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

Sivapalan, Pradeesh; Suppli Ulrik, Charlotte; Sophie Lapperre, Therese; Dahlin Bojesen, Rasmus; Eklöf, Josefin; Browatzki, Andrea; Torgny Wilcke, Jon; Gottlieb, Vibeke; Julius Håkansson, Kjell Erik; Tidemandsen, Casper; Tupper, Oliver; Meteran, Howraman; Bergsøe, Christina; Brøndum, Eva; Bodtger, Uffe; Bech Rasmussen, Daniel; Graff Jensen, Sidse; Pedersen, Lars; Jordan, Alexander; Priemé, Helene; Søborg, Christian; Steffensen, Ida E.; Høgsberg, Dorthe; Wirenfeldt Klausen, Tobias; Steen Frydland, Martin; Lange, Peter; Sverrild, Asger; Ghanizada, Muhzda; Krag Knop, Filip; Biering-Sørensen, Tor; Lundgren, Jens D.; Stæhr Jensen,, Jens-Ulrik

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 years, admitted to hospital for≤48 h (not intensive care) with a positive SARS-CoV-2 RT-PCR test, were recruited. The intervention was 500 mg daily azithromycin for 3 days followed by 250 mg daily azithromycin for 12 days combined with 200 mg twice daily hydroxychloroquine for all 15 days. The control group received placebo/placebo. The primary outcome was days alive and discharged from hospital within 14 days (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 days 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.