Effect of Naltrexone Hydrochloride ER and Bupropion Hydrochloride ER Combination (Contrave®/Mysimba®) on Major Adverse Cardiovascular Events (MACE)

NCT ID: NCT06098079

Last Updated: 2025-11-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE4

Total Enrollment

8600 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-01-03

Study Completion Date

2029-07-31

Brief Summary

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A randomized, double-blinded, placebo controlled study intended to capture cardiovascular outcomes during real-world use of naltrexone/bupropion (NB).

Detailed Description

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This multi-center, prospective, randomized, pragmatic, double-blinded study has been designed to capture cardiovascular (CV) outcomes during the real-world use of NB after initial randomization. The aim of the study is to assess whether patients receiving treatment with NB are at an elevated risk of experiencing MACE compared with patients receiving placebo. Both patient groups will also be counselled to lose weight via a reduced-calorie diet and increased physical activity.

Conditions

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Obesity

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

SUPPORTIVE_CARE

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
Sponsor will be blinded

Study Groups

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Naltrexone/Bupropion (NB)

Patients will be randomly assigned to NB (naltrexone 8 mg and bupropion 90 mg) extended-release oral tablet.

Group Type ACTIVE_COMPARATOR

Naltrexone-Bupropion (NB) Combination

Intervention Type DRUG

A total daily dosage of two NB 8 mg/90 mg tablets twice daily (32 mg/360 mg) is reached at the start of Week 4.

Placebo

Patients will be randomly assigned to placebo.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

A total daily dosage of two placebo tablets twice daily (in an identical, non-medicine containing tablet) is reached at the start of Week 4.

Interventions

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Naltrexone-Bupropion (NB) Combination

A total daily dosage of two NB 8 mg/90 mg tablets twice daily (32 mg/360 mg) is reached at the start of Week 4.

Intervention Type DRUG

Placebo

A total daily dosage of two placebo tablets twice daily (in an identical, non-medicine containing tablet) is reached at the start of Week 4.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Patient age ≥18 years at screening
2. Able to understand the key components of the study, as described in the written informed consent document, and willing and able to provide written informed consent
3. BMI ≥30 kg/m2 (obese) or ≥27 kg/m2 (overweight) in the presence of at least 1 weight-related comorbidity (eg, hypertension, type 2 diabetes mellitus, or dyslipidemia)
4. At increased risk of adverse cardiovascular outcomes:

In the opinion of the investigator, has a high likelihood of cardiovascular disease with at least 1 of the following:
* History of documented MI \>90 days prior to screening
* History of coronary revascularization (ie, coronary artery bypass graft surgery, stent placement, percutaneous transluminal coronary angioplasty, or laser atherectomy) \>90 days prior to screening
* History of carotid or peripheral revascularization (ie, carotid endarterectomy, lower extremity atherosclerotic disease atherectomy, repair of abdominal aorta aneurysm, femoral or popliteal bypass) \>90 days prior to screening
* Angina with ischemic changes (resting echocardiogram (ECHO), ECG changes on a graded exercise test (GXT), or positive cardiac imaging study)
* Ankle brachial index \<0.9 (by simple palpation) within prior 2 years or

Type 2 diabetes mellitus with at least 2 of the following:
* Hypertension (controlled with or without pharmacotherapy at \<145/95 mmHg)
* Dyslipidemia requiring pharmacotherapy
* Documented low HDL cholesterol (\<50 mg/dL in women or \<40 mg/dL in men) within the prior 12 months
* Current tobacco smoker
5. Patients who have completed a washout (2-weeks or 5 half-lives, whichever is longer) of the prohibited concomitant medication(s) at screening
6. Subject willing to comply with daily completion of an eDiary using a mobile smartphone application

Exclusion Criteria

1. Using prescription medications, other than Contrave/Mysimba, or surgical or medical device interventions for weight loss
2. History of MI or stroke within 90 days prior to screening
3. Uncontrolled hypertension, defined as systolic BP ≥160 mmHg and/or \>100 mmHg diastolic BP on the average of 3 seated BP measurements after the patient has been at rest for at least 5 minutes
4. Meets any of the following criteria:

