A UK trial of drugs which could prevent people aged over 50 who are vulnerable to developing serious coronavirus symptoms is now recruiting participants from across the country.
Led by an Oxford University team, the Platform Randomised trial of Interventions against COVID-19 in older peoPLE (PRINCIPLE) trial is testing pre-existing drugs for older patients in the community who show signs of the disease. It aims to slow or halt the progression of the COVID-19 and prevent the need for hospital admission.
PRINCIPLE is the first trial of COVID-19 treatments to take place in primary care, and one of the UK Government’s four national priority platform trials on the disease. More than 500 GP practices across the country are already recruiting people aged 50 and over with underlying health conditions, or people aged over 65 regardless of underlying health conditions, into the trial.
From this week the trial is now also screening participants online. This means that regardless of which GP surgery they are registered with, older people with coronavirus symptoms can now pre-screen for the trial at home via an online questionnaire to see whether they can be included.
PRINCIPLE is trialling a number of low-risk treatments recommended by an expert panel advising the Chief Medical Officer for England. The effectiveness of these treatments will be compared to the current best available care.
In the first phase, the trial is evaluating whether a seven-day course of hydroxychloroquine, a well-known drug used for acute malaria and certain types of arthritis, can reduce the severity of symptoms in vulnerable groups and help avoid hospital admission. The antibiotic azithromycin will soon be added to the trial.
The trial’s Chief Investigator, Professor Chris Butler, Professor of Primary Care in the Nuffield Department of Primary Care Health Sciences, a part-time GP for the Cwm Taf Morgannwg University Health Board, and Fellow of Trinity College, said, ‘The PRINCIPLE trial platform is enabling us to rapidly evaluate potential treatments for COVID-19 in older people who are most at risk of serious complications from the illness. With enough people recruited, this trial will give us the vital information we need to understand whether existing drugs can help people recover sooner and at home, without needing to be admitted to hospital – a significant milestone in the course of this pandemic.
‘As soon as we find that any one of the drugs in our trial is making a critical difference to people’s health, we want it to be part of clinical practice as soon as it can be introduced.’
Dr Rebecca Clark is a Blackpool-based GP whose practice are contacting patients eligible to join the trial. She said, ‘PRINCIPLE is a hugely important community trial, particularly in areas where health systems are under pressure and prevalence of disease puts many of our older patients at increased risk from COVID-19. That’s why it is vital that we urgently identify treatments that can help people to get better more quickly and keep them out of hospital. As a practice running the trial locally, I have been amazed at how straightforward the enrolment process has been for our patients.’
Chief Medical Officer, Professor Chris Whitty said, ‘The Government is working with researchers to find proven, effective treatments for COVID-19. This PRINCIPLE trial is a vital part of this research effort and it’s being scaled up by GP surgeries across the country.
‘I would urge anyone who is contacted to take part in this trial to do so and contribute to helping our world-class scientists find a treatment that will save lives.’
Participants will be closely monitored for the first 28 days of the trial, with a health record notes review taking place for up to three months to understand the longer-term effects of the illness on their health.
Integration of the trial with the Royal College of General Practitioners (RCGP) Research and Surveillance Centre, a rapidly expanding network of over 1,100 GP practices, is enabling this extended follow-up to take place. As well as recruiting patients into the PRINCIPLE trial, GP practices in the network continuously monitor and report on the prevalence of infections and diseases in the community through swab testing, including COVID-19.
Co-Chief Investigator Professor Richard Hobbs, Professor of Primary Care and Head of Oxford University’s Nuffield Department of Primary Care Health Sciences, said, ‘The challenges in developing PRINCIPLE were unprecedented in terms of speed in finalising design, seeking permissions, and then operationalising this key platform trial. It has required months of work to be completed in just a matter of days and weeks.
‘We could not have achieved this without extraordinary levels of support from our digital partners at EMIS, TPP and NHS-X, our research delivery partners in the National Institute for Health Research and the RCGP, and the many practices agreeing to support the trial. In particular, our thanks go to the patients who are falling ill and are yet agreeing to join this study.’
The PRINCIPLE trial platform has received £1.7 million from UK Research and Innovation (UKRI) and the Department of Health and Social Care through the National Institute for Health Research (NIHR). It is part of a wider £24.6 million rapid research response investment by the UK Government to support looking at ways to tackle the coronavirus outbreak.
Professor Fiona Watt, Executive Chair of the Medical Research Council, which funded the trial with the NIHR, said, ‘This trial is very important. It is focussed on older people and those with co-morbidities, who are much more likely to be hospitalised with COVID-19. We need more people to join the trial to see if we can identify a drug that helps prevent people reaching hospital and speeds up their recovery.’
For details of participating GP surgeries, and a link to the online screening questionnaire, visit https://www.phctrials.ox.ac.uk/principle
PRINCIPLE is led from the Primary Care Clinical Trials Unit at the University of Oxford.