Use of the oral beta blocker bisoprolol to reduce the rate of exacerbation in people with chronic obstructive pulmonary disease (COPD): a randomised controlled trial. (BICS)

Seonaidh Cotton; Graham Devereux; Hassan Abbas; Andrew H Briggs; Karen Campbell; Rekha Chaudhuri; Gourab  Choudhury; Dana Dawson; Anthony De Soyza; Shona Fielding; Simon Gompertz; John Haughney; Chim C Lang; Amanda Lee; Graeme MacLennan; William  MacNee; Kirsty McCormack; Nicola McMeekin; Nicholas L Mills; Alyn Morice; John Norrie; Linda Petrie; David Price; Philip  Short; Jørgen Vestbo; Paul  Walker; Jadwiga A Wedzicha; Andrew Wilson; Brian J  Lipworth

doi:10.1186/s13063-022-06226-8

Use of the oral beta blocker bisoprolol to reduce the rate of exacerbation in people with chronic obstructive pulmonary disease (COPD): a randomised controlled trial. (BICS)

Seonaidh Cotton, Graham Devereux^* (Corresponding Author), Hassan Abbas, Andrew H Briggs, Karen Campbell, Rekha Chaudhuri, Gourab Choudhury, Dana Dawson, Anthony De Soyza, Shona Fielding, Simon Gompertz, John Haughney, Chim C Lang, Amanda Lee, Graeme MacLennan, William MacNee, Kirsty McCormack, Nicola McMeekin, Nicholas L Mills, Alyn MoriceJohn Norrie, Linda Petrie, David Price, Philip Short, Jørgen Vestbo, Paul Walker, Jadwiga A Wedzicha, Andrew Wilson, Brian J Lipworth

^*Corresponding author for this work

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

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Abstract

Background: Chronic Obstructive Pulmonary Disease (COPD) is associated with significant morbidity, mortality and healthcare costs. Beta-blockers are well-established drugs widely used to treat cardiovascular conditions. Observational studies consistently report that beta5 blocker use in people with COPD is associated with a reduced risk of COPD exacerbations.
The bisoprolol in COPD study (BICS) investigates whether adding bisoprolol to routine COPD treatment has clinical and cost-effective benefits. A sub-study will risk stratify participants for heart failure to investigate whether any beneficial effect of bisoprolol is restricted to those with unrecognised heart disease.

Methods: BICS is a pragmatic randomised parallel group double-blind placebo-controlled trial conducted in UK primary and secondary care sites. The major inclusion criteria are an established predominant respiratory diagnosis of COPD (post-bronchodilator FEV1<80% predicted, FEV1/FVC<0.7), a self-reported history of ≥2 exacerbations requiring treatment with antibiotics and/or oral corticosteroids in a 12-month period since March 2019, age ≥40 years and a smoking history ≥10 pack years. A computerised randomisation system will allocate 1574 participants with equal probability to intervention or control groups, stratified by centre, and recruitment in primary/secondary care. The intervention is bisoprolol (1.25 mg tablets) or identical placebo. The dose of bisoprolol/placebo is titrated up to a maximum of 4 tablets a day (5mg bisoprolol) over four-seven weeks depending on tolerance to up-dosing of bisoprolol/placebo – these titration assessments are completed by telephone or video call.
Participants complete the remainder of the 52-week treatment period on the final titrated dose (1,2,3,4 tablets) and during that time are followed up at 26 and 52 weeks by telephone or video call. The primary outcome is the total number of participant reported COPD exacerbations requiring oral corticosteroids and/or antibiotics during the 52-week treatment period. A sub-study will risk stratify participants for heart failure by echocardiography and
measurement of blood biomarkers.

Discussion: The demonstration that bisoprolol reduces the incidence of exacerbations would be relevant not only to patients and clinicians but also to healthcare providers, in the UK and globally.

Original language	English
Article number	307
Number of pages	16
Journal	Trials
Volume	23
Issue number	1
Early online date	14 Apr 2022
DOIs	https://doi.org/10.1186/s13063-022-06226-8
Publication status	Published - 14 Apr 2022

Bibliographical note

Acknowledgments
We are grateful for the secretarial and data co-ordination support from Janice Cruden. We would like to acknowledge the principal investigators and staff based in trial recruitment sites across the country, the Clinical Research Networks and staff in the Clinical Trials Pharmacy, and the support of the Trial Steering and Data Monitoring Committees. In particular, we have been grateful for the input to the Trial Steering Committee from two lay representatives,
Mr Alister Laird and Mr Dave Bertin.

Funding {4b}
This project was funded by the National Institute for Health Research, Health Technology Assessment Programme (project number 15/130/20). The cardiac sub-study is funded by British Heart Foundation (BHF) Project Grant no. PG/17/64/33205. This report presents independent research commissioned by the National Institute for Health Research (NIHR). The views and opinions expressed by authors in this publication are those of the authors and do not necessarily reflect those of the NHS, the NIHR, MRC, CCF, NETSCC, the Health
Technology Assessment programme or the Department of Health.

Keywords

COPD
exacerbation
randomised controlled trial
bisoprol
beta blocker

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Data from: Use of the oral beta blocker bisoprolol to reduce the rate of exacerbation in people with chronic obstructive pulmonary disease (COPD): a randomised controlled trial (BICS)
Cotton, S. (Creator), Devereux, G. (Creator), Abbas, H. (Creator), Briggs, A. (Creator), Campbell, K. (Creator), Chaudhuri, R. (Creator), Choudhury, G. (Creator), Dawson, D. (Creator), De Soyza, A. (Creator), Fielding, S. (Creator), Gompertz, S. (Creator), Haughney, J. (Creator), Lang, C. C. (Creator), Lee, A. (Creator), MacLennan, G. (Creator), MacNee, W. (Creator), McCormack, K. (Creator), McMeekin, N. (Creator), Mills, N. L. (Creator), Morice, A. (Creator), Norrie, J. (Creator), Petrie, M. C. (Creator), Price, D. (Creator), Short, P. (Creator), Vestbo, J. (Creator), Walker, P. (Creator), Wedzicha, J. (Creator), Wilson, A. (Creator) & Lipworth, B. J. (Creator), Figshare, 2022
DOI: 10.6084/m9.figshare.c.5949862.v1, https://springernature.figshare.com/collections/Use_of_the_oral_beta_blocker_bisoprolol_to_reduce_the_rate_of_exacerbation_in_people_with_chronic_obstructive_pulmonary_disease_COPD_a_randomised_controlled_trial_BICS_/5949862/1
Dataset

Cite this

Cotton, S., Devereux, G., Abbas, H., Briggs, A. H., Campbell, K., Chaudhuri, R., Choudhury, G., Dawson, D., De Soyza, A., Fielding, S., Gompertz, S., Haughney, J., Lang, C. C., Lee, A., MacLennan, G., MacNee, W., McCormack, K., McMeekin, N., Mills, N. L., ... Lipworth, B. J. (2022). Use of the oral beta blocker bisoprolol to reduce the rate of exacerbation in people with chronic obstructive pulmonary disease (COPD): a randomised controlled trial. (BICS). Trials, 23(1), Article 307. https://doi.org/10.1186/s13063-022-06226-8

Cotton, S, Devereux, G, Abbas, H, Briggs, AH, Campbell, K, Chaudhuri, R, Choudhury, G, Dawson, D, De Soyza, A, Fielding, S, Gompertz, S, Haughney, J, Lang, CC, Lee, A , MacLennan, G, MacNee, W, McCormack, K, McMeekin, N, Mills, NL, Morice, A, Norrie, J, Petrie, L, Price, D, Short, P, Vestbo, J, Walker, P, Wedzicha, JA, Wilson, A & Lipworth, BJ 2022, 'Use of the oral beta blocker bisoprolol to reduce the rate of exacerbation in people with chronic obstructive pulmonary disease (COPD): a randomised controlled trial. (BICS)', Trials, vol. 23, no. 1, 307. https://doi.org/10.1186/s13063-022-06226-8

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abstract = "Background: Chronic Obstructive Pulmonary Disease (COPD) is associated with significant morbidity, mortality and healthcare costs. Beta-blockers are well-established drugs widely used to treat cardiovascular conditions. Observational studies consistently report that beta5 blocker use in people with COPD is associated with a reduced risk of COPD exacerbations.The bisoprolol in COPD study (BICS) investigates whether adding bisoprolol to routine COPD treatment has clinical and cost-effective benefits. A sub-study will risk stratify participants for heart failure to investigate whether any beneficial effect of bisoprolol is restricted to those with unrecognised heart disease.Methods: BICS is a pragmatic randomised parallel group double-blind placebo-controlled trial conducted in UK primary and secondary care sites. The major inclusion criteria are an established predominant respiratory diagnosis of COPD (post-bronchodilator FEV1<80% predicted, FEV1/FVC<0.7), a self-reported history of ≥2 exacerbations requiring treatment with antibiotics and/or oral corticosteroids in a 12-month period since March 2019, age ≥40 years and a smoking history ≥10 pack years. A computerised randomisation system will allocate 1574 participants with equal probability to intervention or control groups, stratified by centre, and recruitment in primary/secondary care. The intervention is bisoprolol (1.25 mg tablets) or identical placebo. The dose of bisoprolol/placebo is titrated up to a maximum of 4 tablets a day (5mg bisoprolol) over four-seven weeks depending on tolerance to up-dosing of bisoprolol/placebo – these titration assessments are completed by telephone or video call.Participants complete the remainder of the 52-week treatment period on the final titrated dose (1,2,3,4 tablets) and during that time are followed up at 26 and 52 weeks by telephone or video call. The primary outcome is the total number of participant reported COPD exacerbations requiring oral corticosteroids and/or antibiotics during the 52-week treatment period. A sub-study will risk stratify participants for heart failure by echocardiography andmeasurement of blood biomarkers.Discussion: The demonstration that bisoprolol reduces the incidence of exacerbations would be relevant not only to patients and clinicians but also to healthcare providers, in the UK and globally.",

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note = "Acknowledgments We are grateful for the secretarial and data co-ordination support from Janice Cruden. We would like to acknowledge the principal investigators and staff based in trial recruitment sites across the country, the Clinical Research Networks and staff in the Clinical Trials Pharmacy, and the support of the Trial Steering and Data Monitoring Committees. In particular, we have been grateful for the input to the Trial Steering Committee from two lay representatives, Mr Alister Laird and Mr Dave Bertin. Funding {4b} This project was funded by the National Institute for Health Research, Health Technology Assessment Programme (project number 15/130/20). The cardiac sub-study is funded by British Heart Foundation (BHF) Project Grant no. PG/17/64/33205. This report presents independent research commissioned by the National Institute for Health Research (NIHR). The views and opinions expressed by authors in this publication are those of the authors and do not necessarily reflect those of the NHS, the NIHR, MRC, CCF, NETSCC, the Health Technology Assessment programme or the Department of Health.",

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T2 - a randomised controlled trial. (BICS)

AU - Cotton, Seonaidh

AU - Devereux, Graham

AU - Abbas, Hassan

AU - Briggs, Andrew H

AU - Campbell, Karen

AU - Chaudhuri, Rekha

AU - Choudhury, Gourab

AU - Dawson, Dana

AU - De Soyza, Anthony

AU - Fielding, Shona

AU - Gompertz, Simon

AU - Haughney, John

AU - Lang, Chim C

AU - Lee, Amanda

AU - MacLennan, Graeme

AU - MacNee, William

AU - McCormack, Kirsty

AU - McMeekin, Nicola

AU - Mills, Nicholas L

AU - Morice, Alyn

AU - Norrie, John

AU - Petrie, Linda

AU - Price, David

AU - Short, Philip

AU - Vestbo, Jørgen

AU - Walker, Paul

AU - Wedzicha, Jadwiga A

AU - Wilson, Andrew

AU - Lipworth, Brian J

N1 - Acknowledgments We are grateful for the secretarial and data co-ordination support from Janice Cruden. We would like to acknowledge the principal investigators and staff based in trial recruitment sites across the country, the Clinical Research Networks and staff in the Clinical Trials Pharmacy, and the support of the Trial Steering and Data Monitoring Committees. In particular, we have been grateful for the input to the Trial Steering Committee from two lay representatives, Mr Alister Laird and Mr Dave Bertin. Funding {4b} This project was funded by the National Institute for Health Research, Health Technology Assessment Programme (project number 15/130/20). The cardiac sub-study is funded by British Heart Foundation (BHF) Project Grant no. PG/17/64/33205. This report presents independent research commissioned by the National Institute for Health Research (NIHR). The views and opinions expressed by authors in this publication are those of the authors and do not necessarily reflect those of the NHS, the NIHR, MRC, CCF, NETSCC, the Health Technology Assessment programme or the Department of Health.

