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 M. Isbel; Henry Krum; Elaine M. Pascoe; Vlado Perkovic; Anish Scaria; Andrew M. Tonkin; Liza A. Vergara; Carmel M. Hawley; Adeera Levin; David Hare; Andrew Martin; David C. Wheeler; Gregory Fulcher; Helen Brown; David Colquhoun; Dariusz Korczyk; Amanda Mather; Andrew Wong; Matthew Roberts; Francesco Ierino; Pascal Bisscheroux; Alastair Gillies; Leanne Garvey; Ken Soon Tan; Erica Lennan; Nicole Isbel; Markus Pitkin; Karin Ahearn; Robert P. Carroll; Eileen Scott; Bruce Cooper; Jacqueline Pearse; Paul Snelling; Jenny Burman; Samantha Hand; Eugenie Pedagogos; Connie Karschimkus; Helen Pilmore; Andrew Pilmore; Robert Walker; Gaye Ellis; Mark R. Marshall; Cecilia Paul; Carmel M. Hawley; David Johnson; Sunil Badve; Jean Helyar; Alicia Morrish; Elaine M. Pascoe; Peta Anne Paul-Brent; Donna Reidlinger; Liza A. Vergara; Lei Zhang; BLOCADE Study Collaborative Group

doi:10.1053/j.ajkd.2015.10.029

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 M. Isbel, Henry Krum, Elaine M. Pascoe, Vlado Perkovic, Anish Scaria, Andrew M. Tonkin, Liza A. Vergara, Carmel M. Hawley, Adeera Levin, David Hare, Andrew Martin, David C. Wheeler, Gregory Fulcher, Helen BrownDavid Colquhoun, Dariusz Korczyk, Amanda Mather, Andrew Wong, Matthew Roberts, Francesco Ierino, Pascal Bisscheroux, Alastair Gillies, Leanne Garvey, Ken Soon Tan, Erica Lennan, Nicole Isbel, Markus Pitkin, Karin Ahearn, Robert P. Carroll, Eileen Scott, Bruce Cooper, Jacqueline Pearse, Paul Snelling, Jenny Burman, Samantha Hand, Eugenie Pedagogos, Connie Karschimkus, Helen Pilmore, Andrew Pilmore, Robert Walker, Gaye Ellis, Mark R. Marshall, Cecilia Paul, Carmel M. Hawley, David Johnson, Sunil Badve, Jean Helyar, Alicia Morrish, Elaine M. Pascoe, Peta Anne Paul-Brent, Donna Reidlinger, Liza A. Vergara, Lei Zhang, BLOCADE Study Collaborative Group

Menzies School of Health Research

Research output: Contribution to journal › Article › peer-review

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 language	English
Pages (from-to)	902-911
Number of pages	10
Journal	American Journal of Kidney Diseases
Volume	67
Issue number	6
DOIs	https://doi.org/10.1053/j.ajkd.2015.10.029
Publication status	Published - 1 Jun 2016

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Roberts, M. A., Pilmore, H. L., Ierino, F. L., Badve, S. V., Cass, A., Garg, A. X., Isbel, N. M., Krum, H., Pascoe, E. M., Perkovic, V., Scaria, A., Tonkin, A. M., Vergara, L. A., Hawley, C. M., Levin, A., Hare, D., Martin, A., Wheeler, D. C., Fulcher, G., ... BLOCADE Study Collaborative Group (2016). The β-Blocker to Lower Cardiovascular Dialysis Events (BLOCADE) feasibility study: A randomized controlled trial. American Journal of Kidney Diseases, 67(6), 902-911. https://doi.org/10.1053/j.ajkd.2015.10.029

@article{21a11ea4fcad40a590677fb62adc52a2,

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).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.",

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",

author = "Roberts, {Matthew A.} and Pilmore, {Helen L.} and Ierino, {Francesco L.} and Badve, {Sunil V.} and Alan Cass and Garg, {Amit X.} and Isbel, {Nicole M.} and Henry Krum and Pascoe, {Elaine M.} and Vlado Perkovic and Anish Scaria and Tonkin, {Andrew M.} and Vergara, {Liza A.} and Hawley, {Carmel M.} and Adeera Levin and David Hare and Andrew Martin and Wheeler, {David C.} and Gregory Fulcher and Helen Brown and David Colquhoun and Dariusz Korczyk and Amanda Mather and Andrew Wong and Matthew Roberts and Francesco Ierino and Pascal Bisscheroux and Alastair Gillies and Leanne Garvey and Tan, {Ken Soon} and Erica Lennan and Nicole Isbel and Markus Pitkin and Karin Ahearn and Carroll, {Robert P.} and Eileen Scott and Bruce Cooper and Jacqueline Pearse and Paul Snelling and Jenny Burman and Samantha Hand and Eugenie Pedagogos and Connie Karschimkus and Helen Pilmore and Andrew Pilmore and Robert Walker and Gaye Ellis and Marshall, {Mark R.} and Cecilia Paul and Hawley, {Carmel M.} and David Johnson and Sunil Badve and Jean Helyar and Alicia Morrish and Pascoe, {Elaine M.} and Paul-Brent, {Peta Anne} and Donna Reidlinger and Vergara, {Liza A.} and Lei Zhang and {BLOCADE Study Collaborative Group}",

