Bariatric Surgery for Cardiovascular Complications

(BRAVE Trial)

Overseen By Sumathy Rangarajan, MSc

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Population Health Research Institute

Disqualifiers: Recent heart events, Pregnancy, Prior bariatric, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 6 years

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether bariatric surgery (also known as weight loss surgery) can better prevent major heart problems in people with severe obesity (BMI of 30 or more) and serious heart issues compared to usual medical weight management. Researchers will also examine how the surgery might affect mental health and other health markers. The trial includes two groups: one receiving bariatric surgery and the other following a medical weight management program, which involves lifestyle and diet changes. It suits those who are significantly overweight and at high risk of heart disease, such as individuals with a history of heart attacks or strokes. As an unphased trial, this study provides a unique opportunity to contribute to groundbreaking research that could enhance heart health strategies for those with severe obesity.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that weight-loss surgeries like gastric bypass and sleeve gastrectomy have been performed for many years and are usually well-tolerated. Studies have found that these surgeries can help reduce obesity and related health problems. However, they carry some risks. For instance, the chance of death from gastric bypass and sleeve gastrectomy is about 0.5%. More complex surgeries, such as the duodenal switch, have a slightly higher risk of about 1%.

Although these numbers might seem low, it's important to remember that all surgeries involve risks, such as infection, blood clots, or anesthesia issues. Many individuals undergo these surgeries safely and experience significant health improvements afterward. It is crucial to discuss the possible risks and benefits with healthcare providers to determine if this option is suitable. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these treatments because they offer distinct approaches to managing cardiovascular complications linked to obesity. Unlike standard medical weight management, which typically involves dietary and lifestyle changes, bariatric surgery provides a more direct intervention by physically altering the digestive system. This can lead to more significant and rapid weight loss, potentially reducing cardiovascular risks more effectively. The surgical options, such as gastric bypass or sleeve gastrectomy, are tailored to the individual's needs and can lead to long-term health improvements. This dual approach of surgery and medical weight management offers a comprehensive strategy that could lead to better outcomes for patients struggling with obesity-related heart issues.

What evidence suggests that bariatric surgery might be an effective treatment for cardiovascular complications?

This trial will compare Bariatric Surgery with Medical Weight Management for cardiovascular complications. Studies have shown that weight loss surgeries, such as gastric bypass and sleeve gastrectomy, effectively aid weight loss and improve health in individuals with severe obesity. Research indicates that these surgeries result in greater weight loss than diet and lifestyle changes alone. For some, weight loss surgery also reduces the risk of heart problems. Long-term studies have found that these surgeries lead to better weight loss and improved metabolism, which affects how the body uses food and energy. However, these surgeries may involve more complications than non-surgical methods, so it's important to consider both the benefits and risks. ^{1 2 6 7 8}

Who Is on the Research Team?

Salim Yusuf, DPhil, DSc (Oxon), FRCPC, FRSC

Principal Investigator

Population Health Research Institute

Are You a Good Fit for This Trial?

This trial is for adults with severe obesity (BMI ≥35 kg/m2) and high-risk cardiovascular disease, including heart failure, stroke history, or peripheral arterial disease. Candidates must not have had recent hospital admissions for heart issues or bariatric surgery (except gastric banding), be pregnant, or unable to consent.

Inclusion Criteria

I have had surgery or amputation due to poor blood flow in my limbs or have significant narrowing of my arteries.

Body mass index ≥35 kg/m2

I have had a stroke before.

Exclusion Criteria

I cannot have weight loss surgery due to health risks.

Life expectancy <2 years from non-cardiovascular causes

Inability to provide informed consent

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo either bariatric surgery or medical weight management to reduce cardiovascular events

6 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 years

What Are the Treatments Tested in This Trial?

Interventions

• Bariatric Surgery
• Medical Weight Management

Trial Overview The study compares the effectiveness of bariatric surgery versus medical weight management in reducing major cardiovascular events in severely obese patients with high-risk CVD. It also assesses the cost-effectiveness and impact on mental health and cardiac function.

How Is the Trial Designed?

Group I: Bariatric Surgery Experimental Treatment 1 Intervention

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. .

Group II: Medical Weight Management Active Control 1 Intervention

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.

