When administered in early COVID-19, the inhaled glucocorticoid budesonide may reduce the necessity for urgent medical care and may reduce the time to recovery, according to study results published in The Lancet Respiratory Medicine.
Results from previous studies, conducted in vitro, suggest that the replication of SARS-CoV-2 is reduced in airway epithelial cells with inhaled glucocorticoid use. Additionally, inhaled glucocorticoids may lead to the downregulation of angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) expression, both of which are essential for viral entry.
Researchers conducted a phase 2, open-label, parallel-group, randomized controlled trial (Steroids in COVID-19 [STOIC]; ClinicalTrials.gov Identifier: NCT04416399) to determine the efficacy of inhaled budesonide in adults with early COVID-19 and whether its use would affect the likelihood of urgent care or hospitalization, clinical recovery, and physiologic parameters such as temperature or oxygenation. The investigators also assessed the effects of inhaled budesonide on the SARS-CoV-2 viral load.
Of the 167 patients who were assessed for eligibility, 146 participants were included in the intention-to-treat analysis (budesonide, n=73; usual care, n=73) and 139 patients had available data for per protocol analyses (budesonide, n=70; usual care, n=69 patients). The dose for budesonide was 400 μg per actuation. Participants were asked to take 2 inhalations twice a day until symptoms resolved.
The primary outcome of the study was COVID-19-linked urgent care visit. Secondary outcomes included self-reported clinical recovery, viral symptoms according to the Common Cold Questionnaire (CCQ) and the InFLUenza Patient Reported Outcome Questionnaire (FLUPro), body temperature, blood oxygen saturation, and SARS-CoV-2 viral load.
The majority of patients in the budesonide and usual care groups were women (56% and 59%, respectively), were White (93% in both groups), and presented with cough, fever, and headache at baseline. At randomization, the median lowest oxygen saturations recorded for both groups was 96% and the mean SARS-CoV-2 viral cycle thresholds to the budesonide and usual care groups were 32.6 and 31.8, respectively.
COVID-19-related urgent care visits were reported in 14% and 1% of patients in the usual care and budesonide groups, respectively, in the per-protocol population (P =.004), and in 15% and 3% of patients in the usual care and budesonide groups, respectively, in the intention-to-treat population (P =.009). Results suggested that the number needed to treat with inhaled budesonide to reduce the need for COVID-19-related urgent care or hospitalization was 8.
In the per-protocol population, self-reporter clinical recovery was 1 day earlier in the budesonide cohort compared with the usual care cohort (P =.007). The mean times to recovery with budesonide and usual care were 8 days and 12 days, respectively. Compared with usual care, inhaled budesonide was association with a lower proportion of days with fever in the first 14 days of the analysis (Wilcoxon test P =.051), and fewer persistent symptoms at days 14 and 28 (P =.003). As-needed antipyretic medication was also not required as frequently with budesonide compared with usual care (P =.025).
Results of the Common Cold Questionnaire and the FLUPro Questionnaire more than 14 days was significantly better in patients treated with inhaled budesonide compared with usual care (Common Cold Questionnaire, P =.016; FLUPro, P =.044). Both blood oxygen saturations and SARS-CoV-2 viral loads with not significantly vary between the 2 cohorts.
Following independent statistical review, it was noted that the study outcomes would not change with additional participant enrollment; therefore, the investigation was stopped early.
“Our findings require urgent validation and dissemination, especially in the setting of a treatment given early that is widely available and relatively safe,” the investigators concluded.
Disclosure: This research was funded by AstraZeneca. Please see the original reference for a full list of authors’ disclosures.
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. Lancet Respir Med. Published online April 9, 2021. doi:10.1016/S2213-2600(21)00160-0