Hydroxychloroquine in mild-to-moderate coronavirus disease 2019: a placebo-controlled double blind trial

Abstract

\n Objectives\n To determine whether hydroxychloroquine decreases the risk of adverse outcome in patients with mild-to-moderate COVID-19 at high risk of worsening.\n \n Methods\n 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: need for supplemental oxygen, age ≥75\xa0years, age between 60 - 74\xa0years and presence of at least one comorbidity. Severely ill patients requiring oxygen therapy > 3L/min or intensive care were excluded. Eligible patients were randomized in a 1:1 ratio to receive either 800mg hydroxychloroquine on Day 0 followed by 400mg per day for 8\xa0days or a placebo. The primary endpoint was a composite of death or start of invasive mechanical ventilation within 14\xa0days following randomization. Secondary endpoints included mortality and clinical evolution at Day 14 and 28, viral shedding at Day 5 and 10.\n \n Results\n 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 (interquartile range 58 – 86) years and 151/250 (60.4%) patients required oxygen therapy. The primary endpoint occurred in 9/124 (7.3%) patients in the hydroxychloroquine group and 8/123 (6.5%) patients in the placebo group (relative risk 1.12; 95% confidence interval 0.45– 2.80). The rate of positive SARS-CoV-2 RT-PCR at day 5 and 10 was 72.8% (75/103) and 57.1% (52/91) in the hydroxychloroquine group, versus 73.0% (73/100) and 56.6% (47/83) in the placebo group, respectively. No difference was observed between the two groups in any of the other secondary endpoints.\n \n Conclusion\n In this underpowered 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.\n