Clinical trial NCT01350336: Bronchial Thermoplasty in Severe Persistent Asthma
Official title: Post-FDA Approval Clinical Trial Evaluating Bronchial Thermoplasty in Severe Persistent Asthma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Severe Asthma
Lead sponsor: Boston Scientific Corporation
Sponsor class: INDUSTRY
First posted: 2011-05-09
Enrollment: 284
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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).

Eligibility criteria: 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.

Primary outcomes:
measure: Subjects Experiencing Severe Exacerbations (Rates)
timeFrame: Year 1 vs. Year 2, 3, 4, 5
Secondary outcomes:
measure: Rates of Severe Exacerbations
timeFrame: Year 1-5
measure: Respiratory Adverse Event Rates
timeFrame: Year 1-5
measure: Subjects With Respiratory Adverse Events
timeFrame: Year 1-5
measure: Emergency Room Visits for Respiratory Symptoms Rates
timeFrame: Year 1-5
measure: Subjects With Emergency Room Visits for Respiratory Symptoms
timeFrame: Year 1-5
measure: Hospitalizations for Respiratory Symptoms Rates
timeFrame: Year 1-5
measure: Subjects With Hospitalizations for Respiratory Symptoms
timeFrame: Year 1-5
measure: Respiratory Serious Adverse Events Rates
timeFrame: Year 1-5
measure: Subjects With Respiratory Serious Adverse Events
timeFrame: Year 1-5
measure: Pre-bronchodilator FEV1
timeFrame: Year 1-5
measure: Post-bronchodilator FEV1
timeFrame: Year 1-5
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham Lung Health Center
state: Alabama
city: New Haven
country: United States
facility: Yale University Center for Asthma and Airway Disease
state: Connecticut
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: New Orleans
country: United States
facility: LSU Health Sciences
state: Louisiana
city: Boston
country: United States
facility: St. Elizabeth's Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Burlington
country: United States
facility: Lahey Clinic
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Grand Rapids
country: United States
facility: Spectrum Health Hospitals
state: Michigan
city: Saint Paul
country: United States
facility: HealthPartners Specialty Center, Lung and Sleep Health
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: DuBois
country: United States
facility: DuBois Regional Medical Center
state: Pennsylvania
city: Hershey
country: United States
facility: Pennsylvania State Hershey
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Charlottesville
country: United States
facility: University of Virginia Medical Center
state: Virginia
city: Richmond
country: United States
facility: Pulmonary Associates of Richmond
state: Virginia
city: Tacoma
country: United States
facility: Franciscan Research Center (St. Joseph Medical Center)
state: Washington
city: Tacoma
country: United States
facility: MultiCare Pulmonary Specialists
state: Washington
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
city: Surrey
country: Canada
facility: Surrey Memorial Hospital
state: British Columbia
city: Vancouver
country: Canada
facility: Vancouver General Hospital, University of British Columbia
state: British Columbia
city: Montreal
country: Canada
facility: Montreal Chest Institute
state: Quebec
city: Sainte-Foy
country: Canada
facility: Hospital Laval Centre de Pneumologie
state: Quebec
Study officials:
affiliation: Boston Scientific Corporation
name: Thomas S Bowman, MD
role: STUDY_DIRECTOR
References:
citation: 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.