Cytel has designed and implemented a novel adaptive platform trial for early stage COVID-19. The severity of the coronavirus emerges in five stages, with the majority of clinical trials focusing on therapies for the final stage of the disease. According to the Cytel Clinical Trial Tracker, only 6 of 2000 trials are focused on early stages; staggering given that only 5% of coronavirus cases are considered severe.
This unwillingness to focus on early stages of coronavirus might seem justified given the urgency of supporting those in near death situations. Unfortunately, it also means that the scientific community is missing an opportunity to learn more about how this disease operates before it becomes severe.
Low and middle income countries (LMIC) face the brunt of this oversight, as by the time the deadly disease reaches its fifth stage, individuals in these countries must overpower it while struggling with other comorbidities like severe malnutrition, HIV and latent tuberculosis. By participating in this project, Cytel and its partners are helping develop trial infrastructure in Brazil and South Africa.
Meeting Design Challenges with Expert Trial Design
Adaptive platform trials are ideally suited to the COVID-19 challenge, as they allow the flexibility that is needed when so much is unknown, without sacrificing statistical rigor: multiple treatments can be simultaneously tested, arms can be added as new candidate treatments emerge, and arms can be dropped as candidate treatments are found to be ineffective or harmful.
The master protocol design allows for data-pooling and rapid discovery across therapies under study. Active arms can be added and dropped, while being compared to the same control, ensuring that trial resources and patient allocation are optimized. As knowledge accelerates and new comparator arms emerge, the platform design ensures that the comparator can be quickly replaced by the new one.
The TOGETHER Trial
The goal of the TOGETHER trial is to determine the effectiveness, safety, and pharmacokinetics of repurposing three existing interventions as possible treatments for COVID-19, compared to a placebo (Ascorbic acid), for treatment of high-risk adults who do not require hospitalization, within 48 hours of being diagnosed. An additional, smaller cohort of just-diagnosed low-risk adults is also being recruited.
The primary endpoints are progression to lower respiratory tract infection and presence of viral detected by nasal swabs at the 10th day after randomization. The secondary endpoints are severe adverse events; prevalence and number of days of hospitalization; proportion of days after randomization with fever, respiratory symptoms, or oxygen saturation under 93% for more than one hour; proportion and quantity of virus detected from nasal swabs collected at defined points between the first and 14th day after randomization.
The trial also introduces operational innovations and increases safety by using telemedicine and self-administered swabs and surveys, minimizing in-person contact between trial participants and study staff.
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