title: 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).
  
  
  METHODS
  Pilot RCT.
  
  
  METHODS
  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.
  
  
  METHODS
  After a 6-week run-in with the β-blocker carvedilol, we randomly assigned participants to treatment with carvedilol or placebo for 12 months.
  
  
  METHODS
  The prespecified primary outcome was the proportion of participants who tolerated carvedilol, 6.25mg, 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Renal Medicine, Eastern Health Clinical School, Monash University, Melbourne, Australia. Electronic address: matthew.roberts@easternhealth.org.au.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Roberts
authors.affiliation: Department of Renal Medicine, Auckland City Hospital, Auckland, New Zealand.
authors.forename: Helen L
authors.initials: HL
authors.lastname: Pilmore
authors.affiliation: Department of Nephrology, Austin Health, Melbourne, Australia; Department of Medicine, University of Melbourne, Melbourne, Australia.
authors.forename: Francesco L
authors.initials: FL
authors.lastname: Ierino
authors.affiliation: Australasian Kidney Trials Network, The University of Queensland, Brisbane, Australia; Department of Nephrology, St George Hospital, Sydney, Australia.
authors.forename: Sunil V
authors.initials: SV
authors.lastname: Badve
authors.affiliation: Menzies School of Health Research, Charles Darwin University, Darwin, Northern Territory, Australia.
authors.forename: Alan
authors.initials: A
authors.lastname: Cass
authors.affiliation: Division of Nephrology, Department of Medicine, Western University, London, Canada.
authors.forename: Amit X
authors.initials: AX
authors.lastname: Garg
authors.affiliation: Department of Nephrology, Princess Alexandra Hospital, Brisbane, Australia.
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Isbel
authors.affiliation: Centre of Cardiovascular Research and Education in Therapeutics, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia.
authors.forename: Henry
authors.initials: H
authors.lastname: Krum
authors.affiliation: Australasian Kidney Trials Network, The University of Queensland, Brisbane, Australia.
authors.forename: Elaine M
authors.initials: EM
authors.lastname: Pascoe
authors.affiliation: George Institute for Global Health, University of Sydney, Sydney, Australia.
authors.forename: Vlado
authors.initials: V
authors.lastname: Perkovic
authors.affiliation: Australasian Kidney Trials Network, The University of Queensland, Brisbane, Australia.
authors.forename: Anish
authors.initials: A
authors.lastname: Scaria
authors.affiliation: Cardiovascular Research Unit, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Tonkin
authors.affiliation: Australasian Kidney Trials Network, The University of Queensland, Brisbane, Australia.
authors.forename: Liza A
authors.initials: LA
authors.lastname: Vergara
authors.affiliation: Australasian Kidney Trials Network, The University of Queensland, Brisbane, Australia; Department of Nephrology, Princess Alexandra Hospital, Brisbane, Australia.
authors.forename: Carmel M
authors.initials: CM
authors.lastname: Hawley
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000368:Aged; D002227:Carbazoles / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000517:prevention & control*; D000077261:Carvedilol; D004311:Double-Blind Method; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011412:Propanolamines / Q000627:therapeutic use*; D006435:Renal Dialysis
chemical_list: D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol
keywords: Beta-blocker; Dilatrend; adrenergic receptor blockade; bradycardia; cardiovascular disease (CVD); cardiovascular mortality; carvedilol; dialysis; drug tolerability; end-stage kidney disease (ESKD); feasibility study; hemodialysis; intradialytic hypotension (IDH); randomized controlled trial (RCT); study recruitment