Asthma Intervention Research 2 (AIR2) Trial

Asthma Clinical 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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00231114
• Other study ID #: 04-02
• Status: Completed
• Phase: N/A
• First received: September 30, 2005
• Last updated: March 28, 2014
• Start date: September 2005
• Est. completion date: April 2013

Study information

• Verified date: March 2014
• Source: Asthmatx, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 297
• Est. completion date: April 2013
• Est. primary completion date: August 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Asthma

Intervention

Device:
• Alair System
Treatment of airways with the Alair System
• Alair System
Sham treatment of airways with the Alair System

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide
Australia	John Hunter Hospital	New Lambton Heights	New South Wales
Australia	Sir Charles Gairdner Hospital	Perth	Western Australia
Brazil	Hospital Sao Lucas da PUCRS	Porto Alegre	RS
Brazil	Irmandade Santa Casa de Miscericordia de Porto Alegre	Porto Alegre
Brazil	Hospital Universitario Clementino Fraga Filho	Rio de Janeiro
Brazil	Faculdade da Medicina do ABC	Sao Paulo
Canada	Firestone Institute of Respiratory Health, St. Joseph's Healthcare	Hamilton	Ontario
Canada	Montreal Chest Institute, McGill University	Montreal	Quebec
Canada	Hopital Laval, Centre de Pneumologie	Sainte-Foy	Quebec
Denmark	Odense Universitets Hospital, University of Odense	Odense
Netherlands	Universitair Medisch Centrum	Groningen
United Kingdom	Birmingham Heartlands Hospital	Birmingham
United Kingdom	Gartnavel General Hospital, University of Glasgow	Glasgow	Scotland
United Kingdom	Glenfield General Hospital, Univ. Hospitals of Leicester	Leicester
United Kingdom	Chelsea & Westminster Healthcare NHS Trust	London
United Kingdom	Northwest Lung Research Center, Univ. of Manchester	Manchester
United States	Virginia Hospital Center	Arlington	Virginia
United States	Johns Hopkins University School of Medicine	Baltimore	Maryland
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Brigham and Womens's Hospital	Boston	Massachusetts
United States	University of Chicago	Chicago	Illinois
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	National Jewish Medical and Research Center	Denver	Colorado
United States	Henry Ford Medical Center	Detroit	Michigan
United States	Duke University Medical Center	Durham	North Carolina
United States	Baylor College of Medicine	Houston	Texas
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	Clinical Research Solutions, PC - Baptist Hospitals of East Tennesse	Knoxville	Tennessee
United States	University of Southern California, Adult Asthma and Allergy Center	Los Angeles	California
United States	University of Wisconsin Hospital	Madison	Wisconsin
United States	Saint Vincent Catholic Medical Center	New York	New York
United States	Peoria Pulmonary Associates, Ltd.	Peoria	Illinois
United States	Hospital of the University of Pennyslvania	Philadelphia	Pennsylvania
United States	Pulmonary Associates, PA	Phoenix	Arizona
United States	Swedish Medical Center	Seattle	Washington
United States	Washington University School of Medicine	St. Louis	Missouri
United States	HealthPartners Specialty Center, Lung and Sleep Health	St. Paul	Minnesota
United States	Veritas Clinical Specialties	Topeka	Kansas

Sponsors (2)

Lead Sponsor	Collaborator
Asthmatx, Inc.	Boston Scientific Corporation

Countries where clinical trial is conducted

United States,  Australia,  Brazil,  Canada,  Denmark,  Netherlands,  United Kingdom, 

References & Publications (3)

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, Ja — View 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. — View 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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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	Yes
Other	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	Yes
Other	Days Lost From Work/School/Other Activities Due to Asthma		12 Months	No
Other	Unscheduled Physician Office Visits for Respiratory Symptoms		12 Months	Yes
Other	Emergency Room Visits for Respiratory Symptoms		12 Months	Yes
Other	Hospitalizations for Respiratory Symptoms		12 Months	Yes
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes

External Links

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