Azithromycin for treatment of hospitalised COVID-19 patients: a randomised, multicentre, open-label clinical trial (DAWn-AZITHRO).

BACKGROUND AND OBJECTIVES

Azithromycin was rapidly adopted as a repurposed drug to treat coronavirus disease 2019 (COVID-19) early in the pandemic. We aimed to evaluate its efficacy in patients hospitalised for COVID-19.

METHODS

In a series of randomised, open-label, phase 2 proof-of-concept, multicentre clinical trials (Direct Antivirals Working against the novel coronavirus (DAWn)), several treatments were compared with standard of care. In 15 Belgian hospitals, patients hospitalised with moderate to severe COVID-19 were allocated 2:1 to receive standard of care plus azithromycin or standard of care alone. The primary outcome was time to live discharge or sustained clinical improvement, defined as a two-point improvement on the World Health Organization (WHO) ordinal scale sustained for at least 3 days.

RESULTS

Patients were included between April 22 and December 17, 2020. When 15-day follow-up data were available for 160 patients (56% of preset cohort), an interim analysis was performed at request of the independent Data Safety and Monitoring Board. Subsequently, DAWn-AZITHRO was stopped for futility. In total, 121 patients were allocated to the treatment arm and 64 patients to the standard-of-care arm. We found no effect of azithromycin on the primary outcome with a hazard ratio of 1.044 (95% CI 0.772-1.413; p=0.7798). None of the predefined subgroups showed significant interaction as covariates in the Fine-Gray regression analysis. No benefit of azithromycin was found on any of the short- and longer-term secondary outcomes.

CONCLUSION

Time to clinical improvement is not influenced by azithromycin in patients hospitalised with moderate to severe COVID-19.

Informations de copyright

Copyright ©The authors 2022.

Déclaration de conflit d'intérêts

The DAWn-AZITHRO investigators: T. Van Assche, T. Devos, G. Meyfroidt, H. Ceunen, B. Debaveye, M. ‘t Lam, K. Haesendonck, L. Goegebeur, J. Neyts, E. Van Wijngaerden and P. De Munter. Conflict of interest: I. Gyselinck declares funding for the present work from the COVID-19 fund of the KU and UZ Leuven. Conflict of interest: L. Liesenborghs declares funding for the present work from the COVID-19 fund of the KU and UZ Leuven. Conflict of interest: A. Belmans declares funding for the present work from the COVID-19 fund of the KU and UZ Leuven. Conflict of interest: M.M. Engelen declares funding for the present work from the COVID-19 fund of the KU and UZ Leuven. Conflict of interest: A. Betrains declares funding for the present work from the COVID-19 fund of the KU and UZ Leuven. Conflict of interest: Q. Van Thillo declares funding for the present work from the COVID-19 fund of the KU and UZ Leuven. Conflict of interest: P.A.H. Nguyen declares funding for the present work from the COVID-19 fund of the KU and UZ Leuven. Conflict of interest: P. Goeminne declares payment or honoraria for lectures from AstraZeneca, GlaxoSmithKline and Chiesi, and advisory board participation for Chiesi and GlaxoSmithKline, all in the 26 months prior to manuscript submission; in addition they declare the following unpaid roles: EMBARC board member; BeRS board member; ERS group 10 board member. Conflict of interest: A-C. Soenen declares funding for the present work from the COVID-19 fund of the KU and UZ Leuven. Conflict of interest: N. De Maeyer declares funding for the present work from the COVID-19 fund of the KU and UZ Leuven. Conflict of interest: C. Pilette declares funding for the present work from the COVID-19 fund of the KU and UZ Leuven. Conflict of interest: E. Papleux declares funding for the present work from the COVID-19 fund of the KU and UZ Leuven. Conflict of interest: E. Vanderhelst declares funding for the present work from the COVID-19 fund of the KU and UZ Leuven. Conflict of interest: A. Derweduwen declares funding for the present work from the COVID-19 fund of the KU and UZ Leuven. Conflict of interest: P. Alexander declares funding for the present work from the COVID-19 fund of the KU and UZ Leuven. Conflict of interest: B. Bouckaert declares funding for the present work from the COVID-19 fund of the KU and UZ Leuven. Conflict of interest: J-B. Martinot declares funding for the present work from the COVID-19 fund of the KU and UZ Leuven. Conflict of interest: L. Decoster declares funding for the present work from the COVID-19 fund of the KU and UZ Leuven. Conflict of interest: K. Vandeurzen declares funding for the present work from the COVID-19 fund of the KU and UZ Leuven. Conflict of interest: R. Schildermans declares funding for the present work from the COVID-19 fund of the KU and UZ Leuven. Conflict of interest: P. Verhamme declares funding for the present work from the COVID-19 fund of the KU and UZ Leuven. Conflict of interest: W. Janssens declares participation on an advisory board on antiretrovirals for Gilead Sciences in 2018, and support for attending meetings from Gilead Sciences (EACS 2019) and Sanofi Pasteur (ISTM 2019); in addition, they were secretary of the Belgische Vereniging voor Infectiologie en Klinische Microbiologie until 2020. Conflict of interest: R. Vos declares funding for the present work from the COVID-19 fund of the KU and UZ Leuven.