CSP #2026 - Beta Blocker Dialyzability on Cardiovascular Outcomes

End-Stage Renal Disease Clinical Trial

— BRAVO  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05931276
• Other study ID #: 2026
• Status: Recruiting
• Phase: Phase 3
• Start date: May 22, 2024
• Est. completion date: December 31, 2027

Study information

• Verified date: May 2024
• Source: VA Office of Research and Development
• Contact: Jade Fiotto
• Phone: (617) 232-9500
• Email: Jade.Fiotto[@]va.gov
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 2540
• Est. completion date: December 31, 2027
• Est. primary completion date: November 3, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Eligible patients are those (including men, women and minorities)

• On hemodialysis

• Received one of the following beta blockers through the VA pharmacy prescribed by a VA provider: metoprolol (succinate or tartrate), atenolol, labetalol, carvedilol, bisoprolol, nadolol, pindolol, nebivolol

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

Related Conditions & MeSH terms

• End-Stage Kidney Disease
• End-Stage Renal Disease
• Kidney Diseases
• Kidney Failure, Chronic

Intervention

Drug:
• Metoprolol Succinate
a dialyzable, beta-1 selective beta blocker
• Carvedilol
a non-dialyzable, non-selective beta blocker with alpha-1 antagonist properties

Locations

Country	Name	City	State
United States	VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA	Boston	Massachusetts
United States	Minneapolis VA Health Care System, Minneapolis, MN	Minneapolis	Minnesota
United States	VA NY Harbor Healthcare System, New York, NY	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
VA Office of Research and Development

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	All-cause hospitalization	All-cause hospitalization	Randomization to time to event; average follow-up 3 years
Other	ED visit or hospitalization possibly related to low BP including falls, fractures, hypotension, or serious injury	Number of emergency department visits or hospitalization for events that may be a consequence of low blood pressure or beta blocker excess or withdrawal including falls, fractures, hypotension, or serious injury	Number of events; average follow-up 3 years
Other	Use of BP raising medications	Use and dose of midodrine	Use of drug; average follow-up 3 years
Other	ED or hospital visits for atrial fibrillation and uncontrolled rate	Emergency department visit or hospitalization for atrial fibrillation with uncontrolled rate (to capture poor control with beta blocker withdrawal)	Randomization to time to event; average follow-up 3 yars
Primary	Time 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	Randomization to time to event; average follow-up 3 years
Secondary	Non-fatal myocardial infarction	Non-fatal myocardial infarction	Randomization to time to event; average follow-up 3 years
Secondary	Non-fatal stroke	Non-fatal stroke	Randomization to time to event; average follow-up 3 years
Secondary	Hospitalization for heart failure	Hospitalization for heart failure	Randomization to time to event; average follow-up 3 years
Secondary	All-cause mortality	All-cause mortality	Randomization to time to event; average follow-up 3 years