ASTRO: Adjuvant STeroid Outcomes in idiopathic subglottic stenosis: A randomized trial

PROJECT SUMMARY/ABSTRACT Idiopathic subglottic stenosis (iSGS) is a debilitating and life-threatening disease where scar tissue narrows the airway, severely limiting an individual’s ability to breathe and communicate. The cause is not completely delineated but appears related to the activation of a pro-inflammatory cascade. Treatment is procedural with the goal of increasing airway diameter to improve breathing. The most commonly employed treatment approach is intermittent endoscopic dilation, typically performed every 12-18 months. Adjunctive methods to prolong the period between operations are highly desirable to the iSGS patient community. One promising potential adjunctive method is serial intralesional steroid injections (SILSI), or serial injection of steroids into the affected airway in the clinic setting. While initial single-institution retrospective series showed potential for prolongation of the inter-operative interval, secondary analysis of a multi-institutional prospective cohort study did not show a clear benefit. Given disparate results and the importance of developing effective adjunctive methods, a prospective randomized trial is critical to evaluate the effectiveness and determine which iSGS patients may benefit most from this adjunctive treatment. CCC MPIs, Drs. Alexander Hillel and Alexander Gelbard, along with DCC MPIs, Drs. Dan Hanley and Gayane Yenokyan, will lead a multicenter, prospective, randomized, double- blinded, placebo-controlled trial titled, ASTRO: Adjuvant STeRoid injection Outcomes in idiopathic subglottic stenosis. This trial was developed in partnership with both patient and clinician stakeholders and is designed to evaluate the safety and efficacy of SILSI in iSGS patients. 226 iSGS participants will be recruited across 10 high- volume academic sites and randomized to SILSI or placebo (intralipid preparation simulating appearance of triamcinolone) in a 1:1 ratio following a standardized endoscopic dilation. Participants will undergo a series of three injections, spaced one month apart and beginning one month after endoscopic dilation. Our primary outcome measure is percent peak expiratory flow, which is a biomarker of disease recurrence in iSGS. The study aims are to: (1) Compare change in peak expiratory flow in iSGS patients with and without adjuvant SILSI from 1 month to 6 months after endoscopic dilation (primary endpoint) and 1 month to 12 months after dilation (secondary endpoint); (2) Compare secondary outcomes in iSGS patients with and without adjuvant SILSI including patient-reported outcome measures of breathing, QoL, voice, and swallow function as well as toxicity profile and safety events, including return to the operating room for a recurrent procedure and death; and (3) Characterize heterogeneity in SILSI treatment response based on demographic, clinical, surgeon, and genomic characteristics as assessed using established single nucleotide polymorphisms (SNPs) proven to dictate steroid responsiveness in patients with asthma. This represents the first interventional trial in iSGS and fills a critical knowledge gap by assessing the efficacy and safety of SILSI for iSGS, providing an evidence-based foundation to change clinical practice.