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

  1. RECOVERY Collaborative Group
  2. Peter W Horby
  3. Guilherme Pessoa-Amorim
  4. Natalie Staplin
  5. Jonathan R Emberson
  6. Mark Campbell
  7. Enti Spata
  8. Leon Peto
  9. Nigel J Brunskill
  10. Simon Tiberi
  11. Victor Chew
  12. Thomas Brown
  13. Hasan Tahir
  14. Beate Ebert
  15. David Chadwick
  16. Tony Whitehouse
  17. Rahuldeb Sarkar
  18. Clive Graham
  19. J Kenneth Baillie
  20. Buddha Basnyat
  21. Maya H Buch
  22. Lucy C Chappell
  23. Jeremy Day
  24. Saul N Faust
  25. Raph L Hamers
  26. Thomas Jaki
  27. Edmund Juszczak
  28. Katie Jeffery
  29. Wei Shen Lim
  30. Alan Montgomery
  31. Andrew Mumford
  32. Kathryn Rowan
  33. Guy Thwaites
  34. Marion Mafham
  35. Richard Haynes
  36. Martin J Landray

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Abstract

Background

Aspirin has been proposed as a treatment for COVID-19 on the basis of its antithrombotic properties.

Methods

In this randomised, controlled, open-label platform trial, several possible treatments were compared with usual care in patients hospitalised with COVID-19. Eligible and consenting adults were randomly allocated in a 1:1 ratio to either usual standard of care plus 150mg aspirin once daily until discharge or usual standard of care alone using web-based simple (unstratified) randomisation with allocation concealment. The primary outcome was 28-day mortality. The trial is registered with ISRCTN (50189673) and clinicaltrials.gov ( NCT04381936 ).

Findings

Between 01 November 2020 and 21 March 2021, 7351 patients were randomly allocated to receive aspirin and 7541 patients to receive usual care alone. Overall, 1222 (17%) patients allocated to aspirin and 1299 (17%) patients allocated to usual care died within 28 days (rate ratio 0·96; 95% confidence interval [CI] 0·89-1·04; p=0·35). Consistent results were seen in all pre-specified subgroups of patients. Patients allocated to aspirin had a slightly shorter duration of hospitalisation (median 8 vs. 9 days) 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 those 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 an absolute reduction in thrombotic events of 0.6% (SE 0.4%) and an absolute increase in major bleeding events of 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 (Grant ref: MC_PC_19056), and the Wellcome Trust (Grant Ref: 222406/Z/20/Z) through the COVID-19 Therapeutics Accelerator.

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  1. ScreenIT

    SciScore for 10.1101/2021.06.08.21258132: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsIRB: The trial is conducted in accordance with the principles of the International Conference on Harmonisation–Good Clinical Practice guidelines and approved by the UK Medicines and Healthcare products Regulatory Agency (MHRA) and the Cambridge East Research Ethics Committee (ref: 20/EE/0101).
    Consent: Written informed consent was obtained from all patients, or a legal representative if they were too unwell or unable to provide consent.
    Sex as a biological variablenot detected.
    RandomizationStudy design and participants: The Randomised Evaluation of COVID-19 therapy (RECOVERY) trial is an investigator-initiated, individually randomised, controlled, open-label, platform trial to evaluate the effects of potential treatments in patients hospitalised with COVID-19.
    BlindingAs the trial progressed, the trial steering committee, whose members were unaware of the results of the trial comparisons, determined that sufficient patients should be enrolled to provide at least 90% power at a two-sided significance level of 1% to detect a clinically relevant proportional reduction in 28-day mortality of 12.5% between the two groups.
    Power AnalysisAs the trial progressed, the trial steering committee, whose members were unaware of the results of the trial comparisons, determined that sufficient patients should be enrolled to provide at least 90% power at a two-sided significance level of 1% to detect a clinically relevant proportional reduction in 28-day mortality of 12.5% between the two groups.

    Table 2: Resources

    No key resources detected.

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    The trial also had some limitations. Detailed information on radiological or physiological outcomes was not collected. Although this randomised trial is open label (i.e., participants and local hospital staff are aware of the assigned treatment), the primary and secondary outcomes are unambiguous and were ascertained without bias through linkage to routine health records. However, it cannot be excluded that reporting of thromboembolic and bleeding events might have been influenced by knowledge of treatment allocation. Nevertheless, the proportional effects of aspirin on these events were very similar to those reported in previous large clinical trials of aspirin in people with prior cardiovascular disease.6 The RECOVERY trial only studied hospitalised COVID-19 patients and, therefore, is not able to provide evidence on the safety and efficacy of aspirin used in other patient groups. Further studies to identify the safety and efficacy of aspirin in non-hospitalised patients are needed and are ongoing. In summary, the results of this large, randomised trial do not support the addition of aspirin to standard thromboprophylaxis or therapeutic anticoagulation in patients hospitalised with COVID-19.

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04381936RecruitingRandomised Evaluation of COVID-19 Therapy

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • No funding statement was detected.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

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  2. Version published to 10.1101/2021.06.08.21258132v1 on medRxiv