Bronchial Thermoplasty in Severe Persistent Asthma (PAS2)

Post-FDA Approval Clinical Trial Evaluating Bronchial Thermoplasty in Severe Persistent Asthma

As Conditions of Approval of the PMA for the Alair System, the FDA requires Boston Scientific to generate data to assess the durability of the BT treatment effect as well as safety data in the intended use population in the United States.

Study Overview

• Status: Completed
• Conditions: Severe Asthma
• Intervention / Treatment: Device: Alair System

Detailed Description

This is a multicenter, open-label, single arm study designed to demonstrate durability of the treatment effect and to evaluate the short-term and longer-term safety profile of the Alair System in the United States in the intended use population (patients 18 years and older with severe persistent asthma).

• Study Type: Interventional
• Enrollment (Actual): 284
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Surrey, British Columbia, Canada, V3T 0G9
      • Surrey Memorial Hospital
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Vancouver General Hospital, University of British Columbia
  • Quebec
    • Montreal, Quebec, Canada, H2X 2P4
      • Montreal Chest Institute
    • Sainte-Foy, Quebec, Canada, G1V 4G5
      • Hospital Laval Centre de Pneumologie
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham Lung Health Center
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale University Center for Asthma and Airway Disease
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • LSU Health Sciences
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02135
      • St. Elizabeth's Medical Center
    • Burlington, Massachusetts, United States, 01805
      • Lahey Clinic
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
    • Grand Rapids, Michigan, United States, 49503
      • Spectrum Health Hospitals
  • Minnesota
    • Saint Paul, Minnesota, United States, 55103
      • HealthPartners Specialty Center, Lung and Sleep Health
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
  • Pennsylvania
    • DuBois, Pennsylvania, United States, 15801
      • Dubois Regional Medical Center
    • Hershey, Pennsylvania, United States, 17033
      • Pennsylvania State Hershey
    • Philadelphia, Pennsylvania, United States, 19104
      • UNIVERSITY of PENNSYLVANIA
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Medical Center
    • Richmond, Virginia, United States, 23225
      • Pulmonary Associates of Richmond
  • Washington
    • Tacoma, Washington, United States, 98405
      • MultiCare Pulmonary Specialists
    • Tacoma, Washington, United States, 98405
      • Franciscan Research Center (St. Joseph Medical Center)
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subject is an adult between the ages of 18 to 65 years.
2. Subject is able to read, understand, and sign a written Informed Consent to participate in the study and able to comply with the study protocol.

3. Subject has asthma and is taking regular maintenance medication that includes:

   1. Inhaled corticosteroid (ICS) at a dosage greater than 1000μg beclomethasone per day or equivalent, AND long acting β2-agonist (LABA) at a dosage of ≥80μg per day Salmeterol or equivalent.
   2. Other asthma medications such as leukotriene modifiers, or anti-IgE, are acceptable (Subjects on Xolair® must have been on Xolair for greater than 1 year).
   3. Oral corticosteroids (OCS) at a dosage of up to, but not greater than 10mg per day are acceptable.*
4. Subject has a pre-bronchodilator FEV1 of greater than or equal to 60% of predicted.
5. Subject is a non-smoker for 1 year or greater (if former smoker, less than 10 pack years total smoking history).
6. Subject is able to undergo outpatient (same day) bronchoscopy in the opinion of the investigator or per hospital guidelines.
7. Subject has at least 2 days of asthma symptoms in the last 4 weeks.

8. Subject has an AQLQ score during the baseline period of 6.25 or less.

   • NOTE: Subjects on a dosage regimen of 20mg OCS every other day may be included as this is equivalent to an average daily dosage of 10mg.

Exclusion Criteria:

1. Subject is participating in another clinical trial within 6 weeks of the Baseline Period involving respiratory intervention that could affect the outcome measures of this Study.

2. Over the last 7 days of a 4 week medication stable period, subject requirement for rescue medication use other than for prophylactic use for exercise exceeds an average of:

