Inhaled ciclesonide did not shorten duration of mild to moderate symptoms of COVID-19 in outpatients, but lessened hospitalizations.
Inhaled ciclesonide did not shorten duration of mild to moderate symptoms of COVID-19 in outpatients, but appeared to reduce risk of hospitalization, in a double-blind, placebo-controlled trial.
Brian Clemency, DO, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York and colleagues found the median time to alleviation of all COVID-19-related symptoms (the primary endpoint of the trial) was 19 days with active drug or placebo.
Those receiving the active ciclesonide, however, had fewer subsequent emergency department visits of hospitalizations related to COVID-19, a secondary endpoint (odds ratio, 0.18; 95% CI, 0.04-0.85).
Acknowledging that secondary measures are considered exploratory, Clemency and colleagues nevertheless observed, "this outcome may be more relevant to the patients and health care systems than complete resolution of symptoms. Inhaled steroids may represent a relatively low-cost intervention to prevent emergency department visits or hospital admissions due to COVID-19," they explained.
The rationale for the trial was based partly on the success of systemic administration of the corticosteroid, dexamethasone, in severe COVID-19 illness; and their interest in providing benefit for less severely affected populations.In addition, the investigators noted that ciclesonide has been associated with several potentially helpful effects distinct from the benefit of corticosteroids for various respiratory diseases, including inhibiting the PAKI enzyme—a pathogenic pathway for SARS-CoV-2 associated with the angiotensin-converting enzyme 2.
The alleviation of symptoms was chosen as the primary endpoint of the trial rather than reduction of hospitalization after preliminary data demonstrated substantially lower than expected rates of emergency department visits or hospitalizations among study participants.
The randomized, placebo-controlled double blind trial enrolled 400 participants from outpatients at multiple sites with confirmed COVID-19 and related mild to moderate symptoms and without initial requirement for hospitalization. Symptoms included cough, dyspnea, chills, feeling feverish, repeated shaking with chills, muscle pain, headache, sore throat, and new loss of taste or smell.
Participants were randomized to self-administer a ciclesonide metered-dose inhaler (MDI) (n=197),2 actuations twice daily (640mcg total daily dose) or an identical appearing placebo MDI (n=203) for 30 days.The dosing corresponded to the highest approved by the FDA for maintenance treatment of asthma.
The participants were instructed on self-administration of the MDI, provided with a 30 day supply as well as a pulse oximeter for at-home oxygen saturation level monitoring. They also received an electronic diary smart-phone application with "push reminders" to report and rate symptoms on a subjective 4-point scale within 1 hour of each self-administered dosage. Clinicians contacted participants approximately every 2 days for the first 2 weeks, and on day 21; and conducted a study visit on or around day 30 to ascertain health status and elicit report of any adverse events.
In addition to finding that all symptoms were alleviated by median 19 days with either active or placebo treatment, the investigators found no difference between groups in the time to alleviation of any individual symptom, including cough, dyspnea, loss of taste or smell. They also found that participants with at least 1 moderate or severe symptom of cough, dyspnea, chills or feeling feverish had a similar time to alleviation as those with only mild symptoms.
Clemency and colleagues suggest that there could have been different results if the study had focused on patients with severe symptoms, or with high risk for disease progression.
"Further studies of the efficacy of inhaled steroids among populations of pediatric patients, geriatric patients and patients with known risk factors are needed to explore the efficacy of inhaled steroids among patients at higher risk for severe disease progression, hospitalization, and death of COVID-19," the investigators declared.