Asthma Intervention Research (AIR) Trial

Study Overview
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Brief Summary
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The purpose of this study is to demonstrate the effectiveness and safety of the Alair System for the treatment of asthma. This will be a multicenter, randomized controlled study comparing the effects of treatment with the Alair System to standard drug therapy. One-hundred and ten subjects will be randomized 1:1 to either the Alair Group (Medical management + Alair treatment),or Control Group (Medical management only).

Detailed Description
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Multicenter, randomized, controlled clinical trial conducted at 11 Investigational Sites in 4 countries (Canada, United Kingdom, Denmark, and Brazil). Subjects underwent Baseline evaluations, Alair treatments or Control Visits, and follow-up evaluations at 12-Weeks, 6-Months, and 12-Months after the last Treatment or Control Visit. In order to maximize the power of the study, Baseline and Follow-up testing was conducted in 2 parts. In the first part subjects continued to take their asthma maintenance medications (inhaled corticosteroids (ICS) and long acting β2-agonists (LABA) during the test period. This is designated as the ON-LABA Phase. Following ON-LABA testing subjects were asked to abstain from LABA for the second part of the testing, and these results are designated as the OFF-LABA Phase.

Official Title
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Multicenter Randomized Clinical Trial of the Alair System for the Bronchial Thermoplasty Treatment of Asthma

Conditions
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Asthma

Intervention / Treatment
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* Procedure: Bronchial thermoplasty with the Alair System
* Drug: Conventional therapy with ICS+LABA


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ambulatory adult; age 18-65 years Asthma requiring regular maintenance medication that includes inhaled corticosteroid (at least 200 μg beclomethasone per day or equivalent) AND long acting ß2 agonist (LABA) (at least 100 mg salmeterol per day or equivalent) Pre-bronchodilator FEV1 60-85% (patients stabilized on inhaled corticosteroids and long acting β2 agonists) PC20 < 8 mg/ml per methacholine inhalation test using standardized methods. Demonstration of worsening of asthma following 2-week withdrawal of LABA, as documented by either: an increase of at least 0.5 in the Juniper Asthma Control Questionnaire score, relative to the Questionnaire score in the 2 weeks preceding withdrawal of LABA, OR a decline of at least 5% in the average am Peak Expiratory Flow during the second week of LABA abstinence relative to the average am Peak Expiratory Flow during the week immediately preceding LABA withdrawal Non-smoker x 1 year or greater (if former smoker, less than 10 pack years total smoking history) Willingness and ability to give written Informed Consent Willingness and ability to comply with the study protocol, including requirements for taking and abstaining from medications. Exclusion Criteria: Participation in another clinical trial involving respiratory intervention that could affect the outcome measures of this study, either within 6 weeks of the pretreatment evaluation, or during the study period Current or recent respiratory tract infection (resolved less than 6 weeks from pretreatment evaluation) History of recurrent (³ 3 infections/year) lower respiratory tract infection requiring antibiotics. With the exception of the use of a prophylactic bronchodilator for exercise, requirement for more than 4 puffs in a 24-hour period of a short-acting b2-adrenergic agonist such as albuterol or salbutamol 100 mg/puff or equivalent within the seven days immediately prior to commencement of Enrollment Testing, Part I. Unstable asthma as defined by the need for an extra visit to a healthcare provider, increase in or introduction of new maintenance or symptom relieving medications (including new requirement for IV or nebulized medications) within 6 weeks of enrollment Use of an internal or external pacemaker or internal cardiac defibrillator Significant co-morbid illness such as cancer, renal failure, liver disease or cerebral vascular disease POST-bronchodilator FEV1 of less than 65%. Known systemic hypersensitivity or contraindication to methacholine chloride or other parasympathomimetic agents Known sensitivity to medications required to perform bronchoscopy, including lidocaine, atropine and benzodiazepines Use of a systemic b-adrenergic blocking agent Pregnancy Nursing mother History of epilepsy Cardiovascular disease, including bradycardia, angina, cardiac dysrhythmia, conduction defect or cardiac myopathy Myocardial infarction or stroke within 6 months of the pretreatment evaluation Any active disease left untreated, Bleeding diathesis, platelet dysfunction, thrombocytopenia with platelet count less than 125,000/mm2 or known coagulopathy (INR > 1.5) Use of anticoagulants Insulin-dependent diabetes Psychiatric disorder which in the judgement of the investigator could interfere with provision of informed consent, completion of tests, therapy, or follow-up Presence of segmental atelectasis, lobar consolidation, significant or unstable pulmonary infiltrate, or pneumothorax, confirmed on x-ray Interstitial lung disease Uncontrolled hypertension (>200 mmHg systolic or >100mmHg diastolic pressure) Known aortic aneurysm

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Alair Group<br>Conventional therapy with ICS+LABA plus bronchial thermoplasty with the Alair System. | Procedure: Bronchial thermoplasty with the Alair System<br>* Conventional therapy with ICS+LABA plus bronchial thermoplasty with the Alair System.<br>|
| Active Comparator: Control Group<br>Conventional therapy with ICS+LABA. | Drug: Conventional therapy with ICS+LABA<br>* Conventional therapy with ICS+LABA.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mild Exacerbation Rate (OFF-LABA) (Change From Baseline) | Average change from Baseline across 12-Week, 6-Month, and 12-Month (OFF-LABA) Follow-up visits. A mild exacerbation was defined as 2 consecutive days when at least one of the following occurs: 1. Morning peak expiratory flow falls at least 20% below the average morning peak flow recorded during the 7 days immediately prior to Enrollment testing; 2. More than 3 more puffs of rescue short acting bronchodilator are required than the average usage during the 7 days immediately prior to Enrollment testing; 3. Awakening at night with asthma symptoms. | Baseline, 12 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pre-Bronchodilator FEV1 (Percent Predicted) (Change From Baseline) | Percent change from Baseline at 12-Weeks (ON-LABA) and 12-Weeks, 6-Months, and 12-Months (OFF-LABA) Follow-up Visits in pre-bronchodilator forced expiratory volume in 1 second (FEV1) (percent predicted). | Baseline, 12 Months | 
| Post-Bronchodilator FEV1 (Percent Predicted) (Change From Baseline) | Percent change from Baseline at 12-Weeks (ON-LABA) and 12-Weeks, 6-Months, and 12-Months (OFF-LABA) Follow-up Visits in post-bronchodilator forced expiratory volume in 1 second (FEV1) (percent predicted). | Baseline, 12 Months | 
| Methacholine PC20 (Change From Baseline) | Change from Baseline at 12-Weeks, 6-Months, and 12-Months (OFF-LABA) Follow-up Visits in PC20 - provocative concentration of Provocholine (a brand of methacholine chloride) resulting in a drop of FEV1 of 20% or more from baseline. The patient inhales an aerosol of one or more concentrations of methacholine. The lower the concentration of methacholine that provokes a 20% (or greater) fall in FEV1, the more responsive or hyperresponsive the airways are. Conversely, a rise in methacholine PC20 indicates airways that have become less reactive. | Baseline, 12 Months | 
| Peak Expiratory Flow (Morning and Evening) (Change From Baseline) | Change from Baseline at 12-Weeks (ON-LABA) and 12-Weeks, 6-Months, and 12-Months (OFF-LABA) Follow-up Visits in morning and evening Peak Expiratory Flow (PEF). The peak expiratory flow rate measures the maximal rate at which a person can exhale air. | Baseline, 12 Months | 
| Asthma Control Questionnaire (ACQ) Score (Change From Baseline) | Change from Baseline at 12-Weeks (ON-LABA) and 12-Weeks, 6-Months, and 12-Months (OFF-LABA) Follow-up Visits in Asthma Control Questionnaire (ACQ) Score. The ACQ is a self-administered patient questionnaire that assesses individual subject asthma control. The ACQ comprises 6 questions that relate to the patient's asthma symptoms, activity limitations, and daily rescue bronchodilator use, and FEV1. Each question is scored from 0 (best) to 6 (worst) and averaged, resulting in a total score from 0 to 6. A decrease in the ACQ score indicates better asthma control. | Baseline, 12 Months | 
| Use of Rescue Medications (Change From Baseline) | Change from Baseline at 12-Weeks (ON-LABA) and 12-Weeks, 6-Months, and 12-Months (OFF-LABA) Follow-up Visits in use of rescue medications (short acting bronchodilators) measured in puffs per week. Subjects recorded their use of rescue medication for asthma symptoms in their Daily Diary throughout the study. | Baseline, 12 Months | 
| Use of Maintenance Medications (Change From Baseline) | Change from Baseline at 12-Months (OFF-LABA) Follow-up Visit in use of maintenance medications (inhaled corticosteroids and/or long-acting beta-agonists). | Baseline, 12 Months | 
| Asthma Quality of Life Questionnaire (AQLQ) Score (Change From Baseline) | Change from Baseline at 12-Weeks (ON-LABA) and 12-Weeks, 6-Months, and 12-Months (OFF-LABA) Follow-up Visits in AQLQ score. The AQLQ consists of 32 questions (scale from 1 to 7, where 7 reflects a higher quality of life). The AQLQ score is the mean of the scores from the 32 individual questions. An increase in the AQLQ score indicates a better quality of life. A within-subject change in score of 0.5 represents the minimal important difference (MID). | Baseline, 12 Months | 
| Total Symptom Score (Change From Baseline) | Change from Baseline at 12-Weeks (ON-LABA) and 12-Weeks, 6-Months, and 12-Months (OFF-LABA) Follow-up Visits in Total Symptom Score. Total Symptom Score comprises the sum of six asthma symptom measurements. Each symptom is scored on a scale of 0 to 3 each day by the subject. The sum of the scores for these 6 symptoms comprises the Total Symptom Score, which measures overall asthma symptoms. The maximum score possible is 18. A lower Total Symptom score represents better asthma control. | Baseline, 12 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Asthma, Bronchial Thermoplasty, Airway Hyperresponsiveness