RANDOMIZED, CONTROLLED TRIAL OF EXHALATION DELIVERY SYSTEM WITH FLUTICASONE FOR CHRONIC RHINOSINUSITIS WITHOUT NASAL POLYPS

Introduction: There are no FDA‐approved medications for the >20 million chronic rhinosinusitis patients without nasal polyps. The Exhalation Delivery System with Fluticasone (EDS‐FLU) is an intranasal steroid in a device that delivers drug to regions above the inferior turbinate and behind the nasal valve. Methods: In this phase 3, 24‐week, randomized, controlled trial evaluating EDS‐FLU versus EDS‐placebo twice daily in chronic sinusitis without polyps, co‐primary endpoints were combined symptom score (CSS; week 4) and average of percentages of CT‐opacified volume across ethmoid/maxillary sinuses (APOV; week 24). Other outcomes included Quality‐of‐Life (SNOT‐22, SF‐36), Sleep (PSQI), and Patient‐reported Global Impression of Change (PGIC). Results: Baseline scores suggest moderate‐severe disease: mean CSS=6.0; APOV=62.0%. Both EDS‐FLU doses [186µg (n=74) and 372µg (n=74)] significantly reduced both symptoms and sinus opacification versus EDS‐placebo (n=75): CSS least‐square (LS) mean change, EDS‐placebo, ‐0.81; EDS‐FLU 186µg, ‐1.54 (p<.05); EDS‐FLU 372µg, ‐1.74, (p<.001); APOV LS mean change +1.19, ‐7.00 (p<.001), ‐5.14 (p<.01), respectively. EDS‐FLU (n=145) vs EDS‐placebo (n=75) also significantly improved secondary measures at Week 24 including SNOT‐22 (LS mean ‐17.5 vs ‐8.7, p=.001); SF‐36v2 (LS Mean PCS 4.9 vs 1.8, p=.002); PSQI Global score (LS mean ‐1.54 vs ‐.33; p<.001); and PGIC (60% vs 25% much/very much improved; p<.001). Adverse events (≥3% of patients and >EDS‐placebo) were COVID‐19, epistaxis, headache, and depression. Conclusion: EDS‐FLU is the first and only drug to show improvement in a phase 3 trial in both symptoms and sinus opacification in chronic rhinosinusitis without nasal polyps.