A Cluster-Randomized Trial of Hydroxychloroquine for Prevention of Covid-19

Mitjà , Oriol; Corbacho-Monné, Marc; Ubals, Maria; Alemany, Andrea; Suñer, Clara; Tebé, Cristian; Tobias, Aurelio; Peñafiel, Judith; Ballana, Ester; Pérez, Carla A.; Admella, Pol; Riera-Martí, Núria; Laporte, Pep; Mitjà , Jordi; Clua, Mireia; Bertran, Laia; Sarquella, Maria; Gavilán, Sergi; Ara, Jordi; Argimon, Josep M.; Cuatrecasas, Gabriel; Cañadas, Paz; Elizalde-Torrent, Aleix; Fabregat, Robert; Farré, Magí; Forcada, Anna; Flores-Mateo, Gemma; López, Cristina; Muntada, Esteve; Nadal, Núria; Narejos, Silvia; Nieto, Aroa; Prat, Nuria; Puig, Jordi; Quiñones, Carles; Ramírez-Viaplana, Ferran; Reyes-Urueña, Juliana; Riveira-Muñoz, Eva; Ruiz, Lidia; Sanz, Sergi; Sentís, Alexis; Sierra, Alba; Velasco, César; Vivanco-Hidalgo, Rosa M.; Zamora, Juani; Casabona, Jordi; Vall-Mayans, Martí; González-Beiras, Camila; Clotet, Bonaventura

BACKGROUND: Current strategies for preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are limited to nonpharmacologic interventions. Hydroxychloroquine 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 involving asymptomatic contacts of patients with polymerase-chain-reaction (PCR)–confirmed Covid-19 in Catalonia, Spain. We randomly assigned clusters of contacts to the hydroxychloroquine group (which received the drug at a dose of 800 mg once, followed by 400 mg daily for 6 days) or to the usual-care group (which received no specific therapy). The primary outcome was PCR-confirmed, symptomatic Covid-19 within 14 days. The secondary outcome was SARS-CoV-2 infection, defined by symptoms compatible with Covid-19 or a positive PCR test regardless of symptoms. Adverse events were assessed for up to 28 days. RESULTS: The analysis included 2314 healthy contacts of 672 index case patients with Covid-19 who were identified between March 17 and April 28, 2020. A total of 1116 contacts were randomly assigned to receive hydroxychloroquine and 1198 to receive usual care. Results were similar in the hydroxychloroquine and usual-care groups with respect to the incidence of PCR-confirmed, symptomatic Covid-19 (5.7% and 6.2%, respectively; risk ratio, 0.86 [95% confidence interval, 0.52 to 1.42]). In addition, hydroxychloroquine was not associated with a lower incidence of SARS-CoV-2 transmission than usual care (18.7% and 17.8%, respectively). The incidence of adverse events was higher in the hydroxychloroquine group than in the usual-care group (56.1% vs. 5.9%), but no treatment-related serious adverse events were reported. CONCLUSIONS: Postexposure therapy with hydroxychloroquine did not prevent SARS-CoV-2 infection or symptomatic Covid-19 in healthy persons exposed to a PCR-positive case patient. (Funded by the crowdfunding campaign YoMeCorono and others; BCN-PEP-CoV2 ClinicalTrials.gov number, NCT04304053.)