Published: 18 September 2020
Read more about the PRINCIPLE trial and its progress
Treating COVID-19 in the community
The Platform Randomised trial of Interventions against Covid-19 In older peoPLE (PRINCIPLE) trial is the first study to test potential treatments for COVID-19 that can be taken at home. Funded by NIHR and UK Research and Innovation, the trial is one of the UK government’s national priority platform trials into COVID-19, which are being delivered across the NHS with support from NIHR’s Clinical Research Network.
Led by a team at the University of Oxford, PRINCIPLE was initially set up to test drugs that could reduce overall recovery time and the burden of symptoms, and prevent the need for hospital admission, in people over 50 with COVID-19. The study was looking at patients who are especially vulnerable to COVID-19 because of pre-existing health conditions such as heart disease or a weakened immune system.
In March 2021, the trial expanded recruitment to anyone aged 18-64 with shortness of breath from COVID-19 or certain underlying health conditions that put them at risk of severe illness. People aged over 65 with symptoms can also take part, even if they don’t have any underlying conditions.
More than 800 GP practices across the country are recruiting participants who have COVID-19 symptoms, with nearly 5,000 people recruited as of May 2021. The trial is also screening participants online, which means that older people with coronavirus symptoms can pre-screen for the trial at home, regardless of which GP surgery they are registered with, to see whether they are eligible to take part.
Could existing treatments help tackle COVID-19?
The PRINCIPLE trial is evaluating drugs that are already in use for other health conditions, to see if they could help to treat COVID-19.
Initially the study investigated whether a seven-day course of hydroxychloroquine could reduce the severity of COVID-19 symptoms. However, evidence emerged from other research studies showing that the drug isn’t beneficial for COVID-19, so this drug is no longer part of the PRINCIPLE trial.
The antibiotics doxycycline and azithromycin were also tested as part of the trial - these drugs are both already widely prescribed and are thought to have antiviral and anti-inflammatory properties. However, PRINCIPLE found that neither of these antibiotics had a beneficial effect in patients aged over 50 treated at home in the early stages of COVID-19.
In November 2020, PRINCIPLE turned its sights to the inhaled corticosteroid budesonide, which is often used to treat asthma and chronic obstructive pulmonary disease. In some patients with COVID-19, the body’s immune response to the virus can cause high levels of inflammation that can damage cells in the airways and lungs. Inhaling budesonide into the airways targets the anti-inflammatory treatment where it is needed most, and can potentially minimise any lung damage that might otherwise be caused by the virus.
PRINCIPLE found that treatment with budesonide reduces recovery time in patients with COVID-19 who are treated at home and in other community settings. The treatment, which was used in people aged over 50 who were at higher risk of a poor outcome from the illness, shortened recovery time by around two and a half to three days.
"PRINCIPLE, the world’s largest platform trial of community-based treatments for COVID-19, has found evidence that a relatively cheap, widely available drug with very few side effects helps people at higher risk of worse outcomes from COVID-19 recover quicker, stay better once they feel recovered, and improves their wellbeing."
Professor Chris Butler, Joint Chief Investigator, a South Wales GP and Professor of Primary Care from the University of Oxford’s Nuffield Department of Primary Care Health Sciences
The trial is now investigating only two drugs that were added to the study in spring 2021, bringing the total number of existing drugs evaluated by PRINCIPLE up to six.
In March 2021, the study began evaluating colchicine, an inexpensive anti-inflammatory commonly used to treat gout, as the fifth medication to be investigated in PRINCIPLE. In Canada’s ColCorona trial, the drug has recently shown promise in reducing hospital admissions, yet little is known about its effectiveness in reducing recovery time or the burden of the illness.
The antiviral drug favipiravir was added to PRINCIPLE in April 2021. Favipiravir is an antiviral drug that has been licenced in Japan since 2014 to treat influenza. It works by inhibiting a viral enzyme called RNA polymerase, preventing viral replication within human cells. This viral enzyme is common to several viruses, including SARS-CoV-2, which causes COVID-19.
The drug has shown positive results against SARS-CoV-2 in laboratory and animal studies, with small pilot studies in humans demonstrating some benefit in reducing symptoms and the duration of illness.
Helping patients recover sooner
Angela Houghton-Cole took part in PRINCIPLE - she’s living with Type 2 diabetes and developed symptoms of COVID-19 on 30 April 2020.
“I didn’t have a temperature, but I just couldn’t stop coughing and my chest felt really tight,” said the 52 year-old, who lives in Congleton, East Cheshire, with husband Martin.
“I was sent home from work and isolated myself. The coughing was so severe that I ached for a number of days afterwards and I also had a terrible headache.”
Mrs Houghton-Cole called her GP at Readesmoor Medical Centre in Congleton. In addition to receiving medical advice, she was told she also fitted the PRINCIPLE trial criteria due to her pre-existing health conditions and COVID-19 symptoms.
Her participation involved taking a tablet twice a day for seven days while continuing to self-isolate. It also involved completing a 28-day online diary of how she was feeling. Her COVID-19 swab was later shown to be negative.
“My GP sent me all the information and I was able to talk it over with my husband and mum before making my decision. Ultimately, I felt that if I could contribute towards research that will help us better understand this awful virus and possibly help other people in the future, then it was something I wanted to be part of.”
Professor Chris Butler, Chief Investigator for the trial, explained its importance in helping patients and taking pressure off NHS hospitals. “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," he said. "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.”