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

Matthew A. Roberts, Helen L Pilmore, Francesco L Ierino, Sunil V Badve, Alan Cass, Amit X Garg, Nicole Isbel, Henry Krum, Elaine M Pascoe, Vlado Perkovic, Anish Scaria, Andrew M. Tonkin, Liza A Vergara, Carmel M. Hawley, BLOCADE Study Collaborative Group, Lei Zhang

Research output: Contribution to journalArticleResearchpeer-review

27 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)902-911
Number of pages10
JournalAmerican Journal of Kidney Diseases
Volume67
Issue number6
DOIs
Publication statusPublished - 1 Jun 2016

Keywords

  • adrenergic receptor blockade
  • Beta-blocker
  • bradycardia
  • cardiovascular disease (CVD)
  • cardiovascular mortality
  • carvedilol
  • dialysis
  • Dilatrend
  • drug tolerability
  • end-stage kidney disease (ESKD)
  • feasibility study
  • hemodialysis
  • intradialytic hypotension (IDH)
  • randomized controlled trial (RCT)
  • study recruitment

Cite this