Bariatric Surgery for the Reduction of cArdioVascular Events Randomized Controlled Trial (BRAVE)

The primary objective of this study is to evaluate if, in patients with severe obesity (body mass index (BMI) ≥30 kg/m2) and high-risk cardiovascular disease (CVD), bariatric surgery compared to medical weight management (MWM) safely reduces the risk of major cardiovascular events. The cost-effectiveness of bariatric surgery will also be examined. Separate sub-studies will be performed to examine the relationship between bariatric surgery and mental health and cognition (BRAVE-Mind), cardiac structure and function, genomics, proteomics and metabolomics.

Study Overview

• Status: Recruiting
• Conditions: Bariatric Surgery Candidate; Cardiovascular Complication
• Intervention / Treatment: Behavioral: Medical Weight Management; Procedure: Bariatric Surgery

• Study Type: Interventional
• Enrollment (Estimated): 700
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jorge Wong, MD, MPH, FRCPC; Phone Number: 40309 905-521-2100; Email: jorge.wong@phri.ca
• Study Contact Backup: Name: Sumathy Rangarajan, MSc; Phone Number: 905-296-5792; Email: sumathy.rangarajan@phri.ca

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8L 2X2
      • Recruiting
      • Hamilton Health Sciences
      • Contact: Jorge Wong, MD; Phone Number: 41149 905-527-4322; Email: jorge.wong@phri.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Body mass index ≥30 kg/m2; OR BMI ≥30 kg/m2 to 34.9 kg/m2 and have type 2 diabetes or are >55 years of age
2. Age ≥18 years

3. High-risk CVD, defined as the presence of any one of the following:

   1. High-risk coronary artery disease (CAD) (i.e., history of MI, percutaneous coronary intervention, coronary artery bypass grafting, or stenoses ≥ 50% in 2 or more major coronary arteries)
   2. Left ventricular ejection fraction (LVEF) < 40%
   3. Heart failure with preserved ejection fraction (LVEF > 40%) and either HF hospitalization in the last 2-years or N-terminal pro b-type natriuretic peptide (NT-proBNP) > 300 pg/ml or BNP > 100 pg/ml in the past 12 months
   4. Documented atrial fibrillation (AF) with CHA2DS2-VASc ≥2 stroke risk score
   5. History of any stroke
   6. Documented peripheral arterial disease (PAD) (i.e., peripheral revascularization of the iliac, infra-inguinal or carotid arteries; limb or foot amputation for arterial vascular disease; or ≥50% carotid or peripheral artery stenosis)

Exclusion Criteria:

1. Hospital admission for HF, myocardial infarction, stroke or coronary revascularization within 30 days of randomization
2. Percutaneous coronary intervention with a drug eluting stent within 90 days of randomization.
3. Pregnancy
4. Contraindication to bariatric surgery
5. Prior bariatric surgery, other than gastric banding
6. Life expectancy <2 years from non-cardiovascular causes
7. Inability to provide informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Medical Weight Management; MWM corresponds to standard medical practice for weight loss that is available at the local participating centre, and thus reflects the local standard of care. MWM will typically consist of dietary, lifestyle and/or behavioral modification counseling, which may include nutritional counseling, safe weight management and/or making healthy lifestyle changes. MWM may also include the implementation of a low caloric diet, which may comprise the use of adjuvant meal replacements and/or anti-obesity mediations at the discretion of the treating physician and according to local practice guidelines.	Behavioral: Medical Weight Management; The current standard medical practice for weight loss that is available at the local participating centre, reflecting the local standard of care
Experimental: Bariatric Surgery; The bariatric surgery procedures performed in BRAVE include either gastric bypass, sleeve gastrectomy, or duodenal switch, performed at the discretion of the surgeon and according to local practice standards. Sleeve gastrectomy will be performed as a stand-alone procedure, but may also be performed as part of a planned duodenal switch. Gastric banding is not permitted. Patients may receive a low fat, high protein meal replacement preceding surgery to reduce the size of the liver. Perioperative use of aspirin, thienopyridines (clopidogrel, ticagrelor or prasugrel), and anti-thrombotic therapy (compression stockings and subcutaneous heparin) should follow local guidelines and will be left at the discretion of the individual surgeons. .	Procedure: Bariatric Surgery; Bariatric surgery involves either gastric bypass, sleeve gastrectomy, or duodenal switch, performed at the discretion of the surgeon and according to local practice standards.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiovascular Outcomes	Composite of cardiovascular mortality, myocardial infarction (MI), stroke, and hospitalization for heart failure (HF).	Through study completion, expected average of 6 years
BRAVE-Mind Sub-study Measures	Depressive symptoms asessed with the Patient Health Questionnaire-8 (PHQ-8); Global cognitive function assessed with the Montreal Cognitive Assessment (MoCA)Secondary Outcome Measures:; Executive function and processing speed assessed with the Number Symbol Coding Task (NSCT); Functional capacity assessed with the Standardized Assessment of Global Activities in the Elderly (SAGE); Anxiety symptoms assessed with the Generalized Anxiety Disorder-7 (GAD-7); Nonnormative eating symptoms assessed with the Loss of Control Over Eating-Brief (LOCES-B)	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause mortality		Through study completion, expected average of 6 years
Cardiovascular mortality		Through study completion, expected average of 6 years
Myocardial infarction		Through study completion, expected average of 6 years
Stroke		Through study completion, expected average of 6 years
Hospitalization for heart failure		Through study completion, expected average of 6 years
New onset or remission of type 2 diabetes as per Diabetes Canada / American Diabetes Association Guidelines		Through study completion, expected average of 6 years
New onset atrial fibrillation as assessed by ECG or heart rhythm monitoring		Through study completion, expected average of 6 years
Cost effectiveness analysis, measured in quality adjusted life years	Economic evaluation to compare the costs and health outcomes associated with bariatric surgery and medical weight management	Through study completion, expected average of 6 years

Other Outcome Measures

Outcome Measure	Time Frame
Change in quality of life assessed by EQ5D questionnaire	Through study completion, expected average of 6 years
Change in quality of life assessed by Laval questionnaire	Through study completion, expected average of 6 years
Change in weight	Through study completion, expected average of 6 years
Number of hospital admissions irrespective of cause	Through study completion, expected average of 6 years
Number of participants with a new cancer diagnosis	Through study completion, expected average of 6 years

Collaborators and Investigators

• Sponsor: Population Health Research Institute
• Investigators: Principal Investigator: Salim Yusuf, DPhil, DSc (Oxon), FRCPC, FRSC, Population Health Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): November 2, 2020
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027

Study Registration Dates

• First Submitted: June 13, 2022
• First Submitted That Met QC Criteria: September 4, 2022
• First Posted (Actual): September 8, 2022

Study Record Updates

• Last Update Posted (Actual): May 28, 2026
• Last Update Submitted That Met QC Criteria: May 25, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Therapeutics; Surgical Procedures, Operative; Bariatrics; Obesity Management; Bariatric Surgery
• Other Study ID Numbers: BRAVE-Full Trial

Drug and device information, study documents

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