Inhaled budesonide in the treatment of early COVID-19 (STOIC): a phase 2, open-label, randomised controlled trial

Abstract

Background Multiple early reports of patients admitted to hospital with COVID-19 showed that patients with chronic respiratory disease were significantly under-represented in these cohorts. We hypothesised that the widespread use of inhaled glucocorticoids among these patients was responsible for this finding, and tested if inhaled glucocorticoids would be an effective treatment for early COVID-19. Methods We performed an open-label, parallel-group, phase 2, randomised controlled trial (Steroids in COVID-19; STOIC) of inhaled budesonide, compared with usual care, in adults within 7 days of the onset of mild COVID-19 symptoms. The trial was done in the community in Oxfordshire, UK. Participants were randomly assigned to inhaled budsonide or usual care stratified for age (≤40 years or >40 years), sex (male or female), and number of comorbidities (≤1 and ≥2). Randomisation was done using random sequence generation in block randomisation in a 1:1 ratio. Budesonide dry powder was delivered using a turbohaler at a dose of 400 μg per actuation. Participants were asked to take two inhalations twice a day until symptom resolution. The primary endpoint was COVID-19-related urgent care visit, including emergency department assessment or hospitalisation, analysed for both the per-protocol and intention-to-treat (ITT) populations. The secondary outcomes were self-reported clinical recovery (symptom resolution), viral symptoms measured using the Common Cold Questionnare (CCQ) and the InFLUenza Patient Reported Outcome Questionnaire (FLUPro), body temperature, blood oxygen saturations, and SARS-CoV-2 viral load. The trial was stopped early after independent statistical review concluded that study outcome would not change with further participant enrolment. This trial is registered with ClinicalTrials.gov , NCT04416399 . Findings From July 16 to Dec 9, 2020, 167 participants were recruited and assessed for eligibility. 21 did not meet eligibility criteria and were excluded. 146 participants were randomly assigned—73 to usual care and 73 to budesonide. For the per-protocol population (n=139), the primary outcome occurred in ten (14%) of 70 participants in the usual care group and one (1%) of 69 participants in the budesonide group (difference in proportions 0·131, 95% CI 0·043 to 0·218; p=0·004). For the ITT population, the primary outcome occurred in 11 (15%) participants in the usual care group and two (3%) participants in the budesonide group (difference in proportions 0·123, 95% CI 0·033 to 0·213; p=0·009). The number needed to treat with inhaled budesonide to reduce COVID-19 deterioration was eight. Clinical recovery was 1 day shorter in the budesonide group compared with the usual care group (median 7 days [95% CI 6 to 9] in the budesonide group vs 8 days [7 to 11] in the usual care group; log-rank test p=0·007). The mean proportion of days with a fever in the first 14...

ProLung™-budesonideInhibits SARS-CoV-2 Replication and Reduces Lung Inflammation

“…Inhaled steroid, budesonide, has recently been shown to decrease respiratory symptoms. and possible progression to COVID-19 (6). Other studies have shown that inhaled steroids may decrease the ACE2 receptor, which may also be beneficial in decreasing SARS-CoV-2 binding (7).…”

“…Dexamethasone, a steroid, offers a significant benefit to decreasing inflammation with severe respiratory distress in COVID-19 (5). Inhaled steroids such as budesonide, are also showing a decrease in the respiratory symptoms with COVID-19 (6). Other studies have shown that inhaled steroids may decrease the ACE2 receptor, which may also be beneficial in decreasing the binding of SARS-CoV-2 virus (7).…”

The Fight against COVID-19 on the Multi-Protease Front and Surroundings: Could an Early Therapeutic Approach with Repositioning Drugs Prevent the Disease Severity?

“…The utility of corticosteroids emerged from the observation that patients with chronic respiratory disease, who make widespread use of inhaled glucocorticoids, were significantly underrepresented among those admitted to hospital with COVID-19 [135]. In a recent randomized controlled trial [136], the early administration (within seven days of the onset of mild symptoms) of inhaled budesonide, reduced the likelihood of needing urgent medical attention and reduced recovery time in adults after early COVID-19. An interesting observational matched-cohort study showed that early home treatment of 90 consecutive patients with mild COVID-19 by their family physicians according to a pathophysiologic and pharmacologic rationale almost completely prevented the need for hospital admission, due to progression toward more severe illness, compared to 90 age-, sex-, and comorbidities-matched patients who received other therapeutic treatments [67].…”

What we know and still ignore on COVID-19 immune pathogenesis and a proposal based on experience of allergic disorders.

“…Such explanation seems to be true also in asthmatic patients, controlled with inhaled corticosteroids (ICS), who display similar morbidity of infection of general population [36]. Indeed, budesonide (an ICS), largely employed in asthma, if administered at the initial phase of infection, has been recently shown to markedly reduce viral load and persistence, duration and severity of symptoms and timing of recovery in infected nonasthmatic patients [37]. Indeed, ICS are able to impair ACE2 expression on respiratory mucosa through the inhibition of type I IFN [38,39].…”