The β-Blocker to Lower Cardiovascular Dialysis Events (BLOCADE) feasibility study: A randomized controlled trial

Abstract

Background β-Blocking agents reduce cardiovascular mortality in patients with heart disease, but their potential benefit in dialysis patients is unclear. We aimed to determine the feasibility of a randomized controlled trial (RCT). Study Design Pilot RCT. Setting & Participants Patients who received dialysis for 3 or more months and were 50 years or older (or ≥18 years with diabetes or cardiovascular disease) were recruited from 11 sites in Australia and New Zealand. We aimed to recruit 150 participants. Intervention After a 6-week run-in with the β-blocker carvedilol, we randomly assigned participants to treatment with carvedilol or placebo for 12 months. Outcomes & Measurements The prespecified primary outcome was the proportion of participants who tolerated carvedilol, 6.25 mg, twice daily during the run-in period. After randomization, we report participant withdrawal and the incidence of intradialytic hypotension (IDH). Results Of 1,443 patients screened, 354 were eligible, 91 consented, and 72 entered the run-in stage. 49 of 72 run-in participants (68%; 95% CI, 57%-79%) achieved the primary outcome. 5 of the 23 withdrawals from run-in were attributable to bradycardia or hypotension. After randomization, 10 of 26 allocated to carvedilol and 4 of 23 allocated to placebo withdrew. 4 participants randomly assigned to carvedilol withdrew because of bradycardia or hypotension. Overall, there were 4 IDH events per 100 hemodialysis sessions; in participants allocated to carvedilol versus placebo, respectively, there were 7 versus 2 IDH events per 100 hemodialysis sessions (P = 0.1) in the 2 weeks immediately following a dose increase and 4 versus 3 IDH events per 100 hemodialysis sessions after no dose increase (P = 0.7). Limitations Unable to recruit planned sample size. Conclusions Recruiting patients receiving dialysis to an RCT of β-blocker versus placebo will prove challenging. Possible solutions include international collaboration and exploring novel trial designs such as a registry-based RCT.