Azithromycin and hydroxychloroquine in hospitalised patients with confirmed COVID-19–a randomised double-blinded placebo-controlled trial

Abstract

Background Combining the antibiotic azithromycin and hydroxychloroquine induces airway immunomodulatory effects, with the latter also having in vitro antiviral properties. This may improve outcomes in patients hospitalised for COVID-19. Methods Placebo-controlled double-blind randomised multicentre trial. Patients ≥18\u2005years, admitted to hospital for≤48\u2005h (not intensive care) with a positive SARS-CoV-2 RT-PCR test, were recruited. The intervention was 500\u2005mg daily azithromycin for 3\u2005days followed by 250\u2005mg daily azithromycin for 12\u2005days combined with 200\u2005mg twice daily hydroxychloroquine for all 15\u2005days. The control group received placebo/placebo. The primary outcome was days alive and discharged from hospital within 14\u2005days (DAOH14). Results After randomisation of 117 patients, at the first planned interim analysis, the data and safety monitoring board recommended stopping enrolment due to futility, based on pre-specified criteria. Consequently, the trial was terminated on February 1, 2021. A total of 61 patients received the combined intervention and 56 patients received placebo. In the intervention group, patients had a median of 9.0 DAOH14 (IQR, 3–11) versus. 9.0 DAOH14 (IQR, 7–10) in the placebo group (p=0.90). The primary safety outcome, death from all causes on day 30, occurred for 1 patient in the intervention group versus. 2 patients receiving placebo (p=0.52), and readmittance or death within 30\u2005days occurred for 9 patients in the intervention group versus. 6 patients receiving placebo (p=0.57). Conclusions The combination of azithromycin and hydroxychloroquine did not improve survival or length of hospitalisation in patients with COVID-19.