A Cluster-Randomized Trial of Hydroxychloroquine as Prevention of Covid-19 Transmission and Disease

Mitja, O.; Ubals, M.; Corbacho, M.; Alemany, A.; Suner, C.; Tebe, C.; Tobias, A.; Penafiel, J.; Ballana, E.; Perez, C. A.; Admella, P.; Riera-Marti, N.; Laporte, P.; Mitja, J.; Clua, M.; Bertran, L.; Gavilan, S.; Ara, J.; Sarquella, M.; Argimon, J. M.; Cuatrecasas, G.; Canadas, P.; Elizalde-Torrent, A.; Fabregat, R.; Farre, M.; Forcada, A.; Flores-Mateo, G.; Lopez, C.; Muntada, E.; Nadal, N.; Narejos, S.; Gil-Ortega, A. N.; Prat, N.; Puig, J.; Quinones, C.; Ramirez-Viaplana, F.; Reyes-Uruena, J.; Riveira-Munoz, E.; Ruiz, L.; Sanz, S.; Sentis, A.; Sierra, A.; Velasco, C.; Vivanco-Hidalgo, R. M.

Background Current strategies for preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections are limited to non-pharmacological interventions. Hydroxychloroquine (HCQ) has been proposed as a postexposure therapy to prevent Coronavirus disease 2019 (Covid-19) but definitive evidence is lacking. Methods We conducted an open-label, cluster-randomized trial including asymptomatic contacts exposed to a PCR-positive Covid-19 case in Catalonia, Spain. Clusters were randomized to receive no specific therapy (control arm) or HCQ 800mg once, followed by 400mg daily for 6 days (intervention arm). The primary outcome was PCR-confirmed symptomatic Covid-19 within 14 days. The secondary outcome was SARS-CoV-2 infection, either symptomatically compatible or a PCR-positive result regardless of symptoms. Adverse events (AEs) were assessed up to 28 days. Results The analysis included 2,314 healthy contacts of 672 Covid-19 index cases identified between Mar 17 and Apr 28, 2020. A total of 1,198 were randomly allocated to usual care and 1,116 to HCQ therapy. There was no significant difference in the primary outcome of PCR-confirmed, symptomatic Covid-19 disease (6.2% usual care vs. 5.7% HCQ; risk ratio 0.89 [95% confidence interval 0.54-1.46]), nor evidence of beneficial effects on prevention of SARS-CoV-2 transmission (17.8% usual care vs. 18.7% HCQ). The incidence of AEs was higher in the intervention arm than in the control arm (5.9% usual care vs 51.6% HCQ), but no treatment-related serious AEs were reported. Conclusions Postexposure therapy with HCQ did not prevent SARS-CoV-2 disease and infection in healthy individuals exposed to a PCR-positive case. Our findings do not support HCQ as postexposure prophylaxis for Covid-19.