Real-World Evidence on the Cardiovascular Safety of CONTRAVE® in the United States (U.S.)

NCT ID: NCT06090461

Last Updated: 2025-06-25

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 31889 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2014-09-30
• Study Completion Date: 2022-12-31

Brief Summary

The fixed-dose combination of naltrexone 8mg and bupropion 90mg extended-release oral tablet is marketed under the trade name CONTRAVE® in the U.S. In this protocol, the investigators propose to generate real-world evidence (RWE) from electronic health records (EHR) and linked claims data to assess the cardiovascular safety of CONTRAVE® and all combined use of naltrexone and bupropion (NB) in usual clinical practice.

Detailed Description

The study will assess whether patients who initiate treatment with NB are at an elevated risk of MACE compared with patients who initiated treatment with lorcaserin, an active comparator chosen to reduce potential confounding.

The cohorts for all study objectives will be drawn from a large electronic health records (EHR) data source, representing a geographically diverse patient population. The data will include diagnoses, procedures, medications (prescribed and administered), clinical measures (biometric and laboratory values), and observations derived from clinical notes. A subset of the population will have linked, adjudicated claims data available to support sensitivity analyses.

The study's main objective is to compare the incidence of the primary endpoint (MACE) between initiators of NB and initiators of lorcaserin. The study will also compare the incidence of the secondary endpoint, consisting of each component of MACE, between initiators of NB and initiators of lorcaserin, across the following subgroups: Patients with obesity (i.e., most recent BMI measurement ≥30 kg/m2); Patients with a diagnosis of hypertension, regardless of BMI; Patients with a diagnosis of type 2 diabetes mellitus, regardless of BMI; Patients with a diagnosis of dyslipidemia, regardless of BMI.

The study's additional objectives aimed at testing the robustness of the methods are:

To assess the comparability of findings from an EHR study to those of a 2018 clinical trial, aligning with the Randomized Control Trials Duplicated Using Prospective Longitudinal Insurance Claims: Applying Techniques of Epidemiology (RCT DUPLICATE) Initiative; To quantify differences in cardiovascular safety endpoints between the clinical trial and the results of this EHR study; To conduct other sensitivity analyses, including a self-controlled, case-crossover analysis to quantify the potential effect of NB on MACE.

Conditions

Obesity

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: RETROSPECTIVE

Study Groups

Contrave/Mysimba

A fixed-dose combination of 8 milligrams (mg) of naltrexone hydrochloride (HCl) (an opioid receptor antagonist), and 90 mg of bupropion HCl (a selective neuronal re-uptake inhibitor of noradrenaline and dopamine), delivered through extended-release oral tablets.

No interventions assigned to this group

Lorcaserin

A total of one 10 mg tablet administered orally twice daily; or one 20 mg tablet administered orally once daily. Lorcaserin was included as an active comparator to reduce bias.

No interventions assigned to this group

Naltrexone and Bupropion (N&B)

N\&B concomitant use, ultimately as a proxy for initiation, was defined as a record for naltrexone followed by initiation of bupropion, or bupropion followed by initiation of naltrexone, within 15 days of each other.

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• Have at least one prescription for NB between September 2014 and February 2020, including concurrent prescriptions (within 15 days) for naltrexone and bupropion; or have at least one prescription for lorcaserin;
• Have at least 180 days of data available prior to cohort entry with no evidence of prescriptions or dispensings of NB or lorcaserin;
• Have at least one BMI value available in the 180 days prior to cohort entry, inclusive of the index date;
• Have documentation of at least one outpatient medical visit 180 or more days prior to cohort entry, and at least one healthcare interaction in the 180 days prior to cohort entry;
• Are at least 18 years of age on the cohort entry date.

For the main objective, patients are not eligible if they have a diagnosis of any of the following conditions in the 180 days before the cohort entry date:

• Epilepsy;
• Bulimia;
• Anorexia nervosa;
• Surgical procedure for weight loss.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Currax Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Currax Pharmaceuticals

Brentwood, Tennessee, United States

Countries

United States

References

Kyle M, Burns D, Murray CR, Watson H, Swaney J, Spevack S, Leonhard M, Simon M, Moynihan E, Lapane KL, Wang SV, Longo CL, Ritchey ME, Dore DD. Cardiovascular safety of fixed-dose extended-release naltrexone/bupropion in clinical practice. Obes Pillars. 2025 Feb 17;13:100169. doi: 10.1016/j.obpill.2025.100169. eCollection 2025 Mar.

Reference Type: RESULT

PMID: 40104005 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

Cardiovascular Safety Study

Identifier Type: -

Identifier Source: org_study_id