Methylprednisolone as Adjunctive Therapy for Patients Hospitalized With Coronavirus Disease 2019 (COVID-19; Metcovid): A Randomized, Double-blind, Phase IIb, Placebo-controlled Trial
Christiane Maria Prado Jeronimo, Maria Eduarda Leão Farias, Fernando Fonseca Almeida Val, Vanderson Souza Sampaio, Marcia Almeida Araújo Alexandre, Gisely Cardoso Melo, Izabella Picinin Safe, Mayla Gabriela Silva Borba, Rebeca Linhares Abreu Netto, Alex Bezerra Silva Maciel, João Ricardo Silva Neto, Lucas Barbosa Oliveira, Erick Frota Gomes Figueiredo, Kelry Mazurega Oliveira Dinelly, Maria Gabriela de Almeida Rodrigues, Marcelo Brito, Maria Paula Gomes Mourão, Guilherme Augusto Pivoto João, Ludhmila Abrahão Hajjar, Quique Bassat, Gustavo Adolfo Sierra Romero, Felipe Gomes Naveca, Heline Lira Vasconcelos, Michel de Araújo Tavares, José Diego Brito-Sousa, Fabio Trindade Maranhão Costa, Maurício Lacerda Nogueira, Djane Clarys Baía-da-Silva, Mariana Simão Xavier, Wuelton Marcelo Monteiro, Marcus Vinícius Guimarães Lacerda, Metcovid Team, Adria de Lemos Vasconcelos, Adriana Ferreira Praia Marins, Alexandre de Oliveira Trindade, Aline Sales Mendes Záu, Amanda Carvalho de Oliveira, Ana Carolina Azevedo Furtado, Ana Paula Coelho Rocha, Anderson da Silva Souza, Andiana de Souza Dias, Aníbal Belém, Anna Gabriela Rezende Dos Santos, Antonny Michael da Silva Sousa, Beatriz França da Silva, Beatriz Leitão Franco, Bernardo Maia da Silva, 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, Debora Camila Gomes Duarte, Ejandre Garcia Negreiros da Silva, Elias da Silva Lemos, Elisângela de Fátima Ponte Frota, Elizandra Freitas do Nascimento, Elson Silva de Almeida, Elyana Almeida Marques, Emanuel Medeiros Marinho de Almeida, Emanuelle Lira da Silva, Ester Galvão Dos Santos, Ezequiel da Silva Oliveira, Fábio Manabu Martins Shimizu, Fabíola Ramalho Ferreira de Souza, Felipe da Silva do Vale, Fernanda Dos Santos de Almeida Lima, Fernando Hugo Jesus da Fonseca, Flávia Alencar Fontenelle, Francielen de Azevedo Furtado, Gabrielle Da Silva Pereira, Geísa Aleixo Bezerra, Guilherme Kemeron Maciel Salazar, Handerson da Silva Pereira, Hilda Ferreira de Melo, Ingrid Nascimento Oliveira, Ivanildo Vieira Pereira Filho, Jacimara Vasques Gomes, Jaily E Silva Rosa, Jonas Mota Lemos, Josué Nélio Brutus, Karina Pinheiro Pessoa, Laleyska Deucylane Costa Rodrigues, Larissa Esthefani Barros Cirino, Lauro Fragata Mourão Filho, Leandro Moura, Lisiane Rísia Pinto Barbosa, Lorenna Pereira de Souza, Lucas Barbosa Oliveira, Luiz Carlos de Lima Ferreira, Marcela Menezes Dos Santos, Marcus Vinicius Ramos da Silva, Mauro Pereira Rodrigues, Mayara Tavares de Menezes, Micaela Maciel Dos Santos Mota, Monique Freire, Nadya Fonseca Corrêa, Nagila Morais 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 A 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, Christiane Maria Prado Jeronimo, Maria Eduarda Leão Farias, Fernando Fonseca Almeida Val, Vanderson Souza Sampaio, Marcia Almeida Araújo Alexandre, Gisely Cardoso Melo, Izabella Picinin Safe, Mayla Gabriela Silva Borba, Rebeca Linhares Abreu Netto, Alex Bezerra Silva Maciel, João Ricardo Silva Neto, Lucas Barbosa Oliveira, Erick Frota Gomes Figueiredo, Kelry Mazurega Oliveira Dinelly, Maria Gabriela de Almeida Rodrigues, Marcelo Brito, Maria Paula Gomes Mourão, Guilherme Augusto Pivoto João, Ludhmila Abrahão Hajjar, Quique Bassat, Gustavo Adolfo Sierra Romero, Felipe Gomes Naveca, Heline Lira Vasconcelos, Michel de Araújo Tavares, José Diego Brito-Sousa, Fabio Trindade Maranhão Costa, Maurício Lacerda Nogueira, Djane Clarys Baía-da-Silva, Mariana Simão Xavier, Wuelton Marcelo Monteiro, Marcus Vinícius Guimarães Lacerda, Metcovid Team, Adria de Lemos Vasconcelos, Adriana Ferreira Praia Marins, Alexandre de Oliveira Trindade, Aline Sales Mendes Záu, Amanda Carvalho de Oliveira, Ana Carolina Azevedo Furtado, Ana Paula Coelho Rocha, Anderson da Silva Souza, Andiana de Souza Dias, Aníbal Belém, Anna Gabriela Rezende Dos Santos, Antonny Michael da Silva Sousa, Beatriz França da Silva, Beatriz Leitão Franco, Bernardo Maia da Silva, 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, Debora Camila Gomes Duarte, Ejandre Garcia Negreiros da Silva, Elias da Silva Lemos, Elisângela de Fátima Ponte Frota, Elizandra Freitas do Nascimento, Elson Silva de Almeida, Elyana Almeida Marques, Emanuel Medeiros Marinho de Almeida, Emanuelle Lira da Silva, Ester Galvão Dos Santos, Ezequiel da Silva Oliveira, Fábio Manabu Martins Shimizu, Fabíola Ramalho Ferreira de Souza, Felipe da Silva do Vale, Fernanda Dos Santos de Almeida Lima, Fernando Hugo Jesus da Fonseca, Flávia Alencar Fontenelle, Francielen de Azevedo Furtado, Gabrielle Da Silva Pereira, Geísa Aleixo Bezerra, Guilherme Kemeron Maciel Salazar, Handerson da Silva Pereira, Hilda Ferreira de Melo, Ingrid Nascimento Oliveira, Ivanildo Vieira Pereira Filho, Jacimara Vasques Gomes, Jaily E Silva Rosa, Jonas Mota Lemos, Josué Nélio Brutus, Karina Pinheiro Pessoa, Laleyska Deucylane Costa Rodrigues, Larissa Esthefani Barros Cirino, Lauro Fragata Mourão Filho, Leandro Moura, Lisiane Rísia Pinto Barbosa, Lorenna Pereira de Souza, Lucas Barbosa Oliveira, Luiz Carlos de Lima Ferreira, Marcela Menezes Dos Santos, Marcus Vinicius Ramos da Silva, Mauro Pereira Rodrigues, Mayara Tavares de Menezes, Micaela Maciel Dos Santos Mota, Monique Freire, Nadya Fonseca Corrêa, Nagila Morais 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 A 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
Abstract
Background: Steroid 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.
Methods: A 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.
Results: From 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.
Conclusions: The 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 registration: NCT04343729.
Keywords: Brazil; SARS-CoV-2; coronavirus; corticosteroid; inflammation.
© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.
Source: PubMed