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

Gates Open Research

article

Gilmar Reis¹  Eduardo Augusto dos Santos Moreira Silva¹  Daniela Carla Medeiros Silva¹  Kristian Thorlund³  Lehana Thabane³  Gordon H. Guyatt³  Jamie I. Forrest⁴  Alla V. Glushchenko³  Cameron Chernecki⁴  Paula McKay³  Sheila Sprague³  Ofir Harari⁴  Hinda Ruton⁴  Craig R. Rayner⁶  Edward J. Mills³ 

[1] Cardiologia Assistencial e de Pesquisa, Cardresearch;Pontificia Universidade Católica de Minas Gerais;Faculty of Health Sciences, McMaster University;Cytel;University of British Columbia;Certara Inc., Certara Inc, Princeton;Monash University, Monash Institute of Pharmaceutical Sciences

关键词: COVID-19;    SARS-CoV-2;    repurposed drugs;    RCT;    adaptive design;    early treatment;    outpatient care;    master protocol;   

DOI  :  10.12688/gatesopenres.13304.2

学科分类：电子与电气工程

来源: American Journal Of Pharmtech Research

【 摘 要 】

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

【 授权许可】

CC BY