Clinical efficacy of hydroxychloroquine in patients with covid-19 pneumonia who require oxygen: observational comparative study using routine care data
Authors: Mahévas Matthieu , Tran Viet-Thi , Roumier Mathilde , Chabrol Amélie , Paule Romain , Guillaud Constance , Fois Elena , Lepeule Raphael , Szwebel Tali-Anne , Lescure François-Xavier , Schlemmer Frédéric , Matignon Marie , Khellaf Mehdi , Crickx Etienne , Terrier Benjamin , Morbieu Caroline , Legendre Paul , Dang Julien , Schoindre Yoland , Pawlotsky Jean-Michel , Michel Marc , Perrodeau Elodie , Carlier Nicolas , Roche Nicolas , de Lastours Victoire , Ourghanlian Clément , Kerneis Solen , Ménager Philippe , Mouthon Luc , Audureau Etienne , Ravaud Philippe , Godeau Bertrand , Gallien Sébastien , Costedoat-Chalumeau Nathalie 
Published: May 2020

Abstract

Objective
To assess the effectiveness of hydroxychloroquine in patients admitted to hospital with coronavirus disease 2019 (covid-19) pneumonia who require oxygen.

Design
Comparative observational study using data collected from routine care.

Setting
Four French tertiary care centres providing care to patients with covid-19 pneumonia between 12 March and 31 March 2020.

Participants
181 patients aged 18-80 years with documented severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia who required oxygen but not intensive care.

Interventions
Hydroxychloroquine at a dose of 600 mg/day within 48 hours of admission to hospital (treatment group) versus standard care without hydroxychloroquine (control group).

Main outcome measures
The primary outcome was survival without transfer to the intensive care unit at day 21. Secondary outcomes were overall survival, survival without acute respiratory distress syndrome, weaning from oxygen, and discharge from hospital to home or rehabilitation (all at day 21). Analyses were adjusted for confounding factors by inverse probability of treatment weighting.

Results
In the main analysis, 84 patients who received hydroxychloroquine within 48 hours of admission to hospital (treatment group) were compared with 89 patients who did not receive hydroxychloroquine (control group). Eight additional patients received hydroxychloroquine more than 48 hours after admission. In the weighted analyses, the survival rate without transfer to the intensive care unit at day 21 was 76% in the treatment group and 75% in the control group (weighted hazard ratio 0.9, 95% confidence interval 0.4 to 2.1). Overall survival at day 21 was 89% in the treatment group and 91% in the control group (1.2, 0.4 to 3.3). Survival without acute respiratory distress syndrome at day 21 was 69% in the treatment group compared with 74% in the control group (1.3, 0.7 to 2.6). At day 21, 82% of patients in the treatment group had been weaned from oxygen compared with 76% in the control group (weighted risk ratio 1.1, 95% confidence interval 0.9 to 1.3). Eight patients in the treatment group (10%) experienced electrocardiographic modifications that required discontinuation of treatment.

Conclusions
Hydroxychloroquine has received worldwide attention as a potential treatment for covid-19 because of positive results from small studies. However, the results of this study do not support its use in patients admitted to hospital with covid-19 who require oxygen.