enrolment. * Any history of uncorrected congenital malformation of the gastrointestinal tract that would predispose for intussusception. * Any contraindication as stated in the updated and approved Prescribing Information **Healthy Volunteers:** True **Maximum Age:** 19 Weeks **Minimum Age:** 6 Weeks **Sex:** ALL **Standard Ages:** - CHILD ### Contacts Locations Module #### Locations **Location 1:** **City:** Colombo **Country:** Sri Lanka **Facility:** GSK Investigational Site **Zip:** 03 #### Overall Officials **Official 1:** **Affiliation:** GlaxoSmithKline **Name:** GSK Clinical Trials **Role:** STUDY_DIRECTOR ### References Module #### References **Citation:** Ruberu D et al. Post-marketing surveillance of a live-attenuated human rotavirus vaccine (Rotarix™) in India and Sri Lanka. Abstract presented at the 9th International Congress of Tropical Pediatrics (ICTP). Bangkok, Thailand, 18-20 October 2011. **Citation:** Bravo L, Chitraka A, Liu A, Choudhury J, Kumar K, Berezo L, Cimafranca L, Chatterjee P, Garg P, Siriwardene P, Bernardo R, Mehta S, Balasubramanian S, Karkada N, Htay Han H. Reactogenicity and safety of the human rotavirus vaccine, Rotarix in The Philippines, Sri Lanka, and India: a post-marketing surveillance study. Hum Vaccin Immunother. 2014;10(8):2276-83. doi: 10.4161/hv.29280. **PMID:** 25424932 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000012088 - Term: Reoviridae Infections - ID: D000012327 - Term: RNA Virus Infections - ID: D000014777 - Term: Virus Diseases - ID: D000007239 - Term: Infections ### 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: LOW - As Found: Unknown - ID: M6368 - Name: Communicable Diseases - Relevance: LOW - As Found: Unknown - ID: M8875 - Name: Gastroenteritis - Relevance: LOW - As Found: Unknown - ID: M15220 - Name: Rotavirus Infections - Relevance: HIGH - As Found: Infections, Rotavirus - ID: M17522 - Name: Virus Diseases - Relevance: LOW - As Found: Unknown - ID: M15149 - Name: RNA Virus Infections - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000012400 - Term: Rotavirus Infections ### 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 ## Results Section ### Adverse Events Module #### Event Groups **Group ID:** EG000 **Title:** Rotarix Group **Description:** Subjects received 2 oral doses of Rotarix vaccine at an interval of at least 4 weeks between doses. The first dose was given from the age of 6 weeks and vaccination with both doses was to be completed by 24 weeks of age. **ID:** EG000 **Other Num Affected:** 247 **Other Num at Risk:** 522 **Serious Number Affected:** 1 **Serious Number At Risk:** 522 **Title:** Rotarix Group **Frequency Threshold:** 4.6 #### Other Events **Term:** Cough **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** **Term:** Diarrhoea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** **Term:** Loss of appetite **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** **Term:** Irritability **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** **Term:** Fever **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** **Term:** Vomiting **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** #### Serious Events **Term:** Crying **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 522 ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 522 **Units:** Participants ### Group **ID:** BG000 **Title:** Rotarix Group **Description:** Subjects received 2 oral doses of Rotarix vaccine at an interval of at least 4 weeks between doses. The first dose was given from the age of 6 weeks and vaccination with both doses was to be completed by 24 weeks of age. ### Measure #### Measurement **Group ID:** BG000 **Spread:** 5.62 **Value:** 12.5 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 267 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 255 **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:** weeks ### Measure 2 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Sex: Female, Male **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 ### 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:** 78 **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 71 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 24 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 124 **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:** 152 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 45 **Title:** #### Outcome Measure 3 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 25 **Title:** #### Outcome Measure 4 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** Grade 2 fever was defined as axillary temperature \> 38.0 to \<= 39.0 degrees Celsius and grade 3 fever as axillary temperature \> 39.0 degrees Celsius. Grade 2 vomiting was defined as 2 episodes of vomiting per day and grade 3 as 3 or more episodes of vomiting per day. Grade 2 diarrhoea was defined as 4-5 looser than normal stools per day and grade 3 as 6 or more looser than normal stools a day. **Parameter Type:** NUMBER **Population Description:** Analysis was performed on the Total Vaccinated Cohort, which consisted of all vaccinated subjects with at least one vaccine administration documented. **Reporting Status:** POSTED **Time Frame:** During the 8-day solicited follow-up period **Title:** Number of Subjects With at Least One >= Grade "2" Fever, Vomiting or Diarrhoea **Type:** PRIMARY **Unit of Measure:** subjects ##### Group **Description:** Subjects received 2 oral doses of Rotarix vaccine at an interval of at least 4 weeks between doses. The first dose was given from the age of 6 weeks and vaccination with both doses was to be completed by 24 weeks of age. **ID:** OG000 **Title:** Rotarix Group #### Outcome Measure 2 **Description:** Solicited symptoms included cough, diarrhoea, irritability, loss of appetite, fever (degrees Celsius) and vomiting. **Parameter Type:** NUMBER **Population Description:** Analysis was performed on the Total Vaccinated Cohort, which consisted of all vaccinated subjects with at least one vaccine administration documented. **Reporting Status:** POSTED **Time Frame:** During the 8-day follow-up period **Title:** Number of Subjects Reporting Each Type of Solicited General Symptoms **Type:** SECONDARY **Unit of Measure:** subjects ##### Group **Description:** Subjects received 2 oral doses of Rotarix vaccine at an interval of at least 4 weeks between doses. The first dose was given from the age of 6 weeks and vaccination with both doses was to be completed by 24 weeks of age. **ID:** OG000 **Title:** Rotarix Group #### Outcome Measure 3 **Description:** Unsolicited AEs cover any AE reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. **Parameter Type:** NUMBER **Population Description:** Analysis was performed on the Total Vaccinated Cohort, which consisted of all vaccinated subjects with at least one vaccine administration documented. **Reporting Status:** POSTED **Time Frame:** During the 31-day follow-up period **Title:** Number of Subjects Reporting Unsolicited Adverse Events (AEs) **Type:** SECONDARY **Unit of Measure:** subjects ##### Group **Description:** Subjects received 2 oral doses of Rotarix vaccine at an interval of at least 4 weeks between doses. The first dose was given from the age of 6 weeks and vaccination with both doses was to be completed by 24 weeks of age. **ID:** OG000 **Title:** Rotarix Group #### Outcome Measure 4 **Description:** SAEs assessed include medical occurrences that result in death, is life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject **Parameter Type:** NUMBER **Population Description:** Analysis was performed on the Total Vaccinated Cohort, which consisted of all vaccinated subjects with at least one vaccine administration documented. **Reporting Status:** POSTED **Time Frame:** Throughout the study period (Day 0 to Month 3 or 4) **Title:** Number of Subjects Reporting Serious Adverse Events (SAEs) **Type:** SECONDARY **Unit of Measure:** subjects ##### Group **Description:** Subjects received 2 oral doses of Rotarix vaccine at an interval of at least 4 weeks between doses. The first dose was given from the age of 6 weeks and vaccination with both doses was to be completed by 24 weeks of age. **ID:** OG000 **Title:** Rotarix Group ### Participant Flow Module #### Group **Description:** Subjects received 2 oral doses of Rotarix vaccine at an interval of at least 4 weeks between doses. The first dose was given from the age of 6 weeks and vaccination with both doses was to be completed by 24 weeks of age. **ID:** FG000 **Title:** Rotarix Group #### Period **Title:** Overall Study ##### Withdraw **Type:** Adverse Event ###### Reason **Group ID:** FG000 **Number of Subjects:** 1 ##### Withdraw **Type:** Protocol Violation ###### Reason **Group ID:** FG000 **Number of Subjects:** 14 ##### Withdraw **Type:** Withdrawal by Subject ###### Reason **Group ID:** FG000 **Number of Subjects:** 4 ##### Withdraw **Type:** Lost to Follow-up ###### Reason **Group ID:** FG000 **Number of Subjects:** 5 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 522 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 498 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 24 **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT00896779 **Brief Title:** Lucentis in Advanced Macular Degeneration **Official Title:** Lucentis in Advanced Macular Degeneration #### Organization Study ID Info **ID:** SU-04202009-2338 #### Organization **Class:** OTHER **Full Name:** Stanford University ### Status Module #### Completion Date **Date:** 2013-09 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2015-06-29 **Type:** ESTIMATED **Last Update Submit Date:** 2015-06-01 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2013-09 **Type:** ACTUAL #### Results First Post Date **Date:** 2015-05-27 **Type:** ESTIMATED **Results First Submit Date:** 2015-05-07 **Results First Submit QC Date:** 2015-05-07 #### Start Date **Date:** 2009-10 **Status Verified Date:** 2015-06 #### Study First Post Date **Date:** 2009-05-12 **Type:** ESTIMATED **Study First Submit Date:** 2009-05-08 **Study First Submit QC Date:** 2009-05-11 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** Genentech, Inc. **Class:** OTHER **Name:** California Pacific Medical Center **Class:** OTHER **Name:** Pacific Eye Associates #### Lead Sponsor **Class:** OTHER **Name:** Steven R. Sanislo #### Responsible Party **Investigator Affiliation:** Stanford University **Investigator Full Name:** Steven R. Sanislo **Investigator Title:** MD/PI **Type:** SPONSOR_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** Patients with low vision (visual acuity 20/400 or worse) were excluded from the large Phase III ranibizumab clinical trials. It is not known if treatment with ranibizumab results in improved visual function in such patients.Since ranibizumab has been shown to be the most effective therapy for exudative macular degeneration we propose to treat all patients in this study with monthly ranibizumab intravitreal injections. Patients will be assigned to one of two groups by the flip of a coin. Group #1 for "heads" and Group #2 for "tails". Group #1 patients will be treated for 3 monthly injections of 0.5 mg of ranibizumab and then as needed therapy. Group #2 will be treated with 6 monthly injections of 0.5 mg of ranibizumab and then as needed therapy. **Detailed Description:** The duration of the study is up to 13 months. This includes up to 30 days during which tests will be performed before treatment. Only one eye will be chosen for the study. Patients can receive up to 12 injections of ranibizumab during this study (the first dose\[s\], plus additional doses \[re treatment as often as every 22 days\] if the doctor determines that additional doses are required). In addition to study drug injections. Several eye examinations and procedures will be performed to evaluate response to treatment. These include: visual acuity testing (eye chart), contrast sensitivity testing, reading speed testing, measurement of time to complete typical daily activities, measurement of the thickness of the central retina, measurement of your central visual field. On the screening visit and two more times during the study fluorescein angiography will be performed. The screening tests included the following: * A review of your medical history * A review of any medications you are or have been taking * Eye examinations, including visual acuity testing (reading letters on an eye chart) * Blood pressure measurement Woman of childbearing potential must also take a urine pregnancy test during the screening period to rule out pregnancy. Upon completion of the study at Month 12 and if it were to occur; early termination visit, the following procedures will be performed: vision exam,OCT,microperimetry,FA/Photos,VFQ,reading performance, contrast sensitivity and TIADL. ### Conditions Module **Conditions:** - Macular Degeneration ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### 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:** Group 1: 3 monthly injections of 0.5mg then prn **Intervention Names:** - Drug: ranibizumab **Label:** ranibizumab Group 1 **Type:** OTHER #### Arm Group 2 **Description:** Group 2: 6 monthly injections of 0.5 mg then prn **Intervention Names:** - Drug: ranibizumab **Label:** ranibizumab Group 2 **Type:** OTHER ### Interventions #### Intervention 1 **Arm Group Labels:** - ranibizumab Group 1 - ranibizumab Group 2 **Description:** Group 1 - 0.5mg intravitreal injection every month for 3 months then as needed for 12 months Group 2 -0.5mg intravitreal injection every month for 6 months then as needed for 12 months **Name:** ranibizumab **Other Names:** - Lucentis **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Change in vision from baseline measurement at 12 months. Standard ETDRS chart (80 letters) was used to determine visual acuity with test luminance of 45 cd/m \^2 at 8 feet. Number of correctly read letters were reported. **Measure:** Mean Change in Visual Acuity **Time Frame:** 12 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: Subjects will be eligible if the following criteria are met: * Ability to provide written informed consent and comply with study assessments for the full duration of the study. * Age \> 50 years. * Low vision AMD patients with a VA of 20/400 or worse. * Evidence of active exudation as manifested by subretinal or intraretinal fluid on OCT or fresh appearing subretinal hemorrhage on fundus examination. Exclusion Criteria: Subjects who meet any of the following criteria will be excluded from this study: * Pregnancy (positive pregnancy test) or lactation. * Premenopausal women not using adequate contraception. The following are considered effective means of contraception: surgical sterilization or use of oral contraceptives, barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel, an IUD, or contraceptive hormone implant or patch. * Any other condition that the investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated. * Participation in another simultaneous medical investigation or trial. * Concurrent eye disease in the study eye that could compromise visual acuity (e.g., diabetic retinopathy, advanced glaucoma). **Minimum Age:** 50 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** San Francisco **Country:** United States **Facility:** California Pacific Medical Center **State:** California **Zip:** 94107 **Location 2:** **City:** Stanford **Country:** United States **Facility:** Stanford University School of Medicine **State:** California **Zip:** 94305 #### Overall Officials **Official 1:** **Affiliation:** Stanford University **Name:** Dr. Steven R. Sanislo **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000012162 - Term: Retinal Degeneration - ID: D000012164 - Term: Retinal Diseases - ID: D000005128 - Term: Eye Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC11 - Name: Eye Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M11260 - Name: Macular Degeneration - Relevance: HIGH - As Found: Macular Degeneration - ID: M14997 - Name: Retinal Degeneration - Relevance: LOW - As Found: Unknown - ID: M14999 - Name: Retinal Diseases - Relevance: LOW - As Found: Unknown - ID: M8271 - Name: Eye Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000008268 - Term: Macular Degeneration ### Intervention Browse Module - Ancestors - ID: D000020533 - Term: Angiogenesis Inhibitors - ID: D000043924 - Term: Angiogenesis Modulating Agents - ID: D000006133 - Term: Growth Substances - ID: D000045505 - Term: Physiological Effects of Drugs - 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 ### Intervention Browse Module - Browse Leaves - ID: M472 - Name: Ranibizumab - Relevance: HIGH - As Found: Dysfunction - 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: D000069579 - Term: Ranibizumab ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module #### Event Groups **Group ID:** EG000 **Title:** Ranibizumab Group 1 **Description:** Group 1: 3 monthly injections of 0.5mg then prn **ID:** EG000 **Other Num Affected:** 4 **Other Num at Risk:** 8 **Serious Number At Risk:** 8 **Title:** Ranibizumab Group 1 **Group ID:** EG001 **Title:** Ranibizumab Group 2 **Description:** Group 2: 6 monthly injections of 0.5 mg then prn **ID:** EG001 **Other Num Affected:** 4 **Other Num at Risk:** 12 **Serious Number At Risk:** 12 **Title:** Ranibizumab Group 2 **Frequency Threshold:** 0 #### Other Events **Term:** laceration right leg **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** **Term:** laceration left leg **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** **Term:** Mild pneumonia **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** **Term:** Seasonal allergies **Organ System:** Immune system disorders **Source Vocabulary:** **Term:** Worsening glaucoma - which eye was not specified **Organ System:** Eye disorders **Source Vocabulary:** **Term:** visual disturbance - fellow eye **Organ System:** Eye disorders **Source Vocabulary:** **Term:** development of choroidal neovascularization - fellow eye **Organ System:** Eye disorders **Source Vocabulary:** **Term:** bruised sturnum **Notes:** Due to auto accident **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** **Term:** subconjuctival hemorrhage - treatment eye **Organ System:** Eye disorders **Source Vocabulary:** **Term:** intraretinal hemorrhage - treatment eye **Organ System:** Eye disorders **Source Vocabulary:** **Term:** vitamin D deficiency **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** **Term:** intestinal flu **Organ System:** Gastrointestinal disorders **Source Vocabulary:** **Term:** rash **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** **Term:** pinched nerve **Organ System:** Nervous system disorders **Source Vocabulary:** **Term:** stroke **Organ System:** Nervous system disorders **Source Vocabulary:** **Term:** endophthalmitis - fellow eye **Organ System:** Eye disorders **Source Vocabulary:** **Term:** cold **Organ System:** Immune system disorders **Source Vocabulary:** **Term:** ache left eye - treatment eye **Notes:** after injection procedure **Organ System:** Eye disorders **Source Vocabulary:** **Term:** corneal abrasion - both eyes **Organ System:** Eye disorders **Source Vocabulary:** **Time Frame:** 12 months ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 8 **Group ID:** BG001 **Value:** 12 **Group ID:** BG002 **Value:** 20 **Units:** Participants ### Group **ID:** BG000 **Title:** Ranibizumab Group 1 **Description:** Group 1: 3 monthly injections of 0.5mg then prn ### Group **ID:** BG001 **Title:** Ranibizumab Group 2 **Description:** Group 2: 6 monthly injecions of 0.5mg then prn ### Group **ID:** BG002 **Title:** Total **Description:** Total of all reporting groups ### Measure #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** <=18 years #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** Between 18 and 65 years #### Measurement **Group ID:** BG000 **Value:** 8 #### Measurement **Group ID:** BG001 **Value:** 12 #### Measurement **Group ID:** BG002 **Value:** 20 **Category Title:** >=65 years **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Lower Limit:** 68 **Upper Limit:** 94 **Value:** 81 #### Measurement **Group ID:** BG001 **Lower Limit:** 71 **Upper Limit:** 97 **Value:** 84 #### Measurement **Group ID:** BG002 **Lower Limit:** 68 **Upper Limit:** 97 **Value:** 83 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 3 #### Measurement **Group ID:** BG001 **Value:** 8 #### Measurement **Group ID:** BG002 **Value:** 11 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 5 #### Measurement **Group ID:** BG001 **Value:** 4 #### Measurement **Group ID:** BG002 **Value:** 9 **Category Title:** Male **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 8 #### Measurement **Group ID:** BG001 **Value:** 12 #### Measurement **Group ID:** BG002 **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 **Dispersion Type:** FULL_RANGE **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 ### Limitations and Caveats **Description:** Limitations include small number of subjects analyzed and no control group that were untreated. ### Point of Contact **Email:** [email protected] **Organization:** Stanford University **Phone:** 650-723-6995 **Title:** Steven Sanislo, MD ## Results Section - Outcome Measures Module ### Outcome Measure 1 #### Analysis **CI Lower Limit:** **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.02 **P-Value Comment:** **Parameter Type:** **Parameter Value:** **Statistical Comment:** **Statistical Method:** t-test, 2 sided **Tested Non-Inferiority:** False #### Analysis **CI Lower Limit:** **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.06 **P-Value Comment:** **Parameter Type:** **Parameter Value:** **Statistical Comment:** **Statistical Method:** t-test, 2 sided **Tested Non-Inferiority:** False ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 14.2 - **Upper Limit:** - **Value:** 15.0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 8.6 - **Upper Limit:** - **Value:** 5.6 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** Change in vision from baseline measurement at 12 months. Standard ETDRS chart (80 letters) was used to determine visual acuity with test luminance of 45 cd/m \^2 at 8 feet. Number of correctly read letters were reported. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Reporting Status:** POSTED **Time Frame:** 12 months **Title:** Mean Change in Visual Acuity **Type:** PRIMARY **Unit of Measure:** letters ##### Group **Description:** Group 1: 3 monthly injections of raibizumab 0.5mg then injections as needed for 12 months **ID:** OG000 **Title:** Ranibizumab Group 1 ##### Group **Description:** Group 2: 6 monthly injections of raibizumab 0.5mg then injections as needed for 12 months **ID:** OG001 **Title:** Ranibizumab Group 2 ### Participant Flow Module #### Group **Description:** Group 1: 3 monthly injections of raibizumab 0.5mg then injections as needed for 12 months **ID:** FG000 **Title:** Ranibizumab Group 1 #### Group **Description:** Group 1: 6 monthly injections of raibizumab 0.5mg then injections as needed for 12 months **ID:** FG001 **Title:** Ranibizumab Group 2 #### Period **Title:** Overall Study ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 8 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 12 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 8 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 11 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 1 **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT00359879 **Brief Title:** Comparison of Exenatide Taken Before Lunch and Dinner With Before Breakfast and Dinner in Patients With Type 2 Diabetes **Official Title:** Safety and Efficacy of Exenatide Taken Before Lunch and Before Dinner Compared With Before Breakfast and Before Dinner in Patients With Type 2 Diabetes Using Oral Antidiabetic Therapy #### Organization Study ID Info **ID:** H8O-CR-GWBH #### Organization **Class:** INDUSTRY **Full Name:** AstraZeneca ### Status Module #### Completion Date **Date:** 2007-07 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2015-02-23 **Type:** ESTIMATED **Last Update Submit Date:** 2015-02-20 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2007-07 **Type:** ACTUAL #### Start Date **Date:** 2006-09 **Status Verified Date:** 2015-01 #### Study First Post Date **Date:** 2006-08-03 **Type:** ESTIMATED **Study First Submit Date:** 2006-08-01 **Study First Submit QC Date:** 2006-08-01 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** Eli Lilly and Company #### Lead Sponsor **Class:** INDUSTRY **Name:** AstraZeneca #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** This trial is designed to compare the effects of twice-daily (before lunch and before dinner) exenatide plus oral antidiabetic (OAD) agents and twice-daily (before breakfast and before dinner) exenatide plus OAD with respect to glycemic control (HbA1c) in patients with type 2 diabetes. ### Conditions Module **Conditions:** - Type 2 Diabetes **Keywords:** - diabetes - exenatide - Lilly - Amylin ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 377 **Type:** ACTUAL **Phases:** - PHASE3 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Intervention Names:** - Drug: exenatide **Label:** 1 - exenatide before breakfast and dinner **Type:** EXPERIMENTAL #### Arm Group 2 **Intervention Names:** - Drug: exenatide **Label:** 2 - exenatide before lunch and dinner **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - 2 - exenatide before lunch and dinner **Description:** subcutaneous injection, 5mcg or 10mcg, twice a day (before lunch and dinner) **Name:** exenatide **Other Names:** - Byetta **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - 1 - exenatide before breakfast and dinner **Description:** subcutaneous injection, 5mcg or 10mcg, twice a day (before breakfast and dinner) **Name:** exenatide **Other Names:** - Byetta **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Evaluate the change in glycemic control as measured by HbA1c from Baseline to Week 12 **Measure:** Change in HbA1c (glycosylated hemoglobin) from Baseline to Week 12 **Time Frame:** Baseline, Week 12 #### Secondary Outcomes **Description:** Change in body weight (kg) from Baseline to Week 12, and if measured, at each visit in between (Weeks 4 and 8) **Measure:** Change in body weight from Baseline to Week 12, and if measured, at each visit **Time Frame:** Baseline, Weeks 4, 8, 12 **Description:** Change in FGS from Baseline to Week 12, and if measured, at each visit in between (Weeks 4 and 8) **Measure:** Change in fasting serum glucose (FGS) from Baseline to Week 12, and if measured, at each visit **Time Frame:** Baseline, Weeks 4, 8, 12 **Description:** Changes in glucose measured at different times throughout the day derived from 7-point SMBG profile (glucose measurements before and 2 hours after the start of the morning, midday, and evening meals, and at bedtime) **Measure:** Changes in self-monitored blood glucose (SMBG) profile from Baseline through Week 12 **Time Frame:** Baseline, Weeks 4, 8, 12 ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Diagnosed with type 2 diabetes. * Have been treated with one of the following treatment regimens for at least three months prior to screening: \*metformin alone; \*sulfonylurea (SU) alone; \*thiazolidinedione (TZD) alone; \*a combination of metformin and SU; \*a combination of metformin and TZD. * HbA1c between 7.1% and 10.0%, inclusive. * Body Mass Index (BMI) \> 25 kg/m\^2 and \< 45 kg/m\^2 Exclusion Criteria: * Have participated in an interventional, medical, surgical, or pharmaceutical study (a study in which an experimental drug, medical, or surgical treatment was given) within 30 days prior to screening. * Have characteristics contraindicating metformin, SU, or TZD use. * Are receiving chronic (lasting longer than 2 weeks) systemic glucocorticoid therapy (excluding topical and inhaled preparations) or have received such therapy within 2 weeks immediately prior to screening. * Have used any prescription drug to promote weight loss within 3 months prior to screening. * Are currently treated (for greater than 2 consecutive weeks) with any of the following excluded medications: \*insulin within 3 months prior to screening; \*alpha-glucosidase inhibitors within 3 months prior to screening; \*meglitinides within 3 months prior to screening; \*drugs that directly affect gastrointestinal motility **Maximum Age:** 75 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Campinas **Country:** Brazil **Facility:** Research Site **Location 2:** **City:** Curitiba **Country:** Brazil **Facility:** Research Site **Location 3:** **City:** Fortaleza **Country:** Brazil **Facility:** Research Site **Location 4:** **City:** Goiania **Country:** Brazil **Facility:** Research Site **Location 5:** **City:** Porto Alegre **Country:** Brazil **Facility:** Research Site **Location 6:** **City:** Rio de Janeiro **Country:** Brazil **Facility:** Research Site **Location 7:** **City:** Salvador **Country:** Brazil **Facility:** Research Site **Location 8:** **City:** Sao Jose Do Rio Preto **Country:** Brazil **Facility:** Research Site **Location 9:** **City:** Sao Paulo **Country:** Brazil **Facility:** Research Site **Location 10:** **City:** Guadalajara **Country:** Mexico **Facility:** Research Site **State:** Jalisco **Location 11:** **City:** Monterrey **Country:** Mexico **Facility:** Research Site **State:** Nuevo Leon **Location 12:** **City:** Merida **Country:** Mexico **Facility:** Research Site **State:** Yucatan **Location 13:** **City:** Aguascalientes **Country:** Mexico **Facility:** Research Site **Location 14:** **City:** Mexico City **Country:** Mexico **Facility:** Research Site **Location 15:** **City:** San Luis Potosi **Country:** Mexico **Facility:** Research Site #### Overall Officials **Official 1:** **Affiliation:** Eli Lilly and Company **Name:** James Malone, MD **Role:** STUDY_DIRECTOR ### References Module #### References **Citation:** Forti A, Garcia EG, Yu MB, Jimenez MC, Brodows RG, Oliveira JH. Efficacy and safety of exenatide administered before the two largest daily meals of Latin American patients with type 2 diabetes. Curr Med Res Opin. 2008 Sep;24(9):2437-47. doi: 10.1185/03007990802282398. Epub 2008 Jul 24. **PMID:** 18662495 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000044882 - Term: Glucose Metabolism Disorders - ID: D000008659 - Term: Metabolic Diseases - ID: D000004700 - Term: Endocrine System Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC18 - Name: Nutritional and Metabolic Diseases - Abbrev: BC19 - Name: Gland and Hormone Related Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M7115 - Name: Diabetes Mellitus - Relevance: HIGH - As Found: Diabetes - ID: M7119 - Name: Diabetes Mellitus, Type 2 - Relevance: HIGH - As Found: Type 2 Diabetes - ID: M11639 - Name: Metabolic Diseases - Relevance: LOW - As Found: Unknown - ID: M25403 - Name: Glucose Metabolism Disorders - Relevance: LOW - As Found: Unknown - ID: M7862 - Name: Endocrine System Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000003920 - Term: Diabetes Mellitus - ID: D000003924 - Term: Diabetes Mellitus, Type 2 ### Intervention Browse Module - Ancestors - ID: D000097789 - Term: Glucagon-Like Peptide-1 Receptor Agonists - ID: D000007004 - Term: Hypoglycemic Agents - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000019440 - Term: Anti-Obesity Agents - 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: AnObAg - Name: Anti-Obesity Agents - Abbrev: Gast - Name: Gastrointestinal Agents ### Intervention Browse Module - Browse Leaves - ID: M10054 - Name: Hypoglycemic Agents - Relevance: LOW - As Found: Unknown - ID: M1726 - Name: Exenatide - Relevance: HIGH - As Found: 4 hours - ID: M29005 - Name: Islet Amyloid Polypeptide - Relevance: LOW - As Found: Unknown - ID: M9043 - Name: Glucagon - Relevance: LOW - As Found: Unknown - ID: M3401 - Name: Glucagon-Like Peptide-1 Receptor Agonists - Relevance: LOW - As Found: Unknown - ID: M26997 - Name: Glucagon-Like Peptide 1 - Relevance: LOW - As Found: Unknown - ID: M21396 - Name: Anti-Obesity 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: D000077270 - Term: Exenatide ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05198479 **Acronym:** SG-AAA-II-01 **Brief Title:** Phase II 177Lu-DOTATATE Study in Metastatic NPC With a Safety Run-in **Official Title:** A Biomarker Enrichment, Phase II Study of 177Lu-DOTATATE in Metastatic Nasopharyngeal Cancer With a Safety Run-in #### Organization Study ID Info **ID:** SG-AAA-II-01 #### Organization **Class:** OTHER **Full Name:** National Cancer Centre, Singapore ### Status Module #### Completion Date **Date:** 2025-09-30 **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:** 2024-12-31 **Type:** ESTIMATED #### Start Date **Date:** 2023-05-05 **Type:** ACTUAL **Status Verified Date:** 2023-10 #### Study First Post Date **Date:** 2022-01-20 **Type:** ACTUAL **Study First Submit Date:** 2022-01-06 **Study First Submit QC Date:** 2022-01-06 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** Novartis **Class:** INDUSTRY **Name:** Advanced Accelerator Applications #### Lead Sponsor **Class:** OTHER **Name:** National Cancer Centre, Singapore #### 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 the first phase II study of 177Lu-DOTA0-Tyr3-Octreotate in metastatic NPC. Patients whom have failed 2 or more lines of therapy or exhausted standard therapy and are avid on 68Ga-DOTATATE imaging will be eligible to receive up to 4 cycles of 177Lu-DOTA0-Tyr3-Octreotate. The primary outcome will be progression free survival at 6 months. **Detailed Description:** This would be an open label, single arm, single centre, phase II study designed to evaluate the efficacy of 177Lu-DOTA0-Tyr3-Octreotate in Metastatic NPC. Patients will first need to go for a 68Ga-DOTATATE scan to determine if they are suitable for 177Lu-DOTA0-Tyr3-Octreotate therapy. A'Hern single stage phase II design (A'Hern, 2001) will be used for conducting the trial. The null hypothesis that the true PFS rate at 6 months is 10% will be tested against the alternate hypothesis of 25%. A total number of 25 patients will be recruited. If there are 5 or more patients who are alive and progression free among these 25 patients at 6 months, we reject the null hypothesis and claim that the treatment is promising. The design controls the type I error rate at 9.8% and yields a power of 78.6% when the true PFS rate at 6 months is 25%. The first 5 patients will receive 180mCi of 177Lu-DOTA0-Tyr3-Octreotate for the first cycle followed by 200mCi for the remaining 3 cycles if there are no \> Grade 2 toxicities after the first cycle. If there are \>G2 toxicities, the remaining cycles will proceed at 180mCi. A safety review will be done after the first 5 patients. If there are no significant toxicities, the remaining patients will receive 200mCi for 4 cycles. If there are significant toxicities in patients receiving 200mCi for the 2nd to 4th cycle, the remaining patients will receive 180mCi for 4 cycles. If there are significant toxicities in patients receiving 180mCi for the 2nd to 4th cycle, the remaining patients will receive 160mCi for 4 cycles. Dosimetry scans will be done after each cycle of 177Lu-DOTA0-Tyr3-Octreotate at 1h and 96h. Safety and tolerability of 177LuDOTA0-Tyr3-Octreotate will be assessed for the duration of study treatment. FDG PET/CT scan and 68Ga-DOTATATE scan will be performed at baseline and after cycle 1 (week 4) and cycle 4 (week 28). CT scans will be done at week 12, 24, then 3-monthly starting from week 40. 177Lu-DOTA0-Tyr3-Octreotate treatment will be continued until progression of disease, unacceptable toxicity, or another discontinuation criterion is met. In the case of toxicity, dose adjustment is permitted. A treatment cycle is eight weeks (56 days) and will be repeated without therapy interruption for 4 cycles unless there is dose limiting toxicities. ### Conditions Module **Conditions:** - Metastatic Nasopharyngeal Cancer **Keywords:** - Peptide Receptor Radionuclide therapy (PRRT) - 177Lu-DOTA0-Tyr3-Octreotate - Radionuclide therapy - Metastatic Nasopharyngeal Carcinoma - Theragnostics ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 25 **Type:** ESTIMATED **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Treatment with 177Lu-DOTATATE consist of a cumulative dose of 23.68 - 29.6 GBq (640 - 800 mCi) 177Lu-DOTA0-Tyr3-Octreotate; Four administrations of 5.92 - 7.4 GBq (160 - 200 mCi) 177Lu-DOTA0-Tyr3-Octreotate; Concomitant amino acids will be given with each administration for kidney protection; 177Lu-DOTA0-Tyr3-Octreotate will be administered at 8±1-week intervals, which can be extended up to 16 weeks to accommodate resolving acute toxicity. **Intervention Names:** - Radiation: 77 Lu-DOTA0-Tyr3-Octreotate **Label:** Arm 177 Lu-DOTA0-Tyr3-Octreotate **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Arm 177 Lu-DOTA0-Tyr3-Octreotate **Description:** Treatment will consist of a cumulative dose of 23.68 - 29.6 GBq (640 - 800 mCi) 177Lu-DOTA0 -Tyr3-Octreotate; Four administrations of 5.92 - 7.4 GBq (160 - 200 mCi) 177Lu-DOTA0-Tyr3-Octreotate; Concomitant amino acids will be given with each administration for kidney protection; 177Lu-DOTA0-Tyr3-Octreotate will be administered at 8±1-week intervals, which can be extended up to 16 weeks to accommodate resolving acute toxicity. **Name:** 77 Lu-DOTA0-Tyr3-Octreotate **Type:** RADIATION ### Outcomes Module #### Primary Outcomes **Description:** PFS is defined as the time from the date of initiating study treatment to the date of documented disease progression as determined by RECIST Criteria, Version 1.1 or death from any cause. Point estimates for median PFS and PFS rate at 6 month, with corresponding 95% Confidence Intervals (CIs), will be estimated using the Kaplan-Meier method. **Measure:** Progression Free Survival (PFS). **Time Frame:** Within 76 weeks of start of study treatment. #### Secondary Outcomes **Description:** ORR is defined as the percentage of patients who had a partial response or complete response according to RECIST 1.1. The ORR and 95% CI will be calculated. **Measure:** Objective Response Rate (ORR). **Time Frame:** Within 76 weeks of start of study treatment. **Description:** TTP is defined as the time (number of days) from start of study treatment to objective tumour progression. **Measure:** Time to Tumour Progression (TTP) **Time Frame:** Within 76 weeks of start of study treatment. **Description:** OS is defined as the time from the date of start of study treatment to the date of death due to any cause or the date of last contact (censored observation) at the date of data cut-off. **Measure:** Overall Survival (OS). **Time Frame:** Within 76 weeks of start of study treatment. ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * a histologically confirmed diagnosis of NPC * metastatic NPC that has failed two or more lines of therapy or exhausted standard therapy * an Eastern Cooperative Oncology Group performance status of 0-2 * age 21-75 years, a life expectancy of more than 3 months * no prior use of radionuclide therapy * no prior radiotherapy to more than 25% of bone marrow * less than 50% of bone marrow involved on 68Ga-DOTATATE scan * Krenning score ≥ 3 and at least 75% concordance between 68Ga-DOTATATE scan and 18F-FDG PET scan * at least 1 bidimensionally measurable (2 cm) site of disease. * A wash-out period of at least 3 weeks from the last dose of prior chemotherapy is required before the administration of the first dose of 177Lu-DOTATATE. * adequate hematologic, renal, and liver function using standard laboratory measurements * no history of other malignancy, except treated basal cell and squamous cell skin carcinomas Exclusion Criteria: * Serum creatinine \>120 μmol/L or 1.2 mg/dL, or a measured creatinine clearance (or measured glomerular filtration rate (GFR) using plasma clearance methods, not gamma camera-based) of \<50 mL/min. * Hb concentration \<5.0 mmol/L (\<8.0 g/dL); WBC \<3x10\^9/L (3000/mm3); platelets \<75x10\^9/L (75x10\^3/mm3). * Total bilirubin \>3 x ULN. * Serum albumin \<3.0 g/dL unless prothrombin time is within the normal range. * Pregnancy (see protocol Appendix 6). * For female patients of childbearing potential (defined as \< 2 years after last menstruation and not surgically sterile) and male patients, who are not surgically sterile or with female partners of childbearing potential: absence of effective, non-hormonal means of contraception (intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal gel) as defined in Appendix 6. * Peptide receptor radionuclide therapy (PRRT) at any time prior to enrolment in the study. * Targeted surgery, radiotherapy (external beam), chemotherapy, embolization, interferons, mTOR-inhibitors or other investigational therapy within 3 weeks prior to enrolment in the study. * Known brain metastases, unless these metastases have been treated and stabilized for at least 24 weeks, prior to enrolment in the study. Patients with a history of brain metastases should have a head CT/MRI to document stable disease prior to enrolment in the study. * Uncontrolled congestive heart failure (NYHA II, III, IV). * Uncontrolled diabetes mellitus as defined by a fasting blood glucose \>2 ULN. * Any patient receiving treatment with short or long acting somatostatin analogs. * Patients with any other significant medical, psychiatric, or surgical condition, currently uncontrolled by treatment, which may interfere with completion of the study. * Urinary incontinence. * Other known co-existing malignancies except non-melanoma skin cancer and carcinoma in situ of the uterine cervix, unless definitively treated and proven no evidence of recurrence for 5 years. * Patients who have not provided a signed an informed consent form to participate in the study, obtained prior to the start of any protocol related activities. * Patients who are unable to comply with relevant contact precautions post Lutetium therapy. * Patients with a synchronous local nasopharyngeal recurrence, with prior high-dose irradiation to the primary tumour. * Patients with active Hepatitis B (HBsAg positive) or Hepatitis C (HCV Ab positive) infection will be excluded. * Patients with known history of Human Immunodeficiency Virus (HIV) will be excluded. **Maximum Age:** 75 Years **Minimum Age:** 21 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Daniel Tan, BSc, MBBS, PhD **Phone:** +65 6436 8000 **Role:** CONTACT #### Locations **Location 1:** **City:** Singapore **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Daniel Tan, BSc, MBBS, PhD - **Phone:** +65 6436 8000 - **Role:** CONTACT ***Contact 2:*** - **Email:** [email protected] - **Name:** Wen-Long Nei - **Phone:** +65 6436 8000 - **Role:** CONTACT ***Contact 3:*** - **Name:** Daniel Tan, BSc, MBBS, PhD - **Role:** PRINCIPAL_INVESTIGATOR ***Contact 4:*** - **Name:** Wen-Long Nei, MBBS, FRCR - **Role:** PRINCIPAL_INVESTIGATOR **Country:** Singapore **Facility:** National Cancer Centre Singapore **Status:** RECRUITING **Location 2:** **City:** Singapore **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Kelvin Loke, MBBS, MRCP(UK), FAMS - **Phone:** +65 6326 5104 - **Role:** CONTACT ***Contact 2:*** - **Name:** Kelvin Loke, MBBS, MRCP(UK), FAMS - **Role:** PRINCIPAL_INVESTIGATOR **Country:** Singapore **Facility:** Singapore General Hospital **Status:** RECRUITING #### Overall Officials **Official 1:** **Affiliation:** National Cancer Centre, Singapore **Name:** Daniel Tan, BSc, MBBS, PhD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** UNDECIDED ## Derived Section ### Condition Browse Module - Ancestors - ID: D000010610 - Term: Pharyngeal Neoplasms - ID: D000010039 - Term: Otorhinolaryngologic Neoplasms - ID: D000006258 - Term: Head and Neck Neoplasms - ID: D000009371 - Term: Neoplasms by Site - ID: D000009369 - Term: Neoplasms - ID: D000009302 - Term: Nasopharyngeal Diseases - ID: D000010608 - Term: Pharyngeal Diseases - ID: D000009057 - Term: Stomatognathic Diseases - ID: D000010038 - Term: Otorhinolaryngologic Diseases - ID: D000002277 - Term: Carcinoma - ID: D000009375 - Term: Neoplasms, Glandular and Epithelial - ID: D000009370 - Term: Neoplasms by Histologic Type ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: All - Name: All Conditions - Abbrev: BC07 - Name: Mouth and Tooth Diseases - Abbrev: BC09 - Name: Ear, Nose, and Throat Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M5534 - Name: Carcinoma - Relevance: LOW - As Found: Unknown - ID: M1730 - Name: Nasopharyngeal Carcinoma - Relevance: HIGH - As Found: Nasopharyngeal Cancer - ID: M12254 - Name: Nasopharyngeal Neoplasms - Relevance: HIGH - As Found: Nasopharyngeal Cancer - ID: M13517 - Name: Pharyngeal Neoplasms - Relevance: LOW - As Found: Unknown - ID: M12962 - Name: Otorhinolaryngologic Neoplasms - Relevance: LOW - As Found: Unknown - ID: M9348 - Name: Head and Neck Neoplasms - Relevance: LOW - As Found: Unknown - ID: M12253 - Name: Nasopharyngeal Diseases - Relevance: LOW - As Found: Unknown - ID: M13515 - Name: Pharyngeal Diseases - Relevance: LOW - As Found: Unknown - ID: M12017 - Name: Stomatognathic Diseases - Relevance: LOW - As Found: Unknown - ID: M12961 - Name: Otorhinolaryngologic Diseases - 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: T4047 - Name: Nasopharyngeal Carcinoma - Relevance: HIGH - As Found: Nasopharyngeal Cancer ### Condition Browse Module - Meshes - ID: D000009303 - Term: Nasopharyngeal Neoplasms - ID: D000077274 - Term: Nasopharyngeal Carcinoma ### Intervention Browse Module - Browse Branches - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M108723 - Name: Lutetium Lu 177 dotatate - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT01689779 **Brief Title:** High Dose Preoperative Cholecalciferol Supplementation and Perioperative Vitamin D Status **Official Title:** Effect of High-dose Cholecalciferol Supplementation on Perioperative Vitamin D Status in Colorectal Surgery Patients #### Organization Study ID Info **ID:** 2012P001852 #### Organization **Class:** OTHER **Full Name:** Massachusetts General Hospital ### Status Module #### Completion Date **Date:** 2015-05 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2017-09-28 **Type:** ACTUAL **Last Update Submit Date:** 2017-08-29 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2015-05 **Type:** ACTUAL #### Results First Post Date **Date:** 2017-09-28 **Type:** ACTUAL **Results First Submit Date:** 2017-03-28 **Results First Submit QC Date:** 2017-08-29 #### Start Date **Date:** 2013-01 **Status Verified Date:** 2017-08 #### Study First Post Date **Date:** 2012-09-21 **Type:** ESTIMATED **Study First Submit Date:** 2012-09-04 **Study First Submit QC Date:** 2012-09-17 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** Bio-Tech Pharmacal, Inc. #### Lead Sponsor **Class:** OTHER **Name:** Massachusetts General Hospital #### Responsible Party **Investigator Affiliation:** Massachusetts General Hospital **Investigator Full Name:** Sadeq A. Quraishi **Investigator Title:** Assistant Professor of Anaesthesia, Harvard Medical School **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** A growing body of evidence suggests that robust postoperative immune function is associated with a lower risk of surgical site infections (SSIs). At the same time, vitamin D is increasingly recognized as a key regulator of the innate and adaptive immune systems. The investigators elected to conduct the current study in patients who will undergo colorectal surgery since these patients are historically at higher risk of developing SSIs and therefore would be ideal for future investigations. **Detailed Description:** While vitamin D insufficiency \[25(OH)D \<30 ng/mL\] is common in the general population, hypovitaminosis D may affect 40-80% of patients in the perioperative setting. Recent evidence also suggests that surgical stress may be associated with a 40% reduction in circulating 25(OH)D levels when compared to preoperative values. Moreover, the derangement in perioperative 25(OH)D levels may be sustained for up to 3 months after surgery. This finding has potential implications regarding modifiable risk factors for surgical site infections (SSIs), which account for nearly 40% of all nosocomial infections. On aggregate, SSIs result in 3.7 million extra hospital days per annum and an added burden of $1.6 billion in annual healthcare costs. A growing body of evidence suggests that robust postoperative immune function is associated with a lower risk of SSIs. At the same time, vitamin D is increasingly recognized as a key regulator of the innate and adaptive immune systems. Yet, optimization of perioperative vitamin D status remains grossly understudied. Although our overarching aim is to study the impact of vitamin D status on SSIs, the focus of the current investigation is to determine whether the administration of a "bolus" oral dose of cholecalciferol (vitamin D3) in the preoperative setting alters vitamin D status in the perioperative setting (compared to a placebo). The investigators elected to conduct the current study in patients who will undergo colorectal surgery since these patients are historically at higher risk of developing SSIs and therefore would be ideal for future investigations. ### Conditions Module **Conditions:** - Hypovitaminosis D **Keywords:** - vitamin D - surgery - acute stress ### 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:** 60 **Type:** ACTUAL **Phases:** - PHASE3 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** A maximum of 40 patients will receive a one-time oral dose of 100,000 IU cholecalciferol 3-7 days before their scheduled elective surgery. **Intervention Names:** - Drug: 100,000 IU cholecalciferol **Label:** Cholecalciferol **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** A maximum of 40 patients will receive a one-time oral sugar pill 3-7 days before their scheduled elective surgery. **Intervention Names:** - Drug: Placebo **Label:** Placebo **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Cholecalciferol **Description:** active drug **Name:** 100,000 IU cholecalciferol **Other Names:** - vitamin D3 **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Placebo **Description:** comparator drug **Name:** Placebo **Other Names:** - sugar pill **Type:** DRUG ### Outcomes Module #### Other Outcomes **Description:** The goal is to determine whether pre-operative supplementation with 100,000 IU cholecalciferol (vs. placebo) alters the natural course of changes in vitamin D status within 10-18 days after surgery. To assess vitamin D status, we will measure: 1) 25(OH)D and 2) LL-37. **Measure:** Percent (%) Change in Pre-surgical 25(OH)D 2 Weeks After Surgery **Time Frame:** Patients will be followed between the day of surgery and an average duration of 14 days after surgery **Description:** The goal is to determine whether pre-operative supplementation with 100,000 IU cholecalciferol (vs. placebo) alters the natural course of changes in vitamin D status within 10-18 days after surgery. To assess vitamin D status, we will measure: 1) 25(OH)D and 2) LL-37. **Measure:** Percent (%) Change in Pre-surgical LL-37 2 Weeks After Surgery **Time Frame:** Patients will be followed between the day of surgery and an average duration of 14 days after surgery #### Primary Outcomes **Description:** 3-7 days before surgery, patients will receive 100,000 IU of cholecalciferol (vs. placebo) during their pre-op assessment. They will also have their baseline vitamin D status measured during this initial visit. The main study outcome is to determine if 100,000 IU cholecalciferol can be given preoperatively to safely boost vitamin D status. To assess vitamin D status, we will measure: 1) 25(OH)D and 2) LL37 **Measure:** Percent (%) Change in 25(OH)D 5 Days Following Supplementation With 100,000 IU Cholecalciferol **Time Frame:** Patients will be followed between the initial preoperative evaluation day and an average duration of 5 days **Description:** 3-7 days before surgery, patients will receive 100,000 IU of cholecalciferol (vs. placebo) during their pre-op assessment. They will also have their baseline vitamin D status measured during this initial visit. The main study outcome is to determine if 100,000 IU cholecalciferol can be given preoperatively to safely boost vitamin D status. To assess vitamin D status, we will measure: 1) 25(OH)D and 2) LL37 **Measure:** Percent (%) Change in LL-37 5 Days Following Supplementation With 100,000 IU Cholecalciferol **Time Frame:** Patients will be followed between the initial preoperative evaluation day and an average duration of 5 days #### Secondary Outcomes **Description:** The goal is to determine whether pre-operative supplementation with 100,000 IU cholecalciferol (vs. placebo) alters the natural course of short-term changes in vitamin D status following surgery. To assess vitamin D status, we will measure: 1) 25(OH)D and 2) LL37. **Measure:** Percent (%) Change in Pre-surgical 25(OH)D Within 24 Hours of Surgery **Time Frame:** Patients will be followed between the day of surgery and 1 day after surgery **Description:** The goal is to determine whether pre-operative supplementation with 100,000 IU cholecalciferol (vs. placebo) alters the natural course of short-term changes in vitamin D status following surgery. To assess vitamin D status, we will measure: 1) 25(OH)D and 2) LL37. **Measure:** Percent (%) Change in Pre-surgical LL-37 Within 24 Hours of Surgery **Time Frame:** Patients will be followed between the day of surgery and 1 day after surgery ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Men and women; * 18 years or older; * Scheduled for elective (non-emergent) colorectal surgery; * Cleared for anesthesia; and * Expected to stay overnight following surgery Exclusion Criteria: * Scheduled for a purely laparoscopic procedure; * Diagnosis of a terminal illness and/or in hospice care; * Inability to sign informed consent; * Inability to comply with study protocol; * Intending to start vitamin D supplementation within 30 days of surgery; * Intending to leave the Boston area during the follow-up period; * History of renal stones or hypercalcemia; * Medical conditions that can cause hypercalcemia (e.g. metastatic cancer, sarcoidosis, myeloma primary hyperparathyroidism) * History of hypercalcemia * History of severe anemia (Hematocrit \<25%) * Medications that affect vitamin D metabolism (e.g. anti-epileptics, tuberculosis medication); and * Already enrolled or planning to enroll in a research study that would conflict with full participation in the current study or confound the observation or interpretation of the study findings **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Boston **Country:** United States **Facility:** Massachusetts General Hospital **State:** Massachusetts **Zip:** 02114 #### Overall Officials **Official 1:** **Affiliation:** Massachusetts General Hospital **Name:** Sadeq A Quraishi, MD, MHA **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000003677 - Term: Deficiency Diseases - ID: D000044342 - Term: Malnutrition - ID: D000009748 - Term: Nutrition Disorders - ID: D000001851 - Term: Bone Diseases, Metabolic - ID: D000001847 - Term: Bone Diseases - ID: D000009140 - Term: Musculoskeletal Diseases - ID: D000008659 - Term: Metabolic Diseases - ID: D000002128 - Term: Calcium Metabolism Disorders ### Condition Browse Module - Browse Branches - Abbrev: BC18 - Name: Nutritional and Metabolic Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC05 - Name: Musculoskeletal Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M17551 - Name: Vitamin D Deficiency - Relevance: HIGH - As Found: Hypovitaminosis D - ID: M15108 - Name: Rickets - Relevance: HIGH - As Found: Hypovitaminosis D - ID: M4660 - Name: Avitaminosis - Relevance: HIGH - As Found: Hypovitaminosis - ID: M6879 - Name: Deficiency Diseases - Relevance: LOW - As Found: Unknown - ID: M25306 - Name: Malnutrition - Relevance: LOW - As Found: Unknown - ID: M12684 - Name: Nutrition Disorders - Relevance: LOW - As Found: Unknown - ID: M5126 - Name: Bone Diseases - Relevance: LOW - As Found: Unknown - ID: M5130 - Name: Bone Diseases, Metabolic - Relevance: LOW - As Found: Unknown - ID: M12097 - Name: Musculoskeletal Diseases - Relevance: LOW - As Found: Unknown - ID: M11639 - Name: Metabolic Diseases - Relevance: LOW - As Found: Unknown - ID: M5391 - Name: Calcium Metabolism Disorders - Relevance: LOW - As Found: Unknown - ID: T170 - Name: Acute Graft Versus Host Disease - Relevance: LOW - As Found: Unknown - ID: T5019 - Name: Rickets - Relevance: HIGH - As Found: Hypovitaminosis D ### Condition Browse Module - Meshes - ID: D000012279 - Term: Rickets - ID: D000001361 - Term: Avitaminosis - ID: D000014808 - Term: Vitamin D Deficiency ### Intervention Browse Module - Ancestors - ID: D000014815 - Term: Vitamins - ID: D000018977 - Term: Micronutrients - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000050071 - Term: Bone Density Conservation Agents - ID: D000077264 - Term: Calcium-Regulating Hormones and Agents ### Intervention Browse Module - Browse Branches - Abbrev: BDCA - Name: Bone Density Conservation Agents - Abbrev: Micro - Name: Micronutrients - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Vi - Name: Vitamins ### Intervention Browse Module - Browse Leaves - ID: M17550 - Name: Vitamin D - Relevance: HIGH - As Found: Ultrasound - ID: M6003 - Name: Cholecalciferol - Relevance: HIGH - As Found: 2.5 - 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: M9789 - Name: Hormones - 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: T442 - Name: Cholecalciferol - Relevance: HIGH - As Found: 2.5 - ID: T479 - Name: Vitamin D3 - Relevance: HIGH - As Found: Unacceptable - ID: T440 - Name: Calciferol - Relevance: HIGH - As Found: 2.5 ### Intervention Browse Module - Meshes - ID: D000014807 - Term: Vitamin D - ID: D000002762 - Term: Cholecalciferol ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module #### Event Groups **Group ID:** EG000 **Title:** Cholecalciferol **Deaths Num Affected:** 1 **Deaths Num At Risk:** 28 **Description:** 40 patients will receive 100,000 IU cholecalciferol orally 3-7 days before surgery. 100, 000 IU cholecalciferol **ID:** EG000 **Other Num at Risk:** 28 **Serious Number At Risk:** 28 **Title:** Cholecalciferol **Group ID:** EG001 **Title:** Sugar Pill **Deaths Num Affected:** 1 **Deaths Num At Risk:** 32 **Description:** 40 patients will receive a sugar pill orally 3-7 days before surgery. Placebo: sugar pill **ID:** EG001 **Other Num at Risk:** 32 **Serious Number At Risk:** 32 **Title:** Sugar Pill **Frequency Threshold:** 0 **Time Frame:** Data was collected over a period of 30 days post drug administration ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 28 **Group ID:** BG001 **Value:** 32 **Group ID:** BG002 **Value:** 60 **Units:** Participants ### Group **ID:** BG000 **Title:** Cholecalciferol **Description:** 40 patients will receive 100,000 IU cholecalciferol orally 3-7 days before surgery. 100, 000 IU cholecalciferol ### Group **ID:** BG001 **Title:** Sugar Pill **Description:** 40 patients will receive a sugar pill orally 3-7 days before surgery. Placebo: sugar pill ### Group **ID:** BG002 **Title:** Total **Description:** Total of all reporting groups ### Measure #### Measurement **Group ID:** BG000 **Spread:** 13 **Value:** 56 #### Measurement **Group ID:** BG001 **Spread:** 13 **Value:** 61 #### Measurement **Group ID:** BG002 **Spread:** 13 **Value:** 57 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 14 #### Measurement **Group ID:** BG001 **Value:** 20 #### Measurement **Group ID:** BG002 **Value:** 34 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 14 #### Measurement **Group ID:** BG001 **Value:** 12 #### Measurement **Group ID:** BG002 **Value:** 26 **Category Title:** Male **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** American Indian or Alaska Native #### Measurement **Group ID:** BG000 **Value:** 1 #### Measurement **Group ID:** BG001 **Value:** 1 #### Measurement **Group ID:** BG002 **Value:** 2 **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:** 2 #### Measurement **Group ID:** BG001 **Value:** 2 #### Measurement **Group ID:** BG002 **Value:** 4 **Category Title:** Black or African American #### Measurement **Group ID:** BG000 **Value:** 25 #### Measurement **Group ID:** BG001 **Value:** 28 #### Measurement **Group ID:** BG002 **Value:** 53 **Category Title:** White #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** More than one race #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** Unknown or Not Reported **Class Title:** **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 ## Results Section - More Information Module ### Certain Agreement ### Limitations and Caveats **Description:** A small sample size and a relatively homogenous patient cohort at a major teaching hospital limit the generalizability of results. ### Point of Contact **Email:** [email protected] **Organization:** Massachusetts General Hospital **Phone:** 617-726-3030 **Title:** Sadeq A. Quraishi, MD ## 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:** 6 - **Upper Limit:** - **Value:** 8 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 4 - **Upper Limit:** - **Value:** -2 **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 6 - **Upper Limit:** - **Value:** -5 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 4 - **Upper Limit:** - **Value:** -4 **Title:** #### Outcome Measure 3 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 7 - **Upper Limit:** - **Value:** 3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 11 - **Upper Limit:** - **Value:** 1 **Title:** #### Outcome Measure 4 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 17 - **Upper Limit:** - **Value:** -10 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 12 - **Upper Limit:** - **Value:** -5 **Title:** #### Outcome Measure 5 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 24 - **Upper Limit:** - **Value:** -3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 31 - **Upper Limit:** - **Value:** -5 **Title:** #### Outcome Measure 6 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 27 - **Upper Limit:** - **Value:** 16 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 37 - **Upper Limit:** - **Value:** 2 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** 3-7 days before surgery, patients will receive 100,000 IU of cholecalciferol (vs. placebo) during their pre-op assessment. They will also have their baseline vitamin D status measured during this initial visit. The main study outcome is to determine if 100,000 IU cholecalciferol can be given preoperatively to safely boost vitamin D status. To assess vitamin D status, we will measure: 1) 25(OH)D and 2) LL37 **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Data are presented as percent change in levels between baseline assessment and day of surgery **Reporting Status:** POSTED **Time Frame:** Patients will be followed between the initial preoperative evaluation day and an average duration of 5 days **Title:** Percent (%) Change in 25(OH)D 5 Days Following Supplementation With 100,000 IU Cholecalciferol **Type:** PRIMARY **Unit of Measure:** percent change in 25(OH)D ##### Group **Description:** 40 patients will receive 100,000 IU cholecalciferol orally 3-7 days before surgery. 100, 000 IU cholecalciferol **ID:** OG000 **Title:** Cholecalciferol ##### Group **Description:** 40 patients will receive a sugar pill orally 3-7 days before surgery. Placebo: sugar pill **ID:** OG001 **Title:** Sugar Pill #### Outcome Measure 2 **Description:** The goal is to determine whether pre-operative supplementation with 100,000 IU cholecalciferol (vs. placebo) alters the natural course of short-term changes in vitamin D status following surgery. To assess vitamin D status, we will measure: 1) 25(OH)D and 2) LL37. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Data are presented as percent change in levels between baseline assessment and day after surgery **Reporting Status:** POSTED **Time Frame:** Patients will be followed between the day of surgery and 1 day after surgery **Title:** Percent (%) Change in Pre-surgical 25(OH)D Within 24 Hours of Surgery **Type:** SECONDARY **Unit of Measure:** Percent change in 25(OH)D ##### Group **Description:** 40 patients will receive 100,000 IU cholecalciferol orally 3-7 days before surgery. 100, 000 IU cholecalciferol **ID:** OG000 **Title:** Cholecalciferol ##### Group **Description:** 40 patients will receive a sugar pill orally 3-7 days before surgery. Placebo: sugar pill **ID:** OG001 **Title:** Sugar Pill #### Outcome Measure 3 **Description:** The goal is to determine whether pre-operative supplementation with 100,000 IU cholecalciferol (vs. placebo) alters the natural course of changes in vitamin D status within 10-18 days after surgery. To assess vitamin D status, we will measure: 1) 25(OH)D and 2) LL-37. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Data are presented as percent change in levels between baseline assessment and 2 weeks after surgery **Reporting Status:** POSTED **Time Frame:** Patients will be followed between the day of surgery and an average duration of 14 days after surgery **Title:** Percent (%) Change in Pre-surgical 25(OH)D 2 Weeks After Surgery **Type:** OTHER_PRE_SPECIFIED **Unit of Measure:** Percent change in 25(OH)D ##### Group **Description:** 40 patients will receive 100,000 IU cholecalciferol orally 3-7 days before surgery. 100, 000 IU cholecalciferol **ID:** OG000 **Title:** Cholecalciferol ##### Group **Description:** 40 patients will receive a sugar pill orally 3-7 days before surgery. Placebo: sugar pill **ID:** OG001 **Title:** Sugar Pill #### Outcome Measure 4 **Description:** 3-7 days before surgery, patients will receive 100,000 IU of cholecalciferol (vs. placebo) during their pre-op assessment. They will also have their baseline vitamin D status measured during this initial visit. The main study outcome is to determine if 100,000 IU cholecalciferol can be given preoperatively to safely boost vitamin D status. To assess vitamin D status, we will measure: 1) 25(OH)D and 2) LL37 **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Data are presented as percent change in levels between baseline assessment and day of surgery **Reporting Status:** POSTED **Time Frame:** Patients will be followed between the initial preoperative evaluation day and an average duration of 5 days **Title:** Percent (%) Change in LL-37 5 Days Following Supplementation With 100,000 IU Cholecalciferol **Type:** PRIMARY **Unit of Measure:** percent change in LL-37 ##### Group **Description:** 40 patients will receive 100,000 IU cholecalciferol orally 3-7 days before surgery. 100, 000 IU cholecalciferol **ID:** OG000 **Title:** Cholecalciferol ##### Group **Description:** 40 patients will receive a sugar pill orally 3-7 days before surgery. Placebo: sugar pill **ID:** OG001 **Title:** Sugar Pill #### Outcome Measure 5 **Description:** The goal is to determine whether pre-operative supplementation with 100,000 IU cholecalciferol (vs. placebo) alters the natural course of short-term changes in vitamin D status following surgery. To assess vitamin D status, we will measure: 1) 25(OH)D and 2) LL37. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Data are presented as percent change in levels between baseline assessment and day after surgery **Reporting Status:** POSTED **Time Frame:** Patients will be followed between the day of surgery and 1 day after surgery **Title:** Percent (%) Change in Pre-surgical LL-37 Within 24 Hours of Surgery **Type:** SECONDARY **Unit of Measure:** Percent change in LL-37 ##### Group **Description:** 40 patients will receive 100,000 IU cholecalciferol orally 3-7 days before surgery. 100, 000 IU cholecalciferol **ID:** OG000 **Title:** Cholecalciferol ##### Group **Description:** 40 patients will receive a sugar pill orally 3-7 days before surgery. Placebo: sugar pill **ID:** OG001 **Title:** Sugar Pill #### Outcome Measure 6 **Description:** The goal is to determine whether pre-operative supplementation with 100,000 IU cholecalciferol (vs. placebo) alters the natural course of changes in vitamin D status within 10-18 days after surgery. To assess vitamin D status, we will measure: 1) 25(OH)D and 2) LL-37. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Data are presented as percent change in levels between baseline assessment and 2 weeks after surgery **Reporting Status:** POSTED **Time Frame:** Patients will be followed between the day of surgery and an average duration of 14 days after surgery **Title:** Percent (%) Change in Pre-surgical LL-37 2 Weeks After Surgery **Type:** OTHER_PRE_SPECIFIED **Unit of Measure:** Percent change in LL-37 ##### Group **Description:** 40 patients will receive 100,000 IU cholecalciferol orally 3-7 days before surgery. 100, 000 IU cholecalciferol **ID:** OG000 **Title:** Cholecalciferol ##### Group **Description:** 40 patients will receive a sugar pill orally 3-7 days before surgery. Placebo: sugar pill **ID:** OG001 **Title:** Sugar Pill ### Participant Flow Module #### Group **Description:** 40 patients will receive 100,000 IU cholecalciferol orally 3-7 days before surgery. 100, 000 IU cholecalciferol **ID:** FG000 **Title:** Cholecalciferol #### Group **Description:** 40 patients will receive a sugar pill orally 3-7 days before surgery. Placebo: sugar pill **ID:** FG001 **Title:** Sugar Pill #### Period **Title:** Overall Study ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 28 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 32 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 28 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 32 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 0 **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT01234779 **Brief Title:** A Study of RO4917838 (Bitopertin) in Patients With Acute Exacerbation of Schizophrenia **Official Title:** A Phase II, Multi-center, Randomized, 4-week, Double-blind, Parallel Group, Placebo and Active-controlled Trial of the Safety and Efficacy of RO4917838 vs. Placebo in Patients With an Acute Exacerbation of Schizophrenia #### Organization Study ID Info **ID:** WN25333 #### Organization **Class:** INDUSTRY **Full Name:** Hoffmann-La Roche #### Secondary ID Infos **ID:** 2010-021984-33 ### Status Module #### Completion Date **Date:** 2012-09 **Type:** ACTUAL #### Disp First Post Date **Date:** 2013-10-30 **Type:** ESTIMATED **Disp First Submit Date:** 2013-10-07 **Disp First Submit QC Date:** 2013-10-07 #### Expanded Access Info #### Last Update Post Date **Date:** 2016-11-02 **Type:** ESTIMATED **Last Update Submit Date:** 2016-11-01 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2012-09 **Type:** ACTUAL #### Start Date **Date:** 2011-02 **Status Verified Date:** 2016-11 #### Study First Post Date **Date:** 2010-11-04 **Type:** ESTIMATED **Study First Submit Date:** 2010-11-03 **Study First Submit QC Date:** 2010-11-03 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Hoffmann-La Roche #### Responsible Party **Type:** SPONSOR ### Description Module **Brief Summary:** This randomized, double-blind, placebo- and active-controlled, parallel group study will evaluate the safety and efficacy of RO4917838 (bitopertin) in patients with acute exacerbation of schizophrenia. Patients will be randomized to receive either RO4917838 10 mg or RO4917838 30 mg or olanzapine 15 mg or placebo orally daily for 4 weeks as inpatients, with a 4-week follow-up period. ### Conditions Module **Conditions:** - Schizophrenia ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** DOUBLE **Who Masked:** - PARTICIPANT - INVESTIGATOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 301 **Type:** ACTUAL **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Intervention Names:** - Drug: bitopertin [RO4917838] **Label:** A **Type:** EXPERIMENTAL #### Arm Group 2 **Intervention Names:** - Drug: bitopertin [RO4917838] **Label:** B **Type:** EXPERIMENTAL #### Arm Group 3 **Intervention Names:** - Drug: olanzapine **Label:** C **Type:** ACTIVE_COMPARATOR #### Arm Group 4 **Intervention Names:** - Drug: placebo **Label:** D **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - A **Description:** 10 mg orally daily, 4 weeks **Name:** bitopertin [RO4917838] **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - B **Description:** 30 mg orally daily, 4 weeks **Name:** bitopertin [RO4917838] **Type:** DRUG #### Intervention 3 **Arm Group Labels:** - C **Description:** 15 mg orally daily, 4 weeks **Name:** olanzapine **Type:** DRUG #### Intervention 4 **Arm Group Labels:** - D **Description:** orally daily, 4 weeks **Name:** placebo **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Measure:** Change in Positive and Negative Syndrome Scale (PANSS) total score **Time Frame:** from baseline to Day 28 **Measure:** Safety: Incidence adverse events **Time Frame:** 8 weeks #### Secondary Outcomes **Measure:** Clinical response, defined as at least 30% or 50% improvement from baseline PANSS total score **Time Frame:** from baseline to Day 28 **Measure:** Change in symptomatology as measured by the PANSS factor and subscale scores **Time Frame:** from baseline to Day 28 **Measure:** Global improvement as measured by the Clinical Global Impressions-Severity (CGI-S) scale **Time Frame:** from baseline to Day 28 **Measure:** Global improvement as measured by the Clinical Global Impressions-Change (CGI-C) rating scale **Time Frame:** from baseline to Day 28 **Measure:** Observable behavioural change as determined by the Nurses' Observation Scale For Inpatient Evaluation (NOSIE) **Time Frame:** from baseline to Day 28 **Measure:** Time to readiness for discharge from inpatient unit as assessed by the Readiness For Hospital Discharge Questionnaire (RDQ) **Time Frame:** from baseline to Day 28 ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Adult patients, 18-65 years of age * Diagnosis of schizophrenia (Diagnostic and Statistical Manual of Mental Disorders DSM IV-TR) * Acute exacerbation which began within the prior 8 weeks * Female patients must be surgically sterile or post-menopausal, or agree to use effective contraception for the duration of the study Exclusion Criteria: * Current psychiatric diagnosis other than schizophrenia * Alcohol or substance dependence within 3 months or abuse within 1 month (except for nicotine) * Electro-convulsive therapy (ECT) within the prior 6 months * Previous treatment with RO4917838 or another GLYT inhibitor * Current treatment with olanzapine, or previous treatment with intolerability or lack of response * Treatment with long-acting injectable antipsychotic within 2 dosing intervals * Treatment with \> 2 antipsychotics within 3 months * History of neuroleptic malignant syndrome * Have treatment-resistant schizophrenia as judged by treating physician or have failed two trials according to criteria in protocol **Maximum Age:** 65 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Little Rock **Country:** United States **State:** Arkansas **Zip:** 72201 **Location 2:** **City:** Cerritos **Country:** United States **State:** California **Zip:** 90703 **Location 3:** **City:** Oceanside **Country:** United States **State:** California **Zip:** 92056 **Location 4:** **City:** Pico Rivera **Country:** United States **State:** California **Zip:** 90660 **Location 5:** **City:** San Diego **Country:** United States **State:** California **Zip:** 92121 **Location 6:** **City:** Lauderhill **Country:** United States **State:** Florida **Zip:** 33021 **Location 7:** **City:** North Miami **Country:** United States **State:** Florida **Zip:** 33161 **Location 8:** **City:** Atlanta **Country:** United States **State:** Georgia **Zip:** 30308 **Location 9:** **City:** Lake Charles **Country:** United States **State:** Louisiana **Zip:** 70601 **Location 10:** **City:** Flowood **Country:** United States **State:** Mississippi **Zip:** 39232 **Location 11:** **City:** St. Louis **Country:** United States **State:** Missouri **Zip:** 63141 **Location 12:** **City:** Willingboro **Country:** United States **State:** New Jersey **Zip:** 08046 **Location 13:** **City:** Holliswood **Country:** United States **State:** New York **Zip:** 11423 **Location 14:** **City:** New York **Country:** United States **State:** New York **Zip:** 11004 **Location 15:** **City:** Cincinnati **Country:** United States **State:** Ohio **Zip:** 45219 **Location 16:** **City:** Philadelphia **Country:** United States **State:** Pennsylvania **Zip:** 19139 **Location 17:** **City:** Charlesston **Country:** United States **State:** South Carolina **Zip:** 29405 **Location 18:** **City:** Austin **Country:** United States **State:** Texas **Zip:** 78754 **Location 19:** **City:** Irving **Country:** United States **State:** Texas **Zip:** 75062 **Location 20:** **City:** Arad **Country:** Romania **Zip:** 310022 **Location 21:** **City:** Bucuresti **Country:** Romania **Zip:** 010825 **Location 22:** **City:** Bucuresti **Country:** Romania **Zip:** 041902 **Location 23:** **City:** Bucuresti **Country:** Romania **Zip:** 041914 **Location 24:** **City:** Foscani **Country:** Romania **Zip:** 620165 **Location 25:** **City:** Oradea **Country:** Romania **Zip:** 410154 **Location 26:** **City:** Targoviste **Country:** Romania **Zip:** 130086 **Location 27:** **City:** Gatchina **Country:** Russian Federation **Zip:** 188357 **Location 28:** **City:** Moscow **Country:** Russian Federation **Zip:** 117152 **Location 29:** **City:** Petrozavodsk **Country:** Russian Federation **Zip:** 186131 **Location 30:** **City:** St Petersburg **Country:** Russian Federation **Zip:** 190005 **Location 31:** **City:** St Petersburg **Country:** Russian Federation **Zip:** 193167 **Location 32:** **City:** St Petersburg **Country:** Russian Federation **Zip:** 194044 **Location 33:** **City:** St Petersburg **Country:** Russian Federation **Zip:** 197341 **Location 34:** **City:** St. Petersburg **Country:** Russian Federation **Zip:** 192019 **Location 35:** **City:** Talagi **Country:** Russian Federation **Zip:** 163530 **Location 36:** **City:** Bojnice **Country:** Slovakia **Zip:** 972 01 **Location 37:** **City:** Bratislava **Country:** Slovakia **Zip:** 826 06 **Location 38:** **City:** Liptovsky Mikulas **Country:** Slovakia **Zip:** 3123 **Location 39:** **City:** Michalovce **Country:** Slovakia **Zip:** 071 01 **Location 40:** **City:** Dnipropetrovsk **Country:** Ukraine **Zip:** 49027 **Location 41:** **City:** Donetsk **Country:** Ukraine **Zip:** 83008 **Location 42:** **City:** Kherson,Vil. Stepanivka **Country:** Ukraine **Zip:** 73488 **Location 43:** **City:** Kyiv **Country:** Ukraine **Zip:** 02660 **Location 44:** **City:** Kyiv **Country:** Ukraine **Zip:** 04080 **Location 45:** **City:** Poltava **Country:** Ukraine **Zip:** 36006 **Location 46:** **City:** Vinnytsya **Country:** Ukraine **Zip:** 21005 #### Overall Officials **Official 1:** **Affiliation:** Hoffmann-La Roche **Name:** Clinical Trials **Role:** STUDY_DIRECTOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000019967 - Term: Schizophrenia Spectrum and Other Psychotic Disorders - ID: D000001523 - Term: Mental Disorders ### Condition Browse Module - Browse Branches - Abbrev: BXM - Name: Behaviors and Mental Disorders - Abbrev: All - Name: All Conditions - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M15376 - Name: Schizophrenia - Relevance: HIGH - As Found: Schizophrenia - ID: M4815 - Name: Mental Disorders - Relevance: LOW - As Found: Unknown - ID: M14473 - Name: Psychotic Disorders - Relevance: LOW - As Found: Unknown - ID: M21838 - Name: Schizophrenia Spectrum and Other Psychotic Disorders - Relevance: LOW - As Found: Unknown - ID: T170 - Name: Acute Graft Versus Host Disease - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000012559 - Term: Schizophrenia ### Intervention Browse Module - Ancestors - 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: D000014150 - Term: Antipsychotic Agents - ID: D000014149 - Term: Tranquilizing Agents - ID: D000002492 - Term: Central Nervous System Depressants - ID: D000011619 - Term: Psychotropic Drugs - ID: D000017367 - Term: Selective Serotonin Reuptake Inhibitors - ID: D000014179 - Term: Neurotransmitter Uptake Inhibitors - ID: D000049990 - Term: Membrane Transport Modulators - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000018377 - Term: Neurotransmitter Agents - ID: D000018490 - Term: Serotonin Agents ### Intervention Browse Module - Browse Branches - Abbrev: AnEm - Name: Antiemetics - Abbrev: CNSDep - Name: Central Nervous System Depressants - Abbrev: PsychDr - Name: Psychotropic Drugs - Abbrev: Gast - Name: Gastrointestinal Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M1675 - Name: Olanzapine - Relevance: HIGH - As Found: Tailored - ID: M4251 - Name: Antiemetics - Relevance: LOW - As Found: Unknown - ID: M8881 - Name: Gastrointestinal Agents - Relevance: LOW - As Found: Unknown - ID: M16904 - Name: Antipsychotic Agents - Relevance: LOW - As Found: Unknown - ID: M14474 - Name: Psychotropic Drugs - Relevance: LOW - As Found: Unknown - ID: M19649 - Name: Selective Serotonin Reuptake Inhibitors - Relevance: LOW - As Found: Unknown - ID: M15512 - Name: Serotonin - Relevance: LOW - As Found: Unknown - ID: M20504 - Name: Neurotransmitter Agents - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000077152 - Term: Olanzapine ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05645679 **Acronym:** HYBRID **Brief Title:** Efficacy and Safety of HYbrid Argon Plasma Coagulation Technique in Patients With Barrett's Esophagus-Related Dysplasia **Official Title:** Efficacy and Safety of HYbrid Argon Plasma Coagulation Technique in Patients With Barrett's Esophagus-Related Dysplasia: a Multicenter Italian Prospective stuDy #### Organization Study ID Info **ID:** 2858 #### Organization **Class:** OTHER **Full Name:** Istituto Clinico Humanitas ### Status Module #### Completion Date **Date:** 2024-12-31 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2022-12-09 **Type:** ACTUAL **Last Update Submit Date:** 2022-12-01 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2024-12-31 **Type:** ESTIMATED #### Start Date **Date:** 2021-04-02 **Type:** ACTUAL **Status Verified Date:** 2022-12 #### Study First Post Date **Date:** 2022-12-09 **Type:** ACTUAL **Study First Submit Date:** 2022-12-01 **Study First Submit QC Date:** 2022-12-01 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Istituto Clinico Humanitas #### 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:** Background Barrett's esophagus (BE) is defined by AGA as "a change in the esophageal epithelium of any length that can be recognized at upper endoscopy and is confirmed to have intestinal metaplasia by biopsy". It is a pre-malignant condition and may progress to low grade dysplasia, high grade dysplasia and ultimately esophageal adenocarcinoma which has poor prognosis with a 5-year survival rate of only 5-20%.Radiofrequency ablation (RFA) is a standard modality and well-studied endoscopic treatment for dysplastic BE. While the rate of complete eradication of dysplasia has been reported to be between 78% - 94% with RFA, the rate of complications associated with this procedure has been reported to be as high as 19.1%, and the costs are high. In a randomized clinical trial in patients with BE and low-grade dysplasia by Phoa et al in 2014, 68 patients underwent radiofrequency ablation therapy with a median of three ablation sessions per patient while 68 patients were randomized to endoscopic surveillance. In this study, a total of 13 patients (19.1%) experienced an adverse event in the treatment group versus no adverse events in the control group. Eight patients (11.8%) developed esophageal strictures which required a median of one dilation, three patients were noted to have small mucosal lacerations, one patient developed retrosternal pain treated with analgesics while one patient developed abdominal pain requiring hospitalization and treatment with analgesia. Several other studies have reported the rate of complications ranging between 5% to 19.1% and stricture formation being the most common among them. Hybrid argon plasma coagulation (H-APC) is a newer technique that involves submucosal fluid injection prior to performing APC. The injection of solutions (e.g., 0.9% sodium chloride solution (normal sterile saline) with or without supplementation of epinephrine, methylcellulose solution, hydroxyethyl starch, hyaluronic acid, autologous blood or blood substitute fluids) into the submucosa to limit the depth of thermal injury has been established both in pre-clinical studies for different tissues of the gastrointestinal tract and in the clinical practice for EMR and ESD, respectively. ### Conditions Module **Conditions:** - Barrett's Esophagus ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 50 **Type:** ESTIMATED **Study Type:** OBSERVATIONAL ### Arms Interventions Module ### Interventions #### Intervention 1 **Description:** Hybrid Argon Plasma Coagulation System **Name:** Hybrid Argon Plasma Coagulation System **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Description:** percentage of patients with complete eradication of all Barrett's epithelium on endoscopy and CE-IM in all biopsies obtained at the first follow-up endoscopy after the maximum of 5 treatment sessions (and escape treatment(s) if necessary). the percentage of patients with CE-D in all biopsies obtained at the first follow-up endoscopy after the maximum of 5 treatment sessions (and escape treatment(s) if necessary). **Measure:** Efficacy of the Hybrid Argon Plasma Coagulation Technique **Time Frame:** 2 years ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: - Patients with histopathologically confirmed LGD or HGD, or residual BE (Prague Classification ≤C3 / ≤M5) after endoscopic resection of a focal lesion containing LGD, HGD or early (≤T1sm1) cancer in the participating centres are eligible for study participation. Exclusion Criteria: * Younger than 18 years of age at time of consent * Esophageal stenosis preventing advancement of a therapeutic endoscope * Prior distal oesophagectomy * Previous ablation therapy of the esophagus * Active oesophagitis grade B or higher (patients can be included after appropriate treatment of reflux oesophagitis) * History of oesophageal varices * Achalasia * Severe medical comorbidities precluding endoscopy * Uncontrolled coagulopathy * Pregnant or planning to become pregnant during period of study participation * Life expectancy ≤2 years, as judged by the site investigator **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Patients with histopathologically confirmed LGD or HGD, or residual BE (Prague Classification ≤C3 / ≤M5) after endoscopic resection of a focal lesion containing LGD, HGD or early (≤T1sm1) cancer in the participating centres are eligible for study participation. ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Alessandro Repici, MD **Phone:** 0039-02-82247493 **Role:** CONTACT #### Locations **Location 1:** **City:** Milano **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Alessandro Repici, MD - **Phone:** 0039-02-82244507 - **Role:** CONTACT **Country:** Italy **Facility:** Humanitas Research Hospital **Status:** RECRUITING **Zip:** 20089 ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000011230 - Term: Precancerous Conditions - ID: D000009369 - Term: Neoplasms - ID: D000004935 - Term: Esophageal Diseases - ID: D000005767 - Term: Gastrointestinal Diseases - ID: D000004066 - Term: Digestive System Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC06 - Name: Digestive System Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M4765 - Name: Barrett Esophagus - Relevance: HIGH - As Found: Barrett's Esophagus - ID: M14111 - Name: Precancerous Conditions - Relevance: LOW - As Found: Unknown - ID: M8085 - Name: Esophageal 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 ### Condition Browse Module - Meshes - ID: D000001471 - Term: Barrett Esophagus ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00840879 **Brief Title:** Meloxicam 15 mg Tablets Under Non-Fasting Conditions **Official Title:** A Two-Way Crossover, Open-Label, Single-Dose, Fed, Bioequivalence Study of Meloxicam 15 mg Tablets Versus Mobic® 15 mg Tablets in Normal Healthy Non-Smoking Male and Female Subjects #### Organization Study ID Info **ID:** 2825 #### Organization **Class:** INDUSTRY **Full Name:** Teva Pharmaceuticals USA ### Status Module #### Completion Date **Date:** 2004-02 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2009-09-11 **Type:** ESTIMATED **Last Update Submit Date:** 2009-09-01 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2004-02 **Type:** ACTUAL #### Results First Post Date **Date:** 2009-08-04 **Type:** ESTIMATED **Results First Submit Date:** 2009-06-30 **Results First Submit QC Date:** 2009-06-30 #### Start Date **Date:** 2004-02 **Status Verified Date:** 2009-09 #### Study First Post Date **Date:** 2009-02-10 **Type:** ESTIMATED **Study First Submit Date:** 2009-02-06 **Study First Submit QC Date:** 2009-02-06 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Teva Pharmaceuticals USA ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** The objective of this study is to compare the rate and extent of absorption of meloxicam from a test formulation Meloxicam 15 mg Tablets versus the reference Mobic® 15 mg Tablets under fed conditions. **Detailed Description:** Criteria for Evaluation: FDA Bioequivalence Criteria Statistical Methods: FDA bioequivalence statistical methods ### Conditions Module **Conditions:** - Healthy **Keywords:** - Bioequivalence - Healthy Subjects ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** CROSSOVER ##### Masking Info **Masking:** NONE #### Enrollment Info **Count:** 28 **Type:** ACTUAL **Phases:** - PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Meloxicam 15 mg Tablet (test) dosed in first period followed by Mobic® 15 mg Tablet (reference) dosed in second period **Intervention Names:** - Drug: Meloxicam 15 mg Tablets **Label:** Meloxicam **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Mobic® 15 mg Tablet (reference) dosed in first period followed by Meloxicam 15 mg Tablet (test) dosed in second period **Intervention Names:** - Drug: Mobic® 15 mg Tablets **Label:** Mobic® **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Meloxicam **Description:** 1 x 15 mg, single-dose fed **Name:** Meloxicam 15 mg Tablets **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Mobic® **Description:** 1 x 15 mg, single-dose fed **Name:** Mobic® 15 mg Tablets **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Bioequivalence based on Cmax **Measure:** Cmax - Maximum Observed Concentration **Time Frame:** Blood samples collected over 96 hour period **Description:** Bioequivalence based on AUC0-inf **Measure:** AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) **Time Frame:** Blood samples collected over 96 hour period **Description:** Bioequivalence based on AUC0-t **Measure:** AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant) **Time Frame:** Blood samples collected over 96 hour period ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Non-smoking male or female with a minimum age of 18 years (i.e. non-smoker or non tobacco user for at least 90 days prior to pre-study medical). * Body mass Index (BMI = weight/height²) greater than or equal to 18.5 kg/m² and less than or equal to 29.9 kg/m². * Availability of subject for the entire study period and willingness to adhere to protocol requirements, as evidenced by a signed Informed Consent Form. * Normal findings in the physical examination, 12-lead ECG and vital signs (blood pressure between 100-140/60-90 mmHg, heart rate between 50-99 beats/min, temperature between 35.8ºC and 37.5ºC). * Negative for drugs of abuse, nicotine, alcohol, hepatitis B-surface antigen, hepatitis C and HIV, and for female subjects, pregnancy (serum ß-CG). * No clinical laboratory values outside of the acceptable range as defined by BCR, unless the Principal Investigator decides they are not clinically significant. * Female subjects who are surgically sterile for at least six months or post-menopausal for at least one year, or who will avoid pregnancy prior to the study, during the study and up until one month after the end of the study. Exclusion Criteria: * Known history of hypersensitivity to meloxicam (for example Mobic®), or related drugs such as any other non-steroidal anti-inflammatory drugs (NSAID) such as acetylsalicyclic acid (e.g. Excedrin®, Aspirin®), ibuprofen (e.g. Motrin®), celecoxib (e.g. Celebrex®), Feldene®, Indocin®, Naprosyn®, Vioxx®, Toradol®, Clinoril®, Tolectin®, or Lodine®. * Known history or presence of cardiac, pulmonary, gastrointestinal, endocrine, musculoskeletal, neurological, hematological, or liver disease, unless judged not clinically significant by the Principal Investigator, or medical designate. * Any history or presence of peptic ulcer disease, gastrointestinal bleeding, or kidney disease. * Known history or presence of food allergies, or any condition known to interfere with the absorption, distribution, metabolism or excretion of drugs. * Any clinically significant illness during the last four weeks prior to entry into this study. * Presence of any significant physical or organ abnormality. * Any subject with history of drug abuse. * Any psychiatric or psychological disease (including depression) unless deemed not clinically significant by the Principal Investigator, or medical designate. * Use of any prescription medication within 14 days preceding entry into this study. * Use of over-the-counter (OTC) medication within seven days preceding entry into this study (except for spermicidal/barrier contraceptive products). * Female subjects: use of oral contraceptives or contraceptive implants (such as Norplant®) within 30 days prior to drug administration or a depot injection of progestogen drug (e.g. Depo-Provera®) within one year prior to drug administration. * Female subjects: presence of pregnancy or lactation. * Female subjects at risk of becoming pregnant must consent to using two medically acceptable methods of contraception throughout the entire study, including the washout period and for one month after the completion of the study. Medically acceptable barrier methods of contraception that may be used by the subject and/or partner include diaphragm with spermicide, IUD, condom with foam, and vaginal spermicidal suppository. Complete abstinence can be used alone as a method of contraception. * Any subject who has had blood drawn within 56 days preceding this study, taken during the conduct of any clinical study at a facility other than BCR or within the lockout period specified by a previous study conducted at BCR. * Participation in a clinical trial with an investigational drug within 30 days preceding this study. * Any subject who has donated blood within 56 days preceding this study. * Any subject who has participated as a plasma donor in a plasmapheresis program within seven days preceding this study. * Any subject with a recent (less than one year) history of alcohol abuse. * Significant or recent history of asthma (after 12 years of age), or familial history of asthma or aspirin-sensitive asthma, sever bronchospasm, nasal polyps or chronic sinusitis. * Intolerance to venipuncture. **Healthy Volunteers:** True **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Toronto **Country:** Canada **Facility:** Biovail Contract Research **State:** Ontario **Zip:** M1L4S4 #### Overall Officials **Official 1:** **Affiliation:** Biovail Contract Research **Name:** Paul Y. Tam, M.D. **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Intervention Browse Module - Ancestors - ID: D000000894 - Term: Anti-Inflammatory Agents, Non-Steroidal - ID: D000018712 - Term: Analgesics, Non-Narcotic - ID: D000000700 - Term: Analgesics - ID: D000018689 - Term: Sensory System Agents - ID: D000018373 - Term: Peripheral Nervous System Agents - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000000893 - Term: Anti-Inflammatory Agents - ID: D000018501 - Term: Antirheumatic Agents - ID: D000052246 - Term: Cyclooxygenase 2 Inhibitors - ID: D000016861 - Term: Cyclooxygenase Inhibitors - ID: D000004791 - Term: Enzyme Inhibitors - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action ### Intervention Browse Module - Browse Branches - Abbrev: Infl - Name: Anti-Inflammatory Agents - Abbrev: ARhu - Name: Antirheumatic Agents - Abbrev: Analg - Name: Analgesics - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M1713 - Name: Meloxicam - Relevance: HIGH - As Found: Onset of - ID: M4217 - Name: Anti-Inflammatory Agents - Relevance: LOW - As Found: Unknown - ID: M4218 - Name: Anti-Inflammatory Agents, Non-Steroidal - Relevance: LOW - As Found: Unknown - ID: M4032 - Name: Analgesics - Relevance: LOW - As Found: Unknown - ID: M20786 - Name: Analgesics, Non-Narcotic - Relevance: LOW - As Found: Unknown - ID: M20604 - Name: Antirheumatic Agents - Relevance: LOW - As Found: Unknown - ID: M27009 - Name: Cyclooxygenase 2 Inhibitors - Relevance: LOW - As Found: Unknown - ID: M19209 - Name: Cyclooxygenase Inhibitors - Relevance: LOW - As Found: Unknown - ID: M7951 - Name: Enzyme Inhibitors - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000077239 - Term: Meloxicam ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 14 **Group ID:** BG001 **Value:** 14 **Group ID:** BG002 **Value:** 28 **Units:** Participants ### Group **ID:** BG000 **Title:** Meloxicam (Test) First **Description:** Meloxicam 15 mg Tablet (test) dosed in first period followed by Mobic® 15 mg Tablet (reference) dosed in second period ### Group **ID:** BG001 **Title:** Mobic® (Reference) First **Description:** Mobic® 15 mg Tablet (reference) dosed in first period followed by Meloxicam 15 mg Tablet (test) dosed in second period ### Group **ID:** BG002 **Title:** Total **Description:** Total of all reporting groups ### Measure #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** <=18 years #### Measurement **Group ID:** BG000 **Value:** 14 #### Measurement **Group ID:** BG001 **Value:** 14 #### Measurement **Group ID:** BG002 **Value:** 28 **Category Title:** Between 18 and 65 years #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** >=65 years **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 8 #### Measurement **Group ID:** BG001 **Value:** 6 #### Measurement **Group ID:** BG002 **Value:** 14 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 6 #### Measurement **Group ID:** BG001 **Value:** 8 #### Measurement **Group ID:** BG002 **Value:** 14 **Category Title:** Male **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 8 #### Measurement **Group ID:** BG001 **Value:** 13 #### Measurement **Group ID:** BG002 **Value:** 21 **Class Title:** Caucasian #### Measurement **Group ID:** BG000 **Value:** 4 #### Measurement **Group ID:** BG001 **Value:** 1 #### Measurement **Group ID:** BG002 **Value:** 5 **Class Title:** Black #### Measurement **Group ID:** BG000 **Value:** 2 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 2 **Class Title:** Asian ### Measure #### Measurement **Group ID:** BG000 **Value:** 14 #### Measurement **Group ID:** BG001 **Value:** 14 #### Measurement **Group ID:** BG002 **Value:** 28 **Class Title:** Canada **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:** NUMBER **Title:** Race/Ethnicity, 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:** Principal Investigator is not permitted to discuss or publish trial results. **Restriction Type:** OTHER **Restrictive Agreement:** True ### Point of Contact **Email:** [email protected] **Organization:** Teva Pharmaceuticals USA **Phone:** 1-866-384-5525 **Title:** Manager, Biopharmaceutics ## Results Section - Outcome Measures Module ### Outcome Measure 1 #### Analysis **CI Lower Limit:** 90.96 **CI Number of Sides:** **CI Percentage Value:** 90 **CI Upper Limit:** 105.90 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** Bioequivalence is established when 90% Confidence Interval falls within 80-125. **Group Description:** **Non-Inferiority Comment:** Analysis of variance (ANOVA) was performed on pharmacokinetic parameters of AUC0-t, AUCinf and Cmax. **Non-Inferiority Type:** NON_INFERIORITY_OR_EQUIVALENCE **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Test/Ref Ratio of LS Means x 100 **Parameter Value:** 98.15 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** True ### Outcome Measure 2 #### Analysis **CI Lower Limit:** 91.82 **CI Number of Sides:** **CI Percentage Value:** 90 **CI Upper Limit:** 101.07 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** Bioequivalence is established when 90% Confidence Interval falls within 80-125. **Group Description:** **Non-Inferiority Comment:** Analysis of variance (ANOVA) was performed on pharmacokinetic parameters of AUC0-t, AUCinf and Cmax. **Non-Inferiority Type:** NON_INFERIORITY_OR_EQUIVALENCE **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Test/Ref Ratio of LS Means x 100 **Parameter Value:** 96.34 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** True ### Outcome Measure 3 #### Analysis **CI Lower Limit:** 93.31 **CI Number of Sides:** **CI Percentage Value:** 90 **CI Upper Limit:** 102.42 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** Bioequivalence is established when 90% Confidence Interval falls within 80-125. **Group Description:** **Non-Inferiority Comment:** Analysis of variance (ANOVA) was performed on pharmacokinetic parameters of AUC0-t, AUCinf and Cmax. **Non-Inferiority Type:** NON_INFERIORITY_OR_EQUIVALENCE **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Test/Ref Ratio of LS Means x 100 **Parameter Value:** 97.76 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** True ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Anticipated Posting Date:** 2009-06 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.22 - **Upper Limit:** - **Value:** 1.32 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.29 - **Upper Limit:** - **Value:** 1.36 **Title:** #### Outcome Measure 2 **Anticipated Posting Date:** 2009-06 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 15.88 - **Upper Limit:** - **Value:** 40.50 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 17.62 - **Upper Limit:** - **Value:** 42.38 **Title:** #### Outcome Measure 3 **Anticipated Posting Date:** 2009-06 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 12.33 - **Upper Limit:** - **Value:** 37.11 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 12.70 - **Upper Limit:** - **Value:** 38.00 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** Bioequivalence based on Cmax **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** One subject had a pre-dose concentration greater than 5% of the individuals Cmax value and was excluded from the statistical analysis. Data from all other subjects who completed the study was used in the statistical analysis. **Reporting Status:** POSTED **Time Frame:** Blood samples collected over 96 hour period **Title:** Cmax - Maximum Observed Concentration **Type:** PRIMARY **Unit of Measure:** µg/mL ##### Group **Description:** Meloxicam 15 mg Tablet (test) dosed in either period **ID:** OG000 **Title:** Meloxicam ##### Group **Description:** Mobic® 15 mg Tablet (reference) dosed in either period **ID:** OG001 **Title:** Mobic® #### Outcome Measure 2 **Description:** Bioequivalence based on AUC0-inf **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** One subject had a pre-dose concentration greater than 5% of the individuals Cmax value and was excluded from the statistical analysis. Data from all other subjects who completed the study was used in the statistical analysis. **Reporting Status:** POSTED **Time Frame:** Blood samples collected over 96 hour period **Title:** AUC0-inf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) **Type:** PRIMARY **Unit of Measure:** µg*h/mL ##### Group **Description:** Meloxicam 15 mg Tablet (test) dosed in either period **ID:** OG000 **Title:** Meloxicam ##### Group **Description:** Mobic® 15 mg Tablet (reference) dosed in either period **ID:** OG001 **Title:** Mobic® #### Outcome Measure 3 **Description:** Bioequivalence based on AUC0-t **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** One subject had a pre-dose concentration greater than 5% of the individuals Cmax value and was excluded from the statistical analysis. Data from all other subjects who completed the study was used in the statistical analysis. **Reporting Status:** POSTED **Time Frame:** Blood samples collected over 96 hour period **Title:** AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant) **Type:** PRIMARY **Unit of Measure:** µg*h/mL ##### Group **Description:** Meloxicam 15 mg Tablet (test) dosed in either period **ID:** OG000 **Title:** Meloxicam ##### Group **Description:** Mobic® 15 mg Tablet (reference) dosed in either period **ID:** OG001 **Title:** Mobic® ### Participant Flow Module #### Group **Description:** Meloxicam 15 mg Tablet (test) dosed in first period followed by Mobic® 15 mg Tablet (reference) dosed in second period **ID:** FG000 **Title:** Meloxicam (Test) First #### Group **Description:** Mobic® 15 mg Tablet (reference) dosed in first period followed by Meloxicam 15 mg Tablet (test) dosed in second period **ID:** FG001 **Title:** Mobic® (Reference) First #### Period **Title:** First Intervention ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 14 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 14 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 14 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 14 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 0 #### Period **Title:** Washout: 14 Days ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 14 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 14 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 14 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 14 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 0 #### Period **Title:** Second Intervention ##### Withdraw **Type:** Withdrawal by Subject ###### Reason **Group ID:** FG000 **Number of Subjects:** 1 ###### Reason **Group ID:** FG001 **Number of Subjects:** 0 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 14 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 14 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 13 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 14 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 1 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 0 **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT00732979 **Acronym:** IVC CLAMP **Brief Title:** Infrahepatic Inferior Vena Cava Clamping During Hepatectomy **Official Title:** IVC CLAMP: Infrahepatic Inferior Vena Cava Clamping During Hepatectomy - A Randomized Controlled Trial #### Organization Study ID Info **ID:** NNR-01 #### Organization **Class:** OTHER **Full Name:** Heidelberg University ### Status Module #### Completion Date **Date:** 2011-12 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2013-05-17 **Type:** ESTIMATED **Last Update Submit Date:** 2013-05-16 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2011-12 **Type:** ACTUAL #### Start Date **Date:** 2008-03 **Status Verified Date:** 2013-05 #### Study First Post Date **Date:** 2008-08-12 **Type:** ESTIMATED **Study First Submit Date:** 2008-08-07 **Study First Submit QC Date:** 2008-08-11 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Heidelberg University #### Responsible Party **Investigator Affiliation:** Heidelberg University **Investigator Full Name:** Nuh Rahbari **Investigator Title:** MD **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** Intraoperative blood loss is a major concern during hepatic resection, as it has been shown to adversely affect patients' perioperative outcome. Reduction of central venous pressure during parenchymal transection has been shown to effectively lower liver hemorrhage. While CVP reduction is mainly achieved via fluid restriction and diuretics, dehydration may impair organ function. Moreover, it may lead to hemodynamic instability, particularly in case of severe bleeding. For this reason the technique of infrahepatic inferior vena cava clamping has been suggested which is able to lower CVP without the need for fluid restriction. In the present study the two strategies to reduce CVP and by this intraoperative bleeding, namely fluid restriction and inferior vena cava clamping are compared with intraoperative blood loss as primary endpoint. ### Conditions Module **Conditions:** - Hemorrhage **Keywords:** - Elective - hepatic - resection - due to any - reason. ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** DOUBLE **Who Masked:** - PARTICIPANT - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 152 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Infrahepatic inferior vena cava clamping The inferior vena cava is circumferentially dissected below the liver and clamped with a vascular clamp. Patients in this study group will receive intravenous volume for maintenance of fluid hemostasis according to local standards. **Intervention Names:** - Procedure: Infrahepatic inferior vena cava clamping **Label:** A **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Patients in this study group undergo hepatic resection following current standards of the Departments of Surgery and Anesthesiology, University of Heidelberg. Current practice consists of no type of vascular control in combination with CVP reduction below \< 5mmHg. CVP reduction is mainly attained using restricted intravenous fluid administration. **Intervention Names:** - Procedure: No infrahepatic inferior vena cava clamping **Label:** B **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - A **Description:** The inferior vena cava is circumferentially dissected below the liver and clamped with a vascular clamp. Patients in this study group will receive intravenous volume for maintenance of fluid hemostasis according to local standards. **Name:** Infrahepatic inferior vena cava clamping **Type:** PROCEDURE #### Intervention 2 **Arm Group Labels:** - B **Description:** Patients in this study group undergo hepatic resection following current standards of the Departments of Surgery and Anesthesiology, University of Heidelberg. Current practice consists of no type of vascular control in combination with CVP reduction below \< 5mmHg. CVP reduction is mainly attained using restricted intravenous fluid administration. **Name:** No infrahepatic inferior vena cava clamping **Type:** PROCEDURE ### Outcomes Module #### Primary Outcomes **Measure:** Intraoperative blood loss **Time Frame:** End of operation ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Aged 18 years * Scheduled for elective hepatic resection due to any reason * American Society of Anesthesiologists (ASA) score I to III * Written informed consent Exclusion Criteria: * Medical conditions exposing patient at increased risk for not tolerating liver resection: * Cirrhosis (Child-Pugh B and C) * (Hereditary) coagulopathy * Medical conditions exposing patient at increased risk for not tolerating this trial's study interventions: * Severe heart disease (e.g. severe CAD requiring intervention, NYHA IV) * Pulmonary hypertension * Renal insufficiency (serum creatinin \>2mg/dl or \>177µmol/l; conversion factor 88.4 or requiring dialysis) * Severe hypernatremia (serum sodium \>155mmol/l) * Severe hyperchloremia * For female subjects: pregnancy and lactation * Impaired mental state or language problems * Participation in other clinical trials or observation period of competing trials interfering with the endpoints of this trial * Former participation in the clinical trial * Expected lack of compliance **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Heidelberg **Country:** Germany **Facility:** Department of General, Visceral and Transplantation Surgery, University of Heidelberg **Zip:** 69120 ### References Module #### References **Citation:** Rahbari NN, Koch M, Zimmermann JB, Elbers H, Bruckner T, Contin P, Reissfelder C, Schmidt T, Weigand MA, Martin E, Buchler MW, Weitz J. Infrahepatic inferior vena cava clamping for reduction of central venous pressure and blood loss during hepatic resection: a randomized controlled trial. Ann Surg. 2011 Jun;253(6):1102-10. doi: 10.1097/SLA.0b013e318214bee5. **PMID:** 21412143 **Citation:** Rahbari NN, Zimmermann JB, Koch M, Bruckner T, Schmidt T, Elbers H, Reissfelder C, Weigand MA, Buchler MW, Weitz J. IVC CLAMP: infrahepatic inferior vena cava clamping during hepatectomy--a randomised controlled trial in an interdisciplinary setting. Trials. 2009 Oct 13;10:94. doi: 10.1186/1745-6215-10-94. **PMID:** 19825186 ## 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: M9556 - Name: Hemorrhage - Relevance: HIGH - As Found: Hemorrhage ### Condition Browse Module - Meshes - ID: D000006470 - Term: Hemorrhage ### Intervention Browse Module - Browse Branches - Abbrev: CNSDep - Name: Central Nervous System Depressants - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Hemat - Name: Hematinics - Abbrev: Coag - Name: Coagulants - Abbrev: HB - Name: Herbal and Botanical ### Intervention Browse Module - Browse Leaves - ID: M4107 - Name: Anesthetics - Relevance: LOW - As Found: Unknown - ID: M11110 - Name: Liver Extracts - Relevance: LOW - As Found: Unknown - ID: M9576 - Name: Hemostatics - Relevance: LOW - As Found: Unknown - ID: T204 - Name: Kava - Relevance: HIGH - As Found: Umbilical Cord Blood ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT06099379 **Acronym:** SPECTRE **Brief Title:** Modulation of THC Effects by CBD: a Dose-ranging Study **Official Title:** Modulation of ∆9-tetrahydrocannabinol Acute Psychoactive Effects by Ranging Doses of Cannabidiol in Healthy, Occasional Cannabis Users: a Controlled, Triple Blind, Randomized, Cross-over Study #### Organization Study ID Info **ID:** 2024-11772 #### Organization **Class:** OTHER **Full Name:** Centre hospitalier de l'Université de Montréal (CHUM) ### Status Module #### Completion Date **Date:** 2025-12-31 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-04-30 **Type:** ACTUAL **Last Update Submit Date:** 2024-04-29 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2025-07-31 **Type:** ESTIMATED #### Start Date **Date:** 2024-05 **Type:** ESTIMATED **Status Verified Date:** 2024-04 #### Study First Post Date **Date:** 2023-10-25 **Type:** ACTUAL **Study First Submit Date:** 2023-09-29 **Study First Submit QC Date:** 2023-10-23 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Centre hospitalier de l'Université de Montréal (CHUM) #### 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 purposes of this study are 1) to determine if CBD modulates THC-induced acute psychoactive effects at different CBD:THC ratios, compared with the control product (0:20, 20:20, 40:20, 80:20, 120:20) and 2) to determine if different doses of CBD modulate other THC induced behavioral effects, compared with the control product and 3)To explore qualitatively whether CBD modulates THC effects by mechanisms that are not detected with standard clinical research tools. **Detailed Description:** Despite more than 40 years of research on the active compounds present in the cannabis plant, the influence of CBD consumption on the metabolism, pharmacology, and behavioral effects of THC remains fragmentary and scarcely documented in vivo in humans. Cannabis users are currently encouraged to choose products containing CBD, but evidence is lacking regarding its potential benefits when consumed jointly with THC across different ratios. Given the recent cannabis legalization in Canada and the widespread use of inhalation as the preferred mode of administration for non-therapeutic cannabis, closing this knowledge gap will help ensure public safety and allow regulatory bodies and public health authorities to elaborate more refined cannabis use guidelines and harm reduction strategies. It will also empower people who use cannabis to make more informed purchasing decisions and will drive the incubation of future research endeavors in the fields of medical and social sciences. The aim of this study is to improve our understanding of the (acute) behavioral and pharmacological effects of different doses of CBD administered concomitantly with THC via inhalation in individuals who engage in occasional cannabis use, taking into consideration multiple factors that can modulate such effects. This study will put to the test conceptions surrounding the interaction between specific cannabinoids by evaluating the role of CBD on the modulation of THC's effects pertaining to cognition, behavior, subjective experience, and physiological parameters. ### Conditions Module **Conditions:** - Cannabis - THC ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** CROSSOVER **Intervention Model Description:** In this crossover design, participants will be administered all phytocannabinoid doses contained in the four CBD:THC products and the control product (THC only) during participation in the study. Participant will be randomly assigned to one of the predetermined sequences with a CBD:THC product or control product at 5 dosages (CBD:THC of 0:20 mg, 20:20 mg, 40:20 mg, 80:20 mg and 120:20 mg). Participants will be randomized based on a balanced 5 by 5 Latin square. ##### Masking Info **Masking:** QUADRUPLE **Who Masked:** - PARTICIPANT - CARE_PROVIDER - INVESTIGATOR - OUTCOMES_ASSESSOR **Primary Purpose:** OTHER #### Enrollment Info **Count:** 100 **Type:** ESTIMATED **Phases:** - PHASE1 - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Group will receive four doses of CBD:THC ratio (20:20 mg, 40:20 mg, 80:20 mg and 120:20 mg) and a control product CBD:THC ratio (0:20 mg). Group will attend a total of five study visits (one for each study product) with at least 1 week between each visit. The order in which the study products will be administered depend on the randomization sequence. **Intervention Names:** - Drug: ∆9-tetrahydrocannabinol **Label:** CBD:THC Group 1 **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Group will receive four doses of CBD:THC ratio (20:20 mg, 40:20 mg, 80:20 mg and 120:20 mg) and a control product CBD:THC ratio (0:20 mg). Group will attend a total of five study visits (one for each study product) with at least 1 week between each visit. The order in which the study products will be administered depend on the randomization sequence. **Intervention Names:** - Drug: ∆9-tetrahydrocannabinol **Label:** CBD:THC Group 2 **Type:** EXPERIMENTAL #### Arm Group 3 **Description:** Group will receive four doses of CBD:THC ratio (20:20 mg, 40:20 mg, 80:20 mg and 120:20 mg) and a control product CBD:THC ratio (0:20 mg). Group will attend a total of five study visits (one for each study product) with at least 1 week between each visit. The order in which the study products will be administered depend on the randomization sequence. **Intervention Names:** - Drug: ∆9-tetrahydrocannabinol **Label:** CBD:THC Group 3 **Type:** EXPERIMENTAL #### Arm Group 4 **Description:** Group will receive four doses of CBD:THC ratio (20:20 mg, 40:20 mg, 80:20 mg and 120:20 mg) and a control product CBD:THC ratio (0:20 mg). Group will attend a total of five study visits (one for each study product) with at least 1 week between each visit. The order in which the study products will be administered depend on the randomization sequence. **Intervention Names:** - Drug: ∆9-tetrahydrocannabinol **Label:** CBD:THC Group 4 **Type:** EXPERIMENTAL #### Arm Group 5 **Description:** Group will receive four doses of CBD:THC ratio (20:20 mg, 40:20 mg, 80:20 mg and 120:20 mg) and a control product CBD:THC ratio (0:20 mg). Group will attend a total of five study visits (one for each study product) with at least 1 week between each visit. The order in which the study products will be administered depend on the randomization sequence. **Intervention Names:** - Drug: ∆9-tetrahydrocannabinol **Label:** CBD:THC Group 5 **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - CBD:THC Group 1 - CBD:THC Group 2 - CBD:THC Group 3 - CBD:THC Group 4 - CBD:THC Group 5 **Description:** Phytocannabinoids from plant inflorescences (CBD and THC dominant) - inhaled **Name:** ∆9-tetrahydrocannabinol **Other Names:** - Cannabidiol **Type:** DRUG ### Outcomes Module #### Other Outcomes **Description:** Plasma levels of CBD will be determined by high performance liquid chromatography-tandem mass spectrometry. **Measure:** Change in plasma concentrations of CBD **Time Frame:** Prior to the Product administration and 5,15, 80, 110, and 140 minutes after administration **Description:** Plasma levels of THC will be determined by high performance liquid chromatography-tandem mass spectrometry. **Measure:** Change in plasma concentrations of THC **Time Frame:** Prior to the Product administration and 5,15, 80, 110, and 140 minutes after administration **Description:** Plasma levels of CBD and THC will be determined by high performance liquid chromatography-tandem mass spectrometry. **Measure:** Change in plasma concentrations of Anandamide (AEA) **Time Frame:** Prior to the Product administration and 5,15, 80, 110, and 140 minutes after administration **Description:** Plasma levels of CBD and THC will be determined by high performance liquid chromatography-tandem mass spectrometry. **Measure:** Change in plasma concentrations of 2-Arachidonoylglycerol (2-AG) **Time Frame:** Prior to the Product administration and 5,15, 80, 110, and 140 minutes after administration **Description:** To explore potential genetic factors that could explain at least in part some of the participants' responses to the study outcomes and that have been associated with specific candidate genes (e.g., COMT, AKT1, DRD2, FAAH and cytochrome P450 genes). Using buccal swabs from EndoDNA test kits. These DNA tests will be used to map known genetic variants associated with the endocannabinoidome and related physiological systems to identify specific genotypes that correlate with neurocognitive and behavioral effects measured for each study product for an example application of the method). **Measure:** Genetic markers **Time Frame:** Baseline, Prior to the Product administration (only at visite 1) #### Primary Outcomes **Description:** Based on the scores obtained on the observer items (objective) and the participant-rated items (subjective) from the Clinician Administered Dissociative State Scale (CADSS). The CADSS is a 28-item validated instrument, includes 5 observer items and 23 participant self-report items rated on a 5-point scale, ranging from 0 (not at all) to 4 (extremely) on eight items. The score will reflect the extent to which participants were observed to be under the effect of cannabinoids, i.e., in adissociative state. **Measure:** Objective and subjective measures of cannabinoids effect **Time Frame:** Prior to the Product administration ,10 minutes and 80 minutes after inhalation #### Secondary Outcomes **Description:** Will be measured by the Positive and Negative Affect Schedule (PANAS). The PANAS is a 20-item validated questionnaire, used in both non-clinical and clinical populations. **Measure:** Positive and Negative Affect **Time Frame:** Prior to the Product administration , 10 minutes and 80 minutes post inhalation **Description:** Auditory oscillations, using an electroencephalogram (EEG), will be probe in response to 40-Hz FM and ascending/descending AM stimuli, using a 16-channel system with 250-Hz sampling rate and 24-bit resolution (model g.Nautilus PRO 16 g.SAHARA, g.tec, Schiedlberg, Austria). **Measure:** Neural oscillations **Time Frame:** Prior to the Product administration, 80 minutes post inhalation and at the end of the study visit, approximatively 140 minutes after inhalation **Description:** Symptoms of anxiety will be assessed using the States-Trait-Anxiety-Inventory (STAI). It consists of two 20-item self-report scales (trait and state anxiety) that measure the severity of anxiety in adults. Both subscales are composed of 20 statements rated on a 4-point Likert scale ranging from 1 ("not at all" and "almost never" for the state and trait subscales, respectively) to 4 ("very much" and "almost always" for the state and trait subscales, respectively). **Measure:** Anxiety Symptoms **Time Frame:** Prior to the Product administration, 10 minutes and 80 minutes after inhalation **Description:** Drug Effect Questionnaire (twenty-three-item) will be use to assess participant's physical signs, symptoms associated with cannabis inhalation and desire to use the product. The Drug Effects Questionnaire uses visual analogue scale, ranging from 0 (not at all) to 100 (extremely). **Measure:** Subjective Drug Effects **Time Frame:** 10 minutes and 80 minutes after inhalation **Description:** Subjective effects of cannabis will be assessed using the Cannabis Experience Questionnaire (CEQ), The CEQ measures participants' subjective experiences with cannabis consumption and consists of two subscales: pleasurable experiences (18 items), psychosis-like experiences (25 items), and after-effect experiences measuring the consequences of cannabis after use (12 items). Each item of each subscale is rated on a 5-point Likert scale, ranging from 1 (not at all) to 5 (extremely). **Measure:** Experience with Study Products **Time Frame:** 140 minutes after inhalation **Description:** This will help determine if different doses of CBD can modulate the feeling of paranoia and/or anxiety triggered by social interactions, in comparison to the control product. The research staff will give to the participant five dollars in cash. The participant will then be escorted out of the research center by a member of the research staff for a 10-minute walk to the hospital pharmacy with the instruction of purchasing an item of their choosing with the money. Once the task is completed, the participant will be escorted back to the research center. The research staff will walk approximately two meters behind the participant during the whole procedure and will be instructed not to engage in any conversation, unless the participant needs assistance or feels abnormally anxious. **Measure:** Social Exposition Challenge **Time Frame:** 70 minutes after inhalation **Description:** The Cambridge Neuropsychological Test Automated Battery tests will be used for the rapid assessment of multiple cognitive components. **Measure:** Change on cognition **Time Frame:** Prior to the Product administration (only at Visite 1) and 10 minutes after inhalation at each visit **Description:** To assess the success of the blind iwith the Blinding Success Questionnaire (BSQ). The specific aims of testing the blind are to a) determine which research product participants think they received and b) examine the associations between the research product participants think they received and their expectations, subjective cannabis perceptions, treatment outcomes, and side effects. **Measure:** Success of Blinding Questionnaire **Time Frame:** 10 minutes and 140 minutes after inhalation **Description:** When the participant inhales the investigational product, research staff will fill a questionnaire assessing participant compliance. **Measure:** Inhalation Adherence **Time Frame:** During inhalation procedure **Description:** Adverse events will be collected prior to administration of the study product (T0) and following administration of the study product (T1, T2 and T3). **Measure:** Change in Safety **Time Frame:** Baseline,10 minutes, 80 minutes and 140 minutes after inhalation **Description:** Signs of intoxication will be assess using the modified Standardized Field Sobriety Test. **Measure:** Visit Intoxication Assessment **Time Frame:** Through study visit completion, approximatively 140 minutes after product inhalation ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Between 21 and 49 years of age, inclusively; 2. Have used cannabis at least once in their lifetime and have used cannabis three days or less in the 30 days prior to enrollment; 3. Be able to provide a signed informed consent; 4. Willing to comply with study procedures and requirements as per protocol; 5. Have a forced expiratory volume in first second (FEV) less than or equal to 90 %; 6. Able to communicate and understand English or French language; 7. For female participants: a. No childbearing potential, defined as: i. postmenopausal (12 months of spontaneous amenorrhea and ≥ 45 years of age); or ii. Documented surgically sterilized (i.e., tubal ligation, hysterectomy, or bilateral oophorectomy); or b. For female of childbearing potential: i. Must have negative pregnancy test result at screening and at subsequent visits. ii. AND have no pregnancy plan while on the study iii. AND must agree to use a medically accepted method of birth control throughout the study. Exclusion criteria Participants will be excluded if any of the following criteria are met: 1. Any disabling medical condition, as assessed by medical history, physical exam, vital signs and/or laboratory assessments that, in the opinion of the study physician, precludes safe participation in the study or the ability to provide fully informed consent; 2. Severe psychiatric condition (history of schizophrenia, schizoaffective disorder or bipolar disorder; current acute psychosis, mania or current suicidality based on the Mini International Neuropsychiatric Interview); 3. Any other disabling, unstable or acute mental condition that, in the opinion of the study physician, precludes safe participation in the study or ability to provide fully informed consent; 4. Known chronic liver disease or aspartate transaminase/alanine transaminase (AST/ALT) two times higher than upper limit of normal values at screening visit; 5. Blood pressure higher than 130/80 mmHg; 6. Kidney disorders; 7. Bleeding disorders; 8. Current moderate or severe DSM-5 substance use disorder (except nicotine) according to SCID-V; 9. Currently pregnant, breastfeeding or planning to become pregnant either at screening or while enrolled in the study; 10. Pending legal action or other reason that, in the opinion of the study physician, might prevent study completion; 11. Use of medication within 7 days of experimental sessions; which, in the opinion of the Investigator, may interact with cannabis. 12. Participation in clinical studies or undergoing other investigational procedure involving cannabis or cannabinoids administration within 30 days prior to randomization. 13. Resting heart rate over 100 beats per minute. 14. Current body mass index (BMI) over 29.9 kg/m2. 15. Any clinically significant electrocardiogram abnormalities at screening visit. **Healthy Volunteers:** True **Maximum Age:** 49 Years **Minimum Age:** 21 Years **Sex:** ALL **Standard Ages:** - ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Pamela Lachance, PhD **Phone:** 514-890-8000 **Phone Ext:** 30938 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** François-Olivier Hébert, PhD **Phone:** 581 741-4941 **Role:** CONTACT #### Overall Officials **Official 1:** **Affiliation:** CRCHUM **Name:** Didier Jutras-Aswad, MD, MS **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000019966 - Term: Substance-Related Disorders - ID: D000064419 - Term: Chemically-Induced Disorders - ID: D000001523 - Term: Mental Disorders ### Condition Browse Module - Browse Branches - Abbrev: BC25 - Name: Substance Related Disorders - Abbrev: BXM - Name: Behaviors and Mental Disorders - Abbrev: All - Name: All Conditions - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M5449 - Name: Marijuana Abuse - Relevance: HIGH - As Found: Cannabis - ID: M21837 - Name: Substance-Related Disorders - Relevance: LOW - As Found: Unknown - ID: M30302 - Name: Chemically-Induced Disorders - Relevance: LOW - As Found: Unknown - ID: M4815 - Name: Mental Disorders - Relevance: LOW - As Found: Unknown - ID: M14473 - Name: Psychotic Disorders - Relevance: LOW - As Found: Unknown - ID: T170 - Name: Acute Graft Versus Host Disease - Relevance: LOW - As Found: Unknown - ID: T4202 - Name: Oculocerebral Syndrome With Hypopigmentation - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000002189 - Term: Marijuana Abuse ### Intervention Browse Module - Ancestors - ID: D000000927 - Term: Anticonvulsants - ID: D000006213 - Term: Hallucinogens - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000011619 - Term: Psychotropic Drugs - ID: D000018712 - Term: Analgesics, Non-Narcotic - ID: D000000700 - Term: Analgesics - ID: D000018689 - Term: Sensory System Agents - ID: D000018373 - Term: Peripheral Nervous System Agents - ID: D000063386 - Term: Cannabinoid Receptor Agonists - ID: D000063385 - Term: Cannabinoid Receptor Modulators - ID: D000018377 - Term: Neurotransmitter Agents - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000006728 - Term: Hormones - ID: D000006730 - Term: Hormones, Hormone Substitutes, and Hormone Antagonists ### Intervention Browse Module - Browse Branches - Abbrev: AntiConv - Name: Anticonvulsants - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Analg - Name: Analgesics - Abbrev: PsychDr - Name: Psychotropic Drugs ### Intervention Browse Module - Browse Leaves - ID: M5445 - Name: Cannabidiol - Relevance: HIGH - As Found: Sarcoma - ID: M16527 - Name: Dronabinol - Relevance: HIGH - As Found: MRS - ID: M4246 - Name: Anticonvulsants - Relevance: LOW - As Found: Unknown - ID: M9305 - Name: Hallucinogens - Relevance: LOW - As Found: Unknown - ID: M14474 - Name: Psychotropic Drugs - Relevance: LOW - As Found: Unknown - ID: M4032 - Name: Analgesics - Relevance: LOW - As Found: Unknown - ID: M20786 - Name: Analgesics, Non-Narcotic - Relevance: LOW - As Found: Unknown - ID: M20504 - Name: Neurotransmitter Agents - 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: D000013759 - Term: Dronabinol - ID: D000002185 - Term: Cannabidiol ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05112679 **Acronym:** OPORP **Brief Title:** Limb Health and Socket Pressure in Response to Powered Ankle Protheses **Official Title:** Limb Health and Socket Pressure in Response to Powered Ankle Prostheses #### Organization Study ID Info **ID:** 12350 #### Organization **Class:** OTHER **Full Name:** Indiana University ### Status Module #### Completion Date **Date:** 2023-07-19 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2023-10-03 **Type:** ACTUAL **Last Update Submit Date:** 2023-09-29 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2023-07-19 **Type:** ACTUAL #### Start Date **Date:** 2021-11-15 **Type:** ACTUAL **Status Verified Date:** 2023-09 #### Study First Post Date **Date:** 2021-11-09 **Type:** ACTUAL **Study First Submit Date:** 2021-08-13 **Study First Submit QC Date:** 2021-11-04 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** University of Notre Dame **Class:** FED **Name:** United States Department of Defense #### Lead Sponsor **Class:** OTHER **Name:** Indiana University #### Responsible Party **Investigator Affiliation:** Indiana University **Investigator Full Name:** Dr. Sashwati Roy **Investigator Title:** Professor of Surgery **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** True **Is FDA Regulated Drug:** False **Is US Export:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** this project seeks to understand and quantify the effects of powered transtibial prostheses on socket loading and direct measures of residual limb health so as to inform the optimization of prosthesis fit. **Detailed Description:** Some estimates suggest that by 2050, as many as 3.6 million people in the United States will be living with limb loss, and at least 60% of them will have had at least a foot removed For military personnel, combat-related amputations remain one of the most common major disabling war-related injuries from modern armed conflict. Technological advancements in active prosthetic devices for individuals with transtibial amputation offer the potential for superior function in key areas that could lead to higher rates of RTD and improved quality of life. Currently intended primarily for individuals with a K-level of 3 or 4, active transtibial prostheses that provide controlled plantar/dorsiflexion in either swing (microprocessor-controlled prostheses) or late stance (prostheses with powered propulsion) are likely to become the gold standard in the future as technology continues to improve Indeed, users of these types of prostheses have higher mobility than those using any of the other four categories of prosthetic ankle-foot mechanisms for unlimited community ambulators. Note that a major insurer has recently declared microprocessor-controlled ankle-foot prostheses medically necessary for members whose functional level is 3 or above.The PROPRIO FOOT® by Ossur, is a microprocessor-controlled prosthesis that regulates the angle of ankle dorsiflexion during the swing phase. This added ankle control of these devices reduces the risk of falls by increasing toe clearance supports more natural standing posture on slopes and improves stair and slope ascent/descent capability by adapting to the change in terrain.On stairs, the PROPRIO FOOT® has been shown to improve affected leg knee kinematics (increased knee flexion) and kinetics (increased knee moment) instance. These improvements also contributed to higher interlimb symmetry reduced energetic cost of slope ascent and higher Amputee Mobility Predictor with a Prosthesis (AMPPRO) scores . Although the ankle of the PROPRIO FOOT® can be controlled in swing, the device does not have adequate power to provide an active propulsion instance. The Empower ankle by Ottobock is a powered prosthesis that provides active propulsion in late stance to mimic the positive work performed by the ankle plantar flexors in push-off. The Empower has been shown to improve affected leg kinematics (increased ankle range of motion and reduced knee flexion) on smooth flat ground ramp ascent and gravel\]. In terms of kinetics, the Empower likewise results in increased ankle power on level ground stairs and ramps . Active prostheses like the PROPRIO FOOT® and Empower ankle offer great potential to more completely restore the locomotor capabilities of individuals with transtibial amputation, perhaps enhancing RTD for military personnel. As with all prosthetic components, though, these active devices are of little use if they induce pain and/or injury at the residual limb to the degree that the user will simply not wear them. The investigators will examine how optimal fit of lower limb prostheses can impact individuals comfort and/or reduce irritation. ### Conditions Module **Conditions:** - Pressure Ulcer, Ankle - Prosthesis User - Prosthesis Durability - Mobility Limitation - Skin Wound - Amputation; Traumatic, Foot - Amputation - Limb Deficiencies ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** SUPPORTIVE_CARE #### Enrollment Info **Count:** 6 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** microprocessor-controlled prosthesis that regulates the angle of ankle dorsiflexion during the swing phase **Intervention Names:** - Device: PROPRIO FOOT® by Ossur **Label:** Proprio Foot **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** a powered prosthesis that provides active propulsion in late stance to mimic the positive work performed by the ankle plantar-flexors in push-off. The Empower has been shown to improve affected leg kinematics (increased ankle range of motion and reduced knee flexion) on smooth flat ground, ramp ascent, and gravel **Intervention Names:** - Device: Empower ankle by Ottobock **Label:** Empower Ankle **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Proprio Foot **Description:** Active prostheses like the PROPRIO FOOT® offer great potential to more completely restore the locomotor capabilities of individuals with transtibial amputation, perhaps enhancing RTD for military personnel. The investigators will examine factors of socket loading and direct measures of residual limb health so as to inform the optimization of prosthesis fit. The testing will consist of walking on a treadmill and the use of a 3D motion capture camera to track movement and angles of the participant's upper and lower extremities. Ascending and descending on stairs and ramps with the device will be completed. Participants will also have laser speckle imaging to measure blood flow to skin and transepidermal water loss measurement to check skin health. **Name:** PROPRIO FOOT® by Ossur **Type:** DEVICE #### Intervention 2 **Arm Group Labels:** - Empower Ankle **Description:** Active prostheses -such as the Empower ankle offer great potential to more completely restore the locomotor capabilities of individuals with transtibial amputation, perhaps enhancing RTD for military personnel. The investigators will examine factors of socket loading and direct measures of residual limb health so as to inform the optimization of prosthesis fit. The testing will consist of walking on a treadmill and the use of a 3D motion capture camera to track movement and angles of the participant's upper and lower extremities. Ascending and descending on stairs and ramps with the device will be completed. Participants will also have laser speckle imaging to measure blood flow to skin and trans epidermal water loss measurement to check skin health. **Name:** Empower ankle by Ottobock **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Description:** effects of a powered transtibial prosthesis on the socket pressure for level-ground walking, stair ascent/descent, and ramp ascent/descent in comparison to a microprocessor-controlled prosthesis and a passive prosthesis **Measure:** Effects of use of a powered transtibial prosthesis on socket pressure **Time Frame:** 4 weeks #### Secondary Outcomes **Description:** Changes measured with laser speckle imaging. **Measure:** Change in Skin Perfusion **Time Frame:** 4 weeks **Description:** Water loss change is measured via the TEWL device- the reduction in the score denotes improvement in water loss **Measure:** Change in transepidermal water loss **Time Frame:** 4 weeks **Description:** Change in PEQ-13 score over the course of 4 weeks **Measure:** Change in PEQ-13 Score **Time Frame:** 4 weeks **Description:** Change in Socket Comfort Score over the course of 4 weeks **Measure:** Socket Comfort Score **Time Frame:** 4 weeks ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Ages 18 and above * Weight ≤ 280 lb * Ambulate at a K3 level or higher-level determined from patient EHR * At least 3 months post-amputation per physician discretion * Residual limb length greater than 4.5 inches * Use of a passive prosthesis * Unilateral transtibial amputees * Must be able to ambulate without any assistive devices * Subjects must be able to follow directions and give informed consent on their own Exclusion Criteria: * Conditions and/or co-morbidities that would prevent wearing a prosthetic socket, affect gait, or influence function of the contralateral limb * Other amputees * Cognitive deficits or mental health problems that would limit ability to consent and participate fully in the study protocol * Women who are pregnant or who plan to become pregnant in the near future * Individuals diagnosed with renal failure * Participants unwilling to wear a cloth face covering for the duration of each visit **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Indianapolis **Country:** United States **Facility:** Indiana University Health Methodist Hospital **State:** Indiana **Zip:** 46228 #### Overall Officials **Official 1:** **Affiliation:** Indiana University **Name:** Sashwati Roy, PhD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **Access Criteria:** Email study contact **Description:** The investigators will share deidentified patient data consisting of the patient PEQ and comfort scores and transpepidermal water loss data upon request. **Info Types:** - SAP - ICF **IPD Sharing:** YES **Time Frame:** 6 months after completion ## Document Section ### Large Document Module #### Large Docs - Date: 2022-10-25 - Filename: ICF_000.pdf - Has ICF: True - Has Protocol: False - Has SAP: False - Label: Informed Consent Form - Size: 253196 - Type Abbrev: ICF - Upload Date: 2023-08-29T13:43 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000012883 - Term: Skin Ulcer - ID: D000012871 - Term: Skin Diseases - ID: D000014947 - Term: Wounds and Injuries - ID: D000011183 - Term: Postoperative Complications - ID: D000010335 - Term: Pathologic Processes ### Condition Browse Module - Browse Branches - Abbrev: BC26 - Name: Wounds and Injuries - Abbrev: All - Name: All Conditions - Abbrev: BC17 - Name: Skin and Connective Tissue Diseases - Abbrev: BC23 - Name: Symptoms and General Pathology ### Condition Browse Module - Browse Leaves - ID: M17685 - Name: Wounds and Injuries - Relevance: LOW - As Found: Unknown - ID: M6870 - Name: Pressure Ulcer - Relevance: HIGH - As Found: Pressure Ulcer - ID: M17206 - Name: Ulcer - Relevance: LOW - As Found: Unknown - ID: M26689 - Name: Mobility Limitation - Relevance: HIGH - As Found: Mobility Limitation - ID: M14338 - Name: Prosthesis Failure - Relevance: HIGH - As Found: Prosthesis Durability - ID: M4009 - Name: Amputation, Traumatic - Relevance: HIGH - As Found: Amputation; Traumatic - ID: M15686 - Name: Skin Ulcer - Relevance: LOW - As Found: Unknown - ID: M15674 - Name: Skin Diseases - Relevance: LOW - As Found: Unknown - ID: M14065 - Name: Postoperative Complications - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000003668 - Term: Pressure Ulcer - ID: D000051346 - Term: Mobility Limitation - ID: D000011475 - Term: Prosthesis Failure - ID: D000000673 - Term: Amputation, Traumatic ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT02023879 **Brief Title:** Phase III Study To Evaluate Alirocumab in Patients With Hypercholesterolemia Not Treated With a Statin (ODYSSEY CHOICE II) **Official Title:** A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study Evaluating the Efficacy and Safety of Alirocumab in Patients With Primary Hypercholesterolemia Not Treated With a Statin #### Organization Study ID Info **ID:** EFC13786 #### Organization **Class:** INDUSTRY **Full Name:** Sanofi #### Secondary ID Infos **ID:** 2013-002659-14 **Type:** EUDRACT_NUMBER **Domain:** UTN **ID:** U1111-1146-3517 **Type:** OTHER ### Status Module #### Completion Date **Date:** 2017-06-30 **Type:** ACTUAL #### Disp First Post Date **Date:** 2015-11-01 **Type:** ESTIMATED **Disp First Submit Date:** 2015-10-08 **Disp First Submit QC Date:** 2015-10-08 #### Expanded Access Info #### Last Update Post Date **Date:** 2018-07-27 **Type:** ACTUAL **Last Update Submit Date:** 2018-06-29 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2014-10-27 **Type:** ACTUAL #### Results First Post Date **Date:** 2017-03-15 **Type:** ACTUAL **Results First Submit Date:** 2017-01-24 **Results First Submit QC Date:** 2017-01-24 #### Start Date **Date:** 2013-12-16 **Status Verified Date:** 2018-06 #### Study First Post Date **Date:** 2013-12-30 **Type:** ESTIMATED **Study First Submit Date:** 2013-12-06 **Study First Submit QC Date:** 2013-12-24 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** Regeneron Pharmaceuticals #### Lead Sponsor **Class:** INDUSTRY **Name:** Sanofi #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** Primary Objective: To demonstrate the reduction of low-density lipoprotein cholesterol (LDL-C) by a regimen of Alirocumab including a starting dose of 150 mg every 4 weeks (Q4W) as add-on to non-statin lipid modifying background therapy or as monotherapy in comparison with placebo in participants with primary hypercholesterolemia not treated with a statin. Secondary Objective: * To evaluate the effects on other lipid parameters of Alirocumab 150 mg Q4W versus placebo. * To evaluate the safety and tolerability of Alirocumab 150 mg Q4W. Alirocumab 75 mg Q2W was added as a calibrator arm. **Detailed Description:** The core study duration was approximately 35 weeks per participant (screening: 3 weeks, double-blind treatment period: 24 weeks; follow-up: 8 weeks). Participants who successfully completed the treatment period had the possibility to participate in an optional open-label treatment period with Alirocumab 150 mg Q4W until second quarter 2017 or until the drug is commercially available in the country, whatever occurred first. ### Conditions Module **Conditions:** - Hypercholesterolemia ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** A double-blind treatment period of 24 weeks (3 parallel arms) followed by an open-label extension period (single arm) ##### Masking Info **Masking:** TRIPLE **Masking Description:** Masking during the double-blind treatment period **Who Masked:** - PARTICIPANT - CARE_PROVIDER - INVESTIGATOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 233 **Type:** ACTUAL **Phases:** - PHASE3 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Period 1: Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks. Period 2: Alirocumab 150 mg SC injection every 4 weeks (Q4W) from Week 24 until second quarter 2017 or until the drug is commercially available in the country, whatever occurred first. Alirocumab dose could be either up-titrated to 150 mg Q2W from Week 36 or maintained according to the investigator judgement and low-density lipoprotein cholesterol (LDL-C) values. Subsequent down titration to 150 mg Q4W was allowed. **Intervention Names:** - Drug: Alirocumab - Drug: Placebo (for Alirocumab) - Drug: Non-statin LMT - Other: Diet Alone **Label:** Placebo Q2W **Type:** PLACEBO_COMPARATOR #### Arm Group 2 **Description:** Period 1: Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted LDL-C levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or \<30% LDL-C reduction from baseline. Period 2: Alirocumab 150 mg SC injection Q4W from Week 24 until second quarter 2017 or until the drug is commercially available in the country, whatever occurred first. Alirocumab dose could be either up-titrated to 150 mg Q2W from Week 36 or maintained according to the investigator judgement and LDL-C values. Subsequent down titration to 150 mg Q4W was allowed. **Intervention Names:** - Drug: Alirocumab - Drug: Non-statin LMT - Other: Diet Alone **Label:** Alirocumab 75 mg Q2W/Up to 150 mg Q2W (Calibrator) **Type:** OTHER #### Arm Group 3 **Description:** Period 1: Alirocumab 150 mg SC injection Q4W alternating with placebo (for alirocumab) Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted LDL-C levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or \<30% LDL-C reduction from baseline. Period 2: Alirocumab 150 mg SC injection Q4W from Week 24 until second quarter 2017 or until the drug is commercially available in the country, whatever occurred first. Alirocumab dose could be either up-titrated to 150 mg Q2W from Week 36 or maintained according to the investigator judgement and LDL-C values. Subsequent down titration to 150 mg Q4W was allowed. **Intervention Names:** - Drug: Alirocumab - Drug: Placebo (for Alirocumab) - Drug: Non-statin LMT - Other: Diet Alone **Label:** Alirocumab 150 mg Q4W/Up to 150 mg Q2W **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Alirocumab 150 mg Q4W/Up to 150 mg Q2W - Alirocumab 75 mg Q2W/Up to 150 mg Q2W (Calibrator) - Placebo Q2W **Description:** Solution for injection in the abdomen, thigh, or outer area of the upper arm by self-injection or by another designated person using auto-injector (also known as pre-filled pen). **Name:** Alirocumab **Other Names:** - SAR236553 - REGN727 - Praluent® **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Alirocumab 150 mg Q4W/Up to 150 mg Q2W - Placebo Q2W **Description:** Solution for injection in the abdomen, thigh, or outer area of the upper arm by self-injection or by another designated person using auto-injector (also known as pre-filled pen). **Name:** Placebo (for Alirocumab) **Type:** DRUG #### Intervention 3 **Arm Group Labels:** - Alirocumab 150 mg Q4W/Up to 150 mg Q2W - Alirocumab 75 mg Q2W/Up to 150 mg Q2W (Calibrator) - Placebo Q2W **Description:** Ezetimibe or Fenofibrate at stable dose as background therapy. **Name:** Non-statin LMT **Type:** DRUG #### Intervention 4 **Arm Group Labels:** - Alirocumab 150 mg Q4W/Up to 150 mg Q2W - Alirocumab 75 mg Q2W/Up to 150 mg Q2W (Calibrator) - Placebo Q2W **Description:** Stable cholesterol-lowering diet as background therapy. **Name:** Diet Alone **Type:** OTHER ### Outcomes Module #### Other Outcomes **Description:** Mean percent changes (and standard deviations) observed during the open-label extension period are provided. **Measure:** Percent Change From Baseline in Calculated LDL-C at Week 32, 36, 48, 72, 96, 120, 144, 168 On-Treatment Analysis in Open Label Extension Treatment Phase **Time Frame:** Baseline, Week 32, 36, 48, 72, 96, 120, 144 and Week 168 #### Primary Outcomes **Description:** Adjusted Least-squares (LS) means and standard errors at Week 24 were obtained from a mixed-effect model with repeated measures (MMRM) to account for missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment were used in the model (ITT analysis). **Measure:** Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-Treat (ITT Analysis) **Time Frame:** From Baseline to Week 24 #### Secondary Outcomes **Description:** Adjusted LS means and standard errors at Week 24 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection) (on-treatment analysis). **Measure:** Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis **Time Frame:** From Baseline to Week 24 **Description:** Adjusted LS means and standard errors at Week 12 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment. **Measure:** Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis **Time Frame:** From Baseline to Week 24 **Description:** Adjusted LS means and standard errors at Week 12 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection). **Measure:** Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis **Time Frame:** From Baseline to Week 24 **Description:** Adjusted LS means and standard errors at Week 12 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment and assigning a weight of 0.25 for Week 9, 10, 11 and 12 time points. **Measure:** Percent Change From Baseline in Calculated LDL-C to Averaged Weeks 9 to 12 - ITT- Analysis **Time Frame:** From Baseline to Week 24 **Description:** Adjusted LS means and standard errors at Week 12 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection) and assigning a weight of 0.25 for Week 9, 10, 11 and 12 time points. **Measure:** Percent Change From Baseline in Calculated LDL-C at Averaged Week 9 to 12 - On-Treatment Analysis **Time Frame:** From Baseline to Week 24 **Description:** Adjusted LS means and standard errors at Week 24 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment. **Measure:** Percent Change From Baseline in Apolipoprotein (Apo) B at Week 24 - ITT Analysis **Time Frame:** From Baseline to Week 24 **Description:** Adjusted LS means and standard errors at Week 24 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection). **Measure:** Percent Change From Baseline in Apo B at Week 24 - On-treatment Analysis **Time Frame:** From Baseline to Week 24 **Description:** Adjusted LS means and standard errors at Week 24 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment. **Measure:** Percent Change From Baseline in Non-HDL-C at Week 24 - ITT Analysis **Time Frame:** From Baseline to Week 24 **Description:** Adjusted LS means and standard errors at Week 24 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection). **Measure:** Percent Change From Baseline in Non-HDL-C at Week 24 - On-treatment Analysis **Time Frame:** From Baseline to Week 24 **Description:** Adjusted LS means and standard errors at Week 24 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment. **Measure:** Percent Change From Baseline in Total-C at Week 24 - ITT Analysis **Time Frame:** From Baseline to Week 24 **Description:** Adjusted LS means and standard errors at Week 12 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment. **Measure:** Percent Change From Baseline in Apo B at Week 12 - ITT Analysis **Time Frame:** From Baseline to Week 24 **Description:** Adjusted LS means and standard errors at Week 12 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment. **Measure:** Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis **Time Frame:** From Baseline to Week 24 **Description:** Adjusted LS means and standard errors at Week 12 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment. **Measure:** Percent Change From Baseline in Total-C at Week 12 - ITT Analysis **Time Frame:** From Baseline to Week 24 **Description:** Moderate CV risk: 10-year fatal cardiovascular disease (CVD) risk Systemic Coronary Risk Evaluation (SCORE) ≥1 and \<5%. High CV risk: 10-year fatal CVD risk SCORE ≥5% or moderate chronic kidney disease or type 1 or type 2 diabetes mellitus without target organ damage or familial hypercholesterolemia. Very high CV risk: history of documented coronary heart disease, ischemic stroke, peripheral artery disease, transient ischemic attack, abdominal aortic aneurysm, or carotid artery occlusion \>50% without symptoms; carotid endarterectomy or carotid artery stent procedure; renal artery stenosis, or renal artery stent procedure; or type 1 or type 2 diabetes mellitus with target organ damage. Adjusted percentages at Week 24 were obtained from a multiple imputation approach model for handling of missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment were included. **Measure:** Percentage of Very High Cardiovascular (CV) Risk Participants Achieving Calculated LDL-C <70 mg/dL (<1.81 mmol/L) or Moderate or High CV Risk Participants Achieving Calculated LDL-C <100 mg/dL (<2.59 mmol/L) at Week 24 - ITT Analysis **Time Frame:** From Baseline to Week 24 **Description:** Adjusted percentages at Week 24 from multiple imputation approach including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection). **Measure:** Percentage of Very High CV Risk Participants Achieving Calculated LDL-C< 70 mg/dL (<1.81 mmol/L) or Moderate or High CV Risk Participants Achieving Calculated LDL-C< 100 mg/dL (<2.59 mmol/L) at Week 24 - On-treatment Analysis **Time Frame:** From Baseline to Week 24 **Description:** Adjusted percentages at Week 24 from last observation carried forward (LOCF) approach including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. **Measure:** Percentage of Participants Achieving Calculated LDL-C< 70 mg/dL (<1.81 mmol/L) at Week 24 - ITT Analysis **Time Frame:** From Baseline to Week 24 **Description:** Adjusted percentages at Week 24 from LOCF approach including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection). **Measure:** Percentage of Participants Achieving Calculated LDL-C <70 mg/dL (<1.81 mmol/L) at Week 24 - On-treatment Analysis **Time Frame:** From Baseline to Week 24 **Description:** Adjusted means and standard errors at Week 24 from a multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment. **Measure:** Percent Change From Baseline in Lipoprotein (a) at Week 24 - ITT Analysis **Time Frame:** From Baseline to Week 24 **Description:** Adjusted means and standard errors at Week 12 from a multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. **Measure:** Percent Change From Baseline in Lipoprotein (a) at Week 12 - ITT Analysis **Time Frame:** From Baseline to Week 24 **Description:** Adjusted LS means and standard errors at Week 24 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment. **Measure:** Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis **Time Frame:** From Baseline to Week 24 **Description:** Adjusted LS means and standard errors at Week 12 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment. **Measure:** Percent Change From Baseline in HDL-C at Week 12 - ITT Analysis **Time Frame:** From Baseline to Week 24 **Description:** Adjusted means and standard errors at Week 24 from a multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment. **Measure:** Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis **Time Frame:** From Baseline to Week 24 **Description:** Adjusted means and standard errors at Week 12 from a multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment. **Measure:** Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis **Time Frame:** From Baseline to Week 24 **Description:** Adjusted LS means and standard errors at Week 24 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment. **Measure:** Percent Change From Baseline in Apo A-1 at Week 24 - ITT Analysis **Time Frame:** From Baseline to Week 24 **Description:** Adjusted LS means and standard errors at Week 12 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment. **Measure:** Percent Change From Baseline in Apo A-1 at Week 12 - ITT Analysis **Time Frame:** From Baseline to Week 24 ### Eligibility Module **Eligibility Criteria:** Inclusion criteria: Participants with primary hypercholesterolemia (heterozygous familial hypercholesterolemia \[heFH\] or non-FH) not adequately controlled with their non-statin LMT (either ezetimibe or fenofibrate) or diet alone. Exclusion criteria: * LDL-C \<70 mg/dL (1.81 mmol/L) at screening for statin intolerant participants at very high cardiovascular (CV) risk; * LDL-C \<100 mg/dL (\<2.59 mmol/L) at screening for statin intolerant participants at high or moderate CV risk or, participants not fulfilling the statin intolerant definition at moderate CV risk; * LDL-C ≥160 mg/dL (≥4.1 mmol/L) at screening for participants receiving diet only or, participants not fulfilling the statin intolerant definition at moderate CV risk and receiving a non-statin LMT. The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial. **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Beverly Hills **Country:** United States **Facility:** Investigational Site Number 840703 **State:** California **Zip:** 90211 **Location 2:** **City:** Atlantis **Country:** United States **Facility:** Investigational Site Number 840704 **State:** Florida **Zip:** 33462 **Location 3:** **City:** Jacksonville **Country:** United States **Facility:** Investigational Site Number 840708 **State:** Florida **Zip:** 32216 **Location 4:** **City:** Sarasota **Country:** United States **Facility:** Investigational Site Number 840701 **State:** Florida **Zip:** 34239 **Location 5:** **City:** Fall River **Country:** United States **Facility:** Investigational Site Number 840706 **State:** Massachusetts **Zip:** 02720 **Location 6:** **City:** Saint Louis **Country:** United States **Facility:** Investigational Site Number 840705 **State:** Missouri **Zip:** 63131 **Location 7:** **City:** Durham **Country:** United States **Facility:** Investigational Site Number 840707 **State:** North Carolina **Zip:** 27710 **Location 8:** **City:** Summerville **Country:** United States **Facility:** Investigational Site Number 840702 **State:** South Carolina **Zip:** 29485 **Location 9:** **City:** Ashford **Country:** Australia **Facility:** Investigational Site Number 036703 **Zip:** 5035 **Location 10:** **City:** Perth **Country:** Australia **Facility:** Investigational Site Number 036702 **Zip:** 6000 **Location 11:** **City:** Woolloongabba **Country:** Australia **Facility:** Investigational Site Number 036701 **Zip:** 4102 **Location 12:** **City:** Antwerpen **Country:** Belgium **Facility:** Investigational Site Number 056702 **Zip:** 2060 **Location 13:** **City:** Haine-Saint-Paul **Country:** Belgium **Facility:** Investigational Site Number 056703 **Zip:** 7100 **Location 14:** **City:** Leuven **Country:** Belgium **Facility:** Investigational Site Number 056701 **Zip:** 3000 **Location 15:** **City:** Chicoutimi **Country:** Canada **Facility:** Investigational Site Number 124703 **Zip:** G7H 7P2 **Location 16:** **City:** Quebec **Country:** Canada **Facility:** Investigational Site Number 124701 **Zip:** G1V 4M6 **Location 17:** **City:** Sherbrooke **Country:** Canada **Facility:** Investigational Site Number 124704 **Zip:** J1H 1Z1 **Location 18:** **City:** Toronto **Country:** Canada **Facility:** Investigational Site Number 124706 **Zip:** M9V 4B4 **Location 19:** **City:** Vancouver **Country:** Canada **Facility:** Investigational Site Number 124702 **Zip:** V5Z 1M9 **Location 20:** **City:** Victoria **Country:** Canada **Facility:** Investigational Site Number 124705 **Zip:** V8T 5G4 **Location 21:** **City:** Aarhus **Country:** Denmark **Facility:** Investigational Site Number 208703 **Zip:** 8200 **Location 22:** **City:** Esbjerg **Country:** Denmark **Facility:** Investigational Site Number 208702 **Zip:** 6700 **Location 23:** **City:** Glostrup **Country:** Denmark **Facility:** Investigational Site Number 208701 **Zip:** 2600 **Location 24:** **City:** Hvidovre **Country:** Denmark **Facility:** Investigational Site Number 208704 **Zip:** 2650 **Location 25:** **City:** Køge **Country:** Denmark **Facility:** Investigational Site Number 208705 **Zip:** 4600 **Location 26:** **City:** Amsterdam **Country:** Netherlands **Facility:** Investigational Site Number 528701 **Zip:** 1105 AZ **Location 27:** **City:** Den Helder **Country:** Netherlands **Facility:** Investigational Site Number 528708 **Zip:** 1782 GZ **Location 28:** **City:** Hoogeveen **Country:** Netherlands **Facility:** Investigational Site Number 528702 **Zip:** 7909 AA **Location 29:** **City:** Hoorn **Country:** Netherlands **Facility:** Investigational Site Number 528703 **Zip:** 1625 HV **Location 30:** **City:** Rotterdam **Country:** Netherlands **Facility:** Investigational Site Number 528706 **Zip:** 3045 PM **Location 31:** **City:** Sneek **Country:** Netherlands **Facility:** Investigational Site Number 528709 **Zip:** 8601 ZK **Location 32:** **City:** Utrecht **Country:** Netherlands **Facility:** Investigational Site Number 528704 **Zip:** 3584 CX **Location 33:** **City:** Venlo **Country:** Netherlands **Facility:** Investigational Site Number 528707 **Zip:** 5912 BL **Location 34:** **City:** Auckland **Country:** New Zealand **Facility:** Investigational Site Number 554702 **Zip:** 1023 **Location 35:** **City:** Christchurch **Country:** New Zealand **Facility:** Investigational Site Number 554701 **Zip:** 8011 **Location 36:** **City:** A Coruna **Country:** Spain **Facility:** Investigational Site Number 724703 **Zip:** 15006 **Location 37:** **City:** Barcelona **Country:** Spain **Facility:** Investigational Site Number 724707 **Zip:** 08025 **Location 38:** **City:** Barcelona **Country:** Spain **Facility:** Investigational Site Number 724710 **Zip:** 08035 **Location 39:** **City:** Córdoba **Country:** Spain **Facility:** Investigational Site Number 724702 **Zip:** 14004 **Location 40:** **City:** Granada **Country:** Spain **Facility:** Investigational Site Number 724705 **Zip:** 18012 **Location 41:** **City:** Sant Joan Despí **Country:** Spain **Facility:** Investigational Site Number 724709 **Zip:** 08970 **Location 42:** **City:** Santiago De Compostela **Country:** Spain **Facility:** Investigational Site Number 724706 **Zip:** 15706 **Location 43:** **City:** Zaragoza **Country:** Spain **Facility:** Investigational Site Number 724701 **Zip:** 50009 #### Overall Officials **Official 1:** **Affiliation:** Sanofi **Name:** Clinical Sciences & Operations **Role:** STUDY_DIRECTOR ### References Module #### References **Citation:** Stroes E, Guyton JR, Lepor N, Civeira F, Gaudet D, Watts GF, Baccara-Dinet MT, Lecorps G, Manvelian G, Farnier M; ODYSSEY CHOICE II Investigators. Efficacy and Safety of Alirocumab 150 mg Every 4 Weeks in Patients With Hypercholesterolemia Not on Statin Therapy: The ODYSSEY CHOICE II Study. J Am Heart Assoc. 