Pre-exposure prophylaxis with hydroxychloroquine for COVID-19: a double-blind, placebo-controlled randomized clinical trial


Por: Grau-Pujol, B, Camprubi-Ferrer, D, Marti-Soler, H, Fernandez-Pardos, M, Carreras-Abad, C, Velasco-de Andres, M, Ferrer, E, Muelas-Fernandez, M, Jullien, S, Barilaro, G, Ajanovic, S, Vera, I, Moreno, L, Gonzalez-Redondo, E, Cortes-Serra, N, Roldan, M, Artes-de Arcos, A, Mur, I, Domingo, P, Garcia, F, Guinovart, C, Munoz, J

Publicada: 15 nov 2021
Resumen:
Background: Pre-exposure prophylaxis (PrEP) is a promising strategy to break COVID-19 transmission. Although hydroxychloroquine was evaluated for treatment and post-exposure prophylaxis, it is not evaluated for COVID-19 PrEP yet. The aim of this study was to evaluate the efficacy and safety of PrEP with hydroxychloroquine against placebo in healthcare workers at high risk of SARS-CoV-2 infection during an epidemic period. Methods: We conducted a double-blind placebo-controlled randomized clinical trial in three hospitals in Barcelona, Spain. From 350 adult healthcare workers screened, we included 269 participants with no active or past SARS-CoV-2 infection (determined by a negative nasopharyngeal SARS-CoV-2 PCR and a negative serology against SARS-CoV-2). Participants allocated in the intervention arm (PrEP) received 400 mg of hydroxychloroquine daily for the first four consecutive days and subsequently, 400 mg weekly during the study period. Participants in the control group followed the same treatment schedule with placebo tablets. Results: 52.8% (142/269) of participants were in the hydroxychloroquine arm and 47.2% (127/269) in the placebo arm. Given the national epidemic incidence decay, only one participant in each group was diagnosed with COVID-19. The trial was stopped due to futility and our study design was deemed underpowered to evaluate any benefit regarding PrEP efficacy. Both groups showed a similar proportion of participants experiencing at least one adverse event (AE) (p=0.548). No serious AEs were reported. Almost all AEs (96.4%, 106/110) were mild. Only mild gastrointestinal symptoms were significantly higher in the hydroxychloroquine arm compared to the placebo arm (27.4% (39/142) vs 15.7% (20/127), p=0.041). Conclusions: Although the efficacy of PrEP with hydroxychloroquine for preventing COVID-19 could not be evaluated, our study showed that PrEP with hydroxychloroquine at low doses is safe.

Filiaciones:
Grau-Pujol, B:
 Univ Barcelona, Barcelona Inst Global Hlth ISGlobal, Hosp Clin, Rossello 132 4rt 1a, Barcelona 08036, Spain

 Ctr Invest Saude Manhica CISM, Maputo, Mozambique

 Mundo Sano Fdn, Buenos Aires, DF, Argentina

Camprubi-Ferrer, D:
 Univ Barcelona, Barcelona Inst Global Hlth ISGlobal, Hosp Clin, Rossello 132 4rt 1a, Barcelona 08036, Spain

Marti-Soler, H:
 Univ Barcelona, Barcelona Inst Global Hlth ISGlobal, Hosp Clin, Rossello 132 4rt 1a, Barcelona 08036, Spain

Fernandez-Pardos, M:
 Univ Barcelona, Barcelona Inst Global Hlth ISGlobal, Hosp Clin, Rossello 132 4rt 1a, Barcelona 08036, Spain

Carreras-Abad, C:
 Univ Barcelona, Barcelona Inst Global Hlth ISGlobal, Hosp Clin, Rossello 132 4rt 1a, Barcelona 08036, Spain

Velasco-de Andres, M:
 Univ Barcelona, Barcelona Inst Global Hlth ISGlobal, Hosp Clin, Rossello 132 4rt 1a, Barcelona 08036, Spain

Ferrer, E:
 Univ Barcelona, Barcelona Inst Global Hlth ISGlobal, Hosp Clin, Rossello 132 4rt 1a, Barcelona 08036, Spain

Muelas-Fernandez, M:
 Univ Barcelona, Barcelona Inst Global Hlth ISGlobal, Hosp Clin, Rossello 132 4rt 1a, Barcelona 08036, Spain

Jullien, S:
 Univ Barcelona, Barcelona Inst Global Hlth ISGlobal, Hosp Clin, Rossello 132 4rt 1a, Barcelona 08036, Spain

Barilaro, G:
 Univ Barcelona, Barcelona Inst Global Hlth ISGlobal, Hosp Clin, Rossello 132 4rt 1a, Barcelona 08036, Spain

Ajanovic, S:
 Univ Barcelona, Barcelona Inst Global Hlth ISGlobal, Hosp Clin, Rossello 132 4rt 1a, Barcelona 08036, Spain

Vera, I:
 Univ Barcelona, Barcelona Inst Global Hlth ISGlobal, Hosp Clin, Rossello 132 4rt 1a, Barcelona 08036, Spain

Moreno, L:
 Univ Barcelona, Hosp Clin, Infect Dis Dept, IDIBAPS, Barcelona, Spain

Gonzalez-Redondo, E:
 Univ Barcelona, Hosp Clin, Infect Dis Dept, IDIBAPS, Barcelona, Spain

Cortes-Serra, N:
 Univ Barcelona, Barcelona Inst Global Hlth ISGlobal, Hosp Clin, Rossello 132 4rt 1a, Barcelona 08036, Spain

Roldan, M:
 Univ Barcelona, Barcelona Inst Global Hlth ISGlobal, Hosp Clin, Rossello 132 4rt 1a, Barcelona 08036, Spain

Artes-de Arcos, A:
 Univ Barcelona, Barcelona Inst Global Hlth ISGlobal, Hosp Clin, Rossello 132 4rt 1a, Barcelona 08036, Spain

Mur, I:
 Hosp Santa Creu & Sant Pau, Infect Dis Unit, Inst Invest Biomed St Pau, Barcelona 08025, Spain

Domingo, P:
 Hosp Santa Creu & Sant Pau, Infect Dis Unit, Inst Invest Biomed St Pau, Barcelona 08025, Spain

Garcia, F:
 Univ Barcelona, Hosp Clin, Infect Dis Dept, IDIBAPS, Barcelona, Spain

 Univ Barcelona, Hosp Clin, IDIBAPS, Aids Res Grp,Retrovirol & Viral Immunopathol, Barcelona, Spain

Guinovart, C:
 Univ Barcelona, Barcelona Inst Global Hlth ISGlobal, Hosp Clin, Rossello 132 4rt 1a, Barcelona 08036, Spain

Munoz, J:
 Univ Barcelona, Barcelona Inst Global Hlth ISGlobal, Hosp Clin, Rossello 132 4rt 1a, Barcelona 08036, Spain
ISSN: 17456215





Trials
Editorial
BMC, CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND, Reino Unido
Tipo de documento: Article
Volumen: 22 Número: 1
Páginas:
WOS Id: 000718825900001
ID de PubMed: 34781981
imagen gold, Green Published

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