Azithromycin and hydroxychloroquine in hospitalised patients with confirmed COVID-19: a randomised double-blinded placebo-controlled trial
Pradeesh Sivapalan, Charlotte Suppli Ulrik, Thérèse Lapperre, Rasmus Dahlin Bojesen, Josefin Eklöf, Andrea Browatzki, Jon Torgny Wilcke, Vibeke Gottlieb, Kjell Erik Julius Håkansson, Casper Tidemandsen, Oliver Djurhuus Tupper, Howraman Meteran, Christina Marisa Bergsøe, Eva Brøndum, Uffe Bødtger, Daniel Bech Rasmussen, Sidse Graff Jensen, Lars Pedersen, Alexander Jordan, Helene Priemé, Christian Søborg, Ida Steffensen, Dorthe Sandbæk Høgsberg, Tobias Wirenfeldt Klausen, Martin Frydland, Peter Lange, Asger Sverrild, Muzhda Ghanizada, Filip K. Knop, Tor Biering‐Sørensen, Jens Lundgren, Jens‐Ulrik Stæhr Jensen
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 coronavirus disease 2019 (COVID-19). Methods Placebo-controlled double-blind randomised multicentre trial. Patients aged ≥18 years, admitted to hospital for ≤48 h (not intensive care) with a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcription 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 1 February 2021. 61 patients received the combined intervention and 56 patients received placebo. In the intervention group, patients had a median (interquartile range) 9.0 (3–11) DAOH14 versus 9.0 (7–10) DAOH14 in the placebo group (p=0.90). The primary safety outcome, death from all causes on day 30, occurred for one patient in the intervention group versus two patients receiving placebo (p=0.52), and readmittance or death within 30 days occurred for nine patients in the intervention group versus six 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.