Inhaled budesonide (Pulmicort), a steroid generally used to treat asthma, dramatically reduced the need for hospitalization in COVID-19 patients within a week of symptom onset, a small randomized trial in the U.K. found.
Among 139 patients with mild COVID-19 symptoms, 10 in the control group required either a COVID-19-related urgent care or emergency department (ED) visit or hospitalization compared to one in the intervention group by day 28 of follow-up, reported Mona Bafadhel, PhD, of the University of Oxford in England, and colleagues.
This resulted in a number needed to treat of eight to prevent COVID-19 deterioration in one patient, they reported in a medRxiv preprint that had not undergone peer review.
Bafadhel and colleagues said they stopped the trial early when it was determined further enrollment would not change the study outcome.
“There have been important breakthroughs in [hospitalized] COVID-19 patients, but equally important is treating early disease to prevent clinical deterioration … especially to the billions of people worldwide who have limited access to hospital care,” Bafadhel said in a statement. “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 authors noted the underrepresentation of patients with asthma and chronic obstructive pulmonary disease (COPD) among patients hospitalized with COVID-19 in early data, and hypothesized it could be due to “the widespread use of inhaled glucocorticoids” in this population. They added the main reason these patients might be prescribed inhaled glucocorticoids is to reduce exacerbations often recognized to be “viral in etiology.”
The Steroids in COVID-19 (STOIC) trial was an open-label phase II study examining adults with symptoms suggestive of COVID-19 within 7 days. They were randomized to usual care or budesonide dry powder inhaler twice a day, and seen by a respiratory research nurse on day 0, day 7, and day 14 to perform PCR testing for SARS-CoV-2. Patients filled out a symptom diary, took daily readings at home with a pulse oximeter and thermometer, and recorded adverse events.
Those allocated to the intervention group were instructed to stop using the inhaler when they felt better, and all participants were seen on day 28 for serum antibody testing for SARS-CoV-2. Primary outcome was a COVID-related urgent care or ED visit or hospitalization.
From July to December 2020, 146 participants were randomized 1:1 to the intervention or control arm in a per protocol analysis. Median duration of symptoms prior to randomization was 3 days, and median time to symptom resolution was 8 days. Inhalers were used for a median of 7 days.
The primary outcome occurred in 10 participants in the control arm and one in the intervention arm, for a relative risk reduction of 90%, though for the intention-to-treat population, it was 11 in the control arm and two in the intervention arm.
Examining secondary outcomes, self-reported clinical recovery occurred one day sooner with the intervention than in the control group (median 7 days vs 8 days, respectively). Self-reported symptoms persisted at day 14 in seven patients in the intervention group versus 21 patients in the control group.
The mean proportion of days with fever during the first 14 days was lower in the intervention group, and fewer participants in the intervention group had at least 1 day of fever.
“In high income countries, inhaled budesonide could work as an adjunct to reduce pressure on health care systems until widespread SARS-CoV-2 vaccination can be achieved,” Bafadhel and colleagues wrote, noting the efficacy is also unlikely to be affected by any emergent SARS-CoV-2 variant.
Limitations to the data include its open-label nature and that it was stopped early, with statistical power calculations from the best available predictions in early 2020. However, the researchers added that “in trial design for a new disease, with no known effective treatment, statistical assumptions are thus arbitrary.”
The study was funded by the Oxford NIHR Biomedical Research Centre and AstraZeneca.