Clinical trial NCT00231114: Asthma Intervention Research 2 (AIR2) Trial
Official title: Safety and Effectiveness of the Alair® System for the Treatment of Asthma: A Multicenter Randomized Clinical Trial(Asthma Intervention Research (AIR2) Trial)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Asthma
Keywords: Asthma
Lead sponsor: Boston Scientific Corporation
Sponsor class: INDUSTRY
First posted: 2005-10-04
Enrollment: 297
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: 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.

Primary outcomes:
measure: Integrated Asthma Quality of Life Questionnaire (AQLQ) Score (Change From Baseline)
timeFrame: Baseline, 12 Months
Secondary outcomes:
measure: Percent Symptom-Free Days (Change From Baseline)
timeFrame: Baseline, 12 Months
measure: Total Symptom Score (Change From Baseline)
timeFrame: Baseline, 12 Months
measure: Number of Puffs of Rescue Medication Used (Change From Baseline)
timeFrame: Baseline, 12 Months
measure: Percent Days Rescue Medication Used (Change From Baseline)
timeFrame: Baseline, 12 Months
measure: Asthma Control Questionnaire (ACQ) Score (Change From Baseline)
timeFrame: Baseline, 12 Months
measure: Morning Peak Expiratory Flow (amPEF) (Change From Baseline)
timeFrame: Baseline, 12 Months
measure: Pre-Bronchodilator FEV1 (Percent Predicted) (Change From Baseline)
timeFrame: Baseline, 12 Months
measure: Post-Bronchodilator FEV1 (Percent Predicted) (Change From Baseline)
timeFrame: Baseline, 12 Months
Other outcomes:
measure: Rate of Severe Exacerbations Requiring Systemic Corticosteroids
timeFrame: Baseline, 12 Months
measure: Percentage of Subjects With Severe Exacerbations Requiring Systemic Corticosteroids
timeFrame: Baseline, 12 Months
measure: Days Lost From Work/School/Other Activities Due to Asthma
timeFrame: 12 Months
measure: Unscheduled Physician Office Visits for Respiratory Symptoms
timeFrame: 12 Months
measure: Emergency Room Visits for Respiratory Symptoms
timeFrame: 12 Months
measure: Hospitalizations for Respiratory Symptoms
timeFrame: 12 Months
Locations:
city: Phoenix
country: United States
facility: Pulmonary Associates, PA
state: Arizona
city: Los Angeles
country: United States
facility: University of Southern California, Adult Asthma and Allergy Center
state: California
city: Denver
country: United States
facility: National Jewish Medical and Research Center
state: Colorado
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Peoria
country: United States
facility: Peoria Pulmonary Associates, Ltd.
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Topeka
country: United States
facility: Veritas Clinical Specialties
state: Kansas
city: Baltimore
country: United States
facility: Johns Hopkins University School of Medicine
state: Maryland
city: Boston
country: United States
facility: Brigham and Womens's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Medical Center
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: New York
country: United States
facility: Saint Vincent Catholic Medical Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Philadelphia
country: United States
facility: Hospital of the University of Pennyslvania
state: Pennsylvania
city: Knoxville
country: United States
facility: Clinical Research Solutions, PC - Baptist Hospitals of East Tennesse
state: Tennessee
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Arlington
country: United States
facility: Virginia Hospital Center
state: Virginia
city: Seattle
country: United States
facility: Swedish Medical Center
state: Washington
city: Madison
country: United States
facility: University of Wisconsin Hospital
state: Wisconsin
city: New Lambton Heights
country: Australia
facility: John Hunter Hospital
state: New South Wales
city: Perth
country: Australia
facility: Sir Charles Gairdner Hospital
state: Western Australia
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
city: Porto Alegre
country: Brazil
facility: Hospital Sao Lucas da PUCRS
state: RS
city: Porto Alegre
country: Brazil
facility: Irmandade Santa Casa de Miscericordia de Porto Alegre
city: Rio de Janeiro
country: Brazil
facility: Hospital Universitario Clementino Fraga Filho
city: Sao Paulo
country: Brazil
facility: Faculdade da Medicina do ABC
city: Hamilton
country: Canada
facility: Firestone Institute of Respiratory Health, St. Joseph's Healthcare
state: Ontario
city: Montreal
country: Canada
facility: Montreal Chest Institute, McGill University
state: Quebec
city: Sainte-Foy
country: Canada
facility: Hopital Laval, Centre de Pneumologie
state: Quebec
city: Odense
country: Denmark
facility: Odense Universitets Hospital, University of Odense
city: Groningen
country: Netherlands
facility: Universitair Medisch Centrum
city: Glasgow
country: United Kingdom
facility: Gartnavel General Hospital, University of Glasgow
state: Scotland
city: Birmingham
country: United Kingdom
facility: Birmingham Heartlands Hospital
city: Leicester
country: United Kingdom
facility: Glenfield General Hospital, Univ. Hospitals of Leicester
city: London
country: United Kingdom
facility: Chelsea & Westminster Healthcare NHS Trust
city: Manchester
country: United Kingdom
facility: Northwest Lung Research Center, Univ. of Manchester
Study officials:
affiliation: Asthmatx, Inc.
name: Narinder S Shargill, PhD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.