Inhaled Glucocorticoids Don’t Show Clear Benefit in COVID-19 Outpatients

The use of fluticasone furoate did not result in a shorter time to recovery than placebo for non-hospitalized COVID-19 patients who received a dose of 200 μg once daily for 14 days. The inhaled glucocorticoid also didn’t prevent hospitalization or death among the outpatients, according to a new study. Here are more details.

DURHAM, NC — Inhaled glucocorticoids do not show effectiveness in shortening the time to symptom resolution or preventing hospitalization or death among outpatients with mild-to-moderate COVID-19, according to a recent study.

The report in the New England Journal of Medicine discusses the results of a decentralized, double-blind, randomized, placebo-controlled platform trial in the United States to assess the use of repurposed medications in outpatients with confirmed infection with SARS-CoV-2.

ACTIV-6 Study Group researchers based at Duke University Medical School randomly assigned a group of outpatients to receive inhaled fluticasone furoate at a dose of 200 μg once daily for 14 days or placebo. The nonhospitalized adults were 30 years of age or older who had at least two symptoms of acute infection that had been present for no more than 7 days before enrollment

Defined as the primary outcome was the time to sustained recovery, Hospitalization or death by day 28 and a composite outcome of the need for an urgent-care or emergency department visit or hospitalization or death through day 28 were listed as key secondary outcomes.

The authors advise that, of the 1,407 enrolled participants who underwent randomization, 715 were assigned to receive inhaled fluticasone furoate and 692 to receive placebo, and 656 and 621, respectively, and were included in the analysis.

“There was no evidence that the use of fluticasone furoate resulted in a shorter time to recovery than placebo (hazard ratio, 1.01; 95% credible interval, 0.91 to 1.12; posterior probability of benefit [defined as a hazard ratio >1], 0.56),” according to the researchers. “A total of 24 participants (3.7%) in the fluticasone furoate group had urgent-care or emergency department visits or were hospitalized, as compared with 13 participants (2.1%) in the placebo group (hazard ratio, 1.9; 95% credible interval, 0.8 to 3.5). Three participants in each group were hospitalized, and no deaths occurred. Adverse events were uncommon in both groups.”

The study team reports that treatment with inhaled fluticasone furoate for 14 days did not result in a shorter time to recovery than placebo among U.S. outpatients with COVID-19.

“As the coronavirus disease 2019 (Covid-19) pandemic continues, the need for early therapies to prevent progression to severe disease is ongoing,” the authors suggest. “New oral antiviral therapies are being used to an increasing degree in high-income countries, with a resulting benefit in unvaccinated persons. However, antivirals are unavailable in most low- and middle-income countries, and vaccination rates are variable. Thus, effective therapies are still needed for persons with symptomatic infection to hasten clinical recovery.”

They note that two open-label randomized trials “involving the use of inhaled budesonide at a dose of 800 μg twice daily for 14 days showed benefits for faster time to recovery and strong trends in decreased hospitalizations or deaths. Conversely, three randomized trials of inhaled ciclesonide (at a dose of 640 μg per day), two of which were double-blind trials, showed no change in symptom duration, and the analyses showed variable decreases — or possible increases — in the use of health care resources.”

The researchers further point out that the five trials of inhaled glucocorticoids were conducted among predominantly unvaccinated persons. Because of conflicting results, regulatory authorities and guideline committees did not recommend inhaled glucocorticoid therapy for use as an early treatment option in COVID-19.

The current study team sought to investigate inhaled fluticasone furoate in a double-blind, randomized, placebo-controlled platform trial to assess the use of repurposed drugs in non-hospitalized patients with milder symptoms. “Fluticasone propionate has approximately four times the relative systemic steroid potency of budesonide, and fluticasone furoate has greater receptor affinity than the propionate ester, allowing for once-daily dosing,” they write.

.”Although no deaths occurred and hospitalizations were rare and similar in both groups, the number of urgent-care and emergency department visits was higher in the fluticasone furoate group than in the placebo group,” the researchers note. “Overall, the lack of treatment effect and the possible increase in health care visits observed with inhaled fluticasone furoate as compared with placebo (3.2% vs. 1.6%) suggest that inhaled fluticasone furoate is not a favorable COVID-19 therapy.”

They raise the possibility that, because fluticasone and budesonide are different glucocorticoids, “there could be a budesonide-specific effect.” The researchers also point out that vaccinated participants in the previous inhaled glucocorticoids trials fared better.

“Our trial did not identify a clinically relevant effect associated with inhaled fluticasone furoate at a daily dose of 200 μg for 14 days as outpatient treatment for Covid-19 when delivered directly to the participant along with written instructions for use of the inhaler,” the study concludes. “We also did not observe a faster time to clinical recovery with fluticasone furoate as compared with placebo in the population studied, unlike results shown in previous open-label trials of inhaled steroids, nor did we observe an effect on prevention of clinical progression.”