These findings, noted the authors, require urgent validation and dissemination, especially in the setting of a treatment given early that is widely available and relatively
APRIL 12, 2021
Phase II study shows positive results of inhaled budesonide in treatment of early COVID-19
Early administration of inhaled budesonide reduced the likelihood of needing urgent medical care and reduced time to recovery after early coronavirus disease 2019 (COVID-19) in adults, according to a study published in The Lancet Respiratory Medicine.
“To our knowledge, this is the first interventional trial to study the efficacy of inhaled corticosteroids in early COVID-19 illness,” wrote Sanjay Ramakrishnan, University of Oxford, Oxford, United Kingdom, and colleagues.
“In this open-label, parallel-group, phase 2, randomised controlled trial, inhaled budesonide, when given to adults with early COVID-19, reduced the likelihood of requiring urgent care, emergency department consultation, or hospitalisation,” the researchers reported. “There was also a quicker resolution of fever, a known poor prognostic marker in COVID-19, and self-reported and questionnaire-reported symptom resolution was faster. There were fewer participants with persistent COVID-19 symptoms at days 14 and 28 after budesonide therapy compared with usual care.”
In the study, 146 participants were randomly assigned to usual care (n = 73) and budesonide (n = 73), with a median duration of mild COVID-19 symptoms of 3 days (interquartile range [IQR] 2–4), from July 16 to December 9, 2020. Participants were asked to take two inhalations of budesonide dry powder at a dose of 800 μg per actuation, twice a day until symptom resolution. Budesonide was taken for a median duration of 7 days (IQR 4–10).
The primary endpoint was COVID-19-related urgent care visit, including emergency department assessment or hospitalisation. Meanwhile, the secondary outcomes were self-reported clinical recovery (symptom resolution), viral symptoms measured using the Common Cold Questionnaire (CCQ) and the InFLUenza Patient Reported Outcome Questionnaire (FLUPro), body temperature, blood oxygen saturations, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load.
The researchers reported that the primary outcome occurred in 11 (15%) of 73 participants in the usual care group compared to 2 (3%) of 73 participants in the budesonide group (difference in proportion 0.123, 95% confidence interval [CI] 0.033–0.213; P = 0.009) in the intention-to-treat analysis (n = 146). Meanwhile, in the per-protocol analysis (n = 136), the primary outcome occurred in 10 of 70 participants (14%) in the usual care group compared to 1 of 69 participant (1%) in the budesonide group (difference in proportions 0.131, 95% CI 0.043–0.218; P = 0.004), indicating a relative risk reduction of 91% for budesonide.
Additionally, clinical recovery was 1 day shorter in the budesonide group compared with the usual care group (median, 7 days [95% CI 6 to 9] vs 8 days [7 to 11]; log-rank test P = 0.007). Similarly, the mean proportion of days with a fever in the first 14 days was lower in the budesonide group than in the usual care group (2% vs 8%; Wilcoxon test P = 0.051) and the proportion of participants with at least 1 day of fever was lower in the budesonide group when compared with the usual care group.
Further, as-needed antipyretic medication was required for fewer proportions of days in the budesonide group compared with the usual care group (27% [IQR 0–50] vs 50% [15–71]; P = 0.025). Meanwhile, fewer participants randomly assigned to budesonide had persistent symptoms at days 14 and 28 compared with participants receiving usual care (difference in proportions 0.204, 95% CI 0.075 to 0.334; P = 0.003).
Moreover, the mean total score change in the CCQ and FLUPro over 14 days was significantly better in the budesonide group compared with the usual care group (CCQ mean difference −0.12, 95% CI −0.21 to −0.02, P = 0.016; FLUPro mean difference −0.10, 95% CI −0.21 to 0.00, P = 0.044). However, blood oxygen saturations and SARS-CoV-2 load, measured by cycle threshold, were not different between the groups. Further, the researchers united that the trial was stopped early after independent statistical review concluded that study outcome would not change with further participant enrolment.
“We have shown that the inhaled glucocorticoid budesonide, given for a short duration, might be an effective treatment of early COVID-19 in adults,” the authors wrote. “This effect, with a relative reduction of 91% of clinical deterioration is equivalent to the efficacy seen after the use of COVID-19 vaccines and greater than that reported in any treatments used in hospitalised patients and patients with severe COVID-19.”
“Our findings indicate that the primary outcome events were not mild events, despite occurring in participants with a mean age of 45 years with a spectrum of COVID-19 complications from deterioration of a premorbid condition (diabetic ketoacidosis), to the need for prolonged respiratory support,” the authors added.
These findings, noted the authors, require urgent validation and dissemination, especially in the setting of a treatment given early that is widely available and relatively safe. Reference: https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(21)00160-0/fulltextSOURCE: The Lancet Respiratory Medicine