Methylprednisolone as Adjunctive Therapy for Patients Hospitalized With Coronavirus Disease 2019 (COVID-19; Metcovid): A Randomized, Double-blind, Phase IIb, Placebo-controlled Trial

Clinical Infectious Diseases - Tập 72 Số 9 - Trang e373-e381 - 2021
Christiane Maria Prado Jerônimo1,2, Maria Eduarda Leão de Farias1,3, Fernando Val1,2, Vanderson de Souza Sampaio1,4,2, Márcia Almeida Araújo Alexandre1, Gisely Cardoso de Melo1,2, Izabella Picinin Safe1, Mayla Gabriela Silva Borba1,2, Rebeca Linhares Abreu Netto1,2, Alex Bezerra da Silva Maciel1,2, João Ricardo Silva Neto1, Lucas Barbosa Oliveira1,2, Erick Frota Gomes Figueiredo1,2, Kelry Mazurega Oliveira Dinelly1,2, Maria Gabriela de Almeida Rodrigues1,2, Marcelo Augusto Mota Brito1,2, Maria Paula Gomes Mourão1,2, Guilherme Augusto Pivoto João1,2, Roberto Botelho5, Quique Bassat6,7,8,9,10, Gustavo Adolfo Sierra Romero11, Felipe Gomes Naveca3, Heline Lira Vasconcelos1, Michel de Araújo Tavares12, José Diego Brito-Sousa1,2, Fábio Trindade Maranhão Costa13, Maurício Lacerda Nogueira14, Djane Clarys Baía-da-Silva1,2, Mariana Simão Xavier1,15, Wuelton Marcelo Monteiro1,2, Marcus Lacerda1,3,2, Adria de Lemos Vasconcelos, Adriana Ferreira Praia Marins, Alexandre de Oliveira Trindade1, Aline Sales Mendes Záu, Amanda Carvalho de Oliveira, Ana Carolina Azevedo Furtado, Ana Paula Coelho Rocha, Anderson da Silva Souza1,4,2, Andiana de Souza Dias, Aníbal Belém, Anna Gabriela Rezende dos Santos, Antonny Michael da Silva Sousa, Beatriz França da Silva1,2, B Franco, Bernardo Maia da Silva1,2, Bleno Leonam Gonçalves da Costa, Camila Miriam Suemi Sato Barros do Amaral, Carla C. Judice, Carlos Eduardo Padron de Morais, Cecília Cunha Camilo, Danielle Severino Sena da Silva, Débora Duarte, Ejandre Garcia Negreiros da Silva1,2, Elias da Silva Lemos, Elisângela de Fátima Ponte Frota, Elizandra Freitas do Nascimento, Elson Silva de Almeida1,2, Elyana Almeida Marques, Emanuel Medeiros Marinho de Almeida1,2, Emanuelle Lira da Silva1,2, Ester Galvão dos Santos, Ezequiel da Silva Oliveira, Fábio Manabu Martins Shimizu, Fabíola Ramalho Ferreira de Souza, Felipe da Silva do Vale3, Fernanda dos Santos Lima, Fernando Hugo Jesus da Fonseca, Flávia Alencar Fontenelle, Francielen de Azevedo Furtado, Gabrielle da Silva Pereira, Geísa Aleixo Bezerra5,1,16, Guilherme Kemeron Maciel Salazar, Handerson da Silva Pereira, Hilda Ferreira de Melo, Ingrid Nascimento Oliveira1,2, Ivanildo Vieira Pereira Filho, Jacimara Vasques Gomes3, Jaily e Silva Rosa, J. M. Carvalho Lemos, Josué Nélio Brutus, Karina Pessoa, Laleyska Deucylane Costa Rodrigues, Larissa Esthefani Barros Cirino, Lauro Fragata Mourão Filho, Leandro Barbosa de Moura1,2, Lisiane Rísia Pinto Barbosa, Lorenna Pereira de Souza, Luíz Carlos de Lima Ferreira, Marcela Menezes dos Santos, Marcus Vinicius Ramos da Silva1,2, Mauro Pereira Rodrigues1,2, Mayara Tavares de Menezes, Micaela Maciel dos Santos Mota, Monique Freire Santana, Nadya Fonseca Corrêa, N. M. Magalhães Rocha, Najara Bittencourt, Natália Guedes de Melo Silva, Priscilla de Oliveira Saraiva, Quézia de Sousa Monteiro, Rafael Theodoro dos Santos, Raíssa Soares Freire, Rebecca Augusta de Araújo Pinto, Reinan Brotas Ferreira, Rodrigo Saboia de Lima, Rosângela Francisca Tanantas de Melo, Sabrina Teixeira Saenz, Salete Sara Alvarez Fernandes, Sheila Vítor-Silva, Tânia Maria Rodrigues de Oliveira, Tatyana Almeida Tavella, Thais Tavares Câmara, Thalie Cavalcante Santos, Thiago Serrão Pinto, Tilza Waleska Rocha dos Santos, Valdinete Alves do Nascimento, Wanessa Pessoa Sousa Barbosa, Wellinthon Ferreira de Melo, Wlademir Braga Salgado Sobrinho
1Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Brazil
2Universidade do Estado do Amazonas, Manaus, Brazil
3Instituto Leônidas and Maria Deane, Fiocruz Amazonas, Manaus, Brazil
4Fundação de Vigilância em Saúde do Amazonas, Manaus, Brazil
5Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
6Centro de Investigação em Saúde de Manhiça, Maputo, Mozambique
7Consorcio de Investigación Biomédica en Red de Epidemiología y Salud Pública, Madrid, Spain
8Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain
9Instituto de Salud Global de Barcelona (ISGlobal), Hospital Clínic–Universitat de Barcelona, Barcelona, Spain
10Pediatric Infectious Diseases Unit, Pediatrics Department, Hospital Sant Joan de Déu (University of Barcelona), Barcelona, Spain
11Núcleo de Medicina Tropical, Universidade de Brasília, Brasília, Brazil
12Universidade Federal do Amazonas, Manaus, Brazil
13Universidade Estadual de Campinas, Campinas, Brazil
14Faculdade de Medicina de São José do Rio Preto, São José do Rio Preto, Brazil
15Instituto Nacional de Infectologia Carlos Chagas, Fiocruz, Rio de Janeiro, Brazil
16Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Av. Pedro Teixeira 25, Dom Pedro, Manaus, Amazonas, Manaus, 69040-000, Brazil

Tóm tắt

AbstractBackgroundSteroid use for coronavirus disease 2019 (COVID-19) is based on the possible role of these drugs in mitigating the inflammatory response, mainly in the lungs, triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study aimed to evaluate the efficacy of methylprednisolone (MP) among hospitalized patients with suspected COVID-19.MethodsA parallel, double-blind, placebo-controlled, randomized, Phase IIb clinical trial was performed with hospitalized patients aged ≥18 years with clinical, epidemiological, and/or radiological suspected COVID-19 at a tertiary care facility in Manaus, Brazil. Patients were randomly allocated (1:1 ratio) to receive either intravenous MP (0.5 mg/kg) or placebo (saline solution) twice daily for 5 days. A modified intention-to-treat (mITT) analysis was conducted. The primary outcome was 28-day mortality.ResultsFrom 18 April to 16 June 2020, 647 patients were screened, 416 were randomized, and 393 were analyzed as mITT, with 194 individuals assigned to MP and 199 to placebo. SARS-CoV-2 infection was confirmed by reverse transcriptase polymerase chain reaction in 81.3%. The mortality rates at Day 28 were not different between groups. A subgroup analysis showed that patients over 60 years old in the MP group had a lower mortality rate at Day 28. Patients in the MP arm tended to need more insulin therapy, and no difference was seen in virus clearance in respiratory secretion until Day 7.ConclusionsThe findings of this study suggest that a short course of MP in hospitalized patients with COVID-19 did not reduce mortality in the overall population.Clinical Trials RegistrationNCT04343729.

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Clinical Infectious Diseases

Tập 72 Số 9

e373-e381

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