Matthew A Roberts1, Helen L Pilmore2, Francesco L Ierino3, Sunil V Badve4, Alan Cass5, Amit X Garg6, Nicole M Isbel7, Henry Krum8, Elaine M Pascoe9, Vlado Perkovic10, Anish Scaria9, Andrew M Tonkin11, Liza A Vergara9, Carmel M Hawley12. 1. Department of Renal Medicine, Eastern Health Clinical School, Monash University, Melbourne, Australia. Electronic address: matthew.roberts@easternhealth.org.au. 2. Department of Renal Medicine, Auckland City Hospital, Auckland, New Zealand. 3. Department of Nephrology, Austin Health, Melbourne, Australia; Department of Medicine, University of Melbourne, Melbourne, Australia. 4. Australasian Kidney Trials Network, The University of Queensland, Brisbane, Australia; Department of Nephrology, St George Hospital, Sydney, Australia. 5. Menzies School of Health Research, Charles Darwin University, Darwin, Northern Territory, Australia. 6. Division of Nephrology, Department of Medicine, Western University, London, Canada. 7. Department of Nephrology, Princess Alexandra Hospital, Brisbane, Australia. 8. Centre of Cardiovascular Research and Education in Therapeutics, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia. 9. Australasian Kidney Trials Network, The University of Queensland, Brisbane, Australia. 10. George Institute for Global Health, University of Sydney, Sydney, Australia. 11. Cardiovascular Research Unit, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia. 12. Australasian Kidney Trials Network, The University of Queensland, Brisbane, Australia; Department of Nephrology, Princess Alexandra Hospital, Brisbane, Australia.
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, 6.25mg, 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). 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.
RCT Entities:
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, 6.25mg, 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). 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.
Authors: Magdalene M Assimon; M Alan Brookhart; Jason P Fine; Gerardo Heiss; J Bradley Layton; Jennifer E Flythe Journal: Am J Kidney Dis Date: 2018-04-10 Impact factor: 8.860
Authors: Meaghan Lunney; Marinella Ruospo; Patrizia Natale; Robert R Quinn; Paul E Ronksley; Ioannis Konstantinidis; Suetonia C Palmer; Marcello Tonelli; Giovanni Fm Strippoli; Pietro Ravani Journal: Cochrane Database Syst Rev Date: 2020-02-27