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C-reactive protein point-of-care testing for safely reducing antibiotics for acute exacerbations of chronic obstructive pulmonary disease: the PACE RCT

C-reactive protein point-of-care testing for safely reducing antibiotics for acute exacerbations of chronic obstructive pulmonary disease: the PACE RCT
C-reactive protein point-of-care testing for safely reducing antibiotics for acute exacerbations of chronic obstructive pulmonary disease: the PACE RCT

Background: Most patients presenting with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) in primary care are prescribed antibiotics, but these may not be beneficial, and they can cause side effects and increase the risk of subsequent resistant infections. Point-of-care tests (POCTs) could safely reduce inappropriate antibiotic prescribing and antimicrobial resistance. Objective: To determine whether or not the use of a C-reactive protein (CRP) POCT to guide prescribing decisions for AECOPD reduces antibiotic consumption without having a negative impact on chronic obstructive pulmonary disease (COPD) health status and is cost-effective. Design: A multicentre, parallel-arm, randomised controlled open trial with an embedded process, and a health economic evaluation. Setting: General practices in Wales and England. A UK NHS perspective was used for the economic analysis. Participants: Adults (aged ≥ 40 years) with a primary care diagnosis of COPD, presenting with an AECOPD (with at least one of increased dyspnoea, increased sputum volume and increased sputum purulence) of between 24 hours’ and 21 days’ duration. Intervention: CRP POCTs to guide antibiotic prescribing decisions for AECOPD, compared with usual care (no CRP POCT), using remote online randomisation. Main outcome measures: Patient-reported antibiotic consumption for AECOPD within 4 weeks post randomisation and COPD health status as measured with the Clinical COPD Questionnaire (CCQ) at 2 weeks. For the economic evaluation, patient-reported resource use and the EuroQol-5 Dimensions were included. Results: In total, 653 participants were randomised from 86 general practices. Three withdrew consent and one was randomised in error, leaving 324 participants in the usual-care arm and 325 participants in the CRP POCT arm. Antibiotics were consumed for AECOPD by 212 out of 274 participants (77.4%) and 150 out of 263 participants (57.0%) in the usual-care and CRP POCT arm, respectively [adjusted odds ratio 0.31, 95% confidence interval (CI) 0.20 to 0.47]. The CCQ analysis comprised 282 and 281 participants in the usual-care and CRP POCT arms, respectively, and the adjusted mean CCQ score difference at 2 weeks was 0.19 points (two-sided 90% CI –0.33 to –0.05 points). The upper limit of the CI did not contain the prespecified non-inferiority margin of 0.3. The total cost from a NHS perspective at 4 weeks was £17.59 per patient higher in the CRP POCT arm (95% CI –£34.80 to £69.98; p = 0.408). The mean incremental cost-effectiveness ratios were £222 per 1% reduction in antibiotic consumption compared with usual care at 4 weeks and £15,251 per quality-adjusted life-year gained at 6 months with no significant changes in sensitivity analyses. Patients and clinicians were generally supportive of including CRP POCT in the assessment of AECOPD. Conclusions: A CRP POCT diagnostic strategy achieved meaningful reductions in patient-reported antibiotic consumption without impairing COPD health status or increasing costs. There were no associated harms and both patients and clinicians valued the diagnostic strategy. Future work: Implementation studies that also build on our qualitative findings could help determine the effect of this intervention over the longer term. Trial registration: Current Controlled Trials ISRCTN24346473.