* Confirmed end-stage renal disease (ie, a degree of kidney failure severe enough to require dialysis or kidney transplantation for survival characterized by a severe reduction in glomerular filtration rate \[\<15 mL/minute/1.73 m2\] and other manifestations including increased serum creatinine),
* Severe hepatic impairment (Child-Pugh score 10 to 15 \[Class C\]),
* Hemodynamic instability, including patients with severe heart failure (New York Heart Association Class IV)
5. Seizure disorders or history of seizures, not including subjects with a history of pediatric febrile seizures
6. Use of other bupropion-containing products (including but not limited to Wellbutrin, Wellbutrin SR, Wellbutrin XL, and Aplenzin)
7. Active anorexia nervosa or bulimia
8. Chronic opioid or opiate agonist (eg, methadone) or partial agonists (eg, buprenorphine) use, or acute opioid withdrawal or has a positive urine drug result for opioids at screening
9. Undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs
10. Concomitant administration of MAOIs. This also includes use of reversible MAOIs, such as linezolid or intravenous methylene blue. At least 14 days should elapse between discontinuation of MAOIs and initiation of treatment with Contrave/Mysimba.
11. Subject has any disease or condition, or use of any pharmacological agent to treat the disease/condition, that, in the opinion of the investigator, would contraindicate study participation
12. Known allergy to bupropion, naltrexone, or any other component of Contrave/Mysimba
13. Pregnant or nursing
14. Known life-threatening arrythmias, including Brugada syndrome
15. Participation in any other concurrent investigational trial
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Currax Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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TrialMed Birmingham (DRS)

Birmingham, Alabama, United States

Site Status NOT_YET_RECRUITING

Accel Research Sites Network

Birmingham, Alabama, United States

Site Status RECRUITING

Cullman Clinical Trials

Cullman, Alabama, United States

Site Status TERMINATED

AMR Mobile

Mobile, Alabama, United States

Site Status RECRUITING

Velocity Clinical Research, Mobile

Mobile, Alabama, United States

Site Status RECRUITING

Sun City Research

Glendale, Arizona, United States

Site Status RECRUITING

Cardiovascular Consultants/NextStage Clinical Research

Glendale, Arizona, United States

Site Status TERMINATED

Desert Clinical Research

Mesa, Arizona, United States

Site Status RECRUITING

Velocity Clinical Research, Phoenix

Phoenix, Arizona, United States

Site Status RECRUITING

Fiel Family & Sports Medicine CCT Research

Tempe, Arizona, United States

Site Status RECRUITING

Synexus Clinical Research US; Inc.

Tucson, Arizona, United States

Site Status RECRUITING

Velocity Clinical Research, Gardena

Anderson, California, United States

Site Status RECRUITING

Velocity Clinical Research

Chula Vista, California, United States

Site Status RECRUITING

Velocity Clinical Research, Huntington Park

Huntington Park, California, United States

Site Status RECRUITING

Velocity Clinical Research, San Diego

La Mesa, California, United States

Site Status RECRUITING

Chemidox Clinical Trials Inc.

Lancaster, California, United States

Site Status RECRUITING

Long Beach Clinical Trials

Long Beach, California, United States

Site Status RECRUITING

Velocity Clinical Research

Los Angeles, California, United States

Site Status TERMINATED

Valley Vitality Ventures

Manteca, California, United States

Site Status RECRUITING

National Institute of Clinical Research, Inc.

Pomona, California, United States

Site Status RECRUITING

Velocity Clinical Research, San Bernardino

San Bernardino, California, United States

Site Status RECRUITING

Velocity Clinical Research at Coastal Heart Medical Group

Santa Ana, California, United States

Site Status TERMINATED

Velocity Clinical Research of Santa Ana

Santa Ana, California, United States

Site Status TERMINATED

Velocity Clinical Research, Van Nuys

Van Nuys, California, United States

Site Status ACTIVE_NOT_RECRUITING

Providere Research

West Covina, California, United States

Site Status RECRUITING

Velocity Clinical Research, Denver

Englewood, Colorado, United States

Site Status RECRUITING

ABMED Clinical Research

Cape Coral, Florida, United States

Site Status ACTIVE_NOT_RECRUITING

LMG Research

Coral Gables, Florida, United States

Site Status RECRUITING

JY Research Institute

Cutler Bay, Florida, United States

Site Status RECRUITING

Delray Physician Center

Delray Beach, Florida, United States

Site Status RECRUITING

D&H Doral Research Center

Doral, Florida, United States

Site Status RECRUITING

Accel Research Sites Network - Edgewater

Edgewater, Florida, United States

Site Status TERMINATED

Velocity Clinical Research (New Smyrna Beach)

Edgewater, Florida, United States

Site Status RECRUITING

IMRC Fort Lauderdale

Fort Lauderdale, Florida, United States

Site Status RECRUITING

Southwest General Healthcare Center

Fort Myers, Florida, United States

Site Status RECRUITING

G+C Research Group

Hialeah, Florida, United States

Site Status TERMINATED

Qway Research

Hialeah, Florida, United States

Site Status RECRUITING

Conveinent Medical Research

Hialeah, Florida, United States

Site Status RECRUITING

Ilumina Medical Research

Kissimmee, Florida, United States

Site Status RECRUITING

Altus Research

Lake Worth, Florida, United States

Site Status RECRUITING

D&H Pompano Research Center, LLC

Margate, Florida, United States

Site Status RECRUITING

Optimal Research, LLC. - Melbourne

Melbourne, Florida, United States

Site Status RECRUITING

Advanced Clinical Research

Miami, Florida, United States

Site Status RECRUITING

Medical Research Center Westchester

Miami, Florida, United States

Site Status RECRUITING

Century Research

Miami, Florida, United States

Site Status TERMINATED

ITB Research

Miami, Florida, United States

Site Status RECRUITING

Entrust Clinical Research

Miami, Florida, United States

Site Status RECRUITING

Janus Clinical Research

Miami, Florida, United States

Site Status RECRUITING

Miami Beach Clinical Research

Miami Beach, Florida, United States

Site Status RECRUITING

Innovia Research Center

Miramar, Florida, United States

Site Status RECRUITING

Healix Clinical Research

New Smyrna Beach, Florida, United States

Site Status RECRUITING

Biscayne Clinical Research Inc

North Miami, Florida, United States

Site Status RECRUITING

IMRC At Palmetto Bay

Palmetto Bay, Florida, United States

Site Status RECRUITING

New Horizons Research

Palmetto Bay, Florida, United States

Site Status RECRUITING

Best Choice Medical and Research Services

Pembroke Pines, Florida, United States

Site Status RECRUITING

Bolanos Clnical Research

Pembroke Pines, Florida, United States

Site Status RECRUITING

Cordova Research Institute

Sweetwater, Florida, United States

Site Status RECRUITING

D&H Tamarac Research Center, LLC

Tamarac, Florida, United States

Site Status RECRUITING

Synexus Clinical Research US, Inc. - The Villages

The Villages, Florida, United States

Site Status RECRUITING

Advanced Clinical Research Atlanta

Atlanta, Georgia, United States

Site Status RECRUITING

Clincept Clinical Research

Columbus, Georgia, United States

Site Status RECRUITING

Accel Research Sites (ARSN) - Neurostudies

Decatur, Georgia, United States

Site Status RECRUITING

Velocity Clinical Research, Savannah

Savannah, Georgia, United States

Site Status RECRUITING

NextStage Clinical Research-Chicago

Glen Ellyn, Illinois, United States

Site Status TERMINATED

JAELEX Research

Round Lake Beach, Illinois, United States

Site Status TERMINATED

Indiana Medical Research Institute

Merriville, Indiana, United States

Site Status RECRUITING

Velocity Clinical Research

Valparaiso, Indiana, United States

Site Status RECRUITING

Velocity Clinical Research

Sioux City, Iowa, United States

