Aspirin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial
Aspirin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial
Background
Aspirin has been proposed as a treatment for COVID-19 on the basis of its anti-thrombotic properties. We aimed to evaluate the efficacy and safety of aspirin in patients admitted to hospital with COVID-19.
Methods
In this randomised, controlled, open-label, platform trial, several possible treatments were compared with usual care in patients hospitalised with COVID-19. The trial took place at 177 hospitals in the UK, two hospitals in Indonesia, and two hospitals in Nepal. Eligible and consenting adults were randomly allocated in a 1:1 ratio to either usual standard of care plus 150 mg aspirin once per day until discharge or usual standard of care alone using web-based simple (unstratified) randomisation with allocation concealment. The primary outcome was 28 day mortality. All analyses were done by intention to treat. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936).
Findings
Between Nov 1, 2020, and March 21, 2021, 14 892 (66%) of 22 560 patients enrolled into the RECOVERY trial were eligible to be randomly allocated to aspirin. 7351 patients were randomly allocated (1:1) to receive aspirin and 7541 patients to receive usual care alone. Overall, 1222 (17%) of 7351 patients allocated to aspirin and 1299 (17%) of 7541 patients allocated to usual care died within 28 days (rate ratio 0·96, 95% CI 0·89–1·04; p=0·35). Consistent results were seen in all prespecified subgroups of patients. Patients allocated to aspirin had a slightly shorter duration of hospitalisation (median 8 days, IQR 5 to >28, vs 9 days, IQR 5 to >28) and a higher proportion were discharged from hospital alive within 28 days (75% vs 74%; rate ratio 1·06, 95% CI 1·02–1·10; p=0·0062). Among patients not on invasive mechanical ventilation at baseline, there was no significant difference in the proportion meeting the composite endpoint of invasive mechanical ventilation or death (21% vs 22%; risk ratio 0·96, 95% CI 0·90–1·03; p=0·23). Aspirin use was associated with a reduction in thrombotic events (4·6% vs 5·3%; absolute reduction 0·6%, SE 0·4%) and an increase in major bleeding events (1·6% vs 1·0%; absolute increase 0·6%, SE 0·2%).
Interpretation
In patients hospitalised with COVID-19, aspirin was not associated with reductions in 28 day mortality or in the risk of progressing to invasive mechanical ventilation or death, but was associated with a small increase in the rate of being discharged alive within 28 days.
Funding
UK Research and Innovation (Medical Research Council), National Institute of Health Research, and the Wellcome Trust through the COVID-19 Therapeutics Accelerator.
Adult, Aged, Aged, 80 and over, Aspirin/therapeutic use, COVID-19/drug therapy, Female, Hospitalization/statistics & numerical data, Humans, Indonesia, Length of Stay/statistics & numerical data, Male, Middle Aged, Mortality/trends, Nepal, Time Factors, Treatment Outcome, United Kingdom
143-151
Faust, Saul
f97df780-9f9b-418e-b349-7adf63e150c1
Fletcher, Sophie
d05721e8-8943-4f13-a1f5-4ba183741c89
RECOVERY Collaborative Group
8 January 2022
Faust, Saul
f97df780-9f9b-418e-b349-7adf63e150c1
Fletcher, Sophie
d05721e8-8943-4f13-a1f5-4ba183741c89
Abstract
Background
Aspirin has been proposed as a treatment for COVID-19 on the basis of its anti-thrombotic properties. We aimed to evaluate the efficacy and safety of aspirin in patients admitted to hospital with COVID-19.
Methods
In this randomised, controlled, open-label, platform trial, several possible treatments were compared with usual care in patients hospitalised with COVID-19. The trial took place at 177 hospitals in the UK, two hospitals in Indonesia, and two hospitals in Nepal. Eligible and consenting adults were randomly allocated in a 1:1 ratio to either usual standard of care plus 150 mg aspirin once per day until discharge or usual standard of care alone using web-based simple (unstratified) randomisation with allocation concealment. The primary outcome was 28 day mortality. All analyses were done by intention to treat. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936).
