Bariatric Surgery for the Reduction of cArdioVascular Events Feasibility Trial

Cardiovascular Diseases Clinical Trial

— BRAVE  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04226664
• Other study ID #: 8047
• Status: Recruiting
• Phase: N/A
• Start date: October 30, 2020
• Est. completion date: May 2023

Study information

• Verified date: March 2022
• Source: Hamilton Health Sciences Corporation
• Contact: Tara McCready, PhD, MBA
• Phone: 905-521-2100
• Email: tara.mccready[@]phri.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: May 2023
• Est. primary completion date: February 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cardiovascular Diseases
• Obesity, Morbid

Intervention

Procedure:
• Bariatric surgery
Although there may be slight variation by centre, Gastric Bypass generally involves creation of a 30-50 cc stomach pouch, which is anastamosed with a Roux limb of jejunum 75-100 cm in length and a biliary limb of 20-30 cm in length. The operation creates a small gastric pouch, with nutrients bypassing the duodenum and proximal jejunum. Sleeve Gastrectomy involves decreasing the size of the stomach to approximately 15% of its original size by resecting a large portion of the stomach along the greater curvature.

Locations

Country	Name	City	State
Canada	St. Joseph's Healthcare Hamilton	Hamilton	Ontario

Sponsors (3)

Lead Sponsor	Collaborator
Hamilton Health Sciences Corporation	Population Health Research Institute, St. Joseph's Healthcare Hamilton

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Recruitment rate	Recruitment rate (target of 60 patients over 24 months or 1.25 patients per centre per month)	24 months (or when recruitment is complete)
Primary	Time to intervention administration	Target of bariatric surgery performed within 30 days of randomization in >80%	30 days
Primary	Crossover rate	Crossover rate between control and intervention arm	At study completion (an average of 1.5 years follow-up)
Secondary	Change in weight at 1 year	Change in weight in kilograms at 1 year	12 months
Secondary	Change in BMI at 1 year	BMI (kg/m^2) will be calculated using weight in kg at 1 year, and height	12 months
Secondary	Composite outcome of cardiovascular mortality, myocardial infarction (MI), stroke and hospitalization for heart failure (HF)	Composite outcome of cardiovascular mortality, myocardial infarction, stroke and hospitalization for heart failure	12 months, and through study completion (an average of 1.5 years follow-up)
Secondary	Change in percent excess weight loss (%) at 1 year	Excess weight loss is a standard outcome measure in obesity research. It is calculated as the percentage of excess body weight lost after surgery. Excess body weight (kg) is calculated as current weight (kg) minus ideal body weight (kg) for a given height. Ideal body weight (kg) is taken from standardized tables.	12 months
Secondary	Change in New York Heart Association (NYHA) Functional Classification at 1 year	NYHA Class is a standardized classification system for severity of heart failure symptoms, and ranges from class I to class IV, with IV being the most severe symptoms and class.	12 months
Secondary	Change in 6-minute walk test distance (m) at 1 year	The 6 Minute Walk Test is an exercise test used to assess aerobic capacity and endurance. The distance covered over a time of 6 minutes is used as the outcome. Longer distances indicate better performance.	12 months
Secondary	Change in 36-Item Short Form Survey (SF-36) questionnaire score at 1 year	The SF-36 is a measure of health-related quality-of-life. It includes eight health domains: physical functioning (10 items), bodily pain (2 items), role limitations due to physical health problems (4 items), role limitations due to personal or emotional problems (4 items), emotional well-being (5 items), social functioning (2 items), energy/fatigue (4 items), and general health perceptions (5 items). Scores for each domain range from 0 to 100, with a higher score defining a more favorable health state.	12 months
Secondary	Change in EuroQuol (EQ-5D-5L) quality of life questionnaire score at 1 year	EQ-5D-5L is a standardized instrument for measuring health status, which includes a descriptive system asking about 5 health dimensions as well as an evaluation of overall health status with a visual analogue scale. The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels from which respondents choose one response: no problems, slight problems, moderate problems, severe problems and extreme problems. The visual analogue scale asks individuals to mark their health status on the day of the interview on a 20 cm vertical scale with end points of 0 and 100. Zero corresponds to " the worst health you can imagine", and 100 corresponds to "the best health you can imagine".	12 months
Secondary	Number of participants with new onset Atrial Fibrillation (AF) at 1 year	Will determine the number of participants who receive a new clinical diagnosis of AF during the study follow-up.	12 months, and through study completion (an average of 1.5 years follow-up)

External Links

•   Population Health Research Institute
•   St. Joseph's Heathcare Hamilton Bariatric Surgery Program