Azithromycin versus standard care in patients with mild-to-moderate COVID-19 (ATOMIC2): an open-label, randomised trial
MD Timothy S C Hinks, Lucy Cureton, PhD Ruth Knight, Ariel Wang, PhD Jennifer L Cane, PhD Vicki S Barber, PhD Joanna Black, MSc Susan J Dutton, MD James Melhorn, Maisha Jabeen, Phil Moss, MD Rajendar Garlapati, Tanya Baron, Graham Johnson, Fleur Cantle, David Clarke, Samer Elkhodair, Jonathan Underwood, Daniel Lasserson, Ian D Pavord, Sophie Morgan, Prof Duncan Richards
The Lancet Respiratory Medicine, doi:10.1016/s2213-2600(21)00263-0
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.
Contributors TSCH, VSB, JB, SJD, MJ, JM, DL, IDP, and DR contributed to conceptualisation and design of the protocol. SJD performed the power calculation. TSCH, LC, VSB, SM, JLC, JM, MJ, DL, PM, RG, TB, GJ, FC, DC, SE, JU, LC, and DC contributed to acquisition of study data. Data were analysed by AW, SJD, and RK. AW, RK, SJD, and LC have accessed and verified the data. TSCH drafted this submission, which was approved by all authors. All authors had full access to all the data in the study and final responsibility for the decision to submit for publication.
Declaration of interests TSCH has received grants from Pfizer, University of Oxford, the Wellcome Trust, The Guardians of the Beit Fellowship, and the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC) during the conduct of the study; and personal fees from Astra Zeneca, TEVA, and Peer Voice, outside of the submitted work. MJ has received grants from the University of Oxford and NIHR Oxford Biomedical Research Centre. DR has undertaken paid consultancy for GlaxoSmithKline outside of the submitted work. IDP reports personal fees from AstraZeneca, Boehringer Ingelheim, Aerocrine, Almirall, Novartis, GlaxoSmithKline, Genentech, Regeneron, Teva, Chiesi, Sanofi, Circassia, and Knopp; and grants from NIHR, outside of the submitted work. JU has received honoraria for preparation of educational materials and has served on an advisory board for Gilead Sciences and ViiV Healthcare, outside of the..
References
Altenburg, De Graaff, Van Der Werf, Boersma, Immunomodulatory effects of macrolide antibiotics -part 1: biological mechanisms, Respiration
Andreani, Bideau, Duflot, In vitro testing of combined hydroxychloroquine and azithromycin on SARS-CoV-2 shows synergistic effect, Microb Pathog
Arabi, Deeb, Al-Hameed, Macrolides in critically ill patients with Middle East respiratory syndrome, Int J Infect Dis
Baden, Rubin, Covid-19 -The search for effective therapy, N Engl J Med
Brown, Peltan, Kumar, Hydroxychloroquine vs. azithromycin for hospitalized patients with COVID-19 (HAHPS): results of a randomized, active comparator trial, Ann Am Thorac Soc
Cao, Wang, Wen, A Trial of lopinavir-ritonavir in adults hospitalized with severe Covid-19, N Engl J Med
Cavalcanti, Zampieri, Rosa, Hydroxychloroquine with or without azithromycin in mild-to-moderate Covid-19, N Engl J Med
Chen, Nirula, Heller, SARS-CoV-2 Neutralizing antibody LY-CoV555 in outpatients with Covid-19, N Engl J Med
Doan, Hinterwirth, Arzika, Reduction of coronavirus burden with mass azithromycin distribution, Clin Infect Dis
Fragkou, Belhadi, Peiffer-Smadja, Review of trials currently testing treatment and prevention of COVID-19, Clin Microbiol Infect
Furtado, Berwanger, Fonseca, Azithromycin in addition to standard of care versus standard of care alone in the treatment of patients admitted to the hospital with severe COVID-19 in Brazil (COALITION II): a randomised clinical trial, Lancet
Gautret, Lagier, Parola, Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial, Int J Antimicrob Agents
Gill, Poduval, Thakur, Iqbal, COVID-19, community trials, and inclusion, Lancet
Group, Azithromycin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial, Lancet
Hinks, Barber, Black, A multi-centre open-label two-arm randomised superiority clinical trial of azithromycin versus usual care in ambulatory COVID-19: study protocol for the ATOMIC2 trial, Trials
Horby, Lim, Emberson, Dexamethasone in hospitalized patients with Covid-19, N Engl J Med
Jin, Pang, Zhang, Core outcome set for clinical trials on coronavirus disease 2019 (COS-COVID), Engineering
Johnston, Brown, Stewart, Hydroxychloroquine with or without azithromycin for treatment of early SARS-CoV-2 infection among high-risk outpatient adults: a randomized clinical trial, EClinicalMedicine
Lane, Weaver, Kostka, Risk of hydroxychloroquine alone and in combination with azithromycin in the treatment of rheumatoid arthritis: a multinational, retrospective study, Lancet Rheumatol
Langford, So, Raybardhan, Bacterial co-infection and secondary infection in patients with COVID-19: a living rapid review and meta-analysis, Clin Microbiol Infect
Lundgren, Grund, Barkauskas, A neutralizing monoclonal antibody for hospitalized patients with Covid-19, N Engl J Med
Martinez, Compounds with therapeutic potential against novel respiratory 2019 coronavirus, Antimicrob Agents Chemother
Oliver, Hinks, Azithromycin in viral infections, Rev Med Virol
Omrani, Pathan, Thomas, Randomized doubleblinded placebo-controlled trial of hydroxychloroquine with or without azithromycin for virologic cure of non-severe Covid-19, EClinicalMedicine
Parnham, Haber, Ej, Perletti, Verleden et al., Azithromycin: mechanisms of action and their relevance for clinical applications, Pharmacol Ther
Serisier, Risks of population antimicrobial resistance associated with chronic macrolide use for inflammatory airway diseases, Lancet Respir Med
Svanström, Pasternak, Hviid, Use of azithromycin and death from cardiovascular causes, N Engl J Med
Touret, Gilles, Barral, In vitro screening of a FDA approved chemical library reveals potential inhibitors of SARS-CoV-2 replication, Sci Rep
Trial, Group, Azithromycin for community treatment of suspected COVID-19 in people at increased risk of an adverse clinical course in the UK (PRINCIPLE): a randomised, controlled, open-label, adaptive platform trial, Lancet
Watson, Whiting, Brush, Interpreting a covid-19 test result, BMJ
Who, WHO R&D blueprint novel coronavirus COVID-19 therapeutic trial synopsis
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'clinical trial',
'volume': '33',
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