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

Adult Anti-Infective Agents / adverse effects COVID-19 / prevention & control Disease Transmission, Infectious / prevention & control Double-Blind Method Female Humans Hydroxychloroquine / adverse effects Male Middle Aged Patient Compliance SARS-CoV-2 Treatment Failure Viral Load

Journal

The New England journal of medicine

ISSN: 1533-4406

Titre abrégé: N Engl J Med

Pays: United States

ID NLM: 0255562

Informations de publication

Date de publication:
04 02 2021

Historique:

pubmed: 9 12 2020

medline: 10 2 2021

entrez: 8 12 2020

Statut: ppublish

Résumé

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. 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. 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. 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.).

Sections du résumé

BACKGROUND

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.).

Identifiants

DOI: 10.1056/NEJMoa2021801 PMID: 33289973 PMC: PMC7722693

pubmed: 33289973

doi: 10.1056/NEJMoa2021801

pmc: PMC7722693

doi:

Substances chimiques

Anti-Infective Agents 0

Hydroxychloroquine 4QWG6N8QKH

Banques de données

ClinicalTrials.gov

['NCT04304053']

Types de publication

Journal Article Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

417-427

Investigateurs

Albert Tuldrà (A)

Xavi Serrano (X)

Estefany Uría (E)

Cristina Herrero (C)

Sílvia Gel (S)

Alberto Alomar (A)

Ricard Esteve (R)

Anna Maria Soley (AM)

Clara Muntaner-Virgili (C)

Alejandro Hueso-Mor (A)

Laura Calvo (L)

Itziar Gamboa (I)

Anna I Garcia-Diaz (AI)

Kilian Griñan (K)

Sara Castells-Büchle (S)

Alex Alonso-Vallés (A)

Carolina Rebato (C)

Mercè Juan (M)

Dolors Palacín (D)

José López (J)

Elisenda Molas (E)

Anna Serra (A)

Sílvia Sarrà (S)

Enric Fericgla (E)

Laura Latorre (L)

Guillem Turmo (G)

Rosa López (R)

Vanesa Villa (V)

Laura Martín (L)

Cristina Aragón (C)

Mireia Vilageli (M)

Paula Martínez (P)

Cristina Naqui (C)

Judith Martínez (J)

Paula Puche (P)

Emma Yana (E)

Magalí Urrea (M)

Carmen Barjau (C)

Roser Utrillo (R)

Joan Enric Torra (JE)

Marta Gilabert (M)

Carme Domènech (C)

Judit Cartiel (J)

Israel López (I)

Olga Pérez (O)

Santiago Rosell (S)

Patricia Cobarsi (P)

Cristina Miranda (C)

Míriam López (M)

Anna Martínez (A)

Toni Jou (T)

Cristina Segundo (C)

Nalia López (N)

Carla Estany (C)

Deborah Paris (D)

Sonia Clemares (S)

Lara Teruel (L)

Jorge Romaní (J)

Lourdes Mateu (L)

Roger Paredes (R)

Eulàlia Grau (E)

Cristian Ramírez (C)

Cecilia Cabrera (C)

Francesc Cunyat (F)

Roger Badia (R)

Jordi Senserrich (J)

Ana Jordán (A)

M Lluïsa Rodríguez (ML)

Ferran Tarrés (F)

Carlos Ávila (C)

Àngel Bayón (À)

Raquel Ortiz (R)

Ana Barajas (A)

Sònia Pedreño (S)

Emma Albacar (E)

Xavier Núñez (X)

Roger Vinyeta (R)

Norma Caritg (N)

Rosa Bosch (R)

Natàlia Martí (N)

Paola Castro (P)

Lluís Monset (L)

Dolors Molera (D)

Dagda Bermúdez (D)

Clara Moliner (C)

Gemma Tobajas (G)

Mireia Bolívar-Prados (M)

Pere Clavé (P)

Laia Egea-Cortés (L)

Yesika Díaz (Y)

Sergio Moreno-Fornés (S)

Marcos Montoro-Fernández (M)

Borja Velasco-Regúlez (B)

Didier Domínguez (D)

Lourdes Pons (L)

Juan Carlos Becerra (JC)

Esther Diaz Soler (E)