PY - 2022/4/14

Y1 - 2022/4/14

N2 - Background: Chronic Obstructive Pulmonary Disease (COPD) is associated with significant morbidity, mortality and healthcare costs. Beta-blockers are well-established drugs widely used to treat cardiovascular conditions. Observational studies consistently report that beta5 blocker use in people with COPD is associated with a reduced risk of COPD exacerbations.The bisoprolol in COPD study (BICS) investigates whether adding bisoprolol to routine COPD treatment has clinical and cost-effective benefits. A sub-study will risk stratify participants for heart failure to investigate whether any beneficial effect of bisoprolol is restricted to those with unrecognised heart disease.Methods: BICS is a pragmatic randomised parallel group double-blind placebo-controlled trial conducted in UK primary and secondary care sites. The major inclusion criteria are an established predominant respiratory diagnosis of COPD (post-bronchodilator FEV1<80% predicted, FEV1/FVC<0.7), a self-reported history of ≥2 exacerbations requiring treatment with antibiotics and/or oral corticosteroids in a 12-month period since March 2019, age ≥40 years and a smoking history ≥10 pack years. A computerised randomisation system will allocate 1574 participants with equal probability to intervention or control groups, stratified by centre, and recruitment in primary/secondary care. The intervention is bisoprolol (1.25 mg tablets) or identical placebo. The dose of bisoprolol/placebo is titrated up to a maximum of 4 tablets a day (5mg bisoprolol) over four-seven weeks depending on tolerance to up-dosing of bisoprolol/placebo – these titration assessments are completed by telephone or video call.Participants complete the remainder of the 52-week treatment period on the final titrated dose (1,2,3,4 tablets) and during that time are followed up at 26 and 52 weeks by telephone or video call. The primary outcome is the total number of participant reported COPD exacerbations requiring oral corticosteroids and/or antibiotics during the 52-week treatment period. A sub-study will risk stratify participants for heart failure by echocardiography andmeasurement of blood biomarkers.Discussion: The demonstration that bisoprolol reduces the incidence of exacerbations would be relevant not only to patients and clinicians but also to healthcare providers, in the UK and globally.

AB - Background: Chronic Obstructive Pulmonary Disease (COPD) is associated with significant morbidity, mortality and healthcare costs. Beta-blockers are well-established drugs widely used to treat cardiovascular conditions. Observational studies consistently report that beta5 blocker use in people with COPD is associated with a reduced risk of COPD exacerbations.The bisoprolol in COPD study (BICS) investigates whether adding bisoprolol to routine COPD treatment has clinical and cost-effective benefits. A sub-study will risk stratify participants for heart failure to investigate whether any beneficial effect of bisoprolol is restricted to those with unrecognised heart disease.Methods: BICS is a pragmatic randomised parallel group double-blind placebo-controlled trial conducted in UK primary and secondary care sites. The major inclusion criteria are an established predominant respiratory diagnosis of COPD (post-bronchodilator FEV1<80% predicted, FEV1/FVC<0.7), a self-reported history of ≥2 exacerbations requiring treatment with antibiotics and/or oral corticosteroids in a 12-month period since March 2019, age ≥40 years and a smoking history ≥10 pack years. A computerised randomisation system will allocate 1574 participants with equal probability to intervention or control groups, stratified by centre, and recruitment in primary/secondary care. The intervention is bisoprolol (1.25 mg tablets) or identical placebo. The dose of bisoprolol/placebo is titrated up to a maximum of 4 tablets a day (5mg bisoprolol) over four-seven weeks depending on tolerance to up-dosing of bisoprolol/placebo – these titration assessments are completed by telephone or video call.Participants complete the remainder of the 52-week treatment period on the final titrated dose (1,2,3,4 tablets) and during that time are followed up at 26 and 52 weeks by telephone or video call. The primary outcome is the total number of participant reported COPD exacerbations requiring oral corticosteroids and/or antibiotics during the 52-week treatment period. A sub-study will risk stratify participants for heart failure by echocardiography andmeasurement of blood biomarkers.Discussion: The demonstration that bisoprolol reduces the incidence of exacerbations would be relevant not only to patients and clinicians but also to healthcare providers, in the UK and globally.

KW - COPD

KW - exacerbation

KW - randomised controlled trial

KW - bisoprol

KW - beta blocker

U2 - 10.1186/s13063-022-06226-8

DO - 10.1186/s13063-022-06226-8

M3 - Article

C2 - 35422024

SN - 1745-6215

VL - 23

JO - Trials

JF - Trials

IS - 1

M1 - 307

ER -

Use of the oral beta blocker bisoprolol to reduce the rate of exacerbation in people with chronic obstructive pulmonary disease (COPD): a randomised controlled trial. (BICS)

Abstract

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Data from: Use of the oral beta blocker bisoprolol to reduce the rate of exacerbation in people with chronic obstructive pulmonary disease (COPD): a randomised controlled trial (BICS)

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