Timothy S C Hinks1, Lucy Cureton2, Ruth Knight2, Ariel Wang3, Jennifer L Cane3, Vicki S Barber3, Joanna Black3, Susan J Dutton3, James Melhorn4, Maisha Jabeen3, Phil Moss5, Rajendar Garlapati6, Tanya Baron7, Graham Johnson8, Fleur Cantle9, David Clarke10, Samer Elkhodair11, Jonathan Underwood12, Daniel Lasserson13, Ian D Pavord3, Sophie Morgan3, Duncan Richards3. 1. Respiratory Medicine Unit and National Institute for Health Research Oxford Biomedical Research Centre, Nuffield Department of Medicine Experimental Medicine, University of Oxford, Oxford, UK. Electronic address: timothy.hinks@ndm.ox.ac.uk. 2. Oxford Clinical Trials Research Unit, Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Botnar Research Centre, University of Oxford, Oxford, UK. 3. Respiratory Medicine Unit and National Institute for Health Research Oxford Biomedical Research Centre, Nuffield Department of Medicine Experimental Medicine, University of Oxford, Oxford, UK. 4. University Hospital Llandough, Cardiff, UK. 5. Emergency Department Clinical Research Unit, St George's Hospital, London, UK. 6. Accident and Emergency, East Lancashire NHS Hospitals, Blackburn, UK. 7. Emergency Department, Oxford University Hospitals NHS Foundation Trust, Oxford, UK. 8. University Hospitals of Derby and Burton, Royal Derby Hospital, Derby, UK; University of Nottingham, Lenton, Nottingham UK. 9. Department of Emergency Medicine, King's College Hospital, London, UK. 10. Royal Berkshire Hospital, Reading, UK. 11. Emergency Department, University College London Hospital, London UK. 12. Department of Infectious Diseases, Cardiff and Vale University Health Board, Cardiff, UK; Division of Infection and Immunity, Cardiff University, Cardiff, UK. 13. Department of Geratology, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford, UK; Department of Acute Medicine, Sandwell and West Birmingham Hospitals NHS Trust, City Hospital, Birmingham, UK; Warwick Medical School, University of Warwick, Coventry, UK.
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, addingazithromycin 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.
RCT Entities:
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-19infection, 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: Bernardo A Martinez-Guerra; Maria F Gonzalez-Lara; Carla M Roman-Montes; Karla M Tamez-Torres; Francisco E Dardón-Fierro; Sandra Rajme-Lopez; Carla Medrano-Borromeo; Alejandra Martínez-Valenzuela; Edgar Ortiz-Brizuela; Jose Sifuentes-Osornio; Alfredo Ponce-de-Leon Journal: Emerg Microbes Infect Date: 2022-12 Impact factor: 7.163