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


Journal

The European respiratory journal
ISSN: 1399-3003
Titre abrégé: Eur Respir J
Pays: England
ID NLM: 8803460

Informations de publication

Date de publication:
01 2022
Historique:
received: 15 03 2021
accepted: 22 05 2021
pubmed: 5 6 2021
medline: 12 1 2022
entrez: 4 6 2021
Statut: epublish

Résumé

Combining the antibiotic azithromycin and hydroxychloroquine induces airway immunomodulatory effects, with the latter also having 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). 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 The combination of azithromycin and hydroxychloroquine did not improve survival or length of hospitalisation in patients with COVID-19.

Sections du résumé

BACKGROUND
Combining the antibiotic azithromycin and hydroxychloroquine induces airway immunomodulatory effects, with the latter also having
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
CONCLUSIONS
The combination of azithromycin and hydroxychloroquine did not improve survival or length of hospitalisation in patients with COVID-19.

Identifiants

pubmed: 34083403
pii: 13993003.00752-2021
doi: 10.1183/13993003.00752-2021
pmc: PMC8186006
pii:
doi:

Substances chimiques

Hydroxychloroquine 4QWG6N8QKH
Azithromycin 83905-01-5

Types de publication

Journal Article Multicenter Study Randomized Controlled Trial

Langues

eng

Sous-ensembles de citation

IM

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright ©The authors 2022.

Déclaration de conflit d'intérêts

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.

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Auteurs

Pradeesh Sivapalan (P)

Dept of Internal Medicine, Pulmonary Medicine Section, Gentofte University Hospital, Hellerup, Denmark.

Charlotte Suppli Ulrik (CS)

Dept of Respiratory Medicine, Respiratory Research Unit, Hvidovre and Amager University Hospital, Hvidovre, Denmark jens.ulrik.jensen@regionh.dk.

Therese Sophie Lapperre (TS)

Dept of Respiratory Medicine, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark.

Rasmus Dahlin Bojesen (RD)

Dept of Surgery, Slagelse Hospital, Slagelse, Denmark.
Dept of Respiratory Medicine, Næstved Hospital, Næstved, Denmark.

Josefin Eklöf (J)

Dept of Internal Medicine, Pulmonary Medicine Section, Gentofte University Hospital, Hellerup, Denmark.

Andrea Browatzki (A)

Dept of Respiratory and Infectious Diseases, Nordsjællands Hospital, Hillerød, Denmark.

Jon Torgny Wilcke (JT)

Dept of Internal Medicine, Pulmonary Medicine Section, Gentofte University Hospital, Hellerup, Denmark.

Vibeke Gottlieb (V)

Dept of Internal Medicine, Pulmonary Medicine Section, Gentofte University Hospital, Hellerup, Denmark.

Kjell Erik Julius Håkansson (KEJ)

Dept of Respiratory Medicine, Respiratory Research Unit, Hvidovre and Amager University Hospital, Hvidovre, Denmark.

Casper Tidemandsen (C)

Dept of Respiratory Medicine, Respiratory Research Unit, Hvidovre and Amager University Hospital, Hvidovre, Denmark.

Oliver Tupper (O)

Dept of Respiratory Medicine, Respiratory Research Unit, Hvidovre and Amager University Hospital, Hvidovre, Denmark.

Howraman Meteran (H)

Dept of Internal Medicine, Pulmonary Medicine Section, Gentofte University Hospital, Hellerup, Denmark.

Christina Bergsøe (C)

Dept of Respiratory Medicine, Respiratory Research Unit, Hvidovre and Amager University Hospital, Hvidovre, Denmark.

Eva Brøndum (E)

Dept of Respiratory Medicine, Respiratory Research Unit, Hvidovre and Amager University Hospital, Hvidovre, Denmark.

Uffe Bødtger (U)

Dept of Respiratory Medicine, Næstved Hospital, Næstved, Denmark.
Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark.

Daniel Bech Rasmussen (D)

Dept of Surgery, Slagelse Hospital, Slagelse, Denmark.

Sidse Graff Jensen (S)

Dept of Internal Medicine, Pulmonary Medicine Section, Gentofte University Hospital, Hellerup, Denmark.

Lars Pedersen (L)

Dept of Respiratory Medicine, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark.

Alexander Jordan (A)

Dept of Internal Medicine, Pulmonary Medicine Section, Gentofte University Hospital, Hellerup, Denmark.

Helene Priemé (H)

Dept of Medicine, Section of Respiratory Medicine, Herlev Hospital, Herlev, Denmark.

Christian Søborg (C)

Dept of Medicine, Section of Respiratory Medicine, Herlev Hospital, Herlev, Denmark.

Ida E Steffensen (IE)

Dept of Medicine, Section of Respiratory Medicine, Herlev Hospital, Herlev, Denmark.

Dorthe Høgsberg (D)

Dept of Internal Medicine, Pulmonary Medicine Section, Gentofte University Hospital, Hellerup, Denmark.

Tobias Wirenfeldt Klausen (TW)

Dept of Medicine, Section of Respiratory Medicine, Herlev Hospital, Herlev, Denmark.

Martin Steen Frydland (MS)

Dept of Respiratory Medicine, Respiratory Research Unit, Hvidovre and Amager University Hospital, Hvidovre, Denmark.

Peter Lange (P)

Dept of Medicine, Section of Respiratory Medicine, Herlev Hospital, Herlev, Denmark.
Institute of Public Health, Section of Epidemiology, University of Copenhagen, Copenhagen, Denmark.

Asger Sverrild (A)

Dept of Respiratory Medicine, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark.

Muhzda Ghanizada (M)

Dept of Respiratory Medicine, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark.

Filip K Knop (FK)

Center for Clinical Metabolic Research, Gentofte University Hospital, Hellerup, Denmark.
Dept of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Tor Biering-Sørensen (T)

Dept of Cardiology, Gentofte University Hospital, Hellerup, Denmark.

Jens D Lundgren (JD)

Dept of Infectious Medicine, Rigshospitalet, Copenhagen, Denmark.

Jens-Ulrik Stæhr Jensen (JS)

Dept of Internal Medicine, Pulmonary Medicine Section, Gentofte University Hospital, Hellerup, Denmark.
Dept of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

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