Early treatment with an asthma drug budesonide shortens recovery time in COVID-19 patients aged over 50 who are treated at home or in other community settings.
The Platform Randomised Trial of Interventions against COVID-19 in Older People (PRINCIPLE) trial is led by the University of Oxford. It is funded by UK Research and Innovation and the National Institute for Health Research (NIHR) through the COVID-19 Rapid Response rolling call.
It is the world’s largest Phase 3 platform randomised controlled trial to find clear evidence of an effective COVID-19 treatment for use in primary care that can significantly shorten recovery time.
The latest findings have the potential to change how COVID-19 is treated in its early stages in non-hospital, community settings both in the UK and internationally.
Inhaled budesonide is a safe, relatively inexpensive and readily available corticosteroid commonly used around the world in inhalers to treat asthma and chronic obstructive pulmonary disease. It was added to the PRINCIPLE trial on 28 November 2020.
To provide real-time information in the pandemic, these preliminary results will be posted on the medRxiv preprint server and submitted to a journal to undergo peer review.
For the interim report, a total of 961 patients were randomly assigned to receive inhaled budesonide at home. These were compared with 1819 patients randomly assigned to the usual standard of NHS care alone. Of these, 751 people in the budesonide group, and 1028 in the usual care group were SARS-CoV-2 positive and included in the primary interim analysis.
Based on the interim analysis using the latest data from 25 March 2021, the results showed the estimated median time to self-reported recovery for inhaled budesonide was:
- 3.01 days shorter compared to usual care (95% Bayesian credible interval 1.13 to 5.42 days)
- with a high probability (0.999) of being superior to the usual standard of care.
32% of those taking inhaled budesonide, compared to 22% in the usual care group, recovered within the first 14 days since being randomised into the trial. And they have subsequently remained well until 28 days (relative risk 1.46, 95% CI 1.23 – 1.74).
Participants in the budesonide group also reported greater wellbeing after two weeks (mean difference in WHO-5 Wellbeing score + 3.37, 95% CI 0.97 – 5.76, p = 0.006).
Among patients who had completed all 28 days of study follow up by 25 March 2021:
- 8.5% (59/692) in the budesonide group were hospitalised with COVID-19
- 10.3% (100/968) in the usual care group (estimated percentage benefit, 2.1% [95% BCI -0.7% – 4.8%], probability of superiority 0.928).
Fewer people than expected were admitted to hospital in the trial, and COVID-19 cases and hospitalisations continue to drop in the UK. Therefore, it is unclear from this interim analysis whether budesonide reduces hospitalisations.
Joint Chief Investigator, Professor Richard Hobbs, head of Oxford University’s Nuffield Department of Primary Care Health Sciences, said: "For the first time we have high-quality evidence of an effective treatment that can be rolled out across the community for people who are at most risk of developing more severe illness from COVID-19. Unlike other proven treatments, budesonide is effective as a treatment at home and during the early stages of the illness. This is a significant milestone for this pandemic and a major achievement for community-based research."
Professor Fiona Watt, executive chair of the Medical Research Council, which co-funded the study, said: "Researchers involved in the PRINCIPLE trial have overcome considerable logistical hurdles to set up a world-leading rigorous drug trial in people’s homes. We are now rewarded with the first inexpensive and widely available drug that can shorten recovery times for COVID-19 patients in the community. People around the world will be helped to recover faster thanks to these exciting new results."
