A multi-center, adaptive, randomized, platform trial to evaluate the effect of repurposed medicines in outpatients with early coronavirus disease 2019 (COVID-19) and high-risk for complications: the TOGETHER master trial protocol

• DOI: 10.12688/gatesopenres.13304.2
• Publication Date: 2021-11-08T08:20:07Z
• Authors: Gilmar Reis; Eduardo Augusto d...; Daniela Carla Med...; Kristian Thorlund; Lehana Thabane; Gordon H. Guyatt; Jamie I. Forrest; Alla V. Glushchenko; Cameron Chernecki; Paula McKay; Sheila Sprague; Ofir Harari; Hinda Ruton; Craig R. Rayner; Edward J. Mills
• Keywords: Interim analysis; Clinical endpoint; Surrogate endpoint

<ns3:p><ns3:bold>B</ns3:bold><ns3:bold>ackground: </ns3:bold>There remains a need for an effective and affordable outpatient treatment early COVID-19. Multiple repurposed drugs have shown promise in treating We describe master protocol that will assess the efficacy of different as treatments COVID-19 among outpatients at high risk severe complications.</ns3:p><ns3:p> <ns3:bold>Methods: </ns3:bold>The TOGETHER Trial is multi-center platform adaptive randomized, placebo-controlled, clinical trial. Patients are included if they least 18 years age, positive antigen test acute respiratory syndrome coronavirus 2 (SARS-CoV-2), indication disease severity, including co-morbidities, older or body mass index. Eligible patients randomized with equal chance to investigational product (IP) placebo.The primary endpoint hospitalization defined either retention emergency setting greater than 6 hours transfer tertiary hospital due Secondary outcomes include mortality, adverse events, adherence, viral clearance. Scheduled interim analyses conducted reviewed by Data Safety Monitoring Committee (DSMC), who make recommendations on continuing stopping each IP. The design go-no-go decision rules extended dynamically incorporate external evidence interventions from ongoing independent trials.</ns3:p><ns3:p> <ns3:bold>Discussion: </ns3:bold>Results this trial assist identification therapeutics diagnosed novel methodological extension one first its kind may provide highly valuable information all trials going forward.</ns3:p><ns3:p> <ns3:bold>Clinicaltrials.gov registration: </ns3:bold>NCT04727424 (27/01/2021)</ns3:p>