Author | Borba, Mayla Gabriela Silva | |
Author | Val, Fernando Fonseca Almeida | |
Author | Sampaio, Vanderson Souza | |
Author | Alexandre, Marcia Almeida Araújo | |
Author | Melo, Gisely Cardoso | |
Author | Brito, Marcelo | |
Author | Mourão, Maria Paula Gomes | |
Author | Sousa, José Diego Brito | |
Author | Silva, Djane Baia da | |
Author | Guerra, Marcus Vinitius Farias | |
Author | Hajjar, Ludhmila Abrahão | |
Author | Pinto, Rosemary Costa | |
Author | Balieiro, Antonio Alcirley Silva | |
Author | Pacheco, Antônio Guilherme Fonseca | |
Author | Santos Jr., James Dean Oliveira | |
Author | Naveca, Felipe Gomes | |
Author | Xavier, Mariana Simão | |
Author | Siqueira, André Machado | |
Author | Schwarzbold, Alexandre | |
Author | Croda, Júlio | |
Author | Nogueira, Maurício Lacerda | |
Author | Romero, Gustavo Adolfo Sierra | |
Author | Bassat, Quique | |
Author | Fontes, Cor Jesus | |
Author | Albuquerque, Bernardino Cláudio | |
Author | Daniel-Ribeiro, Cláudio Tadeu | |
Author | Monteiro, Wuelton Marcelo | |
Author | Lacerda, Marcus Vinícius Guimarães | |
Author | CloroCovid-19 Team | |
Access date | 2020-04-27T14:57:45Z | |
Available date | 2020-04-27T14:57:45Z | |
Document date | 2020 | |
Citation | BORBA, Mayla Gabiela Silva et al. Effect of High vs Low Doses of Chloroquine Diphosphate as Adjunctive Therapy for Patients Hospitalized With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection A Randomized Clinical Trial. JAMA Network Open, v. 3, (4.23), e 208857, p. 1-14, Apr. 2020. | pt_BR |
ISSN | 2574-3805 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/40984 | |
Language | eng | pt_BR |
Publisher | JAMA Network | pt_BR |
Rights | open access | pt_BR |
Subject in Portuguese | SARS-CoV-2 | pt_BR |
Subject in Portuguese | Difosfato de cloroquina | pt_BR |
Subject in Portuguese | Terapia Adjunta | pt_BR |
Subject in Portuguese | Pacientes | pt_BR |
Subject in Portuguese | Ensaio Clínico Randomizado | pt_BR |
Subject in Portuguese | Doses altas versus baixas | pt_BR |
Subject in Portuguese | COVID-19 | pt_BR |
Subject in Portuguese | Coronavírus | pt_BR |
Title | Effect of High vs Low Doses of Chloroquine Diphosphate as Adjunctive Therapy for Patients Hospitalized With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection: A Randomized Clinical Trial | pt_BR |
Type | Article | pt_BR |
DOI | 10.1001/jamanetworkopen.2020.8857 | |
Abstract | There is no specific antiviral therapy recommended for coronavirus disease 2019 (COVID-19). In vitro studies indicate that the antiviral effect of chloroquine diphosphate (CQ) requires a high concentration of the drug. OBJECTIVE To evaluate the safety and efficacy of 2 CQ dosages in patients with severe COVID-19.
IMPORTANCE There is no specific antiviral therapy recommended for coronavirus disease 2019 (COVID-19). In vitro studies indicate that the antiviral effect of chloroquine diphosphate (CQ) requires a high concentration of the drug. OBJECTIVE To evaluate the safety and efficacy of 2 CQ dosages in patients with severe COVID-19. DESIGN, SETTING, AND PARTICIPANTS This parallel, double-masked, randomized, phase IIb clinical trial with 81 adult patients who were hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was conducted from March 23 to April 5, 2020, at a tertiary care facility in Manaus, Brazilian Amazon. INTERVENTIONS Patients were allocated to receive high-dosage CQ (ie, 600 mg CQ twice daily for 10 days) or low-dosage CQ (ie, 450 mg twice daily on day 1 and once daily for 4 days). MAIN OUTCOMES AND MEASURES Primary outcome was reduction in lethality by at least 50% in the high-dosage group compared with the low-dosage group. Data presented here refer primarily to safety and lethality outcomes during treatment on day 13. Secondary end points included participant clinical status, laboratory examinations, and electrocardiogram results. Outcomes will be presented to day 28. Viral respiratory secretion RNA detection was performed on days 0 and 4. RESULTS Out of a predefined sample size of 440 patients, 81 were enrolled (41 [50.6%] to highdosage group and 40 [49.4%] to low-dosage group). Enrolled patients had a mean (SD) age of 51.1 (13.9) years, and most (60 [75.3%]) were men. Older age (mean [SD] age, 54.7 [13.7] years vs 47.4 [13.3] years) and more