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

A Phase IV Study to Assess the Effect of Naltrexone Hydrochloride Extended Release (ER) and Bupropion Hydrochloride ER Combination (Contrave®/Mysimba®) on the Occurrence of Major Adverse Cardiovascular Events

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

Study Overview

• Status: Active, not recruiting
• Conditions: Obesity
• Intervention / Treatment: Drug: Naltrexone-Bupropion (NB) Combination; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Estimated): 8600
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35216
      • Accel Research Sites Network
    • Birmingham, Alabama, United States, 35211
      • TrialMed Birmingham (DRS)
    • Cullman, Alabama, United States, 35055
      • Cullman Clinical Trials
    • Mobile, Alabama, United States, 36608
      • AMR Mobile
    • Mobile, Alabama, United States, 36608
      • Velocity Clinical Research, Mobile
  • Arizona
    • Glendale, Arizona, United States, 85304
      • Sun City Research
    • Glendale, Arizona, United States, 85306
      • Cardiovascular Consultants/NextStage Clinical Research
    • Mesa, Arizona, United States, 85213
      • Desert Clinical Research
    • Phoenix, Arizona, United States, 85006
      • Velocity Clinical Research, Phoenix
    • Tempe, Arizona, United States, 85283
      • Fiel Family & Sports Medicine CCT Research
    • Tucson, Arizona, United States, 85741
      • Synexus Clinical Research US; Inc.
  • California
    • Anderson, California, United States, 90247
      • Velocity Clinical Research, Gardena
    • Chula Vista, California, United States, 91911
      • Velocity Clinical Research
    • Huntington Park, California, United States, 90255
      • Velocity Clinical Research, Huntington Park
    • La Mesa, California, United States, 91942
      • Velocity Clinical Research, San Diego
    • Lancaster, California, United States, 93534
      • Chemidox Clinical Trials Inc.
    • Long Beach, California, United States, 90806
      • Long Beach Clinical Trials
    • Los Angeles, California, United States, 90057
      • Velocity Clinical Research
    • Manteca, California, United States, 95350
      • Valley Vitality Ventures
    • Pomona, California, United States, 91768
      • National Institute of Clinical Research, Inc.
    • San Bernardino, California, United States, 92408
      • Velocity Clinical Research, San Bernardino
    • Santa Ana, California, United States, 92704
      • Velocity Clinical Research at Coastal Heart Medical Group
    • Santa Ana, California, United States, 92704
      • Velocity Clinical Research of Santa Ana
    • Van Nuys, California, United States, 91405
      • Velocity Clinical Research, Van Nuys
    • West Covina, California, United States, 91790
      • Providere Research
  • Colorado
    • Englewood, Colorado, United States, 80110
      • Velocity Clinical Research, Denver
  • Florida
    • Cape Coral, Florida, United States, 33914
      • ABMED Clinical Research
    • Coral Gables, Florida, United States, 33134
      • LMG Research
    • Cutler Bay, Florida, United States, 33189
      • JY Research Institute
    • Delray Beach, Florida, United States, 33445
      • Delray Physician Center
    • Doral, Florida, United States, 33122
      • D&H Doral Research Center
    • Edgewater, Florida, United States, 32132
      • Accel Research Sites Network - Edgewater
    • Edgewater, Florida, United States, 32132
      • Velocity Clinical Research (New Smyrna Beach)
    • Fort Lauderdale, Florida, United States, 33316
      • IMRC Fort Lauderdale
    • Fort Myers, Florida, United States, 33907
      • Southwest General Healthcare Center
    • Hialeah, Florida, United States, 33010
      • Qway Research
    • Hialeah, Florida, United States, 33010
      • G+C Research Group
    • Hialeah, Florida, United States, 33013
      • Conveinent Medical Research
    • Kissimmee, Florida, United States, 34744
      • Ilumina Medical Research
    • Lake Worth, Florida, United States, 33461
      • Altus Research
    • Margate, Florida, United States, 33063
      • D&H Pompano Research Center, LLC
    • Melbourne, Florida, United States, 32934
      • Optimal Research, LLC. - Melbourne
    • Miami, Florida, United States, 33173
      • Century Research
    • Miami, Florida, United States, 33176
      • Entrust Clinical Research
    • Miami, Florida, United States, 33173
      • ITB Research
    • Miami, Florida, United States, 33156
      • Advanced Clinical Research
    • Miami, Florida, United States, 33165
      • Medical Research Center Westchester
    • Miami, Florida, United States, 33186
      • Janus Clinical Research
    • Miami Beach, Florida, United States, 33141
      • Miami Beach Clinical Research
    • Miramar, Florida, United States, 33027
      • Innovia Research Center
    • New Smyrna Beach, Florida, United States, 32168
      • Healix Clinical Research
    • North Miami, Florida, United States, 33169
      • Biscayne Clinical Research Inc
    • Palmetto Bay, Florida, United States, 33157
      • IMRC At Palmetto Bay
    • Palmetto Bay, Florida, United States, 33176
      • New Horizons Research
    • Pembroke Pines, Florida, United States, 33024
      • Best Choice Medical and Research Services
    • Pembroke Pines, Florida, United States, 33028
      • Bolanos Clnical Research
    • Sweetwater, Florida, United States, 33182
      • Cordova Research Institute
    • Tamarac, Florida, United States, 33321
      • D&H Tamarac Research Center, LLC
    • The Villages, Florida, United States, 32162
      • Synexus Clinical Research US, Inc. - The Villages
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Advanced Clinical Research Atlanta
    • Columbus, Georgia, United States, 31904
      • Clincept Clinical Research
    • Decatur, Georgia, United States, 30030
      • Accel Research Sites (ARSN) - Neurostudies
    • Savannah, Georgia, United States, 31406
      • Velocity Clinical Research, Savannah
  • Illinois
    • Glen Ellyn, Illinois, United States, 60137
      • NextStage Clinical Research-Chicago
    • Round Lake Beach, Illinois, United States, 60073
      • JAELEX Research
  • Indiana
    • Merriville, Indiana, United States, 46410
      • Indiana Medical Research Institute
    • Valparaiso, Indiana, United States, 46383
      • Velocity Clinical Research
  • Iowa
    • Sioux City, Iowa, United States, 51106
      • Velocity Clinical Research
  • Kansas
    • El Dorado, Kansas, United States, 67042
      • AMR - El Dorado
    • Kansas City, Kansas, United States, 66210