Findings
Between Nov 1, 2020, and March 21, 2021, 14 892 (66%) of 22 560 patients enrolled into the RECOVERY trial were eligible to be randomly allocated to aspirin. 7351 patients were randomly allocated (1:1) to receive aspirin and 7541 patients to receive usual care alone. Overall, 1222 (17%) of 7351 patients allocated to aspirin and 1299 (17%) of 7541 patients allocated to usual care died within 28 days (rate ratio 0·96, 95% CI 0·89–1·04; p=0·35). Consistent results were seen in all prespecified subgroups of patients. Patients allocated to aspirin had a slightly shorter duration of hospitalisation (median 8 days, IQR 5 to >28, vs 9 days, IQR 5 to >28) and a higher proportion were discharged from hospital alive within 28 days (75% vs 74%; rate ratio 1·06, 95% CI 1·02–1·10; p=0·0062). Among patients not on invasive mechanical ventilation at baseline, there was no significant difference in the proportion meeting the composite endpoint of invasive mechanical ventilation or death (21% vs 22%; risk ratio 0·96, 95% CI 0·90–1·03; p=0·23). Aspirin use was associated with a reduction in thrombotic events (4·6% vs 5·3%; absolute reduction 0·6%, SE 0·4%) and an increase in major bleeding events (1·6% vs 1·0%; absolute increase 0·6%, SE 0·2%).
Interpretation
In patients hospitalised with COVID-19, aspirin was not associated with reductions in 28 day mortality or in the risk of progressing to invasive mechanical ventilation or death, but was associated with a small increase in the rate of being discharged alive within 28 days.
Funding
UK Research and Innovation (Medical Research Council), National Institute of Health Research, and the Wellcome Trust through the COVID-19 Therapeutics Accelerator.
More information
e-pub ahead of print date: 17 November 2021
Published date: 8 January 2022
Additional Information:
Funding Information:
Above all, we would like to thank the thousands of patients who participated in this trial. We would also like to thank the many doctors, nurses, pharmacists, other allied health professionals, and research administrators at the participating hospitals in Nepal and Indonesia and at 176 UK National Health Service hospital organisations across the whole of the UK, supported by staff at the National Institute of Health Research (NIHR) Clinical Research Network, NHS DigiTrials, Public Health England, Department of Health and Social Care, the Intensive Care National Audit and Research Centre, Public Health Scotland, National Records Service of Scotland, the Secure Anonymised Information Linkage at the University of Swansea, and the NHS in England, Scotland, Wales, and Northern Ireland. The RECOVERY trial is supported by grants to the University of Oxford from the UK Research and Innovation (UKRI) and the NIHR (grant reference MC_PC_19056), the Department of Health and Social Care (DHSC), UKRI, and NIHR COVID-19 Rapid Response Grant (COV19-RECPLA), and the Wellcome Trust (grant referebce 222406/Z/20/Z) through the COVID-19 Therapeutics Accelerator. Core funding is provided by the NIHR Oxford Biomedical Research Centre, Wellcome, the Bill & Melinda Gates Foundation, the Foreign, Commonwealth, and Development Department, Health Data Research UK, the Medical Research Council Population Health Research Unit, the NIHR Health Protection Unit in Emerging and Zoonotic Infections, and NIHR Clinical Trials Unit Support Funding. TJ is supported by a grant from the UK Medical Research Council (MC_UU_00002/14) and an NIHR Senior Research Fellowship (NIHR-SRF-2015-08-001). WSL is supported by core funding provided by NIHR Nottingham Biomedical Research Centre. Combiphar supplied colchicine free of charge for use in this trial in Indonesia. AbbVie contributed some supplies of lopinavir-ritonavir for use in this trial. Tocilizumab was provided free of charge for this trial by Roche Products. Casivirimab and imdevimab was provided free of charge for this trial by Regeneron. The views expressed in this publication are our own and not necessarily those of the NHS or the NIHR. Writing committee (on behalf of the RECOVERY Collaborative Group), Peter W Horby,* Guilherme Pessoa-Amorim,* Natalie Staplin,* Jonathan R Emberson, Mark Campbell, Enti Spata, Leon Peto, Nigel J Brunskill, Simon Tiberi, Victor Chew, Thomas Brown, Hasan Tahir, Beate Ebert, David Chadwick, Tony Whitehouse, Rahuldeb Sarkar, Clive Graham, J Kenneth Baillie, Buddha Basnyat, Maya H Buch, Lucy C Chappell, Jeremy Day, Saul N Faust, Raph L Hamers, Thomas Jaki, Edmund Juszczak, Katie Jeffery, Wei Shen Lim, Alan Montgomery, Andrew Mumford, Kathryn Rowan, Guy Thwaites, Marion Mafham,? Richard Haynes,? and Martin J Landray?. *PWH, GP-A, and NS contributed equally. ?MM, RH, and MJL contributed equally.