Site Status RECRUITING

AMR - El Dorado

El Dorado, Kansas, United States

Site Status RECRUITING

Velocity Clinical Research, Kansas City

Kansas City, Kansas, United States

Site Status TERMINATED

AMR Wichita West

Wichita, Kansas, United States

Site Status TERMINATED

AMR Wichita East

Wichita, Kansas, United States

Site Status RECRUITING

Wichita Surgical Specialists

Wichita, Kansas, United States

Site Status RECRUITING

Velocity Clinical Research

Baton Rouge, Louisiana, United States

Site Status RECRUITING

Tandem Clinical Research

Covington, Louisiana, United States

Site Status NOT_YET_RECRUITING

Velocity Clinical Research

Covington, Louisiana, United States

Site Status RECRUITING

Velocity Clinical Research

Lafayette, Louisiana, United States

Site Status RECRUITING

AMR New Orleans

New Orleans, Louisiana, United States

Site Status TERMINATED

Velocity Clinical Research, New Orleans

New Orleans, Louisiana, United States

Site Status RECRUITING

Velocity Clinical Research

Slidell, Louisiana, United States

Site Status TERMINATED

Regenerative Orthopedics and Sports Medicine- NextStage Clinical Research

North Bethesda, Maryland, United States

Site Status TERMINATED

Advanced Primary Care & Geriatrics/CCT Research

Rockville, Maryland, United States

Site Status RECRUITING

Velocity Clinical Research, Rockville

Rockville, Maryland, United States

Site Status RECRUITING

Activmed Practices and Research, Inc

Methuen, Massachusetts, United States

Site Status RECRUITING

Dearborn Cardiology

Dearborn, Michigan, United States

Site Status TERMINATED

Velocity Clinical Research

Gulfport, Mississippi, United States

Site Status RECRUITING

Clay Platte Family Medicine

Kansas City, Missouri, United States

Site Status RECRUITING

St. Louis Medical Professionals/CCT Research

St Louis, Missouri, United States

Site Status RECRUITING

Velocity Clinical Research, Grand Island

Grand Island, Nebraska, United States

Site Status RECRUITING

Velocity Clinical Research at Pioneer Heart Institute

Lincoln, Nebraska, United States

Site Status TERMINATED

Velocity Clinical Research

Lincoln, Nebraska, United States

Site Status RECRUITING

Velocity Clinical Research, Norfolk

Norfolk, Nebraska, United States

Site Status RECRUITING

Meridian Clinical Research - Velocity

Omaha, Nebraska, United States

Site Status RECRUITING

Midwest Regional Health Services

Omaha, Nebraska, United States

Site Status TERMINATED

Avacare

Las Vegas, Nevada, United States

Site Status RECRUITING

Santa Rosa Urgent Care Primary Care/CCT Research

Las Vegas, Nevada, United States

Site Status TERMINATED

Las Vegas Clinical Trials

North Las Vegas, Nevada, United States

Site Status RECRUITING

ActivMed Practices and Research

Portsmouth, New Hampshire, United States

Site Status TERMINATED

Velocity Clinical Research

Albuquerque, New Mexico, United States

Site Status RECRUITING

Axces Research Group

Santa Fe, New Mexico, United States

Site Status TERMINATED

Velocity Clinical Research

Binghamton, New York, United States

Site Status RECRUITING

Synexus Clinical Research US, Inc. - New York

New York, New York, United States

Site Status TERMINATED

Velocity Clinical Research

Vestal, New York, United States

Site Status TERMINATED

Velocity Clinical Research, Durham

Durham, North Carolina, United States

Site Status RECRUITING

Velocity Clinical Research

Beachwood, Ohio, United States

Site Status RECRUITING

Velocity Clinical Research, Mt. Auburn

Cincinnati, Ohio, United States

Site Status RECRUITING

Velocity Clinical Research, Cincinnati

Cincinnati, Ohio, United States

Site Status RECRUITING

Velocity Clinical Research

Cincinnati, Ohio, United States

Site Status RECRUITING

NexGen Research

Lima, Ohio, United States

Site Status RECRUITING

NextStage Clinical Research - Tulsa

Tulsa, Oklahoma, United States

Site Status RECRUITING

Velocity Clinical Research, Grants Pass

Grants Pass, Oregon, United States

Site Status TERMINATED

Velocity Clinical Research, Medford

Medford, Oregon, United States

Site Status RECRUITING

Hatboro Medical Associates/Avacare Research

Horsham, Pennsylvania, United States

Site Status RECRUITING

Mercado Medical Practice/CCT Research

Philadelphia, Pennsylvania, United States

Site Status TERMINATED

Velocity Clinical Research (Providence)

East Greenwich, Rhode Island, United States

Site Status RECRUITING

Velocity Clinical Research

Anderson, South Carolina, United States

Site Status RECRUITING

Velocity Clinical Research

Charleston, South Carolina, United States

Site Status TERMINATED

Velocity Clinical Research

Columbia, South Carolina, United States

Site Status RECRUITING

Velocity Clinical Research

Gaffney, South Carolina, United States

Site Status RECRUITING

Velocity Clinical Research

Greenville, South Carolina, United States

Site Status TERMINATED

Coastal Carolina Research Center

North Charleston, South Carolina, United States

Site Status RECRUITING

Velocity Clinical Research, Spartanburg

Spartanburg, South Carolina, United States

Site Status RECRUITING

Velocity Clinical Research, Union

Union, South Carolina, United States

Site Status RECRUITING

Velocity Clinical Research, Abilene

Abilene, Texas, United States

Site Status RECRUITING

Optimal Research, LLC. - Austin

Austin, Texas, United States

Site Status RECRUITING

Velocity Clinical Research

Austin, Texas, United States

Site Status RECRUITING

Advanced Cardiovascular Specialists/NextStage Clinical Research

Beaumont, Texas, United States

Site Status RECRUITING

HDH Research

Houston, Texas, United States

Site Status RECRUITING

All-American Orthopedics-NextStage Clinical Research

Houston, Texas, United States

Site Status RECRUITING

NextStage Clinical Research-Lubbock/SWAT Surgical Associates-NextStage Clinical Research

Lubbock, Texas, United States

Site Status TERMINATED

NextStage Clinical Research-Port Arthur/Gulf Coast Cardiology

Port Arthur, Texas, United States

Site Status RECRUITING

Synexus Clinical Research US; Inc.

