CSP #2026 - Beta Blocker Dialyzability on Cardiovascular Outcomes

NCT ID: NCT05931276

Last Updated: 2026-01-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

2540 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-05-22

Study Completion Date

2028-12-31

Brief Summary

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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

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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.

Conditions

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End-Stage Kidney Disease End-Stage Renal Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

The study design is a multicenter clinically integrated prospective randomized open-label blinded-endpoint (PROBE) trial
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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

Group Type ACTIVE_COMPARATOR

Metoprolol Succinate

Intervention Type DRUG

a dialyzable, beta-1 selective beta blocker

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)

Group Type ACTIVE_COMPARATOR

Carvedilol

Intervention Type DRUG

a non-dialyzable, non-selective beta blocker with alpha-1 antagonist properties

Interventions

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Metoprolol Succinate

a dialyzable, beta-1 selective beta blocker

Intervention Type DRUG

Carvedilol

a non-dialyzable, non-selective beta blocker with alpha-1 antagonist properties

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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VA Office of Research and Development

FED

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Areef Ishani, MD MS

Role: STUDY_CHAIR

Minneapolis VA Health Care System, Minneapolis, MN

Locations

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VA Long Beach Healthcare System, Long Beach, CA

Long Beach, California, United States

Site Status RECRUITING

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

Gainesville, Florida, United States

Site Status RECRUITING

Atlanta VA Medical and Rehab Center, Decatur, GA

Decatur, Georgia, United States

Site Status RECRUITING

Iowa City VA Health Care System, Iowa City, IA

Iowa City, Iowa, United States

Site Status RECRUITING

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

Boston, Massachusetts, United States

Site Status NOT_YET_RECRUITING

Minneapolis VA Health Care System, Minneapolis, MN

Minneapolis, Minnesota, United States

Site Status RECRUITING

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

Omaha, Nebraska, United States

Site Status RECRUITING

New Mexico VA Health Care System, Albuquerque, NM

Albuquerque, New Mexico, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Christopher M Donnelly

Role: CONTACT

Jade Fiotto

Role: CONTACT

(617) 232-9500

Facility Contacts

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Srihari Raju, MD

Role: primary

Srihari Raju, MD

Role: primary

Srihari Raju, MD

Role: primary

Srihari Raju, MD

Role: primary

Jade Fiotto, MPH

Role: primary

617-232-9500

Areef Ishani, MD MS

Role: primary

612-467-4431 ext. 314431

Srihari Raju, MD

Role: primary

Srihari Raju, MD

Role: primary

References

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Leatherman SM, Ishani A. Point-of-Care Clinical Trials in Nephrology. J Am Soc Nephrol. 2024 Jun 1;35(6):812-814. doi: 10.1681/ASN.0000000000000340. Epub 2024 Feb 29. No abstract available.

Reference Type DERIVED
PMID: 38419159 (View on PubMed)

Other Identifiers

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2026

Identifier Type: -

Identifier Source: org_study_id

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