Hydroxychloroquine in mild-to-moderate COVID-19: a placebo-controlled double blind trial

Dubée, Vincent; Roy, Pierre-Marie; Vielle, Bruno; Parot-Schinkel, Elsa; Blanchet, Odile; Darsonval, Astrid; Lefeuvre, Caroline; Abbara, Chadi; Boucher, Sophie; Devaud, Edouard; Robineau, Olivier; Rispal, Patrick; Guimard, Thomas; d’Anglejean, Emma; Diamantis, Sylvain; Custaud, Marc-Antoine; Pellier, Isabelle; Mercat, Alain

OBJECTIVES: To determine whether hydroxychloroquine decreases the risk of adverse outcome in patients with mild-to-moderate COVID-19 at high risk of worsening. 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: need for supplemental oxygen, age ≥75 years, age between 60 - 74 years 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 days or a placebo. The primary endpoint was a composite of death or start of invasive mechanical ventilation 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 (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. CONCLUSION: 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.