Led by the University of Oxford, the Platform Randomised trial of Interventions against Covid-19 In older peoPLE (PRINCIPLE) Trial is evaluating treatments that can help people aged over 50 recover more quickly from Covid-19 illness and prevent the need for hospital admission. The study has so far recruited more than 2100 volunteers from across the UK.
Inhaled budesonide is commonly prescribed as part of the long-term management of asthma and chronic obstructive pulmonary disease, with no serious side-effects associated with short-term use.
In some patients with Covid-19, the body mounts a significant immune response to fight the virus, causing high levels of inflammation that can damage human cells in the airways and lungs. Inhaling budesonide into the airways targets anti-inflammatory treatment where it is needed most, and can potentially minimise any lung damage that might otherwise be caused by the virus.
SARS-CoV-2 (the virus that causes Covid-19) binds to ACE2 (angiotensin-converting enzyme 2) receptors lining cells in the airways, gaining entry to human cells and replicating within. Laboratory studies suggest that inhaled corticosteroids reduce the number of ACE2 receptors in the airways, and so may block entry of the virus into human cells.
Professor Chris Butler, from the Nuffield Department of Primary Care Health Sciences, Lead of the PRINCIPLE trial, said “Budesonide is relatively inexpensive, safe and easy-to-administer drug for respiratory conditions that may have a role to play in treating Covid-19. It is only through enrolling volunteers on a randomised controlled trial like PRINCIPLE that we can assess whether there are clear benefits or harms associated with potential treatments like budesonide. We need many more volunteers to join the trial so we can get the answers we really need to keep people with Covid-19 out of hospital. Like vaccines and preventative measures, treatments have an important role to play in minimising the burden of this disease on society.”
Patients enrolled in the study will be randomly assigned to receive an inhaler in the post and the usual standard-of-care from their clinician. They will be asked to inhale two puffs twice a day for 14 days with each puff providing a 400 microgram dose of budesonide. They will be followed-up for 28 days and will be compared with participants who have been assigned to receive the usual standard-of-care only.
Professor Richard Hobbs, from the Nuffield Department of Primary Care Health Sciences, Co-Lead of the PRINCIPLE Trial, said “We are continuously evaluating different treatments that might be suitable to help people with Covid-19 to recover at home without needing to go into hospital. We know from hospital-based trials, like RECOVERY, that intravenous corticosteroid treatment with dexamethasone can reduce mortality in patients who are already hospitalised. If we find that budesonide is an effective way of treating Covid-19 illness and preventing hospital admission, then it could be rolled out quickly across the UK following regulatory approval.”
The PRINCIPLE trial is primarily evaluating whether treatment prescribed in the first 14 days of Covid-19 illness can speed up recovery and prevent the need for hospital admission. It is open across the UK to people aged over 50 with certain underlying health conditions, or anyone aged over 65. Those with coronavirus symptoms, or a positive test result, can join easily join from home 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 other treatments currently being evaluated in the PRINCIPLE trial are doxycycline and azithromycin, which are both commonly-prescribed antibiotics thought to have additional anti-inflammatory properties.
The PRINCIPLE Trial is conducted by the Primary Care Clinical Trials Unit in Oxford University’s Nuffield Department of Primary Care Health Sciences. It is funded by 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.
The trial 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.
To find out more about how to join the study, visit www.principletrial.org