End-Stage Kidney Disease, End-Stage Renal Disease
Conditions
Keywords
Dialysis, beta-Blockers, Adrenergic, Cardiovascular Diseases, Point of Care Research, Comparative Effectiveness Research, Metoprolol Succinate, Carvedilol, Hemodialysis
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.
Interventions
DRUGMetoprolol Succinate
a dialyzable, beta-1 selective beta blocker
DRUGCarvedilol
a non-dialyzable, non-selective beta blocker with alpha-1 antagonist properties
Sponsors
VA Office of Research and Development
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
The study design is a multicenter clinically integrated prospective randomized open-label blinded-endpoint (PROBE) trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to major cardiovascular event | Randomization to time to event; average follow-up 3 years | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Non-fatal stroke | Randomization to time to event; average follow-up 3 years | Non-fatal stroke |
| Hospitalization for heart failure | Randomization to time to event; average follow-up 3 years | Hospitalization for heart failure |
| All-cause mortality | Randomization to time to event; average follow-up 3 years | All-cause mortality |
| Non-fatal myocardial infarction | Randomization to time to event; average follow-up 3 years | Non-fatal myocardial infarction |
Other
| Measure | Time frame | Description |
|---|---|---|
| ED visit or hospitalization possibly related to low BP including falls, fractures, hypotension, or serious injury | Number of events; 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 |
| Use of BP raising medications | Use of drug; average follow-up 3 years | Use and dose of midodrine |
| ED or hospital visits for atrial fibrillation and uncontrolled rate | Randomization to time to event; average follow-up 3 yars | Emergency department visit or hospitalization for atrial fibrillation with uncontrolled rate (to capture poor control with beta blocker withdrawal) |
| All-cause hospitalization | Randomization to time to event; average follow-up 3 years | All-cause hospitalization |
Countries
United States
Contacts
Primary ContactChristopher M Donnelly
Backup ContactJade Fiotto
Outcome results
None listed