Effect of Naltrexone Hydrochloride ER and Bupropion Hydrochloride ER Combination (Contrave®/Mysimba®) on Major Adverse Cardiovascular Events (MACE)
- Conditions
- Obesity
- Interventions
- Drug: Naltrexone-Bupropion (NB) CombinationDrug: Placebo
- Registration Number
- NCT06098079
- Lead Sponsor
- Currax Pharmaceuticals
- Brief Summary
A randomized, double-blinded, placebo controlled study intended to capture cardiovascular outcomes during real-world use of naltrexone/bupropion (NB).
- Detailed Description
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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 8600
-
Patient age ≥18 years at screening
-
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
-
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)
-
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
-
Patients who have completed a washout (2-weeks or 5 half-lives, whichever is longer) of the prohibited concomitant medication(s) at screening
-
Subject willing to comply with daily completion of an eDiary using a mobile smartphone application
-
Using prescription medications, other than Contrave/Mysimba, or surgical or medical device interventions for weight loss
-
History of MI or stroke within 90 days prior to screening
-
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
-
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)
-
Seizure disorders or history of seizures, not including subjects with a history of pediatric febrile seizures
-
Use of other bupropion-containing products (including but not limited to Wellbutrin, Wellbutrin SR, Wellbutrin XL, and Aplenzin)
-
Active anorexia nervosa or bulimia
-
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
-
Undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs
-
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.
-
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
-
Known allergy to bupropion, naltrexone, or any other component of Contrave/Mysimba
-
Pregnant or nursing
-
Known life-threatening arrythmias, including Brugada syndrome
-
Participation in any other concurrent investigational trial
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Naltrexone/Bupropion (NB) Naltrexone-Bupropion (NB) Combination Patients will be randomly assigned to NB (naltrexone 8 mg and bupropion 90 mg) extended-release oral tablet. Placebo Placebo Patients will be randomly assigned to placebo.
- Primary Outcome Measures
Name Time Method Occurrence of Cardiovascular Death Treatment initiation through 1 year following treatment termination. Occurrence of cardiovascular death in number of study patients receiving NB compared with number of study patients receiving placebo.
Occurrence of Non-fatal Myocardial Infarction (MI) Treatment initiation through 1 year following treatment termination. Occurrence of MI in number of study patients receiving NB compared with number of study patients receiving placebo. MI will be identified using current standard diagnostic criteria, such as the 2017 Cardiovascular and Stroke Endpoints Definitions for Clinical Trials.
Occurrence of Non-fatal Stroke Treatment initiation through 1 year following treatment termination. Occurrence of non-fatal stroke in number of study patients receiving NB compared with number of study patients receiving placebo. Stroke will be identified using current standard diagnostic criteria, such as the 2017 Cardiovascular and Stroke Endpoints Definitions for Clinical Trials.
- Secondary Outcome Measures
Name Time Method Comparative Rates of Non-fatal Myocardial Infarction (MI) Treatment initiation through 1 year following treatment termination. Comparative rates of non-fatal MI between number of study patients receiving NB compared to number of study patients receiving placebo.
Comparative Rates of Non-fatal Stroke Treatment initiation through 1 year following treatment termination. Comparative rates of non-fatal stroke between number of study patients receiving NB compared to number of study patients receiving placebo.
Comparative Rates of Cardiovascular Death Treatment initiation through 1 year following treatment termination. Comparative rates of cardiovascular death between number of study patients receiving NB compared to number of study patients receiving placebo.
Related Research Topics
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Trial Locations
- Locations (104)
AMR Mobile
🇺🇸Mobile, Alabama, United States
Velocity Clinical Research, Mobile
🇺🇸Mobile, Alabama, United States
Sun City Research
🇺🇸Glendale, Arizona, United States
Cardiovascular Consultants/NextStage Clinical Research
🇺🇸Glendale, Arizona, United States
Desert Clinical Research
🇺🇸Mesa, Arizona, United States
Velocity Clinical Research, Phoenix
🇺🇸Phoenix, Arizona, United States
Fiel Family & Sports Medicine CCT Research
🇺🇸Tempe, Arizona, United States
Velocity Clinical Research, Gardena
🇺🇸Anderson, California, United States
Velocity Clinical Research
🇺🇸Austin, Texas, United States
Velocity Clinical Research, Huntington Park
🇺🇸Huntington Park, California, United States
Velocity Clinical Research, San Diego
🇺🇸La Mesa, California, United States
Chemidox Clinical Trials Inc.
🇺🇸Lancaster, California, United States
Valley Vitality Ventures
🇺🇸Manteca, California, United States
Velocity Clinical Research, San Bernardino
🇺🇸San Bernardino, California, United States
Velocity Clinical Research at Coastal Heart Medical Group
🇺🇸Santa Ana, California, United States
Velocity Clinical Research of Santa Ana
🇺🇸Santa Ana, California, United States
ITB Research
🇺🇸Miami, Florida, United States
AMR Wichita West
🇺🇸Wichita, Kansas, United States
Accel Research Sites Network
🇺🇸Birmingham, Alabama, United States
Cullman Clinical Trials
🇺🇸Cullman, Alabama, United States
Velocity Clinical Research, Van Nuys
🇺🇸Van Nuys, California, United States
Providere Research
🇺🇸West Covina, California, United States
Velocity Clinical Research, Denver
🇺🇸Englewood, Colorado, United States
ABMED Clinical Research
🇺🇸Cape Coral, Florida, United States
LMG Research
🇺🇸Coral Gables, Florida, United States
JY Research Institute
🇺🇸Cutler Bay, Florida, United States
Delray Physician Center
🇺🇸Delray Beach, Florida, United States
Accel Research Sites Network - Edgewater
🇺🇸Edgewater, Florida, United States
Velocity Clinical Research (New Smyrna Beach)
🇺🇸Edgewater, Florida, United States
IMRC Fort Lauderdale
🇺🇸Fort Lauderdale, Florida, United States
Southwest General Healthcare Center
🇺🇸Fort Myers, Florida, United States
G+C Research Group
🇺🇸Hialeah, Florida, United States
Conveinent Medical Research
🇺🇸Hialeah, Florida, United States
Ilumina Medical Research
🇺🇸Kissimmee, Florida, United States
Optimal Research, LLC. - Melbourne
🇺🇸Melbourne, Florida, United States
Miami Beach Clinical Research
🇺🇸Miami Beach, Florida, United States
Advanced Clinical Research
🇺🇸Miami, Florida, United States
Medical Research Center Westchester
🇺🇸Miami, Florida, United States
Century Research
🇺🇸Miami, Florida, United States
Entrust Clinical Research
🇺🇸Miami, Florida, United States
Janus Clinical Research
🇺🇸Miami, Florida, United States
Innovia Research Center
🇺🇸Miramar, Florida, United States
Biscayne Clinical Research Inc
🇺🇸North Miami, Florida, United States
IMRC At Palmetto Bay
🇺🇸Palmetto Bay, Florida, United States
New Horizons Research
🇺🇸Palmetto Bay, Florida, United States
Best Choice Medical and Research Services
🇺🇸Pembroke Pines, Florida, United States
Synexus Clinical Research US, Inc. - The Villages
🇺🇸The Villages, Florida, United States
Advanced Clinical Research Atlanta
🇺🇸Atlanta, Georgia, United States
Clincept Clinical Research
🇺🇸Columbus, Georgia, United States
Accel Research Sites (ARSN) - Neurostudies
🇺🇸Decatur, Georgia, United States
Velocity Clinical Research, Savannah
🇺🇸Savannah, Georgia, United States
NextStage Clinical Research-Chicago
🇺🇸Glen Ellyn, Illinois, United States
JAELEX Research
🇺🇸Round Lake Beach, Illinois, United States
Indiana Medical Research Institute
🇺🇸Merriville, Indiana, United States
AMR - El Dorado
🇺🇸El Dorado, Kansas, United States
Velocity Clinical Research, Kansas City
🇺🇸Kansas City, Kansas, United States
AMR Wichita East
🇺🇸Wichita, Kansas, United States
Wichita Surgical Specialists
🇺🇸Wichita, Kansas, United States
AMR New Orleans
🇺🇸New Orleans, Louisiana, United States
Velocity Clinical Research, New Orleans
🇺🇸New Orleans, Louisiana, United States
Regenerative Orthopedics and Sports Medicine- NextStage Clinical Research
🇺🇸North Bethesda, Maryland, United States
Advanced Primary Care & Geriatrics/CCT Research
🇺🇸Rockville, Maryland, United States
Velocity Clinical Research, Rockville
🇺🇸Rockville, Maryland, United States
Activmed Practices and Research, Inc
🇺🇸Methuen, Massachusetts, United States
Dearborn Cardiology
🇺🇸Dearborn, Michigan, United States
Clay Platte Family Medicine
🇺🇸Kansas City, Missouri, United States
St. Louis Medical Professionals/CCT Research
🇺🇸Saint Louis, Missouri, United States
Velocity Clinical Research, Grand Island
🇺🇸Grand Island, Nebraska, United States
Velocity Clinical Research at Pioneer Heart Institute
🇺🇸Lincoln, Nebraska, United States
Velocity Clinical Research, Norfolk
🇺🇸Norfolk, Nebraska, United States
Meridian Clinical Research - Velocity
🇺🇸Omaha, Nebraska, United States
Midwest Regional Health Services
🇺🇸Omaha, Nebraska, United States
Healor Primary Care/CCT Research
🇺🇸Las Vegas, Nevada, United States
Santa Rosa Urgent Care Primary Care/CCT Research
🇺🇸Las Vegas, Nevada, United States
Las Vegas Clinical Trials
🇺🇸North Las Vegas, Nevada, United States
ActivMed Practices and Research
🇺🇸Portsmouth, New Hampshire, United States
Axces Research Group
🇺🇸Santa Fe, New Mexico, United States
Synexus Clinical Research US, Inc. - New York
🇺🇸New York City, New York, United States
Velocity Clinical Research, Durham
🇺🇸Durham, North Carolina, United States
Velocity Clinical Research, Mt. Auburn
🇺🇸Cincinnati, Ohio, United States
Velocity Clinical Research, Cincinnati
🇺🇸Cincinnati, Ohio, United States
NextStage Clinical Research - Tulsa
🇺🇸Tulsa, Oklahoma, United States
Velocity Clinical Research, Grants Pass
🇺🇸Grants Pass, Oregon, United States
Velocity Clinical Research, Medford
🇺🇸Medford, Oregon, United States
Mercado Medical Practice/CCT Research
🇺🇸Philadelphia, Pennsylvania, United States
Velocity Clinical Research (Providence)
🇺🇸East Greenwich, Rhode Island, United States
Coastal Carolina Research Center
🇺🇸North Charleston, South Carolina, United States
Velocity Clinical Research, Spartanburg
🇺🇸Spartanburg, South Carolina, United States
Velocity Clinical Research, Union
🇺🇸Union, South Carolina, United States
Velocity Clinical Research, Abilene
🇺🇸Abilene, Texas, United States
Optimal Research, LLC. - Austin
🇺🇸Austin, Texas, United States
Advanced Cardiovascular Specialists/NextStage Clinical Research
🇺🇸Beaumont, Texas, United States
HDH Research
🇺🇸Houston, Texas, United States
All-American Orthopedics-NextStage Clinical Research
🇺🇸Houston, Texas, United States
NextStage Clinical Research-Lubbock/SWAT Surgical Associates-NextStage Clinical Research
🇺🇸Lubbock, Texas, United States
NextStage Clinical Research-Port Arthur/Gulf Coast Cardiology
🇺🇸Port Arthur, Texas, United States
Olympus Clinical Research
🇺🇸Sugarland, Texas, United States
Waco Cardiology Consultants
🇺🇸Waco, Texas, United States
Velocity Clinical Research, Salt Lake City
🇺🇸West Jordan, Utah, United States
Charlottesville Medical Research
🇺🇸Charlottesville, Virginia, United States
Velocity Clinical Research, Hampton
🇺🇸Hampton, Virginia, United States
AMR Norfolk
🇺🇸Norfolk, Virginia, United States
Velocity Clinical Research, Suffolk, VA
🇺🇸Suffolk, Virginia, United States
Evergreen Surgical
🇺🇸Eau Claire, Wisconsin, United States