      • Velocity Clinical Research, Kansas City
    • Wichita, Kansas, United States, 67205
      • AMR Wichita West
    • Wichita, Kansas, United States, 67207
      • AMR Wichita East
    • Wichita, Kansas, United States, 67214
      • Wichita Surgical Specialists
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Velocity Clinical Research
    • Covington, Louisiana, United States, 70433
      • Velocity Clinical Research
    • Lafayette, Louisiana, United States, 70508
      • Velocity Clinical Research
    • New Orleans, Louisiana, United States, 70119
      • AMR New Orleans
    • New Orleans, Louisiana, United States, 70119
      • Velocity Clinical Research, New Orleans
    • Slidell, Louisiana, United States, 70458
      • Velocity Clinical Research
  • Maryland
    • North Bethesda, Maryland, United States, 20852
      • Regenerative Orthopedics and Sports Medicine- NextStage Clinical Research
    • Rockville, Maryland, United States, 20854
      • Velocity Clinical Research, Rockville
    • Rockville, Maryland, United States, 20852
      • Praveen K Gupta, MD/Avacare
  • Massachusetts
    • Methuen, Massachusetts, United States, 01844
      • Activmed Practices and Research, Inc
  • Michigan
    • Dearborn, Michigan, United States, 48126
      • Dearborn Cardiology
  • Mississippi
    • Gulfport, Mississippi, United States, 39503
      • Velocity Clinical Research
  • Missouri
    • Kansas City, Missouri, United States, 64151
      • Clay Platte Family Medicine
    • St Louis, Missouri, United States, 63119
      • St. Louis Medical Professionals/CCT Research
    • St Louis, Missouri, United States, 63131
      • Velocity Clinical Research (St. Louis)
  • Nebraska
    • Grand Island, Nebraska, United States, 68803
      • Velocity Clinical Research, Grand Island
    • Lincoln, Nebraska, United States, 68510
      • Velocity Clinical Research
    • Lincoln, Nebraska, United States, 68506
      • Velocity Clinical Research at Pioneer Heart Institute
    • Norfolk, Nebraska, United States, 68701
      • Velocity Clinical Research, Norfolk
    • Omaha, Nebraska, United States, 68144
      • Midwest Regional Health Services
    • Omaha, Nebraska, United States, 68134
      • Meridian Clinical Research - Velocity
  • Nevada
    • Las Vegas, Nevada, United States, 89102
      • Avacare
    • Las Vegas, Nevada, United States, 89119
      • Santa Rosa Urgent Care Primary Care/CCT Research
    • North Las Vegas, Nevada, United States, 89119
      • Las Vegas Clinical Trials
  • New Hampshire
    • Portsmouth, New Hampshire, United States, 03801
      • ActivMed Practices and Research
  • New Mexico
    • Albuquerque, New Mexico, United States, 87107
      • Velocity Clinical Research
    • Santa Fe, New Mexico, United States, 87505
      • Axces Research Group
  • New York
    • Binghamton, New York, United States, 13905
      • Velocity Clinical Research
    • New York, New York, United States, 10017
      • Synexus Clinical Research US, Inc. - New York
    • Vestal, New York, United States, 13850
      • Velocity Clinical Research
  • North Carolina
    • Durham, North Carolina, United States, 27701
      • Velocity Clinical Research, Durham
  • Ohio
    • Beachwood, Ohio, United States, 44122
      • Velocity Clinical Research
    • Cincinnati, Ohio, United States, 45246
      • Velocity Clinical Research
    • Cincinnati, Ohio, United States, 45219
      • Velocity Clinical Research, Mt. Auburn
    • Cincinnati, Ohio, United States, 45242
      • Velocity Clinical Research, Cincinnati
    • Lima, Ohio, United States, 45801
      • NexGen Research
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74136
      • NextStage Clinical Research - Tulsa
  • Oregon
    • Grants Pass, Oregon, United States, 97527
      • Velocity Clinical Research, Grants Pass
    • Medford, Oregon, United States, 97504
      • Velocity Clinical Research, Medford
  • Pennsylvania
    • Horsham, Pennsylvania, United States, 19044
      • Hatboro Medical Associates/Avacare Research
    • Philadelphia, Pennsylvania, United States, 19111
      • Mercado Medical Practice/CCT Research
  • Rhode Island
    • East Greenwich, Rhode Island, United States, 02818
      • Velocity Clinical Research (Providence)
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • Velocity Clinical Research
    • Charleston, South Carolina, United States, 29414
      • Velocity Clinical Research
    • Columbia, South Carolina, United States, 29204
      • Velocity Clinical Research
    • Gaffney, South Carolina, United States, 29340
      • Velocity Clinical Research
    • Greenville, South Carolina, United States, 29615
      • Velocity Clinical Research
    • North Charleston, South Carolina, United States, 29405
      • Coastal Carolina Research Center
    • Spartanburg, South Carolina, United States, 29303
      • Velocity Clinical Research, Spartanburg
    • Union, South Carolina, United States, 29379
      • Velocity Clinical Research, Union
  • Texas
    • Abilene, Texas, United States, 79606
      • Velocity Clinical Research, Abilene
    • Austin, Texas, United States, 78759
      • Velocity Clinical Research
    • Austin, Texas, United States, 78705
      • Optimal Research, LLC. - Austin
    • Beaumont, Texas, United States, 77702
      • Advanced Cardiovascular Specialists/NextStage Clinical Research
    • Houston, Texas, United States, 77022
      • HDH Research
    • Houston, Texas, United States, 77058
      • All-American Orthopedics-NextStage Clinical Research
    • Lubbock, Texas, United States, 79410
      • NextStage Clinical Research-Lubbock/SWAT Surgical Associates-NextStage Clinical Research
    • Port Arthur, Texas, United States, 77642
      • NextStage Clinical Research-Port Arthur/Gulf Coast Cardiology
    • San Antonio, Texas, United States, 78229
      • Synexus Clinical Research US; Inc.
    • Sugarland, Texas, United States, 77479
      • Olympus Clinical Research
    • Waco, Texas, United States, 76712
      • Waco Cardiology Consultants
  • Utah
    • West Jordan, Utah, United States, 84088
      • Velocity Clinical Research, Salt Lake City
  • Virginia
    • Charlottesville, Virginia, United States, 22911
      • Charlottesville Medical Research
    • Hampton, Virginia, United States, 23666
      • Velocity Clinical Research, Hampton
    • Norfolk, Virginia, United States, 23502
      • AMR Norfolk
    • Suffolk, Virginia, United States, 23435
      • Velocity Clinical Research, Suffolk, VA
  • Wisconsin
    • Eau Claire, Wisconsin, United States, 54701
      • Evergreen Surgical

