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

We do not yet have any treatments for COVID-19 patients, so we are now running a clinical trial to test out drugs which may work. Most COVID 19 cases are managed in the community and it is essential that we find treatments that help reduce hospital admission and speed recovery. The risk of complications from suspected COVID-19 infection is generally greater in people aged 50 years and older with underlying health conditions and in those aged 65 years and older. Therefore, we will ask these two groups to take part in our trial. The first drug we will evaluate is hydroxychloroquine, which is already used for other illnesses, but but it has not been tested in patients with suspected COVIS-19 in the community. Therefore, we do not yet know if hydroxychloroquine, (or any future treatments that we include in the trial), given to COVID-19 patients, will help reduce the need for hospitalisation or speed up recovery. All people initially included in the study will have a test for COVID-19, and will either receive usual best care, or usual best care plus the drug we are testing, currently hydroxychloroquine. We will include 3000 people in the study in the first instance.

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.