Methylprednisolone as Adjunctive Therapy for Patients Hospitalized With Coronavirus Disease 2019 (COVID-19; Metcovid): A Randomized, Double-blind, Phase IIb, Placebo-controlled Trial
Authors: Jeronimo Christiane Maria Prado , Farias Maria Eduarda Leão , Val Fernando Fonseca Almeida , Sampaio Vanderson Souza , Alexandre Marcia Almeida Araújo , Melo Gisely Cardoso , Safe Izabella Picinin , Borba Mayla Gabriela Silva , Netto Rebeca Linhares Abreu , Maciel Alex Bezerra Silva , Neto João Ricardo Silva , Oliveira Lucas Barbosa , Figueiredo Erick Frota Gomes , Oliveira Dinelly Kelry Mazurega , de Almeida Rodrigues Maria Gabriela , Brito Marcelo , Mourão Maria Paula Gomes , Pivoto João Guilherme Augusto , Hajjar Ludhmila Abrahão , Bassat Quique , Romero Gustavo Adolfo Sierra , Naveca Felipe Gomes , Vasconcelos Heline Lira , de Araújo Tavares Michel , Brito-Sousa José Diego , Costa Fabio Trindade Maranhão , Nogueira Maurício Lacerda , Baía-da-Silva Djane Clarys , Xavier Mariana Simão , Monteiro Wuelton Marcelo , Lacerda Marcus Vinícius Guimarães ,   Metcovid Team, 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 
Published: August 2020

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.