2016 Sep 13;5(9):e003421. doi: 10.1161/JAHA.116.003421. **PMID:** 27625344 ## 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: D000091362 - Term: PCSK9 Inhibitors - ID: D000000924 - Term: Anticholesteremic Agents - ID: D000000960 - Term: Hypolipidemic Agents - ID: D000000963 - Term: Antimetabolites - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000015842 - Term: Serine Proteinase Inhibitors - ID: D000011480 - Term: Protease Inhibitors - ID: D000004791 - Term: Enzyme Inhibitors - ID: D000057847 - Term: Lipid Regulating Agents - ID: D000007155 - Term: Immunologic Factors - ID: D000045505 - Term: Physiological Effects of Drugs ### Intervention Browse Module - Browse Branches - Abbrev: PhSol - Name: Pharmaceutical Solutions - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Lipd - Name: Lipid Regulating Agents - Abbrev: Infe - Name: Anti-Infective Agents - Abbrev: AA - Name: Amino Acids ### Intervention Browse Module - Browse Leaves - ID: M21860 - Name: Pharmaceutical Solutions - Relevance: LOW - As Found: Unknown - ID: M347350 - Name: Alirocumab - Relevance: HIGH - As Found: Testicular - ID: M409 - Name: Ezetimibe - Relevance: LOW - As Found: Unknown - ID: M14218 - Name: Fenofibrate - Relevance: LOW - As Found: Unknown - ID: M21155 - Name: Hydroxymethylglutaryl-CoA Reductase Inhibitors - Relevance: LOW - As Found: Unknown - ID: M4225 - Name: Antibodies - Relevance: LOW - As Found: Unknown - ID: M4230 - Name: Antibodies, Monoclonal - Relevance: HIGH - As Found: Testicular - ID: M10184 - Name: Immunoglobulins - Relevance: LOW - As Found: Unknown - ID: M2849 - Name: PCSK9 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: M14343 - Name: Protease Inhibitors - Relevance: LOW - As Found: Unknown - ID: M18391 - Name: Serine Proteinase Inhibitors - Relevance: LOW - As Found: Unknown - ID: M19609 - Name: HIV Protease Inhibitors - Relevance: LOW - As Found: Unknown - ID: M7951 - Name: Enzyme Inhibitors - Relevance: LOW - As Found: Unknown - ID: M28883 - Name: Lipid Regulating Agents - Relevance: LOW - As Found: Unknown - ID: M10201 - Name: Immunologic Factors - Relevance: LOW - As Found: Unknown - ID: T18 - Name: Serine - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: C000571059 - Term: Alirocumab - ID: D000000911 - Term: Antibodies, Monoclonal ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module **Description:** Reported AEs/deaths are treatment-emergent ie; AEs that developed/worsened and deaths that occurred 'on treatment'; from 1st dose up to last dose (active/placebo depending on Q2W/Q4W dosing) in DB period+70 days, truncated at the day before 1st dose in OL period for participants entering in OL period; from 1st dose up to last dose in OL period+70 days. #### Event Groups **Group ID:** EG000 **Title:** Placebo Q2W **Deaths Num At Risk:** 58 **Description:** Participants exposed to placebo SC injection Q2W added to stable non-statin LMT or diet alone (mean exposure of 23 weeks). **ID:** EG000 **Other Num Affected:** 28 **Other Num at Risk:** 58 **Serious Number Affected:** 4 **Serious Number At Risk:** 58 **Title:** Placebo Q2W **Group ID:** EG001 **Title:** Alirocumab 75 mg Q2W/Up150 mg Q2W **Deaths Num At Risk:** 115 **Description:** Participants exposed to alirocumab 75 mg Q2W/up to 150 mg Q2W SC injection added to stable non-statin LMT or diet alone (mean exposure of 23 weeks). **ID:** EG001 **Other Num Affected:** 61 **Other Num at Risk:** 115 **Serious Number Affected:** 7 **Serious Number At Risk:** 115 **Title:** Alirocumab 75 mg Q2W/Up150 mg Q2W **Group ID:** EG002 **Title:** Alirocumab 150 mg Q4W/Up150 mg Q2W **Deaths Num At Risk:** 58 **Description:** Participants exposed to alirocumab 150 mg Q4W/up to 150 mg Q2W SC injection added to stable non-statin LMT or diet alone (mean exposure of 22 weeks). **ID:** EG002 **Other Num Affected:** 29 **Other Num at Risk:** 58 **Serious Number Affected:** 7 **Serious Number At Risk:** 58 **Title:** Alirocumab 150 mg Q4W/Up150 mg Q2W **Group ID:** EG003 **Title:** Alirocumab 150 mg Q4W (After Placebo Q2W) **Deaths Num At Risk:** 51 **Description:** Participants exposed to alirocumab 150 mg Q4W SC injection added to stable non-statin LMT or diet alone (mean exposure of 128 weeks) after having received Placebo Q2W for 24 weeks. **ID:** EG003 **Other Num Affected:** 42 **Other Num at Risk:** 51 **Serious Number Affected:** 15 **Serious Number At Risk:** 51 **Title:** Alirocumab 150 mg Q4W (After Placebo Q2W) **Group ID:** EG004 **Title:** Alirocumab 150 mg Q4W (After Alirocumab 75 Q2W/Up150 Q2W) **Deaths Num Affected:** 2 **Deaths Num At Risk:** 106 **Description:** Participants exposed to alirocumab 150 mg Q4W SC injection added to stable non-statin LMT or diet alone (mean exposure of 117 weeks) after having received Alirocumab 75 mg Q2W/Up to 150 mg Q2W for 24 weeks. **ID:** EG004 **Other Num Affected:** 71 **Other Num at Risk:** 106 **Serious Number Affected:** 28 **Serious Number At Risk:** 106 **Title:** Alirocumab 150 mg Q4W (After Alirocumab 75 Q2W/Up150 Q2W) **Group ID:** EG005 **Title:** Alirocumab 150 mg Q4W (After Alirocumab 150 Q4W/Up150 Q2W) **Deaths Num Affected:** 1 **Deaths Num At Risk:** 48 **Description:** Participants exposed to alirocumab 150 mg Q4W SC injection added to stable non-statin LMT or diet alone (mean exposure of 119 weeks) after having received Alirocumab 150 mg Q4W/Up to 150 mg Q2W for 24 weeks. **ID:** EG005 **Other Num Affected:** 31 **Other Num at Risk:** 48 **Serious Number Affected:** 14 **Serious Number At Risk:** 48 **Title:** Alirocumab 150 mg Q4W (After Alirocumab 150 Q4W/Up150 Q2W) **Frequency Threshold:** 5 #### Other Events **Term:** Diarrhoea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 20.0 **Term:** Nausea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 20.0 **Term:** Fatigue **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 20.0 **Term:** Injection site reaction **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 20.0 **Term:** Non-cardiac chest pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 20.0 **Term:** Oedema peripheral **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 20.0 **Term:** Bronchitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 20.0 **Term:** Influenza **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 20.0 **Term:** Pharyngitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 20.0 **Term:** Sinusitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 20.0 **Term:** Upper respiratory tract infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 20.0 **Term:** Urinary tract infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 20.0 **Term:** Viral upper respiratory tract infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 20.0 **Term:** Fall **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 20.0 **Term:** Laceration **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 20.0 **Term:** Gout **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 20.0 **Term:** Hyperkalaemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 20.0 **Term:** Arthralgia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 20.0 **Term:** Back pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 20.0 **Term:** Muscle spasms **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 20.0 **Term:** Musculoskeletal pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 20.0 **Term:** Myalgia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 20.0 **Term:** Neck pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 20.0 **Term:** Osteoarthritis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 20.0 **Term:** Pain in extremity **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 20.0 **Term:** Dizziness **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 20.0 **Term:** Headache **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 20.0 **Term:** Depression **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA 20.0 **Term:** Cough **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 20.0 **Term:** Dry skin **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA 20.0 **Term:** Rash **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA 20.0 **Term:** Hypertension **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA 20.0 #### Serious Events **Term:** Anaemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 51 **Group ID:** EG004 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Term:** Haemorrhagic anaemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 51 **Group ID:** EG004 **Num Affected:** 1 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Term:** Acute coronary syndrome **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 51 **Group ID:** EG004 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Term:** Acute myocardial infarction **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 51 **Group ID:** EG004 **Num Affected:** 3 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Term:** Angina pectoris **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 51 **Group ID:** EG004 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Term:** Angina unstable **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 51 **Group ID:** EG004 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Term:** Aortic valve stenosis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 51 **Group ID:** EG004 **Num Affected:** 1 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Term:** Atrial fibrillation **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 51 **Group ID:** EG004 **Num At Risk:** 106 **Group ID:** EG005 **Num Affected:** 1 **Num At Risk:** 48 **Term:** Cardiac failure congestive **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 51 **Group ID:** EG004 **Num Affected:** 2 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Term:** Cardio-respiratory arrest **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 51 **Group ID:** EG004 **Num At Risk:** 106 **Group ID:** EG005 **Num Affected:** 1 **Num At Risk:** 48 **Term:** Cardiomyopathy **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 51 **Group ID:** EG004 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Term:** Coronary artery disease **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 51 **Group ID:** EG004 **Num Affected:** 2 **Num At Risk:** 106 **Group ID:** EG005 **Num Affected:** 1 **Num At Risk:** 48 **Term:** Mitral valve incompetence **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 51 **Group ID:** EG004 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Term:** Myocardial infarction **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 51 **Group ID:** EG004 **Num Affected:** 1 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Term:** Vertigo **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Ear and labyrinth disorders **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 51 **Group ID:** EG004 **Num Affected:** 1 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Term:** Basedow's disease **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Endocrine disorders **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 51 **Group ID:** EG004 **Num Affected:** 1 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Term:** Retinal detachment **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Eye disorders **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 51 **Group ID:** EG004 **Num Affected:** 1 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Term:** Abdominal pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 51 **Group ID:** EG004 **Num Affected:** 1 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Term:** Abdominal pain upper **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 51 **Group ID:** EG004 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Term:** Abdominal wall haematoma **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 51 **Group ID:** EG004 **Num Affected:** 1 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Term:** Constipation **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 51 **Group ID:** EG004 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Term:** Faecaloma **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 51 **Group ID:** EG004 **Num At Risk:** 106 **Group ID:** EG005 **Num Affected:** 1 **Num At Risk:** 48 **Term:** Gastrointestinal haemorrhage **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 51 **Group ID:** EG004 **Num Affected:** 1 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Term:** Retroperitoneal haematoma **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 51 **Group ID:** EG004 **Num Affected:** 1 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Term:** Small intestinal obstruction **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 51 **Group ID:** EG004 **Num Affected:** 1 **Num At Risk:** 106 **Group ID:** EG005 **Num Affected:** 1 **Num At Risk:** 48 **Term:** Volvulus **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 51 **Group ID:** EG004 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Term:** Chest pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 51 **Group ID:** EG004 **Num Affected:** 1 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Term:** Non-cardiac chest pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 51 **Group ID:** EG004 **Num Affected:** 2 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Term:** Biliary colic **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 51 **Group ID:** EG004 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Term:** Cholelithiasis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 51 **Group ID:** EG004 **Num Affected:** 1 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Term:** Appendicitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 51 **Group ID:** EG004 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Term:** Arthritis bacterial **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 51 **Group ID:** EG004 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Term:** Cellulitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 51 **Group ID:** EG004 **Num At Risk:** 106 **Group ID:** EG005 **Num Affected:** 1 **Num At Risk:** 48 **Term:** Device related infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 51 **Group ID:** EG004 **Num Affected:** 1 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Term:** Hepatitis E **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 51 **Group ID:** EG004 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Term:** Pneumonia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 51 **Group ID:** EG004 **Num Affected:** 1 **Num At Risk:** 106 **Group ID:** EG005 **Num Affected:** 2 **Num At Risk:** 48 **Term:** Urinary tract infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 51 **Group ID:** EG004 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Term:** Craniocerebral injury **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 51 **Group ID:** EG004 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Term:** Fall **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 2 **Num At Risk:** 51 **Group ID:** EG004 **Num Affected:** 1 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Term:** Femur fracture **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 51 **Group ID:** EG004 **Num Affected:** 1 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Term:** Humerus fracture **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 51 **Group ID:** EG004 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Term:** Intentional overdose **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 51 **Group ID:** EG004 **Num Affected:** 1 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Term:** Jaw fracture **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 51 **Group ID:** EG004 **Num At Risk:** 106 **Group ID:** EG005 **Num Affected:** 1 **Num At Risk:** 48 **Term:** Multiple fractures **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 51 **Group ID:** EG004 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Term:** Post procedural haematoma **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 51 **Group ID:** EG004 **Num Affected:** 1 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Term:** Radius fracture **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 51 **Group ID:** EG004 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Term:** Rib fracture **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 51 **Group ID:** EG004 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Term:** Road traffic accident **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 51 **Group ID:** EG004 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Term:** Spinal fracture **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 51 **Group ID:** EG004 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Term:** Subdural haematoma **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 51 **Group ID:** EG004 **Num Affected:** 1 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Term:** Traumatic haemothorax **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 51 **Group ID:** EG004 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Term:** Traumatic renal injury **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 51 **Group ID:** EG004 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Term:** Vascular pseudoaneurysm **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 51 **Group ID:** EG004 **Num Affected:** 1 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Term:** Arthritis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 51 **Group ID:** EG004 **Num At Risk:** 106 **Group ID:** EG005 **Num Affected:** 1 **Num At Risk:** 48 **Term:** Lumbar spinal stenosis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 51 **Group ID:** EG004 **Num At Risk:** 106 **Group ID:** EG005 **Num Affected:** 1 **Num At Risk:** 48 **Term:** Musculoskeletal chest pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 51 **Group ID:** EG004 **Num At Risk:** 106 **Group ID:** EG005 **Num Affected:** 1 **Num At Risk:** 48 **Term:** Myalgia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 51 **Group ID:** EG004 **Num At Risk:** 106 **Group ID:** EG005 **Num Affected:** 1 **Num At Risk:** 48 **Term:** Osteoarthritis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 51 **Group ID:** EG004 **Num Affected:** 1 **Num At Risk:** 106 **Group ID:** EG005 **Num Affected:** 1 **Num At Risk:** 48 **Term:** Rhabdomyolysis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 51 **Group ID:** EG004 **Num At Risk:** 106 **Group ID:** EG005 **Num Affected:** 1 **Num At Risk:** 48 **Term:** Rheumatoid arthritis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 51 **Group ID:** EG004 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Term:** Spinal osteoarthritis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 51 **Group ID:** EG004 **Num Affected:** 1 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Term:** Adenocarcinoma of colon **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 51 **Group ID:** EG004 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Term:** Basal cell carcinoma **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 51 **Group ID:** EG004 **Num Affected:** 2 **Num At Risk:** 106 **Group ID:** EG005 **Num Affected:** 1 **Num At Risk:** 48 **Term:** Benign fallopian tube neoplasm **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 51 **Group ID:** EG004 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Term:** Bladder transitional cell carcinoma **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 51 **Group ID:** EG004 **Num Affected:** 1 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Term:** Breast cancer **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 51 **Group ID:** EG004 **Num At Risk:** 106 **Group ID:** EG005 **Num Affected:** 1 **Num At Risk:** 48 **Term:** Meningioma **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 51 **Group ID:** EG004 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Term:** Oesophageal squamous cell carcinoma **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 51 **Group ID:** EG004 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Term:** Prostate cancer **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 58 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 51 **Group ID:** EG004 **Num Affected:** 2 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Term:** Skin cancer **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 51 **Group ID:** EG004 **Num Affected:** 1 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Term:** Uterine leiomyoma **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 51 **Group ID:** EG004 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Term:** Arachnoiditis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 51 **Group ID:** EG004 **Num Affected:** 1 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Term:** Cerebellar infarction **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 51 **Group ID:** EG004 **Num At Risk:** 106 **Group ID:** EG005 **Num Affected:** 1 **Num At Risk:** 48 **Term:** Cerebrovascular accident **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 51 **Group ID:** EG004 **Num Affected:** 1 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Term:** Essential tremor **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 51 **Group ID:** EG004 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Term:** Hypoxic-ischaemic encephalopathy **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 51 **Group ID:** EG004 **Num At Risk:** 106 **Group ID:** EG005 **Num Affected:** 1 **Num At Risk:** 48 **Term:** Multiple sclerosis relapse **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 51 **Group ID:** EG004 **Num Affected:** 1 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Term:** Presyncope **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 51 **Group ID:** EG004 **Num Affected:** 2 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Term:** Syncope **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 51 **Group ID:** EG004 **Num Affected:** 3 **Num At Risk:** 106 **Group ID:** EG005 **Num Affected:** 2 **Num At Risk:** 48 **Term:** Transient ischaemic attack **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 51 **Group ID:** EG004 **Num Affected:** 1 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Term:** Depression **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 51 **Group ID:** EG004 **Num Affected:** 1 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Term:** Mental disorder **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 51 **Group ID:** EG004 **Num At Risk:** 106 **Group ID:** EG005 **Num Affected:** 1 **Num At Risk:** 48 **Term:** Suicide attempt **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 51 **Group ID:** EG004 **Num Affected:** 1 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Term:** Acute kidney injury **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 51 **Group ID:** EG004 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Term:** Nephrolithiasis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num Affected:** 1 **Num At Risk:** 51 **Group ID:** EG004 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Term:** Chronic obstructive pulmonary disease **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 51 **Group ID:** EG004 **Num At Risk:** 106 **Group ID:** EG005 **Num Affected:** 1 **Num At Risk:** 48 **Term:** Epistaxis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 51 **Group ID:** EG004 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Term:** Pulmonary embolism **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 51 **Group ID:** EG004 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Term:** Haematoma **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 51 **Group ID:** EG004 **Num Affected:** 1 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Term:** Hypertensive crisis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 51 **Group ID:** EG004 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Term:** Hypotension **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 51 **Group ID:** EG004 **Num Affected:** 2 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Term:** Hypovolaemic shock **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 51 **Group ID:** EG004 **Num Affected:** 1 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Term:** Peripheral artery occlusion **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num Affected:** 1 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 51 **Group ID:** EG004 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Term:** Peripheral artery stenosis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 51 **Group ID:** EG004 **Num At Risk:** 106 **Group ID:** EG005 **Num Affected:** 1 **Num At Risk:** 48 **Term:** Peripheral ischaemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA 20.0 ##### Stats **Group ID:** EG000 **Num At Risk:** 58 **Group ID:** EG001 **Num At Risk:** 115 **Group ID:** EG002 **Num At Risk:** 58 **Group ID:** EG003 **Num At Risk:** 51 **Group ID:** EG004 **Num Affected:** 1 **Num At Risk:** 106 **Group ID:** EG005 **Num At Risk:** 48 **Time Frame:** All Adverse Events (AE) were collected from signature of informed consent form up to study completion (up to 176 weeks) regardless of seriousness or relationship to investigational product. ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 58 **Group ID:** BG001 **Value:** 116 **Group ID:** BG002 **Value:** 59 **Group ID:** BG003 **Value:** 233 **Units:** Participants ### Group **ID:** BG000 **Title:** Placebo Q2W **Description:** Period 1: Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks. Period 2: Alirocumab 150 mg SC injection every 4 weeks (Q4W) from Week 24 until second quarter 2017 or until the drug is commercially available in the country, whatever occurred first. Alirocumab dose could be either up-titrated to 150 mg Q2W from Week 36 or maintained according to the investigator judgement and low-density lipoprotein cholesterol (LDL-C) values. Subsequent down titration to 150 mg Q4W was allowed. ### Group **ID:** BG001 **Title:** Alirocumab 75 mg Q2W/Up to 150 mg Q2W (Calibrator) **Description:** Period 1: Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted LDL-C levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or \<30% LDL-C reduction from baseline. Period 2: Alirocumab 150 mg SC injection Q4W from Week 24 until second quarter 2017 or until the drug is commercially available in the country, whatever occurred first. Alirocumab dose could be either up-titrated to 150 mg Q2W from Week 36 or maintained according to the investigator judgement and LDL-C values. Subsequent down titration to 150 mg Q4W was allowed. ### Group **ID:** BG002 **Title:** Alirocumab 150 mg Q4W/Up to 150 mg Q2W **Description:** Period 1: Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted LDL-C levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or \<30% LDL-C reduction from baseline. Period 2: Alirocumab 150 mg SC injection Q4W from Week 24 until second quarter 2017 or until the drug is commercially available in the country, whatever occurred first. Alirocumab dose could be either up-titrated to 150 mg Q2W from Week 36 or maintained according to the investigator judgement and LDL-C values. Subsequent down titration to 150 mg Q4W was allowed. ### Group **ID:** BG003 **Title:** Total **Description:** Total of all reporting groups ### Measure #### Measurement **Group ID:** BG000 **Spread:** 10.7 **Value:** 63.1 #### Measurement **Group ID:** BG001 **Spread:** 9.9 **Value:** 62.5 #### Measurement **Group ID:** BG002 **Spread:** 10.0 **Value:** 64.2 #### Measurement **Group ID:** BG003 **Spread:** 10.1 **Value:** 63.1 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 27 #### Measurement **Group ID:** BG001 **Value:** 47 #### Measurement **Group ID:** BG002 **Value:** 29 #### Measurement **Group ID:** BG003 **Value:** 103 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 31 #### Measurement **Group ID:** BG001 **Value:** 69 #### Measurement **Group ID:** BG002 **Value:** 30 #### Measurement **Group ID:** BG003 **Value:** 130 **Category Title:** Male **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 1 #### Measurement **Group ID:** BG001 **Value:** 7 #### Measurement **Group ID:** BG002 **Value:** 4 #### Measurement **Group ID:** BG003 **Value:** 12 **Category Title:** Hispanic or Latino #### Measurement **Group ID:** BG000 **Value:** 57 #### Measurement **Group ID:** BG001 **Value:** 109 #### Measurement **Group ID:** BG002 **Value:** 54 #### Measurement **Group ID:** BG003 **Value:** 220 **Category Title:** Not Hispanic or Latino #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 1 #### Measurement **Group ID:** BG003 **Value:** 1 **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 #### Measurement **Group ID:** BG003 **Value:** 0 **Category Title:** American Indian or Alaska Native #### Measurement **Group ID:** BG000 **Value:** 1 #### Measurement **Group ID:** BG001 **Value:** 4 #### Measurement **Group ID:** BG002 **Value:** 3 #### Measurement **Group ID:** BG003 **Value:** 8 **Category Title:** Asian #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 1 #### Measurement **Group ID:** BG002 **Value:** 0 #### Measurement **Group ID:** BG003 **Value:** 1 **Category Title:** Native Hawaiian or Other Pacific Islander #### Measurement **Group ID:** BG000 **Value:** 1 #### Measurement **Group ID:** BG001 **Value:** 3 #### Measurement **Group ID:** BG002 **Value:** 1 #### Measurement **Group ID:** BG003 **Value:** 5 **Category Title:** Black or African American #### Measurement **Group ID:** BG000 **Value:** 56 #### Measurement **Group ID:** BG001 **Value:** 108 #### Measurement **Group ID:** BG002 **Value:** 55 #### Measurement **Group ID:** BG003 **Value:** 219 **Category Title:** White #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 #### Measurement **Group ID:** BG003 **Value:** 0 **Category Title:** More than one race #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 #### Measurement **Group ID:** BG003 **Value:** 0 **Category Title:** Unknown or Not Reported **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Spread:** 47.3 **Value:** 158.5 #### Measurement **Group ID:** BG001 **Spread:** 44.6 **Value:** 154.5 #### Measurement **Group ID:** BG002 **Spread:** 69.1 **Value:** 163.9 #### Measurement **Group ID:** BG003 **Spread:** 52.4 **Value:** 157.9 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Spread:** 1.226 **Value:** 4.106 #### Measurement **Group ID:** BG001 **Spread:** 1.154 **Value:** 4.002 #### Measurement **Group ID:** BG002 **Spread:** 1.789 **Value:** 4.245 #### Measurement **Group ID:** BG003 **Spread:** 1.356 **Value:** 4.089 **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 **Description:** Calculated LDL-C from Friedewald formula (LDL-C = Total cholesterol \[Total-C\] - High-Density Lipoprotein Cholesterol \[HDL-C\] - \[Triglyceride/5\]). **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** Calculated LDL-C in mg/dL **Unit of Measure:** mg/dL ### Measure 6 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** Calculated LDL-C in mmol/L **Unit of Measure:** mmol/L ## Results Section - More Information Module ### Certain Agreement **Other Details:** If no publication has occurred within 12 months of the completion of the study, the Investigator shall have the right to publish/present independently the results of the study. The Investigator shall provide the Sponsor with a copy of any such presentation/publication for comment at least 30 days before any presentation/submission for publication. If requested by the Sponsor, any presentation/submission shall be delayed up to 90 days, to allow the Sponsor to preserve its proprietary rights. **Restriction Type:** OTHER **Restrictive Agreement:** True ### Limitations and Caveats **Description:** The systematic randomization error was not anticipated to have an impact on the power of the study. The sample size to detect a difference in efficacy endpoints was reached (it was increased to obtain additional safety data) and blind was maintained. ### Point of Contact **Email:** [email protected] **Organization:** Sanofi **Title:** Trial Transparency Team ## Results Section - Outcome Measures Module ### Outcome Measure 1 #### Analysis **CI Lower Limit:** -62.9 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -49.9 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** Alirocumab 150 mg Q4W/Up to 150 mg Q2W vs. Placebo **Group Description:** Alirocumab 150 mg Q4W/up to 150 mg Q2W was compared to placebo group using an appropriate contrast statement. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** <0.0001 **P-Value Comment:** Threshold for significance at 0.05 level. **Parameter Type:** Least square (LS) mean difference **Parameter Value:** -56.4 **Statistical Comment:** **Statistical Method:** Mixed Models Analysis **Tested Non-Inferiority:** ### Outcome Measure 2 #### Analysis **CI Lower Limit:** -65.6 **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:** Alirocumab 150 mg Q4W/Up to 150 mg Q2W vs. Placebo **Group Description:** A hierarchical testing procedure was used to control type I error and handle multiple secondary endpoint analyses. Testing was then performed sequentially in the order the endpoints are reported. The hierarchical testing sequence continued only when previous endpoint was statistically significant at 0.05 level. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** <0.0001 **P-Value Comment:** Threshold for significance at 0.05 level. **Parameter Type:** LS Mean Difference **Parameter Value:** -59.7 **Statistical Comment:** **Statistical Method:** Mixed Models Analysis **Tested Non-Inferiority:** ### Outcome Measure 3 #### Analysis **CI Lower Limit:** -51.8 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -38.1 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** Alirocumab 150 mg Q4W/Up to 150 mg Q2W vs. Placebo **Group Description:** Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** <0.0001 **P-Value Comment:** Threshold for significance at 0.05 level. **Parameter Type:** LS Mean Difference **Parameter Value:** -44.9 **Statistical Comment:** **Statistical Method:** Mixed Models Analysis **Tested Non-Inferiority:** ### Outcome Measure 4 #### Analysis **CI Lower Limit:** -54.8 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -41.9 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** Alirocumab 150 mg Q4W/Up to 150 mg Q2W vs. Placebo **Group Description:** Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** <0.0001 **P-Value Comment:** Threshold for significance at 0.05 level. **Parameter Type:** LS Mean Difference **Parameter Value:** -48.4 **Statistical Comment:** **Statistical Method:** Mixed Models Analysis **Tested Non-Inferiority:** ### Outcome Measure 5 #### Analysis **CI Lower Limit:** -61.1 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -49.8 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** Alirocumab 150 mg Q4W/Up to 150 mg Q2W vs. Placebo **Group Description:** Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** <0.0001 **P-Value Comment:** Threshold for significance at 0.05 level. **Parameter Type:** LS Mean Difference **Parameter Value:** -55.5 **Statistical Comment:** **Statistical Method:** Mixed Models Analysis **Tested Non-Inferiority:** ### Outcome Measure 6 #### Analysis **CI Lower Limit:** -63.8 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -53.4 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** Alirocumab 150 mg Q4W/Up to 150 mg Q2W vs. Placebo **Group Description:** Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** <0.0001 **P-Value Comment:** Threshold for significance at 0.05 level. **Parameter Type:** LS Mean Difference **Parameter Value:** -58.6 **Statistical Comment:** **Statistical Method:** Mixed Models Analysis **Tested Non-Inferiority:** ### Outcome Measure 7 #### Analysis **CI Lower Limit:** -52.4 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -40.4 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** Alirocumab 150 mg Q4W/Up to 150 mg Q2W vs. Placebo **Group Description:** Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** <0.0001 **P-Value Comment:** Threshold for significance at 0.05 level. **Parameter Type:** LS Mean Difference **Parameter Value:** -46.4 **Statistical Comment:** **Statistical Method:** Mixed Models Analysis **Tested Non-Inferiority:** ### Outcome Measure 8 #### Analysis **CI Lower Limit:** -54.3 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -42.8 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** Alirocumab 150 mg Q4W/Up to 150 mg Q2W vs. Placebo **Group Description:** Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** <0.0001 **P-Value Comment:** Threshold for significance at 0.05 level. **Parameter Type:** LS Mean Difference **Parameter Value:** -48.6 **Statistical Comment:** **Statistical Method:** Mixed Models Analysis **Tested Non-Inferiority:** ### Outcome Measure 9 #### Analysis **CI Lower Limit:** -54.9 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -43.2 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** Alirocumab 150 mg Q4W/Up to 150 mg Q2W vs. Placebo **Group Description:** Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** <0.0001 **P-Value Comment:** Threshold for significance at 0.05 level. **Parameter Type:** LS Mean Difference **Parameter Value:** -49.0 **Statistical Comment:** **Statistical Method:** Mixed Models Analysis **Tested Non-Inferiority:** ### Outcome Measure 10 #### Analysis **CI Lower Limit:** -57.1 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -46.4 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** Alirocumab 150 mg Q4W/Up to 150 mg Q2W vs. Placebo **Group Description:** Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** <0.0001 **P-Value Comment:** Threshold for significance at 0.05 level. **Parameter Type:** LS Mean Difference **Parameter Value:** -51.7 **Statistical Comment:** **Statistical Method:** Mixed Models Analysis **Tested Non-Inferiority:** ### Outcome Measure 11 #### Analysis **CI Lower Limit:** -39.8 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -30.8 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** Alirocumab 150 mg Q4W/Up to 150 mg Q2W vs. Placebo **Group Description:** Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** <0.0001 **P-Value Comment:** Threshold for significance at 0.05 level. **Parameter Type:** LS Mean Difference **Parameter Value:** -35.3 **Statistical Comment:** **Statistical Method:** Mixed Models Analysis **Tested Non-Inferiority:** ### Outcome Measure 12 #### Analysis **CI Lower Limit:** -44.3 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -32.1 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** Alirocumab 150 mg Q4W/Up to 150 mg Q2W vs. Placebo **Group Description:** Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** <0.0001 **P-Value Comment:** Threshold for significance at 0.05 level. **Parameter Type:** LS Mean Difference **Parameter Value:** -38.2 **Statistical Comment:** **Statistical Method:** Mixed Models Analysis **Tested Non-Inferiority:** ### Outcome Measure 13 #### Analysis **CI Lower Limit:** -43.9 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -31.8 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** Alirocumab 150 mg Q4W/Up to 150 mg Q2W vs. Placebo **Group Description:** Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** <0.0001 **P-Value Comment:** Threshold for significance at 0.05 level. **Parameter Type:** LS Mean Difference **Parameter Value:** -37.9 **Statistical Comment:** **Statistical Method:** Mixed Models Analysis **Tested Non-Inferiority:** ### Outcome Measure 14 #### Analysis **CI Lower Limit:** -30.9 **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:** Alirocumab 150 mg Q4W/Up to 150 mg Q2W vs. Placebo **Group Description:** Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** <0.0001 **P-Value Comment:** Threshold for significance at 0.05 level. **Parameter Type:** LS Mean Difference **Parameter Value:** -26.3 **Statistical Comment:** **Statistical Method:** Mixed Models Analysis **Tested Non-Inferiority:** ### Outcome Measure 15 #### Analysis **CI Lower Limit:** 29.1 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 2690.1 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** Alirocumab 150 mg Q4W/Up to 150 mg Q2W vs. Placebo **Group Description:** Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** <0.0001 **P-Value Comment:** Threshold for significance at 0.05 level. **Parameter Type:** Odds Ratio (OR) **Parameter Value:** 279.8 **Statistical Comment:** Multiple imputation approach followed by logistic regression model. **Statistical Method:** Regression, Logistic **Tested Non-Inferiority:** ### Outcome Measure 16 #### Analysis **CI Lower Limit:** 36.2 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 3479.5 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** Alirocumab 150 mg Q4W/Up to 150 mg Q2W vs. Placebo **Group Description:** Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** <0.0001 **P-Value Comment:** Threshold for significance at 0.05 level. **Parameter Type:** Odds Ratio (OR) **Parameter Value:** 354.7 **Statistical Comment:** Multiple imputation approach followed by logistic regression model. **Statistical Method:** Regression, Logistic **Tested Non-Inferiority:** ### Outcome Measure 17 #### Analysis **CI Lower Limit:** 20.0 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 9999 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** Alirocumab 150 mg Q4W/Up to 150 mg Q2W vs. Placebo (Confidence interval should be read as 20.0 to \>9999) **Group Description:** Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** <0.0001 **P-Value Comment:** Threshold for significance at 0.05 level. **Parameter Type:** Odds Ratio (OR) **Parameter Value:** 126.0 **Statistical Comment:** LOCF approach followed by logistic regression model. **Statistical Method:** Regression, Logistic **Tested Non-Inferiority:** ### Outcome Measure 18 #### Analysis **CI Lower Limit:** 22.2 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 9999 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** Alirocumab 150 mg Q4W/Up to 150 mg Q2W vs. Placebo (Confidence interval should be read as 20.0 to \>9999) **Group Description:** Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** <0.0001 **P-Value Comment:** Threshold for significance at 0.05 level. **Parameter Type:** Odds Ratio (OR) **Parameter Value:** 141.5 **Statistical Comment:** LOCF approach followed by logistic regression model. **Statistical Method:** Regression, Logistic **Tested Non-Inferiority:** ### Outcome Measure 19 #### Analysis **CI Lower Limit:** -29.8 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -9.4 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** Alirocumab 150 mg Q4W/Up to 150 mg Q2W vs. Placebo **Group Description:** Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0002 **P-Value Comment:** Threshold for significance at 0.05 level. **Parameter Type:** Adjusted mean difference **Parameter Value:** -19.6 **Statistical Comment:** Multiple imputation approach followed by robust regression model. **Statistical Method:** Regression, Robust **Tested Non-Inferiority:** ### Outcome Measure 20 #### Analysis **CI Lower Limit:** -17.1 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 1.2 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** Alirocumab 150 mg Q4W/Up to 150 mg Q2W vs. Placebo **Group Description:** Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant). **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0892 **P-Value Comment:** Threshold for significance at 0.05 level. **Parameter Type:** Adjusted mean difference **Parameter Value:** -7.9 **Statistical Comment:** Multiple imputation approach followed by robust regression model. **Statistical Method:** Regression, Robust **Tested Non-Inferiority:** ### Outcome Measure 21 ### Outcome Measure 22 ### Outcome Measure 23 ### Outcome Measure 24 ### Outcome Measure 25 ### Outcome Measure 26 ### Outcome Measure 27 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 2.3 - **Upper Limit:** - **Value:** 4.7 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.6 - **Upper Limit:** - **Value:** -53.5 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 2.3 - **Upper Limit:** - **Value:** -51.7 **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 2.1 - **Upper Limit:** - **Value:** 5.1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.5 - **Upper Limit:** - **Value:** -55.3 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 2.1 - **Upper Limit:** - **Value:** -54.6 **Title:** #### Outcome Measure 3 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 2.5 - **Upper Limit:** - **Value:** 3.2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.7 - **Upper Limit:** - **Value:** -50.8 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 2.4 - **Upper Limit:** - **Value:** -41.7 **Title:** #### Outcome Measure 4 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 2.3 - **Upper Limit:** - **Value:** 3.6 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.6 - **Upper Limit:** - **Value:** -51.5 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 2.3 - **Upper Limit:** - **Value:** -44.8 **Title:** #### Outcome Measure 5 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 2.0 - **Upper Limit:** - **Value:** 3.2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.4 - **Upper Limit:** - **Value:** -53.6 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 2.0 - **Upper Limit:** - **Value:** -52.3 **Title:** #### Outcome Measure 6 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.9 - **Upper Limit:** - **Value:** 3.6 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.3 - **Upper Limit:** - **Value:** -54.1 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 1.9 - **Upper Limit:** - **Value:** -55.0 **Title:** #### Outcome Measure 7 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 2.1 - **Upper Limit:** - **Value:** 7.5 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.5 - **Upper Limit:** - **Value:** -39.7 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 2.2 - **Upper Limit:** - **Value:** -38.9 **Title:** #### Outcome Measure 8 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 2.0 - **Upper Limit:** - **Value:** 7.7 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.4 - **Upper Limit:** - **Value:** -41.2 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 2.1 - **Upper Limit:** - **Value:** -40.9 **Title:** #### Outcome Measure 9 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 2.1 - **Upper Limit:** - **Value:** 4.8 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.5 - **Upper Limit:** - **Value:** -45.3 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 2.1 - **Upper Limit:** - **Value:** -44.2 **Title:** #### Outcome Measure 10 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.9 - **Upper Limit:** - **Value:** 5.0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.3 - **Upper Limit:** - **Value:** -46.9 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 1.9 - **Upper Limit:** - **Value:** -46.7 **Title:** #### Outcome Measure 11 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.6 - **Upper Limit:** - **Value:** 3.0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.1 - **Upper Limit:** - **Value:** -34.0 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 1.6 - **Upper Limit:** - **Value:** -32.3 **Title:** #### Outcome Measure 12 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 2.2 - **Upper Limit:** - **Value:** 7.0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.6 - **Upper Limit:** - **Value:** -38.4 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 2.2 - **Upper Limit:** - **Value:** -31.3 **Title:** #### Outcome Measure 13 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 2.2 - **Upper Limit:** - **Value:** 3.0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.5 - **Upper Limit:** - **Value:** -43.4 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 2.2 - **Upper Limit:** - **Value:** -34.9 **Title:** #### Outcome Measure 14 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.6 - **Upper Limit:** - **Value:** 1.8 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.2 - **Upper Limit:** - **Value:** -32.6 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 1.6 - **Upper Limit:** - **Value:** -24.5 **Title:** #### Outcome Measure 15 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1.8 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 70.3 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 63.9 **Title:** #### Outcome Measure 16 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1.8 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 72.7 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 67.7 **Title:** #### Outcome Measure 17 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0.0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 60.0 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 50.0 **Title:** #### Outcome Measure 18 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0.0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 61.7 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 50.9 **Title:** #### Outcome Measure 19 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 3.7 - **Upper Limit:** - **Value:** 4.1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 2.6 - **Upper Limit:** - **Value:** -21.8 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 3.7 - **Upper Limit:** - **Value:** -15.5 **Title:** #### Outcome Measure 20 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 3.4 - **Upper Limit:** - **Value:** 2.2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 2.4 - **Upper Limit:** - **Value:** -16.5 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 3.3 - **Upper Limit:** - **Value:** -5.7 **Title:** #### Outcome Measure 21 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.9 - **Upper Limit:** - **Value:** -2.4 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.4 - **Upper Limit:** - **Value:** 7.4 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 2.0 - **Upper Limit:** - **Value:** 7.7 **Title:** #### Outcome Measure 22 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.9 - **Upper Limit:** - **Value:** -0.8 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.3 - **Upper Limit:** - **Value:** 6.8 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 1.9 - **Upper Limit:** - **Value:** 8.6 **Title:** #### Outcome Measure 23 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 3.8 - **Upper Limit:** - **Value:** 1.1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 2.7 - **Upper Limit:** - **Value:** -10.6 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 3.9 - **Upper Limit:** - **Value:** -9.2 **Title:** #### Outcome Measure 24 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 3.9 - **Upper Limit:** - **Value:** 2.1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 2.7 - **Upper Limit:** - **Value:** -11.3 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 3.8 - **Upper Limit:** - **Value:** -3.0 **Title:** #### Outcome Measure 25 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.5 - **Upper Limit:** - **Value:** 3.4 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.1 - **Upper Limit:** - **Value:** 8.2 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 1.5 - **Upper Limit:** - **Value:** 10.0 **Title:** #### Outcome Measure 26 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.5 - **Upper Limit:** - **Value:** 2.6 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.1 - **Upper Limit:** - **Value:** 5.9 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 1.5 - **Upper Limit:** - **Value:** 7.6 **Title:** #### Outcome Measure 27 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 18.8 - **Upper Limit:** - **Value:** -37.3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 21.2 - **Upper Limit:** - **Value:** -41.1 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 13.3 - **Upper Limit:** - **Value:** -46.9 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 48 - **Group ID:** OG001 - **Value:** 98 - **Group ID:** OG002 - **Value:** 45 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 22.0 - **Upper Limit:** - **Value:** -36.1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 21.2 - **Upper Limit:** - **Value:** -39.2 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 13.7 - **Upper Limit:** - **Value:** -43.1 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 48 - **Group ID:** OG001 - **Value:** 96 - **Group ID:** OG002 - **Value:** 46 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 24.2 - **Upper Limit:** - **Value:** -46.5 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 18.7 - **Upper Limit:** - **Value:** -49.2 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 21.7 - **Upper Limit:** - **Value:** -48.7 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 47 - **Group ID:** OG001 - **Value:** 91 - **Group ID:** OG002 - **Value:** 44 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 20.6 - **Upper Limit:** - **Value:** -50.8 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 19.5 - **Upper Limit:** - **Value:** -53.7 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 21.3 - **Upper Limit:** - **Value:** -52.3 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 50 - **Group ID:** OG001 - **Value:** 94 - **Group ID:** OG002 - **Value:** 47 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 20.4 - **Upper Limit:** - **Value:** -49.8 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 19.6 - **Upper Limit:** - **Value:** -52.8 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 22.0 - **Upper Limit:** - **Value:** -46.8 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 48 - **Group ID:** OG001 - **Value:** 90 - **Group ID:** OG002 - **Value:** 44 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 20.9 - **Upper Limit:** - **Value:** -50.6 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 18.7 - **Upper Limit:** - **Value:** -53.7 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 24.1 - **Upper Limit:** - **Value:** -51.8 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 46 - **Group ID:** OG001 - **Value:** 81 - **Group ID:** OG002 - **Value:** 37 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 17.6 - **Upper Limit:** - **Value:** -52.7 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 23.7 - **Upper Limit:** - **Value:** -48.7 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 20.9 - **Upper Limit:** - **Value:** -49.4 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 38 - **Group ID:** OG001 - **Value:** 72 - **Group ID:** OG002 - **Value:** 29 **Units:** Participants **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 24.2 - **Upper Limit:** - **Value:** -47.8 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 17.1 - **Upper Limit:** - **Value:** -66.2 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 4.6 - **Upper Limit:** - **Value:** -60.0 **Title:** **Denomination:** - **Group ID:** OG000 - **Value:** 4 - **Group ID:** OG001 - **Value:** 13 - **Group ID:** OG002 - **Value:** 4 **Units:** Participants ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** Adjusted Least-squares (LS) means and standard errors at Week 24 were obtained from a mixed-effect model with repeated measures (MMRM) to account for missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment were used in the model (ITT analysis). **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** ITT population that included all randomized participants with one baseline and at least one post-baseline calculated LDL-C value on- or off-treatment. **Reporting Status:** POSTED **Time Frame:** From Baseline to Week 24 **Title:** Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-Treat (ITT Analysis) **Type:** PRIMARY **Unit of Measure:** percent change ##### Group **Description:** Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks. **ID:** OG000 **Title:** Placebo Q2W ##### Group **Description:** Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or \<30% LDL-C reduction from baseline. **ID:** OG001 **Title:** Alirocumab 75 mg Q2W/Up to 150 mg Q2W (Calibrator) ##### Group **Description:** Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or \<30% LDL-C reduction from baseline. **ID:** OG002 **Title:** Alirocumab 150 mg Q4W/Up to 150 mg Q2W #### Outcome Measure 2 **Description:** Adjusted LS means and standard errors at Week 24 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection) (on-treatment analysis). **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** Modified ITT (mITT) population that included all randomized and treated participants with one baseline and at least one post-baseline calculated LDL-C value on-treatment. **Reporting Status:** POSTED **Time Frame:** From Baseline to Week 24 **Title:** Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis **Type:** SECONDARY **Unit of Measure:** percent change ##### Group **Description:** Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks. **ID:** OG000 **Title:** Placebo Q2W ##### Group **Description:** Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or \<30% LDL-C reduction from baseline. **ID:** OG001 **Title:** Alirocumab 75 mg Q2W/Up to 150 mg Q2W ##### Group **Description:** Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or \<30% LDL-C reduction from baseline. **ID:** OG002 **Title:** Alirocumab 150 mg Q4W/Up to 150 mg Q2W #### Outcome Measure 3 **Description:** Adjusted LS means and standard errors at Week 12 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** ITT population. **Reporting Status:** POSTED **Time Frame:** From Baseline to Week 24 **Title:** Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis **Type:** SECONDARY **Unit of Measure:** percent change ##### Group **Description:** Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks. **ID:** OG000 **Title:** Placebo Q2W ##### Group **Description:** Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or \<30% LDL-C reduction from baseline. **ID:** OG001 **Title:** Alirocumab 75 mg Q2W/Up to 150 mg Q2W ##### Group **Description:** Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or \<30% LDL-C reduction from baseline. **ID:** OG002 **Title:** Alirocumab 150 mg Q4W/Up to 150 mg Q2W #### Outcome Measure 4 **Description:** Adjusted LS means and standard errors at Week 12 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection). **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** mITT population. **Reporting Status:** POSTED **Time Frame:** From Baseline to Week 24 **Title:** Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis **Type:** SECONDARY **Unit of Measure:** percent change ##### Group **Description:** Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks. **ID:** OG000 **Title:** Placebo Q2W ##### Group **Description:** Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or \<30% LDL-C reduction from baseline. **ID:** OG001 **Title:** Alirocumab 75 mg Q2W/Up to 150 mg Q2W ##### Group **Description:** Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or \<30% LDL-C reduction from baseline. **ID:** OG002 **Title:** Alirocumab 150 mg Q4W/Up to 150 mg Q2W #### Outcome Measure 5 **Description:** Adjusted LS means and standard errors at Week 12 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment and assigning a weight of 0.25 for Week 9, 10, 11 and 12 time points. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** ITT population. **Reporting Status:** POSTED **Time Frame:** From Baseline to Week 24 **Title:** Percent Change From Baseline in Calculated LDL-C to Averaged Weeks 9 to 12 - ITT- Analysis **Type:** SECONDARY **Unit of Measure:** percent change ##### Group **Description:** Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks. **ID:** OG000 **Title:** Placebo Q2W ##### Group **Description:** Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or \<30% LDL-C reduction from baseline. **ID:** OG001 **Title:** Alirocumab 75 mg Q2W/Up to 150 mg Q2W ##### Group **Description:** Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or \<30% LDL-C reduction from baseline. **ID:** OG002 **Title:** Alirocumab 150 mg Q4W/Up to 150 mg Q2W #### Outcome Measure 6 **Description:** Adjusted LS means and standard errors at Week 12 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection) and assigning a weight of 0.25 for Week 9, 10, 11 and 12 time points. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** mITT population. **Reporting Status:** POSTED **Time Frame:** From Baseline to Week 24 **Title:** Percent Change From Baseline in Calculated LDL-C at Averaged Week 9 to 12 - On-Treatment Analysis **Type:** SECONDARY **Unit of Measure:** percent change ##### Group **Description:** Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks. **ID:** OG000 **Title:** Placebo Q2W ##### Group **Description:** Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or \<30% LDL-C reduction from baseline. **ID:** OG001 **Title:** Alirocumab 75 mg Q2W/Up to 150 mg Q2W ##### Group **Description:** Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or \<30% LDL-C reduction from baseline. **ID:** OG002 **Title:** Alirocumab 150 mg Q4W/Up to 150 mg Q2W #### Outcome Measure 7 **Description:** Adjusted LS means and standard errors at Week 24 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** ITT population. Number of participants analyzed = participants of the ITT population with available data at specified time-points. **Reporting Status:** POSTED **Time Frame:** From Baseline to Week 24 **Title:** Percent Change From Baseline in Apolipoprotein (Apo) B at Week 24 - ITT Analysis **Type:** SECONDARY **Unit of Measure:** percent change ##### Group **Description:** Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks. **ID:** OG000 **Title:** Placebo Q2W ##### Group **Description:** Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or \<30% LDL-C reduction from baseline. **ID:** OG001 **Title:** Alirocumab 75 mg Q2W/Up to 150 mg Q2W ##### Group **Description:** Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or \<30% LDL-C reduction from baseline. **ID:** OG002 **Title:** Alirocumab 150 mg Q4W/Up to 150 mg Q2W #### Outcome Measure 8 **Description:** Adjusted LS means and standard errors at Week 24 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection). **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** mITT population. Number of participants analyzed = participants of the mITT population with available data at specified time-points. **Reporting Status:** POSTED **Time Frame:** From Baseline to Week 24 **Title:** Percent Change From Baseline in Apo B at Week 24 - On-treatment Analysis **Type:** SECONDARY **Unit of Measure:** percent change ##### Group **Description:** Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks. **ID:** OG000 **Title:** Placebo Q2W ##### Group **Description:** Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or \<30% LDL-C reduction from baseline. **ID:** OG001 **Title:** Alirocumab 75 mg Q2W/Up to 150 mg Q2W ##### Group **Description:** Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or \<30% LDL-C reduction from baseline. **ID:** OG002 **Title:** Alirocumab 150 mg Q4W/Up to 150 mg Q2W #### Outcome Measure 9 **Description:** Adjusted LS means and standard errors at Week 24 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** ITT population. **Reporting Status:** POSTED **Time Frame:** From Baseline to Week 24 **Title:** Percent Change From Baseline in Non-HDL-C at Week 24 - ITT Analysis **Type:** SECONDARY **Unit of Measure:** percent change ##### Group **Description:** Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks. **ID:** OG000 **Title:** Placebo Q2W ##### Group **Description:** Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or \<30% LDL-C reduction from baseline. **ID:** OG001 **Title:** Alirocumab 75 mg Q2W/Up to 150 mg Q2W ##### Group **Description:** Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or \<30% LDL-C reduction from baseline. **ID:** OG002 **Title:** Alirocumab 150 mg Q4W/Up to 150 mg Q2W #### Outcome Measure 10 **Description:** Adjusted LS means and standard errors at Week 24 from MMRM model including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection). **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** mITT population. **Reporting Status:** POSTED **Time Frame:** From Baseline to Week 24 **Title:** Percent Change From Baseline in Non-HDL-C at Week 24 - On-treatment Analysis **Type:** SECONDARY **Unit of Measure:** percent change ##### Group **Description:** Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks. **ID:** OG000 **Title:** Placebo Q2W ##### Group **Description:** Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or \<30% LDL-C reduction from baseline. **ID:** OG001 **Title:** Alirocumab 75 mg Q2W/Up to 150 mg Q2W ##### Group **Description:** Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or \<30% LDL-C reduction from baseline. **ID:** OG002 **Title:** Alirocumab 150 mg Q4W/Up to 150 mg Q2W #### Outcome Measure 11 **Description:** Adjusted LS means and standard errors at Week 24 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** ITT population. **Reporting Status:** POSTED **Time Frame:** From Baseline to Week 24 **Title:** Percent Change From Baseline in Total-C at Week 24 - ITT Analysis **Type:** SECONDARY **Unit of Measure:** percent change ##### Group **Description:** Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks. **ID:** OG000 **Title:** Placebo Q2W ##### Group **Description:** Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or \<30% LDL-C reduction from baseline. **ID:** OG001 **Title:** Alirocumab 75 mg Q2W/Up to 150 mg Q2W ##### Group **Description:** Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or \<30% LDL-C reduction from baseline. **ID:** OG002 **Title:** Alirocumab 150 mg Q4W/Up to 150 mg Q2W #### Outcome Measure 12 **Description:** Adjusted LS means and standard errors at Week 12 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** ITT population. Number of participants analyzed = participants of the ITT population with available data at specified time-points. **Reporting Status:** POSTED **Time Frame:** From Baseline to Week 24 **Title:** Percent Change From Baseline in Apo B at Week 12 - ITT Analysis **Type:** SECONDARY **Unit of Measure:** percent change ##### Group **Description:** Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks. **ID:** OG000 **Title:** Placebo Q2W ##### Group **Description:** Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or \<30% LDL-C reduction from baseline. **ID:** OG001 **Title:** Alirocumab 75 mg Q2W/Up to 150 mg Q2W ##### Group **Description:** Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or \<30% LDL-C reduction from baseline. **ID:** OG002 **Title:** Alirocumab 150 mg Q4W/Up to 150 mg Q2W #### Outcome Measure 13 **Description:** Adjusted LS means and standard errors at Week 12 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** ITT population. **Reporting Status:** POSTED **Time Frame:** From Baseline to Week 24 **Title:** Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis **Type:** SECONDARY **Unit of Measure:** percent change ##### Group **Description:** Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks. **ID:** OG000 **Title:** Placebo Q2W ##### Group **Description:** Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or \<30% LDL-C reduction from baseline. **ID:** OG001 **Title:** Alirocumab 75 mg Q2W/Up to 150 mg Q2W ##### Group **Description:** Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or \<30% LDL-C reduction from baseline. **ID:** OG002 **Title:** Alirocumab 150 mg Q4W/Up to 150 mg Q2W #### Outcome Measure 14 **Description:** Adjusted LS means and standard errors at Week 12 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** ITT population. **Reporting Status:** POSTED **Time Frame:** From Baseline to Week 24 **Title:** Percent Change From Baseline in Total-C at Week 12 - ITT Analysis **Type:** SECONDARY **Unit of Measure:** percent change ##### Group **Description:** Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks. **ID:** OG000 **Title:** Placebo Q2W ##### Group **Description:** Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or \<30% LDL-C reduction from baseline. **ID:** OG001 **Title:** Alirocumab 75 mg Q2W/Up to 150 mg Q2W ##### Group **Description:** Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or \<30% LDL-C reduction from baseline. **ID:** OG002 **Title:** Alirocumab 150 mg Q4W/Up to 150 mg Q2W #### Outcome Measure 15 **Description:** Moderate CV risk: 10-year fatal cardiovascular disease (CVD) risk Systemic Coronary Risk Evaluation (SCORE) ≥1 and \<5%. High CV risk: 10-year fatal CVD risk SCORE ≥5% or moderate chronic kidney disease or type 1 or type 2 diabetes mellitus without target organ damage or familial hypercholesterolemia. Very high CV risk: history of documented coronary heart disease, ischemic stroke, peripheral artery disease, transient ischemic attack, abdominal aortic aneurysm, or carotid artery occlusion \>50% without symptoms; carotid endarterectomy or carotid artery stent procedure; renal artery stenosis, or renal artery stent procedure; or type 1 or type 2 diabetes mellitus with target organ damage. Adjusted percentages at Week 24 were obtained from a multiple imputation approach model for handling of missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment were included. **Parameter Type:** NUMBER **Population Description:** ITT population. **Reporting Status:** POSTED **Time Frame:** From Baseline to Week 24 **Title:** Percentage of Very High Cardiovascular (CV) Risk Participants Achieving Calculated LDL-C <70 mg/dL (<1.81 mmol/L) or Moderate or High CV Risk Participants Achieving Calculated LDL-C <100 mg/dL (<2.59 mmol/L) at Week 24 - ITT Analysis **Type:** SECONDARY **Unit of Measure:** percentage of participants ##### Group **Description:** Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks. **ID:** OG000 **Title:** Placebo Q2W ##### Group **Description:** Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or \<30% LDL-C reduction from baseline. **ID:** OG001 **Title:** Alirocumab 75 mg Q2W/Up to 150 mg Q2W ##### Group **Description:** Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or \<30% LDL-C reduction from baseline. **ID:** OG002 **Title:** Alirocumab 150 mg Q4W/Up to 150 mg Q2W #### Outcome Measure 16 **Description:** Adjusted percentages at Week 24 from multiple imputation approach including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection). **Parameter Type:** NUMBER **Population Description:** mITT population. **Reporting Status:** POSTED **Time Frame:** From Baseline to Week 24 **Title:** Percentage of Very High CV Risk Participants Achieving Calculated LDL-C< 70 mg/dL (<1.81 mmol/L) or Moderate or High CV Risk Participants Achieving Calculated LDL-C< 100 mg/dL (<2.59 mmol/L) at Week 24 - On-treatment Analysis **Type:** SECONDARY **Unit of Measure:** percentage of participants ##### Group **Description:** Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks. **ID:** OG000 **Title:** Placebo Q2W ##### Group **Description:** Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or \<30% LDL-C reduction from baseline. **ID:** OG001 **Title:** Alirocumab 75 mg Q2W/Up to 150 mg Q2W ##### Group **Description:** Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or \<30% LDL-C reduction from baseline. **ID:** OG002 **Title:** Alirocumab 150 mg Q4W/Up to 150 mg Q2W #### Outcome Measure 17 **Description:** Adjusted percentages at Week 24 from last observation carried forward (LOCF) approach including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. **Parameter Type:** NUMBER **Population Description:** ITT population. **Reporting Status:** POSTED **Time Frame:** From Baseline to Week 24 **Title:** Percentage of Participants Achieving Calculated LDL-C< 70 mg/dL (<1.81 mmol/L) at Week 24 - ITT Analysis **Type:** SECONDARY **Unit of Measure:** percentage of participants ##### Group **Description:** Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks. **ID:** OG000 **Title:** Placebo Q2W ##### Group **Description:** Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or \<30% LDL-C reduction from baseline. **ID:** OG001 **Title:** Alirocumab 75 mg Q2W/Up to 150 mg Q2W ##### Group **Description:** Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or \<30% LDL-C reduction from baseline. **ID:** OG002 **Title:** Alirocumab 150 mg Q4W/Up to 150 mg Q2W #### Outcome Measure 18 **Description:** Adjusted percentages at Week 24 from LOCF approach including available post-baseline on-treatment data from Week 4 to Week 24 (i.e. up to 21 days after last injection). **Parameter Type:** NUMBER **Population Description:** mITT population. **Reporting Status:** POSTED **Time Frame:** From Baseline to Week 24 **Title:** Percentage of Participants Achieving Calculated LDL-C <70 mg/dL (<1.81 mmol/L) at Week 24 - On-treatment Analysis **Type:** SECONDARY **Unit of Measure:** percentage of participants ##### Group **Description:** Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks. **ID:** OG000 **Title:** Placebo Q2W ##### Group **Description:** Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or \<30% LDL-C reduction from baseline. **ID:** OG001 **Title:** Alirocumab 75 mg Q2W/Up to 150 mg Q2W ##### Group **Description:** Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or \<30% LDL-C reduction from baseline. **ID:** OG002 **Title:** Alirocumab 150 mg Q4W/Up to 150 mg Q2W #### Outcome Measure 19 **Description:** Adjusted means and standard errors at Week 24 from a multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment. **Dispersion Type:** Standard Error **Parameter Type:** MEAN **Population Description:** ITT population. **Reporting Status:** POSTED **Time Frame:** From Baseline to Week 24 **Title:** Percent Change From Baseline in Lipoprotein (a) at Week 24 - ITT Analysis **Type:** SECONDARY **Unit of Measure:** percent change ##### Group **Description:** Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks. **ID:** OG000 **Title:** Placebo Q2W ##### Group **Description:** Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or \<30% LDL-C reduction from baseline. **ID:** OG001 **Title:** Alirocumab 75 mg Q2W/Up to 150 mg Q2W ##### Group **Description:** Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or \<30% LDL-C reduction from baseline. **ID:** OG002 **Title:** Alirocumab 150 mg Q4W/Up to 150 mg Q2W #### Outcome Measure 20 **Description:** Adjusted means and standard errors at Week 12 from a multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment. **Dispersion Type:** Standard Error **Parameter Type:** MEAN **Population Description:** ITT population. **Reporting Status:** POSTED **Time Frame:** From Baseline to Week 24 **Title:** Percent Change From Baseline in Lipoprotein (a) at Week 12 - ITT Analysis **Type:** SECONDARY **Unit of Measure:** percent change ##### Group **Description:** Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks. **ID:** OG000 **Title:** Placebo Q2W ##### Group **Description:** Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or \<30% LDL-C reduction from baseline. **ID:** OG001 **Title:** Alirocumab 75 mg Q2W/Up to 150 mg Q2W ##### Group **Description:** Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or \<30% LDL-C reduction from baseline. **ID:** OG002 **Title:** Alirocumab 150 mg Q4W/Up to 150 mg Q2W #### Outcome Measure 21 **Description:** Adjusted LS means and standard errors at Week 24 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** ITT population. **Reporting Status:** POSTED **Time Frame:** From Baseline to Week 24 **Title:** Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis **Type:** SECONDARY **Unit of Measure:** percent change ##### Group **Description:** Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks. **ID:** OG000 **Title:** Placebo Q2W ##### Group **Description:** Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or \<30% LDL-C reduction from baseline. **ID:** OG001 **Title:** Alirocumab 75 mg Q2W/Up to 150 mg Q2W ##### Group **Description:** Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or \<30% LDL-C reduction from baseline. **ID:** OG002 **Title:** Alirocumab 150 mg Q4W/Up to 150 mg Q2W #### Outcome Measure 22 **Description:** Adjusted LS means and standard errors at Week 12 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** ITT population. **Reporting Status:** POSTED **Time Frame:** From Baseline to Week 24 **Title:** Percent Change From Baseline in HDL-C at Week 12 - ITT Analysis **Type:** SECONDARY **Unit of Measure:** percent change ##### Group **Description:** Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks. **ID:** OG000 **Title:** Placebo Q2W ##### Group **Description:** Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or \<30% LDL-C reduction from baseline. **ID:** OG001 **Title:** Alirocumab 75 mg Q2W/Up to 150 mg Q2W ##### Group **Description:** Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or \<30% LDL-C reduction from baseline. **ID:** OG002 **Title:** Alirocumab 150 mg Q4W/Up to 150 mg Q2W #### Outcome Measure 23 **Description:** Adjusted means and standard errors at Week 24 from a multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment. **Dispersion Type:** Standard Error **Parameter Type:** MEAN **Population Description:** ITT population. **Reporting Status:** POSTED **Time Frame:** From Baseline to Week 24 **Title:** Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis **Type:** SECONDARY **Unit of Measure:** percent change ##### Group **Description:** Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks. **ID:** OG000 **Title:** Placebo Q2W ##### Group **Description:** Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or \<30% LDL-C reduction from baseline. **ID:** OG001 **Title:** Alirocumab 75 mg Q2W/Up to 150 mg Q2W ##### Group **Description:** Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or \<30% LDL-C reduction from baseline. **ID:** OG002 **Title:** Alirocumab 150 mg Q4W/Up to 150 mg Q2W #### Outcome Measure 24 **Description:** Adjusted means and standard errors at Week 12 from a multiple imputation approach followed by robust regression model including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment. **Dispersion Type:** Standard Error **Parameter Type:** MEAN **Population Description:** ITT population. **Reporting Status:** POSTED **Time Frame:** From Baseline to Week 24 **Title:** Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis **Type:** SECONDARY **Unit of Measure:** percent change ##### Group **Description:** Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks. **ID:** OG000 **Title:** Placebo Q2W ##### Group **Description:** Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or \<30% LDL-C reduction from baseline. **ID:** OG001 **Title:** Alirocumab 75 mg Q2W/Up to 150 mg Q2W ##### Group **Description:** Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or \<30% LDL-C reduction from baseline. **ID:** OG002 **Title:** Alirocumab 150 mg Q4W/Up to 150 mg Q2W #### Outcome Measure 25 **Description:** Adjusted LS means and standard errors at Week 24 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** ITT population. Number of participants analyzed = participants of the ITT population with available data at specified time-points. **Reporting Status:** POSTED **Time Frame:** From Baseline to Week 24 **Title:** Percent Change From Baseline in Apo A-1 at Week 24 - ITT Analysis **Type:** SECONDARY **Unit of Measure:** percent change ##### Group **Description:** Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks. **ID:** OG000 **Title:** Placebo Q2W ##### Group **Description:** Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or \<30% LDL-C reduction from baseline. **ID:** OG001 **Title:** Alirocumab 75 mg Q2W/Up to 150 mg Q2W ##### Group **Description:** Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or \<30% LDL-C reduction from baseline. **ID:** OG002 **Title:** Alirocumab 150 mg Q4W/Up to 150 mg Q2W #### Outcome Measure 26 **Description:** Adjusted LS means and standard errors at Week 12 from MMRM including all available post-baseline data from Week 4 to Week 24 regardless of status on-or off-treatment. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** ITT population. Number of participants analyzed = participants of the ITT population with available data at specified time-points. **Reporting Status:** POSTED **Time Frame:** From Baseline to Week 24 **Title:** Percent Change From Baseline in Apo A-1 at Week 12 - ITT Analysis **Type:** SECONDARY **Unit of Measure:** percent change ##### Group **Description:** Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks. **ID:** OG000 **Title:** Placebo Q2W ##### Group **Description:** Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or \<30% LDL-C reduction from baseline. **ID:** OG001 **Title:** Alirocumab 75 mg Q2W/Up to 150 mg Q2W ##### Group **Description:** Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted low-density lipoprotein cholesterol (LDL-C) levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or \<30% LDL-C reduction from baseline. **ID:** OG002 **Title:** Alirocumab 150 mg Q4W/Up to 150 mg Q2W #### Outcome Measure 27 **Description:** Mean percent changes (and standard deviations) observed during the open-label extension period are provided. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Open-label extension population included all participants who received at least one dose or part of dose of Alirocumab during the open label extension period. Here, "number analyzed" signifies the number of participants evaluable for each specified time-point. **Reporting Status:** POSTED **Time Frame:** Baseline, Week 32, 36, 48, 72, 96, 120, 144 and Week 168 **Title:** Percent Change From Baseline in Calculated LDL-C at Week 32, 36, 48, 72, 96, 120, 144, 168 On-Treatment Analysis in Open Label Extension Treatment Phase **Type:** OTHER_PRE_SPECIFIED **Unit of Measure:** percent change ##### Group **Description:** Alirocumab 150 mg SC injection Q4W from Week 24 until second quarter 2017 or until the drug is commercially available in the country, whatever occurred first, in participants who received placebo (for Alirocumab) Q2W for 24 weeks during the double-blind period. Alirocumab dose could be either up-titrated to 150 mg Q2W from Week 36 or maintained according to the investigator judgement and low-density lipoprotein cholesterol (LDL-C) values. Subsequent down titration to 150 mg Q4W was allowed. **ID:** OG000 **Title:** Alirocumab 150 mg Q4W (After Placebo Q2W) ##### Group **Description:** Alirocumab 150 mg SC injection Q4W from Week 24 until second quarter 2017 or until the drug is commercially available in the country, whatever occurred first, in participants who received Alirocumab 75 mg Q2W/Up to 150 mg Q2W for 24 weeks during the double-blind period. Alirocumab dose could be either up-titrated to 150 mg Q2W from Week 36 or maintained according to the investigator judgement and low-density lipoprotein cholesterol (LDL-C) values. Subsequent down titration to 150 mg Q4W was allowed. **ID:** OG001 **Title:** Alirocumab 150 mg QW4 (After Alirocumab 75 Q2W/Up 150 Q2W) ##### Group **Description:** Alirocumab 150 mg SC injection Q4W from Week 24 until second quarter 2017 or until the drug is commercially available in the country, whatever occurred first, in participants who received 150 mg Q4W/Up to 150 mg Q2W for 24 weeks during the double-blind period. Alirocumab dose could be either up-titrated to 150 mg Q2W from Week 36 or maintained according to the investigator judgement and low-density lipoprotein cholesterol (LDL-C) values. Subsequent down titration to 150 mg Q4W was allowed. **ID:** OG002 **Title:** Alirocumab 150 mg Q4W (After Alirocumab 150 Q4W/Up 150 Q2W) ### Participant Flow Module #### Group **Description:** Period 1: Placebo (for Alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable non-statin lipid modifying therapy (LMT) or diet alone for 24 weeks. Period 2: Alirocumab 150 mg SC injection every 4 weeks (Q4W) from Week 24 until second quarter 2017 or until the drug is commercially available in the country, whatever occurred first. Alirocumab dose could be either up-titrated to 150 mg Q2W from Week 36 or maintained according to the investigator judgement and low-density lipoprotein cholesterol (LDL-C) values. Subsequent down titration to 150 mg Q4W was allowed. **ID:** FG000 **Title:** Placebo Q2W #### Group **Description:** Period 1: Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted LDL-C levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or \<30% LDL-C reduction from baseline. Period 2: Alirocumab 150 mg SC injection Q4W from Week 24 until second quarter 2017 or until the drug is commercially available in the country, whatever occurred first. Alirocumab dose could be either up-titrated to 150 mg Q2W from Week 36 or maintained according to the investigator judgement and LDL-C values. Subsequent down titration to 150 mg Q4W was allowed. **ID:** FG001 **Title:** Alirocumab 75 mg Q2W/Up to 150 mg Q2W (Calibrator) #### Group **Description:** Period 1: Alirocumab 150 mg SC injection Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or \<30% LDL-C reduction from baseline. Period 2: Alirocumab 150 mg SC injection Q4W from Week 24 until second quarter 2017 or until the drug is commercially available in the country, whatever occurred first. Alirocumab dose could be either up-titrated to 150 mg Q2W from Week 36 or maintained according to the investigator judgement and LDL-C values. Subsequent down titration to 150 mg Q4W was allowed. **ID:** FG002 **Title:** Alirocumab 150 mg Q4W/Up to 150 mg Q2W #### Period **Title:** Period 1: 24-Week Double-blind Treatment ##### Withdraw **Type:** Adverse Event ###### Reason **Group ID:** FG000 **Number of Subjects:** 2 ###### Reason **Group ID:** FG001 **Number of Subjects:** 2 ###### Reason **Group ID:** FG002 **Number of Subjects:** 5 ##### Withdraw **Type:** Poor compliance to protocol ###### Reason **Group ID:** FG000 **Number of Subjects:** 0 ###### Reason **Group ID:** FG001 **Number of Subjects:** 2 ###### Reason **Group ID:** FG002 **Number of Subjects:** 1 ##### Withdraw **Type:** Physician Decision ###### Reason **Group ID:** FG000 **Number of Subjects:** 0 ###### Reason **Group ID:** FG001 **Number of Subjects:** 1 ###### Reason **Group ID:** FG002 **Number of Subjects:** 0 ##### Withdraw **Type:** Consent withdrawn by participant ###### Reason **Group ID:** FG000 **Number of Subjects:** 1 ###### Reason **Group ID:** FG001 **Number of Subjects:** 0 ###### Reason **Group ID:** FG002 **Number of Subjects:** 1 ##### Withdraw **Type:** Randomized but not treated ###### Reason **Group ID:** FG000 **Number of Subjects:** 0 ###### Reason **Group ID:** FG001 **Number of Subjects:** 1 ###### Reason **Group ID:** FG002 **Number of Subjects:** 1 ##### Withdraw **Type:** Other than specified above ###### Reason **Group ID:** FG000 **Number of Subjects:** 1 ###### Reason **Group ID:** FG001 **Number of Subjects:** 3 ###### Reason **Group ID:** FG002 **Number of Subjects:** 1 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 58 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 116 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 59 ##### Milestone **Type:** Treated ###### Achievement **Group ID:** FG000 **Number of Subjects:** 58 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 115 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 58 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 54 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 107 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 50 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 4 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 9 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 9 #### Period **Title:** Extension Open Label Treatment ##### Withdraw **Type:** Adverse Event ###### Reason **Group ID:** FG000 **Number of Subjects:** 1 ###### Reason **Group ID:** FG001 **Number of Subjects:** 7 ###### Reason **Group ID:** FG002 **Number of Subjects:** 3 ##### Withdraw **Type:** Poor compliance to protocol ###### 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:** Participant moved ###### Reason **Group ID:** FG000 **Number of Subjects:** 1 ###### Reason **Group ID:** FG001 **Number of Subjects:** 2 ###### Reason **Group ID:** FG002 **Number of Subjects:** 0 ##### Withdraw **Type:** Other than specified above ###### Reason **Group ID:** FG000 **Number of Subjects:** 2 ###### Reason **Group ID:** FG001 **Number of Subjects:** 7 ###### Reason **Group ID:** FG002 **Number of Subjects:** 2 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 51 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 106 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 48 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 46 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 89 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 43 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 5 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 17 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 5 **Pre-Assignment Details:** Randomization was stratified by statin intolerant status \& background therapy (non-statin lipid therapy vs diet). Randomization followed a 1:2:1 ratio for placebo, Alirocumab 75 mg and Alirocumab 150 mg instead of 1:1:2 as initially planned due to systematic error in treatment allocation algorithm discovered after all participants were randomized. **Recruitment Details:** The study was conducted at 43 centers in 8 countries. A total of 402 participants were screened between December-2013 and May-2014, of whom 233 were randomized for double-blind (DB) treatment period and 169 were screen failures. Out of 233 randomized for DB period, 205 participants entered the optional open-label (OL) extension period. **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT02842879 **Brief Title:** Outpatient Foley Cervix Priming **Official Title:** Outpatient Versus Inpatient Cervix Priming With Foley Catheter #### Organization Study ID Info **ID:** SantaMariaPortugal #### Organization **Class:** OTHER **Full Name:** Hospital de Santa Maria, Portugal ### Status Module #### Completion Date **Date:** 2015-12 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2016-07-25 **Type:** ESTIMATED **Last Update Submit Date:** 2016-07-20 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2015-12 **Type:** ACTUAL #### Start Date **Date:** 2014-01 **Status Verified Date:** 2016-07 #### Study First Post Date **Date:** 2016-07-25 **Type:** ESTIMATED **Study First Submit Date:** 2016-07-15 **Study First Submit QC Date:** 2016-07-20 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Hospital de Santa Maria, Portugal #### Responsible Party **Investigator Affiliation:** Hospital de Santa Maria, Portugal **Investigator Full Name:** Catarina Policiano **Investigator Title:** Dr. Catarina Policiano **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** The aim was to conduct a non-blinded prospective randomized study at a tertiary hospital. Inclusion criteria: term pregnancy with a single fetus in cephalic presentation, Bishop score \< 6, gestational age \> 41 weeks or medical indication for induction of labor. Patients will be randomized to outpatient or inpatient cervix priming with Foley catheter. The primary outcome will be to compare the variation of Bishop score (difference between Bishop score before and after application of Foley catheter) between outpatient and inpatient groups. Secondary comparisons include: mode of delivery, Foley catheter application-to-delivery time, inpatient time, sequential use of prostaglandins, infection and maternal pain. ### Conditions Module **Conditions:** - Outpatient Mechanical Cervix Priming ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** SUPPORTIVE_CARE #### Enrollment Info **Count:** 120 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Patients randomized to outpatient cervix priming will have the insertion of the catheter in the same conditions defined by the Department protocol for inpatient cervix priming. They will be discharged after a reassuring cardiotocogram following the introduction of the Foley catheter. When discharged, the patients will be instructed to apply manual traction to the catheter every 6 hours and they will be given a written document with all the information that should bring them back to hospital. **Intervention Names:** - Other: Outpatient Foley cervix priming **Label:** Outpatient Foley cervix priming **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** The introduction of a deflated catheter (Foley catheter nº 16F) through the outer cervix orifice is preceded by iodine disinfection of the cervix. The intracervical catheter is distended with 40mL of a saline solution. The end of the catheter is taped to the medial portion of the thigh and manual traction is applied to the catheter every 6 hours. If it is not spontaneously extruded it is removed after 24h. Cervix priming occurs in an inpatient setting. **Label:** Inpatient Foley cervix priming **Type:** NO_INTERVENTION ### Interventions #### Intervention 1 **Arm Group Labels:** - Outpatient Foley cervix priming **Description:** Outpatient setting for cervix priming with Foley catheter **Name:** Outpatient Foley cervix priming **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Measure:** variation of bishop score (difference between bishop score before and after application of foley catheter) **Time Frame:** up to 24 months #### Secondary Outcomes **Measure:** mode of delivery **Time Frame:** up to 24 months **Measure:** induction-to-delivery time **Time Frame:** up to 24 months **Measure:** maternal pain evaluated by visual analog scale for pain **Time Frame:** up to 24 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * women with a single fetus in cephalic presentation * Bishop score \< 6 * Gestational age \> 41 weeks or medical indication for induction of labor submitted to cervix priming with Foley catheter Exclusion Criteria: * women with a fetus in noncephalic presentation * an indication for elective cesarean delivery * spontaneous labor * hydramnios (amniotic fluid index ≥ 25) * nonreassuring cardiotocogram * multiple pregnancy * rupture of membranes * active vaginal bleeding * indication for prophylaxis of Streptococcus group B infection * HIV infection * cervical injury * previous cesarean section with recurrent indication **Healthy Volunteers:** True **Maximum Age:** 45 Years **Minimum Age:** 15 Years **Sex:** FEMALE **Standard Ages:** - CHILD - ADULT ### Contacts Locations Module #### Overall Officials **Official 1:** **Affiliation:** Hospital de Santa Maria, Centro Hospitalar Lisboa Norte **Name:** Catarina Policiano, MD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** YES ### References Module #### References **Citation:** Alfirevic Z, Gyte GM, Nogueira Pileggi V, Plachcinski R, Osoti AO, Finucane EM. Home versus inpatient induction of labour for improving birth outcomes. Cochrane Database Syst Rev. 2020 Aug 27;8(8):CD007372. doi: 10.1002/14651858.CD007372.pub4. **PMID:** 32852803 **Citation:** Policiano C, Pimenta M, Martins D, Clode N. Outpatient versus inpatient cervix priming with Foley catheter: A randomized trial. Eur J Obstet Gynecol Reprod Biol. 2017 Mar;210:1-6. doi: 10.1016/j.ejogrb.2016.11.026. Epub 2016 Nov 27. **PMID:** 27923165 ## Derived Section ### Intervention Browse Module - Browse Branches - Abbrev: PhSol - Name: Pharmaceutical Solutions - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Micro - Name: Micronutrients - Abbrev: Infe - Name: Anti-Infective Agents ### Intervention Browse Module - Browse Leaves - ID: M21860 - Name: Pharmaceutical Solutions - Relevance: LOW - As Found: Unknown - ID: M10488 - Name: Iodine - Relevance: LOW - As Found: Unknown - ID: M229695 - Name: Cadexomer iodine - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT02551679 **Brief Title:** ACP-01 in Patients With Critical Limb Ischemia **Official Title:** A Randomized Double Blind Placebo Controlled Clinical Study to Assess Blood-Derived Autologous Angiogenic Cell Precursor Therapy in Patients With Critical Limb Ischemia (ACP-CLI) **NCT ID Aliases:** - NCT02140931 #### Organization Study ID Info **ID:** HS 12-01. #### Organization **Class:** INDUSTRY **Full Name:** Hemostemix ### Status Module #### Completion Date **Date:** 2021-04 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2023-11-28 **Type:** ACTUAL **Last Update Submit Date:** 2023-11-22 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2020-04 **Type:** ACTUAL #### Results First Post Date **Date:** 2023-11-18 **Type:** ACTUAL **Results First Submit Date:** 2023-09-09 **Results First Submit QC Date:** 2023-10-30 #### Start Date **Date:** 2014-08 **Type:** ACTUAL **Status Verified Date:** 2023-11 #### Study First Post Date **Date:** 2015-09-16 **Type:** ESTIMATED **Study First Submit Date:** 2015-09-14 **Study First Submit QC Date:** 2015-09-14 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Hemostemix #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** The primary objective of this study is to determine the efficacy and safety of intramuscular injection of ACP-01, comprised of blood-derived autologous ACPs, in subjects with critical limb ischemia who are receiving standard of care therapy and have no endovascular or surgical revascularization options. **Detailed Description:** This prospective, randomized, double-blind, placebo controlled study will assess the efficacy and safety of autologous ACPs administered intramuscularly into the lower extremity of subjects with CLI who lack surgical or endovascular revascularization options. A total of approximately 95 subjects will be randomized to treatment with ACP-01 or placebo using a 2:1 randomization scheme, respectively, stratified by site. The study will continue until all subjects treated experience the study event (either de novo gangrene, doubling of wound size, major amputation, or death) or are event-free for at least 26 weeks. Subjects treated will be followed for no longer than 52 weeks. One futility analysis for potentially stopping study enrollment will be performed. Subjects treated at each investigative site will provide written informed consent prior to the conduct of any study-related procedures. Thereafter, they will be screened and those meeting the inclusion/exclusion criteria will be enrolled into the trial and undergo all the study procedures including intramuscular injection of the investigational medicinal product (IMP = ACP-01 or placebo). The IMP will be administered in addition to any conventional treatment the subject is receiving. The control group will receive placebo injections into the lower extremity to ensure blinding of the assessors and the subjects. The placebo will consist of the same medium used in the ACP product suspension. The study consists of four periods: Screening period, Treatment period, Acute safety follow-up and Long term follow-up periods. The total duration of study participation, including follow-up, is at least 26 weeks. Subjects will be followed for up to 52 weeks and at least until the last subject has completed his/her 26 week visit. ### Conditions Module **Conditions:** - Critical Limb Ischemia **Keywords:** - Stem cells - Autologous - Vascular disease - Peripheral arterial disease - Regenerative medicine - Amputation ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** DOUBLE **Who Masked:** - PARTICIPANT - INVESTIGATOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 67 **Type:** ACTUAL **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Injection into lower extremity **Intervention Names:** - Biological: ACP-01 **Label:** ACP-01 **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** Injection into lower extremity **Intervention Names:** - Biological: Placebo **Label:** Placebo **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - ACP-01 **Description:** Injection into lower extremity **Name:** ACP-01 **Type:** BIOLOGICAL #### Intervention 2 **Arm Group Labels:** - Placebo **Description:** Injection into lower extremity **Name:** Placebo **Type:** BIOLOGICAL ### Outcomes Module #### Other Outcomes **Measure:** Change From Baseline in the Dose and Quantity of Analgesic Drugs Used by the Subject **Time Frame:** 1 - 52 wks **Measure:** Reduction in Total Hospitalization Time of Subjects Treated With ACP-01 Compared to Subjects Treated With Placebo **Time Frame:** 1 - 52 wks **Description:** Change in quality of life according to the Vascular Quality of Life Questionnaire. **Measure:** Change From Baseline in Quality of Life **Time Frame:** 1 - 52 wks **Measure:** Change From Baseline in Ankle Pressure **Time Frame:** 1 - 52 wks **Measure:** Change From Baseline in Toe Pressure **Time Frame:** 1 - 52 wks #### Primary Outcomes **Description:** Number of subject with doubling of wound size, major amputation or death **Measure:** Wound Size, Amputation or Survival **Time Frame:** Baseline vs. 1 year #### Secondary Outcomes **Description:** Change in pain score according to the Visual Analog Scale (VAS) for Pain. The visual VAS is a validated, subjective measure for acute and chronic pain. Scores are recorded by making a handwritten mark on a 10-cm line that represents a continuum between the two ends of the scale-"no pain" on the left end (0 cm) of the scale and the "worst pain" on the right end of the scale (10 cm). Measurements from the starting point (left end) of the scale to the subjects' marks are recorded in centimeters and are interpreted as their pain. The values ar used to track pain progression for a subject and to compare pain between subjects. **Measure:** Pain Level **Time Frame:** Baseline vs. 1 year **Description:** Change in ulcer size **Measure:** Ulcer Size **Time Frame:** Baseline vs. 1 year ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Subject is diagnosed with critical limb ischemia. * Subject has hemodynamic indicators of severe peripheral arterial occlusive disease. * Subject is not a candidate for standard revascularization treatment options for peripheral arterial disease. * Subject must be on standard of care medical therapy for peripheral vascular disease. * Male or female age 18 and above. * Non-pregnant, non-lactating female. * Subject is able to understand and provide voluntary signed informed consent. Exclusion Criteria: * Uncorrected aorto-iliac occlusive disease. * Subjects who, in the opinion of the investigator, have a vascular disease prognosis that indicates they would require a major amputation in a time frame shortly after administration of the IMP (investigational drug or placebo). * Advanced Critical Limb Ischemia (CLI) presenting as severe ischemic or dry gangrene. * Lower extremity non-treated active infection. * Hypercoagulable state. * Subject received a blood transfusion during the previous 4 weeks (to exclude the potential of non-autologous ACPs in the harvested blood). * Inability to communicate that may interfere with clinical evaluation. * Recent major non-vascular operation. * Myocardial infarction or uncontrolled myocardial ischemia or persistent severe heart failure. * Severe aortic stenosis. * Renal failure. * Hepatic failure. * Anemia. * Major stroke. * Diagnosis of malignancy. * Concurrent chronic or acute infectious disease and uncontrolled infectious symptoms. * Severe concurrent disease (other than Peripheral Vascular Disease (PAD)). * Bleeding diathesis. * Participation at the same time in another investigational product or device study. * Chronic cytotoxic drug treatment. * Life expectancy of less than 6 months. * Subject unlikely to be available for follow-up. * Acute worsening of CLI. **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Sacramento **Country:** United States **Facility:** UC Davis CTSC Clinical Research Center **State:** California **Zip:** 95817 **Location 2:** **City:** Aurora **Country:** United States **Facility:** Rocky Mountain Regional VA Medical Center **State:** Colorado **Zip:** 80045 **Location 3:** **City:** Gainesville **Country:** United States **Facility:** University of Florida **State:** Florida **Zip:** 32610 **Location 4:** **City:** Miami **Country:** United States **Facility:** Clinovation Research, LLC **State:** Florida **Zip:** 33126 **Location 5:** **City:** Winter Haven **Country:** United States **Facility:** Clinical Research of Central Florida **State:** Florida **Zip:** 33880 **Location 6:** **City:** Decatur **Country:** United States **Facility:** Decatur Memorial Hospital **State:** Illinois **Zip:** 62526 **Location 7:** **City:** Maywood **Country:** United States **Facility:** Loyola University Medical Center **State:** Illinois **Zip:** 60153 **Location 8:** **City:** Worcester **Country:** United States **Facility:** University of Massachusetts Medical School **State:** Massachusetts **Zip:** 01655 **Location 9:** **City:** Lebanon **Country:** United States **Facility:** Dartmouth-Hitchcock Medical Center **State:** New Hampshire **Location 10:** **City:** Greensboro **Country:** United States **Facility:** Moses H. Cone Memorial Hospital **State:** North Carolina **Zip:** 27401 **Location 11:** **City:** Winston-Salem **Country:** United States **Facility:** Wake Forest Baptist Health **State:** North Carolina **Zip:** 27157 **Location 12:** **City:** Oklahoma City **Country:** United States **Facility:** University of Oklahoma Health Sciences Center **State:** Oklahoma **Zip:** 73104 **Location 13:** **City:** Philadelphia **Country:** United States **Facility:** Temple University Hosptial **State:** Pennsylvania **Zip:** 19140 **Location 14:** **City:** Charleston **Country:** United States **Facility:** Medical University of South Carolina **State:** South Carolina **Zip:** 29425 **Location 15:** **City:** Houston **Country:** United States **Facility:** Houston Methodist DeBakey Heart & Vascular Center **State:** Texas **Zip:** 77030 **Location 16:** **City:** San Antonio **Country:** United States **Facility:** Clinical Trials of Texas, Inc. (CTT) **State:** Texas **Zip:** 78229 **Location 17:** **City:** Vancouver **Country:** Canada **Facility:** Vancouver General Hospital **State:** British Columbia **Zip:** V5Z 1K3 **Location 18:** **City:** London **Country:** Canada **Facility:** London Health Sciences Centre **State:** Ontario **Zip:** N6A 5W9 **Location 19:** **City:** Toronto **Country:** Canada **Facility:** Toronto General Hospital **State:** Ontario **Zip:** M5G 2C4 ### References Module #### See Also Links **Label:** Hemostemix Inc. website **URL:** http://www.hemostemix.com ## Document Section ### Large Document Module #### Large Docs - Date: 2019-10-18 - Filename: Prot_000.pdf - Has ICF: False - Has Protocol: True - Has SAP: False - Label: Study Protocol - Size: 706020 - Type Abbrev: Prot - Upload Date: 2023-09-09T14:02 - Date: 2021-06-01 - Filename: SAP_001.pdf - Has ICF: False - Has Protocol: False - Has SAP: True - Label: Statistical Analysis Plan - Size: 345491 - Type Abbrev: SAP - Upload Date: 2023-09-09T14:04 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000010335 - Term: Pathologic Processes - ID: D000058729 - Term: Peripheral Arterial Disease - ID: D000050197 - Term: Atherosclerosis - ID: D000001161 - Term: Arteriosclerosis - ID: D000001157 - Term: Arterial Occlusive Diseases - ID: D000014652 - Term: Vascular Diseases - ID: D000002318 - Term: Cardiovascular Diseases - ID: D000016491 - Term: Peripheral Vascular Diseases - ID: D000002908 - Term: Chronic Disease - ID: D000020969 - Term: Disease Attributes ### Condition Browse Module - Browse Branches - 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: M17400 - Name: Vascular Diseases - Relevance: LOW - As Found: Unknown - ID: M10543 - Name: Ischemia - Relevance: HIGH - As Found: Ischemia - ID: M2714 - Name: Chronic Limb-Threatening Ischemia - Relevance: HIGH - As Found: Critical Limb Ischemia - ID: M29213 - Name: Peripheral Arterial Disease - Relevance: LOW - As Found: Unknown - ID: M18894 - Name: Peripheral Vascular Diseases - Relevance: LOW - As Found: Unknown - ID: M26188 - Name: Atherosclerosis - 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: 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: D000089802 - Term: Chronic Limb-Threatening Ischemia - ID: D000007511 - Term: Ischemia ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module #### Event Groups **Group ID:** EG000 **Title:** ACP-01 **Deaths Num Affected:** 5 **Deaths Num At Risk:** 46 **Description:** Injection into lower extremity ACP-01: Injection into lower extremity **ID:** EG000 **Other Num at Risk:** 46 **Serious Number Affected:** 2 **Serious Number At Risk:** 46 **Title:** ACP-01 **Group ID:** EG001 **Title:** Placebo **Deaths Num Affected:** 1 **Deaths Num At Risk:** 21 **Description:** Injection into lower extremity Placebo: Injection into lower extremity **ID:** EG001 **Other Num at Risk:** 21 **Serious Number Affected:** 1 **Serious Number At Risk:** 21 **Title:** Placebo **Frequency Threshold:** 0 #### Serious Events **Term:** acute myocardial infarction **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA (10.0) ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 46 **Num Events:** 2 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 21 **Num Events:** 1 **Term:** Cardiac failure **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA (10.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 46 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 21 **Num Events:** 1 **Term:** Cardiac failure congestive **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA (10.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 46 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 21 **Num Events:** 1 **Term:** Cardiovascular disorder **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA (10.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 46 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 21 **Term:** Aortic valve stenosis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA (10.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 46 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 21 **Term:** Gangrene **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (10.0) ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 46 **Num Events:** 2 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 21 **Num Events:** 1 **Term:** Localized infection **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (10.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 46 **Num Events:** 1 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 21 **Num Events:** 1 **Term:** Osteomyelitis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (10.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 46 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 21 **Term:** Sepsis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (10.0) ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 46 **Num Events:** 2 **Group ID:** EG001 **Num At Risk:** 21 **Term:** Infection **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (10.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 46 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 21 **Num Events:** 1 **Term:** Pneumonia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (10.0) ##### Stats **Group ID:** EG000 **Num At Risk:** 46 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 21 **Num Events:** 1 **Term:** Vascular stent infection **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (10.0) ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 46 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 21 **Time Frame:** 1 year ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 46 **Group ID:** BG001 **Value:** 21 **Group ID:** BG002 **Value:** 67 **Units:** Participants ### Group **ID:** BG000 **Title:** ACP-01 **Description:** Injection into lower extremity ACP-01: Injection into lower extremity ### Group **ID:** BG001 **Title:** Placebo **Description:** Injection into lower extremity Placebo: Injection into lower extremity ### Group **ID:** BG002 **Title:** Total **Description:** Total of all reporting groups ### Measure #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** <=18 years #### Measurement **Group ID:** BG000 **Value:** 10 #### Measurement **Group ID:** BG001 **Value:** 4 #### Measurement **Group ID:** BG002 **Value:** 14 **Category Title:** Between 18 and 65 years #### Measurement **Group ID:** BG000 **Value:** 36 #### Measurement **Group ID:** BG001 **Value:** 17 #### Measurement **Group ID:** BG002 **Value:** 53 **Category Title:** >=65 years **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Spread:** 13.19 **Value:** 70 #### Measurement **Group ID:** BG001 **Spread:** 9.86 **Value:** 72 #### Measurement **Group ID:** BG002 **Spread:** 12.2 **Value:** 70.9 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 17 #### Measurement **Group ID:** BG001 **Value:** 8 #### Measurement **Group ID:** BG002 **Value:** 25 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 29 #### Measurement **Group ID:** BG001 **Value:** 13 #### Measurement **Group ID:** BG002 **Value:** 42 **Category Title:** Male **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** American Indian or Alaska Native #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 1 #### Measurement **Group ID:** BG002 **Value:** 1 **Category Title:** Asian #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** Native Hawaiian or Other Pacific Islander #### Measurement **Group ID:** BG000 **Value:** 3 #### Measurement **Group ID:** BG001 **Value:** 2 #### Measurement **Group ID:** BG002 **Value:** 5 **Category Title:** Black or African American #### Measurement **Group ID:** BG000 **Value:** 43 #### Measurement **Group ID:** BG001 **Value:** 18 #### Measurement **Group ID:** BG002 **Value:** 61 **Category Title:** White #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** More than one race #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** Unknown or Not Reported **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 8 #### Measurement **Group ID:** BG001 **Value:** 5 #### Measurement **Group ID:** BG002 **Value:** 13 **Class Title:** Canada #### Measurement **Group ID:** BG000 **Value:** 38 #### Measurement **Group ID:** BG001 **Value:** 16 #### Measurement **Group ID:** BG002 **Value:** 54 **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:** 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 **Restriction Type:** LTE60 **Restrictive Agreement:** True ### Point of Contact **Email:** [email protected] **Organization:** Hemostemix **Phone:** 2022978858 **Title:** Dr. Fraser Henderson ## Results Section - Outcome Measures Module ### Outcome Measure 1 #### Analysis **CI Lower Limit:** 0.577 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 7.255 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** The primary hypothesis of this study is that ACP-01 is superior to placebo in terms of the earlier time from treatment with Investigational Medicinal Product (IMP) to either de-novo gangrene, or doubling of wound size, or major amputation, or death. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.258 **P-Value Comment:** **Parameter Type:** Cox Proportional Hazard **Parameter Value:** 2.046 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** ### Outcome Measure 2 ### Outcome Measure 3 ### Outcome Measure 4 ### Outcome Measure 5 ### Outcome Measure 6 ### Outcome Measure 7 ### Outcome Measure 8 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 12 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 9.479 - **Upper Limit:** - **Value:** 38.75 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 14.036 - **Upper Limit:** - **Value:** 44.44 **Title:** #### Outcome Measure 3 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.07 - **Upper Limit:** - **Value:** 1.6 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.59 - **Upper Limit:** - **Value:** 1.8 **Title:** #### Outcome Measure 4 #### Outcome Measure 5 #### Outcome Measure 6 #### Outcome Measure 7 #### Outcome Measure 8 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** Number of subject with doubling of wound size, major amputation or death **Parameter Type:** NUMBER **Population Description:** The primary endpoint was time from treatment to either de-novo gangrene in the treated limb, or doubling of wound size in the treated limb, or major amputation in the treated limb, or death. **Reporting Status:** POSTED **Time Frame:** Baseline vs. 1 year **Title:** Wound Size, Amputation or Survival **Type:** PRIMARY **Unit of Measure:** participants ##### Group **Description:** Injection into lower extremity ACP-01: Injection into lower extremity The primary endpoint was time from treatment to either de-novo gangrene in the treated limb, or doubling of wound size in the treated limb, or major amputation in the treated limb, or death. The primary outcome was analyzed using a Cox proportional hazards model to generate an HR adjusted for recruitment site. Kaplan-Meier survival curves were created for visual presentation of time-to-event comparisons. For subjects who were lost to follow-up or completed 12 months study visit without a study event, the time to event was censored by the subject's last follow-up date in the study. **ID:** OG000 **Title:** ACP-01 ##### Group **Description:** Injection into lower extremity Placebo: Injection into lower extremity The primary endpoint was time from treatment to either de-novo gangrene in the treated limb, or doubling of wound size in the treated limb, or major amputation in the treated limb, or death. The primary outcome was analyzed using a Cox proportional hazards model to generate an HR adjusted for recruitment site. Kaplan-Meier survival curves were created for visual presentation of time-to-event comparisons. For subjects who were lost to follow-up or completed 12 months study visit without a study event, the time to event was censored by the subject's last follow-up date in the study. **ID:** OG001 **Title:** Placebo #### Outcome Measure 2 **Description:** Change in pain score according to the Visual Analog Scale (VAS) for Pain. The visual VAS is a validated, subjective measure for acute and chronic pain. Scores are recorded by making a handwritten mark on a 10-cm line that represents a continuum between the two ends of the scale-"no pain" on the left end (0 cm) of the scale and the "worst pain" on the right end of the scale (10 cm). Measurements from the starting point (left end) of the scale to the subjects' marks are recorded in centimeters and are interpreted as their pain. The values ar used to track pain progression for a subject and to compare pain between subjects. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Reporting Status:** POSTED **Time Frame:** Baseline vs. 1 year **Title:** Pain Level **Type:** SECONDARY **Unit of Measure:** units on a scale ##### Group **Description:** Injection into lower extremity ACP-01: Injection into lower extremity **ID:** OG000 **Title:** ACP-01 ##### Group **Description:** Injection into lower extremity Placebo: Injection into lower extremity **ID:** OG001 **Title:** Placebo #### Outcome Measure 3 **Description:** Change in ulcer size **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Reporting Status:** POSTED **Time Frame:** Baseline vs. 1 year **Title:** Ulcer Size **Type:** SECONDARY **Unit of Measure:** cm^2 ##### Group **Description:** Injection into lower extremity ACP-01: Injection into lower extremity **ID:** OG000 **Title:** ACP-01 ##### Group **Description:** Injection into lower extremity Placebo: Injection into lower extremity **ID:** OG001 **Title:** Placebo #### Outcome Measure 4 **Reporting Status:** NOT_POSTED **Time Frame:** 1 - 52 wks **Title:** Change From Baseline in the Dose and Quantity of Analgesic Drugs Used by the Subject **Type:** OTHER_PRE_SPECIFIED #### Outcome Measure 5 **Reporting Status:** NOT_POSTED **Time Frame:** 1 - 52 wks **Title:** Reduction in Total Hospitalization Time of Subjects Treated With ACP-01 Compared to Subjects Treated With Placebo **Type:** OTHER_PRE_SPECIFIED #### Outcome Measure 6 **Description:** Change in quality of life according to the Vascular Quality of Life Questionnaire. **Reporting Status:** NOT_POSTED **Time Frame:** 1 - 52 wks **Title:** Change From Baseline in Quality of Life **Type:** OTHER_PRE_SPECIFIED #### Outcome Measure 7 **Reporting Status:** NOT_POSTED **Time Frame:** 1 - 52 wks **Title:** Change From Baseline in Ankle Pressure **Type:** OTHER_PRE_SPECIFIED #### Outcome Measure 8 **Reporting Status:** NOT_POSTED **Time Frame:** 1 - 52 wks **Title:** Change From Baseline in Toe Pressure **Type:** OTHER_PRE_SPECIFIED ### Participant Flow Module #### Group **Description:** Injection into lower extremity ACP-01: Injection into lower extremity **ID:** FG000 **Title:** ACP-01 #### Group **Description:** Injection into lower extremity Placebo: Injection into lower extremity **ID:** FG001 **Title:** Placebo #### Period **Title:** Overall Study ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 46 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 21 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 27 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 19 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 19 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 2 **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT01993979 **Acronym:** POUT **Brief Title:** A Phase III Randomised Trial of Peri-Operative Chemotherapy Versus sUrveillance in Upper Tract Urothelial Cancer (POUT) **Official Title:** A Phase III Randomised Trial of Peri-Operative Chemotherapy Versus sUrveillance in Upper Tract Urothelial Cancer #### Organization Study ID Info **ID:** ICR-CTSU/2011/10031 #### Organization **Class:** OTHER **Full Name:** Institute of Cancer Research, United Kingdom #### Secondary ID Infos **ID:** 2011-002577-33 **Type:** EUDRACT_NUMBER **Domain:** ISRCTN **ID:** ISRCTN98387754 **Type:** REGISTRY **Domain:** Cancer Research UK (CR UK) **ID:** CRUK/11/027 **Type:** OTHER_GRANT **Domain:** Main REC **ID:** 11/NW/0782 **Type:** OTHER ### Status Module #### Completion Date **Date:** 2022-05 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** ACTIVE_NOT_RECRUITING #### Last Update Post Date **Date:** 2020-05-04 **Type:** ACTUAL **Last Update Submit Date:** 2020-04-30 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2018-11-07 **Type:** ACTUAL #### Start Date **Date:** 2012-05 **Status Verified Date:** 2020-04 #### Study First Post Date **Date:** 2013-11-25 **Type:** ESTIMATED **Study First Submit Date:** 2013-11-19 **Study First Submit QC Date:** 2013-11-19 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** Cancer Research UK #### Lead Sponsor **Class:** OTHER **Name:** Institute of Cancer Research, United Kingdom #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** POUT is a multi-centred randomised controlled phase III trial. 345 patients who have undergone nephro-ureterectomy, are surgically staged pT2-pT4, N0-3 or are pT1 and node positive, and who are fit for adjuvant chemotherapy, will be randomised to four cycles of adjuvant platinum based chemotherapy (experimental group) or surveillance (control group). Participants will be followed up according to routine practice. Primary endpoint: Disease-free survival (DFS) Secondary endpoints: * Overall Survival * Metastasis free survival * Incidence of bladder second primary tumours * Incidence of contralateral primary tumours * Acute and late toxicity * Treatment compliance * Quality of life ### Conditions Module **Conditions:** - Transitional Cell Carcinoma of Ureter **Keywords:** - Adjuvant chemotherapy - Surveillance - Nephro-ureterectomy ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 261 **Type:** ACTUAL **Phases:** - PHASE3 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Patients allocated to surveillance will be seen at 4, 7, 10 and 13 weeks post randomisation - equivalent to the end of cycle in patients receiving chemotherapy - in order to collect details of early treatment failure in this group and comparative data relating to toxicity and quality of life. Patients on surveillance will then be followed up for signs of recurrence at the same intervals as those who received chemotherapy **Intervention Names:** - Other: Surveillance **Label:** Surveillance **Type:** OTHER #### Arm Group 2 **Description:** Patients allocated adjuvant chemotherapy will receive 4 x 21 day cycles of gemcitabine-cisplatin. Patients who have a sub-optimal renal function (GFR 30-49ml/min) will receive carboplatin instead of cisplatin. **Intervention Names:** - Drug: Chemotherapy **Label:** Chemotherapy **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Chemotherapy **Name:** Chemotherapy **Other Names:** - Gemcitabine - Cisplatin - Carboplatin **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Surveillance **Description:** Patients will be closely monitored for early signs of recurrence, for which they will receive treatment as decided in discussion between the clinician and patient. This may include chemotherapy. **Name:** Surveillance **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** To determine whether adjuvant combination chemotherapy improves the disease-free survival for patients with resected histologically confirmed muscle invasive (pT2-T4, N0-3) or node positive upper tract TCC. **Measure:** Disease-free survival (DFS) **Time Frame:** 3 years #### Secondary Outcomes **Description:** Whether adjuvant platinum-based chemotherapy improves overall survival in this patient group **Measure:** Overall survival **Time Frame:** Patients followed-up for 5 years **Description:** To determine whether adjuvant platinum-based chemotherapy improves metastasis free survival in this patient group. **Measure:** Metastasis free survival **Time Frame:** Patients are followed up for 5 years **Description:** Whether adjuvant platinum-based chemotherapy reduces incidence of second primary urothelial cancers **Measure:** Incidence of bladder second primary tumours **Time Frame:** Patients are followed up for 5 years **Description:** To determine whether adjuvant platinum-based chemotherapy reduces incidence of contralateral primary urothelial cancers. **Measure:** Incidence of contralateral primary tumours **Time Frame:** Patients are followed up for 5 years **Description:** To assess the toxicity of chemotherapy in this patient group. **Measure:** Acute and late toxicity **Time Frame:** Patients are followed up for 5 years **Description:** To assess the relative quality of life in patients undergoing adjuvant chemotherapy or surveillance in this patient group. **Measure:** Quality of life (QoL) **Time Frame:** Patients' QoL will be assessed over 2 years ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Written informed consent * ≥18 years of age * Post radical nephro-ureterectomy for upper tract tumour with predominant TCC component - squamoid differentiation or mixed TCC/SCC is permitted. * Histologically confirmed TCC staged pT2-pT4 pN0-3 M0 or pTany N1-3 M0 (providing all grossly abnormal nodes are resected). Patients with microscopically positive margins on pathology may be entered (providing all grossly abnormal disease was resected). * Satisfactory haematological profile (ANC\> 1.5 x 109/L, platelet count ≥ 100 x 109/L) and liver function tests (bilirubin \< 1.5 x ULN, AST and Alkaline phosphatase \< 2.5 x ULN), Glomerular filtration rate ≥30 mls/min. * Fit and willing to receive adjuvant chemotherapy with first cycle to be commenced within 90 days of radical nephro-ureterectomy if allocated * WHO performance status 0-1. * Available for long-term follow-up Exclusion Criteria: * Evidence of distant metastases * Pure adenocarcinoma, squamous cell carcinoma or small cell or other variant histology * Un-resected macroscopic nodal disease * Concurrent muscle invasive bladder cancer (patients with concurrent Non-muscle invasive bladder cancer (NMIBC) will be eligible) * GFR \<30 ml/minute. NB Gemcitabine-carboplatin can only be given for patients with suboptimal renal function for cisplatin i.e. for GFR 30-49ml/min. Patients with poor performance status or co-morbidities that would make them unfit for chemotherapy are ineligible for the trial * Significant co-morbid conditions that would interfere with administration of protocol treatment * Pregnancy; lactating women or women of childbearing potential unwilling or unable to use adequate non-hormonal contraception (male patients should also use contraception if sexually active); * Previous malignancy in the last 5 years except for previous NMIBC, adequately controlled non melanoma skin tumours, CIS of cervix or LCIS of breast or localised prostate cancer in patients who have a life expectancy of over 5 years upon trial entry. **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Ashford-Kent **Country:** United Kingdom **Facility:** William Harvey Hospital **State:** England **Zip:** TN24 0LZ **Location 2:** **City:** Barnstaple **Country:** United Kingdom **Facility:** North Devon District Hospital **State:** England **Zip:** EX31 4JB **Location 3:** **City:** Basildon **Country:** United Kingdom **Facility:** Basildon University Hospital **State:** England **Zip:** SS16 5NL **Location 4:** **City:** Canterbury **Country:** United Kingdom **Facility:** Kent and Canterbury Hospital **State:** England **Zip:** CT2 3NG **Location 5:** **City:** Hampstead, London **Country:** United Kingdom **Facility:** Royal Free Hospital **State:** England **Zip:** NW3 2QG **Location 6:** **City:** Ipswich **Country:** United Kingdom **Facility:** Ipswich Hospital NHS Trust **State:** England **Zip:** IP4 5PD **Location 7:** **City:** Leeds **Country:** United Kingdom **Facility:** St. James's University Hospital **State:** England **Zip:** LS9 7TF **Location 8:** **City:** London **Country:** United Kingdom **Facility:** Barts and the London School of Medicine **State:** England **Zip:** EC1M 6BQ **Location 9:** **City:** Maidstone **Country:** United Kingdom **Facility:** Maidstone Hospital **State:** England **Zip:** ME16 9QQ **Location 10:** **City:** Manchester **Country:** United Kingdom **Facility:** Christie Hospital NHS Trust **State:** England **Zip:** M20 4BX **Location 11:** **City:** Margate **Country:** United Kingdom **Facility:** Queen Elizabeth The Queen Mother Hospital **State:** England **Zip:** CT9 4AN **Location 12:** **City:** Merseyside **Country:** United Kingdom **Facility:** Clatterbridge Centre for Oncology NHS Trust **State:** England **Zip:** CH63 4JY **Location 13:** **City:** Nottingham **Country:** United Kingdom **Facility:** Nottingham City Hospital NHS Trust **State:** England **Zip:** NG5 1PB **Location 14:** **City:** Peterborough **Country:** United Kingdom **Facility:** Peterborough Hospitals Trust **State:** England **Zip:** PE3 6DA **Location 15:** **City:** Preston **Country:** United Kingdom **Facility:** Rosemere Cancer Centre at Royal Preston Hospital **State:** England **Zip:** PR2 9HT **Location 16:** **City:** Sheffield **Country:** United Kingdom **Facility:** Cancer Research Centre at Weston Park Hospital **State:** England **Zip:** S1O 2SJ **Location 17:** **City:** Surrey **Country:** United Kingdom **Facility:** Royal Marsden Hosital, Sutton **State:** England **Zip:** SM2 5PT **Location 18:** **City:** Westcliff-On-Sea **Country:** United Kingdom **Facility:** Southend University Hospital NHS Foundation Trust **State:** England **Zip:** SS0 0RY **Location 19:** **City:** Wolverhampton **Country:** United Kingdom **Facility:** New Cross Hospital **State:** England **Zip:** WV10 0QP **Location 20:** **City:** Ayr **Country:** United Kingdom **Facility:** Ayr Hospital **State:** Scotland **Zip:** KA6 6DX **Location 21:** **City:** Cardiff **Country:** United Kingdom **Facility:** Velindre Cancer Center at Velinde Hospital **State:** Wales **Zip:** CF14 2TL **Location 22:** **City:** Swansea **Country:** United Kingdom **Facility:** Singleton Hospital **State:** Wales **Zip:** SA 2 8QA **Location 23:** **City:** Bristol **Country:** United Kingdom **Facility:** Bristol Haematology and Oncology Centre **Location 24:** **City:** Bristol **Country:** United Kingdom **Facility:** Southmead Hospital **Location 25:** **City:** Chelsea **Country:** United Kingdom **Facility:** Royal Marsden Hospital **Zip:** SW3 6JJ **Location 26:** **City:** Coventry **Country:** United Kingdom **Facility:** University Hospitals Coventry and Warwickshire NHS Trust **Location 27:** **City:** Dartford **Country:** United Kingdom **Facility:** Darent Valley Hospital **Location 28:** **City:** Derby **Country:** United Kingdom **Facility:** Royal Derby Hospital **Location 29:** **City:** Dorset **Country:** United Kingdom **Facility:** Royal Bournemouth General Hospital **Location 30:** **City:** Edinburgh **Country:** United Kingdom **Facility:** Western General Hospital **Zip:** EH4 2XU **Location 31:** **City:** Exeter **Country:** United Kingdom **Facility:** Royal Devon and Exeter Hospital **Location 32:** **City:** Glasgow **Country:** United Kingdom **Facility:** Beatson West of Scotland Cancer Centre **Location 33:** **City:** Guildford **Country:** United Kingdom **Facility:** Royal Surrey County Hospital **Zip:** GU2 7XX **Location 34:** **City:** Halifax **Country:** United Kingdom **Facility:** Calderdale Royal Infirmary **Location 35:** **City:** Huddersfield **Country:** United Kingdom **Facility:** Huddersfield Royal Infirmary **Location 36:** **City:** Inverness **Country:** United Kingdom **Facility:** Caithness General Hospital **Zip:** IV2 3UJ **Location 37:** **City:** Inverness **Country:** United Kingdom **Facility:** Raigmore Hospital **Zip:** IV2 3UJ **Location 38:** **City:** Leicester **Country:** United Kingdom **Facility:** Leicester Royal Infirmary **Location 39:** **City:** Lincoln **Country:** United Kingdom **Facility:** Lincoln County Hospital **Zip:** LN2 5QY **Location 40:** **City:** Liverpool **Country:** United Kingdom **Facility:** Royal Liverpool University Hospital **Zip:** L7 8XP **Location 41:** **City:** London **Country:** United Kingdom **Facility:** Guy's Hospital **Zip:** SE1 9RT **Location 42:** **City:** London **Country:** United Kingdom **Facility:** Charing Cross Hospital **Location 43:** **City:** London **Country:** United Kingdom **Facility:** Northwick Park Hospital **Location 44:** **City:** Manchester **Country:** United Kingdom **Facility:** Manchester Royal Infirmary **Zip:** M13 9WL **Location 45:** **City:** Middlesbrough **Country:** United Kingdom **Facility:** James Cook University Hospital **Location 46:** **City:** Newcastle upon Tyne **Country:** United Kingdom **Facility:** Freeman Hospital **Location 47:** **City:** Norwich **Country:** United Kingdom **Facility:** Norfolk and Norwich University Hospital **Zip:** NR4 7UY **Location 48:** **City:** Portsmouth **Country:** United Kingdom **Facility:** Queen Alexandra Hospital, **Location 49:** **City:** Rhyl **Country:** United Kingdom **Facility:** Glan Clywd Hospital **Zip:** LL18 5UJ **Location 50:** **City:** Romford, Essex **Country:** United Kingdom **Facility:** Queen's Hospital, **Location 51:** **City:** Shrewsbury **Country:** United Kingdom **Facility:** Royal Shrewsbury Hospital **Zip:** SY3 8XQ **Location 52:** **City:** Southampton **Country:** United Kingdom **Facility:** Southampton General Hospital **Location 53:** **City:** Stevenage **Country:** United Kingdom **Facility:** Lister Hospital **Zip:** SG1 4AA **Location 54:** **City:** Stockton-on-Tees **Country:** United Kingdom **Facility:** University Hospital of North Tees **Zip:** TS19 8PE **Location 55:** **City:** Surrey **Country:** United Kingdom **Facility:** Frimley Park Hospital **Zip:** GU16 7UJ **Location 56:** **City:** Sutton **Country:** United Kingdom **Facility:** The Royal Marsden Hospital **Zip:** SM2 5PT **Location 57:** **City:** Taunton **Country:** United Kingdom **Facility:** Musgrove Park Hospital **Location 58:** **City:** Torbay **Country:** United Kingdom **Facility:** Torbay District General Hospital **Zip:** TQ2 7AA **Location 59:** **City:** Treliske **Country:** United Kingdom **Facility:** Royal Cornwall Hospital **Zip:** TR1 3LJ **Location 60:** **City:** Worthing **Country:** United Kingdom **Facility:** Worthing Hospital **Zip:** BN11 2DH **Location 61:** **City:** York **Country:** United Kingdom **Facility:** York District Hospital **Zip:** YO31 8HE #### Overall Officials **Official 1:** **Affiliation:** Lancashire Teaching Hospitals NHS Foundation Trust **Name:** Dr Alison Birtle **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### References **Citation:** Birtle A, Johnson M, Chester J, Jones R, Dolling D, Bryan RT, Harris C, Winterbottom A, Blacker A, Catto JWF, Chakraborti P, Donovan JL, Elliott PA, French A, Jagdev S, Jenkins B, Keeley FX Jr, Kockelbergh R, Powles T, Wagstaff J, Wilson C, Todd R, Lewis R, Hall E. Adjuvant chemotherapy in upper tract urothelial carcinoma (the POUT trial): a phase 3, open-label, randomised controlled trial. Lancet. 2020 Apr 18;395(10232):1268-1277. doi: 10.1016/S0140-6736(20)30415-3. Epub 2020 Mar 5. **PMID:** 32145825 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000002277 - Term: Carcinoma - ID: D000009375 - Term: Neoplasms, Glandular and Epithelial - ID: D000009370 - Term: Neoplasms by Histologic Type - ID: D000009369 - Term: Neoplasms ### 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: M5551 - Name: Carcinoma, Transitional Cell - Relevance: HIGH - As Found: Transitional Cell 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: T5693 - Name: Transitional Cell Carcinoma - Relevance: HIGH - As Found: Transitional Cell Carcinoma ### Condition Browse Module - Meshes - ID: D000002295 - Term: Carcinoma, Transitional Cell ### Intervention Browse Module - Ancestors - ID: D000000970 - Term: Antineoplastic Agents - ID: D000000964 - Term: Antimetabolites, Antineoplastic - ID: D000000963 - Term: Antimetabolites - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action ### Intervention Browse Module - Browse Branches - Abbrev: ANeo - Name: Antineoplastic Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M6182 - Name: Cisplatin - Relevance: HIGH - As Found: High - ID: M2985 - Name: Gemcitabine - Relevance: HIGH - As Found: Activity - ID: M18650 - Name: Carboplatin - Relevance: HIGH - As Found: System - ID: M4281 - Name: Antimetabolites - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000002945 - Term: Cisplatin - ID: D000016190 - Term: Carboplatin - ID: D000093542 - Term: Gemcitabine ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT02052479 **Brief Title:** Insulin Differences Between African-American and Caucasian Female Adolescents With Polycystic Ovary Syndrome (PCOS) **Official Title:** Differences in Insulin Secretion and Insulin Sensitivity/Resistance in African-American and Caucasian Adolescent Females With Polycystic Ovary Syndrome #### Organization Study ID Info **ID:** 297013 #### Organization **Class:** OTHER **Full Name:** Nationwide Children's Hospital ### Status Module #### Completion Date **Date:** 2015-06 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2019-10-07 **Type:** ACTUAL **Last Update Submit Date:** 2019-10-03 **Overall Status:** TERMINATED #### Primary Completion Date **Date:** 2015-06 **Type:** ACTUAL #### Start Date **Date:** 2014-01 **Type:** ACTUAL **Status Verified Date:** 2019-10 #### Study First Post Date **Date:** 2014-02-03 **Type:** ESTIMATED **Study First Submit Date:** 2014-01-29 **Study First Submit QC Date:** 2014-01-30 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Nationwide Children's Hospital #### Responsible Party **Investigator Affiliation:** Nationwide Children's Hospital **Investigator Full Name:** Rachel-Marie Cazeau **Investigator Title:** Pediatric Endocrinology Fellow **Type:** PRINCIPAL_INVESTIGATOR ### Description Module **Brief Summary:** The purpose of this research study is to see if there are differences between African-American and Caucasian girls with Polycystic Ovary Syndrome (PCOS) in how their bodies respond to a type of sugar, called glucose, the body's main source of energy. PCOS is one of the most common endocrine disorders among females. Features can include anovulation (eggs are not released from the ovaries) resulting in irregular menstrual periods, excessive amounts of androgenic (male) hormones resulting in acne and hirsutism (excessive hair growth on the face and body), and polycystic ovaries (small sac-like structures \[cysts\] on your ovaries) seen on ultrasound. Girls with PCOS also have higher levels of insulin in their bodies (called hyperinsulinism) but are not able to use insulin very well (called insulin resistance) resulting in an increased risk of diabetes. Diabetes is when you have high levels of glucose (sugar) in your blood. Many studies have looked at how bodies respond to glucose and have shown that compared to Caucasians, healthy African-Americans produce much more insulin (hyperinsulinism) but are not able to use it as well (insulin resistance) in childhood, adolescence, and adulthood. Insulin is a hormone that helps glucose move from the blood into the muscles for the body to use as energy. PCOS is associated with increased levels of insulin (hyperinsulinism) and not being able to use it as well (insulin resistance). So we want to see if there is a difference in insulin production (secretion) and insulin resistance between African-Americans and Caucasians girls with PCOS. To do this, we will look at blood glucose and insulin levels in response to giving glucose in African-American and Caucasian girls who have PCOS. The results of this study may ultimately help to more effectively target treatment therapy in individuals with PCOS that have increased insulin secretion and/or increased insulin resistance. **Detailed Description:** PCOS is the most common endocrine abnormality of reproductive-aged women in the United States, affecting approximately 5 million women (1). The exact prevalence of PCOS in the adolescent population is unknown mainly attributed to the diagnostic challenge PCOS presents as the characteristics of normal puberty overlap with the signs and symptoms of PCOS (2). The key features of PCOS include menstrual irregularity, hyper¬androgenism, and polycystic ovarian morphology on ultrasound. However, clinical presentation may vary. It is a complex heterogeneous condition with life-long psychological, reproductive, and metabolic manifestations that impact a woman's health throughout her lifespan. PCOS is associated with major metabolic consequences including hyperinsulinism (i.e. increased insulin secretion), insulin resistance (i.e. decreased insulin sensitivity), obesity, type 2 diabetes mellitus, dyslipidemia, cardiovascular disease, endothelial dysfunction, defective fibrino¬lysis, as well as endometrial carcinoma (3). Particular disease processes show a predilection for certain racial and ethnic groups. African-American \[AA\] adults are at increased risk of obesity, type 2 diabetes mellitus, cardiovascular disease mortality, and hyper¬tension compared to Caucasian \[CA\] adults. Past studies (4-9) have found that AAs have increased insulin secretion and decreased insulin sensitivity compared to their CA counterparts in adolescence and adulthood and even in childhood. These findings are secondary to the combination of increased insulin secretion and resistance with decreased insulin sensitivity and clearance noted in African-Americans. It is this combination of altered glucose metabolism that places AAs at increased risk of cardiovascular and metabolic morbidity. It has been proposed that hyperinsulinism or increased insulin secretion is a compensatory response by the pancreatic β-cell to increased insulin resistance. However, it has also been speculated that it is insulin resistance that is the compensatory response occurring in response to insulin hyper-secretion caused by pancreatic β-cell dysregulation (10-11). Hyperinsulinism and insulin resistance are known inherent features of PCOS. Several studies have demonstrated significant hyperinsulinism with insulin resistance and lowered insulin sensitivity in adolescents and adults with PCOS when compared to BMI-matched healthy control subjects (12-18). Marked differences in insulin sensitivity/resistance and PCOS phenotype have been reported in adults of different races/ethnicities with PCOS (19-23), however; other studies have refuted these claims (24-27). The objective of this study is to examine the differences in insulin secretion between AA and CA adolescents with PCOS. We will also examine differences in insulin sensitivity/resistance between AA and CA adolescents with PCOS. Primary Aim: To determine the influence of racial/ethnic background on insulin secretion in adolescent females with PCOS. Secondary Aim: To determine the influence of racial/ethnic background on insulin sensitivity/resistance in adolescent females with PCOS. Hypothesis: AA adolescent females with PCOS will have increased insulin secretion and decreased insulin sensitivity (i.e. increased insulin resistance) compared to CA adolescent females with PCOS. To address this hypothesis, we will utilize one of the gold standards endorsed by the American Diabetes Association that satisfactorily assess insulin secretion and insulin sensitivity/resistance. The method utilized in this study is the frequently sampled intravenous glucose tolerance test with minimal model analysis (MINMOD FSIVGTT) (28-32). Using the data that is gathered as part of our primary and secondary aims, we will also conduct an exploratory analysis to examine the influence of PCOS phenotype on insulin secretion and insulin sensitivity/resistance and the influence of racial/ethnic background on PCOS phenotype. ### Conditions Module **Conditions:** - Polycystic Ovary Syndrome - PCOS **Keywords:** - Polycystic Ovary Syndrome - PCOS - Secondary Amenorrhea - Hirsutism - Hyperandrogenism - Insulin Resistance ### Design Module #### Design Info **Allocation:** NON_RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** DIAGNOSTIC #### Enrollment Info **Count:** 12 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Frequently Sampled Intravenous Glucose Tolerance Test with minimal model analysis (MINMOD FSIVGTT) **Intervention Names:** - Other: Frequently Sampled Intravenous Glucose Tolerance Test (FSIVGTT) **Label:** Polycystic Ovary Synrome, PCOS, Caucasian, No treatment **Type:** OTHER #### Arm Group 2 **Description:** Frequently Sampled Intravenous Glucose Tolerance Test with minimal model analysis (MINMOD FSIVGTT) **Intervention Names:** - Other: Frequently Sampled Intravenous Glucose Tolerance Test (FSIVGTT) **Label:** Polycystic Ovary Synrome, PCOS, African-American, No treatment **Type:** OTHER ### Interventions #### Intervention 1 **Arm Group Labels:** - Polycystic Ovary Synrome, PCOS, African-American, No treatment - Polycystic Ovary Synrome, PCOS, Caucasian, No treatment **Name:** Frequently Sampled Intravenous Glucose Tolerance Test (FSIVGTT) **Type:** OTHER ### Outcomes Module #### Other Outcomes **Description:** Using the data that is gathered as part of our primary and secondary aims, we will also conduct an exploratory analysis to examine the influence of PCOS phenotype on insulin secretion and insulin sensitivity/resistance and the influence of racial/ethnic background on PCOS phenotype. **Measure:** Exploratory Analysis **Time Frame:** -10, 0, 2, 4, 6, 8, 12, 14, 16, 19, 22, 27, 32, 42, 52, 62, 72, 82, and 92 minutes #### Primary Outcomes **Description:** The objective of this study is to examine the differences in insulin secretion between AA and CA adolescents with PCOS. Primary Aim: To determine the influence of racial/ethnic background on insulin secretion in adolescent females with PCOS. **Measure:** Insulin Secretion **Time Frame:** -10, 0, 2, 4, 6, 8, 12, 14, 16, 19, 22, 27, 32, 42, 52, 62, 72, 82, and 92 minutes #### Secondary Outcomes **Description:** The objective of this study is to examine differences in insulin sensitivity/resistance between AA and CA adolescents with PCOS. Secondary Aim: To determine the influence of racial/ethnic background on insulin sensitivity/resistance in adolescent females with PCOS. **Measure:** Insulin Sensitivity/Resistance **Time Frame:** -10, 0, 2, 4, 6, 8, 12, 14, 16, 19, 22, 27, 32, 42, 52, 62, 72, 82, and 92 minutes ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Children and adolescents ages 12-18 years * African-American and Caucasian females * Menarchal for at least 2 years * Hemoglobin A1C \<6.5% * Medical Condition: Polycystic Ovary Syndrome (PCOS) - based on AES criteria: HA in addition to ANOV and/or PCO * Hyperandrogenism (required): Serum Testosterone \> 50 ng/dl or Free Testosterone (%) \> 1.4% or Free Testosterone \> 7 pg/mL * Oligo- and/or Anovulation: menstrual cycles lengths \> 35 days and/or \< 8 menstrual cycles a year * Polycystic Ovaries: transabdominal or trans-vaginal ultrasound finding of 12 or more follicles measuring 2-6 mm in diameter or increased ovarian volume (\> 10 mL) * Medications: Medication-naive to treatment therapy with Metformin, Oral Contraceptives, and Anti-androgen medications Exclusion Criteria: * Ages \<12 or \>18 * Prepubertal, Premenarche * Hemoglobin A1C ≥6.5% * Medical Conditions: Hypothyroidism, Hyperthyroidism, Diabetes Mellitus, Congenital Adrenal Hyperplasia, Hyperprolactinemia, Pregnancy * Medications: Past and/or Present treatment therapy with Metformin, Oral Contraceptives, Anti-androgen medications, Insulin or oral hypoglycemic agents **Maximum Age:** 18 Years **Minimum Age:** 12 Years **Sex:** FEMALE **Standard Ages:** - CHILD - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Columbus **Country:** United States **Facility:** Clinical Research Center at The Ohio University Wexner Medical Center / Nationwide Children's Hospital **State:** Ohio **Zip:** 43205 ### References Module #### See Also Links **Label:** Information on Polycystic Ovary Syndrome **URL:** http://www.hormone.org/diseases-and-conditions/womens-health/polycystic-ovary-syndrome ## Derived Section ### Condition Browse Module - Ancestors - ID: D000004194 - Term: Disease - ID: D000010335 - Term: Pathologic Processes - ID: D000010048 - Term: Ovarian Cysts - ID: D000003560 - Term: Cysts - 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: D000091662 - Term: Genital Diseases - ID: D000006058 - Term: Gonadal Disorders - ID: D000004700 - Term: Endocrine System Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC18 - Name: Nutritional and Metabolic Diseases - 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: BC20 - Name: Immune System Diseases - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: BC16 - Name: Diseases and Abnormalities at or Before Birth - Abbrev: BC17 - Name: Skin and Connective Tissue Diseases ### Condition Browse Module - Browse Leaves - ID: M10370 - Name: Insulin Resistance - Relevance: LOW - As Found: Unknown - ID: M13970 - Name: Polycystic Ovary Syndrome - Relevance: HIGH - As Found: Polycystic Ovary Syndrome - ID: M10018 - Name: Hypersensitivity - Relevance: LOW - As Found: Unknown - ID: M16355 - Name: Syndrome - Relevance: HIGH - As Found: Syndrome - ID: M12307 - Name: Neoplasm Metastasis - Relevance: LOW - As Found: Unknown - ID: M19834 - Name: Hyperandrogenism - Relevance: LOW - As Found: Unknown - ID: M3909 - Name: Amenorrhea - Relevance: LOW - As Found: Unknown - ID: M9704 - Name: Hirsutism - Relevance: LOW - As Found: Unknown - ID: M6765 - Name: Cysts - Relevance: LOW - As Found: Unknown - ID: M12971 - Name: Ovarian Cysts - 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: M9163 - Name: Gonadal Disorders - Relevance: LOW - As Found: Unknown - ID: M7862 - Name: Endocrine System Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000011085 - Term: Polycystic Ovary Syndrome - ID: D000013577 - Term: Syndrome ### Intervention Browse Module - Browse Branches - Abbrev: Hypo - Name: Hypoglycemic Agents - Abbrev: All - Name: All Drugs and Chemicals ### 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 ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT06143579 **Brief Title:** A Study of HAIC Combined With Lenvatinib and Envolizumab in Potentially Resectable Hepatocellular Carcinoma **Official Title:** FOLFOX-Hepatic Arterial Infusion Chemotherapy (HAIC) Combined With Lenvatinib and Envolizumab in Potentially Resectable Hepatocellular Carcinoma:A Single-arm, Open-label, Single Center, Phase II Trial #### Organization Study ID Info **ID:** B2023-561-01 #### Organization **Class:** OTHER **Full Name:** Sun Yat-sen University ### Status Module #### Completion Date **Date:** 2026-12-31 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2023-11-22 **Type:** ACTUAL **Last Update Submit Date:** 2023-11-16 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2025-03-03 **Type:** ESTIMATED #### Start Date **Date:** 2023-12-15 **Type:** ESTIMATED **Status Verified Date:** 2023-11 #### Study First Post Date **Date:** 2023-11-22 **Type:** ACTUAL **Study First Submit Date:** 2023-11-16 **Study First Submit QC Date:** 2023-11-16 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Sun Yat-sen University #### Responsible Party **Investigator Affiliation:** Sun Yat-sen University **Investigator Full Name:** Zhongguo Zhou **Investigator Title:** Clinical Professor **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** This is a single term, open label, single Center, Phase II Trial. The study is to explore the efficacy and safety of FOLFOX-HAIC combined with Lenvatinib and Envolizumab in the treatment of patients with potentially resectable HCC. **Detailed Description:** At present, surgery is the preferred modality for the treatment of HCC patients with radical cure and long-term survival. However, 70% to 80% of HCC is advanced, and only 15% to 30% of patients are able to undergo surgical resection. For unresectable HCC, transformation therapy is currently used, and the response rate can be effectively increased through the "TKI plus IO" or "TKI plus IO and local therapy" regimen. For locally advanced HCC (stage III-IV), HAIC or HAIC + systemic therapy is recommended. And the first-line treatment of advanced HCC, TKI (Lenvatinib, Donafenib) or IO combined TKI are recommended. For patients with potentially resectable HCC, there are currently few explorations, and more effective treatment options and evidence-based medical evidence are needed. Therefore, this study investigated the efficacy and safety of FOLFOX-HAIC combined with Lenvatinib and Envolizumab in the treatment of patients with potentially resectable HCC, and explored the relationship between biomarkers, prognostic factors and efficacy. ### Conditions Module **Conditions:** - Potentially Resectable Hepatocellular Carcinoma **Keywords:** - HAIC - Lenvatinib - Envolizumab - PD-L1 - TKI - potentially resectable HCC ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 48 **Type:** ESTIMATED **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** FOLFOX-HAIC + Lenvatinib + Envolizumab **Intervention Names:** - Drug: FOLFOX-HAIC+Lenvatinib+Envolizumab **Label:** Treatment **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Treatment **Description:** FOLFOX-HAIC: Oxaliplatin 130 or 85 mg/m2; leucovorin 200 mg/m2; fluorouracil 400 mg/m2 intravenous bolus followed by fluorouracil 2400 mg/m2 continuous infusion over 23 hours, Q3W, 2 to 4 cycles; Lenvatinib: 8 mg/day (BW \< 60 kg) or 12 mg/day (BW ≥ 60 kg), PO, 3-4 cycles; Envolizumab: 300 mg, SC, Q3W, 3-4 cycles. **Name:** FOLFOX-HAIC+Lenvatinib+Envolizumab **Other Names:** - KN035 **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Defined as the proportion of patients with AE, treatment-related AE (TRAE), immune-related AE (irAE), serious adverse event (SAE), assessed by NCI CTCAE v5.0 **Measure:** AEs **Time Frame:** Up to 60 days after last treatment or 30 days after surgery **Description:** Defined as proportion of patients who have a best response of CR or PR **Measure:** Overall response rate (ORR) **Time Frame:** At the end of Cycle 4 (each cycle is 21 days) #### Secondary Outcomes **Description:** According to post-operative pathology, the proportion of tumor necrosis, viable. tumor cells, and tumor infiltrating lymphocytes indicated by surgical resected specimens. **Measure:** Pathological complete response (pCR) **Time Frame:** At the end of the surgery **Description:** Survival tumor ≤10% after surgery **Measure:** Major Pathological Response(MPR) **Time Frame:** At the end of the surgery **Description:** The tumor was completely removed during surgery, and the resection margin was negative when observed microscopically without residual components of the tumor **Measure:** R0 resection rate **Time Frame:** At the end of the surgery **Description:** Subjects underwent radical resection from the start until the date of the first documented tumor into recurrence or death from any cause in, whichever occurred first within 1 year after surgery **Measure:** 1-year recurrence-free survival(RFS) rate **Time Frame:** Up to one years **Description:** Subjects underwent radical resection from the start until the date of the first documented tumor into recurrence or death from any cause, whichever occurred first **Measure:** Recurrence-free survival(RFS) **Time Frame:** Up to two years **Description:** Defined as the time from enrollment to death from any cause **Measure:** Overall survival (OS) **Time Frame:** Up to two years ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Patients who have signed ICF and are able to perform follow-up visits and relevant procedures required in the protocol; 2. Age ≥ 18 years (at the time of signing the ICF); 3. Clinically, histologically or pathologically confirmed hepatocellular carcinoma without extrahepatic metastases; 4. No previous treatment containing PD- (L) 1 inhibitor and Lenvatinib; 5. Potentially resectable HCC: (1)At least one measurable lesion (according to RECIST 1.1 criteria); (2)Patients with stage IIb/IIIa (equivalent to BCLC B/C) with portal vein tumor thrombus (according to Japanese PVTT grading criteria Vp3-Vp4) or more than three tumor nodules; (3)According to the assessment of the site multidisciplinary team (MDT), like surgical resection is not currently the treatment of choice; 6. ECOG score: 0 \~ 1; 7. Child-Pugh score of ≤ 7 8. Estimated survival of more than 6 months; 9. Vital organ function meets the following requirements: (1) Blood routine: Absolute neutrophil count (ANC) ≥ 1.5 × 109/L; Platelet count (PLT) ≥ 100 × 109/L; Hemoglobin (HGB) ≥ 90 g/L; (2) Liver function: Serum creatinine (Cr) ≤ 1.5 × upper limit of normal (ULN) or clearance of creatinine ≥ 50 mL/min (Cockcroft-Gault formula); Total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN); Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels ≤ 2.5 × upper limit of normal (ULN); (3) Kidney function: Urine protein \< 2 +; if urine protein ≥ 2 +, 24-h urine protein quantitation test result should be ≤ 1 g; 10. Normal coagulation function, no active bleeding and thrombosis (1) International normalized ratio (INR) ≤ 1.5 × ULN; (2) Active partial thromboplastin time (APTT) ≤ 1.5 × ULN; (3) Prothrombin time (PT) ≤ 1.5 × ULN; 11. Female patients of childbearing age or male patients with female sexual partners of childbearing age should take effective contraceptive measures during study treatment and for 3 months after the end of study treatment; serum or urine HCG tests must be negative and must be non-lactating within 7 days before study enrollment; 12. Patients should be compliant and cooperative with safety and survival follow-up. Exclusion Criteria: 1. Participate in other interventional clinical studies; 2. Previous or concurrent other malignancies; 3. History of liver transplantation or undergo liver transplantation; 4. History of hypersensitivity to macromolecular protein preparations, the study drug or any of the excipients; 5. Active autoimmune disease or history of autoimmune diseases (such as the following, but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism, previous thyroid surgery); Require bronchodilators for medical intervention of asthma; the patient has vitiligo or has complete remission of asthma in childhood, no intervention is required after adults can be included; 6. Use immunosuppressive agents, or systemic or absorbable local hormone therapy to achieve immunosuppressive purposes (dose \> 10 mg/day prednisone or other effective hormones), and continue to use within 2 weeks before enrollment; 7. Uncontrolled cardiac clinical symptoms or diseases, for example: (1) NYHA class 2 or higher heart failure;(2) Unstable angina pectoris; (3) Myocardial infarction within 1 year; (4) Clinically significant supraventricular or ventricular arrhythmia requiring treatment or intervention; 8. Use traditional Chinese medicine immunomodulator within 2 weeks before enrollment; 9. Severe active infection or unexplained fever \> 38.5 degrees during screening and before the first dose (subjects can be enrolled due to tumor-induced fever at the investigator discretion); 10. Congenital or acquired immunodeficiency: (1)HIV infection; (2)Active hepatitis (hepatitis B reference: HBV DNA ≥ 1000 IU/mL; hepatitis C reference: HCV RNA ≥ 1000 IU/mL); chronic hepatitis B virus carriers, HBV DNA \< 2000 IU/ml, must receive concurrent antiviral therapy during the trial to be enrolled; 11. Live vaccines less than 4 weeks prior to study medication or likely during the study; 12. History of psychiatric drug abuse, alcoholism, or drug abuse; 13. Chinese herbal medicine within 4 weeks prior to first treatment; 14. Factors that may cause forced halfway termination of this study, such as other serious diseases (including mental illness) requiring concomitant treatment, serious laboratory abnormalities, accompanied by family or social factors, which may affect the subject' s safety, the collection of data and samples, or other circumstances which are unsuitable for subject enrollment as judged by the investigator. **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Zhongguo Zhou **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Chaoqun Li **Phone:** +86 20-87343879 **Role:** CONTACT #### Overall Officials **Official 1:** **Affiliation:** Sun Yat-sen University **Name:** Zhongguo Zhou **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Zhou M, Wang H, Zeng X, Yin P, Zhu J, Chen W, Li X, Wang L, Wang L, Liu Y, Liu J, Zhang M, Qi J, Yu S, Afshin A, Gakidou E, Glenn S, Krish VS, Miller-Petrie MK, Mountjoy-Venning WC, Mullany EC, Redford SB, Liu H, Naghavi M, Hay SI, Wang L, Murray CJL, Liang X. Mortality, morbidity, and risk factors in China and its provinces, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2019 Sep 28;394(10204):1145-1158. doi: 10.1016/S0140-6736(19)30427-1. Epub 2019 Jun 24. Erratum In: Lancet. 2020 Jul 4;396(10243):26. **PMID:** 31248666 **Citation:** Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin. 2023 Jan;73(1):17-48. doi: 10.3322/caac.21763. **PMID:** 36633525 **Citation:** Akateh C, Black SM, Conteh L, Miller ED, Noonan A, Elliott E, Pawlik TM, Tsung A, Cloyd JM. Neoadjuvant and adjuvant treatment strategies for hepatocellular carcinoma. World J Gastroenterol. 2019 Jul 28;25(28):3704-3721. doi: 10.3748/wjg.v25.i28.3704. **PMID:** 31391767 **Citation:** Zhang T, Zhang L, Xu Y, Lu X, Zhao H, Yang H, Sang X. Neoadjuvant therapy and immunotherapy strategies for hepatocellular carcinoma. Am J Cancer Res. 2020 Jun 1;10(6):1658-1667. eCollection 2020. **PMID:** 32642282 **Citation:** Papadopoulos KP, Harb W, Peer CJ, Hua Q, Xu S, Lu H, Lu N, He Y, Xu T, Dong R, Gong J, Liu D. First-in-Human Phase I Study of Envafolimab, a Novel Subcutaneous Single-Domain Anti-PD-L1 Antibody, in Patients with Advanced Solid Tumors. Oncologist. 2021 Sep;26(9):e1514-e1525. doi: 10.1002/onco.13817. Epub 2021 May 27. **PMID:** 33973293 **Citation:** Chen M, Jiang M, Wang X, Shen L, Li J. Envafolimab - first PD-1/PD-L1 antibody to be administered by subcutaneous injection for microsatellite instability-high or deficient mismatch repair advanced solid tumors. Expert Opin Biol Ther. 2022 Oct;22(10):1227-1232. doi: 10.1080/14712598.2022.2125799. Epub 2022 Sep 20. **PMID:** 36124972 **Citation:** Shimizu T, Nakajima TE, Yamamoto N, Yonemori K, Koyama T, Kondo S, Sunakawa Y, Izawa N, Horie Y, Xiang S, Xu S, Qin L, Gong J, Liu D. Phase I study of envafolimab (KN035), a novel subcutaneous single-domain anti-PD-L1 monoclonal antibody, in Japanese patients with advanced solid tumors. Invest New Drugs. 2022 Oct;40(5):1021-1031. doi: 10.1007/s10637-022-01287-7. Epub 2022 Aug 6. **PMID:** 35932387 **Citation:** Huang X, Xu L, Ma T, Yin X, Huang Z, Ran Y, Ni Y, Bi X, Che X. Lenvatinib Plus Immune Checkpoint Inhibitors Improve Survival in Advanced Hepatocellular Carcinoma: A Retrospective Study. Front Oncol. 2021 Nov 16;11:751159. doi: 10.3389/fonc.2021.751159. eCollection 2021. **PMID:** 34868952 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009375 - Term: Neoplasms, Glandular and Epithelial - ID: D000009370 - Term: Neoplasms by Histologic Type - ID: D000009369 - Term: Neoplasms - ID: D000000230 - Term: Adenocarcinoma - ID: D000008113 - Term: Liver Neoplasms - ID: D000004067 - Term: Digestive System Neoplasms - ID: D000009371 - Term: Neoplasms by Site - ID: D000004066 - Term: Digestive System Diseases - ID: D000008107 - Term: Liver Diseases ### 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: HIGH - As Found: Carcinoma - ID: M9613 - Name: Carcinoma, Hepatocellular - Relevance: HIGH - As Found: Hepatocellular 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: M3585 - Name: Adenocarcinoma - Relevance: LOW - As Found: Unknown - ID: M11113 - Name: Liver Neoplasms - Relevance: LOW - As Found: Unknown - ID: M8886 - Name: Gastrointestinal Neoplasms - Relevance: LOW - As Found: Unknown - ID: M7256 - Name: Digestive System Neoplasms - Relevance: LOW - As Found: Unknown - ID: M7255 - Name: Digestive System Diseases - Relevance: LOW - As Found: Unknown - ID: M8883 - Name: Gastrointestinal Diseases - Relevance: LOW - As Found: Unknown - ID: M11107 - Name: Liver Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000002277 - Term: Carcinoma - ID: D000006528 - Term: Carcinoma, Hepatocellular ### Intervention Browse Module - Ancestors - ID: D000000970 - Term: Antineoplastic Agents - ID: D000047428 - Term: Protein Kinase Inhibitors - ID: D000004791 - Term: Enzyme Inhibitors - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action ### Intervention Browse Module - Browse Branches - Abbrev: Micro - Name: Micronutrients - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: ANeo - Name: Antineoplastic Agents ### Intervention Browse Module - Browse Leaves - ID: M6191 - Name: Leucovorin - Relevance: LOW - As Found: Unknown - ID: M8600 - Name: Fluorouracil - Relevance: LOW - As Found: Unknown - ID: M353738 - Name: Lenvatinib - Relevance: HIGH - As Found: Fibrillation - ID: M1674 - Name: Oxaliplatin - 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: C000531958 - Term: Lenvatinib ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT02694679 **Brief Title:** Randomized Controlled Trial of Social Network Targeting in Honduras **Official Title:** Randomized Controlled Trial of Social Network Targeting to Magnify Population-Level MNCH Behavior Change in Honduras #### Organization Study ID Info **ID:** 1506016012 #### Organization **Class:** OTHER **Full Name:** Yale University ### Status Module #### Completion Date **Date:** 2020-01 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2023-08-08 **Type:** ACTUAL **Last Update Submit Date:** 2023-08-04 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2020-01 **Type:** ACTUAL #### Start Date **Date:** 2015-06 **Type:** ACTUAL **Status Verified Date:** 2023-08 #### Study First Post Date **Date:** 2016-02-29 **Type:** ESTIMATED **Study First Submit Date:** 2016-02-24 **Study First Submit QC Date:** 2016-02-24 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** Inter-American Development Bank **Class:** OTHER **Name:** University of California, San Diego #### Lead Sponsor **Class:** OTHER **Name:** Yale University #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** Social network targeting strategies can be used to improve the delivery and uptake of health interventions. We will enroll approximately 30,000 individuals into a randomized controlled trial of different targeting algorithms in order to explore how social network dynamics affect the uptake, diffusion, and group-level normative reinforcement of key neonatal and infant health behaviors and attitudes in 176 rural villages in the Copan region of Honduras. Our goal is to develop methods by which global health practitioners can exploit face-to-face social network interactions in order to maximize uptake of neonatal and infant health interventions. The villages will be randomly assigned to 16 cells of 11 villages each in a 2 x 8 factorial design of different targeting algorithms. **Detailed Description:** Honduras has one of the highest neonatal mortality rates in Latin America despite having made significant strides in reducing neonatal, infant, and child mortality in the last several decades. Although many neonatal and infant deaths can be prevented through provision of clinical care services, emerging evidence also suggests that a substantial reduction in neonatal and infant mortality can also be achieved with simple, low-cost interventions within family and community settings. This is particularly important in areas where functional community health facilities are not available. Family and community outreach programs can serve to educate families about beneficial home care practices. In order to accelerate neonatal mortality reduction , there is an urgent need to develop innovative solutions that are not only effective, but also more easily implementable and more readily scalable. An important component of this challenge, which has hitherto not been effectively measured and understood with respect to neonatal mortality, is the "embeddedness" of individuals within social networks. Hence, through a large-scale randomized controlled trial (RCT) in rural Honduras, we will deploy and assess social network targeting algorithms in order to maximize diffusion and adoption of the "Changing behaviors to improve neonatal, child, and maternal health using communication and social networks at the community level intervention (CBNH)". The CBNH intervention is a household-level intervention package that targets health behaviors surrounding neonatal and maternal health, and diarrhea and respiratory illness prevention and management implemented by the Inter-American Development Bank (IADB) and their partners. This RCT is aimed at discerning optimal methods for targeting delivery of the intervention to the population. Specifically we will (1) test what percentage of a community needs to be in a program to achieve social norms change around key neonatal care behaviors, and (2) test whether so-called nominated-friend-targeting, a method that targets individuals who are more highly connected in the network, is more effective than a control strategy. Our 2x8 factorial design will examine how large a subset of the population should be used as a "seed" group in order to maximize the chances of spread of the effect, and the efficiency with which such an intervention might be delivered in the future. To do this, we will assign each of the 176 study villages to either one of the two groups: 1)random assignment (active comparator), where "seed" individuals are chose at random or 2) friend-of-random assignment (experimental), where "seed" individuals are chosen on the basis of being named as a friend of a randomly selected individual. Each of the groups of villages will also be assigned to one of eight treatment percentages (0%, 5%, 10%, 20%, 30% 50%, 75%, 100%), where each represents the percent of targeted households in that village to receive the CBNH health intervention. ### Conditions Module **Conditions:** - Preterm Delivery - Hypothermia - Diarrhea - Upper Respiratory Infection - Omphalitis **Keywords:** - social networks, maternal and child health, global health ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** FACTORIAL ##### Masking Info **Masking:** NONE **Primary Purpose:** OTHER #### Enrollment Info **Count:** 31195 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** The CBNH intervention will be delivered to 0% of population targeted households in the village. **Label:** Random 0 **Type:** NO_INTERVENTION #### Arm Group 2 **Description:** The CBNH intervention will be delivered to a random 5% of targeted households in the village. **Intervention Names:** - Behavioral: CBNH **Label:** Random 5 **Type:** ACTIVE_COMPARATOR #### Arm Group 3 **Description:** The CBNH intervention will be delivered to a random 10% of targeted households in the village. **Intervention Names:** - Behavioral: CBNH **Label:** Random 10 **Type:** ACTIVE_COMPARATOR #### Arm Group 4 **Description:** The CBNH intervention will be delivered to a random 20% of targeted households in the village. **Intervention Names:** - Behavioral: CBNH **Label:** Random 20 **Type:** ACTIVE_COMPARATOR #### Arm Group 5 **Description:** The CBNH intervention will be delivered to a random 30% of targeted households in the village. **Intervention Names:** - Behavioral: CBNH **Label:** Random 30 **Type:** ACTIVE_COMPARATOR #### Arm Group 6 **Description:** The CBNH intervention will be delivered to a random 50% of targeted households in the village. **Intervention Names:** - Behavioral: CBNH **Label:** Random 50 **Type:** ACTIVE_COMPARATOR #### Arm Group 7 **Description:** The CBNH intervention will be delivered to a random 75% of targeted households in the village. **Intervention Names:** - Behavioral: CBNH **Label:** Random 75 **Type:** ACTIVE_COMPARATOR #### Arm Group 8 **Description:** The CBNH intervention will be delivered to a random 100% of targeted households in the village. **Intervention Names:** - Behavioral: CBNH **Label:** Random 100 **Type:** ACTIVE_COMPARATOR #### Arm Group 9 **Description:** CBNH 0% of population targeted **Label:** Friendship 0 **Type:** NO_INTERVENTION #### Arm Group 10 **Description:** The CBNH intervention will be delivered to 5% of households identified through friendship nomination. **Intervention Names:** - Behavioral: CBNH **Label:** Friendship 5 **Type:** EXPERIMENTAL #### Arm Group 11 **Description:** The CBNH intervention will be delivered to 10% of households identified through friendship nomination. **Intervention Names:** - Behavioral: CBNH **Label:** Friendship 10 **Type:** EXPERIMENTAL #### Arm Group 12 **Description:** The CBNH intervention will be delivered to 20% of households identified through friendship nomination. **Intervention Names:** - Behavioral: CBNH **Label:** Friendship 20 **Type:** EXPERIMENTAL #### Arm Group 13 **Description:** The CBNH intervention will be delivered to 30% of households identified through friendship nomination. **Intervention Names:** - Behavioral: CBNH **Label:** Friendship 30 **Type:** EXPERIMENTAL #### Arm Group 14 **Description:** The CBNH intervention will be delivered to 50% of households identified through friendship nomination. **Intervention Names:** - Behavioral: CBNH **Label:** Friendship 50 **Type:** EXPERIMENTAL #### Arm Group 15 **Description:** The CBNH intervention will be delivered to 75% of households identified through friendship nomination. **Intervention Names:** - Behavioral: CBNH **Label:** Friendship 75 **Type:** EXPERIMENTAL #### Arm Group 16 **Description:** The CBNH intervention will be delivered to 100% of households identified through friendship nomination. **Intervention Names:** - Behavioral: CBNH **Label:** Friendship 100 **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Friendship 10 - Friendship 100 - Friendship 20 - Friendship 30 - Friendship 5 - Friendship 50 - Friendship 75 - Random 10 - Random 100 - Random 20 - Random 30 - Random 5 - Random 50 - Random 75 **Description:** The household-level intervention package targets health behaviors surrounding neonatal and maternal health, and diarrhea and respiratory illness prevention and management. **Name:** CBNH **Type:** BEHAVIORAL ### Outcomes Module #### Primary Outcomes **Measure:** Speed of adoption of intervention and fraction of adoption of CBNH intervention (participant survey). **Time Frame:** 24 Months **Measure:** Percent of participants reporting paternal involvement during pregnancy and postpartum care (participant survey). **Time Frame:** 24 Months **Measure:** Percent of newborns with appropriate umbilical cord care (participant survey) **Time Frame:** 24 Months **Measure:** Percent of children under 5 with diarrheal illness in the last 4 weeks (participant survey) **Time Frame:** 24 Months **Measure:** Percent of children under age 5 with symptoms of acute respiratory illness in the last 4 weeks (participant survey). **Time Frame:** 24 months **Measure:** Percent of women experiencing a pregnancy danger sign who sought professional medical care (participant survey). **Time Frame:** 24 months **Measure:** Percent of children experiencing a newborn danger sign who were taken to professional medical care (participant survey) **Time Frame:** 24 months **Measure:** Percent of children who were breastfed exclusively during first 6 months (participant survey) **Time Frame:** 24 Months **Measure:** Percentage of deliveries taking place in medical facilities (participant survey, medical records). **Time Frame:** 24 months **Measure:** Receipt of post-natal care medical check-up within 7 days of delivery - Mother (participant survey, medical records). **Time Frame:** 24 months **Measure:** Receipt of post-natal care medical check-up within 7 days of delivery - Newborn (participant survey, medical records). **Time Frame:** 24 months **Measure:** Percent of newborns receiving appropriate thermal care during first 7 days after birth (participant survey). **Time Frame:** 24 months #### Secondary Outcomes **Measure:** Knowledge/attitudes about thermal care in newborns (Participant survey) **Time Frame:** 24 months **Measure:** Knowledge/attitudes about paternal involvement (Participant survey) **Time Frame:** 24 months **Measure:** Knowledge/attitudes about proper cord care (Participant survey) **Time Frame:** 24 months **Measure:** Knowledge/attitudes about prevention and/or treatment of diarrhea (Participant survey) **Time Frame:** 24 months **Measure:** Knowledge/attitudes about prevention and/or treatment of respiratory illness (Participant survey) **Time Frame:** 24 months **Measure:** Knowledge about danger signs during pregnancy (Participant survey). **Time Frame:** 24 months **Measure:** Knowledge about danger signs for newborns (Participant survey). **Time Frame:** 24 months **Measure:** Knowledge/attitudes about facility-based births (Participant survey). **Time Frame:** 24 months **Measure:** Knowledge/attitudes about post-natal care for women (Participant survey). **Time Frame:** 24 months **Measure:** Knowledge/attitudes about post-natal care for newborns (Participant survey). **Time Frame:** 24 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: People who live or work in target villages, ages 12 and up - Exclusion Criteria: People who do not live or work in the sample villages, and those who are prisoners, mentally impaired, or under age 12 years. - **Healthy Volunteers:** True **Minimum Age:** 12 Years **Sex:** ALL **Standard Ages:** - CHILD - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** New Haven **Country:** United States **Facility:** Yale Institute for Network Science **State:** Connecticut **Zip:** 06520 **Location 2:** **City:** Copan Ruinas **Country:** Honduras **Facility:** Community intervention **State:** Copan #### Overall Officials **Official 1:** **Affiliation:** Yale University **Name:** Nicholas Christakis, MD, PhD **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### References **Citation:** Shakya HB, Stafford D, Hughes DA, Keegan T, Negron R, Broome J, McKnight M, Nicoll L, Nelson J, Iriarte E, Ordonez M, Airoldi E, Fowler JH, Christakis NA. Exploiting social influence to magnify population-level behaviour change in maternal and child health: study protocol for a randomised controlled trial of network targeting algorithms in rural Honduras. BMJ Open. 2017 Mar 13;7(3):e012996. doi: 10.1136/bmjopen-2016-012996. **PMID:** 28289044 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000012817 - Term: Signs and Symptoms, Digestive - ID: D000001832 - Term: Body Temperature Changes - ID: D000007239 - Term: Infections - ID: D000012140 - Term: Respiratory Tract Diseases - ID: D000007752 - Term: Obstetric Labor, Premature - ID: D000007744 - Term: Obstetric Labor Complications - ID: D000011248 - Term: Pregnancy Complications - ID: D000005261 - Term: Female Urogenital Diseases and Pregnancy Complications - ID: D000091642 - Term: Urogenital Diseases ### 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: BC08 - Name: Respiratory Tract (Lung and Bronchial) 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: M10085 - Name: Hypothermia - Relevance: HIGH - As Found: Hypothermia - ID: M25869 - Name: Premature Birth - Relevance: HIGH - As Found: Preterm Delivery - ID: M14978 - Name: Respiratory Tract Infections - Relevance: HIGH - As Found: Upper Respiratory Infection - ID: M7159 - Name: Diarrhea - Relevance: HIGH - As Found: Diarrhea - ID: M15622 - Name: Signs and Symptoms, Digestive - Relevance: LOW - As Found: Unknown - ID: M5111 - Name: Body Temperature Changes - Relevance: LOW - As Found: Unknown - ID: M14977 - Name: Respiratory Tract Diseases - Relevance: LOW - As Found: Unknown - ID: M10772 - Name: Obstetric Labor, Premature - Relevance: LOW - As Found: Unknown - ID: M10764 - Name: Obstetric Labor Complications - Relevance: LOW - As Found: Unknown - ID: M14127 - Name: Pregnancy Complications - Relevance: LOW - As Found: Unknown - ID: M2875 - Name: Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M27093 - Name: Female Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M8399 - Name: Female Urogenital Diseases and Pregnancy Complications - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000012141 - Term: Respiratory Tract Infections - ID: D000047928 - Term: Premature Birth - ID: D000003967 - Term: Diarrhea - ID: D000007035 - Term: Hypothermia ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00203879 **Brief Title:** Study of MAGE-3/Melan-A/gp 100/NA17 and rhIL-12 With/Out Low Dose IL-2 in Metastatic Melanoma **Official Title:** Randomized Phase II Study of Immunization With MAGE-3/Melan-A/gp 100/NA17 Peptide-Pulsed Autologous PBMC and rhIL-12 With or Without Low Dose IL-2 Inpatients With Metastatic Melanoma **NCT ID Aliases:** - NCT00064168 #### Organization Study ID Info **ID:** 11447A #### Organization **Class:** OTHER **Full Name:** University of Chicago ### Status Module #### Completion Date **Date:** 2007-05 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2013-09-05 **Type:** ESTIMATED **Last Update Submit Date:** 2013-09-04 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2006-05 **Type:** ACTUAL #### Start Date **Date:** 2002-02 **Status Verified Date:** 2013-09 #### Study First Post Date **Date:** 2005-09-20 **Type:** ESTIMATED **Study First Submit Date:** 2005-09-12 **Study First Submit QC Date:** 2005-09-12 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** University of Chicago #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** Purpose of investigation: Primary hypotheses: Immunization of patients with 4 melanoma antigen peptides will induce augmented specific IFN-y-producing CD8+ T cells against all 4 antigens simultaneously. Immunization with 4 melanoma antigen peptides will increase the response rate from 10% to 30%. Administration of low-dose IL-2 following each vaccine will result in a greater than 3-fold increase in specific T cells compared to no IL-2. Secondary hypotheses: Immunization will clear the blood of detectable circulating melanoma cells. Tumors that grow despite induction of melanoma antigen-specific T cells may lack expression of antigens, class I MHC, or the TAP peptide transporter, or may fail to show increased expression of mRNA for IFN-y or perforin. Tumors that resist vaccination may express a different array of genes than those that are susceptible to vaccination. **Detailed Description:** Based on the above preclinical and Phase I results, a logical strategy for a second generation melanoma vaccine has emerged. A randomized Phase II study in metastatic melanoma patients will be undertaken. Patients first will be HLA-typed; HLA-A2-positive patients will be eligible for screening. When feasible, each patient will undergo a tumor biopsy to screen for expression of MAGE-3, Melan-A, gplOO, and NAI 7 using RT-PCR and immunohistochemistry, to determine whether T cells are present in the lesion, to measure cytokine gene expression by RT-PCR, and to perform gene array analysis. In addition, blood cells will be analyzed for certain parameters of T cell function. Patients will be randomized to cohorts A (no IL-2) or B (with low-dose IL-2). For treatment, peripheral blood will be collected and fractionated by density centrifugation to isolate PBMC as a source of APC. The PBMC will be divided into four pools, each of which will be incubated with one of the following peptides: MAGE-3, Melan-A, gp 100, or Ni 7A. The peptide-loaded cells will then be washed and recombined into a single suspension in PBS, and lethally irradiated. Approximately 120 x 106 pulsed cells will be injected subcutaneously at a site near a lymph node not thought to be involved with tumor. The subcutaneous route has been selected for the reasons of safety, efficacy in the preclinical model, and the goal of targeting the vaccine to a draining lymph node. rhIL-12 (4 .tg straight dose) will then be given subcutaneously adjacent to the vaccine site days 1,3, and 5 of each cycle. This dose and schedule was found to be effective in our phase I study. In one-half of the patients (cohort B), IL-2 (I MU straight dose) will be administered subcutaneously daily, days 7-18. Re-immunization along with rhIL-12 followed by IL-2 (if assigned) will be performed at 3 week intervals as in cycle I. On day 1 of each cycle, peripheral blood will be collected to measure peptide-specific IFN-y production. Before treatment and after every 3 cycles, PBMC will be collected to quantify peptide specific CD8 T cells by flow cytometric analysis with peptide/HLA-A2 tetramers, and evidence for a molecular response will be assessed by performing RT-PCR. for melanoma antigens on peripheral blood samples. In addition, prior to treatment, after the first 3 cycles, and at the time of going off- study, a tumor biopsy will be performed to assess the immune response in the tumor microenvironment, including gene array analysis. It is hoped that these studies will uncover the reason for lack of clinical response in patients with residual tumors. Clinical response will be assessed as a secondary outcome. ### Conditions Module **Conditions:** - Metastatic Melanoma **Keywords:** - metastatic melanoma ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 19 **Type:** ACTUAL **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** MAGE-3/Melan-A/gp100/NA17 Peptide-pulsed autologous PBMC, rhIL-12 with IL-2 **Intervention Names:** - Drug: MAGE-3/Melan-A/gp100/NA PBMC, rhIL-12 (drug) **Label:** 1 **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** MAGE-3/Melan-A/gp100/NA17 Peptide-pulsed autologous PBMC, rhIL-12 without IL-2 **Intervention Names:** - Drug: MAGE-3/Melan-A/gp100/NA17 Peptide-pulsed autologous PBMC, rhIL-12 with IL-2 **Label:** 2 **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - 1 **Description:** draft **Name:** MAGE-3/Melan-A/gp100/NA PBMC, rhIL-12 (drug) **Other Names:** - draft **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - 2 **Description:** MAGE-3/Melan-A/gp100/NA17 Peptide-pulsed autologous PBMC, rhIL-12 with IL-2 **Name:** MAGE-3/Melan-A/gp100/NA17 Peptide-pulsed autologous PBMC, rhIL-12 with IL-2 **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Measure:** The primary hypothesis is immunization of patients with 4 melanoma antigen peptides will induce augmented specific IFN-.-producing CD8+ T cells against all 4 antigens simultaneously, and to determine the clinical response rate. **Time Frame:** draft ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Histologically-confirmed melanoma with evidence of metastatic disease, either by radiologic or physical examination. In transit metastases are allowed. Biopsy should be performed to reconfirm the diagnosis in cases of doubt. * Life expectancy of at least 12 weeks. * Karnofsky performance status index \>/=70. * Written informed consent * Adequate hematopoietic, renal, and hepatic function * LDH \<1.25 x ULN * HLA typing: patient must express HLA-A2. * Tumor biopsy: patient must agree to undergo biopsy of accessible tumor before and after therapy, when feasible, to study tumor cell properties and characteristics of immune cells. Exclusion Criteria: * Significant cardiovascular disease, or cardiac arrhythmia requiring medical intervention. * Pregnant or nursing women. * Biological therapy in the 4 weeks prior to the start of dosing. * Prior therapy with a melanoma vaccine containing MAGE-3, Melan-A, gplOO, NA17 peptides. * Patients with intrinsic immunosuppression, including seropositivity for HIV antibody. Patient should be tested if risk factors are identified. * Serious concurrent infection, including active tuberculosis, hepatitis B, or hepatitis C. * Concurrent systemic corticosteroids (except physiologic replacement doses) or other immunosuppressive drugs (eg. cyclosporin A). * Psychiatric illness that may make compliance to the clinical protocol unmanageable or may compromise the ability of the patient to give informed consent. * Active or history of autoimmune disease including but not limited to: rheumatoid arthritis (RF-positive with current or recent flare), inflammatory bowel disease, systemic lupus erythematosis (clinical evidence with ANA 1:80 or greater), ankylosing spondylitis, scleroderma, multiple sclerosis, autoimmune hemolytic anemia, and immune thrombocytopenic purpura. * Active gastrointestinal bleeding or uncontrolled peptic ulcer disease. Presence of untreated brain metastases. All patients must undergo brain imaging as part of the pre-study evaluation. Only patients with no brain metastases, or with brain lesions successfully treated by stereotactic radiation or surgical removal without recurrence at 28 day follow-up, will be eligible. **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Chicago **Country:** United States **Facility:** The University of Chicago **State:** Illinois **Zip:** 60637 #### Overall Officials **Official 1:** **Affiliation:** University of Chicago **Name:** Thomas Gajewski, M.D., Ph.D. **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - 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: D000009369 - Term: Neoplasms - ID: D000009380 - Term: Neoplasms, Nerve Tissue - ID: D000018326 - Term: Nevi and Melanomas - ID: D000012878 - Term: Skin Neoplasms - ID: D000009371 - Term: Neoplasms by Site - 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 - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M11528 - Name: Melanoma - Relevance: HIGH - As Found: Melanoma - 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: M15674 - Name: Skin Diseases - 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: D000008545 - Term: Melanoma ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT01663779 **Brief Title:** Comparison of Ultrasound-guided Versus Blind Insertion of Radial Artery Catheters **Official Title:** Comparison of Ultrasound-guided Versus Blind Insertion of Radial Artery Catheters. #### Organization Study ID Info **ID:** 1206010421 #### Organization **Class:** OTHER **Full Name:** Yale University ### Status Module #### Completion Date **Date:** 2014-08 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2015-08-31 **Type:** ESTIMATED **Last Update Submit Date:** 2015-08-05 **Overall Status:** TERMINATED #### Primary Completion Date **Date:** 2014-08 **Type:** ACTUAL #### Results First Post Date **Date:** 2015-08-31 **Type:** ESTIMATED **Results First Submit Date:** 2015-03-30 **Results First Submit QC Date:** 2015-08-05 #### Start Date **Date:** 2012-08 **Status Verified Date:** 2015-08 #### Study First Post Date **Date:** 2012-08-13 **Type:** ESTIMATED **Study First Submit Date:** 2012-08-08 **Study First Submit QC Date:** 2012-08-10 **Why Stopped:** Inability to recruit further. ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Yale University #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** Arterial catheterization is frequently performed on critically ill patients for invasive blood pressure monitoring and/or frequent blood draws, especially arterial blood gas analysis. The distal part of the radial artery (wrist) is the preferred access site. The potential complications of the procedure are mostly minor and comprise temporary occlusion of the radial artery (RA), hematoma, local infection or bleeding from the puncture site. Major complications including vessel aneurysm or occlusion with threat to hand viability are rare. The standard approach to catheterization is "blind" puncture of the RA while locating its pulse by palpation, followed by threading a 20 Gauge (20G) angio-catheter into the vessel. Alternatively ultrasound can be used to locate the vessel and guide needle insertion. To our knowledge, four prospective randomized trials (PRT)5-8 comparing palpation with ultrasound-guided RA catheterization have been conducted so far and one meta-analysis looked at the pooled data obtained from these. The results showed that ultrasound guidance increased the first-attempt success rate at RA catheterization by 71% compared to palpation. The use of ultrasound also significantly reduced the time to successful catheterization, the number of punctures as well as the amount of catheters required per procedure. None of the prior randomized trials has been conducted in an ICU setting and in three out of the four studies the arterial lines were placed in patients undergoing elective surgery. The investigators hypothesized that ultrasound could improve first attempt success rate while placing arterial catheters in an ICU setting. Ultrasound may also reduce total time to successful insertion and reduce complications. The investigators plan to randomize patients to either a palpation technique or ultrasound guided catheter insertion and record the above outcomes. **Detailed Description:** The study will be conducted in a prospective randomized design on the patient population of the Surgical Intensive Care Unit (SICU) at Yale New Haven Hospital. All SICU patients in whom the indication for arterial catheterization has been established by the attending physician will be eligible for consented randomization to either the "Palpation" or the "Ultrasound" group. Once consent from the patient or his/her surrogate has been obtained, eligible patients will be randomized to either the "Palpation" or the "Ultrasound" group. Sequentially numbered sealed envelopes will be maintained in the SICU. Catheter insertion: The side of insertion (left/right arm) is chosen by the operator. The wrist is positioned by the operator, the skin disinfected and the area draped in a sterile fashion. "Palpation" group": The artery is punctured after location by palpation only. "Ultrasound" group": The artery is punctured under real-time ultrasound only with the probe draped in a sterile sheath. The time from the first skin puncture to confirmed intra-arterial position of the catheter by observing blood return from the catheter is measured with a chronometer by a second person. An arterial pressure waveform must be observed on the monitor to validate intra-arterial catheter placement. Radial artery cannulation will be performed using the "Radial Artery Catheterization Set with Integral Needle Protection" (Ref. RA-04020-SP, Arrows International Inc., Reading PA 19605, USA) containing a 20G catheter on a 22 gauge (22G) puncture needle and a 0.46 mm spring-wire guide. For ultrasound-guided catheter insertion, operators will use the "Site-Rite 6 Ultrasound System" with a linear vascular access probe (5-10 MHz) (Bard Access Systems Inc., 605 North 5600 West, Salt Lake City, UT 84116, USA). Operators: RA catheterization is a typical teaching procedure frequently performed in the ICU. In our unit, arterial lines are placed by either post graduate year 2 (PGY-2) residents (surgery \& anesthesia) rotating through the SICU on a monthly basis, or by mid-level providers who are in the unit for indeterminate periods of time. For our study, this will be an important point, as one of our goals will be to demonstrate a learning effect, which is less likely to be observable among the PGY-2 residents who will be present in the unit for a month only. All operators will get instructions (lecture and hands-on training on vascular phantom at the beginning of their SICU rotation) on the use of ultrasound for vascular access and will at all times have the opportunity to exercise their skills on a vessel phantom. Each successful vessel puncture on the vessel phantom must be recorded by the operator, including time and date. For each operator performing the ultrasound-guided insertion on a patient, one of the investigators will be present for supervision and data collection, but not for assistance with insertion, unless required for failure after having used both methods. Cross-over: After three failed attempts at catheterization with the allocated first method, the alternative method must be used; the operator can opt to puncture the RA on the opposite arm. Timing of the first method ends when the operator decides to abandon the third attempt. Timing for the new method starts at the new first skin puncture. Follow up: All catheters will be monitored daily and on days 1 and 3 with clinical and ultrasound examination for the development of complications. The catheter will be followed daily for functional outcomes defined as the quality of the arterial waveform on the monitor and the ability to draw blood from the catheter. The day on which the catheter ceases to function for each of these purposes will be recorded as well as the day of catheter removal. ### Conditions Module **Conditions:** - Severe Sepsis ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 50 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Ultrasound guided radial artery catheterization. **Intervention Names:** - Procedure: Ultrasound guided radial artery catheterization. **Label:** Ultrasound radial artery catheter **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Blind insertion of radial artery catheterization **Intervention Names:** - Procedure: Blind insertion of radial artery catheterization **Label:** Palpation based artery catheterization **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Ultrasound radial artery catheter **Description:** Radial artery catheters will be placed with the assistance of bedside ultrasound. **Name:** Ultrasound guided radial artery catheterization. **Type:** PROCEDURE #### Intervention 2 **Arm Group Labels:** - Palpation based artery catheterization **Description:** Radial artery catheters will be placed by the palpation technique only. **Name:** Blind insertion of radial artery catheterization **Type:** PROCEDURE ### Outcomes Module #### Primary Outcomes **Description:** first pass success when attempting arterial catheterization of the artery **Measure:** First Pass Success When Attempting Arterial Catheterization. **Time Frame:** Immediate, upon study entry ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * All surgical intensive care unit patients at Yale New Haven Hospital in whom the indication for arterial catheterization has been established by the attending physician will be eligible for consented randomization to either the "Palpation" or the "Ultrasound" group. Exclusion Criteria: * The patient or his/her surrogate declines to participate or the patient lacks a radial artery into which a catheter can be place. **Minimum Age:** 16 Years **Sex:** ALL **Standard Ages:** - CHILD - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** New Haven **Country:** United States **Facility:** Yale New Haven Hospital **State:** Connecticut **Zip:** 06510 #### Overall Officials **Official 1:** **Affiliation:** Yale University **Name:** Kevin M Schuster, MD **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### References **Citation:** Flumignan RL, Trevisani VF, Lopes RD, Baptista-Silva JC, Flumignan CD, Nakano LC. Ultrasound guidance for arterial (other than femoral) catheterisation in adults. Cochrane Database Syst Rev. 2021 Oct 12;10(10):CD013585. doi: 10.1002/14651858.CD013585.pub2. **PMID:** 34637140 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000007239 - Term: Infections - ID: D000018746 - Term: Systemic Inflammatory Response Syndrome - ID: D000007249 - Term: Inflammation - ID: D000010335 - Term: Pathologic Processes ### Condition Browse Module - Browse Branches - Abbrev: BC01 - Name: Infections - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M20864 - Name: Sepsis - Relevance: HIGH - As Found: Severe Sepsis - ID: M16869 - Name: Toxemia - 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: M16355 - Name: Syndrome - Relevance: LOW - As Found: Unknown - ID: M20818 - Name: Systemic Inflammatory Response Syndrome - Relevance: LOW - As Found: Unknown - ID: M10293 - Name: Inflammation - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000018805 - Term: Sepsis ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module #### Event Groups **Group ID:** EG000 **Title:** Ultrasound **Description:** ultrasound artery **ID:** EG000 **Other Num Affected:** 1 **Other Num at Risk:** 27 **Serious Number At Risk:** 27 **Title:** Ultrasound **Group ID:** EG001 **Title:** Palpation **Description:** palpation artery **ID:** EG001 **Other Num at Risk:** 23 **Serious Number At Risk:** 23 **Title:** Palpation **Frequency Threshold:** 1 #### Other Events **Term:** subcutaneous hematoma <1cm **Assessment Type:** SYSTEMATIC_ASSESSMENT **Notes:** subcutaneous hematoma \<1cm developed in 1 patient in the ultrasound group. Resolved with no intervention in 3 days. **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** **Time Frame:** entire study ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 27 **Group ID:** BG001 **Value:** 23 **Group ID:** BG002 **Value:** 50 **Units:** Participants ### Group **ID:** BG000 **Title:** Ultrasound Radial Artery Catheter **Description:** Ultrasound guided radial artery catheterization. Ultrasound guided radial artery catheterization.: Radial artery catheters will be placed with the assistance of bedside ultrasound. ### Group **ID:** BG001 **Title:** Palpation Based Artery Catheterization **Description:** Blind insertion of radial artery catheterization Blind insertion of radial artery catheterization: Radial artery catheters will be placed by the palpation technique only. ### Group **ID:** BG002 **Title:** Total **Description:** Total of all reporting groups ### Measure #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** <=18 years #### Measurement **Group ID:** BG000 **Value:** 22 #### Measurement **Group ID:** BG001 **Value:** 18 #### Measurement **Group ID:** BG002 **Value:** 40 **Category Title:** Between 18 and 65 years #### Measurement **Group ID:** BG000 **Value:** 5 #### Measurement **Group ID:** BG001 **Value:** 5 #### Measurement **Group ID:** BG002 **Value:** 10 **Category Title:** >=65 years **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 27 #### Measurement **Group ID:** BG001 **Value:** 23 #### Measurement **Group ID:** BG002 **Value:** 50 **Class Title:** unknown ### Measure #### Measurement **Group ID:** BG000 **Value:** 27 #### Measurement **Group ID:** BG001 **Value:** 23 #### Measurement **Group ID:** BG002 **Value:** 50 **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 **Description:** Gender was not collected as a baseline variable. **Parameter Type:** NUMBER **Title:** Sex/Gender, Customized **Unit of Measure:** participants ### Measure 3 **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:** Yale School of Medicine **Phone:** 203-785-2572 **Title:** Kevin M. Schuster ## Results Section - Outcome Measures Module ### Outcome Measure 1 #### Analysis **CI Lower Limit:** 3 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 7 **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:** <0.01 **P-Value Comment:** **Parameter Type:** Odds Ratio (OR) **Parameter Value:** 5 **Statistical Comment:** **Statistical Method:** Chi-squared **Tested Non-Inferiority:** False ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 22 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 10 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** first pass success when attempting arterial catheterization of the artery **Parameter Type:** NUMBER **Reporting Status:** POSTED **Time Frame:** Immediate, upon study entry **Title:** First Pass Success When Attempting Arterial Catheterization. **Type:** PRIMARY **Unit of Measure:** participants ##### Group **Description:** ultrasound atery **ID:** OG000 **Title:** Ultrasound ##### Group **Description:** palpation artery **ID:** OG001 **Title:** Palpation ### Participant Flow Module #### Group **Description:** Ultrasound guided radial artery catheterization. Ultrasound guided radial artery catheterization.: Radial artery catheters will be placed with the assistance of bedside ultrasound. **ID:** FG000 **Title:** Ultrasound Radial Artery Catheter #### Group **Description:** Blind insertion of radial artery catheterization Blind insertion of radial artery catheterization: Radial artery catheters will be placed by the palpation technique only. **ID:** FG001 **Title:** Palpation Based Artery Catheterization #### Period **Title:** Overall Study ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 27 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 23 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 27 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 23 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 0 **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT02222779 **Brief Title:** Quantification of Transition Metals **Official Title:** Quantification of Transition Metals in Patients at the Cologne University Hospital #### Organization Study ID Info **ID:** KPUK-14-Metal #### Organization **Class:** OTHER **Full Name:** University of Cologne ### Status Module #### Expanded Access Info **Last Known Status:** NOT_YET_RECRUITING #### Last Update Post Date **Date:** 2014-08-21 **Type:** ESTIMATED **Last Update Submit Date:** 2014-08-20 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2019-08 **Type:** ESTIMATED #### Start Date **Date:** 2014-09 **Status Verified Date:** 2014-08 #### Study First Post Date **Date:** 2014-08-21 **Type:** ESTIMATED **Study First Submit Date:** 2014-08-20 **Study First Submit QC Date:** 2014-08-20 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** University of Cologne #### Responsible Party **Investigator Affiliation:** University of Cologne **Investigator Full Name:** Ali Mohammad Nejad Sigaroudi **Investigator Title:** Quantification of Transition Metals in Patients at the Cologne University Hospital **Type:** PRINCIPAL_INVESTIGATOR ### Description Module **Brief Summary:** In this trial, concentrations of transition metals of interest are quantified in surplus cerebrospinal fluid (CSF) and blood serum samples. Quantification of the transition metals will be performed by inductively coupled plasma mass spectrometry (ICP-MS). The treating physicians as well as the patients will not be informed about the results of drug concentrations. **Detailed Description:** Samples used include: Remaining portions of samples collected for diagnostic or therapeutic reasons (paired CSF and blood serum samples). No lumbar puncture will be done specifically for this protocol. The objective of this study is to gain an overview about transition metals concentrations in blood serum and CSF in order to provide preliminary data on patients. The effect of neurodegenerative diseases on metals or the other way round will be assessed if possible. ### Conditions Module **Conditions:** - Neurodegenerative Diseases - Infections ### Design Module #### Bio Spec **Description:** Remaining portions of samples collected for diagnostic or therapeutic reasons (paired CSF and blood serum samples). No lumbar puncture will be done specifically for this protocol. **Retention:** SAMPLES_WITHOUT_DNA #### Design Info **Observational Model:** ECOLOGIC_OR_COMMUNITY #### Enrollment Info **Count:** 3000 **Type:** ESTIMATED **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Label:** Patients with Parkinson´s Disease #### Arm Group 2 **Label:** Patient´s with Alzheimer´s Disease #### Arm Group 3 **Label:** Patients with Multiple Sclerosis #### Arm Group 4 **Label:** Patients with any other neurodegenerative diseases ### Outcomes Module #### Primary Outcomes **Measure:** Transition metal concentration **Time Frame:** 5 years ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: • * The trial will include any patient (with various diseases, especially neurodegenerative diseases) who received a lumbar puncture. Exclusion Criteria: * • The lower age limit is 18 years. In concordance with the objective of the project there is no specific exclusion criteria. **Healthy Volunteers:** True **Minimum Age:** 18 Years **Sampling Method:** PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** neurodegenerative diseases infections ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Uwe Fuhr, Professor **Phone:** 0049221478 **Phone Ext:** 5230 **Role:** CONTACT #### Locations **Location 1:** **City:** Cologne **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Uwe Fuhr, Professor - **Phone:** 0049221478 - **Phone Ext:** 5230 - **Role:** CONTACT **Country:** Germany **Facility:** Department of Pharmacology **State:** Northrhine Westphalia **Zip:** 50829 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009422 - Term: Nervous System Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC01 - Name: Infections - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: BC10 - Name: Nervous 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: M21558 - Name: Neurodegenerative Diseases - Relevance: HIGH - As Found: Neurodegenerative Diseases ### Condition Browse Module - Meshes - ID: D000019636 - Term: Neurodegenerative Diseases ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT02337179 **Brief Title:** Male Circumcision Services for HIV Prevention in the Dominican Republic **Official Title:** A Pilot Study to Introduce Male Circumcision (MC) Services to Prevent HIV Infection in Two High Prevalence Areas of the Dominican Republic (DR) #### Organization Study ID Info **ID:** 2010-0863 #### Organization **Class:** OTHER **Full Name:** University of Illinois at Chicago ### Status Module #### Completion Date **Date:** 2017-04-01 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2017-05-02 **Type:** ACTUAL **Last Update Submit Date:** 2017-05-01 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2014-06 **Type:** ACTUAL #### Start Date **Date:** 2011-02 **Type:** ACTUAL **Status Verified Date:** 2017-05 #### Study First Post Date **Date:** 2015-01-13 **Type:** ESTIMATED **Study First Submit Date:** 2015-01-07 **Study First Submit QC Date:** 2015-01-08 ### Sponsor Collaborators Module #### Collaborators **Class:** UNKNOWN **Name:** Instituto Dermatologico y Cirugia de Piel #### Lead Sponsor **Class:** OTHER **Name:** University of Illinois at Chicago #### Responsible Party **Investigator Affiliation:** University of Illinois at Chicago **Investigator Full Name:** Maximo Brito **Investigator Title:** Associate Professor of Medicine & Vice Chair for Urban Global Health **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** The purpose of this study is to determine the feasibility of introducing voluntary medical male circumcision as a form of HIV prevention in high HIV prevalence areas in the Dominican Republic. **Detailed Description:** Voluntary Medical Male circumcision (VMMC) is an effective strategy to reduce the risk of HIV acquisition in heterosexual men. Observational data and randomized controlled trails (RCTs) conducted in Africa(1,2,3) suggest that the procedure reduces the risk of HIV acquisition by 50-76% in heterosexual males. VMMC has also been shown to reduce the incidence of other sexually transmitted infections (STI), including herpes simplex virus type 2 (HSV-2) and human papilloma virus (HPV) in men(4), and Chlamydia(5), trichomonas vaginalis (TV), bacterial vaginosis (BV) and HPV in their female partners(6). The results of the RCT's are generating increased demand for safe and affordable MC services in areas of moderate-to-high HIV prevalence where the MC rates are low. Latin America is a region where circumcision of males is uncommon(7). In the Dominican Republic (DR), which is the focus of this study, a 2007 nationwide household survey found that only 13.7% of men between the ages of 15-59 were circumcised(8). AIDS is the leading cause of death in the Caribbean basin among adults aged 15-44 years. There are approximately 240,000 people currently living with the disease, most of them residing in the Dominican Republic (DR) and Haiti(9). The prevalence of HIV infection in the DR is approximately 0.8% nationwide(8) but it is higher in selected high-risk populations, such as among people living in the "bateyes", the small towns surrounding sugar cane plantations, where the prevalence is 3.2%(10). In pregnant women seeking prenatal care at the main hospital in the Altagracia province HIV seroprevalence is 4.5 %(11). One of the areas of highest prevalence (1.2%) in the country is Region V of health, which includes the provinces of La Altagracia, El Seibo, Hato Mayor, La Romana and San Pedro de Macorís. Prevalence is also higher in the urban slums of the capital city, Santo Domingo. The public health impact of introducing MC as a strategy to prevent HIV/STI transmission in areas of high HIV/STI prevalence and low MC rates can be significant. In addition to decreasing the rates of HIV and other STI, the intervention could indirectly help decrease the rates of HPV associated cervical cancer. The study proposed here is to develop, implement, monitor and evaluate pilot MC services in selected sites to assess the acceptability, uptake, safety and demand for these services, and to use these data to develop, in collaboration with the Dominican Ministry of Health (MoH), a proposal to the National Institute of Mental Health (NIMH) for support of operations research concerning the safety, uptake, and efficacy of MC interventions in the DR. 1. Specific Aims: Based on the results of numerous observational studies and the three RCTs the World Health Organization (WHO) and the Joint United Nations Programme on HIV/AIDS (UNAIDS) have endorsed VMMC as a biomedical intervention for HIV prevention. As such, countries with a high prevalence of HIV in the population are encouraged to examine the feasibility of offering MC services as part of the portfolio of HIV prevention strategies at a national level. The specific aims for this project are: 1. To develop culturally appropriate education materials about the benefits of VMMC for clients attending pilot healthcare centers. 2. To train a core group of providers on proper surgical and counseling techniques to provide comprehensive VMMC services. 3. To determine the acceptability, uptake and demand for MC services in key areas of high HIV prevalence. H1: The acceptability and uptake among high risk men will be around 60%. 4. To assess the safety and adverse events of performing circumcision in resource constrained settings. H2: VMMC will result in a complication rate of less than 2%. 5. To assess sexual risk behaviors, perceptions of sexual function and sexual pleasure in men before and after VMMC. H3: there will be no differences in risk behaviors, sexual function and pleasure after VMMC. 6. Estimate point prevalence of most common STI in a subset of circumcised men and preserve a small sample of blood to test future scientific hypothesis and/or newer testing techniques as they become available. 7. To build collaborations with the MoH and other partners in the DR and at UIC to develop a proposal to NIMH for operational research in the context of larger scale MC service provision. 2. Background and significance: b.1. Male Circumcision to Prevent HIV Transmission Male circumcision is perhaps one of the oldest surgical procedures performed on humans. The millenary practice of removing the male foreskin has cultural, religious and medical dimensions that have been widely studied. Around the world, the procedure is mostly performed for religious reasons in persons of the Jewish and Muslim faiths. Medical indications for MC include phimosis, paraphimosis and balanitis, among others(12). Early evidence of a relationship between MC and HIV infection came from a number of smaller, mostly observational studies, done in Africa(13). These historical data were validated with the completion of three large RCTs in South Africa, Kenya and Uganda, which have shown an overall decrease of 50-76% in the risk of acquiring HIV infection in circumcised males when compared to controls(1,2,3). The pathogenesis of the initial infection at the level of the foreskin involves tissue macrophages, cell receptors and a moist, poorly keratinized inner prepuce. The first cellular target of the HIV virion on the human genitalia are the tissue dendritic cells in the lamina propria of the submucosa(14). These cells express surface CD4 receptors and CCR5 co-receptors for which HIV has high affinity. In intact human skin, the dendritic cells are shielded from the outer environment by the relatively thick layer of keratin covering the surface of the epithelia. Tissue studies of the human foreskin have shown that the inner lining of the prepuce, exposed during a penile erection, has a thin keratin layer that is very susceptible to microscopic abrasions and can expose the tissue macrophages making them vulnerable to infection by HIV(15). b.2. MC for STI prevention: MC is an effective strategy to decrease the risk of infection with HIV and other STI in heterosexual males. A beneficial effect has also been observed in decreasing the risk of STI in females. The RCTs confirmed that VMMC decreases herpes simplex virus type 2 (HSV-2) acquisition by 29%, and HPV prevalence by 34% in men(4). Among female partners of circumcised men, bacterial vaginosis was reduced by 40%, and trichomonas vaginalis infection was reduced by 48%(6). Genital ulcer disease was also reduced among males and their female partners by approximately half(16). b.3. HIV in the Caribbean and the Dominican Republic: The significant decrease in the rate of HIV acquisition observed among circumcised males who participated in the African RCT is generating an increased demand for safe and affordable VMMC services in areas of high HIV prevalence where the procedure is not routinely performed. Latin America is one of such areas where routine circumcision of males is uncommon(7). In the Dominican Republic, only 13.7% of men between the ages of 15-59 years are circumcised(8). The Caribbean is the region of the world with the highest HIV prevalence outside of sub-Saharan Africa (1.0%)(9). Approximately 240,000 individuals are currently living with the disease. Among the Caribbean countries, the Dominican Republic and Haiti report the highest prevalence in the region. According to data from a recent In the DR, the prevalence of HIV infection is 0.8% nationwide(8), however, the numbers are higher in selected populations and in certain geographic locations. The Dominican healthcare system is administratively divided in 9 regions, which include the country's 31 provinces. Region 0 of health includes the National District and the provinces of Santo Domingo and Monte Plata. The city of Santo Domingo is the capital and financial center of the DR. It has an estimated population of 2.7 million people spread in an area of about 1,400 KM2. 90% of the population lives in an urban setting in this province(17). The overall prevalence of HIV is around 0.7 % in the entire region but is higher in vulnerable groups such as commercial sex workers (CSW) (3.3%), Men who Have Sex with Men (MSM) (5.9%) and drug users (7.1%)(18). Regions V and VII report the highest prevalence of HIV in the country, 1.2 % and 1.5% respectively(8). Specific populations within these provinces have rates of HIV considerably higher than the national average. For instance, prevalence is 3.2% in the bateyes, the small communities surrounding sugar cane plantations, where a mixed population of Dominicans and Haitian migrant workers cohabitate. Our team has conducted preliminary studies in the Altagracia Province, part of Region V, since it reports the highest province-specific HIV rates and the lowest circumcision rates in the country. A survey of pregnant women seeking prenatal care at the main hospital in the province found an HIV seroprevalence of 4.5 %11. The prevalence of HIV is 5.2% in CSW, 7.6% in MSM and 8.5 % among drug users(18). c) Preliminary studies: The parent study for this project is a RCT of VMMC to reduce HIV incidence in Kisumu, Kenya whose principal investigator is Prof. Robert C. Bailey, a co-investigator in the current proposal(3). The main objective of that trial was to assess the effectiveness of VMMC in reducing HIV incidence in young, sexually active men. The protective effect found in an intent-to-treat analysis was 53% and in an as treated analysis adjusting for cross-overs and men found to be HIV seropositive at baseline estimated the protective effect to be 60%. Adverse events related to the surgical procedure were few, just 1.5%. Behavioral disinhibition (risk compensation) on the part of circumcised men was small and not significant. Drs. Brito and Bailey conducted a feasibility study of healthcare facilities in the Altagracia province in the Dominican Republic during June and July of 2007. A total of 37 healthcare facilities were surveyed. The study found that most facilities lacked appropriate equipment to perform surgical procedures and only four (11%) had a surgical theater. 43 healthcare workers, the majority of them physicians (91%), were interviewed for the study. Only 23 % of the personnel had experience performing MC and a significant number of providers (76%) believed they needed comprehensive training in the procedure prior to starting a MC program. Quantitative and qualitative studies to assess the acceptability of MC among men, women and providers in the Altagracia Province were conducted in 2008. In these studies, 73% of men thought that MC improved hygiene and approximately one third knew that it reduces the risk of penile cancer or STI. Only a small percentage (21%) knew that MC helps prevent HIV infection. When first asked, 29% of participants reported that they would be willing to be circumcised if the procedure was offered to them. However, after an educational session detailing the benefits of the procedure for HIV and STI prevention, the acceptability increased to 67%. Such increment was also observed in previous studies done in Botswana(19) and Thailand(20)where acceptability increased from 61 % to 81% and from 14% to 66%, respectively, after a similar information session. In multivariate analysis, the strongest predictors of men's acceptability of circumcision, before the information session, were Haitian nationality (OR=1.86, 95% CI 1.01-3.41), thinking that circumcision improves hygiene (OR=2.78, 95% CI 1.29-6.0) and not believing that having a circumcision decreases sexual pleasure (OR=2.18, 95% CI 1.20-3.94). These results have been published (21, 22). We also conducted 13 focus group discussions (FGD), 6 with women and 7 with men, each consisting of 6-10 participants (mean=7.9, SD=1.3). One additional FGD was conducted with six physicians, two males and four females, working in rural clinics around the province. Findings of this qualitative study showed that a significant number of participants might be willing to be circumcised, or agree with circumcision for their partners, to improve hygiene, prevent diseases and treat medical conditions, such as phimosis, which can result in pain during intercourse. These results are consistent with our quantitative study on men's acceptability of MC. Perhaps one of the most important findings of the FGD was the enthusiastic endorsement of MC by women, a fact that has potential implications for the successful implementation of a circumcision program in the country (22). Overall, our preliminary data suggest that men are willing to be circumcised provided they receive information about the benefits of the procedure. Before recommending the introduction of VMMC services as part of a comprehensive package of HIV and other STI prevention strategies, these findings need to be confirmed by studying the uptake of VMMC among sexually active men in selected clinics that serve clients in high prevalence areas. In addition, there is need to identify potential barriers to offering MC services in high risk communities prior to proposing to implement a large-scale intervention. In order to properly address these concerns, we will conduct a pilot study that will provide the necessary preliminary data to design a proposal to the NIMH to conduct operational research around a large-scale implementation project. d) Experimental design and methods: d.1. Pilot study design The study will be conducted at two sites: the STI clinic at Instituto Dermatologico and Cirugia de Piel (IDCP) in Santo Domingo and the Clínica de Familia in La Romana, Dominican Republic. These sites have been selected on the basis of: 1) high numbers of male clients at risk for HIV and STI infection in communities served by the clinics; 2) high level of acceptability of MC among men in the communities served by the clinics (bateyes of Altagracia); 3) the availability of service providers willing to be trained; 4) the availability of equipment; and 5) the availability of infrastructure, including a minor surgical theater, sterilization facilities and HIV voluntary counseling and testing (VCT) and STI management. During the first phase of the study, culturally appropriate educational material will be created in Spanish by the principal investigator and local collaborators. Focus Group Discussions (FGD) and in-depth interviews will be conducted with members of the community to learn the educational needs of the community and to assess their opinions on how to best deliver the information on MC that will be contained in the educational materials. We plan to conduct the FGD in the communities served by the Instituto Dermatologico and the Clinica de Familia, the two main study sites. The plan is to assemble groups of 6-12 participants from the population living in these communities. Community leaders, health promoters, teachers and primary care physicians will be asked to help identify and invite volunteers from their respective communities to participate in the study. There will be no difference in the recruitment process for men and women. They will be recruited from the same venues (schools, clubs, community centers) . Participants will be invited to participate by research personnel with the help of local leaders. These local leaders may be of both genders and will help recruit participants from either gender. The focus groups will be gender-specific. The moderator will explain the purpose of the study to participants. Verbal consent will be obtained from all participants and an information sheet outlining the objectives of the study, their privacy and confidentiality rights and our contact information will be distributed. The document will highlight the voluntary nature of the subject's participation and their right to leave the discussion at anytime if they so desire. The study meets the definition of "minimal risk", therefore, we are requesting a waiver of written consent. We believe this will further preserve the confidentiality of the participants. The goal is to conduct no more than 15 FGD. Participants in the FGD will be divided by gender. We plan to recruit approximately the same number of men and women for the FGD. In addition to the FGD, several in-depth individual interviews may be conducted using the same guide than in the FGD. A script will be followed to conduct the FGD. The discussions will be stimulated by using a list of carefully crafted questions on the subject of MC. These questions are designed to obtain information on the following aspects relevant to our investigation: 1. Perception of the population about the frequency of MC in community men. 2. Opinions on the best way to educate men in the community about the benefits of circumcision. 3. Opinions about the content of the educational materials educational and how information should be delivered. 4. Where should these educational material be posted or distributed to capture the most number of men. 5. Opinions on the best venue to organize educational sessions featuring a circumcised man that would be available to answer question from men in the community about his satisfaction with his circumcision. 6. Perceptions about who would be a good person to educate men about the benefits of circumcision in the community. 7. Opinions on the best way to involve women in the community in a campaign to recruit men for circumcision. The moderator and a research assistant (RA) will lead the discussions. All FGD will be audiotaped and detailed notes will be taken. The content of the recordings will be transcribed shortly after the end of the meeting. The PI, a native Spanish speaker, will be responsible for translating the recordings from Spanish to English. The English-version transcripts will be coded using the program ATLAS.ti vers. 5.2 based on template of topical categories drawn from questions and issues covered in the discussion guides and from themes emerging from the discussions themselves. The interviews will be conducted by one of the co-investigators. Verbal consent will be obtained and a document containing information about the study will be provided to the participants. All data obtained during this study, including recordings and notes will be de-indentified. The names of the participants will not be recorded to protect their confidentiality. Data Management All notes, audio recordings and study material obtained during the FGD and interviews will be kept in a locked filing cabinet in an office at the Instituto Dermatologico, Dominican Republic and in the PI's office at the UIC campus upon the investigator's return to Chicago. All data will be de-identified to preserve confidentiality. Names will not be recorded. Verbal informed consent will be sought; there will be no signed consent forms to identify individuals. The participants have the right to review the audio recordings. If a participant requests to listen to the recordings, one of the co-investigators will schedule an appointment for the subject to come to the research site and, in an unoccupied office, will playback the recording for him/her and answer all the questions that the subject may have. If the participant wishes to erase part or all of his/her responses, it will be done on the spot, in his/her presence, using the digital recorder. The data obtained during these FGD and interviews will inform the design of the educational materials. Once created, these materials will be tested for clarity and appropriateness of language by soliciting input from community health promoters and peer advocates working at the IDCP. Once it is determined that the educational materials are suitable to distribute to clients, we will submit to the Institutional Review Board for approval. Once approved, pamphlets and posters will be printed and distributed at the site clinics and the surrounding communities. During the second phase, selected providers will be trained. This will include counselors in HIV counseling and testing, and medical doctors by an experienced urologist on the appropriate technique for VMMC using the "Manual for Male Circumcision Under Local Anesthesia" published by WHO, UNAIDS. Supervision and evaluation of trainees will be conducted following the protocol used during the parent RCT. Study subjects will be recruited in a variety of ways. In Santo Domingo, fliers will be posted in bars and night clubs frequented by men at high risk for HIV/STI acquisition. A group of volunteer commercial sex workers working on an HIV vaccine trial will be asked to refer their clients for the study. Men seeking care for STI at the clinic will also be invited to participate. In La Romana, men attending the Clínica de Familia will be invited to participate. In addition, a group of outreach workers will visit the "bateyes", the communities surrounding sugar cane fields where migrant laborers live, to educate men about MC and invite them to participate in the study. Men between 18-40 years will be provided with information about the study and will be invited to participate. If they express an interest in participating, informed consent will be obtained. The participant will go over the consent form with the counselor, who will assess his level of understanding and answer any questions. If there are no temporary or permanent excluding conditions, the participant will be asked to give informed consent for enrollment in the study. Men who elect to be circumcised will be fully informed about the benefits and risks of the procedure, as well as the surgical method to be used. After the informed consent is signed, a "Locator Information Form" containing confidential data such as subject's name and address will be completed. Only selected research staff will have access to this information, which will be filed separate from the rest of the study forms. A de-identified "demographic information form and behavioral questionnaire" will be completed next. Testing for HIV infection will be carried out using a rapid test. The test kits to be used are the synthetic peptide test, Determine HIV 1/2, and the recombinant antigen test Unigold HIV 1/2 Recombinant. Results are provided to the clients, with appropriate counseling, at the same visit. Participants are taught to observe, read and interpret the tests for themselves in the company of the counselor. Men with positive results will be informed of their HIV status and will be followed-up at the study clinic and referred for a confirmatory HIV-ELISA and, if confirmed, for HIV treatment. Serologic testing for HSV-2, hepatitis B surface antigen (HBV), and hepatitis C antibody (HCV) will be performed using an ELISA test. A serum Rapid Plasma Reagin test (RPR) will be performed to test for syphilis. Chlamydia and gonorrhea testing will be performed in urine using a Polymerase Chain Reaction (PCR) assay. All participants who test positive for Chlamydia, syphilis and gonorrhea will be offered treatment free of charge. Participants who test positive for HSV-2 and have active genital lesions will be offered treatment free of charge. Those who test positive but have no active lesions will be counseled on safe sex practices and the risk of transmission to their partners as there is no recommended treatment for asymptomatic individuals infected with HSV-2. HIV, HBV, and HCV positive participants will be referred for evaluation and treatment at Clinica de la Familia in La Romana as these are chronic diseases that require long term treatment usually covered under government programs. If a participant is found to have a treatable STD and he does not return to the site, he will be called by the study investigators using the phone number provided by the participant at enrolment to ensure treatment is provided. If there is a temporary, medically curable condition present, such that it would be advisable to defer potential surgery, then the participant will be treated and asked to return for re-evaluation for study eligibility when he is cured. Men found to have an STD or to be HIV-positive will be referred for immediate care. Once enrollment is completed, participants will be given an appointment for the surgery. Circumcision will be performed soon after informed consent, preferably within a few days. All surgeries will be done under local anesthesia in a clinic by trained clinicians, using the standardized forceps-guided method described by Krieger and colleagues and contained in the WHO MC manual(23). Circumcised men will be counseled to refrain from sex for six weeks post-surgery and counseled about risk of HIV infection through open wounds during the healing process. They will be checked for complications and asked about their sexual activity seven days after the procedure. Men without complications will be followed six months after surgery with behavioral risk assessment, HIV testing and counseling. Men may come to the study sites for unscheduled visits at any time during the 6 month follow-up. All men will be counseled at enrollment and all follow-up visits to reduce their risk for HIV infection by consistent condom use and, where applicable, reductions in numbers of sex partners. Counselling on condom use and sexual risk reduction will be provided by trained, experienced, native-speaking counsellors. MC services will be offered at the selected two sites for 1 year. The estimated cost per circumcision is $40. We expect to recruit five clients per week at each site for a total convenience sample of 575 subjects in one year. During the second year of the project, we will continue to assess behavioral risk factors for the first six months and work on analyzing the data during the last semester of the project. Circumcision Procedure Prior to surgery, the clinician will obtain a complete medical history and perform a physical exam. A brief description of the procedure follows. The patient lies on his back in a comfortable position. The pubic area is shaved clean with a disposable razor and the hair is picked up with a dressing tape. The surgeon scrubs up and puts on 2 pairs of sterile gloves. The client's skin is prepared with Betadine solution, making sure that the inner surface of the prepuce and the glans are clean and the skin is dry. The outer pair of gloves is then removed. The client is draped with two drapes and a center "O" towel, and then, using 2% lidocaine without epinephrine, a dorsal nerve block and a field block with special attention to the ventral nerve, is performed. Normally, no more than 10ml of 2% lidocaine will be used. The anesthetic effect of the nerve block is checked, and revised if necessary. The prepuce is held with two mosquito forceps, one on each lateral aspect, then a curved mark is made with sterile disposable marking pens, outlining the planned surgical cut. The mark is made one cm proximal to the coronal sulcus all round, and parallel to the coronal sulcus. The prepuce is clamped along the mark with a Kocher clamp while retracting the glans, ensuring that the glans itself is not clamped. The prepuce is excised using a surgical blade along the mark. Bleeders are identified, clamped and tied. They are sutured, and if necessary ligated, using 3/0 plain catgut. After ligating all the bleeders, the area is irrigated with normal saline and then inspected for more bleeders, which are identified and tied. Using 3/0 chromic catgut on a taper 4/8 circle needle, a U-shaped horizontal mattress stitch is made on the ventral side of the penis (frenulum) to join the skin at the "V" shaped cut, which is then tied and tagged with a mosquito forceps. Using vertical mattress stitches, four quarters are tagged, and a vertical mattress stitch added, after which a simple stitch is put at the center of every two mattress stitches (a total of at least 16 stitches). The area is irrigated with normal saline and other simple stitches added as required. The wound is dressed with Sofratulle, then with a regular dressing bandage and a strapping. The client is advised to rest for 30 minutes, and if stable, discharged home on mild analgesics. Upon completion of the procedure the surgeon completes a procedure form. The excised foreskin tissue is taken to the laboratory with no identifiers, discarded with other laboratory waste, and incinerated with other biological waste within three days. Participants will be given verbal and written instructions on postoperative wound care and counseled to refrain from sexual activity for at least six weeks after the procedure. They will also be encouraged to come to the clinic or contact a clinician at any time with medical problems. Day 7 Post Circumcision Visit: Circumcised men will be asked to return to the clinic 7 days after the procedure to check the wound, to see if it is healing properly, to check for complications, and to ask about their sexual activity, their level of pain, resumption of work or other activities, and their satisfaction with the procedure and care at the clinic. As with all visits, any adverse events will be recorded. Blood and urine will be collected for STD testing at this visit. Six month post operative visit: During this visit a brief exam to confirmed proper wound healing will be performed. A behavioral and satisfaction questionnaire will be administered. Unscheduled Follow-up Visits: Ad hoc clinic visits will be encouraged to check and treat for complications of the procedure. At such visits, medical examinations and laboratory testing will be conducted as indicated, and appropriate treatment provided free of charge. Medical referral will be made if required. d.2. Data analysis Each enrolled participant will be assigned a confidential code, which will be used in all study forms. Only the principal investigators and research assistants will have access to the "locator information form" containing personal information. This form, which links the subject's confidential code to his name, will be stored in separate locked filing cabinets at the local principal investigator's offices. The locator information forms, which contain the personal information on the subjects, will be kept for 1.5 years in case we need to contact one of the subjects for an unexpected occurrence or with a question. After the end of that period, these locator forms will be destroyed at the research offices at the respective study sites using a micro cut shredder. Data will be coded and entered into computer datasets by trained personnel. Data extracted from questionnaires will be tabulated and analyzed using SAS statistical software version 9.1. and will be analyzed at the University of Illinois, College of Medicine, in Chicago by the principal investigator A questionnaire asking specific demographic information will be administered. The following variables will be recorded: age, religion, place of residence (urban/rural), education level, occupation and marital status. Simple descriptive statistics will be calculated and the effect of these variables on the willingness, uptake and rate of adverse events of VMMC will be estimated. In addition, we plan to estimate the effect of demographic characteristics on sexual behavior and disinhibition after the procedure. ### Conditions Module **Conditions:** - Circumcision, Male - HIV - AIDS ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 539 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Eligible men will be circumcised according to protocol **Intervention Names:** - Procedure: Voluntary medical male circumcision **Label:** Voluntary medical male circumcision **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Voluntary medical male circumcision **Description:** Male Circumcision Under Local Anesthesia using the Forceps Guided Method **Name:** Voluntary medical male circumcision **Type:** PROCEDURE ### Outcomes Module #### Primary Outcomes **Measure:** Number and percentage of participants who agreed to undergo circumcision after being offered. **Time Frame:** 13 months #### Secondary Outcomes **Measure:** Number and percentage of adverse events by severity (mild, moderate, severe) **Time Frame:** 23 months **Measure:** Number and percentage of individuals who use illicit drugs **Time Frame:** 23 months **Measure:** Number and percentage of men who have sex with men **Time Frame:** 23 months **Measure:** Number and percentage of individuals who had ≥ 2 sex partners over the last 30 days **Time Frame:** 23 months **Measure:** Number and percentage of individuals who experienced problems with penis and foreskin prior to circumcision **Time Frame:** 23 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Uncircumcised men; 2. Aged 18-40 years Exclusion Criteria: 1. Foreskin covering less than half of the glans; 2. Bleeding disorders; 3. Keloid formation; 4. Other conditions that might unduly increase the risks of elective surgery. **Healthy Volunteers:** True **Maximum Age:** 40 Years **Minimum Age:** 18 Years **Sex:** MALE **Standard Ages:** - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Chicago **Country:** United States **Facility:** University of Illinois at Chicago **State:** Illinois **Zip:** 60612 **Location 2:** **City:** Santo Domingo **Country:** Dominican Republic **Facility:** Instituto Dermatologico y Cirugia de Piel #### Overall Officials **Official 1:** **Affiliation:** University of Illinois at Chicago **Name:** Maximo O Brito, MD, MPH **Role:** PRINCIPAL_INVESTIGATOR **Official 2:** **Affiliation:** Instituto Dermatologico y Cirugia de Piel **Name:** Yeycy Donastorg, MD **Role:** STUDY_DIRECTOR ### References Module #### References **Citation:** Auvert B, Taljaard D, Lagarde E, Sobngwi-Tambekou J, Sitta R, Puren A. Randomized, controlled intervention trial of male circumcision for reduction of HIV infection risk: the ANRS 1265 Trial. PLoS Med. 2005 Nov;2(11):e298. doi: 10.1371/journal.pmed.0020298. Epub 2005 Oct 25. Erratum In: PLoS Med. 2006 May;3(5):e298. **PMID:** 16231970 **Citation:** Gray RH, Kigozi G, Serwadda D, Makumbi F, Watya S, Nalugoda F, Kiwanuka N, Moulton LH, Chaudhary MA, Chen MZ, Sewankambo NK, Wabwire-Mangen F, Bacon MC, Williams CF, Opendi P, Reynolds SJ, Laeyendecker O, Quinn TC, Wawer MJ. Male circumcision for HIV prevention in men in Rakai, Uganda: a randomised trial. Lancet. 2007 Feb 24;369(9562):657-66. doi: 10.1016/S0140-6736(07)60313-4. **PMID:** 17321311 **Citation:** Bailey RC, Moses S, Parker CB, Agot K, Maclean I, Krieger JN, Williams CF, Campbell RT, Ndinya-Achola JO. Male circumcision for HIV prevention in young men in Kisumu, Kenya: a randomised controlled trial. Lancet. 2007 Feb 24;369(9562):643-56. doi: 10.1016/S0140-6736(07)60312-2. **PMID:** 17321310 **Citation:** Tobian AA, Serwadda D, Quinn TC, Kigozi G, Gravitt PE, Laeyendecker O, Charvat B, Ssempijja V, Riedesel M, Oliver AE, Nowak RG, Moulton LH, Chen MZ, Reynolds SJ, Wawer MJ, Gray RH. Male circumcision for the prevention of HSV-2 and HPV infections and syphilis. N Engl J Med. 2009 Mar 26;360(13):1298-309. doi: 10.1056/NEJMoa0802556. **PMID:** 19321868 **Citation:** Castellsague X, Peeling RW, Franceschi S, de Sanjose S, Smith JS, Albero G, Diaz M, Herrero R, Munoz N, Bosch FX; IARC Multicenter Cervical Cancer Study Group. Chlamydia trachomatis infection in female partners of circumcised and uncircumcised adult men. Am J Epidemiol. 2005 Nov 1;162(9):907-16. doi: 10.1093/aje/kwi284. Epub 2005 Sep 21. **PMID:** 16177149 **Citation:** Gray RH, Kigozi G, Serwadda D, Makumbi F, Nalugoda F, Watya S, Moulton L, Chen MZ, Sewankambo NK, Kiwanuka N, Sempijja V, Lutalo T, Kagayii J, Wabwire-Mangen F, Ridzon R, Bacon M, Wawer MJ. The effects of male circumcision on female partners' genital tract symptoms and vaginal infections in a randomized trial in Rakai, Uganda. Am J Obstet Gynecol. 2009 Jan;200(1):42.e1-7. doi: 10.1016/j.ajog.2008.07.069. Epub 2008 Oct 30. **PMID:** 18976733 **Citation:** Drain PK, Halperin DT, Hughes JP, Klausner JD, Bailey RC. Male circumcision, religion, and infectious diseases: an ecologic analysis of 118 developing countries. BMC Infect Dis. 2006 Nov 30;6:172. doi: 10.1186/1471-2334-6-172. **PMID:** 17137513 **Citation:** CESDEM. Encuesta Demográfica y de Salud, República Dominicana. 2007. (accessed January 2, 2010 at (http://www.cesdem.com/html/encuesta_demografica_y_de_salud_2007.pdf ) **Citation:** Joint United Nations Programme on HIV /AIDS. 2009 Report on the global AIDS epidemic. (Accessed February 2, 2010 , at http://www.unaids.org/en/KnowledgeCentre/HIVData/GlobalReport/ **Citation:** CESDEM. Encuesta Sociodemográfica y sobre VIH/SIDA en los Bateyes Estatales de la República Dominicana. 2007. (accessed January 2, 2009 at http://www.cesdem.com/html/encuesta_sociodemografica_y_sobre_vih_sida_en_los_bateyes_estatales_de_la_republica_dominicana.pdf ) **Citation:** Secretaria de Estado de Salud Publica. Encuesta de seroprevalencia de la infección VIH basadas en puestos centinela. 2006. **Citation:** UNAIDS. Male circumcision: global trends and determinants of prevalence, safety and acceptability. (accessed February 23, 2010 at ( http://whqlibdoc.who.int/publications/2007/9789241596169_eng.pdf ) **Citation:** Weiss HA, Quigley MA, Hayes RJ. Male circumcision and risk of HIV infection in sub-Saharan Africa: a systematic review and meta-analysis. AIDS. 2000 Oct 20;14(15):2361-70. doi: 10.1097/00002030-200010200-00018. **PMID:** 11089625 **Citation:** Kahn JO, Walker BD. Acute human immunodeficiency virus type 1 infection. N Engl J Med. 1998 Jul 2;339(1):33-9. doi: 10.1056/NEJM199807023390107. No abstract available. **PMID:** 9647878 **Citation:** McCoombe SG, Short RV. Potential HIV-1 target cells in the human penis. AIDS. 2006 Jul 13;20(11):1491-5. doi: 10.1097/01.aids.0000237364.11123.98. **PMID:** 16847403 **Citation:** Gray RH, Serwadda D, Tobian AA, Chen MZ, Makumbi F, Suntoke T, Kigozi G, Nalugoda F, Iga B, Quinn TC, Moulton LH, Laeyendecker O, Reynolds SJ, Kong X, Wawer MJ. Effects of genital ulcer disease and herpes simplex virus type 2 on the efficacy of male circumcision for HIV prevention: Analyses from the Rakai trials. PLoS Med. 2009 Nov;6(11):e1000187. doi: 10.1371/journal.pmed.1000187. Epub 2009 Nov 24. **PMID:** 19936044 **Citation:** ONE. VIII Censo nacional de poblacion y vivienda 2002. (accessed February 23, 2010 at(http://onedatabase.indotel.net.do/cgibin/RpWebEngine.exe/PortalAction?&MODE=MAIN&BASE=CPV2002&MAIN=WebServerMain.inl ) **Citation:** COPRESIDA. Primera encuesta de vigilancia de comportamiento con vinculacion serologica en poblaciones vulnerables 2008. 1: 39-88. **Citation:** Kebaabetswe P, Lockman S, Mogwe S, Mandevu R, Thior I, Essex M, Shapiro RL. Male circumcision: an acceptable strategy for HIV prevention in Botswana. Sex Transm Infect. 2003 Jun;79(3):214-9. doi: 10.1136/sti.79.3.214. **PMID:** 12794204 **Citation:** Tieu HV, Phanuphak N, Ananworanich J, Vatanparast R, Jadwattanakul T, Pharachetsakul N, Mingkwanrungrueng P, Buajoom R, Teeratakulpisarn S, Teeratakulpisarn N, Methajittiphun P, Hammer SM, Ann Chiasson M, Phanuphak P. Acceptability of male circumcision for the prevention of HIV among high-risk heterosexual men in Thailand. Sex Transm Dis. 2010 Jun;37(6):352-5. doi: 10.1097/OLQ.0b013e3181c9963a. **PMID:** 20145588 **Citation:** Brito MO, Caso LM, Balbuena H, Bailey RC. Acceptability of male circumcision for the prevention of HIV/AIDS in the Dominican Republic. PLoS One. 2009 Nov 2;4(11):e7687. doi: 10.1371/journal.pone.0007687. **PMID:** 19888322 **Citation:** Brito M, Luna M, Bailey RC. Feasibility of introducing male circumcision (MC) in the Dominican Republic : AIDS 2008 - XVII International AIDS Conference: Abstract no. MOPE0548. **Citation:** WHO. Manual for MC under local anesthesia 2009. (accessed February 23, 2010 at(http://www.who.int/hiv/pub/malecircumcision/local_anaesthesia/en/index.html ) **Citation:** Brito MO, Lerebours L, Volquez C, Basora E, Khosla S, Lantigua F, Flete R, Rosario R, Rodriguez LA, Fernandez M, Donastorg Y, Bailey RC. A Clinical Trial to Introduce Voluntary Medical Male Circumcision for HIV Prevention in Areas of High Prevalence in the Dominican Republic. PLoS One. 2015 Sep 14;10(9):e0137376. doi: 10.1371/journal.pone.0137376. eCollection 2015. **PMID:** 26367187 ## Derived Section ### Condition Browse Module - Browse Branches - Abbrev: BC01 - Name: Infections - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: BXS - Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions - Abbrev: BC20 - Name: Immune System Diseases ### Condition Browse Module - Browse Leaves - ID: M10283 - Name: Infections - Relevance: LOW - As Found: Unknown - ID: M6368 - Name: Communicable Diseases - Relevance: LOW - As Found: Unknown - ID: M3522 - Name: Acquired Immunodeficiency Syndrome - Relevance: LOW - As Found: Unknown - ID: M18250 - Name: HIV Infections - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Browse Branches - Abbrev: CNSDep - Name: Central Nervous System Depressants - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M4107 - Name: Anesthetics - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05424679 **Brief Title:** Piloting +Connection is Medicine / The Healing Spirits Program **Official Title:** Piloting +Connection is Medicine / The Healing Spirits Program #### Organization Study ID Info **ID:** IRB00020570 #### Organization **Class:** OTHER **Full Name:** Johns Hopkins Bloomberg School of Public Health ### Status Module #### Completion Date **Date:** 2023-06-30 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2023-07-07 **Type:** ACTUAL **Last Update Submit Date:** 2023-07-05 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2023-06-30 **Type:** ACTUAL #### Start Date **Date:** 2022-08-24 **Type:** ACTUAL **Status Verified Date:** 2023-07 #### Study First Post Date **Date:** 2022-06-21 **Type:** ACTUAL **Study First Submit Date:** 2022-06-15 **Study First Submit QC Date:** 2022-06-15 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Johns Hopkins Bloomberg School of Public Health #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False ### Description Module **Brief Summary:** This study aims to assess what benefit, if any, an individualized coping plan and facilitating connections to care through referral coordination in conjunction with culturally tailored caring messages, (herein called the +Connection is Medicine intervention (Navajo Nation study name; +CiM)/The Healing Spirits Program (White Mountain Apache Tribe Study Name; HSP) have on the mental health of American Indian (AI) youth and caregivers who were previously identified as having high levels of anxiety and depression as part of their participation in a cohort study called Project SafeSchools (NIH Grant No.: OT2HD107543). **Detailed Description:** The investigators will conduct a Pilot Randomized Controlled Trial (RCT) among caregivers and youth (11-16 years old) who score at elevated risk of anxiety or depression. Participants will be recruited from the sample of individuals who have scored "at risk" on a mental health screening assessment tool in an ongoing cohort study, Project SafeSchools (NIH Grant No.: OT2HD107543). All persons who screen "at risk" will be approached for this pilot study using the study's standardized recruitment script. Parent/Caregiver participants and youth participants may be enrolled separately. All potential study participants will be screened for eligibility after going through the consent/assent process. This is to confirm that potential participants are still presenting with elevated mental health scores at the start of enrollment. For parent/caregiver participants, the screening will utilize the same assessments as those used in the Project SafeSchools cohort study. All youth participants will complete a version of the brief screening tool as well. The screening tool plus a set of additional questions related to the interventions will be administered at 30 days post consent, and again at 90 days post consent to all participants. These additional assessments are needed to understand the immediate impact of the intervention approaches. Additional participant data from the Project SafeSchools study will be analyzed to better understand symptoms prior to the pilot study enrollment, and as a longer-term outcome assessment for the pilot study. If promising, the results of this study will inform a future fully powered study to test these interventions at scale. This pilot intervention will utilize a randomized controlled design, in which both the intervention and control groups receive individualized coping plans, facilitated connections to care, and COVID-19 safety messages. The intervention group also will receive regular caring messages. ### Conditions Module **Conditions:** - Mental Health Issue - Depressive Symptoms - Anxiety **Keywords:** - American Indians and Alaska Natives - COVID-19 - Safety Planning Intervention - Mental Health ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** This pilot intervention trial will utilize a randomized controlled design with 1:1 allocation to either the intervention or control group. Both intervention and control groups will receive individualized coping plans, facilitated connections to care, and COVID-19 safety messages. The intervention group will receive caring messages sent on a standardized schedule in addition to what the control group receives. ##### Masking Info **Masking:** NONE **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 144 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Individuals randomized to the intervention group will receive an evidence-based tool (coping plan + two additional check-in calls or visits), up to three COVID-19 safety messages, information on and facilitated referrals to community support services (e.g., tribal behavioral health), and up to seven culturally responsive caring messages (i.e. Caring Contacts) from the research team over a period of three months. **Intervention Names:** - Behavioral: Safety Planning Intervention - Behavioral: Caring Contacts **Label:** Intervention group **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Individuals randomized to the control group will receive an evidence-based tool (coping plan + two additional check-in calls or visits), up to three COVID-19 safety messages, and information on and facilitated referrals to community support services (e.g., tribal behavioral health) from the research team over a period of three months. **Intervention Names:** - Behavioral: Safety Planning Intervention **Label:** Control group **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Control group - Intervention group **Description:** The Safety Planning Intervention is a brief intervention that directly targets suicide risk with demonstrated efficacy and is a recommended best practice for suicide prevention. The intervention aims to provide participants with an individualized set of steps that can be used progressively to both reduce risk and maintain safety when under particular stress. It also includes a series of brief telephone calls to revise the safety plan and facilitate connections to care. The study team will adapt the intervention to target a larger range of mental health distress. **Name:** Safety Planning Intervention **Type:** BEHAVIORAL #### Intervention 2 **Arm Group Labels:** - Intervention group **Description:** Caring contacts is a cost and time effective suicide prevention intervention. It traditionally utilizes letters and postcards that are sent to an individual to remind them that they are cared about and that they matter. Research suggests that this intervention significantly reduces the likelihood of dying by suicide and suicide attempt over a person's lifetime. This intervention has the potential to reach more individuals at risk in the community. In this study, the research team will allow participants to receive these messages by postcard/MMS and will adapt the intervention to align with cultural values. **Name:** Caring Contacts **Type:** BEHAVIORAL ### Outcomes Module #### Other Outcomes **Description:** Investigators developed 4 items that measure connection to peers and family for use in the study. The Communal Mastery scale measures problem solving through the participant's community and social network. Three items from the Communal Mastery scale relevant to the intervention are included. All seven items are scored on a four-point Likert-type scale, with total possible range from 7-28. Higher scores represent higher levels of connectedness. **Measure:** Group differences in mean scores for caregiver social connectedness over time as assessed by a subset of questions that measure connection to others and several from the Communal Mastery scale **Time Frame:** Baseline-3-months post-baseline; secondary data analysis to measure trends over 12-18 months **Description:** 8 items out of 28 items in the brief COPE that are relevant to the intervention, focusing on coping behaviors that could be modified through the coping plan. Items are answered on a Likert-type scale. For this study, scores can range from 8 to 32 with higher scores representing higher levels of coping behavior. **Measure:** Group differences in mean scores for caregiver and youth coping behaviors over time as assessed by a subset of questions from the Brief COPE Inventory **Time Frame:** Baseline-3-months post-baseline **Description:** Two items related to social connections from the Child/Youth Resilience Scale were selected to assess youth resilience. Each question is rated on a scale of 1-5, for an overall scale score of 2-10. Higher scores represent a better outcome of more youth resilience. **Measure:** Group differences in mean scores for youth resilience over time as assessed by two items from the Child/Youth Resilience Scale **Time Frame:** Baseline-3-months post-baseline; secondary data analysis to measure trends over 12-18 months **Description:** Two items related to self-harm that were internally developed by the study team. The first item is answered yes or no. The second item asks about recency if the first item is yes. These items will be treated as indicator variables and will not be scored as a scale. **Measure:** Group differences in youth self-harm scored as individual indicator variables on two internally developed items **Time Frame:** Baseline-3-months post-baseline; secondary data analysis to measure trends over 12-18 months **Description:** One item related to knowledge of coping strategies was internally developed by the study team. Items are scored using a Likert-type scale, with 0 indicating strong disagreement with a statement and 5 indicating strong agreement with a statement. Higher scores on this item will indicate more knowledge of coping strategies. **Measure:** Group differences in means scores for youth knowledge of coping strategies as assessed by one internally developed item **Time Frame:** Baseline-3-months post-baseline **Description:** This is an internally developed questionnaire that includes 1 item on knowledge of mental health services in the community, 1 item on accessibility of mental health resources, 1 item on use of services in the previous 30 days, and 1 item on difficulties accessing services in the previous 30 days. The items on knowledge of services and accessibility of services are scored using a Likert-type scale, with 0 indicating strong disagreement with the statement and 5 indicating strong agreement with the statement. Items will be scored separately, with higher scores on each item indicating greater knowledge or accessibility. The two items on services use in the previous 30 days and difficulties accessing services in the previous 30 days use a single dichotomous answer (yes or no). These items will be analyzed separately with a dichotomous variable with yes representing service use or difficulties with service use in the past 30 days. **Measure:** Group differences in caregiver and youth mental health service knowledge, access, and use scored as individual indicator variables on an internally developed questionnaire **Time Frame:** Baseline-3-months post-baseline **Description:** This is an internally developed, 7-item inventory on participants' attitudes towards specific COVID-19 related behaviors, including masking, testing, and vaccinations. Scale scores range from 0-28, with higher score representing more positive attitudes towards COVID-19 prevention behaviors and attitudes. **Measure:** Group differences in average scores for caregiver and youth COVID-19 behaviors and attitudes as assessed by an internally developed questionnaire **Time Frame:** Baseline-3-months post-baseline #### Primary Outcomes **Description:** The Kessler Psychological Distress Scale is a six item self-report questionnaire that gathers information about a person's psychological distress. It uses a 0-24 scale, where a score of 13+ is considered high risk. **Measure:** Group differences in mean scores for caregiver general distress over time as assessed by the Kessler Psychological Distress Scale **Time Frame:** Baseline-3 months post-baseline; secondary data analysis to measure trends over 12-18 months **Description:** The SDQ is a self-report questionnaire that can be used with youth ages 11-17. The emotional symptoms subscale is used in the questionnaire, which consists of 5 items. The questionnaire uses a 0-10 scale where a score of 5+ is considered high risk. **Measure:** Group differences in mean scores for youth emotional problems over time as assessed by the Strengths and Difficulties Questionnaire **Time Frame:** Baseline-3 months post-baseline; secondary data analysis to measure trends over 12-18 months #### Secondary Outcomes **Description:** The CESDR-10 is a revised 10 item self-report questionnaire which measures depressive symptoms in general populations. It utilizes a 0-30 scale, in which a score of 8+ is considered high risk. The CESDR-10 also has one item that asks about recent suicide ideation. **Measure:** Group differences in mean scores for caregiver and youth depressive symptoms over time as assessed by the Center for Epidemiologic Studies Depression Scale-Revised-10 **Time Frame:** Baseline-3 months post-baseline; secondary data analysis to measure trends over 12-18 months (caregivers only) **Description:** PROMIS is an eight-statement survey that measures emotional distress due to anxiety that has been experienced over the previous seven days. It uses a five-point Likert scale, 1 indicating 'never' to 5 indicating 'always'. The survey is scored from 8-40 with a score of 17+ indicating high risk. **Measure:** Group differences in mean scores for caregiver anxiety over time as assessed by the Patient-Reported Outcome Measurement Information System **Time Frame:** Baseline-3 months post-baseline; secondary data analysis to measure trends over 12-18 months **Description:** The SCARED survey can be used with those aged 8-18 years. It includes 41 items and five scales which measure somatic/panic, general anxiety, separation anxiety, social phobia, and school phobia. SCARED uses a 0-82 scale where a score of 25+ is high risk. **Measure:** Group differences in mean scores for youth anxiety over time as assessed by the Screen for Child Anxiety Related Emotional Disorders **Time Frame:** Baseline-3 months post-baseline; secondary data analysis to measure trends over 12-18 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: - All participants must be parents/caregivers or index youth enrolled in a cohort study called Project SafeSchools. Adult participants * Have elevated levels of mental distress as reported in a Project SafeSchools assessment. * Agreement to be re-contacted for future research as part of their Project SafeSchools consent. * Meeting symptom eligibility criteria at a screening assessment/baseline visit indicating mental distress. Youth participants: * Are 11-16 years old * Agreement from parent/caregiver to be re-contacted for future research from their Project SafeSchools consent form. * Meeting symptom eligibility criteria based on a self-report screening assessment/baseline visit indicating mental distress. For the inclusion criteria, mental distress is defined as meeting eligibility cutoff scores on the following instruments: Adult Participants * General Distress (Kessler) * Anxiety (PROMIS) * Depression (CESDR-10) * Recent Suicide Ideation (either CESDR-10 or Ideation Questionnaire) Youth Participants: * Depression (CESDR-10) * Emotional Problems (SDQ Emotional Problems Subscale) * Anxiety (SCARED) * Recent Ideation (Ideation question on CESDR-10 or ideation questionnaire) Exclusion Criteria: * Inability to cognitively complete interventions and assessments **Healthy Volunteers:** True **Minimum Age:** 11 Years **Sex:** ALL **Standard Ages:** - CHILD - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Chinle **Country:** United States **Facility:** Johns Hopkins Center for American Indian Health - Chinle Site **State:** Arizona **Zip:** 86503 **Location 2:** **City:** Tuba City **Country:** United States **Facility:** Johns Hopkins Center for American Indian Health - Tuba City Site **State:** Arizona **Zip:** 86045 **Location 3:** **City:** Whiteriver **Country:** United States **Facility:** Johns Hopkins Center for American Indian Health - Whiteriver Site **State:** Arizona **Zip:** 85941 **Location 4:** **City:** Shiprock **Country:** United States **Facility:** Johns Hopkins Center for American Indian Health - Shiprock Site **State:** New Mexico **Zip:** 87420 #### Overall Officials **Official 1:** **Affiliation:** Johns Hopkins Bloomberg School of Public Health **Name:** Emily Haroz, PhD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **Description:** INSERT **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000001526 - Term: Behavioral Symptoms ### Condition Browse Module - Browse Branches - Abbrev: BC01 - Name: Infections - Abbrev: BC08 - Name: Respiratory Tract (Lung and Bronchial) Diseases - Abbrev: All - Name: All Conditions - Abbrev: BXM - Name: Behaviors and Mental Disorders ### Condition Browse Module - Browse Leaves - ID: M2561 - Name: COVID-19 - Relevance: LOW - As Found: Unknown - ID: M4324 - Name: Anxiety Disorders - Relevance: LOW - As Found: Unknown - ID: M7058 - Name: Depression - Relevance: HIGH - As Found: Depressive Symptoms - ID: M7061 - Name: Depressive Disorder - Relevance: LOW - As Found: Unknown - ID: M4818 - Name: Behavioral Symptoms - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000003863 - Term: Depression ### Intervention Browse Module - Browse Branches - Abbrev: CNSDep - Name: Central Nervous System Depressants - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Ot - Name: Other Dietary Supplements ### Intervention Browse Module - Browse Leaves - ID: M4854 - Name: Benzocaine - Relevance: LOW - As Found: Unknown - ID: T433 - Name: Tannic Acid - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT01128179 **Brief Title:** Effects of Lanthanum Carbonate on FGF-23 in Subjects With Stage 3 CKD **Official Title:** A Proof of Concept, Phase 2a, Double-blind, Parallel Group, Randomised, Placebo-controlled Study to Assess the Effect of Lanthanum Carbonate on Intact FGF23 in Normo-phosphataemic Subjects With Stage 3 Chronic Kidney Disease #### Organization Study ID Info **ID:** SPD405-703 #### Organization **Class:** INDUSTRY **Full Name:** Takeda #### Secondary ID Infos **ID:** 2009-016531-35 **Type:** EUDRACT_NUMBER ### Status Module #### Completion Date **Date:** 2012-04-16 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2021-06-09 **Type:** ACTUAL **Last Update Submit Date:** 2021-05-24 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2012-04-16 **Type:** ACTUAL #### Results First Post Date **Date:** 2013-05-22 **Type:** ESTIMATED **Results First Submit Date:** 2013-03-20 **Results First Submit QC Date:** 2013-03-25 #### Start Date **Date:** 2010-12-06 **Type:** ACTUAL **Status Verified Date:** 2021-05 #### Study First Post Date **Date:** 2010-05-21 **Type:** ESTIMATED **Study First Submit Date:** 2010-05-20 **Study First Submit QC Date:** 2010-05-20 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Shire #### Responsible Party **Type:** SPONSOR ### Description Module **Brief Summary:** To assess the effects of 12 weeks of treatment with lanthanum carbonate compared with placebo on serum intact Fibroblast Growth Factor 23 (FGF23) levels. ### Conditions Module **Conditions:** - Chronic Kidney Disease ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** DOUBLE **Who Masked:** - PARTICIPANT - INVESTIGATOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 35 **Type:** ACTUAL **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Intervention Names:** - Drug: Lanthanum carbonate **Label:** Lanthanum carbonate **Type:** EXPERIMENTAL #### Arm Group 2 **Intervention Names:** - Drug: Placebo **Label:** Placebo **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Lanthanum carbonate **Description:** 1000 mg in chewable tablets administered three times a day (for a total of 3000 mg/day) for 12 weeks **Name:** Lanthanum carbonate **Other Names:** - Fosrenol/Foznol **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Placebo **Description:** Matching placebo chewable tablets administered 3 times a day for 12 weeks **Name:** Placebo **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** FGF-23 plays an important role in mineral metabolism in chronic kidney disease patients. It is secreted by bone cells in response to hyperphosphatemia. It acts to decrease renal phosphate reabsorption. Administration of a phosphate-binder (i.e. lanthanum carbonate) was expected to produce a reduction in FGF-23 levels. **Measure:** Natural Logarithm Transformed Serum Intact Fibroblast Growth Factor (FGF-23) Levels at Week 12 Last Observation Carried Forward (LOCF) **Time Frame:** 12 Weeks #### Secondary Outcomes **Measure:** Change From Baseline in Serum Intact Parathyroid Hormone (iPTH) Values at Week 12 (LOCF) **Time Frame:** 12 Weeks **Measure:** Change From Baseline in 1,25-Dihydroxy Vitamin D Values at Week 12 (LOCF) **Time Frame:** 12 weeks **Measure:** Change From Baseline in Urinary Fractional Excretion of Phosphate Values at Week 12 (LOCF) **Time Frame:** 12 weeks **Measure:** Change From Baseline in Serum Phosphate Values at Week 12 (LOCF) **Time Frame:** 12 weeks **Measure:** Change From Baseline in Serum Total Calcium Values at Week 12 (LOCF) **Time Frame:** 12 weeks **Measure:** Change From Baseline in Calcium-Phosphate Product Values at Week 12 (LOCF) **Time Frame:** 12 weeks ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: Subjects meeting all of the criteria listed below may be included in the study: 1. ≥18 years old. 2. Male, or non-pregnant, non-lactating females who agree to comply with any applicable contraceptive requirements of the protocol. 3. Been in the care of a physician for CKD for \>2 months, and are not expected to begin dialysis for at least 6 months. 4. Screening serum c-terminal FGF23 \> 50.0RU/mL. 5. Screening estimated glomerular filtration rate (eGFR) of 30-59mL/min/1.73m2 using the MDRD formula. 6. Normal serum phosphate (0.808-1.55mmol/L). 7. Endogenous 25-hydroxy Vitamin D levels \>20ng/mL. 8. Adequate protein diet (includes 2-3 portions of protein-rich food per day). 9. An understanding, ability, and willingness to fully comply with study procedures and restrictions. 10. Ability to provide written, signed, and dated (personally) informed consent to participate in the study. Exclusion Criteria 1. Vitamin D supplementation required. 2. Compounds containing calcium, phosphate, aluminium or magnesium required. 3. Acute renal failure. 4. Rapidly progressing glomerulonephritis. 5. Vegetarian diet. 6. Known allergy to iodine. 7. Clinically significant uncontrolled concurrent illness, which, in the opinion of the Investigator, would impair subjects' ability to give informed consent or take part in or complete this clinical study. 8. Cirrhosis or other clinically significant liver disease (aspartate transaminase (AST) or alanine transaminase (ALT) \>3 times the upper limit of normal or bilirubin \>2 times the upper limit of normal). 9. Past (treated within the last 5 years) or present GI disorders including uncontrolled peptic ulcer, Crohn's disease (or other conditions where the integrity of the GI tract may be compromised), malignancy, or GI bleed within the last 6 months. 10. Life-threatening malignancy or current multiple myeloma. 11. Known to be Human Immunodeficiency Virus (HIV) positive. 12. History of poor compliance with diet or medication that in the Investigator's opinion may interfere with adherence to the protocol. 13. History of alcohol or other substance abuse within 6 months prior to screening. 14. Subjects must not have used another investigational medicinal product or taken part in a clinical trial within the last 30 days prior to enrolment. 15. Subjects who have previously been enrolled into this study and subsequently withdrawn. **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Saint Ouen **Country:** France **Facility:** Dr Pablo Urena Torres **State:** Paris **Zip:** 93400 #### Overall Officials **Official 1:** **Affiliation:** Takeda **Name:** Study Director **Role:** STUDY_DIRECTOR ### References Module #### References **Citation:** Urena-Torres P, Prie D, Keddad K, Preston P, Wilde P, Wan H, Copley JB. Changes in fibroblast growth factor 23 levels in normophosphatemic patients with chronic kidney disease stage 3 treated with lanthanum carbonate: results of the PREFECT study, a phase 2a, double blind, randomized, placebo-controlled trial. BMC Nephrol. 2014 May 5;15:71. doi: 10.1186/1471-2369-15-71. **PMID:** 24885942 ## Derived Section ### Condition Browse Module - Ancestors - 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: D000051437 - Term: Renal Insufficiency - ID: D000002908 - Term: Chronic Disease - ID: D000020969 - Term: Disease Attributes - ID: D000010335 - Term: Pathologic Processes ### Condition Browse Module - Browse Branches - Abbrev: BXS - Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M10698 - Name: Kidney Diseases - Relevance: HIGH - As Found: Kidney Disease - ID: M26717 - Name: Renal Insufficiency, Chronic - Relevance: HIGH - As Found: Chronic Kidney Disease - ID: M26718 - Name: Renal Insufficiency - 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: 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: D000007674 - Term: Kidney Diseases - ID: D000051436 - Term: Renal Insufficiency, Chronic ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module #### Event Groups **Group ID:** EG000 **Title:** Lanthanum Carbonate **Description:** 1000 mg in chewable tablets (given as 2 x 500 mg tablets) administered three times a day (for a total of 3000 mg/day) for 12 weeks **ID:** EG000 **Other Num Affected:** 2 **Other Num at Risk:** 23 **Serious Number Affected:** 2 **Serious Number At Risk:** 23 **Title:** Lanthanum Carbonate **Group ID:** EG001 **Title:** Placebo **Description:** Matching placebo chewable tablets administered 3 times a day for 12 weeks **ID:** EG001 **Other Num at Risk:** 12 **Serious Number At Risk:** 12 **Title:** Placebo **Frequency Threshold:** 5 #### Other Events **Term:** Constipation **Organ System:** Gastrointestinal disorders **Source Vocabulary:** #### Serious Events **Term:** Cardiac failure **Organ System:** Cardiac disorders ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 23 **Group ID:** EG001 **Num At Risk:** 12 **Term:** Myocardial ischemia **Organ System:** Cardiac disorders ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 23 **Group ID:** EG001 **Num At Risk:** 12 **Term:** Pancreatitis acute **Organ System:** Gastrointestinal disorders ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 23 **Group ID:** EG001 **Num At Risk:** 12 ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 23 **Group ID:** BG001 **Value:** 12 **Group ID:** BG002 **Value:** 35 **Units:** Participants ### Group **ID:** BG000 **Title:** Lanthanum Carbonate **Description:** 1000 mg in chewable tablets (given as 2 x 500 mg tablets) administered three times a day (for a total of 3000 mg/day) for 12 weeks ### Group **ID:** BG001 **Title:** Placebo **Description:** Matching placebo chewable tablets administered 3 times a day for 12 weeks ### Group **ID:** BG002 **Title:** Total **Description:** Total of all reporting groups ### Measure #### Measurement **Group ID:** BG000 **Spread:** 13.9 **Value:** 66.0 #### Measurement **Group ID:** BG001 **Spread:** 13.2 **Value:** 69.4 #### Measurement **Group ID:** BG002 **Spread:** 13.6 **Value:** 67.2 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 23 #### Measurement **Group ID:** BG001 **Value:** 12 #### Measurement **Group ID:** BG002 **Value:** 35 **Class Title:** >=18 years ### Measure #### Measurement **Group ID:** BG000 **Value:** 10 #### Measurement **Group ID:** BG001 **Value:** 7 #### Measurement **Group ID:** BG002 **Value:** 17 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 13 #### Measurement **Group ID:** BG001 **Value:** 5 #### Measurement **Group ID:** BG002 **Value:** 18 **Category Title:** Male **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 23 #### Measurement **Group ID:** BG001 **Value:** 12 #### Measurement **Group ID:** BG002 **Value:** 35 **Class Title:** France **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:** Region of Enrollment **Unit of Measure:** Participants **Population Description:** The Safety Analysis Set was defined as all randomized subjects who received at least 1 dose of investigational product. This population was used in all safety reporting. ## Results Section - More Information Module ### Certain Agreement **Other Details:** If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually. **Restriction Type:** OTHER **Restrictive Agreement:** True ### Point of Contact **Email:** [email protected] **Organization:** Shire **Phone:** +1 866 842 5335 **Title:** Study Director ## Results Section - Outcome Measures Module ### Outcome Measure 1 #### Analysis **CI Lower Limit:** -0.3389 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 0.1146 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Assuming that the natural logarithm transformed serum intact FGF-23 is normally distributed with a mean of 3.5 and a standard deviation of 0.46, 33 subjects randomised 2:1 (lanthanum carbonate to placebo) will be sufficient to detect with 80% power at the 5% 2-sided significance level a decrease of 0.5 in the mean difference (placebo minus lanthanum carbonate) of the log-transformed data at Week 12. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER_LEGACY **Other Analysis Description:** **P-Value:** 0.3186 **P-Value Comment:** The a priori significance level was 5%. There was no adjustment for multiple comparisons. **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** -0.1121 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** ### Outcome Measure 2 #### Analysis **CI Lower Limit:** -6.15 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 19.23 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** The null hypothesis was that there would be no difference between the 2 treatment groups in the mean change from baseline of serum iPTH at Week 12 (LOCF) in an analysis of covariance (ANCOVA) with treatment as a factor and the baseline iPTH as a covariate. The study was not powered for the analysis of this parameter. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER_LEGACY **Other Analysis Description:** **P-Value:** 0.2995 **P-Value Comment:** The p-value was unadjusted and had no a priori significance level. **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 6.54 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** ### Outcome Measure 3 #### Analysis **CI Lower Limit:** -5.36 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 15.57 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** The null hypothesis was that there would be no difference between the 2 treatment groups in the mean change from baseline of 1,25-Dihydroxy Vitamin D at Week 12 (LOCF) when utilizing an analysis of covariance (ANCOVA) with treatment as a factor and the baseline 1,25-Dihydroxy Vitamin D as a covariate. The study was not powered for the analysis of this parameter. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER_LEGACY **Other Analysis Description:** **P-Value:** 0.3252 **P-Value Comment:** The p-value was unadjusted and had no a priori significance level. **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 5.11 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** ### Outcome Measure 4 #### Analysis **CI Lower Limit:** -8.845 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 1.403 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** The null hypothesis was that there would be no difference between the 2 treatment groups in the mean change from baseline of Urinary Fractional Excretion of Phosphate at Week 12 (LOCF) when utilizing an analysis of covariance (ANCOVA) with treatment as a factor and the baseline Urinary Fractional Excretion of Phosphate as a covariate. The study was not powered for the analysis of this parameter. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER_LEGACY **Other Analysis Description:** **P-Value:** 0.1459 **P-Value Comment:** The p-value was unadjusted and had no a priori significance level. **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** -3.7 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** ### Outcome Measure 5 #### Analysis **CI Lower Limit:** -0.1492 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 0.0897 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** The null hypothesis was that there would be no difference between the 2 treatment groups in the mean change from baseline of Serum Phosphate at Week 12 (LOCF) in an analysis of covariance (ANCOVA) with treatment as a factor and the baseline Serum Phosphate as a covariate. The study was not powered for the analysis of this parameter **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER_LEGACY **Other Analysis Description:** **P-Value:** 0.6134 **P-Value Comment:** The p-value was unadjusted and had no a priori significance level. **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** -0.0297 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** ### Outcome Measure 6 #### Analysis **CI Lower Limit:** -0.0739 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 0.1328 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** The null hypothesis was that there would be no difference between the 2 treatment groups in the mean change from baseline of Serum Total Calcium at Week 12 (LOCF) in an analysis of covariance (ANCOVA) with treatment as a factor and the baseline Serum Total Calcium as a covariate. The study was not powered for the analysis of this parameter. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER_LEGACY **Other Analysis Description:** **P-Value:** 0.5636 **P-Value Comment:** The p-value was unadjusted and had no a priori significance level. **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 0.0294 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** ### Outcome Measure 7 #### Analysis **CI Lower Limit:** -0.2811 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 0.2553 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** The null hypothesis was that there would be no difference between the 2 treatment groups in the mean change from baseline of Calcium-Phosphate Product at Week 12 (LOCF) in an analysis of covariance (ANCOVA) with treatment as a factor and the baseline Calcium-Phosphate Product as a covariate. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER_LEGACY **Other Analysis Description:** **P-Value:** 0.9220 **P-Value Comment:** The p-value was unadjusted and had no a priori significance level. **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** -0.0129 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.0709 - **Upper Limit:** - **Value:** 4.0089 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.0844 - **Upper Limit:** - **Value:** 4.1210 **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 3.96 - **Upper Limit:** - **Value:** 1.67 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 4.72 - **Upper Limit:** - **Value:** -4.87 **Title:** #### Outcome Measure 3 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 3.22 - **Upper Limit:** - **Value:** -1.75 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 3.85 - **Upper Limit:** - **Value:** -6.86 **Title:** #### Outcome Measure 4 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.5 - **Upper Limit:** - **Value:** -5.9 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.9 - **Upper Limit:** - **Value:** -2.2 **Title:** #### Outcome Measure 5 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.0371 - **Upper Limit:** - **Value:** 0.0053 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.0443 - **Upper Limit:** - **Value:** 0.0350 **Title:** #### Outcome Measure 6 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.0323 - **Upper Limit:** - **Value:** 0.0242 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.0385 - **Upper Limit:** - **Value:** -0.0052 **Title:** #### Outcome Measure 7 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.0833 - **Upper Limit:** - **Value:** 0.0581 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.0993 - **Upper Limit:** - **Value:** 0.0710 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** FGF-23 plays an important role in mineral metabolism in chronic kidney disease patients. It is secreted by bone cells in response to hyperphosphatemia. It acts to decrease renal phosphate reabsorption. Administration of a phosphate-binder (i.e. lanthanum carbonate) was expected to produce a reduction in FGF-23 levels. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** Per-protocol (PP) set are subjects who received at least 1 dose of investigational product and who had primary data assessment available from Week 2 or later and who did not have pre-defined major protocol deviations that could have affected the primary variable. **Reporting Status:** POSTED **Time Frame:** 12 Weeks **Title:** Natural Logarithm Transformed Serum Intact Fibroblast Growth Factor (FGF-23) Levels at Week 12 Last Observation Carried Forward (LOCF) **Type:** PRIMARY **Unit of Measure:** pg/ml ##### Group **Description:** 1000 mg in chewable tablets (given as 2 x 500 mg tablets) administered three times a day (for a total of 3000 mg/day) for 12 weeks **ID:** OG000 **Title:** Lanthanum Carbonate ##### Group **Description:** Matching placebo chewable tablets administered 3 times a day for 12 weeks **ID:** OG001 **Title:** Placebo #### Outcome Measure 2 **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** PP **Reporting Status:** POSTED **Time Frame:** 12 Weeks **Title:** Change From Baseline in Serum Intact Parathyroid Hormone (iPTH) Values at Week 12 (LOCF) **Type:** SECONDARY **Unit of Measure:** pg/ml ##### Group **Description:** 1000 mg in chewable tablets (given as 2 x 500 mg tablets) administered three times a day (for a total of 3000 mg/day) for 12 weeks **ID:** OG000 **Title:** Lanthanum Carbonate ##### Group **Description:** Matching placebo chewable tablets administered 3 times a day for 12 weeks **ID:** OG001 **Title:** Placebo #### Outcome Measure 3 **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** PP **Reporting Status:** POSTED **Time Frame:** 12 weeks **Title:** Change From Baseline in 1,25-Dihydroxy Vitamin D Values at Week 12 (LOCF) **Type:** SECONDARY **Unit of Measure:** pg/ml ##### Group **Description:** 1000 mg in chewable tablets (given as 2 x 500 mg tablets) administered three times a day (for a total of 3000 mg/day) for 12 weeks **ID:** OG000 **Title:** Lanthanum Carbonate ##### Group **Description:** Matching placebo chewable tablets administered 3 times a day for 12 weeks **ID:** OG001 **Title:** Placebo #### Outcome Measure 4 **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** PP **Reporting Status:** POSTED **Time Frame:** 12 weeks **Title:** Change From Baseline in Urinary Fractional Excretion of Phosphate Values at Week 12 (LOCF) **Type:** SECONDARY **Unit of Measure:** percentage of excretion of phosphate ##### Group **Description:** 1000 mg in chewable tablets (given as 2 x 500 mg tablets) administered three times a day (for a total of 3000 mg/day) for 12 weeks **ID:** OG000 **Title:** Lanthanum Carbonate ##### Group **Description:** Matching placebo chewable tablets administered 3 times a day for 12 weeks **ID:** OG001 **Title:** Placebo #### Outcome Measure 5 **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** PP **Reporting Status:** POSTED **Time Frame:** 12 weeks **Title:** Change From Baseline in Serum Phosphate Values at Week 12 (LOCF) **Type:** SECONDARY **Unit of Measure:** mmol/L ##### Group **Description:** 1000 mg in chewable tablets (given as 2 x 500 mg tablets) administered three times a day (for a total of 3000 mg/day) for 12 weeks **ID:** OG000 **Title:** Lanthanum Carbonate ##### Group **Description:** Matching placebo chewable tablets administered 3 times a day for 12 weeks **ID:** OG001 **Title:** Placebo #### Outcome Measure 6 **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** PP **Reporting Status:** POSTED **Time Frame:** 12 weeks **Title:** Change From Baseline in Serum Total Calcium Values at Week 12 (LOCF) **Type:** SECONDARY **Unit of Measure:** mmol/L ##### Group **Description:** 1000 mg in chewable tablets (given as 2 x 500 mg tablets) administered three times a day (for a total of 3000 mg/day) for 12 weeks **ID:** OG000 **Title:** Lanthanum Carbonate ##### Group **Description:** Matching placebo chewable tablets administered 3 times a day for 12 weeks **ID:** OG001 **Title:** Placebo #### Outcome Measure 7 **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** PP **Reporting Status:** POSTED **Time Frame:** 12 weeks **Title:** Change From Baseline in Calcium-Phosphate Product Values at Week 12 (LOCF) **Type:** SECONDARY **Unit of Measure:** mmol^2/L^2 ##### Group **Description:** 1000 mg in chewable tablets (given as 2 x 500 mg tablets) administered three times a day (for a total of 3000 mg/day) for 12 weeks **ID:** OG000 **Title:** Lanthanum Carbonate ##### Group **Description:** Matching placebo chewable tablets administered 3 times a day for 12 weeks **ID:** OG001 **Title:** Placebo ### Participant Flow Module #### Group **Description:** 1000 mg in chewable tablets (given as 2 x 500 mg tablets) administered three times a day (for a total of 3000 mg/day) for 12 weeks **ID:** FG000 **Title:** Lanthanum Carbonate #### Group **Description:** Matching placebo chewable tablets administered 3 times a day for 12 weeks **ID:** FG001 **Title:** Placebo #### Period **Title:** Overall Study ##### Withdraw **Type:** Death ###### 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:** 1 ###### Reason **Group ID:** FG001 **Number of Subjects:** 0 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 23 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 12 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 21 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 12 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 2 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 0 **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT03056079 **Acronym:** COVARIANT **Brief Title:** Cytokine and Visual Outcome Variations in Eyes Receiving Aflibercept **Official Title:** Cytokine and Visual Outcome Variations in Eyes Receiving a Variable Dosing Aflibercept Treatment: The COVARIANT Study #### Organization Study ID Info **ID:** COVARIANT #### Organization **Class:** OTHER **Full Name:** Unity Health Toronto ### Status Module #### Completion Date **Date:** 2024-02-28 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** RECRUITING #### Last Update Post Date **Date:** 2021-04-28 **Type:** ACTUAL **Last Update Submit Date:** 2021-04-27 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2024-02-28 **Type:** ESTIMATED #### Start Date **Date:** 2017-02-28 **Type:** ACTUAL **Status Verified Date:** 2021-04 #### Study First Post Date **Date:** 2017-02-17 **Type:** ACTUAL **Study First Submit Date:** 2017-02-01 **Study First Submit QC Date:** 2017-02-13 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Unity Health Toronto #### 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:** Objective: To determine the association between baseline aqueous cytokine levels and treatment intervals for patients under a variable dosing regimen with intravitreal aflibercept in patients with neovascular age-related macular degeneration (nAMD), macular edema secondary to retinal vein occlusion (RVO) and diabetic macular edema (DME). Methods: A prospective, single-centre study will be performed containing 3 sub-studies according to each study population: nAMD, macular edema secondary to RVO and DME. Inclusion criteria are: patients followed at St. Michael's Hospital with the diagnosis of nAMD, macular edema secondary to RVO or DME. Patients will be excluded if visual acuity is worse than counting fingers, with macular pathologies causing any structural changes to the retina, have received anti-VEGF injections or photocoagulation therapy 6 months prior to study, intraocular surgery 3 months prior to study, any history of vitreoretinal surgery or ocular inflammation in the study eye, use of systemic or topical anti-inflammatory or steroids, patients on dialysis for renal failure, allergy to the study drug or fluorescein, \<18 years old, women who are pregnant. All patients will be treated with aflibercept intravitreal injections on a variable dosing regimen: Patients with DME will be examined monthly and receive mandatory injection for the first three months (baseline, weeks 4 and 8). Afterwards, they will continue to be seen monthly and the need for new injections will be decided upon the clinical findings at each visit. An anterior chamber (AC) tap will be done if an injection is required at the visit. Patients with nAMD and RVO will be examined monthly and receive mandatory injection for the first three months. From weeks 12 until 72 (month 18), the visits will be scheduled at increasing 2-weeks intervals based on the stability of the ocular condition and response to treatment. At each visit, an injection and AC tap will be performed. The maximum interval in between injections is 12 weeks. If the disease becomes unstable, the interval in between injections is shortened and, once it stabilizes, the treatment frequency is extended again. In all patients, baseline aqueous humour specimens will be obtained prior to the first aflibercept intravitreal injection and follow-up samples will be taken immediately prior to subsequent injections based on the treatment regimens for cytokine analysis in the end of the follow-up. ### Conditions Module **Conditions:** - Age Related Macular Degeneration - Diabetic Macular Edema - Retinal Vein Occlusion - Macular Edema **Keywords:** - neovascular age related macular degeneration - diabetic macular edema - retinal vein occlusion - aflibercept - aqueous humor cytokine ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP **Intervention Model Description:** This study will contain 3 populations of patients which will all receive aflibercept injections: one with neovascular age-related macular degeneration, other with diabetic macular edema and a third with macular edema secondary to retinal vein occlusion. ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 168 **Type:** ESTIMATED **Phases:** - PHASE4 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Patients presenting to St. Michael's Hospital retina clinic with neovascular AMD, macular edema secondary to retinal vein occlusion and diabetic macular edema treated with intravitreal aflibercept in a variable dosing regimen. **Intervention Names:** - Drug: Intravitreal aflibercept **Label:** AMD/RVO/DME **Type:** OTHER ### Interventions #### Intervention 1 **Arm Group Labels:** - AMD/RVO/DME **Description:** Patients will receive intravitreal aflibercept on a variable dosing regimen and have aqueous humor sample obtained for cytokine analysis at every visit when an intravitreal injection is done. **Name:** Intravitreal aflibercept **Other Names:** - Eylea **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Optimal interval between injections based on aqueous cytokine levels **Measure:** Association between cytokine levels and optimal treatment interval **Time Frame:** 18 months #### Secondary Outcomes **Description:** Aqueous cytokine curves for each patient based on the relationship between cytokine levels and treatment response **Measure:** Individualized aqueous cytokine curves relationship with treatment response **Time Frame:** 18 months **Description:** Cytokine threshold level below which visual and anatomic outcomes are greatest **Measure:** Cytokine threshold level with visual and anatomic outcomes **Time Frame:** 18 months **Description:** To assess Snellen Best Corrected Visual Acuity (BCVA) change at months 1 and 2, and at the visits scheduled for each injection throughout an 18 months period. **Measure:** Snellen BCVA change **Time Frame:** months 1 and 2, and at the visits scheduled for each injection throughout an 18 months period. **Description:** Visual acuity (ETDRS) change at month 2 (at the third injection), at the visits closest to injection of months 6, 12 and 18. **Measure:** ETDRS visual acuity change **Time Frame:** month 2, at the visits closest to injection of months 6, 12 and 18. **Description:** Anatomic OCT change (Macular Volume, Central Macular Thickness) at months 1 and 2, and at the visits scheduled for each injection throughout an 18 months period. **Measure:** Optical coherence tomography change **Time Frame:** months 1 and 2, and at the visits scheduled for each injection throughout an 18 months period. **Description:** Average number of injections needed in a variable dosing regimen protocol over an 18 months period. **Measure:** Average number of injections needed **Time Frame:** 18 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Diagnosis of active choroidal neovascularization secondary to AMD in the study eye * Diagnosis of macular edema secondary to RVO: central macular thickness \>310μm due to intraretinal or subretinal edema in the study eye as measured on OCT * Diagnosis of DME with central macular thickness \>310μm in the study eye as measured on OCT in patients with diabetes mellitus types 1 or 2 Exclusion Criteria: * • Previous intravitreal drug injections in either eye within 6 months prior to study enrollment * Visual acuity worse than counting fingers * Patients with other macular pathologies causing structural changes to the retina * Patients with large submacular hemorrhages or extensive fibrosis occupying the majority (\>50%) of the lesion * Intraocular surgery in the study eye 3 months prior to study enrollment * Previous vitreoretinal surgery in the study eye * Previous photodynamic or macular photocoagulation therapy within the past 6 months in the study eye in patients with AMD * Previous photocoagulation therapy within 6 months in the study eye or anticipated need for during the course of the study in patients with RVO * Presence of active proliferative diabetic retinopathy or patients who have had pan-retinal photocoagulation within 6 months or patients where the need to pan-retinal photocoagulation is anticipated during the course of the study in patients with DME * History of intraocular inflammation in the study eye * Patients on systemic or topical anti-inflammatory or steroids medications * Patients receiving dialysis for renal failure * Known allergy to the study drug or fluorescein * Patients who are pregnant * Unwilling or unable to follow or comply with all study related procedures or to sign consent form **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Rajeev Muni **Phone:** 416-867-7411 **Role:** CONTACT #### Locations **Location 1:** **City:** Toronto **Contacts:** ***Contact 1:*** - **Name:** Rajeev H Muni, FRCSC - **Role:** PRINCIPAL_INVESTIGATOR **Country:** Canada **Facility:** Department of Ophthalmology, St Michael's Hospital **State:** Ontario **Status:** RECRUITING **Zip:** M5C 2T2 **Location 2:** **City:** Toronto **Contacts:** ***Contact 1:*** - **Name:** Peter Kertes - **Role:** CONTACT **Country:** Canada **Facility:** Sunnybrook Health Sciences Centre **Status:** RECRUITING #### Overall Officials **Official 1:** **Affiliation:** Unity Health Toronto **Name:** Rajeev Muni **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000012162 - Term: Retinal Degeneration - ID: D000012164 - Term: Retinal Diseases - ID: D000005128 - Term: Eye Diseases - ID: D000020246 - Term: Venous Thrombosis - ID: D000013927 - Term: Thrombosis - ID: D000016769 - Term: Embolism and Thrombosis - ID: D000014652 - Term: Vascular Diseases - ID: D000002318 - Term: Cardiovascular Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC11 - Name: Eye Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: BC14 - Name: Heart and Blood Diseases ### Condition Browse Module - Browse Leaves - ID: M11261 - Name: Macular Edema - Relevance: HIGH - As Found: Macular Edema - ID: M7657 - Name: Edema - Relevance: HIGH - As Found: Edema - ID: M15005 - Name: Retinal Vein Occlusion - Relevance: HIGH - As Found: Retinal Vein Occlusion - ID: M11260 - Name: Macular Degeneration - Relevance: HIGH - As Found: Age-related Macular Degeneration - ID: M14997 - Name: Retinal Degeneration - Relevance: LOW - As Found: Unknown - ID: M14999 - Name: Retinal Diseases - Relevance: LOW - As Found: Unknown - ID: M8271 - Name: Eye Diseases - Relevance: LOW - As Found: Unknown - ID: M16686 - Name: Thrombosis - Relevance: LOW - As Found: Unknown - ID: M22071 - Name: Venous Thrombosis - Relevance: LOW - As Found: Unknown - ID: M7784 - Name: Embolism - Relevance: LOW - As Found: Unknown - ID: M19128 - Name: Embolism and Thrombosis - Relevance: LOW - As Found: Unknown - ID: M17400 - Name: Vascular Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000008268 - Term: Macular Degeneration - ID: D000008269 - Term: Macular Edema - ID: D000012170 - Term: Retinal Vein Occlusion - ID: D000004487 - Term: Edema ### Intervention Browse Module - Ancestors - ID: D000020533 - Term: Angiogenesis Inhibitors - ID: D000043924 - Term: Angiogenesis Modulating Agents - ID: D000006133 - Term: Growth Substances - ID: D000045505 - Term: Physiological Effects of Drugs - 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 ### Intervention Browse Module - Browse Leaves - ID: M257727 - Name: Aflibercept - Relevance: HIGH - As Found: Magnetic Resonance Imaging - 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: C000533178 - Term: Aflibercept ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04371679 **Acronym:** COVID-HO **Brief Title:** Changes in Cardiac and Pulmonary Hemodynamics as Predictor of Outcome in Hospitalized COVID-19 Patients **Official Title:** Changes in Cardiac and Pulmonary Hemodynamics as Predictor of Outcome in Hospitalized COVID-19 Patients #### Organization Study ID Info **ID:** Covid-HO #### Organization **Class:** OTHER **Full Name:** Hasselt University ### Status Module #### Completion Date **Date:** 2022-12-01 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** RECRUITING #### Last Update Post Date **Date:** 2022-03-15 **Type:** ACTUAL **Last Update Submit Date:** 2022-03-14 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2022-10-01 **Type:** ESTIMATED #### Start Date **Date:** 2020-04-01 **Type:** ACTUAL **Status Verified Date:** 2022-03 #### Study First Post Date **Date:** 2020-05-01 **Type:** ACTUAL **Study First Submit Date:** 2020-04-30 **Study First Submit QC Date:** 2020-04-30 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Hasselt University #### Responsible Party **Investigator Affiliation:** Hasselt University **Investigator Full Name:** prof. dr. Paul Dendale **Investigator Title:** Head of Cardiology **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** The primary objective of the study is to evaluate cardiac and pulmonary hemodynamic changes over time as predictor of disease progression and outcome in COVID-19 patients admitted to ICU. The primary endpoint is the occurrence of a major event predefined as either: death (all-cause mortality) or discharge from ICU (limit of 4 months). This is a uni-center prospective observational cohort study with an inclusion period of 2 months. The end of the study is foreseen in 6 months. **Detailed Description:** Background COVID-19 can lead to a bilateral pneumonia overwhelming the lungs causing dyspnea and respiratory distress. Up to 20% of the infected population is hospitalized and 5% is submitted to the intensive care unit (ICU). Up to 31% of patients in ICU develop sepsis and 61% develop ARDS with a deadly outcome at ICU of 38%. While sepsis typically causes diffuse vasodilation, the pulmonary vasculature resistance in ARDS is high. Although heart failure is per definition not the cause of ARDS, the resulting elevated pressures in the pulmonary circulation affect right and left heart function. Early detection in alterations of cardiac and pulmonary hemodynamics might prompt to actions to prevent ARDS. Primary objective To evaluate cardiac and pulmonary hemodynamic changes over time as predictor of disease progression and outcome in COVID-19 patients admitted to ICU. Secondary objective * Analysis of prognostic factors based on the data at initial presentation * Performing a trajectory analysis of the time course during ICU stay to determine what leads to optimal outcome - gain insight in the pathophysiology of the cardio-pulmonary evolution of COVID-19 pts * Feasibility study for the creation of an individualized expected data-trajectory for new cases and continuously updating its visualization in relation to the expected trajectory related to an improved outcome * Evaluate how Machine Learning, based on manifold learning for quantifying information similarity and its temporal evolution, is able to predict outcome using rich data in a limited number of patients Primary Endpoint Occurrence of a major event predefined as either: * Death (all-cause mortality) * Discharge from ICU (limit of 4 months) Secondary Endpoint * Decrease of left ventricular (LV) function defined by LV global longitudinal strain (GLS) \> 5% (absolute value) and LV S' as compared to the initial evaluation * Evolution of LV diastolic function related to prognosis - Doppler Data and ML interpretation * Decrease of right ventricular (RV) function by RV GLS \> 5% (absolute values) or decrease of RV S' to an absolute value \<9.5 cm/s * Dynamic RV response to PEEP maneuver to differentiate intrinsic RV dysfunction from excessive PEEP. * Changes in pulmonary arterial compliance from RVOT-VTI and PASP Methods Uni-center cohort study (Prospective Observational) Duration of the study Duration of the inclusion period: 2 months Duration of participation for each patient: average 4 weeks until death or discharge from ICU Duration of data processing and reports: 4 months Total duration of the study: 6 months ### Conditions Module **Conditions:** - Covid-19 ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** RETROSPECTIVE #### Enrollment Info **Count:** 40 **Type:** ESTIMATED **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Patients admitted at ICU that are intubated and ventilated **Intervention Names:** - Other: No interventions planned **Label:** Endotracheal intubation and ventilation #### Arm Group 2 **Description:** Patients admitted at ICU who are non-invasively ventilated **Intervention Names:** - Other: No interventions planned **Label:** Non-Invasive Ventilation ### Interventions #### Intervention 1 **Arm Group Labels:** - Endotracheal intubation and ventilation - Non-Invasive Ventilation **Description:** No interventions planned. Observational. **Name:** No interventions planned **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** Covid-19 pneumonia that requires ICU admission can go either way. **Measure:** Death (all-cause mortality) or discharge from ICU (limit of 4 months) **Time Frame:** 4 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Patient admitted to ICU that is COVID-19 positive based on rt-PCR * Ventilated or not ventilated * No restrictions on age * No restrictions on comorbidities or a diversity of underlying pathology (malignancies, COPD, ...) Exclusion Criteria: * Patients that are not COVID-19 tested (rt-PCR) or where the diagnosis is pending. * Patients that refuse their participation in the study. * Patients under legal protection, or deprived of their liberty. * Patients that are so critically ill that a minimum of 1 follow-up is very unlikely to be realised **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - CHILD - ADULT - OLDER_ADULT **Study Population:** All consecutive COVID-19 positive patients that are admitted to the ICU ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Lieven Herbots, MD, PhD **Phone:** +3211309579 **Role:** CONTACT #### Locations **Location 1:** **City:** Hasselt **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Lieven Herbots - **Role:** CONTACT **Country:** Belgium **Facility:** Jessa Hospital **Status:** RECRUITING **Zip:** 3500 #### Overall Officials **Official 1:** **Affiliation:** Hartcentrum Hasselt **Name:** Lieven Herbots, MD, PhD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000011024 - Term: Pneumonia, Viral - ID: D000011014 - Term: Pneumonia - ID: D000012141 - Term: Respiratory Tract Infections - ID: D000007239 - Term: Infections - ID: D000014777 - Term: Virus Diseases - ID: D000018352 - Term: Coronavirus Infections - ID: D000003333 - Term: Coronaviridae Infections - ID: D000030341 - Term: Nidovirales Infections - ID: D000012327 - Term: RNA Virus Infections - ID: D000008171 - Term: Lung Diseases - ID: D000012140 - Term: Respiratory Tract Diseases ### 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

## Protocol Section ### Identification Module **NCT ID:** NCT02785679 **Brief Title:** The Influence of Early and Continuous Exposure of Infants to Cow's Milk Formula on the Prevention of Milk Allergy **Official Title:** The Influence of Early and Continuous Exposure of Infants to Cow's Milk Formula on the Prevention of Milk Allergy #### Organization Study ID Info **ID:** 011-16-MMC #### Organization **Class:** OTHER **Full Name:** Meir Medical Center ### Status Module #### Completion Date **Date:** 2021-12-31 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** RECRUITING #### Last Update Post Date **Date:** 2021-04-14 **Type:** ACTUAL **Last Update Submit Date:** 2021-04-13 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2021-08-31 **Type:** ESTIMATED #### Start Date **Date:** 2018-03-20 **Type:** ACTUAL **Status Verified Date:** 2021-04 #### Study First Post Date **Date:** 2016-05-30 **Type:** ESTIMATED **Study First Submit Date:** 2016-05-25 **Study First Submit QC Date:** 2016-05-27 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** Schneider Children's Hospital #### Lead Sponsor **Class:** OTHER **Name:** Meir Medical Center #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Cow's milk protein (CMP) allergy is one of the most common food allergies and potentially a fatal one. Early feeding with CMP has been considered in the past as a risk factor for development of CMP allergy in high risk infants. Although other studies argue with this assumption and suggest early exposure to CMP might be protective against atopic dermatitis and CMP allergy. A cohort study that first introduction of CMP after 15-30 days of age, raised the risk for CMP allergy.The aim of this study is to investigate if early and continuous exposure to CMF will decrease CMP allergy rate. **Detailed Description:** Background: Cow's milk protein (CMP) allergy is one of the most common food allergies and potentially a fatal one. The incidence of milk allergy is 1.5-3% in the first year of life, but only 60% of the reactions are IgE mediated. CMP allergy tends to resolve in approximately 45-50% of the infants at 1 year of age, in 60-75% at the age of 2, and 85-90% at 3 years. The range for IgE mediated CMP allergy is 29-76%. A recent study suggested that the natural history of CMP allergy might have changed over time, with slower rates of resolution and a higher proportion of children with disease persisting into adolescence and adulthood. In the past it has been described that there is more incidence of CMP allergy in children from families with positive history of allergy. Early feeding with CMP has been considered in the past as a risk factor for development of CMP allergy in high risk infants. Although other studies argue with this assumption and suggest early exposure to CMP might be protective against atopic dermatitis and CMP allergy. A cohort study that first introduction of CMP after 15-30 days of age, raised the risk for CMP allergy. A recent study on peanut allergy found that continuous early exposure to peanut dramatically decreased the incidence of peanut allergy. The research in the field of food allergy and especially in CMP allergy is very alert those days. But as far as the investigators knowledge, there are no prospective studies from the first days of life that examined the influence of early and continuous exposure to cow's milk formula (CMF) on CMP allergy. The existing data related to CMP allergy is controversial and inconclusive. Thus, no one can rely on it to establish clear recommendations for parents when is the best time to combine CMF in the infants diet. Working hypothesis and aims: The aim of the study is to investigate if early and continuous exposure to CMF will decrease CMP allergy rate. The investigators assumption is that the rate of CMP allergy in the intervention groups and in infants who are only feed by CMF, will be lower than in the group of infants who are exclusively breast feed. Methods: Recruitment of 2,500 infants from first day of life and divide the participants into 4 groups: 1. Exclusive breast feeding. 2. Exclusive CMF feeding. 3. Breast feeding with 20 cc of CMF per day. 4. Breast feeding with one meal per day of CMF. The mother will complete a survey questionnaire before the labor. Infants will be followed for 1 year. During this follow-up period -the participants will be examined by an allergologist at the age of 2 month and 1 year. In between, the infants will be followed by a phone questionnaire once in a month. Specific CM IgE analysis from umbilical cord blood and skin test at 2 month of age will be performed. Inclusion criteria - Term and near term newborns (gestational age of at least 36 weeks), normal birth weight, normal perinatal follow-up and without congenital defects. Expected results: The rate of CMP allergy in the intervention groups and in the group on exclusively CMF feeding will be lower than in the group on exclusive breast feeding. Importance: If the investigators will be able to prove the study hypothesis (and even if not), it will have a significant influence on the diet recommendations for infants. Probable implications to Medicine: If the investigators will get the expected results, the recommendations that exist today for infant's feeding can be changed. ### Conditions Module **Conditions:** - Cow Milk Allergy - Newborns **Keywords:** - Allergy - Cow's milk - breast feeding - Cow's milk formula - prevention ### Design Module #### Design Info **Allocation:** NON_RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 2500 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Exclusive breast feeding **Label:** Exclusive breast feeding **Type:** NO_INTERVENTION #### Arm Group 2 **Description:** Exclusive CMF feeding **Label:** Exclusive CMF feeding **Type:** NO_INTERVENTION #### Arm Group 3 **Description:** Breast feeding with addition (as intervention) of 20 cc of cow's milk formula (CMF) per day **Intervention Names:** - Dietary Supplement: cow's milk formula **Label:** Breast feeding with small amount of CMF **Type:** ACTIVE_COMPARATOR #### Arm Group 4 **Description:** Breast feeding with addition (as intervention) of one meal per day of cow's milk formula (CMF) **Intervention Names:** - Dietary Supplement: cow's milk formula **Label:** Breast feeding with one meal of CMF **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Breast feeding with one meal of CMF - Breast feeding with small amount of CMF **Description:** addition of cow's milk formula in two different dosage - one only 20ml per day and one group a full meal per day **Name:** cow's milk formula **Type:** DIETARY_SUPPLEMENT ### Outcomes Module #### Primary Outcomes **Description:** Measure the rate of cow's milk allergy infants in each group and compare the rate of allergy between the groups. **Measure:** The incidence of cow's milk allergy in the intervention groups **Time Frame:** 1 year ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Term and near term newborns (gestational age of at least 36 weeks) * normal birth weight * normal perinatal follow-up (physiological neonatal jaundice is not an exclusion criteria) * without congenital defects Exclusion Criteria: * Preterm newborns * Congenital defects * Newborn suffering from acute event **Healthy Volunteers:** True **Maximum Age:** 2 Days **Minimum Age:** 2 Hours **Sex:** ALL **Standard Ages:** - CHILD ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Idit Lachover- Roth, MD **Phone:** 972-9-7472320 **Role:** CONTACT #### Locations **Location 1:** **City:** Kfar Saba **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Idit Lachover - Roth, MD - **Phone:** 972-54-3152585 - **Role:** CONTACT **Country:** Israel **Facility:** Meir medical center **Status:** RECRUITING #### Overall Officials **Official 1:** **Affiliation:** allergy and immunology unit, MeirMc **Name:** Ronit Confino- Cohen, MD **Role:** STUDY_DIRECTOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000007154 - Term: Immune System Diseases - ID: D000005512 - Term: Food Hypersensitivity - ID: D000006969 - Term: Hypersensitivity, Immediate ### Condition Browse Module - Browse Branches - Abbrev: BC20 - Name: Immune System Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M10018 - Name: Hypersensitivity - Relevance: HIGH - As Found: Allergy - ID: M18719 - Name: Milk Hypersensitivity - Relevance: HIGH - As Found: Milk Allergy - ID: M10200 - Name: Immune System Diseases - Relevance: LOW - As Found: Unknown - ID: M8636 - Name: Food Hypersensitivity - Relevance: LOW - As Found: Unknown - ID: M10020 - Name: Hypersensitivity, Immediate - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000006967 - Term: Hypersensitivity - ID: D000016269 - Term: Milk Hypersensitivity ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05472779 **Acronym:** TAPER **Brief Title:** Periurethral vs Intravaginal Estrogen for Prevention of Recurrent Urinary Tract Infections **Official Title:** Periurethral vs Intravaginal Estrogen for Prevention of Recurrent Urinary Tract Infections: TAPER (Techniques of APplying Vaginal Estrogen for Prevention of Recurrent Urinary Tract Infections) Trial #### Organization Study ID Info **ID:** STUDY22010147 #### Organization **Class:** OTHER **Full Name:** University of Pittsburgh ### Status Module #### Completion Date **Date:** 2025-01-01 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-01-09 **Type:** ACTUAL **Last Update Submit Date:** 2024-01-05 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2024-07-31 **Type:** ESTIMATED #### Start Date **Date:** 2023-01-03 **Type:** ACTUAL **Status Verified Date:** 2024-01 #### Study First Post Date **Date:** 2022-07-25 **Type:** ACTUAL **Study First Submit Date:** 2022-07-21 **Study First Submit QC Date:** 2022-07-21 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Stephanie Wang Zuo #### Responsible Party **Investigator Affiliation:** University of Pittsburgh **Investigator Full Name:** Stephanie Wang Zuo **Investigator Title:** UPMC Fellow **Type:** SPONSOR_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** True **Is US Export:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Due to rising antibiotic resistance, there has been a focus on non-antibiotic prophylactic measures for postmenopausal patients with recurrent urinary tract infections (rUTI), one of which is the safe and efficacious option of vaginal estrogen therapy. Standard application of vaginal estrogen cream entails intravaginal application of the cream twice a week, but some providers counsel patients with rUTI to apply a small, pea-sized amount to the periurethral area. This ideally reduces the amount of vaginal estrogen used while attaining a similar effect. However, to date, there is no data to prove that the periurethral technique of application is similar or non-inferior to intravaginal application in preventing UTI. ### Conditions Module **Conditions:** - Recurrent Urinary Tract Infection ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** SINGLE **Who Masked:** - INVESTIGATOR **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 108 **Type:** ESTIMATED **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Intravaginal application of 1 gram estradiol cream at bedtime twice a week for 6 months **Intervention Names:** - Drug: Intravaginal application of estradiol cream **Label:** Intravaginal Estrogen Application **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** Periurethral application of 0.5 gram estradiol cream at bedtime twice a week for 6 months **Intervention Names:** - Drug: Periurethral application of estradiol cream **Label:** Periurethral Estrogen Application **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Periurethral Estrogen Application **Description:** The experimental group will apply estradiol cream in a different location (periurethral) and at a smaller dose (0.5 gram) compared to the control group. **Name:** Periurethral application of estradiol cream **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Intravaginal Estrogen Application **Description:** The control group will apply 1 gram estradiol cream intravaginally using an applicator. **Name:** Intravaginal application of estradiol cream **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Measure:** Percentage of participants who are UTI-free at 6 months **Time Frame:** 6 months #### Secondary Outcomes **Description:** Questionnaire assessment of urinary symptoms and symptom distress (Urogenital Distress Inventory, Short Form), total score range 0-100 with higher numbers representing worse urinary symptoms **Measure:** Change from baseline in urinary symptoms at 6 months **Time Frame:** Baseline, 6 months **Description:** Questionnaire assessment of vaginal symptoms and bother using 5-point Likert scale, developed by research team **Measure:** Change from baseline in vaginal symptoms at 6 months **Time Frame:** Baseline, 6 months **Description:** Questionnaire assessment of sexual function (Female Sexual Function Index-6) with scores ranging from 2 to 30, with 19 and below denoting sexual dysfunction. **Measure:** Change from baseline in sexual function at 6 months **Time Frame:** Baseline, 6 months **Description:** Estradiol cream tubes will be weighed at each research visit in grams **Measure:** Amount of estrogen cream used **Time Frame:** 6 months **Description:** Questionnaire assessment of patient experience using 5-point Likert and open-ended questions, developed by the research team **Measure:** Participant experience with use of estrogen cream **Time Frame:** 6 months **Description:** Assessment using pH strips during pelvic examination **Measure:** Change from baseline in vaginal pH at 6 months **Time Frame:** Baseline, 6 months **Description:** Assessment of vaginal cell types using a superficial swab, collected from proximal vagina **Measure:** Change from baseline in vaginal maturation index at 6 months **Time Frame:** Baseline, 6 months **Description:** Clean catch urine and vaginal swab sample collection with quantification of Lactobacillus **Measure:** Change from baseline in Vaginal and urinary Lactobacillus levels at 6 months **Time Frame:** Baseline, 6 months **Description:** Clean catch urine and vaginal swab sample collection for quantification of E. coli **Measure:** Change from baseline in Vaginal and urinary E. coli levels at 6 months **Time Frame:** Baseline, 6 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Postmenopausal (definition: No menses for 1 or more years or surgical menopause (bilateral oophorectomy). If there is a past history of hysterectomy, patient must be age 56 or older (95th percentile for age at menopause) or have laboratory evidence of menopause (ie. FSH \>30)) * Meets criteria for recurrent urinary tract infections (UTIs) with 2 or more UTI in 6 months or 3 or more UTI in 1 year * May include patients who used vaginal estrogen previously if they have stopped use for 3 or more months prior to inclusion into study. * Patients must be recommended vaginal estrogen as part of normal clinical care for prevention of recurrent UTI Exclusion Criteria: * Current use of vaginal or oral estrogen products * Inability or refusal to use vaginal estrogen * Daily antibiotic use * Significant vaginal stenosis (eg. due to lichen sclerosis, radiation or obliterative prolapse surgery) that would prohibit use of a vaginal applicator (ie. genital hiatus \<1cm) * Inability to use vaginal applicator and without caregiver who can administer (eg. provider-managed pessary use, significant arthritis) * Frequent (1x weekly or more frequent) use of bladder instillations containing an antibiotic * Known hydronephrosis as a result of incomplete bladder emptying * Use of intermittent or indwelling urinary catheterization * Known bladder stones, mesh erosion into bladder, or foreign object in bladder * Unable to consent for self * Active treatment for an estrogen-dependent malignancy **Minimum Age:** 18 Years **Sex:** FEMALE **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Stephanie W Zuo, MD **Phone:** 412-270-4818 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Lindsey Baranski **Phone:** 412-641-7894 **Role:** CONTACT #### Locations **Location 1:** **City:** Cranberry Township **Contacts:** ***Contact 1:*** - **Name:** Lindsey Baranski - **Role:** CONTACT **Country:** United States **Facility:** UPMC Lemieux Sports Complex **State:** Pennsylvania **Status:** RECRUITING **Zip:** 16066 **Location 2:** **City:** Erie **Contacts:** ***Contact 1:*** - **Name:** Linda Paterniti - **Role:** CONTACT **Country:** United States **Facility:** UPMC Hamot **State:** Pennsylvania **Status:** RECRUITING **Zip:** 16550 **Location 3:** **City:** Pittsburgh **Contacts:** ***Contact 1:*** - **Name:** Lindsey Baranski - **Role:** CONTACT **Country:** United States **Facility:** University of Pittsburgh Medical Center-Magee Womens Hospital **State:** Pennsylvania **Status:** RECRUITING **Zip:** 15213 **Location 4:** **City:** Pittsburgh **Contacts:** ***Contact 1:*** - **Name:** Lindsey Baranski - **Role:** CONTACT **Country:** United States **Facility:** UPMC Passavant-McCandless **State:** Pennsylvania **Status:** RECRUITING **Zip:** 15237 #### Overall Officials **Official 1:** **Affiliation:** University of Pittsburgh Medical Center **Name:** Stephanie W Zuo, MD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000020969 - Term: Disease Attributes - ID: D000010335 - Term: Pathologic Processes - 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 ### 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 ### 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: M17302 - Name: Urinary Tract Infections - Relevance: HIGH - As Found: Urinary Tract Infections - ID: M14850 - Name: Recurrence - Relevance: HIGH - As Found: Recurrent - ID: M22700 - Name: Disease Attributes - 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 ### Condition Browse Module - Meshes - ID: D000007239 - Term: Infections - ID: D000003141 - Term: Communicable Diseases - ID: D000014552 - Term: Urinary Tract Infections - ID: D000012008 - Term: Recurrence ### Intervention Browse Module - Ancestors - ID: D000004967 - Term: Estrogens - ID: D000006728 - Term: Hormones - ID: D000006730 - Term: Hormones, Hormone Substitutes, and Hormone Antagonists - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000080066 - Term: Contraceptive Agents, Hormonal - ID: D000003270 - Term: Contraceptive Agents - ID: D000012102 - Term: Reproductive Control Agents - ID: D000003271 - Term: Contraceptive Agents, Female ### Intervention Browse Module - Browse Branches - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Repr - Name: Reproductive Control Agents ### Intervention Browse Module - Browse Leaves - ID: M8116 - Name: Estrogens - Relevance: LOW - As Found: Unknown - ID: M266279 - Name: Estradiol 17 beta-cypionate - Relevance: HIGH - As Found: Cell lymphoma - ID: M266280 - Name: Estradiol 3-benzoate - Relevance: HIGH - As Found: Cell lymphoma - ID: M8108 - Name: Estradiol - Relevance: HIGH - As Found: Cell lymphoma - ID: M234941 - Name: Polyestradiol phosphate - Relevance: HIGH - As Found: Cell lymphoma - ID: M9789 - Name: Hormones - Relevance: LOW - As Found: Unknown - ID: M9788 - Name: Hormone Antagonists - 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: M6495 - Name: Contraceptive Agents, Female - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: C000007630 - Term: Estradiol 17 beta-cypionate - ID: C000074283 - Term: Estradiol 3-benzoate - ID: D000004958 - Term: Estradiol - ID: C000008958 - Term: Polyestradiol phosphate ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04604379 **Acronym:** DYSCOVER **Brief Title:** A Study to Review Treatment Outcomes From Treatment With Dysport® Injections in Adults for Upper and/or Lower Limb Focal Spasticity **Official Title:** A Multicentre, Non-interventional Retrospective Study of Treatment Outcomes From Treatment With Dysport ® (Clostridium Botulinum Type A Toxin-haemagglutinin Complex, Abobotulinumtoxin-A) Injections in Adults for Upper and/or Lower Limb Focal Spasticity in Real-world Clinical Practice in the United Kingdom #### Organization Study ID Info **ID:** A-GB-52120-277 #### Organization **Class:** INDUSTRY **Full Name:** Ipsen ### Status Module #### Completion Date **Date:** 2021-05-28 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2021-06-21 **Type:** ACTUAL **Last Update Submit Date:** 2021-06-18 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2021-05-28 **Type:** ACTUAL #### Start Date **Date:** 2021-02-04 **Type:** ACTUAL **Status Verified Date:** 2021-06 #### Study First Post Date **Date:** 2020-10-27 **Type:** ACTUAL **Study First Submit Date:** 2020-10-21 **Study First Submit QC Date:** 2020-10-26 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Ipsen #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** The aim of this retrospective study is to describe the real-world outcomes with the treatment of adult patients with Dysport® injections for focal upper limb spasticity (ULS) and/or focal lower limb spasticity (LLS) in NHS hospital settings in the United Kingdom (UK). ### Conditions Module **Conditions:** - Upper and/or Lower Limb Focal Spasticity **Keywords:** - Spasticity ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** RETROSPECTIVE #### Enrollment Info **Count:** 123 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Outcomes Module #### Primary Outcomes **Measure:** Average total dose of AboBoNT-A for focal upper limb and/or lower limb spasticity per treatment session **Time Frame:** From baseline (when each patient received their first treatment) to 52 weeks (±6 weeks) post baseline **Measure:** Average interval between AboBoNT-A injections throughout the observation period for focal ULS and/or LLS **Time Frame:** From baseline to 52 weeks (±6 weeks) post baseline #### Secondary Outcomes **Measure:** Average age at diagnosis of neurological condition **Time Frame:** Baseline **Measure:** Average age at first AboBoNT-A injection **Time Frame:** Baseline **Measure:** Average age at diagnosis of spasticity **Time Frame:** Baseline **Measure:** Sex distribution (Male, Female) **Time Frame:** Baseline **Measure:** Presence of underlying neurological condition: stroke, injury, chronic disease (multiple sclerosis, other) **Time Frame:** Baseline **Description:** Data collected at index date up to 6 weeks prior to index date (when each patient received their first treatment) **Measure:** Presence of location of spasticity (specify: right lower limb, left lower limb, right upper limb, left upper limb, unilateral, bilateral spasticity for lower and upper limb) **Time Frame:** Baseline **Measure:** Presence of previous spasticity-related treatments ongoing at index event, if available: antispasticity medications, pain medications and opioids, neurolytic agent, surgery, physiotherapy and occupational therapy **Time Frame:** Baseline **Measure:** Presence of comorbidities: bowel conditions (irritable bowel syndrome, irritable bowel disease), urinary tract infections, chest infections, anxiety or depression, alcohol dependence/substance abuse. **Time Frame:** Baseline ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Adult patients diagnosed with focal ULS and/or LLS for whom aboBoNT-A (Dysport®) was prescribed in line with the SmPC (according to clinician judgement). * Patients initiated on aboBoNT-A for focal ULS after the 31st January 2016 and/or for focal LLS after the 06th December 2016. * Patients receiving ≥1 injection(s) (i.e. ≥1 treatment cycle) of aboBoNT-A during the observation period, in line with Dysport® Summary of Product Characteristics (SmPC). * Patients aged ≥18 years old at the time of the first aboBoNT-A injection for focal ULS and/or LLS. * Patient is naïve to treatment with any type of BoNT-A during the 6 months prior to initiation of aboBoNT-A. * Patients treated at the participating centre for the duration of the observation period, with data recorded in the medical records available for review. Exclusion Criteria: * Patients with an interval of \<12 weeks between aboBoNT-A treatments * Patients are participating (or who have participated) in an interventional clinical trial of an investigational medicinal product indicated for spasticity which may influence and confound the real-world data collected for this study. * Patients treated with aboBoNT-A off-license, this may include off-license indications, muscles indicated for injection or dosing **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** 3-5 Secondary care centres in the UK ### Contacts Locations Module #### Locations **Location 1:** **City:** London **Country:** United Kingdom **Facility:** Kings College Hospital **Location 2:** **City:** Norwich **Country:** United Kingdom **Facility:** Colman Hospital **Location 3:** **City:** York **Country:** United Kingdom **Facility:** York Hospital #### Overall Officials **Official 1:** **Affiliation:** Ipsen **Name:** Ipsen Medical Director **Role:** STUDY_DIRECTOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009135 - Term: Muscular Diseases - ID: D000009140 - Term: Musculoskeletal Diseases - ID: D000009122 - Term: Muscle Hypertonia - ID: D000020879 - Term: Neuromuscular Manifestations - ID: D000009461 - Term: Neurologic Manifestations - ID: D000009422 - Term: Nervous System Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC05 - Name: Musculoskeletal Diseases - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M12085 - Name: Muscle Spasticity - Relevance: HIGH - As Found: Spasticity - ID: M12092 - Name: Muscular Diseases - Relevance: LOW - As Found: Unknown - ID: M12097 - Name: Musculoskeletal Diseases - Relevance: LOW - As Found: Unknown - ID: M12079 - Name: Muscle Hypertonia - Relevance: LOW - As Found: Unknown - ID: M22619 - Name: Neuromuscular Manifestations - Relevance: LOW - As Found: Unknown - ID: M12404 - Name: Neurologic Manifestations - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000009128 - Term: Muscle Spasticity ### Intervention Browse Module - Browse Branches - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Coag - Name: Coagulants ### Intervention Browse Module - Browse Leaves - ID: M21257 - Name: Botulinum Toxins, Type A - Relevance: LOW - As Found: Unknown - ID: M250193 - Name: abobotulinumtoxinA - Relevance: LOW - As Found: Unknown - ID: M9476 - Name: Hemagglutinins - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04250779 **Acronym:** MOMMIASTHMA1 **Brief Title:** Evaluating Efficacy of Smart Device in Assisting With Inhaler Technique and Adherence **Official Title:** Evaluating Efficacy of Smart Device in Assisting With Inhaler Technique and Adherence #### Organization Study ID Info **ID:** MOMMIASTHMA1 #### Organization **Class:** OTHER **Full Name:** Landon Pediatric Foundation ### Status Module #### Completion Date **Date:** 2021-12-01 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** RECRUITING #### Last Update Post Date **Date:** 2020-09-16 **Type:** ACTUAL **Last Update Submit Date:** 2020-09-13 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2021-07-01 **Type:** ESTIMATED #### Start Date **Date:** 2019-07-01 **Type:** ACTUAL **Status Verified Date:** 2020-01 #### Study First Post Date **Date:** 2020-01-31 **Type:** ACTUAL **Study First Submit Date:** 2020-01-29 **Study First Submit QC Date:** 2020-01-29 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** Cognita Labs LLC #### Lead Sponsor **Class:** OTHER **Name:** Landon Pediatric Foundation #### 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:** Asthma affects over 10 million children in the U.S., and poses a significant health and cost burden. Metered dose inhaler (MDI) is the most common method of treatment. Studies show that up to 80% of patients demonstrate incorrect use of MDIs, which results in suboptimal medication delivery to the lungs. Asthma control can be followed by symptoms, rescue medication usage and measures of airflow obstruction. Current options to monitor control include an asthma diary (relies on consistent use by the patient), pharmacy records of medication dispensing (dispensing does not equal usage), and peak expiratory flow (PEF) meters (significant variability in technique leading to inconsistent results). CapMedic is a smart inhaler and home spirometer device which aims to assist with correct MDI usage and to monitor asthma control. CapMedic fits on top of the MDI inhaler and provides live audio-visual-haptic cues to guide the patient for correctly using their inhaler. CapMedic includes a built-in forced expiratory flow in 1 second (FEV1, a measure of airflow) and PEF meter. It will utilize the same audio-visual-haptic hardware to implement live cues that encourage patient's effort in performing accurate at-home FEV1/PEF test. Cap will also be able to log medication usage and Medic application will allow patients to keep an asthma symptom diary. **Detailed Description:** CapMedic is a smart inhaler and home spirometer device which aims to assist with correct MDI usage and to monitor asthma control. CapMedic fits on top of the MDI inhaler and provides live audio-visual-haptic cues to guide the patient for correctly using their inhaler. CapMedic includes a built-in forced expiratory flow in 1 second (FEV1, a measure of airflow) and PEF meter. It will utilize the same audio-visual-haptic hardware to implement live cues that encourage patient's effort in performing accurate at-home FEV1/PEF test. Cap will also be able to log medication usage and Medic application will allow patients to keep an asthma symptom diary. ### Conditions Module **Conditions:** - Asthma - Adherence, Medication - Childhood Asthma ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** Research will initially involve collection of data describing the participants' current use of their medication following standard education. Subsequent phases will add audio / haptic coaching to the process of administering medication by MDI, and follow the same participants to determine whether or not there is improvement in technique and adherence to therapy. The device will be used with a placebo inhaler (given AFTER the participant's regular medication is taken by standard techniques), to determine how participants use the device, and to identify the most effective coaching interventions for this age group. This is to ensure that the device does not interfere with delivery of routine asthma controller medications. The data will be used to develop a subsequent, longer term study in which we will evaluate the effect of the coaching device on asthma control, when it is used with the subject's controller medication. ##### Masking Info **Masking:** SINGLE **Who Masked:** - PARTICIPANT **Primary Purpose:** SUPPORTIVE_CARE #### Enrollment Info **Count:** 50 **Type:** ESTIMATED **Phases:** - EARLY_PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** In this arm, patients are provided with standard-of-care instructions on using MDIs correctly and regularly at home. The MDI usage is recorded using CapMedic device with active guidance turned off. **Intervention Names:** - Behavioral: Video-based guidance **Label:** Control Group **Type:** PLACEBO_COMPARATOR #### Arm Group 2 **Description:** In this arm, patients are provided with active guidance from CapMedic device on using MDIs correctly and regularly at home. The MDI usage is recorded using CapMedic device with active guidance turned on. **Intervention Names:** - Device: CapMedic smart inhaler device **Label:** Treatment Group **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Treatment Group **Description:** The CapMedic device provides active coaching to promote correct and regular use of MDI. **Name:** CapMedic smart inhaler device **Type:** DEVICE #### Intervention 2 **Arm Group Labels:** - Control Group **Description:** Patients are shown a video of how to use inhalers correctly and any questions are answered by the clinician. They are also encouraged to use inhalers regularly and correctly at home. **Name:** Video-based guidance **Type:** BEHAVIORAL ### Outcomes Module #### Primary Outcomes **Description:** Correctness of Inhaler Use measured using CapMedic device during recruitment. Competence is measured as a score out of 4 for 4 steps of MDI use: 1. Shaking, 2. Orientation, 3. Coordination 4. Duration of inhalation **Measure:** MDI use Competence in Clinic **Time Frame:** 1 day **Description:** Correctness of Inhaler Use measured using CapMedic device at home. Competence is measured as a score out of 4 for 4 steps of MDI use: 1. Shaking, 2. Orientation, 3. Coordination 4. Duration of inhalation **Measure:** MDI use Competence at home **Time Frame:** 8 weeks #### Secondary Outcomes **Description:** PEF measured using CapMedic device during recruitment. PEF is measured in L/min. **Measure:** PEF Lung Function in Clinic **Time Frame:** 1 day **Description:** FEV1 measured using CapMedic device during recruitment. FEV1 is measured in L. **Measure:** FEV1 Lung Function in Clinic **Time Frame:** 1 day **Description:** PEF measured using CapMedic device at home. PEF is measured in L/min. **Measure:** PEF Lung Function at home **Time Frame:** 8 weeks **Description:** FEV1 measured using CapMedic device at home. FEV1 is measured in L. **Measure:** FEV1 Lung Function at home **Time Frame:** 8 weeks **Description:** Regularity of MDI use measured by CapMedic device at home, measured as a % of puffs taken per week compared to prescribed dosage. **Measure:** MDI use Adherence **Time Frame:** 8 weeks ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Diagnosis of Asthma * Regular user of MDI * Asthma Control Test (ACT) scores between 15 and 25 * FEV1 between 60-80% of predicted (persistent mild-moderate) * Disease severity in the range mild-moderate * Access to a Smartphone and internet during the entire duration of the study. * Cognitively able to utilize the device and express interest in participating. Exclusion Criteria: * Patients without asthma * With developmental disabilities * Do not speak English * Do not own a Smartphone **Minimum Age:** 8 Years **Sex:** ALL **Standard Ages:** - CHILD - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Chris Landon, M.D. **Phone:** 8053401366 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Emilie Paronyan **Phone:** 8184393664 **Role:** CONTACT #### Locations **Location 1:** **City:** Ventura **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Chris Landon, MD - **Phone:** 805-641-4490 - **Role:** CONTACT ***Contact 2:*** - **Name:** Chris Landon, MD - **Role:** PRINCIPAL_INVESTIGATOR **Country:** United States **Facility:** Pediatric Diagnostic Center **State:** California **Status:** RECRUITING **Zip:** 93003 ### References Module #### References **Citation:** Chan A, De Simoni A, Wileman V, Holliday L, Newby CJ, Chisari C, Ali S, Zhu N, Padakanti P, Pinprachanan V, Ting V, Griffiths CJ. Digital interventions to improve adherence to maintenance medication in asthma. Cochrane Database Syst Rev. 2022 Jun 13;6(6):CD013030. doi: 10.1002/14651858.CD013030.pub2. **PMID:** 35691614 ## 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 ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04140279 **Brief Title:** A Study to Evaluate the Effect of Latanoprostene Bunod Ophthalmic Solution 0.024% on Episcleral Venous Pressure and Outflow Facility in Participants With Ocular Hypertension **Official Title:** Effect of Latanoprostene Bunod Ophthalmic Solution 0.024% on Episcleral Venous Pressure and Outflow Facility in Ocular Hypertensive Subjects #### Organization Study ID Info **ID:** 899 #### Organization **Class:** INDUSTRY **Full Name:** Bausch & Lomb Incorporated ### Status Module #### Completion Date **Date:** 2023-08 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-03-04 **Type:** ACTUAL **Last Update Submit Date:** 2024-02-29 **Overall Status:** WITHDRAWN #### Primary Completion Date **Date:** 2023-08 **Type:** ESTIMATED #### Start Date **Date:** 2022-05-13 **Type:** ESTIMATED **Status Verified Date:** 2024-02 #### Study First Post Date **Date:** 2019-10-25 **Type:** ACTUAL **Study First Submit Date:** 2019-10-24 **Study First Submit QC Date:** 2019-10-24 **Why Stopped:** It never started ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Bausch & Lomb Incorporated #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** True ### Description Module **Brief Summary:** The primary objective of this study is to determine the effect of latanoprostene bunod (LBN) ophthalmic solution 0.024% (a single dose and 7 days of once daily \[QD\] dosing) on 2 aspects of aqueous humor (AqH) dynamics (episcleral venous pressure \[EVP\] and outflow facility) in participants with ocular hypertension (OHT). **Detailed Description:** All participants will receive both the investigational (LBN ophthalmic solution 0.024%) and placebo treatments, with 1 eye receiving LBN 0.024% and the contralateral eye receiving placebo. Each participant will be randomized as to which eye (right or left) will receive LBN 0.024% versus placebo. All participants will undergo a minimum 14-day to maximum 42-day washout period prior to the start of study drug administration. ### Conditions Module **Conditions:** - Ocular Hypertension **Keywords:** - Eye Diseases ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** All participants will receive both the investigational and placebo treatments, with 1 eye receiving LBN 0.024% and the contralateral eye receiving placebo. ##### Masking Info **Masking:** SINGLE **Who Masked:** - INVESTIGATOR **Primary Purpose:** TREATMENT #### Enrollment Info **Type:** ACTUAL **Phases:** - PHASE4 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Participants will receive LBN ophthalmic solution 0.024% in the applicable eye identified during randomization. The first dose will be instilled in the morning (AM) at approximately 11 AM on Day 1 and the remaining 6 doses will be instilled once per day in the evening at approximately 8 PM. **Intervention Names:** - Drug: Latanoprostene Bunod **Label:** Latanoprostene Bunod **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Participants will receive Renu MultiPlus Lubricating and Rewetting Drops (placebo) in the applicable eye identified during randomization. The first dose will be instilled in the morning (AM) at approximately 11 AM on Day 1 and the remaining 6 doses will be instilled once per day in the evening at approximately 8 PM. **Intervention Names:** - Drug: Placebo **Label:** Placebo **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Latanoprostene Bunod **Description:** Ophthalmic solution **Name:** Latanoprostene Bunod **Other Names:** - Vyzulta® **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Placebo **Description:** Ophthalmic solution, no active ingredient. **Name:** Placebo **Other Names:** - Bausch + Lomb ReNu MultiPlus® Lubricating and Rewetting Drops **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** EVP will be measured non-invasively by using a custom-designed slit-lamp mounted venomanometer. This device utilizes the pressure chamber technique, in which a clear flexible balloon is placed against the surface of the eye, and the pressure is increased until an episcleral vein is noted to blanche. Each EVP measurement will be determined from the mean of up to 3 readings. EVP (millimeters of mercury \[mmHg\]) will be assessed at 1, 3, and 5 hours post instillation for changes from baseline following a single dose of drug on the first day of treatment and at approximately 12, 16 and 20 hours post-instillation after 7 days of QD in the evening treatment. **Measure:** Change From Baseline in Episcleral Venous Pressure (EVP) at Intervals on Days 1 and 8 **Time Frame:** Baseline, 1, 3, and 5 hours post-instillation at Day 1 and 12, 16, and 20 hours post-instillation at Day 8 **Description:** EVP will be measured non-invasively by using a custom-designed slit-lamp mounted venomanometer. This device utilizes the pressure chamber technique, in which a clear flexible balloon is placed against the surface of the eye, and the pressure is increased until an episcleral vein is noted to blanche. Each EVP measurement will be determined from the mean of up to 3 readings. Diurnal EVP will be computed for Days 1 and 8 separately as the mean of the posttreatment values observed on the day for each eye. Change from the mean of 2 sets of baseline measurements will be computed for each post-treatment time (including diurnal means) as the post-treatment value minus the baseline value for each eye. The difference between treatments (LBN minus placebo) in change from baseline will be computed for each participant. **Measure:** Change From Baseline in Diurnal (Daytime) EVP at Days 1 and 8 **Time Frame:** Baseline, Day 1, Day 8 **Description:** Outflow facility will be measured non-invasively by using constant weight tonography. Four-minute tracings with a 5.5-gram or 7.5-gram weight or two-minute tracings with a 10-gram weight will be used, and tonographic outflow facility will be calculated from the pressure decay curves and standard tables. Outflow facility (mmHg) will be assessed at 1, 3, and 5 hours post instillation for changes from baseline following a single dose of drug on the first day of treatment and at approximately 12, 16 and 20 hours post-instillation after 7 days of QD in the evening treatment. **Measure:** Change From Baseline in Trabecular Outflow Facility at Intervals on Days 1 and 8 **Time Frame:** Baseline, 1, 3, and 5 hours post-instillation at Day 1 and 12, 16, and 20 hours post-instillation at Day 8 **Description:** Outflow facility will be measured non-invasively by using constant weight tonography. Four-minute tracings with a 5.5-gram or 7.5-gram weight or 2-minute tracings with a 10-gram weight will be used, and tonographic outflow facility will be calculated from the pressure decay curves and standard tables. Diurnal trabecular outflow facility will be computed for Days 1 and 8 separately as the mean of the posttreatment values observed on the day for each eye. Change from the mean of 2 sets of baseline measurements will be computed for each post-treatment time (including diurnal means) as the post-treatment value minus the baseline value for each eye. The difference between treatments (LBN minus placebo) in change from baseline will be computed for each participant. **Measure:** Change From Baseline in Diurnal (Daytime) Trabecular Outflow Facility at Days 1 and 8 **Time Frame:** Baseline, Day 1, Day 8 ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: General Inclusion Criteria * Participants must be able to read, understand, and provide written informed consent on the Institutional Review Board (IRB) approved informed consent form (ICF) and are able and willing to comply with all treatment and follow-up/study procedures. * Females of childbearing potential must have a negative urine pregnancy test result at the screening examination and must agree to use an acceptable method of contraception throughout their participation in the study. Ocular Inclusion Criteria * Participants must have a diagnosis of OHT in both eyes (intraocular pressure \[IOP\] ≥22 mmHg prior to starting treatment with IOP-lowering medication) without evidence of glaucomatous optic neuropathy or visual field loss and must also have been receiving IOP-lowering medication for ≥3 months prior to Screening (Visit 1). * Participants must undergo a washout of any existing ocular hypotensive medications in order to determine eligibility. Washout period will vary with the class of medication used (2-6 weeks). * Participants must meet the following IOP requirements at Visit 3 (Eligibility Visit at End of Washout): 1. Intraocular pressure ≥22 mmHg and ≤32 mmHg in both eyes. 2. An increase in IOP of 20% over the Screening (Visit 1) IOP. 3. The difference in IOP between eyes ≤4 mmHg. * Participants must have a best corrected visual acuity (BCV A) in each eye of 20/50 (logarithm of the minimum angle of resolution \[logMAR\] +0.4) or better. Exclusion Criteria: General Exclusion Criteria * Participation in any drug or device clinical investigation within 30 days prior to Visit 1 (Screening) or anticipation of participating in any other drug or device clinical investigation within the duration of this study. * Participants with a history or presence of chronic generalized systemic disease that the Investigator feels might increase the risk to the participant or confound the results of the study. * Female participants who are pregnant or breastfeeding. Drug Therapies * Participants with an anticipated need to initiate or modify medication (systemic or topical) that is known to affect IOP (for example, steroids, α-adrenergic agonists, β-adrenergic antagonists, calcium channel blockers, angiotensin-converting enzyme \[ACE\] inhibitors, and angiotensin II receptor blockers). * Participants with known hypersensitivity or contraindications to latanoprostene bunod or any of the ingredients in the study drugs. Ocular Exclusion Criteria: Diseases * Participants who are unable to discontinue contact lens use during and for 15 minutes following instillation of study drug and for 24 hours before check-in and during each study visit. * Participants with a central corneal thickness less than 480 μm or greater than 600 micrometer (μm) in either eye. * Participants with any condition that prevents reliable applanation tonometry (for example, significant corneal surface abnormalities) in either eye. * Participants who are monocular. * Participants with ocular conditions, which, in the opinion of the Investigator, will impact the study measurements, such as: 1. Active optic disc hemorrhage in either eye. 2. Current or a history of central/branch retinal vein or artery occlusion in either eye. 3. Current or a history of macular edema in either eye. 4. Very narrow angles (3 quadrants with less than Grade 2 according to Shaffer's anterior chamber angle grading system) and participants with angle closure, congenital, and secondary glaucoma, and with history of angle closure in either eye. 5. Diagnosis of a clinically significant or progressive retinal disease (for example, diabetic retinopathy, exudative or severe non-exudative macular degeneration) in either eye. * Participants with any intraocular infection or inflammation in either eye within 3 months prior to Visit 1 (Screening). * Myopia greater than -4.00 diopter (D), or hyperopia greater than +2.000 Surgery * Participants with a history of ocular laser surgery in either eye within the 3 months (90 days) prior to Visit 1 (Screening). * Participants with a history of laser trabeculoplasty, cyclophotocoagulation or glaucoma surgical procedures at any time prior to Visit 1 (Screening). * Participants with a history of incisional ocular surgery other than routine uncomplicated cataract surgery or severe trauma in either eye within the 3 months (90 days) prior to Visit 1 (Screening). **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Rochester **Country:** United States **Facility:** Bausch Site 001 **State:** Minnesota **Zip:** 55905 #### Overall Officials **Official 1:** **Affiliation:** Bausch & Lomb Incorporated **Name:** Anya Loncaric **Role:** STUDY_DIRECTOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000014652 - Term: Vascular Diseases - ID: D000002318 - Term: Cardiovascular Diseases - ID: D000005128 - Term: Eye Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC11 - Name: Eye Diseases ### Condition Browse Module - Browse Leaves - ID: M10024 - Name: Hypertension - Relevance: HIGH - As Found: Hypertension - ID: M8271 - Name: Eye Diseases - Relevance: LOW - As Found: Unknown - ID: M12731 - Name: Ocular Hypertension - Relevance: HIGH - As Found: Ocular Hypertension - ID: M17400 - Name: Vascular Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000009798 - Term: Ocular Hypertension - ID: D000006973 - Term: Hypertension ### 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: M12814 - Name: Ophthalmic Solutions - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04752579 **Brief Title:** Effects of a Mat Pilates Exercise Program on Elderly Women With Chronic Nonspecific Low Back Pain **Official Title:** Effects of a Mat Pilates Exercise Program on Pain, Functional Ability and Balance in Elderly Women With Chronic Nonspecific Low Back Pain #### Organization Study ID Info **ID:** EC-48/2021 #### Organization **Class:** OTHER **Full Name:** Aristotle University Of Thessaloniki ### Status Module #### Completion Date **Date:** 2021-12-30 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2023-07-20 **Type:** ACTUAL **Last Update Submit Date:** 2023-07-18 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2021-12-30 **Type:** ACTUAL #### Start Date **Date:** 2021-01-01 **Type:** ACTUAL **Status Verified Date:** 2023-07 #### Study First Post Date **Date:** 2021-02-12 **Type:** ACTUAL **Study First Submit Date:** 2021-02-09 **Study First Submit QC Date:** 2021-02-09 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Aristotle University Of Thessaloniki #### Responsible Party **Investigator Affiliation:** Aristotle University Of Thessaloniki **Investigator Full Name:** LYTRAS DIMITRIOS **Investigator Title:** Dimitrios Lytras PT, PhD, Postdoctoral Research Fellow Affiliation: Aristotle University of Thessaloniki **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** The technique of Pilates exercises on a mat has proven to be effective and practically applicable to patients with chronic back pain. However, its application in women over 65 years has not been adequately studied. Objective: This assessor-blind randomized clinical trial aims to study the effect of a mat Pilates exercise program on pain and functional ability of elderly women with chronic nonspecific low back pain. Methods: 60 elderly women with chronic nonspecific low back pain (duration of symptoms more than 12 weeks) are expected to participate in this study. Participants will be divided into two groups of 30 people each; one being intervention and one control. The intervention group will follow a custom mat Pilates program (twice per week) for 10 weeks, while the control group will not follow any treatment. Pain, functionality, balance, the number of painkillers administered, and adherence to exercise will be assessed at the beginning and end of the study and will be re-examined six months later. **Detailed Description:** The technique of Pilates exercises on a mat has proven to be effective and practically applicable to patients with chronic back pain. However, its application in women over 65 years has not been adequately studied. Objective: This assessor-blind randomized clinical trial aims to study the effect of a mat Pilates exercise program on pain and functional ability of elderly women with chronic nonspecific low back pain. Methods: 60 non-active elderly women with chronic nonspecific low back pain (duration of symptoms more than 12 weeks) are expected to participate in this study. Participants will be divided into two groups of 30 people each; one being intervention and one control. The intervention group will follow a custom mat Pilates program (twice per week), while the control group will not follow any treatment. Primary outcomes will include pain with the visual analog scale for pain and functionality with the Roland-Morris Questionnaire (RMQ). Secondary outcomes will include the balance with the Berg balance scale and the Timed Up and Go test, the number of painkillers administered, and the adherence to the exercise that will be evaluated at the beginning and at the end of the study and re-evaluated six months after the end of the intervention. The treatment period will be 10 weeks. ### Conditions Module **Conditions:** - Low Back Pain **Keywords:** - Mat-pilates exercises - elderly - chronic low back pain - physical therapy - rehabilitation ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** Parallel Assignment ##### Masking Info **Masking:** SINGLE **Masking Description:** A masked assessor conducted the measurements. **Who Masked:** - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 63 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Participants allocated to this group will receive a 10-week Pilates exercise program with each session having a duration of 45'. **Intervention Names:** - Other: Pilates exercise program **Label:** Pilates exercise program **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Participants allocated to this group received general consulting instructions and a home-based general exercise sheet **Intervention Names:** - Other: Pilates exercise program **Label:** Control **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Control - Pilates exercise program **Description:** The program will be individually supervised and will be conducted twice a week at the physiotherapy center. • Slow execution of 7-10 repetitions of the following Pilates exercises: Pelvic Curl, Pilates Single Legs Lifts \& Leg Change, Twist Supine Pilates exercise, Chest Lifts Pilates Exercise, Chest Lift with Rotation Pilates exercise, 100's Prep Pilates Exercise, Single Leg Stretch Pilates Exercise, Front Support Pilates Exercise and Basic Back Extension Pilates Exercise. After the 6th week, while the person will be familiar with the basic exercises of the Pilates method the following exercises will be added: Leg Pull Front, Side Bend Pilates Exercise, Sphinx - Abdominal Lift Pilates Exercise, Shoulder Bridge Prep Pilates and Shoulder Bridge Pilates Exercise. Each session will be completed with breathing exercises and stretching exercises of the torso and lower limbs for 5 minutes. **Name:** Pilates exercise program **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** VAS is a card with an uncalibrated scale ranging from 0-100mm on the one side with each millimeter representing one pain level (0 representing no pain and 100 representing the worst pain in life). The patient subjectively estimated their pain level by marking a vertical line on the uncalibrated scale between 0 and 100. Then the exact value of pain intensity could be obtained with a single ruler. Hence, the higher the value, the more intense the pain. VAS is widely used as it is easy to implement and is characterized by good psychometric propert **Measure:** Changes in Low back pain intensity with the Visual Analogue Scale (VAS) **Time Frame:** pre-treatment, Week: 10, 6-month follow-up **Description:** Disability associated with low back pain in the last 24 hours will be assessed using the Greek version of the Roland Morris Disability Questionnaire (Boscainos et al., 2003). This questionnaire has showed good test -retest reliability with intraclass correlation (ICC) ranging from 0.42 to 0.91 (Macedo et al., 2010), while Boscainos (2003), reports that the internal consistency reliability for the Greek version reached a Cronbach's alpha coefficient of 0.885. This questionnaire consists of 24 items that are related to daily activities which patients often report difficulty performing due to low back pain. Every positive answer earns a point and the final score is calculated by adding all the points. Thus, the higher the score is, the greater the limitation (Stratford, 1996). **Measure:** Changes in Roland Morris Disability Questionnaire **Time Frame:** pre-treatment, Week: 10, 6-month follow-up **Description:** The TUG test is a performance-based measure of functional mobility that was initially developed to identify mobility and dynamic balance impairments in older adults (Cameron and Monroe, 2007; Swearingen and Brach, 2001; Podsiadlo and Richardson, 1991). The TUG test has demonstrated high interrater and intrarater reliability when used to examine elderly adults (Cameron and Monroe, 2007; Swearingen and Brach, 2001). The test requires the subject to rise from a chair, walk three meters at a comfortable pace to a mark placed on the floor, turn around, walk back to the starting point, and return to sitting on the chair. The test's score is the time it takes the subject to complete the test. **Measure:** Changes in Timed Up and Go (TUG) Test **Time Frame:** pre-treatment, Week: 10, 6-month follow-up **Description:** The Berg balance scale is a tool suggested by Berg (Berg et al., 1989; Berg et al., 1992) to evaluate balance in the elderly. The test involves performing 14 tests of gradually increasing difficulty where in each one, the subject is asked to maintain a given position for a specific time or conduct specific tasks. Each of the 14 tests on the list is graded according to the balancing ability of the examinee from 0 to 4 points (with 0 indicating low balance ability while 4 high). Accord to Berg et al. (1992), a score of 56 indicates functional balance whereas a score lower than 45 indicates notable balance deficits, which have been related to increased fall risk. **Measure:** Changes in Berg Balance Scale **Time Frame:** pre-treatment, Week: 10, 6-month follow-up #### Secondary Outcomes **Description:** Participants will be asked to write down in a special diary the number of pills administered (anti-inflammatory and/or painkillers) during the follow-up period. The log will be kept kept on a weekly basis and the assessor will collect the data by phone 2-3 times a month. **Measure:** Changes in the number of pills consumed via Pill Consumption Log **Time Frame:** pre-treatment, Month: 1,3,6, post-intervention **Description:** After the ten weeks the participants of both groups will be asked to perform the specific exercise programs twice per week for a period of three months recording the adherence or not to the exercise programs in a weekly diary while the assessor will collect the data by phone 2-3 times a month. **Measure:** Changes in adherence to exercise via Exercise Diary keeping **Time Frame:** Time Frame: pre-treatment, Month: 1,3,6, post-intervention ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Symptoms of chronic back pain lasting more than 12 weeks * Score on the Visual Analog Scale for pain less than 70mm * Timed Up and Go test score less than 15sec Exclusion Criteria: * Low back pain due to a serious pathology that refers to a red flag such as malignancy, vertebral fracture, osteomyelitis, rheumatoid arthritis, Cauda Equina Syndrome (CES) * Participation in another exercise program in the last six months * Diagnosed with neurodegenerative disease (e.g., Parkinson's disease) * Recent stroke * Senile dementia **Gender Based:** True **Gender Description:** Female **Maximum Age:** 85 Years **Minimum Age:** 65 Years **Sex:** FEMALE **Standard Ages:** - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Thessaloniki **Country:** Greece **Facility:** Department of Physical Education and Sports Sciences **State:** Thermi **Zip:** 57001 #### Overall Officials **Official 1:** **Affiliation:** Aristotle University Of Thessaloniki **Name:** Evaggelos Sykaras, PhD **Role:** STUDY_DIRECTOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000010146 - Term: Pain - ID: D000009461 - Term: Neurologic Manifestations ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC10 - Name: Nervous System Diseases - 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: M12404 - Name: Neurologic Manifestations - Relevance: LOW - As Found: Unknown - ID: T1303 - Name: Chronic Graft Versus Host Disease - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000001416 - Term: Back Pain - ID: D000017116 - Term: Low Back Pain ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03947879 **Brief Title:** The Effect of Pharmaceutical Grade L-glutamine (Endari) on Glycemic Control in Patients With Diabetes Mellitus Type II **Official Title:** The Effect of Pharmaceutical Grade L-glutamine (Endari) on Glycemic Control in Patients With Diabetes Mellitus Type II #### Organization Study ID Info **ID:** 2018-119 #### Organization **Class:** OTHER **Full Name:** Hawaii Pacific Health ### Status Module #### Completion Date **Date:** 2022-05 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** NOT_YET_RECRUITING #### Last Update Post Date **Date:** 2019-05-13 **Type:** ACTUAL **Last Update Submit Date:** 2019-05-10 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2021-05 **Type:** ESTIMATED #### Start Date **Date:** 2019-05 **Type:** ESTIMATED **Status Verified Date:** 2019-05 #### Study First Post Date **Date:** 2019-05-13 **Type:** ACTUAL **Study First Submit Date:** 2019-04-17 **Study First Submit QC Date:** 2019-05-10 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Hawaii Pacific Health #### Responsible Party **Investigator Affiliation:** Hawaii Pacific Health **Investigator Full Name:** Charles R Zerez, PhD, MD **Investigator Title:** Internal Medicine Physician **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** True **Is US Export:** True **Oversight Has DMC:** False ### Description Module **Brief Summary:** The study is an initial non-blinded, non-placebo controlled trial to determine the efficacy of L-glutamine in lowering blood sugar in patients with diabetes mellitus type II without sickle cell anemia. **Detailed Description:** The protocol will consist of starting patients on 15 g of L glutamine twice daily by mouth. This is the same dose that is used to treat patient with sickle cell anemia. They will be given this medication for a total of 3 months. Their other medications will remain the same. At the conclusion of the 3 months, the patients will be taken off of the glutamine and will continue their other medications. The investigators will monitor the patients an additional 3 months (6 months after the initiation of the study) off the L-glutamine. In this manner, the investigators will have a washout period. The outcome will be a comparison of the results before the initiation of the L-glutamine, to the results after treatment, and after the washout. Data analysis will consist of comparing the patient's fasting glucose and hemoglobin A1c values. The investigators will also check the levels of fructosamine. This is a standard test that is done in any clinical laboratory. To help determine the mechanism for the L-glutamine effect, the investigators will also measure the complete blood count, chemistry panel, hepatic function panel, urine micro-albumin, patients' weight, and waist circumference. The investigators will use the Student t-test for statistical analysis. Significance will be tested at the 0.05 level. The investigators will collect demographic information on the patients in the study. Age, sex, duration of diabetes, smoking history, and race will be noted. The investigators will use regression analysis to determine whether these factors have any effects on the observed results. ### Conditions Module **Conditions:** - Diabetes Mellitus, Type 2 ### Design Module #### Design Info **Allocation:** NON_RANDOMIZED **Intervention Model:** CROSSOVER ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 25 **Type:** ESTIMATED **Phases:** - PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Treatment with L-glutamine for 3 months. **Intervention Names:** - Drug: L-glutamine **Label:** L-glutamine **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** No L-glutamine for 3 months. **Intervention Names:** - Other: No L-glutamine **Label:** No L-glutamine **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - L-glutamine **Description:** 15 g of L-glutamine twice daily by mouth for 3 months. **Name:** L-glutamine **Other Names:** - Endari **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - No L-glutamine **Description:** The same patients will be given no L-glutamine for 3 months. **Name:** No L-glutamine **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** Change in fasting glucose **Measure:** Change in fasting glucose **Time Frame:** 3 months and 6 months **Description:** Change in hemoglobin A1c **Measure:** Change in hemoglobin A1c **Time Frame:** 3 months and 6 months #### Secondary Outcomes **Description:** Change in fructosamine level **Measure:** Change in fructosamine **Time Frame:** 3 months and 6 months **Description:** Change in complete blood count **Measure:** Change in complete blood count **Time Frame:** 3 months and 6 months **Description:** Change in blood chemistry **Measure:** Change in blood chemistry **Time Frame:** 3 months and 6 months **Description:** Chang e in hepatic function **Measure:** Change in hepatic function **Time Frame:** 3 months and 6 months **Description:** Change in urine microalbumin **Measure:** Change in microablbumin **Time Frame:** 3 months and 6 months **Description:** Change in weight **Measure:** Change in weight **Time Frame:** 3 months and 6 months **Description:** Change in waist circumference **Measure:** Change in waist circumference **Time Frame:** 3 months and 6 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Confirmed diagnosis of diabetes mellitus type II * Patient of Straub Medical Center, Internal Medicine Clinic Exclusion Criteria: * Renal and liver impairment ( GFR less than 40) * Transaminitis (elevation of AST of ALT more than 2 fold) * Patient with sickle cell anemia **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Charles Zerez, MD, PhD **Phone:** 808-522-4000 **Role:** CONTACT #### Overall Officials **Official 1:** **Affiliation:** Straub Medical Center **Name:** Charles Zerez, MD, PhD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## 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: M11639 - Name: Metabolic Diseases - Relevance: LOW - As Found: Unknown - ID: M25403 - Name: Glucose Metabolism Disorders - Relevance: LOW - As Found: Unknown - ID: M7862 - Name: Endocrine System Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000003920 - Term: Diabetes Mellitus - ID: D000003924 - Term: Diabetes Mellitus, Type 2 ### Intervention Browse Module - Browse Branches - Abbrev: AA - Name: Amino Acids - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: T6 - Name: Glutamine - Relevance: HIGH - As Found: Bladder Cancer ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT06231979 **Brief Title:** Adding Dexmedetomidine to Bupivacaine for Bilateral Erector Spinae Block **Official Title:** Effects of Adding Dexmedetomidine to Bupivacaine for Bilateral Erector Spinae Block in Lumbar Fusion Surgeries #### Organization Study ID Info **ID:** Erector Spinae Block #### Organization **Class:** OTHER **Full Name:** Assiut University ### Status Module #### Completion Date **Date:** 2025-10-01 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-01-30 **Type:** ACTUAL **Last Update Submit Date:** 2024-01-29 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2025-01-01 **Type:** ESTIMATED #### Start Date **Date:** 2024-02-25 **Type:** ESTIMATED **Status Verified Date:** 2024-01 #### Study First Post Date **Date:** 2024-01-30 **Type:** ACTUAL **Study First Submit Date:** 2023-12-24 **Study First Submit QC Date:** 2024-01-29 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Assiut University #### Responsible Party **Investigator Affiliation:** Assiut University **Investigator Full Name:** Mohammed Ali Hassan Refaat AL-Quossi **Investigator Title:** assistent lecture **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False ### Description Module **Brief Summary:** The aim of this study is to compare the analgesic effect of bilateral US-guided ESPB using bupivacaine alone versus bupivacaine and DEX in lumbar fusion surgeries. **Detailed Description:** Surgical treatment of adult lumbar spinal disorders is associated with a substantial risk of perioperative complications. The improvement in management and the development of new techniques in anesthesia and surgical sciences have led to substantial reduction of complications related to lumbar spine surgeries. Understanding these complications is important and valuable for both the patient and the surgeon. Nevertheless, complications represent undesirable consequences of lumbar spine surgery in adult patients. Degenerative lumbar disease is one of the most common chronic diseases worldwide. The general incidence of lumbar stenosis accompanied by a significant deterioration in the quality of life reaches 5 % among patients aged \< 50 years and approximately 10 - 15 % among elderly patients (50 - 70 years old) Moreover, lumbar stenosis appears to be one of the most common causes of decompression and fusion interventions in the lumbar spine in \> 50 years old patients Lumbar surgeries refer to any type of surgical intervention involving any lumbar spine or lower back (between one or more of the L1 - S1 level), including operations for trauma and deformity. The complexity of procedures leads to an increase in comorbidities Major lumbar spine surgery causes severe postoperative pain, which typically persists for at least three days Risk factors most frequently associated with mortality include but are not limited to patients' age, sex, and comorbidity status Postoperative pain is one of the most troublesome pains for the surgical patients and is one of the causes of morbidity and prolonged hospital stay. Various studies have reported that maximal pain occurs in the first 4 postoperative hours and gradually declines by the third postoperative day . Opiates and non-steroidal anti-inflammatory drugs have been routinely used across the world. Recent resurge of regional anesthetic techniques offer some advantages, especially reduced postoperative nausea and vomiting and less sedation . Ultrasound (US)-guided erector spinae plane blockade (ESPB) was first developed by Forero in 2016 as an easy and safe way of managing thoracic neuropathic pain. Since that time, this block has gained in popularity and has been used to effectively provide analgesia for a variety of surgeries, including spine surgery . Erector spinae plane blockade may also have a better safety profile when compared with neuraxial analgesia, perhaps because of direct visualization of the needle under ultrasonography guidance and the ease of placement, although this has not been decisively proven One disadvantage of this block is the short duration of action after a single injection Dexmedetomidine (DEX), is a highly selective and potent central alpha-2 adrenergic receptor agonist. Administration of this adjuvant in miscellaneous methods has received considerable attention in recent years Due to its analgesic and sedative effects, besides the lack of any respiratory-sparing effects, administration of this adjuvant is effective in reducing the need for opioids in the perioperative period and may even result in cooperative sedation. The neuraxial administration of dexmedetomidine has nociceptive effects on somatic and visceral pains. It also reduces postoperative pain and prolongs analgesia. Local anesthetic combined with DEX has been reported to prolong analgesia following several blocks. However, it is presently unclear whether adjuncts such as DEX will significantly prolong the duration of ESPB in lumbar fusion surgery. Oxidative stress is a condition caused by an imbalance between the production and accumulation of reactive oxygen species (ROS) and the body's ability to detoxify these products. An excess of ROS causes damage to all cellular components. The process of oxidative stress causes the peroxidation of lipids and proteins, the formation of lipid peroxides, DNA fragmentation, and the development of cell death. ROS activity is usually assessed indirectly by measuring stable products derived from the interaction of these radicals with cellular components. The most-studied cellular antioxidants are superoxide dismutase (SOD) , glutathione peroxidase 1 (GPX1) and human malondialdehyde (MDA). These enzymes provide the first line of defense against tissue damage caused by ROS. As part of the antioxidant pathway, SOD accelerates the conversion of superoxide to H2O2, while catalase and GPX convert H2O2 to water. SOD and GPX can be measured in serum or plasma to establish the levels of oxidative stress and antioxidant capacity of the body. ### Conditions Module **Conditions:** - Erector Spinae Block - Lumbar Fusion Surgeries - Dexmedetomidine ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** TRIPLE **Who Masked:** - PARTICIPANT - CARE_PROVIDER - INVESTIGATOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 48 **Type:** ESTIMATED **Phases:** - PHASE4 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Patients will receive US-guided ESPB with 18 mL of bupivacaine 0.25 % and 1 μg/kg DEX diluted with saline to reach total volume 20 mL per side. **Intervention Names:** - Drug: Dexmedetomidine - Drug: Bupivacain **Label:** Dexmedetomidine group **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Patients will receive US-guided ESPB with 18 mL of bupivacaine 0.25 % and 2 mL normal saline 0.9 % per side as control group. **Intervention Names:** - Drug: Bupivacain - Drug: Normal saline **Label:** Bupivacaine group **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Dexmedetomidine group **Description:** 1 μg/kg Dexmedetomidine per side in erector spinae block **Name:** Dexmedetomidine **Other Names:** - DEX **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Bupivacaine group - Dexmedetomidine group **Description:** 18 mL of bupivacaine 0.25 % per side in erector spinae block **Name:** Bupivacain **Other Names:** - Bup **Type:** DRUG #### Intervention 3 **Arm Group Labels:** - Bupivacaine group **Description:** 2 ml normal saline 0.9% per side in erector spinae block **Name:** Normal saline **Other Names:** - Normal saline sodium chloride 0.9% **Type:** DRUG ### Outcomes Module #### Other Outcomes **Description:** Change in stress marker Glutathione peroxidase 1 level in serum after centrifugation between preoperative at time of cannulation and 24h. Postoperative. **Measure:** Change in stress marker Glutathione peroxidase 1 **Time Frame:** 24 hours postoperative. #### Primary Outcomes **Measure:** the cummulative opioid consumption during first 48 h postoperatively. **Time Frame:** 48 hours postoperatively. #### Secondary Outcomes **Description:** Change in stress marker Super Oxide Dismutase (SOD) level in serum after centrifugation between preoperative at time of cannulation and 24h. Postoperative. **Measure:** Change in stress marker Super Oxide Dismutase (SOD) . **Time Frame:** 24 hours postoperative. **Measure:** Postoperative pain score using Visual Analogue Scale (VAS). **Time Frame:** immediately postoperative ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Patients of both genders * age between 18-65 years * American Society of Anesthesiologists (ASA) physical status I-II\*\* * scheduled for lumbar spine fusion surgeries ( 2 or 3 level lumbar fusion with or without decompression ) under general anesthesia . Exclusion Criteria: * Patient refusal. * Patient with chronic use of opioid analgesia. * Uncooperative patients with communication difficulties, which might prevent a reliable postoperative assessment. * Contraindication to regional anesthesia (bleeding disorder, use of any anticoagulants, local infection). Known allergy to local anesthetics. **Healthy Volunteers:** True **Maximum Age:** 65 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### References Module #### References **Citation:** Kalff R, Ewald C, Waschke A, Gobisch L, Hopf C. Degenerative lumbar spinal stenosis in older people: current treatment options. Dtsch Arztebl Int. 2013 Sep;110(37):613-23; quiz 624. doi: 10.3238/arztebl.2013.0613. Epub 2013 Sep 13. **PMID:** 24078855 **Citation:** Liu C, Guo C, Meng F, Zhu Z, Xia W, Liu H. Perioperative risk factors related to complications of lumbar spine fusion surgery in elderly patients. BMC Musculoskelet Disord. 2023 Jul 14;24(1):573. doi: 10.1186/s12891-023-06689-z. **PMID:** 37452304 **Citation:** Dhillon KS. Spinal Fusion for Chronic Low Back Pain: A 'Magic Bullet' or Wishful Thinking? Malays Orthop J. 2016 Mar;10(1):61-68. **PMID:** 28435551 **Citation:** Proietti L, Scaramuzzo L, Schiro' GR, Sessa S, Logroscino CA. Complications in lumbar spine surgery: A retrospective analysis. Indian J Orthop. 2013 Jul;47(4):340-5. doi: 10.4103/0019-5413.114909. **PMID:** 23960276 **Citation:** El-Sadawy Ali Eid M, Ibrahim Mohamed Hashesh M and Ahmed El-Badawy Mohamed M. Comparative Study Between Bupivacaine Alone Versus Bupivacaine With Fentanyl, And Bupivacaine With Dexamethasone In Ultrasound Guided Erector Spinae Plane Block For Postoperative Pain Relief In Patients Undergoing Lumber Spine Surgeries. Al-Azhar Medical Journal. 2022;51(1):507-18. **Citation:** Poorman GW, Moon JY, Wang C, Horn SR, Beaubrun BM, Bono OJ, Francis AM, Jalai CM, Passias PG. Rates of Mortality in Lumbar Spine Surgery and Factors Associated With Its Occurrence Over a 10-Year Period: A Study of 803,949 Patients in the Nationwide Inpatient Sample. Int J Spine Surg. 2018 Oct 15;12(5):617-623. doi: 10.14444/5076. eCollection 2018 Oct. **PMID:** 30364742 **Citation:** Gan TJ. Poorly controlled postoperative pain: prevalence, consequences, and prevention. J Pain Res. 2017 Sep 25;10:2287-2298. doi: 10.2147/JPR.S144066. eCollection 2017. **PMID:** 29026331 **Citation:** Huang J, Liu JC. Ultrasound-guided erector spinae plane block for postoperative analgesia: a meta-analysis of randomized controlled trials. BMC Anesthesiol. 2020 Apr 14;20(1):83. doi: 10.1186/s12871-020-00999-8. **PMID:** 32290814 **Citation:** Abdelbadie M. Analgesic efficacy of the erector spinae plane block using bupivacaine vs. bupivacaine/magnesium sulphate in patients undergoing lumbar spine surgery: a randomized, double-blinded comparative study. Anaesthesia, Pain & Intensive Care. 2022;26(4):439-44. **Citation:** Forero M, Adhikary SD, Lopez H, Tsui C, Chin KJ. The Erector Spinae Plane Block: A Novel Analgesic Technique in Thoracic Neuropathic Pain. Reg Anesth Pain Med. 2016 Sep-Oct;41(5):621-7. doi: 10.1097/AAP.0000000000000451. **PMID:** 27501016 **Citation:** Qiu Y, Zhang TJ, Hua Z. Erector Spinae Plane Block for Lumbar Spinal Surgery: A Systematic Review. J Pain Res. 2020 Jul 1;13:1611-1619. doi: 10.2147/JPR.S256205. eCollection 2020. **PMID:** 32669870 **Citation:** Coviello A, Vargas M, Castellano G, Maresca A, Servillo G. Ultrasound-guided Erector Spinae Plane Block (US-ESPB)-Anesthetic block: Case report. Clin Case Rep. 2020 Sep 10;8(12):2885-2888. doi: 10.1002/ccr3.3253. eCollection 2020 Dec. **PMID:** 33363844 **Citation:** Stondell C, Roberto R. Erector Spinae Plane Blocks With Liposomal Bupivacaine for Pediatric Scoliosis Surgery. J Am Acad Orthop Surg Glob Res Rev. 2022 Jan 21;6(1):e21.00272. doi: 10.5435/JAAOSGlobal-D-21-00272. **PMID:** 35061632 **Citation:** Bhushan S, Huang X, Su X, Luo L, Xiao Z. Ultrasound-guided erector spinae plane block for postoperative analgesia in patients after liver surgery: A systematic review and meta-analysis on randomized comparative studies. Int J Surg. 2022 Jul;103:106689. doi: 10.1016/j.ijsu.2022.106689. Epub 2022 Jun 1. **PMID:** 35662584 **Citation:** Schnabel A, Reichl SU, Weibel S, Kranke P, Zahn PK, Pogatzki-Zahn EM, Meyer-Friessem CH. Efficacy and safety of dexmedetomidine in peripheral nerve blocks: A meta-analysis and trial sequential analysis. Eur J Anaesthesiol. 2018 Oct;35(10):745-758. doi: 10.1097/EJA.0000000000000870. **PMID:** 30095549 **Citation:** Kaye AD, Chernobylsky DJ, Thakur P, Siddaiah H, Kaye RJ, Eng LK, Harbell MW, Lajaunie J, Cornett EM. Dexmedetomidine in Enhanced Recovery After Surgery (ERAS) Protocols for Postoperative Pain. Curr Pain Headache Rep. 2020 Apr 2;24(5):21. doi: 10.1007/s11916-020-00853-z. **PMID:** 32240402 **Citation:** Gousheh M, Akhondzadeh R, Rashidi M, Olapour A, Moftakhar F. Comparison of Dexmedetomidine and Morphine as Adjuvants to Bupivacaine for Epidural Anesthesia in Leg Fracture Surgery: A Randomized Clinical Trial. Anesth Pain Med. 2019 Aug 27;9(4):e91480. doi: 10.5812/aapm.91480. eCollection 2019 Aug. **PMID:** 31803587 **Citation:** Gao X, Zhao T, Xu G, Ren C, Liu G, Du K. The Efficacy and Safety of Ultrasound-Guided, Bi-Level, Erector Spinae Plane Block With Different Doses of Dexmedetomidine for Patients Undergoing Video-Assisted Thoracic Surgery: A Randomized Controlled Trial. Front Med (Lausanne). 2021 Nov 25;8:577885. doi: 10.3389/fmed.2021.577885. eCollection 2021. **PMID:** 34901039 **Citation:** Pizzino G, Irrera N, Cucinotta M, Pallio G, Mannino F, Arcoraci V, Squadrito F, Altavilla D, Bitto A. Oxidative Stress: Harms and Benefits for Human Health. Oxid Med Cell Longev. 2017;2017:8416763. doi: 10.1155/2017/8416763. Epub 2017 Jul 27. **PMID:** 28819546 **Citation:** Su LJ, Zhang JH, Gomez H, Murugan R, Hong X, Xu D, Jiang F, Peng ZY. Reactive Oxygen Species-Induced Lipid Peroxidation in Apoptosis, Autophagy, and Ferroptosis. Oxid Med Cell Longev. 2019 Oct 13;2019:5080843. doi: 10.1155/2019/5080843. eCollection 2019. **PMID:** 31737171 **Citation:** Savic Vujovic K, Zivkovic A, Dozic I, Cirkovic A, Medic B, Srebro D, Vuckovic S, Milovanovic J, Jotic A. Oxidative Stress and Inflammation Biomarkers in Postoperative Pain Modulation in Surgically Treated Patients with Laryngeal Cancer-Pilot Study. Cells. 2023 May 14;12(10):1391. doi: 10.3390/cells12101391. **PMID:** 37408225 **Citation:** Bhattacharyya A, Chattopadhyay R, Mitra S, Crowe SE. Oxidative stress: an essential factor in the pathogenesis of gastrointestinal mucosal diseases. Physiol Rev. 2014 Apr;94(2):329-54. doi: 10.1152/physrev.00040.2012. **PMID:** 24692350 ## Derived Section ### Intervention Browse Module - Ancestors - ID: D000000779 - Term: Anesthetics, Local - ID: D000000777 - Term: Anesthetics - ID: D000002492 - Term: Central Nervous System Depressants - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000018689 - Term: Sensory System Agents - ID: D000018373 - Term: Peripheral Nervous System Agents - ID: D000006993 - Term: Hypnotics and Sedatives - ID: D000018712 - Term: Analgesics, Non-Narcotic - ID: D000000700 - Term: Analgesics - ID: D000058647 - Term: Adrenergic alpha-2 Receptor Agonists - 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 ### Intervention Browse Module - Browse Branches - Abbrev: Analg - Name: Analgesics - Abbrev: CNSDep - Name: Central Nervous System Depressants - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M22662 - Name: Dexmedetomidine - Relevance: HIGH - As Found: Twice daily - ID: M5315 - Name: Bupivacaine - Relevance: HIGH - As Found: Following - ID: M4107 - Name: Anesthetics - Relevance: LOW - As Found: Unknown - ID: M4109 - Name: Anesthetics, Local - Relevance: LOW - As Found: Unknown - ID: M10043 - Name: Hypnotics and Sedatives - Relevance: LOW - As Found: Unknown - ID: M4032 - Name: Analgesics - Relevance: LOW - As Found: Unknown - ID: M20786 - Name: Analgesics, Non-Narcotic - Relevance: LOW - As Found: Unknown - 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 ### Intervention Browse Module - Meshes - ID: D000020927 - Term: Dexmedetomidine - ID: D000002045 - Term: Bupivacaine ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT02915679 **Acronym:** DOCS **Brief Title:** Pain Perception in Suicidal Behavior Vulnerability **Official Title:** Pain Perception in Suicidal Behavior Vulnerability #### Organization Study ID Info **ID:** UF 9185 #### Organization **Class:** OTHER **Full Name:** University Hospital, Montpellier #### Secondary ID Infos **Domain:** Agence Nationale de Sécurité des Médicaments **ID:** 2013-A01029-36 **Type:** OTHER ### Status Module #### Completion Date **Date:** 2021-05-06 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2022-01-11 **Type:** ACTUAL **Last Update Submit Date:** 2021-12-20 **Overall Status:** TERMINATED #### Primary Completion Date **Date:** 2021-05-06 **Type:** ACTUAL #### Start Date **Date:** 2015-06-17 **Status Verified Date:** 2021-12 #### Study First Post Date **Date:** 2016-09-27 **Type:** ESTIMATED **Study First Submit Date:** 2016-08-01 **Study First Submit QC Date:** 2016-09-23 **Why Stopped:** difficulty in recruiting ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** University Hospital, Montpellier #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** In France, almost 1 death on 50 is a suicide. The suicide occurs in unbearable psychic pain where mental trouble has a major influence. It is classified as preventable mortality. According to interpersonal psychological theory of suicide, the repeated exposition to stressful and painful events (as physical abuse) would facilitate suicide attempt through the increased pain tolerance. The social pain (or psychical pain on the broader sense) and physical pain are closely linked. The investigators hypothesize that the measure of painful perception will be significantly superior on suicidals attempters compared to non-attempters. It will be the case for recent suicide attempters and former suicide attempters, suggesting a suicidal vulnerability trait. Moreover, the investigators expect that social distress induced by a social exclusion paradigm will be significantly superior on suicide attempters compared to non-attempters. The aim of the study is to investigate the physical and psychic pain on depressed subjects with or without history of suicide attempts. After a clinical evaluation (psychiatric symptomatology, personality trait, suicidal dimension), subjects will be submitted to a painful thermic stimulation and will participate at a computer test of social exclusion (named Cyberball). **Detailed Description:** 242 depressed patients ( 81 recent suicide attempters, 81 former suicide attempters, 80 non-attempters) First visit : clinical assessment Second visit : pain evaluation and blood sample (from one day to a week maximum after the first visit). ### Conditions Module **Conditions:** - Major Depressive Episode **Keywords:** - Suicidal behavior - psychological and social pain - physical pain - pain perception ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** OTHER #### Enrollment Info **Count:** 167 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** All the participants performed blood sample for genetic purpose, psychiatric assessment and pain investigation: * 81 depressed patients admitted after a recent suicidal act (\<8 days) * 81 depressed subjects with a past history of suicidal act (\>1month) * 80 depressed subjects without any personal history of suicidal behaviour **Intervention Names:** - Other: Blood sample for genetic purpose, psychiatric assessment and pain investigation **Label:** Study participant **Type:** OTHER ### Interventions #### Intervention 1 **Arm Group Labels:** - Study participant **Description:** All the participant will performed the same evaluation and blood analysis: * A clinical assessment by psychiatrics assessing psychiatric disorder and suicidal behavior * Thermal stimulation for pain assessment * Computer game named Cyberball: test of social exclusion * Self report questionnaire for the assessment of reject sensitivity, relationship style, impulsivity, childhood trauma. * Routine blood sampling **Name:** Blood sample for genetic purpose, psychiatric assessment and pain investigation **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** temperature measured when the subject will perceive as intolerable the pain following a painful stimulation performed using a thermode **Measure:** Pain tolerance reported by the patient **Time Frame:** During thermal stimulation #### Secondary Outcomes **Description:** comparison between the three groups of the pain intensity (assessed by likert scale) at constant temperature (43 ° C) **Measure:** Pain intensity reported by the patient **Time Frame:** During thermal stimulation **Description:** comparison between the three groups of the pain threshold (temperature perceived as painful) **Measure:** Pain threshold reported by the patient **Time Frame:** During thermal stimulation **Description:** comparison between the three groups of the temperature assessed at 4/10 on a visual analogic painful scale, kinetics of pain intensity by visual analog scale (VAS) scale. **Measure:** Temperature assessed at 4/10 on likert scale **Time Frame:** During thermal stimulation performed at the inclusion **Description:** comparison between the three groups of kinetics of pain intensity by visual analog scale (VAS) scale. **Measure:** Kinetics of pain intensity **Time Frame:** During thermal stimulation performed at the inclusion **Description:** comparison between the three groups of the score of social distress scale after cyberball game **Measure:** Social distress perception assessed by social distress questionnaire **Time Frame:** At V2 (one week maximum after the inclusion) **Description:** comparison between the three groups of the score of social distress scale after cyberball game **Measure:** Social distress perception assessed by the Rejection Sensitivity Questionnaire (RSQ) **Time Frame:** At the inclusion **Description:** comparison between the three groups of the score of social rejection sensitivity by RSQ **Measure:** Social rejection sensitivity assessed by the Rejection Sensitivity Questionnaire (RSQ) **Time Frame:** At the inclusion **Description:** comparison between the three groups of the score of psychological pain intensity assessed by VAS scale. **Measure:** Psychological pain intensity **Time Frame:** At V2 (one week maximum after the inclusion) **Description:** comparison between the three groups of the cardiac frequency. **Measure:** Measure of cardiac frequency in response to thermal pain **Time Frame:** At V2 (one week maximum after the inclusion) ### Eligibility Module **Eligibility Criteria:** Inclusion criteria: * aged by 18 years old * came from West Europe, excepted Basque and Sardinian (because of genetics analysis) * main diagnosis of major depressive episode (DSM V criteria) * not having take antalgics in the 24 hours before assessment * received a minimal psychotrope treatment (clinician evaluation) * Able to understand nature, aims, methodology of the study * Agree to cooperate in clinical and biological assessment * Having signed informed consent Specific inclusion criteria : 81 recent suicide attempters (being hospitalised for suicidal attempts and having realised a suicide attempts 8 days before inclusion) 81 former suicide attempters (having realised in his lifetime a suicide attempt, one month before inclusion) Exclusion criteria: * Current diagnosis of manic, hypomanic or alcohol dependance or substance abuse in the last 6 months, or diagnosis of schizophrenia or schizoaffective disorder in his lifetime * Current algic and chronic neurologic disease * Current or actual treatment by tricyclic antidepressant and Serotonin and norepinephrine reuptake inhibitors(SNRIs) * Pregnancy * Patients on protective measure **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Montpellier **Country:** France **Facility:** Montpellier Hospital University **Zip:** 34295 ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M13066 - Name: Pain - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03355079 **Brief Title:** Efficacy Study of Long-term Parenteral Nutrition With SmofKabiven® E in Lung Cancer Patients Under Anticancer Therapy **Official Title:** Efficacy of Long-term Parenteral Nutrition With SmofKabiven® E Concomitant to Chemo- and/or Immunotherapy: A Prospective, Randomised, Controlled, Open, Multicentre, Two-stage, Adaptive Clinical Trial in Metastatic Non-small Cell Lung Cancer #### Organization Study ID Info **ID:** SMKV-013-CP4 #### Organization **Class:** INDUSTRY **Full Name:** Fresenius Kabi ### Status Module #### Completion Date **Date:** 2019-04-05 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2019-05-01 **Type:** ACTUAL **Last Update Submit Date:** 2019-04-29 **Overall Status:** TERMINATED #### Primary Completion Date **Date:** 2019-04-05 **Type:** ACTUAL #### Start Date **Date:** 2018-02-28 **Type:** ACTUAL **Status Verified Date:** 2019-04 #### Study First Post Date **Date:** 2017-11-28 **Type:** ACTUAL **Study First Submit Date:** 2017-11-16 **Study First Submit QC Date:** 2017-11-21 **Why Stopped:** Low Patient Recruitment ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Fresenius Kabi #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** The purpose of this study is to determine the efficacy of long-term addition of SmofKabiven® E to normal oral nutrition after routine dietary counseling as compared to standard of care nutrition in which oral nutrition is the primary nutritional support. It takes place in lung cancer patients under chemo- and/or immunotherapy. Efficacy will be determined primarily by calculating the change of patient's body weight from before start of study treatment to end of treatment, and comparing this change between both treatment groups. ### Conditions Module **Conditions:** - Cancer-related Malnutrition ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** SUPPORTIVE_CARE #### Enrollment Info **Count:** 2 **Type:** ACTUAL **Phases:** - PHASE4 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** SmofKabiven® E, with or without addition of Suppliven®, Vitalipid® Adult and/or Soluvit® will be administered at 5-7 days per week for up to 9 +/-1 weeks in addition to standard of care oral nutrition as per routine dietary counseling, to reach the patient's target energy intake. **Intervention Names:** - Drug: SmofKabiven® E **Label:** SmofKabiven® E + standard oral nutrition **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** The patients will consume standard of care oral nutrition as per routine dietary counseling, to reach their target energy intake. Standard of care tube feeding or parenteral nutrition is allowed to start earliest 3 weeks after baseline visit, if required. **Label:** Standard oral nutrition **Type:** NO_INTERVENTION ### Interventions #### Intervention 1 **Arm Group Labels:** - SmofKabiven® E + standard oral nutrition **Description:** In the intervention arm, SmofKabiven® E, with or without addition of Suppliven®, Vitalipid® Adult and/or Soluvit®, will be administered in addition to standard of care oral nutrition as per dietary counseling, whereas in the control arm, oral nutrition as per dietary counseling is the primary nutritional support. **Name:** SmofKabiven® E **Type:** DRUG ### Outcomes Module #### Other Outcomes **Measure:** Aspartate Aminotransferase **Time Frame:** From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline **Measure:** Alanine Aminotransferase **Time Frame:** From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline **Measure:** Alkaline phosphatase **Time Frame:** From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline **Measure:** Gamma-Glutamyl Transferase **Time Frame:** From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline **Measure:** Direct bilirubin **Time Frame:** From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline **Measure:** Total bilirubin **Time Frame:** From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline **Measure:** Internal Normalized Ratio **Time Frame:** From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline **Measure:** Serum creatinine **Time Frame:** From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline **Measure:** Serum urea **Time Frame:** From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline **Measure:** Serum sodium **Time Frame:** From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline **Measure:** Serum potassium **Time Frame:** From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline **Measure:** Serum total calcium **Time Frame:** From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline **Measure:** Serum magnesium **Time Frame:** From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline **Measure:** Serum chloride **Time Frame:** From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline **Measure:** Serum phosphate **Time Frame:** From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline **Measure:** Serum bicarbonate **Time Frame:** From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline **Measure:** Serum glucose **Time Frame:** From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline **Measure:** Serum triglycerides **Time Frame:** From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline **Measure:** Red blood cell count **Time Frame:** From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline **Measure:** Total white blood cell count **Time Frame:** From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline **Measure:** Differential blood count **Time Frame:** From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline **Measure:** Haemoglobin **Time Frame:** From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline **Measure:** Haematocrit **Time Frame:** From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline **Measure:** Platelet count **Time Frame:** From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline **Measure:** C-reactive protein **Time Frame:** From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline **Measure:** Blood pressure **Time Frame:** From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline **Measure:** Heart rate **Time Frame:** From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline **Measure:** Body temperature **Time Frame:** From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline **Measure:** Infection rate including catheter-related blood stream infections demonstrated by positive blood culture **Time Frame:** From baseline every 2-3 weeks until final visit at 9 +/-1 weeks after baseline #### Primary Outcomes **Measure:** Change in total body weight (kg) **Time Frame:** Every 2-3 weeks, for up to 9 +/-1 weeks #### Secondary Outcomes **Measure:** Serum albumin **Time Frame:** Every 2-3 weeks from baseline to final visit at 9 +/1 weeks after baseline **Measure:** Serum transthyretin **Time Frame:** Every 2-3 weeks from baseline to final visit at 9 +/1 weeks after baseline **Measure:** Nutritional Risk Index **Time Frame:** Every 2-3 weeks from baseline to final visit at 9 +/1 weeks after baseline **Measure:** Unplanned PN or tube feeding according to standard of care in control group **Time Frame:** Every 2-3 weeks from baseline to final visit at 9 +/1 weeks after baseline **Measure:** Early termination of PN due to improvement in test group **Time Frame:** Every 2-3 weeks from baseline to final visit at 9 +/1 weeks after baseline **Measure:** Lean body mass determined from computer tomography (CT) scan at 3rd lumbar vertebra **Time Frame:** Baseline to final visit at 9 +/1 weeks after baseline **Measure:** Optional: lean tissue mass, phase angle and hydration status including intra- and extracellular body water with bioelectrical impedance analysis (BIA), if BIA device is available. **Time Frame:** Baseline to final visit at 9 +/1 weeks after baseline **Measure:** Karnofsky performance status **Time Frame:** Every 2-3 weeks from baseline to final visit at 9 +/1 weeks after baseline **Measure:** ECOG performance status **Time Frame:** Time Frame: Every 2-3 weeks from baseline to final visit at 9 +/1 weeks after baseline **Measure:** Handgrip strength in kg, using hand dynamometer **Time Frame:** Every 2-3 weeks from baseline to final visit at 9 +/1 weeks after baseline **Measure:** Actual and target number of completed chemotherapy and/or immunotherapy cycles **Time Frame:** Every 2-3 weeks from baseline to 3 months after baseline **Measure:** Actual dose and target chemotherapy and/or immunotherapy dose administered **Time Frame:** Every 2-3 weeks from baseline to 3 months after baseline **Measure:** Chemotherapy and/or immunotherapy toxicities according to NCI-CTC v4.0 including dose-limiting toxicities **Time Frame:** Every 2-3 weeks from baseline to final visit at 9 +/1 weeks after baseline **Measure:** Fatigue using the brief fatigue inventory (BFI questionnaire) **Time Frame:** Every 2-3 weeks from baseline to final visit at 9 +/1 weeks after baseline **Measure:** Overall survival **Time Frame:** Until 6 months post baseline **Measure:** Progression-free survival **Time Frame:** At 3 and 6 months post baseline **Measure:** Partial response rate (as per RECIST v 1.1) **Time Frame:** At 9 +/-1 weeks, 3 months and 6 months after baseline **Measure:** Complete response rate (as per RECIST v 1.1) **Time Frame:** At 9 +/-1 weeks, 3 months and 6 months after baseline **Measure:** Unplanned hospitalization **Time Frame:** From baseline until 6 months after baseline **Measure:** Quality of life (Functional Assessment of Cancer Therapy- General [FACT-G] score) **Time Frame:** From baseline until final visit at 9 +/-1 weeks after baseline **Measure:** Number of patients terminating anti-cancer and nutrition therapy as part of end-of-life care **Time Frame:** From baseline until final visit at 9 +/-1 weeks after baseline **Description:** measured by indirect calorimetry **Measure:** Resting energy expenditure **Time Frame:** From baseline until final visit at 9 +/-1 weeks after baseline **Measure:** Ocurrence of unplanned admission to nursing home **Time Frame:** From baseline until final visit at 9 +/-1 weeks after baseline ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Metastatic non-small cell lung cancer patient * Adult ≥ 18 years * Starting any 1st, 2nd or 3rd line chemotherapy and/or immunotherapy administered via a central venous catheter (including implanted ports), or receiving the 2nd cycle of aforementioned anticancer treatment * An energy gap of ≥ 40 % and/or 1000 kcal between the target energy intake (30 ± 5 kcal/kg/day) and the actual energy intake at screening, irrespective of weight loss * Functional digestive tract allowing oral intake * If female of childbearing potential, willing to use a sufficiently safe contraception method throughout participation in the study * Signed informed consent from patient or legal representative Exclusion Criteria: * Parenteral nutrition (PN) administered during the preceding month (the sole administration of intravenous glucose is allowed), or standard of care PN planned to start within 3 weeks after baseline visit * More than 1600 kcal/day required as PN * Tube feeding at screening, or planned to start within 3 weeks after baseline visit * Body mass index (BMI) \> 30 kg/m2 * Performance status \> 3 Eastern Cooperative Oncology Group (ECOG) score * Life expectancy \< 3 months * Active bloodstream infection demonstrated by positive blood culture at Screening * Hypersensitivity to fish-, egg, soya- or peanut protein or to any of the active substances or excipients in SmofKabiven E * Severe blood coagulation disorders * Congenital errors of amino acid metabolism * Pathologically elevated serum levels of any of the included electrolytes * General contraindications to infusion therapy: acute pulmonary oedema, hyperhydration, decompensated cardiac insufficiency * Hemophagocytotic Syndrome * Severe hyperlipidemia (serum triglycerides \> 353 mg/dL) * Severe liver insufficiency: liver enzymes (aspartate aminotransferase \[AST\], alanine aminotransferase \[ALT\], gamma glutamyl transferase \[GGT\]) or conjugated bilirubin exceeding 3 x upper limit of normal range, or International Normalised Ratio (INR) \> 2 * Severe renal dysfunction (estimated glomerular filtration rate \[eGFR\] \< 30 ml/min/1.73m2) and patients on renal replacement therapy * Uncontrolled hyperglycaemia * Unstable conditions (e.g., embolism, metabolic acidosis, hypotonic dehydration) * Pregnancy or lactation * Contraindications to any of the study assessment methods including computer tomography and indirect calorimetry * Participation in a clinical study with an investigational drug or investigational medical device within one month prior to start of study or during study * Prior inclusion in the present study **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Paris **Country:** France **Facility:** Hôpital Cochin **Zip:** 75014 #### Overall Officials **Official 1:** **Affiliation:** Hôpital Cochin, Paris **Name:** Jean-Philippe Durand, MD **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009748 - Term: Nutrition Disorders ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC08 - Name: Respiratory Tract (Lung and Bronchial) Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC18 - Name: Nutritional and Metabolic Diseases ### Condition Browse Module - Browse Leaves - ID: M11172 - Name: Lung Neoplasms - Relevance: LOW - As Found: Unknown - ID: M5546 - Name: Carcinoma, Non-Small-Cell Lung - Relevance: LOW - As Found: Unknown - ID: M25306 - Name: Malnutrition - Relevance: HIGH - As Found: Malnutrition - ID: M12684 - Name: Nutrition Disorders - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000044342 - Term: Malnutrition ### Intervention Browse Module - Browse Branches - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M2853 - Name: Immunomodulating Agents - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT02342379 **Brief Title:** TH-302 in Combination With Bevacizumab for Glioblastoma **Official Title:** A Phase 2, Investigator Initiated Study to Determine the Safety and Efficacy of TH-302 in Combination With Bevacizumab for Glioblastoma Following Bevacizumab Failure #### Organization Study ID Info **ID:** CTRC 12-0105 #### Organization **Class:** OTHER **Full Name:** The University of Texas Health Science Center at San Antonio #### Secondary ID Infos **Domain:** UT Health Science Center Institutional Review Board **ID:** HSC20130212H **Type:** OTHER ### Status Module #### Completion Date **Date:** 2019-12-04 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2020-04-10 **Type:** ACTUAL **Last Update Submit Date:** 2020-04-09 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2019-01-04 **Type:** ACTUAL #### Results First Post Date **Date:** 2020-04-10 **Type:** ACTUAL **Results First Submit Date:** 2020-02-07 **Results First Submit QC Date:** 2020-04-09 #### Start Date **Date:** 2015-05 **Status Verified Date:** 2020-04 #### Study First Post Date **Date:** 2015-01-19 **Type:** ESTIMATED **Study First Submit Date:** 2015-01-14 **Study First Submit QC Date:** 2015-01-16 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** The University of Texas Health Science Center at San Antonio #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** Dual center, single arm, two-stage, non-blinded, prospective study of combination therapy bevacizumab at 10mg/kg and TH-302 at 670mg/m2 every 2 weeks (6 week cycle) until disease progression. ### Conditions Module **Conditions:** - Glioblastoma ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 35 **Type:** ACTUAL **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Patients will be treated with combination of bevacizumab and TH-302. **Intervention Names:** - Drug: Bevacizumab - Drug: TH-302 **Label:** Bevacizumab and TH-302 **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Bevacizumab and TH-302 **Description:** 10mg/kg **Name:** Bevacizumab **Other Names:** - Avastin **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Bevacizumab and TH-302 **Description:** 670mg/m2 **Name:** TH-302 **Other Names:** - MSC2491899A **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Safety lab tests and adverse event assessment **Measure:** Number of Patients With Adverse Events **Time Frame:** 4 months #### Secondary Outcomes **Description:** Progression of disease by RANO criteria: The RANO criteria divides response into four types of response based on imaging and clinical features 1. complete response 2. partial response 3. stable disease 4. progression **Measure:** Progression Free Survival **Time Frame:** 4 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * At least 18 years of age * Ability to understand the purposes and risks of the study and has signed a written informed consent form approved by the investigator's IRB/Ethics Committee * Histologically confirmed glioblastoma * Progression following both standard combined modality treatment with radiation and temozolomide chemotherapy, as well as bevacizumab * Recovered from toxicities of prior therapy to grade 0 or 1 * ECOG performance status ≤ 2 * Life expectancy of at least 3 months * Acceptable liver function: 1. Bilirubin ≤ 1.5 times upper limit of normal 2. AST (SGOT) and ALT (SGPT) ≤ 3.0 times upper limit of normal (ULN); * Acceptable renal function: a. Serum creatinine ≤ULN * Acceptable hematologic status (without hematologic support): 1. ANC ≥1500 cells/uL 2. Platelet count ≥100,000/uL 3. Hemoglobin ≥9.0 g/dL * All women of childbearing potential must have a negative serum pregnancy test and male and female subjects must agree to use effective means of contraception (surgical sterilization or the use or barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel or an IUD) with their partner from entry into the study through 6 months after the last dose Exclusion Criteria: * The subject is receiving warfarin (or other coumarin derivatives) and is unable to switch to low molecular weight heparin (LMWH) before the first dose of study drug. * The subject has evidence of acute intracranial or intratumoral hemorrhage either by MRI or computerized tomography (CT) scan. Subjects with resolving hemorrhage, punctate hemorrhage, or hemosiderin are eligible. * The subject is unable to undergo MRI scan (eg, has pacemaker). * The subject has received enzyme-inducing anti-epileptic agents within 14 days of study drug (eg, carbamazepine, phenytoin, phenobarbital, primidone). * The subject has not recovered to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade ≤ 1 from AEs (except alopecia, anemia and lymphopenia) due to surgery, antineoplastic agents, investigational drugs, or other medications that were administered prior to study drug. * The subject has evidence of wound dehiscence * Severe chronic obstructive or other pulmonary disease with hypoxemia (requires supplementary oxygen, symptoms due to hypoxemia or oxygen saturation \<90% by pulse oximetry after a 2 minute walk) or in the opinion of the investigator any physiological state likely to cause normal tissue hypoxia * The subject is pregnant or breast-feeding. * The subject has serious intercurrent illness, such as: 1. hypertension (two or more blood pressure \[BP\] readings performed at screening of \> 150 mmHg systolic or \> 100 mmHg diastolic) despite optimal treatment 2. non-healing wound, ulcer, or bone fracture 3. significant cardiac arrhythmias 4. untreated hypothyroidism 5. uncontrolled active infection 6. symptomatic congestive heart failure or unstable angina pectoris within 3 months prior study drug 7. myocardial infarction, stroke, transient ischemic attack within 6 months 8. gastrointestinal perforation, abdominal fistula, intra- abdominal abscess within 1 year 9. history or clinical evidence of pancreatitis within 2 years * The subject has inherited bleeding diathesis or coagulopathy with the risk of bleeding. * The subject has received any of the following prior anticancer therapy: 1. Non-standard radiation therapy such as brachytherapy, systemic radioisotope therapy, or intra-operative radiotherapy (IORT). Note: stereotactic radiosurgery (SRS) is allowed 2. Non-bevacizumab systemic therapy (including investigational agents and small-molecule kinase inhibitors) or non-cytotoxic hormonal therapy (eg, tamoxifen) within 7 days or 5 half-lives, whichever is shorter, prior first dose of study drug 3. Biologic agents (antibodies, immune modulators, vaccines, cytokines) within 21 days prior to first dose of study drug 4. Nitrosoureas or mitomycin C within 42 days, or metronomic/protracted low-dose chemotherapy within 14 days, or other cytotoxic chemotherapy within 28 days, prior to first dose of study drug 5. Prior treatment with carmustine wafers 6. Prior treatment with TH-302 **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Boston **Country:** United States **Facility:** Dana-Farber Cancer Institute **State:** Massachusetts **Zip:** 02215 **Location 2:** **City:** San Antonio **Country:** United States **Facility:** University of Texas Health Science Center San Antonio at the Cancer Therapy and Research Center **State:** Texas **Zip:** 78229 #### Overall Officials **Official 1:** **Affiliation:** University of Texas Health Science Center San Antonio at the Cancer Therapy and Research Center **Name:** Andrew Brenner, MD **Role:** PRINCIPAL_INVESTIGATOR ## Document Section ### Large Document Module #### Large Docs - Date: 2017-04-04 - Filename: Prot_SAP_000.pdf - Has ICF: False - Has Protocol: True - Has SAP: True - Label: Study Protocol and Statistical Analysis Plan - Size: 1992823 - Type Abbrev: Prot_SAP - Upload Date: 2020-01-10T16:14 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000001254 - Term: Astrocytoma - ID: D000005910 - Term: Glioma - ID: D000018302 - Term: Neoplasms, Neuroepithelial - ID: D000017599 - Term: Neuroectodermal Tumors - ID: D000009373 - Term: Neoplasms, Germ Cell and Embryonal - ID: D000009370 - Term: Neoplasms by Histologic Type - ID: D000009369 - Term: Neoplasms - ID: D000009375 - Term: Neoplasms, Glandular and Epithelial - ID: D000009380 - Term: Neoplasms, Nerve Tissue ### 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: M9019 - Name: Glioblastoma - Relevance: HIGH - As Found: Glioblastoma - ID: M4561 - Name: Astrocytoma - Relevance: LOW - As Found: Unknown - ID: M9020 - Name: Glioma - Relevance: LOW - As Found: Unknown - ID: M20446 - Name: Neoplasms, Neuroepithelial - 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: M12320 - Name: Neoplasms, Glandular and Epithelial - Relevance: LOW - As Found: Unknown - ID: M12325 - Name: Neoplasms, Nerve Tissue - Relevance: LOW - As Found: Unknown - ID: T2518 - Name: Glioblastoma - Relevance: HIGH - As Found: Glioblastoma - ID: T2519 - Name: Glioma - Relevance: LOW - As Found: Unknown - ID: T4092 - Name: Neuroepithelioma - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000005909 - Term: Glioblastoma ### Intervention Browse Module - Ancestors - ID: D000074322 - Term: Antineoplastic Agents, Immunological - ID: D000000970 - Term: Antineoplastic Agents - ID: D000020533 - Term: Angiogenesis Inhibitors - ID: D000043924 - Term: Angiogenesis Modulating Agents - ID: D000006133 - Term: Growth Substances - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000006131 - Term: Growth Inhibitors ### Intervention Browse Module - Browse Branches - Abbrev: ANeo - Name: Antineoplastic Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M246 - Name: Bevacizumab - Relevance: HIGH - As Found: Non- - ID: M1346 - Name: Antineoplastic Agents, Immunological - 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: D000068258 - Term: Bevacizumab ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module #### Event Groups **Group ID:** EG000 **Title:** Bevacizumab and TH-302 **Deaths Num At Risk:** 35 **Description:** Patients will be treated with combination of bevacizumab and TH-302. Bevacizumab: 10mg/kg TH-302: 670mg/m2 **ID:** EG000 **Other Num Affected:** 35 **Other Num at Risk:** 35 **Serious Number At Risk:** 35 **Title:** Bevacizumab and TH-302 **Frequency Threshold:** 0 #### Other Events **Term:** Abscess (left axillary abscess) **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** **Term:** Anemia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** **Term:** Anorexia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** **Term:** Cognitive Disturbance **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** **Term:** confusion **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** **Term:** Nasal congestion **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** **Term:** Constipation **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** **Term:** Decreased Appetite **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** **Term:** Decreased Platelets **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** **Term:** Dermatitis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** **Term:** Diarrhea **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** **Term:** Dry Skin **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** **Term:** Edema (pedal) **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** **Term:** Epistaxis (intermittent) **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Notes:** Bleeding of the nose **Organ System:** Vascular disorders **Source Vocabulary:** **Term:** Facial Erythema **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** **Term:** Blurred vision/diplopia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Eye disorders **Source Vocabulary:** **Term:** Fatigue **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** **Term:** Fever **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** **Term:** Flu **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Notes:** Upper respiratory tract infection **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** **Term:** Headache **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** **Term:** Heartburn **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** **Term:** Hemorrhoid **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** **Term:** Herpes Simplex Virus **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** **Term:** Hoarsness **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** **Term:** Hyperglycemia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Endocrine disorders **Source Vocabulary:** **Term:** Hyperkeratosis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Notes:** palmar plantar erythrodysethesia syndrome **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** **Term:** Hyperpigmentation **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** **Term:** Hypertension **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Notes:** High blood pressure **Organ System:** Cardiac disorders **Source Vocabulary:** **Term:** Kratoderma **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** **Term:** Leukopenia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Notes:** Decreased white blood cell count **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** **Term:** Lung Infection (PNA) **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** **Term:** Mouth Sores **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** **Term:** Anal Mucositis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** **Term:** Oral Mucositis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** **Term:** Perianal Mucositis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** **Term:** Rectal Mucositis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** **Term:** Vaginal Mucositis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Reproductive system and breast disorders **Source Vocabulary:** **Term:** Nausea **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** **Term:** Neutropenia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** **Term:** Pain, abdominal **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** **Term:** Pain, rectal **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** **Term:** Phlebitis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Notes:** Left anticubital fossa **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** **Term:** Photosensitivity Reaction **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** **Term:** Proteinuria **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Endocrine disorders **Source Vocabulary:** **Term:** Pruritis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** **Term:** Rash **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** **Term:** Scar **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** **Term:** Skin Abrasion **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** **Term:** Skin Atrophy **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Notes:** Peeling **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** **Term:** Skin Irritation **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Notes:** Groin **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** **Term:** Skin excoriation **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Notes:** Right armpit **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** **Term:** Other skin excoriation **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Notes:** Labial/vaginal/rectal **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** **Term:** Skin Ulceration **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** **Term:** Small intestine perforation **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** **Term:** Thrombocytopenia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** **Term:** Dysuria **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** **Term:** Urinary Tract Infection **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** **Term:** Vaginal Infection **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Reproductive system and breast disorders **Source Vocabulary:** **Term:** Vomiting **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** **Term:** Weakness **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Notes:** Left sided weakness **Organ System:** General disorders **Source Vocabulary:** **Term:** Wound complication **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Notes:** Delayed healing of right chest wall **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** **Time Frame:** Adverse events are collected from start of drug administration until 30 days after study drug is discontinued, giving a total of 5 months potential evaluation period. ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 35 **Units:** Participants ### Group **ID:** BG000 **Title:** Bevacizumab and TH-302 **Description:** Patients will be treated with combination of bevacizumab and TH-302. Bevacizumab: 10mg/kg TH-302: 670mg/m2 ### Measure #### Measurement **Group ID:** BG000 **Value:** 1 **Class Title:** 18-21 years #### Measurement **Group ID:** BG000 **Value:** 4 **Class Title:** 22-29 years #### Measurement **Group ID:** BG000 **Value:** 7 **Class Title:** 30-39 years #### Measurement **Group ID:** BG000 **Value:** 4 **Class Title:** 40-49 years #### Measurement **Group ID:** BG000 **Value:** 11 **Class Title:** 50-59 years #### Measurement **Group ID:** BG000 **Value:** 6 **Class Title:** 60-69 years #### Measurement **Group ID:** BG000 **Value:** 2 **Class Title:** 70-79 years ### Measure #### Measurement **Group ID:** BG000 **Value:** 11 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 24 **Category Title:** Male **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 10 **Class Title:** White : Female #### Measurement **Group ID:** BG000 **Value:** 15 **Class Title:** White : Male #### Measurement **Group ID:** BG000 **Value:** 0 **Class Title:** Black or African American : Female #### Measurement **Group ID:** BG000 **Value:** 1 **Class Title:** Black or African American : Male #### Measurement **Group ID:** BG000 **Value:** 1 **Class Title:** White/Hispanic or Latino : Female #### Measurement **Group ID:** BG000 **Value:** 6 **Class Title:** White/Hispanic or Latino : Male #### Measurement **Group ID:** BG000 **Value:** 0 **Class Title:** Asian : Female #### Measurement **Group ID:** BG000 **Value:** 2 **Class Title:** Asian : Male ### Measure #### Measurement **Group ID:** BG000 **Value:** 35 **Class Title:** United States **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 ### Measure 3 **Parameter Type:** NUMBER **Title:** Race/Ethnicity, 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 **PI Sponsor Employee:** True ### Point of Contact **Email:** [email protected] **Organization:** University of Texas Health San Antonio **Phone:** 210-450-5936 **Title:** Andrew Brenner, MD, PhD ## 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:** 35 **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 32 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** Safety lab tests and adverse event assessment **Parameter Type:** COUNT_OF_PARTICIPANTS **Reporting Status:** POSTED **Time Frame:** 4 months **Title:** Number of Patients With Adverse Events **Type:** PRIMARY **Unit of Measure:** Participants ##### Group **Description:** Patients will be treated with combination of bevacizumab and TH-302. Bevacizumab: 10mg/kg TH-302: 670mg/m2 **ID:** OG000 **Title:** Bevacizumab and TH-302 #### Outcome Measure 2 **Description:** Progression of disease by RANO criteria: The RANO criteria divides response into four types of response based on imaging and clinical features 1. complete response 2. partial response 3. stable disease 4. progression **Parameter Type:** NUMBER **Population Description:** 3 of the enrolled participants were not evaluable **Reporting Status:** POSTED **Time Frame:** 4 months **Title:** Progression Free Survival **Type:** SECONDARY **Unit of Measure:** Number of participants ##### Group **Description:** Patients will be treated with combination of bevacizumab and TH-302. Bevacizumab: 10mg/kg TH-302: 670mg/m2 **ID:** OG000 **Title:** Bevacizumab and TH-302 ### Participant Flow Module #### Group **Description:** Patients will be treated with combination of bevacizumab and TH-302. Bevacizumab: 10mg/kg TH-302: 670mg/m2 **ID:** FG000 **Title:** Bevacizumab and TH-302 #### Period **Title:** Overall Study ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 35 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 35 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 0 **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT05656079 **Acronym:** easy laugh **Brief Title:** To Evaluate the Cardiac Safety of Pegylated Liposomal Doxorubicin Concurrently Plus Trastuzumab and Pertuzumab in the Adjuvant Setting for Early-stage HER-2-positive Breast Cancer: a Multicenter, Randomized Controlled Clinical Study **Official Title:** To Evaluate the Cardiac Safety of Pegylated Liposomal Doxorubicin Concurrently Plus Trastuzumab and Pertuzumab in the Adjuvant Setting for Early-stage HER-2-positive Breast Cancer: a Multicenter, Randomized Controlled Clinical Study #### Organization Study ID Info **ID:** kazuma #### Organization **Class:** OTHER **Full Name:** Shanghai Pudong Hospital ### Status Module #### Completion Date **Date:** 2025-09 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2022-12-19 **Type:** ACTUAL **Last Update Submit Date:** 2022-12-11 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2024-09 **Type:** ESTIMATED #### Start Date **Date:** 2021-07-01 **Type:** ACTUAL **Status Verified Date:** 2022-12 #### Study First Post Date **Date:** 2022-12-19 **Type:** ACTUAL **Study First Submit Date:** 2022-12-11 **Study First Submit QC Date:** 2022-12-11 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** CSPC Ouyi Pharmaceutical Co., Ltd. #### Lead Sponsor **Class:** OTHER **Name:** Shanghai Pudong Hospital #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False ### Description Module **Brief Summary:** To evaluate the safety and efficacy of pegylated liposomal doxorubicin/cyclophosphamide/trastuzumab/pertuzumab followed by docetaxel/ trastuzumab/pertuzumab compared with epirubicin/cyclophosphamide followed by docetaxel/trastuzumab/pertuzumab in the adjuvant treatment of early breast cancer. ### Conditions Module **Conditions:** - Breast Cancer ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 204 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Pegylated liposomal doxorubicin 35 mg/m2, i.v. d1 +Cyclophosphamide 600 mg/m2 , i.v. d1 +Trastuzumab (8 mg/kg loading dose at first day only, then 6 mg/kg), i.v. d1+Pertuzumab (840 mg loading dose at first day only, then 420 mg), i.v. d1 ； q3w, for 4 cycles followed by Docetaxel 75mg/m2 , i.v. d1+ Pertuzumab 420 mg, i.v. d1+Trastuzumab 6 mg/kg, i.v. d1； q3w, for 4 cycles. After the completion of adjuvant therapy, patients are required to receive a total of 1 year of treatment with trastuzumab combined with pertuzumab. **Intervention Names:** - Drug: Pegylated liposomal doxorubicin - Drug: Cyclophosphamid - Drug: Trastuzumab - Drug: Pertuzumab - Drug: Docetaxel **Label:** pegylated liposomal doxorubicin；cyclophosphamide；trastuzumab；pertuzumab ；docetaxel **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Epirubicin 90 mg/m2 , i.v. d1 +Cyclophosphamide 600 mg/m2 , i.v. d1； q3w, for 4 cycles followed by Docetaxel 75mg/m2 , i.v. d1+Trastuzumab (8 mg/kg loading dose at first day only, then 6 mg/kg), i.v. d1+Pertuzumab (840 mg loading dose at first day only, then 420 mg), i.v. d1； q3w, for 4 cycles. After the completion of adjuvant therapy, patients are required to receive a total of 1 year of treatment with trastuzumab combined with pertuzumab. **Intervention Names:** - Drug: Epirubicin - Drug: Cyclophosphamid - Drug: Trastuzumab - Drug: Pertuzumab - Drug: Docetaxel **Label:** Epirubicin；cyclophosphamide f；docetaxel；trastuzumab；pertuzumab **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - pegylated liposomal doxorubicin；cyclophosphamide；trastuzumab；pertuzumab ；docetaxel **Description:** Drug: Pegylated liposomal doxorubicin (35 mg/m2) will be administered by an intravenous infusion on day 1 of each21-day cycle. **Name:** Pegylated liposomal doxorubicin **Other Names:** - duomeisu - Doxorubicin Hydrochloride Liposome Injection **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Epirubicin；cyclophosphamide f；docetaxel；trastuzumab；pertuzumab **Description:** Drug: Epirubicin (90 mg/m2) will be administered by an intravenous infusion on day 1 of each 21-day cycle. **Name:** Epirubicin **Other Names:** - biaoroubixing **Type:** DRUG #### Intervention 3 **Arm Group Labels:** - Epirubicin；cyclophosphamide f；docetaxel；trastuzumab；pertuzumab - pegylated liposomal doxorubicin；cyclophosphamide；trastuzumab；pertuzumab ；docetaxel **Description:** Drug: Cyclophosphamide (600 mg/m2) will be administered by an intravenous infusion on day 1 of each 21-day cycle. **Name:** Cyclophosphamid **Other Names:** - huanlinxianan **Type:** DRUG #### Intervention 4 **Arm Group Labels:** - Epirubicin；cyclophosphamide f；docetaxel；trastuzumab；pertuzumab - pegylated liposomal doxorubicin；cyclophosphamide；trastuzumab；pertuzumab ；docetaxel **Description:** Drug: Trastuzumab (8 mg/kg loading dose at first day only, then 6 mg/kg) will be administered by an intravenous infusion on day 1 of each 21-day cycle. **Name:** Trastuzumab **Other Names:** - qutuozhudankang **Type:** DRUG #### Intervention 5 **Arm Group Labels:** - Epirubicin；cyclophosphamide f；docetaxel；trastuzumab；pertuzumab - pegylated liposomal doxorubicin；cyclophosphamide；trastuzumab；pertuzumab ；docetaxel **Description:** Drug: Pertuzumab (840 mg loading dose at first day only, then 420 mg) will be administered by an intravenous infusion on day 1 of each 21-day cycle. **Name:** Pertuzumab **Other Names:** - patuozhudankang **Type:** DRUG #### Intervention 6 **Arm Group Labels:** - Epirubicin；cyclophosphamide f；docetaxel；trastuzumab；pertuzumab - pegylated liposomal doxorubicin；cyclophosphamide；trastuzumab；pertuzumab ；docetaxel **Description:** Drug: Docetaxel (75mg/m2) will be administered by an intravenous infusion on day 1 of each 21-day cycle. **Name:** Docetaxel **Other Names:** - duoxitasai **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Measure:** 1-year incidence of cardiotoxicity **Time Frame:** 1-year ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. 18-70 years old, Female; 2. Subjects with histopathologically confirmed invasive breast cancer; 3. HER2-positive breast cancer (Immunohistochemistry score of 3+ or fluorescence in situ hybridization positivity); 4. No distant metastasis; 5. Lymph node positive or negative, primary tumour≥2cm; 6. Lymph node negative，primary tumour≤2cm and any of the following factors; 1) Histological grade 3; 2) ER negative (\<10%) and PR negative (\<20%); 3) Age\<35 years old; 4) Pathological hint: vascular invasion or intravascular cancer thrombus; 7. Surgery was completed and chemotherapy was started within 8 weeks after surgery; 8. Before and after chemotherapy LVEF≥55%; 9. ECOG performance status of 0-1; 10. Signed the informed consent. Exclusion Criteria: 1. Subjects who are known to be allergic or intolerant to chemotherapy drugs or their excipients; 2. Previously suffered from invasive breast cancer, and other malignant tumors within 5 years (excluding carcinoma in situ of the cervix, carcinoma in situ of the rectum, carcinoma in situ of melanoma, basal cell carcinoma of the skin, and squamous cell carcinoma); 3. For breast cancer, have received any anti-tumor therapy before randomization (except surgical treatment before enrollment); 4. Hematopoietic function, renal function and liver function meet one of the following conditions: 1) Neutrophil count ≤1.5×109/L; 2) Platelet count ≤ 50×109/L; 3) Hemoglobin ≤ 8.0g/dL; 4) Creatinine clearance rate ≤30ml/min; 5) AST and ALT ≥ 2.5 times the upper limit of normal in subjects without liver metastases; 6) Bilirubin ≥ 2 times the upper limit of normal; 7) APTT/PT≥1.5 times the upper limit of normal; 5. Have a history of cardiovascular disease or associated with severe cardiovascular disease, lung disease; 6. Active hypertension: systolic blood pressure ≥ 180mmHg, diastolic blood pressure ≥ 90mmHg; 7. NYHA cardiac insufficiency grading ≥ Ⅲ grade; 8. Severe, uncontrollable systemic disease; 9. Subjects who are pregnant or breastfeeding, or subjects who cannot ensure effective contraceptive measures during the study treatment; 10. Subjects who participated in other clinical trials at the same time; 11. Subjects determined by the investigator to be inappropriate to participate in this study. **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:** Yongping Li **Phone:** 021 68035102 **Role:** CONTACT #### Locations **Location 1:** **City:** Shanghai **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Yongping Li - **Role:** CONTACT **Country:** China **Facility:** Shanghai Pudong Hospital **Status:** RECRUITING ## 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 ### Intervention Browse Module - Ancestors - ID: D000007166 - Term: Immunosuppressive Agents - ID: D000007155 - Term: Immunologic Factors - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000018501 - Term: Antirheumatic Agents - ID: D000018906 - Term: Antineoplastic Agents, Alkylating - ID: D000000477 - Term: Alkylating Agents - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000000970 - Term: Antineoplastic Agents - ID: D000019653 - Term: Myeloablative Agonists - ID: D000050257 - Term: Tubulin Modulators - ID: D000050256 - Term: Antimitotic Agents - ID: D000050258 - Term: Mitosis Modulators - ID: D000000903 - Term: Antibiotics, Antineoplastic - ID: D000059005 - Term: Topoisomerase II Inhibitors - ID: D000059003 - Term: Topoisomerase Inhibitors - ID: D000004791 - Term: Enzyme Inhibitors - ID: D000074322 - Term: Antineoplastic Agents, Immunological ### 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: M6727 - Name: Cyclophosphamide - Relevance: HIGH - As Found: Cycle - ID: M7492 - Name: Doxorubicin - Relevance: HIGH - As Found: Women - ID: M227339 - Name: Liposomal doxorubicin - Relevance: HIGH - As Found: Sexual - ID: M17954 - Name: Epirubicin - Relevance: HIGH - As Found: 12 hours - ID: M1668 - Name: Docetaxel - Relevance: HIGH - As Found: Physical - ID: M325 - Name: Trastuzumab - Relevance: HIGH - As Found: Medication - ID: M289243 - Name: Pertuzumab - Relevance: HIGH - As Found: Safety Study - 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: M20942 - Name: Antineoplastic Agents, Alkylating - Relevance: LOW - As Found: Unknown - ID: M3820 - Name: Alkylating 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 - 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 - ID: M1346 - Name: Antineoplastic Agents, Immunological - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000003520 - Term: Cyclophosphamide - ID: D000077143 - Term: Docetaxel - ID: D000004317 - Term: Doxorubicin - ID: C000506643 - Term: Liposomal doxorubicin - ID: D000068878 - Term: Trastuzumab - ID: D000015251 - Term: Epirubicin - ID: C000485206 - Term: Pertuzumab ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00669279 **Brief Title:** Effect of Carvedilol Controlled-Release (CR) and Atenolol on Central Blood Pressure **Official Title:** Non-Invasive Determination of Central Aortic Blood Pressure in Hypertensive Patients Treated With Controlled-Release Carvedilol or Atenolol #### Organization Study ID Info **ID:** 8COG11059 #### Organization **Class:** OTHER **Full Name:** University of Florida ### Status Module #### Completion Date **Date:** 2010-07 **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:** 2010-07 **Type:** ACTUAL #### Results First Post Date **Date:** 2012-03-23 **Type:** ESTIMATED **Results First Submit Date:** 2011-12-05 **Results First Submit QC Date:** 2012-02-17 #### Start Date **Date:** 2008-04 **Status Verified Date:** 2017-09 #### Study First Post Date **Date:** 2008-04-30 **Type:** ESTIMATED **Study First Submit Date:** 2008-04-28 **Study First Submit QC Date:** 2008-04-29 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** GlaxoSmithKline #### Lead Sponsor **Class:** OTHER **Name:** University of Florida #### 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 research study is to determine whether atenolol or controlled release carvedilol lower blood pressure in the body as effectively as in the arm. Blood pressure measured in the aorta, a large blood vessel carrying blood away from the heart, may be a better measure of the harmful effects of high blood pressure on the body's organs. In the past, blood pressure has only been measured in the arms. However, blood pressure in the arms may not accurately reflect the blood pressure in the aorta and thus may mislead doctors treating high blood pressure. For this reason, we are testing whether two different medications for blood pressure, both in a class called beta blockers, have similar effects on blood pressure in the arm and aorta. **Detailed Description:** Carvedilol reduces aortic wave reflection and improves left ventricular/vascular coupling: a comparison with atenolol (CENTRAL Study) is a prospective, open-label, comparative, randomized control trial that evaluated brachial and central hemodynamic profiles in patients taking atenolol or controlled-release carvedilol. ### Conditions Module **Conditions:** - Hypertension ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** SINGLE **Who Masked:** - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 41 **Type:** ACTUAL **Phases:** - PHASE4 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Intervention Names:** - Drug: Carvedilol CR **Label:** Carvedilol CR **Type:** EXPERIMENTAL #### Arm Group 2 **Intervention Names:** - Drug: Atenolol **Label:** Atenolol **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Carvedilol CR **Description:** Dose titration of 20mg by mouth once daily for 1 week, then 40mg by mouth once daily for 1 week, then 80mg by mouth once daily for 2 weeks **Name:** Carvedilol CR **Other Names:** - Coreg CR **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Atenolol **Description:** Dose titration of 25mg by mouth once daily for 1 week, then 50mg by mouth once daily for 1 week, then 100mg by mouth once daily for 2 weeks **Name:** Atenolol **Other Names:** - Tenormin **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Measure:** Central Aortic Blood Pressure **Time Frame:** Measured at baseline and 4 weeks. #### Secondary Outcomes **Measure:** Peripheral Blood Pressure **Time Frame:** Measured at baseline, 2 weeks, and 4 weeks. ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * At least 18 years of age * Hypertension (untreated or treated with no more then one anti-hypertensive drug) Exclusion Criteria: * Secondary forms of hypertension (including sleep apnea) * Patients currently treated with two or more antihypertensive drugs * Patients taking antihypertensive drugs with properly measured clinic systolic blood pressure greater then 170mmHg * Isolated systolic hypertension * Other diseases requiring treatment with blood pressure lowering medications * Heart rate less then 55 beats/min (in the absence of beta-blocker therapy) * Known cardiovascular disease including history of angina pectoris, heart failure, presence of a cardiac pacemaker, history of myocardial infarction or revascularization procedure, or cerebrovascular disease (including stroke and TIA) * Known diabetes mellitus (Type 1 or 2) * Renal insufficiency defined as a serum creatinine greater then 1.5mg/dL in males and 1.4mg/dL in females * Primary renal disease * Pregnancy or lactation * History of Raynaud's syndrome * Alcoholism and recreational drug use (due to compliance concerns) **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Gainesville **Country:** United States **Facility:** University of Florida **State:** Florida **Zip:** 32610 #### Overall Officials **Official 1:** **Affiliation:** University of Florida **Name:** Benjamin Epstein, Pharm.D. **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: BC14 - Name: Heart and Blood Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M10024 - Name: Hypertension - Relevance: HIGH - As Found: Hypertension - ID: M17400 - Name: Vascular Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000006973 - Term: Hypertension ### Intervention Browse Module - Ancestors - ID: D000000319 - Term: Adrenergic beta-Antagonists - ID: D000018674 - Term: Adrenergic Antagonists - 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: D000000959 - Term: Antihypertensive Agents - ID: D000000975 - Term: Antioxidants - ID: D000020011 - Term: Protective Agents - ID: D000002121 - Term: Calcium Channel Blockers - ID: D000049990 - Term: Membrane Transport Modulators - ID: D000077264 - Term: Calcium-Regulating Hormones and Agents - ID: D000014665 - Term: Vasodilator Agents - ID: D000058668 - Term: Adrenergic alpha-1 Receptor Antagonists - ID: D000000317 - Term: Adrenergic alpha-Antagonists - ID: D000000889 - Term: Anti-Arrhythmia Agents - ID: D000013565 - Term: Sympatholytics - ID: D000001337 - Term: Autonomic Agents - ID: D000018373 - Term: Peripheral Nervous System Agents - ID: D000058671 - Term: Adrenergic beta-1 Receptor Antagonists ### Intervention Browse Module - Browse Branches - Abbrev: AnAg - Name: Antihypertensive Agents - Abbrev: ChanBlk - Name: Channel Blockers - Abbrev: VaDiAg - Name: Vasodilator Agents - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: AnArAg - Name: Anti-Arrhythmia Agents - Abbrev: BDCA - Name: Bone Density Conservation Agents ### Intervention Browse Module - Browse Leaves - ID: M1718 - Name: Carvedilol - Relevance: HIGH - As Found: B-cell lymphoma - ID: M4568 - Name: Atenolol - Relevance: HIGH - As Found: Minocycline - ID: M3671 - Name: Adrenergic beta-Antagonists - Relevance: LOW - As Found: Unknown - ID: M20746 - Name: Adrenergic Agents - Relevance: LOW - As Found: Unknown - ID: M20755 - Name: Adrenergic Antagonists - Relevance: LOW - As Found: Unknown - ID: M20504 - Name: Neurotransmitter Agents - Relevance: LOW - As Found: Unknown - ID: M4277 - Name: Antihypertensive Agents - Relevance: LOW - As Found: Unknown - ID: M4292 - Name: Antioxidants - Relevance: LOW - As Found: Unknown - ID: M21869 - Name: Protective Agents - Relevance: LOW - As Found: Unknown - ID: M5381 - Name: Calcium - Relevance: LOW - As Found: Unknown - ID: M5384 - Name: Calcium Channel Blockers - Relevance: LOW - As Found: Unknown - ID: M5398 - Name: Calcium, Dietary - Relevance: LOW - As Found: Unknown - ID: M9789 - Name: Hormones - Relevance: LOW - As Found: Unknown - ID: M17412 - Name: Vasodilator Agents - Relevance: LOW - As Found: Unknown - ID: M29194 - Name: Adrenergic alpha-1 Receptor Antagonists - Relevance: LOW - As Found: Unknown - ID: M3669 - Name: Adrenergic alpha-Antagonists - Relevance: LOW - As Found: Unknown - ID: M4213 - Name: Anti-Arrhythmia Agents - Relevance: LOW - As Found: Unknown - ID: M16344 - Name: Sympatholytics - Relevance: LOW - As Found: Unknown - ID: M29197 - Name: Adrenergic beta-1 Receptor Antagonists - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000001262 - Term: Atenolol - ID: D000077261 - Term: Carvedilol ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module #### Event Groups **Group ID:** EG000 **Title:** Carvedilol CR **Description:** Controlled-release carvedilol 20 mg - Forced titration occurred in carvedilol to 40 mg at week one, and to 80 mg at week two. **ID:** EG000 **Other Num at Risk:** 22 **Serious Number At Risk:** 22 **Title:** Carvedilol CR **Group ID:** EG001 **Title:** Atenolol **Description:** Atenolol 25 mg once daily - Forced titration occurred in atenolol to 50 mg at week one, and to 100 mg at week two. **ID:** EG001 **Other Num at Risk:** 19 **Serious Number At Risk:** 19 **Title:** Atenolol **Frequency Threshold:** 0 ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 22 **Group ID:** BG001 **Value:** 19 **Group ID:** BG002 **Value:** 41 **Units:** Participants ### Group **ID:** BG000 **Title:** Carvedilol CR **Description:** Controlled-release carvedilol 20 mg - Forced titration occurred in carvedilol to 40 mg at week one, and to 80 mg at week two. ### Group **ID:** BG001 **Title:** Atenolol **Description:** Atenolol 25 mg once daily - Forced titration occurred in atenolol to 50 mg at week one, and to 100 mg at week two. ### Group **ID:** BG002 **Title:** Total **Description:** Total of all reporting groups ### Measure #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** <=18 years #### Measurement **Group ID:** BG000 **Value:** 22 #### Measurement **Group ID:** BG001 **Value:** 19 #### Measurement **Group ID:** BG002 **Value:** 41 **Category Title:** Between 18 and 65 years #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** >=65 years **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Spread:** 13.1 **Value:** 47.7 #### Measurement **Group ID:** BG001 **Spread:** 9.9 **Value:** 46.1 #### Measurement **Group ID:** BG002 **Spread:** 11.5 **Value:** 46.9 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 13 #### Measurement **Group ID:** BG001 **Value:** 13 #### Measurement **Group ID:** BG002 **Value:** 26 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 9 #### Measurement **Group ID:** BG001 **Value:** 6 #### Measurement **Group ID:** BG002 **Value:** 15 **Category Title:** Male **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 22 #### Measurement **Group ID:** BG001 **Value:** 19 #### Measurement **Group ID:** BG002 **Value:** 41 **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 ### Limitations and Caveats **Description:** Small sample size, short duration. ### Point of Contact **Email:** [email protected] **Organization:** University of Florida **Phone:** 3523590945 **Title:** Dr. Benjamin J Epstein ## 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:** 10.4 - **Upper Limit:** - **Value:** -16.1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 18.7 - **Upper Limit:** - **Value:** -16.0 **Title:** #### Outcome Measure 2 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Dispersion Type:** Standard Error **Parameter Type:** MEAN **Reporting Status:** POSTED **Time Frame:** Measured at baseline and 4 weeks. **Title:** Central Aortic Blood Pressure **Type:** PRIMARY **Unit of Measure:** mmHg ##### Group **Description:** Controlled-release carvedilol 20 mg - Forced titration occurred in carvedilol to 40 mg at week one, and to 80 mg at week two. **ID:** OG000 **Title:** Carvedilol CR ##### Group **Description:** Atenolol 25 mg once daily - Forced titration occurred in atenolol to 50 mg at week one, and to 100 mg at week two. **ID:** OG001 **Title:** Atenolol #### Outcome Measure 2 **Reporting Status:** NOT_POSTED **Time Frame:** Measured at baseline, 2 weeks, and 4 weeks. **Title:** Peripheral Blood Pressure **Type:** SECONDARY ### Participant Flow Module #### Group **Description:** Controlled-release carvedilol 20 mg - Forced titration occurred in carvedilol to 40 mg at week one, and to 80 mg at week two. **ID:** FG000 **Title:** Carvedilol CR #### Group **Description:** Atenolol 25 mg once daily - Forced titration occurred in atenolol to 50 mg at week one, and to 100 mg at week two. **ID:** FG001 **Title:** Atenolol #### Period **Title:** Overall Study ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 22 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 19 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 22 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 19 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 0 **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT00079079 **Brief Title:** Cisplatin or Carboplatin Combined With Gemcitabine in Locally Advanced, Recurrent, or Metastatic Malignant Salivary Gland Tumor **Official Title:** A Phase II Study of Cisplatin and Gemcitabine in Patients With Locally Advanced/Recurrent or Metastatic Malignant Salivary Gland Tumors #### Organization Study ID Info **ID:** HN4 #### Organization **Class:** NETWORK **Full Name:** Canadian Cancer Trials Group #### Secondary ID Infos **Domain:** PDQ **ID:** CAN-NCIC-HN4 **Type:** OTHER **Domain:** LILLY **ID:** LILLY-CAN-NCIC-HN4 **Type:** OTHER **Domain:** PDQ **ID:** CDR0000353487 **Type:** OTHER ### Status Module #### Completion Date **Date:** 2009-02-10 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2023-08-04 **Type:** ACTUAL **Last Update Submit Date:** 2023-08-03 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2008-09-29 **Type:** ACTUAL #### Start Date **Date:** 2003-10-27 **Type:** ACTUAL **Status Verified Date:** 2020-04 #### Study First Post Date **Date:** 2004-03-09 **Type:** ESTIMATED **Study First Submit Date:** 2004-03-08 **Study First Submit QC Date:** 2004-03-08 ### 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, such as cisplatin, carboplatin, and gemcitabine, work in different ways to stop tumor cells from dividing so they stop growing or die. Giving more than one drug may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving gemcitabine together with either cisplatin or carboplatin works in treating patients with locally advanced, recurrent, or metastatic malignant salivary gland tumor (cancer). **Detailed Description:** OBJECTIVES: Primary * Determine the activity of cisplatin or carboplatin in combination with gemcitabine, in terms of response rate, in patients with locally advanced, recurrent, or metastatic malignant salivary gland tumor. Secondary * Determine the complete response in patients treated with these regimens. * Determine the duration of response in patients treated with these regimens. * Determine the toxicity profile of these regimens in these patients. * Determine the overall survival of patients treated with these regimens. OUTLINE: This is a multicenter study. Patients receive gemcitabine IV over 30 minutes on days 1 and 8. Patients also receive either cisplatin IV over 1 hour on day 2 OR carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients are followed at 4 weeks, every 3 months for 1 year, and then every 6 months thereafter until relapse. PROJECTED ACCRUAL: A total of 11- 34 patients will be accrued for this study within 1.5-3 years. ### Conditions Module **Conditions:** - Head and Neck Cancer **Keywords:** - stage II salivary gland cancer - stage III salivary gland cancer - stage IV salivary gland cancer - recurrent salivary gland cancer - salivary gland acinic cell tumor - salivary gland adenoid cystic carcinoma - salivary gland poorly differentiated carcinoma - high-grade salivary gland mucoepidermoid carcinoma - low-grade salivary gland mucoepidermoid carcinoma - salivary gland malignant mixed cell type tumor - salivary gland adenocarcinoma - salivary gland anaplastic carcinoma - salivary gland squamous cell carcinoma ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 34 **Type:** ACTUAL **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module ### Interventions #### Intervention 1 **Name:** carboplatin **Type:** DRUG #### Intervention 2 **Name:** cisplatin **Type:** DRUG #### Intervention 3 **Name:** gemcitabine hydrochloride **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Measure:** Objective response measured by RECIST criteria after accrual of 11 evaluable patients #### Secondary Outcomes **Measure:** Toxicity assessed by NCI CTC v2.0 **Measure:** Overall survival ### Eligibility Module **Eligibility Criteria:** DISEASE CHARACTERISTICS: * Histologically or cytologically confirmed malignant salivary gland tumor * All histological subtypes eligible * Locally advanced, recurrent, or metastatic disease * Considered incurable by radiotherapy or surgery * Low- to intermediate-grade mucoepidermoid tumor or acinic cell carcinoma allowed provided patients are symptomatic OR at imminent risk of developing symptoms attributable to metastatic disease * Disease must meet 1 of the following criteria: * Metastatic disease that is chemonaïve * Metastatic disease that has progressed after a prior non-cisplatin/carboplatin/gemcitabine regimen * Local and/or distant recurrence after curative surgery and/or radiotherapy * Locally advanced disease not suitable for surgery or radiotherapy * At least 1 site of unidimensionally measurable disease documented by 1 of the following: * At least 20 mm by X-ray, physical exam, or non-spiral CT scan * At least 10 mm by spiral CT scan * No bone metastases as only site of measurable disease * No known brain metastasis PATIENT CHARACTERISTICS: Age * 18 and over Performance status * ECOG 0-2 Life expectancy * At least 12 weeks Hematopoietic * Absolute granulocyte count ≥ 1,500/mm\^3 * Platelet count ≥ 100,000/mm\^3 Hepatic * AST/ALT no greater than 3 times upper limit of normal Renal * Creatinine clearance at least 60 mL/min (for cisplatin) OR 30-59 mL/min (for carboplatin) Cardiovascular * No symptomatic congestive heart failure * No unstable angina * No cardiac arrhythmia Other * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No other serious illness or medical condition that would preclude study participation * No active uncontrolled infection * No neurologic disorder or psychiatric illness that would preclude study compliance * No other malignancy within the past 5 years except adequately treated non-melanoma skin cancer or carcinoma in situ of the cervix PRIOR CONCURRENT THERAPY: Biologic therapy * Not specified Chemotherapy * See Disease Characteristics * At least 4 weeks since prior chemotherapy for locally advanced, recurrent, or metastatic disease and recovered * Must have been a non-cisplatin/carboplatin/gemcitabine-containing regimen * More than 12 months since prior adjuvant chemotherapy (including cisplatin/carboplatin-based regimens) and recovered * No prior gemcitabine Endocrine therapy * Not specified Radiotherapy * See Disease Characteristics * At least 4 weeks since prior radiotherapy and recovered * No prior radiotherapy to only site of measurable disease unless there is documented disease progression after therapy Surgery * See Disease Characteristics * At least 21 days since prior surgery and recovered Other * More than 30 days since prior anticancer therapy * More than 30 days since prior investigational agents * No other concurrent anticancer therapy * No other concurrent investigational agents **Maximum Age:** 120 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Winnipeg **Country:** Canada **Facility:** CancerCare Manitoba **State:** Manitoba **Zip:** R3E 0V9 **Location 2:** **City:** London **Country:** Canada **Facility:** London Regional Cancer Program at London Health Sciences Centre **State:** Ontario **Zip:** N6A 4L6 **Location 3:** **City:** Ottawa **Country:** Canada **Facility:** Ottawa Hospital Regional Cancer Centre - General Campus **State:** Ontario **Zip:** K1H 8L6 **Location 4:** **City:** Toronto **Country:** Canada **Facility:** Princess Margaret Hospital **State:** Ontario **Zip:** M5G 2M9 #### Overall Officials **Official 1:** **Affiliation:** Princess Margaret Hospital, Canada **Name:** Lillian L. Siu, MD, FRCPC **Role:** STUDY_CHAIR ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Laurie SA, Siu LL, Winquist E, Maksymiuk A, Harnett EL, Walsh W, Tu D, Parulekar WR. A phase 2 study of platinum and gemcitabine in patients with advanced salivary gland cancer: a trial of the NCIC Clinical Trials Group. Cancer. 2010 Jan 15;116(2):362-8. doi: 10.1002/cncr.24745. **PMID:** 19924794 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000006258 - Term: Head and Neck Neoplasms - ID: D000009371 - Term: Neoplasms by Site - ID: D000009369 - Term: Neoplasms - ID: D000009062 - Term: Mouth Neoplasms - ID: D000009059 - Term: Mouth Diseases - ID: D000009057 - Term: Stomatognathic Diseases - ID: D000012466 - Term: Salivary Gland Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: BC07 - Name: Mouth and Tooth Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M9348 - Name: Head and Neck Neoplasms - Relevance: LOW - As Found: Unknown - ID: M5534 - Name: Carcinoma - Relevance: LOW - As Found: Unknown - ID: M5550 - Name: Carcinoma, Squamous Cell - Relevance: LOW - As Found: Unknown - ID: M3585 - Name: Adenocarcinoma - Relevance: LOW - As Found: Unknown - ID: M14850 - Name: Recurrence - Relevance: LOW - As Found: Unknown - ID: M15287 - Name: Salivary Gland Neoplasms - Relevance: HIGH - As Found: Salivary Gland Tumors - ID: M6733 - Name: Carcinoma, Adenoid Cystic - Relevance: LOW - As Found: Unknown - ID: M20412 - Name: Carcinoma, Acinar Cell - Relevance: LOW - As Found: Unknown - ID: M20422 - Name: Carcinoma, Mucoepidermoid - Relevance: LOW - As Found: Unknown - ID: M20442 - Name: Mucoepidermoid Tumor - Relevance: LOW - As Found: Unknown - ID: M12022 - Name: Mouth Neoplasms - 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 - ID: M15285 - Name: Salivary Gland Diseases - Relevance: LOW - As Found: Unknown - ID: T201 - Name: Adenoid Cystic Carcinoma - Relevance: LOW - As Found: Unknown - ID: T105 - Name: Acinic Cell Carcinoma - Relevance: LOW - As Found: Unknown - ID: T3898 - Name: Mucoepidermoid Carcinoma - Relevance: LOW - As Found: Unknown - ID: T4265 - Name: Oral Cancer - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000012468 - Term: Salivary Gland Neoplasms ### Intervention Browse Module - Ancestors - ID: D000000970 - Term: Antineoplastic Agents - ID: D000000964 - Term: Antimetabolites, Antineoplastic - ID: D000000963 - Term: Antimetabolites - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action ### Intervention Browse Module - Browse Branches - Abbrev: ANeo - Name: Antineoplastic Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M6182 - Name: Cisplatin - Relevance: LOW - As Found: Unknown - ID: M2985 - Name: Gemcitabine - Relevance: HIGH - As Found: Suspension - ID: M18650 - Name: Carboplatin - Relevance: HIGH - As Found: System - ID: M4281 - Name: Antimetabolites - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000016190 - Term: Carboplatin - ID: D000093542 - Term: Gemcitabine ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00505479 **Brief Title:** Iodine Status in Pregnant Women and Their Newborns: is Congenital Hypothyroidism Related to Iodine Deficiency in Pregnancy? #### Organization Study ID Info **ID:** G20020584 #### Organization **Class:** OTHER **Full Name:** Zhejiang University ### Status Module #### Completion Date **Date:** 2010-05 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** RECRUITING #### Last Update Post Date **Date:** 2007-07-23 **Type:** ESTIMATED **Last Update Submit Date:** 2007-07-20 **Overall Status:** UNKNOWN #### Start Date **Date:** 2007-05 **Status Verified Date:** 2007-07 #### Study First Post Date **Date:** 2007-07-23 **Type:** ESTIMATED **Study First Submit Date:** 2007-07-20 **Study First Submit QC Date:** 2007-07-20 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Zhejiang University ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** Iodine is an essential component of thyroid hormone, which is necessary for many metabolic processes as well as the maturation of the CNS. Deficiencies of iodine have deleterious effects on both pregnant women and infants. The iodine status of the population after implementation of the universal salt iodization program in Zhejiang province has not been known. This study was to determine whether pregnant women show evidence of iodine deficiency, and to examine the correlation between maternal urine iodine concentration and newborn thyroid function. **Detailed Description:** Iodine is an essential component of thyroid hormone, which is necessary for many metabolic processes as well as the maturation of the CNS. Deficiencies of iodine have deleterious effects on both pregnant women and infants. The iodine status of the population after implementation of the universal salt iodization program in Zhejiang province has not been known. This study was to determine whether pregnant women show evidence of iodine deficiency, and to examine the correlation between maternal urine iodine concentration and newborn thyroid function. Healthy women at 12 weeks' gestation and over from four different areas in Zhejiang province were enrolled to participate this program from May 2007 to May 2010. Women consented to provide urine samples and salt samples during pregnancy (12, 16, 24 weeks' gestation and before delivery), and give permission to access their newborn's TSH value. Urinary iodine concentration (UIC) was determined by ammonium persulfate digestion microplate method, and TSH was determined by a time resolved fluoro-immunoassay (TRFIA). The diagnostic standard for congenital hypothyroidism was: TSH ≥ 20 mU/L and declined FT4 levels. Compare the correlation to effects with different level of iodine content in salt, maternal UIC and neonatal TSH. Investigate the optimal level of iodine content in salt in different areas in ZheJiang province. ### Conditions Module **Conditions:** - Congenital Hypothyroidism - Pregnancy - Iodine Deficiency **Keywords:** - Congenital Hypothyroidism - pregnancy - iodine - deficiency ### Design Module #### Design Info **Time Perspective:** PROSPECTIVE **Study Type:** OBSERVATIONAL ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Pregnant women in Zhejiang province (and their newborns) Exclusion Criteria: * Endocrine disease **Healthy Volunteers:** True **Maximum Age:** 40 Years **Minimum Age:** 20 Years **Sex:** FEMALE **Standard Ages:** - ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Zhengyan Zhao, M.D. **Phone:** 008657187061007 **Role:** CONTACT #### Locations **Location 1:** **City:** Hangzhou **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Zhengyan Zhao, M.D. - **Phone:** 008657187061007 - **Role:** CONTACT ***Contact 2:*** - **Name:** Zhengyan Zhao, M.D. - **Role:** PRINCIPAL_INVESTIGATOR **Country:** China **Facility:** Children's Hospital Zhejiang University School of Medicine **State:** Zhejiang **Status:** RECRUITING **Zip:** 310003 #### Overall Officials **Official 1:** **Affiliation:** Children's Hospital Zhejiang University School of Medicine **Name:** zhengyan Zhao, M.D. **Role:** STUDY_DIRECTOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000013959 - Term: Thyroid Diseases - ID: D000004700 - Term: Endocrine System Diseases - ID: D000004392 - Term: Dwarfism - ID: D000001848 - Term: Bone Diseases, Developmental - ID: D000001847 - Term: Bone Diseases - ID: D000009140 - Term: Musculoskeletal Diseases - ID: D000001849 - Term: Bone Diseases, Endocrine - ID: D000030342 - Term: Genetic Diseases, Inborn ### Condition Browse Module - Browse Branches - Abbrev: BC19 - Name: Gland and Hormone Related Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC05 - Name: Musculoskeletal Diseases - Abbrev: BC16 - Name: Diseases and Abnormalities at or Before Birth - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M10087 - Name: Hypothyroidism - Relevance: HIGH - As Found: Hypothyroidism - ID: M6623 - Name: Congenital Hypothyroidism - Relevance: HIGH - As Found: Congenital Hypothyroidism - ID: M16718 - Name: Thyroid Diseases - Relevance: LOW - As Found: Unknown - ID: M7862 - Name: Endocrine System Diseases - Relevance: LOW - As Found: Unknown - ID: M7566 - Name: Dwarfism - Relevance: LOW - As Found: Unknown - ID: M5126 - Name: Bone Diseases - Relevance: LOW - As Found: Unknown - ID: M5127 - Name: Bone Diseases, Developmental - Relevance: LOW - As Found: Unknown - ID: M12097 - Name: Musculoskeletal Diseases - Relevance: LOW - As Found: Unknown - ID: M5128 - Name: Bone Diseases, Endocrine - Relevance: LOW - As Found: Unknown - ID: M23686 - Name: Genetic Diseases, Inborn - Relevance: LOW - As Found: Unknown - ID: T1512 - Name: Congenital Hypothyroidism - Relevance: HIGH - As Found: Congenital Hypothyroidism ### Condition Browse Module - Meshes - ID: D000003409 - Term: Congenital Hypothyroidism - ID: D000007037 - Term: Hypothyroidism ### Intervention Browse Module - Browse Branches - Abbrev: Micro - Name: Micronutrients - Abbrev: Infe - Name: Anti-Infective Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M10488 - Name: Iodine - Relevance: LOW - As Found: Unknown - ID: M229695 - Name: Cadexomer iodine - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05818579 **Brief Title:** Virtual Reality for Mental Well-being in Older People With Physical Disabilities **Official Title:** The Effects of Therapeutic Virtual Reality Experience to Promote Mental Well-being in Older People Living With Physical Disabilities in Long-term Care Facilities #### Organization Study ID Info **ID:** MHI2_0071 #### Organization **Class:** OTHER **Full Name:** Tung Wah College ### Status Module #### Completion Date **Date:** 2025-05-14 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2023-04-19 **Type:** ACTUAL **Last Update Submit Date:** 2023-04-05 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2025-02-14 **Type:** ESTIMATED #### Start Date **Date:** 2024-02-15 **Type:** ESTIMATED **Status Verified Date:** 2023-04 #### Study First Post Date **Date:** 2023-04-19 **Type:** ACTUAL **Study First Submit Date:** 2023-04-05 **Study First Submit QC Date:** 2023-04-05 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** Chinese University of Hong Kong **Class:** UNKNOWN **Name:** Golden Age Foundation **Class:** OTHER **Name:** Pok Oi Hospital #### Lead Sponsor **Class:** OTHER **Name:** Tung Wah College #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** Objectives This study aims to examine the effects of the therapeutic virtual reality (VR) experience in older people with physical disabilities in long-term care facilities (LTCF) in 1) increasing mental well-being, 2) reducing depressive symptoms, 3) reducing loneliness, 4) increasing health-related quality of life, and 5) increasing perceived social support. If this intervention is successful, this study will yield new knowledge about the effects of this innovative intervention. Also, an innovative VR intervention will be available to promote the mental well-being of older residents in LTCF. Trial design This study employs a single-blinded, two-parallel-group (intervention-to-control group ratio=1:1), non-inferiority, randomized controlled trial. Study setting This study will be conducted in the LTCF. Participants will be recruited from Care \& Attention Homes for the Elderly and Nursing Homes under the governance of the Social Welfare Department in Hong Kong. Eligibility criteria Inclusion: 1) Aged 60 years or above; 2) LTCF residents; and 3) Physical disability, defined as the Modified Barthel Index (MBI) score of ≤ 90 (i.e., moderately dependent or worse). Exclusion: 1) Probably dementia, as defined by a Montreal Cognitive Assessment score of \< 20, 2) Severe visual impairment, as defined by a lens-corrected visual acuity score of \< 6/60, 3) Severe hearing impairment, as defined by failed whispered voice test, 4) Bilateral upper limb paralysis, as defined by the Medical Research Council Muscle Power Scale of \< 4, or 5) Participated in any VR activities in the past six months or concurrently. Consent All participants will be asked to give their written informed consent to participate in the proposed study. Groups Participants allocated to the intervention group will participate in the 6-week VR experience programme. Participants allocated to the control will receive the usual care provided by the LTCF, such as personal care, regular basic medical and nursing care, and social support, as committed by the Social Welfare Department. The participants allocated to the intervention group receive the same usual care provided by the LTCF. The research team does not interfere with the services provided to the participants in either group. Outcomes Demographic data including age, gender, level of education, number of chronic illnesses, length of stay in the LTCF, and experience of participation in VR activities will be collected. Outcomes include mental well-being, depressive symptoms, loneliness, health-related quality of life, and perceived social support. Participant timeline Potential participants will be recruited in the phase of Enrolment, in which the eligibility screen and informed consent will be implemented. Then, in the phase of the Pre-treatment Assessment (i.e., T0,), demographic and outcome data will be collected. Subsequently, in the phase allocation, participants will be randomly allocated to either the therapeutic virtual reality experience group or the control group. Then, interventions will be implemented. In the phase of the Post-treatment Assessment (i.e., T1), outcome data will be collected once again. Analysis methods Demographic and outcome data collected at baseline will be reported either as means with standard deviation or as frequencies with percentages according to their levels of measurement as a whole sample and by groups. Generalized estimating equations (GEE) will be employed to separately test the hypothesis on the five outcomes as dependent variables (i.e., mental well-being, depressive symptoms, loneliness, health-related quality of life, perceived social support), The independent variables will be the same across all GEEs: group (two categories: intervention and control groups), timepoint (two categories: T0 and T1), and group x timepoint. The primary interpretation of the results will be based on the intention-to-treat analysis without adjusting for covariates. The level of significance will be set at 0.05. Missing data will be managed following a practical guide with flowcharts using various methods (e.g., multiple imputation, single imputation, or no imputation). ### Conditions Module **Conditions:** - Mental Health Wellness 1 - Physical Disability **Keywords:** - Mental wellbeing - Virtual reality - Physical disability - Older people ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** SINGLE **Masking Description:** In the proposed study, only the outcome assessor will be blinded to the group labels. Participants and interventionists are impossible to be blinded in this study. The group labels will not be known to the outcome assessors and will not appear on any documents that the outcome assessors can access. The participants, family members, and staff members of the LTCF are prohibited to disclose the group labels of the participants to the outcome assessors. **Who Masked:** - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 216 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** The investigators will administer a virtual reality experience programme to promote mental wellbeing of the participants **Intervention Names:** - Other: Virtual reality experience **Label:** Virtual reality **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** The investigators will not provide any interventions to the participants. **Label:** Usual care **Type:** NO_INTERVENTION ### Interventions #### Intervention 1 **Arm Group Labels:** - Virtual reality **Description:** The VR experience is launched on the participants using all-in-one VR head-mount devices. Tablet computers are used to optimize the settings by the intervention facilitators. Each session lasts for approximately one hour with 10 minutes spent on the briefing, 20 minutes spent on the VR experience, and 30 minutes spent on the post-VR group discussion. There are two sessions per week. The whole course lasts for six weeks and there are a total of 12 sessions. **Name:** Virtual reality experience **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** The World Health Organization Five Well-being Index will be used to measure mental well-being. **Measure:** Mental well-being **Time Frame:** 6 weeks #### Secondary Outcomes **Description:** The 9-item Patient Health Questionnaire will be used to measure depressive symptoms over the past two weeks. **Measure:** Depressive symptoms **Time Frame:** 6 weeks **Description:** The Chinese version of the 6-item De Jong Gierveld Loneliness Scale will be used to measure loneliness. **Measure:** Loneliness **Time Frame:** 6 weeks **Description:** The Hong Kong version of the EuroQol 5-dimensions instrument with a five-level scale will be used to measure health-related quality of life. **Measure:** Health-related quality of life **Time Frame:** 6 weeks **Description:** The Chinese version of the Multiple Scale of Perceived Social Support (MSPSS) will be used to measure perceived social support. **Measure:** Perceived social support **Time Frame:** 6 weeks ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Aged 60 years or above; * LTCF residents; and * Physical disability, defined as the Modified Barthel Index (MBI) score of ≤ 90 (i.e., moderately dependent or worse). Exclusion Criteria: * Probably dementia, as defined by a Montreal Cognitive Assessment (MoCA) score of \< 20, * Severe visual impairment, as defined by a lens-corrected visual acuity score of \< 6/60, * Severe hearing impairment, as defined by failed whispered voice test. * Bilateral upper limb paralysis, as defined by the Medical Research Council Muscle Power Scale of \< 4. or * Participated in any virtual reality activities in the past six months or concurrently. **Minimum Age:** 60 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Rick Kwan, PhD **Phone:** 852-34686813 **Phone Ext:** 6813 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Fowie Ng, PhD **Phone:** 852-34686789 **Phone Ext:** 6789 **Role:** CONTACT ### IPD Sharing Statement Module **Description:** The data will be provided upon request. **IPD Sharing:** UNDECIDED ### References Module #### See Also Links **Label:** List of approved project, Mental Health Initiative Funding Scheme Phase 2, Health Bureau, Hong Kong Government **URL:** https://www.healthbureau.gov.hk/en/fund/210700_mhifs/approved_projects_2.html ## Derived Section ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT02387879 **Brief Title:** A Non-interventional,Observational Post Authorization Study of Patients With Multiple Myeloma Treated With Lenalidomide TR **Official Title:** A Non-interventional, Multi-center, Observational Post Authorization Safety Study of Patients With Relapse/Refractory Multiple Myeloma Treated With Lenalidomide in Turkey #### Organization Study ID Info **ID:** CC-5013-PASS-TR #### Organization **Class:** INDUSTRY **Full Name:** Celgene ### Status Module #### Completion Date **Date:** 2022-12-31 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** ACTIVE_NOT_RECRUITING #### Last Update Post Date **Date:** 2019-09-26 **Type:** ACTUAL **Last Update Submit Date:** 2019-09-25 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2021-12-31 **Type:** ESTIMATED #### Start Date **Date:** 2013-12-25 **Type:** ACTUAL **Status Verified Date:** 2019-09 #### Study First Post Date **Date:** 2015-03-13 **Type:** ESTIMATED **Study First Submit Date:** 2015-02-05 **Study First Submit QC Date:** 2015-03-09 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Celgene #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** CC-5013-PASS-TR/A non-interventional, multi-center, observational post authorization safety study of patients with relapsed/refractory multiple myeloma treated with Lenalidomide in Turkey. The study is anticipated to last for approximately 8 years. Recruitment period will continue until 500 subjects have commenced the third cycle of treatment with lenalidomide. **Detailed Description:** Objectives: - Primary: To characterize and determine the incidence of adverse events of special interest; in subjects treated with Lenalidomide in real life setting in given indication. - Secondary: 1. To observe the basic adverse event management approaches of physicians 2. To evaluate the effectiveness of Lenalidomide in given indication and to evaluate the prescription line. 3. To monitor the reasons of patients' noncompliance with lenalidomide usage recommended in Patient Information Leaflet. Subjects will be recruited from approximately 36 hematology/oncology sites in Turkey. In all cases, the decision to treat the patient will be made prior to the decision to enter the subject into the study. All subjects enrolled will be prospectively followed up for up to 36 months, where feasible, following the end of observed treatment period. This 36 month observation period will start from end of treatment. The observation follow up period will end 36 months after the end of lenalidomide or background observed treatment period, or at time of death, withdrawal of consent, or loss to follow up. Following completion of treatment, subjects will be followed up after 30 days and then every 6 months to assess status. Patients who are eligible and signed a consent form will be recruited consecutively. Subjects who temporarily discontinue treatment for any reason for more than 30 days will be withdrawn from treatment observation but will be observed for safety for up to 36 months (from the end of treatment). If the reason for discontinuation for subjects is due to an adverse event, the follow up of the adverse event will not be time limited and will continue until resolution or stabilization or when, in the opinion of the investigator, no additional useful information can be obtained from the event or the subject withdraws their consent to any more data being collected. Subjects will discontinue from the study if they switch to another treatment. No intervention will be performed to physician. Treatment will be according to physician's regular clinical practice. All treatments will be prescribed by the treating investigator in accordance with regular clinical practice. All assessments will be made according to the regular clinical practice of the treating investigator. Therefore if a parameter is requested on the case report form (CRF) but the investigator's normal practice is not to carry out such an assessment, then the field will not be completed. Statistical Analysis: Data from all subjects who receive at least one dose of treatment will be included in the safety analysis. Adverse events will be classified using the MedDRA classification system. The severity of the toxicities will be graded according to the NCI CTCAE V. 4.03 whenever possible. Adverse event frequency will be tabulated by body system and MedDRA term. In the by subject analysis, a subject having the same event more than once will be counted only once. Adverse events will be summarized by worst NCI CTCAE V. 4.03 grade. Adverse events leading to death or to discontinuation from treatment, study-drug-related events, and serious adverse events will be listed separately. The Kaplan-Meier procedures will be used to characterize time to onset and time to resolution for adverse events of special interest. Multivariate logistic regression will be used to determine the demographic and baseline characteristics most predictive of developing adverse events of interest. A forward selection stepwise procedure will be used to identify the subset of relevant factors. Summary tables will also be provided for clinically relevant subgroups. Analyses will be undertaken to explore the course of neuropathy for subjects who have pre-existing neuropathy at baseline. Specifically, cross-tabulations will be used to summarize changes in severity observed during lenalidomide treatment and summary statistics will be provided for other relevant variables. ### Conditions Module **Conditions:** - Multiple Myeloma **Keywords:** - Multiple Myeloma - PASS - Observational - Non-interventional - Relapse - Refractory - CC-5013 - Lenalidomide - Turkey ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 500 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Subjects should be chosen among relapse/refractory multiple myeloma patients who have received at least one prior antimyeloma chemotherapy regimen (excluding treatment regimens with steroid only) with adequate dose and duration (≥2 cycles) or who have relapse/refractory multiple myeloma after stem cell transplantation. Patients who are eligible for the study will be consecutively enrolled in the study until the targeted patient number is reached. The responsible investigator will be requested to keep a log of subjects who are invited to enter the study. In the case of any of these subjects will not be enrolled in the study, this information will be documented together with its reason **Label:** Group 1 ### Outcomes Module #### Primary Outcomes **Description:** Number of participants with Adverse Events **Measure:** Adverse Events (AEs) **Time Frame:** Up to 5 years ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Male or female multiple myeloma patients with ≥18 years of age. * Subjects who understand and voluntarily sign an informed consent * Subjects who are receiving lenalidomide treatment in combination with dexamethasone not longer than four weeks. Exclusion Criteria: * - Refusal to participate in the study. * Patients who are currently on an interventional clinical trial * Subjects who previously received lenalidomide treatment and whose treatment is ceased or who had a treatment interruption for four weeks or longer. **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** It will continue until 500 subjects have commenced the third cycle of treatment with lenalidomide. As a condition of market authorization, subjects should be chosen among relapsed/refractory multiple myeloma patients who have received at least one prior antimyeloma chemotherapy regimen (excluding treatment regimens with steroid only) with adequate dose and duration (≥2 cycles) or who have relapsed/refractory multiple myeloma after stem cell transplantation. Patients who are eligible for the study will be consecutively enrolled in the study until the targeted patient number is reached. The responsible investigator will be requested to keep a log of subjects who are invited to enter the study. In the case of any of these subjects will not be enrolled in the study, this information will be documented together with its reason. ### Contacts Locations Module #### Locations **Location 1:** **City:** Adana **Country:** Turkey **Facility:** Baskent University Adana Application and Research Hospital **Zip:** 01250 **Location 2:** **City:** Adana **Country:** Turkey **Facility:** Cukurova University Medical Faculty **Zip:** 01330: **Location 3:** **City:** Ankara **Country:** Turkey **Facility:** Gulhane Military Medical Academy **Zip:** 06010: **Location 4:** **City:** Ankara **Country:** Turkey **Facility:** Ankara University Medical Faculty **Zip:** 06100: **Location 5:** **City:** Ankara **Country:** Turkey **Facility:** Ankara Numune Training and Research Hospital **Zip:** 06100 **Location 6:** **City:** Ankara **Country:** Turkey **Facility:** Diskapi Yildirim Beyazit Training and Research Hospital **Zip:** 06110 **Location 7:** **City:** Ankara **Country:** Turkey **Facility:** Dr. Abdurrahman Yurtaslan Ankara Onkology Training and Research Hospital **Zip:** 06200 **Location 8:** **City:** Ankara **Country:** Turkey **Facility:** Hacettepe University Medical Faculty **Zip:** 06230 **Location 9:** **City:** Ankara **Country:** Turkey **Facility:** Ankara Bayindir Hospital **Zip:** 06250 **Location 10:** **City:** Ankara **Country:** Turkey **Facility:** Baskent University Ankara Hospital **Zip:** 06490 **Location 11:** **City:** Ankara **Country:** Turkey **Facility:** Gazi University Medical Faculty **Zip:** 06560 **Location 12:** **City:** Antalya **Country:** Turkey **Facility:** Antalya Medstar Hospital **Zip:** 07030 **Location 13:** **City:** Antalya **Country:** Turkey **Facility:** Akdeniz University Medical Faculty **Zip:** 07070: **Location 14:** **City:** Bursa **Country:** Turkey **Facility:** Ali Osman Sonmez Oncology Hospital **Zip:** 16040 **Location 15:** **City:** Bursa **Country:** Turkey **Facility:** Uludag University Medical Faculty **Zip:** 16059 **Location 16:** **City:** Denizli **Country:** Turkey **Facility:** Pamukkale University Medical Faculty **Zip:** 20070 **Location 17:** **City:** Diyarbakir **Country:** Turkey **Facility:** Dicle University Medical Faculty **Zip:** 21280: **Location 18:** **City:** Edirne **Country:** Turkey **Facility:** Trakya University Medical Faculty **Zip:** 22030 **Location 19:** **City:** Eskisehir **Country:** Turkey **Facility:** Osmangazi University Medical Faculty **Zip:** 26480 **Location 20:** **City:** Gaziantep **Country:** Turkey **Facility:** Gaziantep University Medical Faculty **Zip:** 27310 **Location 21:** **City:** Istanbul **Country:** Turkey **Facility:** Istanbul University Istanbul Medical Faculty **Zip:** 34093 **Location 22:** **City:** Istanbul **Country:** Turkey **Facility:** Istanbul University Cerrahpasa Medical Faculty **Zip:** 34098 **Location 23:** **City:** Istanbul **Country:** Turkey **Facility:** Bakırkoy Dr.Sadi Konuk Training and Research Hospital **Zip:** 34147 **Location 24:** **City:** Istanbul **Country:** Turkey **Facility:** Medipol University Medical Faculty **Zip:** 34214 **Location 25:** **City:** Istanbul **Country:** Turkey **Facility:** Kartal Training and Research Hospital **Zip:** 34865 **Location 26:** **City:** Istanbul **Country:** Turkey **Facility:** Marmara University Pendik Training and Research **Zip:** 34890: **Location 27:** **City:** Izmir **Country:** Turkey **Facility:** Ege University Medical Faculty **Zip:** 35100 **Location 28:** **City:** Izmir **Country:** Turkey **Facility:** Dokuz Eylul University Medical Faculty **Zip:** 35340: **Location 29:** **City:** Izmir **Country:** Turkey **Facility:** Izmir Medical Park Hospital **Zip:** 35575 **Location 30:** **City:** Kayseri **Country:** Turkey **Facility:** Erciyes University Medical Faculty **Zip:** 38039 **Location 31:** **City:** Kocaeli **Country:** Turkey **Facility:** Kocaeli University Medical Faculty **Zip:** 41380 **Location 32:** **City:** Konya **Country:** Turkey **Facility:** Necmettin Erbakan University Meram Medical Faculty **Zip:** 42090 **Location 33:** **City:** Malatya **Country:** Turkey **Facility:** Inonu University Medical Faculty **Zip:** 44280 **Location 34:** **City:** Manisa **Country:** Turkey **Facility:** Celal Bayar University Medical Faculty **Zip:** 45030 **Location 35:** **City:** Mersin **Country:** Turkey **Facility:** Mersin University Medical Faculty **Zip:** 33343: **Location 36:** **City:** Samsun **Country:** Turkey **Facility:** Ondokuz Mayis University Medical Faculty **Zip:** 55139 **Location 37:** **City:** Tekirdag **Country:** Turkey **Facility:** Namik Kemal University Medical Faculty **Zip:** 59100 **Location 38:** **City:** Trabzon **Country:** Turkey **Facility:** Karadeniz Technical University Medical Faculty **Zip:** 61080 #### Overall Officials **Official 1:** **Affiliation:** Celgene **Name:** Margaret Atiba-Davies, PhD **Role:** STUDY_DIRECTOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009370 - Term: Neoplasms by Histologic Type - ID: D000009369 - Term: Neoplasms - ID: D000020141 - Term: Hemostatic Disorders - ID: D000014652 - Term: Vascular Diseases - ID: D000002318 - Term: Cardiovascular Diseases - ID: D000010265 - Term: Paraproteinemias - ID: D000001796 - Term: Blood Protein Disorders - ID: D000006402 - Term: Hematologic Diseases - ID: D000006474 - Term: Hemorrhagic Disorders - ID: D000008232 - Term: Lymphoproliferative Disorders - ID: D000007160 - Term: Immunoproliferative Disorders - ID: D000007154 - Term: Immune System Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC04 - Name: Neoplasms - Abbrev: BC14 - Name: Heart and Blood Diseases - 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: M12058 - Name: Multiple Myeloma - Relevance: HIGH - As Found: Multiple Myeloma - ID: M27588 - Name: Neoplasms, Plasma Cell - Relevance: HIGH - As Found: Multiple Myeloma - ID: M12315 - Name: Neoplasms by Histologic Type - Relevance: LOW - As Found: Unknown - ID: M21977 - Name: Hemostatic Disorders - Relevance: LOW - As Found: Unknown - ID: M5059 - Name: Blood Coagulation Disorders - Relevance: LOW - As Found: Unknown - ID: M17400 - Name: Vascular Diseases - Relevance: LOW - As Found: Unknown - ID: M13178 - Name: Paraproteinemias - Relevance: LOW - As Found: Unknown - ID: M5077 - Name: Blood Protein Disorders - Relevance: LOW - As Found: Unknown - ID: M9490 - Name: Hematologic Diseases - Relevance: LOW - As Found: Unknown - ID: M9560 - Name: Hemorrhagic Disorders - Relevance: LOW - As Found: Unknown - ID: M11225 - Name: Lymphoproliferative Disorders - 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: T3947 - Name: Multiple Myeloma - Relevance: HIGH - As Found: Multiple Myeloma ### Condition Browse Module - Meshes - ID: D000009101 - Term: Multiple Myeloma - ID: D000054219 - Term: Neoplasms, Plasma Cell ### Intervention Browse Module - Browse Branches - Abbrev: ANeo - Name: Antineoplastic Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M1725 - Name: Lenalidomide - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03030079 **Brief Title:** Electrical Stimulus Therapy for Chronic Phantom Limb Pain **Official Title:** Exploratory Study of Electrical Stimulus as a Treatment Option for Chronic Phantom Limb Pain #### Organization Study ID Info **ID:** 16-1063 #### Organization **Class:** OTHER **Full Name:** University of Colorado, Denver ### Status Module #### Completion Date **Date:** 2023-06-28 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2023-12-11 **Type:** ACTUAL **Last Update Submit Date:** 2023-12-08 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2023-06-27 **Type:** ACTUAL #### Start Date **Date:** 2017-01-01 **Type:** ACTUAL **Status Verified Date:** 2023-12 #### Study First Post Date **Date:** 2017-01-24 **Type:** ESTIMATED **Study First Submit Date:** 2017-01-13 **Study First Submit QC Date:** 2017-01-19 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** Hanger Clinic: Prosthetics & Orthotics #### Lead Sponsor **Class:** OTHER **Name:** University of Colorado, Denver #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** True **Is FDA Regulated Drug:** False **Is US Export:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** The goal of this pilot study is to assess the effectiveness of an electrical stimulation therapy option for the treatment of chronic phantom limb pain in upper or lower limb amputees. This therapy has been previously used for sports and joint injuries and is marketed for relaxation of muscle spasms, re-education of muscle action, prevention of disuse atrophy, increased local blood circulation, and maintaining or increasing range of motion. The investigators would like to explore the idea that physically exercising the muscles of the residual limb and increasing blood flow to the site of amputation through the promotion of motor contraction using electrical stimulation decreases chronic phantom limb pain. **Detailed Description:** There are a large number of people living with an amputation due mainly to cardiovascular disease, diabetes, and trauma; and of these there is evidence to show that up to 80% of amputees experience phantom limb pain (PLP). PLP is classified as cramping, burning, shooting, or stabbing pain in the missing limb following an amputation. Current treatments include pharmacological drugs, anesthesia, additional surgery, mirror therapy, transcutaneous electrical nerve stimulation (TENS) and others. TENS, as usually implemented, has been used to effectively reduce pain in multiple spots of the body, but has shown little effect in reducing phantom limb pain especially long term even with varying the frequency and intensity of the electrical stimulation. These current treatments can be invasive, costly, and have shown only to offer immediate relief. Using an electrical stimulator at a higher intensity has proven to to reduce pain and increase healing in numerous sports and joint related injuries. Anecdotally, the investigators have learned that a similar treatment protocol when applied to persons with phantom limb pain can mitigate their pain. The goal of this pilot study is to assess the effectiveness of higher intensity electrical stimulation in the management of PLP and also to acquire data to inform the investigators to the most appropriate study design and power for a future more formal clinical trial. To accomplish this the investigators will utilize the ACP Omnistim FX2 Pro electrical stimulator, that has been provided to us by Accelerated Care Plus (ACP) Corporation, to physically exercise the muscles of the residual limb and hence increase the local blood flow and explore it's potential for treatment of PLP both short and long term. The self-identified subject will be hooked up to the ACP electrical stimulator using surface electrodes that will pass a current through the skin first at a low intensity for 5 minutes to allow the subject to adjust to the tingling sensation. The current will then be gradually increased to a level sufficient to elicit a non-painful motor contraction for 15 minutes. Using a numerical pain scale and short answer questions about the characteristics of the pain the investigators will track both short term and long term changes in pain. ### Conditions Module **Conditions:** - Phantom Limb Pain ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** DEVICE_FEASIBILITY #### Enrollment Info **Count:** 10 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Explore the efficacy of an electrical stimulus regimen on the treatment of chronic phantom limb pain using a standard-of-care electrical stimulation system **Intervention Names:** - Device: Experimental Electrical Stimulation Regimen **Label:** Experimental Electrical stimulation Regimen **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Experimental Electrical stimulation Regimen **Description:** The electrodes will pass an electrical current through the skin and into the muscle first at a low intensity for 5 minutes to allow the subject to adjust to the sensation. The current will then be gradually increased to a level sufficient to elicit a non-painful motor contraction. The subject will sit in a relaxed position as the electrical stimulator contracts the muscles for a duration of 15 minutes. **Name:** Experimental Electrical Stimulation Regimen **Other Names:** - Device: Omnistim FX2 Pro **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Description:** Pain level data will be taken before and after each session to analyze any short term decreases in pain using a self-reported numeric 10-point pain scale. T- tests will be used for within subject testing looking at pre and post treatment measures to quantify a decrease in pain. **Measure:** Use of electrical stimulus medium frequency alternating current for short term decreased Phantom Limb Pan **Time Frame:** After each 20 minute treatment session up to 5 weeks **Description:** An overall sustained decrease in phantom limb pain will be assessed weekly using a self-reported numeric 10-point pain scale. ANOVAs will be used to look at trends in post treatment measures over time. **Measure:** Assess the effectiveness of reducing chronic phantom limb pain long term. **Time Frame:** Weekly for 5 weeks ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Self-identified adult volunteers with a limb deficiency with a well-healed site of amputation * Subjects experiencing at least a 4 out of 10 of chronic phantom limb pain based on a numeric 10-point pain scale. * Any ethnicity and gender * Age (18-85 years) * Able to understand and follow directions in English, assessed by their ability to respond during the recruitment and consent processes. Exclusion Criteria: * Subjects that are not able to understand the procedures and who are unable to come to the facility. * Any individual whose amputation site is not completely healed * Anyone with cardiac demand pacemakers and/or implanted defibrillator. **Healthy Volunteers:** True **Maximum Age:** 85 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Aurora **Country:** United States **Facility:** Children's Hospital Colorado Research Institute **State:** Colorado **Zip:** 80045 #### Overall Officials **Official 1:** **Affiliation:** University of Colorado, Denver **Name:** Richard Weir, PhD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000010468 - Term: Perceptual Disorders - ID: D000019954 - Term: Neurobehavioral Manifestations - ID: D000009461 - Term: Neurologic Manifestations - ID: D000009422 - Term: Nervous System Diseases - ID: D000010149 - Term: Pain, Postoperative - ID: D000011183 - Term: Postoperative Complications - ID: D000010335 - Term: Pathologic Processes - ID: D000010146 - Term: Pain ### Condition Browse Module - Browse Branches - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: BXM - Name: Behaviors and Mental Disorders - Abbrev: All - Name: All Conditions - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M13498 - Name: Phantom Limb - Relevance: HIGH - As Found: Phantom Limb - ID: M13066 - Name: Pain - Relevance: LOW - As Found: Unknown - ID: M13379 - Name: Perceptual Disorders - Relevance: LOW - As Found: Unknown - ID: M21826 - Name: Neurobehavioral Manifestations - Relevance: LOW - As Found: Unknown - ID: M12404 - Name: Neurologic Manifestations - Relevance: LOW - As Found: Unknown - ID: M13069 - Name: Pain, Postoperative - Relevance: LOW - As Found: Unknown - ID: M14065 - Name: Postoperative Complications - Relevance: LOW - As Found: Unknown - ID: T1303 - Name: Chronic Graft Versus Host Disease - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000010591 - Term: Phantom Limb ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04435379 **Brief Title:** Study to Assess VPM1002 in Reducing Hospital Admissions and/or Severe Respiratory Infectious Diseases in Elderly in COVID-19 Pandemic **Official Title:** A Phase III, Randomized, Double-blind, Placebo-controlled, Multicentre, Clinical Trial to Assess the Efficacy and Safety of VPM1002 in Reducing Hospital Admissions and/or Severe Respiratory Infectious Diseases in Elderly in the SARS-CoV-2 Pandemic by Modulating the Immune System #### Organization Study ID Info **ID:** VPM1002-DE-3.07CoV #### Organization **Class:** INDUSTRY **Full Name:** Vakzine Projekt Management GmbH #### Secondary ID Infos **ID:** 2020-001675-33 **Type:** EUDRACT_NUMBER ### Status Module #### Completion Date **Date:** 2021-10-12 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2021-10-26 **Type:** ACTUAL **Last Update Submit Date:** 2021-10-25 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2021-10-12 **Type:** ACTUAL #### Start Date **Date:** 2020-06-18 **Type:** ACTUAL **Status Verified Date:** 2021-10 #### Study First Post Date **Date:** 2020-06-17 **Type:** ACTUAL **Study First Submit Date:** 2020-06-16 **Study First Submit QC Date:** 2020-06-16 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** FGK Clinical Research GmbH #### Lead Sponsor **Class:** INDUSTRY **Name:** Vakzine Projekt Management GmbH #### 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 aim of this study is to investigate whether vaccination of elderly with VPM1002 could reduce hospital admissions and/or severe respiratory infectious diseases in the SARS-CoV-2 pandemic . VPM1002 is a vaccine that is a further development of the old Bacillus Calmette-Guérin (BCG) vaccine, which has been used successfully as a vaccine against tuberculosis for about 100 years, especially in developing countries. VPM1002 has been shown in various clinical studies to be significantly safer than the BCG vaccine. VPM1002 strengthens the body's immune defence and vaccination with BCG reduces the frequency of respiratory diseases. It is therefore assumed that a VPM1002 vaccination could also provide (partial) protection against COVID-19 disease caused by the "new corona virus" SARS-CoV 2. **Detailed Description:** Based on the evidence that BCG \[Bacille Calmette-Guérin\] vaccine 1. can potentiate immune responses to other vaccines through induction of trained innate immunity and heterologous adaptive immunity, and 2. can reduce the incidence of respiratory infections, exert antiviral effects in experimental models, and reduce viremia in an experimental human model of viral infection, it is hypothesized that BCG vaccination may induce (partial) protection against the susceptibility to and/or severity of SARS-CoV-2 infections. VPM1002 is being developed with the aim to replace BCG by a vaccine that has a better safety profile and superior efficacy. Evidence from pre-clinical and clinical studies demonstrate that VPM1002 is safer and is more immunogenic than the existing BCG vaccine (for more information, please revert to the IB). It is therefore anticipated that VPM1002 will also perform better in reducing the severity of the symptoms of an infection with the SARS-CoV-2 than the BCG vaccine. Further, manufacturing of VPM1002 using state-of-the-art production methods will help hasten the production of millions of doses in a very short time and thus would be beneficial in the current SARS-CoV-2 pandemic situation. The current trial will assess the efficacy and safety of VPM1002 to reduce the hospital admissions and clinical consequences of SARS-CoV-2 infections in the elderly population in the SARS-CoV-2 pandemic by modulating the immune system. A total of 2038 adults aged 60 or above will be enrolled across involved clinical trial sites in Germany. Informed consent will be obtained from the subjects willing to take part in the trial. This will be followed by assessment of the eligibility criteria. Subjects who fulfil the inclusion/exclusion criteria will be centrally randomized in a 1:1 ratio to receive a single dose (0.1 ml) of either VPM1002 or Placebo. All subjects will be requested to sign into a web-based tool designed for this trial. Every subject is encouraged to name a designated caregiver who may provide follow-up data in case of hospitalisation or severe illness of the study subject. All subjects will be followed-up entirely remotely. The questionnaires will be designed to collect data regarding hospitalisation, adverse events (AE)/serious adverse events (SAE), ICU admissions and other secondary endpoints. The investigators will review the outcome and safety data. The duration of follow-up will be 240 days. Subjects with confirmed SARS-CoV-2 infection (with or without symptoms) will be followed for at least 6 weeks (from the date of test result), independent of the total trial duration. ### Conditions Module **Conditions:** - Infection, Respiratory Tract **Keywords:** - infectious respiratory diseases ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** Subjects who fulfil the inclusion/exclusion criteria will be centrally randomized in a 1:1 ratio to receive a single dose (0.1 ml) of either VPM1002 or Placebo. ##### Masking Info **Masking:** TRIPLE **Masking Description:** The reconstitution of trial intervention will be done by unblinded site personnel who will not be involved in the collection or evaluation of outcome data. Administration of the trial intervention will be done by blinded site personnel. **Who Masked:** - PARTICIPANT - INVESTIGATOR - OUTCOMES_ASSESSOR **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 2038 **Type:** ACTUAL **Phases:** - PHASE3 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** The active ingredient of the recombinant BCG vaccine, VPM1002, is Mycobacterium bovis rBCGΔureC::hly, freeze-dried and standardized to the number of viable mycobacteria (colony forming units; CFU) per application. Dose: 2-8 x 10e5 CFU VPM1002 administered in 0.1 ml reconstituted suspension. **Intervention Names:** - Biological: VPM1002 **Label:** VPM1002 **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Physiological saline 0.1ml **Intervention Names:** - Biological: Placebo **Label:** Placebo **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - VPM1002 **Description:** The investigational product will be administered via intradermal injection with a 1.0-ml syringe, sub-graduated into hundredths of ml (1/100 ml), and fitted with a short bevel needle (25G/0.50 mm or 26G/0.45 mm, 10 mm in length). **Name:** VPM1002 **Type:** BIOLOGICAL #### Intervention 2 **Arm Group Labels:** - Placebo **Description:** The investigational product will be administered via intradermal injection with a 1.0-ml syringe, sub-graduated into hundredths of ml (1/100 ml), and fitted with a short bevel needle (25G/0.50 mm or 26G/0.45 mm, 10 mm in length). **Name:** Placebo **Type:** BIOLOGICAL ### Outcomes Module #### Primary Outcomes **Measure:** Number of days with severe respiratory disease at hospital and/or at home **Time Frame:** From day 0 to day 240 #### Secondary Outcomes **Measure:** Cumulative incidence of hospital admissions **Time Frame:** From day 0 to day 240 **Measure:** Cumulative incidence of documented SARS-CoV-2 infection **Time Frame:** From day 0 to day 240 **Measure:** Number of days with self-reported fever (≥ 38 ºC) **Time Frame:** From day 0 to day 240 **Measure:** Number of days with self-reported acute respiratory symptoms **Time Frame:** From day 0 to day 240 **Measure:** Cumulative incidence of self-reported acute respiratory symptoms **Time Frame:** From day 0 to day 240 **Measure:** Cumulative incidence of death for any reason **Time Frame:** From day 0 to day 240 **Measure:** Cumulative incidence of death due to documented SARS-CoV-2 infection **Time Frame:** From day 0 to day 240 **Measure:** Cumulative incidence of ICU admission for any reason **Time Frame:** From day 0 to day 240 **Measure:** Cumulative incidence of ICU admission due to documented SARS-CoV-2 infection **Time Frame:** From day 0 to day 240 **Measure:** Cumulative incidence of hospital admission due to documented SARSCoV- 2 infection **Time Frame:** From day 0 to day 240 ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Male or female adult (≥ 60 years) 2. Subject is contractually capable, able to understand information on study and has signed informed consent sheet 3. Subject has access to an internet-enabled electronic device Exclusion Criteria: 1. Known active or latent Mycobacterium tuberculosis infection 2. Fever (\> 38 °C) or respiratory tract infection within the past 24 hours 3. Current active viral or bacterial infection 4. Expected vaccination during the study period; vaccinations against influenza and pneumococcal disease are allowed with ≥ 4 weeks between these vaccinations and the trial vaccination 5. Participation in another interventional study within 30 days before screening and during this study 6. Known hypersensitivity or allergy to (components of) the VPM1002 vaccine or serious adverse reactions to prior Bacille Calmette-Guérin (BCG) administration 7. Severely immunocompromised subjects, including: 1. subjects with known infection by the human immunodeficiency virus (HIV-1); 2. subjects with solid organ transplantation; 3. subjects with bone marrow transplantation; 4. subjects under chemotherapy, immunotherapy, or radiotherapy; 5. subjects with primary immunodeficiency; 6. treatment with any anti-cytokine therapies; 7. treatment with oral or intravenous steroids defined as daily doses of 10 mg prednisone or equivalent for longer than 3 months, or likely use of oral or intravenous steroids in the next 4 weeks; 8. History of malignancies, unless the subject has been free of the disease for ≥ 2 years; exception: subjects with adequately treated basal or squamous cell cancer or other localized non-melanoma skin cancer and adequately treated carcinoma in situ of the cervix may participate in the trial 9. Previous positive SARS-CoV-2 test result 10. Person is an employee of the sponsor, a relative of the sponsor or investigator, or is employed in the same department as the investigator **Healthy Volunteers:** True **Minimum Age:** 60 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Stuttgart **Country:** Germany **Facility:** Hautarztpraxis Dres. Leitz & Kollegen **State:** Baden-Württemberg **Zip:** 70178 **Location 2:** **City:** Cottbus **Country:** Germany **Facility:** MECS Cottbus GmbH **State:** Brandenburg **Zip:** 03050 **Location 3:** **City:** Frankfurt **Country:** Germany **Facility:** Studienzentrum Dr. Keller **State:** Hessen **Zip:** 60389 **Location 4:** **City:** Hannover **Country:** Germany **Facility:** Klinische Forschung Hannover Mitte GmbH **State:** Niedersachsen **Zip:** 30159 **Location 5:** **City:** Hannover **Country:** Germany **Facility:** Medizinische Hochschule Hannover **State:** Niedersachsen **Zip:** 30625 **Location 6:** **City:** Essen **Country:** Germany **Facility:** Medizentrum Essen Borbeck **State:** Nordrhein-Westfalen **Zip:** 45355 **Location 7:** **City:** Mainz **Country:** Germany **Facility:** BAG Dres. med. Quist PartG **State:** Rheinland-Pfalz **Zip:** 55128 **Location 8:** **City:** Leipzig **Country:** Germany **Facility:** SIBAmed GmbH & Co. KG **State:** Sachsen **Zip:** 04103 **Location 9:** **City:** Erfurt **Country:** Germany **Facility:** SocraTec R&D GmbH **State:** Thüringen **Zip:** 99084 **Location 10:** **City:** Berlin **Country:** Germany **Facility:** emovis GmbH **Zip:** 10629 **Location 11:** **City:** Berlin **Country:** Germany **Facility:** Klinische Forschung Berlin GbR **Zip:** 10787 **Location 12:** **City:** Hamburg **Country:** Germany **Facility:** Klinische Forschung Hamburg GmbH **Zip:** 20253 #### Overall Officials **Official 1:** **Affiliation:** Vakzine Projekt Management GmbH **Name:** Leander Grode, Dr. rer. nat. **Role:** STUDY_DIRECTOR ### IPD Sharing Statement Module **Description:** There is uncertainty whether the European Union General Data Protection Regulation allows dissemination of individual participant data to other researchers. Some reasons why the EU Regulation would not allow this are the lack of suitable safeguards when personal data are transferred to any researcher asking for it and the impairment of the rights of the subjects for erasure of their data once they are disseminated. **IPD Sharing:** NO ### References Module #### References **Citation:** Blossey AM, Bruckner S, May M, Parzmair GP, Sharma H, Shaligram U, Grode L, Kaufmann SHE, Netea MG, Schindler C. VPM1002 as Prophylaxis Against Severe Respiratory Tract Infections Including Coronavirus Disease 2019 in the Elderly: A Phase 3 Randomized, Double-Blind, Placebo-Controlled, Multicenter Clinical Study. Clin Infect Dis. 2023 Apr 3;76(7):1304-1310. doi: 10.1093/cid/ciac881. **PMID:** 36358012 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000020969 - Term: Disease Attributes - ID: D000010335 - Term: Pathologic Processes - 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: LOW - As Found: Unknown - ID: M10283 - Name: Infections - Relevance: HIGH - As Found: Infectious - ID: M6368 - Name: Communicable Diseases - Relevance: HIGH - As Found: Infectious Disease - ID: M14957 - Name: Respiration Disorders - Relevance: LOW - As Found: Unknown - ID: M14977 - Name: Respiratory Tract Diseases - Relevance: LOW - As Found: Unknown - ID: M14978 - Name: Respiratory Tract Infections - Relevance: HIGH - As Found: Infections, Respiratory Tract - ID: M22700 - Name: Disease Attributes - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000003141 - Term: Communicable Diseases - ID: D000007239 - Term: Infections - ID: D000012141 - Term: Respiratory Tract Infections ### Intervention Browse Module - Browse Branches - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M17360 - Name: Vaccines - Relevance: LOW - As Found: Unknown - ID: M4793 - Name: BCG Vaccine - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05878379 **Brief Title:** Effect of a Dietary Iron Program on Iron Status and IQ in Children in Phatthalung Province, Thailand **Official Title:** The Effects of a Dietary Iron Program on Iron Status and Cognitive Function Amoung School Children in Phatthalung Province, Southern Thailand #### Organization Study ID Info **ID:** MUPH 2018-048 #### Organization **Class:** OTHER **Full Name:** Mahidol University ### Status Module #### Completion Date **Date:** 2018-10-30 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2023-05-26 **Type:** ACTUAL **Last Update Submit Date:** 2023-05-18 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2018-10-30 **Type:** ACTUAL #### Start Date **Date:** 2018-05-02 **Type:** ACTUAL **Status Verified Date:** 2023-05 #### Study First Post Date **Date:** 2023-05-26 **Type:** ACTUAL **Study First Submit Date:** 2023-04-05 **Study First Submit QC Date:** 2023-05-18 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Mahidol University #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Iron deficiency (ID) continues to be one of the most prevalent disorders, which can adversely affect cognitive ability in childhood. Our aim was to determine the effect of a dietary iron education program (DIP) on children's iron status and intelligence quotient (IQ) score. This pre-test (week 1) post-test (week 16) quasi-experimental study with follow-up (week 18) utilized constructs from the Health Belief Model. Children and caregivers participated in the DIP which incorporated group talks, presentations, brainstorming, game-based learning and cooking sessions from weeks 2-15. Knowledge of ID and dietary iron, perceived susceptibility and severity, benefits and barriers for changing behavior, dietary intake, iron status and IQ score were determined at all timepoints (weeks 1, 16, and 18). **Detailed Description:** 1. Objective The objective of this study was to determine whether an education-based dietary iron program that involved school teachers, parents and children could increase iron status and intelligence quotient (IQ) score in a group of schoolchildren. 2. Methods 2.1 Study design A quasi-experimental study (pre-test post-test design with follow-up) was used in this study that was based on the Health Belief Model as its theoretical framework. 2.2 Study Setting and Participants Child-parent/caregiver dyads were recruited from one purposively selected government-administered primary school in Phatthalung province. Schools were not involved in any other programs, located in a rural area, and had at least 200 children studying in grades 4-5. Hookworm screening was done 6 weeks before program implementation by the local government screening program. All children who were studying in grades 4-5 in the selected school were invited to participate. Out of 190 children, 34 children who were mildly anemic were enrolled in the study, together with their parents/caregivers. Sample size was calculated based on serum ferritin concentrations among school-aged children from a study by Rahman et al. \[17\]. Informed written consent was obtained from child-parent/caregiver dyads prior to program implementation. 2.3 Procedure for the intervention The Health Belief Model underpinned the development of the dietary iron program, which focused on the importance of adequate dietary iron consumption and emphasized prevention of iron deficiency (ID) and iron deficiency anemia (IDA). It was implemented from weeks 2 to 15 of the study. Child-parent/caregiver dyads and teachers received an ID/IDA booklet that included information about anemia, causes of ID, iron-rich food, iron concentration in traditional foods, dietary enhancers and inhibitors of iron absorption, and recipes for iron-rich local and culturally appropriate meals for teachers, parents/caregivers and children, as part of the dietary iron program. Teachers who were involved in school lunch design participated for discussing and planning iron-rich school lunch menus, and observed teaching and learning process with the use of media and games during the iron lessons for children. Four lessons were conducted for parents/caregivers. The first lesson was discussion that addressed parental perceptions about children's susceptibility to ID and IDA and the severity of ID and IDA concerning cognitive function. In the second lesson, parents/caregivers were asked to list the benefits and barriers for changing behavior with regards to preparing more iron-rich foods in the home. Then, the principal researcher invited parents/caregivers to brainstorm and share ways to overcome these barriers. Cooking classes for preparing iron-rich meals at home were conducted. Parents/caregivers voted for two iron-rich meals that they wanted to cook and then they prepared and cooked them in the classes. For the final lesson, the principal researcher visited each parent/caregiver to discuss the barriers they faced when trying to incorporate more iron-rich meals into their child's diet at home. Three lessons were conducted for the children, one per month. In the first lesson, group talks and games were used to engage the children about the causes and effects of ID and IDA. The second lesson focused on iron-rich food. After that, the children partook in games that entailed writing names of food ingredients that contained iron and circling pictures of iron-rich foods, and describing the sensations associated with consuming these foods. Both positive and negative answers from children were selected for discussion, and approaches for consuming more iron-rich food were brainstormed. A market assignment was set to help the children remember the names of iron-rich food and recognize the foods when they visited a market with their parents. The last lesson was a cooking class. After each cooking class finished, the researcher and a teacher encouraged them to eat this meal together. 2.4 Measurement outcomes The main outcome for this study was the effect of an education-based dietary iron program on iron status and intelligence quotient (IQ) score among children before program implementation (week 1) and at week 16 (immediately after program implementation) and at 18 weeks (follow-up appointment to determine the sustainability of the intervention). All of the outcome variables were measured at different time points. Children's knowledge towards ID and IDA was determined using a questionnaire, while children's iron intake was estimated by using three days of 24-hour recalls (2 school days and 1 weekend day). Portion sizes were estimated by using household portion sizes (rice-serving spoon, tablespoon, teaspoon and glass). IQ score was measured by a trained child psychologist by using the Standard Progressive Matrices (SPM) parallel version. Iron status was determined from blood samples drawn by medical technologists in the first-aid rooms. Concentration of hemoglobin, serum ferritin and serum C-reactive protein were measured by laboratory staff at hematology laboratory at N-health laboratory, Bangkok Dusit Medical Service Hospital (BDMS), Songkla province, using the hemoglobin assay kit (Colorimetric), chemiluminescent immunoassay (CMIA) and high-sensitivity C-reactive protein methods, respectively. Iron status was defined iron-replete: hemoglobin \>115 g/l and serum ferritin level \> 30 µg/l; anemia: hemoglobin \<115 g/l and serum ferritin level \>30 µg/l; mild-moderate iron depletion with anemia: hemoglobin 80-114 g/l and serum ferritin level \<30 µg/l.; mild iron depletion without anemia: serum ferritin level \< 30 µg/l and hemoglobin\>115 g/l. In addition, parents/caregivers were assessed by using a questionnaire toward knowledge and perceptions consisted of perceived susceptibility, severity, benefits and barriers in relation to ID and IDA. 2.5 Data Analysis Data from questionnaires were recorded using EpiData version 3.1, while 24-hour dietary recall data were entered into INMUCAL V3, which is a nutrient composition database of dietary items commonly consumed in Thailand. Portion sizes were converted into grams before entering data, and energy and nutrient intakes were calculated. Statistical analysis was carried out by using SPSS version 18. Frequencies, percentage, mean (SD) and median (25th-75th percentile) were calculated for demographic characteristics of participant knowledge, perceptions, iron intake, iron status, and IQ score. The One-Way Repeated Measures ANOVA and Friedman's Two-Way Analysis of Variance by Ranks were used to compare mean differences in knowledge score and perception score of IDA and ID prevention among parents/caregivers, total iron intake, heme iron intake, non-heme iron intake, iron status and IQ score among children at different time points. The Monte Carlo exact test was used to compare the number of children in grades 4-5 who met/did not meet the Thai DRI for iron at pre-test, post-test and follow-up. Differences were considered to be significantly different when p\<0.05. 2.6 Ethical approval The study was granted ethical approval by the Committee of the Ethical Review for Human Research, Faculty of Public Health, Mahidol University Thailand 9 March 2018 (COA. No. MUPH 2018-048). ### Conditions Module **Conditions:** - Iron Deficiency, Anaemia in Children **Keywords:** - Iron deficiency - Iron status - Cognitive function - education ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP **Intervention Model Description:** Quasi-experimental (pre-test post-test) design with follow-up / Behavioral intervention, based on the Health Belief Model ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 34 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** The dietary iron program was administered from weeks 2 to 15 in between pre-test and post-test measurements **Intervention Names:** - Behavioral: Dietary Iron Program **Label:** Dietary Iron Program **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Dietary Iron Program **Description:** Teachers Lesson 1: Discuss about causes, prevention and effects of anemia and ID, dietary iron, dietary enhancers and inhibitors of iron absorption, and school lunch menu Lesson 2: Participate in and observe how to teach children in an iron curriculum Caregivers Lesson 1: Presentation and group talk about causes, prevention, and effects of anemia and ID, dietary iron, and dietary enhancers and inhibitors of iron absorption Lesson 2: Discuss benefits and barriers of changing to an iron-rich meal at home Lesson 3: Cooking class for preparing an iron-rich meal at home (2 times) Lesson 4: Home visit Children Lesson 1: Group talk about causes and effects of anemia and ID Games: "Where are you from?" Lesson 2: Presentation and group talk about dietary iron, and dietary enhancers and inhibitors of iron absorption, and iron-rich food Games: "What is the winner?" Assignment: Market assignment Lesson 3: Cooking class (2 times) **Name:** Dietary Iron Program **Type:** BEHAVIORAL ### Outcomes Module #### Primary Outcomes **Description:** For outcome 1, individuals were categorized as either: (1.) iron replete, (2.) Iron deficient, (3.) Iron deficient with mild-moderate anemia (4.) mild-moderately anemic **Measure:** Iron Status **Time Frame:** Change from baseline (week 1) to post-test (week 16), and change from post-test (week 16) to follow-up (week 18) #### Secondary Outcomes **Description:** Outcome 2 was measured as the number of IQ points (continuous data) **Measure:** Intelligence quotient (IQ) score **Time Frame:** Change from baseline (week 1) to post-test (week 16), and change from post-test (week 16) to follow-up (week 18) ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Children who were studying in grades 4 and 5 of the selected school Exclusion Criteria: * Severe illness, including severe anemia (hemoglobin \<4.96 mmol/L or \<80 g/L) * Post-menarche * Use of vitamin or mineral supplements up to 30 days before program implementation **Healthy Volunteers:** True **Maximum Age:** 11 Years **Minimum Age:** 9 Years **Sex:** ALL **Standard Ages:** - CHILD ### Contacts Locations Module #### Locations **Location 1:** **City:** Phattalung **Country:** Thailand **Facility:** Ms Witchada Simla **State:** Phattalung Province **Zip:** 93210 #### Overall Officials **Official 1:** **Affiliation:** Thaksin University (Phatthalung Campus), Thailand **Name:** Witchada Simla, MSc **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **Description:** IDP will not be shared with researchers outside of the research team. **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000019189 - Term: Iron Metabolism Disorders - ID: D000008659 - Term: Metabolic Diseases - ID: D000000747 - Term: Anemia, Hypochromic - ID: D000000740 - Term: Anemia - ID: D000006402 - Term: Hematologic Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC15 - Name: Blood and Lymph Conditions - Abbrev: BC18 - Name: Nutritional and Metabolic Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M20857 - Name: Anemia, Iron-Deficiency - Relevance: HIGH - As Found: Iron Deficiency - ID: M2781 - Name: Iron Deficiencies - Relevance: HIGH - As Found: Iron Deficiency - ID: M4070 - Name: Anemia - Relevance: LOW - As Found: Unknown - ID: M11639 - Name: Metabolic Diseases - Relevance: LOW - As Found: Unknown - ID: M21177 - Name: Iron Metabolism Disorders - Relevance: LOW - As Found: Unknown - ID: M4077 - Name: Anemia, Hypochromic - Relevance: LOW - As Found: Unknown - ID: M9490 - Name: Hematologic Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000018798 - Term: Anemia, Iron-Deficiency - ID: D000090463 - Term: Iron Deficiencies ### 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: Micro - Name: Micronutrients - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M10533 - Name: Iron - Relevance: HIGH - As Found: Streptococcus pneumoniae serotype - ID: M21009 - Name: Micronutrients - Relevance: LOW - As Found: Unknown - ID: M16885 - Name: Trace Elements - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000007501 - Term: Iron ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05667779 **Brief Title:** A Study Evaluating Safety, Tolerability, and Pharmacokinetics of QRL-101 in Healthy Participants **Official Title:** A Randomized, Placebo-Controlled, Double-blind, Single Ascending Dose, First in Human Phase 1 Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of QRL-101 in Healthy Participants #### Organization Study ID Info **ID:** QRL-101-01 #### Organization **Class:** INDUSTRY **Full Name:** QurAlis Corporation #### Secondary ID Infos **ID:** 2022-002484-30 **Type:** EUDRACT_NUMBER ### Status Module #### Completion Date **Date:** 2023-12-27 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2024-04-15 **Type:** ACTUAL **Last Update Submit Date:** 2024-04-12 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2023-12-27 **Type:** ACTUAL #### Start Date **Date:** 2022-12-22 **Type:** ACTUAL **Status Verified Date:** 2024-04 #### Study First Post Date **Date:** 2022-12-29 **Type:** ACTUAL **Study First Submit Date:** 2022-12-19 **Study First Submit QC Date:** 2022-12-19 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** QurAlis Corporation #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Is US Export:** True **Oversight Has DMC:** False ### Description Module **Brief Summary:** The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics (PK) of ascending single doses of QRL-101 in male and female healthy participants. The findings from this study will be used to inform the development of QRL-101 for people living with ALS. **Detailed Description:** Phase 1, single-site study to evaluate the safety, tolerability, and pharmacokinetics (PK) of ascending single doses of QRL-101 administered orally in healthy male and female participants. Up to 16 cohorts of 8 participants each, randomized 6:2 (QRL-101: placebo) will be tested. The approximate total duration of study participation for each participant may be up to 40 days. ### Conditions Module **Conditions:** - Healthy Volunteers **Keywords:** - Healthy Volunteers ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** This study will be a randomized, double-blind, placebo-controlled single ascending dose (SAD) study in healthy participants with the primary goal of evaluating the safety and tolerability of QRL-101. ##### Masking Info **Masking:** DOUBLE **Masking Description:** A participant and investigator-blinded, randomized, placebo-controlled design will be used to minimize bias in this study. **Who Masked:** - PARTICIPANT - INVESTIGATOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 88 **Type:** ACTUAL **Phases:** - PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Single-ascending doses of QRL-101 will be administered orally to healthy participants **Intervention Names:** - Drug: QRL-101 **Label:** QRL-101 **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Single-ascending doses of comparator placebo will be administered orally to healthy participants **Intervention Names:** - Other: Placebo **Label:** Placebo **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - QRL-101 **Description:** Single-ascending doses of QRL-101 will be orally administered. The dose levels may change subject to available nonclinical, clinical, safety, and PK data. **Name:** QRL-101 **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Placebo **Description:** A placebo comparator will be administered at all dose levels. **Name:** Placebo **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** Endpoints: A summary of treatment emergent adverse events (AEs), serious adverse events (SAEs), and other non-serious adverse events, regardless of causality, will be reported in the Reported Adverse Events module. **Measure:** Number of participants with one or more treatment emergent adverse events and serious adverse events. **Time Frame:** Baseline through Follow up (Day 10) #### Secondary Outcomes **Description:** Endpoint: Maximum observed concentration (Cmax) of QRL-101 **Measure:** Pharmacokinetics (plasma): Maximum observed concentration of QRL-101 **Time Frame:** Baseline through Follow up (Day 10) **Description:** Endpoint: Area under the concentration time curve from zero to infinity (AUC 0-24h) of QRL-101 **Measure:** Pharmacokinetics (plasma): Area under the concentration time curve from 0 to 24 h (AUC 0-24h) of QRL-101 **Time Frame:** Baseline through Follow up (Day 10) **Description:** Endpoint: Time of maximum concentration (Tmax) of QRL-101 **Measure:** Pharmacokinetics (plasma): Time of maximum concentration of QRL-101 **Time Frame:** Baseline through Follow up (Day 10) ### Eligibility Module **Eligibility Criteria:** INCLUSION CRITERIA 1. Age 18 to 70 years of age inclusive at the time of signing the informed consent. 2. Clinical chemistry laboratory values within acceptable range for the population, as per investigator judgment. 3. Body mass index of 18 to 32 kg/m2 (inclusive). 4. Willing and able to practice effective contraception. EXCLUSION CRITERIA 1. Currently enrolled in any other clinical trial involving a study drug or off-label use of a drug or device, or any other type of medical research judged not to be scientifically or medically compatible with this study. 2. Any participant in \>4 studies a year and/or has participated in a clinical trial within 1 month of expected dosing date. 3. History or presence of medical illness including, but not limited to, any cardiovascular, hepatic, respiratory, hematological, endocrine, psychiatric, or neurological disease, convulsions, or any clinically significant laboratory abnormality that, in the judgment of the investigator, indicate a medical problem that would preclude study participation. \*Other inclusion and exclusion criteria may apply\* **Healthy Volunteers:** True **Maximum Age:** 70 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Groningen **Country:** Netherlands **Facility:** ICON plc. Van Swietenlaan 6 **Zip:** 9728 NZ #### Overall Officials **Official 1:** **Affiliation:** ICON plc **Name:** Salah Hadi, MD **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03286179 **Acronym:** STEWARD **Brief Title:** Standardizing Emergency Work-ups Around Risk Data **Official Title:** Standardizing Emergency Work-ups Around Risk Data (STEWARD): The CREST Network Chest Pain Project #### Organization Study ID Info **ID:** CN-16-2648 #### Organization **Class:** OTHER **Full Name:** Kaiser Permanente ### Status Module #### Completion Date **Date:** 2020-06-01 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2020-08-12 **Type:** ACTUAL **Last Update Submit Date:** 2020-08-11 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2019-12-31 **Type:** ACTUAL #### Start Date **Date:** 2018-07-01 **Type:** ACTUAL **Status Verified Date:** 2020-08 #### Study First Post Date **Date:** 2017-09-18 **Type:** ACTUAL **Study First Submit Date:** 2017-09-13 **Study First Submit QC Date:** 2017-09-13 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Kaiser Permanente #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Chest pain is the second leading reason for emergency department (ED) visits in the United States. Resource utilization for this ED subpopulation is particularly high, in part due to a dearth of accepted standardized clinical approaches and general overestimation of risk on the part of both providers and patients. This prospective observational cohort study seeks to address this issue by providing externally validated risk scores for major adverse cardiac events using a web-based clinical decision support platform (RISTRA) embedded within the electronic health record at 13 Kaiser Permanente Northern California (KPNC) EDs over a 12-month period. The decision support will provide risk estimates specific to the KPNC patient population. This studies hypothesis is that the provision of more accurate risk estimation for major adverse cardiac events will improve informed decision making by both providers and patients, resulting in less provocative testing and lower ED lengths of stay amongst low risk patients, as well as improving medical management among non-low risk patients and decreasing future rates of major adverse cardiac events. ### Conditions Module **Conditions:** - Acute Coronary Syndrome - Chest Pain - Risk Reduction ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 13419 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module ### Interventions #### Intervention 1 **Description:** Provision of estimated risk for major cardiac events at 60 days based on the modified HEART and/or EDACS, using KPNC specific estimates derived from an internal validation study **Name:** modified HEART score and/or Emergency Department Assessment of Chest pain Risk Score (EDACS) **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** A composite outcome of either acute myocardial infarction, cardiac arrest, malignant arrhythmia, cardiac-related mortality **Measure:** Major adverse cardiac event (MACE) **Time Frame:** 12 months #### Secondary Outcomes **Description:** Treadmill stress test, myocardial perfusion imaging, stress echocardiography, CT coronary angiography, catheter-based coronary angiography **Measure:** Provocative and anatomic cardiac testing rates **Time Frame:** 12 months **Description:** Total hours spent in the emergency department among study eligible patients **Measure:** Emergency department length of stay **Time Frame:** 12 months **Description:** Percentage of hospital admissions among study eligible patients **Measure:** Hospital admission rate **Time Frame:** 12 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Emergency department chief complaint of chest pain or chest discomfort * Clinical concern for possible cardiac ischemia **Healthy Volunteers:** True **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Adult patients presenting to KPNC emergency departments with above elgibilty criteria ### Contacts Locations Module #### Locations **Location 1:** **City:** Antioch **Country:** United States **Facility:** Kaiser Permanente Antioch Emergency Department **State:** California **Zip:** 94531 **Location 2:** **City:** Fremont **Country:** United States **Facility:** Kaiser Permanente Fremont Emergency Department **State:** California **Zip:** 94538 **Location 3:** **City:** Oakland **Country:** United States **Facility:** Kaiser Permanente Oakland Emergency Department **State:** California **Zip:** 94611 **Location 4:** **City:** Richmond **Country:** United States **Facility:** Kaiser Permanente Richmond Emergency Department **State:** California **Zip:** 94801 **Location 5:** **City:** Roseville **Country:** United States **Facility:** Kaiser Permanente Roseville Emergency Department **State:** California **Zip:** 95661 **Location 6:** **City:** Sacramento **Country:** United States **Facility:** Kaiser Permanente South Sacramento Emergency Department **State:** California **Zip:** 95823 **Location 7:** **City:** Sacramento **Country:** United States **Facility:** Kaiser Permanente Sacramento Emergency Department **State:** California **Zip:** 95825 **Location 8:** **City:** San Francisco **Country:** United States **Facility:** Kaiser Permanente San Francisco Emergency Department **State:** California **Zip:** 94115 **Location 9:** **City:** San Leandro **Country:** United States **Facility:** Kaiser Permanente San Leandro Emergency Department **State:** California **Zip:** 94577 **Location 10:** **City:** San Rafael **Country:** United States **Facility:** Kaiser Permanente San Rafael Emergency Department **State:** California **Zip:** 94903 **Location 11:** **City:** South San Francisco **Country:** United States **Facility:** Kaiser Permanente South San Francisco Emergency Department **State:** California **Zip:** 94080 **Location 12:** **City:** Walnut Creek **Country:** United States **Facility:** Kaiser Permanente Walnut Creek Emergency Department **State:** California **Zip:** 94596 ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Sabbatini AK, Nallamothu BK, Kocher KE. Reducing variation in hospital admissions from the emergency department for low-mortality conditions may produce savings. Health Aff (Millwood). 2014 Sep;33(9):1655-63. doi: 10.1377/hlthaff.2013.1318. **PMID:** 25201672 **Citation:** Venkatesh AK, Dai Y, Ross JS, Schuur JD, Capp R, Krumholz HM. Variation in US hospital emergency department admission rates by clinical condition. Med Care. 2015 Mar;53(3):237-44. doi: 10.1097/MLR.0000000000000261. **PMID:** 25397965 **Citation:** Newman DH, Ackerman B, Kraushar ML, Lederhandler MH, Masri A, Starikov A, Tsao DT, Meyers HP, Shah KH. Quantifying Patient-Physician Communication and Perceptions of Risk During Admissions for Possible Acute Coronary Syndromes. Ann Emerg Med. 2015 Jul;66(1):13-8, 18.e1. doi: 10.1016/j.annemergmed.2015.01.027. Epub 2015 Mar 4. **PMID:** 25748480 **Citation:** Than MP, Pickering JW, Aldous SJ, Cullen L, Frampton CM, Peacock WF, Jaffe AS, Goodacre SW, Richards AM, Ardagh MW, Deely JM, Florkowski CM, George P, Hamilton GJ, Jardine DL, Troughton RW, van Wyk P, Young JM, Bannister L, Lord SJ. Effectiveness of EDACS Versus ADAPT Accelerated Diagnostic Pathways for Chest Pain: A Pragmatic Randomized Controlled Trial Embedded Within Practice. Ann Emerg Med. 2016 Jul;68(1):93-102.e1. doi: 10.1016/j.annemergmed.2016.01.001. **PMID:** 26947800 **Citation:** Mahler SA, Riley RF, Hiestand BC, Russell GB, Hoekstra JW, Lefebvre CW, Nicks BA, Cline DM, Askew KL, Elliott SB, Herrington DM, Burke GL, Miller CD. The HEART Pathway randomized trial: identifying emergency department patients with acute chest pain for early discharge. Circ Cardiovasc Qual Outcomes. 2015 Mar;8(2):195-203. doi: 10.1161/CIRCOUTCOMES.114.001384. Epub 2015 Mar 3. **PMID:** 25737484 **Citation:** Mark DG, Huang J, Ballard DW, Kene MV, Sax DR, Chettipally UK, Lin JS, Bouvet SC, Cotton DM, Anderson ML, McLachlan ID, Simon LE, Shan J, Rauchwerger AS, Vinson DR, Reed ME; Kaiser Permanente CREST Network Investigators [Link]. Graded Coronary Risk Stratification for Emergency Department Patients With Chest Pain: A Controlled Cohort Study. J Am Heart Assoc. 2021 Nov 16;10(22):e022539. doi: 10.1161/JAHA.121.022539. Epub 2021 Nov 6. **PMID:** 34743565 **Citation:** Mark DG, Huang J, Kene MV, Sax DR, Cotton DM, Lin JS, Bouvet SC, Chettipally UK, Anderson ML, McLachlan ID, Simon LE, Shan J, Rauchwerger AS, Vinson DR, Ballard DW, Reed ME; Kaiser Permanente CREST Network Investigators. Prospective Validation and Comparative Analysis of Coronary Risk Stratification Strategies Among Emergency Department Patients With Chest Pain. J Am Heart Assoc. 2021 Apr 6;10(7):e020082. doi: 10.1161/JAHA.120.020082. Epub 2021 Mar 31. **PMID:** 33787290 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000020969 - Term: Disease Attributes - ID: D000010335 - Term: Pathologic Processes - ID: D000017202 - Term: Myocardial Ischemia - ID: D000006331 - Term: Heart Diseases - ID: D000002318 - Term: Cardiovascular Diseases - ID: D000014652 - Term: Vascular Diseases - 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: BC14 - Name: Heart and Blood Diseases - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M7796 - Name: Emergencies - Relevance: HIGH - As Found: Emergency - ID: M27545 - Name: Acute Coronary Syndrome - Relevance: HIGH - As Found: Acute Coronary Syndrome - ID: M16355 - Name: Syndrome - Relevance: LOW - As Found: Unknown - ID: M13066 - Name: Pain - Relevance: LOW - As Found: Unknown - ID: M5882 - Name: Chest Pain - Relevance: HIGH - As Found: Chest Pain - ID: M22700 - Name: Disease Attributes - Relevance: LOW - As Found: Unknown - ID: M10543 - Name: Ischemia - 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: M9419 - Name: Heart Diseases - Relevance: LOW - As Found: Unknown - ID: M17400 - Name: Vascular Diseases - 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: D000054058 - Term: Acute Coronary Syndrome - ID: D000004630 - Term: Emergencies - ID: D000002637 - Term: Chest Pain ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT01583179 **Brief Title:** Duration of Analgesic Effect for Ultrasound Guided Supraclavicular Blocks With the Addition of Buprenorphine to Local Anesthetic Solution **Official Title:** Duration of Analgesic Effect for Ultrasound Guided Supraclavicular Blocks With the Addition of Buprenorphine to Local Anesthetic Solution #### Organization Study ID Info **ID:** 2011-0781 #### Organization **Class:** OTHER **Full Name:** University of Wisconsin, Madison #### Secondary ID Infos **Domain:** UW, Madison **ID:** SMPH/ANESTHESIO **Type:** OTHER **Domain:** UW, Madison **ID:** A530900 **Type:** OTHER ### Status Module #### Completion Date **Date:** 2015-12 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2019-09-11 **Type:** ACTUAL **Last Update Submit Date:** 2019-09-10 **Overall Status:** TERMINATED #### Primary Completion Date **Date:** 2014-03 **Type:** ACTUAL #### Results First Post Date **Date:** 2019-09-11 **Type:** ACTUAL **Results First Submit Date:** 2019-08-19 **Results First Submit QC Date:** 2019-09-10 #### Start Date **Date:** 2012-04 **Type:** ACTUAL **Status Verified Date:** 2019-09 #### Study First Post Date **Date:** 2012-04-23 **Type:** ESTIMATED **Study First Submit Date:** 2012-04-19 **Study First Submit QC Date:** 2012-04-19 **Why Stopped:** The study was closed prematurely due to low enrollment and anticipation of future barriers in enrollment ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** University of Wisconsin, Madison #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** The patients included will be those who have already agreed to have a brachial plexus nerve block for surgery. A flip of the coin will decide who gets and additive called buprenorphine in their block or not. They will both contain the same amount and type of numbing medicine. The goal will be to see if the additive extends the life of the pain control portion of the ultrasound guided supraclavicular nerve block. ### Conditions Module **Conditions:** - Regional Block for Pain Control - Supraclavicular Block - Ultrasound Guided Block - Block Additive **Keywords:** - nerve block - outpatient surgery ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** QUADRUPLE **Who Masked:** - PARTICIPANT - CARE_PROVIDER - INVESTIGATOR - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 26 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** will get only local anesthetic and epinephrine in block. no additive in block **Label:** Control group **Type:** NO_INTERVENTION #### Arm Group 2 **Description:** will receive local anesthetic, epinephrine and the additive buprenorphine to nerve block **Intervention Names:** - Drug: Buprenorphine **Label:** buprenorphine **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - buprenorphine **Description:** added to nerve block, 0.3mg one time peripheral block use **Name:** Buprenorphine **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Time in minutes until first pain medication was take by participant post-operatively **Measure:** Time Until First Pain Medication Post-operatively **Time Frame:** 48 hrs #### Secondary Outcomes **Description:** pain score on post operative day 1 was measured on a scale 1-10. higher scores correlates with more severe pain. score range is from '0' (no pain) to 10 (pain as severe as it can be) **Measure:** Pain Score on Post Operative Day 1 **Time Frame:** 1 day postoperative ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. American Society of Anesthesiologists (ASA) physical status 1-3 2. Age 18-79, inclusive 3. BMI \<36 kg/m\^2 4. Patient consenting to single injection brachial plexus nerve block as primary anesthetic for a procedure Exclusion Criteria: 1. Patients with coagulation disorders 2. Clinically significant pulmonary disease 3. Clinically significant cardiac disease 4. Neurologic deficit in surgical extremity 5. Allergy to bupivacaine or buprenorphine 6. Intolerance of narcotics 7. Local infection over intended area of needle insertion 8. Hepatic failure or renal failure 9. Significant psychiatric disease, including drug abuse 10. Seizure disorder 11. Possible pregnancy or lactation by patient report 12. Use of narcotic medication greater than 2 times a week for greater than 1 week. 13. Patients for whom the surgeon requests a shorter-acting block **Maximum Age:** 79 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Madison **Country:** United States **Facility:** University of Wisconsin **State:** Wisconsin **Zip:** 53705 #### Overall Officials **Official 1:** **Affiliation:** University of Wisconsin School of Medicine and Public Health, Madison **Name:** Melanie Donnelly, MD **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M13066 - Name: Pain - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Ancestors - ID: D000000701 - Term: Analgesics, Opioid - ID: D000009294 - Term: Narcotics - ID: D000002492 - Term: Central Nervous System Depressants - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000000700 - Term: Analgesics - ID: D000018689 - Term: Sensory System Agents - ID: D000018373 - Term: Peripheral Nervous System Agents - ID: D000009292 - Term: Narcotic Antagonists ### Intervention Browse Module - Browse Branches - Abbrev: CNSDep - Name: Central Nervous System Depressants - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: PhSol - Name: Pharmaceutical Solutions - Abbrev: Analg - Name: Analgesics - Abbrev: VaCoAg - Name: Vasoconstrictor Agents - Abbrev: Resp - Name: Respiratory System Agents - Abbrev: NarcAntag - Name: Narcotic Antagonists ### Intervention Browse Module - Browse Leaves - ID: M4107 - Name: Anesthetics - Relevance: LOW - As Found: Unknown - ID: M21860 - Name: Pharmaceutical Solutions - Relevance: LOW - As Found: Unknown - ID: M4032 - Name: Analgesics - Relevance: LOW - As Found: Unknown - ID: M4109 - Name: Anesthetics, Local - Relevance: LOW - As Found: Unknown - ID: M7992 - Name: Epinephrine - Relevance: LOW - As Found: Unknown - ID: M5317 - Name: Buprenorphine - Relevance: HIGH - As Found: Aortic - ID: M30371 - Name: Racepinephrine - Relevance: LOW - As Found: Unknown - ID: M211043 - Name: Epinephryl borate - Relevance: LOW - As Found: Unknown - ID: M4033 - Name: Analgesics, Opioid - Relevance: LOW - As Found: Unknown - ID: M12245 - Name: Narcotics - Relevance: LOW - As Found: Unknown - ID: M12243 - Name: Narcotic Antagonists - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000002047 - Term: Buprenorphine ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module **Description:** Adverse events were not monitored. The study was closed prematurely due to low enrollment and anticipation of future barriers in enrollment #### Event Groups **Group ID:** EG000 **Title:** Control Group **Description:** will get only local anesthetic and epinephrine in block. no additive in block **ID:** EG000 **Title:** Control Group **Group ID:** EG001 **Title:** Buprenorphine **Description:** will receive local anesthetic, epinephrine and the additive buprenorphine to nerve block Buprenorphine: added to nerve block, 0.3mg one time peripheral block use **ID:** EG001 **Title:** Buprenorphine **Frequency Threshold:** 0 ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 14 **Group ID:** BG001 **Value:** 12 **Group ID:** BG002 **Value:** 26 **Units:** Participants ### Group **ID:** BG000 **Title:** Control Group **Description:** will get only local anesthetic and epinephrine in block. no additive in block ### Group **ID:** BG001 **Title:** Buprenorphine **Description:** will receive local anesthetic, epinephrine and the additive buprenorphine to nerve block Buprenorphine: added to nerve block, 0.3mg one time peripheral block use ### Group **ID:** BG002 **Title:** Total **Description:** Total of all reporting groups ### Measure #### Measurement **Group ID:** BG000 **Value:** 3 #### Measurement **Group ID:** BG001 **Value:** 3 #### Measurement **Group ID:** BG002 **Value:** 6 **Category Title:** 20-29 #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 2 #### Measurement **Group ID:** BG002 **Value:** 2 **Category Title:** 30-39 #### Measurement **Group ID:** BG000 **Value:** 4 #### Measurement **Group ID:** BG001 **Value:** 1 #### Measurement **Group ID:** BG002 **Value:** 5 **Category Title:** 40-49 #### Measurement **Group ID:** BG000 **Value:** 3 #### Measurement **Group ID:** BG001 **Value:** 3 #### Measurement **Group ID:** BG002 **Value:** 6 **Category Title:** 50-59 #### Measurement **Group ID:** BG000 **Value:** 3 #### Measurement **Group ID:** BG001 **Value:** 2 #### Measurement **Group ID:** BG002 **Value:** 5 **Category Title:** 60-69 #### Measurement **Group ID:** BG000 **Value:** 1 #### Measurement **Group ID:** BG001 **Value:** 1 #### Measurement **Group ID:** BG002 **Value:** 2 **Category Title:** 70-79 **Class Title:** Age of participants ### Measure #### Measurement **Group ID:** BG000 **Value:** 8 #### Measurement **Group ID:** BG001 **Value:** 6 #### Measurement **Group ID:** BG002 **Value:** 14 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 6 #### Measurement **Group ID:** BG001 **Value:** 6 #### Measurement **Group ID:** BG002 **Value:** 12 **Category Title:** Male **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** Hispanic or Latino #### Measurement **Group ID:** BG000 **Value:** 12 #### Measurement **Group ID:** BG001 **Value:** 11 #### Measurement **Group ID:** BG002 **Value:** 23 **Category Title:** Not Hispanic or Latino #### Measurement **Group ID:** BG000 **Value:** 2 #### Measurement **Group ID:** BG001 **Value:** 1 #### Measurement **Group ID:** BG002 **Value:** 3 **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:** 0 #### Measurement **Group ID:** BG001 **Value:** 1 #### Measurement **Group ID:** BG002 **Value:** 1 **Category Title:** Black or African American #### Measurement **Group ID:** BG000 **Value:** 11 #### Measurement **Group ID:** BG001 **Value:** 11 #### Measurement **Group ID:** BG002 **Value:** 22 **Category Title:** White #### Measurement **Group ID:** BG000 **Value:** 1 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 1 **Category Title:** More than one race #### Measurement **Group ID:** BG000 **Value:** 2 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 2 **Category Title:** Unknown or Not Reported **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 ### 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 ## Results Section - More Information Module ### Certain Agreement **PI Sponsor Employee:** True ### Point of Contact **Email:** [email protected] **Organization:** University of Wisconsin-Madison **Phone:** 720-848-0000 **Title:** Melanie Donnelly ## 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:** 250 - **Upper Limit:** - **Value:** 965 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 311 - **Upper Limit:** - **Value:** 862 **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 4.25 - **Spread:** - **Upper Limit:** 7.75 - **Value:** 6.5 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 1.75 - **Spread:** - **Upper Limit:** 8.25 - **Value:** 4.5 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** Time in minutes until first pain medication was take by participant post-operatively **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** The study was closed prematurely due to low enrollment and anticipation of future barriers in enrollment.The Overall Number of Participants Analyzed represents the Number of Participants with evaluable data. **Reporting Status:** POSTED **Time Frame:** 48 hrs **Title:** Time Until First Pain Medication Post-operatively **Type:** PRIMARY **Unit of Measure:** Time in minutes ##### Group **Description:** will get only local anesthetic and epinephrine in block. no additive in block **ID:** OG000 **Title:** Control Group ##### Group **Description:** will receive local anesthetic, epinephrine and the additive buprenorphine to nerve block Buprenorphine: added to nerve block, 0.3mg one time peripheral block use **ID:** OG001 **Title:** Buprenorphine #### Outcome Measure 2 **Description:** pain score on post operative day 1 was measured on a scale 1-10. higher scores correlates with more severe pain. score range is from '0' (no pain) to 10 (pain as severe as it can be) **Dispersion Type:** Inter-Quartile Range **Parameter Type:** MEDIAN **Population Description:** The study was closed prematurely due to low enrollment and anticipation of future barriers in enrollment **Reporting Status:** POSTED **Time Frame:** 1 day postoperative **Title:** Pain Score on Post Operative Day 1 **Type:** SECONDARY **Unit of Measure:** score on a scale ##### Group **Description:** will get only local anesthetic and epinephrine in block. no additive in block **ID:** OG000 **Title:** Control Group ##### Group **Description:** will receive local anesthetic, epinephrine and the additive buprenorphine to nerve block Buprenorphine: added to nerve block, 0.3mg one time peripheral block use **ID:** OG001 **Title:** Buprenorphine ### Participant Flow Module #### Group **Description:** will get only local anesthetic and epinephrine in block. no additive in block **ID:** FG000 **Title:** Control Group #### Group **Description:** will receive local anesthetic, epinephrine and the additive buprenorphine to nerve block Buprenorphine: added to nerve block, 0.3mg one time peripheral block use **ID:** FG001 **Title:** Buprenorphine #### Period **Title:** Overall Study ##### Withdraw **Type:** Screen failure ###### Reason **Group ID:** FG000 **Number of Subjects:** 1 ###### Reason **Group ID:** FG001 **Number of Subjects:** 2 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 14 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 12 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 13 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 10 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 1 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 2 **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT00602979 **Brief Title:** Comparison Study in Adult Surgical Patients of 5 Airway Devices **Official Title:** Prospective, Randomized Comparison of Intubating Conditions With Airtraq Optical, Storz DCI Video, McGRATH Video, GlideScope Video, & Macintosh Laryngoscope in Randomly Selected Elective Adult Surgical Patients #### Organization Study ID Info **ID:** 0710009433 #### Organization **Class:** OTHER **Full Name:** Weill Medical College of Cornell University ### Status Module #### Completion Date **Date:** 2011-07 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2017-05-19 **Type:** ACTUAL **Last Update Submit Date:** 2017-04-10 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2009-09 **Type:** ACTUAL #### Results First Post Date **Date:** 2017-05-19 **Type:** ACTUAL **Results First Submit Date:** 2017-02-17 **Results First Submit QC Date:** 2017-04-10 #### Start Date **Date:** 2008-04 **Status Verified Date:** 2017-04 #### Study First Post Date **Date:** 2008-01-28 **Type:** ESTIMATED **Study First Submit Date:** 2008-01-15 **Study First Submit QC Date:** 2008-01-15 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** King Systems Corporation **Class:** INDUSTRY **Name:** KARL STORZ Endoscopy-America, Inc. #### Lead Sponsor **Class:** OTHER **Name:** Weill Medical College of Cornell University #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** The placement of endotracheal tubes (intubation) is a physiologically stressful procedure for patients. Laryngoscopes are devices-typically composed of a blade attached to a handle with a light source-that allow examination of the upper airway through the mouth, often for the purposes of intubation. Recently some new laryngoscope devices (including the Airtraq® Optical Laryngoscope, the Storz DCI Video laryngoscope®, McGRATH® Video Laryngoscope, and the GlideScope®) have been developed, which may either decrease the stress related to intubation (reduce neck extension, reduce risk of complications or reduce time elapsed during intubation) or improve intubation success (reduce the number of attempts at intubating). Data are being collected in this study to determine which of these commonly-used devices may be better, particularly in comparison to the current hospital standard, the Macintosh laryngoscope. All of the devices to be used in this study are currently cleared or exempt by the Food and Drug Administration (FDA). **Detailed Description:** Historically, optical and video laryngoscopes have been used as alternative airway management devices for the difficult airway, and as rescue devices. Their use by experienced laryngoscopists has not been compared in a prospective, randomized, head-to-head comparison for routine airway management in adult surgical patients. Video and optical laryngoscopes have been developed to improve the laryngeal view for tracheal intubation and to decrease physiological stress associated with the procedure. The objective of this study is to determine whether these devices offer superior intubating conditions for routine surgical management, over the Macintosh laryngoscope, which is the current standard. The devices to be compared in this study are the most commonly used video and optical laryngoscopes on the market and are cleared or exempt by the Food and Drug Administration (FDA). Eligible subjects include elective adult surgical patients with an ASA status between 1 and 3 requiring general endotracheal anesthesia. Subjects with a BMI ≥ 40, or undergoing surgery in close proximity to the neck will be excluded. Prior to surgery, subjects will receive a pre-anesthesia evaluation with particular attention to the airway using the Mallampati classification system; atlanto-occipital joint extension; thyro-mental distance; temporomandibular joint function; inter-incisor distance; and dental assessment. Subjects will be randomized for intubation with one of the five laryngoscopes in equal proportions. The following data were recorded: total intubation time, maximum neck extension using an angle gauge, glottic view, assessed by the anesthesiologist using the Cook modification of the Cormack-Lehane grading system (Figure 1), and ease of tracheal intubation using a 5-point rating scale; 5 (excellent) to 1 (poor). Subjects were queried about soreness or painful swallowing in the PACU and a week later via a phone call. ### Conditions Module **Conditions:** - Laryngoscopy - Intubation **Keywords:** - endotracheal intubation - intubation - laryngoscopy - laryngoscope - surgery ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** SINGLE **Who Masked:** - PARTICIPANT **Primary Purpose:** SUPPORTIVE_CARE #### Enrollment Info **Count:** 240 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Macintosh laryngoscope (control group/direct laryngoscopy) - current standard **Intervention Names:** - Device: Macintosh laryngoscope **Label:** Macintosh laryngoscope **Type:** OTHER #### Arm Group 2 **Description:** Airtraq® Optical Laryngoscope (an experimental group/indirect laryngoscopy) **Intervention Names:** - Device: Airtraq® Optical Laryngoscope **Label:** Airtraq Optical Laryngoscope **Type:** OTHER #### Arm Group 3 **Description:** Storz DCI Video Laryngoscope® (an experimental group/indirect laryngoscopy) **Intervention Names:** - Device: Storz DCI Video Laryngoscope® **Label:** Storz DCI Video Laryngoscope **Type:** OTHER #### Arm Group 4 **Description:** GlideScope® Video Laryngoscope (an experimental group/indirect laryngoscopy) **Intervention Names:** - Device: GlideScope® Video Laryngoscope **Label:** GlideScope Video Laryngoscope **Type:** OTHER #### Arm Group 5 **Description:** McGRATH® Video Laryngoscope (an experimental group/indirect laryngoscopy) **Intervention Names:** - Device: McGRATH® Video Laryngoscope **Label:** McGRATH Video Laryngoscope **Type:** OTHER ### Interventions #### Intervention 1 **Arm Group Labels:** - Macintosh laryngoscope **Description:** Used during laryngoscopy to facilitate intubation. **Name:** Macintosh laryngoscope **Type:** DEVICE #### Intervention 2 **Arm Group Labels:** - Airtraq Optical Laryngoscope **Description:** Used during laryngoscopy to facilitate intubation. **Name:** Airtraq® Optical Laryngoscope **Type:** DEVICE #### Intervention 3 **Arm Group Labels:** - Storz DCI Video Laryngoscope **Description:** Used during laryngoscopy to facilitate intubation **Name:** Storz DCI Video Laryngoscope® **Type:** DEVICE #### Intervention 4 **Arm Group Labels:** - GlideScope Video Laryngoscope **Description:** Used during laryngoscopy to facilitate intubation **Name:** GlideScope® Video Laryngoscope **Type:** DEVICE #### Intervention 5 **Arm Group Labels:** - McGRATH Video Laryngoscope **Description:** Used during laryngoscopy to facilitate intubation **Name:** McGRATH® Video Laryngoscope **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Description:** Percentage distribution of Cook's modification of Cormack-Lehane's grading system. This is a classification that records the best laryngeal view obtained with or without anterior laryngeal pressure. Each study subject will receive a grade of 1, 2A, 2B, 3A, 3B, or 4 in the Cormack-Lehane grading system. Grades 1 and 2A classify as an easy view: when the laryngeal inlet is visible. Grades 2B and 3A classify as restricted: when the posterior glottic structures are visible or the epiglottis is visible and can be lifted. Grades 3B and 4 classify as difficult: when the epiglottis cannot be lifted or when no laryngeal structures are visible. Cook's modification of Cormack-Lehane's Grades 1=1, 2=2A,3=2B, 4=3A, 5=3B, 6=4. **Measure:** Percentage Distribution of Cook's Modification of Cormack-Lehane's Grading System. Each Study Subject Will Receive a Grade of 1, 2A, 2B, 3A, 3B, or 4 in the Cormack-Lehane Grading System. **Time Frame:** 1 time during laryngoscopy ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Elective adult surgical patient requiring general endotracheal anesthesia. * Males and Females. * ASA Physical Status 1-3. * Age 18 years of age and older Exclusion Criteria: * Body Mass Index (BMI) ≥35kg/m2. * If subject is of childbearing potential, a positive pregnancy test at the time of study enrollment. * Has physical, mental, or medical conditions which, in the opinion of the Investigator, could compromise the subject's welfare, ability to communicate with the study staff, complete study activities, or would otherwise contraindicate study participation. * Intubated prior to surgery. * Severe cardiovascular, hepatic or renal disease. * Need for nasal intubation. * An investigator of this study. * Inclusion in another clinical research study. * Subject's refusal or inability to agree to and to sign the Informed Consent Form in English. * Subject requiring awake airway management. **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Overall Officials **Official 1:** **Affiliation:** Weill Medical College of Cornell University **Name:** Jon Samuels, MD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Cook TM. A new practical classification of laryngeal view. Anaesthesia. 2000 Mar;55(3):274-9. doi: 10.1046/j.1365-2044.2000.01270.x. **PMID:** 10671848 ## Derived Section ### Misc Info Module #### Removed Countries - Country: United States - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module #### Event Groups **Group ID:** EG000 **Title:** Macintosh Laryngoscope **Deaths Num At Risk:** 48 **Description:** Macintosh laryngoscope (control group/direct laryngoscopy) - current standard Macintosh laryngoscope: Used during laryngoscopy to facilitate intubation. **ID:** EG000 **Other Num at Risk:** 48 **Serious Number Affected:** 2 **Serious Number At Risk:** 48 **Title:** Macintosh Laryngoscope **Group ID:** EG001 **Title:** Airtraq Optical Laryngoscope **Deaths Num At Risk:** 48 **Description:** Airtraq® Optical Laryngoscope (an experimental group/indirect laryngoscopy) Airtraq® Optical Laryngoscope: Used during laryngoscopy to facilitate intubation. **ID:** EG001 **Other Num at Risk:** 48 **Serious Number At Risk:** 48 **Title:** Airtraq Optical Laryngoscope **Group ID:** EG002 **Title:** Storz DCI Video Laryngoscope **Deaths Num At Risk:** 48 **Description:** Storz DCI Video Laryngoscope® (an experimental group/indirect laryngoscopy) Storz DCI Video Laryngoscope®: Used during laryngoscopy to facilitate intubation **ID:** EG002 **Other Num at Risk:** 48 **Serious Number At Risk:** 48 **Title:** Storz DCI Video Laryngoscope **Group ID:** EG003 **Title:** GlideScope Video Laryngoscope **Deaths Num At Risk:** 48 **Description:** GlideScope® Video Laryngoscope (an experimental group/indirect laryngoscopy) GlideScope® Video Laryngoscope: Used during laryngoscopy to facilitate intubation **ID:** EG003 **Other Num at Risk:** 48 **Serious Number At Risk:** 48 **Title:** GlideScope Video Laryngoscope **Group ID:** EG004 **Title:** McGRATH Video Laryngoscope **Deaths Num At Risk:** 48 **Description:** McGRATH® Video Laryngoscope (an experimental group/indirect laryngoscopy) McGRATH® Video Laryngoscope: Used during laryngoscopy to facilitate intubation **ID:** EG004 **Other Num Affected:** 1 **Other Num at Risk:** 48 **Serious Number Affected:** 1 **Serious Number At Risk:** 48 **Title:** McGRATH Video Laryngoscope **Frequency Threshold:** 2 #### Other Events **Term:** Swollen Lip **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** #### Serious Events **Term:** Corneal Laceration **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Eye disorders ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 48 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 48 **Group ID:** EG002 **Num At Risk:** 48 **Group ID:** EG003 **Num At Risk:** 48 **Group ID:** EG004 **Num At Risk:** 48 **Term:** Iliac Vein Rupture **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 48 **Num Events:** 1 **Group ID:** EG001 **Num At Risk:** 48 **Group ID:** EG002 **Num At Risk:** 48 **Group ID:** EG003 **Num At Risk:** 48 **Group ID:** EG004 **Num At Risk:** 48 **Term:** Right Tonsillar Pillar Laceration **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders ##### Stats **Group ID:** EG000 **Num At Risk:** 48 **Group ID:** EG001 **Num At Risk:** 48 **Group ID:** EG002 **Num At Risk:** 48 **Group ID:** EG003 **Num At Risk:** 48 **Group ID:** EG004 **Num Affected:** 1 **Num At Risk:** 48 **Num Events:** 1 ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 48 **Group ID:** BG001 **Value:** 48 **Group ID:** BG002 **Value:** 48 **Group ID:** BG003 **Value:** 48 **Group ID:** BG004 **Value:** 48 **Group ID:** BG005 **Value:** 240 **Units:** Participants ### Group **ID:** BG000 **Title:** Macintosh Laryngoscope **Description:** Macintosh laryngoscope (control group/direct laryngoscopy) - current standard Macintosh laryngoscope: Used during laryngoscopy to facilitate intubation. ### Group **ID:** BG001 **Title:** Airtraq Optical Laryngoscope **Description:** Airtraq® Optical Laryngoscope (an experimental group/indirect laryngoscopy) Airtraq® Optical Laryngoscope: Used during laryngoscopy to facilitate intubation. ### Group **ID:** BG002 **Title:** Storz DCI Video Laryngoscope **Description:** Storz DCI Video Laryngoscope® (an experimental group/indirect laryngoscopy) Storz DCI Video Laryngoscope®: Used during laryngoscopy to facilitate intubation ### Group **ID:** BG003 **Title:** GlideScope Video Laryngoscope **Description:** GlideScope® Video Laryngoscope (an experimental group/indirect laryngoscopy) GlideScope® Video Laryngoscope: Used during laryngoscopy to facilitate intubation ### Group **ID:** BG004 **Title:** McGRATH Video Laryngoscope **Description:** McGRATH® Video Laryngoscope (an experimental group/indirect laryngoscopy) McGRATH® Video Laryngoscope: Used during laryngoscopy to facilitate intubation ### Group **ID:** BG005 **Title:** Total **Description:** Total of all reporting groups ### Measure #### Measurement **Group ID:** BG000 **Spread:** 16.9 **Value:** 50.3 #### Measurement **Group ID:** BG001 **Spread:** 13.5 **Value:** 46.1 #### Measurement **Group ID:** BG002 **Spread:** 15.4 **Value:** 47.8 #### Measurement **Group ID:** BG003 **Spread:** 15.2 **Value:** 50.0 #### Measurement **Group ID:** BG004 **Spread:** 15.8 **Value:** 49.3 #### Measurement **Group ID:** BG005 **Spread:** 15.4 **Value:** 48.7 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 20 #### Measurement **Group ID:** BG001 **Value:** 25 #### Measurement **Group ID:** BG002 **Value:** 21 #### Measurement **Group ID:** BG003 **Value:** 25 #### Measurement **Group ID:** BG004 **Value:** 23 #### Measurement **Group ID:** BG005 **Value:** 114 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 28 #### Measurement **Group ID:** BG001 **Value:** 23 #### Measurement **Group ID:** BG002 **Value:** 27 #### Measurement **Group ID:** BG003 **Value:** 23 #### Measurement **Group ID:** BG004 **Value:** 25 #### Measurement **Group ID:** BG005 **Value:** 126 **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 ### Point of Contact **Email:** [email protected] **Organization:** Weill Cornell Medicine **Phone:** 212-746-2953 **Title:** Michele Steinkamp ## 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:** 1.96 - **Upper Limit:** - **Value:** 1.98 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.44 - **Upper Limit:** - **Value:** 1.18 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 0.54 - **Upper Limit:** - **Value:** 1.27 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** 0.59 - **Upper Limit:** - **Value:** 1.47 - **Comment:** - **Group ID:** OG004 - **Lower Limit:** - **Spread:** 0.34 - **Upper Limit:** - **Value:** 1.13 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** Percentage distribution of Cook's modification of Cormack-Lehane's grading system. This is a classification that records the best laryngeal view obtained with or without anterior laryngeal pressure. Each study subject will receive a grade of 1, 2A, 2B, 3A, 3B, or 4 in the Cormack-Lehane grading system. Grades 1 and 2A classify as an easy view: when the laryngeal inlet is visible. Grades 2B and 3A classify as restricted: when the posterior glottic structures are visible or the epiglottis is visible and can be lifted. Grades 3B and 4 classify as difficult: when the epiglottis cannot be lifted or when no laryngeal structures are visible. Cook's modification of Cormack-Lehane's Grades 1=1, 2=2A,3=2B, 4=3A, 5=3B, 6=4. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Reporting Status:** POSTED **Time Frame:** 1 time during laryngoscopy **Title:** Percentage Distribution of Cook's Modification of Cormack-Lehane's Grading System. Each Study Subject Will Receive a Grade of 1, 2A, 2B, 3A, 3B, or 4 in the Cormack-Lehane Grading System. **Type:** PRIMARY **Unit of Measure:** units on a scale ##### Group **Description:** Macintosh laryngoscope (control group/direct laryngoscopy) - current standard Macintosh laryngoscope: Used during laryngoscopy to facilitate intubation. **ID:** OG000 **Title:** Macintosh Laryngoscope ##### Group **Description:** Airtraq® Optical Laryngoscope (an experimental group/indirect laryngoscopy) Airtraq® Optical Laryngoscope: Used during laryngoscopy to facilitate intubation. **ID:** OG001 **Title:** Airtraq Optical Laryngoscope ##### Group **Description:** Storz DCI Video Laryngoscope® (an experimental group/indirect laryngoscopy) Storz DCI Video Laryngoscope®: Used during laryngoscopy to facilitate intubation **ID:** OG002 **Title:** Storz DCI Video Laryngoscope ##### Group **Description:** GlideScope® Video Laryngoscope (an experimental group/indirect laryngoscopy) GlideScope® Video Laryngoscope: Used during laryngoscopy to facilitate intubation **ID:** OG003 **Title:** GlideScope Video Laryngoscope ##### Group **Description:** McGRATH® Video Laryngoscope (an experimental group/indirect laryngoscopy) McGRATH® Video Laryngoscope: Used during laryngoscopy to facilitate intubation **ID:** OG004 **Title:** McGRATH Video Laryngoscope ### Participant Flow Module #### Group **Description:** Macintosh laryngoscope (control group/direct laryngoscopy) - current standard Macintosh laryngoscope: Used during laryngoscopy to facilitate intubation. **ID:** FG000 **Title:** Macintosh Laryngoscope #### Group **Description:** Airtraq® Optical Laryngoscope (an experimental group/indirect laryngoscopy) Airtraq® Optical Laryngoscope: Used during laryngoscopy to facilitate intubation. **ID:** FG001 **Title:** Airtraq Optical Laryngoscope #### Group **Description:** Storz DCI Video Laryngoscope® (an experimental group/indirect laryngoscopy) Storz DCI Video Laryngoscope®: Used during laryngoscopy to facilitate intubation **ID:** FG002 **Title:** Storz DCI Video Laryngoscope #### Group **Description:** GlideScope® Video Laryngoscope (an experimental group/indirect laryngoscopy) GlideScope® Video Laryngoscope: Used during laryngoscopy to facilitate intubation **ID:** FG003 **Title:** GlideScope Video Laryngoscope #### Group **Description:** McGRATH® Video Laryngoscope (an experimental group/indirect laryngoscopy) McGRATH® Video Laryngoscope: Used during laryngoscopy to facilitate intubation **ID:** FG004 **Title:** McGRATH Video Laryngoscope #### Period **Title:** Overall Study ##### Withdraw **Type:** Lost to Follow-up ###### Reason **Group ID:** FG000 **Number of Subjects:** 3 ###### Reason **Group ID:** FG001 **Number of Subjects:** 2 ###### Reason **Group ID:** FG002 **Number of Subjects:** 3 ###### Reason **Group ID:** FG003 **Number of Subjects:** 2 ###### Reason **Group ID:** FG004 **Number of Subjects:** 3 ##### Withdraw **Type:** Failed Intubation ###### Reason **Group ID:** FG000 **Number of Subjects:** 0 ###### Reason **Group ID:** FG001 **Number of Subjects:** 1 ###### Reason **Group ID:** FG002 **Number of Subjects:** 0 ###### Reason **Group ID:** FG003 **Number of Subjects:** 1 ###### Reason **Group ID:** FG004 **Number of Subjects:** 0 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 48 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 48 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 48 ###### Achievement **Group ID:** FG003 **Number of Subjects:** 48 ###### Achievement **Group ID:** FG004 **Number of Subjects:** 48 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 45 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 45 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 45 ###### Achievement **Group ID:** FG003 **Number of Subjects:** 45 ###### Achievement **Group ID:** FG004 **Number of Subjects:** 45 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 3 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 3 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 3 ###### Achievement **Group ID:** FG003 **Number of Subjects:** 3 ###### Achievement **Group ID:** FG004 **Number of Subjects:** 3 **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT06153979 **Brief Title:** Investigation of Immune Amnesia Following Measles Infection in Select African Regions **Official Title:** Investigation of Immune Amnesia Following Measles Infection in Select African Regions #### Organization Study ID Info **ID:** Measles West Africa 01 #### Organization **Class:** NIH **Full Name:** National Institute of Allergy and Infectious Diseases (NIAID) ### Status Module #### Completion Date **Date:** 2025-06 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-03-08 **Type:** ACTUAL **Last Update Submit Date:** 2024-03-06 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2025-06 **Type:** ESTIMATED #### Start Date **Date:** 2024-01-16 **Type:** ACTUAL **Status Verified Date:** 2024-03 #### Study First Post Date **Date:** 2023-12-01 **Type:** ACTUAL **Study First Submit Date:** 2023-10-25 **Study First Submit QC Date:** 2023-11-29 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** Johns Hopkins University #### Lead Sponsor **Class:** NIH **Name:** National Institute of Allergy and Infectious Diseases (NIAID) #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False ### Description Module **Brief Summary:** The goal of this observational study is to investigate the effects of measles virus (MeV) infection on pre-existing immunity, vaccine response, and susceptibility to subsequent illness in children aged 1-15 either with or without acute MeV infection. **Detailed Description:** This is a prospective, observational, longitudinal study to be conducted in West Africa. Eligible children will be enrolled into 1 of 2 arms: acute MeV infection (cases) or no acute MeV infection (controls) as assessed using upper respiratory specimens and blood samples. Blood samples will be collected at screening/enrollment (Day 0) and follow-up visits on Day 14, Week 13, and Week 52, and tested for humoral and cellular immune responses to endemic pathogens to determine changes in antibody diversity and antibody secreting cells (ASCs). All children in each arm will receive rabies vaccination (standard 3-dose series given as pre-exposure prophylaxis \[PrEP\]), with the first dose randomized to either Week 8 or Week 47 after enrollment. Biological samples will be collected after vaccination to assess if the immune stimulus (rabies vaccine) response differs: 1) between children with and without MeV infection, and 2) based on the timing of the receipt of the rabies vaccine. ### Conditions Module **Conditions:** - Measles Infection ### Design Module #### Bio Spec **Description:** Blood samples and upper respiratory specimens will be stored for analysis in repositories in each participating country. **Retention:** SAMPLES_WITH_DNA #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 256 **Type:** ESTIMATED **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Participants have acute MeV infection. **Intervention Names:** - Biological: Verorab **Label:** Group 1 - Actue MeV Infection #### Arm Group 2 **Description:** Participants do not have acute MeV infection. **Intervention Names:** - Biological: Verorab **Label:** Group 2 - No Actue MeV Infection ### Interventions #### Intervention 1 **Arm Group Labels:** - Group 1 - Actue MeV Infection - Group 2 - No Actue MeV Infection **Description:** Participants in each group will receive rabies vaccination (standard 3-dose series given as PrEP), with the first dose randomized to either Week 8 or Week 47 after enrollment. **Name:** Verorab **Type:** BIOLOGICAL ### Outcomes Module #### Primary Outcomes **Description:** Mean change in a panel of antibody levels over 13 weeks as measured by multiplex serological methods and targeted ELISAs for confirmation. **Measure:** Change in pre-existing immunity **Time Frame:** Week 13 after baseline **Description:** Proportion of subjects with rabies virus neutralizing antibodies (RVNA) titer ≥ 0.5 IU/mL as measured by rapid fluorescent focus inhibition test **Measure:** Effect of MeV infection on immune response to a controlled immune stimulus (rabies vaccination) **Time Frame:** 14 days after last PrEP regimen vaccination **Description:** Proportion of subjects with an RVNA titer ≥ lower limit of quantification **Measure:** Effect of MeV infection on immune response to a controlled immune stimulus **Time Frame:** 5-6 weeks after the first rabies vaccine dose **Description:** Geometric mean RVNA titer **Measure:** Effect of MeV infection on immune response to a controlled immune stimulus **Time Frame:** 5-6 weeks after the first rabies vaccine dose #### Secondary Outcomes **Description:** Mean number of non-study sick visit healthcare system encounters during the 1-year follow-up. **Measure:** Change in healthcare system encounters **Time Frame:** 1 year following enrollment **Description:** Mean change in a panel of antibody levels over 52 weeks as measured by multiplex serological methods and targeted ELISAs for confirmation. **Measure:** Change in pre-existing immunity **Time Frame:** Week 52 after baseline ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Aged 1 to 15 years. * Ability of the participant's legal or culturally acceptable representative to provide informed consent. * Ability to give assent, as appropriate. * Stated willingness of parent/guardian and participant as appropriate, to comply with all study procedures. * Willingness to receive rabies vaccine. * Meet the criteria for assignment to Group 1 or Group 2, as follows: * Group 1, cases (acute MeV infection): * Clinical signs and symptoms suggestive of acute MeV infection (Koplik spots or skin rash) AND * Laboratory confirmed measles: * Upper respiratory specimen (swab) PCR for measles positive, OR * Serum IgM for measles positive. * Group 2, controls (no acute MeV infection): * No clinical signs and symptoms suggestive of acute MeV infection (Koplik spots or skin rash) AND * Upper respiratory specimen (swab) PCR negative for MeV AND * Serum measles IgM negative AND * Serum measles IgG positive and previously vaccinated for measles (2nd dose will be offered if appropriate). If serum measles IgG is negative, participant must be willing to be vaccinated regardless of prior measles vaccine history to meet this criterion. Exclusion Criteria: * HIV infection or any other immunosuppressive condition or medications. * Pregnant or lactating. * History of prior measles or immunologic evidence of prior measles in the absence of prior measles vaccination. * Severe anemia, defined as hemoglobin less than 8 g/dL. * Any acute or chronic condition which, in the opinion of the investigator, constitutes a contraindication to participation in this study. **Healthy Volunteers:** True **Maximum Age:** 15 Years **Minimum Age:** 1 Year **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - CHILD **Study Population:** Specific study sites within each country will be in areas experiencing measles outbreaks. ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Karine G Fouth Tchos, M.D., M.Ph. **Phone:** 240-627-3641 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Esther Akpa, MSN, MPH, RN **Phone:** 301-761-7677 **Role:** CONTACT #### Locations **Location 1:** **City:** Conakry **Country:** Guinea **Facility:** Partnership of Clinical Research in Guinea, Partenariat Pour La Recherche Clinique en Guinée (PREGUI) **Status:** RECRUITING **Location 2:** **City:** Bamako **Country:** Mali **Facility:** University Clinical Research Center (UCRC) University of Sciences, Techniques and Technologies of Bamako **Status:** RECRUITING #### Overall Officials **Official 1:** **Affiliation:** National Institute of Allergy and Infectious Diseases (NIAID) **Name:** Katy Saliba, Sc.M., Ph.D. **Role:** STUDY_DIRECTOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000020969 - Term: Disease Attributes - ID: D000010335 - Term: Pathologic Processes - ID: D000018185 - Term: Morbillivirus Infections - ID: D000018184 - Term: Paramyxoviridae Infections - ID: D000018701 - Term: Mononegavirales Infections - ID: D000012327 - Term: RNA Virus Infections - ID: D000014777 - Term: Virus Diseases - ID: D000008569 - Term: Memory Disorders - ID: D000019954 - Term: Neurobehavioral Manifestations - ID: D000009461 - Term: Neurologic Manifestations - ID: D000009422 - Term: Nervous System Diseases - ID: D000019965 - Term: Neurocognitive Disorders - ID: D000001523 - Term: Mental Disorders ### Condition Browse Module - Browse Branches - Abbrev: BC01 - Name: Infections - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: BC10 - Name: Nervous System Diseases - Abbrev: BXM - Name: Behaviors and Mental Disorders - 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: HIGH - As Found: Infection - ID: M11440 - Name: Measles - Relevance: HIGH - As Found: Measles - ID: M3985 - Name: Amnesia - Relevance: HIGH - As Found: Amnesia - ID: M22700 - Name: Disease Attributes - Relevance: LOW - As Found: Unknown - ID: M20330 - Name: Paramyxoviridae Infections - Relevance: LOW - As Found: Unknown - ID: M20778 - Name: Mononegavirales 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: M11552 - Name: Memory Disorders - Relevance: LOW - As Found: Unknown - ID: M21826 - Name: Neurobehavioral Manifestations - Relevance: LOW - As Found: Unknown - ID: M12404 - Name: Neurologic Manifestations - Relevance: LOW - As Found: Unknown - ID: M21836 - Name: Neurocognitive Disorders - Relevance: LOW - As Found: Unknown - ID: M4815 - Name: Mental Disorders - Relevance: LOW - As Found: Unknown - ID: M14473 - Name: Psychotic Disorders - Relevance: LOW - As Found: Unknown - ID: T3653 - Name: Measles - Relevance: HIGH - As Found: Measles ### Condition Browse Module - Meshes - ID: D000007239 - Term: Infections - ID: D000003141 - Term: Communicable Diseases - ID: D000008457 - Term: Measles - ID: D000000647 - Term: Amnesia ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00796679 **Brief Title:** Oral Paricalcitol in Stage 3 - 5 Chronic Kidney Disease **Official Title:** A Prospective, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy of Oral Paricalcitol in Retarding Cardiac Hypertrophy, Reducing Inflammation and Atherosclerosis in Stage 3 - 5 Chronic Kidney Disease #### Organization Study ID Info **ID:** A10-003 #### Organization **Class:** OTHER **Full Name:** The University of Hong Kong ### Status Module #### Completion Date **Date:** 2011-06 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2017-01-10 **Type:** ESTIMATED **Last Update Submit Date:** 2017-01-07 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2011-06 **Type:** ACTUAL #### Start Date **Date:** 2008-10 **Status Verified Date:** 2017-01 #### Study First Post Date **Date:** 2008-11-24 **Type:** ESTIMATED **Study First Submit Date:** 2008-11-20 **Study First Submit QC Date:** 2008-11-21 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** Abbott #### Lead Sponsor **Class:** OTHER **Name:** The University of Hong Kong #### Responsible Party **Investigator Affiliation:** The University of Hong Kong **Investigator Full Name:** Dr. Angela Yee-Moon Wang **Investigator Title:** Dr. **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** The purpose of this study is to test the hypothesis that selective vitamin D receptor activation reduces left ventricular hypertrophy and ameliorates inflammation and atherosclerosis in stage 3 -5 chronic kidney disease. **Detailed Description:** Cardiovascular disease is the leading cause of mortality and morbidity in patients with chronic kidney disease. According to a previous study, only 15.6% of the patients beginning dialysis therapy had a normal echocardiogram, with left ventricular hypertrophy, left ventricular dilatation and systolic dysfunction occurring in 40.7%, 28% and 15.6% of patients, respectively. In addition, these patients are at an accelerated risk of developing atherosclerosis. The Kidney Disease Outcome Quality Initiative guideline recently raised concerns of a high prevalence of vitamin D deficiency in chronic kidney disease patients not yet requiring dialysis treatment. In addition, very recent data suggested that vitamin D deficiency is an important predictor of mortality in end-stage renal disease patients. Furthermore, hemodialysis patients treated with paricalcitol, a selective vitamin D receptor activator, showed a significantly lower risk of cardiovascular death than those not receiving vitamin D therapy. A number of studies also showed positive benefit of vitamin D receptor activator treatment on regression of left ventricular hypertrophy in dialysis patients. However, there is so far no data in patients with stage 3 and 4 chronic kidney disease where a high prevalence of vitamin D deficiency and cardiac hypertrophy has been reported. ### Conditions Module **Conditions:** - Chronic Kidney Disease **Keywords:** - paricalcitol - chronic kidney disease - cardiac hypertrophy ### 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:** 60 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** paricalcitol **Intervention Names:** - Drug: paricalcitol **Label:** 1 **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** placebo **Intervention Names:** - Drug: paricalcitol **Label:** 2 **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - 1 - 2 **Description:** oral paricalcitol capsule 1 microgram once daily if iPTH \<500pg/mL or 2 microgram once daily if iPTH \>=500pg/mL. Thereafter, dose titration in 1 microgram decrement will be done based on safety reasons (that is, for low PTH or high calcium and phosphorus level). The duration of treatment will be for 1 year. **Name:** paricalcitol **Other Names:** - Zemplar **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Measure:** Change in left ventricular mass index determined by MRI **Time Frame:** 1 year #### Secondary Outcomes **Measure:** Change in left atrial and ventricular volumes, systolic and diastolic function, carotid intima-media thickness, flow mediated dilation, pulse wave velocity, serum inflammatory and cardiac biomarkers, intact PTH, 24-hour urine protein and renal function **Time Frame:** 1 year ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Patient with stage 3 -5 chronic kidney disease (that is, eGFR \< 60 ml/min per 1.73m2) diagnosed for more than 2 months and not expected to start dialysis within the next 12 months, and * Patient with screening echocardiography showing evidence of left ventricular hypertrophy * Patient has not received vitamin D therapy in the previous 4 weeks * For entry into the Treatment Phase, the subject must have: * screening iPTH \>= 55 pg/ml or 5.8pmol/L (determined by the Nichols second-generation assay or similar assay) * serum calcium \< 10.2 mg/dL (2.55 mmol/L) * serum phosphorus =\< 5.2mg/dL (1.68mmol/L) * Ca\*P product \< 54 mg2/dL2 (4.36mmol2/L2) * If female, subject is either not of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy), or is of childbearing potential and practicing birth control measures. * Patients who provide informed consent for the study Exclusion Criteria: * Patient with a history of an allergic reaction or significant sensitivity to vitamin D or vitamin D related compounds. * Patient with history of renal stones * Patient with current malignancy * Patients with clinically significant gastrointestinal disease or liver disease * Patient with acute renal failure in the recent three months * Patient with a history of drug or alcohol abuse within six months prior to the screening phase * Patient is known to be human immunodeficiency virus (HIV) positive. * Patient with evidence of poor compliance with diet and medication. * Patient currently receiving medications that may affect calcium, phosphorus metabolism such as calcitonin, cinacalcet, bisphophonates or vitamin D compounds (other than study drug), or other drugs that may affect calcium or bone metabolism, other than females on stable estrogen and/or progestin therapy. * Patients with active granulomatous disease * Patient with pregnancy * Patients currently receiving glucocorticoid steroid or other immunosuppressive treatment or had been administered glucocorticoid or other immunosuppressive treatment for more than 14 days within recent 6 months. * Patients with contraindication for MRI examination **Maximum Age:** 75 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Hong Kong **Country:** Hong Kong **Facility:** Queen Mary Hospital **Zip:** 0000 **Location 2:** **City:** Hong Kong **Country:** Hong Kong **Facility:** University of Hong Kong, Queen Mary Hospital **Zip:** 0000 #### Overall Officials **Official 1:** **Affiliation:** Queen Mary Hospital, University of Hong Kong **Name:** Angela YM Wang, MD, FRCP **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### References **Citation:** Wang AY, Fang F, Chan J, Wen YY, Qing S, Chan IH, Lo G, Lai KN, Lo WK, Lam CW, Yu CM. Effect of paricalcitol on left ventricular mass and function in CKD--the OPERA trial. J Am Soc Nephrol. 2014 Jan;25(1):175-86. doi: 10.1681/ASN.2013010103. Epub 2013 Sep 19. Erratum In: J Am Soc Nephrol. 2019 Mar;30(3):516. **PMID:** 24052631 ## Derived Section ### Condition Browse Module - Ancestors - 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: D000051437 - Term: Renal Insufficiency - 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: BXS - Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M10293 - Name: Inflammation - Relevance: LOW - As Found: Unknown - ID: M10698 - Name: Kidney Diseases - Relevance: HIGH - As Found: Kidney Disease - ID: M26188 - Name: Atherosclerosis - Relevance: LOW - As Found: Unknown - ID: M10035 - Name: Hypertrophy - Relevance: LOW - As Found: Unknown - ID: M26717 - Name: Renal Insufficiency, Chronic - Relevance: HIGH - As Found: Chronic Kidney Disease - ID: M26718 - Name: Renal Insufficiency - 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: 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: HIGH - As Found: Chronic ### Condition Browse Module - Meshes - ID: D000007674 - Term: Kidney Diseases - ID: D000051436 - Term: Renal Insufficiency, Chronic ### 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: LOW - As Found: Unknown - ID: M5398 - Name: Calcium, Dietary - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05052879 **Brief Title:** Efficacy and Safety of Toronto Association in the Treatment of Erectile Dysfunction and Premature Ejaculation **Official Title:** National, Multicenter, Randomized, Double-blind, Double-dummy, Phase III Clinical Trial to Evaluate the Efficacy and Safety of Toronto Association in the Treatment of Erectile Dysfunction and Premature Ejaculation #### Organization Study ID Info **ID:** EMS0220 - TORONTO #### Organization **Class:** INDUSTRY **Full Name:** EMS ### Status Module #### Completion Date **Date:** 2026-08 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2023-04-12 **Type:** ACTUAL **Last Update Submit Date:** 2023-04-11 **Overall Status:** NOT_YET_RECRUITING #### Primary Completion Date **Date:** 2026-05 **Type:** ESTIMATED #### Start Date **Date:** 2024-07 **Type:** ESTIMATED **Status Verified Date:** 2023-04 #### Study First Post Date **Date:** 2021-09-22 **Type:** ACTUAL **Study First Submit Date:** 2021-09-14 **Study First Submit QC Date:** 2021-09-14 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** EMS #### 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 purpose of this study is to evaluate the efficacy and safety of Toronto association in the treatment of both sexual dysfunction: erectile dysfunction and premature ejaculation. ### Conditions Module **Conditions:** - Erectile Dysfunction - Premature Ejaculation **Keywords:** - Erectile dysfunction - Premature Ejaculation ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** DOUBLE **Who Masked:** - PARTICIPANT - INVESTIGATOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 232 **Type:** ESTIMATED **Phases:** - PHASE3 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** The study is double-dummy. The patient must take 2 tablets before the sexual intercourse, as follows: 1 tablet of Toronto association, oral; 1 tablet of tadalafil placebo, oral. **Intervention Names:** - Drug: Toronto association - Other: Tadalafil placebo **Label:** TORONTO 20 + 30/60 **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** The study is double-dummy. The patient must take 2 tablets before the sexual intercourse, as follows: 1 tablet of tadalafil , oral; 1 tablet of Toronto association placebo, oral. **Intervention Names:** - Drug: Tadalafil - Other: Toronto association placebo **Label:** TADALAFIL **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - TORONTO 20 + 30/60 **Description:** Toronto association coated tablet, 20 mg + 30 mg or 20 mg + 60 mg, oral, 2 hours before the sexual intercourse. **Name:** Toronto association **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - TADALAFIL **Description:** Tadalafil coated tablet, 20 mg, oral, 2 hours before the sexual intercourse. **Name:** Tadalafil **Type:** DRUG #### Intervention 3 **Arm Group Labels:** - TORONTO 20 + 30/60 **Description:** Tadalafil placebo coated tablet, oral, 2 hours before the sexual intercourse. **Name:** Tadalafil placebo **Type:** OTHER #### Intervention 4 **Arm Group Labels:** - TADALAFIL **Description:** Toronto association placebo coated tablet, oral, 2 hours before the sexual intercourse. **Name:** Toronto association placebo **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** The treatment response will be based on the participant's questionnaire answer after the treatment. **Measure:** Percentage of participants with treatment response after 4 weeks of treatment. **Time Frame:** 4 weeks **Description:** The treatment response will be based on the participant's questionnaire answer after the treatment. **Measure:** Percentage of participants with treatment response after 8 weeks of treatment. **Time Frame:** 8 weeks #### Secondary Outcomes **Description:** Incidence and severity of adverse events recorded during the study. **Measure:** Adverse events **Time Frame:** 103 days ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Ability to confirm voluntary participation and agree to all trial purposes by signing and dating the informed consent forms; * Male participants, with age greater than or equal to 18 years; * Heterosexual, sexually active participants in a stable and monogamous relationship for at least 6 months before screening and who plan to maintain this relationship throughout the study period; * Participants with erectile dysfunction, in stable and effective treatment with PDE-5 inhibitors; * Participants diagnosed with premature ejaculation; * Participants with IELT ≤ 2 minutes; * Participants with score ≥ 25 points in the erectile function questionnaire; * Participants (or partners) who use at least one contraceptive method. Exclusion Criteria: * Any clinical and laboratory findings that, in the judgment of the investigator, may interfere with the safety of research participants; * Participation in a clinical trial in the year prior to this study; * Known hypersensitivity to any of the formula compounds; * Participants with cardiovascular disease for whom sexual activity is inadvisable * History or current experience of surgical interventions or radiotherapy in the pelvic region, neurological conditions, trauma or infections that are associated with the symptoms premature ejaculation; * Diagnosis of other diseases or conditions in the urinary tract; * Participants with conditions that may predispose them to priapism; * History of severe psychiatric or psychosocial disorders; * Participant whose partner has clinically important sexual dysfunctions. **Minimum Age:** 18 Years **Sex:** MALE **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Arthur M Kummer, MD **Phone:** +551938879851 **Role:** CONTACT ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000007752 - Term: Obstetric Labor, Premature - ID: D000007744 - Term: Obstetric Labor Complications - ID: D000011248 - Term: Pregnancy Complications - ID: D000005261 - Term: Female Urogenital Diseases and Pregnancy Complications - ID: D000091642 - Term: Urogenital Diseases - ID: D000005832 - Term: Genital Diseases, Male - ID: D000091662 - Term: Genital Diseases - ID: D000012735 - Term: Sexual Dysfunction, Physiological - ID: D000052801 - Term: Male Urogenital Diseases - ID: D000020018 - Term: Sexual Dysfunctions, Psychological - ID: D000001523 - Term: Mental Disorders - ID: D000097910 - Term: Ejaculatory Dysfunction ### Condition Browse Module - Browse Branches - Abbrev: BXS - Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions - Abbrev: All - Name: All Conditions - Abbrev: BXM - Name: Behaviors and Mental Disorders ### Condition Browse Module - Browse Leaves - ID: M25869 - Name: Premature Birth - Relevance: HIGH - As Found: Premature - ID: M29853 - Name: Premature Ejaculation - Relevance: HIGH - As Found: Premature Ejaculation - ID: M10217 - Name: Erectile Dysfunction - Relevance: HIGH - As Found: Erectile Dysfunction - ID: M10772 - Name: Obstetric Labor, Premature - Relevance: LOW - As Found: Unknown - ID: M10764 - Name: Obstetric Labor Complications - Relevance: LOW - As Found: Unknown - ID: M14127 - Name: Pregnancy Complications - Relevance: LOW - As Found: Unknown - ID: M2875 - Name: Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M27093 - Name: Female Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M8399 - Name: Female Urogenital Diseases and Pregnancy Complications - Relevance: LOW - As Found: Unknown - ID: M2876 - Name: Genital Diseases - Relevance: LOW - As Found: Unknown - ID: M8944 - Name: Genital Diseases, Male - Relevance: LOW - As Found: Unknown - ID: M15546 - Name: Sexual Dysfunction, Physiological - Relevance: LOW - As Found: Unknown - ID: M27095 - Name: Male Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M21873 - Name: Sexual Dysfunctions, Psychological - Relevance: LOW - As Found: Unknown - ID: M4815 - Name: Mental Disorders - Relevance: LOW - As Found: Unknown - ID: M14473 - Name: Psychotic Disorders - Relevance: LOW - As Found: Unknown - ID: M3452 - Name: Ejaculatory Dysfunction - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000047928 - Term: Premature Birth - ID: D000007172 - Term: Erectile Dysfunction - ID: D000061686 - Term: Premature Ejaculation ### Intervention Browse Module - Ancestors - ID: D000014665 - Term: Vasodilator Agents - ID: D000058986 - Term: Phosphodiesterase 5 Inhibitors - ID: D000010726 - Term: Phosphodiesterase Inhibitors - ID: D000004791 - Term: Enzyme Inhibitors - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000064804 - Term: Urological Agents ### Intervention Browse Module - Browse Branches - Abbrev: VaDiAg - Name: Vasodilator Agents - Abbrev: Urol - Name: Urological Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M279 - Name: Tadalafil - Relevance: HIGH - As Found: Gestational - ID: M17412 - Name: Vasodilator Agents - Relevance: LOW - As Found: Unknown - ID: M29332 - Name: Phosphodiesterase 5 Inhibitors - 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 ### Intervention Browse Module - Meshes - ID: D000068581 - Term: Tadalafil ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03708679 **Brief Title:** Effects of Menstrual Cycle on Preoperative Anxiety **Official Title:** Are Menstruel Cycle Phases Effective on Preoperative Anxiety? Prospective, Clinical Study #### Organization Study ID Info **ID:** Menstruel Cycle Anxiety #### Organization **Class:** OTHER **Full Name:** Yuzuncu Yıl University ### Status Module #### Completion Date **Date:** 2018-12-20 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2019-01-08 **Type:** ACTUAL **Last Update Submit Date:** 2019-01-06 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2018-11-30 **Type:** ACTUAL #### Start Date **Date:** 2018-09-15 **Type:** ACTUAL **Status Verified Date:** 2019-01 #### Study First Post Date **Date:** 2018-10-17 **Type:** ACTUAL **Study First Submit Date:** 2018-10-13 **Study First Submit QC Date:** 2018-10-13 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Yuzuncu Yıl University #### Responsible Party **Investigator Affiliation:** Yuzuncu Yıl University **Investigator Full Name:** Nureddin YUZKAT **Investigator Title:** Assist. Prof **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** The investigators aimed to investigate the effect of menstrual cycle phases on preoperative anxiety in women under general anesthesia. **Detailed Description:** In preoperative period, preoperative anxiety is experienced in different degrees due to surgery and anesthesia. Preoperative anxiety is a condition that negatively affects anesthesia, surgery and postoperative recovery. It is reported that the incidence of preoperative anxiety in the western population is between 60% and 80%. In the pre-operative period, there are many causes of anxiety related to the patient's health and the concerns about the operation, uncertainty of the outcome, non-wake up after surgery, pain hearing and waking during surgery. It has been reported that anxiety increases direct blood pressure and changes pulse rate. It is stated that anxiety also affects the awakening criteria in postoperative period. This may cause hemodynamic instability in anesthesia applications. Hormonal, physical and psychological fluctuations occur in women due to menstrual cycle. Therefore, it is reported that there is a strong relationship between the menstrual cycle and the person's emotional state. It is known that women feel good in the first phase of the cycle and they experience emotional, physical and behavioral disorders towards the end of the cycle. Studies have shown that anesthetic requirements, postoperative analgesic requirement and incidence of nausea vomiting may change with the phases of the cycle. Similarly, in the luteal phase of the cycle, it has been suggested that luteinizing hormones cause sensitization in opioid receptors and increase sensitivity to pain. In addition, depressive symptoms increase before menstruation. In this process, some women may have pre-menstrual dysphoric discomfort, irritability, mood swings, depression, flare, anger, restlessness, anorexia, sleep disturbance, and fatigue. Our hypothesis is that preop anxiety will be higher in the surgeries planned in the luteal phase. We aimed to investigate the effect of menstrual cycle phases on preoperative anxiety in women under general anesthesia. Material Method Ethics Committee approval was obtained before the study. After the written consent of the patients were obtained, they started to the study. The study was planned as a randomized prospective study between February 2018 and February 2019. The study groups were selected from patients who presented to the preop anesthesia polyclinic in elective conditions, septo-rinoplasty operation under general anesthesia. Assuming that there would be a 5-point difference in anxiety scores among the groups, it was decided to take 40 cases for each group with a 0.75 standard effect size, 80% power, and 5% error. Patients were randomly assigned to two groups of 40 patients. The patients were randomized by sequential addition to the groups determined in the order of their inclusion. Study inclusion criteria: The study included 80 women with ASA I-II, aged 18 to 45 years, who were accepted to participate in the study, were smoking, did not use oral contraceptives, had no menstrual irregularity (regular 28 ± 2 days menstrual cycle). Study exclusion criteria: In preop evaluation patients had difficulties in communication, amenorrhea, pregnancy, delirium, psychological illness, major depressive disorder, patients with a history of acute illness (such as in intensive care unit follow-up), which may affect cognitive function and daily life activities in the last 6 months, malignancy, acute renal failure, substance abuse and patients older than 45 years and male sex will be excluded from the study. Groups: Information about menstrual cycle patterns was obtained from all cases. The days of the menstrual cycle will be determined starting from counting the first day of the last cycle. Patients with menstrual cycle between 8-12 days were called Group F (Follicular phase). Patients with menstrual cycle between 20-24 were called Group L (Luteal phase). The follow-up of the cases and the recording of the measurements were performed by an anesthesiologist who did not know which group the cases were in. Procedure to be Applied: The sex, age, height and ASA scores of the patients were recorded preoperatively. The STAI instantaneous anxiety inventory, which measures situational anxiety in the preop unit, will be completed. In this form, there are 20 expressions, each is scored between the values of 1 to 4. The total STAI score will be determined by subtracting the sum of the scores given to the expressions expressing positive emotions (1, 2, 5, 8, 10, 11, 15, 16, 19 and 20) from the sum of the scores given to the expressions expressing negative emotions (3, 4, 6, 7, 9, 12, 13, 14, 17 ve 18), then constant 50 number will be added to this value. In preop unit and operation room, hemodynamic parameters (systolic, diastolic and mean arterial pressure (MAP), heart rate (HR) and peripheral oxygen saturation values preop at 15th, 10th, 5th, before induction, after induction at 1th and intubation at 1st, 5th and 15th minutes will be recorded. Instead of patients who do not want to be included in the study or who are excluded from the study for any reason, according to the results of the power analysis, a targeted number of patients will be included in the study randomly. ### Conditions Module **Conditions:** - Menstrual Cycle - Perioperative Hypertension - Anxiety ### Design Module #### Design Info **Observational Model:** OTHER **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 100 **Type:** ACTUAL **Patient Registry:** True **Study Type:** OBSERVATIONAL **Target Duration:** 1 Month ### Arms Interventions Module #### Arm Group 1 **Description:** Patients with menstrual cycle between 8-12 days were called Group F (Follicular phase) **Label:** Group F #### Arm Group 2 **Description:** Patients with menstrual cycle between 20-24 were called Group L (Luteal phase) **Label:** Group L ### Outcomes Module #### Primary Outcomes **Description:** Preoperative anxiety level will be measured by State-Trait Anxiety Inventory (STAI) form. **Measure:** Preoperative Anxiety **Time Frame:** 1 month ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * The study included 80 women with ASA I-II, * Aged 18 to 45 years, who were accepted to participate in the study, * were smoking, * did not use oral contraceptives, * had no menstrual irregularity (regular 28 ± 2 days menstrual cycle) Exclusion Criteria: * In preop evaluation patients had difficulties in communication, * amenorrhea, * pregnancy, * delirium, * psychological illness, * major depressive disorder, * patients with a history of acute illness (such as in intensive care unit follow-up), * which may affect cognitive function and daily life activities in the last 6 months, * malignancy, * acute renal failure, * substance abuse and patients older than 45 years and male sex will be excluded from the study. **Gender Based:** True **Gender Description:** The study is performed on female gender with menstrual cycle. **Maximum Age:** 45 Years **Minimum Age:** 18 Years **Sampling Method:** PROBABILITY_SAMPLE **Sex:** FEMALE **Standard Ages:** - ADULT **Study Population:** It will be operated for elective surgery, aged 18 to 45 years, who were accepted to participate in the study, ### Contacts Locations Module #### Locations **Location 1:** **City:** Van **Country:** Turkey **Facility:** Van yuzuncu Yıl University, Dursun Odabas Medical Center #### Overall Officials **Official 1:** **Affiliation:** Yuzuncu Yıl University **Name:** Nureddin Yuzkat, Assist Prof **Role:** STUDY_CHAIR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000001523 - Term: Mental Disorders ### Condition Browse Module - Browse Branches - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: All - Name: All Conditions - Abbrev: BXM - Name: Behaviors and Mental Disorders ### Condition Browse Module - Browse Leaves - ID: M10024 - Name: Hypertension - Relevance: LOW - As Found: Unknown - ID: M4324 - Name: Anxiety Disorders - Relevance: HIGH - As Found: Anxiety - ID: M4815 - Name: Mental Disorders - Relevance: LOW - As Found: Unknown - ID: M14473 - Name: Psychotic Disorders - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000001008 - Term: Anxiety Disorders ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT02963779 **Brief Title:** A Study of LY2775240 in Healthy Participants **Official Title:** A 2-Part, Safety, Tolerability, and Pharmacokinetic Study of LY2775240 in Healthy Subjects #### Organization Study ID Info **ID:** 16450 #### Organization **Class:** INDUSTRY **Full Name:** Eli Lilly and Company #### Secondary ID Infos **Domain:** Eli Lilly and Company **ID:** I8W-MC-PDBA **Type:** OTHER ### Status Module #### Completion Date **Date:** 2017-10-05 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2017-11-07 **Type:** ACTUAL **Last Update Submit Date:** 2017-11-03 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2017-10-05 **Type:** ACTUAL #### Start Date **Date:** 2016-12 **Status Verified Date:** 2017-11 #### Study First Post Date **Date:** 2016-11-15 **Type:** ESTIMATED **Study First Submit Date:** 2016-11-10 **Study First Submit QC Date:** 2016-11-10 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Eli Lilly and Company #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** This study is conducted to determine the side effects related to LY2775240 given orally to healthy participants. Blood tests will be done to check how much LY2775240 is absorbed into the bloodstream and how long the body takes to get rid of it. Each participant will enroll in either Part A or Part B of the study, which will last about 14 weeks and 8 weeks respectively, including screening. ### Conditions Module **Conditions:** - Healthy ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** CROSSOVER ##### Masking Info **Masking:** DOUBLE **Who Masked:** - PARTICIPANT - INVESTIGATOR **Primary Purpose:** BASIC_SCIENCE #### Enrollment Info **Count:** 35 **Type:** ACTUAL **Phases:** - PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Escalating oral doses of LY2775240 administered in healthy participants **Intervention Names:** - Drug: LY2775240 **Label:** LY2775240 (Part A) **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Oral dose of LY2775240 in healthy participants **Intervention Names:** - Drug: LY2775240 **Label:** LY2775240 (Part B) **Type:** EXPERIMENTAL #### Arm Group 3 **Description:** Placebo administered orally in healthy participants **Intervention Names:** - Drug: Placebo **Label:** Placebo (Part A) **Type:** PLACEBO_COMPARATOR #### Arm Group 4 **Description:** Oral dose of apremilast in healthy participants **Intervention Names:** - Drug: Apremilast **Label:** Apremilast (Part B) **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - LY2775240 (Part A) - LY2775240 (Part B) **Description:** Administered orally **Name:** LY2775240 **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Placebo (Part A) **Description:** Administered orally **Name:** Placebo **Type:** DRUG #### Intervention 3 **Arm Group Labels:** - Apremilast (Part B) **Description:** Administered orally **Name:** Apremilast **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Measure:** Number of Participants with One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration **Time Frame:** Baseline through to final follow-up at approximately Week 14 #### Secondary Outcomes **Measure:** Pharmacokinetics: Area Under the Concentration Curve (AUC) of LY2775240 **Time Frame:** Baseline through Day 5 **Measure:** Pharmacokinetics: Time to Maximal Blood Concentration of LY2775240 **Time Frame:** Baseline through Day 5 **Measure:** Pharmacokinetics: Maximum Concentration of LY2775240 in Blood **Time Frame:** Baseline through Day 5 ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Overtly healthy adult male or a female who cannot get pregnant * Have a screening body mass index (BMI) of greater than 18 and less than or equal to 32 kilograms per meter square (kg/m²), inclusive * Have normal blood pressure, pulse rate, electrocardiogram (ECG) and medical test results that are acceptable for the study Exclusion Criteria: * Are currently participating in or completed a clinical trial within the last 30 days from a clinical trial or any other type of medical research judged to be incompatible with this study * Have known allergies to compounds or drugs similar to LY2775240 or apremilast * Have previously participated or withdrawn from this study * Have or used to have health problems or medical test results or ECG readings that, in the opinion of the doctor, could make it unsafe to participate, or could interfere with understanding the results of the study **Healthy Volunteers:** True **Maximum Age:** 65 Years **Minimum Age:** 21 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Singapore **Country:** Singapore **Facility:** For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician. #### Overall Officials **Official 1:** **Affiliation:** Eli Lilly and Company **Name:** Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) **Role:** STUDY_DIRECTOR ## Derived Section ### Intervention Browse Module - Ancestors - ID: D000000894 - Term: Anti-Inflammatory Agents, Non-Steroidal - ID: D000018712 - Term: Analgesics, Non-Narcotic - ID: D000000700 - Term: Analgesics - ID: D000018689 - Term: Sensory System Agents - ID: D000018373 - Term: Peripheral Nervous System Agents - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000000893 - Term: Anti-Inflammatory Agents - ID: D000018501 - Term: Antirheumatic Agents - ID: D000058988 - Term: Phosphodiesterase 4 Inhibitors - ID: D000010726 - Term: Phosphodiesterase Inhibitors - ID: D000004791 - Term: Enzyme Inhibitors - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action ### Intervention Browse Module - Browse Branches - Abbrev: Infl - Name: Anti-Inflammatory Agents - Abbrev: ARhu - Name: Antirheumatic Agents - Abbrev: Analg - Name: Analgesics - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M341074 - Name: Apremilast - Relevance: HIGH - As Found: Ask - ID: M4217 - Name: Anti-Inflammatory Agents - Relevance: LOW - As Found: Unknown - ID: M4218 - Name: Anti-Inflammatory Agents, Non-Steroidal - Relevance: LOW - As Found: Unknown - ID: M4032 - Name: Analgesics - Relevance: LOW - As Found: Unknown - ID: M20786 - Name: Analgesics, Non-Narcotic - Relevance: LOW - As Found: Unknown - ID: M20604 - Name: Antirheumatic Agents - Relevance: LOW - As Found: Unknown - ID: M29334 - Name: Phosphodiesterase 4 Inhibitors - 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 ### Intervention Browse Module - Meshes - ID: C000505730 - Term: Apremilast ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT01706679 **Acronym:** ATX-101-11-24 **Brief Title:** Evaluation of the Effect of ATX-101 on QT/QTc Intervals **Official Title:** A Four-Arm, Parallel Design, Randomized, Double-Blinded, Placebo and Active Controlled Study for the Evaluation of the Effect of Maximum Therapeutic and Supratherapeutic Single-Dose ATX-101 on the QT/QTc Intervals in Healthy Volunteers #### Organization Study ID Info **ID:** ATX-101-11-24 #### Organization **Class:** INDUSTRY **Full Name:** Kythera Biopharmaceuticals ### Status Module #### Completion Date **Date:** 2013-06 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2013-11-14 **Type:** ESTIMATED **Last Update Submit Date:** 2013-11-12 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2013-02 **Type:** ACTUAL #### Start Date **Date:** 2012-10 **Status Verified Date:** 2012-10 #### Study First Post Date **Date:** 2012-10-15 **Type:** ESTIMATED **Study First Submit Date:** 2012-10-11 **Study First Submit QC Date:** 2012-10-11 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Kythera Biopharmaceuticals #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** To evaluate the effect of maximum therapeutic and supratherapeutic doses of ATX-101 treatment on Fridericia's corrected QT interval (QTcF). ### Conditions Module **Conditions:** - Healthy **Keywords:** - Healthy volunteers ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** DOUBLE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 218 **Type:** ACTUAL **Phases:** - PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** ATX-101 10 mg/ml **Intervention Names:** - Drug: ATX-101 (10 mg/ml) **Label:** Maximum therapeutic dose of ATX-101 **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** ATX-101 20 mg/ml **Intervention Names:** - Drug: ATX-101 (20 mg/ml) **Label:** Supratherapeutic dose of ATX-101 **Type:** ACTIVE_COMPARATOR #### Arm Group 3 **Description:** moxifloxacin (400mg) **Intervention Names:** - Drug: Moxifloxacin (400 mg) **Label:** Moxifloxacin **Type:** ACTIVE_COMPARATOR #### Arm Group 4 **Description:** placebo vehicle (PBS) **Intervention Names:** - Drug: Placebo vehicle (PBS) **Label:** Placebo vehicle **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Maximum therapeutic dose of ATX-101 **Name:** ATX-101 (10 mg/ml) **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Supratherapeutic dose of ATX-101 **Name:** ATX-101 (20 mg/ml) **Type:** DRUG #### Intervention 3 **Arm Group Labels:** - Moxifloxacin **Name:** Moxifloxacin (400 mg) **Type:** DRUG #### Intervention 4 **Arm Group Labels:** - Placebo vehicle **Name:** Placebo vehicle (PBS) **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** The primary endpoint will be the mean change between time-matched measurements of QTcF for ATX-101 and placebo after baseline adjustment calculating the upper bound of the one-sided 95% confidence interval. A negative TQT study can be claimed if each upper bound of the one-sided 95% CI is below 10 msec. **Measure:** The effect of maximum therapeutic and supratherapeutic doses of ATX-101 treatment on Fridericia's corrected QT interval (QTcF) **Time Frame:** 2.5 days #### Secondary Outcomes **Measure:** To evaluate change from placebo and baseline of the maximum therapeutic and supratherapeutic doses of ATX-101 treatment on QT interval corrected for individuals **Time Frame:** 2.5 days ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Males or nonpregnant, nonlactating females who are aged 18 to 65 years (inclusive). Females must have a negative serum human chorionic gonadotropin (hCG) test result from a sample obtained during the screening period and after admission to the research facility, but before the dose of study material. Females of postmenopausal status must not have had menses for at least one year and if younger than 55 years of age must have a serum FSH level ≥ 35 mIU/mL. Females of childbearing potential must agree to practice adequate contraception, in the judgment of the investigator, during the course of the trial. * Body Mass Index (BMI) in the range of 20 - 38 kg/m2 (inclusive). Refer to Appendix A. * Presence of sufficient submental fat into which 25 subcutaneous injections spaced on a 1.0-cm grid can be safely administered based on the investigator's judgment. * Normal vital signs after 10 minutes resting in a supine position: * Systolic Blood Pressure: 90 mm Hg to 140 mm Hg * Diastolic Blood Pressure: 45 mm Hg to 90 mm Hg * Heart Rate: 45 bpm to 100 bpm * Normal Resting ECG * PR Interval: 120 msec to 220 msec * QRS Duration: \< 120 msec * QTcF Duration: \< 450 msec * Serum hemoglobin test result of 11.0 g/dL or greater and negative hepatitis B, hepatitis C, and HIV test result within 28 days before the dose of study material. * Willing and able to comply with and understand the visit schedule and all of the protocol-specified tests and procedures. * Medically able to undergo the administration of study material as determined by clinical and laboratory evaluations obtained within 28 days before dosing with study material for which the investigator identifies no clinically significant abnormality. * Signed informed consent obtained before any study-specific procedure is conducted. Exclusion Criteria: * Any prescription medication taken within 14 days (or 5 elimination half-lives, whichever is longer) of Study Day -2, or have taken any over-the-counter medications, including topical medications, herbal or dietary supplements/remedies within 7 days of Study Day 2, or planned concomitant medication while in the study (except for acetaminophen up to 2 g/day and hormonal birth control). * A history of additional risk factors for Torsade de Pointes (e.g. hypokalemia, history of drowning survival, family history of Long QT Syndrome, family history of Short QT Syndrome, or family history of unexplainable early sudden death). * Participation in a study of an investigational drug or device within 30 days prior to the baseline ECG. * Any condition that, in the judgment of the investigator, would place a subject at undue risk, or potentially compromise the results or interpretation of the study. * Uncontrolled cardiac arrhythmias, for example, atrial fibrillation with a ventricular response at rest \> 100 beats per minute. * Known abnormality of any cardiac valve (either stenosis or regurgitation) that is greater than moderate in severity. * Subjects not in sinus rhythm at screening. * Hypersensitivity to Moxifloxacin * History or presence of significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, or psychiatric disease. * Use of tobacco or nicotine-containing products within 3 months prior to dose. * History of any intervention to treat submental fat (e.g. liposuction, surgery, or lipolytic agents). * History of trauma associated with the chin or neck areas, which in the judgment of the investigator may affect evaluation of safety of treatment. * Loose skin in the neck or chin area for which reduction in submental fat may, in the judgment of the investigator, result in a cosmetically unacceptable outcome. * Prominent platysmal bands at rest that interfere with the evaluation of submental fat. * Evidence of any cause of enlargement in the submental area other than localized subcutaneous fat. * Any blood donation or significant blood loss within 56 days before the dose of study material or plasma donation within 7 days of Day -1. * A result on coagulation tests (PT, PTT) obtained within 28 days before the dose of study material that indicates the presence of any clinically significant bleeding disorder. * Any medical condition that would interfere with the assessment of safety in this trial or would compromise the ability of the subject to undergo study procedures or to give informed consent. * Treatment with oral anticoagulants (e.g. warfarin) within 30 days before dosing with study material. * Treatment with radio frequency, laser procedure, chemical peels, or dermal fillers in the neck or chin within 12 months before dosing with the study material, or botulinum toxin injections in the neck or chin area within 6 months before dosing with the study material. * History of sensitivity to any components of the study material. * History of drug or alcohol abuse, in the judgment of the investigator, within two years before dosing with the study material. * Presence of positive urine drug or alcohol screening test result obtained from a sample obtained during the screening period and/or after admission to the research facility for the confinement period, but before dosing with the study material. * Previous enrollment in a trial of ATX-101. * Treatment with an investigational device or agent within 30 days prior to the baseline ECG. **Healthy Volunteers:** True **Maximum Age:** 65 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Miramar **Country:** United States **Facility:** Comprehensive Clinical Development **State:** Florida **Zip:** 33027 #### Overall Officials **Official 1:** **Affiliation:** Comprehensive Clinical Development **Name:** Royce Morrison, MD, PhD **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### 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 ### Intervention Browse Module - Browse Branches - Abbrev: Infe - Name: Anti-Infective Agents - Abbrev: ANeo - Name: Antineoplastic Agents - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Repr - Name: Reproductive Control Agents ### Intervention Browse Module - Browse Leaves - ID: M1722 - Name: Moxifloxacin - Relevance: HIGH - As Found: Range - ID: M266292 - Name: Norgestimate, ethinyl estradiol drug combination - Relevance: LOW - As Found: Unknown - ID: M4222 - Name: Anti-Bacterial Agents - Relevance: LOW - As Found: Unknown - ID: M4214 - Name: Anti-Infective Agents - Relevance: LOW - As Found: Unknown - ID: M7951 - Name: Enzyme Inhibitors - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000077266 - Term: Moxifloxacin ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00432679 **Brief Title:** A Study Of BRL49653C For The Treatment Of Type 2 Diabetes (Combination Therapy With Sulfonyl Urea) -With Placebo Study **Official Title:** Clinical Evaluation of Rosiglitazone Maleate (BRL49653C) in Patients With Type 2 Diabetes Mellitus (Combination Therapy With Sulfonyl Urea) - A Placebo-Controlled Double-Blind Study - #### Organization Study ID Info **ID:** AVD105248 #### Organization **Class:** INDUSTRY **Full Name:** GlaxoSmithKline ### Status Module #### Completion Date **Date:** 2007-03-28 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2022-12-12 **Type:** ACTUAL **Last Update Submit Date:** 2022-11-15 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2007-03-28 **Type:** ACTUAL #### Results First Post Date **Date:** 2019-02-08 **Type:** ACTUAL **Results First Submit Date:** 2017-08-24 **Results First Submit QC Date:** 2018-08-30 #### Start Date **Date:** 2006-05-24 **Type:** ACTUAL **Status Verified Date:** 2022-11 #### Study First Post Date **Date:** 2007-02-08 **Type:** ESTIMATED **Study First Submit Date:** 2007-02-06 **Study First Submit QC Date:** 2007-02-06 ### 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 was designed to compare the efficacy and safety of BRL49653C versus placebo with concomitant use of sulfonyl urea (SU). ### Conditions Module **Conditions:** - Diabetes Mellitus, Type 2 **Keywords:** - rosiglitazone - Avandia - type 2 diabetes mellitus - diabetes ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** DOUBLE **Who Masked:** - PARTICIPANT - INVESTIGATOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 149 **Type:** ACTUAL **Phases:** - PHASE3 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** study drug **Intervention Names:** - Drug: Rosiglitazone (BRL49653C) **Label:** arm 1 **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - arm 1 **Description:** study drug **Name:** Rosiglitazone (BRL49653C) **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Baseline value was value on Day 0. Change from Baseline was defined as value at Week 16 minus Baseline value. The full analysis set used which was defined as remaining after participant who infringed on the following events were excluded from the randomized participants, who did not take the investigational drug during or after the treatment period (amount of investigational drug taken was zero tablets) and who were not measured for HbA1c even once as the observation period Baseline value or in the treatment period (after the investigational drug was prescribed), or for whom the above were unavailable (including cases that the above were considered missing measurements due to a defective sample). **Measure:** Change From Baseline in Glycosylated Hemoglobin (HbA1c) After 16 Weeks of Treatment in Rosiglitazone Group and Placebo Group **Time Frame:** Baseline (Day 0) and Week 16 #### Secondary Outcomes **Description:** Baseline value was value on Day 0. Change from Baseline was defined as value at Week 16 minus Baseline value. **Measure:** Change From Baseline After 16 Weeks of Treatment in Fasting Plasma Glucose (FPG) **Time Frame:** Baseline (Day 0) and Week 16 **Description:** Baseline value was value on Day 0. Change from Baseline was defined as value at Week 16 minus Baseline value. **Measure:** Change From Baseline After 16 Weeks of Treatment in Fasting Insulin **Time Frame:** Baseline (Day 0) and Week 16 **Description:** Baseline value was value on Day 0. Change from Baseline was defined as value at Week 16 minus Baseline value. **Measure:** Change From Baseline After 16 Weeks of Treatment in Fasting Proinsulin **Time Frame:** Baseline (Day 0) and Week 16 **Description:** Baseline value was value on Day 0. Change from Baseline was defined as value at Week 16 minus Baseline value. **Measure:** Change From Baseline After 16 Weeks of Treatment in Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) **Time Frame:** Baseline (Day 0) and Week 16 **Description:** Baseline value was value on Day 0. Change from Baseline was defined as value at Week 16 minus Baseline value. **Measure:** Change From Baseline After 16 Weeks of Treatment in Homeostasis Model Assessment of Beta-cell Function (HOMA-beta) **Time Frame:** Baseline (Day 0) and Week 16 **Description:** Baseline value was value on Day 0. Change from Baseline was defined as value at Week 16 minus Baseline value. **Measure:** Change From Baseline After 16 Weeks of Treatment in Adiponectin **Time Frame:** Baseline (Day 0) and Week 16 **Description:** Baseline value was value on Day 0. Change from Baseline was defined as value at Week 16 minus Baseline value. **Measure:** Change From Baseline After 16 Weeks of Treatment in Leptin and High Sensitivity C-reactive Protein (Hs-CRP) **Time Frame:** Baseline (Day 0) and Week 16 **Description:** The specified criteria for HbA1c was, if the decrease from the observation period Baseline value meets the following conditions: 1) decrease from the observation period Baseline value is 0.7% or more; 2) fell below 6.5%; 3) satisfied either 1 or 2 noted above. And for FPG was, if the decrease from the observation period Baseline value meets the following conditions: 1) decrease of 30 mg per decilliter or more from the observation period Baseline value; 2) fell below 126 mg per deciliter; 3) satisfied either 1 or 2 noted above. **Measure:** Percentage of Participants With Changes in HbA1c and FPG Meeting Specified Criteria After 16 Weeks of Treatment **Time Frame:** Up to Week 16 ### Eligibility Module **Eligibility Criteria:** Inclusion criteria: * Patients with type 2 diabetes mellitus managed by SU will be candidate for this study. These candidates will be checked up on their clinical laboratory data, and must have adequate blood, liver and kidney function. Exclusion criteria: * Patient with serious cardiovascular disease or serious hepatic disease will not be eligible. **Minimum Age:** 20 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Kanagawa **Country:** Japan **Facility:** GSK Investigational Site **Zip:** 212-0024 **Location 2:** **City:** Kumamoto **Country:** Japan **Facility:** GSK Investigational Site **Zip:** 862-0976 **Location 3:** **City:** Oita **Country:** Japan **Facility:** GSK Investigational Site **Zip:** 870-0039 **Location 4:** **Facility:** GSK Investigational Site #### Overall Officials **Official 1:** **Affiliation:** GlaxoSmithKline **Name:** GSK Clinical Trials **Role:** STUDY_DIRECTOR ### IPD Sharing Statement Module **IPD Sharing:** NO ### References Module #### Available IPDs **Comment:** For additional information about this study please refer to the GSK Clinical Study Register **ID:** AVD105248 **Type:** Dataset Specification **URL:** https://www.clinicalstudydatarequest.com **Comment:** For additional information about this study please refer to the GSK Clinical Study Register **ID:** AVD105248 **Type:** Individual Participant Data Set **URL:** https://www.clinicalstudydatarequest.com **Comment:** For additional information about this study please refer to the GSK Clinical Study Register **ID:** AVD105248 **Type:** Clinical Study Report **URL:** https://www.clinicalstudydatarequest.com **Comment:** For additional information about this study please refer to the GSK Clinical Study Register **ID:** AVD105248 **Type:** Annotated Case Report Form **URL:** https://www.clinicalstudydatarequest.com **Comment:** For additional information about this study please refer to the GSK Clinical Study Register **ID:** AVD105248 **Type:** Statistical Analysis Plan **URL:** https://www.clinicalstudydatarequest.com **Comment:** For additional information about this study please refer to the GSK Clinical Study Register **ID:** AVD105248 **Type:** Informed Consent Form **URL:** https://www.clinicalstudydatarequest.com **Comment:** For additional information about this study please refer to the GSK Clinical Study Register **ID:** AVD105248 **Type:** Study Protocol **URL:** https://www.clinicalstudydatarequest.com #### References **Citation:** This study has not been published in the scientific literature. #### See Also Links **Label:** Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research. **URL:** https://www.clinicalstudydatarequest.com ## 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: M11639 - Name: Metabolic Diseases - Relevance: LOW - As Found: Unknown - ID: M25403 - Name: Glucose Metabolism Disorders - Relevance: LOW - As Found: Unknown - ID: M7862 - Name: Endocrine System Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000003920 - Term: Diabetes Mellitus - ID: D000003924 - Term: Diabetes Mellitus, Type 2 ### Intervention Browse Module - Ancestors - ID: D000007004 - Term: Hypoglycemic Agents - ID: D000045505 - Term: Physiological Effects of Drugs ### Intervention Browse Module - Browse Branches - Abbrev: Infe - Name: Anti-Infective Agents - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Hypo - Name: Hypoglycemic Agents ### Intervention Browse Module - Browse Leaves - ID: M1804 - Name: Carbamide Peroxide - Relevance: LOW - As Found: Unknown - ID: M245808 - Name: Maleic acid - Relevance: LOW - As Found: Unknown - ID: M1677 - Name: Rosiglitazone - Relevance: HIGH - As Found: Telemedicine - ID: M10054 - Name: Hypoglycemic Agents - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000077154 - Term: Rosiglitazone ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module **Description:** Full analysis set was used for reporting non-SAE and SAE. #### Event Groups **Group ID:** EG000 **Title:** Rosiglitazone 4 mg Orally Once Daily **Deaths Num At Risk:** 74 **Description:** Participants in this arm were randomized to receive rosiglitazone (BRL49653C) 4 mg tablets orally once daily before or after breakfast for 16 weeks. Participants also received either of concomitant medication (sulphonylureas) glibenclamide (1.25 to 5 mg), gliclazide (40 to 80 mg) or glimepiride (1 to 3 mg) per day during study. **ID:** EG000 **Other Num Affected:** 61 **Other Num at Risk:** 74 **Serious Number Affected:** 1 **Serious Number At Risk:** 74 **Title:** Rosiglitazone 4 mg Orally Once Daily **Group ID:** EG001 **Title:** Placebo **Deaths Num At Risk:** 75 **Description:** Participants in this arm were randomized to receive rosiglitazone placebo tablets orally once daily before or after breakfast for 16 weeks. Participants also received either of concomitant medication (sulphonylureas) glibenclamide (1.25 to 5 mg), gliclazide (40 to 80 mg) or glimepiride (1 to 3 mg) per day during study. **ID:** EG001 **Other Num Affected:** 53 **Other Num at Risk:** 75 **Serious Number Affected:** 1 **Serious Number At Risk:** 75 **Title:** Placebo **Frequency Threshold:** 0 #### Other Events **Term:** Blood creatine phosphokinase increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA version **Term:** Weight increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA version **Term:** Blood triglyccrides increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA version **Term:** Blood pressure increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA version **Term:** Brain natriuretic peptide increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA version **Term:** Blood cholesterol increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA version **Term:** Urine ketone body present **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA version **Term:** Blood urine present **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA version **Term:** Hjgh density lipoprotein decreased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA version **Term:** Low density lipoprotein increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA version **Term:** Protein urine present **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA version **Term:** Blood albumin decreased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA version **Term:** Blood uric acid increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA version **Term:** Liver function test abnormal **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA version **Term:** Monocyte count increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA version **Term:** Neutrophll count decreased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA version **Term:** Reticulocyte count increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA version **Term:** Weight decreased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA version **Term:** White blood cell count decreased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA version **Term:** White blood cell count increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA version **Term:** Blood alkaline phosphatase increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA version **Term:** Nasopharyngitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA version **Term:** Pharyngitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA version **Term:** Cystitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA version **Term:** Gastroenteritis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA version **Term:** Hordeolum **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA version **Term:** Bronchitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA version **Term:** Bronchitis acute **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA version **Term:** Chronic sinusitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA version **Term:** Gastrointestinal infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA version **Term:** Herpes simplex **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA version **Term:** Impetigo **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA version **Term:** lnfluenza **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA version **Term:** Skin infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA version **Term:** Diarrhoea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA version **Term:** Constipation **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA version **Term:** Gastritis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA version **Term:** Reflux ocsophagitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA version **Term:** Stomach discomfort **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA version **Term:** Abdominal pain upper **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA version **Term:** Enterocolitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA version **Term:** Periodontitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA version **Term:** Anal fistula **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA version **Term:** Colitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA version **Term:** Dental caries **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA version **Term:** Gastric ulcer **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA version **Term:** Hiatus hernia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA version **Term:** Stomatitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA version **Term:** Toothache **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA version **Term:** Vomiting **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA version **Term:** Duodenal scarring **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA version **Term:** Epigastric discomfort **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA version **Term:** Upper respiratory tract inflammation **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA version **Term:** Cough **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA version **Term:** Rhinitis allergic **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA version **Term:** Pharyngolaryngeal discomfort **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA version **Term:** Tenosynovitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA version **Term:** Arthralgia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA version **Term:** Back pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA version **Term:** Muscle spasms **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA version **Term:** Neck pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA version **Term:** Musculoskeletal stiffness **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA version **Term:** Joint contracture **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA version **Term:** Myajgia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA version **Term:** Osteoporosis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA version **Term:** Pain in extremity **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA version **Term:** Joint range of motion decreased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA version **Term:** Limb discomfort **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA version **Term:** Oedema peripheral **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA version **Term:** Pyrexia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA version **Term:** Chest discomfort **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA version **Term:** Chest pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA version **Term:** Feeling abnonnal **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA version **Term:** Malaise **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA version **Term:** Oedema **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA version **Term:** Pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA version **Term:** Thirst **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA version **Term:** Contusion **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA version **Term:** Animal bite **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA version **Term:** Arthropod sting **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA version **Term:** Back injury **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA version **Term:** Epicondylitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA version **Term:** Tooth injury **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA version **Term:** Thennal bum **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA version **Term:** Neck injury **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA version **Term:** Tooth fracture **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA version **Term:** Headache **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA version **Term:** Dizziness **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA version **Term:** Hypoaesthcsia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA version **Term:** Areflexia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA version **Term:** Carotid artery stenosis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA version **Term:** Sciatica **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA version **Term:** Tension headache **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA version **Term:** Pruritus **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA version **Term:** Rash **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA version **Term:** Dermatitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA version **Term:** Dermatitis contact **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA version **Term:** Urticaria **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA version **Term:** Conjunctivitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Eye disorders **Source Vocabulary:** MedDRA version **Term:** Cataract **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Eye disorders **Source Vocabulary:** MedDRA version **Term:** Corneal epithelium disorder **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Eye disorders **Source Vocabulary:** MedDRA version **Term:** Diabetic retinopathy **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Eye disorders **Source Vocabulary:** MedDRA version **Term:** Lacrimation increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Eye disorders **Source Vocabulary:** MedDRA version **Term:** Punctate keratitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Eye disorders **Source Vocabulary:** MedDRA version **Term:** Corneal exfoliation **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Eye disorders **Source Vocabulary:** MedDRA version **Term:** Insomnia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA version **Term:** Anxiety **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA version **Term:** Anxiety disorder **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA version **Term:** Bundle branch block right **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA version **Term:** Extrasystoles **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA version **Term:** Palpitations **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA version **Term:** Cholelithiasis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA version **Term:** Hepatic function abnormal **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA version **Term:** Hepatic steatosis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA version **Term:** Hypertension **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA version **Term:** Hyperaemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA version **Term:** Hypoglycaemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA version **Term:** Pollakiuria **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA version **Term:** Urinary retention **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA version **Term:** Ear discomfort **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Ear and labyrinth disorders **Source Vocabulary:** MedDRA version **Term:** Adrenal mass **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Endocrine disorders **Source Vocabulary:** MedDRA version **Term:** Uterine polyp **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Reproductive system and breast disorders **Source Vocabulary:** MedDRA version #### Serious Events **Term:** Liposacromal recurrent **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA version ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 74 **Group ID:** EG001 **Num At Risk:** 75 **Term:** Brain stem infarction **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA version ##### Stats **Group ID:** EG000 **Num At Risk:** 74 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 75 **Time Frame:** All adverse events (AE) and serious adverse events (SAE) were reported during the clinical trial period (from the observation period (Week -4) to the post-trial examination date (up to Week 18 or 2 weeks after the discontinuation). ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 74 **Group ID:** BG001 **Value:** 75 **Group ID:** BG002 **Value:** 149 **Units:** Participants ### Group **ID:** BG000 **Title:** Rosiglitazone 4 mg Orally Once Daily **Description:** Participants in this arm were randomized to receive rosiglitazone (BRL49653C) 4 mg tablets orally once daily before or after breakfast for 16 weeks. Participants also received either of concomitant medication (sulphonylureas) glibenclamide (1.25 to 5 mg), gliclazide (40 to 80 mg) or glimepiride (1 to 3 mg) per day during study. ### Group **ID:** BG001 **Title:** Placebo **Description:** Participants in this arm were randomized to receive rosiglitazone placebo tablets orally once daily before or after breakfast for 16 weeks. Participants also received either of concomitant medication (sulphonylureas) glibenclamide (1.25 to 5 mg), gliclazide (40 to 80 mg) or glimepiride (1 to 3 mg) per day during study. ### Group **ID:** BG002 **Title:** Total **Description:** Total of all reporting groups ### Measure #### Measurement **Group ID:** BG000 **Spread:** 8.81 **Value:** 60.1 #### Measurement **Group ID:** BG001 **Spread:** 9.80 **Value:** 61.6 #### Measurement **Group ID:** BG002 **Spread:** 9.32 **Value:** 60.8 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 27 #### Measurement **Group ID:** BG001 **Value:** 28 #### Measurement **Group ID:** BG002 **Value:** 55 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 47 #### Measurement **Group ID:** BG001 **Value:** 47 #### Measurement **Group ID:** BG002 **Value:** 94 **Category Title:** Male **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** American Indian or Alaska Native #### Measurement **Group ID:** BG000 **Value:** 74 #### Measurement **Group ID:** BG001 **Value:** 75 #### Measurement **Group ID:** BG002 **Value:** 149 **Category Title:** Asian #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** Native Hawaiian or Other Pacific Islander #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** Black or African American #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** White #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** More than one race #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** Unknown or Not Reported **Class Title:** **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 ## 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:** -1.01 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -0.61 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.102 **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER_LEGACY **Other Analysis Description:** **P-Value:** <0.001 **P-Value Comment:** Change from Baseline in HbA1c = Treatment+ Baseline HbA1c+ Gender+ body mass index (BMI) **Parameter Type:** Mean Difference (Net) **Parameter Value:** -0.81 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** ### Outcome Measure 2 #### Analysis **CI Lower Limit:** -32.1 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -12.1 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 5.06 **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER_LEGACY **Other Analysis Description:** **P-Value:** <0.001 **P-Value Comment:** **Parameter Type:** Mean Difference (Net) **Parameter Value:** -22.1 **Statistical Comment:** **Statistical Method:** Unpaired t-test **Tested Non-Inferiority:** ### Outcome Measure 3 #### Analysis **CI Lower Limit:** -0.883 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 2.319 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.8102 **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER_LEGACY **Other Analysis Description:** **P-Value:** 0.377 **P-Value Comment:** **Parameter Type:** Mean Difference (Net) **Parameter Value:** 0.718 **Statistical Comment:** **Statistical Method:** Unpaired t-test **Tested Non-Inferiority:** ### Outcome Measure 4 #### Analysis **CI Lower Limit:** -6.18 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 2.09 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 2.094 **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER_LEGACY **Other Analysis Description:** **P-Value:** 0.330 **P-Value Comment:** **Parameter Type:** Mean Difference (Net) **Parameter Value:** -2.04 **Statistical Comment:** **Statistical Method:** Unpaired t-test **Tested Non-Inferiority:** ### Outcome Measure 5 #### Analysis **CI Lower Limit:** -0.945 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 0.925 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.4730 **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER_LEGACY **Other Analysis Description:** **P-Value:** 0.983 **P-Value Comment:** **Parameter Type:** Mean Difference (Net) **Parameter Value:** -0.010 **Statistical Comment:** **Statistical Method:** Unpaired t-test **Tested Non-Inferiority:** ### Outcome Measure 6 #### Analysis **CI Lower Limit:** 1.191 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 15.248 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 3.5560 **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER_LEGACY **Other Analysis Description:** **P-Value:** 0.022 **P-Value Comment:** **Parameter Type:** Mean Difference (Net) **Parameter Value:** 8.220 **Statistical Comment:** **Statistical Method:** Unpaired t-test **Tested Non-Inferiority:** ### Outcome Measure 7 #### Analysis **CI Lower Limit:** 6.52 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 9.91 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.860 **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER_LEGACY **Other Analysis Description:** **P-Value:** <0.001 **P-Value Comment:** **Parameter Type:** Mean Difference (Net) **Parameter Value:** 8.21 **Statistical Comment:** **Statistical Method:** Unpaired t-test **Tested Non-Inferiority:** ### Outcome Measure 8 #### Analysis **CI Lower Limit:** -0.05 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 1.35 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.355 **Estimate Comment:** Comparison of leptin. **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER_LEGACY **Other Analysis Description:** **P-Value:** 0.069 **P-Value Comment:** **Parameter Type:** Mean Difference (Net) **Parameter Value:** 0.65 **Statistical Comment:** **Statistical Method:** Unpaired t-test **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** -2477.7 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 700.1 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 803.96 **Estimate Comment:** Comparison of hs-CRP **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER_LEGACY **Other Analysis Description:** **P-Value:** 0.271 **P-Value Comment:** **Parameter Type:** Mean Difference (Net) **Parameter Value:** -888.8 **Statistical Comment:** **Statistical Method:** Unpaired t-test **Tested Non-Inferiority:** ### Outcome Measure 9 #### Analysis **CI Lower Limit:** 27.1 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 54.1 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** Comparison of HbA1c, decrease by 0.7% **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER_LEGACY **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 40.6 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** -0.3 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 13.8 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** Comparison of HbA1c, fell below 6.5% **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER_LEGACY **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 6.8 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 27.1 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 54.1 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** Comparison of HbA1c, satisfied either 1 or 2 **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER_LEGACY **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 40.6 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 9.5 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 36.6 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** Comparison of FPG, decrease of 30 milligrams per decilliter **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER_LEGACY **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 23.1 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** -5.1 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 18.9 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** Comparison of FPG, fell below 126 milligrams per deciliter **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER_LEGACY **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 6.9 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** 5.6 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 35.3 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** Comparison of FPG, satisfied either 1 or 2 **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER_LEGACY **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 20.5 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.074 - **Upper Limit:** - **Value:** -0.62 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.073 - **Upper Limit:** - **Value:** 0.19 **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 28.91 - **Upper Limit:** - **Value:** -15.9 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 32.69 - **Upper Limit:** - **Value:** 6.2 **Title:** #### Outcome Measure 3 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 3.2699 - **Upper Limit:** - **Value:** -0.479 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 6.1434 - **Upper Limit:** - **Value:** -1.197 **Title:** #### Outcome Measure 4 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 13.630 - **Upper Limit:** - **Value:** -1.64 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 11.666 - **Upper Limit:** - **Value:** 0.40 **Title:** #### Outcome Measure 5 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 1.5562 - **Upper Limit:** - **Value:** -0.496 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 3.7556 - **Upper Limit:** - **Value:** -0.486 **Title:** #### Outcome Measure 6 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 18.7875 - **Upper Limit:** - **Value:** 3.776 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 24.0408 - **Upper Limit:** - **Value:** -4.444 **Title:** #### Outcome Measure 7 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 7.030 - **Upper Limit:** - **Value:** 9.19 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 2.301 - **Upper Limit:** - **Value:** 0.98 **Title:** #### Outcome Measure 8 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 2.751 - **Upper Limit:** - **Value:** 0.59 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 1.332 - **Upper Limit:** - **Value:** -0.07 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 5376.91 - **Upper Limit:** - **Value:** -189.1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 4349.58 - **Upper Limit:** - **Value:** 699.7 **Title:** #### Outcome Measure 9 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 44.6 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4.0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 6.8 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0.0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 44.6 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4.0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 31.1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 8.0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 16.2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 9.3 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 35.1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 14.7 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** Baseline value was value on Day 0. Change from Baseline was defined as value at Week 16 minus Baseline value. The full analysis set used which was defined as remaining after participant who infringed on the following events were excluded from the randomized participants, who did not take the investigational drug during or after the treatment period (amount of investigational drug taken was zero tablets) and who were not measured for HbA1c even once as the observation period Baseline value or in the treatment period (after the investigational drug was prescribed), or for whom the above were unavailable (including cases that the above were considered missing measurements due to a defective sample). **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Full analysis set used. **Reporting Status:** POSTED **Time Frame:** Baseline (Day 0) and Week 16 **Title:** Change From Baseline in Glycosylated Hemoglobin (HbA1c) After 16 Weeks of Treatment in Rosiglitazone Group and Placebo Group **Type:** PRIMARY **Unit of Measure:** Percentage of Glycosylated Hemoglobin ##### Group **Description:** Participants in this arm were randomized to receive rosiglitazone (BRL49653C) 4 mg tablets orally once daily before or after breakfast for 16 weeks. Participants also received either of concomitant medication (sulphonylureas) glibenclamide (1.25 to 5 mg), gliclazide (40 to 80 mg) or glimepiride (1 to 3 mg) per day during study. **ID:** OG000 **Title:** Rosiglitazone 4 mg Orally Once Daily ##### Group **Description:** Participants in this arm were randomized to receive rosiglitazone placebo tablets orally once daily before or after breakfast for 16 weeks. Participants also received either of concomitant medication (sulphonylureas) glibenclamide (1.25 to 5 mg), gliclazide (40 to 80 mg) or glimepiride (1 to 3 mg) per day during study. **ID:** OG001 **Title:** Placebo #### Outcome Measure 2 **Description:** Baseline value was value on Day 0. Change from Baseline was defined as value at Week 16 minus Baseline value. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Full analysis set used. **Reporting Status:** POSTED **Time Frame:** Baseline (Day 0) and Week 16 **Title:** Change From Baseline After 16 Weeks of Treatment in Fasting Plasma Glucose (FPG) **Type:** SECONDARY **Unit of Measure:** Mg per decilliter ##### Group **Description:** Participants in this arm were randomized to receive rosiglitazone (BRL49653C) 4 mg tablets orally once daily before or after breakfast for 16 weeks. Participants also received either of concomitant medication (sulphonylureas) glibenclamide (1.25 to 5 mg), gliclazide (40 to 80 mg) or glimepiride (1 to 3 mg) per day during study. **ID:** OG000 **Title:** Rosiglitazone 4 mg Orally Once Daily ##### Group **Description:** Participants in this arm were randomized to receive rosiglitazone placebo tablets orally once daily before or after breakfast for 16 weeks. Participants also received either of concomitant medication (sulphonylureas) glibenclamide (1.25 to 5 mg), gliclazide (40 to 80 mg) or glimepiride (1 to 3 mg) per day during study. **ID:** OG001 **Title:** Placebo #### Outcome Measure 3 **Description:** Baseline value was value on Day 0. Change from Baseline was defined as value at Week 16 minus Baseline value. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Full analysis set used. Only those participants available at the specified time points were analyzed. **Reporting Status:** POSTED **Time Frame:** Baseline (Day 0) and Week 16 **Title:** Change From Baseline After 16 Weeks of Treatment in Fasting Insulin **Type:** SECONDARY **Unit of Measure:** Microunits per millilliter ##### Group **Description:** Participants in this arm were randomized to receive rosiglitazone (BRL49653C) 4 mg tablets orally once daily before or after breakfast for 16 weeks. Participants also received either of concomitant medication (sulphonylureas) glibenclamide (1.25 to 5 mg), gliclazide (40 to 80 mg) or glimepiride (1 to 3 mg) per day during study. **ID:** OG000 **Title:** Rosiglitazone 4 mg Orally Once Daily ##### Group **Description:** Participants in this arm were randomized to receive rosiglitazone placebo tablets orally once daily before or after breakfast for 16 weeks. Participants also received either of concomitant medication (sulphonylureas) glibenclamide (1.25 to 5 mg), gliclazide (40 to 80 mg) or glimepiride (1 to 3 mg) per day during study. **ID:** OG001 **Title:** Placebo #### Outcome Measure 4 **Description:** Baseline value was value on Day 0. Change from Baseline was defined as value at Week 16 minus Baseline value. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Full analysis set used. Only those participants available at the specified time points were analyzed. **Reporting Status:** POSTED **Time Frame:** Baseline (Day 0) and Week 16 **Title:** Change From Baseline After 16 Weeks of Treatment in Fasting Proinsulin **Type:** SECONDARY **Unit of Measure:** Picomoles per millilliter ##### Group **Description:** Participants in this arm were randomized to receive rosiglitazone (BRL49653C) 4 mg tablets orally once daily before or after breakfast for 16 weeks. Participants also received either of concomitant medication (sulphonylureas) glibenclamide (1.25 to 5 mg), gliclazide (40 to 80 mg) or glimepiride (1 to 3 mg) per day during study. **ID:** OG000 **Title:** Rosiglitazone 4 mg Orally Once Daily ##### Group **Description:** Participants in this arm were randomized to receive rosiglitazone placebo tablets orally once daily before or after breakfast for 16 weeks. Participants also received either of concomitant medication (sulphonylureas) glibenclamide (1.25 to 5 mg), gliclazide (40 to 80 mg) or glimepiride (1 to 3 mg) per day during study. **ID:** OG001 **Title:** Placebo #### Outcome Measure 5 **Description:** Baseline value was value on Day 0. Change from Baseline was defined as value at Week 16 minus Baseline value. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Full analysis set used. Only those participants available at the specified time points were analyzed. **Reporting Status:** POSTED **Time Frame:** Baseline (Day 0) and Week 16 **Title:** Change From Baseline After 16 Weeks of Treatment in Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) **Type:** SECONDARY **Unit of Measure:** MilliUnit per liter*millimoles per liter ##### Group **Description:** Participants in this arm were randomized to receive rosiglitazone (BRL49653C) 4 mg tablets orally once daily before or after breakfast for 16 weeks. Participants also received either of concomitant medication (sulphonylureas) glibenclamide (1.25 to 5 mg), gliclazide (40 to 80 mg) or glimepiride (1 to 3 mg) per day during study. **ID:** OG000 **Title:** Rosiglitazone 4 mg Orally Once Daily ##### Group **Description:** Participants in this arm were randomized to receive rosiglitazone placebo tablets orally once daily before or after breakfast for 16 weeks. Participants also received either of concomitant medication (sulphonylureas) glibenclamide (1.25 to 5 mg), gliclazide (40 to 80 mg) or glimepiride (1 to 3 mg) per day during study. **ID:** OG001 **Title:** Placebo #### Outcome Measure 6 **Description:** Baseline value was value on Day 0. Change from Baseline was defined as value at Week 16 minus Baseline value. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Full analysis set used. Only those participants available at the specified time points were analyzed. **Reporting Status:** POSTED **Time Frame:** Baseline (Day 0) and Week 16 **Title:** Change From Baseline After 16 Weeks of Treatment in Homeostasis Model Assessment of Beta-cell Function (HOMA-beta) **Type:** SECONDARY **Unit of Measure:** Percentage of normal beta cells function ##### Group **Description:** Participants in this arm were randomized to receive rosiglitazone (BRL49653C) 4 mg tablets orally once daily before or after breakfast for 16 weeks. Participants also received either of concomitant medication (sulphonylureas) glibenclamide (1.25 to 5 mg), gliclazide (40 to 80 mg) or glimepiride (1 to 3 mg) per day during study. **ID:** OG000 **Title:** Rosiglitazone 4 mg Orally Once Daily ##### Group **Description:** Participants in this arm were randomized to receive rosiglitazone placebo tablets orally once daily before or after breakfast for 16 weeks. Participants also received either of concomitant medication (sulphonylureas) glibenclamide (1.25 to 5 mg), gliclazide (40 to 80 mg) or glimepiride (1 to 3 mg) per day during study. **ID:** OG001 **Title:** Placebo #### Outcome Measure 7 **Description:** Baseline value was value on Day 0. Change from Baseline was defined as value at Week 16 minus Baseline value. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Full analysis set used. Only those participants available at the specified time points were analyzed. **Reporting Status:** POSTED **Time Frame:** Baseline (Day 0) and Week 16 **Title:** Change From Baseline After 16 Weeks of Treatment in Adiponectin **Type:** SECONDARY **Unit of Measure:** Micrograms per millilliter ##### Group **Description:** Participants in this arm were randomized to receive rosiglitazone (BRL49653C) 4 mg tablets orally once daily before or after breakfast for 16 weeks. Participants also received either of concomitant medication (sulphonylureas) glibenclamide (1.25 to 5 mg), gliclazide (40 to 80 mg) or glimepiride (1 to 3 mg) per day during study. **ID:** OG000 **Title:** Rosiglitazone 4 mg Orally Once Daily ##### Group **Description:** Participants in this arm were randomized to receive rosiglitazone placebo tablets orally once daily before or after breakfast for 16 weeks. Participants also received either of concomitant medication (sulphonylureas) glibenclamide (1.25 to 5 mg), gliclazide (40 to 80 mg) or glimepiride (1 to 3 mg) per day during study. **ID:** OG001 **Title:** Placebo #### Outcome Measure 8 **Description:** Baseline value was value on Day 0. Change from Baseline was defined as value at Week 16 minus Baseline value. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Full analysis set used. Only those participants available at the specified time points were analyzed. **Reporting Status:** POSTED **Time Frame:** Baseline (Day 0) and Week 16 **Title:** Change From Baseline After 16 Weeks of Treatment in Leptin and High Sensitivity C-reactive Protein (Hs-CRP) **Type:** SECONDARY **Unit of Measure:** Nanograms per millilliter ##### Group **Description:** Participants in this arm were randomized to receive rosiglitazone (BRL49653C) 4 mg tablets orally once daily before or after breakfast for 16 weeks. Participants also received either of concomitant medication (sulphonylureas) glibenclamide (1.25 to 5 mg), gliclazide (40 to 80 mg) or glimepiride (1 to 3 mg) per day during study. **ID:** OG000 **Title:** Rosiglitazone 4 mg Orally Once Daily ##### Group **Description:** Participants in this arm were randomized to receive rosiglitazone placebo tablets orally once daily before or after breakfast for 16 weeks. Participants also received either of concomitant medication (sulphonylureas) glibenclamide (1.25 to 5 mg), gliclazide (40 to 80 mg) or glimepiride (1 to 3 mg) per day during study. **ID:** OG001 **Title:** Placebo #### Outcome Measure 9 **Description:** The specified criteria for HbA1c was, if the decrease from the observation period Baseline value meets the following conditions: 1) decrease from the observation period Baseline value is 0.7% or more; 2) fell below 6.5%; 3) satisfied either 1 or 2 noted above. And for FPG was, if the decrease from the observation period Baseline value meets the following conditions: 1) decrease of 30 mg per decilliter or more from the observation period Baseline value; 2) fell below 126 mg per deciliter; 3) satisfied either 1 or 2 noted above. **Parameter Type:** NUMBER **Population Description:** Full analysis set used. **Reporting Status:** POSTED **Time Frame:** Up to Week 16 **Title:** Percentage of Participants With Changes in HbA1c and FPG Meeting Specified Criteria After 16 Weeks of Treatment **Type:** SECONDARY **Unit of Measure:** Percentage of participants ##### Group **Description:** Participants in this arm were randomized to receive rosiglitazone (BRL49653C) 4 mg tablets orally once daily before or after breakfast for 16 weeks. Participants also received either of concomitant medication (sulphonylureas) glibenclamide (1.25 to 5 mg), gliclazide (40 to 80 mg) or glimepiride (1 to 3 mg) per day during study. **ID:** OG000 **Title:** Rosiglitazone 4 mg Orally Once Daily ##### Group **Description:** Participants in this arm were randomized to receive rosiglitazone placebo tablets orally once daily before or after breakfast for 16 weeks. Participants also received either of concomitant medication (sulphonylureas) glibenclamide (1.25 to 5 mg), gliclazide (40 to 80 mg) or glimepiride (1 to 3 mg) per day during study. **ID:** OG001 **Title:** Placebo ### Participant Flow Module #### Group **Description:** Participants in this arm were randomized to receive rosiglitazone (BRL49653C) 4 milligrams (mg) tablets orally once daily before or after breakfast for 16 weeks. Participants also received either of concomitant medication (sulphonylureas) glibenclamide (1.25 to 5 mg), gliclazide (40 to 80 mg) or glimepiride (1 to 3 mg) per day during study. **ID:** FG000 **Title:** Rosiglitazone 4 mg Orally Once Daily #### Group **Description:** Participants in this arm were randomized to receive rosiglitazone placebo tablets orally once daily before or after breakfast for 16 weeks. Participants also received either of concomitant medication (sulphonylureas) glibenclamide (1.25 to 5 mg), gliclazide (40 to 80 mg) or glimepiride (1 to 3 mg) per day during study. **ID:** FG001 **Title:** Placebo #### Period **Title:** Overall Study ##### Withdraw **Type:** Adverse Event ###### 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:** 3 ###### Reason **Group ID:** FG001 **Number of Subjects:** 2 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 74 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 75 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 69 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 72 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 5 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 3 **Pre-Assignment Details:** Out of 172 participants given consent to participate in the study, 23 participants were withdrawn from the study before randomization. **Recruitment Details:** From 19 April 2006 to 28 March 2007, total of 149 participants were randomized at 22 centers in Japan. **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT04621279 **Acronym:** COOLPRIME **Brief Title:** Cool Prime Comparative Effectiveness Study for Mild HIE **Official Title:** COOLPRIME: Comparative Effectiveness for Cooling Prospectively Infants With Mild Encephalopathy #### Organization Study ID Info **ID:** STU-2022-0714 #### Organization **Class:** OTHER **Full Name:** University of Texas Southwestern Medical Center ### Status Module #### Completion Date **Date:** 2029-01-01 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2023-12-13 **Type:** ACTUAL **Last Update Submit Date:** 2023-12-05 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2027-10-01 **Type:** ESTIMATED #### Start Date **Date:** 2023-07-19 **Type:** ACTUAL **Status Verified Date:** 2023-12 #### Study First Post Date **Date:** 2020-11-09 **Type:** ACTUAL **Study First Submit Date:** 2020-10-23 **Study First Submit QC Date:** 2020-11-02 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** Nationwide Children's Hospital **Class:** OTHER **Name:** University of California, San Francisco **Class:** OTHER **Name:** Children's National Research Institute **Class:** OTHER **Name:** Children's Hospital Los Angeles **Class:** OTHER **Name:** St. Louis University **Class:** OTHER **Name:** University of Washington **Class:** OTHER **Name:** Stanford University **Class:** OTHER **Name:** Children's Hospital of Philadelphia **Class:** OTHER **Name:** University of Utah **Class:** OTHER **Name:** University of Pittsburgh Medical Center **Class:** OTHER **Name:** Emory University **Class:** OTHER **Name:** Children's Hospital Medical Center, Cincinnati **Class:** OTHER **Name:** University College Cork **Class:** OTHER **Name:** The Children's Hospital of San Antonio #### Lead Sponsor **Class:** OTHER **Name:** University of Texas Southwestern Medical Center #### Responsible Party **Investigator Affiliation:** University of Texas Southwestern Medical Center **Investigator Full Name:** Lina Chalak **Investigator Title:** PROFESSOR **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** To determine effectiveness of therapy to improve neurodevelopmental outcomes in infants with mild HIE. To determine the adverse effects of Therapeutic Hypothermia (TH) in mild HIE on the neonate and his/her family. Determine heterogeneity of the treatment effect across key subgroups obtained in the first 6 hours after birth prior to the decision to initiate therapy. **Detailed Description:** This study leverages practice variation within and across 15 participating sites to compare the effectiveness of TH versus normothermia for mild HIE on neurodevelopmental outcomes at 2 years of age.After standardizing all aspects of clinical care for mild HIE (except for TH vs. normothermia)we will enroll 460 infants with mild HIE into the longitudinal, observational comparative effectiveness study.The central aim of the comparative longitudinal cohort of mild HIE is (1) to compare the effectiveness of hypothermia to normothermia on neurodevelopmental outcomes at 2 years, (2) determine the adverse effects of TH on the infant and his/her family; and (3) determine the heterogeneity of treatment effects (moderating effect) across mild HIE subgroups as determined by physiological biomarkers obtained during the 6 hours window to initiate hypothermia. The decision to apply TH or normothermia will be entirely determined by practice parameters at each site. ### Conditions Module **Conditions:** - Mild Hypoxic Ischemic Encephalopathy of Newborn **Keywords:** - mild HIE (Hypoxic Ischemic Encephalopathy) - neonatal encephalopathy - brain ischemia - brain hypoxia ### Design Module #### Design Info **Observational Model:** OTHER **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 460 **Type:** ESTIMATED **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Mild HIE identified in the first 6 hours of life according to the published PRIME study definition: newborn with evidence of encephalopathy (using the validated Sarnat Exam) NOT meeting prior cooling trials criteria. **Intervention Names:** - Procedure: Normothermia - Procedure: Whole body therapeutic hypothermia **Label:** Mild HIE ### Interventions #### Intervention 1 **Arm Group Labels:** - Mild HIE **Description:** Usual care for first 72 hours for neonates with mild encephalopathy maintaining core temperature (36.5°C ± 1 C). **Name:** Normothermia **Type:** PROCEDURE #### Intervention 2 **Arm Group Labels:** - Mild HIE **Description:** Whole-body therapeutic hypothermia (33.5°C ± 0.5°C) for 72 hours began by 6 hours of age for neonates with mild encephalopathy per site standard of care practice. **Name:** Whole body therapeutic hypothermia **Type:** PROCEDURE ### Outcomes Module #### Other Outcomes **Description:** Infant neurological integrity is measured with HNNE (Hammersmith Neonatal Neurological Exams), which is used to assess tone, spontaneous movements, reflexes, and visual and auditory attention allowing for a continuum of assessment from birth to 2 years. The maximum score for any one item is a score of 3 and the minimum is a score of 0. A subscore can be given for each section and the overall global score can be calculated by summing up all 26 items (range: 0-78), with higher scores indicating better neurological performance. The maximum global score is 78. **Measure:** Infant neurological integrity as measured with HNNE **Time Frame:** Discharge **Description:** Infant neurological integrity is measured with HINE (Hammersmith Infant Neurological Exams), which is used to assess tone, spontaneous movements, reflexes, and visual and auditory attention allowing for a continuum of assessment from birth to 2 years. The maximum score for any one item is a score of 3 and the minimum is a score of 0. A subscore can be given for each section and the overall global score can be calculated by summing up all 26 items (range: 0-78), with higher scores indicating better neurological performance. The maximum global score is 78. **Measure:** Infant neurological integrity as measured with HINE **Time Frame:** 3 - 4 months **Description:** Infant neurological integrity is measured with HINE (Hammersmith Infant Neurological Exams), which is used to assess tone, spontaneous movements, reflexes, and visual and auditory attention allowing for a continuum of assessment from birth to 2 years. The maximum score for any one item is a score of 3 and the minimum is a score of 0. A subscore can be given for each section and the overall global score can be calculated by summing up all 26 items (range: 0-78), with higher scores indicating better neurological performance. The maximum global score is 78. **Measure:** Infant neurological integrity as measured with HINE **Time Frame:** 22-26 months **Description:** The Child Behavior Checklist-parent report (CBCL) will provide a profile of behavior and social functioning validated in relation to age and gender. **Measure:** Behavioral tendency CBCL **Time Frame:** 22-26 months of age. **Description:** The Parent Report of Children's Abilities-Revised (PARCA-R) is used against the Mental Development Index of the Bayley Scales. **Measure:** Composite PARCA-R **Time Frame:** 22-26 months of age. **Description:** Impact on Family Scale - Revised **Measure:** IFS-R **Time Frame:** 9-12 months **Description:** Infant Behavior Questionnaire Revised (very short) **Measure:** IBQ-R **Time Frame:** 9-12months #### Primary Outcomes **Description:** Effectiveness of normothermia in infants is measured by Composite Bayley IV score scale, which is. an extensive formal developmental assessment tool for diagnosing developmental delays in early childhood. Possible scores range from 55- 120 where lower scores indicate worse outcome. **Measure:** Effectiveness of normothermia in infants as measured by Composite Bayley IV score **Time Frame:** 22-26 months of age. #### Secondary Outcomes **Description:** Safety will be measured by the presence or absence of a serious adverse event (SAE) at discharge. **Measure:** Adverse events SAE **Time Frame:** Discharge (approximately 7 days) **Description:** Parent-Infant stress and bonding is measured by Mother-to-infant bonding (MIBS) scale, which is a validated questionnaire with good psychometric properties that assesses the mother's feelings towards infant (bondedness) from birth to 4 months. Possible scores range from 0-3, where 0 indicates "not at all" and 3, "very much". **Measure:** Parent-Infant stress and bonding as measured by MIBS **Time Frame:** 3-4 months **Description:** Parent-Infant stress and bonding is measured by Infant Behavior Questionnaire-Revised (IBQR) which measures differences in reactivity and regulation, and the structure of infant temperament and its relation to parental family functioning. Item scores were summed according to IBQR scoring rules to create scores on the 14 scales, with higher scores indicating greater levels of that temperament dimension. **Measure:** Parent-Infant stress and bonding as measured by IBQR **Time Frame:** 3-4 months **Description:** Parent-Infant stress and bonding is measured by Parenting Stress Index (PSI) which is an abbreviated version of the full-length test with 36 items in three domains (Parental Distress, Parent-Child Dysfunctional Interaction, and Difficult Child) that combine to form a Total Stress scale, which helps identify families that are most in need of support services. In general, items are scored using the following 5-point scale: 1) SA (Strongly Agree), 2) A (Agree), 3) NS (Not Sure), 4) D (Disagree), 5) SD (Strongly Disagree). Responses to both the overall stress score and the three subscales are summed to generate representative scores, resulting the total stress score, perceptions of child behavioral problems, parenting distress, and parent-child dysfunctional interactions. **Measure:** Parent-Infant stress and bonding as measured by PSI **Time Frame:** 3-4 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: Infants must meet all 3 inclusion criteria 1. Neonates born at ≥ 35 0/7 weeks 2. Mild Encephalopathy on neonatal neurologic exam within 6 hours after birth: defined as presence of at least 2 signs of mild, moderate, or severe encephalopathy with no more than 2 signs in the moderate or severe category. 3. Perinatal Acidosis based on at least one of the following (A or B): 1. pH ≤ 7.00 in any cord or first infant gas (arterial, venous, or capillary) within ≤ 60 min OR base deficit ≥ 16 in any cord or first infant gas (arterial, venous or capillary) within ≤ 60 min 2. If pH is between 7.01 and 7.15, OR base deficit is between 10 and 15.9 mmol/liter, OR blood gas is not available, an acute perinatal event is an additional criteria required (see below definition) An acute perinatal event is defined by at least one of the following: 1. Apgar score at 10 min ≤ 5 2. Continued need for resuscitation at 10 min (chest compressions, bag mask ventilation, or positive pressure ventilation) 3. Uterine rupture, placental abruption, cord accident (prolapse, rupture, knot or tight nuchal cord) 4. maternal trauma, maternal hemorrhage, or cardiorespiratory arrest 5. fetal exsanguination from either vasa previa or feto-maternal hemorrhage, shoulder dystocia 6. Any evidence suggestive of acute perinatal event. Infants are still eligible for enrollment in the COOLPRIME study if the cord or infant's first blood gas (arterial, venous, or capillary) is obtained \>60 minutes of life. Exclusion Criteria: 1. Gestational age at birth \< 35 0/7 weeks 2. Birth weight \< 1800gm 3. Head circumference \<30cm 4. Congenital or chromosomal anomaly associated with abnormal neurodevelopment or death 5. Moderate or Severe HIE of 3 or more moderate or severe abnormalities on COOLPRIME Sarnat exam within 6 hours of life 6. Any seizures within first six hours of life 7. Redirection of care is being considered **Minimum Age:** 35 Weeks **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - CHILD - ADULT - OLDER_ADULT **Study Population:** Term infants ≥ 35 weeks' gestation with evidence of both perinatal event fetal acidosis and encephalopathy on exam. ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Lina Chalak, MD **Phone:** 214-648-3903 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Pollieanna Sepulveda, MSN, RN **Phone:** 214-648-3698 **Role:** CONTACT #### Locations **Location 1:** **City:** Atlanta **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Megan Moran - **Role:** CONTACT **Country:** United States **Facility:** EMORY University Hospital **State:** Georgia **Status:** RECRUITING **Zip:** 30322 **Location 2:** **City:** Dallas **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Pollieanna M Sepulveda - **Phone:** 214-648-3698 - **Role:** CONTACT **Country:** United States **Facility:** University of Texas Southwestern Medical Center **State:** Texas **Status:** RECRUITING **Zip:** 75208 #### Overall Officials **Official 1:** **Affiliation:** University of Texas Southwestern Medical Center **Name:** Lina Chalak, MD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** UNDECIDED ### References Module #### References **Citation:** Prempunpong C, Chalak LF, Garfinkle J, Shah B, Kalra V, Rollins N, Boyle R, Nguyen KA, Mir I, Pappas A, Montaldo P, Thayyil S, Sanchez PJ, Shankaran S, Laptook AR, Sant'Anna G. Prospective research on infants with mild encephalopathy: the PRIME study. J Perinatol. 2018 Jan;38(1):80-85. doi: 10.1038/jp.2017.164. Epub 2017 Nov 2. **PMID:** 29095433 **Citation:** Chalak LF, Nguyen KA, Prempunpong C, Heyne R, Thayyil S, Shankaran S, Laptook AR, Rollins N, Pappas A, Koclas L, Shah B, Montaldo P, Techasaensiri B, Sanchez PJ, Sant'Anna G. Prospective research in infants with mild encephalopathy identified in the first six hours of life: neurodevelopmental outcomes at 18-22 months. Pediatr Res. 2018 Dec;84(6):861-868. doi: 10.1038/s41390-018-0174-x. Epub 2018 Sep 13. **PMID:** 30250303 **Citation:** Chalak LF, Adams-Huet B, Sant'Anna G. A Total Sarnat Score in Mild Hypoxic-ischemic Encephalopathy Can Detect Infants at Higher Risk of Disability. J Pediatr. 2019 Nov;214:217-221.e1. doi: 10.1016/j.jpeds.2019.06.026. Epub 2019 Jul 10. Erratum In: J Pediatr. 2020 Mar;218:e2. **PMID:** 31301853 **Citation:** El-Dib M, Inder TE, Chalak LF, Massaro AN, Thoresen M, Gunn AJ. Should therapeutic hypothermia be offered to babies with mild neonatal encephalopathy in the first 6 h after birth? Pediatr Res. 2019 Mar;85(4):442-448. doi: 10.1038/s41390-019-0291-1. Epub 2019 Jan 16. **PMID:** 30733613 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000002493 - Term: Central Nervous System Diseases - ID: D000009422 - Term: Nervous System Diseases - ID: D000000860 - Term: Hypoxia - ID: D000012818 - Term: Signs and Symptoms, Respiratory - ID: D000002561 - Term: Cerebrovascular Disorders - ID: D000014652 - Term: Vascular Diseases - ID: D000002318 - Term: Cardiovascular Diseases - ID: D000002534 - Term: Hypoxia, Brain ### 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: M5794 - Name: Brain Ischemia - Relevance: HIGH - As Found: Ischemic Encephalopathy - ID: M10543 - Name: Ischemia - Relevance: LOW - As Found: Unknown - ID: M4185 - Name: Hypoxia - Relevance: LOW - As Found: Unknown - ID: M5783 - Name: Hypoxia, Brain - Relevance: LOW - As Found: Unknown - ID: M5204 - Name: Brain Diseases - Relevance: HIGH - As Found: Encephalopathy - ID: M22660 - Name: Hypoxia-Ischemia, Brain - Relevance: HIGH - As Found: Hypoxic Ischemic Encephalopathy - ID: M5742 - Name: Central Nervous System Diseases - Relevance: LOW - As Found: Unknown - ID: M15623 - Name: Signs and Symptoms, Respiratory - Relevance: LOW - As Found: Unknown - ID: M5810 - Name: Cerebrovascular Disorders - Relevance: LOW - As Found: Unknown - ID: M17400 - Name: Vascular Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000001927 - Term: Brain Diseases - ID: D000002545 - Term: Brain Ischemia - ID: D000020925 - Term: Hypoxia-Ischemia, Brain ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT01722279 **Brief Title:** The Long Term Impact of Bariatric Surgery on Quality of Life **Official Title:** The Long Term Impact of Bariatric Surgery on Quality of Life #### Organization Study ID Info **ID:** 10070 #### Organization **Class:** OTHER **Full Name:** Ascension St. Vincent Carmel Hospital ### Status Module #### Completion Date **Date:** 2012-03 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2012-11-06 **Type:** ESTIMATED **Last Update Submit Date:** 2012-11-02 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2012-03 **Type:** ACTUAL #### Start Date **Date:** 2010-07 **Status Verified Date:** 2012-11 #### Study First Post Date **Date:** 2012-11-06 **Type:** ESTIMATED **Study First Submit Date:** 2012-11-02 **Study First Submit QC Date:** 2012-11-02 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Ascension St. Vincent Carmel Hospital #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** The primary purpose of this study is to examine the breadth, nature, and factors affecting the long term changes in physical and psychological health and quality of life (QOL) following bariatric surgery. Data will be gathered via electronic survey (SurveyMonkey), postal mail, or phone, or using a standardized questionnaire expected to last 25-35 minutes. Archival data available from patient medical records will also be gathered. **Detailed Description:** Information from existing databases and medical records will be used to obtain a list of phone numbers for persons who had roux-en-y bariatric surgery at the SVBCE five or more years ago at the St. Vincent Bariatric Center of Excellence (SVBCE. The interview includes scripts that the caller will use to recruit subjects in either direct conversation, in voice mail or by leaving a message. Recruitment will cease after 400 complete post pilot interviews are obtained. The interview covers topics related to physical and psychological health and quality of life. The number of questions asked will vary from subject to subject since some questions are asked only if a prior question is answered affirmatively. For example, if a subject responds "yes" when asked "have you had plastic surgery?" the subject is then asked what type of procedure they had. The topics covered are as follows: weight, current health, post surgery complications, relationships, work, cross addiction, mental health, diet, television viewing, exercise, and life satisfaction. ### Conditions Module **Conditions:** - Obesity **Keywords:** - bariatric surgery - long-term outcomes - obesity ### Design Module #### Design Info **Observational Model:** CASE_ONLY **Time Perspective:** CROSS_SECTIONAL #### Enrollment Info **Count:** 414 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Survey participants had bariatric surgery at the St. Vincent Bariatric Center of Excellence at least 5 years before completing survey. **Intervention Names:** - Procedure: Bariatric surgery **Label:** Bariatric surgery patients, at least 5 years post-surgery ### Interventions #### Intervention 1 **Arm Group Labels:** - Bariatric surgery patients, at least 5 years post-surgery **Name:** Bariatric surgery **Other Names:** - roux-en-y gastric bypass - gastric band - biliopancreatic diversion with duodenal switch - vertical banded gastroplasty **Type:** PROCEDURE ### Outcomes Module #### Primary Outcomes **Measure:** Flourishing Scale (Diener et al, 2009) **Time Frame:** 5 or more years after bariatric surgery **Measure:** Satisfaction with Life Scale (Diener et al, 1985) **Time Frame:** 5 or more years after bariatric surgery #### Secondary Outcomes **Measure:** Relationship satisfaction **Time Frame:** At least 5 years post-surgery **Description:** Assesses presence of alcohol or other drug use problems, excessive spending, and problematic gambling **Measure:** Substance abuse and behavioral excesses **Time Frame:** At least 5 years post-surgery **Description:** Assesses presence of various obesity-related health problems including diabetes, hypertension, heart disease, stroke, hich cholesterol, sleep apnea, joint pain, etc. **Measure:** Physical Health Problems **Time Frame:** At least 5 years post-surgery **Description:** Assesses pre-surgery weight, current weight, and lowest post-surgical weight. **Measure:** Weight history **Time Frame:** At least 5 years post-surgery **Measure:** Satisfaction with surgery **Time Frame:** At least 5 years post-surgery **Measure:** Contact with Bariatric Center caregivers **Time Frame:** At least 5 years post-surgery ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Bariatric surgery patients of the St. Vincent Bariatric Center of Excellence who had surgery at least 5 years before the survey was administered. Exclusion Criteria: * Patients having bariatric surgery at facilities other than St. Vincent Bariatric Center. * Patients who had bariatric surgery less than 5 years before the survey period. **Minimum Age:** 18 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Bariatric surgery patients of the St. Vincent Bariatric Center of Excellence who had surgery at least 5 years before the survey was administered. ### Contacts Locations Module #### Locations **Location 1:** **City:** Carmel **Country:** United States **Facility:** St. Vincent Carmel Hospital Bariatric Center of Excellence **State:** Indiana **Zip:** 46032 #### Overall Officials **Official 1:** **Affiliation:** St. Vincent Carmel Bariatric Center of Excellence **Name:** Leslie M Schuh, PhD **Role:** PRINCIPAL_INVESTIGATOR ## 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 - Abbrev: BXM - Name: Behaviors and Mental Disorders ### Condition Browse Module - Browse Leaves - ID: M12701 - Name: Obesity - Relevance: LOW - As Found: Unknown - ID: T6034 - Name: Quality of Life - Relevance: HIGH - As Found: Quality of Life ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT05735379 **Brief Title:** Impact in Older Adults of Reducing Anticholinergic and Sedative Rx Burden on Physical Function Measured by Wearables **Official Title:** Impact in Older Adults of Reducing Anticholinergic and Sedative Medication Burden on Physical Function Measured by Clinical Digital Phenotyping in Lab and Real-life Environments #### Organization Study ID Info **ID:** PJT-183968 #### Organization **Class:** OTHER **Full Name:** Centre de recherche du Centre hospitalier universitaire de Sherbrooke ### Status Module #### Completion Date **Date:** 2025-12 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2023-09-18 **Type:** ACTUAL **Last Update Submit Date:** 2023-09-15 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2025-06 **Type:** ESTIMATED #### Start Date **Date:** 2023-03-23 **Type:** ACTUAL **Status Verified Date:** 2023-09 #### Study First Post Date **Date:** 2023-02-21 **Type:** ACTUAL **Study First Submit Date:** 2023-01-26 **Study First Submit QC Date:** 2023-02-09 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Centre de recherche du Centre hospitalier universitaire de Sherbrooke #### Responsible Party **Investigator Affiliation:** Centre de recherche du Centre hospitalier universitaire de Sherbrooke **Investigator Full Name:** Benoit Cossette **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:** Medications with sedative or anticholinergic effects such as antidepressants, benzodiazepines, or opioids have been associated with impaired cognitive and physical function. They are referred to as potentially inappropriate medications or medications that are best avoided by older adults. The accumulated evidence has now shifted the clinical and research focus to evaluating the who, what, and how of the best way to deprescribe (i.e., dose reduction or cessation of these medications). The Drug Burden Index (DBI) allows researchers and clinicians to quantify the cumulative burden of anticholinergic and sedative medications in each patient. Deprescribing these medications is a complex health intervention based on trade-offs between their clinical benefits (e.g., symptom management and prevention of diseases) and their adverse drug events to improve physical and cognitive function. Existing physical function performance metrics, such as gait speed captured in the clinic, are often non-specific and do not reflect real-life performance. Innovative mobility metrics are required to better understand specific deficits with age and disease and the effects of medications on these deficits. The goal of this project is to better characterize the impact of reducing the anticholinergic and sedative medication burden on physical function in older adults by novel mobility metrics in lab and real-life environments. A prospective, longitudinal cohort of 182 community-dwelling older adults (≥ 65 years) with a DBI of ≥ 1 will be completed. Using a quasi-experimental design, recruited patients will undergo a medication deprescribing plan, as part of usual clinical care, that includes three gradual changes to their medication regimen resulting in three DBI levels. At each DBI level, physical function mobility including dual-task tests) will be assessed in the lab with wearable sensors during validated clinical tests such as the Short Physical Performance Battery. Objective balance and mobility metrics (e.g., sway area and frequency, stride length) will be extracted. Physical function will also be assessed continuously in the patient's real-life environment from recruitment to the last lab visit, using wearable (Apple Watch® with ankle inertial measurement unit) and environmental sensors. Cognition will be measured using the Montreal Cognitive Assessment, Trail Making Test Part A \& B, and Digit Symbol Substitution Test. ### Conditions Module **Conditions:** - Deprescribing Anticholinergic and Sedative Medications - Physical Function ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 182 **Type:** ESTIMATED **Phases:** - PHASE4 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Deprescribing plan targeting a reduction in drug burden index score of ≥ 0.5 **Intervention Names:** - Drug: Deprescribing anticholinergic and sedative mediications **Label:** Deprescribing anticholinergic and sedative medications **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Deprescribing anticholinergic and sedative medications **Description:** Deprescribing plan targeting a reduction in Drug Burden Index score of ≥ 0.5 **Name:** Deprescribing anticholinergic and sedative mediications **Other Names:** - Drug cessation or dose reduction **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Gait speed (m/s) **Measure:** Change in gait capacity measured in the lab from baseline to study completion **Time Frame:** Through study completion, an average of 4 months. #### Secondary Outcomes **Description:** Gait activity (number of steps) **Measure:** Change in gait performance measured in real-life settings from baseline to study completion **Time Frame:** Through study completion, an average of 4 months. **Description:** Late-Life Function and Disability Instrument (Late-Life FDI), **Measure:** Change in functional limitations and disability from baseline to study completion **Time Frame:** Through study completion, an average of 4 months. **Description:** Older Adults Resources and Services (OARS) Multidimensional Functional Assessment Questionnaire adapted for the caregiver. **Measure:** Change in caregiver report of the patients' functional status from baseline to study completion **Time Frame:** Through study completion, an average of 4 months. **Description:** Falls nand near falls recorded by patient diary **Measure:** Change in falls and near falls from baseline to study completion **Time Frame:** Through study completion, an average of 4 months. **Description:** Falls and near falls recorded from the Apple Watch® proprietary algorithm. **Measure:** Change in falls and near falls from baseline to study completion **Time Frame:** Through study completion, an average of 4 months. **Description:** Adverse anticholinergic and sedative effects from G-MEDSS **Measure:** Adverse drug events and adverse drug withdrawal events **Time Frame:** Continuous during the deprescribing process **Description:** Full version **Measure:** Change in Montreal Cognitive Assessment (MoCA) from baseline to study completion **Time Frame:** Through study completion, an average of 4 months. **Description:** Part A \& B **Measure:** Change in Trail Making Test (TMT) from baseline to study completion **Time Frame:** Through study completion, an average of 4 months. **Description:** DSST **Measure:** Change in Digit Symbol Substitution Test from baseline to study completion **Time Frame:** Through study completion, an average of 4 months. ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * 65 years and older * community-dwelling * Drug Burden Index score of ≥ 1 * Agree with a deprescribing plan targeting a reduction in Drug Burden Index score of ≥ 0.5. Exclusion Criteria: * Dementia * Need of a walker as a mobility assistive device * Unstable medical condition (≥ 1 unplanned hospitalization or ≥ 2 emergency department visits in the past month). **Minimum Age:** 60 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Marilyn Tousignant, MSc **Phone:** 819-780-2222 **Role:** CONTACT #### Locations **Location 1:** **City:** Sherbrooke **Contacts:** ***Contact 1:*** - **Name:** Marilyn Tousignant - **Role:** CONTACT **Country:** Canada **Facility:** CIUSSS de l'Estrie-CHUS **State:** Quebec **Status:** RECRUITING **Zip:** J1H 4C4 ### IPD Sharing Statement Module **IPD Sharing:** UNDECIDED ## Derived Section ### Intervention Browse Module - Ancestors - ID: D000002492 - Term: Central Nervous System Depressants - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000018678 - Term: Cholinergic Agents - ID: D000018377 - Term: Neurotransmitter Agents - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action ### Intervention Browse Module - Browse Branches - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: CNSDep - Name: Central Nervous System Depressants ### Intervention Browse Module - Browse Leaves - ID: M20760 - Name: Cholinergic Antagonists - Relevance: HIGH - As Found: Chantix - ID: M10043 - Name: Hypnotics and Sedatives - Relevance: HIGH - As Found: Arabic - 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: D000006993 - Term: Hypnotics and Sedatives - ID: D000018680 - Term: Cholinergic Antagonists ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03920579 **Brief Title:** A Clinical Trial to Investigate the Pharmacokinetics and Safety/Tolerability of CKD-386 in Healthy Male Volunteers **Official Title:** A Sequence-randomized, Open-label, 3-way Crossover, Single Oral Dose Clinical Trial to Investigate the Pharmacokinetic Characteristics and Safety/Tolerability According to Formulations of CKD-386 in Healthy Male Volunteers #### Organization Study ID Info **ID:** 183PK18034 #### Organization **Class:** INDUSTRY **Full Name:** Chong Kun Dang Pharmaceutical ### Status Module #### Completion Date **Date:** 2019-05 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** RECRUITING #### Last Update Post Date **Date:** 2019-04-19 **Type:** ACTUAL **Last Update Submit Date:** 2019-04-17 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2019-05 **Type:** ESTIMATED #### Start Date **Date:** 2019-04-01 **Type:** ACTUAL **Status Verified Date:** 2019-04 #### Study First Post Date **Date:** 2019-04-19 **Type:** ACTUAL **Study First Submit Date:** 2019-04-08 **Study First Submit QC Date:** 2019-04-17 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Chong Kun Dang Pharmaceutical #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** a study to investigate the pharmacokinetic characteristics and safety/tolerability according to formulations of CKD-386 in healthy male volunteers **Detailed Description:** A sequence-randomized, open-label, 3-way crossover, single oral dose clinical trial to investigate the pharmacokinetic characteristics and safety/tolerability according to formulations of CKD-386 in healthy male volunteers ### Conditions Module **Conditions:** - Hypertension - Dyslipidemias **Keywords:** - CKD-386 - Pharmacokinetics - D326 - D337 - D013 ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** CROSSOVER ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 30 **Type:** ESTIMATED **Phases:** - PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Period 1: CKD-386 formulation 1(1 tab, once) / Period 2: CKD-386 formulation 2(1 tab, once) / Period 3: D326, D337, D013(3 tabs, once) **Intervention Names:** - Drug: CKD-386 formulation 1 - Drug: CKD-386 formulation 2 - Drug: D326, D337 and D013 **Label:** Sequence 1 **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Period 1: CKD-386 formulation 1(1 tab, once) / Period 2: D326, D337, D013(3 tabs, once) / Period 3: CKD-386 formulation 2(1 tab, once) **Intervention Names:** - Drug: CKD-386 formulation 1 - Drug: CKD-386 formulation 2 - Drug: D326, D337 and D013 **Label:** Sequence 2 **Type:** EXPERIMENTAL #### Arm Group 3 **Description:** Period 1: CKD-386 formulation 2(1 tab, once) / Period 2: D326, D337, D013(3 tabs, once) / Period 3: CKD-386 formulation 1(1 tab, once) **Intervention Names:** - Drug: CKD-386 formulation 1 - Drug: CKD-386 formulation 2 - Drug: D326, D337 and D013 **Label:** Sequence 3 **Type:** EXPERIMENTAL #### Arm Group 4 **Description:** Period 1: CKD-386 formulation 2(1 tab, once) / Period 2: CKD-386 formulation 1(1 tab, once) / Period 3: D326, D337, D013 **Intervention Names:** - Drug: CKD-386 formulation 1 - Drug: CKD-386 formulation 2 - Drug: D326, D337 and D013 **Label:** Sequence 4 **Type:** EXPERIMENTAL #### Arm Group 5 **Description:** Period 1: D326, D337, D013(3 tabs, once) / Period 2: CKD-386 formulation 1(1 tab, once) / Period 3: CKD-386 formulation 2(1 tab, once) **Intervention Names:** - Drug: CKD-386 formulation 1 - Drug: CKD-386 formulation 2 - Drug: D326, D337 and D013 **Label:** Sequence 5 **Type:** EXPERIMENTAL #### Arm Group 6 **Description:** Period 1: D326, D337, D013 (3 tabs, once)/ Period 2: CKD-386 formulation 2(1 tab, once) / Period 3: CKD-386 formulation 1(1 tab, once) **Intervention Names:** - Drug: CKD-386 formulation 1 - Drug: CKD-386 formulation 2 - Drug: D326, D337 and D013 **Label:** Sequence 6 **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Sequence 1 - Sequence 2 - Sequence 3 - Sequence 4 - Sequence 5 - Sequence 6 **Description:** A single oral dose of 1 tablet under fasting conditions for each period **Name:** CKD-386 formulation 1 **Other Names:** - CKD-386 Test 1 **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Sequence 1 - Sequence 2 - Sequence 3 - Sequence 4 - Sequence 5 - Sequence 6 **Description:** A single oral dose of 1 tablet under fasting conditions for each period **Name:** CKD-386 formulation 2 **Other Names:** - CKD-386 Test 2 **Type:** DRUG #### Intervention 3 **Arm Group Labels:** - Sequence 1 - Sequence 2 - Sequence 3 - Sequence 4 - Sequence 5 - Sequence 6 **Description:** A single oral dose of 3 tablets(D326, D337 and D013) under fasting conditions for each period **Name:** D326, D337 and D013 **Other Names:** - CKD-386 Reference **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** AUC0-t: Area under the concentration-time curve from time zero to time **Measure:** AUC0-t of each main component after single dose of CKD-386 formulation 1, CKD-386 formulation 2 or D326, D337, D013 **Time Frame:** 0(predose)~72 hour at Day1~Day3, Day15~Day17, Day29~Day31 **Description:** Cmax: Maximum plasma concentration of the drug **Measure:** Cmax of each main component after single dose of CKD-386 formulation 1, CKD-386 formulation 2 or D326, D337, D013 **Time Frame:** 0(predose)~72 hour at Day1~Day3, Day15~Day17, Day29~Day31 #### Secondary Outcomes **Description:** AUCinf: Area under the concentration-time curve from zero up to ∞ **Measure:** AUCinf each main component or the metabolite of the component after single dose of CKD-386 formulation 1, CKD-386 formulation 2 and D326, D337, D013 **Time Frame:** 0(predose)~72 hour at Day1~D3, Day15~D17, Day29~31 **Description:** Tmax: Time to maximum plasma concentration **Measure:** Tmax of each main component or the metabolite of the component after single dose of CKD-386 formulation 1, CKD-386 formulation 2 and D326, D337, D013 **Time Frame:** 0(predose)~72 hour at Day1~Day3, Day15~Day17, Day29~Day31 **Description:** t1/2: Terminal elimination half-life **Measure:** t1/2 of each main component or the metabolite of the component after single dose of CKD-386 formulation 1, CKD-386 formulation 2 and D326, D337, D013 **Time Frame:** 0(predose)~72 hour at Day1~Day3, Day15~Day17, Day29~Day31 **Description:** CL/F: Apparent total body clearance of the drug **Measure:** CL/F of each main component after single dose of CKD-386 formulation 1, CKD-386 formulation 2 and D326, D337, D013 **Time Frame:** 0(predose)~72 hour at Day1~Day3, Day15~Day17, Day29~Day31 **Description:** Vd/F: Apparent volume of distribution **Measure:** Vd/F of each main component after single dose of CKD-386 formulation 1, CKD-386 formulation 2 and D326, D337, D013 **Time Frame:** 0(predose)~72 hour at Day1~Day3, Day15~Day17, Day29~Day31 **Description:** AUC0-t: Area under the concentration-time curve from time zero to time **Measure:** AUC0-t of the metabolite of each component after single dose of CKD-386 formulation 1, CKD-386 formulation 2 and D326, D337, D013 **Time Frame:** 0(predose)~72 hour at Day1~Day3, Day15~Day17, Day29~Day31 **Description:** Cmax: Maximum plasma concentration of the drug **Measure:** Cmax of the metabolite of each component after single dose of CKD-386 formulation 1, CKD-386 formulation 2 and D326, D337, D013 **Time Frame:** 0(predose)~72 hour at Day1~Day3, Day15~Day17, Day29~Day31 ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Healthy volunteers aged between ≥20 and ≤45 years old 2. Weight ≥ 50 kg, with calculated body mass index(BMI) of ≥ 18.5 and ≤ 27.0 kg/m2 3. Those who have no congenital chronic disease or chronic disease requiring treatment and who have no pathological symptoms or findings 4. Those who are judged to be eligible for clinical trials based on laboratory and ECG results during screening tests 5. Those who voluntarily decide to participate and agree to comply with the cautions after hearing and fully understanding the detailed description of this clinical trial Exclusion Criteria: 1. History of presence of hepatobiliary, renal, cardiovascular, endocrine, respiratory, gastrointestinal, hematological, neurologic, psychiatric or musculoskeletal disorders affecting absorption, distribution, metabolism and excretion of the drug 2. Genetic problems such as galactose intolerance, Lapp lactose deficiency or glucose-galactose malabsorption 3. Those who are deemed unfit by the investigators to participate in the clinical trial for other reasons including the results of laboratory tests **Healthy Volunteers:** True **Maximum Age:** 45 Years **Minimum Age:** 19 Years **Sex:** MALE **Standard Ages:** - ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Dongseong Shin, M.D, Ph.D **Phone:** +82-32-460-9459 **Role:** CONTACT #### Locations **Location 1:** **City:** Incheon **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Dongseong Shin, M.D, Ph.D - **Phone:** +82-32-460-9459 - **Role:** CONTACT **Country:** Korea, Republic of **Facility:** Gachon University Gil Medical Center **Status:** RECRUITING **Zip:** 21565 #### Overall Officials **Official 1:** **Affiliation:** Clinical Trials Center, Gil Medical Center, Incheon, Korea **Name:** Dongseong Shin, M.D, Ph.D **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000052439 - Term: Lipid Metabolism Disorders - ID: D000008659 - Term: Metabolic Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC14 - Name: Heart and Blood Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC18 - Name: Nutritional and Metabolic Diseases ### Condition Browse Module - Browse Leaves - ID: M10024 - Name: Hypertension - Relevance: LOW - As Found: Unknown - ID: M26181 - Name: Dyslipidemias - Relevance: HIGH - As Found: Dyslipidemia - 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: D000050171 - Term: Dyslipidemias ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT02500979 **Brief Title:** Effect of a Fixed Pramlintide: Insulin Dose Ratio on Postprandial Glucose in Type 1 Diabetes Mellitus **Official Title:** A Randomized, Single-Blind, Two-Way Crossover, Placebo-Controlled Phase I Study to Compare the 24-hour Glucose Profile and Safety of Pramlintide and Insulin, Co-Administered in a Fixed-Dose Ratio, Versus Placebo and Insulin in Patients With Type 1 Diabetes Mellitus With Inadequate Glycemic Control #### Organization Study ID Info **ID:** D5570C00002 #### Organization **Class:** INDUSTRY **Full Name:** AstraZeneca ### Status Module #### Completion Date **Date:** 2016-08-05 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2018-11-02 **Type:** ACTUAL **Last Update Submit Date:** 2018-03-12 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2016-08-05 **Type:** ACTUAL #### Results First Post Date **Date:** 2018-11-02 **Type:** ACTUAL **Results First Submit Date:** 2017-08-02 **Results First Submit QC Date:** 2018-03-12 #### Start Date **Date:** 2015-08-17 **Type:** ACTUAL **Status Verified Date:** 2018-03 #### Study First Post Date **Date:** 2015-07-17 **Type:** ESTIMATED **Study First Submit Date:** 2015-07-10 **Study First Submit QC Date:** 2015-07-15 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** Juvenile Diabetes Research Foundation #### Lead Sponsor **Class:** INDUSTRY **Name:** AstraZeneca #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** This study is designed to investigate the clinical efficacy and safety of pramlintide co-administered as a fixed-dose ratio with basal-bolus SC insulin, delivered simultaneously via 2 separate pumps, in subjects with type 1 diabetes who are failing to achieve the desired level of glycemic control using insulin therapy. **Detailed Description:** Potentially eligible subjects with Type 1 diabetes mellitus who are treated with with a basal-bolus insulin regimen through multiple daily injections or insulin pump at a total daily insulin dose ≤60 U, will be eligible. Visit 1 is approximately 3-6 weeks prior to randomization. Given some variability in HbA1c and C-peptide assays, re-testing for HbA1c and C-peptide can be performed within 18 days from the initial visit. Visit 2 is approximately 2-5 weeks prior to randomization. Subjects are on lispro insulin throughout study except during Visit 4 and Visit 5, the domicile 24 hr treatment period, when they are switched to regular insulin U-100. Screen failed patients may be re-screened for inclusion in the study, as long as re-screening takes place at least 3 months after the original screening visit. If a subject is re-screened, he/she must continue to meet all inclusion/exclusion criteria. All study procedures of initial Visit 1 must be repeated at the re-screening visit. ### Conditions Module **Conditions:** - Type 1 Diabetes Mellitus **Keywords:** - Type 1 Diabetes Mellitus; Pramlintide ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** CROSSOVER ##### Masking Info **Masking:** SINGLE **Who Masked:** - PARTICIPANT **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 34 **Type:** ACTUAL **Phases:** - PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Pramlintide will be adiministered by sc infusion at a concentration of 1000ug/mL **Intervention Names:** - Drug: Pramlintide acetate - Drug: Lispro insulin U-100 - Drug: Regular insulin U-100 **Label:** Pramlintide acetate & regular insulin **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Placebo is similar sterile solution without pramlintide. **Intervention Names:** - Drug: Placebo - Drug: Lispro insulin U-100 - Drug: Regular insulin U-100 **Label:** Placebo and regular insulin **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Pramlintide acetate & regular insulin **Description:** Pramlintide acetate administered by a separate pump **Name:** Pramlintide acetate **Other Names:** - Pramlintide: SYMLIN **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Placebo and regular insulin **Description:** Placebo administered by separate pump **Name:** Placebo **Type:** DRUG #### Intervention 3 **Arm Group Labels:** - Placebo and regular insulin - Pramlintide acetate & regular insulin **Description:** Subjects will be stabilized on a separate insulin pump and administered lispro insulin throughout the study, except during both inpatient treatment periods (Visit 4 and Visit 5) **Name:** Lispro insulin U-100 **Other Names:** - Humalog insulin lispro U-100 **Type:** DRUG #### Intervention 4 **Arm Group Labels:** - Placebo and regular insulin - Pramlintide acetate & regular insulin **Description:** Use during two in-patient treatment periods (visits 4 and 5) and administered by separate pump **Name:** Regular insulin U-100 **Other Names:** - Humulin R; U-100 **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** 24-hour MWG mg/dL, defined as total area under the 24-hour tissue glucose curve obtained with CGM, divided by actual time span in the 24-hour period. **Measure:** Efficacy of Pramlintide by Measurement of 24-hour Tissue Mean Weighted Glucose (MWG) Obtained With Continuous Glucose Monitoring (CGM) **Time Frame:** 24 h #### Secondary Outcomes **Description:** Absolute postprandial plasma glucose AUC was measured for the first 3 hours (AUC0-3h) following lunch based on sample availability. (Sample times: 20 hours \[lunch\], 20 hours 45 min, 21 hours, 23 hours, 24 hours). **Measure:** Efficacy of Pramlintide by Measurement of Absolute Plasma Glucose Area Under the Plasma Concentration-time Curve (AUC) Following Lunch **Time Frame:** 3 hours **Description:** Absolute postprandial plasma glucose AUC (AUC0-2h) was measured for the first 2 hours following dinner based on sample availability. (Sample times: 2 hours \[dinner\], 2 hours 45 min, 3 hours, 4 hours). **Measure:** Efficacy of Pramlintide by Measurement of Absolute Plasma Glucose Area Under the Plasma Concentration-time Curve (AUC) Following Dinner **Time Frame:** 2 hours **Description:** Absolute postprandial plasma glucose AUC (AUC0-2h) was measured for the first 2 hours following breakfast based on sample availability. (Sample times: 16 hours \[breakfast\], 16 hours 45 min, 17 hours, 18 hours). **Measure:** Efficacy of Pramlintide by Measurement of Absolute Plasma Glucose Area Under the Plasma Concentration-time Curve (AUC) Following Breakfast **Time Frame:** 2 hours **Description:** Incremental (i.e., baseline-corrected) area under the 24-hour tissue glucose concentration curve (AUC0-24h) measured by continuous glucose monitoring (CGM) with a pre-test, non-fasting tissue glucose value as baseline. (Sample times: 0, 30 min, 2 hours \[dinner\], 2 hours 45 min, 3 hours, 4 hours, 9 hours, 12 hours, 14 hours, 16 hours \[breakfast\], 16 hours 45 min, 17 hours, 18 hours, 20 hours \[lunch\], 20 hours 45 min, 21 hours, 23 hours, 24 hours). **Measure:** Efficacy of Pramlintide by Measurement of Incremental 24-hour Tissue Glucose Area Under the Plasma Concentration-time Curve (AUC) Obtained With Continuous Glucose Monitoring (CGM) **Time Frame:** 24 h **Description:** Absolute mean area under the 24-hour plasma glucose concentration curve, measured as total area under the curve (0 to 24 hours). (Sample times: 0, 30 min, 2 hours \[dinner\], 2 hours 45 min, 3 hours, 4 hours, 9 hours, 12 hours, 14 hours, 16 hours \[breakfast\], 16 hours 45 min, 17 hours, 18 hours, 20 hours \[lunch\], 20 hours 45 min, 21 hours, 23 hours, 24 hours). **Measure:** Efficacy of Pramlintide by Measurement of Absolute 24-hour Plasma Glucose Area Under the Plasma Concentration-time Curve (AUC) **Time Frame:** 24 h **Description:** Incremental (i.e., baseline-corrected) mean area under the 24-hour plasma glucose concentration curve, measured as total area under the curve (0 to 24 hours). (Sample times: 0, 30 min, 2 hours \[dinner\], 2 hours 45 min, 3 hours, 4 hours, 9 hours, 12 hours, 14 hours, 16 hours \[breakfast\], 16 hours 45 min, 17 hours, 18 hours, 20 hours \[lunch\], 20 hours 45 min, 21 hours, 23 hours, 24 hours). **Measure:** Efficacy of Pramlintide by Measurement of Incremental 24-hour Plasma Glucose Area Under the Plasma Concentration-time Curve (AUC) **Time Frame:** 24 hours **Description:** Percent time spent in the normoglycemic range of tissue glucose concentrations between \>70 mg/dL and \<180 mg/dL, measured by CGM. (Sample times: 0, 30 min, 2 hours \[dinner\], 2 hours 45 min, 3 hours, 4 hours, 9 hours, 12 hours, 14 hours, 16 hours \[breakfast\], 16 hours 45 min, 17 hours, 18 hours, 20 hours \[lunch\], 20 hours 45 min, 21 hours, 23 hours, 24 hours). **Measure:** Efficacy of Pramlintide Measured by Percent Time Spent in the Range of >70 mg/dL to <180 mg/dL Tissue Glucose Obtained With Continuous Glucose Monitoring (CGM) **Time Frame:** 24 h **Description:** Absolute mean area under the 24-hour plasma glucagon concentration curve, measured as total area under the curve (total AUC0-24). (Sample times: 0, 30 min, 2 hours \[dinner\], 2 hours 45 min, 3 hours, 4 hours, 9 hours, 12 hours, 14 hours, 16 hours \[breakfast\], 16 hours 45 min, 17 hours, 18 hours, 20 hours \[lunch\], 20 hours 45 min, 21 hours, 23 hours, 24 hours). **Measure:** Efficacy of Pramlintide by Measurement of Absolute 24-hour Plasma Glucagon Area Under the Plasma Concentration-time Curve (AUC) **Time Frame:** 24 h **Description:** Incremental (i.e., baseline-corrected) mean area under the 24-hour plasma glucagon concentration curve with a pre-test, non-fasting plasma glucagon value as baseline. (Sample times: 0, 30 min, 2 hours \[dinner\], 2 hours 45 min, 3 hours, 4 hours, 9 hours, 12 hours, 14 hours, 16 hours \[breakfast\], 16 hours 45 min, 17 hours, 18 hours, 20 hours \[lunch\], 20 hours 45 min, 21 hours, 23 hours, 24 hours). **Measure:** Efficacy of Pramlintide by Measurement of Incremental 24-hour Plasma Glucagon Area Under the Plasma Concentration-time Curve (AUC) **Time Frame:** 24 h **Description:** Fasting plasma glucose concentration at 0600 hours (6:00 AM) **Measure:** Fasting Plasma Glucose Concentration **Time Frame:** 12 hours after dinner meal **Description:** Mean areas under the plasma insulin concentration curves for the 24-hour periods of pramlintide and placebo administration (Sample times: -15 min, 0, 30 min, 1 hour 30 min, 2 hours \[dinner\], 2 hours 15 min, 2 hours 30 min, 2 hours 45 min, 3 hours, 4 hours, 5 hours, 6 hours, 9 hours, 12 hours, 15 hours, 16 hours \[breakfast\], 16 hours 15 min, 16 hours 30 min, 16 hours 45 min, 17 hours, 18 hours, 19 hours, 20 hours \[lunch\], 24 hours). **Measure:** Pharmacokinetics of Insulin as Demonstrated by 24-hour Plasma Insulin Area Under the Plasma Concentration-time Curve (AUC) **Time Frame:** 24 hours **Description:** Mean values of the average plasma insulin concentrations over the 24-hour periods of pramlintide and placebo administration. (Sample times: -15 min, 0, 30 min, 1 hour 30 min, 2 hours \[dinner\], 2 hours 15 min, 2 hours 30 min, 2 hours 45 min, 3 hours, 4 hours, 5 hours, 6 hours, 9 hours, 12 hours, 15 hours, 16 hours \[breakfast\], 16 hours 15 min, 16 hours 30 min, 16 hours 45 min, 17 hours, 18 hours, 19 hours, 20 hours \[lunch\], 24 hours). **Measure:** Pharmacokinetics of Insulin as Demonstrated by 24-hour Average Plasma Insulin Concentration. **Time Frame:** 24 hours **Description:** Mean maximum plasma insulin concentrations over the 24-hour periods of pramlintide and placebo administration. (Sample times: -15 min, 0, 30 min, 1 hour 30 min, 2 hours \[dinner\], 2 hours 15 min, 2 hours 30 min, 2 hours 45 min, 3 hours, 4 hours, 5 hours, 6 hours, 9 hours, 12 hours, 15 hours, 16 hours \[breakfast\], 16 hours 15 min, 16 hours 30 min, 16 hours 45 min, 17 hours, 18 hours, 19 hours, 20 hours \[lunch\], 24 hours). **Measure:** Pharmacokinetics of Insulin as Demonstrated by Maximum Plasma Insulin Concentration **Time Frame:** 24 hours **Description:** Mean time to maximum plasma insulin concentrations over the 24-hour periods of pramlintide and placebo administration. (Sample times: -15 min, 0, 30 min, 1 hour 30 min, 2 hours \[dinner\], 2 hours 15 min, 2 hours 30 min, 2 hours 45 min, 3 hours, 4 hours, 5 hours, 6 hours, 9 hours, 12 hours, 15 hours, 16 hours \[breakfast\], 16 hours 15 min, 16 hours 30 min, 16 hours 45 min, 17 hours, 18 hours, 19 hours, 20 hours \[lunch\], 24 hours). **Measure:** Pharmacokinetics of Insulin as Demonstrated by the Time to the Maximum Plasma Insulin Concentration **Time Frame:** 24 hours ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Provision of informed consent prior to any study-specific procedures * Female and/or male aged between 18 and 70 years * Must have a prior diagnosis of T1DM * Body mass index (BMI) \<30 kg/m2 * Subjects are not on current treatment with pramlintide (Symlin) and have not received pramlintide during the 6-month period prior to enrollment * Subjects should be willing to consume all of the components of the standardized meals administered during the study * Negative serum pregnancy test for female subjects of childbearing potential * Female subjects of childbearing potential must be 1 year postmenopausal, surgically sterile, or using an acceptable method of contraception for the duration of the study * Male subjects must be surgically sterile or using an acceptable method of contraception for the duration of the study Exclusion Criteria: * Recurrent severe hypoglycemia requiring assistance within 6 months before screening * A history of hypoglycemia unawareness * A confirmed diagnosis of gastroparesis * Has been treated, is currently being treated, or is expected to require or undergo treatment with the following medications: * Any oral antihyperglycemic agent or any other injectable antihyperglycemic agent that is not insulin * Drugs that directly affect GI motility (eg, anticholinergic agents such as atropine) * Drugs that slow the intestinal absorption of nutrients (eg, α-glucosidase inhibitors * A history of gastric surgery (such as gastric banding, Roux- and Y bypass) * Is expected to require or undergo treatment with acetaminophen after enrollment and at any point during the study * Has experienced diabetic ketoacidosis within the last 24 weeks * History of hospitalization within the last 6 months for glycemic control (for both hyperglycemia or hypoglycemia) * Subject has any significant disease or disorder, which, in the opinion of the investigator, may either put the subject at risk because of participation in the study, or may influence the results of the study, or the subject's ability to participate in the study * Any clinically relevant abnormal findings, which, in the opinion of the investigator, may put the subject at risk because of his/her participation in the study. * Pregnancy confirmed by a positive pregnancy test, or otherwise verified. * Breast feeding * Positive hepatitis C virus antibody (HCV Ab), hepatitis B virus surface antigen (HBsAg), hepatitis B virus core antibody (anti-Hbc), or human immunodeficiency virus 1/2 antibody (HIV-1/2 Ab) at Screening * History of, or current alcohol or drug abuse * Has donated blood within 2 months of Visit 1 (Screening) or is planning to donate blood during the study * Has had a major surgery or a blood transfusion within 2 months before Visit 1 (screening) * Participation in any clinical study with an investigational drug or new formulation of a marketed drug during the last 1 month prior to Visit 1 **Maximum Age:** 70 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Chula Vista **Country:** United States **Facility:** Research Site **State:** California **Zip:** 91911 **Location 2:** **City:** Portland **Country:** United States **Facility:** Research Site **State:** Oregon **Zip:** 97239 **Location 3:** **City:** Chattanooga **Country:** United States **Facility:** Research Site **State:** Tennessee **Zip:** 37411 #### Overall Officials **Official 1:** **Affiliation:** Medical Director AstraZeneca **Name:** Peter Ohman, MD **Role:** STUDY_DIRECTOR ### References Module #### References **Citation:** Riddle MC, Nahra R, Han J, Castle J, Hanavan K, Hompesch M, Huffman D, Strange P, Ohman P. Control of Postprandial Hyperglycemia in Type 1 Diabetes by 24-Hour Fixed-Dose Coadministration of Pramlintide and Regular Human Insulin: A Randomized, Two-Way Crossover Study. Diabetes Care. 2018 Nov;41(11):2346-2352. doi: 10.2337/dc18-1091. Epub 2018 Sep 13. **PMID:** 30213882 ## 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 Mellitus - 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: D000007004 - Term: Hypoglycemic Agents - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000001067 - Term: Appetite Depressants - ID: D000019440 - Term: Anti-Obesity Agents - ID: D000065091 - Term: Amylin Receptor Agonists - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action ### Intervention Browse Module - Browse Branches - Abbrev: Hypo - Name: Hypoglycemic Agents - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: PhSol - Name: Pharmaceutical Solutions - Abbrev: Micro - Name: Micronutrients - Abbrev: AnObAg - Name: Anti-Obesity Agents ### Intervention Browse Module - Browse Leaves - ID: M10365 - Name: Insulin - Relevance: HIGH - As Found: Day 1 - ID: M21860 - Name: Pharmaceutical Solutions - Relevance: LOW - As Found: Unknown - ID: M173166 - Name: Insulin, Globin Zinc - Relevance: HIGH - As Found: Day 1 - ID: M250016 - Name: Pramlintide - Relevance: HIGH - As Found: Step 1 - ID: M29802 - Name: Insulin Lispro - Relevance: HIGH - As Found: Diary - ID: M17768 - Name: Zinc - Relevance: LOW - As Found: Unknown - ID: M29005 - Name: Islet Amyloid Polypeptide - Relevance: HIGH - As Found: Step 1 - ID: M10054 - Name: Hypoglycemic Agents - Relevance: LOW - As Found: Unknown - ID: M4379 - Name: Appetite Depressants - Relevance: LOW - As Found: Unknown - ID: M21396 - Name: Anti-Obesity Agents - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000007328 - Term: Insulin - ID: C000557859 - Term: Insulin, Globin Zinc - ID: D000061268 - Term: Insulin Lispro - ID: C000105254 - Term: Pramlintide - ID: D000058228 - Term: Islet Amyloid Polypeptide ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module **Description:** This was a crossover study. #### Event Groups **Group ID:** EG000 **Title:** Placebo & Regular Insulin **Description:** Placebo was similar sterile solution without pramlintide **ID:** EG000 **Other Num Affected:** 9 **Other Num at Risk:** 28 **Serious Number At Risk:** 28 **Title:** Placebo & Regular Insulin **Group ID:** EG001 **Title:** Pramlintide & Regular Insulin **Description:** Pramlintide was administered by sc infusion at a concentration of 1000ug/ml **ID:** EG001 **Other Num Affected:** 22 **Other Num at Risk:** 32 **Serious Number At Risk:** 32 **Title:** Pramlintide & Regular Insulin **Frequency Threshold:** 1 #### Other Events **Term:** Anaemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA v.19.0 **Term:** Vomiting **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA v.19.0 **Term:** Nausea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA v.19.0 **Term:** Cardiovascular disorder **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA v.19.0 **Term:** Vitreous Detachment **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Eye disorders **Source Vocabulary:** MedDRA v.19.0 **Term:** Abdominal discomfort **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA v.19.0 **Term:** Fatigue **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA v.19.0 **Term:** Gastroenteritis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA v.19.0 **Term:** Nasopharyngitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA v.19.0 **Term:** Urinary tract infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA v.19.0 **Term:** Contusion **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA v.19.0 **Term:** Dehydration **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA v.19.0 **Term:** Hypoglycaemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA v.19.0 **Term:** Pain in extremity **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA v.19.0 **Term:** Tremor **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA v.19.0 **Term:** Headache **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA v.19.0 **Term:** Anxiety **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA v.19.0 **Term:** Irritability **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA v.19.0 **Term:** Sinus congestion **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA v.19.0 **Term:** Ecchymosis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA v.19.0 **Term:** Hyperhidrosis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA v.19.0 **Term:** Photosensitivity reaction **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA v.19.0 **Term:** Pruritus **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA v.19.0 **Term:** Pruritus allergic **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA v.19.0 **Term:** Scab **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA v.19.0 **Term:** Phlebitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA v.19.0 **Time Frame:** Over two 24-hour treatment periods with a 2-week washout period between periods. ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 16 **Group ID:** BG001 **Value:** 16 **Group ID:** BG002 **Value:** 32 **Units:** Participants ### Group **ID:** BG000 **Title:** Pramlintide First, Then Placebo **Description:** (Treatment Sequence A) - Safety Analysis Set ### Group **ID:** BG001 **Title:** Placebo First, Then Pramlintide **Description:** (Treatment Sequence B) - Safety Analysis Set ### Group **ID:** BG002 **Title:** Total **Description:** Total of all reporting groups ### Measure #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** <=18 years #### Measurement **Group ID:** BG000 **Value:** 14 #### Measurement **Group ID:** BG001 **Value:** 16 #### Measurement **Group ID:** BG002 **Value:** 30 **Category Title:** Between 18 and 65 years #### Measurement **Group ID:** BG000 **Value:** 2 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 2 **Category Title:** >=65 years #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 16 **Group ID:** BG001 **Value:** 16 **Group ID:** BG002 **Value:** 32 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Spread:** 14.83 **Value:** 45.1 #### Measurement **Group ID:** BG001 **Spread:** 12.68 **Value:** 38.9 #### Measurement **Group ID:** BG002 **Spread:** 13.92 **Value:** 42.0 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 16 **Group ID:** BG001 **Value:** 16 **Group ID:** BG002 **Value:** 32 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 13 #### Measurement **Group ID:** BG001 **Value:** 12 #### Measurement **Group ID:** BG002 **Value:** 25 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 3 #### Measurement **Group ID:** BG001 **Value:** 4 #### Measurement **Group ID:** BG002 **Value:** 7 **Category Title:** Male #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 16 **Group ID:** BG001 **Value:** 16 **Group ID:** BG002 **Value:** 32 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 2 #### Measurement **Group ID:** BG002 **Value:** 2 **Category Title:** Hispanic or Latino #### Measurement **Group ID:** BG000 **Value:** 16 #### Measurement **Group ID:** BG001 **Value:** 14 #### Measurement **Group ID:** BG002 **Value:** 30 **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 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 16 **Group ID:** BG001 **Value:** 16 **Group ID:** BG002 **Value:** 32 **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:** 1 #### Measurement **Group ID:** BG002 **Value:** 1 **Category Title:** Asian #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** Native Hawaiian or Other Pacific Islander #### Measurement **Group ID:** BG000 **Value:** 1 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 1 **Category Title:** Black or African American #### Measurement **Group ID:** BG000 **Value:** 15 #### Measurement **Group ID:** BG001 **Value:** 15 #### Measurement **Group ID:** BG002 **Value:** 30 **Category Title:** White #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** More than one race #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** Unknown or Not Reported #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 16 **Group ID:** BG001 **Value:** 16 **Group ID:** BG002 **Value:** 32 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Spread:** 9.012 **Value:** 72.03 #### Measurement **Group ID:** BG001 **Spread:** 8.859 **Value:** 68.73 #### Measurement **Group ID:** BG002 **Spread:** 8.949 **Value:** 70.38 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 16 **Group ID:** BG001 **Value:** 16 **Group ID:** BG002 **Value:** 32 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Spread:** 6.966 **Value:** 168.41 #### Measurement **Group ID:** BG001 **Spread:** 7.684 **Value:** 167.31 #### Measurement **Group ID:** BG002 **Spread:** 7.236 **Value:** 167.86 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 16 **Group ID:** BG001 **Value:** 16 **Group ID:** BG002 **Value:** 32 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Spread:** 2.806 **Value:** 25.38 #### Measurement **Group ID:** BG001 **Spread:** 2.341 **Value:** 24.52 #### Measurement **Group ID:** BG002 **Spread:** 2.579 **Value:** 24.95 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 16 **Group ID:** BG001 **Value:** 16 **Group ID:** BG002 **Value:** 32 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Spread:** 13.177 **Value:** 27.81 #### Measurement **Group ID:** BG001 **Spread:** 10.866 **Value:** 21.94 #### Measurement **Group ID:** BG002 **Spread:** 12.249 **Value:** 24.88 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 16 **Group ID:** BG001 **Value:** 16 **Group ID:** BG002 **Value:** 32 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 10 #### Measurement **Group ID:** BG001 **Value:** 11 #### Measurement **Group ID:** BG002 **Value:** 21 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 16 **Group ID:** BG001 **Value:** 16 **Group ID:** BG002 **Value:** 32 **Class Title:** CSII #### Measurement **Group ID:** BG000 **Value:** 4 #### Measurement **Group ID:** BG001 **Value:** 5 #### Measurement **Group ID:** BG002 **Value:** 9 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 16 **Group ID:** BG001 **Value:** 16 **Group ID:** BG002 **Value:** 32 **Class Title:** MDI #### Measurement **Group ID:** BG000 **Value:** 2 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 2 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 16 **Group ID:** BG001 **Value:** 16 **Group ID:** BG002 **Value:** 32 **Class Title:** Both ### Measure #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 16 **Group ID:** BG001 **Value:** 16 **Group ID:** BG002 **Value:** 32 **Class Title:** <30 mL/min #### Measurement **Group ID:** BG000 **Value:** 2 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 2 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 16 **Group ID:** BG001 **Value:** 16 **Group ID:** BG002 **Value:** 32 **Class Title:** ≥30 to <60 mL/min #### Measurement **Group ID:** BG000 **Value:** 8 #### Measurement **Group ID:** BG001 **Value:** 8 #### Measurement **Group ID:** BG002 **Value:** 16 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 16 **Group ID:** BG001 **Value:** 16 **Group ID:** BG002 **Value:** 32 **Class Title:** ≥60 to <90 mL/min #### Measurement **Group ID:** BG000 **Value:** 6 #### Measurement **Group ID:** BG001 **Value:** 8 #### Measurement **Group ID:** BG002 **Value:** 14 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 16 **Group ID:** BG001 **Value:** 16 **Group ID:** BG002 **Value:** 32 **Class Title:** ≥90 mL/min ### Measure #### Measurement **Group ID:** BG000 **Spread:** 2.767 **Value:** 8.57 #### Measurement **Group ID:** BG001 **Spread:** 3.149 **Value:** 8.15 #### Measurement **Group ID:** BG002 **Spread:** 2.928 **Value:** 8.35 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 15 **Group ID:** BG001 **Value:** 16 **Group ID:** BG002 **Value:** 31 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Spread:** 0.356 **Value:** 7.84 #### Measurement **Group ID:** BG001 **Spread:** 0.574 **Value:** 8.21 #### Measurement **Group ID:** BG002 **Spread:** 0.506 **Value:** 8.03 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 16 **Group ID:** BG001 **Value:** 16 **Group ID:** BG002 **Value:** 32 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Spread:** 0 **Value:** 0.030 #### Measurement **Group ID:** BG001 **Spread:** 0.0141 **Value:** 0.030 #### Measurement **Group ID:** BG002 **Spread:** 0.0100 **Value:** 0.030 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 1 **Group ID:** BG001 **Value:** 2 **Group ID:** BG002 **Value:** 3 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Spread:** 12.525 **Value:** 38.14 #### Measurement **Group ID:** BG001 **Spread:** 8.920 **Value:** 36.58 #### Measurement **Group ID:** BG002 **Spread:** 10.725 **Value:** 37.36 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 16 **Group ID:** BG001 **Value:** 16 **Group ID:** BG002 **Value:** 32 **Class Title:** **Denomination Units Selected:** ## Results Section - Baseline Characteristics Module ### Measure 1 **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received. **Title:** Age, Categorical **Unit of Measure:** Participants ### Measure 2 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Population Description:** Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received. **Title:** Age, Continuous **Unit of Measure:** Years ### Measure 3 **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received. **Title:** Sex: Female, Male **Unit of Measure:** Participants ### Measure 4 **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received. **Title:** Ethnicity (NIH/OMB) **Unit of Measure:** Participants ### Measure 5 **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received. **Title:** Race (NIH/OMB) **Unit of Measure:** Participants ### Measure 6 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Population Description:** Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received. **Title:** Weight **Unit of Measure:** kg ### Measure 7 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Population Description:** Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received. **Title:** Height **Unit of Measure:** cm ### Measure 8 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Population Description:** Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received. **Title:** Body Mass Index **Unit of Measure:** kg/m^2 ### Measure 9 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Population Description:** Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received. **Title:** Duration of Diabetes **Unit of Measure:** Years ### Measure 10 **Description:** Subject's usual method of insulin administration - either multiple daily injections (MDI) or continuous subcutaneous infusion of insulin (CSII), or both. **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received. **Title:** Current Administration of Insulin **Unit of Measure:** Participants ### Measure 11 **Parameter Type:** COUNT_OF_PARTICIPANTS **Population Description:** Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received. **Title:** Renal Status Category **Unit of Measure:** Participants ### Measure 12 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Population Description:** Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received. **Title:** Baseline Fasting Glucose **Unit of Measure:** mmol/L ### Measure 13 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Population Description:** Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received. **Title:** Baseline A1c **Unit of Measure:** % ### Measure 14 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Population Description:** Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received. **Title:** Baseline C-peptide **Unit of Measure:** nmol/L ### Measure 15 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Population Description:** Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received. **Title:** Baseline Insulin **Unit of Measure:** U/day **Population Description:** Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received. ## Results Section - More Information Module ### Certain Agreement ### Limitations and Caveats **Description:** Due to the unavailability of the pramlintide assay, no data are presented for pramlintide PK parameters, and changes in pramlintide concentration could not be related to changes in insulin, plasma glucose, glucagon, or triglycerides. ### Point of Contact **Email:** [email protected] **Organization:** AstraZeneca **Phone:** +1 (301) 398-0120 **Title:** Dr. Peter Ohman ## Results Section - Outcome Measures Module ### Outcome Measure 1 #### Analysis **CI Lower Limit:** -37.8 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -5.2 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 7.88 **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0118 **P-Value Comment:** **Parameter Type:** Least squares mean difference **Parameter Value:** -21.5 **Statistical Comment:** **Statistical Method:** Linear mixed-effects model **Tested Non-Inferiority:** ### Outcome Measure 2 #### Analysis **CI Lower Limit:** -12.356 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -3.438 **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:** 0.0013 **P-Value Comment:** **Parameter Type:** LS mean difference (pramlintide-placebo) **Parameter Value:** -7.897 **Statistical Comment:** **Statistical Method:** Linear mixed effects model **Tested Non-Inferiority:** ### Outcome Measure 3 #### Analysis **CI Lower Limit:** -9.175 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -1.378 **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:** 0.0091 **P-Value Comment:** **Parameter Type:** LS mean difference (pramlintide-placebo) **Parameter Value:** -5.277 **Statistical Comment:** **Statistical Method:** Linear mixed effects model **Tested Non-Inferiority:** ### Outcome Measure 4 #### Analysis **CI Lower Limit:** -7.445 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -1.424 **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:** 0.0057 **P-Value Comment:** **Parameter Type:** LS mean difference (pramlintide-placebo) **Parameter Value:** -4.435 **Statistical Comment:** **Statistical Method:** Linear mixed effects model **Tested Non-Inferiority:** ### Outcome Measure 5 #### Analysis **CI Lower Limit:** -37326 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -20139 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 4163.6 **Estimate Comment:** **Group Description:** **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** <0.0001 **P-Value Comment:** **Parameter Type:** Least squares mean difference **Parameter Value:** -28733 **Statistical Comment:** **Statistical Method:** Linear mixed-effects model **Tested Non-Inferiority:** ### Outcome Measure 6 #### Analysis **CI Lower Limit:** -53.099 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** -3.737 **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:** 0.0258 **P-Value Comment:** **Parameter Type:** LS mean difference **Parameter Value:** -28.418 **Statistical Comment:** **Statistical Method:** Linear mixed-effects model **Tested Non-Inferiority:** ### Outcome Measure 7 ### Outcome Measure 8 #### Analysis **CI Lower Limit:** 1.01 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 1.70 **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:** 0.0456 **P-Value Comment:** **Parameter Type:** LS Mean Ratio (Pramlintide/Placebo) **Parameter Value:** 1.31 **Statistical Comment:** **Statistical Method:** Linear mixed-effects model **Tested Non-Inferiority:** ### Outcome Measure 9 #### Analysis **CI Lower Limit:** 0.896 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 1.011 **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:** 0.1015 **P-Value Comment:** **Parameter Type:** LS mean ratio (pramlintide/placebo) **Parameter Value:** 0.951 **Statistical Comment:** **Statistical Method:** Linear mixed-effects model **Tested Non-Inferiority:** ### Outcome Measure 10 ### Outcome Measure 11 #### Analysis **CI Lower Limit:** 0.901 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 1.307 **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:** 0.3730 **P-Value Comment:** **Parameter Type:** LS mean ratio (pramlintide/placebo) **Parameter Value:** 1.085 **Statistical Comment:** **Statistical Method:** Linear mixed effects model **Tested Non-Inferiority:** ### Outcome Measure 12 ### Outcome Measure 13 ### Outcome Measure 14 ### Outcome Measure 15 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 8.17 - **Upper Limit:** - **Value:** 173.8 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 8.17 - **Upper Limit:** - **Value:** 152.2 **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 31.427 - **Spread:** - **Upper Limit:** 41.039 - **Value:** 36.233 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 23.487 - **Spread:** - **Upper Limit:** 33.185 - **Value:** 28.336 **Title:** #### Outcome Measure 3 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 20.472 - **Spread:** - **Upper Limit:** 26.021 - **Value:** 23.247 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 15.231 - **Spread:** - **Upper Limit:** 20.709 - **Value:** 17.970 **Title:** #### Outcome Measure 4 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 20.817 - **Spread:** - **Upper Limit:** 26.253 - **Value:** 23.535 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 16.280 - **Spread:** - **Upper Limit:** 21.922 - **Value:** 19.101 **Title:** #### Outcome Measure 5 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 3379.8 - **Upper Limit:** - **Value:** 26243 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 3379.8 - **Upper Limit:** - **Value:** -2489 **Title:** #### Outcome Measure 6 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 220.032 - **Spread:** - **Upper Limit:** 267.638 - **Value:** 243.835 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 191.614 - **Spread:** - **Upper Limit:** 239.220 - **Value:** 215.417 **Title:** #### Outcome Measure 7 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 67.6648 - **Upper Limit:** - **Value:** 11.181 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 70.0174 - **Upper Limit:** - **Value:** -12.753 **Title:** #### Outcome Measure 8 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 33.6 - **Spread:** - **Upper Limit:** 56.9 - **Value:** 43.8 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 44.0 - **Spread:** - **Upper Limit:** 74.4 - **Value:** 57.2 **Title:** #### Outcome Measure 9 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 459.096 - **Spread:** - **Upper Limit:** 558.280 - **Value:** 506.265 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 436.759 - **Spread:** - **Upper Limit:** 531.118 - **Value:** 481.633 **Title:** #### Outcome Measure 10 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 58.9024 - **Upper Limit:** - **Value:** -14.954 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 69.2684 - **Upper Limit:** - **Value:** -16.055 **Title:** #### Outcome Measure 11 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 6.631 - **Spread:** - **Upper Limit:** 9.162 - **Value:** 7.794 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 7.196 - **Spread:** - **Upper Limit:** 9.943 - **Value:** 8.459 **Title:** #### Outcome Measure 12 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 178.2360 - **Upper Limit:** - **Value:** 380.525 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 176.7569 - **Upper Limit:** - **Value:** 377.324 **Title:** #### Outcome Measure 13 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 7.4265 - **Upper Limit:** - **Value:** 15.855 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 7.3649 - **Upper Limit:** - **Value:** 15.722 **Title:** #### Outcome Measure 14 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 17.0950 - **Upper Limit:** - **Value:** 33.144 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 16.2315 - **Upper Limit:** - **Value:** 32.838 **Title:** #### Outcome Measure 15 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 7.3466 - **Upper Limit:** - **Value:** 10.556 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 7.6175 - **Upper Limit:** - **Value:** 11.653 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** 24-hour MWG mg/dL, defined as total area under the 24-hour tissue glucose curve obtained with CGM, divided by actual time span in the 24-hour period. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** Full Analysis Set: Of the 33 correctly randomized subjects, 26 (76.5%) had at least 1 efficacy assessment available from each of the 2 crossover periods and were included in the Full Analysis Set. **Reporting Status:** POSTED **Time Frame:** 24 h **Title:** Efficacy of Pramlintide by Measurement of 24-hour Tissue Mean Weighted Glucose (MWG) Obtained With Continuous Glucose Monitoring (CGM) **Type:** PRIMARY **Unit of Measure:** mg/dL ##### Group **Description:** Placebo was similar sterile solution without pramlintide **ID:** OG000 **Title:** Placebo & Regular Insulin ##### Group **Description:** Pramlintide was administered by sc infusion at a concentration of 1000ug/ml **ID:** OG001 **Title:** Pramlintide & Regular Insulin #### Outcome Measure 2 **Description:** Absolute postprandial plasma glucose AUC was measured for the first 3 hours (AUC0-3h) following lunch based on sample availability. (Sample times: 20 hours \[lunch\], 20 hours 45 min, 21 hours, 23 hours, 24 hours). **Dispersion Type:** 95% Confidence Interval **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** Pharmacokinetic/Pharmacodynamic (PK/PD) Analysis Set: Of the 33 correctly randomized subjects, 26 (76.5%) subjects received at least 1 dose of pramlintide and had evaluable PD data and were, therefore, included in the PK/PD Analysis Set. **Reporting Status:** POSTED **Time Frame:** 3 hours **Title:** Efficacy of Pramlintide by Measurement of Absolute Plasma Glucose Area Under the Plasma Concentration-time Curve (AUC) Following Lunch **Type:** SECONDARY **Unit of Measure:** mmol/L*h ##### Group **Description:** Placebo was similar sterile solution without pramlintide **ID:** OG000 **Title:** Placebo & Regular Insulin ##### Group **Description:** Pramlintide was administered by sc infusion at a concentration of 1000ug/ml **ID:** OG001 **Title:** Pramlintide & Regular Insulin #### Outcome Measure 3 **Description:** Absolute postprandial plasma glucose AUC (AUC0-2h) was measured for the first 2 hours following dinner based on sample availability. (Sample times: 2 hours \[dinner\], 2 hours 45 min, 3 hours, 4 hours). **Dispersion Type:** 95% Confidence Interval **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** Pharmacokinetic/Pharmacodynamic (PK/PD) Analysis Set: Of the 33 correctly randomized subjects, 26 (76.5%) subjects received at least 1 dose of pramlintide and had evaluable PD data and were, therefore, included in the PK/PD Analysis Set. **Reporting Status:** POSTED **Time Frame:** 2 hours **Title:** Efficacy of Pramlintide by Measurement of Absolute Plasma Glucose Area Under the Plasma Concentration-time Curve (AUC) Following Dinner **Type:** SECONDARY **Unit of Measure:** mmol/L*h ##### Group **Description:** Placebo was similar sterile solution without pramlintide **ID:** OG000 **Title:** Placebo & Regular Insulin ##### Group **Description:** Pramlintide was administered by sc infusion at a concentration of 1000ug/ml **ID:** OG001 **Title:** Pramlintide & Regular Insulin #### Outcome Measure 4 **Description:** Absolute postprandial plasma glucose AUC (AUC0-2h) was measured for the first 2 hours following breakfast based on sample availability. (Sample times: 16 hours \[breakfast\], 16 hours 45 min, 17 hours, 18 hours). **Dispersion Type:** 95% Confidence Interval **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** Pharmacokinetic/Pharmacodynamic (PK/PD) Analysis Set: Of the 33 correctly randomized subjects, 26 (76.5%) subjects received at least 1 dose of pramlintide and had evaluable PD data and were, therefore, included in the PK/PD Analysis Set. **Reporting Status:** POSTED **Time Frame:** 2 hours **Title:** Efficacy of Pramlintide by Measurement of Absolute Plasma Glucose Area Under the Plasma Concentration-time Curve (AUC) Following Breakfast **Type:** SECONDARY **Unit of Measure:** mmol/L*h ##### Group **Description:** Placebo was similar sterile solution without pramlintide **ID:** OG000 **Title:** Placebo & Regular Insulin ##### Group **Description:** Pramlintide was administered by sc infusion at a concentration of 1000ug/ml **ID:** OG001 **Title:** Pramlintide & Regular Insulin #### Outcome Measure 5 **Description:** Incremental (i.e., baseline-corrected) area under the 24-hour tissue glucose concentration curve (AUC0-24h) measured by continuous glucose monitoring (CGM) with a pre-test, non-fasting tissue glucose value as baseline. (Sample times: 0, 30 min, 2 hours \[dinner\], 2 hours 45 min, 3 hours, 4 hours, 9 hours, 12 hours, 14 hours, 16 hours \[breakfast\], 16 hours 45 min, 17 hours, 18 hours, 20 hours \[lunch\], 20 hours 45 min, 21 hours, 23 hours, 24 hours). **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** Full Analysis Set: Of the 33 correctly randomized subjects, 26 (76.5%) had at least 1 efficacy assessment available from each of the 2 crossover periods and were included in the Full Analysis Set, **Reporting Status:** POSTED **Time Frame:** 24 h **Title:** Efficacy of Pramlintide by Measurement of Incremental 24-hour Tissue Glucose Area Under the Plasma Concentration-time Curve (AUC) Obtained With Continuous Glucose Monitoring (CGM) **Type:** SECONDARY **Unit of Measure:** mg/dL*min ##### Group **Description:** Placebo was similar sterile solution without pramlintide **ID:** OG000 **Title:** Placebo & Regular Insulin ##### Group **Description:** Pramlintide was administered by sc infusion at a concentration of 1000ug/ml **ID:** OG001 **Title:** Pramlintide & Regular Insulin #### Outcome Measure 6 **Description:** Absolute mean area under the 24-hour plasma glucose concentration curve, measured as total area under the curve (0 to 24 hours). (Sample times: 0, 30 min, 2 hours \[dinner\], 2 hours 45 min, 3 hours, 4 hours, 9 hours, 12 hours, 14 hours, 16 hours \[breakfast\], 16 hours 45 min, 17 hours, 18 hours, 20 hours \[lunch\], 20 hours 45 min, 21 hours, 23 hours, 24 hours). **Dispersion Type:** 95% Confidence Interval **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** Pharmacokinetic/Pharmacodynamic (PK/PD) Analysis Set: Of the 33 correctly randomized subjects, 26 (76.5%) subjects received at least 1 dose of pramlintide and had evaluable PD data and were, therefore, included in the PK/PD Analysis Set. **Reporting Status:** POSTED **Time Frame:** 24 h **Title:** Efficacy of Pramlintide by Measurement of Absolute 24-hour Plasma Glucose Area Under the Plasma Concentration-time Curve (AUC) **Type:** SECONDARY **Unit of Measure:** mmol/L*h ##### Group **Description:** Placebo was similar sterile solution without pramlintide **ID:** OG000 **Title:** Placebo & Regular Insulin ##### Group **Description:** Pramlintide was administered by sc infusion at a concentration of 1000ug/ml **ID:** OG001 **Title:** Pramlintide & Regular Insulin #### Outcome Measure 7 **Description:** Incremental (i.e., baseline-corrected) mean area under the 24-hour plasma glucose concentration curve, measured as total area under the curve (0 to 24 hours). (Sample times: 0, 30 min, 2 hours \[dinner\], 2 hours 45 min, 3 hours, 4 hours, 9 hours, 12 hours, 14 hours, 16 hours \[breakfast\], 16 hours 45 min, 17 hours, 18 hours, 20 hours \[lunch\], 20 hours 45 min, 21 hours, 23 hours, 24 hours). **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Pharmacokinetic/Pharmacodynamic (PK/PD) Analysis Set: Of the 33 correctly randomized subjects, 26 (76.5%) subjects received at least 1 dose of pramlintide and had evaluable PD data and were, therefore, included in the PK/PD Analysis Set. **Reporting Status:** POSTED **Time Frame:** 24 hours **Title:** Efficacy of Pramlintide by Measurement of Incremental 24-hour Plasma Glucose Area Under the Plasma Concentration-time Curve (AUC) **Type:** SECONDARY **Unit of Measure:** mmol/L*h ##### Group **Description:** Placebo was similar sterile solution without pramlintide **ID:** OG000 **Title:** Placebo & Regular Insulin ##### Group **Description:** Pramlintide was administered by sc infusion at a concentration of 1000ug/ml **ID:** OG001 **Title:** Pramlintide & Regular Insulin #### Outcome Measure 8 **Description:** Percent time spent in the normoglycemic range of tissue glucose concentrations between \>70 mg/dL and \<180 mg/dL, measured by CGM. (Sample times: 0, 30 min, 2 hours \[dinner\], 2 hours 45 min, 3 hours, 4 hours, 9 hours, 12 hours, 14 hours, 16 hours \[breakfast\], 16 hours 45 min, 17 hours, 18 hours, 20 hours \[lunch\], 20 hours 45 min, 21 hours, 23 hours, 24 hours). **Dispersion Type:** 95% Confidence Interval **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** Full Analysis Set:Of the 33 correctly randomized subjects, 26 (76.5%) had at least 1 efficacy assessment available from each of the 2 crossover periods and were included in the Full Analysis Set. **Reporting Status:** POSTED **Time Frame:** 24 h **Title:** Efficacy of Pramlintide Measured by Percent Time Spent in the Range of >70 mg/dL to <180 mg/dL Tissue Glucose Obtained With Continuous Glucose Monitoring (CGM) **Type:** SECONDARY **Unit of Measure:** Percentage of time ##### Group **Description:** Placebo was similar sterile solution without pramlintide **ID:** OG000 **Title:** Placebo & Regular Insulin ##### Group **Description:** Pramlintide was administered by sc infusion at a concentration of 1000ug/ml **ID:** OG001 **Title:** Pramlintide & Regular Insulin #### Outcome Measure 9 **Description:** Absolute mean area under the 24-hour plasma glucagon concentration curve, measured as total area under the curve (total AUC0-24). (Sample times: 0, 30 min, 2 hours \[dinner\], 2 hours 45 min, 3 hours, 4 hours, 9 hours, 12 hours, 14 hours, 16 hours \[breakfast\], 16 hours 45 min, 17 hours, 18 hours, 20 hours \[lunch\], 20 hours 45 min, 21 hours, 23 hours, 24 hours). **Dispersion Type:** 95% Confidence Interval **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** Pharmacokinetic/Pharmacodynamic (PK/PD) Analysis Set: Of the 33 correctly randomized subjects, 26 (76.5%) subjects received at least 1 dose of pramlintide and had evaluable PD data and were, therefore, included in the PK/PD Analysis Set. **Reporting Status:** POSTED **Time Frame:** 24 h **Title:** Efficacy of Pramlintide by Measurement of Absolute 24-hour Plasma Glucagon Area Under the Plasma Concentration-time Curve (AUC) **Type:** SECONDARY **Unit of Measure:** h*pmol/L ##### Group **Description:** Placebo was similar sterile solution without pramlintide **ID:** OG000 **Title:** Placebo & Regular Insulin ##### Group **Description:** Pramlintide was administered by sc infusion at a concentration of 1000ug/ml **ID:** OG001 **Title:** Pramlintide & Regular Insulin #### Outcome Measure 10 **Description:** Incremental (i.e., baseline-corrected) mean area under the 24-hour plasma glucagon concentration curve with a pre-test, non-fasting plasma glucagon value as baseline. (Sample times: 0, 30 min, 2 hours \[dinner\], 2 hours 45 min, 3 hours, 4 hours, 9 hours, 12 hours, 14 hours, 16 hours \[breakfast\], 16 hours 45 min, 17 hours, 18 hours, 20 hours \[lunch\], 20 hours 45 min, 21 hours, 23 hours, 24 hours). **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Pharmacokinetic/Pharmacodynamic (PK/PD) Analysis Set: Of the 33 correctly randomized subjects, 26 (76.5%) subjects received at least 1 dose of pramlintide and had evaluable PD data and were, therefore, included in the PK/PD Analysis Set. **Reporting Status:** POSTED **Time Frame:** 24 h **Title:** Efficacy of Pramlintide by Measurement of Incremental 24-hour Plasma Glucagon Area Under the Plasma Concentration-time Curve (AUC) **Type:** SECONDARY **Unit of Measure:** pmol/L*h ##### Group **Description:** Placebo was similar sterile solution without pramlintide **ID:** OG000 **Title:** Placebo & Regular Insulin ##### Group **Description:** Pramlintide was administered by sc infusion at a concentration of 1000ug/ml **ID:** OG001 **Title:** Pramlintide & Regular Insulin #### Outcome Measure 11 **Description:** Fasting plasma glucose concentration at 0600 hours (6:00 AM) **Dispersion Type:** 95% Confidence Interval **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** Pharmacokinetic/Pharmacodynamic (PK/PD) Analysis Set: Of the 33 correctly randomized subjects, 26 (76.5%) subjects received at least 1 dose of pramlintide and had evaluable PD data and were, therefore, included in the PK/PD Analysis Set. **Reporting Status:** POSTED **Time Frame:** 12 hours after dinner meal **Title:** Fasting Plasma Glucose Concentration **Type:** SECONDARY **Unit of Measure:** mmol/L ##### Group **Description:** Placebo was similar sterile solution without pramlintide **ID:** OG000 **Title:** Placebo & Regular Insulin ##### Group **Description:** Pramlintide was administered by sc infusion at a concentration of 1000ug/ml **ID:** OG001 **Title:** Pramlintide & Regular Insulin #### Outcome Measure 12 **Description:** Mean areas under the plasma insulin concentration curves for the 24-hour periods of pramlintide and placebo administration (Sample times: -15 min, 0, 30 min, 1 hour 30 min, 2 hours \[dinner\], 2 hours 15 min, 2 hours 30 min, 2 hours 45 min, 3 hours, 4 hours, 5 hours, 6 hours, 9 hours, 12 hours, 15 hours, 16 hours \[breakfast\], 16 hours 15 min, 16 hours 30 min, 16 hours 45 min, 17 hours, 18 hours, 19 hours, 20 hours \[lunch\], 24 hours). **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Pharmacokinetic/Pharmacodynamic (PK/PD) Analysis Set: Of the 33 correctly randomized subjects, 26 (76.5%) subjects received at least 1 dose of pramlintide and had evaluable PD data and were, therefore, included in the PK/PD Analysis Set. **Reporting Status:** POSTED **Time Frame:** 24 hours **Title:** Pharmacokinetics of Insulin as Demonstrated by 24-hour Plasma Insulin Area Under the Plasma Concentration-time Curve (AUC) **Type:** SECONDARY **Unit of Measure:** mU/L*h ##### Group **Description:** Placebo was similar sterile solution without pramlintide **ID:** OG000 **Title:** Placebo & Regular Insulin ##### Group **Description:** Pramlintide was administered by sc infusion at a concentration of 1000ug/ml **ID:** OG001 **Title:** Pramlintide & Regular Insulin #### Outcome Measure 13 **Description:** Mean values of the average plasma insulin concentrations over the 24-hour periods of pramlintide and placebo administration. (Sample times: -15 min, 0, 30 min, 1 hour 30 min, 2 hours \[dinner\], 2 hours 15 min, 2 hours 30 min, 2 hours 45 min, 3 hours, 4 hours, 5 hours, 6 hours, 9 hours, 12 hours, 15 hours, 16 hours \[breakfast\], 16 hours 15 min, 16 hours 30 min, 16 hours 45 min, 17 hours, 18 hours, 19 hours, 20 hours \[lunch\], 24 hours). **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Pharmacokinetic/Pharmacodynamic (PK/PD) Analysis Set: Of the 33 correctly randomized subjects, 26 (76.5%) subjects received at least 1 dose of pramlintide and had evaluable PD data and were, therefore, included in the PK/PD Analysis Set. **Reporting Status:** POSTED **Time Frame:** 24 hours **Title:** Pharmacokinetics of Insulin as Demonstrated by 24-hour Average Plasma Insulin Concentration. **Type:** SECONDARY **Unit of Measure:** mIU/L ##### Group **Description:** Placebo was similar sterile solution without pramlintide **ID:** OG000 **Title:** Placebo & Regular Insulin ##### Group **Description:** Pramlintide was administered by sc infusion at a concentration of 1000ug/ml **ID:** OG001 **Title:** Pramlintide & Regular Insulin #### Outcome Measure 14 **Description:** Mean maximum plasma insulin concentrations over the 24-hour periods of pramlintide and placebo administration. (Sample times: -15 min, 0, 30 min, 1 hour 30 min, 2 hours \[dinner\], 2 hours 15 min, 2 hours 30 min, 2 hours 45 min, 3 hours, 4 hours, 5 hours, 6 hours, 9 hours, 12 hours, 15 hours, 16 hours \[breakfast\], 16 hours 15 min, 16 hours 30 min, 16 hours 45 min, 17 hours, 18 hours, 19 hours, 20 hours \[lunch\], 24 hours). **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Pharmacokinetic/Pharmacodynamic (PK/PD) Analysis Set: Of the 33 correctly randomized subjects, 26 (76.5%) subjects received at least 1 dose of pramlintide and had evaluable PD data and were, therefore, included in the PK/PD Analysis Set. **Reporting Status:** POSTED **Time Frame:** 24 hours **Title:** Pharmacokinetics of Insulin as Demonstrated by Maximum Plasma Insulin Concentration **Type:** SECONDARY **Unit of Measure:** mIU/L ##### Group **Description:** Placebo was similar sterile solution without pramlintide **ID:** OG000 **Title:** Placebo & Regular Insulin ##### Group **Description:** Pramlintide was administered by sc infusion at a concentration of 1000ug/ml **ID:** OG001 **Title:** Pramlintide & Regular Insulin #### Outcome Measure 15 **Description:** Mean time to maximum plasma insulin concentrations over the 24-hour periods of pramlintide and placebo administration. (Sample times: -15 min, 0, 30 min, 1 hour 30 min, 2 hours \[dinner\], 2 hours 15 min, 2 hours 30 min, 2 hours 45 min, 3 hours, 4 hours, 5 hours, 6 hours, 9 hours, 12 hours, 15 hours, 16 hours \[breakfast\], 16 hours 15 min, 16 hours 30 min, 16 hours 45 min, 17 hours, 18 hours, 19 hours, 20 hours \[lunch\], 24 hours). **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** Pharmacokinetic/Pharmacodynamic (PK/PD) Analysis Set: Of the 33 correctly randomized subjects, 26 (76.5%) subjects received at least 1 dose of pramlintide and had evaluable PD data and were, therefore, included in the PK/PD Analysis Set. **Reporting Status:** POSTED **Time Frame:** 24 hours **Title:** Pharmacokinetics of Insulin as Demonstrated by the Time to the Maximum Plasma Insulin Concentration **Type:** SECONDARY **Unit of Measure:** h ##### Group **Description:** Placebo was similar sterile solution without pramlintide **ID:** OG000 **Title:** Placebo & Regular Insulin ##### Group **Description:** Pramlintide was administered by sc infusion at a concentration of 1000ug/ml **ID:** OG001 **Title:** Pramlintide & Regular Insulin ### Participant Flow Module #### Group **Description:** (Treatment Sequence A) **ID:** FG000 **Title:** Pramlintide First, Then Placebo #### Group **Description:** (Treatment Sequence B) **ID:** FG001 **Title:** Placebo First, Then Pramlintide #### Period **Title:** Period 1 ##### Withdraw **Type:** Hyperglycemia ###### Reason **Group ID:** FG000 **Number of Subjects:** 1 ###### Reason **Group ID:** FG001 **Number of Subjects:** 0 ##### Withdraw **Type:** Severe non-compliance to protocol ###### Reason **Group ID:** FG000 **Number of Subjects:** 0 ###### Reason **Group ID:** FG001 **Number of Subjects:** 1 ##### Withdraw **Type:** Adverse Event ###### Reason **Group ID:** FG000 **Number of Subjects:** 1 ###### Reason **Group ID:** FG001 **Number of Subjects:** 0 ##### Withdraw **Type:** Subject decision ###### Reason **Group ID:** FG000 **Number of Subjects:** 2 ###### Reason **Group ID:** FG001 **Number of Subjects:** 0 ##### Milestone **Type:** STARTED **Comment:** (Randomized Analysis Set) ###### Achievement **Group ID:** FG000 **Number of Subjects:** 16 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 17 ##### Milestone **Type:** COMPLETED **Comment:** Number of subjects that entered Period 2 ###### Achievement **Group ID:** FG000 **Number of Subjects:** 12 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 16 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 4 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 1 #### Period **Title:** Period 2 ##### Withdraw **Type:** Change in risk ###### Reason **Group ID:** FG000 **Number of Subjects:** 1 ###### Reason **Group ID:** FG001 **Number of Subjects:** 0 ##### Milestone **Type:** STARTED **Comment:** (Randomized Analysis Set) ###### Achievement **Group ID:** FG000 **Number of Subjects:** 12 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 16 ##### Milestone **Type:** COMPLETED **Comment:** Completed Period 2 ###### Achievement **Group ID:** FG000 **Number of Subjects:** 11 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 16 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 1 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 0 **Pre-Assignment Details:** Eligible study subjects were males and females, aged ≥18 years and ≤70 years at the time of screening with a prior diagnosis of type 1 diabetes mellitus (T1DM) and an HbA1c value of ≥7.2% and ≤9.0% at screening. **Recruitment Details:** The first subject was enrolled in the study (at Visit 2) on 27 August 2015. A total of 79 subjects were screened and 34 subjects were randomized at 3 sites in the United States. One additional subject was randomized in error and was discontinued prior to receiving any study medication. The last subject completed the study on 05 August 2016. **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT03449979 **Acronym:** SSDE **Brief Title:** Single Session of tACS in a Depressive Episode **Official Title:** Rational Optimization of tACS for Targeting Thalamo-Cortical Oscillations (Experiment 3) #### Organization Study ID Info **ID:** 16-1911b #### Organization **Class:** OTHER **Full Name:** University of North Carolina, Chapel Hill #### Secondary ID Infos **ID:** R01MH101547 **Link:** https://reporter.nih.gov/quickSearch/R01MH101547 **Type:** NIH ### Status Module #### Completion Date **Date:** 2019-08-16 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2020-06-04 **Type:** ACTUAL **Last Update Submit Date:** 2020-05-18 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2019-08-16 **Type:** ACTUAL #### Results First Post Date **Date:** 2020-06-04 **Type:** ACTUAL **Results First Submit Date:** 2020-05-18 **Results First Submit QC Date:** 2020-05-18 #### Start Date **Date:** 2018-09-19 **Type:** ACTUAL **Status Verified Date:** 2019-09 #### Study First Post Date **Date:** 2018-02-28 **Type:** ACTUAL **Study First Submit Date:** 2018-02-15 **Study First Submit QC Date:** 2018-02-22 ### Sponsor Collaborators Module #### Collaborators **Class:** NIH **Name:** National Institute of Mental Health (NIMH) #### Lead Sponsor **Class:** OTHER **Name:** University of North Carolina, Chapel Hill #### 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:** Purpose: Investigating the effects of non-invasive transcranial alternating current stimulation (tACS) on healthy participants and participants with mood disorders. Participants: 40 males and females, ages 18-65, with depressed mood; 40 healthy males and females, ages 18-65, free of neurological or psychiatric conditions. Procedures: This is a single visit study with two stimulation conditions (tACS and sham tACS). The session will begin with clinical assessments (including confirmation of diagnosis), followed by an interactive EEG task, then a 7 minute resting state EEG (2 minutes eyes closed, 5 minutes eyes open), followed by the stimulation session (40 minutes of tACS or sham tACS), followed by an additional 5 minute resting state EEG. The stimulation will involved 40 minutes of transcranial alternating current stimulation, 2 mA in amplitude and at individualized alpha frequency (determined by the 2 minutes eyes closed EEG recording; between 8 and 12Hz). **Detailed Description:** Participants will report for a study visit and will review and sign a consent form. Participants will complete several clinical assessments and also take a urine drug test and urine pregnancy test (if applicable). Eligibility will be re-assessed by the investigators before the participant moves on to the next phase. If the participant still qualifies, the participant will first be fitted with two 5x5cm electrodes placed over F3/F4 (10-20 measurement system) and one 5x7cm electrode placed over Cz. In addition, the participant will have a 128-channel EEG net placed on their head. Participants will provide a saliva sample to assess for brain-derived neurotrophic factor (BDNF), which may affect how the participant's brain responds to stimulation. Once the participant is fitted with this equipment, the participant will complete two interactive EEG tasks, then 2-minute resting state EEG with the participant's eyes closed, then a 5-minute resting state EEG with the participant's eyes open. Following these recordings, participants will respond to additional questionnaires. Immediately following this, the participant will receive 40 minutes of stimulation (tACS or sham tACS). During this stimulation, participants will sit comfortably upright and awake. After stimulation has completed, participants will respond to additional questionnaires. Once completed, participants will then complete an additional 5-minute resting state EEG with the participant's eyes open, as well as complete one of the additional interactive EEG tasks. Finally, participants will respond to a blinding questionnaire to assess if the participant thought that the participant received stimulation. Once complete, the participant will leave. This session is estimated to last about 4 hours. ### Conditions Module **Conditions:** - Depression - Major Depressive Disorder - Premenstrual Dysphoric Disorder - Depressive Episode **Keywords:** - tACS - transcranial alternating current stimulation - stimulation - heart rate variability - electroencephalogram - EEG ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** This study recruits both participants currently experiencing a depressive episode (regardless of diagnosis) and those with no history of neurological or psychiatric illness. Randomization will occur in a 1:1 ratio for both of these groups, with half of each group receiving transcranial alternating current stimulation (tACS) at 10 Hz and the other half receiving placebo (or sham) stimulation. ##### Masking Info **Masking:** DOUBLE **Masking Description:** This is a double-blind study, meaning that neither the participant nor the experimenter knows what kind of stimulation the participant is receiving. An unblinded monitor (separate from the staff that interacts with the participant) is responsible for creating the stimulation codes that run each session and for ensuring that these codes worked correctly. **Who Masked:** - PARTICIPANT - INVESTIGATOR **Primary Purpose:** BASIC_SCIENCE #### Enrollment Info **Count:** 84 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Participants in a depressive episode will receive 2 mA of alternating current stimulation at individualized alpha stimulation (between 8 and 12Hz; determined by an EEG recording prior to stimulation) for 40 minutes. tACS stimulation is delivered using the XCSITE100 Stimulator tACS. **Intervention Names:** - Device: XCSITE100 Stimulator tACS **Label:** alpha stimulation in participants in a depressive episode **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Sham Stimulation mimics the physical effects of stimulation, with up to one minute of stimulation during the session. Sham stimulation to participants in a depressive episode is delivered using the XCSITE100 Stimulator Sham. **Intervention Names:** - Device: XCSITE100 Stimulator Sham **Label:** sham stimulation in participants in a depressive episode **Type:** PLACEBO_COMPARATOR #### Arm Group 3 **Description:** Healthy participants will receive 2 mA of alternating current stimulation at individualized alpha stimulation (between 8 and 12Hz; determined by an EEG recording prior to stimulation) for 40 minutes. tACS stimulation is delivered using the XCSITE100 Stimulator tACS. **Intervention Names:** - Device: XCSITE100 Stimulator tACS **Label:** alpha stimulation in healthy participants **Type:** EXPERIMENTAL #### Arm Group 4 **Description:** Sham Stimulation mimics the physical effects of stimulation, with up to one minute of stimulation during the session. Sham stimulation to healthy participants is delivered using the XCSITE100 Stimulator Sham. **Intervention Names:** - Device: XCSITE100 Stimulator Sham **Label:** sham stimulation in healthy participants **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - sham stimulation in healthy participants - sham stimulation in participants in a depressive episode **Description:** The participant will receive up to one minute of tACS stimulation until the stimulation fades. Sham stimulation mimics the skin sensations a participant would experience during a tACS session. **Name:** XCSITE100 Stimulator Sham **Other Names:** - Sham tACS **Type:** DEVICE #### Intervention 2 **Arm Group Labels:** - alpha stimulation in healthy participants - alpha stimulation in participants in a depressive episode **Description:** Transcranial alternating current stimulation (tACS) is a method of noninvasive brain stimulation in which weak electrical current are applied to the scalp in a sine wave pattern to induce cortical oscillations at the frequency at which they are applied. **Name:** XCSITE100 Stimulator tACS **Other Names:** - tACS **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Description:** Fast Fourier transform is applied to 5 minutes of EEG data before and after intervention. Primary outcome is the difference in alpha frequency amplitude (8-12 Hz) in the left frontal cortex from baseline as a result of intervention. **Measure:** Change in Alpha Frequency Electrical Activity in Left Frontal Cortex From Stimulation **Time Frame:** 5 minute recording before and after intervention ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria for individuals with depressed mood: * Ages 18-65 years * Hamilton Depression Rating Scale score \>8 * Capacity to understand all relevant risks and potential benefits of the study (informed consent) * Low suicide risk which will be determined through the use of both the Structured Clinical Interview for the DSM-5 and by scoring less than 3 (0,1, or 2) in the Hamilton rating depression scale. * Negative pregnancy test for female participants Exclusion Criteria for individuals with depressed mood: * DSM-5 diagnosis of alcohol of substance abuse (other than nicotine) within the 12 months * DSM-5 diagnosis of alcohol or substance dependence (other than nicotine) within the last 12 months * DSM-5 diagnosis of personality disorder * Eating disorder (current or within the past 3 months) * Anything that, in the opinion of the investigator, would place the participant at increased risk or preclude the participant's full compliance with or completion of the study * Neurological disorders, including but not limited to history of seizures (except childhood febrile seizures and electro-convulsive therapy (ECT) induced seizures), dementia, history of stroke, Parkinson's disease, multiple sclerosis, cerebral aneurysm. * Medical or neurological illness (unstable cardiac disease, AIDS, malignancy, liver or renal impairment) or treatment for a medical disorder that could interfere with study participation * History of traumatic brain injury, reoccurring seizures or later cognitive rehabilitation or causing cognitive sequelae * History of childhood trauma (determined by the Childhood Trauma Questionnaire) * Prior brain surgery * Any brain devices/implants, including cochlear implants and aneurysm clips * Co-morbid neurological condition (i.e. seizure disorder, brain tumor) * Use of illicit drugs, confirmed by a drug test * Non English speakers * Pregnant or nursing females * Current use of benzodiazepines or anti-epileptic drugs Inclusion Criteria for healthy controls: * Ages 18-65 years * Hamilton Depression Rating Scale score ≤8 * Capacity to understand all relevant risks and potential benefits of the study (informed consent) * Negative pregnancy test for female participants Exclusion Criteria for healthy controls: * History of major neurological or psychiatric illness, including epilepsy * Medication use associated with neurological or psychiatric illnesses * Currently undergoing counseling or psychotherapy treatment for depression, anxiety, eating disorders, PTSD or other behavioral conditions * DSM-5 diagnosis of personality disorder * First degree relative (parent, sibling, child) with major neurological or psychiatric illness * Prior brain surgery * Major head injury * Any brain devices/implants (including cochlear implants and aneurysm clips) * History of childhood trauma (determined by the Childhood Trauma Questionnaire) * Use of illicit drugs, confirmed by a drug test * Braids or other hair styling that prevents direct access to the scalp (if removal not possible) * Skin allergies or very sensitive skin * Non English speakers * Pregnant or nursing females **Healthy Volunteers:** True **Maximum Age:** 65 Years **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 Chapel Hill **State:** North Carolina **Zip:** 27599 #### Overall Officials **Official 1:** **Affiliation:** UNC Chapel Hill **Name:** Flavio Frohlich, PhD **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Document Section ### Large Document Module #### Large Docs - Date: 2019-04-29 - Filename: Prot_SAP_000.pdf - Has ICF: False - Has Protocol: True - Has SAP: True - Label: Study Protocol and Statistical Analysis Plan - Size: 856965 - Type Abbrev: Prot_SAP - Upload Date: 2020-01-14T13:30 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000001526 - Term: Behavioral Symptoms - ID: D000019964 - Term: Mood Disorders - ID: D000001523 - Term: Mental Disorders - ID: D000011293 - Term: Premenstrual Syndrome - ID: D000008599 - Term: Menstruation Disturbances - ID: D000010335 - Term: Pathologic Processes ### 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: M7058 - Name: Depression - Relevance: HIGH - As Found: Depressive Episode - ID: M7061 - Name: Depressive Disorder - Relevance: HIGH - As Found: Depressive Disorder - ID: M7060 - Name: Depressive Disorder, Major - Relevance: HIGH - As Found: Major Depressive Disorder - ID: M30514 - Name: Premenstrual Dysphoric Disorder - Relevance: HIGH - As Found: Premenstrual Dysphoric Disorder - ID: M4818 - Name: Behavioral Symptoms - Relevance: LOW - As Found: Unknown - ID: M21835 - Name: Mood Disorders - Relevance: LOW - As Found: Unknown - ID: M4815 - Name: Mental Disorders - Relevance: LOW - As Found: Unknown - ID: M14473 - Name: Psychotic Disorders - Relevance: LOW - As Found: Unknown - ID: M16355 - Name: Syndrome - Relevance: LOW - As Found: Unknown - ID: M14167 - Name: Premenstrual Syndrome - Relevance: LOW - As Found: Unknown - ID: M11582 - Name: Menstruation Disturbances - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000065446 - Term: Premenstrual Dysphoric Disorder - ID: D000003863 - Term: Depression - ID: D000003866 - Term: Depressive Disorder - ID: D000003865 - Term: Depressive Disorder, Major ### Intervention Browse Module - Browse Branches - Abbrev: Infl - Name: Anti-Inflammatory Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M16975 - Name: Triamcinolone Acetonide - Relevance: LOW - As Found: Unknown - ID: M16974 - Name: Triamcinolone - Relevance: LOW - As Found: Unknown - ID: M237966 - Name: Triamcinolone hexacetonide - Relevance: LOW - As Found: Unknown - ID: M209573 - Name: Triamcinolone diacetate - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module #### Event Groups **Group ID:** EG000 **Title:** Alpha Stimulation in Patients in a Depressive Episode **Deaths Num At Risk:** 21 **Description:** Participants in a depressive episode will receive 2 mA of alternating current stimulation at individualized alpha stimulation (between 8 and 12 Hz; determined by an EEG recording prior to stimulation) for 40 minutes. tACS stimulation is delivered using the XCSITE100 Stimulator tACS. XCSITE100 Stimulator tACS: Transcranial alternating current stimulation (tACS) is a method of noninvasive brain stimulation in which weak electrical current are applied to the scalp in a sine wave pattern to induce cortical oscillations at the frequency at which they are applied. **ID:** EG000 **Other Num Affected:** 12 **Other Num at Risk:** 21 **Serious Number At Risk:** 21 **Title:** Alpha Stimulation in Patients in a Depressive Episode **Group ID:** EG001 **Title:** Sham Stimulation in Patients in a Depressive Episode **Deaths Num At Risk:** 20 **Description:** Sham Stimulation mimics the physical effects of stimulation, with up to one minute of stimulation during the session. Sham stimulation to participants in a depressive episode is delivered using the XCSITE100 Stimulator Sham. XCSITE100 Stimulator Sham: The participant will receive up to one minute of tACS stimulation until the stimulation fades. Sham stimulation mimics the skin sensations a participant would experience during a tACS session. **ID:** EG001 **Other Num Affected:** 7 **Other Num at Risk:** 20 **Serious Number At Risk:** 20 **Title:** Sham Stimulation in Patients in a Depressive Episode **Group ID:** EG002 **Title:** Alpha Stimulation in Healthy Participants **Deaths Num At Risk:** 21 **Description:** Healthy participants will receive 2 mA of alternating current stimulation at individualized alpha stimulation (between 8 and 12 Hz; determined by an EEG recording prior to stimulation) for 40 minutes. tACS stimulation is delivered using the XCSITE100 Stimulator tACS. XCSITE100 Stimulator tACS: Transcranial alternating current stimulation (tACS) is a method of noninvasive brain stimulation in which weak electrical current are applied to the scalp in a sine wave pattern to induce cortical oscillations at the frequency at which they are applied. **ID:** EG002 **Other Num Affected:** 9 **Other Num at Risk:** 21 **Serious Number At Risk:** 21 **Title:** Alpha Stimulation in Healthy Participants **Group ID:** EG003 **Title:** Sham Stimulation in Healthy Participants **Deaths Num At Risk:** 22 **Description:** Sham Stimulation mimics the physical effects of stimulation, with up to one minute of stimulation during the session. Sham stimulation to healthy participants is delivered using the XCSITE100 Stimulator Sham. XCSITE100 Stimulator Sham: The participant will receive up to one minute of tACS stimulation until the stimulation fades. Sham stimulation mimics the skin sensations a participant would experience during a tACS session. **ID:** EG003 **Other Num Affected:** 5 **Other Num at Risk:** 22 **Serious Number At Risk:** 22 **Title:** Sham Stimulation in Healthy Participants **Frequency Threshold:** 0 #### Other Events **Term:** Tingling **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** **Term:** Flickering Lights **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** **Term:** Itching **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** **Term:** Burning sensation **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** **Term:** Scalp pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** **Term:** Neck pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** **Term:** Headache **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** **Time Frame:** Adverse events were collected over the 5 hours of the single session experiment ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 21 **Group ID:** BG001 **Value:** 20 **Group ID:** BG002 **Value:** 21 **Group ID:** BG003 **Value:** 22 **Group ID:** BG004 **Value:** 84 **Units:** Participants ### Group **ID:** BG000 **Title:** Alpha Stimulation in Participants in a Depressive Episode **Description:** Participants in a depressive episode will receive 2 mA of alternating current stimulation at individualized alpha stimulation (between 8 and 12 Hz; determined by an EEG recording prior to stimulation) for 40 minutes. tACS stimulation is delivered using the XCSITE100 Stimulator tACS. XCSITE100 Stimulator tACS: Transcranial alternating current stimulation (tACS) is a method of noninvasive brain stimulation in which weak electrical current are applied to the scalp in a sine wave pattern to induce cortical oscillations at the frequency at which they are applied. ### Group **ID:** BG001 **Title:** Sham Stimulation in Participants in a Depressive Episode **Description:** Sham Stimulation mimics the physical effects of stimulation, with up to one minute of stimulation during the session. Sham stimulation to participants in a depressive episode is delivered using the XCSITE100 Stimulator Sham. XCSITE100 Stimulator Sham: The participant will receive up to one minute of tACS stimulation until the stimulation fades. Sham stimulation mimics the skin sensations a participant would experience during a tACS session. ### Group **ID:** BG002 **Title:** Alpha Stimulation in Healthy Participants **Description:** Healthy participants will receive 2 mA of alternating current stimulation at individualized alpha stimulation (between 8 and 12 Hz; determined by an EEG recording prior to stimulation) for 40 minutes. tACS stimulation is delivered using the XCSITE100 Stimulator tACS. XCSITE100 Stimulator tACS: Transcranial alternating current stimulation (tACS) is a method of noninvasive brain stimulation in which weak electrical current are applied to the scalp in a sine wave pattern to induce cortical oscillations at the frequency at which they are applied. ### Group **ID:** BG003 **Title:** Sham Stimulation in Healthy Participants **Description:** Sham Stimulation mimics the physical effects of stimulation, with up to one minute of stimulation during the session. Sham stimulation to healthy participants is delivered using the XCSITE100 Stimulator Sham. XCSITE100 Stimulator Sham: The participant will receive up to one minute of tACS stimulation until the stimulation fades. Sham stimulation mimics the skin sensations a participant would experience during a tACS session. ### Group **ID:** BG004 **Title:** Total **Description:** Total of all reporting groups ### Measure #### Measurement **Group ID:** BG000 **Spread:** 11.902 **Value:** 28.429 #### Measurement **Group ID:** BG001 **Spread:** 12.227 **Value:** 27.65 #### Measurement **Group ID:** BG002 **Spread:** 11.432 **Value:** 28.095 #### Measurement **Group ID:** BG003 **Spread:** 12.133 **Value:** 27.182 #### Measurement **Group ID:** BG004 **Spread:** 11.831 **Value:** 27.796 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 21 **Group ID:** BG001 **Value:** 20 **Group ID:** BG002 **Value:** 21 **Group ID:** BG003 **Value:** 22 **Group ID:** BG004 **Value:** 84 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 17 #### Measurement **Group ID:** BG001 **Value:** 16 #### Measurement **Group ID:** BG002 **Value:** 17 #### Measurement **Group ID:** BG003 **Value:** 17 #### Measurement **Group ID:** BG004 **Value:** 67 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 4 #### Measurement **Group ID:** BG001 **Value:** 4 #### Measurement **Group ID:** BG002 **Value:** 4 #### Measurement **Group ID:** BG003 **Value:** 5 #### Measurement **Group ID:** BG004 **Value:** 17 **Category Title:** Male #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 21 **Group ID:** BG001 **Value:** 20 **Group ID:** BG002 **Value:** 21 **Group ID:** BG003 **Value:** 22 **Group ID:** BG004 **Value:** 84 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 1 #### Measurement **Group ID:** BG002 **Value:** 6 #### Measurement **Group ID:** BG003 **Value:** 2 #### Measurement **Group ID:** BG004 **Value:** 9 **Category Title:** Hispanic or Latino #### Measurement **Group ID:** BG000 **Value:** 20 #### Measurement **Group ID:** BG001 **Value:** 19 #### Measurement **Group ID:** BG002 **Value:** 14 #### Measurement **Group ID:** BG003 **Value:** 17 #### Measurement **Group ID:** BG004 **Value:** 70 **Category Title:** Not Hispanic or Latino #### Measurement **Group ID:** BG000 **Value:** 1 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 1 #### Measurement **Group ID:** BG003 **Value:** 3 #### Measurement **Group ID:** BG004 **Value:** 5 **Category Title:** Unknown or Not Reported #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 21 **Group ID:** BG001 **Value:** 20 **Group ID:** BG002 **Value:** 21 **Group ID:** BG003 **Value:** 22 **Group ID:** BG004 **Value:** 84 **Class Title:** ### 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 #### Measurement **Group ID:** BG004 **Value:** 0 **Category Title:** American Indian or Alaska Native #### Measurement **Group ID:** BG000 **Value:** 1 #### Measurement **Group ID:** BG001 **Value:** 1 #### Measurement **Group ID:** BG002 **Value:** 4 #### Measurement **Group ID:** BG003 **Value:** 7 #### Measurement **Group ID:** BG004 **Value:** 13 **Category Title:** Asian #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 #### Measurement **Group ID:** BG003 **Value:** 0 #### Measurement **Group ID:** BG004 **Value:** 0 **Category Title:** Native Hawaiian or Other Pacific Islander #### Measurement **Group ID:** BG000 **Value:** 4 #### Measurement **Group ID:** BG001 **Value:** 2 #### Measurement **Group ID:** BG002 **Value:** 2 #### Measurement **Group ID:** BG003 **Value:** 4 #### Measurement **Group ID:** BG004 **Value:** 12 **Category Title:** Black or African American #### Measurement **Group ID:** BG000 **Value:** 15 #### Measurement **Group ID:** BG001 **Value:** 16 #### Measurement **Group ID:** BG002 **Value:** 13 #### Measurement **Group ID:** BG003 **Value:** 10 #### Measurement **Group ID:** BG004 **Value:** 54 **Category Title:** White #### Measurement **Group ID:** BG000 **Value:** 1 #### Measurement **Group ID:** BG001 **Value:** 1 #### Measurement **Group ID:** BG002 **Value:** 2 #### Measurement **Group ID:** BG003 **Value:** 1 #### Measurement **Group ID:** BG004 **Value:** 5 **Category Title:** More than one race #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 #### Measurement **Group ID:** BG003 **Value:** 0 #### Measurement **Group ID:** BG004 **Value:** 0 **Category Title:** Unknown or Not Reported #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 21 **Group ID:** BG001 **Value:** 20 **Group ID:** BG002 **Value:** 21 **Group ID:** BG003 **Value:** 22 **Group ID:** BG004 **Value:** 84 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 21 #### Measurement **Group ID:** BG001 **Value:** 20 #### Measurement **Group ID:** BG002 **Value:** 21 #### Measurement **Group ID:** BG003 **Value:** 22 #### Measurement **Group ID:** BG004 **Value:** 84 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 21 **Group ID:** BG001 **Value:** 20 **Group ID:** BG002 **Value:** 21 **Group ID:** BG003 **Value:** 22 **Group ID:** BG004 **Value:** 84 **Class Title:** United States ### Measure #### Measurement **Group ID:** BG000 **Spread:** 0.088 **Value:** 0.789 #### Measurement **Group ID:** BG001 **Spread:** 0.056 **Value:** 0.812 #### Measurement **Group ID:** BG002 **Spread:** 0.076 **Value:** 0.826 #### Measurement **Group ID:** BG003 **Spread:** 0.095 **Value:** 0.845 #### Measurement **Group ID:** BG004 **Spread:** 0.081 **Value:** 0.818 #### Denomination **Units:** Participants ##### Denomination Counts **Group ID:** BG000 **Value:** 21 **Group ID:** BG001 **Value:** 20 **Group ID:** BG002 **Value:** 21 **Group ID:** BG003 **Value:** 20 **Group ID:** BG004 **Value:** 82 **Class Title:** **Denomination Units Selected:** ## Results Section - Baseline Characteristics Module ### Measure 1 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Title:** Age, Continuous **Unit of Measure:** years ### Measure 2 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Sex: Female, Male **Unit of Measure:** Participants ### Measure 3 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Ethnicity (NIH/OMB) **Unit of Measure:** Participants ### Measure 4 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Race (NIH/OMB) **Unit of Measure:** Participants ### Measure 5 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Region of Enrollment **Unit of Measure:** Participants ### Measure 6 **Dispersion Type:** STANDARD_DEVIATION **Parameter Type:** MEAN **Population Description:** One healthy control participant that received sham stimulation was excluded from analysis as we were unable to find an age and sex matched participant. One healthy control participant that received sham stimulation did not complete the study due to technical difficulties. **Title:** Alpha oscillations in left frontal cortex before stimulation **Unit of Measure:** microvolts **Population Description:** One healthy control participant that received sham stimulation was excluded from analysis as we were unable to find an age and sex matched participant. One healthy control participant that received sham stimulation did not complete the study due to technical difficulties. ## Results Section - More Information Module ### Certain Agreement **PI Sponsor Employee:** True ### Point of Contact **Email:** [email protected] **Organization:** University of North Carolina at Chapel Hill **Phone:** 6617131602 **Title:** Justin Riddle, 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:** Interaction in the effect of tACS on left frontal alpha oscillation in the depressed group. Two-way interaction of within-participant factor of before/after tACS and between-participant factor of alpha-tACS/placebo. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.0852 **P-Value Comment:** **Parameter Type:** **Parameter Value:** **Statistical Comment:** degrees of freedom = (1,39); F-statistic = 3.119 **Statistical Method:** ANOVA **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Interaction in the effect of tACS on left frontal alpha oscillation in the healthy group. Two-way interaction of within-participant factor of before/after tACS and between-participant factor of alpha-tACS/placebo. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.6676 **P-Value Comment:** **Parameter Type:** **Parameter Value:** **Statistical Comment:** degrees of freedom = (1,39); F-statistic = 0.187 **Statistical Method:** ANOVA **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Main effect of alpha-tACS on session (before and after) on left frontal alpha oscillations across both groups (healthy and patient). **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.929 **P-Value Comment:** degrees of freedom = (1,41); F-statistic = 0.008 **Parameter Type:** **Parameter Value:** **Statistical Comment:** **Statistical Method:** ANOVA **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Difference in alpha oscillations after versus before in the depressed cohort (one-tailed Student's t-test) with the hypothesis to decrease pathologically elevate left frontal alpha oscillations **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.1950 **P-Value Comment:** **Parameter Type:** **Parameter Value:** **Statistical Comment:** degrees of freedom = 20; t-statistic = -0.08789 **Statistical Method:** t-test, 1 sided **Tested Non-Inferiority:** #### Analysis **CI Lower Limit:** **CI Number of Sides:** **CI Percentage Value:** **CI Upper Limit:** **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Difference in alpha oscillations after versus before in the healthy cohort (one-tailed Student's t-test) run as a control analysis **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY **Other Analysis Description:** **P-Value:** 0.8603 **P-Value Comment:** **Parameter Type:** **Parameter Value:** **Statistical Comment:** degrees of freedom = 20; t-statistic = 1.1117 **Statistical Method:** t-test, 1 sided **Tested Non-Inferiority:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.022 - **Upper Limit:** - **Value:** -0.005 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.023 - **Upper Limit:** - **Value:** 0.008 - **Comment:** - **Group ID:** OG002 - **Lower Limit:** - **Spread:** 0.017 - **Upper Limit:** - **Value:** 0.004 - **Comment:** - **Group ID:** OG003 - **Lower Limit:** - **Spread:** 0.022 - **Upper Limit:** - **Value:** 0.007 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** Fast Fourier transform is applied to 5 minutes of EEG data before and after intervention. Primary outcome is the difference in alpha frequency amplitude (8-12 Hz) in the left frontal cortex from baseline as a result of intervention. **Dispersion Type:** Standard Deviation **Parameter Type:** MEAN **Population Description:** One of the healthy participants that received sham stimulation could not be age and sex matched, therefore, we did not analyze this participant. **Reporting Status:** POSTED **Time Frame:** 5 minute recording before and after intervention **Title:** Change in Alpha Frequency Electrical Activity in Left Frontal Cortex From Stimulation **Type:** PRIMARY **Unit of Measure:** microvolts ##### Group **Description:** Participants in a depressive episode will receive 2 mA of alternating current stimulation at individualized alpha stimulation (between 8 and 12 Hz; determined by an EEG recording prior to stimulation) for 40 minutes. tACS stimulation is delivered using the XCSITE100 Stimulator tACS. XCSITE100 Stimulator tACS: Transcranial alternating current stimulation (tACS) is a method of noninvasive brain stimulation in which weak electrical current are applied to the scalp in a sine wave pattern to induce cortical oscillations at the frequency at which they are applied. **ID:** OG000 **Title:** Alpha Stimulation in Participants in a Depressive Episode ##### Group **Description:** Sham Stimulation mimics the physical effects of stimulation, with up to one minute of stimulation during the session. Sham stimulation to participants in a depressive episode is delivered using the XCSITE100 Stimulator Sham. XCSITE100 Stimulator Sham: The participant will receive up to one minute of tACS stimulation until the stimulation fades. Sham stimulation mimics the skin sensations a participant would experience during a tACS session. **ID:** OG001 **Title:** Sham Stimulation in Participants in a Depressive Episode ##### Group **Description:** Healthy participants will receive 2 mA of alternating current stimulation at individualized alpha stimulation (between 8 and 12 Hz; determined by an EEG recording prior to stimulation) for 40 minutes. tACS stimulation is delivered using the XCSITE100 Stimulator tACS. XCSITE100 Stimulator tACS: Transcranial alternating current stimulation (tACS) is a method of noninvasive brain stimulation in which weak electrical current are applied to the scalp in a sine wave pattern to induce cortical oscillations at the frequency at which they are applied. **ID:** OG002 **Title:** Alpha Stimulation in Healthy Participants ##### Group **Description:** Sham Stimulation mimics the physical effects of stimulation, with up to one minute of stimulation during the session. Sham stimulation to healthy participants is delivered using the XCSITE100 Stimulator Sham. XCSITE100 Stimulator Sham: The participant will receive up to one minute of tACS stimulation until the stimulation fades. Sham stimulation mimics the skin sensations a participant would experience during a tACS session. **ID:** OG003 **Title:** Sham Stimulation in Healthy Participants ### Participant Flow Module #### Group **Description:** Participants in a depressive episode will receive 2 mA of alternating current stimulation at individualized alpha stimulation (between 8 and 12 Hz; determined by an EEG recording prior to stimulation) for 40 minutes. tACS stimulation is delivered using the XCSITE100 Stimulator tACS. XCSITE100 Stimulator tACS: Transcranial alternating current stimulation (tACS) is a method of noninvasive brain stimulation in which weak electrical current are applied to the scalp in a sine wave pattern to induce cortical oscillations at the frequency at which they are applied. **ID:** FG000 **Title:** Alpha Stimulation in Participants in a Depressive Episode #### Group **Description:** Sham Stimulation mimics the physical effects of stimulation, with up to one minute of stimulation during the session. Sham stimulation to participants in a depressive episode is delivered using the XCSITE100 Stimulator Sham. XCSITE100 Stimulator Sham: The participant will receive up to one minute of tACS stimulation until the stimulation fades. Sham stimulation mimics the skin sensations a participant would experience during a tACS session. **ID:** FG001 **Title:** Sham Stimulation in Participants in a Depressive Episode #### Group **Description:** Healthy participants will receive 2 mA of alternating current stimulation at individualized alpha stimulation (between 8 and 12 Hz; determined by an EEG recording prior to stimulation) for 40 minutes. tACS stimulation is delivered using the XCSITE100 Stimulator tACS. XCSITE100 Stimulator tACS: Transcranial alternating current stimulation (tACS) is a method of noninvasive brain stimulation in which weak electrical current are applied to the scalp in a sine wave pattern to induce cortical oscillations at the frequency at which they are applied. **ID:** FG002 **Title:** Alpha Stimulation in Healthy Participants #### Group **Description:** Sham Stimulation mimics the physical effects of stimulation, with up to one minute of stimulation during the session. Sham stimulation to healthy participants is delivered using the XCSITE100 Stimulator Sham. XCSITE100 Stimulator Sham: The participant will receive up to one minute of tACS stimulation until the stimulation fades. Sham stimulation mimics the skin sensations a participant would experience during a tACS session. **ID:** FG003 **Title:** Sham Stimulation in Healthy Participants #### Period **Title:** Overall Study ##### Withdraw **Type:** Technical difficulty ###### Reason **Group ID:** FG000 **Number of Subjects:** 0 ###### Reason **Group ID:** FG001 **Number of Subjects:** 0 ###### Reason **Group ID:** FG002 **Number of Subjects:** 0 ###### Reason **Group ID:** FG003 **Number of Subjects:** 1 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 21 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 20 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 21 ###### Achievement **Group ID:** FG003 **Number of Subjects:** 22 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 21 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 20 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 21 ###### Achievement **Group ID:** FG003 **Number of Subjects:** 21 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG003 **Number of Subjects:** 1 **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT02255279 **Brief Title:** Safety and Immunogenicity of an Adjuvanted Trivalent Influenza Vaccine in Children 6 to <72 Months of Age in Mexico. **Official Title:** A Phase 3, Observed-Blind, Randomized, Multi-center Study to Evaluate Safety and Immunogenicity of an Adjuvanted Trivalent Influenza Vaccine in Children 6 to <72 Months of Age in Mexico. #### Organization Study ID Info **ID:** V70_50 #### Organization **Class:** INDUSTRY **Full Name:** Novartis ### Status Module #### Completion Date **Date:** 2015-05 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2017-01-27 **Type:** ESTIMATED **Last Update Submit Date:** 2016-11-30 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2015-05 **Type:** ACTUAL #### Results First Post Date **Date:** 2016-02-03 **Type:** ESTIMATED **Results First Submit Date:** 2016-01-04 **Results First Submit QC Date:** 2016-01-04 #### Start Date **Date:** 2014-10 **Status Verified Date:** 2016-01 #### Study First Post Date **Date:** 2014-10-02 **Type:** ESTIMATED **Study First Submit Date:** 2014-09-30 **Study First Submit QC Date:** 2014-09-30 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Novartis Vaccines #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** The administration of adjuvanted Trivalent Influenza Vaccine (aTIV) has come to result in a more immunogenic and effective response compared with conventional influenza vaccines in elderly and adults. The aim of this study is to evaluate safety and immunogenicity of Novartis aTIV in children 6 to \<72 months of age, Mexican population, in comparison to Fluzone, a non-adjuvanted trivalent influenza vaccine (TIV). ### Conditions Module **Conditions:** - Influenza ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** TRIPLE **Who Masked:** - PARTICIPANT - INVESTIGATOR - OUTCOMES_ASSESSOR **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 287 **Type:** ACTUAL **Phases:** - PHASE3 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** aTIV is a trivalent influenza virus vaccine, adjuvanted with MF59C. **Intervention Names:** - Biological: Adjuvanted Trivalent Influenza Vaccine, 1 dose for non-naive subjects (day 1), two doses for naive subjects (day 1 and day 29) **Label:** aTIV **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** TIV is trivalent influenza vaccine licensed in Mexico. **Intervention Names:** - Biological: Non-adjuvanted Trivalent Influenza Vaccine, 1 dose for non-naive subjects (day 1), two doses for naive subjects (day 1 and day 29). **Label:** TIV **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - aTIV **Description:** A 0.25 mL (for children 6 to \<36 months old) and 0.5 mL (for children ≥36 months to \< 72 months old) dose of aTIV, a trivalent (surface antigen, formaldehyde-inactivated) influenza virus vaccine, adjuvanted with MF59C.1, administered at day 1 (for all subjects) and day 29 (for naïve subjects). **Name:** Adjuvanted Trivalent Influenza Vaccine, 1 dose for non-naive subjects (day 1), two doses for naive subjects (day 1 and day 29) **Type:** BIOLOGICAL #### Intervention 2 **Arm Group Labels:** - TIV **Description:** A 0.25 mL (for children 6 to \<36 months old) and 0.5 mL (for children ≥36 months to \< 72 months old) dose of TIV , an egg-derived trivalent split influenza vaccine licensed in Mexico, administered at day 1 (for all subjects) and day 29 (for naïve subjects) **Name:** Non-adjuvanted Trivalent Influenza Vaccine, 1 dose for non-naive subjects (day 1), two doses for naive subjects (day 1 and day 29). **Type:** BIOLOGICAL ### Outcomes Module #### Primary Outcomes **Description:** Number of naive subjects 6 to \< 36 months old reporting solicited local and systemic AEs from Day 1 to Day 7 after first vaccination and from Day 29 to Day 35 after second vaccination. **Measure:** Number of Naive Subjects 6 to < 36 Months Old Reporting Solicited Local and Systemic Adverse Events (AEs) From Day 1 to Day 7 Following Each Vaccination. **Time Frame:** From Day 1 to Day 7 by vaccination **Description:** Number of non-naive subjects 6 to \< 36 months old reporting solicited local and systemic AEs from Day 1 to Day 7 after vaccination. **Measure:** Number of Non-naive Subjects 6 to < 36 Months Old Reporting Solicited Local and Systemic AEs From Day 1 to Day 7 After Vaccination. **Time Frame:** From Day 1 to Day 7 **Description:** Number of naive subjects ≥ 36 months to \< 72 months old reporting solicited local and systemic AEs from Day 1 to Day 7 after first vaccination and from Day 29 to Day 35 after second vaccination. **Measure:** Number of Naive Subjects ≥ 36 Months to < 72 Months Old Reporting Solicited Local and Systemic AEs From Day 1 to Day 7 Following Each Vaccination. **Time Frame:** From Day 1 to Day 7 by vaccination **Description:** Number of non-naive subjects ≥36 months to \< 72 months old reporting solicited local and systemic AEs from Day 1 to Day 7 after vaccination. **Measure:** Number of Non-naive Subjects ≥36 Months to < 72 Months Old Reporting Solicited Local and Systemic AEs From Day 1 to Day 7 Following Each Vaccination. **Time Frame:** From Day 1 to Day 7 **Description:** Number of naive subjects aged 6 to \< 72 months reporting all unsolicited AEs, medically attended AEs, AE leading to study withdrawal and serious AEs (SAEs) from Day 1 to Day 50. **Measure:** Number of Naive Subjects Aged 6 to < 72 Months Reporting All Unsolicited AEs From Day 1 to Day 50. **Time Frame:** From Day 1 to Day 50 **Description:** Number of non-naive subjects aged 6 to \< 72 months reporting all unsolicited AEs, medically attended AEs, AE leading to study withdrawal and SAEs from Day 1 to Day 22. **Measure:** Number of Non-naive Subjects Aged 6 to < 72 Months Reporting All Unsolicited AEs From Day 1 to Day 22 **Time Frame:** From Day 1 to Day 22 **Description:** Antibody response was assessed in terms of GMTs in all three homologous virus strains, 21 days after last immunization, in subjects 6 to \<72 months of age. The study is considered a success if the 21 days after last immunization GMT ratios of aTIV relative to TIV demonstrate as non-inferior with the lower limit (LL) of the two sided 95% confidence interval (CI) above 0.67 (-0.176 on log10 scale) for each vaccine strain (Center for Biologics Evaluation and Research {CBER} Guideline on Seasonal Vaccines May 2007). **Measure:** Geometric Mean Titers (GMTs), in All Three Homologous Virus Strains in Subjects 6 to < 72 Months of Age. **Time Frame:** Day 1 and Day 22 (vaccine non-naïve subjects) or Day 50 (vaccine naïve subjects) post vaccination #### Secondary Outcomes **Description:** Percentages of subjects with seroconversion in all three homologous virus strains, 21 days after last immunization, in subjects 6 to \<72 months of age, defined as: HI ≥ 40 subject with a pre-vaccination HI titer \<10; a minimum 4-fold increase HI titer for subjects with a prevaccination HI titer ≥10, on Day 22 (non-naive subjects) or Day 50 (naive subjects), as applicable. **Measure:** Percentages of Subjects Achieving Seroconversion in Hemagglutination Inhibition (HI) Titers and Vaccine Group Differences at Day 1 and 21 Days After Last Vaccination With aTIV or TIV in Naive and Non-naive Subjects. **Time Frame:** Day 1 and Day 22 (vaccine non-naive subjects) or Day 50 (vaccine naive subjects) post vaccination **Description:** GMRs of HI, day 22/day 1 (non-naive subjects) or day 50/day 1 (naive subjects) in all three homologous virus strains, 21 days after last immunization, in subjects 6 to \<72 months of age. As the non-inferiority of aTIV to TIV has been established, GMT ratio of aTIV relative to TIV in all three homologous virus strains, 21 days after last immunization in subjects 6 to \<72 months of age was evaluated using margins greater than the non-inferiority cut-off of 0.67. **Measure:** Geometric Mean Ratios (GMRs) of HI and Vaccine Group Differences at Day 1 and 21 Days After Last Vaccination With aTIV or TIV in Naive and Non-naive Subjects. **Time Frame:** Day 1 and Day 22 (vaccine non-naive subjects) or Day 50 (vaccine naive subjects) post vaccination **Description:** Percentage of subjects with a HI titer ≥ 40, ≥110 and ≥330 on Day 1, Day 22 (non naïve subjects) or Day 50 (naïve subjects), in all three homologous virus strains, 21 days after last immunization, in subjects 6 to \<72 months of age. **Measure:** Percentages of Subjects With a HI Titer ≥ 40, ≥110 and ≥330 and Vaccine Group Differences at Day 1 and 21 Days After Last Vaccination With aTIV or TIV in Naive and Non-naive Subjects. **Time Frame:** Day 1 and Day 22 (vaccine non-naive subjects) or Day 50 (vaccine naive subjects) post vaccination ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Individuals of \>6 months through \<72 months of age on the day of informed consent. * Individuals whose parent(s)/legal guardian(s) have voluntarily given written informed consent after the nature of the study has been explained according to local regulatory requirements, prior to study entry. * Individuals who can comply with study procedures. * Willingness to allow for serum samples to be stored beyond the study period, for potential additional future testing to better characterize immune response. Exclusion Criteria: * Progressive, unstable or uncontrolled clinical conditions. * Hypersensitivity, including allergy, to any component of vaccines, medicinal products or medical equipment whose use is foreseen in this study. * History of progressive or severe neurologic disorder, seizure disorder or Guillain-Barré syndrome. * Surgery planned during the study period that in the Investigator's opinion would interfere with the study visits schedule. * Known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time. * Any fatal prognosis of an underlying medical condition (\<12 month life expectancy). * Clinical conditions representing a contraindication to intramuscular vaccination and blood draws. * Abnormal function of the immune system resulting from: 1. Clinical conditions. 2. Systemic administration of corticosteroids (PO/IV/IM) for more than 14 consecutive days within 90 days prior to informed consent. 3. Administration of antineoplastic and immunomodulating agents or radiotherapy within 90 days prior to informed consent. * Received immunoglobulins or any blood products within 180 days prior to informed consent. * Received an investigational or non-registered medicinal product within 30 days prior to informed consent. * Study personnel as an immediate family or household member. * Any other clinical condition that, in the opinion of the investigator, might interfere with the results of the study or pose additional risk to the subject due to participation in the study. * Received any influenza vaccine (licensed or investigational) or with laboratory confirmed influenza within 6 months prior enrollment. * Received any other vaccines within 14 days (for inactivated vaccines) or 28 days (for live vaccines) prior to enrolment in this study or who are planning to receive any vaccine within 28 days from the study vaccines. **Healthy Volunteers:** True **Maximum Age:** 71 Months **Minimum Age:** 6 Months **Sex:** ALL **Standard Ages:** - CHILD ### Contacts Locations Module #### Locations **Location 1:** **City:** Colonia Chamilpa, Cuernavaca **Country:** Mexico **Facility:** 03, Centro Médico Universitario **State:** Morelos **Location 2:** **City:** Mérida **Country:** Mexico **Facility:** 02, Unidad de Atencion Medica E Investigacion En Salud S.C (Unamis) **State:** Yucatán **Location 3:** **City:** Mérida **Country:** Mexico **Facility:** 04, Medical Care and Research S.A. de C.V. **State:** Yucatán ### References Module #### References **Citation:** Cruz-Valdez A, Valdez-Zapata G, Patel SS, Castelli FV, Garcia MG, Jansen WT, Arora AK, Heijnen E. MF59-adjuvanted influenza vaccine (FLUAD(R)) elicits higher immune responses than a non-adjuvanted influenza vaccine (Fluzone(R)): A randomized, multicenter, Phase III pediatric trial in Mexico. Hum Vaccin Immunother. 2018 Feb 1;14(2):386-395. doi: 10.1080/21645515.2017.1373227. Epub 2018 Jan 3. **PMID:** 28925801 ## 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 - 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 - Abbrev: Infe - Name: Anti-Infective Agents ### Intervention Browse Module - Browse Leaves - ID: M17360 - Name: Vaccines - Relevance: HIGH - As Found: Other - ID: M8681 - Name: Formaldehyde - Relevance: LOW - As Found: Unknown - ID: M35911 - Name: MF59 oil emulsion - Relevance: LOW - As Found: Unknown - 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 ## Results Section ### Adverse Events Module **Description:** Solicited AEs were collected by the subject parent(s)/legal guardian(s) for 7 days from the day of vaccination/s (Day 1 \& Day 29 for naive; Day 1 for non-naive). Unsolicited AEs were collected from Day 1 to Day 50 for naive, from Day 1 to Day 22 for non-naive. All AEs were monitored until resolution or the investigator assesses them as stable. #### Event Groups **Group ID:** EG000 **Title:** Naive_aTIV (6 Months to < 72 Months) **Description:** A 0.25 mL (for children 6 to \<36 months old) and 0.5 mL (for children ≥36 months to \< 72 months old) dose of aTIV to be administered (Naive). **ID:** EG000 **Other Num Affected:** 58 **Other Num at Risk:** 77 **Serious Number At Risk:** 77 **Title:** Naive_aTIV (6 Months to < 72 Months) **Group ID:** EG001 **Title:** Naive_TIV (6 Months to < 72 Months) **Description:** A 0.25 mL (for children 6 to \<36 months old) and 0.5 mL (for children ≥36 months to \< 72 months old) dose of TIV to be administered (Naive). Enrolled subjects- 79 Exposed subjects- 78 Reason for discrepancy- Before vaccination one subject was withdrawn from study because of the suspected egg allergy. **ID:** EG001 **Other Num Affected:** 52 **Other Num at Risk:** 78 **Serious Number At Risk:** 78 **Title:** Naive_TIV (6 Months to < 72 Months) **Group ID:** EG002 **Title:** Non-naive_aTIV (6 Months to < 72 Months) **Description:** A 0.25 mL (for children 6 to \<36 months old) and 0.5 mL (for children ≥36 months to \< 72 months old) dose of aTIV to be administered (Non-naive). **ID:** EG002 **Other Num Affected:** 35 **Other Num at Risk:** 67 **Serious Number At Risk:** 67 **Title:** Non-naive_aTIV (6 Months to < 72 Months) **Group ID:** EG003 **Title:** Non-naive_TIV (6 Months to < 72 Months) **Description:** A 0.25 mL (for children 6 to \<36 months old) and 0.5 mL (for children ≥36 months to \< 72 months old) dose of TIV to be administered (Non-naive). **ID:** EG003 **Other Num Affected:** 31 **Other Num at Risk:** 64 **Serious Number At Risk:** 64 **Title:** Non-naive_TIV (6 Months to < 72 Months) **Frequency Threshold:** 5 #### Other Events **Term:** Diarrhoea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA (19.0) **Term:** Vomiting **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA (19.0) **Term:** Crying **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA (19.0) **Term:** Fatigue **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA (19.0) **Term:** Injection site erythema **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA (19.0) **Term:** Injection site induration **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA (19.0) **Term:** Injection site pain **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA (19.0) **Term:** Injection site swelling **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA (19.0) **Term:** Pyrexia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA (19.0) **Term:** Conjunctivitis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (19.0) **Term:** Gastroenteritis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (19.0) **Term:** Nasopharyngitis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (19.0) **Term:** Pharyngitis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA (19.0) **Term:** Myalgia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA (19.0) **Term:** Somnolence **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA (19.0) **Term:** Eating disorder **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA (19.0) **Term:** Irritability **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA (19.0) **Term:** Cough **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA (19.0) **Term:** Rhinorrhoea **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA (19.0) **Term:** Arthralgia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA (19.0) **Time Frame:** Throughout the study; Day 1 - Day 50 (naive subjects) and Day 1 - Day 22 (non-naive subjects). ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 144 **Group ID:** BG001 **Value:** 143 **Group ID:** BG002 **Value:** 287 **Units:** Participants ### Group **ID:** BG000 **Title:** aTIV (6 Months to < 72 Months) **Description:** A 0.25 mL (for children 6 to \<36 months old) and 0.5 mL (for children ≥36 months to \< 72 months old) dose of aTIV to be administered. ### Group **ID:** BG001 **Title:** TIV (6 Months to < 72 Months) **Description:** A 0.25 mL (for children 6 to \<36 months old) and 0.5 mL (for children ≥36 months to \< 72 months old) dose of TIV to be administered. ### Group **ID:** BG002 **Title:** Total **Description:** Total of all reporting groups ### Measure #### Measurement **Group ID:** BG000 **Spread:** 18.2 **Value:** 29.5 #### Measurement **Group ID:** BG001 **Spread:** 19.1 **Value:** 30.1 #### Measurement **Group ID:** BG002 **Spread:** 18.6 **Value:** 29.8 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 68 #### Measurement **Group ID:** BG001 **Value:** 72 #### Measurement **Group ID:** BG002 **Value:** 140 **Category Title:** FEMALE #### Measurement **Group ID:** BG000 **Value:** 76 #### Measurement **Group ID:** BG001 **Value:** 71 #### Measurement **Group ID:** BG002 **Value:** 147 **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:** Months ### Measure 2 **Parameter Type:** COUNT_OF_PARTICIPANTS **Title:** Gender **Unit of Measure:** Participants ## Results Section - More Information Module ### Certain Agreement **Other Details:** The terms and conditions of Novartis' agreement with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publications of the pooled data (i.e., data from all sites) in the clinical trial. **Restriction Type:** OTHER **Restrictive Agreement:** True ### Point of Contact **Email:** [email protected] **Organization:** Novartis Vaccines **Title:** Posting Director ## Results Section - Outcome Measures Module ### Outcome Measure 1 ### Outcome Measure 2 ### Outcome Measure 3 ### Outcome Measure 4 ### Outcome Measure 5 ### Outcome Measure 6 ### Outcome Measure 7 #### Analysis **CI Lower Limit:** 3.00 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 5.51 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Geometric mean titers (GMTs), in H1N1 strain of all the tree strains in Subjects 6 to \< 72 months of Age. **Non-Inferiority Comment:** Hypothesis: Demonstrate non-inferiority (NI) of aTIV to TIV: H0 : μAi - μBi ≤ -0.176 (Null) H1 : μAi - μBi \>-0.176 (alternative) (i= H1N1, H3N2, B) μA and μB are means of log10-transformed titers 21 days after last vaccination of the aTIV \& TIV vaccine groups respectively. NI is claimed if LL of 95% CI for GMT ratios is \>0.67. Significance level is α = 2.5% (1-sided), which needs no further adjustment for multiplicity as to reach NI, above hypothesis needs to be rejected for all 3 strains. **Non-Inferiority Type:** NON_INFERIORITY_OR_EQUIVALENCE **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Ratio of GMTs **Parameter Value:** 4.06 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** True #### Analysis **CI Lower Limit:** 2.05 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 3.25 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Geometric mean titers (GMTs), in H3N2 strain of all three homologous virus strains in Subjects 6 to \< 72 months of Age. **Non-Inferiority Comment:** Hypothesis: Demonstrate non-inferiority (NI) of aTIV to TIV: H0 : μAi - μBi ≤ -0.176 (Null) H1 : μAi - μBi \>-0.176 (alternative) (i= H1N1, H3N2, B) μA and μB are means of log10-transformed titers 21 days after last vaccination of the aTIV \& TIV vaccine groups respectively. NI is claimed if LL of 95% CI for GMT ratios is \>0.67. Significance level is α = 2.5% (1-sided), which needs no further adjustment for multiplicity as to reach NI, above hypothesis needs to be rejected for all 3 strains. **Non-Inferiority Type:** NON_INFERIORITY_OR_EQUIVALENCE **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Ratio of GMTs **Parameter Value:** 2.58 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** True #### Analysis **CI Lower Limit:** 3.52 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 6.20 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Geometric mean titers (GMTs), in B strain of all three homologous virus strains in Subjects 6 to \< 72 months of Age. **Non-Inferiority Comment:** Hypothesis: Demonstrate non-inferiority (NI) of aTIV to TIV: H0 : μAi - μBi ≤ -0.176 (Null) H1 : μAi - μBi \>-0.176 (alternative) (i= H1N1, H3N2, B) μA and μB are means of log10-transformed titers 21 days after last vaccination of the aTIV \& TIV vaccine groups respectively. NI is claimed if LL of 95% CI for GMT ratios is \>0.67. Significance level is α = 2.5% (1-sided), which needs no further adjustment for multiplicity as to reach NI, above hypothesis needs to be rejected for all 3 strains. **Non-Inferiority Type:** NON_INFERIORITY_OR_EQUIVALENCE **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Ratio of GMTs **Parameter Value:** 4.67 **Statistical Comment:** **Statistical Method:** ANCOVA **Tested Non-Inferiority:** True ### Outcome Measure 8 #### Analysis **CI Lower Limit:** 8.1 **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:** Percentage of subjects achieving seroconversion in H1N1 strain after last vaccination with aTIV or TIV in naïve and non-naive subjects. **Non-Inferiority Comment:** The following hypotheses should be tested to demonstrate non-inferiority of aTIV to TIV: H0i: πi1 \> πi2-0.1 vs. H1i: πi1 \> πi2- 0.1 where H0i and H1i represent the null and the alternative hypothesis (respectively) of the non- inferiority objective and πi1 and πi2 represent the seroresponse rates 21 days after last immunization of the aTIV and TIV vaccine groups respectively in the i-th strain (H1N1, H3N2, B). The non-inferiority criterion is -0.1 (i.e., -10%). **Non-Inferiority Type:** NON_INFERIORITY_OR_EQUIVALENCE **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Vaccine Group Differences **Parameter Value:** 17 **Statistical Comment:** Binary data were analyzed using loglinear models with a qualitative factor for vaccine group (αik, i = A, B) and center (δlk, k=1). **Statistical Method:** Loglinear model **Tested Non-Inferiority:** True #### Analysis **CI Lower Limit:** -1.8 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 21 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Percentage of subjects achieving seroconversion in H3N2 strain after last vaccination with aTIV or TIV in naive and non-naive subjects. **Non-Inferiority Comment:** The following hypotheses should be tested to demonstrate non-inferiority of aTIV to TIV: H0i: πi1 \> πi2-0.1 vs. H1i: πi1 \> πi2- 0.1 where H0i and H1i represent the null and the alternative hypothesis (respectively) of the non- inferiority objective and πi1 and πi2 represent the seroresponse rates 21 days after last immunization of the aTIV and TIV vaccine groups respectively in the i-th strain (H1N1, H3N2, B). The non-inferiority criterion is -0.1 (i.e., -10%). **Non-Inferiority Type:** NON_INFERIORITY_OR_EQUIVALENCE **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Vaccine Group Differences **Parameter Value:** 10 **Statistical Comment:** Binary data were analyzed using loglinear models with a qualitative factor for vaccine group (αik, i = A, B) and center (δlk, k=1). **Statistical Method:** Loglinear model **Tested Non-Inferiority:** True #### Analysis **CI Lower Limit:** 47.5 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 68.5 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Percentage of subjects achieving seroconversion in B strains after last vaccination with aTIV or TIV in naïve and non naive subjects. **Non-Inferiority Comment:** The following hypotheses should be tested to demonstrate non-inferiority of aTIV to TIV: H0i: πi1 \> πi2-0.1 vs. H1i: πi1 \> πi2- 0.1 where H0i and H1i represent the null and the alternative hypothesis (respectively) of the non- inferiority objective and πi1 and πi2 represent the seroresponse rates 21 days after last immunization of the aTIV and TIV vaccine groups respectively in the i-th strain (H1N1, H3N2, B). The non-inferiority criterion is -0.1 (i.e., -10%). **Non-Inferiority Type:** NON_INFERIORITY_OR_EQUIVALENCE **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Vaccine Group Differences **Parameter Value:** 58 **Statistical Comment:** Binary data were analyzed using loglinear models with a qualitative factor for vaccine group (αik, i = A, B) and center (δlk, k=1). **Statistical Method:** Loglinear model **Tested Non-Inferiority:** True ### Outcome Measure 9 ### Outcome Measure 10 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 35 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 20 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 21 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 15 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 5 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 6 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 8 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 9 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 8 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 7 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 26 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 16 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 17 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 13 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 34 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 27 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 27 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 22 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 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:** 5 **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:** 2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 14 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4 **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:** 7 **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:** 15 **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:** 11 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 18 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 13 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 17 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 9 **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:** 11 **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:** 9 **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:** 11 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 8 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 9 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 5 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 9 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 7 **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:** 2 **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 10 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 7 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 9 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 9 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 7 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 6 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 6 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** #### Outcome Measure 3 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 5 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 **Title:** **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:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** #### Outcome Measure 4 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 17 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 20 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 6 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 6 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 7 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 14 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 16 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 15 - **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:** 6 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 7 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 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 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 8 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 5 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** #### Outcome Measure 5 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 33 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 28 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 26 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 25 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** #### Outcome Measure 6 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 9 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 6 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 3 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 4 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 0 **Title:** #### Outcome Measure 7 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 11 - **Spread:** - **Upper Limit:** 19 - **Value:** 14 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 11 - **Spread:** - **Upper Limit:** 20 - **Value:** 15 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 536 - **Spread:** - **Upper Limit:** 849 - **Value:** 675 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 132 - **Spread:** - **Upper Limit:** 208 - **Value:** 166 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 40 - **Spread:** - **Upper Limit:** 86 - **Value:** 59 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 38 - **Spread:** - **Upper Limit:** 81 - **Value:** 55 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 1077 - **Spread:** - **Upper Limit:** 1521 - **Value:** 1280 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 417 - **Spread:** - **Upper Limit:** 588 - **Value:** 495 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 6.41 - **Spread:** - **Upper Limit:** 8.71 - **Value:** 7.47 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 5.95 - **Spread:** - **Upper Limit:** 8.06 - **Value:** 6.92 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 61 - **Spread:** - **Upper Limit:** 93 - **Value:** 76 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 13 - **Spread:** - **Upper Limit:** 20 - **Value:** 16 **Title:** #### Outcome Measure 8 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 83.2 - **Spread:** - **Upper Limit:** 95 - **Value:** 90 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 65.9 - **Spread:** - **Upper Limit:** 82.7 - **Value:** 75 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 68.4 - **Spread:** - **Upper Limit:** 84.5 - **Value:** 77 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 57.4 - **Spread:** - **Upper Limit:** 75.6 - **Value:** 67 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 69.4 - **Spread:** - **Upper Limit:** 85.3 - **Value:** 78 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 15 - **Spread:** - **Upper Limit:** 31.2 - **Value:** 22 **Title:** #### Outcome Measure 9 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 34 - **Spread:** - **Upper Limit:** 62 - **Value:** 46 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 8.12 - **Spread:** - **Upper Limit:** 15 - **Value:** 11 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 16 - **Spread:** - **Upper Limit:** 28 - **Value:** 21 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 6.26 - **Spread:** - **Upper Limit:** 11 - **Value:** 8.39 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 8.25 - **Spread:** - **Upper Limit:** 13 - **Value:** 10 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 1.84 - **Spread:** - **Upper Limit:** 2.87 - **Value:** 2.30 **Title:** #### Outcome Measure 10 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 23.4 - **Spread:** - **Upper Limit:** 41.3 - **Value:** 32 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 24.4 - **Spread:** - **Upper Limit:** 42.6 - **Value:** 33 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 95.2 - **Spread:** - **Upper Limit:** 99.98 - **Value:** 99 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 81 - **Spread:** - **Upper Limit:** 93.7 - **Value:** 88 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 11.9 - **Spread:** - **Upper Limit:** 27 - **Value:** 19 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 12.7 - **Spread:** - **Upper Limit:** 28.2 - **Value:** 20 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 90.1 - **Spread:** - **Upper Limit:** 98.6 - **Value:** 96 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 58.4 - **Spread:** - **Upper Limit:** 76.4 - **Value:** 68 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 1.5 - **Spread:** - **Upper Limit:** 10 - **Value:** 4 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 3.1 - **Spread:** - **Upper Limit:** 13.6 - **Value:** 7 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 69.4 - **Spread:** - **Upper Limit:** 85.3 - **Value:** 78 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 27.7 - **Spread:** - **Upper Limit:** 46.2 - **Value:** 37 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 46.5 - **Spread:** - **Upper Limit:** 65.4 - **Value:** 56 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 48.3 - **Spread:** - **Upper Limit:** 67.3 - **Value:** 58 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 96.8 - **Spread:** - **Upper Limit:** 100 - **Value:** 100 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 92.4 - **Spread:** - **Upper Limit:** 99.4 - **Value:** 97 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 34.6 - **Spread:** - **Upper Limit:** 53.5 - **Value:** 44 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 34.4 - **Spread:** - **Upper Limit:** 53.4 - **Value:** 44 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 95.2 - **Spread:** - **Upper Limit:** 99.98 - **Value:** 99 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 75.8 - **Spread:** - **Upper Limit:** 90.2 - **Value:** 84 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 24.8 - **Spread:** - **Upper Limit:** 42.8 - **Value:** 33 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 22 - **Spread:** - **Upper Limit:** 39.8 - **Value:** 30 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 78.2 - **Spread:** - **Upper Limit:** 91.8 - **Value:** 86 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 51 - **Spread:** - **Upper Limit:** 69.8 - **Value:** 61 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 4.3 - **Spread:** - **Upper Limit:** 15.5 - **Value:** 9 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 4.4 - **Spread:** - **Upper Limit:** 15.8 - **Value:** 9 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 76.2 - **Spread:** - **Upper Limit:** 90.4 - **Value:** 84 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 23.6 - **Spread:** - **Upper Limit:** 41.6 - **Value:** 32 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0.21 - **Spread:** - **Upper Limit:** 6.2 - **Value:** 2 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 0.02 - **Spread:** - **Upper Limit:** 4.9 - **Value:** 1 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 33.7 - **Spread:** - **Upper Limit:** 52.6 - **Value:** 43 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 2.5 - **Spread:** - **Upper Limit:** 12.5 - **Value:** 6 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 3.2 - **Value:** 0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 3.2 - **Value:** 0 **Title:** **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 3.7 - **Spread:** - **Upper Limit:** 14.5 - **Value:** 8 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 3.2 - **Value:** 0 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** Number of naive subjects 6 to \< 36 months old reporting solicited local and systemic AEs from Day 1 to Day 7 after first vaccination and from Day 29 to Day 35 after second vaccination. **Parameter Type:** NUMBER **Population Description:** Analysis performed on the Solicited Safety Set. **Reporting Status:** POSTED **Time Frame:** From Day 1 to Day 7 by vaccination **Title:** Number of Naive Subjects 6 to < 36 Months Old Reporting Solicited Local and Systemic Adverse Events (AEs) From Day 1 to Day 7 Following Each Vaccination. **Type:** PRIMARY **Unit of Measure:** Participants ##### Group **Description:** A 0.25 mL (for children 6 to \<36 months old) dose of aTIV to be administered. **ID:** OG000 **Title:** Naive_aTIV (6 to <36 Months) ##### Group **Description:** A 0.25 mL (for children 6 to \<36 months old) dose of TIV to be administered. **ID:** OG001 **Title:** Naive_TIV (6 to <36 Months) #### Outcome Measure 2 **Description:** Number of non-naive subjects 6 to \< 36 months old reporting solicited local and systemic AEs from Day 1 to Day 7 after vaccination. **Parameter Type:** NUMBER **Population Description:** Analysis performed on the Solicited Safety Set. **Reporting Status:** POSTED **Time Frame:** From Day 1 to Day 7 **Title:** Number of Non-naive Subjects 6 to < 36 Months Old Reporting Solicited Local and Systemic AEs From Day 1 to Day 7 After Vaccination. **Type:** PRIMARY **Unit of Measure:** Participants ##### Group **Description:** A 0.25 mL (for children 6 to \<36 months old) dose of aTIV to be administered. **ID:** OG000 **Title:** Non-naive_aTIV (6 to <36 Months) ##### Group **Description:** A 0.25 mL (for children 6 to \<36 months old) dose of TIV to be administered. **ID:** OG001 **Title:** Non-naive_TIV (6 to <36 Months) #### Outcome Measure 3 **Description:** Number of naive subjects ≥ 36 months to \< 72 months old reporting solicited local and systemic AEs from Day 1 to Day 7 after first vaccination and from Day 29 to Day 35 after second vaccination. **Parameter Type:** NUMBER **Population Description:** Analysis performed on the Solicited Safety Set. **Reporting Status:** POSTED **Time Frame:** From Day 1 to Day 7 by vaccination **Title:** Number of Naive Subjects ≥ 36 Months to < 72 Months Old Reporting Solicited Local and Systemic AEs From Day 1 to Day 7 Following Each Vaccination. **Type:** PRIMARY **Unit of Measure:** Participants ##### Group **Description:** A 0.5 mL (for children ≥36 months to \< 72 months old) dose of aTIV to be administered. **ID:** OG000 **Title:** Naive_aTIV (≥36 Months to < 72 Months) ##### Group **Description:** A 0.5 mL (for children ≥36 months to \< 72 months old) dose of TIV to be administered. **ID:** OG001 **Title:** Naive_TIV (≥36 Months to < 72 Months) #### Outcome Measure 4 **Description:** Number of non-naive subjects ≥36 months to \< 72 months old reporting solicited local and systemic AEs from Day 1 to Day 7 after vaccination. **Parameter Type:** NUMBER **Population Description:** Analysis performed on the Solicited Safety Set. **Reporting Status:** POSTED **Time Frame:** From Day 1 to Day 7 **Title:** Number of Non-naive Subjects ≥36 Months to < 72 Months Old Reporting Solicited Local and Systemic AEs From Day 1 to Day 7 Following Each Vaccination. **Type:** PRIMARY **Unit of Measure:** Participants ##### Group **Description:** A 0.5 mL (for children ≥36 months to \< 72 months old) dose of aTIV to be administered. **ID:** OG000 **Title:** Non-naive_aTIV (≥36 Months to < 72 Months) ##### Group **Description:** A 0.5 mL (for children ≥36 months to \< 72 months old) dose of TIV to be administered. **ID:** OG001 **Title:** Non-naive_TIV (≥36 Months to < 72 Months) #### Outcome Measure 5 **Description:** Number of naive subjects aged 6 to \< 72 months reporting all unsolicited AEs, medically attended AEs, AE leading to study withdrawal and serious AEs (SAEs) from Day 1 to Day 50. **Parameter Type:** NUMBER **Population Description:** Analysis performed on the Unsolicited Safety Set. **Reporting Status:** POSTED **Time Frame:** From Day 1 to Day 50 **Title:** Number of Naive Subjects Aged 6 to < 72 Months Reporting All Unsolicited AEs From Day 1 to Day 50. **Type:** PRIMARY **Unit of Measure:** Participants ##### Group **Description:** A 0.25 mL (for children 6 to \<36 months old) and 0.5 mL (for children ≥36 months to \< 72 months old) dose of aTIV to be administered. **ID:** OG000 **Title:** Naive_aTIV (6 Months to < 72 Months) ##### Group **Description:** A 0.25 mL (for children 6 to \<36 months old) and 0.5 mL (for children ≥36 months to \< 72 months old) dose of TIV to be administered. **ID:** OG001 **Title:** Naive_TIV (6 Months to < 72 Months) #### Outcome Measure 6 **Description:** Number of non-naive subjects aged 6 to \< 72 months reporting all unsolicited AEs, medically attended AEs, AE leading to study withdrawal and SAEs from Day 1 to Day 22. **Parameter Type:** NUMBER **Population Description:** Analysis performed on the Unsolicited Safety Set. **Reporting Status:** POSTED **Time Frame:** From Day 1 to Day 22 **Title:** Number of Non-naive Subjects Aged 6 to < 72 Months Reporting All Unsolicited AEs From Day 1 to Day 22 **Type:** PRIMARY **Unit of Measure:** Participants ##### Group **Description:** A 0.25 mL (for children 6 to \<36 months old) and 0.5 mL (for children ≥36 months to \< 72 months old) dose of aTIV to be administered. **ID:** OG000 **Title:** Non naive_aTIV (6 Months to < 72 Months) ##### Group **Description:** A 0.25 mL (for children 6 to \<36 months old) and 0.5 mL (for children ≥36 months to \< 72 months old) dose of TIV to be administered. **ID:** OG001 **Title:** Non naive_TIV (6 Months to < 72 Months) #### Outcome Measure 7 **Description:** Antibody response was assessed in terms of GMTs in all three homologous virus strains, 21 days after last immunization, in subjects 6 to \<72 months of age. The study is considered a success if the 21 days after last immunization GMT ratios of aTIV relative to TIV demonstrate as non-inferior with the lower limit (LL) of the two sided 95% confidence interval (CI) above 0.67 (-0.176 on log10 scale) for each vaccine strain (Center for Biologics Evaluation and Research {CBER} Guideline on Seasonal Vaccines May 2007). **Dispersion Type:** 95% Confidence Interval **Parameter Type:** GEOMETRIC_MEAN **Population Description:** Analysis performed on the Per Protocol Set. **Reporting Status:** POSTED **Time Frame:** Day 1 and Day 22 (vaccine non-naïve subjects) or Day 50 (vaccine naïve subjects) post vaccination **Title:** Geometric Mean Titers (GMTs), in All Three Homologous Virus Strains in Subjects 6 to < 72 Months of Age. **Type:** PRIMARY **Unit of Measure:** Titers ##### Group **Description:** A 0.25 mL (for children 6 to \<36 months old) and 0.5 mL (for children ≥36 months to \< 72 months old) dose of aTIV to be administered. **ID:** OG000 **Title:** aTIV (6 Months to < 72 Months) ##### Group **Description:** A 0.25 mL (for children 6 to \<36 months old) and 0.5 mL (for children ≥36 months to \< 72 months old) dose of TIV to be administered. **ID:** OG001 **Title:** TIV (6 Months to < 72 Months) #### Outcome Measure 8 **Description:** Percentages of subjects with seroconversion in all three homologous virus strains, 21 days after last immunization, in subjects 6 to \<72 months of age, defined as: HI ≥ 40 subject with a pre-vaccination HI titer \<10; a minimum 4-fold increase HI titer for subjects with a prevaccination HI titer ≥10, on Day 22 (non-naive subjects) or Day 50 (naive subjects), as applicable. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** NUMBER **Population Description:** Analysis performed on the Per Protocol Set. **Reporting Status:** POSTED **Time Frame:** Day 1 and Day 22 (vaccine non-naive subjects) or Day 50 (vaccine naive subjects) post vaccination **Title:** Percentages of Subjects Achieving Seroconversion in Hemagglutination Inhibition (HI) Titers and Vaccine Group Differences at Day 1 and 21 Days After Last Vaccination With aTIV or TIV in Naive and Non-naive Subjects. **Type:** SECONDARY **Unit of Measure:** Percentages of subjects ##### Group **Description:** A 0.25 mL (for children 6 to \<36 months old) and 0.5 mL (for children ≥36 months to \< 72 months old) dose of aTIV to be administered. **ID:** OG000 **Title:** aTIV (6 Months to < 72 Months) ##### Group **Description:** A 0.25 mL (for children 6 to \<36 months old) and 0.5 mL (for children ≥36 months to \< 72 months old) dose of TIV to be administered. **ID:** OG001 **Title:** TIV (6 Months to < 72 Months) #### Outcome Measure 9 **Description:** GMRs of HI, day 22/day 1 (non-naive subjects) or day 50/day 1 (naive subjects) in all three homologous virus strains, 21 days after last immunization, in subjects 6 to \<72 months of age. As the non-inferiority of aTIV to TIV has been established, GMT ratio of aTIV relative to TIV in all three homologous virus strains, 21 days after last immunization in subjects 6 to \<72 months of age was evaluated using margins greater than the non-inferiority cut-off of 0.67. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** GEOMETRIC_MEAN **Population Description:** Analysis performed on the Per Protocol Set. **Reporting Status:** POSTED **Time Frame:** Day 1 and Day 22 (vaccine non-naive subjects) or Day 50 (vaccine naive subjects) post vaccination **Title:** Geometric Mean Ratios (GMRs) of HI and Vaccine Group Differences at Day 1 and 21 Days After Last Vaccination With aTIV or TIV in Naive and Non-naive Subjects. **Type:** SECONDARY **Unit of Measure:** Ratios ##### Group **Description:** A 0.25 mL (for children 6 to \<36 months old) and 0.5 mL (for children ≥36 months to \< 72 months old) dose of aTIV to be administered. **ID:** OG000 **Title:** aTIV (6 Months to < 72 Months) ##### Group **Description:** A 0.25 mL (for children 6 to \<36 months old) and 0.5 mL (for children ≥36 months to \< 72 months old) dose of TIV to be administered. **ID:** OG001 **Title:** TIV (6 Months to < 72 Months) #### Outcome Measure 10 **Description:** Percentage of subjects with a HI titer ≥ 40, ≥110 and ≥330 on Day 1, Day 22 (non naïve subjects) or Day 50 (naïve subjects), in all three homologous virus strains, 21 days after last immunization, in subjects 6 to \<72 months of age. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** NUMBER **Population Description:** Analysis performed on the Per Protocol Set. **Reporting Status:** POSTED **Time Frame:** Day 1 and Day 22 (vaccine non-naive subjects) or Day 50 (vaccine naive subjects) post vaccination **Title:** Percentages of Subjects With a HI Titer ≥ 40, ≥110 and ≥330 and Vaccine Group Differences at Day 1 and 21 Days After Last Vaccination With aTIV or TIV in Naive and Non-naive Subjects. **Type:** SECONDARY **Unit of Measure:** Percentage of subjects ##### Group **Description:** A 0.25 mL (for children 6 to \<36 months old) and 0.5 mL (for children ≥36 months to \< 72 months old) dose of aTIV to be administered. **ID:** OG000 **Title:** aTIV (6 Months to < 72 Months) ##### Group **Description:** A 0.25 mL (for children 6 to \<36 months old) and 0.5 mL (for children ≥36 months to \< 72 months old) dose of TIV to be administered. **ID:** OG001 **Title:** TIV (6 Months to < 72 Months) ### Participant Flow Module #### Group **Description:** A 0.25 mL (for children 6 to \<36 months old) and 0.5 mL (for children ≥36 months to \< 72 months old) dose of aTIV to be administered. **ID:** FG000 **Title:** aTIV (6 Months to < 72 Months) #### Group **Description:** A 0.25 mL (for children 6 to \<36 months old) and 0.5 mL (for children ≥36 months to \< 72 months old) dose of TIV to be administered. **ID:** FG001 **Title:** TIV (6 Months to < 72 Months) #### Period **Title:** Overall Study ##### Withdraw **Type:** Lost to Follow-up ###### Reason **Group ID:** FG000 **Number of Subjects:** 2 ###### Reason **Group ID:** FG001 **Number of Subjects:** 2 ##### Withdraw **Type:** Protocol Violation ###### Reason **Group ID:** FG000 **Number of Subjects:** 0 ###### Reason **Group ID:** FG001 **Number of Subjects:** 1 ##### Withdraw **Type:** Withdrawal by Subject ###### Reason **Group ID:** FG000 **Number of Subjects:** 3 ###### Reason **Group ID:** FG001 **Number of Subjects:** 6 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 144 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 143 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 139 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 134 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 5 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 9 **Pre-Assignment Details:** All enrolled subjects were included in study. **Recruitment Details:** Subjects were enrolled from 3 study centers in Mexico. **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT00835679 **Brief Title:** Cetuximab and/or Dasatinib in Patients With Colorectal Cancer and Liver Metastases That Can Be Removed by Surgery **Official Title:** A Preoperative Biological Trial of Cetuximab, Dasatinib or the Combination in Colorectal Cancer Patients With Resectable Liver Metastases #### Organization Study ID Info **ID:** NCI-2013-00014 #### Organization **Class:** NIH **Full Name:** National Cancer Institute (NCI) #### Secondary ID Infos **Domain:** CTRP (Clinical Trial Reporting Program) **ID:** NCI-2013-00014 **Type:** REGISTRY **ID:** VU-VICC-GI-0838 **ID:** 8069 **ID:** P30CA068485 **Link:** https://reporter.nih.gov/quickSearch/P30CA068485 **Type:** NIH **ID:** 081338 **Domain:** Vanderbilt-Ingram Cancer Center **ID:** VICC GI 0838 **Type:** OTHER **Domain:** CTEP **ID:** 8069 **Type:** OTHER ### Status Module #### Completion Date **Date:** 2011-08 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2014-05-23 **Type:** ESTIMATED **Last Update Submit Date:** 2014-05-07 **Overall Status:** TERMINATED #### Primary Completion Date **Date:** 2011-02 **Type:** ACTUAL #### Results First Post Date **Date:** 2012-09-07 **Type:** ESTIMATED **Results First Submit Date:** 2012-03-12 **Results First Submit QC Date:** 2012-08-07 #### Start Date **Date:** 2009-12 **Status Verified Date:** 2013-01 #### Study First Post Date **Date:** 2009-02-04 **Type:** ESTIMATED **Study First Submit Date:** 2009-02-03 **Study First Submit QC Date:** 2009-02-03 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** NIH **Name:** National Cancer Institute (NCI) #### Responsible Party **Type:** SPONSOR ### Description Module **Brief Summary:** This phase 0 trial is studying whether 2 weeks of cetuximab and dasatinib will change tumor cells in patients with colorectal cancer and liver metastases that can be removed by surgery. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Dasatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. **Detailed Description:** PRIMARY OBJECTIVES: I. To evaluate the biological effects of cetuximab, dasatinib, or the combination on epidermal growth factor receptor (EGFR)- and Src-signaling pathways in resected colorectal cancer liver metastases. OUTLINE: This is a multicenter study. Patients are initially enrolled in cohort A. Once cohort A is completed, additional patients are enrolled and randomized to treatment in either cohorts B or C. If a significant biological effect is seen in cohorts B or C, additional patients are enrolled in cohort D. COHORT A: Patients receive no systemic neoadjuvant therapy between enrollment and the time of definitive surgical resection of liver metastases. Liver biopsies were performed at surgery since this cohort received no systemic therapy. COHORT B: Patients receive 400 mg/m2 cetuximab intravenously (IV) over 120 minutes on day 1 and 250 mg/m\^2 cetuximab IV over 60-120 minutes on day 8. Definitive surgical resection of liver metastases will take place on day 15. COHORT C: Patients receive dasatinib 100 mg orally once daily on days 1-14. Definitive surgical resection of liver metastases will take place on day 15. COHORT D: Patients receive 400 mg/m\^2 cetuximab IV over 120 minutes on day 1 and 250 mg/m\^2 cetuximab IV over 60-120 minutes on day 8 AND dasatinib 100 mg orally once daily on days 1-14. Definitive surgical resection of liver metastases will take place on day 15. Patients undergo tumor tissue (from initial liver tumor biopsies and liver resection samples), serum, and peripheral blood mononuclear cell sample collection periodically for biomarker analysis via immunohistochemistry (IHC). ### Conditions Module **Conditions:** - Liver Metastases - Mucinous Adenocarcinoma of the Colon - Mucinous Adenocarcinoma of the Rectum - Recurrent Colon Cancer - Recurrent Rectal Cancer - Signet Ring Adenocarcinoma of the Colon - Signet Ring Adenocarcinoma of the Rectum - Stage IV Colon Cancer - Stage IV Rectal Cancer ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** BASIC_SCIENCE #### Enrollment Info **Count:** 9 **Type:** ACTUAL **Phases:** - EARLY_PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Patients receive no systemic neoadjuvant therapy between enrollment and the time of definitive surgical resection of liver metastases. Liver biopsies were performed at surgery since this cohort received no systemic therapy. **Intervention Names:** - Procedure: therapeutic conventional surgery - Other: laboratory biomarker analysis **Label:** Cohort A (no systemic neoadjuvant therapy) **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Patients receive 400 mg/m\^2 cetuximab IV over 120 minutes on day 1 and 250 mg/m\^2 cetuximab IV over 60-120 minutes on day 8. Definitive surgical resection of liver metastases will take place on day 15. **Intervention Names:** - Biological: cetuximab - Procedure: therapeutic conventional surgery - Other: laboratory biomarker analysis **Label:** Cohort B (cetuximab) **Type:** EXPERIMENTAL #### Arm Group 3 **Description:** Patients receive dasatinib 100 mg orally once daily on days 1-14. Definitive surgical resection of liver metastases will take place on day 15. **Intervention Names:** - Drug: dasatinib - Procedure: therapeutic conventional surgery - Other: laboratory biomarker analysis **Label:** Cohort C (dasatinib) **Type:** EXPERIMENTAL #### Arm Group 4 **Description:** Patients receive 400 mg/m\^2 cetuximab IV over 120 minutes on day 1 and 250 mg/m\^2 cetuximab IV over 60-120 minutes on day 8 AND dasatinib 100 mg orally once daily on days 1-14. Definitive surgical resection of liver metastases will take place on day 15. **Intervention Names:** - Biological: cetuximab - Drug: dasatinib - Procedure: therapeutic conventional surgery - Other: laboratory biomarker analysis **Label:** Cohort D (cetuximab, dasatinib) **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Cohort B (cetuximab) - Cohort D (cetuximab, dasatinib) **Description:** Given IV **Name:** cetuximab **Other Names:** - C225 - C225 monoclonal antibody - IMC-C225 - MOAB C225 - monoclonal antibody C225 **Type:** BIOLOGICAL #### Intervention 2 **Arm Group Labels:** - Cohort C (dasatinib) - Cohort D (cetuximab, dasatinib) **Description:** Given orally **Name:** dasatinib **Other Names:** - BMS-354825 - Sprycel **Type:** DRUG #### Intervention 3 **Arm Group Labels:** - Cohort A (no systemic neoadjuvant therapy) - Cohort B (cetuximab) - Cohort C (dasatinib) - Cohort D (cetuximab, dasatinib) **Description:** Undergo surgery **Name:** therapeutic conventional surgery **Type:** PROCEDURE #### Intervention 4 **Arm Group Labels:** - Cohort A (no systemic neoadjuvant therapy) - Cohort B (cetuximab) - Cohort C (dasatinib) - Cohort D (cetuximab, dasatinib) **Description:** Correlative studies **Name:** laboratory biomarker analysis **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** Patients who experienced a pre-to-post treatment reduction of at least 1 scoring level from baseline on preoperative-day 15 in at least 1 biomarker of the pathway being inhibited: epidermal growth factor (EGFR) for Cohort B, sarcoma (Src) for Cohort C, and both EGFR and Src for Cohort D. Blood for these biomarkers will be taken on day of baseline and pre-operatively on day 15. Determined by 0-4-scale scoring with score determined by percentage of tumor cells positively stained for pathway in question: minimum 0 (0%), 1 (1-24%), 2 (25-49%), 3 (50-74%), and maximum 4 (75-100%). **Measure:** Patients With a Biologic Response **Time Frame:** on baseline and preoperatively on day of surgery (day 15) #### Secondary Outcomes **Description:** Patients with pre-to-post treatment reduction at least 1 scoring level from baseline on preoperative-day 15 in at least 1 biomarker: total \& phi-EGFR, phi-MAPK, phi-Akt, Ki67, phi-FAK, phi-paxillin, phi-Src, capase 3. Determined by 0-4-scale scoring with score determined by percentage of tumor cells positively stained for biomarker in question: minimum 0 (0%), 1 (1-24%), 2 (25-49%), 3 (50-74%), and maximum 4 (75-100%) **Measure:** Patients With Reduction of Biomarkers in Tumor Tissue **Time Frame:** study entry to day 15 **Description:** Number of patients with each grade of adverse event (AE) during the specified timeframe using the Common Terminology Criteria for AEs guide, grades 1-5 with one being mild, five is death. **Measure:** Number of Patients With the Given Severity of Adverse Event Within a Specified Duration **Time Frame:** weekly to day 15, and at followup on day 30 **Measure:** Number of Patients With the Given Severity of Post-operative Complications Within the Specified Duration **Time Frame:** From day 15 (day of surgery) to 30 days after surgery ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Patients must have histologically confirmed adenocarcinoma arising from the large intestine that has metastasized to the liver; liver metastases may be synchronous or metachronous * The liver metastases must be considered surgically resectable prior to the initiation of study drugs * Prior chemotherapy or chemoradiotherapy for colorectal cancer is allowed provided that toxicities from prior therapy have resolved to Grade 1 or less; no prior anti-EGFR or anti-Src therapy is allowed * Eastern Cooperative Oncology Group (ECOG) performance status =\< 1 (Karnofsky \>= 70%) * Absolute neutrophil count \>= 1.5 x 10\^9/L * Hemoglobin ≥ 9.0 Gm/dL * Platelets \>= 100 x 10\^9/L * Total bilirubin ≤ 1.5 x institutional upper limit of normal (IULN) * Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\])/alanine transaminase (ALT)(serum glutamic pyruvic transaminase \[SGPT\]) =\< 5 x institutional upper limit of normal * Creatinine =\< 1.5 institutional ULN * Women must have a negative pregnancy test; 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 and for the duration of study participation; 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 * Although KRAS status will be evaluated in the tumor, wild type KRAS status is not an eligibility criterion Exclusion Criteria: * Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier * Patients receiving any other investigational agents * History of allergic reactions attributed to compounds of similar chemical or biologic composition to cetuximab or dasatinib * Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements * Pregnant women are excluded from this study because of the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with cetuximab or dasatinib, breastfeeding should be discontinued if the mother is treated with cetuximab or dasatinib * Patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy; therefore, HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with cetuximab or dasatinib; appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated * Patients on potent CYP3A4 inducers and inhibitors **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 **Location 2:** **City:** Nashville **Country:** United States **Facility:** Vanderbilt-Ingram Cancer Center **State:** Tennessee **Zip:** 37232 #### Overall Officials **Official 1:** **Affiliation:** Vanderbilt-Ingram Cancer Center **Name:** Emily Chan **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000020969 - Term: Disease Attributes - ID: D000010335 - Term: Pathologic Processes - ID: D000015179 - Term: Colorectal Neoplasms - 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: D000002277 - Term: Carcinoma - ID: D000009375 - Term: Neoplasms, Glandular and Epithelial - ID: D000009370 - Term: Neoplasms by Histologic Type - ID: D000009385 - Term: Neoplastic Processes - ID: D000008107 - Term: Liver Diseases - ID: D000018297 - Term: Neoplasms, Cystic, Mucinous, and Serous ### 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 - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M12307 - Name: Neoplasm Metastasis - Relevance: HIGH - As Found: Metastases - ID: M3585 - Name: Adenocarcinoma - Relevance: HIGH - As Found: Adenocarcinoma - ID: M14850 - Name: Recurrence - Relevance: HIGH - As Found: Recurrent - ID: M5545 - Name: Adenocarcinoma, Mucinous - Relevance: HIGH - As Found: Mucinous Adenocarcinoma - ID: M6741 - Name: Cystadenocarcinoma - Relevance: HIGH - As Found: Mucinous Adenocarcinoma - ID: M14846 - Name: Rectal Neoplasms - Relevance: HIGH - As Found: Rectal Cancer - ID: M6338 - Name: Colonic Neoplasms - Relevance: HIGH - As Found: Colon Cancer - ID: M11113 - Name: Liver Neoplasms - Relevance: HIGH - As Found: Liver Metastases - ID: M22700 - Name: Disease Attributes - Relevance: LOW - As Found: Unknown - ID: M17890 - Name: Colorectal Neoplasms - Relevance: LOW - As Found: Unknown - 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: M5534 - Name: Carcinoma - 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: M12330 - Name: Neoplastic Processes - Relevance: LOW - As Found: Unknown - ID: M11107 - Name: Liver Diseases - Relevance: LOW - As Found: Unknown - ID: M20441 - Name: Neoplasms, Cystic, Mucinous, and Serous - Relevance: LOW - As Found: Unknown - ID: T200 - Name: Adenocarcinoma of the Appendix - Relevance: HIGH - As Found: Mucinous Adenocarcinoma ### Condition Browse Module - Meshes - ID: D000000230 - Term: Adenocarcinoma - ID: D000009362 - Term: Neoplasm Metastasis - ID: D000012004 - Term: Rectal Neoplasms - ID: D000003110 - Term: Colonic Neoplasms - ID: D000008113 - Term: Liver Neoplasms - ID: D000002288 - Term: Adenocarcinoma, Mucinous - ID: D000003536 - Term: Cystadenocarcinoma - ID: D000012008 - Term: Recurrence ### Intervention Browse Module - Ancestors - ID: D000007155 - Term: Immunologic Factors - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000000970 - Term: Antineoplastic Agents - ID: D000092004 - Term: Tyrosine Kinase Inhibitors - ID: D000047428 - Term: Protein Kinase 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: Hemat - Name: Hematinics - Abbrev: AA - Name: Amino Acids ### Intervention Browse Module - Browse Leaves - ID: M315 - Name: Cetuximab - Relevance: HIGH - As Found: Appointment - ID: M4225 - Name: Antibodies - Relevance: HIGH - As Found: Program - ID: M4230 - Name: Antibodies, Monoclonal - Relevance: HIGH - As Found: Chemotherapy - ID: M10184 - Name: Immunoglobulins - Relevance: HIGH - As Found: Program - ID: M11110 - Name: Liver Extracts - Relevance: LOW - As Found: Unknown - ID: M410 - Name: Dasatinib - Relevance: HIGH - As Found: Web- - ID: M1346 - Name: Antineoplastic Agents, Immunological - Relevance: HIGH - As Found: Chemotherapy - ID: M19117 - Name: Immunoglobulins, Intravenous - Relevance: LOW - As Found: Unknown - ID: M10201 - Name: Immunologic Factors - Relevance: LOW - As Found: Unknown - ID: M2889 - Name: Tyrosine Kinase 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 - ID: T22 - Name: Tyrosine - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000074322 - Term: Antineoplastic Agents, Immunological - ID: D000068818 - Term: Cetuximab - ID: D000069439 - Term: Dasatinib - ID: D000000906 - Term: Antibodies - ID: D000007136 - Term: Immunoglobulins - ID: D000000911 - Term: Antibodies, Monoclonal ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module #### Event Groups **Group ID:** EG000 **Title:** No Treatment Cohort A **Description:** Patients receive no systemic neoadjuvant therapy between enrollment and the time of definitive surgical resection of liver metastases. Liver biopsies were performed at surgery since this cohort received no systemic therapy. **ID:** EG000 **Other Num at Risk:** 9 **Serious Number At Risk:** 9 **Title:** No Treatment Cohort A **Group ID:** EG001 **Title:** Cetuximab Cohort B **Description:** Patients receive 400 mg/m2 cetuximab intravenously (IV) over 120 minutes on day 1 and 250 mg/m2 cetuximab IV over 60-120 minutes on day 8. Definitive surgical resection of liver metastases will take place on day 15 **ID:** EG001 **Title:** Cetuximab Cohort B **Group ID:** EG002 **Title:** Dasatinib Cohort C **Description:** Patients receive dasatinib 100 mg orally once daily on days 1-14.Definitive surgical resection of liver metastases will take place on day 15 **ID:** EG002 **Title:** Dasatinib Cohort C **Group ID:** EG003 **Title:** Cetuximab + Dasatiib Cohort D **Description:** Patients receive 400 mg/m2 cetuximab intravenously (IV) over 120 minutes on day 1 and 250 mg/m2 cetuximab IV over 60-120 minutes on day 8 AND dasatinib 100 mg orally once daily on days 1-14. Definitive surgical resection of liver metastases will take place on day 15 **ID:** EG003 **Title:** Cetuximab + Dasatiib Cohort D **Frequency Threshold:** 5 ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 9 **Group ID:** BG001 **Value:** 0 **Group ID:** BG002 **Value:** 0 **Group ID:** BG003 **Value:** 0 **Group ID:** BG004 **Value:** 9 **Units:** Participants ### Group **ID:** BG000 **Title:** No Treatment Cohort A **Description:** Patients receive no systemic neoadjuvant therapy between enrollment and the time of definitive surgical resection of liver metastases. Liver biopsies were performed at surgery since this cohort received no systemic therapy. ### Group **ID:** BG001 **Title:** Cetuximab Cohort B **Description:** Patients receive 400 mg/m2 cetuximab intravenously (IV) over 120 minutes on day 1 and 250 mg/m2 cetuximab IV over 60-120 minutes on day 8. Definitive surgical resection of liver metastases will take place on day 15 ### Group **ID:** BG002 **Title:** Dasatinib Cohort C **Description:** Patients receive dasatinib 100 mg orally once daily on days 1-14.Definitive surgical resection of liver metastases will take place on day 15 ### Group **ID:** BG003 **Title:** Cetuximab + Dasatiib Cohort D **Description:** Patients receive 400 mg/m2 cetuximab intravenously (IV) over 120 minutes on day 1 and 250 mg/m2 cetuximab IV over 60-120 minutes on day 8 AND dasatinib 100 mg orally once daily on days 1-14. Definitive surgical resection of liver metastases will take place on day 15 ### Group **ID:** BG004 **Title:** Total **Description:** Total of all reporting groups ### Measure #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG004 **Value:** 0 **Class Title:** <=18 years #### Measurement **Group ID:** BG000 **Value:** 7 #### Measurement **Group ID:** BG004 **Value:** 7 **Class Title:** Between 18 and 65 years #### Measurement **Group ID:** BG000 **Value:** 2 #### Measurement **Group ID:** BG004 **Value:** 2 **Class Title:** >=65 years ### Measure #### Measurement **Group ID:** BG000 **Spread:** 1 **Value:** 58 #### Measurement **Group ID:** BG004 **Spread:** 1 **Value:** 58 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 5 #### Measurement **Group ID:** BG004 **Value:** 5 **Class Title:** Female #### Measurement **Group ID:** BG000 **Value:** 4 #### Measurement **Group ID:** BG004 **Value:** 4 **Class Title:** Male ### Measure #### Measurement **Group ID:** BG000 **Value:** 9 #### Measurement **Group ID:** BG004 **Value:** 9 **Class Title:** United States **Denomination Units Selected:** ## Results Section - Baseline Characteristics Module ### Measure 1 **Parameter Type:** NUMBER **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:** NUMBER **Title:** Gender **Unit of Measure:** participants ### Measure 4 **Parameter Type:** NUMBER **Title:** Region of Enrollment **Unit of Measure:** participants ## Results Section - More Information Module ### Certain Agreement **Restriction Type:** LTE60 **Restrictive Agreement:** True ### Limitations and Caveats **Description:** Due to study design and slow accrual, no drug was received, no biomarkers were determined and no data obtained. "0" data is entered in the outcomes measures database as suggested by CT.gov previously. Detailed explanations are given. ### Point of Contact **Email:** [email protected] **Organization:** Vanderbilt-Ingram Cancer Center **Phone:** 615-343-4677 **Title:** Emily Chan, 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 #### Outcome Measure 2 #### Outcome Measure 3 #### Outcome Measure 4 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** Patients who experienced a pre-to-post treatment reduction of at least 1 scoring level from baseline on preoperative-day 15 in at least 1 biomarker of the pathway being inhibited: epidermal growth factor (EGFR) for Cohort B, sarcoma (Src) for Cohort C, and both EGFR and Src for Cohort D. Blood for these biomarkers will be taken on day of baseline and pre-operatively on day 15. Determined by 0-4-scale scoring with score determined by percentage of tumor cells positively stained for pathway in question: minimum 0 (0%), 1 (1-24%), 2 (25-49%), 3 (50-74%), and maximum 4 (75-100%). **Population Description:** No patients accrued to Cohorts B, C, and D, who were to receive the study drugs. Nine patients were accrued in Cohort A; these patients received no study drugs and were to determine normal levels of selected biomarkers. No biomarkers were determined; no data available. This study was closed prematurely due to slow accrual. **Reporting Status:** POSTED **Time Frame:** on baseline and preoperatively on day of surgery (day 15) **Title:** Patients With a Biologic Response **Type:** PRIMARY ##### Group **Description:** Patients receive no systemic neoadjuvant therapy between enrollment and the time of definitive surgical resection of liver metastases. Liver biopsies were performed at surgery since this cohort received no systemic therapy. **ID:** OG000 **Title:** No Treatment Cohort A ##### Group **Description:** Patients receive 400 mg/m2 cetuximab intravenously (IV) over 120 minutes on day 1 and 250 mg/m2 cetuximab IV over 60-120 minutes on day 8. Definitive surgical resection of liver metastases will take place on day 15 **ID:** OG001 **Title:** Cetuximab Cohort B ##### Group **Description:** Patients receive dasatinib 100 mg orally once daily on days 1-14.Definitive surgical resection of liver metastases will take place on day 15 **ID:** OG002 **Title:** Dasatinib Cohort C ##### Group **Description:** Patients receive 400 mg/m2 cetuximab intravenously (IV) over 120 minutes on day 1 and 250 mg/m2 cetuximab IV over 60-120 minutes on day 8 AND dasatinib 100 mg orally once daily on days 1-14. Definitive surgical resection of liver metastases will take place on day 15 **ID:** OG003 **Title:** Cetuximab +Dasatinib Cohort D #### Outcome Measure 2 **Description:** Patients with pre-to-post treatment reduction at least 1 scoring level from baseline on preoperative-day 15 in at least 1 biomarker: total \& phi-EGFR, phi-MAPK, phi-Akt, Ki67, phi-FAK, phi-paxillin, phi-Src, capase 3. Determined by 0-4-scale scoring with score determined by percentage of tumor cells positively stained for biomarker in question: minimum 0 (0%), 1 (1-24%), 2 (25-49%), 3 (50-74%), and maximum 4 (75-100%) **Population Description:** No patients accrued to Cohorts B, C, and D, who were to receive the study drugs. Nine patients were accrued in Cohort A; these patients received no study drugs and were to determine normal levels of selected biomarkers. No biomarkers were determined; no data available. This study was closed prematurely due to slow accrual. **Reporting Status:** POSTED **Time Frame:** study entry to day 15 **Title:** Patients With Reduction of Biomarkers in Tumor Tissue **Type:** SECONDARY ##### Group **Description:** Patients receive no systemic neoadjuvant therapy between enrollment and the time of definitive surgical resection of liver metastases. Liver biopsies were performed at surgery since this cohort received no systemic therapy. **ID:** OG000 **Title:** No Treatment Cohort A ##### Group **Description:** Patients receive 400 mg/m2 cetuximab intravenously (IV) over 120 minutes on day 1 and 250 mg/m2 cetuximab IV over 60-120 minutes on day 8. Definitive surgical resection of liver metastases will take place on day 15 **ID:** OG001 **Title:** Cetuximab Cohort B ##### Group **Description:** Patients receive dasatinib 100 mg orally once daily on days 1-14.Definitive surgical resection of liver metastases will take place on day 15 **ID:** OG002 **Title:** Dasatinib Cohort C ##### Group **Description:** Patients receive 400 mg/m2 cetuximab intravenously (IV) over 120 minutes on day 1 and 250 mg/m2 cetuximab IV over 60-120 minutes on day 8 AND dasatinib 100 mg orally once daily on days 1-14. Definitive surgical resection of liver metastases will take place on day 15 **ID:** OG003 **Title:** Cetuximab + Dasatiib Cohort D #### Outcome Measure 3 **Description:** Number of patients with each grade of adverse event (AE) during the specified timeframe using the Common Terminology Criteria for AEs guide, grades 1-5 with one being mild, five is death. **Population Description:** No patients accrued to Cohorts B, C, and D, which were to receive the study drugs. Nine patients were accrued in Cohort A; these patients received no study drugs and were to determine normal levels of selected biomarkers. No patients were accrued to Cohorts B, C, D. This study was closed prematurely due to slow accrual. **Reporting Status:** POSTED **Time Frame:** weekly to day 15, and at followup on day 30 **Title:** Number of Patients With the Given Severity of Adverse Event Within a Specified Duration **Type:** SECONDARY ##### Group **Description:** Patients receive no systemic neoadjuvant therapy between enrollment and definitive surgical resection of liver metastases. Liver biopsies were performed at surgery since this cohort received no systemic therapy. **ID:** OG000 **Title:** No Treatment Cohort A ##### Group **Description:** Patients receive 400 mg/m2 cetuximab intravenously (IV) over 120 minutes on day 1 and 250 mg/m2 cetuximab IV over 60-120 minutes on day 8. Definitive surgical resection of liver metastases will take place on day 15 **ID:** OG001 **Title:** Cetuximab Cohort B ##### Group **Description:** Patients receive dasatinib 100 mg orally once daily on days 1-14.Definitive surgical resection of liver metastases will take place on day 15 1-14. **ID:** OG002 **Title:** Dasatinib Cohort C ##### Group **Description:** Patients receive 400 mg/m2 cetuximab intravenously (IV) over 120 minutes on day 1 and 250 mg/m2 cetuximab IV over 60-120 minutes on day 8 AND dasatinib 100 mg orally once daily on days 1-14. Definitive surgical resection of liver metastases will take place on day 15 **ID:** OG003 **Title:** Cetuximab + Dasatinib Cohort D #### Outcome Measure 4 **Population Description:** No patients accrued to Cohorts B, C, and D, which were to receive the study drugs. Nine patients were accrued in Cohort A; these patients received no study drugs and were to determine normal levels of selected biomarkers.No patients received any study drugs. This study was closed prematurely due to slow accrual. **Reporting Status:** POSTED **Time Frame:** From day 15 (day of surgery) to 30 days after surgery **Title:** Number of Patients With the Given Severity of Post-operative Complications Within the Specified Duration **Type:** SECONDARY ##### Group **Description:** Patients receive no systemic neoadjuvant therapy between enrollment and the time of definitive surgical resection of liver metastases. Liver biopsies were performed at surgery since this cohort received no systemic therapy. **ID:** OG000 **Title:** No Treatment Cohort A ##### Group **Description:** Patients receive 400 mg/m2 cetuximab intravenously (IV) over 120 minutes on day 1 and 250 mg/m2 cetuximab IV over 60-120 minutes on day 8. Definitive surgical resection of liver metastases will take place on day 15 **ID:** OG001 **Title:** Cetuximab Cohort B ##### Group **Description:** Patients receive dasatinib 100 mg orally once daily on days 1-14.Definitive surgical resection of liver metastases will take place on day 15 **ID:** OG002 **Title:** Dasatinib Cohort C ##### Group **Description:** Patients receive 400 mg/m2 cetuximab intravenously (IV) over 120 minutes on day 1 and 250 mg/m2 cetuximab IV over 60-120 minutes on day 8 AND dasatinib 100 mg orally once daily on days 1-14. Definitive surgical resection of liver metastases will take place on day 15 **ID:** OG003 **Title:** Cetuximab + Dasatiib Cohort D ### Participant Flow Module #### Group **Description:** Patients receive no systemic neoadjuvant therapy between enrollment and the time of definitive surgical resection of liver metastases. Liver biopsies were performed at surgery since this cohort received no systemic therapy. **ID:** FG000 **Title:** No Treatment Cohort A #### Group **Description:** Patients receive 400 mg/m2 cetuximab intravenously (IV) over 120 minutes on day 1 and 250 mg/m2 cetuximab IV over 60-120 minutes on day 8. Definitive surgical resection of liver metastases will take place on day 15 **ID:** FG001 **Title:** Cetuximab Cohort B #### Group **Description:** Patients receive dasatinib 100 mg orally once daily on days 1-14.Definitive surgical resection of liver metastases will take place on day 15 **ID:** FG002 **Title:** Dasatinib Cohort C #### Group **Description:** Patients receive 400 mg/m2 cetuximab intravenously (IV) over 120 minutes on day 1 and 250 mg/m2 cetuximab IV over 60-120 minutes on day 8 AND dasatinib 100 mg orally once daily on days 1-14. Definitive surgical resection of liver metastases will take place on day 15 **ID:** FG003 **Title:** Cetuximab + Dasatiib Cohort D #### Period **Title:** Overall Study ##### Withdraw **Type:** Withdrawal by Subject ###### Reason **Group ID:** FG000 **Number of Subjects:** 1 ###### Reason **Group ID:** FG001 **Number of Subjects:** 0 ###### Reason **Group ID:** FG002 **Number of Subjects:** 0 ###### Reason **Group ID:** FG003 **Number of Subjects:** 0 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 9 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG003 **Number of Subjects:** 0 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 8 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG003 **Number of Subjects:** 0 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 1 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG003 **Number of Subjects:** 0 **Pre-Assignment Details:** Eleven patients consented, with two ineligible. The study closed prematurely due to slow accrual. **Recruitment Details:** This study was open to accrual from December 2009 to August 2011. **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT00531479 **Brief Title:** Anidulafungin Plus Voriconazole Versus Voriconazole For The Treatment Of Invasive Aspergillosis **Official Title:** A Prospective, Randomized Trial Comparing The Efficacy Of Anidulafungin And Voriconazole In Combination To That Of Voriconazole Alone When Used For Primary Therapy Of Proven Or Probable Invasive Aspergillosis #### Organization Study ID Info **ID:** A8851009 #### Organization **Class:** INDUSTRY **Full Name:** Pfizer ### Status Module #### Completion Date **Date:** 2011-05 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2012-04-30 **Type:** ESTIMATED **Last Update Submit Date:** 2012-04-03 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2011-04 **Type:** ACTUAL #### Results First Post Date **Date:** 2012-04-30 **Type:** ESTIMATED **Results First Submit Date:** 2012-04-03 **Results First Submit QC Date:** 2012-04-03 #### Start Date **Date:** 2008-07 **Status Verified Date:** 2012-04 #### Study First Post Date **Date:** 2007-09-18 **Type:** ESTIMATED **Study First Submit Date:** 2007-09-14 **Study First Submit QC Date:** 2007-09-14 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Pfizer #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** This study compares the effectiveness and safety of the combination of anidulafungin and voriconazole compared to that of voriconazole alone (which is generally considered the standard of care) for the treatment of Invasive Aspergillosis. ### Conditions Module **Conditions:** - Aspergillosis ### 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:** 459 **Type:** ACTUAL **Phases:** - PHASE3 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Voriconazole monotherapy **Intervention Names:** - Drug: voriconazole **Label:** Voriconazole **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** Combination therapy with voriconazole and anidulafungin **Intervention Names:** - Drug: anidulafungin - Drug: voriconazole **Label:** Voriconazole and Anidulafungin **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Voriconazole **Description:** First week: Voriconazole 6 mg/kg IV bid for the first 24 hours, followed by 4 mg/kg IV BID plus anidulafungin placebo IV qd. Second week: Voriconazole 4 mg/kg IV bid or 300 mg PO bid plus anidulafungin placebo IV qd. Third and fourth weeks: Voriconazole 4 mg/kg IV bid OR 300 mg PO bid plus anidulafungin placebo IV qd, OR Voriconazole 4 mg/kg IV bid or 300 mg PO bid monotherapy. Fifth and sixth weeks: Voriconazole 4 mg/kg IV bid or 300 mg PO bid monotherapy. **Name:** voriconazole **Other Names:** - Vfend **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Voriconazole and Anidulafungin **Description:** First week: Voriconazole 6 mg/kg IV bid for the first 24 hours, followed by 4 mg/kg IV bid plus anidulafungin 200 mg IV on day 1, followed by 100 mg IV qd thereafter. Second week: Voriconazole 4 mg/kg IV bid or 300 mg PO bid plus anidulafungin 100 mg IV qd. Third and fourth weeks: Voriconazole 4 mg/kg IV bid OR 300 mg PO bid plus anidulafungin 100 mg IV qd, OR Voriconazole 4 mg/kg IV bid or 300 mg PO bid monotherapy. Fifth and sixth weeks: Voriconazole 4 mg/kg IV bid or 300 mg PO bid monotherapy. **Name:** anidulafungin **Other Names:** - Eraxis **Type:** DRUG #### Intervention 3 **Arm Group Labels:** - Voriconazole and Anidulafungin **Description:** First week: Voriconazole 6 mg/kg IV bid for the first 24 hours, followed by 4 mg/kg IV bid plus anidulafungin 200 mg IV on day 1, followed by 100 mg IV qd thereafter. Second week: Voriconazole 4 mg/kg IV bid or 300 mg PO bid plus anidulafungin 100 mg IV qd. Third and fourth weeks: Voriconazole 4 mg/kg IV bid OR 300 mg PO bid plus anidulafungin 100 mg IV qd, OR Voriconazole 4 mg/kg IV bid or 300 mg PO bid monotherapy. Fifth and sixth weeks: Voriconazole 4 mg/kg IV bid or 300 mg PO bid monotherapy. **Name:** voriconazole **Other Names:** - Vfend **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Number of deaths measured 6 weeks after start of treatment. Time to death defined as date of death minus first treatment date + 1. **Measure:** All-cause Mortality at Week 6 in Participants With Proven or Probable Invasive Aspergillosis **Time Frame:** Day 1 to Day 42 (Week 6) #### Secondary Outcomes **Description:** Number of participants with a successful response (complete or partial global response). Complete response = resolution of all clinical signs and symptoms and \>90% of lesions due to IA that were visible on radiologic studies at baseline (BL); partial response = clinical improvement and \>50% improvement in radiological findings present at BL. **Measure:** Global Response at Week 6 **Time Frame:** Baseline, Day 42 (Week 6) **Description:** Number of deaths due to any cause measured 6 weeks after start of treatment. Time to death defined as date of death minus first treatment date + 1. **Measure:** All-cause Mortality at Week 6 in Participants With Possible, Probable, or Proven Invasive Aspergillosis (IA) **Time Frame:** Day 1 to Day 42 (Week 6) **Description:** Number of deaths due to any cause measured 12 weeks after start of treatment. Time to death defined as date of death minus first treatment date + 1. **Measure:** All-cause Mortality at Week 12 in Participants With Probable or Proven Invasive Aspergillosis (IA) **Time Frame:** Day 1 to Day 84 (Week 12) **Description:** Number of deaths due to Invasive Aspergillosis measured 6 weeks after start of treatment. Time to death defined as date of death minus first treatment date + 1. **Measure:** Mortality Due to Invasive Aspergillosis (IA) at Week 6 in Participants With Probable or Proven IA **Time Frame:** Day 1 to Day 42 (Week 6) **Description:** Survival time from start of treatment. Time to death defined as date of death due to any cause minus first treatment date + 1. **Measure:** Time to Death: All-Cause Mortality **Time Frame:** Day 1 to Day 84 (Week 12) **Description:** Survival time from start of treatment. Time to death defined as date of death due to IA minus first treatment date + 1. **Measure:** Time to Death Due to Invasive Aspergillosis (IA) **Time Frame:** Day 1 to Day 84 (Week 12) ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Immunocompromised state due to either 1. receipt of hematopoeitic stem cell transplantation or 2. hematologic malignancy; * Diagnosis of possible, probable, or proven invasive aspergillosis. Exclusion Criteria: * Patients with aspergilloma or chronic aspergillosis * Receipt of 4 or more days of systemic antifungal treatment for the current episode of invasive aspergillosis * Anticipated survival of less than 5 days or Karnofsky score \<=20 **Minimum Age:** 16 Years **Sex:** ALL **Standard Ages:** - CHILD - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Birmingham **Country:** United States **Facility:** Pfizer Investigational Site **State:** Alabama **Zip:** 35233 **Location 2:** **City:** Birmingham **Country:** United States **Facility:** Pfizer Investigational Site **State:** Alabama **Zip:** 35249 **Location 3:** **City:** Little Rock **Country:** United States **Facility:** Pfizer Investigational Site **State:** Arkansas **Zip:** 72205 **Location 4:** **City:** La Jolla **Country:** United States **Facility:** Pfizer Investigational Site **State:** California **Zip:** 92037 **Location 5:** **City:** LaJolla **Country:** United States **Facility:** Pfizer Investigational Site **State:** California **Zip:** 92093 **Location 6:** **City:** San Diego **Country:** United States **Facility:** Pfizer Investigational Site **State:** California **Zip:** 92103-8976 **Location 7:** **City:** San Francisco **Country:** United States **Facility:** Pfizer Investigational Site **State:** California **Zip:** 94143 **Location 8:** **City:** Gainesville **Country:** United States **Facility:** Pfizer Investigational Site **State:** Florida **Zip:** 32610 **Location 9:** **City:** Miami **Country:** United States **Facility:** Pfizer Investigational Site **State:** Florida **Zip:** 33136 **Location 10:** **City:** Atlanta **Country:** United States **Facility:** Pfizer Investigational Site **State:** Georgia **Zip:** 30322 **Location 11:** **City:** Chicago **Country:** United States **Facility:** Pfizer Investigational Site **State:** Illinois **Zip:** 60612 **Location 12:** **City:** Chicago **Country:** United States **Facility:** Pfizer Investigational Site **State:** Illinois **Zip:** 60637 **Location 13:** **City:** Baltimore **Country:** United States **Facility:** Pfizer Investigational Site **State:** Maryland **Zip:** 21205 **Location 14:** **City:** Baltimore **Country:** United States **Facility:** Pfizer Investigational Site **State:** Maryland **Zip:** 21231-2410 **Location 15:** **City:** Baltimore **Country:** United States **Facility:** Pfizer Investigational Site **State:** Maryland **Zip:** 21231 **Location 16:** **City:** Baltimore **Country:** United States **Facility:** Pfizer Investigational Site **State:** Maryland **Zip:** 21287 **Location 17:** **City:** Detroit **Country:** United States **Facility:** Pfizer Investigational Site **State:** Michigan **Zip:** 48201 **Location 18:** **City:** Detroit **Country:** United States **Facility:** Pfizer Investigational Site **State:** Michigan **Zip:** 48202 **Location 19:** **City:** Rochester **Country:** United States **Facility:** Pfizer Investigational Site **State:** New York **Zip:** 14642 **Location 20:** **City:** Chapel Hill **Country:** United States **Facility:** Pfizer Investigational Site **State:** North Carolina **Zip:** 27514 **Location 21:** **City:** Winston-Salem **Country:** United States **Facility:** Pfizer Investigational Site **State:** North Carolina **Zip:** 27157 **Location 22:** **City:** Portland **Country:** United States **Facility:** Pfizer Investigational Site **State:** Oregon **Zip:** 97239 **Location 23:** **City:** Philadelphia **Country:** United States **Facility:** Pfizer Investigational Site **State:** Pennsylvania **Zip:** 19104 **Location 24:** **City:** Houston **Country:** United States **Facility:** Pfizer Investigational Site **State:** Texas **Zip:** 77030 **Location 25:** **City:** Seattle **Country:** United States **Facility:** Pfizer Investigational Site **State:** Washington **Zip:** 98109 **Location 26:** **City:** Seattle **Country:** United States **Facility:** Pfizer Investigational Site **State:** Washington **Zip:** 98195 **Location 27:** **City:** Westmead **Country:** Australia **Facility:** Pfizer Investigational Site **State:** New South Wales **Zip:** 2145 **Location 28:** **City:** Herston **Country:** Australia **Facility:** Pfizer Investigational Site **State:** Queensland **Zip:** 4029 **Location 29:** **City:** Adelaide **Country:** Australia **Facility:** Pfizer Investigational Site **State:** South Australia **Zip:** 5000 **Location 30:** **City:** Brugge **Country:** Belgium **Facility:** Pfizer Investigational Site **Zip:** 8000 **Location 31:** **City:** Bruxelles **Country:** Belgium **Facility:** Pfizer Investigational Site **Zip:** 1000 **Location 32:** **City:** Leuven **Country:** Belgium **Facility:** Pfizer Investigational Site **Zip:** 3000 **Location 33:** **City:** Yvoir **Country:** Belgium **Facility:** Pfizer Investigational Site **Zip:** B-5530 **Location 34:** **City:** Curitiba **Country:** Brazil **Facility:** Pfizer Investigational Site **State:** PR **Zip:** 80060-900 **Location 35:** **City:** Rio de Janeiro **Country:** Brazil **Facility:** Pfizer Investigational Site **State:** RJ **Zip:** 21941-913 **Location 36:** **City:** Porto Alegre **Country:** Brazil **Facility:** Pfizer Investigational Site **State:** RS **Zip:** 90020-090 **Location 37:** **City:** Winnipeg **Country:** Canada **Facility:** Pfizer Investigational Site **State:** Manitoba **Zip:** R3A 1R9 **Location 38:** **City:** Winnipeg **Country:** Canada **Facility:** Pfizer Investigational Site **State:** Manitoba **Zip:** R3E 0V9 **Location 39:** **City:** Hamilton **Country:** Canada **Facility:** Pfizer Investigational Site **State:** Ontario **Zip:** L8N 3Z5 **Location 40:** **City:** Hamilton **Country:** Canada **Facility:** Pfizer Investigational Site **State:** Ontario **Zip:** L8V 1C3 **Location 41:** **City:** Montreal **Country:** Canada **Facility:** Pfizer Investigational Site **State:** Quebec **Zip:** H1T 2M4 **Location 42:** **City:** Quebec **Country:** Canada **Facility:** Pfizer Investigational Site **Zip:** G1R 2J6 **Location 43:** **City:** Praha 2 **Country:** Czech Republic **Facility:** Pfizer Investigational Site **Zip:** 128 20 **Location 44:** **City:** Nantes **Country:** France **Facility:** Pfizer Investigational Site **State:** Cedex 01 **Zip:** 44093 **Location 45:** **City:** Marseille **Country:** France **Facility:** Pfizer Investigational Site **State:** Cedex 09 **Zip:** 13273 **Location 46:** **City:** Brest **Country:** France **Facility:** Pfizer Investigational Site **Zip:** 29609 **Location 47:** **City:** Creteil **Country:** France **Facility:** Pfizer Investigational Site **Zip:** 94010 **Location 48:** **City:** GRENOBLE Cedex 09 **Country:** France **Facility:** Pfizer Investigational Site **Zip:** 38043 **Location 49:** **City:** Paris **Country:** France **Facility:** Pfizer Investigational Site **Zip:** 75475 **Location 50:** **City:** Rouen Cedex **Country:** France **Facility:** Pfizer Investigational Site **Zip:** 76038 **Location 51:** **City:** Strasbourg **Country:** France **Facility:** Pfizer Investigational Site **Zip:** 67098 **Location 52:** **City:** Berlin **Country:** Germany **Facility:** Pfizer Investigational Site **Zip:** 10117 **Location 53:** **City:** Berlin **Country:** Germany **Facility:** Pfizer Investigational Site **Zip:** 12200 **Location 54:** **City:** Bremen **Country:** Germany **Facility:** Pfizer Investigational Site **Zip:** 28177 **Location 55:** **City:** Dresden **Country:** Germany **Facility:** Pfizer Investigational Site **Zip:** 01307 **Location 56:** **City:** Frankfurt (Oder) **Country:** Germany **Facility:** Pfizer Investigational Site **Zip:** 15236 **Location 57:** **City:** Hamburg **Country:** Germany **Facility:** Pfizer Investigational Site **Zip:** 20246 **Location 58:** **City:** Heidelberg **Country:** Germany **Facility:** Pfizer Investigational Site **Zip:** 69120 **Location 59:** **City:** Homburg/Saar **Country:** Germany **Facility:** Pfizer Investigational Site **Zip:** 66421 **Location 60:** **City:** Koeln **Country:** Germany **Facility:** Pfizer Investigational Site **Zip:** 50937 **Location 61:** **City:** Mainz **Country:** Germany **Facility:** Pfizer Investigational Site **Zip:** 55101 **Location 62:** **City:** Muenchen **Country:** Germany **Facility:** Pfizer Investigational Site **Zip:** 81737 **Location 63:** **City:** Wuerzburg **Country:** Germany **Facility:** Pfizer Investigational Site **Zip:** 97080 **Location 64:** **City:** Thessaloniki **Country:** Greece **Facility:** Pfizer Investigational Site **Zip:** 57010 **Location 65:** **City:** Pune **Country:** India **Facility:** Pfizer Investigational Site **State:** Maharashtra **Zip:** 411004 **Location 66:** **City:** Cuneo **Country:** Italy **Facility:** Pfizer Investigational Site **Zip:** 12100 **Location 67:** **City:** Genova **Country:** Italy **Facility:** Pfizer Investigational Site **Zip:** 16132 **Location 68:** **City:** Milano **Country:** Italy **Facility:** Pfizer Investigational Site **Zip:** 20132 **Location 69:** **City:** Milano **Country:** Italy **Facility:** Pfizer Investigational Site **Zip:** 20162 **Location 70:** **City:** Perugia **Country:** Italy **Facility:** Pfizer Investigational Site **Zip:** 06134 **Location 71:** **City:** Pescara **Country:** Italy **Facility:** Pfizer Investigational Site **Zip:** 65100 **Location 72:** **City:** Roma **Country:** Italy **Facility:** Pfizer Investigational Site **Zip:** 00168 **Location 73:** **City:** Seoul **Country:** Korea, Republic of **Facility:** Pfizer Investigational Site **Zip:** 110-744 **Location 74:** **City:** Seoul **Country:** Korea, Republic of **Facility:** Pfizer Investigational Site **Zip:** 120-752 **Location 75:** **City:** Seoul **Country:** Korea, Republic of **Facility:** Pfizer Investigational Site **Zip:** 135-710 **Location 76:** **City:** Seoul **Country:** Korea, Republic of **Facility:** Pfizer Investigational Site **Zip:** 138-736 **Location 77:** **City:** Seoul **Country:** Korea, Republic of **Facility:** Pfizer Investigational Site **Zip:** 150-713 **Location 78:** **City:** RC Leiden **Country:** Netherlands **Facility:** Pfizer Investigational Site **Zip:** NL-2300 **Location 79:** **City:** Lima **Country:** Peru **Facility:** Pfizer Investigational Site **Zip:** Lima 34 **Location 80:** **City:** Gdansk **Country:** Poland **Facility:** Pfizer Investigational Site **Zip:** 80-952 **Location 81:** **City:** Warszawa **Country:** Poland **Facility:** Pfizer Investigational Site **Zip:** 02-097 **Location 82:** **City:** Lisboa **Country:** Portugal **Facility:** Pfizer Investigational Site **Zip:** 1169-050 **Location 83:** **City:** Lisboa **Country:** Portugal **Facility:** Pfizer Investigational Site **Zip:** 1649-035 **Location 84:** **City:** Moscow **Country:** Russian Federation **Facility:** Pfizer Investigational Site **Zip:** 105229 **Location 85:** **City:** Moscow **Country:** Russian Federation **Facility:** Pfizer Investigational Site **Zip:** 115478 **Location 86:** **City:** Moscow **Country:** Russian Federation **Facility:** Pfizer Investigational Site **Zip:** 125167 **Location 87:** **City:** Saint Petersburg **Country:** Russian Federation **Facility:** Pfizer Investigational Site **Zip:** 197089 **Location 88:** **City:** Singapore **Country:** Singapore **Facility:** Pfizer Investigational Site **Zip:** 119074 **Location 89:** **City:** Singapore **Country:** Singapore **Facility:** Pfizer Investigational Site **Zip:** 169608 **Location 90:** **City:** Badalona **Country:** Spain **Facility:** Pfizer Investigational Site **State:** Barcelona **Zip:** 08916 **Location 91:** **City:** Madrid **Country:** Spain **Facility:** Pfizer Investigational Site **Zip:** 28006 **Location 92:** **City:** Madrid **Country:** Spain **Facility:** Pfizer Investigational Site **Zip:** 28050 **Location 93:** **City:** Salamanca **Country:** Spain **Facility:** Pfizer Investigational Site **Zip:** 37007 **Location 94:** **City:** Valencia **Country:** Spain **Facility:** Pfizer Investigational Site **Zip:** 46010 **Location 95:** **City:** Valencia **Country:** Spain **Facility:** Pfizer Investigational Site **Zip:** 46026 **Location 96:** **City:** Geneve 14 **Country:** Switzerland **Facility:** Pfizer Investigational Site **Zip:** CH-1211 **Location 97:** **City:** Lausanne **Country:** Switzerland **Facility:** Pfizer Investigational Site **Zip:** 1011 **Location 98:** **City:** Kuei-Shan Hsiang **Country:** Taiwan **Facility:** Pfizer Investigational Site **State:** Taoyuan County **Zip:** 333 **Location 99:** **City:** Kaohsiung **Country:** Taiwan **Facility:** Pfizer Investigational Site **Zip:** 807 **Location 100:** **City:** Taipei **Country:** Taiwan **Facility:** Pfizer Investigational Site **Zip:** 112 **Location 101:** **City:** Bangkok **Country:** Thailand **Facility:** Pfizer Investigational Site **Zip:** 10330 **Location 102:** **City:** Bangkok **Country:** Thailand **Facility:** Pfizer Investigational Site **Zip:** 10400 **Location 103:** **City:** Bangkok **Country:** Thailand **Facility:** Pfizer Investigational Site **Zip:** 10700 **Location 104:** **City:** Adana **Country:** Turkey **Facility:** Pfizer Investigational Site **Zip:** 01330 **Location 105:** **City:** Ankara **Country:** Turkey **Facility:** Pfizer Investigational Site **Zip:** 06100 **Location 106:** **City:** London **Country:** United Kingdom **Facility:** Pfizer Investigational Site **Zip:** SE5 9RS **Location 107:** **City:** Manchester **Country:** United Kingdom **Facility:** Pfizer Investigational Site **Zip:** M20 4BX #### Overall Officials **Official 1:** **Affiliation:** Pfizer **Name:** Pfizer CT.gov Call Center **Role:** STUDY_DIRECTOR ### References Module #### References **Citation:** Marr KA, Schlamm HT, Herbrecht R, Rottinghaus ST, Bow EJ, Cornely OA, Heinz WJ, Jagannatha S, Koh LP, Kontoyiannis DP, Lee DG, Nucci M, Pappas PG, Slavin MA, Queiroz-Telles F, Selleslag D, Walsh TJ, Wingard JR, Maertens JA. Combination antifungal therapy for invasive aspergillosis: a randomized trial. Ann Intern Med. 2015 Jan 20;162(2):81-9. doi: 10.7326/M13-2508. Erratum In: Ann Intern Med. 2015 Mar 17;162(6):463. Ann Intern Med. 2019 Feb 5;170(3):220. **PMID:** 25599346 **Citation:** Liu P, Mould DR. Population pharmacokinetic-pharmacodynamic analysis of voriconazole and anidulafungin in adult patients with invasive aspergillosis. Antimicrob Agents Chemother. 2014 Aug;58(8):4727-36. doi: 10.1128/AAC.02809-13. Epub 2014 Jun 9. **PMID:** 24914120 **Citation:** Liu P, Mould DR. Population pharmacokinetic analysis of voriconazole and anidulafungin in adult patients with invasive aspergillosis. Antimicrob Agents Chemother. 2014 Aug;58(8):4718-26. doi: 10.1128/AAC.02808-13. Epub 2014 Jun 9. **PMID:** 24913161 #### 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=A8851009&StudyName=Anidulafungin%20Plus%20Voriconazole%20versus%20Voriconazole%20For%20The%20Treatment%20Of%20Invasive%20Aspergillosis ## Derived Section ### Condition Browse Module - Ancestors - ID: D000009181 - Term: Mycoses - ID: D000001423 - Term: Bacterial Infections and Mycoses - ID: D000007239 - Term: Infections ### 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: M4535 - Name: Aspergillosis - Relevance: HIGH - As Found: Aspergillosis - ID: M12136 - Name: Mycoses - 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: M4721 - Name: Bacterial Infections and Mycoses - Relevance: LOW - As Found: Unknown - ID: T511 - Name: Aspergillosis - Relevance: HIGH - As Found: Aspergillosis ### Condition Browse Module - Meshes - ID: D000001228 - Term: Aspergillosis ### Intervention Browse Module - Ancestors - ID: D000000935 - Term: Antifungal Agents - ID: D000000890 - Term: Anti-Infective Agents - ID: D000058888 - Term: 14-alpha Demethylase Inhibitors - ID: D000065607 - Term: Cytochrome P-450 Enzyme Inhibitors - ID: D000004791 - Term: Enzyme Inhibitors - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000065088 - Term: Steroid Synthesis Inhibitors - ID: D000006727 - Term: Hormone Antagonists - ID: D000006730 - Term: Hormones, Hormone Substitutes, and Hormone Antagonists - ID: D000045505 - Term: Physiological Effects of Drugs - ID: D000065692 - Term: Cytochrome P-450 CYP3A 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: M30607 - Name: Voriconazole - Relevance: HIGH - As Found: Diaphragmatic - ID: M1868 - Name: Anidulafungin - Relevance: HIGH - As Found: JUVÉDERM - ID: M6252 - Name: Clotrimazole - Relevance: LOW - As Found: Unknown - ID: M11796 - Name: Miconazole - Relevance: LOW - As Found: Unknown - ID: M4254 - Name: Antifungal Agents - Relevance: LOW - As Found: Unknown - ID: M4214 - Name: Anti-Infective Agents - Relevance: LOW - As Found: Unknown - ID: M7951 - Name: Enzyme Inhibitors - Relevance: LOW - As Found: Unknown - ID: M30537 - Name: Cytochrome P-450 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 - ID: M30564 - Name: Cytochrome P-450 CYP3A Inhibitors - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000065819 - Term: Voriconazole - ID: D000077612 - Term: Anidulafungin ### Misc Info Module #### Removed Countries - Country: Austria - Country: Saudi Arabia - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module **Description:** The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. #### Event Groups **Group ID:** EG000 **Title:** Voriconazole/Anidulafungin **Description:** Week 1: Voriconazole 6 mg/kg intravenously (IV) twice a day (bid) for 24 hours, followed by voriconazole 4 milligrams per kilogram (mg/kg) IV BID plus anidulafungin 200 mg IV on day 1, followed by 100 mg IV once a day (QD); Week 2: Voriconazole 4 mg/kg IV BID or 300 mg orally (PO) BID plus anidulafungin 100 mg IV QD; Weeks 3 and 4: voriconazole 4 mg/kg IV BID or 300 mg PO BID plus anidulafungin 100 mg IV QD or voriconazole 4 mg/kg IV BID or 300 mg PO BID monotherapy; Weeks 5 and 6: voriconazole 4 mg/kg IV BID or 300 mg PO BID monotherapy. **ID:** EG000 **Other Num Affected:** 194 **Other Num at Risk:** 228 **Serious Number Affected:** 115 **Serious Number At Risk:** 228 **Title:** Voriconazole/Anidulafungin **Group ID:** EG001 **Title:** Voriconazole / Placebo **Description:** Week 1: Voriconazole 6 mg/kg IV BID for 24 hours, followed by voriconazole 4 mg/kg IV BID plus anidulafungin placebo IV QD; Week 2: voriconazole 4 mg/kg IV BID or voriconazole 300 mg PO BID plus anidulafungin placebo IV QD through Day 14; Weeks 3 and 4: voriconazole 4 mg/kg IV BID or 300 mg PO BID plus anidulafungin placebo; Weeks 5 and 6: voriconazole 4 mg/kg IV BID or 300 mg PO BID monotherapy. **ID:** EG001 **Other Num Affected:** 192 **Other Num at Risk:** 226 **Serious Number Affected:** 104 **Serious Number At Risk:** 226 **Title:** Voriconazole / Placebo **Frequency Threshold:** 5 #### Other Events **Term:** Anaemia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA 14.1 **Term:** Tachycardia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 14.1 **Term:** Vision blurred **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Eye disorders **Source Vocabulary:** MedDRA 14.1 **Term:** Abdominal pain **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 14.1 **Term:** Abdominal pain upper **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 14.1 **Term:** Constipation **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 14.1 **Term:** Diarrhoea **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 14.1 **Term:** Dyspepsia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 14.1 **Term:** Nausea **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 14.1 **Term:** Vomiting **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 14.1 **Term:** Chest pain **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 14.1 **Term:** Chills **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 14.1 **Term:** Fatigue **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 14.1 **Term:** Mucosal inflammation **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 14.1 **Term:** Oedema **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 14.1 **Term:** Oedema peripheral **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 14.1 **Term:** Pain **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 14.1 **Term:** Pyrexia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 14.1 **Term:** Fall **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 14.1 **Term:** Aspartate aminotransferase increased **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA 14.1 **Term:** Blood alkaline phosphatase increased **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA 14.1 **Term:** Decreased appetite **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 14.1 **Term:** Hypokalaemia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 14.1 **Term:** Hypomagnesaemia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 14.1 **Term:** Back pain **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 14.1 **Term:** Pain in extremity **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 14.1 **Term:** Headache **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 14.1 **Term:** Agitation **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA 14.1 **Term:** Anxiety **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA 14.1 **Term:** Confusional state **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA 14.1 **Term:** Hallucination, visual **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA 14.1 **Term:** Insomnia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA 14.1 **Term:** Cough **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 14.1 **Term:** Dyspnoea **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 14.1 **Term:** Epistaxis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 14.1 **Term:** Petechiae **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA 14.1 **Term:** Rash **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** MedDRA 14.1 **Term:** Hypertension **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA 14.1 **Term:** Hypotension **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA 14.1 #### Serious Events **Term:** Anaemia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Blood disorder **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 226 **Term:** Disseminated intravascular coagulation **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Febrile neutropenia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 6 **Num At Risk:** 226 **Term:** Neutropenia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 3 **Num At Risk:** 226 **Term:** Pancytopenia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 3 **Num At Risk:** 226 **Term:** Thrombotic microangiopathy **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 226 **Term:** Thrombotic thrombocytopenic purpura **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Arrhythmia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 226 **Term:** Atrial fibrillation **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 4 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 226 **Term:** Bradycardia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Cardiac arrest **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 226 **Term:** Cardio-respiratory arrest **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 226 **Term:** Cardiopulmonary failure **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Extrasystoles **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Myocardial ischaemia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 226 **Term:** Pericardial effusion **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Pulseless electrical activity **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Supraventricular tachycardia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 226 **Term:** Tachycardia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 226 **Term:** Ventricular fibrillation **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Blindness **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Eye disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Blindness unilateral **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Eye disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Abdominal pain **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 226 **Term:** Ascites **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 226 **Term:** Diarrhoea **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 3 **Num At Risk:** 226 **Term:** Duodenal ulcer haemorrhage **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Faecaloma **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Gastric haemorrhage **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Gastrointestinal haemorrhage **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 226 **Term:** Haematemesis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Ileitis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 226 **Term:** Ileus paralytic **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Lower gastrointestinal haemorrhage **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Megacolon **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Neutropenic colitis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Small intestinal obstruction **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 226 **Term:** Upper gastrointestinal haemorrhage **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Vomiting **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 226 **Term:** Asthenia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 226 **Term:** Chest pain **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Death **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 226 **Term:** Disease progression **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 226 **Term:** Fatigue **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** General physical health deterioration **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 226 **Term:** Multi-organ failure **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 5 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 4 **Num At Risk:** 226 **Term:** Pyrexia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 3 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 4 **Num At Risk:** 226 **Term:** Sudden cardiac death **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 226 **Term:** Cholecystitis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 226 **Term:** Cholecystitis acute **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 226 **Term:** Hepatic failure **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Hepatic function abnormal **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 226 **Term:** Hepatic vein occlusion **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Hepatotoxicity **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Hyperbilirubinaemia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Liver disorder **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Hepatobiliary disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Graft versus host disease **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Immune system disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 226 **Term:** Aspergillosis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 6 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 5 **Num At Risk:** 226 **Term:** Bacteraemia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Bacterial sepsis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 226 **Term:** Cytomegalovirus infection **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 226 **Term:** Device related infection **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Disseminated tuberculosis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Endocarditis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 226 **Term:** Enterococcal bacteraemia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Enterococcal sepsis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Escherichia sepsis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Fungal infection **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 226 **Term:** Gastroenteritis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Genital herpes **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 226 **Term:** H1N1 influenza **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Hepatic infection fungal **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Herpes zoster **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Klebsiella bacteraemia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Lung abscess **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 226 **Term:** Lung infection **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Meningitis fungal **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Neutropenic sepsis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Nocardiosis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Oral herpes **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 226 **Term:** Pneumocystis jiroveci pneumonia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 226 **Term:** Pneumonia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 5 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 5 **Num At Risk:** 226 **Term:** Pneumonia staphylococcal **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 226 **Term:** Sepsis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 9 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 7 **Num At Risk:** 226 **Term:** Septic shock **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 10 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 14 **Num At Risk:** 226 **Term:** Sinusitis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 226 **Term:** Sinusitis aspergillus **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 226 **Term:** Staphylococcal bacteraemia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 226 **Term:** Staphylococcal infection **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 226 **Term:** Staphylococcal sepsis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 226 **Term:** Streptococcal sepsis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Systemic candida **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Tuberculosis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Zygomycosis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Complications of transplant surgery **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Fall **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Injury **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 226 **Term:** Subdural haematoma **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Wound **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Blood creatine phosphokinase increased **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** C-reactive protein increased **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 226 **Term:** Cytomegalovirus test positive **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Electrocardiogram QT prolonged **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Hepatic enzyme increased **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 226 **Term:** Lipase increased **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 226 **Term:** Liver function test abnormal **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 226 **Term:** Oxygen saturation decreased **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 226 **Term:** Procalcitonin increased **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 226 **Term:** Transaminases increased **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 226 **Term:** Hypoglycaemia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 226 **Term:** Hypokalaemia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 226 **Term:** Hyponatraemia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 226 **Term:** Hypovolaemia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Lactic acidosis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Metabolic acidosis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Arthralgia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Muscular weakness **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 226 **Term:** Acute leukaemia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 226 **Term:** Acute lymphocytic leukaemia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 226 **Term:** Acute myeloid leukaemia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 6 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 4 **Num At Risk:** 226 **Term:** B-cell lymphoma refractory **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 226 **Term:** Blast cell crisis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Central nervous system lymphoma **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Chronic lymphocytic leukaemia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Chronic lymphocytic leukaemia recurrent **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Leukaemia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Leukaemia plasmacytic **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Lymphoma **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 3 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Multiple myeloma **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 226 **Term:** Neoplasm malignant **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Non-Hodgkin's lymphoma **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Neoplasms benign, malignant and unspecified (incl cysts and polyps) **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Aphasia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 226 **Term:** Cerebellar infarction **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 226 **Term:** Cerebral artery embolism **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 226 **Term:** Cerebral haemorrhage **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 226 **Term:** Cerebral infarction **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Convulsion **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 3 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 226 **Term:** Dizziness **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Encephalopathy **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 226 **Term:** Epilepsy **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 226 **Term:** Grand mal convulsion **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 226 **Term:** Hepatic encephalopathy **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Ischaemic stroke **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 226 **Term:** Loss of consciousness **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 226 **Term:** Petit mal epilepsy **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Toxic neuropathy **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 226 **Term:** Confusional state **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 226 **Term:** Hallucination **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Hallucination, visual **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Acute prerenal failure **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Cystitis haemorrhagic **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Hydronephrosis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Nephritic syndrome **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Oliguria **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 226 **Term:** Renal failure **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 226 **Term:** Renal failure acute **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 5 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Renal impairment **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 226 **Term:** Vaginal haemorrhage **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Reproductive system and breast disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Acute respiratory distress syndrome **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 4 **Num At Risk:** 226 **Term:** Acute respiratory failure **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 226 **Term:** Bronchospasm **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Cough **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Dyspnoea **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 3 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 4 **Num At Risk:** 226 **Term:** Haemoptysis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 3 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 3 **Num At Risk:** 226 **Term:** Hypercapnia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Hypoxia **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 3 **Num At Risk:** 226 **Term:** Lung infiltration **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 226 **Term:** Pleural effusion **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 226 **Term:** Pneumonitis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Pulmonary alveolar haemorrhage **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 226 **Term:** Pulmonary embolism **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 226 **Term:** Pulmonary haemorrhage **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Pulmonary infarction **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 226 **Term:** Pulmonary oedema **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 2 **Num At Risk:** 226 **Term:** Respiratory disorder **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Respiratory distress **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 3 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 6 **Num At Risk:** 226 **Term:** Respiratory failure **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 11 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 14 **Num At Risk:** 226 **Term:** Tachypnoea **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 226 **Term:** Aortic occlusion **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Haematoma **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Hypotension **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 2 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 226 **Term:** Iliac artery thrombosis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num At Risk:** 228 **Group ID:** EG001 **Num Affected:** 1 **Num At Risk:** 226 **Term:** Shock **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Shock haemorrhagic **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 **Term:** Subclavian vein thrombosis **Assessment Type:** NON_SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** MedDRA 14.1 ##### Stats **Group ID:** EG000 **Num Affected:** 1 **Num At Risk:** 228 **Group ID:** EG001 **Num At Risk:** 226 ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 228 **Group ID:** BG001 **Value:** 226 **Group ID:** BG002 **Value:** 454 **Units:** Participants ### Group **ID:** BG000 **Title:** Voriconazole/Anidulafungin **Description:** Week 1: Voriconazole 6 mg/kg intravenously (IV) twice a day (bid) for 24 hours, followed by voriconazole 4 milligrams per kilogram (mg/kg) IV BID plus anidulafungin 200 mg IV on day 1, followed by 100 mg IV once a day (QD); Week 2: Voriconazole 4 mg/kg IV BID or 300 mg orally (PO) BID plus anidulafungin 100 mg IV QD; Weeks 3 and 4: voriconazole 4 mg/kg IV BID or 300 mg PO BID plus anidulafungin 100 mg IV QD or voriconazole 4 mg/kg IV BID or 300 mg PO BID monotherapy; Weeks 5 and 6: voriconazole 4 mg/kg IV BID or 300 mg PO BID monotherapy. ### Group **ID:** BG001 **Title:** Voriconazole / Placebo **Description:** Week 1: Voriconazole 6 mg/kg IV BID for 24 hours, followed by voriconazole 4 mg/kg IV BID plus anidulafungin placebo IV QD; Week 2: voriconazole 4 mg/kg IV BID or voriconazole 300 mg PO BID plus anidulafungin placebo IV QD through Day 14; Weeks 3 and 4: voriconazole 4 mg/kg IV BID or 300 mg PO BID plus anidulafungin placebo; Weeks 5 and 6: voriconazole 4 mg/kg IV BID or 300 mg PO BID monotherapy. ### Group **ID:** BG002 **Title:** Total **Description:** Total of all reporting groups ### Measure #### Measurement **Group ID:** BG000 **Spread:** 15.4 **Value:** 52.0 #### Measurement **Group ID:** BG001 **Spread:** 15.9 **Value:** 51.0 #### Measurement **Group ID:** BG002 **Spread:** 15.7 **Value:** 51.5 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 94 #### Measurement **Group ID:** BG001 **Value:** 95 #### Measurement **Group ID:** BG002 **Value:** 189 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 134 #### Measurement **Group ID:** BG001 **Value:** 131 #### Measurement **Group ID:** BG002 **Value:** 265 **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 **Other Details:** Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results. **Restriction Type:** OTHER **Restrictive Agreement:** True ### 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:** -18.99 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 1.51 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** The 95% CI was based on using Greenwood's formula for the variance of the KM estimator. **Group Description:** All-cause mortality calculated using the Kaplan-Meier (KM) product limit estimator on Day 42 (Week 6) within each stratum and weighted by the harmonic mean of the sample sizes in the strata. Treatment difference (stratified) based on a weighted difference in proportions. Stratification variables were site of infection and host factors. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0434 **P-Value Comment:** P-value based on a 1-sided test and tested against a 1-sided alpha of 0.025 to determine statistical significance. **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** -8.74 **Statistical Comment:** **Statistical Method:** Z test for difference in proportions **Tested Non-Inferiority:** False ### Outcome Measure 2 #### Analysis **CI Lower Limit:** -21.6 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 1.15 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** 95% confidence interval based on the difference in success rates using the normal approximation to the binoial distribution. **Group Description:** Treatment difference (stratified) based on a weighted difference in proportions. Stratification variables: site of infection and host factors. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** **P-Value Comment:** P-value for global response was to be reported only if Week 6 mortality was significant. **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** -10.23 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** False ### Outcome Measure 3 #### Analysis **CI Lower Limit:** -10.77 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 5.56 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** 95% confidence interval based on using Greenwood's formula for the variance of the Kaplan Meier estimator. **Group Description:** Treatment difference (stratified) based on a weighted difference in proportions. Stratification variables: site of infection and host factors. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.2611 **P-Value Comment:** P-Value based on a 1-sided test and tested against a 1-sided alpha of 0.025 to determine statistical significance. **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** -2.6 **Statistical Comment:** **Statistical Method:** Z test for difference in proportions **Tested Non-Inferiority:** False ### Outcome Measure 4 #### Analysis **CI Lower Limit:** -21.44 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 1.09 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** 95% confidence intervalbased on using Greenwood's formula for the variance of the Kaplan Meier estimator. **Group Description:** Treatment difference (stratified) based on a weighted difference in proportions. Stratification variables: site of infection and host factors. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.0383 **P-Value Comment:** P-Value based on a 1-sided test and tested against a 1-sided alpha of 0.025 to determine statistical significance. **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** -10.18 **Statistical Comment:** **Statistical Method:** Z test for difference in proportions **Tested Non-Inferiority:** False ### Outcome Measure 5 #### Analysis **CI Lower Limit:** -15.9 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 3.42 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** 95% confidence interval based on Greenwood's formula for the variance of the Kaplan Meier estimator. **Group Description:** Treatment difference (stratified) based on a weighted difference in proportions. Stratification variables: site of infection and host factors. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.1029 **P-Value Comment:** P-Value based on a one-sided test and tested against a 1-sided alpha of 0.025 to determine statistical significance. **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** -6.24 **Statistical Comment:** **Statistical Method:** Z test for difference in proportions **Tested Non-Inferiority:** False ### Outcome Measure 6 #### Analysis **CI Lower Limit:** 0.46 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 1.04 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** **Group Description:** Hazard Ratio: hazard of death in the Voriconazole/Anidulafungin arm relative to the Voriconazole/Placebo arm, adjusted for host factor status and site of infection. Participants who died beyond Day 84 were censored. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.083 **P-Value Comment:** **Parameter Type:** Hazard Ratio (HR) **Parameter Value:** 0.696 **Statistical Comment:** **Statistical Method:** Cox proportional hazards model **Tested Non-Inferiority:** False ### Outcome Measure 7 #### Analysis **CI Lower Limit:** 0.40 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 95 **CI Upper Limit:** 1.16 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** 95% confidence interval based on Greenwood's formula. **Group Description:** Analysis based on Cox proportional hazards model. Participants who died beyond day 84 were censored. **Non-Inferiority Comment:** **Non-Inferiority Type:** SUPERIORITY_OR_OTHER **Other Analysis Description:** **P-Value:** 0.164 **P-Value Comment:** **Parameter Type:** Hazard Ratio (HR) **Parameter Value:** 0.687 **Statistical Comment:** **Statistical Method:** Cox proportional hazards model **Tested Non-Inferiority:** False ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 26 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 39 **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 44 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 61 **Title:** #### Outcome Measure 3 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 44 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 47 **Title:** #### Outcome Measure 4 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 39 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 55 **Title:** #### Outcome Measure 5 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 23 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 33 **Title:** #### Outcome Measure 6 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 2 - **Spread:** - **Upper Limit:** 84 - **Value:** 30.0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 3 - **Spread:** - **Upper Limit:** 79 - **Value:** 30.0 **Title:** #### Outcome Measure 7 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 2 - **Spread:** - **Upper Limit:** 40 - **Value:** 14.0 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 4 - **Spread:** - **Upper Limit:** 45 - **Value:** 18.5 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** Number of deaths measured 6 weeks after start of treatment. Time to death defined as date of death minus first treatment date + 1. **Parameter Type:** NUMBER **Population Description:** Modified intent-to-treat (MITT) population: all randomized participants with proven or probable IA confirmed by Day 7 following enrollment who received at least 1 dose of study medication. N=number of participants in MITT population at Week 6. Participants not known to have died were censored at last study visit (Day 84). **Reporting Status:** POSTED **Time Frame:** Day 1 to Day 42 (Week 6) **Title:** All-cause Mortality at Week 6 in Participants With Proven or Probable Invasive Aspergillosis **Type:** PRIMARY **Unit of Measure:** participants ##### Group **Description:** Week 1: Voriconazole 6 mg/kg intravenously (IV) twice a day (bid) for 24 hours, followed by voriconazole 4 milligrams per kilogram (mg/kg) IV BID plus anidulafungin 200 mg IV on day 1, followed by 100 mg IV once a day (QD); Week 2: Voriconazole 4 mg/kg IV BID or 300 mg orally (PO) BID plus anidulafungin 100 mg IV QD; Weeks 3 and 4: voriconazole 4 mg/kg IV BID or 300 mg PO BID plus anidulafungin 100 mg IV QD or voriconazole 4 mg/kg IV BID or 300 mg PO BID monotherapy; Weeks 5 and 6: voriconazole 4 mg/kg IV BID or 300 mg PO BID monotherapy. **ID:** OG000 **Title:** Voriconazole/Anidulafungin ##### Group **Description:** Week 1: Voriconazole 6 mg/kg IV BID for 24 hours, followed by voriconazole 4 mg/kg IV BID plus anidulafungin placebo IV QD; Week 2: voriconazole 4 mg/kg IV BID or voriconazole 300 mg PO BID plus anidulafungin placebo IV QD through Day 14; Weeks 3 and 4: voriconazole 4 mg/kg IV BID or 300 mg PO BID plus anidulafungin placebo; Weeks 5 and 6: voriconazole 4 mg/kg IV BID or 300 mg PO BID monotherapy. **ID:** OG001 **Title:** Voriconazole / Placebo #### Outcome Measure 2 **Description:** Number of participants with a successful response (complete or partial global response). Complete response = resolution of all clinical signs and symptoms and \>90% of lesions due to IA that were visible on radiologic studies at baseline (BL); partial response = clinical improvement and \>50% improvement in radiological findings present at BL. **Parameter Type:** NUMBER **Population Description:** MITT; N = number of participants in MITT population at Week 6. Missing data and participants who died at Week 6 were treated as failure. **Reporting Status:** POSTED **Time Frame:** Baseline, Day 42 (Week 6) **Title:** Global Response at Week 6 **Type:** SECONDARY **Unit of Measure:** participants ##### Group **Description:** Week 1: Voriconazole 6 mg/kg intravenously (IV) twice a day (bid) for 24 hours, followed by voriconazole 4 milligrams per kilogram (mg/kg) IV BID plus anidulafungin 200 mg IV on day 1, followed by 100 mg IV once a day (QD); Week 2: Voriconazole 4 mg/kg IV BID or 300 mg orally (PO) BID plus anidulafungin 100 mg IV QD; Weeks 3 and 4: voriconazole 4 mg/kg IV BID or 300 mg PO BID plus anidulafungin 100 mg IV QD or voriconazole 4 mg/kg IV BID or 300 mg PO BID monotherapy; Weeks 5 and 6: voriconazole 4 mg/kg IV BID or 300 mg PO BID monotherapy. **ID:** OG000 **Title:** Voriconazole/Anidulafungin ##### Group **Description:** Week 1: Voriconazole 6 mg/kg IV BID for 24 hours, followed by voriconazole 4 mg/kg IV BID plus anidulafungin placebo IV QD; Week 2: voriconazole 4 mg/kg IV BID or voriconazole 300 mg PO BID plus anidulafungin placebo IV QD through Day 14; Weeks 3 and 4: voriconazole 4 mg/kg IV BID or 300 mg PO BID plus anidulafungin placebo; Weeks 5 and 6: voriconazole 4 mg/kg IV BID or 300 mg PO BID monotherapy. **ID:** OG001 **Title:** Voriconazole / Placebo #### Outcome Measure 3 **Description:** Number of deaths due to any cause measured 6 weeks after start of treatment. Time to death defined as date of death minus first treatment date + 1. **Parameter Type:** NUMBER **Population Description:** Intent-to-treat (ITT) population: participants in MITT analysis set plus participants with possible IA who could not be upgraded to probable or proven IA within 7 days and had received at least 1 dose of study medication. N=number of participants in ITT population at Week 6. **Reporting Status:** POSTED **Time Frame:** Day 1 to Day 42 (Week 6) **Title:** All-cause Mortality at Week 6 in Participants With Possible, Probable, or Proven Invasive Aspergillosis (IA) **Type:** SECONDARY **Unit of Measure:** participants ##### Group **Description:** Week 1: Voriconazole 6 mg/kg intravenously (IV) twice a day (bid) for 24 hours, followed by voriconazole 4 milligrams per kilogram (mg/kg) IV BID plus anidulafungin 200 mg IV on day 1, followed by 100 mg IV once a day (QD); Week 2: Voriconazole 4 mg/kg IV BID or 300 mg orally (PO) BID plus anidulafungin 100 mg IV QD; Weeks 3 and 4: voriconazole 4 mg/kg IV BID or 300 mg PO BID plus anidulafungin 100 mg IV QD or voriconazole 4 mg/kg IV BID or 300 mg PO BID monotherapy; Weeks 5 and 6: voriconazole 4 mg/kg IV BID or 300 mg PO BID monotherapy. **ID:** OG000 **Title:** Voriconazole/Anidulafungin ##### Group **Description:** Week 1: Voriconazole 6 mg/kg IV BID for 24 hours, followed by voriconazole 4 mg/kg IV BID plus anidulafungin placebo IV QD; Week 2: voriconazole 4 mg/kg IV BID or voriconazole 300 mg PO BID plus anidulafungin placebo IV QD through Day 14; Weeks 3 and 4: voriconazole 4 mg/kg IV BID or 300 mg PO BID plus anidulafungin placebo; Weeks 5 and 6: voriconazole 4 mg/kg IV BID or 300 mg PO BID monotherapy. **ID:** OG001 **Title:** Voriconazole / Placebo #### Outcome Measure 4 **Description:** Number of deaths due to any cause measured 12 weeks after start of treatment. Time to death defined as date of death minus first treatment date + 1. **Parameter Type:** NUMBER **Population Description:** MITT; N=number of participants in MITT population at Week 12. **Reporting Status:** POSTED **Time Frame:** Day 1 to Day 84 (Week 12) **Title:** All-cause Mortality at Week 12 in Participants With Probable or Proven Invasive Aspergillosis (IA) **Type:** SECONDARY **Unit of Measure:** participants ##### Group **Description:** Week 1: Voriconazole 6 mg/kg intravenously (IV) twice a day (bid) for 24 hours, followed by voriconazole 4 milligrams per kilogram (mg/kg) IV BID plus anidulafungin 200 mg IV on day 1, followed by 100 mg IV once a day (QD); Week 2: Voriconazole 4 mg/kg IV BID or 300 mg orally (PO) BID plus anidulafungin 100 mg IV QD; Weeks 3 and 4: voriconazole 4 mg/kg IV BID or 300 mg PO BID plus anidulafungin 100 mg IV QD or voriconazole 4 mg/kg IV BID or 300 mg PO BID monotherapy; Weeks 5 and 6: voriconazole 4 mg/kg IV BID or 300 mg PO BID monotherapy. **ID:** OG000 **Title:** Voriconazole/Anidulafungin ##### Group **Description:** Week 1: Voriconazole 6 mg/kg IV BID for 24 hours, followed by voriconazole 4 mg/kg IV BID plus anidulafungin placebo IV QD; Week 2: voriconazole 4 mg/kg IV BID or voriconazole 300 mg PO BID plus anidulafungin placebo IV QD through Day 14; Weeks 3 and 4: voriconazole 4 mg/kg IV BID or 300 mg PO BID plus anidulafungin placebo; Weeks 5 and 6: voriconazole 4 mg/kg IV BID or 300 mg PO BID monotherapy. **ID:** OG001 **Title:** Voriconazole / Placebo #### Outcome Measure 5 **Description:** Number of deaths due to Invasive Aspergillosis measured 6 weeks after start of treatment. Time to death defined as date of death minus first treatment date + 1. **Parameter Type:** NUMBER **Population Description:** MITT; N = number of participants in MITT population at Week 6. Participants who died due to causes other than IA before Week 6 were censored at their time of death in this analysis. **Reporting Status:** POSTED **Time Frame:** Day 1 to Day 42 (Week 6) **Title:** Mortality Due to Invasive Aspergillosis (IA) at Week 6 in Participants With Probable or Proven IA **Type:** SECONDARY **Unit of Measure:** participants ##### Group **Description:** Week 1: Voriconazole 6 mg/kg intravenously (IV) twice a day (bid) for 24 hours, followed by voriconazole 4 milligrams per kilogram (mg/kg) IV BID plus anidulafungin 200 mg IV on day 1, followed by 100 mg IV once a day (QD); Week 2: Voriconazole 4 mg/kg IV BID or 300 mg orally (PO) BID plus anidulafungin 100 mg IV QD; Weeks 3 and 4: voriconazole 4 mg/kg IV BID or 300 mg PO BID plus anidulafungin 100 mg IV QD or voriconazole 4 mg/kg IV BID or 300 mg PO BID monotherapy; Weeks 5 and 6: voriconazole 4 mg/kg IV BID or 300 mg PO BID monotherapy. **ID:** OG000 **Title:** Voriconazole/Anidulafungin ##### Group **Description:** Week 1: Voriconazole 6 mg/kg IV BID for 24 hours, followed by voriconazole 4 mg/kg IV BID plus anidulafungin placebo IV QD; Week 2: voriconazole 4 mg/kg IV BID or voriconazole 300 mg PO BID plus anidulafungin placebo IV QD through Day 14; Weeks 3 and 4: voriconazole 4 mg/kg IV BID or 300 mg PO BID plus anidulafungin placebo; Weeks 5 and 6: voriconazole 4 mg/kg IV BID or 300 mg PO BID monotherapy. **ID:** OG001 **Title:** Voriconazole / Placebo #### Outcome Measure 6 **Description:** Survival time from start of treatment. Time to death defined as date of death due to any cause minus first treatment date + 1. **Dispersion Type:** Full Range **Parameter Type:** MEDIAN **Population Description:** MITT; N = number of participants in MITT population at time of assessment. **Reporting Status:** POSTED **Time Frame:** Day 1 to Day 84 (Week 12) **Title:** Time to Death: All-Cause Mortality **Type:** SECONDARY **Unit of Measure:** days ##### Group **Description:** Week 1: Voriconazole 6 mg/kg intravenously (IV) twice a day (bid) for 24 hours, followed by voriconazole 4 milligrams per kilogram (mg/kg) IV BID plus anidulafungin 200 mg IV on day 1, followed by 100 mg IV once a day (QD); Week 2: Voriconazole 4 mg/kg IV BID or 300 mg orally (PO) BID plus anidulafungin 100 mg IV QD; Weeks 3 and 4: voriconazole 4 mg/kg IV BID or 300 mg PO BID plus anidulafungin 100 mg IV QD or voriconazole 4 mg/kg IV BID or 300 mg PO BID monotherapy; Weeks 5 and 6: voriconazole 4 mg/kg IV BID or 300 mg PO BID monotherapy. **ID:** OG000 **Title:** Voriconazole/Anidulafungin ##### Group **Description:** Week 1: Voriconazole 6 mg/kg IV BID for 24 hours, followed by voriconazole 4 mg/kg IV BID plus anidulafungin placebo IV QD; Week 2: voriconazole 4 mg/kg IV BID or voriconazole 300 mg PO BID plus anidulafungin placebo IV QD through Day 14; Weeks 3 and 4: voriconazole 4 mg/kg IV BID or 300 mg PO BID plus anidulafungin placebo; Weeks 5 and 6: voriconazole 4 mg/kg IV BID or 300 mg PO BID monotherapy. **ID:** OG001 **Title:** Voriconazole / Placebo #### Outcome Measure 7 **Description:** Survival time from start of treatment. Time to death defined as date of death due to IA minus first treatment date + 1. **Dispersion Type:** Full Range **Parameter Type:** MEDIAN **Population Description:** MITT; N = number of participants in MITT population at time of assessment. Participants who died due to causes other than IA were defined as censored at time of death. **Reporting Status:** POSTED **Time Frame:** Day 1 to Day 84 (Week 12) **Title:** Time to Death Due to Invasive Aspergillosis (IA) **Type:** SECONDARY **Unit of Measure:** days ##### Group **Description:** Week 1: Voriconazole 6 mg/kg intravenously (IV) twice a day (bid) for 24 hours, followed by voriconazole 4 milligrams per kilogram (mg/kg) IV BID plus anidulafungin 200 mg IV on day 1, followed by 100 mg IV once a day (QD); Week 2: Voriconazole 4 mg/kg IV BID or 300 mg orally (PO) BID plus anidulafungin 100 mg IV QD; Weeks 3 and 4: voriconazole 4 mg/kg IV BID or 300 mg PO BID plus anidulafungin 100 mg IV QD or voriconazole 4 mg/kg IV BID or 300 mg PO BID monotherapy; Weeks 5 and 6: voriconazole 4 mg/kg IV BID or 300 mg PO BID monotherapy. **ID:** OG000 **Title:** Voriconazole/Anidulafungin ##### Group **Description:** Week 1: Voriconazole 6 mg/kg IV BID for 24 hours, followed by voriconazole 4 mg/kg IV BID plus anidulafungin placebo IV QD; Week 2: voriconazole 4 mg/kg IV BID or voriconazole 300 mg PO BID plus anidulafungin placebo IV QD through Day 14; Weeks 3 and 4: voriconazole 4 mg/kg IV BID or 300 mg PO BID plus anidulafungin placebo; Weeks 5 and 6: voriconazole 4 mg/kg IV BID or 300 mg PO BID monotherapy. **ID:** OG001 **Title:** Voriconazole / Placebo ### Participant Flow Module #### Group **Description:** Week 1: Voriconazole 6 mg/kg intravenously (IV) twice a day (bid) for 24 hours, followed by voriconazole 4 milligrams per kilogram (mg/kg) IV BID plus anidulafungin 200 mg IV on day 1, followed by 100 mg IV once a day (QD); Week 2: Voriconazole 4 mg/kg IV BID or 300 mg orally (PO) BID plus anidulafungin 100 mg IV QD; Weeks 3 and 4: voriconazole 4 mg/kg IV BID or 300 mg PO BID plus anidulafungin 100 mg IV QD or voriconazole 4 mg/kg IV BID or 300 mg PO BID monotherapy; Weeks 5 and 6: voriconazole 4 mg/kg IV BID or 300 mg PO BID monotherapy. **ID:** FG000 **Title:** Voriconazole/Anidulafungin #### Group **Description:** Week 1: Voriconazole 6 mg/kg IV BID for 24 hours, followed by voriconazole 4 mg/kg IV BID plus anidulafungin placebo IV QD; Week 2: voriconazole 4 mg/kg IV BID or voriconazole 300 mg PO BID plus anidulafungin placebo IV QD through Day 14; Weeks 3 and 4: voriconazole 4 mg/kg IV BID or 300 mg PO BID plus anidulafungin placebo; Weeks 5 and 6: voriconazole 4 mg/kg IV BID or 300 mg PO BID monotherapy. **ID:** FG001 **Title:** Voriconazole / Placebo #### Period **Title:** Overall Study ##### Withdraw **Type:** Death ###### Reason **Group ID:** FG000 **Number of Subjects:** 68 ###### Reason **Group ID:** FG001 **Number of Subjects:** 71 ##### Withdraw **Type:** Lost to Follow-up ###### Reason **Group ID:** FG000 **Number of Subjects:** 0 ###### Reason **Group ID:** FG001 **Number of Subjects:** 2 ##### Withdraw **Type:** Other ###### Reason **Group ID:** FG000 **Number of Subjects:** 0 ###### Reason **Group ID:** FG001 **Number of Subjects:** 1 ##### Withdraw **Type:** Withdrawal by Subject ###### Reason **Group ID:** FG000 **Number of Subjects:** 6 ###### Reason **Group ID:** FG001 **Number of Subjects:** 6 ##### Withdraw **Type:** Did not receive treatment ###### Reason **Group ID:** FG000 **Number of Subjects:** 2 ###### Reason **Group ID:** FG001 **Number of Subjects:** 3 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 230 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 229 ##### Milestone **Type:** Treated ###### Achievement **Group ID:** FG000 **Number of Subjects:** 228 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 226 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 154 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 146 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 76 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 83 **Pre-Assignment Details:** Participants were stratified at study entry for host and transplant variables known to have an independent impact on the probablity of death due to invasive aspergillosis (IA) (allogenic hematopoietic stem cell transplant versus other, and pulmonary IA). **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT01377779 **Brief Title:** Efficiency of Intercoat (Oxiplex/AP Gel)in Decreasing Intrauterine Adhesions **Official Title:** Intercoat (Oxiplex/AP Gel) for Preventing Intrauterine Adhesions Following Operative Hysteroscopy for Suspected Retained Products of Conception - a Prospective Randomized Pilot Study #### Organization Study ID Info **ID:** 2*13/09 #### Organization **Class:** OTHER_GOV **Full Name:** Assaf-Harofeh Medical Center ### Status Module #### Completion Date **Date:** 2011-02 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2011-06-21 **Type:** ESTIMATED **Last Update Submit Date:** 2011-06-20 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2010-11 **Type:** ACTUAL #### Start Date **Date:** 2009-09 **Status Verified Date:** 2009-07 #### Study First Post Date **Date:** 2011-06-21 **Type:** ESTIMATED **Study First Submit Date:** 2011-06-15 **Study First Submit QC Date:** 2011-06-20 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER_GOV **Name:** Assaf-Harofeh Medical Center #### Responsible Party **Old Name Title:** Moty Pansky, MD **Old Organization:** Asaf Harofe MC ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** This is a prospective single blind randomized controlled pilot study was designed to investigate whether the biological barrier Intercoat (Oxiplex/AP gel) reduces formation of intrauterine adhesions following hysteroscopic treatment for retained products of conception. **Detailed Description:** Thirty women randomly divided equally into those who received Intercoat following hysteroscopic treatment for retained products of conception (study group) and those who did not receive the gel (controls). Safety and efficacy of the preparation were evaluated. ### Conditions Module **Conditions:** - Asherman Syndrome **Keywords:** - Oxiplex/AP gel - Prevention of Asherman's syndrome - Intra uterine adhesions ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** SINGLE **Who Masked:** - PARTICIPANT **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 60 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** women treated by Intercoat gel following hysteroscopy for retained products of conception **Intervention Names:** - Drug: Oxiplex/AP gel **Label:** Intercoat treatment **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** No additional treatment following hysteroscopy was performed **Intervention Names:** - Drug: Normal Saline **Label:** Control group **Type:** PLACEBO_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Intercoat treatment **Description:** Intrauterine application of Intercoat following hysteroscopy **Name:** Oxiplex/AP gel **Other Names:** - Intercoat **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Control group **Description:** No intrauterine application of Intercoat following hysteroscopy **Name:** Normal Saline **Other Names:** - Distention media **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** women treated by Intercoat following their hysteroscopic procedure were followed for immediate and late adverse effects; fever, increased intrauterine adhesion formation upon follow up and changes in menstrual pattern **Measure:** safety of intrauterine application of Intercoat **Time Frame:** 18 months #### Secondary Outcomes **Description:** intrauterine adhesions were graded according to the AFS score upon hysteroscopic follow up 6-8 weeks following initial treatment **Measure:** efficacy of intrauterine application of Intercoat gel in reducing adhesion formation following hysteroscopic treatment for retained products of conception **Time Frame:** 14 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Age between 18 and 50 years * Availability of the results of vaginal ultrasound or diagnostic hysteroscopy Exclusion Criteria: * Signs of infection upon admission * Ongoing pregnancy **Maximum Age:** 50 Years **Minimum Age:** 18 Years **Sex:** FEMALE **Standard Ages:** - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Zerifin **Country:** Israel **Facility:** Asaf Harofe MC **Zip:** 70300 #### Overall Officials **Official 1:** **Affiliation:** Asaf Harofe MC **Name:** Moty Pansky, MD **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000010335 - Term: Pathologic Processes - ID: D000002921 - Term: Cicatrix - ID: D000005355 - Term: Fibrosis - ID: D000005831 - Term: Genital Diseases, Female - ID: D000052776 - Term: Female Urogenital Diseases - ID: D000005261 - Term: Female Urogenital Diseases and Pregnancy Complications - ID: D000091642 - Term: Urogenital Diseases - ID: D000091662 - Term: Genital Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BXS - Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M16355 - Name: Syndrome - Relevance: LOW - As Found: Unknown - ID: M3620 - Name: Tissue Adhesions - Relevance: HIGH - As Found: Adhesion - ID: M9269 - Name: Gynatresia - Relevance: HIGH - As Found: Asherman Syndrome - ID: M6160 - Name: Cicatrix - Relevance: LOW - As Found: Unknown - ID: M8485 - Name: Fibrosis - Relevance: LOW - As Found: Unknown - ID: M8943 - Name: Genital Diseases, Female - Relevance: LOW - As Found: Unknown - ID: M2876 - Name: Genital Diseases - Relevance: LOW - As Found: Unknown - ID: M2875 - Name: Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M27093 - Name: Female Urogenital Diseases - Relevance: LOW - As Found: Unknown - ID: M14127 - Name: Pregnancy Complications - Relevance: LOW - As Found: Unknown - ID: M8399 - Name: Female Urogenital Diseases and Pregnancy Complications - Relevance: LOW - As Found: Unknown - ID: T509 - Name: Asherman's Syndrome - Relevance: HIGH - As Found: Asherman Syndrome ### Condition Browse Module - Meshes - ID: D000006175 - Term: Gynatresia - ID: D000000267 - Term: Tissue Adhesions ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT01293279 **Acronym:** HCV **Brief Title:** HCV (Hepatitis C Virus) Viral and Host Genotyping (IL28B, Interleukin 28B) in China **Official Title:** HCV Viral Genotyping Distribution and Genetic Variation in IL28B Distributions Among the Han Ethnic Chinese in China #### Organization Study ID Info **ID:** CCgenos #### Organization **Class:** OTHER **Full Name:** Peking University People's Hospital ### Status Module #### Completion Date **Date:** 2011-06 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2011-10-07 **Type:** ESTIMATED **Last Update Submit Date:** 2011-10-06 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2011-06 **Type:** ACTUAL #### Start Date **Date:** 2011-02 **Status Verified Date:** 2011-06 #### Study First Post Date **Date:** 2011-02-10 **Type:** ESTIMATED **Study First Submit Date:** 2011-02-09 **Study First Submit QC Date:** 2011-02-09 ### Sponsor Collaborators Module #### Collaborators **Class:** INDUSTRY **Name:** Bristol-Myers Squibb #### Lead Sponsor **Class:** OTHER **Name:** Peking University People's Hospital #### Responsible Party **Investigator Affiliation:** Peking University People's Hospital **Investigator Full Name:** Lai Wei **Investigator Title:** Professor **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** The primary objective of this study is to estimate the distributions of HCV viral/human genotypes (including IL28B and inosine triphosphatase, ITPA), and HCV RNA level among ITPA gene among 1000 Han ethnic Chinese patients with HCV who are antiviral treatment naive at the time the study is conducted. **Detailed Description:** A sample of 1000 Han ethnic Chinese male or female who are ≥ 18 years old with a recent confirmation of anti-HCV-antibody positive and HCV RNA positive but antiviral treatment naive from 28 university affiliated hospital in China. The primary objective of this study is to estimate the distributions of HCV Viral genotyping(ie, genotype 1 through 6 and their known subtypes), and host genotypes, both inosine triphosphatase (ITPA) gene, and IL28B. This study also collects other data including patients' demographic and clinical characteristics. There is no active antiviral treatments and no follow-up in this study. ### Conditions Module **Conditions:** - Hepatitis C **Keywords:** - HCV viral genotypes - host genotypes - IL28B - ITPA - RNA - China ### Design Module #### Bio Spec **Description:** By having the approvals from the EC and China National Human Genetic Resource Management Office (under China Ministry of Health) and having the patient informed consent, blood samples of all recruited patients will be retained under the proper conditions in Peking University People's Hospital, Beijing, China **Retention:** SAMPLES_WITH_DNA #### Design Info **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 997 **Type:** ESTIMATED **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Han ethnic Chinese male or female ≥ 18 years old with recent a confirmation of anti-HCV-antibody positive and HCV RNA positive but antiviral or interferon treatment naive at the time this study starts from 28 university affiliated hospital throughout China. **Label:** HCV Patients who are treatment naive ### Outcomes Module #### Primary Outcomes **Description:** To describe the distributions of both HCV viral and host genotypes (IL28B and ITPA) among antiviral treatment naive HCV patients **Measure:** Hepatitis C viral and host genotypes **Time Frame:** Confirmation of an HCV infection 30 days prior to the recruitment #### Secondary Outcomes **Description:** To describe the distribution of HCV RNA levels in antiviral treatment-naive HCV patients **Measure:** Hepatitis C RNA levels **Time Frame:** Confirmation of an HCV infection 30 days prior to the recruitment ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * male or female * Han ethnic * ≥ 18 years old * recent confirmation of anti-HCV-antibody positive and HCV RNA positive 30 days prior to the recruitment * antiviral or interferon treatment naive Exclusion Criteria: * \< 18 years old * not Han ethnic * treated by antiviral before this study **Minimum Age:** 18 Years **Sampling Method:** PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** 1000 Han ethnic Chinese in China ### Contacts Locations Module #### Locations **Location 1:** **City:** Beijing **Country:** China **Facility:** Lai Wei **State:** Beijing **Zip:** 100044 #### Overall Officials **Official 1:** **Affiliation:** Peking University People's Hospital, Peking University Hepatology Institute **Name:** Lai Wei, MD **Role:** PRINCIPAL_INVESTIGATOR **Official 2:** **Affiliation:** Bristol-Myers Squibb **Name:** Hong Li, Ph.D., MPH **Role:** STUDY_DIRECTOR ### References Module #### References **Citation:** Wu N, Rao HY, Yang WB, Gao ZL, Yang RF, Fei R, Gao YH, Jin Q, Wei L. Impact of hepatitis C virus genotype 3 on liver disease progression in a Chinese national cohort. Chin Med J (Engl). 2020 Feb 5;133(3):253-261. doi: 10.1097/CM9.0000000000000629. **PMID:** 31934936 **Citation:** Huang R, Rao H, Shang J, Chen H, Li J, Xie Q, Gao Z, Wang L, Wei J, Jiang J, Sun J, Jiang J, Wei L. A cross-sectional assessment of health-related quality of life in Chinese patients with chronic hepatitis c virus infection with EQ-5D. Health Qual Life Outcomes. 2018 Jun 15;16(1):124. doi: 10.1186/s12955-018-0941-8. **PMID:** 29903024 **Citation:** Yan LB, Rao HY, Ma YJ, Bai L, Chen EQ, Du LY, Yang RF, Wei L, Tang H; CCgenos Study Group. Hepatitis B virus infection in Chinese patients with hepatitis C virus infection: prevalence, clinical characteristics, viral interactions and host genotypes: a nationwide cross-sectional study. BMJ Open. 2016 Oct 12;6(10):e012016. doi: 10.1136/bmjopen-2016-012016. **PMID:** 27733412 ## 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 ### 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 ### Condition Browse Module - Browse Leaves - ID: M9592 - Name: Hepatitis A - Relevance: HIGH - As Found: Hepatitis - ID: M9591 - Name: Hepatitis - Relevance: HIGH - As Found: Hepatitis - ID: M17522 - Name: Virus Diseases - Relevance: LOW - As Found: Unknown - ID: M9611 - Name: Hepatitis C - Relevance: HIGH - As Found: Hepatitis C - ID: M11107 - Name: Liver Diseases - Relevance: LOW - As Found: Unknown - ID: M7255 - Name: Digestive System Diseases - Relevance: LOW - As Found: Unknown - ID: M8883 - Name: Gastrointestinal Diseases - Relevance: LOW - As Found: Unknown - ID: M9610 - Name: Hepatitis, Viral, Human - Relevance: LOW - As Found: Unknown - ID: M10283 - Name: Infections - Relevance: LOW - As Found: Unknown - ID: M6368 - Name: Communicable Diseases - Relevance: LOW - As Found: Unknown - ID: M7930 - Name: Enterovirus Infections - Relevance: LOW - As Found: Unknown - ID: M13745 - Name: Picornaviridae Infections - Relevance: LOW - As Found: Unknown - ID: M15149 - Name: RNA Virus Infections - Relevance: LOW - As Found: Unknown - ID: M2593 - Name: Blood-Borne Infections - Relevance: LOW - As Found: Unknown - ID: M20324 - Name: Flaviviridae Infections - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000006506 - Term: Hepatitis A - ID: D000006526 - Term: Hepatitis C - ID: D000006505 - Term: Hepatitis ### Intervention Browse Module - Browse Branches - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Infe - Name: Anti-Infective Agents - Abbrev: ANeo - Name: Antineoplastic Agents ### Intervention Browse Module - Browse Leaves - ID: M4225 - Name: Antibodies - Relevance: LOW - As Found: Unknown - ID: M10184 - Name: Immunoglobulins - Relevance: LOW - As Found: Unknown - ID: M20971 - Name: Hepatitis C Antibodies - Relevance: LOW - As Found: Unknown - ID: M10407 - Name: Interferons - Relevance: LOW - As Found: Unknown - ID: M4314 - Name: Antiviral Agents - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04296279 **Brief Title:** A Trial For The Study of Falciparum Malaria Protein 014 Administered Via Intramuscular Injection in Healthy Adults **Official Title:** Phase 1 Clinical Trial With Controlled Human Malaria Infection (CHMI) for Safety, Protective Efficacy, and Immunogenicity of Plasmodium Falciparum Malaria Protein (FMP014) Administered Intramuscularly With ALFQ Healthy Malaria-Naïve Adults #### Organization Study ID Info **ID:** S-19-05 #### Organization **Class:** FED **Full Name:** U.S. Army Medical Research and Development Command ### Status Module #### Completion Date **Date:** 2022-12 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** RECRUITING #### Last Update Post Date **Date:** 2021-04-19 **Type:** ACTUAL **Last Update Submit Date:** 2021-04-14 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2021-12 **Type:** ESTIMATED #### Start Date **Date:** 2020-03-20 **Type:** ACTUAL **Status Verified Date:** 2021-04 #### Study First Post Date **Date:** 2020-03-05 **Type:** ACTUAL **Study First Submit Date:** 2020-02-18 **Study First Submit QC Date:** 2020-03-02 ### Sponsor Collaborators Module #### Collaborators **Class:** FED **Name:** Walter Reed Army Institute of Research (WRAIR) #### Lead Sponsor **Class:** FED **Name:** U.S. Army Medical Research and Development Command #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** True **Oversight Has DMC:** False ### Description Module **Brief Summary:** A Phase 1, open label clinical study to evaluate the safety, immunogenicity, tolerability and efficacy of Plasmodium falciparum Malaria Protein 014 (FMP014) combined with (ALF with QS-21), saponin molecule derived from the bark of Quillaja species (ALFQ)) in healthy adult volunteers at different doses and dosing schedules. **Detailed Description:** This is an open-label immunization with Controlled Human Malaria Infection (CHMI) study. Healthy, malaria-naïve adults, aged 18-55 years old will be recruited into one of 5 experimental cohorts in 2 parts. In Part A, 2 experimental cohorts of 5 subjects each will receive a series of 3 vaccinations at 0, 1, and 2 months at 2 doses (the "low dose" arm and the "high dose" arm). In Part B, 3 experimental cohorts of 10 subjects will receive a series of 3 vaccinations at 0, 1, 6 months (called the "delayed dose" arm), the "delayed fractional dose" arm is vaccinated at 0, 1, and 6 months with the 6 month dose being 1/5 the other doses, and the "standard" arm" at the 4th, 5th, and 6th month (after the first 2 vaccinations of the other 2 arms in Part B). ### Conditions Module **Conditions:** - Vaccine Reaction **Keywords:** - Plasmodioum falciparum 014 ### Design Module #### Design Info **Allocation:** NON_RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** PREVENTION #### Enrollment Info **Count:** 46 **Type:** ESTIMATED **Phases:** - PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Part A vaccinees in the "low dose" arm will receive the lower dosing (20 μg FMP014 per 0.5 mL ALFQ) approximately 2 weeks prior to each vaccination. Vaccination to be delivered on 0,1,2 month. **Intervention Names:** - Drug: FMP014 - Drug: ALFQ **Label:** Part A - "Low" Dose **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** Part A vaccinees in the "high dose" arm will receive the lower dosing (40 μg FMP014 per 1.0 mL ALFQ) approximately 2 weeks prior to each vaccination. Vaccination to be delivered on 0,1,2 month. **Intervention Names:** - Drug: FMP014 - Drug: ALFQ **Label:** Part A - "High" Dose **Type:** ACTIVE_COMPARATOR #### Arm Group 3 **Description:** Part B vaccinees in the "high dose" arm will receive the lower dosing (40 μg FMP014 per 1.0 mL ALFQ) approximately 2 weeks prior to each vaccination. Vaccination to be delivered on 4,5,6 month. **Intervention Names:** - Drug: FMP014 - Drug: ALFQ **Label:** Part B - "Standard" Dose **Type:** ACTIVE_COMPARATOR #### Arm Group 4 **Description:** Part B vaccinees in the "high dose" arm will receive the lower dosing (40 μg FMP014 per 1.0 mL ALFQ) approximately 2 weeks prior to each vaccination. Vaccination to be delivered on 0,1,6 month. **Intervention Names:** - Drug: FMP014 - Drug: ALFQ **Label:** Part B - "Delayed" Dose **Type:** ACTIVE_COMPARATOR #### Arm Group 5 **Description:** Part B vaccinees in the "high dose" arm will receive the lower dosing (40 μg FMP014 per 1.0 mL ALFQ) approximately 2 weeks prior to each vaccination. Vaccination to be delivered on 0,1,6 month. **Intervention Names:** - Drug: FMP014 - Drug: ALFQ **Label:** Part B - "Delayed Fractional" Dose **Type:** ACTIVE_COMPARATOR #### Arm Group 6 **Description:** Up to 6 subjects will be enrolled (defined as receiving malaria challenge) later in the trial to serve as challenge controls. Additional subjects may be recruited as alternates to ensure that 6 control subjects undergo the challenge. Any alternates not challenged will be released from the study at day of challenge. **Label:** Control **Type:** NO_INTERVENTION ### Interventions #### Intervention 1 **Arm Group Labels:** - Part A - "High" Dose - Part A - "Low" Dose - Part B - "Delayed Fractional" Dose - Part B - "Delayed" Dose - Part B - "Standard" Dose **Description:** Falciparum Malaria Protein-14 **Name:** FMP014 **Type:** DRUG #### Intervention 2 **Arm Group Labels:** - Part A - "High" Dose - Part A - "Low" Dose - Part B - "Delayed Fractional" Dose - Part B - "Delayed" Dose - Part B - "Standard" Dose **Description:** ALF with QS-21, saponin molecule derived from the tree bark of Quillaja species **Name:** ALFQ **Type:** DRUG ### Outcomes Module #### Other Outcomes **Description:** Proportion of vaccinated subjects without P. falciparum parasitemia (defined as one positive qRT-PCR test and/or one positive TBS, whichever is first) following CHMI. Comparisons will be made across treatment groups. **Measure:** Compare the efficacy of standard, delayed dosing, and delayed fractional dosing: Proportion of vaccinated subjects without P. falciparum parasitemia **Time Frame:** 505 Days (+/- 14) #### Primary Outcomes **Description:** To assess the safety of candidate malaria vaccine FMP014/ALFQ. Safety dosage as indicated by incidence of solicited adverse events and serious adverse events through the end of the study. **Measure:** Safety Dosage of Candidate Malaria Vaccine FMP014/ALFQ **Time Frame:** 393 Days (+/- 14) **Description:** Measuring the number of local (signs and symptoms) adverse events reported by candidates receiving the candidate malaria vaccine FMP014/ALFQ. **Measure:** Assess expected immunological response associated with Candidate Malaria Vaccine FMP014/ALFQ **Time Frame:** 393 Days (+/- 14) #### Secondary Outcomes **Description:** Proportion of vaccinated subjects without P.falciparum parasitemia (defined as one positive qRT-PCR test. Time to onset of P. falciparum parasitemia (defined as one positive qRT-PCR test) following CHMI. **Measure:** Determine the number of days before Plasmodium falciparum infection in controlled humans vaccinated with FMP014/ALFQ **Time Frame:** 505 Days (+/- 14) **Description:** Measuring the number of T-cells using peripheral blood mononuclear cells that appear in individuals each day post exposure to FPM014/ALFQ **Measure:** Measure (Quantitative) Immune Responses to CSP, induced by FMP014/ALFQ using various immunoassays. **Time Frame:** 505 Days (+/- 14) **Description:** Measuring quality of life by the Physicians Global Assessment that appear in individuals each day post exposure to FPM014/ALFQ **Measure:** Measure (Qualitative) Immune Responses to CSP, induced by FMP014/ALFQ using various immunoassays. **Time Frame:** 505 Days (+/- 14) ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Healthy adults between the ages 18-55 (inclusive); 2. Able and willing to provide written, informed consent; 3. Able and willing to comply with all research requirements, in the opinion of the Investigator; 4. Agreement to refrain from blood donation during the course of the study. Volunteers who have undergone CHMI can donate to other research once the study is complete but cannot donate to the American Red Cross for at least 3 years after the CHMI event; 5. Laboratory Criteria within 90 days before enrollment: * Hemoglobin ≥ 11.7 g/dL for women; ≥ 12.0 g/dL for men; * White Blood Cell count = 3,800-10,800 cells/mm3; * Platelets = 140,000-400,000/mm3; * Alanine aminotransferase (ALT; SGPT) 9-46 U/L male and 6-29 U/L female; * Serum creatinine ≤ 1.5 mg/dL; * Negative HIV testing (HIV Ab / antigen 4th generation screen with reflex confirmatory RNA testing); * Negative hepatitis B surface antigen (HBsAg) and hepatitis C antibody testing; Note: As above, Grade 1 lab abnormalities detected on screening may be repeated at PI discretion. Persistent Grade 1 abnormalities that are felt to represent the non-pathologic baseline for the subject will be discussed with the research monitor and documented before a subject is enrolled in the trial, and are allowable per discretion and agreement of the PI and Research Monitor 6. Birth control requirements: Female subjects must meet one of the following 2 criteria: * No reproductive potential due to post-menopausal status (12 months of natural \[spontaneous\] amenorrhea) or hysterectomy, bilateral oophorectomy or tubal ligation; * Women of childbearing potential should agree to practice highly effective contraception at least 30 days before enrollment and through 3 months post-CHMI or post-last vaccination (whichever is latest), using one of the following methods: condoms (male or female) with spermicide; diaphragm, or cervical cap with spermicide; intrauterine device; contraceptive pills, patch, injection, intravaginal ring or other FDA-approved contraceptive method; male partner has previously undergone a vasectomy; abstinence. Male subjects are encouraged but not required to practice highly effective contraception to avoid pregnancy in their partner from 30 days prior to enrollment through 60 days post-CHMI. This is due to the potential impact of malaria and antimalarial medications on spermatogenesis. 7. For all female subjects except those with a history of hysterectomy or bilateral oophorectomy, a negative β-HCG pregnancy test (urine) on day of enrollment, each day of vaccination, and the day of CHMI (tubal ligations have a not insignificant failure rate, 12 months of spontaneous amenorrhea does not completely preclude pregnancy and can be a result of polycystic ovarian syndrome); 8. Reachable (24/7) by mobile phone or other method of communication (email, landline, etc) during the period between CHMI and 28 days post-CHMI, per volunteer report; 9. No plans to travel outside the Washington DC metro area (DC, Maryland, and Virginia) between the day of challenge and 28 days post-challenge; For Travel outside the US occurring 28 days post-challenge to a malaria endemic area inclusion will be at the discretion of the PI. 10. If a subject is active duty military, he or she must obtain approval from his or her supervisor per WRAIR Policy 11-45; 11. Must have low (\< 10%) cardiac risk factors according to clinical Gaziano (NHANES I) criteria assessed at screening, and a normal or normal variant ECG; 12. Completion of Study Comprehension Quiz (minimum passing score of 80% with 2 attempts permitted). 13. Subject must be willing to take anti-malarial treatment after CHMI; 14. Subject must provide 2 emergency contacts who will be made aware of the subject's participation in this trial and the vital importance of being reached during the challenge phase of the study. Both contacts must be verified by pone prior to subject enrollment. Verification will be define as either speaking to the emergency contact over the phone, hearing their name included in the voicemail response, or confirming the emergency contact uses the number if a third party answers the phone. Exclusion Criteria: 1. History of malaria infection (any species) or residence in a malaria-endemic area for more than 5 years (includes previous participation in CHMI studies). 2. Previous travel to malaria endemic regions within the past 6 months before study enrollment defined as first vaccination or day of challenge (for infectivity controls) or planned travel to malaria endemic regions during the vaccination, CHMI and 28-day CHMI follow-up period; For Travel outside the US occurring 28 days post-challenge to a malaria endemic area exclusion will be at the discretion of the PI. 3. Any history of receiving a malaria vaccine. 4. Received an investigational product in the 30 days before enrollment, or planned to receive during the study period. 5. Concurrent participation in another clinical research study. 6. Any use of medications that prevent or treat malaria during the 1 month prior to challenge or planned use during the study (outside of the drugs provided by the study team). 7. Any serious medical illness or condition involving the heart, liver, lungs, or kidneys. 8. Any significant risk for developing heart disease in the next 5 years, assessed according to clinical Gaziano (NHANES I) criteria assessed at screening, and an ECG. 9. Receipt of immunoglobulins or blood products within 3 months before enrollment. 10. Any history of anaphylaxis. 11. History of sickle cell trait or disease, or any condition that could affect susceptibility to malaria infection, per subject verbal report. 12. Pregnancy, lactation, or intention to become pregnant during the study, and 3 months after malaria challenge, if applicable. 13. Contraindications or allergies to the use of all 3 proposed anti-malarial medications; Malarone (atovaquone/proguanil), Coartem (artemether/lumefantrine) and chloroquine; contraindication to 1 or 2 is not exclusionary. 14. History of active/recent cancer still within treatment or active surveillance follow-up (except basal cell carcinoma of the skin and cervical carcinoma in situ). Treated/resolved cancers with no likelihood of recurrence may be deemed acceptable at Principal investigator discretion 15. History of autoimmune disease. 16. Significant (eg systemic anaphylaxis) hypersensitivity reactions to mosquito bites (local reactions at the site of mosquito bites are not an exclusion criterion) requiring hospitalization. 17. Suspected or known current alcohol or drug abuse as defined by an alcohol intake of greater than 3 drinks a day on average for a man, and greater than 2 drinks a day on average for a woman. 18. Any other significant disease, disorder or finding which may significantly increase the risk to the volunteer because of participation in the study, affect the ability of the volunteer to give informed consent, participate in the study, or impair interpretation of the study data, in the opinion of the Investigator. 19. Current anti-tuberculosis prophylaxis or treatment. 20. History of splenectomy. 21. History of confirmed or suspected immunodeficiency. 22. History of Hereditary angioedema (HAE), acquired angioedema (AAE), or idiopathic forms of angioedema. 23. History of Asthma that is unstable or required emergent care, urgent care, hospitalization or intubation during the past 2 years. 24. History of Diabetes mellitus (type I or II), with the exception of gestational diabetes. 25. History of Thyroid disease (except for well controlled hypothyroidism). 26. History of Idiopathic urticaria within the past year. 27. History of hypertension that is not well controlled by medication or that is persistently greater than 150/95 at screening... 28. History of bleeding disorder diagnosed by a doctor (eg, factor deficiency, coagulopathy, or platelet disorder requiring special precautions) or significant bruising or bleeding difficulties with IM injections or blood draws. 29. History of chronic or active neurologic disease to include seizure disorder and chronic migraine headaches. Exceptions are: i) childhood febrile seizures, or ii) seizures secondary to alcohol withdrawal more than 3 years ago. 30. Subjects receiving any of the following substances: * Systemic immunosuppressive medications or cytotoxic medications within 12 weeks before enrollment \[with the exception of a short course of corticosteroids (≤ 14 days duration or a single injection) for a self-limited condition at least 2 weeks before enrollment; inhaled, intranasal or topical steroids are not considered exclusionary\] * Treatment with known immunomodulators (other than nonsteroidal anti-inflammatory drugs \[NSAIDs\]) for any reason. * History of receipt of medication that prevent or treat malaria within 1 month of CHMI * Live attenuated vaccines within 30 days before initial study vaccine administration * Medically indicated subunit or killed vaccines, eg, influenza, pneumococcal, or allergy treatment with antigen injections, planned for administration 14 days before or after study vaccine administration 31. History of arthritis diagnosis other than osteoarthritis. 32. History of other diagnosed rheumatoid disorders. 33. Any history of psoriasis (itchy skin rash) or porphyria (rare disturbance of metabolism), since these conditions could get worse after treatment with chloroquine (a medication for treating malaria). 34. Subject must not have a fever in order to receive the study vaccine or participate in the malaria challenge. **Healthy Volunteers:** True **Maximum Age:** 55 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Jack N Hutter MD, MPH&TM, MAJ, MC, USA **Phone:** 301-319-3095 **Role:** CONTACT #### Locations **Location 1:** **City:** Silver Spring **Contacts:** ***Contact 1:*** - **Email:** [email protected] - **Name:** Jack N Hutter, MD, MPH&TM, MAJ, MC, USA - **Phone:** 301-319-3095 - **Role:** CONTACT **Country:** United States **Facility:** Walter Reed Army Institute of Research **State:** Maryland **Status:** RECRUITING **Zip:** 20910 ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Ancestors - ID: D000011528 - Term: Protozoan Infections - ID: D000010272 - Term: Parasitic Diseases - ID: D000007239 - Term: Infections - ID: D000096724 - Term: Mosquito-Borne Diseases - ID: D000079426 - Term: Vector Borne Diseases ### 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: LOW - As Found: Unknown - ID: M6368 - Name: Communicable Diseases - Relevance: LOW - As Found: Unknown - ID: M11280 - Name: Malaria - Relevance: HIGH - As Found: Malaria - ID: M19133 - Name: Malaria, Falciparum - Relevance: HIGH - As Found: Falciparum Malaria - ID: M14388 - Name: Protozoan Infections - Relevance: LOW - As Found: Unknown - ID: M13185 - Name: Parasitic Diseases - Relevance: LOW - As Found: Unknown - ID: M3255 - Name: Mosquito-Borne Diseases - Relevance: LOW - As Found: Unknown - ID: M2054 - Name: Vector Borne Diseases - Relevance: LOW - As Found: Unknown - ID: T3571 - Name: Malaria - Relevance: HIGH - As Found: Malaria ### Condition Browse Module - Meshes - ID: D000008288 - Term: Malaria - ID: D000016778 - Term: Malaria, Falciparum ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT01545479 **Brief Title:** Increased Renal Oxygenation and Angiotensin Converting Enzyme Inhibition **Official Title:** Renal Oxygen Content is Increased in Healthy Subjects After Angiotensin Converting Enzyme Inhibition #### Organization Study ID Info **ID:** 4111/08 #### Organization **Class:** OTHER **Full Name:** Instituto de Cardiologia do Rio Grande do Sul ### Status Module #### Completion Date **Date:** 2010-12 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2012-03-06 **Type:** ESTIMATED **Last Update Submit Date:** 2012-03-01 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2010-10 **Type:** ACTUAL #### Start Date **Date:** 2010-01 **Status Verified Date:** 2012-03 #### Study First Post Date **Date:** 2012-03-06 **Type:** ESTIMATED **Study First Submit Date:** 2012-01-16 **Study First Submit QC Date:** 2012-03-01 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Instituto de Cardiologia do Rio Grande do Sul #### Responsible Party **Investigator Affiliation:** Instituto de Cardiologia do Rio Grande do Sul **Investigator Full Name:** Maria Antonieta Moraes **Investigator Title:** Doctorate **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** It is well established that renal hypoxia is associated with the development of renal injury. The purpose of this study is measure the alterations in renal blood oxygenation after angiotensin II converting enzyme inhibition. The understanding of kidney adaptive mechanisms to renin angiotensin system effects in healthy subjects will be useful for the early detection of renal disease and for the development of new therapies to decrease the progression of the disease and its consequences. **Detailed Description:** Subjects The study will be conducted under a protocol (number 4111/08) approved by the Ethics Committee of the Instituto de Cardiologia do Rio Grande do Sul-Fundação Universitária de Cardiologia/Brazil. After giving their informed consent,the patients will participate in the study. None of the subjects will take medication,food and water overnight. All measurements will be performed at the end of the morning. After control BOLD-MRI measurements acquisition, subjects will take an oral ACE inhibitor (captopril 25 mg). Thirty minutes after captopril administration, without moving from the scanner, blood pressure will be measured and a second BOLD acquisition will be performed to detect a possible alteration in the renal oxygenation. Data will be collected by two radiologists and interpreted by a physician and a physiologist. MR Imaging Technique Images were acquired using 1.5T HDx (Sigma, GE Healthcare, Waukesha, Win) and an 8 channels body coil. Localizer images will be performed with axial and sagittal planes following the long axis of both kidneys, using breath hold and fast spoiled gradient echo (FSPGR) technique. Oblique axial and coronal reference images will be acquired for color maps following approximately the short and long axis of both kidneys using FSPGR with the following parameters: FOV=40cm, matrix 256x128, slice thickness=5cm, slice gap 6cm, 3 slices per plane in one breath hold. TR=150ms, TE=min full, FLIP=90, rBW=62KHz, 1NEX. This sequence provides an excellent contrast between cortex and medulla and avoid the unnecessary use of a contrast agents. BOLD sensitive images will be acquired using the multiple echo FGRE sequence with the same geometrical parameters. The reference images considered will have the following parameters: TR = 60ms, FLIP=30, rBW=60KHz, 16 echoes from TE=2.1ms until 49.6ms, echo interval of 3.2ms, 1 NEX. BOLD imaging Data Processing Bold image processing will be performed using the Function R2\* module for R2\*/T2\* fitting, assuming single exponential decay without constant offset at AW4.3 (GE Healthcare). For visualization and quantification, R2\* parametric maps will be generated for each slice.(11, 18-19) A Puh Talium color table will be used, since it was a dynamic range with minimum value set at 7.0/sec and maximum value at 23/sec. Color will be ranged from blue to red, close to minimum R2\* and below and close to maximum R2\* and above, respectively. The green/yellow will be assumed as intermediate. When a position mismatch due to a different breath hold state, anatomical fat suppressed FSPGR images were used as transparent references over a parametric map or original BOLD images. One slice out of three, which provided the best differentiation between cortex and medulla and minimum partial volume, will be selected for quantification. A total of 6 regions of interest (ROI) with a 9 pixel size were used, 3 positioned at the cortex and 3 at the medulla for each plane. The ROIs will be positioned at the cortex according to the anatomical reference image (light gray) and blue on the parametric map. The ROIs will be positioned at the medulla using either the anatomical reference image (dark gray) or the parametric map that showed a green, yellow and red gradient (figure 1). Areas with susceptibility artifacts, such as bowel gas or areas with renal hilum vessels, will be avoided. Data analysis The statistical analysis will be determined by variance test for three repeated measures (ANOVA). Data are presented as the mean ± SD. P\<0.05 will be considered statistically significant. ### Conditions Module **Conditions:** - Renal Disease **Keywords:** - ECA - BOLD-MRI - kidney ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** HEALTH_SERVICES_RESEARCH #### Enrollment Info **Count:** 5 **Type:** ACTUAL **Phases:** - PHASE4 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** To study the renal blood oxygenation, the subjects took captopril (25mg). **Intervention Names:** - Drug: captopril 25mg **Label:** Captopril 25mg **Type:** OTHER ### Interventions #### Intervention 1 **Arm Group Labels:** - Captopril 25mg **Description:** renal blood oxygenation after captopril **Name:** captopril 25mg **Other Names:** - BOLD-MRI **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Measure:** Measure the renal blood oxigenation after angiotensin converting enzyme inhibition **Time Frame:** up to 12 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * healthy female between 45 and 55 years Exclusion Criteria * man and * health female below 45 and above 55 years **Healthy Volunteers:** True **Maximum Age:** 55 Years **Minimum Age:** 45 Years **Sex:** FEMALE **Standard Ages:** - ADULT ### Contacts Locations Module #### Overall Officials **Official 1:** **Affiliation:** Instituto de Cardiologia do Rio Grande do Sul **Name:** MAntonieta Moraes, Dr **Role:** STUDY_CHAIR ### References Module #### References **Citation:** Stein A, Goldmeier S, Voltolini S, Setogutti E, Feldman C, Figueiredo E, Eick R, Irigoyen M, Rigatto K. Renal oxygen content is increased in healthy subjects after angiotensin-converting enzyme inhibition. Clinics (Sao Paulo). 2012 Jul;67(7):761-5. doi: 10.6061/clinics/2012(07)10. **PMID:** 22892920 ## Derived Section ### Condition Browse Module - Ancestors - 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 ### Condition Browse Module - Browse Branches - Abbrev: BXS - Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M10698 - Name: Kidney Diseases - Relevance: HIGH - As Found: Renal Disease - 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 ### Condition Browse Module - Meshes - ID: D000007674 - Term: Kidney Diseases ### Intervention Browse Module - Ancestors - ID: D000000806 - Term: Angiotensin-Converting Enzyme Inhibitors - ID: D000011480 - Term: Protease Inhibitors - ID: D000004791 - Term: Enzyme Inhibitors - ID: D000045504 - Term: Molecular Mechanisms of Pharmacological Action - ID: D000000959 - Term: Antihypertensive Agents ### Intervention Browse Module - Browse Branches - Abbrev: AnAg - Name: Antihypertensive Agents - Abbrev: All - Name: All Drugs and Chemicals - Abbrev: Infe - Name: Anti-Infective Agents ### Intervention Browse Module - Browse Leaves - ID: M5476 - Name: Captopril - Relevance: HIGH - As Found: Fluid therapy - ID: M7951 - Name: Enzyme Inhibitors - Relevance: LOW - As Found: Unknown - ID: M4134 - Name: Angiotensin-Converting Enzyme Inhibitors - Relevance: LOW - As Found: Unknown - ID: M19609 - Name: HIV Protease Inhibitors - Relevance: LOW - As Found: Unknown - ID: M14343 - Name: Protease Inhibitors - Relevance: LOW - As Found: Unknown - ID: M4277 - Name: Antihypertensive Agents - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000002216 - Term: Captopril ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04755179 **Acronym:** CAPP **Brief Title:** Identification of the Optimal Treatment Strategy for Complex Appendicitis in the Pediatric Population **Official Title:** The Identification of the Optimal Treatment Strategy for Complex Appendicitis in the Pediatric Population #### Organization Study ID Info **ID:** W18_302#18.348 #### Organization **Class:** OTHER **Full Name:** Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) ### Status Module #### Completion Date **Date:** 2023-07-12 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2022-07-25 **Type:** ACTUAL **Last Update Submit Date:** 2022-07-22 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2023-05-12 **Type:** ESTIMATED #### Start Date **Date:** 2019-08-12 **Type:** ACTUAL **Status Verified Date:** 2022-07 #### Study First Post Date **Date:** 2021-02-16 **Type:** ACTUAL **Study First Submit Date:** 2021-01-29 **Study First Submit QC Date:** 2021-02-10 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** ZonMw: The Netherlands Organisation for Health Research and Development **Class:** OTHER **Name:** Amsterdam UMC, location VUmc #### Lead Sponsor **Class:** OTHER **Name:** Ramon Gorter #### Responsible Party **Investigator Affiliation:** Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) **Investigator Full Name:** Ramon Gorter **Investigator Title:** Dr. **Type:** SPONSOR_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Aim of this study is to evaluate the effect of different treatment strategies on overall complications, health related-Quality of Life (hr-QOL) and costs among two subtypes of complex appendicitis in children (\<18 years old). Main research questions: What is the difference in overall complications at three months between: Subgroup 1 (complex appendicitis without abscess/mass formation): Laparoscopic (LA) and open appendectomy (OA) Subgroup 2: (complex appendicitis with abscess/mass formation): Non-operative treatment (NOT) and direct appendectomy **Detailed Description:** Up till now initiated research projects worldwide mainly focus on simple appendicitis (questioning the necessity of an appendectomy). However, complex appendicitis is associated with significant morbidity (up to 30%), prolonged hospital stay and high costs. Identification of the optimal treatment strategy for children with complex appendicitis is therefore essential. Heterogeneity in the treatment of complex appendicitis still exists in daily practice and reflects the lack of high-quality data and emphasizes the need for well-designed studies. Complex appendicitis can be divided into two subtypes: 1. Complex appendicitis without mass/abscess. (subgroup 1) Although (inter)national guidelines agree that appendectomy should be usual care, the optimal approach (open or laparoscopy) is unclear. Laparoscopic appendectomy (LA) is increasingly applied both in adults (80%) and children (60%). Benefits reported for LA in children are, but not limited to, less superficial site infection (SSI), reduced length of hospital stay and significant less postoperative bowel obstruction compared with open appendectomy (OA). Reluctance for usage of LA in this specific subgroup, however, remains due to the potential higher incidence of post-appendectomy abscess formation (PAA) reported. However, the quality of studies on this topic is low and there is considerable inconsistency in results. 2. Complex appendicitis with mass/abscess. (subgroup 2) The recommendation made in our national guideline (to perform direct appendectomy in this subgroup) is not in line with the available literature. A recent Cochrane review on this topic could only include two trials and stated that no firm conclusions could be drawn. An older systematic review, including 7 studies in children, concluded that non-operative treatment (NOT) led to fewer complications, specifically SSI and PAA, when compared to direct appendectomy. Still the recommendation from our national guideline is to perform a direct appendectomy based upon good experiences in the pediatric academic centers. In order to investigate the optimal treatment for children with complex appendicitis we will perform a nationwide, multi-center, comparative, prospective cohort study. For the purpose of this study, treatment strategies will be standardized among the participating hospitals in order to reduce heterogeneity. Prospectively derived, high quality data will be sufficient to answer the research questions regarding the optimal treatment strategy for each subtype of complex appendicitis in the pediatric population. As it is a non-randomized prospective cohort study, propensity score matching technique will be performed in order to estimate the effect of the treatments adjusted for potential confounders. ### Conditions Module **Conditions:** - Appendicitis - Appendix Mass - Appendicitis Perforated **Keywords:** - Complex appendicitis - Children - Treatment ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 1308 **Type:** ESTIMATED **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** All children (\<18 years old) that present with a suspicion of complex appendicitis without clinical or radiological signs of abscess or mass formation. Preoperative suspicion of complex appendicitis is based upon a previously developed clinical scoring system. **Intervention Names:** - Procedure: Laparoscopic appendectomy - Procedure: Open appendectomy **Label:** Complex appendicitis without abscess or mass formation #### Arm Group 2 **Description:** All children (\<18 years old) that present with a suspicion of complex appendicitis with clinical or radiological signs of abscess or mass formation. Preoperative suspicion of complex appendicitis is based upon a previously developed clinical scoring system. **Intervention Names:** - Procedure: Non-operative treatment - Procedure: Direct appendectomy **Label:** Complex appendicitis with abscess or mass formation ### Interventions #### Intervention 1 **Arm Group Labels:** - Complex appendicitis without abscess or mass formation **Description:** Laparoscopic appendectomy is performed according to daily practice but with the following standardized key points: 1. Conventional laparoscopy (three-trocar technique) 2. In case of purulent fluid: Suction and no peritoneal lavage procedure 3. Skelletizing of the mesoappendix (coagulation/clips according to routine practice locally) 4. Appendiceal stump closure: with two endoloops and dissected between the endoloops. In case of involvement of the appendiceal base, the use of endostapler is recommended. 5. Withdrawal of appendix: principle of abdominal wall protection is followed (trocar technique / endobag) 6. No drain placement, no nasogastric tube, and no urinary catheter routinely, only on indication. 7. Closure of wounds as appropriate **Name:** Laparoscopic appendectomy **Type:** PROCEDURE #### Intervention 2 **Arm Group Labels:** - Complex appendicitis without abscess or mass formation **Description:** Open appendectomy will be performed according to the following standardized key points: 1. Gridiron incision at the right lower quadrant. (McBurney's point) 2. After obtaining access to the abdominal cavity the principle of abdominal wall protection will be followed. 3. The appendiceal stump will be closed by ligation, not a purse string suture. 4. Closure of wounds as appropriate **Name:** Open appendectomy **Type:** PROCEDURE #### Intervention 3 **Arm Group Labels:** - Complex appendicitis with abscess or mass formation **Description:** Non-operative treatment consisting of administration of intravenous antibiotics with or without drainage procedures (in case of an abscess), reserving an appendectomy for those not responding or with recurrent disease. One of the two antibiotic regiments: 1. Combination A: 1. Amoxicillin/clavulanic acid 25/2.5mg/kg 6 hourly (total 100/10 mg/kg daily. Maximum 6000/600mg a day) for children \<40 kg OR Amoxicillin/clavulanic acid 1000/200mg/kg 8 hourly (total 3000/6000 mg/kg daily) for children \> 40 kg 2. Gentamicin 7mg/kg once daily 2. Combination B: 1. Cefuroxim 25 mg/kg 6 hourly (total 100 mg/kg/day. Maximum 6gram/day) 2. Metronidazole 10mg/kg 8hourly (total 30 mg/kg/day. Maximum 4000 mg/day) In case of peri-appendicular abscess the decision can be made to perform a drainage procedure either percutaneously or surgical. **Name:** Non-operative treatment **Type:** PROCEDURE #### Intervention 4 **Arm Group Labels:** - Complex appendicitis with abscess or mass formation **Description:** laparoscopic or open appendectomy as described **Name:** Direct appendectomy **Type:** PROCEDURE ### Outcomes Module #### Primary Outcomes **Description:** The proportion of patients experiencing any complication within 3 months after inclusion **Measure:** Overall complications **Time Frame:** 3 months #### Secondary Outcomes **Description:** Proportion patients with a postappendectomy abscess **Measure:** Postappendectomy abscess **Time Frame:** 3 months **Description:** Proportion of patients with a superficial site infection **Measure:** Superficial Site Infection **Time Frame:** 3 months **Description:** Proportion of patients with a secondary/prolonged bowel obstruction **Measure:** Secondary bowel obstruction **Time Frame:** 3 months **Description:** Number of days absent from school, social or sports events **Measure:** Days absent from school, social or sports events **Time Frame:** 30 days, 3 months **Description:** Number of days that parents are absent from work **Measure:** Number of days absent from work **Time Frame:** 30 days, 3 months **Description:** Total number of extra visits to the outpatient clinic, general pratctitioner's office or emergency department **Measure:** Total number of extra visits **Time Frame:** 30 days, 3 months **Description:** Total length of hospital stay during follow-up due to trategy related treatment or complications **Measure:** Length of hospital stay **Time Frame:** 3 months **Description:** Level of pain measured according to the Visual Analogue Scale (0-10 points, higher scores indicating worse outcomes) **Measure:** Level of pain **Time Frame:** at inclusion/baseline (=day 0), 3 days, 5 days, 30 days, 3 months **Description:** Pain medication utilization during admission **Measure:** Pain medication utilization **Time Frame:** 30 days, 3 months **Description:** Proportion of patients not having to undergo appendectomy within 3 months after start of non-operative treatment **Measure:** Need for appendectomy **Time Frame:** 3 months **Description:** Proportion of patients experiencing recurrent appendicitis within 3 months after inclusion **Measure:** Recurrent appendicitis **Time Frame:** 3 months **Description:** Proportion of patients experiencing early failure of initial non-operative treatment **Measure:** Early failure of non-operative treatment **Time Frame:** 3 months **Description:** QoL measured by the validated EQ-5d-Youth / EQ-5d-Proxy questionnaire (0-1 point, higher scores indicating better outcome) **Measure:** Quality of Life questionnaire (EQ-5d-Youth/EQ-5d-Proxy) **Time Frame:** at inclusion/baseline (=day 0), 30 days, 3 months **Description:** QoL measured by the validated Pediatric Quality of Life Inventory 4.0 (PedsQL 4.0) (0-100 points, higher scores indicating better outcome) Labor Questionnaire (HLQ), Medical Consumption Questionnaire (iMCQ) and Productivity Consumption Questionnaire (iPCQ) and gathered actual health care cost **Measure:** Quality of Life questionnaire (PedsQL 4.0) **Time Frame:** at inclusion/baseline (=day 0), 30 days, 3 months **Description:** Medical costs measured by the iMedical Consumption Questionnaire **Measure:** Medical costs (iMCQ) **Time Frame:** at inclusion/baseline (=day 0), 30 days, 3 months **Description:** Non-medical / indirect costs measured by the iProductivity Cost Questionnaire **Measure:** Non-medical / indirect costs (iPCQ) **Time Frame:** at inclusion/baseline (=day 0), 30 days, 3 months **Description:** Quality adjusted life months calculated using outcomes 14 -17 **Measure:** Quality adjusted life months (QALM's) **Time Frame:** 3 months **Description:** Patient satisfaction measured by the Patient Satisfaction Questionnaire (PSQ) (0-100, higher scores indicating better outcome) **Measure:** Patient satisfaction questionnaire (PSQ-18) **Time Frame:** 3 months **Description:** Patient satisfaction measured by the NET PROMOTOR SCORE (0-10, higher scores indicating better outcome) **Measure:** Patient satisfaction questionnaire (Net promotor score) **Time Frame:** 3 months ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: Eligible for inclusion are all children \<18 years old that need to undergo treatment for the suspicion of complex appendicitis. Suspicion of complex appendicitis is based upon the following predefined criteria: 4 or more points on our scoring system developed to predict complex appendicitis. The diagnostic accuracy of this scoring system is 91% (Range: 84-98%). This scoring system consists of five variables (clinical, biochemical and radiological,each awarded points). In case the total score is 4 or more points, the patient is likely to have complex appendicitis. Variables included in the scoring system are: * Diffuse abdominal guarding (3 points) * CRP level more than 38 mg/L (2 points) * Signs on ultrasound / imaging indicative for complex appendicitis (2 points) * More than one day abdominal pain (2 points) * Temperature more than 37.5 degrees Celsius (1 point) Or High index of suspicion of complex appendicitis by the treating physician. If this is the case, the treating physician will make pre-treatment note upon what clinical, biochemical or radiological variable the high index of suspicion is based. Exclusion Criteria: * Adult patients (=18 years old) * Children with a suspicion of simple appendicitis (based upon the previous mentioned scoring system and radiological features) **Maximum Age:** 17 Years **Minimum Age:** 0 Years **Sampling Method:** PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - CHILD **Study Population:** All children that present with a preoperative suspicion of complex appendicitis. This suspicion is based on 4 points or more on the abovementioned complex appendicitis scoring system OR a high index of suspicion of complex appendicitis by the treating physician. ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Ramon Gorter, MD PhD **Phone:** 0031-205665693 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Paul van Amstel, MD **Phone:** 0031-205665693 **Role:** CONTACT #### Locations **Location 1:** **City:** Alkmaar **Contacts:** ***Contact 1:*** - **Name:** Taco Bijlsma, MD PhD - **Role:** CONTACT **Country:** Netherlands **Facility:** Northwest hospital group **Status:** RECRUITING **Location 2:** **City:** Almere **Contacts:** ***Contact 1:*** - **Name:** Gwen Diepenhorst, MD PhD - **Role:** CONTACT **Country:** Netherlands **Facility:** Flevoziekenhuis **Status:** RECRUITING **Location 3:** **City:** Amersfoort **Contacts:** ***Contact 1:*** - **Name:** Esther Consten, MD PhD - **Role:** CONTACT **Country:** Netherlands **Facility:** Meander MC **Status:** RECRUITING **Location 4:** **City:** Amstelveen **Contacts:** ***Contact 1:*** - **Name:** Frank Garssen, MD PhD - **Role:** CONTACT **Country:** Netherlands **Facility:** Hospital Amstelland **Status:** RECRUITING **Location 5:** **City:** Amsterdam **Contacts:** ***Contact 1:*** - **Name:** Ramon Gorter, MD PhD - **Role:** CONTACT **Country:** Netherlands **Facility:** Amsterdam UMC - Location AMC **Status:** RECRUITING **Location 6:** **City:** Amsterdam **Contacts:** ***Contact 1:*** - **Name:** Ramon Gorter, MD PhD - **Role:** CONTACT **Country:** Netherlands **Facility:** Amsterdam UMC - Location VUmc **Status:** RECRUITING **Location 7:** **City:** Amsterdam **Contacts:** ***Contact 1:*** - **Name:** Vanessa Leijdekkers, MD PhD - **Role:** CONTACT **Country:** Netherlands **Facility:** OLVG **Status:** RECRUITING **Location 8:** **City:** Apeldoorn **Contacts:** ***Contact 1:*** - **Name:** Hugo Bolhuis, MD - **Role:** CONTACT **Country:** Netherlands **Facility:** Gelre hospital **Status:** RECRUITING **Location 9:** **City:** Arnhem **Contacts:** ***Contact 1:*** - **Name:** Charlotte Blanken, MD PhD - **Role:** CONTACT **Country:** Netherlands **Facility:** Rijnstate **Status:** NOT_YET_RECRUITING **Location 10:** **City:** Bergen Op Zoom **Contacts:** ***Contact 1:*** - **Name:** Floortje van Eijck, MD PhD - **Role:** CONTACT **Country:** Netherlands **Facility:** Bravis Hospital **Status:** RECRUITING **Location 11:** **City:** Beverwijk **Contacts:** ***Contact 1:*** - **Name:** Annebeth de Vries, MD PhD - **Role:** CONTACT **Country:** Netherlands **Facility:** Red Cross Hospital **Status:** RECRUITING **Location 12:** **City:** Blaricum **Contacts:** ***Contact 1:*** - **Name:** Nanette van Geloven, MD PhD - **Role:** CONTACT **Country:** Netherlands **Facility:** Tergooi **Status:** NOT_YET_RECRUITING **Location 13:** **City:** Breda **Contacts:** ***Contact 1:*** - **Name:** Pieter Boele van Hensbroek, MD PhD - **Role:** CONTACT **Country:** Netherlands **Facility:** Amphia **Status:** RECRUITING **Location 14:** **City:** Capelle Aan Den IJssel **Contacts:** ***Contact 1:*** - **Name:** Richard Groenendijk, MD PhD - **Role:** CONTACT **Country:** Netherlands **Facility:** IJsselland Hospital **Status:** RECRUITING **Location 15:** **City:** Den Haag **Contacts:** ***Contact 1:*** - **Name:** Gerda Zijp, MD PhD - **Role:** CONTACT **Country:** Netherlands **Facility:** Haga/JKZ **Status:** RECRUITING **Location 16:** **City:** Dordrecht **Contacts:** ***Contact 1:*** - **Name:** Maarten Lijkwan, MD PhD - **Role:** CONTACT **Country:** Netherlands **Facility:** Albert Schweitzer Hospital **Status:** RECRUITING **Location 17:** **City:** Eindhoven **Contacts:** ***Contact 1:*** - **Name:** Misha Luyer, MD PhD - **Role:** CONTACT **Country:** Netherlands **Facility:** Catharina hospital **Status:** RECRUITING **Location 18:** **City:** Goes **Contacts:** ***Contact 1:*** - **Name:** Jan Jansen, MD PhD - **Role:** CONTACT **Country:** Netherlands **Facility:** Admiraal de Ruyter Hospital **Status:** NOT_YET_RECRUITING **Location 19:** **City:** Groningen **Contacts:** ***Contact 1:*** - **Name:** Jan Hulscher, MD PhD - **Role:** CONTACT **Country:** Netherlands **Facility:** UMCG **Status:** RECRUITING **Location 20:** **City:** Haarlem **Contacts:** ***Contact 1:*** - **Name:** Steven Oosterling, MD PhD - **Role:** CONTACT **Country:** Netherlands **Facility:** Spaarne Gasthuis **Status:** RECRUITING **Location 21:** **City:** Heerlen **Contacts:** ***Contact 1:*** - **Name:** Evert-Jan Boerma, MD PhD - **Role:** CONTACT **Country:** Netherlands **Facility:** Zuyderland MC **Status:** RECRUITING **Location 22:** **City:** Hoorn **Contacts:** ***Contact 1:*** - **Name:** Louise de Widt, MD PhD - **Role:** CONTACT **Country:** Netherlands **Facility:** Dijklander **Status:** RECRUITING **Location 23:** **City:** Nieuwegein **Contacts:** ***Contact 1:*** - **Name:** Peter Go, MD PhD - **Role:** CONTACT **Country:** Netherlands **Facility:** Sint Antonius Hospital **Status:** RECRUITING **Location 24:** **City:** Nijmegen **Contacts:** ***Contact 1:*** - **Name:** Ivo de Blaauw, MD PhD - **Role:** CONTACT **Country:** Netherlands **Facility:** Radboud UMC **Status:** RECRUITING **Location 25:** **City:** Roermond **Contacts:** ***Contact 1:*** - **Name:** Jeroen Leijtens, MD PhD - **Role:** CONTACT **Country:** Netherlands **Facility:** Laurentius **Status:** RECRUITING **Location 26:** **City:** Rotterdam **Contacts:** ***Contact 1:*** - **Name:** Claudia Keyzer, MD PhD - **Role:** CONTACT **Country:** Netherlands **Facility:** Erasmus MC **Status:** RECRUITING **Location 27:** **City:** Rotterdam **Contacts:** ***Contact 1:*** - **Name:** Marijn Poelman, MD PhD - **Role:** CONTACT **Country:** Netherlands **Facility:** Franciscus Gasthuis & Vlietland **Status:** NOT_YET_RECRUITING **Location 28:** **City:** Rotterdam **Contacts:** ***Contact 1:*** - **Name:** Wouter Vles, MD PhD - **Role:** CONTACT **Country:** Netherlands **Facility:** Ikazia **Status:** RECRUITING **Location 29:** **City:** Rotterdam **Contacts:** ***Contact 1:*** - **Name:** Charles van Rossem, MD PhD - **Role:** CONTACT **Country:** Netherlands **Facility:** Maasstad Hospital **Status:** RECRUITING **Location 30:** **City:** Veldhoven **Contacts:** ***Contact 1:*** - **Name:** Mart Bender, MD PhD - **Role:** CONTACT **Country:** Netherlands **Facility:** Maxima Medical Centre **Status:** RECRUITING **Location 31:** **City:** Zaandam **Contacts:** ***Contact 1:*** - **Name:** Frank den Boer, MD PhD - **Role:** CONTACT **Country:** Netherlands **Facility:** Zaans Medical Centre **Status:** NOT_YET_RECRUITING **Location 32:** **City:** Zwolle **Contacts:** ***Contact 1:*** - **Name:** Vincent Nieuwenhuijs, MD PhD - **Role:** CONTACT **Country:** Netherlands **Facility:** Isala **Status:** RECRUITING #### Overall Officials **Official 1:** **Affiliation:** Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) **Name:** Ramon Gorter, MD PhD **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### References **Citation:** van Amstel P, Bakx R, van der Lee JH, van der Weide MC, Eekelen RV, Derikx JPM, van Heurn ELW, Gorter RR; CAPP collaborative study group. Identification of the optimal treatment strategy for complex appendicitis in the paediatric population: a protocol for a multicentre prospective cohort study (CAPP study). BMJ Open. 2022 Feb 17;12(2):e054826. doi: 10.1136/bmjopen-2021-054826. **PMID:** 35177453 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000059413 - Term: Intraabdominal Infections - ID: D000007239 - Term: Infections - ID: D000005759 - Term: Gastroenteritis - ID: D000005767 - Term: Gastrointestinal Diseases - ID: D000004066 - Term: Digestive System Diseases - ID: D000002429 - Term: Cecal Diseases - ID: D000007410 - Term: Intestinal Diseases ### 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 ### Condition Browse Module - Browse Leaves - ID: M4376 - Name: Appendicitis - Relevance: HIGH - As Found: Appendicitis - ID: M10283 - Name: Infections - Relevance: LOW - As Found: Unknown - ID: M6368 - Name: Communicable Diseases - Relevance: LOW - As Found: Unknown - ID: M29465 - Name: Intraabdominal Infections - Relevance: LOW - As Found: Unknown - ID: M8875 - Name: Gastroenteritis - 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: M5679 - Name: Cecal Diseases - Relevance: LOW - As Found: Unknown - ID: M10444 - Name: Intestinal Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000001064 - Term: Appendicitis ### Intervention Browse Module - Browse Branches - Abbrev: Infe - Name: Anti-Infective Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M3995 - Name: Amoxicillin - Relevance: LOW - As Found: Unknown - ID: M21710 - Name: Clavulanic Acid - Relevance: LOW - As Found: Unknown - ID: M4222 - Name: Anti-Bacterial Agents - Relevance: LOW - As Found: Unknown - ID: M5694 - Name: Cefuroxime - Relevance: LOW - As Found: Unknown - ID: M349210 - Name: Cefuroxime axetil - Relevance: LOW - As Found: Unknown - ID: M4224 - Name: Antibiotics, Antitubercular - Relevance: LOW - As Found: Unknown - ID: M11767 - Name: Metronidazole - Relevance: LOW - As Found: Unknown - ID: M8951 - Name: Gentamicins - Relevance: LOW - As Found: Unknown - ID: M6204 - Name: Clavulanic Acids - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00639379 **Brief Title:** Comparison of Two Toric Contact Lenses on Current Toric Wearers **Official Title:** A Multi-Center, Subject Masked, Randomized, Two Week Crossover Design, Investigation of the Acuvue Cypress Toric Silicone Hydrogel Lens Compared to the Bausch & Lomb SofLens66® Toric Hydrophilic Lens #### Organization Study ID Info **ID:** CR-0802 #### Organization **Class:** INDUSTRY **Full Name:** Johnson & Johnson Vision Care, Inc. ### Status Module #### Completion Date **Date:** 2008-06 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2015-05-21 **Type:** ESTIMATED **Last Update Submit Date:** 2015-05-05 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2008-06 **Type:** ACTUAL #### Results First Post Date **Date:** 2010-07-19 **Type:** ESTIMATED **Results First Submit Date:** 2010-06-18 **Results First Submit QC Date:** 2010-06-18 #### Start Date **Date:** 2008-02 **Status Verified Date:** 2015-05 #### Study First Post Date **Date:** 2008-03-20 **Type:** ESTIMATED **Study First Submit Date:** 2008-03-13 **Study First Submit QC Date:** 2008-03-19 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Johnson & Johnson Vision Care, Inc. #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** The purpose of this study is to evaluate and compare the clinical performance of two toric contact lenses amongst 110 subjects, 2-week, single masked (subject), daily wear, randomized, bilateral, crossover study; 4 weeks duration. Hypotheses include equal or better performance of the test lens over the control lenses for comfort, vision, and toric fit characteristics as well as corneal integrity **Detailed Description:** Up to 7 sites in the US will participate. Each investigator will have both test and control lens types. There will be a maximum of 6 scheduled visits: Visit 1: Habitual lens evaluation / Baseline / Trial fitting Visit 2: Dispensing (to be combined with Visit 1 where possible), Visit 3: Questionnaire only (no exam) 7 days (±2) after dispensing, Visit 4: 2 week follow-up 14 days (±3) after dispensing, and dispense second lens type, Visit 5: Questionnaire only (no exam) 7 days (±2) after 2nd lens dispense, Visit 6: 2 week follow-up 14 days (±3) after 2nd lens dispense ### Conditions Module **Conditions:** - Ametropia **Keywords:** - toric contact lenses - vision - comfort - toric fit characteristics - slit lamp findings ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** CROSSOVER ##### Masking Info **Masking:** SINGLE **Who Masked:** - PARTICIPANT **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 89 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** senofilcon A toric daily wear contact lenses **Intervention Names:** - Device: senofilcon A toric **Label:** senofilcon A **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** alphafilcon A toric daily wear contact lenses **Intervention Names:** - Device: alphafilcon A toric **Label:** alphafilcon A **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - senofilcon A **Description:** silicone hydrogel toric lens, 2 wk replacement, daily wear **Name:** senofilcon A toric **Other Names:** - ACUVUE OASYS **Type:** DEVICE #### Intervention 2 **Arm Group Labels:** - alphafilcon A **Description:** hydrogel toric lens, 2 wk replacement, daily wear **Name:** alphafilcon A toric **Other Names:** - SofLens Toric **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Description:** Number of eyes with lens orientation within 5 degrees of optimal orientation within 1 minute of contact lens insertion. **Measure:** Lens Orientation Within 5 Degrees **Time Frame:** 1 minute after insertion **Description:** Number of eyes with the amount of rotation induced from a blink within 5 degrees of settled orientation. **Measure:** Lens Stability **Time Frame:** 10-15 minutes after insertion **Description:** A weighted combined score calculated from individual comfort-related questions asked on a 1-5 scale: 1=most negative response to 5=most positive response, was used to derive comfort outcomes. The analysis shows the difference in outcome between the test and control. \>0=comfortable, \<0=uncomfortable. **Measure:** Subjective Lens Comfort **Time Frame:** 1 and 2 weeks **Description:** A weighted combined score calculated from individual vision-related questions asked on a 1-5 scale: 1=most negative response to 5=most positive response, was used to derive vision outcomes. The analysis shows the difference in outcome between the test and control. \>0=satisfactory vision, \<0=unsatisfactory vision. **Measure:** Subjective Vision **Time Frame:** 1 and 2 weeks **Description:** Corneal staining measured using the National Eye Institute grading scale of grade 0 = normal, grade 1 = mild, grade 2 = moderate, grade 3 = severe. **Measure:** Overall Corneal Staining **Time Frame:** after 2 weeks use ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. Be at least 18 and less than or equal to 45 years of age, have a need for vision correction and wear contact lenses in BOTH eyes (monovision or uni-ocular fitting is NOT allowed). 2. Be able to read J1 at near WITHOUT the aid of a near addition over the distance prescription. 3. Be a currently successful wearer for at least 3 months of B\&L SofLens 66 Toric hydrogel lenses. 4. Be able and willing to adhere to the instructions set forth in the protocol. 5. Agree to wear their contact lenses in both eyes on a daily wear schedule for at least 8 hours per day every day during the study. 6. Have a distance spectacle spherical component between -1.00 D and -5.25 D with cylinder in the range of 0.75 D to 2.25 D and cylinder axis within 10 ° of the vertical and within 30° of the horizontal in both eyes (when the subject's prescription is presented in minus cylinder form). 7. Have a best corrected manifest refraction visual acuity of at least 20/25 or better in each eye. 8. Be in good general health, based on his/her knowledge. 9. Must be given an explanation of the study objectives, lens and solutions usage requirements and visit schedule. The subject must read, indicate understanding of and agree to begin participation in the clinical study. The subject must then sign the Informed Consent Form in the presence of the Investigator or their designee. Exclusion Criteria: 1. Presbyopic or has the need for a near add for reading. 2. Previous refractive surgery; current or previous orthokeratology treatment. 3. Aphakia, keratoconus or a highly irregular cornea. 4. The presence of ocular or systemic disease or has the need for medication (ocular or systemic) which might interfere with contact lens wear or which would cause the lenses to be removed more than twice a day. (e.g., Sjögren's syndrome, type II diabetes, allergies). 5. A known history of corneal hypoesthesia (reduced corneal sensitivity.) 6. Anterior uveitis or iritis (past or present). 7. A history of recurrent erosions, corneal infiltrates corneal ulcer or fungal infections. 8. Clinically significant (grade 3 or 4) anterior segment abnormalities; inflammations or infections of the eye, eyelids, or associated structures. 9. Slit lamp findings that would contraindicate contact lens wear such as: * Pathological dry eye or associated findings * Pterygium or corneal scars within the visual axis * Neovascularization \>1mm in from the limbus * History of giant papillary conjunctivitis (GPC) worse than Grade 2 * Meibomian gland dysfunction, blepharitis, or seborrhoeic dermatitis 10. Current pregnancy or lactation (to the best of the subject's knowledge). 11. Actively participating in another clinical study at any time during this study. **Healthy Volunteers:** True **Maximum Age:** 45 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Jacksonville **Country:** United States **Facility:** Ted Brink and Associates **State:** Florida **Zip:** 32256 **Location 2:** **City:** Orlando **Country:** United States **Facility:** Eola Eyes **State:** Florida **Zip:** 32801 **Location 3:** **City:** Morrow **Country:** United States **Facility:** Clayton Eye Center **State:** Georgia **Zip:** 30260 **Location 4:** **City:** St Louis **Country:** United States **Facility:** The Koetting Associates Inc. **State:** Missouri **Zip:** 63144 **Location 5:** **City:** Concord **Country:** United States **Facility:** Southern Eyes **State:** North Carolina **Zip:** 28025 **Location 6:** **City:** Beachwood **Country:** United States **Facility:** Western Reserve Vision Care **State:** Ohio **Zip:** 44122 **Location 7:** **City:** Brentwood **Country:** United States **Facility:** Primary Eyecare Group, P.C. **State:** Tennessee **Zip:** 37027 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000005128 - Term: Eye Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC11 - Name: Eye Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M14872 - Name: Refractive Errors - Relevance: HIGH - As Found: Ametropia - ID: M8271 - Name: Eye Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000012030 - Term: Refractive Errors ### Misc Info Module - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module #### Event Groups **Group ID:** EG000 **Title:** Senofilcon A Toric / Alphafilcon A Toric **Description:** senofilcon A toric work bilaterally during first 2-week period, alphafilcon A toric work bilaterally during second 2-week period. **ID:** EG000 **Other Num at Risk:** 44 **Serious Number At Risk:** 44 **Title:** Senofilcon A Toric / Alphafilcon A Toric **Group ID:** EG001 **Title:** Alphafilcon A Toric / Senofilcon A Toric **Description:** alphafilcon A toric work bilaterally during first 2-week period, senofilcon A toric work bilaterally during second 2-week period. **ID:** EG001 **Other Num at Risk:** 45 **Serious Number At Risk:** 45 **Title:** Alphafilcon A Toric / Senofilcon A Toric **Frequency Threshold:** 5 ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 84 **Units:** Participants ### Group **ID:** BG000 **Title:** Total Completed Participants ### Measure #### Measurement **Group ID:** BG000 **Spread:** 8.05 **Value:** 31.6 **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 53 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 31 **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 **Other Details:** The PI may not publish, divulge, reveal, disclose, or use the data and or results of the study without prior written consent of Vistakon. **Restriction Type:** OTHER **Restrictive Agreement:** True ### Point of Contact **Organization:** Vistakon **Phone:** 904-443-3088 **Title:** Kurt Moody, OD ## Results Section - Outcome Measures Module ### Outcome Measure 1 #### Analysis **CI Lower Limit:** 0.436 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 98.98 **CI Upper Limit:** 0.967 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** Odds ratio is senofilcon A toric / alphafilcon A toric. **Group Description:** Alternative hypothesis is that senofilcon A toric is non-inferior to alphafilcon A toric for proportion of eyes with lens orientation within 5 degrees. **Non-Inferiority Comment:** Non-inferiority margin is 0.65 **Non-Inferiority Type:** NON_INFERIORITY_OR_EQUIVALENCE **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Odds Ratio (OR) **Parameter Value:** 0.967 **Statistical Comment:** **Statistical Method:** Regression, Logistic **Tested Non-Inferiority:** True ### Outcome Measure 2 #### Analysis **CI Lower Limit:** 0.680 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 98.98 **CI Upper Limit:** 1.416 **CI Upper Limit Comment:** **Dispersion Type:** **Dispersion Value:** **Estimate Comment:** Odds ratio is senofilcon A toric / alphafilcon A toric. **Group Description:** Alternative hypothesis is that senofilcon A toric is non-inferior to alphafilcon A toric for proportion of eyes with lens stability within 5 degrees. **Non-Inferiority Comment:** Non-inferiority margin = 0.65 **Non-Inferiority Type:** NON_INFERIORITY_OR_EQUIVALENCE **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Odds Ratio (OR) **Parameter Value:** 1.416 **Statistical Comment:** **Statistical Method:** Regression, Logistic **Tested Non-Inferiority:** True ### Outcome Measure 3 #### Analysis **CI Lower Limit:** -0.0517 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 98.98 **CI Upper Limit:** 0.1868 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.0921 **Estimate Comment:** The mean difference is calculated as senofilcon A toric minus alphafilcon A toric. **Group Description:** Alternative hypothesis is that senofilcon A toric is non-inferior to alphafilcon A toric for lens comfort. **Non-Inferiority Comment:** Non-inferiority margin = -0.4 **Non-Inferiority Type:** NON_INFERIORITY_OR_EQUIVALENCE **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** 0.1868 **Statistical Comment:** **Statistical Method:** Mixed Models Analysis **Tested Non-Inferiority:** True ### Outcome Measure 4 #### Analysis **CI Lower Limit:** -0.2337 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 98.98 **CI Upper Limit:** -0.01185 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.08566 **Estimate Comment:** The mean difference is calculated as senofilcon A toric minus alphafilcon A toric. **Group Description:** Alternative hypothesis is that senofilcon A toric is non-inferior to alphafilcon A toric for subjective vision. **Non-Inferiority Comment:** Non-inferiority margin = -0.4 **Non-Inferiority Type:** NON_INFERIORITY_OR_EQUIVALENCE **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** -0.01185 **Statistical Comment:** **Statistical Method:** Mixed Models Analysis **Tested Non-Inferiority:** True ### Outcome Measure 5 #### Analysis **CI Lower Limit:** -0.01267 **CI Number of Sides:** TWO_SIDED **CI Percentage Value:** 98.98 **CI Upper Limit:** 0.01986 **CI Upper Limit Comment:** **Dispersion Type:** STANDARD_ERROR_OF_MEAN **Dispersion Value:** 0.01265 **Estimate Comment:** The mean difference was calculated as senofilcon A toric minus alphafilcon A toric. **Group Description:** Alternative hypothesis is senofilcon A toric is non-inferior to alphafilcon A toric by having a lower level of corneal staining. **Non-Inferiority Comment:** Non-inferiority margin = 0.5 **Non-Inferiority Type:** NON_INFERIORITY_OR_EQUIVALENCE **Other Analysis Description:** **P-Value:** **P-Value Comment:** **Parameter Type:** Mean Difference (Final Values) **Parameter Value:** -0.01267 **Statistical Comment:** **Statistical Method:** **Tested Non-Inferiority:** True ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 128 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 128 **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 144 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** - **Upper Limit:** - **Value:** 138 **Title:** #### Outcome Measure 3 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.08771 - **Upper Limit:** - **Value:** 0.08125 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.08771 - **Upper Limit:** - **Value:** -0.1055 **Title:** #### Outcome Measure 4 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.08885 - **Upper Limit:** - **Value:** -0.0420 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.08885 - **Upper Limit:** - **Value:** -0.0302 **Title:** #### Outcome Measure 5 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** - **Spread:** 0.01174 - **Upper Limit:** - **Value:** 0.04921 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** - **Spread:** 0.01176 - **Upper Limit:** - **Value:** 0.06188 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** Number of eyes with lens orientation within 5 degrees of optimal orientation within 1 minute of contact lens insertion. **Parameter Type:** NUMBER **Population Description:** Subjects/eyes that completed the study were analyzed. A total of 168 eyes/84 subjects were analyzed. **Reporting Status:** POSTED **Time Frame:** 1 minute after insertion **Title:** Lens Orientation Within 5 Degrees **Type:** PRIMARY **Unit of Measure:** Eyes ##### Group **ID:** OG000 **Title:** Senofilcon A Toric ##### Group **ID:** OG001 **Title:** Alphafilcon A Toric #### Outcome Measure 2 **Description:** Number of eyes with the amount of rotation induced from a blink within 5 degrees of settled orientation. **Parameter Type:** NUMBER **Population Description:** Subjects/eyes that completed the study were analyzed. A total of 168 eyes/84 subjects were analyzed. **Reporting Status:** POSTED **Time Frame:** 10-15 minutes after insertion **Title:** Lens Stability **Type:** PRIMARY **Unit of Measure:** Eyes ##### Group **ID:** OG000 **Title:** Senofilcon A Toric ##### Group **ID:** OG001 **Title:** Alphafilcon A Toric #### Outcome Measure 3 **Description:** A weighted combined score calculated from individual comfort-related questions asked on a 1-5 scale: 1=most negative response to 5=most positive response, was used to derive comfort outcomes. The analysis shows the difference in outcome between the test and control. \>0=comfortable, \<0=uncomfortable. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** Subjects that completed the study were analyzed. **Reporting Status:** POSTED **Time Frame:** 1 and 2 weeks **Title:** Subjective Lens Comfort **Type:** PRIMARY **Unit of Measure:** Units on a scale ##### Group **ID:** OG000 **Title:** Senofilcon A Toric ##### Group **ID:** OG001 **Title:** Alphafilcon A Toric #### Outcome Measure 4 **Description:** A weighted combined score calculated from individual vision-related questions asked on a 1-5 scale: 1=most negative response to 5=most positive response, was used to derive vision outcomes. The analysis shows the difference in outcome between the test and control. \>0=satisfactory vision, \<0=unsatisfactory vision. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** Subjects that completed the study were analyzed. **Reporting Status:** POSTED **Time Frame:** 1 and 2 weeks **Title:** Subjective Vision **Type:** PRIMARY **Unit of Measure:** Units on a scale ##### Group **ID:** OG000 **Title:** Senofilcon A Toric ##### Group **ID:** OG001 **Title:** Alphafilcon A Toric #### Outcome Measure 5 **Description:** Corneal staining measured using the National Eye Institute grading scale of grade 0 = normal, grade 1 = mild, grade 2 = moderate, grade 3 = severe. **Dispersion Type:** Standard Error **Parameter Type:** LEAST_SQUARES_MEAN **Population Description:** Subjects that completed the study were analyzed. **Reporting Status:** POSTED **Time Frame:** after 2 weeks use **Title:** Overall Corneal Staining **Type:** PRIMARY **Unit of Measure:** Units on a scale ##### Group **ID:** OG000 **Title:** Senofilcon A Toric ##### Group **ID:** OG001 **Title:** Alphafilcon A Toric ### Participant Flow Module #### Group **Description:** senofilcon A toric work bilaterally during first 2-week period, alphafilcon A toric work bilaterally during second 2-week period. **ID:** FG000 **Title:** Senofilcon A Toric / Alphafilcon A Toric #### Group **Description:** alphafilcon A toric work bilaterally during first 2-week period, senofilcon A toric work bilaterally during second 2-week period. **ID:** FG001 **Title:** Alphafilcon A Toric / Senofilcon A Toric #### Period **Title:** Period 1 - 2 Weeks ##### Withdraw **Type:** Lost to Follow-up ###### Reason **Group ID:** FG000 **Number of Subjects:** 2 ###### Reason **Group ID:** FG001 **Number of Subjects:** 0 ##### Withdraw **Type:** lens issue ###### Reason **Group ID:** FG000 **Number of Subjects:** 3 ###### Reason **Group ID:** FG001 **Number of Subjects:** 0 ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 44 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 45 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 39 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 45 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 5 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 0 #### Period **Title:** Period 2 - 2 Weeks ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 39 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 45 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 39 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 45 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 0 **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT01284179 **Brief Title:** Home Hypnotherapy for Refractory Functional Chest Pain: A Pilot Study **Official Title:** Home Hypnotherapy for Refractory Functional Chest Pain: A Pilot Study #### Organization Study ID Info **ID:** 09-0772 #### Organization **Class:** OTHER **Full Name:** University of North Carolina, Chapel Hill #### Secondary ID Infos **ID:** R24DK067674 **Link:** https://reporter.nih.gov/quickSearch/R24DK067674 **Type:** NIH ### Status Module #### Completion Date **Date:** 2015-12 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2016-12-20 **Type:** ESTIMATED **Last Update Submit Date:** 2016-12-19 **Overall Status:** TERMINATED #### Primary Completion Date **Date:** 2015-12 **Type:** ACTUAL #### Start Date **Date:** 2011-02 **Status Verified Date:** 2016-12 #### Study First Post Date **Date:** 2011-01-26 **Type:** ESTIMATED **Study First Submit Date:** 2011-01-25 **Study First Submit QC Date:** 2011-01-25 **Why Stopped:** Unable to enroll ### Sponsor Collaborators Module #### Collaborators **Class:** NIH **Name:** National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) #### Lead Sponsor **Class:** OTHER **Name:** University of North Carolina, Chapel Hill #### Responsible Party **Investigator Affiliation:** University of North Carolina, Chapel Hill **Investigator Full Name:** Ryan Madanick, MD **Investigator Title:** Assistant Professor of Medicine Director, UNC Gastroenterology & Hepatology Fellowship Program **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** The primary aim is to develop and test the feasibility of a standardized digital audio home-hypnotherapy (HHT) program for patients with refractory functional chest pain (FCP). The secondary aims of this study are: 1. To obtain pilot data to assess the magnitude of the treatment effect of self-hypnosis in refractory FCP for an anticipated future, larger treatment trial; 2. To determine the stability of the treatment effect of HHT in refractory FCP; 3. To assess the relationship between response to HHT and psychological factors; and 4. To assess the relationship between response to HHT and symptomatic dimensions of chest pain (severity, frequency, and duration). 5. To assess the difference **Detailed Description:** Eligible patients with refractory FCP will be randomized to one of 2 arms: the active treatment group, who will receive the HHT program; or a control group. Patients in the active treatment group will receive the 12-week digital audio HHT program. This protocol consists of 7 sessions, each approximately 30-40 minutes, administered every 2 weeks, for a cumulative 12 weeks of treatment, along with a shorter (approximately 12 minute) session administered daily. Patients in the control group will receive a digital audio educational program. Subjects in both groups will be assessed at baseline, 4-6 weeks into treatment, at the end of the treatment, and 3 months after conclusion of the program. Global change in symptoms will be assessed with a 7-point Likert scale. Patients will be considered to respond if they have significant improvement on the Likert scale at the post-treatment visit. Patients will complete a chest pain symptom diary, the SCL-90 and the Coping Strategies Questionnaire-Catastrophizing subscale to assess psychological features, and the SF-36 as a measure of Health Related Quality of Life (HRQOL). ### Conditions Module **Conditions:** - Functional Chest Pain **Keywords:** - Functional Chest Pain - Functional GI Disorders - Home Hypnotherapy ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 8 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Participants will be randomized to either the home hypnotherapy or educational group. The HHT protocol will consist of sequences of two different types of sessions, longer biweekly sessions (LS), each approximately 30-40 minutes in length, and shorter daily sessions (SS), approximately 12 minutes in length. On the first day of each sequence, the patient will listen to the appropriate LS. The patients will listen to the SS on a daily basis in between each LS. Every 2 weeks a new sequence will begin, for a total of 12 weeks of treatment. **Intervention Names:** - Behavioral: Home Hypnotherapy **Label:** Hypnotherapy **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Participants will be randomized to receive either home hypnotherapy or an educational program. The control group will receive an educational digital audio program on MP3 players. These digital audio files will contain general information about FCP and FGIDs. These audio files will be similar to the intervention audio files in length. Patients will be instructed to begin listening on the day of randomization. Patients will be instructed to continue their other medical treatment for chest pain during the study. The control group will be assessed at the same times as the HHT group. **Intervention Names:** - Behavioral: Educational **Label:** Educational **Type:** OTHER ### Interventions #### Intervention 1 **Arm Group Labels:** - Hypnotherapy **Description:** Each session contains the following elements: (1) trance induction consisting of narrowing the focus of attention and eye-closure, (2) trance deepening through imagery, guided dissociation from the here-and-now and graded suggestions of change in mental state, (3) vivid guided imagery that engages all the senses and implies improved health, well-being and a sense of strength and personal power, (4) therapeutic suggestions and imagery, both direct and indirect, for enhanced chest comfort, overall physical comfort and mental well-being and immunity to discomfort, that is suggested will last beyond termination of the session and become more noticeable and permanent over time, and (5) trance termination through direct suggestions and counting. **Name:** Home Hypnotherapy **Type:** BEHAVIORAL #### Intervention 2 **Arm Group Labels:** - Educational **Description:** Educational recordings regarding FCP and FGIDs. **Name:** Educational **Type:** BEHAVIORAL ### Outcomes Module #### Primary Outcomes **Description:** To fulfill Rome III recommendations for the design of treatment trials for Functional Gastrointestinal Disorders (FGIDS),47 we will use a 7-point Likert scale to assess for global change in chest pain. At times V2, V3, and V4, patients will be asked the following question: "Compared to before starting this therapy, how would you rate your chest pain?" The following answers will be given as options: "much better" (+3), "somewhat better" (+2), "minimally better" (+1), "no change" (0), "minimally worse" (-1), "somewhat worse" (-2), "much worse" (-3). **Measure:** Global change in chest pain at the 12 weeks **Time Frame:** 12 Weeks Post Treatment Start #### Secondary Outcomes **Description:** To fulfill Rome III recommendations for the design of treatment trials for Functional Gastrointestinal Disorders (FGIDS),47 we will use a 7-point Likert scale to assess for global change in chest pain. At times V2, V3, and V4, patients will be asked the following question: "Compared to before starting this therapy, how would you rate your chest pain?" The following answers will be given as options: "much better" (+3), "somewhat better" (+2), "minimally better" (+1), "no change" (0), "minimally worse" (-1), "somewhat worse" (-2), "much worse" (-3). **Measure:** Global change in chest pain at 4 weeks **Time Frame:** 4 Weeks Post Treatment Start **Description:** To fulfill Rome III recommendations for the design of treatment trials for Functional Gastrointestinal Disorders (FGIDS),47 we will use a 7-point Likert scale to assess for global change in chest pain. At times V2, V3, and V4, patients will be asked the following question: "Compared to before starting this therapy, how would you rate your chest pain?" The following answers will be given as options: "much better" (+3), "somewhat better" (+2), "minimally better" (+1), "no change" (0), "minimally worse" (-1), "somewhat worse" (-2), "much worse" (-3). **Measure:** Global change in chest pain at 6 weeks **Time Frame:** 6 Weeks Post Treatment Start **Description:** Assessed via daily chest pain diary **Measure:** Change in symptom score at 3 months **Time Frame:** 12 Weeks Post Treatment Start **Description:** Assessed via SF-36 questionnaire and SCL-90 questionnaire. **Measure:** Change in psychometric score at 3 months **Time Frame:** 12 Weeks Post Treatment Start **Description:** Assessed via health related quality of life (HRQOL) questionnaire **Measure:** Change in HRQOL scores at 3 months **Time Frame:** 12 Weeks Post Treatment Start ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Age 18 to 80, male or female. * Patients must fulfill the Rome III criteria for Functional Chest Pain of Presumed Esophageal Origin for the previous 3 months (with symptom onset at least 6 months before diagnosis), including all of the following: * Midline chest pain or discomfort that is not of burning quality * Absence of evidence that gastroesophageal reflux is the cause of the symptom * Absence of histopathology-based esophageal motility disorders * Persistent symptoms despite a trial of antidepressant therapy, as defined by either: * chest pain despite at least a continuous 4-week trial of at least one antidepressant within the last 6 months; or * intolerance of at least one antidepressant within the last 6 months. * Negative cardiac evaluation (negative cardiac stress test or negative coronary angiogram) * Negative gastrointestinal evaluation for cause of the pain, defined by absence of Los Angeles grade C or D erosive esophagitis on endoscopy, persistent chest pain on PPI therapy, and no association of chest pain with reflux episodes on an ambulatory pH or pH-impedance study, defined as a symptom index \<50% or symptom association probability \<95% for chest pain . Exclusion Criteria: * Severe co-morbid illness (cardiac, pulmonary, renal, hematologic, hepatic) * Prior treatment with hypnosis/hypnotherapy for a medical condition * Prior major thoracic surgery * Prior diagnosis of or treatment for dissociative disorders, post-traumatic stress disorder, borderline personality disorder, or other psychiatric disorders that include psychotic features * Pregnancy or planned pregnancy within the upcoming 3 months * Inability or unwillingness to give informed consent **Maximum Age:** 80 Years **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 Chapel Hill **State:** North Carolina **Zip:** 27599 #### Overall Officials **Official 1:** **Affiliation:** UNC-Chapel Hill **Name:** Ryan Madanick, MD **Role:** PRINCIPAL_INVESTIGATOR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000010146 - Term: Pain - ID: D000009461 - Term: Neurologic Manifestations ### Condition Browse Module - Browse Branches - Abbrev: BC23 - Name: Symptoms and General Pathology - Abbrev: All - Name: All Conditions - Abbrev: BC06 - Name: Digestive System Diseases - Abbrev: BC10 - Name: Nervous System Diseases ### Condition Browse Module - Browse Leaves - ID: M13066 - Name: Pain - 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: M5882 - Name: Chest Pain - Relevance: HIGH - As Found: Chest Pain - ID: M12404 - Name: Neurologic Manifestations - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000002637 - Term: Chest Pain ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT06078579 **Brief Title:** Salivary and Serum Leptin Levels in Oral Lichen Planus Patients: A Case-control Study. **Official Title:** Salivary and Serum Leptin Levels in Oral Lichen Planus Patients: A Case-Control Study. #### Organization Study ID Info **ID:** 20723 #### Organization **Class:** OTHER **Full Name:** Cairo University ### Status Module #### Completion Date **Date:** 2024-12-30 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-02-06 **Type:** ACTUAL **Last Update Submit Date:** 2024-02-05 **Overall Status:** RECRUITING #### Primary Completion Date **Date:** 2024-09-30 **Type:** ESTIMATED #### Start Date **Date:** 2023-12-30 **Type:** ACTUAL **Status Verified Date:** 2024-02 #### Study First Post Date **Date:** 2023-10-12 **Type:** ACTUAL **Study First Submit Date:** 2023-09-27 **Study First Submit QC Date:** 2023-10-09 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Cairo University #### Responsible Party **Investigator Affiliation:** Cairo University **Investigator Full Name:** Bahaa Mahmoud Fawzy El Nomrosy **Investigator Title:** Dentist **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** True ### Description Module **Brief Summary:** This study aims to evaluate the levels of leptin in both saliva and serum samples of patients diagnosed with oral lichen. **Detailed Description:** Oral lichen planus is a frequently encountered chronic muco-cutaneous condition with a high prevalence rate. The condition can be classified as an autoimmune disorder.Although the exact cause of this condition is unknown, some potential risk factors should be taken into account, such as systemic disorders, psychogenic diseases, dental restorations, and certain medications. The oral lesions exhibit a mostly bilateral pattern, often manifesting in the inner buccal mucosa. The condition can be classified into three distinct forms, namely the reticular form, atrophic form, and bullous-erosive form. The condition is classified as a premalignant lesion due to its significant likelihood of undergoing malignant transformation. The disease is characterized by the presence of T-lymphocyte infiltration in the basal cell layer of the epithelium and the presence of cytoid bodies, which are distinct histopathologic markers. Leptin, a hormone generated by adipocytes, is involved in immunological responses and contributes to the development of autoimmunity. The presence of dyslipidemia has been found to be associated with lipoprotein (LP) abnormalities. Consequently, this study was undertaken to assess the blood leptin levels and lipid profile in individuals with LP. Leptin, a polypeptide hormone, is produced and released by white adipose tissue. Multiple research have substantiated an increase in leptin levels among persons exhibiting elevated body mass index (BMI) and a higher percentage of total body fat. Additionally, it is involved in the cellular immune response and facilitates the development of autoimmunity. There is a proposition suggesting that leptin has a role in the promotion of cytokine generation and modulation of helper T cells, potentially implicating its involvement in the pathogenesis of psoriasis. The available information about leptin status in dermatological illnesses other than psoriasis is currently sparse. It is plausible that it may have a significant role in the pathogenesis of lichen planus. However, there is a lack of literature regarding the levels of leptin in LP. There is an association between dyslipidemia and LP. Numerous investigations have consistently demonstrated notable deviations in lipid profile levels between individuals with LP and those in normal, healthy control cohorts. These findings have led researchers to posit a correlation between chronic inflammation and dyslipidemia, hence heightening the susceptibility to cardiovascular illnesses. The potential impact of leptin on the progression of LP is being investigated. The objective of this study was to conduct a comparative analysis of blood leptin levels between individuals recently diagnosed with LP and a control group consisting of healthy individuals. Additionally, an assessment was conducted to examine the correlation between leptin levels, lipid profile, and the length of illness. ### Conditions Module **Conditions:** - Oral Lichen Planus - Leptin Levels **Keywords:** - salivary - Serum ### Design Module #### Bio Spec **Description:** ELISA **Retention:** SAMPLES_WITHOUT_DNA #### Design Info **Observational Model:** CASE_CONTROL **Time Perspective:** OTHER #### Enrollment Info **Count:** 79 **Type:** ESTIMATED **Study Type:** OBSERVATIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Assessment of salivary and serum leptin levels **Intervention Names:** - Diagnostic Test: Leptin **Label:** Oral lichen planus patients #### Arm Group 2 **Description:** Assessment of salivary and serum leptin levels **Intervention Names:** - Diagnostic Test: Leptin **Label:** Healthy control group ### Interventions #### Intervention 1 **Arm Group Labels:** - Healthy control group - Oral lichen planus patients **Description:** Assessment of salivary and serum leptin levels in oral lichen planus patients and healthy controls **Name:** Leptin **Type:** DIAGNOSTIC_TEST ### Outcomes Module #### Primary Outcomes **Description:** Assessment of serum leptin levels in in oral lichen planus patients **Measure:** Serum leptin level **Time Frame:** Baseline #### Secondary Outcomes **Description:** Assessment of salivary leptin levels in oral lichen planus patients **Measure:** Salivary leptin levels **Time Frame:** Baseline ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Ages for both sexes fall between 30 and 70. * Symptomatic OLP has been diagnosed clinically and verified histologically. * Participants who sign a written consent form after being fully informed about the study. Exclusion Criteria: * Treatment with a systemic or locally administered systemic medication within the previous three months before the commencement of the research. * Patients now taking or who have just stopped taking an NSAIDs (both steroidal and non steroidal) for pain or inflammation. * Patients who have been diagnosed with a malignant tumor or tumors. * Women who are expecting or nursing. * Inmates, the mentally ill, the elderly, etc, all fall into this category. **Healthy Volunteers:** True **Maximum Age:** 70 Years **Minimum Age:** 30 Years **Sampling Method:** NON_PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** OLP patients and healthy controls were selected will be selected from "out-patient clinic" of Oral Medicine, Periodontology and Oral Diagnosis Department ;Faculty of Dentistry, Cairo university and from "out-patient" of Boulak El Dakroor general hospital. ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Bahaa Ma El Nomrosy, Master **Phone:** +201033559646 **Role:** CONTACT **Contact 2:** **Email:** [email protected] **Name:** Alaa As El shazly, Bachelor **Phone:** 01010223663 **Role:** CONTACT #### Locations **Location 1:** **City:** Cairo **Country:** Egypt **Facility:** Cairo university **Status:** RECRUITING #### Overall Officials **Official 1:** **Affiliation:** Cairo University **Name:** Weam Ah Rashwan, PHD **Role:** STUDY_DIRECTOR **Official 2:** **Affiliation:** Cairo University **Name:** Olfat Ga Shaker, PHD **Role:** STUDY_DIRECTOR ### References Module #### Available IPDs **Comment:** www.researchgate.net/publication/344178013_Serum_Leptin_and_Lipid_Profile_in_Lichen_Planus_A_case_control_study **Type:** Study Protocol **URL:** https://www.ijhsr.org/IJHSR_Vol.5_Issue.10_Oct2015/20.pdf #### References **Citation:** Aryanian Z, Shirzadian A, Hatami P, Dadras H. High Incidence of Metabolic Syndrome Components in Lichen Planus Patients: A Prospective Cross-Sectional Study. Int J Clin Pract. 2022 Jan 31;2022:7184678. doi: 10.1155/2022/7184678. eCollection 2022. **PMID:** 35685585 **Citation:** Matarese G, Moschos S, Mantzoros CS. Leptin in immunology. J Immunol. 2005 Mar 15;174(6):3137-42. doi: 10.4049/jimmunol.174.6.3137. **PMID:** 15749839 ## Document Section ### Large Document Module #### Large Docs - Date: 2023-07-18 - Filename: Prot_000.pdf - Has ICF: False - Has Protocol: True - Has SAP: False - Label: Study Protocol - Size: 658536 - Type Abbrev: Prot - Upload Date: 2023-10-06T03:55 - Date: 2023-07-10 - Filename: SAP_001.pdf - Has ICF: False - Has Protocol: False - Has SAP: True - Label: Statistical Analysis Plan - Size: 740731 - Type Abbrev: SAP - Upload Date: 2023-10-09T10:25 ## 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:** NCT04977479 **Brief Title:** The Safety of Administering a Second Dose of a COVID-19 mRNA Vaccine in Individuals Who Experienced a Systemic Allergic Reaction to an Initial Dose **Official Title:** A Randomized, Placebo-controlled Crossover Study to Assess the Safety of Administering a Second Dose of a COVID-19 mRNA Vaccine in Individuals Who Experienced a Systemic Allergic Reaction to an Initial Dose #### Organization Study ID Info **ID:** 10000460 #### Organization **Class:** NIH **Full Name:** National Institutes of Health Clinical Center (CC) #### Secondary ID Infos **ID:** 000460-I ### Status Module #### Completion Date **Date:** 2023-02-22 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2023-10-16 **Type:** ACTUAL **Last Update Submit Date:** 2023-09-21 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2022-06-17 **Type:** ACTUAL #### Results First Post Date **Date:** 2023-10-16 **Type:** ACTUAL **Results First Submit Date:** 2023-06-16 **Results First Submit QC Date:** 2023-09-21 #### Start Date **Date:** 2021-09-08 **Type:** ACTUAL **Status Verified Date:** 2023-01 #### Study First Post Date **Date:** 2021-07-27 **Type:** ACTUAL **Study First Submit Date:** 2021-07-24 **Study First Submit QC Date:** 2021-07-24 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** NIH **Name:** National Institute of Allergy and Infectious Diseases (NIAID) #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** True ### Description Module **Brief Summary:** Background: Some people have allergic reactions to COVID-19 mRNA vaccines. Researchers want to learn more about these reactions to provide guidance on who can safely receive the vaccines, including a second dose in people who had a reaction to the first. Objective: To study the safety of giving a second mRNA COVID-19 vaccine dose to people who had a systemic allergic reaction to their first dose. Eligibility: People aged 16-69 who had a systemic allergic reaction to their first dose of COVID-19 vaccine. Design: Individuals who have underlying health issues may need to come to the NIH for screening tests to make sure they are safe to receive the vaccine. People who are eligible to participate in the study will be admitted to the NIH hospital and stay for at least 4 days. They will give urine samples. They will have a nasal swab SARS-CoV-2 test. They will have an intravenous line placed in each arm. They will get the study vaccine (Pfizer-BioNTech COVID-19 vaccine) and one dose of placebo on different days. They will have breathing tests. They may have clinical photography if they develop a rash. Participants will have 4 follow-up visits - 2 by phone and 2 in-person visits at the NIH campus . They will have allergy skin testing at one visit. Drops of different allergens or controls will be placed on their back or arm. The skin under each drop will be scratched with a tool. If the results are negative, a small amount of allergen will be injected just below the surface of their skin. Participants who have no or only a mild allergic reaction to the second dose of the vaccine may be eligible to receive a Booster dose at the NIH. Participation will last for approximately 5 months. **Detailed Description:** Study Description: This is a single-site study to determine the safety of administering a dose of the Pfizer-BioNTech mRNA coronavirus disease 2019 (COVID-19) vaccine (Comirnaty) to individuals who experienced a systemic allergic reaction to their first full dose of the same vaccine or the Moderna mRNA vaccine, and to investigate possible mechanisms underlying allergic reactions. Objectives: Primary Objective: 1. Assess the proportion of participants who develop a systemic allergic reaction (Consortium for Food Allergy Research grade 2 reaction and above regardless of tryptase, or CoFAR grade 1 with elevated tryptase \[1.2 X baseline plus 2ng/mL\]) to the Pfizer-BioNTech COVID-19 vaccine after previously demonstrating a systemic allergic reaction (CoFAR Grade 2 or 3 reaction regardless of tryptase OR Grade 1 reaction with elevated tryptase \[1.2 X baseline plus 2ng/mL\]) to their first full dose of the same vaccine or the Moderna COVID-19 vaccine. Secondary Objectives: 1. Assess the proportion of participants who develop a severe systemic allergic reaction (CoFAR Grade 3 reaction or higher regardless of tryptase) to the Pfizer-BioNTech COVID-19 vaccine after previously demonstrating a systemic allergic reaction (CoFAR Grade 2 or 3 reaction regardless of tryptase OR Grade 1 reaction with elevated tryptase \[1.2 X baseline plus 2ng/mL\]) to their first full dose of the same vaccine or the Moderna COVID-19 vaccine. 2. Assess the proportion of participants who develop a mild-moderate allergic reaction (CoFAR Grade 1 or 2 reaction regardless of tryptase) to the Pfizer-BioNTech COVID-19 vaccine after previously demonstrating a systemic allergic reaction (CoFAR Grade 2 or 3 reaction regardless of tryptase OR Grade 1 reaction with elevated tryptase \[1.2 X baseline plus 2ng/mL\]) to their first full dose of the same vaccine or the Moderna COVID-19 vaccine. 3. Assess the proportion of participants with anaphylactic reactions (Levels 1-3) per Brighton Collaboration Criteria (see Appendix B) to the Pfizer-BioNTech COVID-19 vaccine after previously demonstrating a systemic allergic reaction (CoFAR Grade 2 or 3 reaction OR Grade 1 reaction with elevated tryptase \[1.2 X baseline plus 2ng/mL\]) to their first full dose of the same vaccine or the Moderna COVID-19 vaccine. 4. Assess the proportion of participants who develop a systemic allergic reaction (CoFAR Grade 2 reaction or higher regardless of tryptase OR Grade 1 reaction with elevated tryptase \[1.2 X baseline plus 2ng/mL\]) to the Pfizer-BioNTech COVID-19 vaccine after previously demonstrating a systemic allergic reaction (CoFAR Grade 2 or 3 reaction regardless of tryptase OR Grade 1 reaction with elevated tryptase \[1.2 X baseline plus 2ng/mL\]) to their first full dose of the same vaccine or the Moderna COVID-19 vaccine compared to the rate of these reactions following placebo administration. 5. Compare the severity of allergic reactions to the first dose of the Pfizer-BioNTech or Moderna COVID-19 vaccine to the severity of the reaction following administration of a subsequent dose of the Pfizer-BioNTech vaccine in individuals who experienced a systemic allergic reaction (CoFAR grade 2 reaction and above regardless of tryptase, or CoFAR grade 1 with elevated tryptase \[1.2 X baseline plus 2ng/mL\]) to their first full dose of the Pfizer-BioNTech or Moderna COVID-19 vaccine. Exploratory Objectives: 1. Assess the risk of having a systemic allergic reaction to a dose of the Pfizer-BioNTech COVID-19 vaccine in participants who previously demonstrated a systemic allergic reaction (CoFAR Grade 2 or 3 reaction regardless of tryptase OR Grade 1 reaction with elevated tryptase \[1.2 X baseline plus 2ng/mL\]) to their first full dose of the same vaccine or the Moderna COVID-19 according to baseline covariates. 2. Examine possible mechanisms of allergic reactions to mRNA-based COVID-19 vaccines. 3. Assess innate and adaptive immune responses, including functional antibody levels, to the Pfizer-BioNTech COVID-19 vaccine 4. Investigate mental health characteristics of participants who experience an allergic reaction to the COVID-19 vaccine. 5. Assess psychological impact of allergic reactions to the COVID-19 vaccine and examine changes in stress levels over time. 6. Assess anxiety levels in participants and examine changes in anxiety over time. 7. Assess the proportion of participants who experience no reaction or only a mild reaction (CoFAR Grade 2 or below) to a booster dose of the Pfizer-BioNTech vaccine after previously demonstrating a systemic allergic reaction (CoFAR Grade 2 or 3 reaction regardless of tryptase OR Grade 1 reaction with elevated tryptase \[1.2 X baseline plus 2 ng/mL\]) to their first full dose of the Pfizer-BioNTech or Moderna COVID-19 vaccine and no allergic reaction or a mild reaction (CoFAR Grade 2 or below) to a subsequent (second) dose of the Pfizer-BioNTech vaccine. 8. Assess the development of autoantibodies after COVID-19 vaccination. Endpoints:\<TAB\> Primary Endpoint: 1. The proportion of participants who previously demonstrated a systemic allergic reaction (CoFAR Grade 2 or 3 reaction regardless of tryptase OR Grade 1 reaction with elevated tryptase \[1.2 X baseline plus 2ng/mL\]) to their first full dose of the Pfizer-BioNTech or Moderna COVID-19 vaccine who experience a systemic allergic reaction (CoFAR Grade 2 and above reaction regardless of tryptase, or CoFAR grade 1 with elevated tryptase \[1.2 X baseline plus 2ng/mL\]) within the 3-hour post-vaccine observation period to a subsequent dose of the Pfizer-BioNTech vaccine. Secondary Endpoints: 1. The proportion of participants who previously demonstrated a systemic allergic reaction (CoFAR Grade 2 or 3 reaction regardless of tryptase OR Grade 1 reaction with elevated tryptase \[1.2 X baseline plus 2ng/mL\]) to their first full dose of the Pfizer-BioNTech or Moderna COVID-19 vaccine who experience a severe systemic allergic reaction (CoFAR grade 3 reaction and above) within the 3-hour post-vaccine observation period to a subsequent dose of the Pfizer-BioNTech vaccine. 2. The proportion of participants who previously demonstrated a systemic allergic reaction (CoFAR Grade 2 or 3 reaction regardless of tryptase OR Grade 1 reaction with elevated tryptase \[1.2 X baseline plus 2ng/mL\]) to their first full dose of the Pfizer-BioNTech or Moderna COVID-19 vaccine who experience a mild-moderate allergic reaction (CoFAR grade 1 or 2 reaction regardless of tryptase) within the 3-hour post-vaccine observation period to a subsequent dose of the Pfizer-BioNTech vaccine. 3. The proportion of participants who previously demonstrated a systemic allergic reaction (CoFAR Grade 2 or 3 reaction regardless of tryptase OR Grade 1 reaction with elevated tryptase \[1.2 X baseline plus 2ng/mL\]) to their first full dose of the Pfizer-BioNTech or Moderna COVID-19 vaccine who experience an anaphylactic reaction (Levels 1-3) per Brighton Collaboration Criteria within the 3-hour post-vaccine observation period to a subsequent dose of the Pfizer-BioNTech vaccine. 4. The proportion of participants who previously demonstrated a systemic allergic reaction (CoFAR Grade 2 or 3 reaction regardless of tryptase OR Grade 1 reaction with elevated tryptase \[1.2 X baseline plus 2ng/mL\]) to their first full dose of the Pfizer-BioNTech or Moderna COVID-19 vaccine who experience a systemic allergic reaction (CoFAR grade 2 reaction and above regardless of tryptase, or CoFAR grade 1 with elevated tryptase \[1.2 X baseline plus 2ng/mL\]) within the 3-hour post-vaccine observation period to a subsequent dose of the Pfizer-BioNTech vaccine compared to the rate of these reactions following placebo administration. 5. The proportion of participants who previously demonstrated a systemic allergic reaction (CoFAR Grade 2 or 3 reaction regardless of tryptase OR Grade 1 reaction with elevated tryptase \[1.2 X baseline plus 2ng/mL\]) to their first full dose of the Pfizer-BioNTech or Moderna COVID-19 vaccine who develop a lower or higher grade allergic reaction within the 3-hour post-vaccine observation period to a subsequent dose of the Pfizer-BioNTech vaccine. Exploratory Endpoints: 1. Prevalence of polyethylene glycol (PEG) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in each participant at baseline. 2. Changes in anti-PEG and SARS-CoV-2 antibodies in each participant approximately 1 and 5 months after receiving the dose of the Pfizer-BioNTech vaccine administered on study. 3. Prevalence of positive skin testing to the vaccine and/or vaccine components including PEG- and polysorbate 80-containing medications. 4. Changes in biomarkers from baseline to post-dose of the Pfizer-BioNTech vaccine administered on study (e.g., known mediators of systemic reactions due to mast cell activation, markers of inflammatory response, markers of basophil and neutrophil activation, markers associated with activation of the classical and alternative complement pathways or kinin system, proteomics, metabolomics). 5. Changes in blood transcriptomics after vaccination. 6. Changes in innate and adaptive immune responses including functional antibody levels after vaccination. 7. Mental health/anxiety questionnaire scores and anxiety level ratings at baseline. 8. Results of psychiatric consultation/mental health interview. 9. Changes in mental health/anxiety questionnaire scores and anxiety level ratings over the study period. 10. The proportion of participants who previously demonstrated a systemic allergic reaction (CoFAR Grade 2 or 3 reaction regardless of tryptase OR Grade 1 reaction with elevated tryptase \[1.2 X baseline plus 2 ng/mL\]) to their first full dose of the Pfizer-BioNTech or Moderna COVID-19 vaccine and no allergic reaction or a mild reaction (CoFAR Grade 2 or below) to a subsequent (second) dose of the Pfizer-BioNTech vaccine who experience no reaction or only a mild reaction (CoFAR Grade 2 or below) to a booster dose of the Pfizer-BioNTech vaccine administered approximately 5 months after the second dose. 11. Changes in blood transcriptomics after vaccination. 12. Changes in innate and adaptive immune responses including functional antibody levels after vaccination. 13. Mental health/anxiety questionnaire scores and anxiety level ratings at baseline. 14. Results of psychiatric consultation/mental health interview. 15. Changes in mental health/anxiety questionnaire scores and anxiety level ratings over the study period. 16. The proportion of participants who previously demonstrated a systemic allergic reaction (CoFAR Grade 2 or 3 reaction regardless of tryptase OR Grade 1 reaction with elevated tryptase \[1.2 X baseline plus 2 ng/mL\]) to their first full dose of the Pfizer-BioNTech or Moderna COVID-19 vaccine and no allergic reaction or a mild reaction (CoFAR Grade 2 or below) to a subsequent (second) dose of the Pfizer-BioNTech vaccine who experience no reaction or only a mild reaction (CoFAR Grade 2 or below) to a booster dose of the Pfizer-BioNTech vaccine administered approximately 5 months after the second dose. 17. The development of autoantibodies post-second and post-booster doses of the COVID-19 mRNA vaccines. ### Conditions Module **Conditions:** - Systemic Allergic Reaction **Keywords:** - polyethylene glycol (PEG) - Pfizer-BioNTech COVID-19 vaccine - Moderna Covid-19 vaccine - Consortium for Food Allergy Research (CoFAR) - SARS-CoV-2 - Comirnaty ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** CROSSOVER ##### Masking Info **Masking:** QUADRUPLE **Who Masked:** - PARTICIPANT - CARE_PROVIDER - INVESTIGATOR - OUTCOMES_ASSESSOR **Primary Purpose:** BASIC_SCIENCE #### Enrollment Info **Count:** 20 **Type:** ACTUAL **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Participants who experienced a systemic allergic reaction after receiving their first full dose of the Pfizer-BioNTech or Moderna COVID-19 vaccine receives one dose of the active mRNA COVID-19 vaccine (0.3mL) intramuscularly followed by a wash out period of 24 hours then crossover to receive placebo (0.3 mL normal saline) intramuscularly. **Intervention Names:** - Biological: Pfizer-BioNTech COVID-19 Vaccine (Comirnaty) - Other: Placebo **Label:** Blinded Active Vaccine 2 **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** Participants who experienced a systemic allergic reaction after receiving their first full dose of the Pfizer-BioNTech or Moderna COVID-19 vaccine receives one dose of the placebo (0.3 mL normal saline) intramuscularly followed by a wash out period of 24 hours then crossover to receive the active mRNA COVID-19 vaccine (0.3mL) intramuscularly. **Intervention Names:** - Biological: Pfizer-BioNTech COVID-19 Vaccine (Comirnaty) - Other: Placebo **Label:** Blinded Placebo **Type:** PLACEBO_COMPARATOR #### Arm Group 3 **Description:** Participants who did not suffer from a COFAR grade 3 or higher reaction after blinded active vaccine 2 were offered to receive booster dose of the active mRNA COVID-19 vaccine (0.3 mL) intramuscularly 5 months later. **Intervention Names:** - Biological: Pfizer-BioNTech COVID-19 Vaccine (Comirnaty) - Biological: Pfizer-BioNTech COVID-19 Vaccine, Bivalent **Label:** Open-Label Booster Vaccine **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - Blinded Active Vaccine 2 - Blinded Placebo - Open-Label Booster Vaccine **Description:** mRNA vaccine for the prevention of COVID-19. Single dose (0.3mL) via IM. **Name:** Pfizer-BioNTech COVID-19 Vaccine (Comirnaty) **Type:** BIOLOGICAL #### Intervention 2 **Arm Group Labels:** - Blinded Active Vaccine 2 - Blinded Placebo **Description:** Commercially available sterile, preservative-free 0.9% Sodium Chloride Injection, USP. Volume to match active vaccine controlling for and delivered as a single dose via IM. **Name:** Placebo **Type:** OTHER #### Intervention 3 **Arm Group Labels:** - Open-Label Booster Vaccine **Description:** mRNA vaccine booster bivalent (Original and Omicron BA.4/BA.5) for the prevention of COVID-19. Single dose (0.3mL) via IM. **Name:** Pfizer-BioNTech COVID-19 Vaccine, Bivalent **Type:** BIOLOGICAL ### Outcomes Module #### Primary Outcomes **Description:** Proportion of participants who had recurrent systemic allergic reaction following active COVID-19 vaccine dose in this study. Allergic reactions were graded using Consortium of Food Allergy Research (CoFAR) grading scale (Version 3.0) where Grade 1 (mild) = mild symptoms involving one organ system (skin, conjunctiva, upper respiratory or gastrointestinal); Grade 2 (moderate) = mild symptoms involving ≥2 organ system (skin, conjunctiva, upper respiratory or gastrointestinal); Grade 3 (severe)= moderate to severe cardiovascular, lower respiratory or gastrointestinal symptoms, responsive to treatment and/or without end-organ dysfunction; Grade 4 = severe cardiovascular or lower respiratory symptoms, with end-organ dysfunction and/or refractory to treatment; and Grade 5 = death. Systemic allergic reaction was defined as CoFAR grade 1 reaction with elevated tryptase or CoFAR Grade ≥ 2 reaction irrespective of tryptase levels. **Measure:** Proportion of Participants Who Had Recurrent Systemic Allergic Reaction to Vaccine **Time Frame:** Within the 3-hour post-vaccine observation period **Description:** Proportion of participants who had recurrent systemic allergic reaction following active COVID-19 vaccine dose in this study. Allergic reactions were graded using Consortium of Food Allergy Research (CoFAR) grading scale (Version 3.0) where Grade 1 (mild) = mild symptoms involving one organ system (skin, conjunctiva, upper respiratory or gastrointestinal); Grade 2 (moderate) = mild symptoms involving ≥2 organ system (skin, conjunctiva, upper respiratory or gastrointestinal); Grade 3 (severe)= moderate to severe cardiovascular, lower respiratory or gastrointestinal symptoms, responsive to treatment and/or without end-organ dysfunction; Grade 4 = severe cardiovascular or lower respiratory symptoms, with end-organ dysfunction and/or refractory to treatment; and Grade 5 = death. Systemic allergic reaction was defined as CoFAR grade 1 reaction with elevated tryptase or CoFAR Grade ≥ 2 reaction irrespective of tryptase levels. **Measure:** Proportion of Participants Who Had Recurrent Systemic Allergic Reaction to Vaccine **Time Frame:** Within the 3-hour post-vaccine observation period #### Secondary Outcomes **Description:** Proportion of participants who developed severe systemic allergic reaction following active COVID-19 vaccine dose in this study. Allergic reactions were graded using Consortium of Food Allergy Research (CoFAR) grading scale (Version 3.0) where Grade 1 (mild) = mild symptoms involving one organ system (skin, conjunctiva, upper respiratory or gastrointestinal); Grade 2 (moderate) = mild symptoms involving ≥2 organ system (skin, conjunctiva, upper respiratory or gastrointestinal); Grade 3 (severe)= moderate to severe cardiovascular, lower respiratory or gastrointestinal symptoms, responsive to treatment and/or without end-organ dysfunction; Grade 4 = severe cardiovascular or lower respiratory symptoms, with end-organ dysfunction and/or refractory to treatment; and Grade 5 = death. Severe systemic allergic reaction was defined as CoFAR Grade ≥ 3 reaction, regardless of tryptase levels. **Measure:** Proportion of Participants Who Developed Severe Systemic Allergic Reaction to Vaccine **Time Frame:** Within the 3-hour post-vaccine observation period **Description:** Proportion of participants who developed mild or moderate systemic allergic reaction following active COVID-19 vaccine dose in this study. Allergic reactions were graded using Consortium of Food Allergy Research (CoFAR) grading scale (Version 3.0) where Grade 1 (mild) = mild symptoms involving one organ system (skin, conjunctiva, upper respiratory or gastrointestinal); Grade 2 (moderate) = mild symptoms involving ≥2 organ system (skin, conjunctiva, upper respiratory or gastrointestinal); Grade 3 (severe)= moderate to severe cardiovascular, lower respiratory or gastrointestinal symptoms, responsive to treatment and/or without end-organ dysfunction; Grade 4 = severe cardiovascular or lower respiratory symptoms, with end-organ dysfunction and/or refractory to treatment; and Grade 5 = death Mild to moderate systemic allergic reaction was defined as CoFAR Grade 1 or 2 regardless of tryptase level. **Measure:** Proportion of Participants Who Developed Mild or Moderate Systemic Allergic Reaction Following Active Vaccine Dose **Time Frame:** Within the 3-hour post-vaccine observation period **Description:** Proportion of participants who had recurrent systemic allergic reaction following active COVID-19 vaccine dose in this study. Allergic reactions were graded using Consortium of Food Allergy Research (CoFAR) grading scale (Version 3.0) where grade 1 (mild) = mild symptoms involving one organ system (skin, conjunctiva, upper respiratory or gastrointestinal); grade 2 (moderate) = mild symptoms involving =2 organ system (skin, conjunctiva, upper respiratory or gastrointestinal); grade 3 (severe)= moderate to severe cardiovascular, lower respiratory or gastrointestinal symptoms, responsive to tr **Measure:** Proportion of Participants Who Developed Mild or Moderate Systemic Allergic Reaction Following Active Vaccine Dose **Time Frame:** Within the 3-hour post-vaccine observation period **Description:** Proportion of participants with anaphylactic reactions (Levels 1-3) per Brighton Collaboration Criteria to the COVID-19 vaccine after previously demonstrating a systemic allergic reaction to their first full dose of the COVID-19 vaccine. Anaphylaxis was defined using the Brighton Collaboration Criteria as a clinical syndrome characterized by a sudden onset and rapid progression of signs and symptoms involving ≥2 organ systems including skin, cardiovascular, respiratory, gastrointestinal or tryptase elevation (\>upper normal limit). Only specific clinical features from these organ systems meet major and/or minor criteria to provide level of diagnostic certainty for anaphylactic reaction. Reaction meeting levels 1-3 diagnostic certainty are consistent with anaphylaxis **Measure:** Proportion of Participants Who Developed Anaphylactic Reaction Following Active Dose Delivered **Time Frame:** Within the 3-hour post-vaccine observation period **Description:** Proportion of participants with anaphylactic reactions (Levels 1-3) per Brighton Collaboration Criteria to the COVID-19 vaccine after previously demonstrating a systemic allergic reaction to their first full dose of the COVID-19 vaccine. Anaphylaxis was defined using the Brighton Collaboration Criteria as a clinical syndrome characterized by a sudden onset and rapid progression of signs and symptoms involving ≥2 organ systems including skin, cardiovascular, respiratory, gastrointestinal or tryptase elevation (\>upper normal limit). Only specific clinical features from these organ systems meet major and/or minor criteria to provide level of diagnostic certainty for anaphylactic reaction. Reaction meeting levels 1-3 diagnostic certainty are consistent with anaphylaxis. **Measure:** Proportion of Participants Who Developed Anaphylactic Reaction Following Active Vaccine Dose **Time Frame:** Within the 3-hour post-vaccine observation period **Description:** Participants with recurrent systemic allergic reaction following active vaccine dose in this study compared with reaction in placebo. Allergic reactions were graded using Consortium of Food Allergy Research (CoFAR) grading scale (Version 3.0) where Grade 1 (mild)= mild symptoms involving one organ system (skin, conjunctiva, upper respiratory or gastrointestinal); Grade 2 (moderate)= mild symptoms involving ≥2 organ system (skin, conjunctiva, upper respiratory or gastrointestinal); Grade 3 (severe)= moderate to severe cardiovascular, lower respiratory or gastrointestinal symptoms, responsive to treatment and/or without end-organ dysfunction; Grade 4= severe cardiovascular or lower respiratory symptoms, with end-organ dysfunction and/or refractory to treatment; and Grade 5= death Systemic allergic reaction was defined as CoFAR grade 1 reaction with elevated tryptase or CoFAR Grade ≥ 2 reaction irrespective of tryptase level. Outcome was calculated as risk difference estimation. **Measure:** Proportion of Participants Who Had Recurrent Systemic Allergic Reaction Following Active Vaccine Dose Compared With Rate of Reaction in Placebo **Time Frame:** Within the 3-hour post-vaccine observation period **Description:** Proportion of participants with less severe allergic reaction to the vaccine dose in this study than recorded reaction to the first full COVID-19 vaccine dose (pre-study). Allergic reactions were graded using Consortium of Food Allergy Research (CoFAR) grading scale (Version 3.0) where Grade 1 (mild) = mild symptoms involving one organ system (skin, conjunctiva, upper respiratory or gastrointestinal); Grade 2 (moderate) = mild symptoms involving ≥2 organ system (skin, conjunctiva, upper respiratory or gastrointestinal); Grade 3 (severe)= moderate to severe cardiovascular, lower respiratory or gastrointestinal symptoms, responsive to treatment and/or without end-organ dysfunction; Grade 4 = severe cardiovascular or lower respiratory symptoms, with end-organ dysfunction and/or refractory to treatment; and Grade 5 = death. Systemic allergic reaction was defined as CoFAR grade 1 reaction with elevated tryptase or CoFAR Grade ≥ 2 reaction irrespective of tryptase levels. **Measure:** Proportion of Participants With Less Severe Allergic Reaction to the Vaccine Dose Delivered in This Study Than Recorded Reaction to the First Full COVID-19 Vaccine Dose **Time Frame:** Within the 3-hour post-vaccine observation period **Description:** "Proportion of participants with more severe allergic reaction to the vaccine dose in this study than recorded reaction to the first full COVID-19 vaccine dose (pre-study). Allergic reactions were graded using Consortium of Food Allergy Research (CoFAR) grading scale (Version 3.0) where Grade 1 (mild) = mild symptoms involving one organ system (skin, conjunctiva, upper respiratory or gastrointestinal); Grade 2 (moderate) = mild symptoms involving ≥2 organ system (skin, conjunctiva, upper respiratory or gastrointestinal); Grade 3 (severe)= moderate to severe cardiovascular, lower respiratory or gastrointestinal symptoms, responsive to treatment and/or without end-organ dysfunction; Grade 4 = severe cardiovascular or lower respiratory symptoms, with end-organ dysfunction and/or refractory to treatment; and Grade 5 = death Systemic allergic reaction was defined as CoFAR grade 1 reaction with elevated tryptase or CoFAR Grade ≥ 2 reaction irrespective of tryptase levels. **Measure:** Proportion of Participants With More Severe Systemic Allergic Reaction to the Vaccine Dose Delivered in This Study Than Recorded Reaction to the First Full Vaccine Dose **Time Frame:** Within the 3-hour post-vaccine observation period **Description:** "Proportion of participants with more severe allergic reaction to the vaccine dose in this study than recorded reaction to the first full COVID-19 vaccine dose (pre-study). Allergic reactions were graded using Consortium of Food Allergy Research (CoFAR) grading scale (Version 3.0) where Grade 1 (mild) = mild symptoms involving one organ system (skin, conjunctiva, upper respiratory or gastrointestinal); Grade 2 (moderate) = mild symptoms involving ≥2 organ system (skin, conjunctiva, upper respiratory or gastrointestinal); Grade 3 (severe)= moderate to severe cardiovascular, lower respiratory or gastrointestinal symptoms, responsive to treatment and/or without end-organ dysfunction; Grade 4 = severe cardiovascular or lower respiratory symptoms, with end-organ dysfunction and/or refractory to treatment; and Grade 5 = death. Systemic allergic reaction was defined as CoFAR grade 1 reaction with elevated tryptase or CoFAR Grade ≥ 2 reaction irrespective of tryptase levels. **Measure:** Proportion of Participants With More Severe Systemic Allergic Reaction to the Vaccine Dose Delivered in This Study Than Recorded Reaction to the First Full Vaccine Dose **Time Frame:** Within the 3-hour post-vaccine observation period ### Eligibility Module **Eligibility Criteria:** * INCLUSION CRITERIA: In order to be eligible to participate in this study, an individual must meet all of the following criteria: * Ability to provide informed consent. * Stated willingness to comply with all study procedures (including discontinuing medications as needed and availability for the duration of the study. * Aged 16-69 years. * Must have experienced a systemic allergic reaction (CoFAR Grade 2 or 3 reaction regardless of tryptase OR Grade 1 reaction with elevated tryptase \[1.2 X baseline plus 2 ng/mL\] per modified CoFAR Grading Scale for Systemic Allergic Reactions Version 3.0) to the first dose of the Pfizer-BioNTech or Moderna COVID-19 vaccine. Patients without documented hypoxia, hypotension, or evidence of end-organ damage who were treated with epinephrine infusion would be considered as CoFAR Grade 3 reaction and may be eligible per investigator discretion. * Must be at least 28 days out from their first dose of the Moderna vaccine or 21 days from their first dose of the Pfizer-BioNTech vaccine before proceeding with the placebo or vaccine challenge in this study. * Have a primary care physician or other health care provider who will manage their medical care outside of this study. EXCLUSION CRITERIA: An individual who meets any of the following criteria will be excluded from participation in this study: * Experienced a Grade 4 systemic allergic reaction (per CoFAR Grading Scale for Systemic Allergic Reactions Version 3.0) to the first dose of the Pfizer-BioNTech or Moderna COVID-19 vaccine. * Known exposure to SARS-CoV-2 and still within the quarantine window. * Symptoms consistent with acute COVID-19 infection or known COVID-19 infection (positive reverse transcription-polymerase chain reaction \[RT-PCR\] or antigen test) and still within the quarantine window * Have an acute illness, including body temperature greater than 100.4 degrees F, within 14 days prior to enrollment. * History of autoimmune or other disorders requiring systemic immune modulators. * Are moderately or severely immunocompromised. * History of acute urticaria within 28 days prior to enrollment. * Pregnant. * Have received any vaccines within 14 days prior to enrollment. * Scheduled or planned receipt of approved or experimental vaccine prior to visit 3. * Had any allergen immunotherapy administration within 24 hours prior to the first study vaccination or plan to receive within 24 hours after the second study vaccination. * Have received a biological therapy within 6 months prior to enrollment. * Use of systemic steroids for any reason within 28 days prior to enrollment. * Use of zileuton within 14 days prior to enrollment. * Use of EUA monoclonal antibodies casirivimab and indevimab, or bamlanivimab, or any other antibody agent for treatment or prevention of COVID-19 within 3 months of randomization. * Presence of condition(s) that, in the judgment of the investigator or the referring physician, may put the participant at undue risk or make them unsuitable for participation in the study. **Maximum Age:** 69 Years **Minimum Age:** 16 Years **Sex:** ALL **Standard Ages:** - CHILD - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Bethesda **Country:** United States **Facility:** National Institutes of Health Clinical Center **State:** Maryland **Zip:** 20892 #### Overall Officials **Official 1:** **Affiliation:** National Institute of Allergy and Infectious Diseases (NIAID) **Name:** Pamela A Guerrerio, M.D. **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### See Also Links **Label:** NIH Clinical Center Detailed Web Page **URL:** https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_000460-I.html ## Document Section ### Large Document Module #### Large Docs - Date: 2022-10-19 - Filename: Prot_SAP_000.pdf - Has ICF: False - Has Protocol: True - Has SAP: True - Label: Study Protocol and Statistical Analysis Plan - Size: 449133 - Type Abbrev: Prot_SAP - Upload Date: 2023-06-07T12:03 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000011024 - Term: Pneumonia, Viral - ID: D000011014 - Term: Pneumonia - ID: D000012141 - Term: Respiratory Tract Infections - ID: D000007239 - Term: Infections - ID: D000014777 - Term: Virus Diseases - ID: D000018352 - Term: Coronavirus Infections - ID: D000003333 - Term: Coronaviridae Infections - ID: D000030341 - Term: Nidovirales Infections - ID: D000012327 - Term: RNA Virus Infections - ID: D000008171 - Term: Lung Diseases - ID: D000012140 - Term: Respiratory Tract Diseases - ID: D000007154 - Term: Immune System 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: BC20 - Name: Immune System Diseases - Abbrev: BC23 - Name: Symptoms and General Pathology ### Condition Browse Module - Browse Leaves - ID: M2561 - Name: COVID-19 - Relevance: HIGH - As Found: COVID-19 - ID: M10018 - Name: Hypersensitivity - Relevance: HIGH - As Found: Allergic Reaction - ID: M8636 - Name: Food Hypersensitivity - Relevance: LOW - As Found: Unknown - ID: M13904 - Name: Pneumonia - Relevance: LOW - As Found: Unknown - ID: M13914 - Name: Pneumonia, Viral - Relevance: LOW - As Found: Unknown - ID: M10283 - Name: Infections - Relevance: LOW - As Found: Unknown - ID: M6368 - Name: Communicable Diseases - Relevance: LOW - As Found: Unknown - ID: M14978 - Name: Respiratory Tract Infections - Relevance: LOW - As Found: Unknown - ID: M17522 - Name: Virus Diseases - Relevance: LOW - As Found: Unknown - ID: M20490 - Name: Coronavirus Infections - Relevance: LOW - As Found: Unknown - ID: M6555 - Name: Coronaviridae Infections - Relevance: LOW - As Found: Unknown - ID: M23685 - Name: Nidovirales Infections - Relevance: LOW - As Found: Unknown - ID: M15149 - Name: RNA Virus Infections - Relevance: LOW - As Found: Unknown - ID: M11168 - Name: Lung Diseases - Relevance: LOW - As Found: Unknown - ID: M14977 - Name: Respiratory Tract Diseases - Relevance: LOW - As Found: Unknown - ID: M10200 - Name: Immune System Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000086382 - Term: COVID-19 - ID: D000006967 - Term: Hypersensitivity ### 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 #### Submission Tracking ##### First MCP Info ###### Post Date - Date: 2023-07-12 - Type: ACTUAL - Version Holder: 2024-05-24 ## Results Section ### Adverse Events Module **Description:** Adverse events associated with the crossover phase have been grouped under 'Overall Study' due to the brief washout period between the active vaccine and the placebo. #### Event Groups **Group ID:** EG000 **Title:** Blinded Active Vaccine 2 **Deaths Num At Risk:** 16 **Description:** Participants who experienced a systemic allergic reaction after receiving their first full dose of the Pfizer-BioNTech or Moderna COVID-19 vaccine receives one dose of the active mRNA COVID-19 vaccine (0.3mL) intramuscularly **ID:** EG000 **Other Num Affected:** 3 **Other Num at Risk:** 16 **Serious Number At Risk:** 16 **Title:** Blinded Active Vaccine 2 **Group ID:** EG001 **Title:** Placebo **Deaths Num At Risk:** 16 **Description:** Participants who experienced a systemic allergic reaction after receiving their first full dose of the Pfizer-BioNTech or Moderna COVID-19 vaccine receives one dose of placebo (0.3 mL normal saline) intramuscularly. **ID:** EG001 **Other Num at Risk:** 16 **Serious Number At Risk:** 16 **Title:** Placebo **Group ID:** EG002 **Title:** Open-Label Booster Vaccine **Deaths Num At Risk:** 16 **Description:** Participants who did not suffer from a COFAR grade 3 or higher reaction after blinded active vaccine 2 were offered to receive booster dose of the active mRNA COVID-19 vaccine (0.3 mL) intramuscularly 5 months later. **ID:** EG002 **Other Num Affected:** 16 **Other Num at Risk:** 16 **Serious Number At Risk:** 16 **Title:** Open-Label Booster Vaccine **Group ID:** EG003 **Title:** Overall Study **Deaths Num At Risk:** 16 **Description:** Participants who experienced a systemic allergic reaction after receiving their first full dose of the Pfizer-BioNTech or Moderna COVID-19 vaccine receives one dose of the active mRNA COVID-19 vaccine (0.3mL) intramuscularly or placebo (0.3 mL normal saline) intramuscularly in the crossover phase of study. **ID:** EG003 **Other Num Affected:** 16 **Other Num at Risk:** 16 **Serious Number At Risk:** 16 **Title:** Overall Study **Frequency Threshold:** 0 #### Other Events **Term:** Anaemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** **Term:** Eosinophilia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** **Term:** Leukocytosis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** **Term:** Neutrophilia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** **Term:** Thrombocytosis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Blood and lymphatic system disorders **Source Vocabulary:** **Term:** Palpitations **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** **Term:** Sinus tachycardia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** **Term:** Tachycardia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Cardiac disorders **Source Vocabulary:** **Term:** Eustachian tube dysfunction **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Ear and labyrinth disorders **Source Vocabulary:** **Term:** Tinnitus **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Ear and labyrinth disorders **Source Vocabulary:** **Term:** Eye irritation **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Eye disorders **Source Vocabulary:** **Term:** Lacrimation increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Eye disorders **Source Vocabulary:** **Term:** Vision blurred **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Eye disorders **Source Vocabulary:** **Term:** Abdominal distension **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** **Term:** Abdominal hernia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** **Term:** Abdominal pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** **Term:** Abdominal pain upper **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** **Term:** Dry mouth **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** **Term:** Dysphagia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** **Term:** Nausea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** **Term:** Proctitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** **Term:** Toothache **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** **Term:** Vomiting **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Gastrointestinal disorders **Source Vocabulary:** **Term:** Application site pruritus **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** **Term:** Chest discomfort **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** **Term:** Chest pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** **Term:** Chills **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** **Term:** Discomfort **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** **Term:** Facial pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** **Term:** Fatigue **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** **Term:** Feeling abnormal **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** **Term:** Feeling hot **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** **Term:** Gait disturbance **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** **Term:** Injection site erythema **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** **Term:** Injection site induration **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** **Term:** Injection site oedema **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** **Term:** Injection site pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** **Term:** Injection site pruritus **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** **Term:** Injection site reaction **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** **Term:** Injection site warmth **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** **Term:** Non-cardiac chest pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** **Term:** Pyrexia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** **Term:** Tenderness **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** **Term:** Vessel puncture site bruise **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** General disorders **Source Vocabulary:** **Term:** Anaphylactic reaction **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Immune system disorders **Source Vocabulary:** **Term:** Food allergy **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Immune system disorders **Source Vocabulary:** **Term:** Hypersensitivity **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Immune system disorders **Source Vocabulary:** **Term:** Body tinea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** **Term:** Bronchitis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** **Term:** Corona virus infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** **Term:** Gastroenteritis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** **Term:** Otitis externa **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** **Term:** Pneumonia viral **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** **Term:** Upper respiratory tract infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** **Term:** Viral infection **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** **Term:** Vulvovaginal candidiasis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Infections and infestations **Source Vocabulary:** **Term:** Contusion **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** **Term:** Exposure to communicable disease **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** **Term:** Injury **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** **Term:** Ligament sprain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Injury, poisoning and procedural complications **Source Vocabulary:** **Term:** Blood pressure increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** **Term:** Eosinophil count increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** **Term:** Lymphocyte count decreased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** **Term:** Lymphocyte count increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** **Term:** Neutrophil count decreased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** **Term:** Neutrophil count increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** **Term:** Platelet count decreased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** **Term:** White blood cell count decreased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** **Term:** White blood cell count increased **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Investigations **Source Vocabulary:** **Term:** Decreased appetite **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** **Term:** Hypoglycaemia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** **Term:** Polydipsia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Metabolism and nutrition disorders **Source Vocabulary:** **Term:** Arthralgia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** **Term:** Arthritis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** **Term:** Back pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** **Term:** Musculoskeletal chest pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** **Term:** Myalgia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** **Term:** Pain in extremity **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Musculoskeletal and connective tissue disorders **Source Vocabulary:** **Term:** Disturbance in attention **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** **Term:** Dizziness **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** **Term:** Dysgeusia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** **Term:** Headache **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** **Term:** Hypoaesthesia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** **Term:** Migraine **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** **Term:** Nerve compression **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** **Term:** Paraesthesia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** **Term:** Parosmia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** **Term:** Presyncope **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** **Term:** Taste disorder **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Nervous system disorders **Source Vocabulary:** **Term:** Restlessness **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Psychiatric disorders **Source Vocabulary:** **Term:** Micturition urgency **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Renal and urinary disorders **Source Vocabulary:** **Term:** Intermenstrual bleeding **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Reproductive system and breast disorders **Source Vocabulary:** **Term:** Menstruation irregular **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Reproductive system and breast disorders **Source Vocabulary:** **Term:** Pelvic pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Reproductive system and breast disorders **Source Vocabulary:** **Term:** Cough **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** **Term:** Dysphonia **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** **Term:** Dyspnoea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** **Term:** Nasal congestion **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** **Term:** Nasal discomfort **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** **Term:** Oropharyngeal pain **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** **Term:** Rhinorrhoea **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** **Term:** Sneezing **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** **Term:** Throat irritation **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** **Term:** Throat tightness **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** **Term:** Upper-airway cough syndrome **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** **Term:** Wheezing **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Respiratory, thoracic and mediastinal disorders **Source Vocabulary:** **Term:** Ecchymosis **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** **Term:** Erythema **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** **Term:** Mechanical urticaria **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** **Term:** Night sweats **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** **Term:** Pruritus **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** **Term:** Rash **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** **Term:** Rash pruritic **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** **Term:** Skin burning sensation **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Skin and subcutaneous tissue disorders **Source Vocabulary:** **Term:** Bereavement **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Social circumstances **Source Vocabulary:** **Term:** Catheter management **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Surgical and medical procedures **Source Vocabulary:** **Term:** Flushing **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** **Term:** Haematoma **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** **Term:** Hypertension **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** **Term:** Hypotension **Assessment Type:** SYSTEMATIC_ASSESSMENT **Organ System:** Vascular disorders **Source Vocabulary:** **Time Frame:** Blinded Active Vaccine 2 & Placebo - Within 3-hour post-vaccination Overall Study - up to 17 months post intervention in the crossover phase Open-Label Booster Vaccine - up to 11 months post vaccine administration ## Results Section - Baseline Characteristics Module ### Denomination Counts **Group ID:** BG000 **Value:** 8 **Group ID:** BG001 **Value:** 8 **Group ID:** BG002 **Value:** 16 **Units:** Participants ### Group **ID:** BG000 **Title:** Blinded Active Vaccine 2 **Description:** Participants who experienced a systemic allergic reaction after receiving their first full dose of the Pfizer-BioNTech or Moderna COVID-19 vaccine receives one dose of the active mRNA COVID-19 vaccine (0.3mL) intramuscularly followed by a wash out period of 24 hours then crossover to receive placebo (0.3 mL normal saline) intramuscularly. ### Group **ID:** BG001 **Title:** Blinded Placebo **Description:** Participants who experienced a systemic allergic reaction after receiving their first full dose of the Pfizer-BioNTech or Moderna COVID-19 vaccine receives one dose of the placebo (0.3 mL normal saline) intramuscularly followed by a wash out period of 24 hours then crossover to receive the active mRNA COVID-19 vaccine (0.3mL) intramuscularly. ### Group **ID:** BG002 **Title:** Total **Description:** Total of all reporting groups ### Measure #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** <=18 years #### Measurement **Group ID:** BG000 **Value:** 8 #### Measurement **Group ID:** BG001 **Value:** 7 #### Measurement **Group ID:** BG002 **Value:** 15 **Category Title:** Between 18 and 65 years #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 1 #### Measurement **Group ID:** BG002 **Value:** 1 **Category Title:** >=65 years **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 8 #### Measurement **Group ID:** BG001 **Value:** 7 #### Measurement **Group ID:** BG002 **Value:** 15 **Category Title:** Female #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 1 #### Measurement **Group ID:** BG002 **Value:** 1 **Category Title:** Male **Class Title:** ### Measure #### Measurement **Group ID:** BG000 **Value:** 2 #### Measurement **Group ID:** BG001 **Value:** 3 #### Measurement **Group ID:** BG002 **Value:** 5 **Category Title:** Hispanic or Latino #### Measurement **Group ID:** BG000 **Value:** 6 #### Measurement **Group ID:** BG001 **Value:** 5 #### Measurement **Group ID:** BG002 **Value:** 11 **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:** 2 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 2 **Category Title:** Asian #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** Native Hawaiian or Other Pacific Islander #### Measurement **Group ID:** BG000 **Value:** 1 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 1 **Category Title:** Black or African American #### Measurement **Group ID:** BG000 **Value:** 5 #### Measurement **Group ID:** BG001 **Value:** 8 #### Measurement **Group ID:** BG002 **Value:** 13 **Category Title:** White #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** More than one race #### Measurement **Group ID:** BG000 **Value:** 0 #### Measurement **Group ID:** BG001 **Value:** 0 #### Measurement **Group ID:** BG002 **Value:** 0 **Category Title:** Unknown or Not Reported **Class Title:** **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 ## Results Section - More Information Module ### Certain Agreement **PI Sponsor Employee:** True ### Limitations and Caveats **Description:** There was no pre-determined method for addressing causality of adverse events in the crossover phase of the study due to the brief washout period between the active vaccine and placebo administration. ### Point of Contact **Email:** [email protected] **Organization:** National Institute of Allergy and Infectious Diseases **Phone:** 301-402-9782 **Title:** Pamela Frischmeyer-Guerrerio ## 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 ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0.016 - **Spread:** - **Upper Limit:** 0.383 - **Value:** 0.125 **Title:** #### Outcome Measure 2 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0.016 - **Spread:** - **Upper Limit:** 0.383 - **Value:** 0.125 **Title:** #### Outcome Measure 3 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 0.206 - **Value:** 0 **Title:** #### Outcome Measure 4 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0.002 - **Spread:** - **Upper Limit:** 0.302 - **Value:** 0.062 **Title:** #### Outcome Measure 5 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0.04 - **Spread:** - **Upper Limit:** 0.456 - **Value:** 0.188 **Title:** #### Outcome Measure 6 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0.002 - **Spread:** - **Upper Limit:** 0.302 - **Value:** 0.062 **Title:** #### Outcome Measure 7 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0.002 - **Spread:** - **Upper Limit:** 0.302 - **Value:** 0.062 **Title:** #### Outcome Measure 8 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0.002 - **Spread:** - **Upper Limit:** 0.302 - **Value:** 0.062 **Title:** #### Outcome Measure 9 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** -0.134 - **Spread:** - **Upper Limit:** 0.383 - **Value:** 0.125 - **Comment:** - **Group ID:** OG001 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 0 - **Value:** 0 **Title:** #### Outcome Measure 10 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0.04 - **Spread:** - **Upper Limit:** 0.456 - **Value:** 0.188 **Title:** #### Outcome Measure 11 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0.002 - **Spread:** - **Upper Limit:** 0.302 - **Value:** 0.062 **Title:** #### Outcome Measure 12 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 0.206 - **Value:** 0 **Title:** #### Outcome Measure 13 **Class:** ##### Category **Measurements:** - **Comment:** - **Group ID:** OG000 - **Lower Limit:** 0 - **Spread:** - **Upper Limit:** 0.206 - **Value:** 0 **Title:** ## Results Section ### Outcome Measures Module #### Outcome Measure 1 **Description:** Proportion of participants who had recurrent systemic allergic reaction following active COVID-19 vaccine dose in this study. Allergic reactions were graded using Consortium of Food Allergy Research (CoFAR) grading scale (Version 3.0) where Grade 1 (mild) = mild symptoms involving one organ system (skin, conjunctiva, upper respiratory or gastrointestinal); Grade 2 (moderate) = mild symptoms involving ≥2 organ system (skin, conjunctiva, upper respiratory or gastrointestinal); Grade 3 (severe)= moderate to severe cardiovascular, lower respiratory or gastrointestinal symptoms, responsive to treatment and/or without end-organ dysfunction; Grade 4 = severe cardiovascular or lower respiratory symptoms, with end-organ dysfunction and/or refractory to treatment; and Grade 5 = death. Systemic allergic reaction was defined as CoFAR grade 1 reaction with elevated tryptase or CoFAR Grade ≥ 2 reaction irrespective of tryptase levels. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** NUMBER **Population Description:** The analysis included participants who received the active study vaccine in the crossover phase as pre-specified in the protocol to only collect and report data from the active vaccination. **Reporting Status:** POSTED **Time Frame:** Within the 3-hour post-vaccine observation period **Title:** Proportion of Participants Who Had Recurrent Systemic Allergic Reaction to Vaccine **Type:** PRIMARY **Unit of Measure:** Proportion of participants ##### Group **Description:** Participants who experienced a systemic allergic reaction after receiving their first full dose of the Pfizer-BioNTech or Moderna COVID-19 vaccine receives one dose of the active mRNA COVID-19 vaccine (0.3mL) intramuscularly **ID:** OG000 **Title:** Blinded Active Vaccine 2 #### Outcome Measure 2 **Description:** Proportion of participants who had recurrent systemic allergic reaction following active COVID-19 vaccine dose in this study. Allergic reactions were graded using Consortium of Food Allergy Research (CoFAR) grading scale (Version 3.0) where Grade 1 (mild) = mild symptoms involving one organ system (skin, conjunctiva, upper respiratory or gastrointestinal); Grade 2 (moderate) = mild symptoms involving ≥2 organ system (skin, conjunctiva, upper respiratory or gastrointestinal); Grade 3 (severe)= moderate to severe cardiovascular, lower respiratory or gastrointestinal symptoms, responsive to treatment and/or without end-organ dysfunction; Grade 4 = severe cardiovascular or lower respiratory symptoms, with end-organ dysfunction and/or refractory to treatment; and Grade 5 = death. Systemic allergic reaction was defined as CoFAR grade 1 reaction with elevated tryptase or CoFAR Grade ≥ 2 reaction irrespective of tryptase levels. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** NUMBER **Population Description:** The analysis included participants who received both active study vaccines in the crossover phase and the booster dose in the open label phase **Reporting Status:** POSTED **Time Frame:** Within the 3-hour post-vaccine observation period **Title:** Proportion of Participants Who Had Recurrent Systemic Allergic Reaction to Vaccine **Type:** PRIMARY **Unit of Measure:** Proportion of participants ##### Group **Description:** Participants who did not suffer from a COFAR grade 3 or higher reaction after blinded active vaccine 2 were offered to receive booster dose of the active mRNA COVID-19 vaccine (0.3 mL) intramuscularly 5 months later. **ID:** OG000 **Title:** Open-Label Booster Vaccine #### Outcome Measure 3 **Description:** Proportion of participants who developed severe systemic allergic reaction following active COVID-19 vaccine dose in this study. Allergic reactions were graded using Consortium of Food Allergy Research (CoFAR) grading scale (Version 3.0) where Grade 1 (mild) = mild symptoms involving one organ system (skin, conjunctiva, upper respiratory or gastrointestinal); Grade 2 (moderate) = mild symptoms involving ≥2 organ system (skin, conjunctiva, upper respiratory or gastrointestinal); Grade 3 (severe)= moderate to severe cardiovascular, lower respiratory or gastrointestinal symptoms, responsive to treatment and/or without end-organ dysfunction; Grade 4 = severe cardiovascular or lower respiratory symptoms, with end-organ dysfunction and/or refractory to treatment; and Grade 5 = death. Severe systemic allergic reaction was defined as CoFAR Grade ≥ 3 reaction, regardless of tryptase levels. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** NUMBER **Population Description:** The analysis included participants who received the active study vaccine in the crossover phase as pre-specified in the protocol to only collect and report data from the active vaccination. **Reporting Status:** POSTED **Time Frame:** Within the 3-hour post-vaccine observation period **Title:** Proportion of Participants Who Developed Severe Systemic Allergic Reaction to Vaccine **Type:** SECONDARY **Unit of Measure:** Proportion of participants ##### Group **Description:** Participants who experienced a systemic allergic reaction after receiving their first full dose of the Pfizer-BioNTech or Moderna COVID-19 vaccine receives one dose of the active mRNA COVID-19 vaccine (0.3mL) intramuscularly **ID:** OG000 **Title:** Blinded Active Vaccine 2 #### Outcome Measure 4 **Description:** Proportion of participants who developed severe systemic allergic reaction following active COVID-19 vaccine dose in this study. Allergic reactions were graded using Consortium of Food Allergy Research (CoFAR) grading scale (Version 3.0) where Grade 1 (mild) = mild symptoms involving one organ system (skin, conjunctiva, upper respiratory or gastrointestinal); Grade 2 (moderate) = mild symptoms involving ≥2 organ system (skin, conjunctiva, upper respiratory or gastrointestinal); Grade 3 (severe)= moderate to severe cardiovascular, lower respiratory or gastrointestinal symptoms, responsive to treatment and/or without end-organ dysfunction; Grade 4 = severe cardiovascular or lower respiratory symptoms, with end-organ dysfunction and/or refractory to treatment; and Grade 5 = death. Severe systemic allergic reaction was defined as CoFAR Grade ≥ 3 reaction, regardless of tryptase levels. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** NUMBER **Population Description:** The analysis included those who had a systemic allergic reaction following 1st dose of an mRNA vaccine before study and received both active study active vaccines **Reporting Status:** POSTED **Time Frame:** Within the 3-hour post-vaccine observation period **Title:** Proportion of Participants Who Developed Severe Systemic Allergic Reaction to Vaccine **Type:** SECONDARY **Unit of Measure:** Proportion of participants ##### Group **Description:** Participants who did not suffer from a COFAR grade 3 or higher reaction after blinded active vaccine 2 were offered to receive booster dose of the active mRNA COVID-19 vaccine (0.3 mL) intramuscularly 5 months later. **ID:** OG000 **Title:** Open-Label Booster Vaccine #### Outcome Measure 5 **Description:** Proportion of participants who developed mild or moderate systemic allergic reaction following active COVID-19 vaccine dose in this study. Allergic reactions were graded using Consortium of Food Allergy Research (CoFAR) grading scale (Version 3.0) where Grade 1 (mild) = mild symptoms involving one organ system (skin, conjunctiva, upper respiratory or gastrointestinal); Grade 2 (moderate) = mild symptoms involving ≥2 organ system (skin, conjunctiva, upper respiratory or gastrointestinal); Grade 3 (severe)= moderate to severe cardiovascular, lower respiratory or gastrointestinal symptoms, responsive to treatment and/or without end-organ dysfunction; Grade 4 = severe cardiovascular or lower respiratory symptoms, with end-organ dysfunction and/or refractory to treatment; and Grade 5 = death Mild to moderate systemic allergic reaction was defined as CoFAR Grade 1 or 2 regardless of tryptase level. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** NUMBER **Population Description:** The analysis included participants who received the active study vaccine in the crossover phase as pre-specified in the protocol to only collect and report data from the active vaccination. **Reporting Status:** POSTED **Time Frame:** Within the 3-hour post-vaccine observation period **Title:** Proportion of Participants Who Developed Mild or Moderate Systemic Allergic Reaction Following Active Vaccine Dose **Type:** SECONDARY **Unit of Measure:** Proportion of participants ##### Group **Description:** Participants who experienced a systemic allergic reaction after receiving their first full dose of the Pfizer-BioNTech or Moderna COVID-19 vaccine receives one dose of the active mRNA COVID-19 vaccine (0.3mL) intramuscularly **ID:** OG000 **Title:** Blinded Active Vaccine 2 #### Outcome Measure 6 **Description:** Proportion of participants who had recurrent systemic allergic reaction following active COVID-19 vaccine dose in this study. Allergic reactions were graded using Consortium of Food Allergy Research (CoFAR) grading scale (Version 3.0) where grade 1 (mild) = mild symptoms involving one organ system (skin, conjunctiva, upper respiratory or gastrointestinal); grade 2 (moderate) = mild symptoms involving =2 organ system (skin, conjunctiva, upper respiratory or gastrointestinal); grade 3 (severe)= moderate to severe cardiovascular, lower respiratory or gastrointestinal symptoms, responsive to tr **Dispersion Type:** 95% Confidence Interval **Parameter Type:** NUMBER **Population Description:** The analysis included those who had a systemic allergic reaction following 1st dose of an mRNA vaccine before study and received both active study active vaccines **Reporting Status:** POSTED **Time Frame:** Within the 3-hour post-vaccine observation period **Title:** Proportion of Participants Who Developed Mild or Moderate Systemic Allergic Reaction Following Active Vaccine Dose **Type:** SECONDARY **Unit of Measure:** Proportion of participants ##### Group **Description:** Participants who did not suffer from a COFAR grade 3 or higher reaction after blinded active vaccine 2 were offered to receive booster dose of the active mRNA COVID-19 vaccine (0.3 mL) intramuscularly 5 months later. **ID:** OG000 **Title:** Open-Label Booster Vaccine #### Outcome Measure 7 **Description:** Proportion of participants with anaphylactic reactions (Levels 1-3) per Brighton Collaboration Criteria to the COVID-19 vaccine after previously demonstrating a systemic allergic reaction to their first full dose of the COVID-19 vaccine. Anaphylaxis was defined using the Brighton Collaboration Criteria as a clinical syndrome characterized by a sudden onset and rapid progression of signs and symptoms involving ≥2 organ systems including skin, cardiovascular, respiratory, gastrointestinal or tryptase elevation (\>upper normal limit). Only specific clinical features from these organ systems meet major and/or minor criteria to provide level of diagnostic certainty for anaphylactic reaction. Reaction meeting levels 1-3 diagnostic certainty are consistent with anaphylaxis **Dispersion Type:** 95% Confidence Interval **Parameter Type:** NUMBER **Population Description:** The analysis included participants who received the active study vaccine in the crossover phase as pre-specified in the protocol to only collect and report data from the active vaccination. **Reporting Status:** POSTED **Time Frame:** Within the 3-hour post-vaccine observation period **Title:** Proportion of Participants Who Developed Anaphylactic Reaction Following Active Dose Delivered **Type:** SECONDARY **Unit of Measure:** Proportion of participants ##### Group **Description:** Participants who experienced a systemic allergic reaction after receiving their first full dose of the Pfizer-BioNTech or Moderna COVID-19 vaccine receives one dose of the active mRNA COVID-19 vaccine (0.3mL) intramuscularly **ID:** OG000 **Title:** Blinded Active Vaccine 2 #### Outcome Measure 8 **Description:** Proportion of participants with anaphylactic reactions (Levels 1-3) per Brighton Collaboration Criteria to the COVID-19 vaccine after previously demonstrating a systemic allergic reaction to their first full dose of the COVID-19 vaccine. Anaphylaxis was defined using the Brighton Collaboration Criteria as a clinical syndrome characterized by a sudden onset and rapid progression of signs and symptoms involving ≥2 organ systems including skin, cardiovascular, respiratory, gastrointestinal or tryptase elevation (\>upper normal limit). Only specific clinical features from these organ systems meet major and/or minor criteria to provide level of diagnostic certainty for anaphylactic reaction. Reaction meeting levels 1-3 diagnostic certainty are consistent with anaphylaxis. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** NUMBER **Population Description:** The analysis included those who had a systemic allergic reaction following 1st dose of an mRNA vaccine before study and received both active study active vaccines **Reporting Status:** POSTED **Time Frame:** Within the 3-hour post-vaccine observation period **Title:** Proportion of Participants Who Developed Anaphylactic Reaction Following Active Vaccine Dose **Type:** SECONDARY **Unit of Measure:** Proportion of participants ##### Group **Description:** Participants who did not suffer from a COFAR grade 3 or higher reaction after blinded active vaccine 2 were offered to receive booster dose of the active mRNA COVID-19 vaccine (0.3 mL) intramuscularly 5 months later. **ID:** OG000 **Title:** Open-Label Booster Vaccine #### Outcome Measure 9 **Description:** Participants with recurrent systemic allergic reaction following active vaccine dose in this study compared with reaction in placebo. Allergic reactions were graded using Consortium of Food Allergy Research (CoFAR) grading scale (Version 3.0) where Grade 1 (mild)= mild symptoms involving one organ system (skin, conjunctiva, upper respiratory or gastrointestinal); Grade 2 (moderate)= mild symptoms involving ≥2 organ system (skin, conjunctiva, upper respiratory or gastrointestinal); Grade 3 (severe)= moderate to severe cardiovascular, lower respiratory or gastrointestinal symptoms, responsive to treatment and/or without end-organ dysfunction; Grade 4= severe cardiovascular or lower respiratory symptoms, with end-organ dysfunction and/or refractory to treatment; and Grade 5= death Systemic allergic reaction was defined as CoFAR grade 1 reaction with elevated tryptase or CoFAR Grade ≥ 2 reaction irrespective of tryptase level. Outcome was calculated as risk difference estimation. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** NUMBER **Population Description:** The analysis included the proportion of participants who had a systemic allergic reaction after receiving the active study vaccine compared to the proportion who had a systemic allergic reaction after receiving placebo during the crossover phase of the study. **Reporting Status:** POSTED **Time Frame:** Within the 3-hour post-vaccine observation period **Title:** Proportion of Participants Who Had Recurrent Systemic Allergic Reaction Following Active Vaccine Dose Compared With Rate of Reaction in Placebo **Type:** SECONDARY **Unit of Measure:** Proportion of participants ##### Group **Description:** Participants who experienced a systemic allergic reaction after receiving their first full dose of the Pfizer-BioNTech or Moderna COVID-19 vaccine receives one dose of the active mRNA COVID-19 vaccine (0.3mL) intramuscularly in the crossover phase of the study. **ID:** OG000 **Title:** Blinded Active Vaccine 2 ##### Group **Description:** Participants who experienced a systemic allergic reaction after receiving their first full dose of the Pfizer-BioNTech or Moderna COVID-19 vaccine receives one dose placebo (0.3 mL normal saline) intramuscularly in the crossover phase of the study. **ID:** OG001 **Title:** Placebo #### Outcome Measure 10 **Description:** Proportion of participants with less severe allergic reaction to the vaccine dose in this study than recorded reaction to the first full COVID-19 vaccine dose (pre-study). Allergic reactions were graded using Consortium of Food Allergy Research (CoFAR) grading scale (Version 3.0) where Grade 1 (mild) = mild symptoms involving one organ system (skin, conjunctiva, upper respiratory or gastrointestinal); Grade 2 (moderate) = mild symptoms involving ≥2 organ system (skin, conjunctiva, upper respiratory or gastrointestinal); Grade 3 (severe)= moderate to severe cardiovascular, lower respiratory or gastrointestinal symptoms, responsive to treatment and/or without end-organ dysfunction; Grade 4 = severe cardiovascular or lower respiratory symptoms, with end-organ dysfunction and/or refractory to treatment; and Grade 5 = death. Systemic allergic reaction was defined as CoFAR grade 1 reaction with elevated tryptase or CoFAR Grade ≥ 2 reaction irrespective of tryptase levels. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** NUMBER **Population Description:** The analysis included participants who received the active study vaccine in the crossover phase as pre-specified in the protocol to only collect and report data from the active vaccination. **Reporting Status:** POSTED **Time Frame:** Within the 3-hour post-vaccine observation period **Title:** Proportion of Participants With Less Severe Allergic Reaction to the Vaccine Dose Delivered in This Study Than Recorded Reaction to the First Full COVID-19 Vaccine Dose **Type:** SECONDARY **Unit of Measure:** Proportion of participants ##### Group **Description:** Participants who experienced a systemic allergic reaction after receiving their first full dose of the Pfizer-BioNTech or Moderna COVID-19 vaccine receives one dose of the active mRNA COVID-19 vaccine (0.3mL) intramuscularly **ID:** OG000 **Title:** Blinded Active Vaccine 2 #### Outcome Measure 11 **Description:** Proportion of participants with less severe allergic reaction to the vaccine dose in this study than recorded reaction to the first full COVID-19 vaccine dose (pre-study). Allergic reactions were graded using Consortium of Food Allergy Research (CoFAR) grading scale (Version 3.0) where Grade 1 (mild) = mild symptoms involving one organ system (skin, conjunctiva, upper respiratory or gastrointestinal); Grade 2 (moderate) = mild symptoms involving ≥2 organ system (skin, conjunctiva, upper respiratory or gastrointestinal); Grade 3 (severe)= moderate to severe cardiovascular, lower respiratory or gastrointestinal symptoms, responsive to treatment and/or without end-organ dysfunction; Grade 4 = severe cardiovascular or lower respiratory symptoms, with end-organ dysfunction and/or refractory to treatment; and Grade 5 = death. Systemic allergic reaction was defined as CoFAR grade 1 reaction with elevated tryptase or CoFAR Grade ≥ 2 reaction irrespective of tryptase levels. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** NUMBER **Population Description:** The analysis included those who had a systemic allergic reaction following 1st dose of an mRNA vaccine before study and received both active study active vaccines (blinded and open-label) **Reporting Status:** POSTED **Time Frame:** Within the 3-hour post-vaccine observation period **Title:** Proportion of Participants With Less Severe Allergic Reaction to the Vaccine Dose Delivered in This Study Than Recorded Reaction to the First Full COVID-19 Vaccine Dose **Type:** SECONDARY **Unit of Measure:** Proportion of participants ##### Group **Description:** Participants who did not suffer from a COFAR grade 3 or higher reaction after blinded active vaccine 2 were offered to receive booster dose of the active mRNA COVID-19 vaccine (0.3 mL) intramuscularly 5 months later. **ID:** OG000 **Title:** Open-Label Booster Vaccine #### Outcome Measure 12 **Description:** "Proportion of participants with more severe allergic reaction to the vaccine dose in this study than recorded reaction to the first full COVID-19 vaccine dose (pre-study). Allergic reactions were graded using Consortium of Food Allergy Research (CoFAR) grading scale (Version 3.0) where Grade 1 (mild) = mild symptoms involving one organ system (skin, conjunctiva, upper respiratory or gastrointestinal); Grade 2 (moderate) = mild symptoms involving ≥2 organ system (skin, conjunctiva, upper respiratory or gastrointestinal); Grade 3 (severe)= moderate to severe cardiovascular, lower respiratory or gastrointestinal symptoms, responsive to treatment and/or without end-organ dysfunction; Grade 4 = severe cardiovascular or lower respiratory symptoms, with end-organ dysfunction and/or refractory to treatment; and Grade 5 = death Systemic allergic reaction was defined as CoFAR grade 1 reaction with elevated tryptase or CoFAR Grade ≥ 2 reaction irrespective of tryptase levels. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** NUMBER **Population Description:** The analysis included participants who received the active study vaccine in the crossover phase as pre-specified in the protocol to only collect and report data from the active vaccination. **Reporting Status:** POSTED **Time Frame:** Within the 3-hour post-vaccine observation period **Title:** Proportion of Participants With More Severe Systemic Allergic Reaction to the Vaccine Dose Delivered in This Study Than Recorded Reaction to the First Full Vaccine Dose **Type:** SECONDARY **Unit of Measure:** Proportion of participants ##### Group **Description:** Participants who experienced a systemic allergic reaction after receiving their first full dose of the Pfizer-BioNTech or Moderna COVID-19 vaccine receives one dose of the active mRNA COVID-19 vaccine (0.3mL) intramuscularly **ID:** OG000 **Title:** Blinded Active Vaccine 2 #### Outcome Measure 13 **Description:** "Proportion of participants with more severe allergic reaction to the vaccine dose in this study than recorded reaction to the first full COVID-19 vaccine dose (pre-study). Allergic reactions were graded using Consortium of Food Allergy Research (CoFAR) grading scale (Version 3.0) where Grade 1 (mild) = mild symptoms involving one organ system (skin, conjunctiva, upper respiratory or gastrointestinal); Grade 2 (moderate) = mild symptoms involving ≥2 organ system (skin, conjunctiva, upper respiratory or gastrointestinal); Grade 3 (severe)= moderate to severe cardiovascular, lower respiratory or gastrointestinal symptoms, responsive to treatment and/or without end-organ dysfunction; Grade 4 = severe cardiovascular or lower respiratory symptoms, with end-organ dysfunction and/or refractory to treatment; and Grade 5 = death. Systemic allergic reaction was defined as CoFAR grade 1 reaction with elevated tryptase or CoFAR Grade ≥ 2 reaction irrespective of tryptase levels. **Dispersion Type:** 95% Confidence Interval **Parameter Type:** NUMBER **Population Description:** The analysis included those who had a systemic allergic reaction following 1st dose of an mRNA vaccine before study and received both active study active vaccines (blinded and open-label) **Reporting Status:** POSTED **Time Frame:** Within the 3-hour post-vaccine observation period **Title:** Proportion of Participants With More Severe Systemic Allergic Reaction to the Vaccine Dose Delivered in This Study Than Recorded Reaction to the First Full Vaccine Dose **Type:** SECONDARY **Unit of Measure:** Proportion of participants ##### Group **Description:** Participants who did not suffer from a COFAR grade 3 or higher reaction after blinded active vaccine 2 were offered to receive booster dose of the active mRNA COVID-19 vaccine (0.3 mL) intramuscularly 5 months later. **ID:** OG000 **Title:** Open-Label Booster Vaccine ### Participant Flow Module #### Group **Description:** Participants who experienced a systemic allergic reaction after receiving their first full dose of the Pfizer-BioNTech or Moderna COVID-19 vaccine receives one dose of the active mRNA COVID-19 vaccine (0.3mL) intramuscularly followed by a wash out period of 24 hours then crossover to receive placebo (0.3 mL normal saline) intramuscularly. **ID:** FG000 **Title:** Blinded Active Vaccine 2 #### Group **Description:** Participants who experienced a systemic allergic reaction after receiving their first full dose of the Pfizer-BioNTech or Moderna COVID-19 vaccine receives one dose of the placebo (0.3 mL normal saline) intramuscularly followed by a wash out period of 24 hours then crossover to receive the active mRNA COVID-19 vaccine (0.3mL) intramuscularly. **ID:** FG001 **Title:** Blinded Placebo #### Group **Description:** Participants who did not suffer from a COFAR grade 3 or higher reaction after blinded active vaccine 2 were offered to receive booster dose of the active mRNA COVID-19 vaccine (0.3 mL) intramuscularly 5 months later. **ID:** FG002 **Title:** Open-Label Booster Vaccine #### Period **Title:** First Period of Crossover ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 8 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 8 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 0 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 8 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 8 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 0 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 0 #### Period **Title:** Washout Period ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 8 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 8 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 0 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 8 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 8 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 0 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 0 #### Period **Title:** Second Period of Crossover ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 8 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 8 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 0 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 8 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 8 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 0 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 0 #### Period **Title:** Open Label ##### Milestone **Type:** STARTED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 16 ##### Milestone **Type:** COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 16 ##### Milestone **Type:** NOT COMPLETED ###### Achievement **Group ID:** FG000 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG001 **Number of Subjects:** 0 ###### Achievement **Group ID:** FG002 **Number of Subjects:** 0 **Pre-Assignment Details:** Three participants withdrew prior to start of study. One participant was ineligible due to partial 2nd vaccine dose pre-enrollment outside of the study **Has Results:** True

## Protocol Section ### Identification Module **NCT ID:** NCT03942679 **Brief Title:** Platelet Rich Plasma and Supraspinatus Tear **Official Title:** Efficacy of Platelet Rich Plasma Injection in Comparison to Physical Therapy for Treatment of Chronic Partial Supraspinatus Tears #### Organization Study ID Info **ID:** MS/17.08.79 #### Organization **Class:** OTHER **Full Name:** Mansoura University ### Status Module #### Completion Date **Date:** 2020-04-10 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2020-04-16 **Type:** ACTUAL **Last Update Submit Date:** 2020-04-14 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2020-04-01 **Type:** ACTUAL #### Start Date **Date:** 2019-06-01 **Type:** ACTUAL **Status Verified Date:** 2019-05 #### Study First Post Date **Date:** 2019-05-08 **Type:** ACTUAL **Study First Submit Date:** 2019-05-07 **Study First Submit QC Date:** 2019-05-07 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Mansoura University #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False ### Description Module **Brief Summary:** Rheumatology and Rehabilitation Department, Mansoura University Hospital. Forty patients with chronic partial supraspinatus tears will be included in the study. The diagnosis of the supraspinatus tear will be made by ultrasound examination **Detailed Description:** At inclusion in the study, demographic data (age, gender, duration of complaints, and body mass index) will be recorded. Randomization Patients will be randomized into two matched groups: A) PRP-Injection Group - Patients in this group will receive three ultrasound guided PRP injections in the supraspinatus tendon with one week interval (Ilhanli et al., 2015). After the injection, patients will be instructed to limit the use of shoulder for at least 24 hours and to use cold therapy for pain. After the third injection, ROM, and stretching exercises will be allowed and one month after the end of injections, patients will be recommended to begin the strengthening program as tolerated. Exercise is performed with 10 repeats five sessions per week. B) Physical Therapy Group - Patients in this group will be treated with hot pack for 15 minutes, ultrasound in continuous mode (1.5 watt/cm2 for five minutes), trans-cutaneous electrical nerve stimulation in brief-intense mode for 15 minutes, range of motion (ROM), followed by stretching and strengthening exercises with 10 repeats 15 sessions (five sessions per week for three weeks). After the physical therapy, the exercise program will be continued as homework during the follow-up period. Patients in t ### Conditions Module **Conditions:** - Supraspinatus Tear ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** SEQUENTIAL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 40 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Patients in this group will receive three ultrasound guided PRP injections in the supraspinatus tendon with one week interval (Ilhanli et al., 201 **Intervention Names:** - Other: PRP **Label:** PRPinjection group **Type:** OTHER #### Arm Group 2 **Description:** Patients in this group will be treated with hot pack for 15 minutes, ultrasound in continuous mode (1.5 watt/cm2 for five minutes), trans-cutaneous electrical nerve stimulation in brief-intense mode for 15 minutes, range of motion (ROM), followed by stretching and strengthening exercises with 10 repeats 15 sessions (five sessions per week for three weeks **Intervention Names:** - Other: physiotherapy **Label:** physiotherapy group **Type:** OTHER ### Interventions #### Intervention 1 **Arm Group Labels:** - PRPinjection group **Description:** Patients in this group will receive three ultrasound guided PRP injections in the supraspinatus tendon with one week interval (Ilhanli et al., 2015). After the injection, patients will be instructed to limit the use of shoulder for at least 24 hours and to use cold therapy for pain. After the third injection, ROM, and stretching exercises will be allowed and one month after the end of injections, patients will be recommended to begin the strengthening program as tolerated. Exercise is performed with 10 repeats five sessions per week. **Name:** PRP **Type:** OTHER #### Intervention 2 **Arm Group Labels:** - physiotherapy group **Description:** Patients in this group will be treated with hot pack for 15 minutes, ultrasound in continuous mode (1.5 watt/cm2 for five minutes), trans-cutaneous electrical nerve stimulation in brief-intense mode for 15 minutes, range of motion (ROM), followed by stretching and strengthening exercises with 10 repeats 15 sessions (five sessions per week for three weeks). After the physical therapy, the exercise program will be continued as homework during the follow-up period. **Name:** physiotherapy **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** The VAS-pain score is composed of a continuous horizontal line. This line is 100 mm in length. To measure the intensity of pain, the score is anchored by (0 score = no pain) at one end and (100 score = worst imaginable pain) on the other end. The patient places a mark to the VAS line at the point which represents the intensity of his pain **Measure:** change of pain from base line **Time Frame:** immediately before injection,6 weeks after injection,12 weeks after injection **Description:** III. Examination of passive and active range of motion using goniometer based on the description of norkin and white as following * Abduction ;170 * Adduction :50 * Flexion :165 * Extension:60 * Internal rotation at 90 abduction :70 * External rotation at 90 abduction :100 **Measure:** change of range of motion from base line **Time Frame:** immediately before injection,6 weeks after injection,12 weeks after injection #### Secondary Outcomes **Description:** •Disability and health related quality of life will be measured using DASH shoulder rating scale. **Measure:** change of shoulder index score from base line **Time Frame:** immediately before injection,6 weeks after injection,12 weeks after injection **Description:** •US documented pathology will be assessed at diagnosis and at 12 weeks. **Measure:** change of ultrasound pathology from base line **Time Frame:** immediately before injection,,12 weeks after injection ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: chronic partial supraspinatus tears will be included in the study Exclusion Criteria: age \> 80 years, pregnancy, full thickness supraspinatus tears, other rotator cuff lesions with/without supraspinatus tears, systemic disorders such as diabetes rheumatoid arthritis, hematological diseases (co-agulopathy), **Maximum Age:** 60 Years **Minimum Age:** 20 Years **Sex:** ALL **Standard Ages:** - ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Mansoura **Country:** Egypt **Facility:** Reham Magdy Shaat **State:** Dakahlia Provence **Zip:** 050 ### IPD Sharing Statement Module **IPD Sharing:** UNDECIDED ## Derived Section ### Condition Browse Module - Browse Branches - Abbrev: BC26 - Name: Wounds and Injuries - Abbrev: All - Name: All Conditions - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M15241 - Name: Rupture - Relevance: LOW - As Found: Unknown - ID: M22785 - Name: Lacerations - Relevance: LOW - As Found: Unknown - ID: T1303 - Name: Chronic Graft Versus Host Disease - Relevance: LOW - As Found: Unknown ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT02503579 **Brief Title:** The Role of Brain-derived Neurotropic Factor in the Relationship Between Executive Function and Physical Training **Official Title:** What's the Role of Brain-derived Neurotrophic Factor in the Relationship Between Executive Function and Physical Fitness/Training in Typically Developing Children? A Randomized Controlled Study #### Organization Study ID Info **ID:** 2015/0520 #### Organization **Class:** OTHER **Full Name:** University Ghent ### Status Module #### Completion Date **Date:** 2016-02 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2023-12-18 **Type:** ACTUAL **Last Update Submit Date:** 2023-12-12 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2015-12 **Type:** ACTUAL #### Start Date **Date:** 2015-08 **Status Verified Date:** 2023-12 #### Study First Post Date **Date:** 2015-07-21 **Type:** ESTIMATED **Study First Submit Date:** 2015-05-29 **Study First Submit QC Date:** 2015-07-20 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** University Hospital, Ghent #### Lead Sponsor **Class:** OTHER **Name:** University Ghent #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** This doctoral thesis has the aim to identify the role of Brain-derived neurotropic factor in the relationship between physical fitness/activity and executive functions in typically developing children and children with Autism Spectrum Disorder, Development Coordination Disorder , Attention Hyperactive Disorder. **Detailed Description:** Nowadays children are getting more inactive and participate less in sports or daily physical activity. Previous studies have shown that a good physical fitness is associated with improved cognitive functions. While being physical active, physiological changes take places in the brain. Brain-derived neurotropic factor is one of the neurotropins that plays a crucial role in this process. Executive functions are cognitive processes that are responsible for organizing and controlling goal-directed actions. These functions are developing during childhood and play an important role in daily- and school functioning. This doctoral thesis has the aim to identify the role of Brain-derived neurotropic factor in the relationship between physical fitness/activity and executive functions in children. In a first trail the effect of physical fitness and physical training on executive functioning and levels of Brain-derived neurotropic factor will be studied. In a second trail the research question is expanded by investigating the same relations in children with Autism Spectrum Disorder, Development Coordination Disorder , Attention Hyperactive Disorder. Protocol trail 1: The included (typically developing) children will be randomized and stratified for level of physical fitness into 2 groups: the intervention group and the control group. The intervention group will receive physical activity training 2 times a week during 8 weeks. The control group will receive no additional training. At the beginning and the end of the training period both the intervention and control group will be tested for physical fitness and level of executive functioning. Protocol trail 2: Identical protocol to trail 1 except the participants will be children with Autism Spectrum Disorder, Development Coordination Disorder , Attention Hyperactive Disorder in stead of typically developing children. ### Conditions Module **Conditions:** - Executive Dysfunction - Motor Activity - Child **Keywords:** - Brain-derived neurotropic factor - Executive function ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** SINGLE **Who Masked:** - OUTCOMES_ASSESSOR **Primary Purpose:** BASIC_SCIENCE #### Enrollment Info **Count:** 52 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Participant receive a submaximal (60% -75% maximal oxygen uptake) physical activity training of 30 minutes during 8 weeks, 2 times a week. Individual heart rates will be monitored during the training. **Intervention Names:** - Behavioral: physical training **Label:** physical training **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** 1 training at the beginning of the study 1 training at the end of the study **Label:** control **Type:** NO_INTERVENTION ### Interventions #### Intervention 1 **Arm Group Labels:** - physical training **Description:** physical activity program, 30 minutes **Name:** physical training **Type:** BEHAVIORAL ### Outcomes Module #### Primary Outcomes **Description:** Measurement of serum Brain-derived neurotropic factor true blood samples. **Measure:** Change from baseline after 9 weeks in concentration of serum brain-derived neurotropic factor in blood sample. **Time Frame:** Baseline and change from baseline 9 weeks later. **Description:** Measurement of serum Brain-derived neurotropic factor true blood samples. **Measure:** Change from Baseline after acute physical activity in concentration of serum brain-derived neurotropic factor in blood sample **Time Frame:** Baseline and change from baseline after 30 minutes of training. #### Secondary Outcomes **Description:** Questionnaire about daily physical activity. **Measure:** Change of baseline after 9 weeks in Amount of daily physical activity (hours/week) **Time Frame:** Baseline and change from baseline 9 weeks later. **Description:** Physical fitness measurement with maximal endurance test on bicycle using Balke-protocol. **Measure:** Change of baseline after 9 weeks in Maximal Oxygen Uptake during exertion test. **Time Frame:** Baseline and change of baseline 9 week later. **Description:** Physical fitness measurement with maximal endurance test on bicycle using Balke-protocol. **Measure:** Change of baseline after 9 weeks in Maximal heart rate during exertion test. **Time Frame:** Baseline and change of baseline 9 week later. **Description:** EF measurement true computer tasks. **Measure:** Change from Baseline after 9 weeks on Executive functioning test battery. **Time Frame:** Baseline and change of baseline 9 weeks later. **Description:** EF measurement true computer tasks. **Measure:** Change from Baseline after acute physical activity on Executive functioning test battery. **Time Frame:** Baseline and change of baseline after 30 minutes of physical activity. ### Eligibility Module **Eligibility Criteria:** Trail 1 Inclusion Criteria: * typically developing children Exclusion Criteria: * children with: executive function-, neurological- or cognitive disorders Trail 2 Inclusion criteria: * typically developing children (control) * children with Developmental Coordination disorder, Attention deficit disorder or Autism Spectrum disorder Exclusion criteria: * Children with neurological- or cognitive disorders **Healthy Volunteers:** True **Maximum Age:** 10 Years **Minimum Age:** 8 Years **Sex:** ALL **Standard Ages:** - CHILD ### Contacts Locations Module #### Overall Officials **Official 1:** **Affiliation:** Revaki **Name:** Hilde Van Waelvelde, Professor **Role:** PRINCIPAL_INVESTIGATOR ### References Module #### References **Citation:** Latomme J, Calders P, Van Waelvelde H, Marien T, De Craemer M. The Role of Brain-Derived Neurotrophic Factor (BDNF) in the Relation between Physical Activity and Executive Functioning in Children. Children (Basel). 2022 Apr 22;9(5):596. doi: 10.3390/children9050596. **PMID:** 35626772 ## Derived Section ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03860779 **Acronym:** BCSSC **Brief Title:** Biopotentials for Clinician Satisfaction With Sedation in Colonoscopy **Official Title:** Biopotentials for Clinician Satisfaction With Sedation in Colonoscopy #### Organization Study ID Info **ID:** BCSSC #### Organization **Class:** OTHER **Full Name:** University of Ulm ### Status Module #### Completion Date **Date:** 2019-07-01 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2020-05-12 **Type:** ACTUAL **Last Update Submit Date:** 2020-05-09 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2019-07-01 **Type:** ACTUAL #### Start Date **Date:** 2019-03-04 **Type:** ACTUAL **Status Verified Date:** 2020-05 #### Study First Post Date **Date:** 2019-03-04 **Type:** ACTUAL **Study First Submit Date:** 2019-02-28 **Study First Submit QC Date:** 2019-02-28 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** University of Ulm #### Responsible Party **Investigator Affiliation:** University of Ulm **Investigator Full Name:** Alexander Hann **Investigator Title:** Senior Gastroenterologist, Department of Gastroenterology **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** False **Oversight Has DMC:** False ### Description Module **Brief Summary:** Nurse-administered propofol sedation has become the standard procedure for colonoscopy in Germany. Although patient satisfaction with this method is high, there is little data about the satisfaction of the examiner and factors that might negatively influence this satisfaction. Often due to the fact that the sedated patient usually expresses pain by movements of the body and paralinguistic sounds the examination has to pause until the next propofol bolus induces a deeper sedation. In order to measure the correlation of examiner satisfaction and negative factors the investigators initiated this prospective observational study. During this study examiner satisfaction and the correlation with observer reported pain (movements and paralinguistic sounds) will be measured. Additionally different biopotentials (electromyography, skin conductance level, body temperature, pulse) of the patient will be recorded during the examination and feature pattern will be correlated to the observer reported pain in order to detect pain before the expression of pain leads to a pause in the colonoscopy examination. Other factors that might influence examiner satisfaction, like duration to reach the caecum and duration of polypectomy will additionally be evaluated. ### Conditions Module **Conditions:** - Bowel Disease **Keywords:** - colonoscopy - biosignals - pain - sedation ### Design Module #### Design Info **Observational Model:** COHORT **Time Perspective:** PROSPECTIVE #### Enrollment Info **Count:** 112 **Type:** ACTUAL **Study Type:** OBSERVATIONAL ### Outcomes Module #### Primary Outcomes **Description:** Correlation between Clinician Satisfaction with Sedation Instrument (CSSI) and observer reported pain (movements and paralinguistic sounds) during sedation **Measure:** Correlation between clinician satisfaction with sedation and pain experienced during colonoscopy **Time Frame:** 1 day **Description:** Prediction of observer reported pain events (movements and paralinguistic sounds) by biopotential feature pattern. **Measure:** Prediction of observer reported pain by biopotential feature pattern **Time Frame:** 1 day #### Secondary Outcomes **Description:** Correlation between clinician satisfaction with sedation (CSSI) and sedation depth measured by Modified Observer's assessment of Alertness/Sedation Score **Measure:** Correlation between clinician satisfaction with sedation (CSSI) and sedation depth **Time Frame:** 1 day **Description:** Correlation between clinician satisfaction with sedation (CSSI) and frequency of sedation use measured in relation to total examination duration. **Measure:** Correlation between clinician satisfaction with sedation (CSSI) and frequency of sedation use **Time Frame:** 1 day **Description:** Correlation between clinician satisfaction with sedation (CSSI) and resected polyp count **Measure:** Correlation between clinician satisfaction with sedation (CSSI) and resected polyp count **Time Frame:** 1 day **Description:** Correlation between clinician satisfaction with sedation (CSSI) and total polyp resection time **Measure:** Correlation between clinician satisfaction with sedation (CSSI) and total polyp resection time **Time Frame:** 1 day **Description:** Correlation between clinician satisfaction with sedation (CSSI) and time to reach caecum **Measure:** Correlation between clinician satisfaction with sedation (CSSI) and time to reach caecum **Time Frame:** 1 day **Description:** Correlation between clinician satisfaction with sedation (CSSI) and years of experience of assisting nurse **Measure:** Correlation between clinician satisfaction with sedation (CSSI) and years of experience of assisting nurse **Time Frame:** 1 day ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Age above 18 * ASA classification I to II * Indication for colonoscopy with propofol sedation * Written informed consent Exclusion Criteria: * Pregnancy **Minimum Age:** 18 Years **Sampling Method:** PROBABILITY_SAMPLE **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT **Study Population:** Patients scheduled at the University Hospital for a colonoscopy using propofol sedation. ### Contacts Locations Module #### Locations **Location 1:** **City:** Ulm **Country:** Germany **Facility:** University Ulm **Zip:** 89081 #### Overall Officials **Official 1:** **Affiliation:** University Ulm **Name:** Alexander Hann **Role:** PRINCIPAL_INVESTIGATOR ### IPD Sharing Statement Module **IPD Sharing:** UNDECIDED ### References Module #### References **Citation:** Hann A, Gruss S, Goetze S, Mehlhase N, Frisch S, Walter B, Walter S. Autonomous Nervous Response During Sedation in Colonoscopy and the Relationship With Clinician Satisfaction. Front Med (Lausanne). 2021 Jun 16;8:643158. doi: 10.3389/fmed.2021.643158. eCollection 2021. **PMID:** 34222272 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000005767 - Term: Gastrointestinal Diseases - ID: D000004066 - Term: Digestive System Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC06 - Name: Digestive System Diseases - Abbrev: All - Name: All Conditions - Abbrev: BC23 - Name: Symptoms and General Pathology ### Condition Browse Module - Browse Leaves - ID: M10444 - Name: Intestinal Diseases - Relevance: HIGH - As Found: Bowel Disease - ID: M13066 - Name: Pain - 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 ### Condition Browse Module - Meshes - ID: D000007410 - Term: Intestinal Diseases ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT00063479 **Brief Title:** Bisphosphonate Treatment of Osteogenesis Imperfecta **Official Title:** Bisphosphonate Treatment of Osteogenesis Imperfecta #### Organization Study ID Info **ID:** CZOL446H2202 #### Organization **Class:** INDUSTRY **Full Name:** Novartis ### Status Module #### Completion Date **Date:** 2007-05 **Type:** ACTUAL #### Last Update Post Date **Date:** 2017-06-01 **Type:** ACTUAL **Last Update Submit Date:** 2017-05-31 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2007-05 **Type:** ACTUAL #### Start Date **Date:** 2003-06 **Status Verified Date:** 2017-05 #### Study First Post Date **Date:** 2003-06-30 **Type:** ESTIMATED **Study First Submit Date:** 2003-06-27 **Study First Submit QC Date:** 2003-06-27 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Novartis Pharmaceuticals ### Description Module **Brief Summary:** The primary purpose of this trial is to evaluate whether the investigational medication is safe, effective and has the ability to increase spine bone density in osteogenesis imperfecta (OI) patients. ### Conditions Module **Conditions:** - Osteogenesis Imperfecta **Keywords:** - Osteogenesis Imperfecta - OI - bone markers - fracture - bone loss - pediatric - bisphosphonate - brittle bone disease - pamidronate ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 158 **Phases:** - PHASE2 **Study Type:** INTERVENTIONAL ### Arms Interventions Module ### Interventions #### Intervention 1 **Name:** Zoledronic Acid **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Measure:** Change in lumbar spine bone mineral density at month 12 relative to baseline #### Secondary Outcomes **Measure:** Change in Z score of the lumbar spine at month 12 relative to baseline ### Eligibility Module **Eligibility Criteria:** Inclusion * Male or Female children between 3 months and 17 years old * OI type I, III or IV Exclusion * Deformity or abnormality which would prevent spine bone density from being done * Any surgical bone-lengthening procedure * Any kidney diseases or abnormalities * Low calcium or vitamin D levels in the blood Other protocol-defined inclusion/exclusion criteria may apply. **Maximum Age:** 17 Years **Minimum Age:** 3 Months **Sex:** ALL **Standard Ages:** - CHILD ### Contacts Locations Module #### Locations **Location 1:** **City:** Los Angeles **Country:** United States **Facility:** UCLA - Division of Pediatric Nephrology **State:** California **Zip:** 90024 **Location 2:** **City:** Wilmington **Country:** United States **Facility:** Alfred I. DuPont Hospital for Children **State:** Delaware **Zip:** 19899 **Location 3:** **City:** Boise **Country:** United States **Facility:** Intermountain Orthopedics **State:** Idaho **Zip:** 83702 **Location 4:** **City:** Peoria **Country:** United States **Facility:** St. Jude Children's Research Hospital **State:** Illinois **Zip:** 61637 **Location 5:** **City:** Omaha **Country:** United States **Facility:** Children's Hospital **State:** Nebraska **Zip:** 68198 **Location 6:** **City:** Cincinnati **Country:** United States **Facility:** Children's Hospital Medical Center **State:** Ohio **Zip:** 45229 **Location 7:** **City:** Columbus **Country:** United States **Facility:** Children's Hospital **State:** Ohio **Zip:** 43205 **Location 8:** **City:** Portland **Country:** United States **Facility:** Oregon Health Sciences University **State:** Oregon **Zip:** 97201 **Location 9:** **City:** Nashville **Country:** United States **Facility:** Vanderbilt University Medical Center **State:** Tennessee **Zip:** 37232 **Location 10:** **City:** Houston **Country:** United States **Facility:** Texas Children's Hosptial **State:** Texas **Zip:** 77030 ## Derived Section ### Condition Browse Module - Ancestors - ID: D000010009 - Term: Osteochondrodysplasias - ID: D000001848 - Term: Bone Diseases, Developmental - ID: D000001847 - Term: Bone Diseases - ID: D000009140 - Term: Musculoskeletal Diseases - ID: D000030342 - Term: Genetic Diseases, Inborn - ID: D000003095 - Term: Collagen Diseases - ID: D000003240 - Term: Connective Tissue Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC26 - Name: Wounds and Injuries - Abbrev: All - Name: All Conditions - Abbrev: BC05 - Name: Musculoskeletal Diseases - Abbrev: BC16 - Name: Diseases and Abnormalities at or Before Birth - Abbrev: BC17 - Name: Skin and Connective Tissue Diseases - Abbrev: BC18 - Name: Nutritional and Metabolic Diseases - Abbrev: Rare - Name: Rare Diseases ### Condition Browse Module - Browse Leaves - ID: M26370 - Name: Fractures, Bone - Relevance: LOW - As Found: Unknown - ID: M5126 - Name: Bone Diseases - Relevance: LOW - As Found: Unknown - ID: M12936 - Name: Osteogenesis Imperfecta - Relevance: HIGH - As Found: Osteogenesis Imperfecta - ID: M12932 - Name: Osteochondrodysplasias - Relevance: LOW - As Found: Unknown - ID: M12043 - Name: Mucopolysaccharidosis IV - Relevance: LOW - As Found: Unknown - ID: M5127 - Name: Bone Diseases, Developmental - Relevance: LOW - As Found: Unknown - ID: M12097 - Name: Musculoskeletal Diseases - Relevance: LOW - As Found: Unknown - ID: M23686 - Name: Genetic Diseases, Inborn - 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: T4306 - Name: Osteogenesis Imperfecta - Relevance: HIGH - As Found: Osteogenesis Imperfecta - ID: T3909 - Name: Mucopolysaccharidosis Type IV - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000010013 - Term: Osteogenesis Imperfecta ### Intervention Browse Module - Ancestors - ID: D000050071 - Term: Bone Density Conservation Agents - ID: D000045505 - Term: Physiological Effects of Drugs ### Intervention Browse Module - Browse Branches - Abbrev: BDCA - Name: Bone Density Conservation Agents - Abbrev: All - Name: All Drugs and Chemicals ### Intervention Browse Module - Browse Leaves - ID: M1699 - Name: Zoledronic Acid - Relevance: HIGH - As Found: Lymphoblastic - ID: M7346 - Name: Diphosphonates - Relevance: LOW - As Found: Unknown - ID: M1724 - Name: Pamidronate - Relevance: LOW - As Found: Unknown ### Intervention Browse Module - Meshes - ID: D000077211 - Term: Zoledronic Acid ### Misc Info Module #### Removed Countries - Country: Germany - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT04587479 **Brief Title:** A First-in-Human Study of JAB-8263 in Adult Patients With Advanced Solid Tumors **Official Title:** A Phase 1, Multi-Center, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Evidence of Antitumor Activity of JAB-8263 in Adult Subjects With Advanced Solid Tumors #### Organization Study ID Info **ID:** JAB-8263-1001 #### Organization **Class:** INDUSTRY **Full Name:** Jacobio Pharmaceuticals Co., Ltd. ### Status Module #### Completion Date **Date:** 2023-04-30 **Type:** ESTIMATED #### Expanded Access Info **Last Known Status:** RECRUITING #### Last Update Post Date **Date:** 2022-03-14 **Type:** ACTUAL **Last Update Submit Date:** 2022-03-11 **Overall Status:** UNKNOWN #### Primary Completion Date **Date:** 2022-04-30 **Type:** ESTIMATED #### Start Date **Date:** 2020-11-23 **Type:** ACTUAL **Status Verified Date:** 2022-03 #### Study First Post Date **Date:** 2020-10-14 **Type:** ACTUAL **Study First Submit Date:** 2020-10-09 **Study First Submit QC Date:** 2020-10-09 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** INDUSTRY **Name:** Jacobio Pharmaceuticals Co., Ltd. #### Responsible Party **Type:** SPONSOR ### Oversight Module **Is FDA Regulated Device:** False **Is FDA Regulated Drug:** True ### Description Module **Brief Summary:** This is a Phase 1, first-in-human, open-label study of JAB-8263 to determine the maximum tolerated dose (MTD), recommended Phase 2 dose (RP2D) and assess the DLT. 30 subjects with advanced solid tumor will be enrolled. **Detailed Description:** JAB-8263 is a small-molecule inhibitor of the highly conserved bromodomain pockets of the bromodomain and extraterminal (BET) proteins. The objectives of this study are: To determine the maximum-tolerated dose (MTD) and assess the dose-limiting toxicity (DLT) of JAB-8263 as a single agent to adult subjects with advanced solid tumors To assess the safety and tolerability of JAB-8263 To characterize the pharmacokinetic (PK) parameters and pharmacodynamics (PDc) To evaluate preliminary antitumor activity of JAB-8263 ### Conditions Module **Conditions:** - Solid Tumors, Adult ### Design Module #### Design Info **Allocation:** NA **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** NONE **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 30 **Type:** ESTIMATED **Phases:** - PHASE1 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Monotherapy, dose escalation **Intervention Names:** - Drug: JAB-8263 **Label:** JAB-8263 **Type:** EXPERIMENTAL ### Interventions #### Intervention 1 **Arm Group Labels:** - JAB-8263 **Description:** Variable dose, orally Q2D with 28 days each cycle **Name:** JAB-8263 **Type:** DRUG ### Outcomes Module #### Primary Outcomes **Description:** Incidence of dose limiting toxicities (DLTs) in the dose escalation phase. A DLT is defined as an adverse event or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first treatment cycle with JAB-8263 **Measure:** Number of participants with dose limiting toxicities **Time Frame:** Approximately 2.5 years **Description:** Measurements of MTD (i.e. the highest dose of JAB-8263 associated with the occurrence of Dose Limiting Toxicities (DLTs) in \<33% of patients) or the RP2D (i.e. the highest tested dose that is declared safe and tolerable by the Investigators and Sponsor) **Measure:** Find Recommended Phase 2 Dose (RP2D) of JAB-8263 **Time Frame:** Approximately 2.5 years #### Secondary Outcomes **Description:** All patients participating in this study will be assessed for incidence and severity of adverse events (AEs) and serious AEs, including changes in laboratory values, vital signs, electrocardiograms, cardiac imaging and ophthalmological assessments **Measure:** Number of participants with adverse events **Time Frame:** Approximately 2.5 years **Description:** Area under the plasma concentration time curve of JAB-8263 **Measure:** Area under the curve **Time Frame:** Approximately 2.5 years **Description:** Highest observed plasma concentration of JAB-8263 **Measure:** Cmax **Time Frame:** Approximately 2.5 years **Description:** Time of highest observed plasma concentration of JAB-8263 **Measure:** Tmax **Time Frame:** Approximately 2.5 years **Description:** Half life of JAB-8263 **Measure:** T1/2 **Time Frame:** Approximately 2.5 years **Description:** ORR is defined as the proportion of participants with complete response or partial response (CR+PR) **Measure:** Objective response rate ( ORR ) **Time Frame:** Approximately 2.5 years **Description:** DOR is defined as the time from the participant's initial objective response (CR or PR) to study drug therapy, to disease progression or death due to any cause, whichever occurs first. **Measure:** Duration of response ( DOR ) **Time Frame:** Approximately 2.5 years ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: Subjects must meet all the following criteria in order to be included in the research study: 1. Subject must be ≥18 years-of-age at the time of signature of the informed consent form (ICF). 2. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1. 3. Subjects with histologically or cytologically confirmed advanced solid tumors which have progressed despite standard therapy(ies), or are intolerant to standard therapy(ies), or have a tumor for which no standard therapy(ies) exists. 4. Subjects with life expectancy ≥3 months. 5. Patients must have at least one measurable lesion as defined by RECIST v1.1. 6. Patients who have sufficient baseline organ function. Exclusion Criteria: 1. History (≤3 years) of cancer that is histologically distinct from the cancer under study. 2. Known serious allergy to investigational drug or excipients 3. Active brain or spinal metastases 4. History of pericarditis or Grade ≥2 pericardial effusion 5. History of interstitial lung disease. 6. History of Grade ≥2 active infections within 2 weeks 7. Known human immunodeficiency virus (HIV) infection 8. Seropositive for hepatitis B virus (HBV) 9. Seropositive for hepatitis C virus (HCV), or HCV-RNA viral levels are not detectable. 10. Any severe and/or uncontrolled medical conditions 11. History of myocardial infarction, unstable angina pectoris, coronary artery bypass graft, or cerebrovascular accident 12. Impaired cardiac function or clinically significant cardiac diseases 13. QTcF \>470 msec at screening 14. History of medically significant thromboembolic events or bleeding diathesis 15. Unresolved Grade \>1 toxicity 16. History of malignant biliary obstruction 17. Pregnant or breast-feeding **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Central Contacts **Contact 1:** **Email:** [email protected] **Name:** Jacobio Pharmaceuticals **Phone:** 86 10 56315466 **Role:** CONTACT #### Locations **Location 1:** **City:** Denver **Contacts:** ***Contact 1:*** - **Name:** Gerald Falchook, MD - **Role:** CONTACT **Country:** United States **Facility:** SCRI HeatlthONE **State:** Colorado **Status:** RECRUITING **Zip:** 80218 **Location 2:** **City:** Lake City **Contacts:** ***Contact 1:*** - **Name:** Shekeab Jauhari, MD - **Role:** CONTACT **Country:** United States **Facility:** Florida Cancer Center, Lake Mary **State:** Florida **Status:** RECRUITING **Zip:** 32025 **Location 3:** **City:** Nashville **Contacts:** ***Contact 1:*** - **Name:** James M Pauff, MD PhD - **Role:** CONTACT **Country:** United States **Facility:** Tennessee Oncology Nashville **State:** Tennessee **Status:** RECRUITING **Zip:** 37203 #### Overall Officials **Official 1:** **Affiliation:** Jacobio Pharmaceuticals **Name:** Jacobio Pharmaceuticals **Role:** STUDY_DIRECTOR ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Condition Browse Module - Meshes - ID: D000009369 - Term: Neoplasms ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT03940079 **Brief Title:** Efficacy of Computer-Based Cognitive Game Training for Healthy Elderly **Official Title:** Efficacy of Computer-Based Cognitive Game Training on Motor and Cognitive Functions for Healthy Elderly #### Organization Study ID Info **ID:** 201804055RINC #### Organization **Class:** OTHER **Full Name:** National Taiwan University Hospital ### Status Module #### Completion Date **Date:** 2018-06-27 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2020-08-11 **Type:** ACTUAL **Last Update Submit Date:** 2020-08-09 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2018-06-27 **Type:** ACTUAL #### Start Date **Date:** 2018-05-01 **Type:** ACTUAL **Status Verified Date:** 2020-08 #### Study First Post Date **Date:** 2019-05-07 **Type:** ACTUAL **Study First Submit Date:** 2019-05-05 **Study First Submit QC Date:** 2019-05-05 ### 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:** The declination on cognitive and motor functions in older adults increases the difficulty to achieve successful aging. Previous studies had reported that contrast to the traditional cognitive training methods, computer cognitive training (CCT) is comparable or has better effect on the cognitive function improvement with elders.On the other hand, some researchers claimed motor-cognitive dual-task training may possess greater effects than single cognitive training on cognitive functions. However, it is still on debate. Therefore, the research aims to investigate cognitive and motor benefits to healthy older adults over 65s trained by our computer-based cognitive game with high and low level of motor engagements.The research questions include: (1) Is CCT beneficial of cognitive functions? (2) Does CCT with high level of motor engagements (i.e. motor-cognitive dual-task training) have greater effects than single cognitive training on cognitive functions? (3) Can the training effect remain? **Detailed Description:** Quasi-experimental design was adapted in our research.There are four time-series assessments during the experiment: baseline, pretest, posttest, and follow-up. After the baseline assessment, participants were randomized to two groups: gross-motor group (GMG) and fine-motor group (FMG). The intervals between baseline and pretest as well as between pretest and posttest were both 4 weeks, while the interval between posttest and follow-up was 8 weeks. The investigators developed a computer-based cognitive game and compared the efficacy of cognitive and motor functions between computer-based cognitive game combining two different demands on motor control. Investigators hypothesized: All participants who take part in the computer-based cognitive game training don't have learning effects on pretest and are able to improve cognitive functions including short-term memory, divided attention and inhibitory function after intervention; Gross-motor group make more progress than fine-motor group on cognitive and motor functions after intervention. Furthermore, gross-motor group maintained more training effect over cognitive and motor functions at follow-up than fine-motor group. ### Conditions Module **Conditions:** - Aging - Cognitive Function ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL ##### Masking Info **Masking:** NONE **Primary Purpose:** HEALTH_SERVICES_RESEARCH #### Enrollment Info **Count:** 16 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** The participants of GMG received motor-cognitive dual-task training. The sensors used by the participants were four different colored buttons. The participants wear a suit with two buttons on the shoulders and the other two fasten on the knees by velcros. To accomplish the tasks, the participants had to slap the correct colored buttons. The stretching of upper or lower limbs was demanding while slapping, so the participants of GMG received a training which required cognitive and motor functions at the same time. The participants attended 2 sessions per week and lasted for 4 weeks. Each session lasted 75 minutes, mainly including 30 minutes for game introduction and warm-up, 30 minutes for game training, and 15 minutes for rest during the training. Each task lasted 10 minutes, and each session contained 3 tasks. The game difficulty could be adjusted automatically according to the performance of participants. **Intervention Names:** - Device: computer-based cognitive game (including 3 training tasks) **Label:** gross-motor group (GMG) **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** The participants of FMG received cognitive training only. Four colored sensors used by the participants were the keys on the keyboard of the laptop. The participants simply pressed correct colored keys by fingers to complete the tasks. The participants attended 2 sessions per week and lasted for 4 weeks. Each session lasted 75 minutes, mainly including 30 minutes for game introduction and warm-up, 30 minutes for game training, and 15 minutes for rest during the training. Each task lasted 10 minutes, and each session contained 3 tasks. The game difficulty could be adjusted automatically according to the performance of participants. **Intervention Names:** - Device: computer-based cognitive game (including 3 training tasks) **Label:** fine-motor group (FMG) **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - fine-motor group (FMG) - gross-motor group (GMG) **Description:** First task was short-term memory training. Participants were instructed to memorize different colored circles with ordinal numbers which would disappear later. They triggered correct colored sensor in sequence according to their memory. Second task was divided attention training. Different colored circles with ordinal numbers would not disappear this time.The participants should trigger correct colored sensor according to their sequence. Third task was inhibitory function training. There were red and green lights, just like the traffic light, hung up at the upper left of the scene. Red light represented prohibition of triggering the colored sensor, while green light urged to trigger it. Yellow, red, blue and green circles showed up randomly and moved toward the beige region. When the circle came extremely closer to the beige region, the traffic light was randomized to lighten up red or green.The participants should judge and trigger the correct colored sensor. **Name:** computer-based cognitive game (including 3 training tasks) **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Description:** overall cognitive function **Measure:** Change from Baseline Montreal Cognitive Assessment (MoCA) Taiwan Version at the 4th, 8th and 16th weeks **Time Frame:** baseline, 4th weeks pretest, 8th weeks posttest, 16th weeks follow-up **Description:** short-term memory **Measure:** Change from Baseline Digit Span Task-forward (DS-forward) at the 4th, 8th and 16th weeks **Time Frame:** baseline, 4th weeks pretest, 8th weeks posttest, 16th weeks follow-up **Description:** divided attention **Measure:** Change from Baseline Color Trails Test-2 (CTT-2) at the 4th, 8th and 16th weeks **Time Frame:** baseline, 4th weeks pretest, 8th weeks posttest, 16th weeks follow-up **Description:** inhibitory function **Measure:** Change from Baseline Stroop Color Word Test (SCWT) at the 4th, 8th and 16th weeks **Time Frame:** baseline, 4th weeks pretest, 8th weeks posttest, 16th weeks follow-up **Description:** motor function of upper limbs **Measure:** Change from Baseline Nine Hole Peg Test (NHPT) at the 4th, 8th and 16th weeks **Time Frame:** baseline, 4th weeks pretest, 8th weeks posttest, 16th weeks follow-up **Description:** motor function of lower limbs and balance **Measure:** Change from Baseline Get-Up and Go Test (GUG) at the 4th, 8th and 16th weeks **Time Frame:** baseline, 4th weeks pretest, 8th weeks posttest, 16th weeks follow-up **Description:** motor function of lower limbs and balance **Measure:** Change from Baseline Five-Times-Sit-to-Stand Test (FTSST) at the 4th, 8th and 16th weeks **Time Frame:** baseline, 4th weeks pretest, 8th weeks posttest, 16th weeks follow-up #### Secondary Outcomes **Description:** Game assessment was a new way to evaluate cognitive performance of the participant through the score. All participants proceeded all three scenarios but challenged same degree of difficulty. **Measure:** Change from 4th weeks Game1 (first scenario) evaluated the performance of short-term memory at 8th weeks **Time Frame:** 4th weeks pretest, 8th weeks posttest **Description:** Game assessment was a new way to evaluate cognitive performance of the participant through the score. All participants proceeded all three scenarios but challenged same degree of difficulty. **Measure:** Change from 4th weeks Game2 (second scenario) evaluated divided attention at 8th weeks **Time Frame:** 4th weeks pretest, 8th weeks posttest **Description:** Game assessment was a new way to evaluate cognitive performance of the participant through the score. All participants proceeded all three scenarios but challenged same degree of difficulty. **Measure:** Change from 4th weeks Game3 (third scenario) evaluated inhibitory function at 8th weeks **Time Frame:** 4th weeks pretest, 8th weeks posttest ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: 1. ≥ 65 years old 2. Montreal Cognitive Assessment (MoCA) score ≥ 18 3. clear eyesight and hearing 4. both upper and lower limbs are functional 5. normal communication Exclusion Criteria: 1. injury, fracture, and breathing problem 2. surgery during the research 3. severe disease affecting cognitive functions. **Healthy Volunteers:** True **Minimum Age:** 65 Years **Sex:** ALL **Standard Ages:** - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Taipei **Country:** Taiwan **Facility:** National Taiwan University Hospital **Zip:** 100 #### Overall Officials **Official 1:** **Affiliation:** National Taiwan University Hospital **Name:** Central Contact Backup Mao **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:** NCT01763879 **Brief Title:** Pressure-controlled vs Volume Controlled Ventilation on RV Function During OLV **Official Title:** Right Ventricular Function During One-lung Ventilation: The Effects of Pressure Controlled and Volume Controlled Ventilation #### Organization Study ID Info **ID:** 2012081 #### Organization **Class:** OTHER **Full Name:** Imam Abdulrahman Bin Faisal University #### Secondary ID Infos **Domain:** University of Dammam **ID:** 2012081 **Type:** OTHER_GRANT ### Status Module #### Completion Date **Date:** 2013-03 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2013-07-25 **Type:** ESTIMATED **Last Update Submit Date:** 2013-07-24 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2013-01 **Type:** ACTUAL #### Start Date **Date:** 2012-04 **Status Verified Date:** 2013-07 #### Study First Post Date **Date:** 2013-01-09 **Type:** ESTIMATED **Study First Submit Date:** 2012-12-30 **Study First Submit QC Date:** 2013-01-07 ### Sponsor Collaborators Module #### Lead Sponsor **Class:** OTHER **Name:** Imam Abdulrahman Bin Faisal University #### Responsible Party **Type:** SPONSOR ### Oversight Module **Oversight Has DMC:** True ### Description Module **Brief Summary:** The use of pressure controlled ventilation (TV) during one lung ventilation (OLV) for thoracic surgery is associated with comparable oxygenation with volume controlled ventilation (VCV) with added benefits of decreasing airway pressures and shunt fraction. The later may improve the right ventricular (RV) function during OLV. We postulate that the use of PCV during OLV for thoracic surgery would preserve RV function than during VCV. After local ethics committee approval and informed consent, we will randomly allocate 28 patients scheduled for elective thoracic surgery OLV to randomly crossed from PCV to VCV mode (n= 14 for each) during with VT of 6 mL/kg, I: E ratio 1: 2.5, PEEP of 5 cm H2O, recruitment maneuvers and respiratory rate will be adjusted to maintain normocapnia. Intraoperative changes in the right ventricular function (peak systolic and diastolic tricuspid annular velocity (TAV), end-diastolic volume (EDV), end-systolic volume (ESV), and RV fractional area changes (RV-FAC)), hemodynamic and oxygenation parameters, peak and plateau airway pressures, compliance will be recorded. **Detailed Description:** One-lung ventilation (OLV) provides excellent operative field for thoracic procedures, but is opposed by the harmful impairment of cardiac index and right ventricular (RV) function which may influence postoperative morbidity and mortality. In our previous study, we demonstrated significant reductions in RV ejection fraction (REF) and CI values after the initiation of OLV attributable to the increased right ventricular afterload, stroke work and end-diastolic volume augmented by increased airway pressures. This may be harmful with the patients with advanced obstructive lung diseases and those with pulmonary hypertension. Thus there is no doubt that decreases in airway pressures will be associated with better RV function. Volume controlled ventilation (VCV) is the commonly used traditional ventilation mode for OLV during thoracic procedures but its use is associated with deleterious increases in airway pressure which may impede RV function. Pressure controlled ventilation (PCV) is an alternative mode of ventilation which is widely used in the patients with acute respiratory distress syndrome (ARDS) and acute lung injury (ALI), whereby high initial flow rates are delivered to quickly achieve and maintain the set inspiratory pressure followed by rapidly decelerating flow.These high initial flow rates lead to a more rapid alveolar inflation. PCV has been suggested as a useful tool to improve oxygenation as well as decreases in intra-pulmonary shunt (Qs/Qt) and airway pressures compared with VCV during OLV for patients undergoing thoracic surgery. Whereas, others demonstrated comparable arterial oxygenation with the use of PCV and VCV during OLV. However, the use of PCV offers advantages over VCV during OLV in the term of reducing mean and bronchial peak airway pressures and intrapulmonary shunt, hence limiting the risk for barotrauma and impaired RV function. Up to the investigators knowledge, there is no available study of the effects of PCV and VCV on RV function during OLV after thoracic surgery. The investigators hypothesize that the use of PCV during OLV will be associated with preserved RV function than during the use of VCV. They will compare the effects of the use of PCV and VCV with 5 cm H2O level of PEEP and recruitment maneuvers during OLV on the right ventricular function (peak systolic and diastolic tricuspid annular velocity (TAV), end-diastolic volume (EDV), end-systolic volume (ESV), and RV fractional area changes (RV-FAC)), hemodynamic parameters (heart rate (HR), mean arterial blood pressure, (MAP)), oxygenation parameters (arterial oxygen and carbon dioxide tension (PaO2 and PaCO2, respectively), and arterial tension to inspired fraction of oxygen (PaO2/FiO2) ratio), ventilation parameters (peak and plateau airway pressures (Ppk and Ppl, respectively) and compliance) and the ICU and hospital length-of-stays, morbidity and 30-day mortality. Sample size calculation: A priori power analysis of the previous published data11 showed that the investigators will need to study 13 pairs to detect a 20% difference in the mean maximal systolic TAV values (7.0 cm/s) with a SD of 1.4 cm/s, after start of OLV, a type-I error of 0.05 and a power of 90%. We will add 10% more patients for a final sample size of 28 patients to account for patients dropping out during the study. Interventions: In all patients, standard monitors will be applied. A thoracic epidural or paravertebral catheter will be inserted with no more use of local anesthetics during the study to avoid their effects on hypoxic pulmonary vasoconstriction.12 An arterial line (20 G) and a right internal jugular vein catheter will be inserted. Anesthetic technique will be standardized in all studied patients. Anesthesiologists who will give the anaesthetic will be not involved in the patient's assessment. General anesthesia will be induced with propofol (2-3 mg/kg), fentanyl (2-3 µg/kg), and cisatracurium (0.2 mg/kg) will be given to facilitate tracheal intubation with a left-sided double-lumen tube (DLT). The correct position of its tip will be confirmed with a fiberoptic bronchoscope. Anesthesia will be maintained with 1-1.5 minimum alveolar concentration (MAC) of sevoflurane and increments of fentanyl (0.5µg/kg) and cisatracurium (0.04 mg/kg). The patients' lungs will be mechanically ventilated using VCV mode, fraction of inspired oxygen (FiO2) of 0.5 in air, tidal volume (VT) of 8 mL/kg (predicted body weight), inspiratory to expiratory \[I: E\] ratio of 1:2.5, a positive end-expiratory pressure (PEEP) of 5 cm H2O, respiratory rate (R.R) will be adjusted to achieve an PaCO2 of 35-45 mm Hg, peak inspiratory pressures (Ppk) will be limited to 35 cm H2O and a low fresh gas flow (FGF) (\<2 L/min) in a semi closed circuit system. Transesophageal echocardiography (TEE) will be inserted and the right ventricular function will be assessed with the measurements of EDV, ESV, RVEF, both maximal systolic and diastolic TAV at the tricuspid annulus at the RV free wall recorded from the apical 4-chamber views using pulsed wave Doppler tissue imaging. All operations will be performed by the same surgeons. Intraoperative hypoxemia will be defined as decrease in arterial oxygen saturation less than 90% will be treated with increasing of FiO2 to 1.0. Addition of low level of 2 cm H2O of CPAP will be considered if the later fails to correct hypoxemia. 1 Intraoperative fluid therapy will include intravenous infusion of 2 ml/kg/hour of Lactated Ringer's solution and blood losses will be compensated with colloids and with red blood cell concentrates if the hemoglobin levels decreases below 8 to 9 g/dL. Mean arterial blood pressure will be maintained greater than 60 mm Hg using bolus doses of ephedrine 5 mg or phenylephrine 100 ug. Urine output will be maintained to be greater than 0.5 ml/kg/hour. At the end of surgery, the nondependent will be re-expanded and TLV will be resumed as before surgery, sevoflurane will be discontinued, the residual neuromuscular block will be antagonized, and the patient will be extubated. Postoperative analgesia will be accomplished with the use of continuous epidural/paravertebral infusion of bupivacaine 0.125% and fentanyl 2 µg/mL. Statistical Analysis: Data will be tested for normality using the Kolmogorov-Smirnov test. Fisher exact test will be used for categorical data. Repeated two-way ANOVA and paired t-test will be used to study the changes in the primary and secondary endpoints during each intervention. The Wilcoxon 2 rank sum test will be used for the non-parametric values. We will avoid the carryover effect (persistence of the effect of the first intervention on the operative conditions into the second period) through the comparison of the effects of period (time effect) and the order of treatment using independent t-tests. Data will be expressed as mean ± SD, number (%), or median \[range\]. A value of P \< 0.05 will be considered to be statistically significant. ### Conditions Module **Conditions:** - Lung Diseases **Keywords:** - Thoracic surgery - one lung ventilation - pressure-controlled ventilation - volume-controlled ventilation - right ventricular function ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** CROSSOVER ##### Masking Info **Masking:** DOUBLE **Who Masked:** - INVESTIGATOR - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 28 **Type:** ACTUAL **Phases:** - PHASE3 **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** The dependent lung will be ventilated with pressure controlled (PCV) followed by the volume-controlled ventilation (VCV) **Intervention Names:** - Other: The PCV-VCV group **Label:** The PCV-VCV group **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** The dependent lung will be ventilated with volume-controlled ventilation (VCV) followed by the pressure controlled (PCV) **Intervention Names:** - Other: The VCV-PCV group **Label:** The VCV-PCV group **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - The PCV-VCV group **Description:** During the PCV period, the inspiratory pressure will be adjusted to deliver a TV of 6 mL/kg (predicted body weight) to the patient's dependent lung. During the VCV period, the patient's dependent lung will be ventilated with a TV of 6 mL/kg (PBW). Whereas FiO2, I: E ratio, PEEP, frequency, Ppk, and a FGF will be maintained as during two-lung ventilation (TLV) and the lumen of the nondependent lung will be left open to air. Dependent lung recruitment maneuvers will be repeated at 30-minute intervals by raising the inspiratory pressure up to 35 cmH2O for 10 seconds. **Name:** The PCV-VCV group **Type:** OTHER #### Intervention 2 **Arm Group Labels:** - The VCV-PCV group **Description:** During the PCV period, the inspiratory pressure will be adjusted to deliver a TV of 6 mL/kg (predicted body weight) to the patient's dependent lung. During the VCV period, the patient's dependent lung will be ventilated with a TV of 6 mL/kg (PBW). Whereas FiO2, I: E ratio, PEEP, frequency, Ppk, and a FGF will be maintained as during two-lung ventilation (TLV) and the lumen of the nondependent lung will be left open to air. Dependent lung recruitment maneuvers will be repeated at 30-minute intervals by raising the inspiratory pressure up to 35 cmH2O for 10 seconds. **Name:** The VCV-PCV group **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** Peak systolic and diastolic tricuspid annular velocity (TAV) **Measure:** Right ventricular function **Time Frame:** Change from baseline at 30 min after the initiation of the intervention #### Secondary Outcomes **Description:** Blood pressure **Measure:** Blood pressure **Time Frame:** Change from baseline at 30 min after the initiation of the intervention **Description:** the ratio between arterial oxygen tension (PaO2)and inspired fraction of oxygen (FiO2) **Measure:** Pa/FiO2 ratio **Time Frame:** Change from baseline at 30 min after the initiation of the intervention **Description:** Peak and plateau airway pressures **Measure:** Airway pressures **Time Frame:** Change from baseline at 30 min after the initiation of the intervention **Description:** right ventricular end diastolic and systolic volumes **Measure:** Right ventricular volumes **Time Frame:** Change from baseline at 30 min after the initiation of the intervention ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * American Society of Anesthesiologists (ASA) physical class from II to III Exclusion Criteria: * decompensated cardiac (New York Heart Association \>II) * pulmonary (vital capacity or FEV1% \< 50% of the predicted values) * asthma * hepatic diseases. * renal diseases * arrhythmias * pulmonary hypertension (mean pulmonary artery pressure \>30 mm Hg) * body mass index \>35 kg/m2 * previous history of pneumonectomy, bilobectomy, or lobectomy **Maximum Age:** 65 Years **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Al Khubar **Country:** Saudi Arabia **Facility:** Anesthesiology Department **State:** Eastern **Zip:** 31592 #### Overall Officials **Official 1:** **Affiliation:** Assistant Professor **Name:** Mohamed R El Tahan, MD **Role:** STUDY_DIRECTOR **Official 2:** **Affiliation:** Associate Professor **Name:** Roshdi Al Metwally, MD **Role:** PRINCIPAL_INVESTIGATOR **Official 3:** **Affiliation:** Associate Professor **Name:** Hatem Qutub, MD **Role:** STUDY_CHAIR **Official 4:** **Affiliation:** Associate Professor **Name:** Yasser F El Ghoneimy, MD **Role:** STUDY_CHAIR **Official 5:** **Affiliation:** Associate Professor **Name:** Mohamed A Regal, MD **Role:** STUDY_CHAIR **Official 6:** **Affiliation:** Assistant Professor **Name:** Haytham Zien, MD **Role:** STUDY_CHAIR ## Derived Section ### Condition Browse Module - Ancestors - ID: D000012140 - Term: Respiratory Tract Diseases ### Condition Browse Module - Browse Branches - Abbrev: BC08 - Name: Respiratory Tract (Lung and Bronchial) Diseases - Abbrev: All - Name: All Conditions ### Condition Browse Module - Browse Leaves - ID: M11168 - Name: Lung Diseases - Relevance: HIGH - As Found: Lung Disease - ID: M14977 - Name: Respiratory Tract Diseases - Relevance: LOW - As Found: Unknown ### Condition Browse Module - Meshes - ID: D000008171 - Term: Lung Diseases ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT06286579 **Brief Title:** SOI Immediately vs Delayed **Official Title:** The Efficacy of New SOI Implant Surface for Immediately Loaded, Post-extractive Versus Delayed Implants #### Organization Study ID Info **ID:** UNISS_PHD_Osstem_3 #### Organization **Class:** OTHER **Full Name:** Università degli Studi di Sassari ### Status Module #### Completion Date **Date:** 2028-01-31 **Type:** ESTIMATED #### Expanded Access Info #### Last Update Post Date **Date:** 2024-02-29 **Type:** ACTUAL **Last Update Submit Date:** 2024-02-28 **Overall Status:** NOT_YET_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:** 2024-02-29 **Type:** ACTUAL **Study First Submit Date:** 2023-04-24 **Study First Submit QC Date:** 2024-02-28 ### Sponsor Collaborators Module #### Collaborators **Class:** UNKNOWN **Name:** Dr. Dario Melodia **Class:** UNKNOWN **Name:** Dr. Milena Pisano **Class:** UNKNOWN **Name:** Dr. Aurea M. I. Lumbau **Class:** UNKNOWN **Name:** Prof. Silvio Mario Meloni **Class:** UNKNOWN **Name:** Prof. Edoardo Baldoni #### Lead Sponsor **Class:** OTHER **Name:** Università degli Studi di Sassari #### Responsible Party **Investigator Affiliation:** Università degli Studi di Sassari **Investigator Full Name:** Marco Tallarico **Investigator Title:** Assistant 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 aim of this randomized controlled trial is to compare the clinical and radiographic of immediately loaded, immediate (post-extractive, test group) versus delayed (control group) implants with new SOI surface ### Conditions Module **Conditions:** - Dental Implant - Dental Implant-Abutment Design **Keywords:** - Dental Implant - Immediately vs Delayes - Implant-abutment connection ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** PARALLEL **Intervention Model Description:** Randomised controlled trial of parallel group design. ##### Masking Info **Masking:** SINGLE **Masking Description:** One "blinded (when possible)" independent assessor **Who Masked:** - OUTCOMES_ASSESSOR **Primary Purpose:** TREATMENT #### Enrollment Info **Count:** 70 **Type:** ESTIMATED **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Atraumatic tooth extraction and immediately placement of implant with a new surface **Intervention Names:** - Device: Immediately implant placement **Label:** Immediately implant placement **Type:** EXPERIMENTAL #### Arm Group 2 **Description:** Atraumatic tooth extraction, after the site will be left to heal for 4 months, just grafting with A-Oss and suture, according to a socket preservation procedure. Four month later, implant will be place **Intervention Names:** - Device: Delayed **Label:** Delayed implant placement **Type:** ACTIVE_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - Immediately implant placement **Description:** After atraumatic tooth extraction immediate implant placement with SOI surface and loading will be performed with temporary restoration. After osseointegration (8 weeks), the temporary restoration will be modified according to the soft tissue management. After 3 to 4 months, a definitive digital or analog impression will be taken and later definitive restoration will be delivered **Name:** Immediately implant placement **Type:** DEVICE #### Intervention 2 **Arm Group Labels:** - Delayed implant placement **Description:** After atraumatic tooth extraction, the extraction site will be left to heal for 4 months, just grafting with A-Oss and suture, according to a socket preservation procedure. Four month later, implant will be place and immediate loadind with temporary restoration will be performed. After osseointegration (8 weeks), the temporary restoration will be modified according to the soft tissue management. After 3 to 4 months, a definitive digital or analog impression will be taken and later definitive restoration will be delivered **Name:** Delayed **Type:** DEVICE ### Outcomes Module #### Primary Outcomes **Description:** Whether it will not be possible to place the prosthesis because of implant failure or a prosthesis that has to be remade for any reason. **Measure:** Number of prosthesis failure **Time Frame:** Up to 5 years **Description:** defined as implant mobility and/or any infection dictating implant removal, and/or implant fracture and/or any other mechanical complication rendering the implant unusable. The stability of each individual implant will be measured by the local blinded outcome assessors manually tightening the screws with a torque of 30 Ncm at abutment connection, immediately loading, at 1,3 and 5 years after loading for the partial fixed prostheses. Once the single crowns will be cemented, their stability will be assessed by rocking the crown with the handles of two dental instruments. **Measure:** Number of implant failure **Time Frame:** Up to 5 years **Description:** Technical (fracture of the framework and/or the veneering material, screw loosening, etc.) and/or biologic (pain, swelling, suppuration, peri-implantitis, etc.) complication will be considered. **Measure:** Number of complications **Time Frame:** Up to 5 years #### Secondary Outcomes **Description:** Peri-implant marginal bone level changes will be assessed on periapical radiographs took with the paralleling technique at implant placement, at initial loading, 1,3 and 5 years after loading. Ideally digital radiographs should be taken, otherwise radiographs on conventional films will be scanned into TIFF format with a 600 dpi resolution, and stored in a personal computer. Peri-implant marginal bone levels will be measured using the Scion Image (Scion Corporation, Frederick, MD, USA) software. The software will be calibrated for every single image using the known distance of the first two consecutive threads. Measurements of the mesial and distal bone crest level adjacent to each implant will be made to the nearest 0.01 mm. Reference points for the linear measurements will be: the coronal margin of the implant collar and the most coronal point of bone-to-implant contact. Bone levels will be measured. **Measure:** Rate of peri-implant marginal bone level changes **Time Frame:** At 1,3 and 5 years **Description:** Patients will answer the following questions (separately for each implant): 1. Are you satisfied with the function of your implant-supported prostheses? Possible answers: yes absolutely, yes partly, not sure, not really, absolutely not. 2. Are you satisfied with the aesthetic outcome of your implant-supported prostheses? Possible answers: yes absolutely, yes partly, not sure, not really, absolutely not. 3. Would you undergo the same therapy again? Possible answers: "yes" or "no". **Measure:** Valuation of patient satisfaction **Time Frame:** At 1,3 and 5 years **Description:** ISQ was measured and recorded using the IS3 (Osstem), at implant placement, at implants exposure, at the impression time, and prosthetic loading. **Measure:** Rate of implant stability quotient (ISQ) **Time Frame:** Up to 5 years **Description:** The soft tissue biotype will be investigated by the same surgeon at the surgical procedures using a periodontal probe into the sulcus. Greater will be the thickness of the tissue, smaller will be transparency of the periodontal probe. The amount of keratinized tissue will be evaluated 1 year after surgical procedures using a periodontal probe. This outcome will be evaluated according to the distance from the gingival margin to the mucogingival junction **Measure:** Valuation of soft tissue thickness and amount of keratinized tissue **Time Frame:** 1,3 and 5 years **Description:** Esthetic evaluation of occlusal and vestibular pictures will take every years after definite loading was done following the pink esthetic score (PES). In brief, the PES score evaluates seven variables: mesial papilla, distal papilla, soft tissue level, soft tissue contour, alveolar process deficiencies, soft tissue color and texture. A 0-1-2 scoring system was used, 0 being the lowest and 2 being the highest value, with a maximum achievable score of 14 per dental unit. **Measure:** Number of PES score **Time Frame:** 1,3 and 5 years ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Any patient with at least one hopeless tooth in the mandible or maxilla, located between premolars, with intact post extractive alveolus. The implants must to engage at least 3 (mandible) to 5 (maxilla) mm of residual native bone over the socket. * Patients with 18 years or older, and able to sign an informed consent. * Smokers will be included and categorized into: 1) non smokers; 2) moderate smokers (smoking up to 10 cigarettes/day); 3) heavy smokers (smoking more than 11 cigarettes/day). Heavy smokers will be excluded. * Biotype will be categorized in thin (≤1 mm), medium (\>1 - \<2 mm) or thick (≥2 mm). Exclusion Criteria: * General contraindications to implant surgery. * Patients irradiated in the head and neck area. * Immunosuppressed or immunocompromised patients. * Patients treated or under treatment with intravenous amino-bisphosphonates. * Patients with untreated periodontitis. * Patients with poor oral hygiene and motivation. * Uncontrolled diabetes. * Heavy smokers. * Pregnancy or nursing. * Substance abuser. * Psychiatric problems or unrealistic expectations. * Lack of opposite occluding dentition in the area intended for implant placement. * Patients with infection and or inflammation in the area intended for implant placement. * Patients participating in other studies, if the present protocol cannot be properly adhered to. * Patients referred only for implant placement and cannot be followed ant the treating centre. * Patients unable to be followed for 5 years **Healthy Volunteers:** True **Minimum Age:** 18 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Sassari **Country:** Italy **Facility:** Marco Tallarico **Zip:** 07100 ### IPD Sharing Statement Module **IPD Sharing:** NO ## Derived Section ### Misc Info Module - Version Holder: 2024-05-24

## Protocol Section ### Identification Module **NCT ID:** NCT01654679 **Acronym:** Hydrosun **Brief Title:** Impact of Preoperative Local Water-Filtered Infrared-A (wIRA) Irradiation on Postoperative Wound Healing **Official Title:** Impact of Preoperative Local Water-Filtered Infrared-A (wIRA) Irradiation on Postoperative Wound Healing - A Randomized Patient- and Observer Blinded Controlled Clinical Trial #### Organization Study ID Info **ID:** HydrosunWoundHealing #### Organization **Class:** OTHER **Full Name:** German Research Foundation ### Status Module #### Completion Date **Date:** 2012-07 **Type:** ACTUAL #### Expanded Access Info #### Last Update Post Date **Date:** 2012-09-06 **Type:** ESTIMATED **Last Update Submit Date:** 2012-09-05 **Overall Status:** COMPLETED #### Primary Completion Date **Date:** 2010-06 **Type:** ACTUAL #### Start Date **Date:** 2008-08 **Status Verified Date:** 2012-09 #### Study First Post Date **Date:** 2012-08-01 **Type:** ESTIMATED **Study First Submit Date:** 2012-07-22 **Study First Submit QC Date:** 2012-07-28 ### Sponsor Collaborators Module #### Collaborators **Class:** OTHER **Name:** Technical University of Munich #### Lead Sponsor **Class:** OTHER **Name:** German Research Foundation #### Responsible Party **Investigator Affiliation:** German Research Foundation **Investigator Full Name:** Mark Hartel **Investigator Title:** Priv.-Doz. Dr. med. **Type:** PRINCIPAL_INVESTIGATOR ### Oversight Module **Oversight Has DMC:** False ### Description Module **Brief Summary:** The purpose of this study is to dermine whether local-water filtered infrared-A (wIRA) irradiation can reduce postoperative wound infection. wIRA irradiation is applied 20min directly preoperatively, before patients underwent abdominal surgery. The wIRA is a harmless light source, that has been described before. We test the impact and clinical outcome of patients undergoing a one-time preoperative wIRA irradiation on postoperative wound healing. **Detailed Description:** Wound healing is a complex pathophysiological process that is related to pain, discomfort and immobility of patients and when not well controlled may lead to devastating and morbidity related wound infections. Furthermore, prolonged hospital stay, increased pain and consecutive increased drug consumption is often associated with postoperative wound infections. Although the average costs of wound infections are difficult to assess, there is no doubt that a prophylactic tool in controlling postoperative wound healing would have tremendous potential. Recent studies indicate that the application of different forms of thermal energy to the skin surface decreases postoperative wound infections significantly. It is known that high-normal arterial oxygen tension levels have decreased surgical wound infection from 11% to 5%. The application of water-filtered infrared A (wIRA) irradiation has been successfully applied in patients with ulcus cruris and superficial skin-tumors to alleviate pain and regulation of the body temperature in neonatology. The simple preoperative whole body warming for 30 min before surgery resulted in a statistically reduced occurrence of postoperative wound infections. A more recent study showed the beneficial effects of postoperative wIRA application on wound healing. The effects of wIRA leading to this success in therapy can be explained by thermal and non-thermal effects. A major advantage of the wIRA vs. the application of simple warming blankets lies upon the effective penetration of the wIRA applied energy within the deep subcutaneous tissue at depths of 2-3 cm. Further effects of the applied energy lead to vasodilation of capillaries with consecutive effective conduction of energetic blood flow into deeper tissue layers. Non-thermal effects of the wIRA application consist of direct stimulation and active immunomodulation by specialized immune cells. Furthermore, wIRA can induce protective proteins, e.g. ferritin in the skin and potentially influences common cross-talks within cells and extracellular matrices. These effects display regulatory roles in wound repair processes that may also be responsible for positive cosmetic results. More important for the clinical assessment of wound healing in the early phase of hospitalization is the effect of wIRA to significantly reduce postoperative pain. Surgery and postoperative pain evoke stress related effects that are induced by profound neuroendocrine changes in cytokine activity and related processes. Increased blood flow, due to vasodilation, helps to strongly eliminate accumulated pain mediators, lactic acid and potential bacterial toxins. The metabolism is induced and mediates also non-thermal effects such as attraction of immune cells and potential effects on nociceptors. These direct effects of wIRA can be easily followed when postoperative irradiation is performed. The problem of developing wound infections may rely within the first hours after and already during the operation, when the wound gets "preconditioned" with potential mediators or bacteria that may lead to postoperative encountered wound infections. A recent study indicated that immediate postoperative warming for 2 hours after hernia surgery may provide comparable benefits to seven days of warming. According to the idea of preventing deleterious preconditions in the process of wound healing, we tested here, the one time preoperative application of wIRA and its impact on postoperative wound healing and related clinical questions. Comparable to preoperative antibiotic single shot treatment we relied on the expansive impact of preoperative wIRA application. The prospective randomized controlled clinical trial is designed to study the effects of single time preoperative wIRA irradiation on the postoperative outcome of wound infections after visceral surgery. ### Conditions Module **Conditions:** - Wound Infection Rate After Surgery - Impact of Wound Infection on Pain and Wound Healing **Keywords:** - wound infection - surgery - surgical wound infection rate - wound healing ### Design Module #### Design Info **Allocation:** RANDOMIZED **Intervention Model:** SINGLE_GROUP ##### Masking Info **Masking:** DOUBLE **Who Masked:** - PARTICIPANT - INVESTIGATOR **Primary Purpose:** SUPPORTIVE_CARE #### Enrollment Info **Count:** 400 **Type:** ACTUAL **Phases:** - NA **Study Type:** INTERVENTIONAL ### Arms Interventions Module #### Arm Group 1 **Description:** Patients in Group A received local water-filtered infrared A (wIRA) irradiation once for 20 min preoperatively. **Intervention Names:** - Device: wIRA irradiation **Label:** wIRA irradiation **Type:** ACTIVE_COMPARATOR #### Arm Group 2 **Description:** Patients assigned to Group B only received normal visible light application for 20 min prior to surgery. **Intervention Names:** - Other: visible light only **Label:** visible light only **Type:** SHAM_COMPARATOR ### Interventions #### Intervention 1 **Arm Group Labels:** - wIRA irradiation **Description:** wIRA irradiation for 20min prior to surgery. The distance between the light bulb and the skin surface was 27cm. **Name:** wIRA irradiation **Other Names:** - wIRA (Hydrosun® radiator; Hydrosun Medizinaltechnik, Müllheim, Germany) **Type:** DEVICE #### Intervention 2 **Arm Group Labels:** - visible light only **Description:** visible light application at a distance of 27cm from the skin surface with for 20 min. **Name:** visible light only **Other Names:** - Standard light bulb with visible normal conventional light. **Type:** OTHER ### Outcomes Module #### Primary Outcomes **Description:** The rate of wound infection was assessed from day 2 to 8 and day 30 post surgery. The wound infection rate was assessed by a visual analogue scale (VAS) Group A: irradiated with local water-filtered infrared A (wIRA) irradiation Group B: irriadiate with conventional visible light **Measure:** Postoperative wound infection rate **Time Frame:** day 2 to 8 and day 30 #### Secondary Outcomes **Description:** Wound pain was assessed at day 2 to 8 (on a daily basis) and after day 30 post surgery, comparing patients from Group A (wIRA) and group B (only conventional light) application. **Measure:** Wound pain postoperative **Time Frame:** day 2 to 8 and after 30 days **Description:** Wound healing was assessed at day 2 - 8 (daily) and after 30 days with a visual analogue scale (VAS). The wound healing was assessed while comparing the results from group A (wIRA) and group B (conventional light). **Measure:** Wound healing postoperative **Time Frame:** day 2 to 8 and after 30 days ### Eligibility Module **Eligibility Criteria:** Inclusion Criteria: * Patients undergoing aseptic surgery with a median or transverse laparotomy * informed consent * Patients age between 30 and 80 years Exclusion Criteria: * pregnancy * laparoscopic surgery * operation time more than 6 hours * signs of infection (local or systemic) * MRSA positive patients * myocardial infarction within 6 wks prior to surgery * radio- or chemotherapy within 4 wks prior to surgery * body temperature above 38°C for the last 5 days prior to surgery * cachexia * leucocytopenia * liver cirrhosis Child B or C **Maximum Age:** 80 Years **Minimum Age:** 30 Years **Sex:** ALL **Standard Ages:** - ADULT - OLDER_ADULT ### Contacts Locations Module #### Locations **Location 1:** **City:** Munich **Country:** Germany **Facility:** Klinikum rechts der Isar der Technischen Universität **State:** Bavaria **Zip:** 81675 #### Overall Officials **Official 1:** **Affiliation:** Klinikum rechts der Isar, Technische Universität München, Munich, Germany **Name:** Beat M Künzli, MD **Role:** STUDY_DIRECTOR ### References Module #### References **Citation:** Hartel M, Hoffmann G, Wente MN, Martignoni ME, Buchler MW, Friess H. Randomized clinical trial of the influence of local water-filtered infrared A irradiation on wound healing after abdominal surgery. Br J Surg. 2006 Aug;93(8):952-60. doi: 10.1002/bjs.5429. **PMID:** 16845694 **Citation:** Kunzli BM, Liebl F, Nuhn P, Schuster T, Friess H, Hartel M. Impact of preoperative local water-filtered infrared A irradiation on postoperative wound healing: a randomized patient- and observer-blinded controlled clinical trial. Ann Surg. 2013 Dec;258(6):887-94. doi: 10.1097/SLA.0000000000000235. **PMID:** 24169161 ## 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: BC26 - Name: Wounds and Injuries ### Condition Browse Module - Browse Leaves - ID: M10283 - Name: Infections - Relevance: HIGH - As Found: Infection - ID: M6368 - Name: Communicable Diseases - Relevance: HIGH - As Found: Infection - ID: M1112 - Name: Surgical Wound - Relevance: LOW - As Found: Unknown - ID: M17685 - Name: Wounds and Injuries - Relevance: HIGH - As Found: Wound - ID: M13066 - Name: Pain - Relevance: LOW - As Found: Unknown - ID: M17684 - Name: Wound Infection - Relevance: HIGH - As Found: Wound Infection - ID: M16310 - Name: Surgical Wound Infection - 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 - ID: D000014946 - Term: Wound Infection - ID: D000014947 - Term: Wounds and Injuries ### Misc Info Module - Version Holder: 2024-05-24