Treatment Alternatives in iSGS (NoAAC PR-02 Study) (NoAAC PR-02)

Treatment Alternatives in Adult Rare Disease; Assessment of Options in Idiopathic Subglottic Stenosis North American Airway Collaborative PR-02 Study (NoAAC PR-02 Study)

The study is aimed at answering the questions; (1) How well do the most commonly used treatments in iSGS work? and (2) What quality-of-life trade-offs are associated with each approach?

With the results of this trial, the investigators hope to provide information to iSGS patients: (1) Given my personal characteristics, conditions, and preferences, what should I expect will happen to me? and (2) What are my options, and what are the potential benefits and harms of these options?

Study Overview

• Status: Completed
• Conditions: Idiopathic Subglottic Stenosis (iSGS)
• Intervention / Treatment: Procedure: Endoscopic dilation of subglottic stenosis; Procedure: Endoscopic resection of the stenosis; Procedure: Tracheal Resection

Detailed Description

Idiopathic subglottic stenosis (iSGS) is a rare disease in which the trachea narrows for no known reason. Although uncommon (with an estimated incidence of 1:400,000 persons per year), both the disease and its therapies profoundly affect patients' ability to breathe, communicate and swallow. Breathing difficulties (i.e. dyspnea) is the hallmark symptom and the primary cause of death and disability. However, patients can also experience debilitating voice changes and swallowing problems due to the condition or its treatment.

People with this disease often require several surgeries per year. A variety of treatments have been advanced to manage iSGS but are generally categorized into: 1) endoscopic dilation of the tracheal stenosis (accomplished with rigid instruments or inflatable balloons); 2) endoscopic resection of the stenosis (with prolonged medical therapy after surgery); or 3) open neck surgery with resection of the affected tracheal segment with end-to-end anastomosis. Each patient can require repeated surgeries to keep their trachea open, which increases odds of treatment side effects and complications. All approaches have unique and often disabling associated side effects, which can significantly affect a patient's quality of life.

Because the disease is rare, it is difficult for patients to find good information so that they can understand the spectrum of treatment options. This is particularly difficult because most patients present with severe breathing trouble and need treatment quickly, limiting their ability to explore options. Additionally, there is a general lack of high-quality, reliable, and accessible data to inform individual patient decision-making. Imperfect information and limited evidence on treatment outcomes complicate patient decision-making as they try to balance survival, symptoms, and quality of life considerations.

Beyond the gaps in understanding the relative effectiveness of the different treatments available, no studies have explored functional outcomes in iSGS (i.e. how well patients breathe, speak, and swallow after treatments). These endpoints are important to patients and are arguably a primary determinant in decision-making. Direct engagement with patients is critical to understand these quality of life considerations, since patient and physician perspectives aren't always the same. For example, results show that endoscopic dilation is associated with a higher rate of disease recurrence and thus need for repeated surgery. Meanwhile, open tracheal resection is a major surgery with significant immediate perioperative risks and has been associated with alterations in voice and swallowing. Open tracheal resection appears to reduce the risk of disease recurrence, but the degree of benefit, and the trade-offs associated with this approach are unanswered questions.

The proposed study from the North American Airway Collaborative (NoAAC PR- 02) is designed to fill this void. Our prospective study will directly compare the effectiveness of standard of care treatments and assess their associated quality of life tradeoffs in iSGS patients.

• Study Type: Observational
• Enrollment (Actual): 1239

Contacts and Locations

Study Locations

• Australia
  • St Leonards, Australia
    • University of Sydney
• Iceland
  • Reykjavik, Iceland, 101-155
    • Landspitali University Hospital
• United Kingdom
  • London, United Kingdom, W6 8RF
    • Charing Cross Hospital, Imperial College London
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • The University of Alabama at Birmingham
  • Arizona
    • Scottsdale, Arizona, United States, 85054
      • Mayo Clinic
  • California
    • Irvine, California, United States, 92606
      • University of California Irvine
    • Loma Linda, California, United States, 92354
      • Loma Linda University Health Care
    • Los Angeles, California, United States, 90033
      • University of Southern California
    • Los Angeles, California, United States, 90095
      • University of California Los Angeles
    • Palo Alto, California, United States, 94304
      • Stanford University
    • San Diego, California, United States, 92103
      • University of California San Diego
    • San Francisco, California, United States, 94115
      • University of California San Francisco
  • Colorado
    • Denver, Colorado, United States, 80045
      • University of Colorado
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University School of Medicine
    • Augusta, Georgia, United States, 30912
      • Augusta University
  • Illinois
    • Downers Grove, Illinois, United States, 60515
      • Bastian Voice Institute
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Louisiana State University
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Harvard Medical School -Massachusetts Eye and Ear Infirmary
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Minnesota
    • Rochester, Minnesota, United States, 55902
      • Mayo Clinic
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska
  • New York
    • New York, New York, United States, 10016
      • New York University Medical Center
    • Rochester, New York, United States, 14642
      • University of Rochester
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke University
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinatti
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
    • Columbus, Ohio, United States, 43212
      • The Ohio State University Wexner Medical Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah
  • Virginia
    • Charlottesville, Virginia, United States, 22908-0713
      • University of Virginia
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

All clinically confirmed iSGS patients at the participating institutions are eligible for enrollment.

