Antivirals for adult patients hospitalized with SARS-CoV-2 infection: A randomized, Phase II/III, multicenter, placebo-controlled, adaptive study, with multiple arms and stages. COALITION COVID-19 BRAZIL IX - REVOLUTIOn: protocol and statistical analysis plan
Israel Silva Maia, Aline Marcadenti, Fernando Godinho Zampieri, Lucas Petri Damiani, Renato Hideo Nakagawa Santos, Karina Leal Negrelli, Samara Pinheiro do Carmo Gomes, Jaqueline Oliveira Gomes, Mariana Barbosa Dos Santos Carollo, Tamiris Abait Miranda, Eliana Santucci, Nanci Valeis, Ligia Nasi Laranjeira, Glauco Adrieno Westphal, Jacques Gabriel Alvares Horta, Uri Adrian Prync Flato, Camilo Fernandes, Waldemar Carlos Barros, Renata S Bolan, Otávio Celso Eluf Gebara, Meton Soares de Alencar Filho, Victor Augusto Hamamoto, Mauro Esteves Hernandes, Nicole Alberti Golin, Ronald Torres de Olinda, Flávia Ribeiro Machado, Régis Goulart Rosa, Viviane Cordeiro Veiga, Luciano César Pontes de Azevedo, Alvaro Avezum, Renato Delascio Lopes, Tiago Moreno L Souza, Otávio Berwanger, Alexandre Biasi Cavalcanti, Israel Silva Maia, Aline Marcadenti, Fernando Godinho Zampieri, Lucas Petri Damiani, Renato Hideo Nakagawa Santos, Karina Leal Negrelli, Samara Pinheiro do Carmo Gomes, Jaqueline Oliveira Gomes, Mariana Barbosa Dos Santos Carollo, Tamiris Abait Miranda, Eliana Santucci, Nanci Valeis, Ligia Nasi Laranjeira, Glauco Adrieno Westphal, Jacques Gabriel Alvares Horta, Uri Adrian Prync Flato, Camilo Fernandes, Waldemar Carlos Barros, Renata S Bolan, Otávio Celso Eluf Gebara, Meton Soares de Alencar Filho, Victor Augusto Hamamoto, Mauro Esteves Hernandes, Nicole Alberti Golin, Ronald Torres de Olinda, Flávia Ribeiro Machado, Régis Goulart Rosa, Viviane Cordeiro Veiga, Luciano César Pontes de Azevedo, Alvaro Avezum, Renato Delascio Lopes, Tiago Moreno L Souza, Otávio Berwanger, Alexandre Biasi Cavalcanti
Abstract
Repurposed drugs are important in resource-limited settings because the interventions are more rapidly available, have already been tested safely in other populations and are inexpensive. Repurposed drugs are an effective solution, especially for emerging diseases such as COVID-19. The REVOLUTIOn trial has the objective of evaluating three repurposed antiviral drugs, atazanavir, daclatasvir and sofosbuvir, already used for HIV- and hepatitis C virus-infected patients in a randomized, placebo-controlled, adaptive, multiarm, multistage study. The drugs will be tested simultaneously in a Phase II trial to first identify whether any of these drugs alone or in combination reduce the viral load. If they do, a Phase III trial will be initiated to investigate if these medications are capable of increasing the number of days free respiratory support. Participants must be hospitalized adults aged ≥ 18 years with initiation of symptoms ≤ 9 days and SpO2 ≤ 94% in room air or a need for supplemental oxygen to maintain an SpO2 > 94%. The expected total sample size ranges from 252 to 1,005 participants, depending on the number of stages that will be completed in the study. Hence, the protocol is described here in detail together with the statistical analysis plan. In conclusion, the REVOLUTIOn trial is designed to provide evidence on whether atazanavir, daclatasvir or sofosbuvir decrease the SARS-CoV-2 load in patients with COVID-19 and increase the number of days patients are free of respiratory support. In this protocol paper, we describe the rationale, design, and status of the trial. ClinicalTrials.gov identifier: NCT04468087.
Conflict of interest statement
Conflicts of interest: None.
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Source: PubMed