Clinical trial NCT05931276: CSP #2026 - Beta Blocker Dialyzability on Cardiovascular Outcomes
Official title: CSP #2026 - Beta Blocker Dialyzability on Cardiovascular Outcomes (BRAVO)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: End-Stage Kidney Disease
End-Stage Renal Disease
Keywords: Dialysis
beta-Blockers, Adrenergic
Cardiovascular Diseases
Point of Care Research
Comparative Effectiveness Research
Metoprolol Succinate
Carvedilol
Hemodialysis
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
First posted: 2023-07-05
Enrollment: 2540
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The study design is a multicenter clinically integrated prospective randomized open-label blinded-endpoint (PROBE) trial
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* 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

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

Primary outcomes:
measure: Time to major cardiovascular event
timeFrame: Randomization to time to event; average follow-up 3 years
Secondary outcomes:
measure: Non-fatal myocardial infarction
timeFrame: Randomization to time to event; average follow-up 3 years
measure: Non-fatal stroke
timeFrame: Randomization to time to event; average follow-up 3 years
measure: Hospitalization for heart failure
timeFrame: Randomization to time to event; average follow-up 3 years
measure: All-cause mortality
timeFrame: Randomization to time to event; average follow-up 3 years
Other outcomes:
measure: All-cause hospitalization
timeFrame: Randomization to time to event; average follow-up 3 years
measure: ED visit or hospitalization possibly related to low BP including falls, fractures, hypotension, or serious injury
timeFrame: Number of events; average follow-up 3 years
measure: Use of BP raising medications
timeFrame: Use of drug; average follow-up 3 years
measure: ED or hospital visits for atrial fibrillation and uncontrolled rate
timeFrame: Randomization to time to event; average follow-up 3 yars
Locations:
city: Boston
country: United States
facility: VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA
state: Massachusetts
city: Minneapolis
country: United States
facility: Minneapolis VA Health Care System, Minneapolis, MN
state: Minnesota
city: New York
country: United States
facility: VA NY Harbor Healthcare System, New York, NY
state: New York
Study officials:
affiliation: Minneapolis VA Health Care System, Minneapolis, MN
name: Areef Ishani, MD MS
role: STUDY_CHAIR
affiliation: VA NY Harbor Healthcare System, New York, NY
name: James S Kaufman, MD
role: STUDY_CHAIR
References: