Treatment options in idiopathic subglottic stenosis: protocol for a prospective international multicentre pragmatic trial

Abstract

Introduction: Idiopathic subglottic stenosis (iSGS) is an unexplained progressive obstruction of the upper airway that occurs almost exclusively in adult, Caucasian women. The disease is characterised by mucosal inflammation and localised fibrosis resulting in life-threatening blockage of the upper airway. Because of high recurrence rates, patients with iSGS will frequently require multiple procedures following their initial diagnosis. Both the disease and its therapies profoundly affect patients' ability to breathe, communicate and swallow. A variety of treatments have been advanced to manage this condition. However, comparative data on effectiveness and side effects of the unique approaches have never been systematically evaluated. This study will create an international, multi-institutional prospective cohort of patients with iSGS. It will compare three surgical approaches to determine how well the most commonly used treatments in iSGS 'work' and what quality of life (QOL) trade-offs are associated with each approach.

Methods and analysis: A prospective pragmatic trial comparing the 'Standard of Care' for iSGS at multiple international institutions. Patients with a diagnosis of iSGS without clinical or laboratory evidence of vasculitis or a history of endotracheal intubation 2 years prior to symptom onset will be included in the study. Prospective evaluation of disease recurrence requiring operative intervention, validated patient-reported outcome (PRO) measures as well as patient-generated health data (mobile peak flow recordings and daily steps taken) will be longitudinally tracked for 36 months. The primary endpoint is treatment effectiveness defined as time to recurrent operative procedure. Secondary endpoints relate to treatment side effects and include PRO measures in voice, swallowing, breathing and global QOL as well as patient-generated health data.

Ethics and dissemination: This protocol was approved by the local IRB Committee of the Vanderbilt University Medical Center in July 2015. The findings of the trial will be disseminated through peer-reviewed journals, national and international conference presentations and directly to patient with iSGS via social media-based support groups.

Trial registration number: NCT02481817.

Keywords: NoAAC; PR02; iSGS; pragmatic trial; subglottic stenosis.

Figure 1

Diagram of normal trachea (A). Healthy trachea (B). Patient with iSGS with obstructive tracheal scar (C). iSGS, idiopathic subglottic stenosis.

Figure 2

Treatment approaches for iSGS: (A) endoscopic dilation of the tracheal stenosis (accomplished with rigid instruments or inflatable balloons; (B) endoscopic resection of the stenosis (with prolonged medical therapy after surgery; (C) open surgery with resection of the affected tracheal segment with end-to-end anastomosis. iSGS, idiopathic subglottic stenosis.

Figure 3

Kaplan-Meier analysis of NoAAC RP01 study results. Percentage of patients with iSGS avoiding disease recurrence, stratified by treatment type. iSGS, idiopathic subglottic stenosis; NoAAC RP01, North American Airway Collaborative RP-01.

Figure 4

NoAAC PR02 time schedule of enrolment, interventions and assessments and visits for participants. NoAAC PR02, North American Airway Collaborative PR-02; PFT, pulmonary function test.

Figure 5

Schematic overview of NoAAC PR02 trial workflow. Data collection for the proposed clinical cohort study will include the CRFs, implemented in an EDC system. CRFs, case report forms; EDC, electronic data capture; NoAAC PR02, North American Airway Collaborative PR-02; PROs, patient-reported outcomes.

Figure 6

Handheld peak-flow metre (A) along with mobile device software (B) for tracking patient-generated health data (C).