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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Metoprolol Succinate | Active Comparator | Depending on baseline type and dose of beta blocker:
|
|
| Carvedilol | Active Comparator | Depending on baseline type and dose of beta blocker:
|
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Metoprolol Succinate | Drug | a dialyzable, beta-1 selective beta blocker |
| |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Non-fatal myocardial infarction | Non-fatal myocardial infarction | Randomization to time to event; average follow-up 3 years |
| Non-fatal stroke | Non-fatal stroke |
| Measure | Description | Time Frame |
|---|---|---|
| All-cause hospitalization | All-cause hospitalization | Randomization to time to event; average follow-up 3 years |
| ED visit or hospitalization possibly related to low BP including falls, fractures, hypotension, or serious injury |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Christopher M Donnelly | Contact | Christopher.Donnelly2@va.gov | ||
| Jade Fiotto | Contact | (617) 232-9500 | Jade.Fiotto@va.gov |
| Name | Affiliation | Role |
|---|---|---|
| Areef Ishani, MD MS | Minneapolis VA Health Care System, Minneapolis, MN | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| VA Long Beach Healthcare System, Long Beach, CA | Recruiting | Long Beach | California | 90822 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38419159 | Derived | 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. |
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The study design is a multicenter clinically integrated prospective randomized open-label blinded-endpoint (PROBE) trial
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| Carvedilol |
| Drug |
a non-dialyzable, non-selective beta blocker with alpha-1 antagonist properties |
|
| Randomization to time to event; average follow-up 3 years |
| Hospitalization for heart failure | Hospitalization for heart failure | Randomization to time to event; average follow-up 3 years |
| All-cause mortality | All-cause mortality | Randomization to time to event; average follow-up 3 years |
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 |
| Use of BP raising medications | Use and dose of midodrine | Use of drug; average follow-up 3 years |
| 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 |
| North Florida/South Georgia Veterans Health System, Gainesville, FL | Recruiting | Gainesville | Florida | 32608-1135 | United States |
|
| Atlanta VA Medical and Rehab Center, Decatur, GA | Recruiting | Decatur | Georgia | 30033-4004 | United States |
|
| Iowa City VA Health Care System, Iowa City, IA | Recruiting | Iowa City | Iowa | 52246-2292 | United States |
|
| VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA | Not yet recruiting | Boston | Massachusetts | 02130-4817 | United States |
|
| Minneapolis VA Health Care System, Minneapolis, MN | Recruiting | Minneapolis | Minnesota | 55417-2309 | United States |
|
| Omaha VA Nebraska-Western Iowa Health Care System, Omaha, NE | Recruiting | Omaha | Nebraska | 68105-1850 | United States |
|
| New Mexico VA Health Care System, Albuquerque, NM | Recruiting | Albuquerque | New Mexico | 87108-5153 | United States |
|
| ID | Term |
|---|---|
| D007676 | Kidney Failure, Chronic |
| D002318 | Cardiovascular Diseases |
| ID | Term |
|---|---|
| D051436 | Renal Insufficiency, Chronic |
| D051437 | Renal Insufficiency |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D008790 | Metoprolol |
| D000077261 | Carvedilol |
| ID | Term |
|---|---|
| D050198 | Phenoxypropanolamines |
| D011412 | Propanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
| D020005 | Propanols |
| D000588 | Amines |
| D002227 | Carbazoles |
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D006575 | Heterocyclic Compounds, 3-Ring |
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