Description

Inclusion Criteria:

• Greater than 18 years of age.
• The lesion must involve the subglottis.

Exclusion Criteria:

• Less than 18 years of age
• Patients without capacity to consent for themselves
• History of significant laryngotracheal traumatic injury.
• History of endotracheal intubation or tracheotomy within 2 years of presentation.
• Major anterior neck surgery.
• History of neck irradiation.
• History of caustic or thermal injuries to the laryngotracheal complex.
• History of a clinically diagnosed vasculitis or collage vascular disease.
• Positive antinuclear cytoplasmic antibody titers.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

iSGS patients; Participants will receive standard of care treatment at the respective center and will be followed longitudinally for symptom changes, need for further treatment, complications, and will have Patient-reported outcomes (PROs) administered at a priori determined intervals.

Procedure: Endoscopic dilation of subglottic stenosis; This is accomplished with rigid instruments or inflatable balloons.; Procedure: Endoscopic resection of the stenosis; This is accomplished with C02 lasers and paired with prolonged medical therapy after surgery.; Procedure: Tracheal Resection; Resection of the affected tracheal segment with end-to-end anastomosis; Other Names: Cricotracheal Resection; Open Airway Surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Treatment Effectiveness: Time to recurrent procedure	3 years
Treatment Effectiveness: Need for tracheostomy	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
QOL	Patient quality of life assessment: voice (VHI-10)	3 years
QOL	Patient quality of life assessment: dysphagia (EAT-10)	3 years
QOL	Patient quality of life assessment: breathing (COPD dyspnea)	3 years
QOL	Patient quality of life assessment: general quality of life (SF-12)	3 years
Patient Reported Outcome	Non-traditional PRO focused on social support	3 years
Patient Reported Outcome	Non-traditional PRO focused on fear of disease recurrence	3 years
Patient Reported Outcome	Non-traditional PRO focused on disease anxiety and burden	3 years
Patient Reported Outcome	Non-traditional PRO focused on participatory decision-making style	3 years

Collaborators and Investigators

• Sponsor: Vanderbilt University Medical Center
• Collaborators: Patient-Centered Outcomes Research Institute; Johns Hopkins University; University of Colorado, Denver; Mayo Clinic; Baylor College of Medicine; University of California, San Diego; University of California, Los Angeles; University of Miami; University of Alabama at Birmingham; University of Pittsburgh; University of Michigan; University of Iowa; NYU Langone Health; University of Wisconsin, Madison; The Cleveland Clinic; Emory University; Duke University; University of Southern California; Medical College of Wisconsin; Oregon Health and Science University; University of Washington; University of California, San Francisco; Vanderbilt University; Stanford University; Ohio State University; University of California, Irvine; University of Texas; Augusta University; Temple University; University of Utah; University of Virginia; University of Rochester; Loma Linda University; Louisiana State University Health Sciences Center in New Orleans; University of Cincinnati; University of Nebraska; University of Sydney; Massachusetts Eye and Ear Infirmary; Landspitali University Hospital; University of North Carolina; Charing Cross Hospital; North American Airway Collaborative; Bastian Voice Institute
• Investigators: Principal Investigator: Alexander Gelbard, MD, Vanderbilt University Medical Center; Study Chair: David O. Francis, MD, MS, Vanderbilt University Medical Center

Publications and helpful links

General Publications

• Gelbard A, Shyr Y, Berry L, Hillel AT, Ekbom DC, Edell ES, Kasperbauer JL, Lott DG, Donovan DT, Garrett CG, Sandhu G, Daniero JJ, Netterville JL, Schindler JS, Smith ME, Bryson PC, Lorenz RR, Francis DO. Treatment options in idiopathic subglottic stenosis: protocol for a prospective international multicentre pragmatic trial. BMJ Open. 2018 Apr 10;8(4):e022243. doi: 10.1136/bmjopen-2018-022243.

Study record dates

Study Major Dates

• Study Start (Actual): August 28, 2015
• Primary Completion (Actual): September 10, 2020
• Study Completion (Actual): September 10, 2020

Study Registration Dates

• First Submitted: June 22, 2015
• First Submitted That Met QC Criteria: June 24, 2015
• First Posted (Estimate): June 25, 2015

Study Record Updates

• Last Update Posted (Actual): October 28, 2021
• Last Update Submitted That Met QC Criteria: October 27, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathological Conditions, Anatomical; Constriction, Pathologic
• Other Study ID Numbers: 150917

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No