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Effect of Early Treatment With Hydroxychloroquine or Lopinavir and Ritonavir on Risk of Hospitalization Among Patients With COVID-19: The TOGETHER Randomized Clinical Trial.
Reis, Gilmar; Moreira Silva, Eduardo Augusto Dos Santos; Medeiros Silva, Daniela Carla; Thabane, Lehana; Singh, Gurmit; Park, Jay J H; Forrest, Jamie I; Harari, Ofir; Quirino Dos Santos, Castilho Vitor; Guimarães de Almeida, Ana Paula Figueiredo; Figueiredo Neto, Adhemar Dias de; Savassi, Leonardo Cançado Monteiro; Milagres, Aline Cruz; Teixeira, Mauro Martins; Simplicio, Maria Izabel Campos; Ribeiro, Luciene Barra; Oliveira, Rosemary; Mills, Edward J.
  • Reis G; Research Division, Cardresearch-Cardiologia Assistencial e de Pesquisa, Brazil.
  • Moreira Silva EADS; Department of Medicine, Pontifícia Universidade Católica de Minas Gerais, Brazil.
  • Medeiros Silva DC; Research Division, Cardresearch-Cardiologia Assistencial e de Pesquisa, Brazil.
  • Thabane L; Department of Medicine, Pontifícia Universidade Católica de Minas Gerais, Brazil.
  • Singh G; Research Division, Cardresearch-Cardiologia Assistencial e de Pesquisa, Brazil.
  • Park JJH; Department of Medicine, Pontifícia Universidade Católica de Minas Gerais, Brazil.
  • Forrest JI; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada.
  • Harari O; Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
  • Quirino Dos Santos CV; Experimental Medicine, Department of Medicine, The University of British Columbia, Vancouver, British Columbia, Canada.
  • Guimarães de Almeida APF; Cytel Inc, Vancouver, British Columbia, Canada.
  • Figueiredo Neto AD; Experimental Medicine, Department of Medicine, The University of British Columbia, Vancouver, British Columbia, Canada.
  • Savassi LCM; Cytel Inc, Vancouver, British Columbia, Canada.
  • Milagres AC; Cytel Inc, Vancouver, British Columbia, Canada.
  • Teixeira MM; Research Division, Cardresearch-Cardiologia Assistencial e de Pesquisa, Brazil.
  • Simplicio MIC; Department of Medicine, Pontifícia Universidade Católica de Minas Gerais, Brazil.
  • Ribeiro LB; Department of Public Health, Montes Claros State University, Montes Claros, Brazil.
  • Oliveira R; Public Health Fellowship Program, Governador Valadares Public Health Authority, Brazil.
  • Mills EJ; Public Health, Mental and Family Medicine Department, Ouro Preto Federal University, Ouro Preto, Brazil.
JAMA Netw Open ; 4(4): e216468, 2021 04 01.
Artículo en Inglés | MEDLINE | ID: covidwho-1196363
ABSTRACT
Importance Data on the efficacy of hydroxychloroquine or lopinavir-ritonavir for the treatment of high-risk outpatients with COVID-19 in developing countries are needed.

Objective:

To determine whether hydroxychloroquine or lopinavir-ritonavir reduces hospitalization among high-risk patients with early symptomatic COVID-19 in an outpatient setting. Design, Setting, and

Participants:

This randomized clinical trial was conducted in Brazil. Recently symptomatic adults diagnosed with respiratory symptoms from SARS-CoV-2 infection were enrolled between June 2 and September 30, 2020. The planned sample size was 1476 patients, with interim analyses planned after 500 patients were enrolled. The trial was stopped after the interim analysis for futility with a sample size of 685 patients. Statistical analysis was performed in December 2020.

Interventions:

Patients were randomly assigned to hydroxychloroquine (800 mg loading dose, then 400 mg daily for 9 days), lopinavir-ritonavir (loading dose of 800 mg and 200 mg, respectively, every 12 hours followed by 400 mg and 100 mg, respectively, every 12 hours for the next 9 days), or placebo. Main Outcomes and

Measures:

The primary outcomes were COVID-19-associated hospitalization and death assessed at 90 days after randomization. COVID-19-associated hospitalization was analyzed with a Cox proportional hazards model. The trial included the following secondary

outcomes:

all-cause hospitalization, viral clearance, symptom resolution, and adverse events.

Results:

Of 685 participants, 632 (92.3%) self-identified as mixed-race, 377 (55.0%) were women, and the median (range) age was 53 (18-94) years. A total of 214 participants were randomized to hydroxychloroquine; 244, lopinavir-ritonavir; and 227, placebo. At first interim analysis, the data safety monitoring board recommended stopping enrollment of both hydroxychloroquine and lopinavir-ritonavir groups because of futility. The proportion of patients hospitalized for COVID-19 was 3.7% (8 participants) in the hydroxychloroquine group, 5.7% (14 participants) in the lopinavir-ritonavir group, and 4.8% (11 participants) in the placebo group. We found no significant differences between interventions for COVID-19-associated hospitalization (hydroxychloroquine hazard ratio [HR], 0.76 [95% CI, 0.30-1.88]; lopinavir-ritonavir HR, 1.16 [95% CI, 0.53-2.56] as well as for the secondary outcome of viral clearance through day 14 (hydroxychloroquine odds ratio [OR], 0.91 [95% CI, 0.82-1.02]; lopinavir-ritonavir OR, 1.04 [95% CI, 0.94-1.16]). At the end of the trial, there were 3 fatalities recorded, 1 in the placebo group and 2 in the lopinavir-ritonavir intervention group. Conclusions and Relevance In this randomized clinical trial, neither hydroxychloroquine nor lopinavir-ritonavir showed any significant benefit for decreasing COVID-19-associated hospitalization or other secondary clinical outcomes. This trial suggests that expedient clinical trials can be implemented in low-income settings even during the COVID-19 pandemic. Trial Registration ClinicalTrials.gov Identifier NCT04403100.
Asunto(s)

Texto completo: Disponible Colección: Bases de datos internacionales Base de datos: MEDLINE Asunto principal: Ritonavir / Lopinavir / Intervención Médica Temprana / COVID-19 / Hidroxicloroquina Tipo de estudio: Estudio experimental / Estudio observacional / Estudio pronóstico / Ensayo controlado aleatorizado Límite: Femenino / Humanos / Masculino / Middle aged País/Región como asunto: America del Sur / Brasil Idioma: Inglés Revista: JAMA Netw Open Año: 2021 Tipo del documento: Artículo País de afiliación: Jamanetworkopen.2021.6468

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Texto completo: Disponible Colección: Bases de datos internacionales Base de datos: MEDLINE Asunto principal: Ritonavir / Lopinavir / Intervención Médica Temprana / COVID-19 / Hidroxicloroquina Tipo de estudio: Estudio experimental / Estudio observacional / Estudio pronóstico / Ensayo controlado aleatorizado Límite: Femenino / Humanos / Masculino / Middle aged País/Región como asunto: America del Sur / Brasil Idioma: Inglés Revista: JAMA Netw Open Año: 2021 Tipo del documento: Artículo País de afiliación: Jamanetworkopen.2021.6468