San Antonio, Texas, United States

Site Status RECRUITING

Olympus Clinical Research

Sugarland, Texas, United States

Site Status RECRUITING

Waco Cardiology Consultants

Waco, Texas, United States

Site Status RECRUITING

Velocity Clinical Research, Salt Lake City

West Jordan, Utah, United States

Site Status RECRUITING

Charlottesville Medical Research

Charlottesville, Virginia, United States

Site Status RECRUITING

Velocity Clinical Research, Hampton

Hampton, Virginia, United States

Site Status RECRUITING

AMR Norfolk

Norfolk, Virginia, United States

Site Status RECRUITING

Velocity Clinical Research, Suffolk, VA

Suffolk, Virginia, United States

Site Status RECRUITING

Evergreen Surgical

Eau Claire, Wisconsin, United States

Site Status TERMINATED

Countries

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United States

Facility Contacts

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Ramy Toma, MD

Role: primary

Faheem Shaikh, MD

Role: primary

Harry Studdard, MD

Role: primary

Amy McCoy, MD

Role: primary

Juan Rodriguez, MD

Role: primary

David Shockey, MD

Role: primary

Steven Plimpton

Role: primary

Thomas Fiel, MD

Role: primary

Kevin Pounds, MD

Role: primary

Dennis Tsang, MD

Role: primary

Thaidra Gaufin, MD

Role: primary

Stanley Hsia, MD

Role: primary

Scott Overcash, MD

Role: primary

Pamela De Silva, MD

Role: primary

Barry Heller, MD

Role: primary

Abdul Khan, MD

Role: primary

Mallu Reddy, MD

Role: primary

Judith Kirstein, MD

Role: primary

Bernadette Alejandrino, MD

Role: primary

Robert Williams

Role: primary

Luis Cabrera, MD

Role: primary

Nelson Gonzalez, MD

Role: primary

Yvon Petiote, MD

Role: primary

Ana Cury, MD

Role: primary

Margaret Chang, MD

Role: primary

Ihosvani Miguel, MD

Role: primary

Jose Rodriguez, MD

Role: primary

Miguel Chamah,, MD

Role: primary

Jose Barbeito, MD

Role: primary

Luis Alvarado, MD

Role: primary

Samuel Lederman, MD

Role: primary

Jorge Amaya, MD

Role: primary

Murray Kimmel, MD

Role: primary

Lazzaro Garcia, MD

Role: primary

Armando Velez-Pineda, MD

Role: primary

Jacqueline Alvarez

Role: primary

Adolfo Cueli, MD

Role: primary

Julian Guerrero, MD

Role: primary

Ricardo Mauro Perez Rivera, MD

Role: primary

Emilio Pando

Role: primary

Abigail Adams, MD

Role: primary

Anita Petteway, MD

Role: primary

Luis Hernandez Rosado, MD

Role: primary

Derrick Diaz

Role: primary

Franklin Pimentel, MD

Role: primary

Yaolen Bolanos, MD

Role: primary

Guillermo Somodevilla, MD

Role: primary

Eric Spivack, MD

Role: primary

Angela Okolie, MD

Role: primary

Courtney Shelton, MD

Role: primary

Anthony Olofintuyi, MD

Role: primary

Ramana Puppala, MD

Role: primary

Paul Bradley, MD

Role: primary

Arshad Malik, MD

Role: primary

Robert Buynak, MD

Role: primary

Nicholas Bechtold, MD

Role: primary

Michael Rausch, MD

Role: primary

Terry Klein, MD

Role: primary

Nicholas Brown, MD

Role: primary

Katherine Pearce, MD

Role: primary

Tania Levi, MD

Role: primary

William Beacham, MD

Role: primary

Jibran Atwi, MD

Role: primary

Scott Striplin, MD

Role: primary

Ravi Passi, MD

Role: primary

Shishir Khetan, MD

Role: primary

Adam Tanzer, MD

Role: primary

Paul Matherne, MD

Role: primary

Scott Kuennen, MD

Role: primary

Hany Salama, MD

Role: primary

Adam Brosz, MD

Role: primary

Jay Meyer, MD

Role: primary

Charles Harper, MD

Role: primary

Frederick Raiser, MD

Role: primary

Rita Chuang, MD

Role: primary

Alton Walters, MD

Role: primary

Sara Friedman, MD

Role: primary

Frank Eder, MD

Role: primary

William Cromwell, MD

Role: primary

Margaret Rhee, MD

Role: primary

Matthew Wenker, MD

Role: primary

Audrius Rauksenas, MD

Role: primary

Charles Eger, MD

Role: primary

Nonso Ezema, MD

Role: primary

Brian Chalkin, MD

Role: primary

Sarah Smiley, MD

Role: primary

Harris Cohen, MD

Role: primary

David Fried, MD

Role: primary

Charles Thompson, MD

Role: primary

Ronald Cassada, MD

Role: primary

David Erb, MD

Role: primary

Kelly Morales, MD

Role: primary

Farhan Siddiqui, MD

Role: primary

Joseph Boscia, MD

Role: primary

Thomas Headstream, MD

Role: primary

Kristie Miller, MD

Role: primary

Michael Zimmerman, MD

Role: primary

Jorge Hernandez, MD

Role: primary

Francisco Ortiz, MD

Role: primary

Matthew Higgs, MD

Role: primary

Pradip Morbia, MD

Role: primary

Danielle Coulter, MD

Role: primary

Harish Thakker, MD

Role: primary

Donald Cross, MD

Role: primary

Barbara Rizzardi, MD

Role: primary

Kristen Holtz, MD

Role: primary

Thomas Piscitelli, MD

Role: primary

Mary Bailey, MD

Role: primary

Banu Myneni, MD

Role: primary

Other Identifiers

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NB-CVOT3

Identifier Type: -

Identifier Source: org_study_id