Inhaled Fluticasone Furoate for Outpatient Treatment of Covid-19

Abstract

Background: The effectiveness of inhaled glucocorticoids in shortening the time to symptom resolution or preventing hospitalization or death among outpatients with mild-to-moderate coronavirus disease 2019 (Covid-19) is unclear.

Methods: We conducted a decentralized, double-blind, randomized, placebo-controlled platform trial in the United States to assess the use of repurposed medications in outpatients with confirmed coronavirus disease 2019 (Covid-19). Nonhospitalized adults 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 were randomly assigned to receive inhaled fluticasone furoate at a dose of 200 μg once daily for 14 days or placebo. The primary outcome was the time to sustained recovery, defined as the third of 3 consecutive days without symptoms. Key secondary outcomes included 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.

Results: Of the 1407 enrolled participants who underwent randomization, 715 were assigned to receive inhaled fluticasone furoate and 692 to receive placebo, and 656 and 621, respectively, 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). 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.

Conclusions: Treatment with inhaled fluticasone furoate for 14 days did not result in a shorter time to recovery than placebo among outpatients with Covid-19 in the United States. (Funded by the National Center for Advancing Translational Sciences and others; ACTIV-6 ClinicalTrials.gov number, NCT04885530.).

Figure 1. Randomization and Follow-up of the Patients.

Figure 2. Times to Sustained Recovery with Inhaled Fluticasone Furoate or Placebo.

Shown is the Kaplan–Meier curve for the primary outcome of time to recovery with pointwise 95% confidence intervals indicated with shading. Time to sustained recovery was defined as the number of days between the day of receipt of the trial drug or placebo and 3 consecutive days without Covid-19 symptoms, as affirmatively reported by the trial participants. Time-to-recovery data were administratively censored at 28 days. The posterior probability was 0.56 for a faster recovery with inhaled fluticasone furoate than with placebo. The posterior distribution of treatment effect is shown in Figure S2 in the Supplementary Appendix, sensitivity analyses for alternative methods of handling missing daily symptom data are shown in Figure S3, the Kaplan–Meier curve for stratification of matched and unmatched placebo groups is shown in Figure S7, and results of an unplanned analysis in which participants who received unmatched placebos appeared to recover faster than participants who received matched placebos are shown in Figure S4.

Figure 3. Heterogeneity of the Treatment Effect of Time to Recovery.

A hazard ratio greater than 1.0 indicates a faster time to recovery. Trial day 1 was the day receipt of trial medication or placebo began. Modified intention-to-treat data reflects an analysis of participants who underwent randomization and were enrolled within 7 days after symptom onset and received the trial drug or placebo. Shown are the covariate-adjusted and model-based estimates of the treatment effect for selected subgroups.