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

Iwein Gyselinck¹, Laurens Liesenborghs², Ann Belmans³, Matthias M Engelen⁴, Albrecht Betrains^{5

6}, Quentin Van Thillo^{7

8}, Pham Anh Hong Nguyen⁹, Pieter Goeminne¹⁰, Ann-Catherine Soenen¹¹, Nikolaas De Maeyer¹², Charles Pilette¹³, Emmanuelle Papleux¹⁴, Eef Vanderhelst¹⁵, Aurélie Derweduwen¹⁶, Patrick Alexander¹⁷, Bernard Bouckaert¹⁸, Jean-Benoît Martinot¹⁹, Lynn Decoster²⁰, Kurt Vandeurzen²¹, Rob Schildermans²², Peter Verhamme⁴, Wim Janssens¹, Robin Vos¹

Affiliations

¹ Dept of Respiratory Diseases, UZ Leuven and CHROMETA, Research group BREATHE, KU Leuven, Leuven, Belgium.
² Laboratory of Virology and Chemotherapy, Dept of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium.
³ Leuven Biostatistics and Statistical Bioinformatics Centre (L-BioStat), KU Leuven, Leuven and University Hasselt, Hasselt, Belgium.
⁴ Dept of Cardiovascular Diseases, UZ Leuven and Centre for Molecular and Vascular Biology, KU Leuven, Leuven, Belgium.
⁵ Dept of General Internal Medicine, University Hospitals Leuven, Leuven, Belgium.
⁶ Dept of Microbiology, Immunology, and Transplantation, KU Leuven, Leuven, Belgium.
⁷ Center for Cancer Biology, Vlaams Instituut voor Biotechnologie (VIB), Leuven, Belgium.
⁸ Center for Human Genetics, KU Leuven, Leuven, Belgium.
⁹ Dept of Respiratory Diseases, Onze Lieve Vrouw Ziekenhuis, Aalst, Belgium.
¹⁰ Dept of Respiratory Diseases, AZ Nikolaas, Sint-Niklaas, Belgium.
¹¹ Dept of Respiratory Diseases, Jan Yperman Ziekenhuis, Ypres, Belgium.
¹² Dept of Respiratory Diseases, Heilig Hart Ziekenhuis, Leuven, Belgium.
¹³ Dept of Respiratory Diseases, Cliniques Universitaires Saint-Luc, Brussels, Belgium.
¹⁴ Dept of Respiratory Diseases, Hôpitaux Iris Sud, Brussels, Belgium.
¹⁵ Dept of Respiratory Diseases, University Hospital UZ Brussel, Vrije Universiteit Brussel, Brussels, Belgium.
¹⁶ Dept of Respiratory Diseases, AZ Klina, Brasschaat, Belgium.
¹⁷ Dept of Respiratory Diseases, AZ Glorieux, Ronse, Belgium.
¹⁸ Dept of Respiratory Diseases, AZ Delta, Roeselare, Belgium.
¹⁹ Dept of Respiratory Diseases, Centre Hospitalier Universitaire-UC Louvain, Namur, Belgium.
²⁰ Dept of Respiratory Diseases, AZ Turnhout, Turnhout, Belgium.
²¹ Dept of Respiratory Diseases, Mariaziekenhuis Noord Limburg, Pelt, Belgium.
²² Dept of Respiratory Diseases, AZ Sint Lucas, Bruges, Belgium.

PMID: 35233389
PMCID: PMC8801156
DOI: 10.1183/23120541.00610-2021

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

Iwein Gyselinck et al. ERJ Open Res. 2022.

. 2022 Feb 28;8(1):00610-2021.

doi: 10.1183/23120541.00610-2021. eCollection 2022 Jan.

Authors

Affiliations

¹ Dept of Respiratory Diseases, UZ Leuven and CHROMETA, Research group BREATHE, KU Leuven, Leuven, Belgium.
² Laboratory of Virology and Chemotherapy, Dept of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium.
³ Leuven Biostatistics and Statistical Bioinformatics Centre (L-BioStat), KU Leuven, Leuven and University Hasselt, Hasselt, Belgium.
⁴ Dept of Cardiovascular Diseases, UZ Leuven and Centre for Molecular and Vascular Biology, KU Leuven, Leuven, Belgium.
⁵ Dept of General Internal Medicine, University Hospitals Leuven, Leuven, Belgium.
⁶ Dept of Microbiology, Immunology, and Transplantation, KU Leuven, Leuven, Belgium.
⁷ Center for Cancer Biology, Vlaams Instituut voor Biotechnologie (VIB), Leuven, Belgium.
⁸ Center for Human Genetics, KU Leuven, Leuven, Belgium.
⁹ Dept of Respiratory Diseases, Onze Lieve Vrouw Ziekenhuis, Aalst, Belgium.
¹⁰ Dept of Respiratory Diseases, AZ Nikolaas, Sint-Niklaas, Belgium.
¹¹ Dept of Respiratory Diseases, Jan Yperman Ziekenhuis, Ypres, Belgium.
¹² Dept of Respiratory Diseases, Heilig Hart Ziekenhuis, Leuven, Belgium.
¹³ Dept of Respiratory Diseases, Cliniques Universitaires Saint-Luc, Brussels, Belgium.
¹⁴ Dept of Respiratory Diseases, Hôpitaux Iris Sud, Brussels, Belgium.
¹⁵ Dept of Respiratory Diseases, University Hospital UZ Brussel, Vrije Universiteit Brussel, Brussels, Belgium.
¹⁶ Dept of Respiratory Diseases, AZ Klina, Brasschaat, Belgium.
¹⁷ Dept of Respiratory Diseases, AZ Glorieux, Ronse, Belgium.
¹⁸ Dept of Respiratory Diseases, AZ Delta, Roeselare, Belgium.
¹⁹ Dept of Respiratory Diseases, Centre Hospitalier Universitaire-UC Louvain, Namur, Belgium.
²⁰ Dept of Respiratory Diseases, AZ Turnhout, Turnhout, Belgium.
²¹ Dept of Respiratory Diseases, Mariaziekenhuis Noord Limburg, Pelt, Belgium.
²² Dept of Respiratory Diseases, AZ Sint Lucas, Bruges, Belgium.

PMID: 35233389
PMCID: PMC8801156
DOI: 10.1183/23120541.00610-2021

Abstract

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.

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Conflict of interest statement

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.

Figures

**FIGURE 1**
Primary end-point: cumulative incidence function of sustained clinical improvement or live discharge (full analysis set). AZITHRO: azithromycin; SOC: standard of care.

**FIGURE 2**
Forest plot subgroup analyses for primary end-point: time to sustained clinical improvement or discharge (full analysis set). AZITHRO: azithromycin; SOC: standard of care; NC: not calculated.

**FIGURE 3**
Bar chart of daily clinical status (full analysis set). AZITHRO: azithromycin; SOC: standard of care; Hosp.: hospitalised; inv: invasive; MV: mechanical ventilation; ECMO: extracorporeal membrane oxygenation.

See this image and copyright information in PMC

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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

LinkOut - more resources

Full Text Sources

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