The Platform Randomised trial of INterventions against COVID-19 in older peoPLE (PRINCIPLE) trial will involve hundreds of GP practices across the UK and is one of three national priority clinical trials on COVID-19.
The trial has today been awarded a £1.7 million share of the £24.6 million rapid research response funded by UK Research and Innovation (UKRI), and by the Department of Health and Social Care through the National Institute for Health Research (NIHR).
PRINCIPLE will enable researchers to rapidly evaluate different treatments that could stem the progression of COVID-19 symptoms in older people and help ease the burden on hospitals.
Unlike many other clinical trials for COVID-19, which are mostly focussed on providing treatment to those who already have serious symptoms and are admitted to hospital, the PRINCIPLE trial looks to identify treatments that can be prescribed by community-based GPs to slow or halt the progression of the disease and prevent the need for hospitalisation.
Only those at most risk of complications from COVID-19 will be eligible to join the trial via participating GP surgeries.
In the first instance, the trial is evaluating a drug called hydroxychloroquine. This drug is well known and has been used for many years around the world for conditions such as malaria and certain types of arthritis. The drug is not currently used to treat coronavirus infection because it is not yet known whether it is an effective treatment. The trial aims to answer this question. The antibiotic azithromycin will soon be added to the trial.
PRINCIPLE aims to recruit over 3,000 people. This number will be increased if additional treatments are introduced and may also be adjusted in light of results that emerge during the course of 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:
“What’s unique about the PRINCIPLE trial platform is that it’s so flexible. By setting up a nationwide primary care research network across the NHS, we’re able to rapidly evaluate potential new treatments for COVID-19. This trial will allow us to make treatments that are proven to be effective as widely, and as rapidly available as possible. However, we do not want to give people medication that does not work and may simply put them at unnecessary risk of side effects.
“At the moment we really do not have enough information about whether any benefits from taking these medicines for COVID-19 outweigh any possible harms. That is why we urgently need to do a proper trial, so we have the information we need to guide the provision of best care for all.”
Co-Chief Investigator Professor Richard Hobbs, Head of Department in Oxford University’s Nuffield Department of Primary Care Health Sciences, said:
“Our trial is prioritising treatments for those people who are unfortunately at most risk of serious complications from COVID-19 infection. That’s people aged 50 to 64 with pre-existing major illnesses, such as diabetes or compromised immune systems. It is also recruiting patients aged 65 and above without any other known illness. Additionally, as this trial is community-based we’re hoping that it will help to ease the pressure on the NHS during this extraordinary time.
“I really want to thank our team, our partners and the general practices out in the community who are all working so hard to put this trial together so swiftly. Getting a trial off the ground is no easy task at the best of times, so under the current conditions this really is an impressive feat.”
More than 100 GP practices are already actively recruiting participants into PRINCIPLE, with further practices coming on board on a daily basis. Earlier this month, the Chief Medical Officers of England, Wales, Scotland and Northern Ireland, and the NHS Medical Director, wrote to NHS trusts in England asking them to fully support the trial.
PRINCIPLE is managed by Oxford University’s Primary Care Clinical Trials Unit.
More information about the trial can be found at: http://www.principletrial.org
The PRINCIPLE trial is a 'platform trial'. Unlike most traditional types of clinical trial where a single treatment is evaluated, the design of the PRINCIPLE trial allows for the evaluation of several treatments at the same time, and for possibly more people in the trial to get the most effective trial intervention treatment.
For example, if the first treatment evaluated is found to be more effective than the comparison, standard care, then the new treatment will become the new ‘standard of care’ in the trial. Other treatments subsequently introduced into the trial will then be compared to the treatment that has performed best so far in the trial.