Hydroxychloroquine in mild-to-moderate coronavirus disease 2019: a placebo-controlled double blind trial
Vincent Dubée, Pierre-Marie Roy, Bruno Vielle, Elsa Parot-Schinkel, Odile Blanchet, Astrid Darsonval, Caroline Lefeuvre, Chadi Abbara, Sophie Boucher, Edouard Devaud, Olivier Robineau, Patrick Rispal, Thomas Guimard, Emma D’anglejean, Sylvain Diamantis, Marc-Antoine Custaud, Isabelle Pellier, Alain Mercat, Antoine Brangier, Philippe Codron, Jean Michel Lemée, Virginie Pichon, Robin Dhersin, Geoffrey Urbanski, Christian Lavigne, Roxane Courtois, Hélène Danielou, Jonathan Lebreton, Rémi Vatan, Nicolas Crochette, Jean-Baptiste Lainé, Lucia Perez, Sophie Blanchi, Hikombo Hitoto, Louis Bernard, François Maillot, Sylvain Marchand Adam, Jean-Philippe Talarmin, Emeline Gaigneux, Pauline Motte-Vincent, Marine Morrier, Dominique Merrien, Yves Bleher, Maxime Flori, Amélie Ducet-Boiffard, Orane Colin, Ronan Février, Pauline Thill, Macha Tetart, François Demaeght, Barthelemy Lafond-Desmurs, Maxime Pradier, Agnes Meybeck, Marjorie Picaud, Thierry Prazuck, Guillaume Chapelet, Agnès Rouaud, Paul Le Turnier, Simon Sunder, Aurélien Lorleac'h, Christophe Dollon, Antoine Jacquet, Francois Le Vely, Pierre Gazeau, Séverine Ansart, Hélène Roger, François Laterza, Rodolphe Buzelé, Fella Tahmi, Raphael Lepeule, Karine Lacombe, Bénédicte Lefebvre, Thomas Célarier, Amandine Gagneux-Brunon, Elisabeth Botelho-Nevers, Marc Bernard, Camille Garnier, Morgane Mourguet, Gregory Pugnet, Sara Vienne-Noyes, Guillaume Martin-Blondel, Pierre Delobel, Gaspard Grouteau, Alexa Debard, Laurent Guilleminault, Pauline Arias, Catherine Chakvetadze, Clara Flateau, Aude Kopp, Alain Putot, Jeremy Barben, Suzanne Mouries Martin, Valentine Nuss, Lionel Piroth, Yann-Erick Claessens, Veronique Hentgen, Martin Martinot, Maxime Bach-Bunner, Thomas Bonijoly, Simon Gravier, Jean-Marc Michel, Mathilde Andreu, Mélanie Roriz, Aurélie Baldolli, Julia Brochard, Olivier Grossi, Samuel Pineau, Josselin Brisset, Edouard Desvaux, Guillaume Gondran, Jean-François Faucher, Paul-Antoine Quesnel, Holy Bezanahary, Clément Danthu, Blandine Gutierrez, Kim Ly, Yannick Simonneau, Anne Cypierre, Pauline Pinet, Hélène Durox, Sophie Ducroix-Roubertou, Claire Genet, Guillaume Beraud, Gwenael Le Moal, Blandine Rammaert, Jean-Philippe Lanoix, Claire Andrejak, Cédric Joseph, Sandrine Soriot-Thomas, Robin Dhote, Sébastien Abad, Ruben Benainous, Jean-François Boitiaux, Guillaume Briend, Celine Gonfroy, Stanislas Harent, Aurore Lagrange, Alina Tone, Laura Wayenberg, Sophie Desoutter, Nicolas Ettahar, Thomas Gey, Vincent Leroy, Sacha Gaillard, Andrea Toma, Amaury Broussier, Sandrine Etienne, Yann Spivac, Benoit Martha, Nathalie Roch, Pierre Diaz, Danièle N’guyen Baranoff, Stanislas Rebaudet, François Jourda, Valérie Zeller, Boris Bienvenu, Arnaud Boyer, Isabelle Pellier, Alain Mercat, Astrid Darsonval, Odile Blanchet, Marc-Antoine Custaud, Caroline Lefeuvre, Elsa Parot-Schinkel, Bruno Vielle, Marie Briet, Pierre-Marie Roy, Vincent Dubée, Bertrand Guidet, Patrick Mismetti, Eric Vicaut, Olivier Sanchez, Philippe Girard, Antoine Elias, Francis Couturaud, Béatrice Gable, Sybille Lazareff, Loïc Carballido, Catherine Hue, Jean-Marie Chrétien, Adrien Goraguer, Lucie Van Eeckhoutte
Clinical Microbiology and Infection, doi:10.1016/j.cmi.2021.03.005
Objectives: To determine whether hydroxychloroquine decreases the risk of adverse outcome in patients with mild to moderate coronavirus disease 2019 (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 and 74 years and presence of at least one co-morbidity. Severely ill patients requiring oxygen therapy >3 L/min or intensive care were excluded. Eligible patients were randomized in a 1:1 ratio to receive either 800 mg hydroxychloroquine on day 0 followed by 400 mg per day for 8 days or a placebo. The primary end point was a composite of death or start of invasive mechanical ventilation within 14 days following randomization. Secondary end points included mortality and clinical evolution at days 14 and 28, and viral shedding at days 5 and 10. Results: The trial was stopped after 250 patients were included because of a slowing down 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 years (interquartile range 58 e86 years) and 151/250 (60.4%) patients required oxygen therapy. The primary end point occurred in 9/ 124 (7.3%) patients in the hydroxychloroquine group and 8/123 (6.5%) patients in the placebo group
Authors' contributions VD, PMR, HP, EPS and AM conceptualized the study and its methodology, VD and PMR supervised the conduct of the study and wrote the original draft of the manuscript. BV was in charge of data curation and formal analysis. SB, ED, OR, PR, TG, EA, SD and MAC participated in data collection. AD was responsible for preparation and shipping of study drugs. CL and OB were in charge of biological samples. CA was responsible for drug safety. All authors reviewed and edited the manuscript and approved its final version. All authors contributed significantly to the study and agree to be accountable for all aspects of the work. VD, PMR, IP and AM take responsibility for the publication.
Access to data Anonymized individual data are available upon reasonable request to DataManagement.DRCI@chu-angers.fr.
Appendix A. Supplementary data Supplementary data to this article can be found online at https://doi.org/10.1016/j.cmi.2021.03.005.
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