Methylprednisolone as Adjunctive Therapy for Patients Hospitalized With Coronavirus Disease 2019 (COVID-19; Metcovid): A Randomized, Double-blind, Phase IIb, Placebo-controlled Trial
Author:
Jeronimo Christiane Maria Prado12, Farias Maria Eduarda Leão13, Val Fernando Fonseca Almeida12, Sampaio Vanderson Souza124, Alexandre Marcia Almeida Araújo1, Melo Gisely Cardoso12, Safe Izabella Picinin1, Borba Mayla Gabriela Silva12, Netto Rebeca Linhares Abreu12, Maciel Alex Bezerra Silva12, Neto João Ricardo Silva1, Oliveira Lucas Barbosa12, Figueiredo Erick Frota Gomes12, Oliveira Dinelly Kelry Mazurega12, de Almeida Rodrigues Maria Gabriela12, Brito Marcelo12, Mourão Maria Paula Gomes12, Pivoto João Guilherme Augusto12, Hajjar Ludhmila Abrahão5, Bassat Quique678910, Romero Gustavo Adolfo Sierra11, Naveca Felipe Gomes3, Vasconcelos Heline Lira1, de Araújo Tavares Michel12, Brito-Sousa José Diego12, Costa Fabio Trindade Maranhão13, Nogueira Maurício Lacerda14, Baía-da-Silva Djane Clarys12, Xavier Mariana Simão1215, Monteiro Wuelton Marcelo12, Lacerda Marcus Vinícius Guimarães123, de Lemos Vasconcelos Adria, Praia Marins Adriana Ferreira, de Oliveira Trindade Alexandre, Mendes Záu Aline Sales, de Oliveira Amanda Carvalho, Azevedo Furtado Ana Carolina, Coelho Rocha Ana Paula, da Silva Souza Anderson, de Souza Dias Andiana, Belém Aníbal, dos Santos Anna Gabriela Rezende, da Silva Sousa Antonny Michael, da Silva Beatriz França, Franco Beatriz Leitão, da Silva Bernardo Maia, da Costa Bleno Leonam Gonçalves, Sato Barros do Amaral Camila Miriam Suemi, Judice Carla C, de Morais Carlos Eduardo Padron, Camilo Cecília Cunha, Sena da Silva Danielle Severino, Gomes Duarte Debora Camila, da Silva Ejandre Garcia Negreiros, da Silva Lemos Elias, de Fátima Ponte Frota Elisângela, do Nascimento Elizandra Freitas, de Almeida Elson Silva, Marques Elyana Almeida, de Almeida Emanuel Medeiros Marinho, da Silva Emanuelle Lira, dos Santos Ester Galvão, da Silva Oliveira Ezequiel, Martins Shimizu Fábio Manabu, de Souza Fabíola Ramalho Ferreira, da Silva do Vale Felipe, dos Santos de Almeida Lima Fernanda, da Fonseca Fernando Hugo Jesus, Fontenelle Flávia Alencar, de Azevedo Furtado Francielen, Da Silva Pereira Gabrielle, Bezerra Geísa Aleixo, Maciel Salazar Guilherme Kemeron, da Silva Pereira Handerson, de Melo Hilda Ferreira, Oliveira Ingrid Nascimento, Pereira Filho Ivanildo Vieira, Gomes Jacimara Vasques, e Silva Rosa Jaily, Lemos Jonas Mota, Brutus Josué Nélio, Pessoa Karina Pinheiro, Costa Rodrigues Laleyska Deucylane, Barros Cirino Larissa Esthefani, Mourão Filho Lauro Fragata, Moura Leandro, Barbosa Lisiane Rísia Pinto, de Souza Lorenna Pereira, Oliveira Lucas Barbosa, de Lima Ferreira Luiz Carlos, dos Santos Marcela Menezes, da Silva Marcus Vinicius Ramos, Rodrigues Mauro Pereira, de Menezes Mayara Tavares, dos Santos Mota Micaela Maciel, Freire Monique, Corrêa Nadya Fonseca, Rocha Nagila Morais, Bittencourt Najara, de Melo Silva Natália Guedes, de Oliveira Saraiva Priscilla, de Sousa Monteiro Quézia, dos Santos Rafael Theodoro, Freire Raíssa Soares, de Araújo Pinto Rebecca Augusta, Ferreira Reinan Brotas, de Lima Rodrigo Saboia, de Melo Rosângela Francisca Tanantas, Saenz Sabrina Teixeira, Alvarez Fernandes Salete Sara, Vítor-Silva Sheila, de Oliveira Tânia Maria Rodrigues, Tavella Tatyana A, Câmara Thais Tavares, Santos Thalie Cavalcante, Pinto Thiago Serrão, dos Santos Tilza Waleska Rocha, do Nascimento Valdinete Alves, Sousa Barbosa Wanessa Pessoa, de Melo Wellinthon Ferreira, Salgado Sobrinho Wlademir Braga,
Affiliation:
1. Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Brazil 2. Universidade do Estado do Amazonas, Manaus, Brazil 3. Instituto Leônidas and Maria Deane, Fiocruz Amazonas, Manaus, Brazil 4. Fundação de Vigilância em Saúde do Amazonas, Manaus, Brazil 5. Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil 6. Instituto de Salud Global de Barcelona (ISGlobal), Hospital Clínic–Universitat de Barcelona, Barcelona, Spain 7. Centro de Investigação em Saúde de Manhiça, Maputo, Mozambique 8. Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain 9. Pediatric Infectious Diseases Unit, Pediatrics Department, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain 10. Consorcio de Investigación Biomédica en Red de Epidemiología y Salud Pública, Madrid, Spain 11. Núcleo de Medicina Tropical, Universidade de Brasília, Brasília, Brazil 12. Universidade Federal do Amazonas, Manaus, Brazil 13. Universidade Estadual de Campinas, Campinas, Brazil 14. Faculdade de Medicina de São José do Rio Preto, São José do Rio Preto, Brazil 15. Instituto Nacional de Infectologia Carlos Chagas, Fiocruz, Rio de Janeiro, Brazil
Abstract
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.
Funder
Conselho Nacional de Desenvolvimento Científico e Tecnológico Fundação de Amparo à Pesquisa do Estado do Amazonas Fundação de Amparo à Pesquisa do Estado de São Paulo Spanish Ministry of Science and Innovation
Publisher
Oxford University Press (OUP)
Subject
Infectious Diseases,Microbiology (medical)
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