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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
2,540
a dialyzable, beta-1 selective beta blocker
a non-dialyzable, non-selective beta blocker with alpha-1 antagonist properties
VA Long Beach Healthcare System, Long Beach, CA
Long Beach, California, United States
RECRUITINGNorth Florida/South Georgia Veterans Health System, Gainesville, FL
Gainesville, Florida, United States
RECRUITINGAtlanta VA Medical and Rehab Center, Decatur, GA
Decatur, Georgia, United States
RECRUITINGIowa City VA Health Care System, Iowa City, IA
Iowa City, Iowa, United States
RECRUITINGVA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA
Boston, Massachusetts, United States
NOT_YET_RECRUITINGMinneapolis VA Health Care System, Minneapolis, MN
Minneapolis, Minnesota, United States
RECRUITINGOmaha VA Nebraska-Western Iowa Health Care System, Omaha, NE
Omaha, Nebraska, United States
RECRUITINGNew Mexico VA Health Care System, Albuquerque, NM
Albuquerque, New Mexico, United States
RECRUITINGTime to major cardiovascular event
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
Time frame: Randomization to time to event; average follow-up 3 years
Non-fatal myocardial infarction
Non-fatal myocardial infarction
Time frame: Randomization to time to event; average follow-up 3 years
Non-fatal stroke
Non-fatal stroke
Time frame: Randomization to time to event; average follow-up 3 years
Hospitalization for heart failure
Hospitalization for heart failure
Time frame: Randomization to time to event; average follow-up 3 years
All-cause mortality
All-cause mortality
Time frame: Randomization to time to event; average follow-up 3 years
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