CSP #2026 - Beta Blocker Dialyzability on Cardiovascular Outcomes
- Conditions
- End-Stage Renal DiseaseEnd-Stage Kidney Disease
- Interventions
- Registration Number
- NCT05931276
- Lead Sponsor
- VA Office of Research and Development
- Brief 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 2540
- Eligible patients are those (including men, women and minorities)
- On hemodialysis
- Received one of the following beta blockers through the VA pharmacy: metoprolol (succinate or tartrate), atenolol, labetalol, carvedilol, bisoprolol
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Metoprolol Succinate Metoprolol Succinate 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 Carvedilol Carvedilol 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)
- Primary Outcome Measures
Name Time Method Time to major cardiovascular event Randomization to time to event; average follow-up 3 years The Primary outcome measure will be time to a non-fatal adverse cardiovascular event, defined as a composite outcome comprised of the first occurrence after randomization of any of the following: myocardial infarction, stroke, or hospitalization for heart failure, and all-cause mortality
- Secondary Outcome Measures
Name Time Method Non-fatal stroke Randomization to time to event; average follow-up 3 years Non-fatal stroke
Hospitalization for heart failure Randomization to time to event; average follow-up 3 years Hospitalization for heart failure
Non-fatal myocardial infarction Randomization to time to event; average follow-up 3 years Non-fatal myocardial infarction
All-cause mortality Randomization to time to event; average follow-up 3 years All-cause mortality
Trial Locations
- Locations (3)
Minneapolis VA Health Care System, Minneapolis, MN
🇺🇸Minneapolis, Minnesota, United States
VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA
🇺🇸Boston, Massachusetts, United States
VA NY Harbor Healthcare System, New York, NY
🇺🇸New York, New York, United States