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. MethodsThis 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.

Azithromycin in patients with COVID-19: a systematic review and meta-analysis

“… 23–25 In two studies, patients were treated with 500 mg/day for 10 days. 18 , 26 In one study, patients received 500 mg/day for 14 days 27 and in another one 500 mg/day for 3 days. 28 All studies compared the outcomes of patients treated with azithromycin against those for the ones that had only received standard care.…”

“…The meta-analysis showed no difference in death for those treated with or without azithromycin, in observational studies [OR: 0.90 (0.66–1.24)], RCTs [OR: 0.97 (0.87–1.08)] and when studies with both designs were pooled together [OR: 0.95 (0.79–1.13)] ( Figure 2 ). In the study by Hinks and colleagues, 27 the outcome was death or need for admission, and this was used as a proxy for death in the meta-analysis. Excluding this study had minimal effect on the magnitude and the significance of the results, with an overall OR 0.95 (0.79–1.14).…”

COVID-19 Patient Management in Outpatient Setting: A Population-Based Study from Southern Italy

“…A massive use of azithromycin was observed even in asymptomatic patients during the study period, although a large body of evidence documented that this drug is not effective in reducing the risk of COVID-19-related outcomes [ 17 ] or the time to recovery, when compared to the standard care alone [ 18 ]. It was also demonstrated that, when compared to placebo, the treatment with a single dose of azithromycin was not associated with a greater likelihood of being symptom-free within two weeks among outpatients with SARS-CoV-2 infection [ 19 ].…”

Safety and efficacy of fluvoxamine in COVID‐19 ICU patients: An open label, prospective cohort trial with matched controls

“…The WHO Solidarity Trial interim results showed that hydroxychloroquine, lopinavir, remdesivir and interferon beta‐1a had no impact on mortality, hospitalisation duration or initiation of ventilation support in COVID‐19 patients. 7 Among other drugs considered for repurposing, neither azithromycin, 8 metformin 9 nor favipiravir 10 demonstrated significant benefit in the treatment of COVID‐19 patients. Large controversies currently exist around the use of ivermectin in COVID‐19, 11 but both the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) advise against its use for the prevention or treatment of COVID‐19 outside of randomised clinical trials.…”