CSP #2026 - Beta Blocker Dialyzability on Cardiovascular Outcomes (BRAVO)

VA Office of Research and Development

Status and phase: Enrolling; Phase 3

Conditions: End-Stage Renal Disease; End-Stage Kidney Disease

Treatments: Drug: Metoprolol Succinate; Drug: Carvedilol

Study type: Interventional

Funder types: Other U.S. Federal agency

Identifiers

NCT05931276

2026

Details and patient eligibility

About

The investigators aim to determine, using a point-of-care randomized controlled trial design, if hemodialysis patients, who are randomized to metoprolol succinate (a dialyzable, beta-1 selective beta blocker), have an improved cardiovascular outcome compared to those randomized to carvedilol (a non-dialyzable, non-selective beta blocker with alpha-1 antagonist properties). The investigators will also examine intervention practices to identify components that best support engagement and sustainability.

Full description

Approximately 35,000 Veterans have end stage kidney disease (ESKD) with an incidence of 13,000 annually. These numbers are increasing because of the epidemic of diabetes, the most common cause of ESKD, among the Veteran population. Patients with ESKD on hemodialysis have substantial cardiovascular morbidity. Veterans annual mortality is in excess of 15% and more than half the deaths are due to cardiovascular disease. Beta blockers have been shown to prevent cardiovascular events in randomized clinical trials in patients without chronic kidney disease, particularly those with heart failure and after myocardial infarction. Beta blockers are a mainstay of therapy in dialysis patients, with two-thirds of Veterans on dialysis receiving a beta blocker. There are no head-to-head randomized studies comparing the two most commonly used beta blockers in ESKD patients in the United States, metoprolol and carvedilol, but observational studies suggest superior outcomes for patients treated with metoprolol. The identification of the superior beta blocker may significantly improve the morbidity and mortality of the VA dialysis population.

The investigators aim to compare two beta blockers with similar indications, usage and availability within the VA but with major differences in patients dialysis clearance and adrenergic effects. The investigators aim to determine if patients undergoing dialysis have improved survival when using metoprolol succinate, a beta blocker that is removed by dialysis and is beta-1 selective, compared to carvedilol, a beta blocker that is not removed by dialysis and is not beta-selective and is also an alpha-blocker.

Enrollment: 2,540 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• On hemodialysis
• Received one of the following beta blockers through the VA pharmacy: metoprolol (succinate or tartrate), atenolol, labetalol, carvedilol, bisoprolol

Exclusion criteria

• Impaired decision-making capacity
• Patients not receiving carvedilol who have a history of asthma
• known hypersensitivity to any component of either drug
• Provider unwilling to sign a new medication order for a randomized patient
• No surrogate consent will be allowed

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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2,540 participants in 2 patient groups

Metoprolol Succinate

Active Comparator group

Description:

Depending on baseline type and dose of beta blocker: * 25 mg once daily (12.5 mg once daily if \> NYHA class II) * 50 mg (or 25 mg) once daily * 100 mg (or 50 mg) once daily * 200 mg (or 100 mg titrated to 200 mg) once daily

Treatment:

Drug: Metoprolol Succinate

Carvedilol

Active Comparator group

Description:

Depending on baseline type and dose of beta blocker: * 3.125 mg twice daily * 6.25 mg twice daily * 12.5 mg twice daily * 25 mg twice daily (may titrate to 5 0mg twice daily if \> 85 kg)

Treatment:

Drug: Carvedilol