PRINCIPLE Covid-19 treatments trial widens to under 50s, adds colchicine | University of Oxford

PRINCIPLE Covid-19 treatments trial widens to under 50s, adds colchicine

3 March 2021

PRINCIPLE is the UK’s largest national priority platform trial evaluating Covid-19 treatments that can be taken at home to speed-up recovery and prevent hospital admission.

  • Colchicine, an inexpensive anti-inflammatory commonly used to treat gout, is added to the trial and is being evaluated in participants from today. It is the fifth medication to be investigated in PRINCIPLE.
  • For colchicine, the trial widens to include anyone with confirmed or possible Covid-19 who is aged 18-64 with shortness of breath from the illness or certain underlying health conditions, or those aged over 65.
  • The trial can be joined online, over the telephone or via a GP practice.

From today, the UK’s national priority platform trial of Covid-19 treatments for recovery at home launches its investigation of the gout drug colchicine, and expands for the first time to include adults of any age.

Led by University of Oxford researchers, the Platform Randomised trial of Interventions against Covid-19 In older peoPLE (PRINCIPLE) trial is investigating treatments for early-stage Covid-19 that can reduce overall recovery time and the burden of symptoms, and prevent the need for hospital admission.

Colchicine is an inexpensive anti-inflammatory drug widely used in the UK for many years as a treatment for acute gout. In Canada’s ColCorona trial, the drug has recently shown promise in reducing hospital admissions in patients with Covid-19, yet little is known about its effectiveness in reducing recovery time or the burden of the illness.

Previously, only those with Covid-19 aged 50 or over and at most risk of complications from the illness were eligible to join the PRINCIPLE trial. For the colchicine arm, the trial now includes participants either aged 18-64 with shortness of breath from the illness or certain underlying health conditions that put them at risk of severe illness, or those aged over 65. Participants are only eligible to join the trial during the first 14 days of Covid-19 illness.

Since launching in March 2020, PRINCIPLE has so far recruited more than 4400 volunteers from across the UK, making it the largest trial of Covid-19 treatments to take place in community settings.

With the vaccine programme continuing at pace in vulnerable adults, and the remaining urgent need for evidence-based treatments for recovery at home, expanding parts of the trial to people aged under 50 will provide new insights into whether treatments can help those at greater risk of severe Covid-19 illness.

A vast network of community health and care organisations across the UK’s four nations now support patient recruitment into PRINCIPLE, and the Oxford team are today renewing their call for eligible adults with early Covid-19 symptoms to consider joining the trial.

PRINCIPLE trial co-lead, Professor Chris Butler, a general practitioner and Professor of Primary Care at the University Oxford’s Nuffield Department of Primary Care Health Sciences, said: ‘We are asking for eligible volunteers aged over 18 from all across the country to join the PRINCIPLE trial when they first experience Covid-19 symptoms, and help in the search for potential treatments. With Covid-19 still circulating in the community, and little known about the effect of new viral variants on younger adults, it is vital that we seize this window of opportunity to generate high-quality evidence to determine which treatments work, and which don’t.

‘Even with successful vaccines and other preventable measures in place, the availability of treatments with a solid evidence-base has a critical role to play in ending this pandemic, yet there are still very few options for treating Covid-19 before it becomes a severe illness.’

Minister for Innovation Lord Bethell said: ‘The UK continues to be a leading force in finding and rolling out safe and effective treatments for Covid-19, with life-saving treatments dexamethasone and tocilizumab identified by our research. The government-funded PRINCIPLE trial presents an exciting opportunity to find treatments outside of hospital, stopping people’s symptoms from worsening at an earlier stage of the disease.

‘The expansion of the trial, with a new treatment arm that is open to a wider patient cohort, is a promising development - I encourage as many eligible people as possible over the age of 18 to sign up to the trial and play a vital role in finding more treatments for this terrible virus.’

Following a screening questionnaire to confirm eligibility, participants will be randomly assigned a study drug or the usual standard-of-care NHS treatment. Those assigned to colchicine will receive a 14-day course of 500 micrograms (mcg) colchicine tablets, will be followed-up for 28 days and will be compared with participants who have been assigned to receive only the usual standard-of-care.

Those excluded from the colchicine study include women who are pregnant or breastfeeding, people taking certain medications, or those with inflammatory bowel disease.

People with coronavirus symptoms, or a positive test result, can join the trial easily online, over the telephone or via their GP practice from anywhere in the UK, without needing face-to-face visits with the trial team in Oxford.

The decision to widen the trial’s inclusion criteria and include colchicine was made by the University of Oxford researchers and the trial steering committee in conjunction with Chief Medical Officer for England, following a recommendation by the UK COVID-19 Therapeutics Advisory Panel.

The PRINCIPLE trial has so far determined that the antibiotics azithromycin and doxycycline are not effective treatments during the early stages of Covid-19. The trial continues to investigate budesonide, an inhaled corticosteroid, in people aged over 50.

PRINCIPLE is funded by a grant to the University of Oxford from UK Research and Innovation and the Department of Health and Social Care through the National Institute for Health Research as part of the UK Government’s rapid research response fund. To find out more about how to join the study, visit www.principletrial.org or call 0800 138 0880.

Notes for Editors

Contact: Dan Richards-Doran, Head of Communications, Nuffield Department of Primary Care Health Sciences, University of Oxford 01865 617870 dan.richards-doran@phc.ox.ac.uk

About the PRINCIPLE Trial
The UK-wide PRINCIPLE trial platform is led from the Primary Care Clinical Trials Unit at the University of Oxford’s Nuffield Department of Primary Care Health Sciences. The trial is integrated with the Oxford RCGP Research and Surveillance Centre and works closely with the NIHR Clinical Research Network across England and similar networks in the devolved nations. It is supported by a vast network of health and care professionals in care homes, pharmacies, NHS 111 Hubs, hospitals and more than 1000 GP practices across England, Wales, Scotland and Northern Ireland.

Within the University of Oxford, the Nuffield Department of Primary Care Health Sciences is the largest, top-ranked centre for academic primary care in the UK, bringing together academics from many different backgrounds to work together to produce benefits for the NHS, for populations and for patients.

Inclusion in the colchicine arm of the PRINCIPLE trial requires the following:

1. Participant or their legal representative, is willing and able to give informed consent for participation in the study, and is willing to comply with all trial procedures.
2. Suspected COVID-19 using the NHS syndromic definition, OR symptoms consistent with COVID-19*, with a positive test for SARS-CoV-2 infection within the past 14 days.
3. Symptoms must have started within the past 14 days and be ongoing.
AND
4. Participant is aged 65 or over; or aged 18- 64, and is experiencing shortness of breath as part of COVID-19 illness; or aged 18-64 and has any of the following underlying health conditions:
a. Known weakened immune system due to a serious illness or medication (e.g.chemotherapy).
b. Known heart disease and/or a diagnosis of high blood pressure.
c. Known chronic lung disease (e.g. asthma).
d. Known diabetes.
e. Known mild hepatic impairment.
f. Known stroke or neurological problem.
g. Self-report obesity or body mass index ≥35 kg/m2.

*These symptoms may include, but are not limited to, shortness of breath, general feeling of being unwell, muscle pain, diarrhoea and vomiting.

About the University of Oxford
Oxford University has been placed number 1 in the Times Higher Education World University Rankings for the fifth year running, and at the heart of this success is our ground-breaking research and innovation. Oxford is world-famous for research excellence and home to some of the most talented people from across the globe. Our work helps the lives of millions, solving real-world problems through a huge network of partnerships and collaborations. The breadth and interdisciplinary nature of our research sparks imaginative and inventive insights and solutions.

About the National Institute for Health Research
The National Institute for Health Research (NIHR) is the nation's largest funder of health and care research. The NIHR:

  • Funds, supports and delivers high quality research that benefits the NHS, public health and social care.
  • Engages and involves patients, carers and the public in order to improve the reach, quality and impact of research.
  • Attracts, trains and supports the best researchers to tackle the complex health and care challenges of the future.
  • Invests in world-class infrastructure and a skilled delivery workforce to translate discoveries into improved treatments and services.
  • Partners with other public funders, charities and industry to maximise the value of research to patients and the economy.

The NIHR was established in 2006 to improve the health and wealth of the nation through research, and is funded by the Department of Health and Social Care. In addition to its national role, the NIHR supports applied health research for the direct and primary benefit of people in low- and middle-income countries, using UK aid from the UK government.

This work uses data provided by patients and collected by the NHS as part of their care and support and would not have been possible without access to this data. The NIHR recognises and values the role of patient data, securely accessed and stored, both in underpinning and leading to improvements in research and care. www.nihr.ac.uk/patientdata

UK Research and Innovation works in partnership with universities, research organisations, businesses, charities, and government to create the best possible environment for research and innovation to flourish. We aim to maximise the contribution of each of our component parts, working individually and collectively. We work with our many partners to benefit everyone through knowledge, talent and ideas.

Operating across the whole of the UK with a combined budget of more than £8 billion, UK Research and Innovation brings together the seven research councils, Innovate UK and Research England.