1366-5278
1-108
Francis, Nick A
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Gillespie, David
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White, Patrick
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Bates, Janine
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Lowe, Rachel
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Sewell, Bernadette
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Phillips, Rhiannon
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Stanton, Helen
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Kirby, Nigel
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Wootton, Mandy
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Thomas-Jones, Emma
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Hood, Kerenza
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Llor, Carl
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Cals, Jochen
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Melbye, Hasse
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Naik, Gurudutt
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Gal, Micaela
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Fitzsimmons, Deborah
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Alam, Mohammed Fasihul
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Riga, Evgenia
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Cochrane, Ann
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Butler, Christopher C
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Francis, Nick A
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Gillespie, David
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White, Patrick
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Bates, Janine
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Lowe, Rachel
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Sewell, Bernadette
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Stanton, Helen
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Kirby, Nigel
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Wootton, Mandy
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Thomas-Jones, Emma
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Hood, Kerenza
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Llor, Carl
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Cals, Jochen
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Melbye, Hasse
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Naik, Gurudutt
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Gal, Micaela
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Fitzsimmons, Deborah
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Alam, Mohammed Fasihul
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Riga, Evgenia
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Cochrane, Ann
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Butler, Christopher C
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Francis, Nick A, Gillespie, David, White, Patrick, Bates, Janine, Lowe, Rachel, Sewell, Bernadette, Phillips, Rhiannon, Stanton, Helen, Kirby, Nigel, Wootton, Mandy, Thomas-Jones, Emma, Hood, Kerenza, Llor, Carl, Cals, Jochen, Melbye, Hasse, Naik, Gurudutt, Gal, Micaela, Fitzsimmons, Deborah, Alam, Mohammed Fasihul, Riga, Evgenia, Cochrane, Ann and Butler, Christopher C (2020) C-reactive protein point-of-care testing for safely reducing antibiotics for acute exacerbations of chronic obstructive pulmonary disease: the PACE RCT. Health technology assessment (Winchester, England), 24 (15), 1-108. (doi:10.3310/hta24150).

Record type: Article

Abstract

Background: Most patients presenting with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) in primary care are prescribed antibiotics, but these may not be beneficial, and they can cause side effects and increase the risk of subsequent resistant infections. Point-of-care tests (POCTs) could safely reduce inappropriate antibiotic prescribing and antimicrobial resistance. Objective: To determine whether or not the use of a C-reactive protein (CRP) POCT to guide prescribing decisions for AECOPD reduces antibiotic consumption without having a negative impact on chronic obstructive pulmonary disease (COPD) health status and is cost-effective. Design: A multicentre, parallel-arm, randomised controlled open trial with an embedded process, and a health economic evaluation. Setting: General practices in Wales and England. A UK NHS perspective was used for the economic analysis. Participants: Adults (aged ≥ 40 years) with a primary care diagnosis of COPD, presenting with an AECOPD (with at least one of increased dyspnoea, increased sputum volume and increased sputum purulence) of between 24 hours’ and 21 days’ duration. Intervention: CRP POCTs to guide antibiotic prescribing decisions for AECOPD, compared with usual care (no CRP POCT), using remote online randomisation. Main outcome measures: Patient-reported antibiotic consumption for AECOPD within 4 weeks post randomisation and COPD health status as measured with the Clinical COPD Questionnaire (CCQ) at 2 weeks. For the economic evaluation, patient-reported resource use and the EuroQol-5 Dimensions were included. Results: In total, 653 participants were randomised from 86 general practices. Three withdrew consent and one was randomised in error, leaving 324 participants in the usual-care arm and 325 participants in the CRP POCT arm. Antibiotics were consumed for AECOPD by 212 out of 274 participants (77.4%) and 150 out of 263 participants (57.0%) in the usual-care and CRP POCT arm, respectively [adjusted odds ratio 0.31, 95% confidence interval (CI) 0.20 to 0.47]. The CCQ analysis comprised 282 and 281 participants in the usual-care and CRP POCT arms, respectively, and the adjusted mean CCQ score difference at 2 weeks was 0.19 points (two-sided 90% CI –0.33 to –0.05 points). The upper limit of the CI did not contain the prespecified non-inferiority margin of 0.3. The total cost from a NHS perspective at 4 weeks was £17.59 per patient higher in the CRP POCT arm (95% CI –£34.80 to £69.98; p = 0.408). The mean incremental cost-effectiveness ratios were £222 per 1% reduction in antibiotic consumption compared with usual care at 4 weeks and £15,251 per quality-adjusted life-year gained at 6 months with no significant changes in sensitivity analyses. Patients and clinicians were generally supportive of including CRP POCT in the assessment of AECOPD. Conclusions: A CRP POCT diagnostic strategy achieved meaningful reductions in patient-reported antibiotic consumption without impairing COPD health status or increasing costs. There were no associated harms and both patients and clinicians valued the diagnostic strategy. Future work: Implementation studies that also build on our qualitative findings could help determine the effect of this intervention over the longer term. Trial registration: Current Controlled Trials ISRCTN24346473.

