Table 2.

Inhaled corticosteroids

Clinical Trial Name	Study Type	Study Population	Interventions	Outcomes	Limitations	Conclusion
PRINCIPLE55	Open-label RCT	Nonhospitalized COVID-19 patients with ≤ 14 days of symptoms and age ≥ 65 or ≥ 50 with comorbidities	1:1 random assignment of usual standard of care (SOC) alone (n = 787) or standard of care plus budesonide 800 mcg inhaled twice daily for 14 days (n = 1069)	Patients who were hospitalized or died due to COVID-19 within 28 days: 6.8% in budesonide arm vs 8.8% in usual care arm (OR 0.75; 95% CrI, 0.55–1.03) Median time to reported recovery: 11.8 days in budesonide arm vs 14.7 days in usual care arm (HR 1.21; 95% CrI, 1.08–1.36)	Open-label Relied on patient’s self-report for time to recovery	Inhaled budesonide reduced time to patient’s self-reported recovery, but not COVID-19-reported hospitalization or death.
STOIC56	Open-label phase 2 RCT	Nonhospitalized COVID-19 patients with ≤ 7 days of symptoms and age ≥ 18	1:1 random assignment of usual standard of care (SOC) alone (n = 73) or standard of care plus budesonide 800 mcg inhaled twice daily until symptom resolution (n = 73)	Median duration of budesonide use: 7 days Percentage of patients with COVID-19-related urgent care visit or hospitalization: 1% in budesonide arm versus 14% in usual care arm (relative risk reduction 91%).	Open-label Small sample size	Inhaled budesonide may reduce the need for urgent care or ED assessment and/or hospitalization in adult outpatients with mild COVID-19.
Clemency et al.57	Double-blind randomized controlled trial	Nonhospitalized COVID-19 patients with a positive test in the last 72 h age ≥ 12 with ≥ 1 symptom of fever, cough, or dyspnea	1:1 random assignment of placebo meter dose inhaler (MDI) (n = 203) or ciclesonide MDI 160 μg/actuation, 2 actuations twice a day for 30 days (n = 197)	Median time to alleviation of all COVID-19-related symptoms: 19 days in ciclesonide arm vs 19 days in placebo arm (HR 1.08; 95% CI, 0.84–1.38) By Day 30: Alleviation of COVID-19-related symptoms: 70.6% in ciclesonide arm vs 63.5% in placebo arm Subsequent ED visit or hospital admission for COVID-19: 1% in ciclesonide arm vs 5.4% in placebo arm (OR 0.18; 95% CI, 0.04–0.85) Hospital admission or death: 1.5% in ciclesonide arm vs 3.4% in placebo arm (OR 0.45; 95% CI, 0.11–1.84) No deaths seen at 30 days in either group	Relied on patient’s self-report for alleviation of all symptoms Small sample size particularly for ED/hospitalization outcome	Inhaled ciclesonide did not reduce time to reported recovery; however, there was decrease in ED visits and hospitalization in the small sample size of events.
Contain58	Double-blind randomized controlled trial	Nonhospitalized COVID-19 patients age ≥ 18 with ≥ 1 symptom of fever, cough, or dyspnea and symptoms for ≤ 6 days	1:1 random assignment of saline placebo MDI and intranasal saline twice daily for 14 days (n = 98) or ciclesonide MDI 600 μg/actuation and intranasal ciclesonide 100 μg twice a day for 14 days (n = 105)	Percentage of patients with resolution of fever and all respiratory symptoms at Day 7: 40% in ciclesonide arm vs 35% in the placebo arm (adjusted risk difference 5.5%; 95% CI, −7.8% to 18.8%) Percentage of patients with resolution of fever and all respiratory symptoms at Day 14: 66% in ciclesonide arm vs 58% in placebo arm (adjusted risk difference 7.5%; 95% CI, −5.9% to 20.8%) Percentage of patients who were admitted to the hospital by Day 14: 6% in ciclesonide arm vs 3% in placebo arm (adjusted risk difference 2.3%; 95% CI, −3.0% to 7.6%)	Small sample size	Inhaled plus intranasal ciclesonide did not improve resolution of fever and respiratory symptoms in young healthy nonhospitalized patients with COVID-19