Azithromycin in Hospitalised Patients with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Type Journal Article Author Peter W. Horby Author Alistair Roddick Author Enti Spata Author Natalie Staplin Author Jonathan R. Emberson Author Guilherme Pessoa-Amorim Author Leon Peto Author Mark Campbell Author Christopher Brightling Author Ben Prudon Author David Chadwick Author Andrew Ustianowski Author Abdul Ashish Author Stacy Todd Author Bryan Yates Author Robert Buttery Author Stephen Scott Author Diego Maseda Author J. Kenneth Baillie Author Maya H. Buch Author Lucy C. Chappell Author Jeremy N. Day Author Saul N. Faust Author Thomas Jaki Author Katie Jeffery Author Edmund Juszczak Author Wei Shen Lim Author Alan Montgomery Author Andrew Mumford Author Kathryn Rowan Author Guy Thwaites Author Marion Mafham Author Richard Haynes Author Martin J. Landray Author RECOVERY Collaborative Group URL https://www.medrxiv.org/content/10.1101/2020.12.10.20245944v1 Rights © 2020, Posted by Cold Spring Harbor Laboratory. This pre-print is available under a Creative Commons License (Attribution 4.0 International), CC BY 4.0, as described at http://creativecommons.org/licenses/by/4.0/ Pages 2020.12.10.20245944 Publication medRxiv Date 14/12/2020 Extra Publisher: Cold Spring Harbor Laboratory Press DOI 10.1101/2020.12.10.20245944 Library Catalog www.medrxiv.org Language en Abstract SUMMARY Background Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatory actions. We evaluated the efficacy and safety of azithromycin in hospitalised patients with COVID-19. Methods In this randomised, controlled, open-label, adaptive platform trial, several possible treatments were compared with usual care in patients hospitalised with COVID-19 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 daily by mouth or intravenously for 10 days or until discharge (or one of the other treatment arms). Patients were twice as likely to be randomised to usual care as to any of the active treatment groups. The primary outcome was 28-day mortality. The trial is registered with ISRCTN (50189673) and clinicaltrials.gov (NCT04381936). Findings Between 7 April and 27 November 2020, 2582 patients were randomly allocated to receive azithromycin and 5182 patients to receive usual care alone. Overall, 496 (19%) patients allocated to azithromycin and 997 (19%) patients allocated to usual care died within 28 days (rate ratio 1·00; 95% confidence interval [CI] 0·90-1·12; p=0·99). Consistent results were seen in all pre-specified subgroups of patients. There was no difference in duration of hospitalisation (median 12 days vs. 13 days) or the proportion of patients discharged from hospital alive within 28 days (60% vs. 59%; rate ratio 1·03; 95% CI 0·97-1·10; p=0·29). Among those not on invasive mechanical ventilation at baseline, there was no difference in the proportion meeting the composite endpoint of invasive mechanical ventilation or death (21% vs. 22%; risk ratio 0·97; 95% CI 0·89-1·07; p=0·54). Interpretation In patients hospitalised with COVID-19, azithromycin did not provide any clinical benefit. Azithromycin use in patients hospitalised with COVID-19 should be restricted to patients where there is a clear antimicrobial indication. Short Title Azithromycin in Hospitalised Patients with COVID-19 (RECOVERY)