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

Abstract

<h3>Introduction</h3> 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. <h3>Methods</h3> 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). <h3>Results</h3> 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. <h3>Conclusion</h3> 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.