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Naltrexone/Bupropion (NB); Patients will be randomly assigned to NB (naltrexone 8 mg and bupropion 90 mg) extended-release oral tablet.	Drug: 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.
Placebo Comparator: Placebo; Patients will be randomly assigned to placebo.	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of Cardiovascular Death	Occurrence of cardiovascular death in number of study patients receiving NB compared with number of study patients receiving placebo.	Treatment initiation through 1 year following treatment termination.
Occurrence of Non-fatal Myocardial Infarction (MI)	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.	Treatment initiation through 1 year following treatment termination.
Occurrence of Non-fatal Stroke	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.	Treatment initiation through 1 year following treatment termination.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparative Rates of Cardiovascular Death	Comparative rates of cardiovascular death between number of study patients receiving NB compared to number of study patients receiving placebo.	Treatment initiation through 1 year following treatment termination.
Comparative Rates of Non-fatal Myocardial Infarction (MI)	Comparative rates of non-fatal MI between number of study patients receiving NB compared to number of study patients receiving placebo.	Treatment initiation through 1 year following treatment termination.
Comparative Rates of Non-fatal Stroke	Comparative rates of non-fatal stroke between number of study patients receiving NB compared to number of study patients receiving placebo.	Treatment initiation through 1 year following treatment termination.

Collaborators and Investigators

• Sponsor: Currax Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): January 3, 2024
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): July 1, 2029

Study Registration Dates

• First Submitted: October 13, 2023
• First Submitted That Met QC Criteria: October 18, 2023
• First Posted (Actual): October 24, 2023

Study Record Updates

• Last Update Posted (Actual): March 31, 2026
• Last Update Submitted That Met QC Criteria: March 30, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Overweight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Sensory System Agents; Neurotransmitter Agents; Membrane Transport Modulators; Psychotropic Drugs; Cytochrome P-450 Enzyme Inhibitors; Dopamine Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Dopamine Agents; Antidepressive Agents; Alcohol Deterrents; Antidepressive Agents, Second-Generation; Cytochrome P-450 CYP2D6 Inhibitors; Narcotic Antagonists; Naltrexone; Bupropion
• Other Study ID Numbers: NB-CVOT3

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No