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Inhaled fluticasone furoate failed to shorten recovery time for non-hospitalized adults with COVID-19, new data from the adaptive ACTIV-6 trial found.

When used daily for 2 weeks, a quicker COVID-19 recovery time -- considered at least 3 consecutive days without symptoms -- was no more likely with fluticasone furoate than with placebo (HR 1.01, 95% CI 0.91-1.12), according to Susanna Naggie, MD, MHS, of Duke University School of Medicine in Durham, North Carolina, and colleagues.

Yet a numerically higher rate of urgent care/emergency department visits and hospitalizations was observed in the fluticasone furoate group (3.7% vs 2.1%, respectively; HR 1.90, 95% CI 0.90-3.50), the researchers reported in the .

Combined, the lack of treatment effect and that possible increase in healthcare usage suggest that the inhaled glucocorticoid is "not a favorable" therapy for COVID-19, wrote Naggie and co-authors.

But the negative results didn't come as a shock to William Schaffner, MD, of Vanderbilt University in Nashville, Tennessee, who was not involved with the study.

"It was a very good idea and a nice try, but we have been trying to either treat or prevent COVID and other respiratory viruses by interrupting their capacity to multiply on the surface of the respiratory epithelium for a while, and we haven't figured it out yet," Schaffner told 番茄社区app.

Searching for a repurposed drug for COVID-19 is "a worthy goal, but a high-risk venture," Schaffner said. When one is found, its side-effect profile is likely to be well-understood and it could potentially be cheaper.

Thus far, inhaled glucocorticoids have demonstrated mixed efficacy in treating COVID outpatients, with some benefit for shortening recovery time seen with inhaled budesonide in the PRINCIPLE study, which enrolled a considerably older population than ACTIV-6 (mean age 65 vs 47 years).

While the dose of fluticasone furoate used in the current study is about four times more potent than the budesonide dose in PRINCIPLE (and has a longer half-life), they are "different glucocorticoids, and there could be a budesonide-specific effect," Naggie's group pointed out.

In light of a confirming the efficacy of nirmatrelvir/ritonavir (Paxlovid) and molnupiravir, Schaffner said those two oral medications are still the best option for high-risk outpatients with COVID-19.

"Older persons and people with underlying illnesses and those who are immune-compromised are still getting Paxlovid, and there is a general sense that this is helping keep people out of the hospital," he said.

ACTIV-6, part of the National Institutes of Health's ongoing decentralized trial, aims to test the effectiveness of repurposed drugs in reducing the duration and severity of symptoms associated with mild-to-moderate COVID-19. Prior results from ACTIV-6 specifically have shown no benefit with the antiparasitic ivermectin or the depression drug fluvoxamine versus placebo.

The current study included 1,277 patients, with roughly half assigned to the study drug or placebo. Patients entered the trial a mean of 5 days after symptom onset (but no more than 7 days) and had at least two infection symptoms. Some had already received therapeutics, including remdesivir (0.1%), a monoclonal antibody (2.4%), or nirmatrelvir/ritonavir (0.1%).

Median participant age was 45 years, more than 60% were women, with about 80% white, 7.1% Black, 5% Asian, and 12.6% Hispanic. Comorbid conditions included diabetes (9.7%), hypertension (26.1%), and asthma (13%).

Overall, the mean number of days unwell was 11.2 in the fluticasone furoate group and 11.3 in the placebo group. There were three hospitalizations and no deaths through day 28 in each group.

Investigators found no evidence of a positive treatment effect for fluticasone furoate by sex, timing of symptom onset, severity of symptoms, body mass index, age, or calendar period.

About two-thirds were fully vaccinated against COVID-19. Among these 846 subjects, a trend toward a faster recovery time was seen favoring the fluticasone furoate intervention (HR 1.10, 95% CI 0.95-1.28).

Incidence of adverse events was similar in the two groups, experienced by 2% of the fluticasone group and 2.5% of the placebo group. The most common was COVID-19 pneumonia, which occurred in three subjects on fluticasone and one on placebo.

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