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Can the inhaled steroid ciclesonide reduce the time to alleviation of all COVID-19–related symptoms among nonhospitalized participants with symptomatic COVID-19 infection?
In this randomized clinical trial of 400 patients with symptomatic COVID-19, ciclesonide did not reduce the time to alleviation of all COVID-19–related symptoms. However, patients who were treated with ciclesonide had fewer subsequent emergency department visits or hospital admissions for reasons that were related to COVID-19.
The results of this randomized clinical trial suggest that future studies of inhaled steroids are needed to explore their efficacy in patients with a high risk for disease progression and in reducing the incidence of long-term COVID-19 symptoms or postacute sequelae of SARS-CoV-2.
Systemic corticosteroids are commonly used in treating severe COVID-19. However, the role of inhaled corticosteroids in the treatment of patients with mild to moderate disease is less clear.
To determine the efficacy of the inhaled steroid ciclesonide in reducing the time to alleviation of all COVID-19–related symptoms among nonhospitalized participants with symptomatic COVID-19 infection.
Design, Setting, and Participants
This phase 3, multicenter, double-blind, randomized clinical trial was conducted at 10 centers throughout the US and assessed the safety and efficacy of a ciclesonide metered-dose inhaler (MDI) for treating nonhospitalized participants with symptomatic COVID-19 infection who were screened from June 11, 2020, to November 3, 2020.
Participants were randomly assigned to receive ciclesonide MDI, 160 μg per actuation, for a total of 2 actuations twice a day (total daily dose, 640 μg) or placebo for 30 days.
Main Outcomes and Measures
The primary end point was time to alleviation of all COVID-19–related symptoms (cough, dyspnea, chills, feeling feverish, repeated shaking with chills, muscle pain, headache, sore throat, and new loss of taste or smell) by day 30. Secondary end points included subsequent emergency department visits or hospital admissions for reasons attributable to COVID-19.
A total of 413 participants were screened and 400 (96.9%) were enrolled and randomized (197 [49.3%] in the ciclesonide arm and 203 [50.7%] in the placebo arm; mean [SD] age, 43.3 [16.9] years; 221 [55.3%] female; 2 [0.5%] Asian, 47 [11.8%] Black or African American, 3 [0.8%] Native Hawaiian or other Pacific Islander, 345 [86.3%] White, and 1 multiracial individuals [0.3%]; 172 Hispanic or Latino individuals [43.0%]). The median time to alleviation of all COVID-19–related symptoms was 19.0 days (95% CI, 14.0-21.0) in the ciclesonide arm and 19.0 days (95% CI, 16.0-23.0) in the placebo arm. There was no difference in resolution of all symptoms by day 30 (odds ratio, 1.28; 95% CI, 0.84-1.97). Participants who were treated with ciclesonide had fewer subsequent emergency department visits or hospital admissions for reasons related to COVID-19 (odds ratio, 0.18; 95% CI, 0.04-0.85). No participants died during the study.
Conclusions and Relevance
The results of this randomized clinical trial demonstrated that ciclesonide did not achieve the primary efficacy end point of reduced time to alleviation of all COVID-19–related symptoms.
ClinicalTrials.gov Identifier: NCT04377711
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Accepted for Publication: October 3, 2021.
Published Online: November 22, 2021. doi:10.1001/jamainternmed.2021.6759
Corresponding Author: Brian M. Clemency, DO, Department of Emergency Medicine, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, 77 Goodell St, Ste 340, Buffalo, NY 14203 (email@example.com).
Author Contributions: Dr Clemency and Mr Koster had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: Varughese, Phipatanakul, Blaiss.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Clemency, Varughese, Gonzalez-Rojas, Phipatanakul.
Critical revision of the manuscript for important intellectual content: Clemency, Varughese, Morse, Phipatanakul, Koster, Blaiss.
Statistical analysis: Clemency, Gonzalez-Rojas, Koster.
Obtained funding: Clemency.
Administrative, technical, or material support: Clemency, Varughese, Morse, Phipatanakul.
Supervision: Clemency, Morse, Phipatanakul.
Conflict of Interest Disclosures: Dr Clemency reported grants from Covis Pharma, the National Center for Advancing Translational Sciences of the National Institutes of Health (NIH), and the National Heart, Lung, and Blood Institute of the NIH during the conduct of the study as well as grants from National Institute of Allergy and Infectious Diseases outside the submitted work. Dr Varughese reported grants from Covis Pharma during the conduct of the study. Dr Morse reported being a clinical trial investigator for Gilead Sciences Inc, Ridgeback Biotherapeutics, and Roche, grants from the COVID Prevention Network Site, and service as a subinvestigator at several COVID-19 trails ate Wake Forest University outside the submitted work. Dr Phipatanakul reported personal fees from OPhirex during the conduct of the study and personal fees from Genentech/Novartis, Regeneron/Sanofi, and Teva and grants from GSK and the NIH outside the submitted work. Dr Koster reported personal fees from Covis Pharma during the conduct of the study and outside the submitted work. Dr Blaiss reported personal fees from Covis Pharma during the conduct of the study and personal fees from Sanofi, Regeneron, Merck, and Pfizer outside the submitted work. No other disclosures were reported.
Funding/Support: The study was sponsored and funded by Covis Pharma GmbH. Research at the primary site was also supported by the National Center for Advancing Translational Sciences of the (NIH) (grant UL1TR001412; Drs Clemency and Varughese) and the National Heart, Lung, and Blood Institute of the NIH (grant K12HL138052; Dr Clemency).
Role of the Funder/Sponsor: Covis Pharma GmbH had a role in the design and conduct of the study. Covis Pharma GmbH approved the plan for, but did not participate in, the collection, management and analysis of the data. Covis Pharma GmbH approved the decision to submit the manuscript for publication. Changes to the primary end point were made by the study sponsor in consultation with the study steering committee and the US Food and Drug Administration. The NIH had no role in the study design, data collection, data analysis, or decision to publish.
Disclaimer: The views expressed are those of the authors and not necessarily those of Covis Pharma GmbH or the NIH.
Data Sharing Statement: See Supplement 3.
Additional Contributions: We thank Skyler Hime-Rupard, MS, and Yolaine Jeune-Smith, PhD, Cardinal Health Specialty Solutions, for providing medical writing support, which was funded by Covis Pharma GmbH.
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