A placebo-controlled double blind trial of hydroxychloroquine in mild-to-moderate COVID-19

Dubee, V.; Roy, P.-M.; Vielle, B.; Parot-Schinkel, E.; Blanchet, O.; Darsonval, A.; Lefeuvre, C.; Abbara, C.; Boucher, S.; Devaud, E.; Robineau, O.; Rispal, P.; Guimard, T.; D'Anglejan, E.; Diamantis, S.; Custaud, M.-A.; Pellier, I.; Mercat, A.

Background The efficacy of hydroxychloroquine in coronavirus disease 2019 (COVID-19) remains controversial. Methods We conducted a multicentre randomized double-blind placebo-controlled trial evaluating hydroxychloroquine in COVID-19 patients with at least one of the following risk factors for worsening: age 75 years or more, age between 60 and 74 years, and presence of at least one comorbidity, or need for supplemental oxygen (3 L/min or more). Eligible patients were randomized in a 1:1 ratio to receive either 800 mg hydroxychloroquine on Day 0 followed by 400 mg per day for 8 days or a placebo. The primary endpoint was a composite of death or tracheal intubation within 14 days following randomization. Secondary endpoints included mortality and clinical evolution at Day 14 and 28, viral shedding at Day 5 and 10. Results The trial was stopped after 250 patients were included due to a slowdown of the pandemic in France. The intention-to-treat population comprised 123 and 124 patients in the placebo and hydroxychloroquine groups, respectively. The median age was 77 years and 151 patients required oxygen therapy. The primary endpoint occurred in nine patients in the hydroxychloroquine group and eight patients in the placebo group (relative risk 1.12; 95% confidence interval 0.45-2.80; P=0.82). No difference was observed between the two groups in any of the secondary endpoints. Conclusion In this trial involving mainly older patients with mild-to-moderate COVID-19, patients treated with hydroxychloroquine did not experience better clinical or virological outcomes than those receiving the placebo.