Azithromycin versus standard care in patients with mild-to-moderate COVID-19 (ATOMIC2): an open-label, randomised trial.

Abstract

BACKGROUND:

The antibacterial, anti-inflammatory, and antiviral properties of azithromycin suggest therapeutic potential against COVID-19. Randomised data in mild-to-moderate disease are not available. We assessed whether azithromycin is effective in reducing hospital admission in patients with mild-to-moderate COVID-19.

METHODS:

This prospective, open-label, randomised superiority trial was done at 19 hospitals in the UK. We enrolled adults aged at least 18 years presenting to hospitals with clinically diagnosed, highly probable or confirmed COVID-19 infection, with fewer than 14 days of symptoms, who were considered suitable for initial ambulatory management. Patients were randomly assigned (1:1) to azithromycin (500 mg once daily orally for 14 days) plus standard care or to standard care alone. The primary outcome was death or hospital admission from any cause over the 28 days from randomisation. The primary and safety outcomes were assessed according to the intention-to-treat principle. This trial is registered at ClinicalTrials.gov (NCT04381962) and recruitment is closed.

FINDINGS:

298 participants were enrolled from June 3, 2020, to Jan 29, 2021. Three participants withdrew consent and requested removal of all data, and three further participants withdrew consent after randomisation, thus, the primary outcome was assessed in 292 participants (145 in the azithromycin group and 147 in the standard care group). The mean age of the participants was 45·9 years (SD 14·9). 15 (10%) participants in the azithromycin group and 17 (12%) in the standard care group were admitted to hospital or died during the study (adjusted OR 0·91 [95% CI 0·43-1·92], p=0·80). No serious adverse events were reported.

INTERPRETATION:

In patients with mild-to-moderate COVID-19 managed without hospital admission, adding azithromycin to standard care treatment did not reduce the risk of subsequent hospital admission or death. Our findings do not support the use of azithromycin in patients with mild-to-moderate COVID-19.

FUNDING:

National Institute for Health Research Oxford Biomedical Research Centre, University of Oxford and Pfizer.

• Authors: Timothy S C Hinks, Lucy Cureton, Ruth Knight, Ariel Wang, Jennifer L Cane, Vicki S Barber, Joanna Black, Susan J Dutton, James Melhorn, Maisha Jabeen, Phil Moss, Rajendar Garlapati, Tanya Baron, Graham Johnson, Fleur Cantle, David Clarke, Samer Elkhodair, Jonathan Underwood, Daniel Lasserson, Ian D Pavord, Sophie Morgan, Duncan Richards
• Journal: The Lancet. Respiratory medicine (Lancet Respir Med) Vol. 9 Issue 10 Pg. 1130-1140 (10 2021) ISSN: 2213-2619 [Electronic] England
• PMID: 34252378 (Publication Type: Equivalence Trial, Journal Article, Multicenter Study, Randomized Controlled Trial)
• Copyright: Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Chemical References

• Anti-Infective Agents
• Azithromycin

Topics

• Adult
• Anti-Infective Agents (therapeutic use)
• Azithromycin (therapeutic use)
• COVID-19 (virology)
• Female
• Humans
• Male
• Middle Aged
• Patient Admission (statistics & numerical data)
• Prospective Studies
• SARS-CoV-2
• Standard of Care (statistics & numerical data)
• Treatment Outcome
• COVID-19 Drug Treatment