Early treatment with budesonide, a corticosteroid commonly used to treat asthma and and chronic obstructive pulmonary disease (COPD), may reduce by 90% the need for urgent care and hospitalisation in people with COVID-19, the STOIC phase 2 trial found.
The research, led by the University of Oxford, found that inhaled budesonide given to patients with COVID-19 within seven days of the onset of symptoms also reduced recovery time. Budesonide is a corticosteroid used in the long-term management of asthma and chronic obstructive pulmonary disease (COPD).
The phase 2 randomised study was supported by the NIHR Oxford Biomedical Research Centre (BRC).
The findings from 146 people – of whom half took 800 micrograms of the medication twice a day and half were on usual care – suggests that inhaled budesonide reduced the relative risk of requiring urgent care or hospitalisation by 90% in the 28-day study period. Participants allocated the budesonide inhaler also had a quicker resolution of fever, symptoms and fewer persistent symptoms after 28 days.
Professor Mona Bafadhel of the University’s Nuffield Department of Medicine, who led the trial, said: "There have been important breakthroughs in hospitalised COVID-19 patients, but equally important is treating early disease to prevent clinical deterioration and the need for urgent care and hospitalisation, especially to the billions of people worldwide who have limited access to hospital care.
“The vaccine programmes are really exciting, but we know that these will take some time to reach everyone across the world. I am heartened that a relatively safe, widely available and well-studied medicine such as an inhaled steroid could have an impact on the pressures we are experiencing during the pandemic.”
The study also demonstrated that there was a reduction in persistent symptoms in those who received budesonide.
Bafadhel, a respiratory consultant also working at the Oxford University Hospitals NHS Foundation Trust, said: “Although not the primary outcome of study, this is an important finding. I am encouraged to see the reduction in persistent symptoms at 14 and 28 days after treatment with budesonide. Persistent symptoms after the initial COVID-19 illness have emerged as a long-term problem. Any intervention which could address this would be a major step forward.”
The trial was inspired by the fact that, in the early days of the pandemic, patients with chronic respiratory disease, who are often prescribed inhaled steroids, were significantly under-represented among those admitted to hospital with COVID-19.
As well as the Oxford BRC, the STOIC trial was supported by AstraZeneca.
Inhaled budesonide in the treatment of early COVID-19 illness: a randomised controlled trial
Sanjay Ramakrishnan, Dann V Nicolau Jr, Beverly Langford, Mahdi Mahdi, Helen Jeffers, Christine Mwasuku, Karolina Krassowska, Robin Fox, Ian Binnian, Victoria Glover, Stephen Bright, Christopher Butler, Jennifer L Cane, Andreas Halner, Philippa C Matthews, Louise E Donnelly, Jodie L Simpson, Jonathan R Baker, Nabil T Fadai, Stefan Peterson, Thomas Bengtsson, Peter J Barnes, Richard EK Russell, Mona Bafadhel
Published in medRxiv on 4 February 2021
Multiple early hospital cohorts of coronavirus disease 2019 (COVID-19) showed that patients with chronic respiratory disease were significantly under-represented. We hypothesised that the widespread use of inhaled glucocorticoids was responsible for this finding and tested if inhaled glucorticoids would be an effective treatment for early COVID-19 illness.
We conducted a randomised, open label trial of inhaled budesonide, compared to usual care, in adults within 7 days of the onset of mild Covid-19 symptoms. The primary end point was COVID-19-related urgent care visit, emergency department assessment or hospitalisation. The trial was stopped early after independent statistical review concluded that study outcome would not change with further participant enrolment.
146 patients underwent randomisation. For the per protocol population (n=139), the primary outcome occurred in 10 participants and 1 participant in the usual care and budesonide arms respectively (difference in proportion 0.131, p=0.004). The number needed to treat with inhaled budesonide to reduce COVID-19 deterioration was 8. Clinical recovery was 1 day shorter in the budesonide arm compared to the usual care arm (median of 7 days versus 8 days respectively, logrank test p=0.007). Proportion of days with a fever and proportion of participants with at least 1 day of fever was lower in the budesonide arm. Fewer participants randomised to budesonide had persistent symptoms at day 14 and day 28 compared to participants receiving usual care.
Early administration of inhaled budesonide reduced the likelihood of needing urgent medical care and reduced time to recovery following early COVID-19 infection.
(Funded by Oxford NIHR Biomedical Research Centre and AstraZeneca
Bafadhel said: “Although this is a small study, it is encouraging to know that there are at least five other studies being done across the world that are also looking at different classes of inhaled corticosteroids.”
The Guardian reports that one of these, the Principle trial, which is also being led by Oxford researchers, is evaluating budesonide as a treatment for older adults with early COVID-19 symptoms, including those with underlying health conditions.
Bafadhel added: “The vaccines are obviously very exciting, but at the moment there isn’t any drug that treats you when you are poorly, to stop you getting worse. I am heartened that a relatively safe, widely available and well-studied medicine such as an inhaled steroid could have an impact on the pressures we are experiencing during the pandemic.”
Dr James Dodd, a consultant senior lecturer in respiratory medicine at North Bristol Lung Centre and the University of Bristol, said: “If that level of efficacy is reproduced in a larger study, including older age groups with other comorbidities, you really have got potentially a very exciting, cheap, safe, widely available treatment for patients in the community who have just been diagnosed with COVID-19.
“Within a short period of time we could potentially have the first community-based treatment – one which would also presumably be less vulnerable to the virus acquiring new mutations than the vaccines.”
University of Oxford material
medRxiv study (Restricted access)
Full report in The Guardian (Open access)
See also from the MedicalBrief archives:
Budesonide/formerol trial for mild asthma in SA et al