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NCT05931276PHASE3Recruiting

CSP #2026 - Beta Blocker Dialyzability on Cardiovascular Outcomes

VA Office of Research and Development

Start Date

5/22/2024

Completion Date

12/31/2028

Summary

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.

Detailed 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.

Eligibility Criteria

Age Range: 18 years to No maximum

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

Interventions

DRUG

Metoprolol Succinate

DRUG

Carvedilol

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Conditions

End-Stage Kidney DiseaseEnd-Stage Renal Disease

Locations

VA Long Beach Healthcare System, Long Beach, CA

Long Beach, California 90822

United States

North Florida/South Georgia Veterans Health System, Gainesville, FL

Gainesville, Florida 32608-1135

United States

Atlanta VA Medical and Rehab Center, Decatur, GA

Decatur, Georgia 30033-4004

United States

Iowa City VA Health Care System, Iowa City, IA

Iowa City, Iowa 52246-2292

United States

VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA

Boston, Massachusetts 02130-4817

United States

Minneapolis VA Health Care System, Minneapolis, MN

Minneapolis, Minnesota 55417-2309

United States

Omaha VA Nebraska-Western Iowa Health Care System, Omaha, NE

Omaha, Nebraska 68105-1850

United States

New Mexico VA Health Care System, Albuquerque, NM

Albuquerque, New Mexico 87108-5153

United States