Clinical trial NCT04226664: Bariatric Surgery for the Reduction of cArdioVascular Events Feasibility Trial
Official title: Bariatric Surgery for the Reduction of cArdioVascular Events Feasibility Randomized Controlled Trial (BRAVE)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Obesity, Morbid
Cardiovascular Diseases
Keywords: Bariatric Surgery
Lead sponsor: Hamilton Health Sciences Corporation
Sponsor class: OTHER
Collaborators: name: Population Health Research Institute
name: St. Joseph's Healthcare Hamilton
First posted: 2020-01-13
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Individuals who meet study eligibility criteria will be randomized in 1:1 fashion to bariatric surgery (intervention arm) or MWM (control arm).
Primary purpose: TREATMENT

Brief summary: Pilot multicentre, open-label, parallel-arm randomized controlled trial (RCT) of 60 patients to demonstrate the feasibility of enrolling patients with high-risk cardiovascular disease (CVD) into an RCT of bariatric surgery versus medical weight management (MWM).

Detailed description: STUDY OBJECTIVE The primary objective of this pilot study is to assess the feasibility of an RCT of bariatric surgery compared to MWM in patients with morbid obesity and high-risk CVD. If we can demonstrate that this trial is feasible, the next step would be to conduct a large-scale RCT to evaluate the efficacy of bariatric surgery for the reduction of cardiovascular complications in this patient population.

STUDY AIMS:

1. To demonstrate that enrolment of high-risk CVD patients into a bariatric surgery RCT is feasible.
2. To show that it is feasible to perform bariatric surgery in \>80% of patients in the intervention arm within 30 days of randomization.
3. To obtain preliminary information on the perioperative risks of bariatric surgery in patients with high-risk CVD.

STUDY HYPOTHESES Study enrollment will be feasible at a rate of at least 1.25 patients per centre per month. Timely delivery of the intervention is possible, with \>80% of patients undergoing bariatric surgery within 30 days of randomization. The rate of crossover between the control and intervention arms will be low at \<2.5% per year. 30-day mortality rates in the intervention group will be comparable to that of an age and gender matched cohort without CVD who had bariatric surgery at the 2 study sites during the study period.

DESIGN The present study is a multicentre, open-label, parallel-arm feasibility RCT with blinded endpoint assessment (PROBE design) of bariatric surgery compared to MWM in patients with morbid obesity and high-risk CVD.

Individuals who meet study eligibility criteria will be randomized in 1:1 fashion to bariatric surgery (intervention arm) or MWM (control arm). Bariatric surgery will consist of laparoscopic Roux-en-Y gastric bypass or sleeve gastrectomy, performed at the discretion of the surgeon and according to local standards.

Eligibility criteria: Inclusion Criteria:

1. Body mass index \>35 kg/m2
2. Age ≥18 years
3. High-risk CVD, defined as the presence of any one of the following:

   1. History of MI, multi-vessel percutaneous coronary intervention or multi-vessel coronary artery bypass grafting; OR
   2. Coronary artery disease (CAD) with documented stenoses ≥50% in 2 or more major coronary arteries; OR
   3. Symptomatic HF (New York Heart Association class ≥2) on optimal HF therapy for ≥3 months, AND documented HF hospitalization within the last 12 months, OR baseline N-terminal pro B-type natriuretic peptide (NT-pro BNP) \>400 pg/ml;44, 45 OR
   4. Documented AF with CHA2DS2-VASc stroke risk score (congestive heart failure/ left ventricular dysfunction, hypertension, age ≥ 75 years \[2 points\], diabetes, history of stroke/ transient ischemic attack \[2 points\], vascular disease, age 65-74 years and female sex) of ≥2; OR
   5. History of ischemic stroke; OR
   6. Peripheral artery disease, defined as prior aorto-femoral bypass surgery, limb bypass surgery, or percutaneous transluminal angioplasty revascularization of the iliac, infra-inguinal arteries or carotids; or limb or foot amputation for arterial vascular disease; or ≥50% carotid or peripheral artery stenosis
4. Patient is deemed eligible to undergo bariatric surgery according to local practice guidelines

Exclusion Criteria:

1. Hospital admission for HF within 30 days of enrolment
2. Myocardial infarction, stroke or coronary revascularization in prior 30 days.
3. Percutaneous coronary intervention with a drug eluting stent in prior 90 days.
4. Pregnancy
5. Contraindication to bariatric surgery (atrophic gastritis, diabetes mellitus type 1, prior laparotomy, liver cirrhosis with portal hypertension, uncontrolled drug or alcohol dependence, prior bariatric surgery, massive ventral hernia, severe chronic obstructive pulmonary disease)
6. Life expectancy \<2 years from non-cardiovascular causes.
7. Risk of general anesthesia deemed too excessive
8. Current drug or alcohol dependency (within 6 months of referral)
9. Recent major cancer (life threatening, within last 2 years)
10. Untreated or inadequately treated psychiatric illness
11. Inability to provide informed consent

Primary outcomes:
measure: Recruitment rate
timeFrame: 24 months (or when recruitment is complete)
measure: Time to intervention administration
timeFrame: 30 days
measure: Crossover rate
timeFrame: At study completion (an average of 1.5 years follow-up)
Secondary outcomes:
measure: Change in weight at 1 year
timeFrame: 12 months
measure: Change in BMI at 1 year
timeFrame: 12 months
measure: Composite outcome of cardiovascular mortality, myocardial infarction (MI), stroke and hospitalization for heart failure (HF)
timeFrame: 12 months, and through study completion (an average of 1.5 years follow-up)
measure: Change in percent excess weight loss (%) at 1 year
timeFrame: 12 months
measure: Change in New York Heart Association (NYHA) Functional Classification at 1 year
timeFrame: 12 months
measure: Change in 6-minute walk test distance (m) at 1 year
timeFrame: 12 months
measure: Change in 36-Item Short Form Survey (SF-36) questionnaire score at 1 year
timeFrame: 12 months
measure: Change in EuroQuol (EQ-5D-5L) quality of life questionnaire score at 1 year
timeFrame: 12 months
measure: Number of participants with new onset Atrial Fibrillation (AF) at 1 year
timeFrame: 12 months, and through study completion (an average of 1.5 years follow-up)
Other outcomes:
Locations:
city: Hamilton
country: Canada
facility: St. Joseph's Healthcare Hamilton
state: Ontario
Study officials:
affiliation: PHRI, Hamilton Health Sciences, McMaster University
name: Jorge Wong, MD MPH FRCPC
role: PRINCIPAL_INVESTIGATOR
affiliation: St. Joseph's Healthcare, McMaster University
name: Aristithes Doumouras, MD MPH FRCSC
role: PRINCIPAL_INVESTIGATOR
References: