Background Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatory actions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospital with COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients were randomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once per day by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment and were twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants and local study staff were not masked to the allocated treatment, but all others involved in the trial were masked to the outcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) were eligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was 65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomly allocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall, 561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days (rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median 10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days (rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, no significant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilation or death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or other prespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restricted to patients in whom there is a clear antimicrobial indication.
UK Research and Innovation (Medical Research Council) and National Institute of Health Research.
Above all, we would like to thank the thousands of patients who participated in this study. We would also like to thank the many doctors,
nurses, pharmacists, other allied health professionals, and research administrators at 176 NHS hospital organisations across the UK, supported by staff at the NIHR Clinical Research Network, NHS DigiTrials, Public Health England, UK Department of Health and Social Care, Intensive Care National Audit and Research Centre, Public Health Scotland, National Records Service of Scotland, Secure Anonymised Information Linkage at University of Swansea, and the NHS in England, Scotland, Wales, and Northern Ireland. The RECOVERY trial is supported by a grant to the University of Oxford from UK Research and Innovation (Medical Research Council) and NIHR (MC_PC_19056) and by core funding provided by NIHR Oxford Biomedical Research Centre, Wellcome, the Bill & Melinda Gates Foundation, the Department for International Development, 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 UK Medical Research Council (MC_UU_0002/14) and an NIHR Senior
Research Fellowship (NIHR-SRF-2015-08-001). WSL is supported by core funding provided by NIHR Nottingham Biomedical Research Centre.
AbbVie contributed some supplies of lopinavir–ritonavir for use in this study. Tocilizumab was provided free of charge for this study by Roche
Products. REGN-COV2 was provided free of charge for this study by Regeneron. The views expressed in this publication are those of the
authors and not necessarily those of the NHS, UK Research and Innovation, the NIHR, or the UK Department of Health and Social Care.
The authors have no conflict of interest or financial relationships relevant to the submitted work to disclose. No form of payment was
given to anyone to produce the manuscript. All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of
Interest. The Nuffield Department of Population Health at the University of Oxford has a staff policy of not accepting honoraria or consultancy fees directly or indirectly from industry