   1. 8 puffs per day of short-acting bronchodilator, or
   2. 4 puffs per day of long-acting rescue bronchodilator, or
   3. 2 nebulizer treatments per day. At the discretion of the Principal Investigator, subjects considered as unstable on baseline medications may have medications adjusted and re-evaluated after a 4 week medication stabilization period.
3. Subject has a post-bronchodilator FEV1 of less than 65%.
4. Subject has a history of life-threatening asthma, defined by past intubation for asthma, or ICU admission for asthma within the prior 2 years.
5. Subject has 3 or more hospitalizations for exacerbations of asthma in the previous year.
6. Subject has had 4 or more infections of lower respiratory tract (LRTI) requiring antibiotics in the past 12 months.
7. Subject has had 4 or more pulses of systemic corticosteroids (tablets, suspension or injection) for asthma symptoms in the past 12 months.
8. Subject has a known sensitivity to medications required to perform bronchoscopy (such as lidocaine, atropine and benzodiazepines).
9. Subject has other respiratory diseases including emphysema, cystic fibrosis, vocal cord dysfunction, mechanical upper airway obstruction, Churg-Strauss syndrome, and allergic bronchopulmonary aspergillosis (asthma, immediate cutaneous reactivity to A. fumigatus, total serum IgE of >1000ng/mL, elevated specific IgE and IgG to A. fumigatus with or without evidence of central bronchiectasis).
10. Subject has segmental atelectasis, lobar consolidation, significant or unstable pulmonary infiltrate, or pneumothorax, confirmed on x-ray.
11. Subject currently has clinically significant cardiovascular disease, including myocardial infarction, angina, cardiac dysfunction, cardiac dysrhythmia, conduction defect, cardiomyopathy, or stroke.
12. Subject has a known aortic aneurysm.
13. Subject has significant co-morbid illness such as cancer, renal failure, liver disease, or cerebral vascular disease.
14. Subject has uncontrolled hypertension (>200mm Hg systolic or >100mm Hg diastolic pressure).
15. Subject has an implanted electrical stimulation device (e.g., a pacemaker, cardiac defibrillator, or deep nerve or deep brain stimulator).
16. Subject has coagulopathy (INR > 1.5).
17. Subject has any other medical condition that would make them inappropriate for study participation, in the Investigator's opinion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Alair; Alair system	Device: Alair System; Treatment of airways with the Alair System

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subjects Experiencing Severe Exacerbations (Rates)	The primary endpoint will be the proportion of subjects experiencing severe exacerbations during the subsequent 12-month (for Years 2, 3, 4, and 5) compared to the first 12-month after the Alair treatment.	Year 1 vs. Year 2, 3, 4, 5

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rates of Severe Exacerbations	# Severe exacerbations / subject / year	Year 1-5
Respiratory Adverse Event Rates	A respiratory adverse event is defined as any sign, symptom, illness, clinically significant abnormal laboratory value, or other adverse medical event associated with the "Respiratory System" that appears or worsens in a subject during a clinical study, regardless of whether or not it is considered related to the procedure used as part of the protocol.	Year 1-5
Subjects With Respiratory Adverse Events	A respiratory adverse event is defined as any sign, symptom, illness, clinically significant abnormal laboratory value, or other adverse medical event associated with the "Respiratory System" that appears or worsens in a subject during a clinical study, regardless of whether or not it is considered related to the procedure used as part of the protocol.	Year 1-5
Emergency Room Visits for Respiratory Symptoms Rates	Emergency room visits for respiratory symptoms (rates of emergency room visits)	Year 1-5
Subjects With Emergency Room Visits for Respiratory Symptoms	Subjects with Emergency room visits for respiratory symptoms	Year 1-5
Hospitalizations for Respiratory Symptoms Rates	(# hospitalizations for respiratory symptoms / subject / year)	Year 1-5
Subjects With Hospitalizations for Respiratory Symptoms	Subjects with hospitalizations for respiratory symptoms	Year 1-5
Respiratory Serious Adverse Events Rates	The rate of subjects with respiratory serious adverse events (SAEs)	Year 1-5
Subjects With Respiratory Serious Adverse Events	Subjects with Respiratory Serious Adverse Events	Year 1-5
Pre-bronchodilator FEV1	% Predicted Pre-bronchodilator FEV1	Year 1-5
Post-bronchodilator FEV1	% Predicted Post-bronchodilator FEV1	Year 1-5

Collaborators and Investigators

• Sponsor: Boston Scientific Corporation
• Investigators: Study Director: Thomas S Bowman, MD, Boston Scientific Corporation

Publications and helpful links

General Publications

• Chupp G, Kline JN, Khatri SB, McEvoy C, Silvestri GA, Shifren A, Castro M, Bansal S, McClelland M, Dransfield M, Trevor J, Kahlstrom N, Simoff M, Wahidi MM, Lamb CR, Ferguson JS, Haas A, Hogarth DK, Tejedor R, Toth J, Hey J, Majid A, LaCamera P, Fitzgerald JM, Enfield K, Grubb GM, McMullen EA, Olson JL, Laviolette M. Bronchial Thermoplasty in Patients With Severe Asthma at 5 Years: The Post-FDA Approval Clinical Trial Evaluating Bronchial Thermoplasty in Severe Persistent Asthma Study. Chest. 2022 Mar;161(3):614-628. doi: 10.1016/j.chest.2021.10.044. Epub 2021 Nov 10.

Helpful Links

• Bronchial Thermoplasty

Study record dates

Study Major Dates

• Study Start (Actual): April 7, 2011
• Primary Completion (Actual): November 12, 2019
• Study Completion (Actual): March 17, 2020

Study Registration Dates

• First Submitted: April 15, 2011
• First Submitted That Met QC Criteria: May 6, 2011
• First Posted (Estimate): May 9, 2011

Study Record Updates

• Last Update Posted (Actual): March 5, 2021
• Last Update Submitted That Met QC Criteria: February 13, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma
• Other Study ID Numbers: 10-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Time Frame: Following Last Patient Out, when Results are posted.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP