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Clinical efficacy of hydroxychloroquine in patients with COVID-19 pneumonia who require oxygen: observational comparative study using routine care data

Our take —

This observational study does not support the use of hydroxychloroquine in the management of non-severe COVID-19 patients who require supplemental oxygen. The researchers found no significant differences between the treatment and control groups in terms of survival without ICU transfer at day 21, overall survival at day 21, progression to acute respiratory distress syndrome by day 21, and weaning from supplemental oxygen by day 21.

Study design

Retrospective Cohort

Study population and setting

This study included 181 patients, age 18 to 80 years, with documented SARS-CoV-2 pneumonia who required oxygen but not intensive care who were recruited from four French tertiary care centers between March 12 and March 31, 2020. Patients with severe disease, including acute respiratory distress syndrome (ARDS) or progression requiring intensive care, were excluded from the study. Participants were not randomized to “treatment” or “control.” Instead, 84 patients who received hydroxychloroquine within 48 hours of admission to hospital were classified as the treatment group and were compared with 89 patients who did not receive hydroxychloroquine. 8 patients received hydroxychloroquine after 48 hours and were excluded from the primary analysis .

Summary of Main Findings

Hydroxychloroquine use within 48 hours of admission was not associated with clinical benefit. The primary outcome was survival without ICU transfer at day 21. In the weighted analyses, 76% of the treatment group and 75% of the control group survived until day 21 without ICU transfer (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 (weighted HR 1.2, 0.4 to 3.3). Survival without ARDS at day 21 was 69% in the treatment group compared with 74% in the control group (weighted HR 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%) discontinued hydroxychloroquine due to adverse cardiac events.

Study Strengths

Larger sample size than previous observational studies of hydroxychloroquine; propensity score weighted analysis attempts to control for observed confounding variables,


Participants were not randomized to treatment conditions and this thus limits causal interpretation of results. While the matching ensured that the groups being compared were similar with respect to a set of observed baseline characteristics, there may have still been some differences in unobserved characteristics between treatment groups, especially as indicated by some key differences in the COVID-19 related factors (including other treatments, see Table 1). Additionally, four variables could not be adjusted for in the weighted model. Finally, the model did not adjust for differences associated with treatment center.

Value added

Observational study with a larger population than previous hydroxychloroquine studies. Propensity score weighted and unweighted analyses presented.

This review was posted on: 12 June 2020