heart disease (5 of 28 [17.9%] vs 0) were seen in the high-dose group. Viral RNA was detected in 31 of 40 (77.5%) and 31 of 41 (75.6%) patients in the low-dosage and highdosage groups, respectively. Lethality until day 13 was 39.0% in the high-dosage group (16 of 41) and 15.0% in the low-dosage group (6 of 40). The high-dosage group presented more instance of QTc interval greater than 500 milliseconds (7 of 37 [18.9%]) compared with the low-dosage group (4 of 36 [11.1%]). Respiratory secretion at day 4 was negative in only 6 of 27 patients (22.2%). CONCLUSIONS AND RELEVANCE The preliminary findings of this study suggest that the higher CQ dosage should not be recommended for critically ill patients with COVID-19 because of its potential safety hazards, especially when taken concurrently with azithromycin and oseltamivir. These findings cannot be extrapolated to patients with nonsevere COVID-19. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT04323527. | pt_BR |
Affilliation | Fundação de Medicina Tropical Dr Heitor Vieira Dourado. Manaus, AM, Brasil. | pt_BR |
Affilliation | Fundação de Medicina Tropical Dr Heitor Vieira Dourado. Manaus, AM, Brasil. | pt_BR |
Affilliation | Fundação de Medicina Tropical Dr Heitor Vieira Dourado. Manaus, AM, Brasil. | pt_BR |
Affilliation | Fundação de Medicina Tropical Dr Heitor Vieira Dourado. Manaus, AM, Brasil. | pt_BR |
Affilliation | Fundação de Medicina Tropical Dr Heitor Vieira Dourado. Manaus, AM, Brasil. | pt_BR |
Affilliation | Fundação de Medicina Tropical Dr Heitor Vieira Dourado. Manaus, AM, Brasil. | pt_BR |
Affilliation | Fundação de Medicina Tropical Dr Heitor Vieira Dourado. Manaus, AM, Brasil. | pt_BR |
Affilliation | Fundação de Medicina Tropical Dr Heitor Vieira Dourado. Manaus, AM, Brasil. | pt_BR |
Affilliation | Fundação de Medicina Tropical Dr Heitor Vieira Dourado. Manaus, AM, Brasil. | pt_BR |
Affilliation | Fundação de Medicina Tropical Dr Heitor Vieira Dourado. Manaus, AM, Brasil. | pt_BR |
Affilliation | Universidade de São Paulo. Faculdade de Medicina. São Paulo, SP, Brasil. | pt_BR |
Affilliation | Fundação de Vigilância em Saúde do Amazonas, Manaus, AN, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Leônidas and Maria Deane. Manaus, AM, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Presidência. Programa de Computação Científica. Rio de janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal do Amazonas, Manaus, AM, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Leônidas and Maria Deane. Manaus, AM, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Carlos Chagas. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Carlos Chagas. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal de Santa Maria. Santa Maria, RS, Brasil. | pt_BR |
Affilliation | Universidade Federal de Santa Maria. Santa Maria, RS, Brasil / Fundação Oswaldo Cruz. Campo Grande, MS, Brasil. | pt_BR |
Affilliation | Faculdade de Medicina de São José do Rio Preto. São José do Rio Preto, SP, Brasil. | pt_BR |
Affilliation | Universidade de Brasília. Brasília, DF, Brasil. | pt_BR |
Affilliation | ISGlobal. Hospital Clínic–Universitat de Barcelona. Barcelona, Spain / Centro de Investigação em Saúde de Manhiça. Maputo, Mozambique / Pediatric Infectious Diseases Unit, Pediatrics Department, Hospital Sant Joan de Déu, University of Barcelona. Barcelona, Spain / Consorcio de Investigación Biomédica en Red de Epidemiología y Salud Pública. Madrid, Spain | pt_BR |
Affilliation | Universidade Federal de Mato Grosso. Campo Grande, MT, Brasil. | pt_BR |
Affilliation | Universidade Federal do Amazonas. Faculdade de Medicina. Manaus, AM, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação de Medicina Tropical Dr Heitor Vieira Dourado. Manaus, AM, Brasil. | pt_BR |
Affilliation | Fundação de Medicina Tropical Dr Heitor Vieira Dourado. Manaus, AM, Brasil. | pt_BR |
Affilliation | Fundação de Medicina Tropical Dr Heitor Vieira Dourado. Manaus, AM, Brasil. | pt_BR |
Affilliation | COVID Team | pt_BR |
Subject | SARS-CoV-2 | pt_BR |
Subject | Chloroquine Diphosphate | pt_BR |
Subject | Adjunctive Therapy | pt_BR |
Subject | Patients | pt_BR |
Subject | Randomized Clinical Trial | pt_BR |
Subject | High vs Low Doses | pt_BR |
Subject | COVID-19 | pt_BR |
Subject | Coronavirus | pt_BR |