Platform Randomised trial of INterventions against COVID-19 In older peoPLE (PRINCIPLE)

This COVID-19 Rapid Response award is jointly funded (50:50) between the Medical Research Council and the National Institute for Health Research. The figure displayed is the total award amount of the two funders combined, with each partner contributing equally towards the project. COVID-19 disproportionately affects people ≥ 50 years old with comorbidities and those ≥ 65 years old. No specific treatment has yet been proven in rigorous clinical trials to be effective against COVID-19. Most clinical trials are hospital-based. Yet, most cases are managed in the community, so interventions proven to be effective are urgently in primary care that prevent hospitalisation and speed recovery. PRINCIPLE will be a Phase III, platform, response-adaptive, open-label randomised controlled trial in primary care. The platform trial will operate under a master protocol that allows the addition or replacement of further interventions. Outcome data will be analysed as the trial is in progress: if evidence emerges that one arm is more effective, we might be able to allocate more people to that arm. PRINCIPLE will, in the first instance, evaluate usual care plus hydroxychloroquine 200mg twice a day for 7 days. This drug is already in wide use, but not for this indication. The comparator will be usual care without a study drug. Eligible patients will be aged ≥50-64 years with a defined comorbidity, and patients aged ≥65 with or without comorbidity presenting within 7 days since onset of symptoms with a new continuous cough and/or high temperature during time of prevalent COVID-19 infection. Approximately 3000 eligible participants will need to be randomised in the first instance in order to determine whether the first drug we plan to evaluate is more effective than usual care alone in preventing hospital admission and/or death in people with suspected COVID-19.