Bariatric Surgery is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Bariatric Surgery for:

• Severe obesity (BMI ≥35 kg/m2) with comorbidities
• Type 2 diabetes
• Hypertension
• Sleep apnea
• High-risk cardiovascular disease

Approved in United States as Bariatric Surgery for:

• Severe obesity (BMI ≥35 kg/m2) with comorbidities
• Type 2 diabetes
• Hypertension
• Sleep apnea
• High-risk cardiovascular disease

Approved in Canada as Bariatric Surgery for:

• Severe obesity (BMI ≥35 kg/m2) with comorbidities
• Type 2 diabetes
• Hypertension
• Sleep apnea
• High-risk cardiovascular disease

Who Is Running the Clinical Trial?

Population Health Research Institute

Lead Sponsor

Trials

165

Recruited

717,000+

Published Research Related to This Trial

Duodenal switch (DS) surgery can be effective for weight loss in super obese patients, but it carries significant risks, including complications like duodenal stump blowout, which can lead to severe postoperative issues such as bleeding and abdominal pain.

Early diagnosis and appropriate management of duodenal stump leaks are crucial, involving stabilization of the patient and surgical repair, to prevent serious complications following the DS procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Duodenal stump leak following a duodenal switch: A case report. Nelson, L., Moon, RC., Teixeira, AF., et al.[2020]

Bariatric surgery is the most effective long-term treatment for significant weight loss and improving related health issues, such as comorbidities and quality of life, as well as reducing mortality in patients with severe obesity.

While bariatric surgery offers substantial benefits, it also carries risks of immediate and long-term complications, including surgical, nutritional, and psychological issues, highlighting the importance of proper patient preparation and follow-up care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Obesity surgery and its adverse effects]. Ciangura, C., Corigliano, N.[2016]

Bariatric surgery is effective for significant weight loss and improving obesity-related health issues in medically complicated obese patients, highlighting its growing role in treatment.

The article reviews the short- and long-term gastrointestinal complications associated with the four most common bariatric procedures, providing important insights into their safety profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gastrointestinal Complications After Bariatric Surgery. Ma, IT., Madura, JA.[2022]

In a study of 780 patients undergoing laparoscopic bariatric surgery, laparoscopic adjustable gastric banding (LAGB) had the lowest overall complication rate at 9%, compared to 23% for Roux-en-Y gastric bypass (RYGB) and 25% for biliopancreatic diversion with duodenal switch (BPD+/-DS).

LAGB also showed significantly lower rates of severe complications (grades III and IV) at 0.2%, compared to 2% for RYGB and 5% for BPD+/-DS, making it the safest option among the procedures evaluated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Objective comparison of complications resulting from laparoscopic bariatric procedures. Parikh, MS., Laker, S., Weiner, M., et al.[2006]

Surgical methods, particularly vertical banded gastroplasty and Roux-Y gastric bypass, are currently the most effective treatments for severe obesity, as nonsurgical methods often fail to achieve significant long-term weight loss.

The success of these surgeries relies more on patient motivation and behavior than on the technical aspects of the procedures, suggesting that psychological support and lifestyle changes are crucial for achieving and maintaining weight loss.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overview of surgical techniques for treating obesity. Kral, JG.[2018]

In a study of 310 bariatric surgery patients aged 50 and older, 23% had elevated NT-proBNP levels, indicating potential cardiovascular issues that warranted further cardiac evaluation.

Among those with elevated NT-proBNP, 37% showed echocardiographic signs of heart remodeling, highlighting the importance of NT-proBNP as a potential screening tool for cardiovascular risk in older patients undergoing bariatric surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative cardiac screening using NT-proBNP in obese patients 50 years and older undergoing bariatric surgery: a study of 310 consecutive patients. van Veldhuisen, SL., van Woerden, G., Hemels, MEW., et al.[2022]

Bariatric surgery is the most effective long-term treatment for morbid obesity, indicated for patients with a BMI over 40 or over 35 with related health issues, and requires a multidisciplinary approach for optimal outcomes.

While laparoscopic techniques improve recovery, patients face risks of both early complications like thrombo-embolism and late complications such as vitamin deficiencies and bowel obstructions, highlighting the need for careful management and awareness of potential issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Bariatric surgery: surgical techniques and their complications]. Thereaux, J., Veyrie, N., Corigliano, N., et al.[2016]

Bariatric surgery, specifically Roux en-Y Gastric Bypass (RYGB), leads to significant long-term weight loss and improves insulin sensitivity and metabolic health in obese individuals, as shown by various assessments including body composition and insulin sensitivity tests.

The study found that changes in fat cell size and morphology after RYGB are linked to improved metabolic profiles, suggesting that targeting fat cell size reduction could be a future strategy for enhancing insulin sensitivity in obesity treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The 2020 ESPEN Arvid Wretlind lecture: Metabolic response in bariatric surgery - Mechanisms and clinical implications. Thorell, A.[2021]

Bariatric surgery, specifically biliopancreatic diversion with duodenal switch, effectively reduces excess body weight and improves metabolic and cardiovascular health in severely obese patients, as demonstrated in a case study of a 56-year-old man who lost 40% of his body weight after the procedure.

