A Prospective Observational Study of Biopredictors of Bronchial Thermoplasty Response in Patients With Severe Refractory Asthma (BTR Study) (BTR)

Clinical response, as defined by improvement in asthma quality of life, to bronchial thermoplasty in patients with severe refractory asthma can be predicted through the use of clinical, physiologic, biologic and imaging markers.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Device: Alair system

Detailed Description

Primary Aim To assess the relationship between baseline clinical, physiologic, biologic and imaging markers and response to bronchial thermoplasty, defined by improvement in asthma quality of life, in patients with severe refractory asthma.

Secondary Aims

1. To assess the relationship between baseline clinical, physiologic, biologic and imaging markers and response to bronchial thermoplasty, defined by reduction in severe exacerbations or healthcare utilization, in patients with severe refractory asthma.
2. To evaluate if baseline clinical, physiologic, biologic and imaging markers are related to safety of bronchial thermoplasty in patients with severe refractory asthma.
3. To evaluate and validate statistical models that predict response to bronchial thermoplasty in patients with severe refractory asthma.

• Study Type: Observational
• Enrollment (Actual): 133

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States
      • University of Alabama at Birmingham
  • Arizona
    • Tucson, Arizona, United States
      • University of Arizona
  • Colorado
    • Denver, Colorado, United States, 80206
      • National Jewish Health
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Louisiana State University Health Sciences Center in New Orleans
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Nebraska
    • Omaha, Nebraska, United States
      • Creighton University
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic

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

• Sampling Method: Non-Probability Sample

Study Population

Subject Population - Severe Refractory Asthma

Description

Inclusion Criteria:

1. Males or females age 18 or greater and less than 65

2. Subject has asthma and is taking regular maintenance medication for past 12 months that includes:

   • Inhaled corticosteroid (ICS) at a dosage greater than 1000μg beclomethasone per day or equivalent, AND long acting ß2-agonist (LABA) at a dosage of ≥100μg per day Salmeterol or equivalent.
   • 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. Asthma confirmed by: (a) b-agonist reversibility of FEV1 ≥ 12 % following 360mcg albuterol OR (b) methacholine FEV1 PC20 ≤ 8 mg/ml if not receiving an ICS or ≤ 16 mg/ml if receiving an ICS.
4. FEV1 ≥ 50% predicted pre-bronchodilator.
5. Asthma symptoms on at least two days or one night per week over the last 2 weeks.
6. Subject is a non-smoker for 1 year or greater (if former smoker, less than 10 pack years total smoking history).
7. Ability to undergo bronchoscopy in the opinion of the investigator.
8. Ability and willingness to provide informed consent.

Exclusion Criteria:

1. Asthma exacerbation (ED visit, hospitalization, course of increased systemic steroids, or urgent health care visit for asthma) during the prior four weeks.
2. Subject has 3 or more hospitalizations for exacerbations of asthma in the previous year or 1 or more ICU admission for asthma in the previous year.
3. Chronic oral steroid therapy greater than 30 mg per day
4. Subject has other respiratory diseases including interstitial lung disease, emphysema, cystic fibrosis, vocal cord dysfunction, mechanical upper airway obstruction, untreated obstructive sleep apnea, Churg-Strauss syndrome, cardiac dysfunction, and allergic bronchopulmonary aspergillosis (total IgE of >1000 Units/mL with positive specific IgE to aspergillus and evidence of central bronchiectasis) that in the opinion of the investigator would prevent participation in the trial or put the participant at risk by participation.
5. Subject has segmental atelectasis, lobar consolidation, significant or unstable pulmonary infiltrate, or pneumothorax, confirmed on x-ray.
6. Subject has clinically significant cardiovascular disease, including myocardial infarction, angina, cardiac dysrhythmia, conduction defect, cardiomyopathy, aortic aneurysm, or stroke.
7. Subject has uncontrolled hypertension (>200mm Hg systolic or >100mm Hg diastolic pressure).
8. Subject uses an internal or external pacemaker or cardiac defibrillator.
9. Chronic diseases (other than asthma) that in the opinion of the investigator would prevent participation in the trial or put the participant at risk by participation, e.g. chronic diseases of the lung (other than asthma), heart, liver, kidney, or nervous system, or immunodeficiency
10. History of cigarette smoking with > 10 pack years total
11. Use of investigative drugs or intervention trials in the 30 days prior to enrollment or during the duration of the study
12. Any condition or compliance issue which in the opinion of the investigator might interfere with participation in the study

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Severe Asthma Patients; Severe asthma patients symptomatic despite high dose inhaled corticosteroid and long acting beta-agonist	Device: Alair system; Bronchial thermoplasty

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Baseline predictors of response to bronchial thermoplasty defined by improvement in asthma quality of life, in patients with severe refractory asthma.	To assess the relationship between baseline clinical, physiologic, biologic and imaging markers and response to bronchial thermoplasty, defined by improvement in asthma quality of life, in patients with severe refractory asthma.	12 months following last bronchial thermoplasty treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Baseline predictors of severe exacerbations	To assess the relationship between baseline clinical, physiologic, biologic and imaging markers and response to bronchial thermoplasty, defined by reduction in severe exacerbations, in patients with severe refractory asthma.	12 months following last bronchial thermoplasty treatment
Baseline predictors of healthcare utilization	To assess the relationship between baseline clinical, physiologic, biologic and imaging markers and response to bronchial thermoplasty, defined by reduction in healthcare utilization, in patients with severe refractory asthma.	12 months following last bronchial thermoplasty treatment
Baseline predictors of safety of bronchial thermoplasty	To evaluate if baseline clinical, physiologic, biologic and imaging markers are related to safety of bronchial thermoplasty in patients with severe refractory asthma.	12 months following last bronchial thermoplasty treatment
Predictive models of response to bronchial thermoplasty	To evaluate and validate statistical models that predict response to bronchial thermoplasty in patients with severe refractory asthma.	12 months following last bronchial thermoplasty treatment

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: University of Alabama at Birmingham; University of Chicago; The Cleveland Clinic; Creighton University; Louisiana State University Health Sciences Center in New Orleans; University of Arizona; National Jewish Health
• Investigators: Principal Investigator: Mario Castro, MD, MPH, Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start: August 1, 2010
• Primary Completion (Actual): October 1, 2019
• Study Completion (Actual): October 1, 2019

Study Registration Dates

• First Submitted: June 21, 2010
• First Submitted That Met QC Criteria: August 18, 2010
• First Posted (Estimate): August 19, 2010

Study Record Updates

• Last Update Posted (Actual): November 27, 2020
• Last Update Submitted That Met QC Criteria: November 25, 2020
• Last Verified: November 1, 2020

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: 10-0716- 201106118