Asthma Intervention Research 2 (AIR2) Trial

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

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).

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 297
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Australia
  • Adelaide, Australia
    • Royal Adelaide Hospital
  • New South Wales
    • New Lambton Heights, New South Wales, Australia, 2035
      • John Hunter Hospital
  • Western Australia
    • Perth, Western Australia, Australia, 6009
      • Sir Charles Gairdner Hospital
• Brazil
  • Porto Alegre, Brazil, CEP 90035-074
    • Irmandade Santa Casa de Miscericordia de Porto Alegre
  • Rio de Janeiro, Brazil
    • Hospital Universitario Clementino Fraga Filho
  • Sao Paulo, Brazil, CEP 09060-650
    • Faculdade da Medicina do ABC
  • RS
    • Porto Alegre, RS, Brazil, CEP 90610-00
      • Hospital Sao Lucas da PUCRS
• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8N 4A6
      • Firestone Institute of Respiratory Health, St. Joseph's Healthcare
  • Quebec
    • Montreal, Quebec, Canada, H2X 2P4
      • Montreal Chest Institute, McGill University
    • Sainte-Foy, Quebec, Canada, G1V 4GS
      • Hopital Laval, Centre de Pneumologie
• Denmark
  • Odense, Denmark, 5000 Odense C
    • Odense Universitets Hospital, University of Odense
• Netherlands
  • Groningen, Netherlands, 9700 RB
    • Universitair Medisch Centrum
• United Kingdom
  • Birmingham, United Kingdom, B9 5SS
    • Birmingham Heartlands Hospital
  • Leicester, United Kingdom, LE3 9QP
    • Glenfield General Hospital, Univ. Hospitals of Leicester
  • London, United Kingdom, SW10 9NH
    • Chelsea & Westminster Healthcare NHS Trust
  • Manchester, United Kingdom, M23 9LT
    • Northwest Lung Research Center, Univ. of Manchester
  • Scotland
    • Glasgow, Scotland, United Kingdom, G12 0YN
      • Gartnavel General Hospital, University of Glasgow
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85020
      • Pulmonary Associates, PA
  • California
    • Los Angeles, California, United States, 90033
      • University of Southern California, Adult Asthma and Allergy Center
  • Colorado
    • Denver, Colorado, United States, 80206
      • National Jewish Medical and Research Center
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
    • Peoria, Illinois, United States, 61603
      • Peoria Pulmonary Associates, Ltd.
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals and Clinics
  • Kansas
    • Topeka, Kansas, United States, 66606
      • Veritas Clinical Specialties
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Johns Hopkins University School of Medicine
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02115
      • Brigham and Womens's Hospital
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Medical Center
  • Minnesota
    • Saint Paul, Minnesota, United States, 55101
      • HealthPartners Specialty Center, Lung and Sleep Health
  • Missouri
    • Saint Louis, Missouri, United States, 63110-1093
      • Washington University School of Medicine
  • New York
    • New York, New York, United States, 10011
      • Saint Vincent Catholic Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of Pennyslvania
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • Clinical Research Solutions, PC - Baptist Hospitals of East Tennesse
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
  • Virginia
    • Arlington, Virginia, United States, 22205-3698
      • Virginia Hospital Center
  • Washington
    • Seattle, Washington, United States, 98104
      • Swedish Medical Center
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Hospital

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:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Alair; Treatment of airways with the Alair System	Device: Alair System; Treatment of airways with the Alair System; Device: Alair System; Sham treatment of airways with the Alair System
SHAM_COMPARATOR: Sham; Sham treatment of airways	Device: Alair System; Treatment of airways with the Alair System; Device: Alair System; Sham treatment of airways with the Alair System

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Severe Exacerbations Requiring Systemic Corticosteroids	Rate of occurrence of worsening of asthma requiring treatment with oral or intravenous corticosteroids, OR a doubling of the baseline inhaled corticosteroid dose for at least 3 days, OR any temporary increase in the dosage of oral corticosteroids for a Subject taking maintenance oral corticosteroids at Study entry.	Baseline, 12 Months
Percentage of Subjects With Severe Exacerbations Requiring Systemic Corticosteroids	Percent of subjects experiencing worsening of asthma requiring treatment with oral or intravenous corticosteroids, OR a doubling of the baseline inhaled corticosteroid dose for at least 3 days, OR any temporary increase in the dosage of oral corticosteroids for a Subject taking maintenance oral corticosteroids at Study entry.	Baseline, 12 Months
Days Lost From Work/School/Other Activities Due to Asthma		12 Months
Unscheduled Physician Office Visits for Respiratory Symptoms		12 Months
Emergency Room Visits for Respiratory Symptoms		12 Months
Hospitalizations for Respiratory Symptoms		12 Months

Collaborators and Investigators

• Sponsor: Boston Scientific Corporation

Publications and helpful links

General Publications

• Pavord ID, Thomson NC, Niven RM, Corris PA, Chung KF, Cox G, Armstrong B, Shargill NS, Laviolette M; Research in Severe Asthma Trial Study Group. Safety of bronchial thermoplasty in patients with severe refractory asthma. Ann Allergy Asthma Immunol. 2013 Nov;111(5):402-7. doi: 10.1016/j.anai.2013.05.002. Epub 2013 Jun 13.
• Wechsler ME, Laviolette M, Rubin AS, Fiterman J, Lapa e Silva JR, Shah PL, Fiss E, Olivenstein R, Thomson NC, Niven RM, Pavord ID, Simoff M, Hales JB, McEvoy C, Slebos DJ, Holmes M, Phillips MJ, Erzurum SC, Hanania NA, Sumino K, Kraft M, Cox G, Sterman DH, Hogarth K, Kline JN, Mansur AH, Louie BE, Leeds WM, Barbers RG, Austin JH, Shargill NS, Quiring J, Armstrong B, Castro M; Asthma Intervention Research 2 Trial Study Group. Bronchial thermoplasty: Long-term safety and effectiveness in patients with severe persistent asthma. J Allergy Clin Immunol. 2013 Dec;132(6):1295-302. doi: 10.1016/j.jaci.2013.08.009. Epub 2013 Aug 30.
• Castro M, Rubin AS, Laviolette M, Fiterman J, De Andrade Lima M, Shah PL, Fiss E, Olivenstein R, Thomson NC, Niven RM, Pavord ID, Simoff M, Duhamel DR, McEvoy C, Barbers R, Ten Hacken NH, Wechsler ME, Holmes M, Phillips MJ, Erzurum S, Lunn W, Israel E, Jarjour N, Kraft M, Shargill NS, Quiring J, Berry SM, Cox G; AIR2 Trial Study Group. Effectiveness and safety of bronchial thermoplasty in the treatment of severe asthma: a multicenter, randomized, double-blind, sham-controlled clinical trial. Am J Respir Crit Care Med. 2010 Jan 15;181(2):116-24. doi: 10.1164/rccm.200903-0354OC. Epub 2009 Oct 8.
• Castro M, Rubin A, Laviolette M, Hanania NA, Armstrong B, Cox G; AIR2 Trial Study Group. Persistence of effectiveness of bronchial thermoplasty in patients with severe asthma. Ann Allergy Asthma Immunol. 2011 Jul;107(1):65-70. doi: 10.1016/j.anai.2011.03.005. Epub 2011 Apr 14.

Helpful Links

• The AIR2 Extension Study (PAS1) contains the Year 2 to Year 5 Study Results.

Study record dates

Study Major Dates

• Study Start: September 1, 2005
• Primary Completion (ACTUAL): August 1, 2008
• Study Completion (ACTUAL): April 1, 2013

Study Registration Dates

• First Submitted: September 30, 2005
• First Submitted That Met QC Criteria: September 30, 2005
• First Posted (ESTIMATE): October 4, 2005

Study Record Updates

• Last Update Posted (ACTUAL): July 27, 2017
• Last Update Submitted That Met QC Criteria: June 29, 2017
• Last Verified: March 1, 2014

More Information

Terms related to this study

• Keywords: Asthma
• 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: 04-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED