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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02657356




Registration number
NCT02657356
Ethics application status
Date submitted
13/01/2016
Date registered
15/01/2016

Titles & IDs
Public title
Bardoxolone Methyl in Patients With Connective Tissue Disease-associated Pulmonary Arterial Hypertension - CATALYST
Scientific title
A Study of the Efficacy and Safety of Bardoxolone Methyl in Patients With Connective Tissue Disease-associated Pulmonary Arterial Hypertension
Secondary ID [1] 0 0
RTA 402-C-1504
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Connective Tissue Disease-Associated Pulmonary Arterial Hypertension 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Cardiovascular 0 0 0 0
Hypertension
Skin 0 0 0 0
Other skin conditions

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Placebo comparator: Placebo capsules - Placebo capsules will be administered orally once a day for 24 weeks.

Experimental: Bardoxolone methyl capsules - Each patient will receive bardoxolone methyl capsules administered orally once a day for 24 weeks. Starting dosage for each patient is 5 mg and will dose-escalate to 10 mg at Week 4, unless contraindicated clinically.
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Baseline in Six-minute-walk Distance (6MWD) Relative to Placebo at Week 24
Timepoint [1] 0 0
Baseline through 24 weeks after participant receives the first dose
Secondary outcome [1] 0 0
Time to First Persistent Clinical Improvement Event
Timepoint [1] 0 0
Baseline through the end of the study

Eligibility
Key inclusion criteria
* BMI > 18.5 kg/m2;
* Symptomatic pulmonary hypertension WHO/NYHA FC class II and III;
* WHO Group I PAH associated with connective tissue disease;
* Had a diagnostic right heart catheterization performed and documented within 36 months prior to Day 1 that confirmed a diagnosis of PAH according to all the following criteria:

* Mean pulmonary artery pressure = 25 mm Hg (at rest);
* Pulmonary capillary wedge pressure (PCWP) = 15 mm Hg;
* Pulmonary vascular resistance > 240 dyn.sec/cm5 or > 3 mm Hg/liter (L)/minute;
* Has BNP level = 400 pg/mL;
* Had an average 6MWD = 150 meters on two consecutive tests performed on different days prior to randomization, with both tests measuring within 15% of one another;
* Has been receiving no more than two (2) approved disease-specific PAH therapies. PAH therapy must have been at a stable dose for at least 90 days prior to Day 1. No additions or changes should be made to PAH therapies and doses should remain stable for the duration of the study;
* Has maintained a stable dose for 30 days prior to Day 1 if receiving any of the following therapies that may affect PAH: vasodilators (including calcium channel blockers), digoxin, L-arginine supplementation, or oxygen supplementation. No additions or changes should be made to therapies and doses should remain stable for the duration of the study;
* If receiving treatment for CTD with prednisone or any other drugs, doses must remain stable for at least 30 days prior to Day 1 and for the duration of the study Had pulmonary function tests (PFTs) within 90 days prior to Day 1 with total lung capacity = 65% (predicted);
* Had a ventilation-perfusion (V/Q) lung scan, spiral/helical/electron beam computed tomography (CT), or pulmonary angiogram prior to Day 1 that shows no evidence of thromboembolic disease (i.e., should note normal or low probability for pulmonary embolism). If V/Q scan was abnormal (i.e., results other than normal or low probability), then a confirmatory CT or selective pulmonary angiography must exclude chronic thromboembolic pulmonary hypertension;
* Has adequate kidney function defined as an estimated glomerular filtration rate (eGFR) = 45 mL/min/1.73 m2 as measured by the central lab;
* Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures;
* Evidence of a personally signed and dated informed consent document indicating that the patient (or a legally acceptable representative) has been informed of all pertinent aspects of the study prior to initiation of any patient-mandated procedures
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Participation in other investigational clinical studies involving interventional products being tested or used in a way different from the approved form or when used for an unapproved indication within 30 days prior to Day 1;
* Initiation of an exercise program for cardio-pulmonary rehabilitation within 90 days prior to Day 1 or planned initiation during the study;
* Stopped receiving any PAH chronic therapy within 60 days prior to Day 1;
* Received a dose of prednisone > 20 mg/day (or equivalent dose if other corticosteroid) within 30 days prior to Day 1;
* Received intravenous (iv) or subcutaneous (sc) prostacyclin/prostacyclin analogues within 90 days prior to Day 1;
* Received intravenous inotropes within 30 days prior to Day 1;
* Has uncontrolled systemic hypertension as evidenced by sitting systolic blood pressure (BP) > 160 mm Hg or sitting diastolic BP > 100 mm Hg during Screening after a period of rest;
* Has systolic BP < 90 mm Hg during Screening after a period of rest;
* Has a history of clinically significant left-sided heart disease and/or clinically significant cardiac disease, including but not limited to any of the following:

* Congenital or acquired valvular disease if clinically significant apart from tricuspid valvular insufficiency due to pulmonary hypertension;
* Pericardial constriction;
* Restrictive or congestive cardiomyopathy;
* Left ventricular ejection fraction < 40% per echocardiogram (ECHO) within 90 days of Day 1;
* Symptomatic coronary artery disease within the last 3 years;
* Acutely decompensated heart failure within 30 days prior to Day 1, per investigator assessment;
* Has more than two of the following clinical risk factors for left ventricular diastolic dysfunction:

* Age > 65 years;
* BMI = 30 kg/m2;
* History of systemic hypertension;
* History of type 2 diabetes;
* History of atrial fibrillation;
* History of atrial septostomy within 180 days prior to Day 1;
* History of uncontrolled obstructive sleep apnea;
* Has a history of portal hypertension or chronic liver disease, including hepatitis B and/or hepatitis C (with evidence of recent infection and/or active virus replication) defined as mild to severe hepatic impairment (Child-Pugh Class A-C);
* Serum aminotransferase (ALT or AST) levels > 1.5X the upper limit of normal (ULN) at Screening;
* Hemoglobin (Hgb) concentration < 8.5 g/dL at Screening;
* Diagnosis of Down syndrome;
* History of malignancy within 5 years prior to screening, with the exception of localized skin or cervical carcinomas;
* Untreated or uncontrolled active bacterial, fungal, or viral infection;
* Known or suspected active drug or alcohol abuse, per investigator judgment;
* Use of Herbalife supplements within 14 days prior to Day 1;
* Major surgery within 30 days prior to Day 1 or planned to occur during the course of the study;
* Unwilling to practice acceptable methods of birth control (both males who have partners of childbearing potential and females of childbearing potential) during screening, while taking study drug, and for at least 30 days after the last dose of study drug is ingested;
* Use of inhaled nitric oxide within 7 days prior to Screening and Day 1 visits, excluding acute vasodilator testing during diagnostic cardiac catheterization;
* Women who are pregnant or breastfeeding;
* Any disability or impairment that would prohibit performance of the 6MWT;
* Any abnormal laboratory level that, in the opinion of the investigator, would put the patient at risk by trial enrollment;
* Patient is, in the opinion of the investigator, unable to comply with the requirements of the study protocol or is unsuitable for the study for any reason;
* Known hypersensitivity to any component of the study drug;
* Unable to communicate or cooperate with the investigator because of language problems, poor mental development, or impaired cerebral function.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
4/10/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
7/05/2020
Sample size
Target
Accrual to date
Final
202
Recruitment in Australia
Recruitment state(s)
NSW,QLD,TAS
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 0 0
St Vincent's Hospital Sydney - Darlinghurst
Recruitment hospital [3] 0 0
John Hunter Hospital - New Lambton
Recruitment hospital [4] 0 0
Princess Alexandra Hospital - Brisbane
Recruitment hospital [5] 0 0
Royal Hobart Hospital - Hobart
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [3] 0 0
2305 - New Lambton
Recruitment postcode(s) [4] 0 0
4102 - Brisbane
Recruitment postcode(s) [5] 0 0
7000 - Hobart
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
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United States of America
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District of Columbia
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United States of America
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Florida
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United States of America
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Georgia
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United States of America
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Illinois
Country [7] 0 0
United States of America
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Kentucky
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United States of America
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Massachusetts
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United States of America
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Michigan
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Missouri
Country [11] 0 0
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Nebraska
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New Mexico
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New York
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North Carolina
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Ohio
Country [16] 0 0
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Oklahoma
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Oregon
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Pennsylvania
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South Carolina
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Texas
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Utah
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Argentina
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Ciudad Autónoma De BuenosAires
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Argentina
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Mar Del Plata
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Argentina
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Villa Vatteone
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Argentina
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Cordoba
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Argentina
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Corrientes
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Argentina
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Formosa
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Belgium
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Vlaams Brabant
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Belgium
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Brussels
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Brazil
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Ceara
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Brazil
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Rio Grande Do Sul
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Brazil
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Santa Catarina
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Brazil
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Sao Paulo
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Brazil
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São Paulo
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Canada
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Alberta
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Canada
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British Columbia
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Canada
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Ontario
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Canada
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Quebec
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Czechia
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Prague
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Germany
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Baden-Württemberg
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Germany
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Bayern
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Germany
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Mecklenburg-Vorpommern
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Germany
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Berlin
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Germany
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Dresden
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Germany
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Hamburg
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Germany
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Heidelberg
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Germany
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Köln
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Israel
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Jerusalem
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Israel
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Petah Tikva
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Japan
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Bunkyo-ku
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Kanagawa
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Miyagi
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Okayama
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Chiba
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Gunma
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Kobe
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Japan
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Nagoya
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Sapporo
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Japan
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Sendai-shi
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Japan
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Suita
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Japan
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Toyoake
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Mexico
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Distrito Federal
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Mexico
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Jalisco
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Mexico
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Nuevo Leon
Country [65] 0 0
Netherlands
State/province [65] 0 0
Noord-Holland
Country [66] 0 0
Philippines
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Angeles City
Country [67] 0 0
Philippines
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Lipa
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Philippines
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Makati
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Philippines
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Manila
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Philippines
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Quezon City
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Spain
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Cantabria
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Spain
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Barcelona
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Spain
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Las Palmas de Gran Canaria
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Spain
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Madrid
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Spain
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Majadahonda
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Spain
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Toledo
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United Kingdom
State/province [77] 0 0
Glasgow
Country [78] 0 0
United Kingdom
State/province [78] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Reata, a wholly owned subsidiary of Biogen
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://vivli.org/


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT02657356