Inhaled budesonide (Pulmicort), commonly used in asthma, helped COVID-19 outpatients at extra risk for severe illness recover more quickly relative to standard care in the pragmatic PRINCIPLE trial, British researchers said.
In an updated analysis of interim data, through March 25, duration of illness was significantly shorter in the 751 patients assigned to budesonide — by 2.6 days (95% CI 1.0-4.7) — versus standard care, reported Christopher C. Butler, FMedSci, of the University of Oxford in England, and colleagues writing in a medRxiv preprint manuscript that had not been peer reviewed.
Median times to self-reported recovery were 10 days (interquartile range [IQR] 4-25 days) in the budesonide group compared with 13 days (IQR 4 days to no upper bound) among those receiving standard care (n=1,028) in the randomized open-label trial (probability of superiority 0.999).
Rates of hospitalization or death 28 days after treatment assignment were 7.6% with budesonide versus 9.8% for usual care (probability of superiority 0.954).
Some secondary outcomes, including rates of early sustained recovery and further healthcare encounters, also favored the steroid treatment. Others such as supplemental oxygen use or ICU admission occurred too infrequently to provide meaningful data.
In a press release, the investigators said recruitment for the budesonide arm stopped March 31 because “enough patients had been enrolled to establish whether or not the drug had any meaningful benefit on time to recovery.”
Joint chief investigator Richard Hobbs, FMedSci, also at Oxford, declared in the press release that the study demonstrates “budesonide is effective as a treatment at home and during the early stages of the illness.”
Underlying budesonide’s inclusion in PRINCIPLE was prior research indicating that inhaled corticosteroids generally reduce expression of cell-surface proteins, including ACE-2, that serve as entry portals for SARS-CoV-2. Additionally, it was observed early in the pandemic that, against expectations, people with asthma and chronic obstructive pulmonary disease seemed to be at lower risk for severe COVID, which led “to speculation that inhaled corticosteroids used to treat these conditions may be protective,” Butler’s group explained in the manuscript.
Budesonide is cheap and widely available, with extensive clinical experience and safety data, they noted.
In a preliminary study from February by the same group, with data on roughly 70 patients assigned to budesonide and a similar number to usual care, they reported a number needed to treat of eight to prevent COVID deterioration in one patient.
The budesonide arm in PRINCIPLE began November 27. About two-thirds of patients assigned to use the inhalers at home — along with usual care, which was not explicitly defined or characterized — were 65 or older, versus 59% with usual care only. About 80% in both groups reported some type of comorbidity.
The co-primary outcome of “duration of illness” was the time from randomization until the patient reported “feeling recovered.” The other co-primary endpoint was hospitalization or death at day 28 and thus was more objective.
Neither the manuscript nor the press release said anything about potential drug-related adverse effects, except that two patients receiving budesonide were hospitalized with conditions unrelated to COVID-19, with no further explanation.
Butler and colleagues promised to submit a full report for peer-reviewed publication when all patients in the study have completed follow-up; the current manuscript covers about 93% of them.