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Case study: Testing treatments for COVID-19 through GP surgeries - PRINCIPLE

Read more about the PRINCIPLE trial and its progress

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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.

The trial is screening participants online, as well as recruiting through GP surgeries. This means that regardless of which GP surgery they are registered with, older people with coronavirus symptoms can pre-screen for the trial at home via an online questionnaire to see whether they can be included.

More than 800 GP practices across the country are recruiting participants who have COVID-19 symptoms, with more than 4,400 people recruited as of March 2021. 

Could existing treatments help tackle COVID-19?

The trial is screening participants online, as well as recruiting through GP surgeries. This means that regardless of which GP surgery they are registered with, older people with coronavirus symptoms can pre-screen for the trial at home via an online questionnaire to see whether they can be included.

In its first phase, the PRINCIPLE trial evaluated two drugs that are already in use for other health conditions, to see if they could help to treat COVID-19. 

Initially the study was investigating whether a seven-day course of hydroxychloroquine could reduce the severity of COVID-19 symptoms. However, recently further evidence has 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, with no serious side-effects associated with short-term use.

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 anti-inflammatory treatment where it is needed most, and can potentially minimise any lung damage that might otherwise be caused by the virus.

As of March 2021, the study is also 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 government is working with researchers to find proven, effective treatments for COVID-19. The PRINCIPLE trial is a vital part of this research effort and it’s being scaled up by GP surgeries across the country.”
Chief Medical Officer Professor Chris Whitty

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, Professor of Primary Care in the Nuffield Department of Primary Care Health Sciences, is Chief Investigator for the trial and 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. 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.”

 


 

COVID-19: the PRINCIPLE trial

 

The PRINCIPLE trial is the first to test potential treatments for COVID-19 through GP practices - over 800 practices are taking part.

PRINCIPLE has been designated a priority clinical trial COVID-19 by Chief Medical Officers of the UK.

Researchers from Oxford University are leading the trial, with £1.7 million in funding from NIHR and UKRI.

The trial focuses on older people and aims to find treatments that can slow the disease and prevent patients from going to hospital.

People aged 50-64 who have symptoms of COVID-19 and have pre-existing conditions are eligible to join the trial, as well as anyone over 65 or over who has symptoms.

The trial is currently comparing normal care for patients with treatment using the antibiotic azithromycin.

“By carefully evaluating a range of treatments as rapidly as possible, the PRINCIPLE trial aims to find safe and effective treatments for use early on in the illness. This will not only help people get better faster, it will take pressure off our NHS hospitals.” Professor Christopher Butler, Chief Investigator, PRINCIPLE trial.

“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.” Professor Chris Witty, Chief Medical Officer.

PRINCIPLE is a part of a suite of nationally prioritised COVID-19 studies funded and supported by NIHR.