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e-pub ahead of print date: 1 March 2020
Published date: March 2020
Additional Information: Funding Information: Declared competing interests of authors: Christopher C Butler reports that Afinion C-reactive protein devices and associated training given to participating general practices were provided by Alere Inc. (now Abbott Diagnostics, IL, USA) at no cost to the study. He has received fees for participating in a Roche Molecular Systems Advisory Board meeting on 4 and 5 February 2016 about point-of-care testing; held an investigator-initiated grant from Roche Molecular Diagnostics (Roche Molecular Systems Inc., CA, USA) to evaluate the analytic performance of the cobas® Liat® point-of-care device for detecting influenza using samples from a separately funded study; and is part of a publicly funded research consortia that includes industrial partners. He was a member of the Medical Research Council–National Institute for Health Research (MRC–NIHR) Efficacy and Mechanism Evaluation Board (2012–16). He has been a NIHR Senior Investigator since 2016. Kerenza Hood was a member of the Health Technology Assessment (HTA) programme Funding Boards Policy Group (formerly Clinical Studies Group) (2016 to present), the HTA General Board (2016 to present) and the NIHR Clinical Trials Unit Standing Advisory Committee (2014 to 2019). Gurudutt Naik reports non-financial support from Alere Inc. Carl Llor reports grants from the European Commission (Seventh Framework Programme and Horizon 2020), the Catalan Society of Family Medicine, Abbott Diagnostics and Instituto de Salud Carlos III (Spanish Ministry of Health) outside the submitted work. Rhiannon Phillips reports that her current post is a fellowship funded by Health and Care Research Wales as part of the Primary and Emergency Care Research Centre Wales research centre grant. Funding Information: The research reported in this issue of the journal was funded by the HTA programme as project number 12/33/12. The contractual start date was in July 2014. The draft report began editorial review in March 2018 and was accepted for publication in August 2018. The authors have been wholly responsible for all data collection, analysis and interpretation, and for writing up their work. The HTA editors and publisher have tried to ensure the accuracy of the authors’ report and would like to thank the reviewers for their constructive comments on the draft document. However, they do not accept liability for damages or losses arising from material published in this report. Funding Information: This report presents independent research funded 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, NETSCC, the HTA programme or the Department of Health and Social Care. If there are verbatim quotations included in this publication the views and opinions expressed by the interviewees are those of the interviewees and do not necessarily reflect those of the authors, those of the NHS, the NIHR, NETSCC, the HTA programme or the Department of Health and Social Care. Funding Information: Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 15. See the NIHR Journals Library website for further project information. Funding Information: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 15. See the NIHR Journals Library website for further project information. Publisher Copyright: © Queen’s Printer and Controller of HMSO 2020.

Identifiers

Local EPrints ID: 441350
URI: http://eprints.soton.ac.uk/id/eprint/441350
ISSN: 1366-5278
PURE UUID: ec266526-e9da-4b0d-8e8d-542028270fb0
ORCID for Nick A Francis: ORCID iD orcid.org/0000-0001-8939-7312

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Date deposited: 10 Jun 2020 16:31
Last modified: 17 Mar 2024 03:58

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Contributors

Author: Nick A Francis ORCID iD
Author: David Gillespie
Author: Patrick White
Author: Janine Bates
Author: Rachel Lowe
Author: Bernadette Sewell
Author: Rhiannon Phillips
Author: Helen Stanton
Author: Nigel Kirby
Author: Mandy Wootton
Author: Emma Thomas-Jones
Author: Kerenza Hood
Author: Carl Llor
Author: Jochen Cals
Author: Hasse Melbye
Author: Gurudutt Naik
Author: Micaela Gal
Author: Deborah Fitzsimmons
Author: Mohammed Fasihul Alam
Author: Evgenia Riga
Author: Ann Cochrane
Author: Christopher C Butler

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