No evidence of clinical efficacy of hydroxychloroquine in patients hospitalized for COVID-19 infection with oxygen requirement: results of a study using routinely collected data to emulate a target trial

Mahevas, Matthieu; Tran, Viet-Thi; Roumier, Mathilde; Chabrol, Amelie; Paule, Romain; Guillaud, Constance; Gallien, Sebastien; Lepeule, Raphael; Szwebel, Tali-Anne; Lescure, Xavier; Schlemmer, Frederic; Matignon, Marie; Khellaf, Mehdi; Crickx, Etienne; Terrier, Benjamin; Morbieu, Caroline; Legendre, Paul; Dang, Julien; Schoindre, Yoland; Pawlotski, Jean-Michel; Michel, Marc; Perrodeau, Elodie; Carlier, Nicolas; Roche, Nicolas; De Lastours, Victoire; Mouthon, Luc; Audureau, Etienne; Ravaud, Philippe; Godeau, Bertrand; Costedoat, Nathalie

Background Treatments are urgently needed to prevent respiratory failure and deaths from coronavirus disease 2019 (COVID-19). Hydroxychloroquine (HCQ) has received worldwide attention because of positive results from small studies. Methods We used data collected from routine care of all adults in 4 French hospitals with documented SARS-CoV-2 pneumonia and requiring oxygen ≥ 2 L/min to emulate a target trial aimed at assessing the effectiveness of HCQ at 600 mg/day. The composite primary endpoint was transfer to intensive care unit (ICU) within 7 days from inclusion and/or death from any cause. Analyses were adjusted for confounding factors by inverse probability of treatment weighting. Results This study included 181 patients with SARS-CoV-2 pneumonia; 84 received HCQ within 48 hours of admission (HCQ group) and 97 did not (no-HCQ group). Initial severity was well balanced between the groups. In the weighted analysis, 20.2% patients in the HCQ group were transferred to the ICU or died within 7 days vs 22.1% in the no-HCQ group (16 vs 21 events, relative risk [RR] 0.91, 95% CI 0.47-1.80). In the HCQ group, 2.8% of the patients died within 7 days vs 4.6% in the no-HCQ group (3 vs 4 events, RR 0.61, 95% CI 0.13-2.89), and 27.4% and 24.1%, respectively, developed acute respiratory distress syndrome within 7 days (24 vs 23 events, RR 1.14, 95% CI 0.65-2.00). Eight patients receiving HCQ (9.5%) experienced electrocardiogram modifications requiring HCQ discontinuation. Interpretation These results do not support the use of HCQ in patients hospitalised for documented SARS-CoV-2-positive hypoxic pneumonia.