Compared with placebo, treatment with a combination of inhaled and intranasal ciclesonide was not associated with a significant decrease in respiratory symptoms among adults with COVID-19, according to results of a study published in BMJ.

The Inhaled Ciclesonide for the Treatment of COVID-19 in Nonhospitalized Adults (CONTAIN) trial was conducted in Canada. The researchers sought to evaluate the resolution of respiratory symptoms in adults with COVID-9. Patients who tested positive for SARS-CoV-2 infection at various health centers were recruited via phone or advertisements on social media. Patients were randomly assigned in a 1:1 fashion to receive either a combination of inhaled and intranasal ciclesonide (n=105) or placebo (n=98). On days 1, 3, 7, 10, 14, and 29, participants responded to surveys about their COVID-19 symptoms.

Among a total of 203 patients in both the ciclesonide and placebo groups, the median ages were 35 (IQR, 27-47) and 35 (IQR, 27-45) years, 51% and 56% were men, 62% and 59% were White, symptoms began 3 (IQR, 2-4) and 3 (IQR, 2-4) days prior to screening, 51% and 45% had “very good” self-reported health, and 82% and 78% had no comorbidities, respectively.

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The most frequently reported respiratory symptoms included cough, fatigue, myalgia, dyspnea, and sinus congestion.

At day 7, fever and respiratory symptoms resolved among 37% of the included patients. Of note, the proportion of patients whose symptoms resolved was not significantly different between the 2 groups (adjusted risk difference [aRD], 5.5%; 95% CI, -7.8 to 18.8). Further analysis showed that the proportion of patients with resolved symptoms at day 14 also was not significantly different between those in the ciclesonide vs placebo groups (66% vs 58%; aRD, 7.5%; 95% CI, -5.9 to 20.8).

Although no deaths were reported, hospitalization occurred among 6 and 3 patients in the ciclesonide and placebo groups, respectively.

Adverse events occurred more frequently among patients who received ciclesonide vs those who received placebo (22% vs 15%), with headache and nausea as the most frequently reported events.

This study was limited by its small sample size. In addition, the study was prematurely terminated due to the COVID-19 pandemic.

According to the researchers, treatment with ciclesonide “failed to show a statistically significant improvement in [respiratory] symptoms among [patients with COVID19].” They concluded that “open label studies should be avoided, and additional placebo controlled studies should examine the effect of different classes of inhaled corticosteroids.”

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.


Ezer N, Belga S, Daneman N, et al. Inhaled and intranasal ciclesonide for the treatment of covid-19 in adult outpatients: CONTAIN phase II randomised controlled trial. BMJ. 2021;375:e068060. doi:10.1136/bmj-2021-068060