Aspirin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

RECOVERY Collaborative Group

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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.

Original languageEnglish
Pages (from-to)143-151
JournalThe Lancet
Volume399
Issue number10320
Early online date17 Nov 2021
DOIs
Publication statusPublished - 8 Jan 2022

Bibliographical note

Funding UK Research and Innovation (Medical Research Council), National Institute of Health Research, and the Wellcome Trust through the COVID-19 Therapeutics Accelerator.
Acknowledgments
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.

Data Availability Statement

The protocol, consent form, statistical analysis plan, definition and derivation of clinical characteristics and outcomes, training materials, regulatory documents, and other relevant study materials are available online at https://www.recoverytrial.net. As described in the protocol, the trial Steering Committee will facilitate the use of the study data and approval will not be unreasonably withheld. Deidentified participant data will be made available to researchers registered with an appropriate institution within 3 months of publication. However, the Steering Committee will need to be satisfied that any proposed publication is of high quality, honours the commitments made to the study participants in the consent documentation and ethical approvals, and is compliant with relevant legal and regulatory requirements (eg, relating to data protection and privacy). The Steering Committee will have the right to review and comment on any draft manuscripts before publication. Data will be made available in line with the policy and procedures described at https://www.ndph.ox.ac.uk/data-access. Individuals wishing to request access should complete the form at https://www.ndph.ox.ac.uk/files/about/data_access_enquiry_form_13_6_2019.docx and e-mail data.access@ndph.ox.ac.uk.

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