TY - JOUR

T1 - Azithromycin and hydroxychloroquine in hospitalised patients with confirmed COVID-19

T2 - a randomised double-blinded placebo-controlled trial

AU - Sivapalan, Pradeesh

AU - Ulrik, Charlotte Suppli

AU - Lapperre, Therese Sophie

AU - Bojesen, Rasmus Dahlin

AU - Eklöf, Josefin

AU - Browatzki, Andrea

AU - Wilcke, Jon Torgny

AU - Gottlieb, Vibeke

AU - Håkansson, Kjell Erik Julius

AU - Tidemandsen, Casper

AU - Tupper, Oliver

AU - Meteran, Howraman

AU - Bergsøe, Christina

AU - Brøndum, Eva

AU - Bødtger, Uffe

AU - Rasmussen, Daniel Bech

AU - Jensen, Sidse Graff

AU - Pedersen, Lars

AU - Jordan, Alexander

AU - Priemé, Helene

AU - Søborg, Christian

AU - Steffensen, Ida E.

AU - Høgsberg, Dorthe

AU - Klausen, Tobias Wirenfeldt

AU - Frydland, Martin Steen

AU - Lange, Peter

AU - Sverrild, Asger

AU - Ghanizada, Muhzda

AU - Knop, Filip K.

AU - Biering-Sørensen, Tor

AU - Lundgren, Jens D.

AU - Jensen, Jens Ulrik Stæhr

AU - ProPAC-COVID writing group on behalf of the ProPAC-COVID Study Group

N1 - Publisher Copyright: Copyright © The authors 2022.

PY - 2022

Y1 - 2022

N2 - 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.

AB - 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.

U2 - 10.1183/13993003.00752-2021

DO - 10.1183/13993003.00752-2021

M3 - Journal article

C2 - 34083403

AN - SCOPUS:85123390021

VL - 59

JO - The European Respiratory Journal

JF - The European Respiratory Journal

SN - 0903-1936

IS - 1

M1 - 2100752

ER -