Study of Mitomycin-C Application in Laryngotracheal Stenosis

Study Overview
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Brief Summary
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This is a randomized, prospective, double-blind, placebo-controlled clinical trial of the use of mitomycin-C topical application as an adjunctive treatment in the endoscopic surgical treatment of patients with laryngotracheal stenosis. We hypothesize that the use of mitomycin-C improves patient outcome in the endoscopic surgical treatment of laryngotracheal stenosis.

Detailed Description
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Obstruction of the upper airway caused by laryngotracheal stenosis (LTS) often results in severe morbidity and even mortality. Treatment of LTS continues to present a challenge and a wide array of surgical techniques have been employed. Despite multiple endoscopic and/or open reconstructive procedures, patients often experience restenosis as a result of the abnormal wound-healing process that initially instigated the airway obstruction. The high rate of stenosis relapse has therefore motivated researchers to find new methods to modulate and control the wound-healing process of the airway. Although other adjuvant treatments such as steroids and antibiotics have been investigated in LTS, much attention in recent years has turned to the use of topical mitomycin-C (MMC). As a topical application, MMC has been shown to inhibit fibroblast proliferation in wound-healing processes. The use of MMC in the treatment of airway stenosis was first reported in 1998 and is now routinely used in the endoscopic management of LTS. However, despite numerous animal and human studies, the benefit of MMC in LTS patients remains questionable. While previously published retrospective data suggest that the addition of MMC improves outcome, there have been no prospective studies to directly address the efficacy of MMC in endoscopic LTS surgery. This study will be the first randomized, prospective, double-blind, placebo controlled clinical trial designed to investigate the efficacy of MMC as an adjunctive therapy to endoscopic surgical treatment in patients with LTS. In addition, the study will investigate the relationship between patient symptoms and objective pulmonary function measurements. Ultimately, the results of this study may influence the treatment and evaluation of patients with laryngotracheal stenosis.

Official Title
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A Randomized Study of Mitomycin-C Application in the Endoscopic Surgical Treatment of Patients With Laryngotracheal Stenosis

Conditions
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Laryngeal Stenosis, Subglottic Stenosis, Tracheal Stenosis

Intervention / Treatment
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* Drug: Mitomycin -C
* Other: Saline application


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with laryngotracheal stenosis, including subglottic stenosis or tracheal stenosis Patients with disease amenable to treatment with endoscopic CO2 laser radial incisions and balloon dilation Age greater than or equal to 18 years Exclusion Criteria: Age less than 18 years Pregnancy Patients with glottic and supraglottic stenosis Patients with disease not amenable to treatment with endoscopic CO2 laser radial incisions and balloon dilation Patients with cartilaginous subglottic or tracheal stenosis

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mitomycin-C<br>Patients will undergo standard endoscopic surgical treatment for LTS involving CO2 laser radial incisions and balloon dilation, as well as topical application of MMC in the radial incisions. | Drug: Mitomycin -C<br>* Topical mitomycin-C at a dosage of 0.4mg/ml will be applied to cottonoid pledgets and placed into the radial incisions for 3 minutes.<br>|
| Placebo Comparator: Saline<br>Patients will undergo standard endoscopic surgical treatment for LTS involving CO2 laser radial incisions and balloon dilation, as well as topical application of isotonic saline in the radial incisions. | Other: Saline application<br>* Isotonic saline will be applied to cottonoid pledgets and placed into the patient's radial incisions for 3 minutes as the placebo intervention.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Repeat Surgery | Length of time between surgeries for laryngotracheal stenosis during the study | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Symptom Improvement | Symptom improvement was measured using the Clinical COPD Questionnaire, a 10-point patient reported symptom score. Duration of symptom improvement was defined as the time from surgery to the time that symptoms to worsened beyond a CCQ score of 1 or the time to the subsequent surgery if CCQ never exceeded 1 | 24 months | 
| Peak Inspiratory Flow Measurement | Change in maximum inspiratory air flow from preoperative value to highest postoperative value within 3 months of surgery. Calculation details: Highest postoperative value within 3 months of surgery minus preoperative value. | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mitomycin-C, laryngotracheal stenosis, subglottic stenosis, tracheal stenosis, endoscopic airway surgery