Study of Mitomycin-C Application in Laryngotracheal Stenosis

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

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.

Study Overview

• Status: Terminated
• Conditions: Tracheal Stenosis; Laryngeal Stenosis; Subglottic Stenosis
• Intervention / Treatment: Drug: Mitomycin -C; Other: Saline application

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94115
      • UCSF - Voice and Swallowing Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mitomycin-C; 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; 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.
Placebo Comparator: Saline; 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; Isotonic saline will be applied to cottonoid pledgets and placed into the patient's radial incisions for 3 minutes as the placebo intervention.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Investigators: Principal Investigator: Katherine C Yung, MD, University of California, San Francisco

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2012
• Primary Completion (Actual): February 1, 2018
• Study Completion (Actual): February 1, 2018

Study Registration Dates

• First Submitted: January 27, 2012
• First Submitted That Met QC Criteria: January 31, 2012
• First Posted (Estimate): February 1, 2012

Study Record Updates

• Last Update Posted (Actual): May 22, 2019
• Last Update Submitted That Met QC Criteria: April 26, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: mitomycin-C; tracheal stenosis; laryngotracheal stenosis; subglottic stenosis; endoscopic airway surgery
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Congenital Abnormalities; Otorhinolaryngologic Diseases; Pathological Conditions, Anatomical; Laryngeal Diseases; Tracheal Diseases; Respiratory System Abnormalities; Constriction, Pathologic; Tracheal Stenosis; Laryngostenosis; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Alkylating Agents; Antibiotics, Antineoplastic; Mitomycins; Mitomycin
• Other Study ID Numbers: Laryngotracheal Stenosis