Asthma Intervention Research 2 (AIR2) Trial

Study Overview
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Brief Summary
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The objective of this randomized, double blind, sham-controlled study is to demonstrate the safety and effectiveness of the Alair System in a population of subjects with severe asthma who are still symptomatic despite being managed on conventional therapy of high doses of inhaled corticosteroids and long-acting β2-agonists. The primary efficacy endpoint will be the difference between Study groups in the change in Asthma Quality of Life Questionnaire (AQLQ) score from Baseline and the average score from the 6-, 9-, and 12-month follow-up visits. All other outcome measures assessed at 12 months post-treatment. This will be a multicenter, randomized, double-blind, sham-controlled study comparing the effects of treatment with the Alair System to conventional therapy of inhaled corticosteroids (ICS) and long-acting β2-agonists (LABA). A Bayesian adaptive approach to sample size selection is used with a randomization scheme of 2:1 (two Alair Group Subjects for every one Control Group Subject).

Official Title
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Safety and Effectiveness of the Alair® System for the Treatment of Asthma: A Multicenter Randomized Clinical Trial(Asthma Intervention Research (AIR2) Trial)

Conditions
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Asthma

Intervention / Treatment
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* Device: Alair System
* Device: Alair System


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is an adult between the ages of 18 to 65 years. Subject has asthma and is taking regular maintenance medication that includes Inhaled corticosteroid (ICS) AND long acting ß2-agonist (LABA). Subject has a Pre-bronchodilator Forced Expiratory Volume in one second (FEV1) of greater than or equal to 60% of predicted after medication stabilization during the Baseline Period. Subject has a PC20 < 8 mg/ml per methacholine inhalation test using standardized methods. PC20 is a provocative concentration of Provocholine® (a brand of methacholine chloride) resulting in a drop of FEV1 of 20% or more from Baseline. Subject has at least two days of asthma symptoms during the 4-weeks of the Baseline Diary Period. Subject is a non-smoker for 1 year or greater (if former smoker, less than 10 pack years total smoking history). Exclusion Criteria: Subject has a Post-bronchodilator FEV1 of less than 65%. Subject has 3 or more hospitalizations for exacerbations of asthma in the previous year; OR a history of life-threatening asthma, defined by past intubations for asthma, or ICU admission for asthma within the prior 24 months. Subject has a history of recurrent lower respiratory tract infections requiring antibiotics (more than 3 in the past 12 months). Subject has a history of recurrent oral steroid use for asthma (4 or more pulses of oral steroids in the past 12 months). Subject has a known sensitivity to medications required to perform bronchoscopy (such as lidocaine, atropine and benzodiazepines). Subject has known systemic hypersensitivity or contraindication to Methacholine chloride or other parasympathomimetic agents. Subject has other medical criteria.

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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Alair<br>Treatment of airways with the Alair System | Device: Alair System<br>* Treatment of airways with the Alair System<br>|
| Sham Comparator: Sham<br>Sham treatment of airways | Device: Alair System<br>* Sham treatment of airways with the Alair System<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Integrated Asthma Quality of Life Questionnaire (AQLQ) Score (Change From Baseline) | Change between Baseline and the average of 6-, 9-, and 12-month Follow-Up Visits. The AQLQ consists of 32 questions (scale from 1 to 7, where 7 reflects a higher quality of life). An increase in the AQLQ score indicates a better quality of life. The average of the 6-, 9-, and 12-month differences in the AQLQ Score are referred to as the Integrated AQLQ Score. | Baseline, 12 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Symptom-Free Days (Change From Baseline) | Change between Baseline and 12-month Follow-Up Visit. Symptom-Free Days were defined as days when Subject reported no cough, wheeze, breathlessness, or sputum during the daytime, and no wheeze, cough, or awakenings due to asthma symptoms during nighttime. | Baseline, 12 Months | 
| Total Symptom Score (Change From Baseline) | Change from Baseline and 12-month Follow-Up Visit. Total Symptom Score comprises the sum of these six asthma symptom measurements: wheeze during the night, cough during the night, wheeze during the day, cough during the day, breathlessness during the day, and sputum production during the day. Each of these symptoms 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 | 
| Number of Puffs of Rescue Medication Used (Change From Baseline) | Change between Baseline and 12-Month Follow-up Visit. Average number of puffs per week. Rescue medications for asthma are short-acting beta-agonists that bring quick relief of asthma symptoms. | Baseline, 12 Months | 
| Percent Days Rescue Medication Used (Change From Baseline) | Change between Baseline and 12-Month Follow-up Visit. Rescue medications for asthma are short-acting beta-agonists that bring quick relief of asthma symptoms. | Baseline, 12 Months | 
| Asthma Control Questionnaire (ACQ) Score (Change From Baseline) | Change between Baseline and 12-month Follow-Up Visit. The ACQ is a self-administered patient questionnaire that also includes the patient's FEV1 value (% Predicted) 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 (Better) to 6 (Worse). A decrease in the ACQ score indicates better asthma control. | Baseline, 12 Months | 
| Morning Peak Expiratory Flow (amPEF) (Change From Baseline) | Change between Baseline and 12-month Follow-Up Visit. The peak expiratory flow rate measures the maximal rate at which a person can exhale air. | Baseline, 12 Months | 
| Pre-Bronchodilator FEV1 (Percent Predicted) (Change From Baseline) | Change between Baseline and 12-month Follow-Up Visit. The FEV1 is the volume of air expired during the first second of a maximal effort expiration started at total lung capacity. | Baseline, 12 Months | 
| Post-Bronchodilator FEV1 (Percent Predicted) (Change From Baseline) | Change between Baseline and 12-month Follow-Up Visit. The FEV1 is the volume of air expired during the first second of a maximal effort expiration started at total lung capacity. | Baseline, 12 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Asthma