year = "2016",

month = jun,

day = "1",

doi = "10.1053/j.ajkd.2015.10.029",

language = "English",

volume = "67",

pages = "902--911",

journal = "American Journal of Kidney Diseases",

issn = "0272-6386",

publisher = "W.B. Saunders",

number = "6",

}

Roberts, MA, Pilmore, HL, Ierino, FL, Badve, SV, Cass, A, Garg, AX, Isbel, NM, Krum, H, Pascoe, EM, Perkovic, V, Scaria, A, Tonkin, AM, Vergara, LA, Hawley, CM, Levin, A, Hare, D, Martin, A, Wheeler, DC, Fulcher, G, Brown, H, Colquhoun, D, Korczyk, D, Mather, A, Wong, A, Roberts, M, Ierino, F, Bisscheroux, P, Gillies, A, Garvey, L, Tan, KS, Lennan, E, Isbel, N, Pitkin, M, Ahearn, K, Carroll, RP, Scott, E, Cooper, B, Pearse, J, Snelling, P, Burman, J, Hand, S, Pedagogos, E, Karschimkus, C, Pilmore, H, Pilmore, A, Walker, R, Ellis, G, Marshall, MR, Paul, C, Hawley, CM, Johnson, D, Badve, S, Helyar, J, Morrish, A, Pascoe, EM, Paul-Brent, PA, Reidlinger, D, Vergara, LA, Zhang, L & BLOCADE Study Collaborative Group 2016, 'The β-Blocker to Lower Cardiovascular Dialysis Events (BLOCADE) feasibility study: A randomized controlled trial', American Journal of Kidney Diseases, vol. 67, no. 6, pp. 902-911. https://doi.org/10.1053/j.ajkd.2015.10.029

TY - JOUR

T1 - The β-Blocker to Lower Cardiovascular Dialysis Events (BLOCADE) feasibility study

T2 - A randomized controlled trial

AU - Roberts, Matthew A.

AU - Pilmore, Helen L.

AU - Ierino, Francesco L.

AU - Badve, Sunil V.

AU - Cass, Alan

AU - Garg, Amit X.

AU - Isbel, Nicole M.

AU - Krum, Henry

AU - Pascoe, Elaine M.

AU - Perkovic, Vlado

AU - Scaria, Anish

AU - Tonkin, Andrew M.

AU - Vergara, Liza A.

AU - Hawley, Carmel M.

AU - Levin, Adeera

AU - Hare, David

AU - Martin, Andrew

AU - Wheeler, David C.

AU - Fulcher, Gregory

AU - Brown, Helen

AU - Colquhoun, David

AU - Korczyk, Dariusz

AU - Mather, Amanda

AU - Wong, Andrew

AU - Roberts, Matthew

AU - Ierino, Francesco

AU - Bisscheroux, Pascal

AU - Gillies, Alastair

AU - Garvey, Leanne

AU - Tan, Ken Soon

AU - Lennan, Erica

AU - Isbel, Nicole

AU - Pitkin, Markus

AU - Ahearn, Karin

AU - Carroll, Robert P.

AU - Scott, Eileen

AU - Cooper, Bruce

AU - Pearse, Jacqueline

AU - Snelling, Paul

AU - Burman, Jenny

AU - Hand, Samantha

AU - Pedagogos, Eugenie

AU - Karschimkus, Connie

AU - Pilmore, Helen

AU - Pilmore, Andrew

AU - Walker, Robert

AU - Ellis, Gaye

AU - Marshall, Mark R.

AU - Paul, Cecilia

AU - Hawley, Carmel M.

AU - Johnson, David

AU - Badve, Sunil

AU - Helyar, Jean

AU - Morrish, Alicia

AU - Pascoe, Elaine M.

AU - Paul-Brent, Peta Anne

AU - Reidlinger, Donna

AU - Vergara, Liza A.

AU - Zhang, Lei

AU - BLOCADE Study Collaborative Group

PY - 2016/6/1

Y1 - 2016/6/1

N2 - 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.

AB - 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.

KW - adrenergic receptor blockade

KW - Beta-blocker

KW - bradycardia

KW - cardiovascular disease (CVD)

KW - cardiovascular mortality

KW - carvedilol

KW - dialysis

KW - Dilatrend

KW - drug tolerability

KW - end-stage kidney disease (ESKD)

KW - feasibility study

KW - hemodialysis

KW - intradialytic hypotension (IDH)

KW - randomized controlled trial (RCT)

KW - study recruitment

UR - http://www.scopus.com/inward/record.url?scp=84951182519&partnerID=8YFLogxK

U2 - 10.1053/j.ajkd.2015.10.029

DO - 10.1053/j.ajkd.2015.10.029

M3 - Article

C2 - 26717861

SN - 0272-6386

VL - 67

SP - 902

EP - 911

JO - American Journal of Kidney Diseases

JF - American Journal of Kidney Diseases

IS - 6

ER -

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

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