Bariatric Surgery for the Reduction of cArdioVascular Events Randomized Controlled Trial

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate if, in patients with severe obesity (body mass index (BMI) ≥35 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, cardiac structure and function, genomics, proteomics and metabolomics.

Official Title
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Bariatric Surgery for the Reduction of cArdioVascular Events Randomized Controlled Trial

Conditions
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Cardiovascular Complication, Bariatric Surgery Candidate

Intervention / Treatment
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* Procedure: Bariatric Surgery
* Behavioral: Medical Weight Management


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body mass index ≥35 kg/m2 Age ≥18 years High-risk CVD, defined as the presence of any one of the following: 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) Left ventricular ejection fraction (LVEF) < 40% 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 Documented atrial fibrillation (AF) with CHA2DS2-VASc ≥2 stroke risk score History of any stroke 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: Hospital admission for HF, myocardial infarction, stroke or coronary revascularization within 30 days of randomization Percutaneous coronary intervention with a drug eluting stent within 90 days of randomization. Pregnancy Contraindication to bariatric surgery Prior bariatric surgery, other than gastric banding Life expectancy <2 years from non-cardiovascular causes Inability to provide informed consent

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Medical Weight Management<br>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<br>* The current standard medical practice for weight loss that is available at the local participating centre, reflecting the local standard of care<br>|
| Experimental: Bariatric Surgery<br>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<br>* Bariatric surgery involves either gastric bypass, sleeve gastrectomy, or duodenal switch, performed at the discretion of the surgeon and according to local practice standards.<br>|

What is the study measuring?
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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 | 

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 |