Funding Information:
Above all, we would like to thank the thousands of patients who participated in this trial. We would also like to thank the many doctors, nurses, pharmacists, other allied health professionals, and research administrators at the participating hospitals in Nepal and Indonesia and at 176 UK National Health Service hospital organisations across the whole of the UK, supported by staff at the National Institute of Health Research (NIHR) Clinical Research Network, NHS DigiTrials, Public Health England, Department of Health and Social Care, the Intensive Care National Audit and Research Centre, Public Health Scotland, National Records Service of Scotland, the Secure Anonymised Information Linkage at the University of Swansea, and the NHS in England, Scotland, Wales, and Northern Ireland. The RECOVERY trial is supported by grants to the University of Oxford from the UK Research and Innovation (UKRI) and the NIHR (grant reference MC_PC_19056), the Department of Health and Social Care (DHSC), UKRI, and NIHR COVID-19 Rapid Response Grant (COV19-RECPLA), and the Wellcome Trust (grant referebce 222406/Z/20/Z) through the COVID-19 Therapeutics Accelerator. Core funding is provided by the NIHR Oxford Biomedical Research Centre, Wellcome, the Bill & Melinda Gates Foundation, the Foreign, Commonwealth, and Development Department, Health Data Research UK, the Medical Research Council Population Health Research Unit, the NIHR Health Protection Unit in Emerging and Zoonotic Infections, and NIHR Clinical Trials Unit Support Funding. TJ is supported by a grant from the UK Medical Research Council (MC_UU_00002/14) and an NIHR Senior Research Fellowship (NIHR-SRF-2015-08-001). WSL is supported by core funding provided by NIHR Nottingham Biomedical Research Centre. Combiphar supplied colchicine free of charge for use in this trial in Indonesia. AbbVie contributed some supplies of lopinavir-ritonavir for use in this trial. Tocilizumab was provided free of charge for this trial by Roche Products. Casivirimab and imdevimab was provided free of charge for this trial by Regeneron. The views expressed in this publication are our own and not necessarily those of the NHS or the NIHR.
Publisher Copyright:
© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license
Copyright:
Copyright 2022 Elsevier B.V., All rights reserved.
Keywords:
Adult, Aged, Aged, 80 and over, Aspirin/therapeutic use, COVID-19/drug therapy, Female, Hospitalization/statistics & numerical data, Humans, Indonesia, Length of Stay/statistics & numerical data, Male, Middle Aged, Mortality/trends, Nepal, Time Factors, Treatment Outcome, United Kingdom
Identifiers
Local EPrints ID: 457090
URI: http://eprints.soton.ac.uk/id/eprint/457090
ISSN: 0140-6736
PURE UUID: 4c92fdfc-7665-4228-8e99-1aa1e1f2c09b
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Date deposited: 23 May 2022 17:12
Last modified: 17 Mar 2024 03:06
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