Effect of early treatment with metformin on risk of emergency care and hospitalization among patients with COVID-19: The TOGETHER randomized platform clinical trial
Gilmar Reis, Eduardo Augusto, Moreira Santos, Silva, Daniela Carla Medeiros, Lehana Thabane, Aline Cruz Milagres, Thiago Santiago Ferreira, Castilho Vitor Quirino, Santos, Adhemar Dias, Figueiredo Neto, Eduardo Diniz Callegari, Leonardo Cançado, Monteiro Savassi, Maria Izabel Campos, Luciene Barra, Rosemary Oliveira, Ofir Harari, Holly Bailey, Jamie I Forrest, Alla Glushchenko, Sheila Sprague, Paula Mckay, Craig R Rayner, Hinda Ruton, Gordon H Guyatt, Edward J Mills
doi:10.17605/OSF.IO/EG37X)
Background Observational studies have postulated a therapeutic role of metformin in treating COVID-19. We conducted an adaptive platform clinical trial to determine whether metformin is an effective treatment for high-risk patients with early COVID-19 in an outpatient setting. Methods The TOGETHER Trial is a placebo-controled, randomized, platform clinical trial conducted in Brazil. Eligible participants were symptomatic adults with a positive antigen test for SARS-CoV-2. We enroled eligible patients over the age of 50 years or with a known risk factor for disease severity. Patients were randomly assigned to receive either placebo or metformin (750 mg twice daily for 10 days or placebo, twice daily for 10 days). The primary outcome was hospitalization defined as either retention in a COVID-19 emergency setting for > 6 h or transfer to tertiary hospital due to COVID-19 at 28 days post randomization. Secondary outcomes included viral clearance at day 7, time to hospitalization, mortality, and adverse drug reactions. We used a Bayesian framework to determine probability of success of the intervention compared to placebo.
Supplementary materials Supplementary material associated with this article can be found, in the online version, at doi:10.1016/j. lana.2021.100142.
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