Does inhaled budesonide (Pulmicort) safely reduce the likelihood of requiring emergency department consultation or hospitalization in patients with new-onset, symptomatic COVID-19?
Inhaled budesonide, 800 mcg twice daily, significantly reduces the likelihood that patients with early COVID-19 will require emergency department evaluation or hospitalization (number needed to treat [NNT] = 7 to 8). This is a widely available, relatively inexpensive drug with the potential for great benefit. There are seven other trials underway looking at inhaled budesonide or ciclesonide (Alvesco); the results are urgently awaited. (Level of Evidence = 1b−)
From previous randomized trials, we know that oral corticosteroids such as methylprednisolone are only helpful in more severely ill patients with COVID-19, and there was a trend toward worse outcomes in those with mild disease, perhaps by suppressing immune function systemically. Observational studies have shown an association between inhaled corticosteroids and better outcomes in patients with mild disease.
The researchers identified adults with less than seven days of cough, and either fever or anosmia or both (N = 146). They randomized the patients to receive budesonide using 400-mcg actuations, with two actuations twice daily, or usual care. A nurse did a swab for SARS-CoV-2, which was positive for 94% of patients. Groups were balanced at randomization. Four patients withdrew consent before receiving the allocated intervention, one in each group needed urgent care before they could be swabbed, and one withdrew because they found the inhaler too burdensome, leaving a per-protocol population of 139 patients. Patients in the budesonide group were told to stop using the inhaler when they had recovered (median = seven days), and all patients were followed up for 28 days.
It does not appear that outcomes were assessed in a masked manner, and the study was stopped early because of the large benefit. In the entire population, the primary outcome of urgent emergency department visits or hospitalization occurred less often in the budesonide group using an intention-to-treat analysis (3% vs. 15%; P = .009; NNT = 8). The magnitude of benefit was similar in the per-protocol population (1% vs. 14%; NNT = 7). Time to recovery was also approximately one day faster in the budesonide group, and symptom resolution was more rapid. Adverse events (sore throat [four patients] and dizziness [one patient]) were minor and self-limited. The open-label design, early trial shutdown, and failure to mask outcome assessment are limitations, but the magnitude of benefit was large enough that this treatment should be considered for all patients with mild symptoms of COVID-19.
Study design: Randomized controlled trial (single-blinded)
Funding source: Industry and government
Setting: Emergency department
Reference: Ramakrishnan S, Nicolau DV Jr., Langford B, et al. Inhaled budesonide in the treatment of early COVID-19 (STOIC): a phase 2, open-label, randomised controlled trial [published online April 9, 2021]. Lancet Respir Med. Accessed June 4, 2021. https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(21)00160-0/fulltext
Editor's Note: Dr. Ebell is deputy editor for evidence-based medicine for AFP and cofounder and editor-in-chief of Essential Evidence Plus, published by Wiley-Blackwell.