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Randomized Controlled Trial
. 2022 Jan 6;59(1):2100752.
doi: 10.1183/13993003.00752-2021. Print 2022 Jan.

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

Pradeesh Sivapalan  1 , Charlotte Suppli Ulrik  2 , Therese Sophie Lapperre  3 , Rasmus Dahlin Bojesen  4   5 , Josefin Eklöf  1 , Andrea Browatzki  6 , Jon Torgny Wilcke  1 , Vibeke Gottlieb  1 , Kjell Erik Julius Håkansson  7 , Casper Tidemandsen  7 , Oliver Tupper  7 , Howraman Meteran  1 , Christina Bergsøe  7 , Eva Brøndum  7 , Uffe Bødtger  5   8 , Daniel Bech Rasmussen  4 , Sidse Graff Jensen  1 , Lars Pedersen  3 , Alexander Jordan  1 , Helene Priemé  9 , Christian Søborg  9 , Ida E Steffensen  9 , Dorthe Høgsberg  1 , Tobias Wirenfeldt Klausen  9 , Martin Steen Frydland  7 , Peter Lange  9   10 , Asger Sverrild  3 , Muhzda Ghanizada  3 , Filip K Knop  11   12 , Tor Biering-Sørensen  13 , Jens D Lundgren  14 , Jens-Ulrik Stæhr Jensen  1   12 ; ProPAC-COVID writing group on behalf of the ProPAC-COVID Study Group
Affiliations
Randomized Controlled Trial

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

Pradeesh Sivapalan et al. Eur Respir J. .

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.

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Conflict of interest statement

Conflict of interest: P. Sivapalan reports fees from Boehringer Ingelheim, outside the submitted work. C.S. Ulrik reports fees from Boehringer Ingelheim, AZ, GSK, TEVA, Novartis, ALK-Abello, Mundipharma, Sanofi Genzyme, Orion Pharma and Actelion, outside the submitted work. K.E.J. Håkansson reports personal fees from AstraZeneca, Chiesi and TEVA, outside the submitted work. T. Biering-Sørensen has received research grants from GE Healthcare and Sanofi Pasteur, as well as personal fees from Sanofi Pasteur, Novartis and Amgen, outside the submitted work. None of the other authors have any conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Consolidated Standards of Reporting of Randomised Trials diagram. COVID-19: coronavirus disease 2019; GI: gastrointestinal; eGFR: estimated glomerular filtration rate.
FIGURE 2
FIGURE 2
Days alive and out of hospital at a) 14 days and b) 30 days. IQR: interquartile range.
FIGURE 3
FIGURE 3
Clinical status (coronavirus disease 2019 outcomes scale category) on a) day 5 and b) day 15. ECMO: extracorporeal membrane oxygenation.
See this image and copyright information in PMC

Comment in

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