Laryngeal Stenosis, Subglottic Stenosis, Tracheal Stenosis
Conditions
Keywords
mitomycin-C, laryngotracheal stenosis, subglottic stenosis, tracheal stenosis, endoscopic airway surgery
Brief summary
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
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.
Interventions
DRUGMitomycin -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.
OTHERSaline application
Isotonic saline will be applied to cottonoid pledgets and placed into the patient's radial incisions for 3 minutes as the placebo intervention.
Sponsors
University of California, San Francisco
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Repeat Surgery | 24 months | Length of time between surgeries for laryngotracheal stenosis during the study |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Symptom Improvement | 24 months | 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 |
| Peak Inspiratory Flow Measurement | 3 months | 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. |
Countries
United States
Participant flow
Recruitment details
Recruited from the UCSF Voice and Swallowing Center clinic from August 1, 2012 to February 1, 2018
Participants by arm
| Arm | Count |
|---|---|
| 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.
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. | 9 |
| 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.
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. | 6 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Saline | Total | Mitomycin-C |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 4 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 11 Participants | 6 Participants |
| Age, Continuous | 57.1 Years of age STANDARD_DEVIATION 12.4 | 53 Years of age STANDARD_DEVIATION 11.6 | 48 Years of age STANDARD_DEVIATION 8.3 |
| Age of Onset | 52.2 Years STANDARD_DEVIATION 13.5 | 49 Years STANDARD_DEVIATION 12.3 | 44.2 Years STANDARD_DEVIATION 9.2 |
| Average prior laryngotracheal stenosis surgeries | 1.1 Surgeries STANDARD_DEVIATION 1.5 | 2 Surgeries STANDARD_DEVIATION 3.5 | 4 Surgeries STANDARD_DEVIATION 4.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 3 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 12 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Etiology Granulomatosis with Polyangiitis | 2 Participants | 3 Participants | 1 Participants |
| Etiology Idiopathic | 6 Participants | 11 Participants | 5 Participants |
| Etiology Post-Intubation | 1 Participants | 1 Participants | 0 Participants |
| Prior laryngotracheal stenosis surgery No | 5 Participants | 6 Participants | 1 Participants |
| Prior laryngotracheal stenosis surgery Yes | 4 Participants | 9 Participants | 5 Participants |
| Prior treatment with Kenalog No | 7 Participants | 9 Participants | 2 Participants |
| Prior treatment with Kenalog Yes | 2 Participants | 6 Participants | 4 Participants |
| Prior treatment with Mitomycin C No | 6 Participants | 8 Participants | 2 Participants |
| Prior treatment with Mitomycin C Yes | 3 Participants | 7 Participants | 4 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) White | 8 Participants | 12 Participants | 4 Participants |
| Sex: Female, Male Female | 9 Participants | 13 Participants | 4 Participants |
| Sex: Female, Male Male | 0 Participants | 2 Participants | 2 Participants |
| Site Subglottis | 8 Participants | 13 Participants | 5 Participants |
| Site Subglottis and Trachea | 0 Participants | 1 Participants | 1 Participants |
| Site Trachea | 1 Participants | 1 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 6 |
| other Total, other adverse events | 0 / 9 | 0 / 6 |
| serious Total, serious adverse events | 0 / 9 | 0 / 6 |
Outcome results
Primary
Time to Repeat Surgery
Length of time between surgeries for laryngotracheal stenosis during the study
Time frame: 24 months
Population: Patients who did not undergo a subsequent surgery after the initial study surgery were excluded as a surgical interval could not be calculated. There were two patients in each arm that did not have subsequent surgeries
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Saline | Time to Repeat Surgery | 17.9 Months | Standard Deviation 15.7 |
| Mitomycin-C | Time to Repeat Surgery | 17.4 Months | Standard Deviation 12.8 |
p-value: 0.95t-test, 2 sided
Secondary
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
Time frame: 24 months
Population: Time to symptom score (CCQ) progression was calculated for each surgery performed during the study with available CCQ data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Saline | Duration of Symptom Improvement | 4.1 Months | Standard Deviation 6.7 |
| Mitomycin-C | Duration of Symptom Improvement | 6.0 Months | Standard Deviation 6.4 |
p-value: 0.52t-test, 2 sided
Secondary
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.
Time frame: 3 months
Population: Improvement in peak inspiratory flow (PIF) was calculated for each surgery performed during the study with available PIF data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Saline | Peak Inspiratory Flow Measurement | 1.1 Liters per second | Standard Deviation 1.5 |
| Mitomycin-C | Peak Inspiratory Flow Measurement | 1.3 Liters per second | Standard Deviation 0.96 |
p-value: 0.64t-test, 2 sided