Trial of Hydroxychloroquine to Prevent Covid-19 Transmission and Disease

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

View ORCID ProfileOriol Mitja, Maria Ubals, Marc Corbacho, Andrea Alemany, Clara Suner, Cristian Tebe, Aurelio Tobias, Judith Penafiel, Ester Ballana, Carla A Perez, Pol Admella, Nuria Riera-Marti, Pep Laporte, Jordi Mitja, Mireia Clua, Laia Bertran, Sergi Gavilan, Jordi Ara, Maria Sarquella, Josep M Argimon, Gabriel Cuatrecasas, Paz Canadas, Aleix Elizalde-Torrent, Robert Fabregat, Magi Farre, Anna Forcada, Gemma Flores-Mateo, Cristina Lopez, Esteve Muntada, Nuria Nadal, Silvia Narejos, Aroa N Gil-Ortega, Nuria Prat, Jordi Puig, Carles Quinones, Ferran Ramirez-Viaplana, Juliana Reyes-Uruena, Eva Riveira-Munoz, Lidia Ruiz, Sergi Sanz, Alexis Sentis, Alba Sierra, Cesar Velasco, Rosa Maria Vivanco-Hidalgo, Juani Zamora, Jordi Casabona, Marti Vall-Mayans, Camila G-Beiras, Bonaventura Clotet

doi: https://doi.org/10.1101/2020.07.20.20157651

This article is a preprint and has not been certified by peer review [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.

PDF: https://www.medrxiv.org/content/10.1101/2020.07.20.20157651v1.full.pdf+html

Abstract

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.

Competing Interest Statement

The authors have declared no competing interest.

Clinical Trial

NCT04304053

Funding Statement

Crowdfunding campaign YoMeCorono (https://www.yomecorono.com/), Laboratorios Rubio, Laboratorios Gebro Pharma, Zurich Seguros, SYNLAB Barcelona, and Generalitat de Catalunya. Laboratorios Rubio also contributed to the study with the required doses of hydroxychloroquine (Dolquine).

https://www.medrxiv.org/content/10.1101/2020.07.20.20157651v1