The surgery led to significant improvements in the patient's lipid profile, better control of hypertension and diabetes, and enhanced heart function, indicating substantial metabolic and cardiovascular benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabolic and cardiovascular improvements after biliopancreatic diversion in a severely obese patient. Woods, P., Paquette, C., Martin, J., et al.[2018]

Bariatric procedures have become increasingly popular for achieving significant and lasting weight loss, addressing obesity and its related health issues.

This report highlights two specific cases of serious cardiovascular complications (aortic dissection and aneurysm) that occurred in the late postoperative period following bariatric surgery, emphasizing the need for awareness of potential risks associated with these procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aortic complications after bariatric surgery. Gaia, DF., Palma, JH., Branco, JN., et al.[2022]

Biliopancreatic bypass with duodenal switch led to significant weight loss in patients, dropping from an average of 153.8 kg to 92.7 kg within one year, indicating its efficacy for treating morbid obesity.

However, the procedure is associated with a high risk of nutritional deficiencies and complications, particularly in patients with common channels shorter than 100 cm, suggesting that this surgery should be performed with caution.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Nutritional status after surgical treatment of obesity]. Tonstad, S., Sundfør, T., Myrvoll, EA.[2008]

Bariatric surgery, such as Roux-en-Y gastric bypass and biliopancreatic diversion, is effective for long-term weight loss and reducing health risks in morbidly obese individuals, but it can lead to serious nutritional complications that may require revisional surgery.

In a study of four patients who underwent revisional surgery due to complications, one patient died, highlighting that while revision surgery is rare, it carries increased risks and can involve different surgical approaches depending on the patient's condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Revisional surgery in severe nutritional complications after bariatric surgical procedures: report of four cases from a single institution and review of the literature. Braga, JGR., Concon, MM., Lima, AP., et al.[2021]

In a study of 617 patients who underwent Roux-en-Y gastric bypass, Medicare beneficiaries experienced similar long-term weight loss and comorbidity resolution as non-Medicare patients after 10 years, indicating the procedure's effectiveness across different insurance statuses.

Despite Medicare patients being older and having a higher preoperative body mass index, their outcomes were equivalent to those of non-Medicare patients, supporting the case for continued Medicare coverage of bariatric surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ten-year outcomes of Roux-en-Y gastric bypass are equivalent in patients with Medicare disability and non-Medicare patients. Michaels, AD., Mehaffey, JH., Hawkins, RB., et al.[2019]

Citations

1. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2819400

Ten-Year Outcomes Following Roux-en-Y Gastric Bypass ... In this randomized clinical trial, BMI reduction was greater after DS, but RYGB had a better risk profile over 10 years.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11148687/

Ten-Year Outcomes Following Roux-en-Y Gastric Bypass ... This randomized clinical trial compares 10-year outcomes of Roux-en-Y-gastric bypass and duodenal switch surgery among patients with severe obesity.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10514119/

Long-term Follow-up 15 Years After Duodenal Switch or ... In conclusion, we could verify that BPD/DS results in superior weight loss and metabolic control, at the cost of more complications, when ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1550728911004886

Comparative early outcomes of three laparoscopic bariatric ... Although no fatal outcomes occurred after SG, this procedure did not demonstrate a reduced risk of postoperative complications compared with RYGB with a ...

5. asmbs.org asmbs.org/patients/bariatric-surgery-procedures/

Bariatric Surgery Procedures The goal of these operations is to modify the stomach and intestines to treat obesity and related diseases.

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0039606012003741

Benefits and complications of the duodenal switch ... Benefits and complications of the duodenal switch/biliopancreatic diversion compared to the Roux-en-Y gastric bypass - ScienceDirect.

7. mayoclinic.org mayoclinic.org/tests-procedures/biliopancreatic-diversion-with-duodenal-switch/about/pac-20385180

Biliopancreatic diversion with duodenal switch (BPD/DS) Learn about a two-part weight-loss procedure that involves making the stomach smaller and reconnecting parts of the small intestine.

8. ahajournals.org ahajournals.org/doi/10.1161/cir.0b013e3182149099

Bariatric Surgery and Cardiovascular Risk Factors Gastric bypass and sleeve gastrectomy mortality is 0.5%, and malabsorptive operations tend to carry a higher average mortality rate of 1%. More ...