AIR2 Extension Study to Demonstrate Longer-term (> 1 Year) Durability of Effectiveness (PAS1)

The objective of this study is to evaluate durability of effectiveness (beyond one year) of the Alair System in patients with severe persistent asthma. The study will consist of Alair-group subjects who are currently in the follow-up phase (out to 5 years) of the AIR2 Trial (Protocol #04-02, clinicaltrials.gov number NCT00231114).

Durability of the treatment effect will be evaluated by comparing the proportion of subjects who experience severe exacerbations during the first year after Alair treatment with the proportion of subjects who experience severe exacerbations during subsequent 12 month periods out to 5 years.

All Alair group subjects in the AIR2 Trial are being followed out to 5 years as per the AIR2 Trial protocol. The data that are to be used to determine durability of effectiveness as described in the present protocol (Protocol #10-01) are being collected under the existing AIR2 Trial protocol (Protocol # 04-02).

Study Hypothesis: An empirical demonstration of the durability of the treatment effect will be used to show that the proportion of subjects experiencing severe exacerbations for the first year compared with the proportions of subjects experiencing severe exacerbations in subsequent years do not get substantially worse.

The primary statistical objective is to demonstrate that the proportion of subjects who experience severe exacerbations in the subsequent 12-month follow-up (for Year 2, Year 3, Year 4 and Year 5 [in 12-month periods]) is not statistically worse when compared with the proportion of first 12-months, which begins 6-weeks after the last Alair treatment. This objective will be met if the upper 95% confidence limit of the difference in proportions (i.e., the subsequent 12-month proportion minus the first 12-month proportion) is less than 20%.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Device: Bronchial Thermoplasty with the Alair System

Detailed Description

This will be an open-label, single arm study designed to demonstrate the durability of effectiveness (beyond one year) of the Alair System in patients with severe persistent asthma.

Durability of treatment effect will be evaluated by comparison of the proportion of subjects experiencing severe exacerbations during the first year after the Alair treatment to subsequent 12-month periods out to 5 years.

The 12-month periods will begin 6 weeks post-last Alair bronchoscopy.

• Study Type: Observational
• Enrollment (Actual): 181

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

• Sampling Method: Non-Probability Sample

Study Population

All Alair group subjects who have participated in the AIR2 Trial (NCT00231114) and were not lost to follow-up at the end of the 12 month premarket visit, and those who are willing to comply with the study protocol and routine visits for the duration of the study will be included in the post-approval study.

Description

Inclusion Criteria:

• All Alair group subjects who have participated in the AIR2 Trial (NCT00231114) and were not lost to follow-up at the end of the 12 month premarket visit, and those who are willing to comply with the study protocol and routine visits for the duration of the study will be included in the post-approval study

Exclusion Criteria:

• None.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Alair Group; Subjects who underwent treatment with the Alair System in the AIR2 Trial (Protocol No. 04-02, NCT00231114)	Device: Bronchial Thermoplasty with the Alair System; Bronchial Thermoplasty with the Alair System

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severe Exacerbations	The primary endpoint will be the proportion of subjects experiencing severe exacerbations during the first year after the Alair treatment compared to subsequent 12-month periods out to 5 years. This objective will be met if the upper 95% confidence limit of the difference in proportions (i.e., the subsequent 12-month proportion minus the first 12-month proportion) is less than 20%. Severe exacerbation is defined as 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 entry into the AIR2 Trial (Protocol #04-02).	12 month periods out to 5 Years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severe Exacerbations	Number of severe exacerbations per subject per year. Severe exacerbation is defined as 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 entry into the AIR2 Trial (Protocol #04-02).	12 Month periods out to 5 years
Respiratory Adverse Events	Number of respiratory adverse events per subject per year. A respiratory adverse event is defined as any sign, symptom, illness, clinically significant abnormal laboratory value, or other adverse medical event associated with the "Respiratory System" that appears or worsens in a subject during a clinical study, regardless of whether or not it is considered related to the procedure used as part of the protocol.	12 Month periods out to 5 years
Respiratory Adverse Events	Proportion of subjects experiencing one or more respiratory adverse event in each of the years 1 through 5 following the Alair treatment. A respiratory adverse event is defined as any sign, symptom, illness, clinically significant abnormal laboratory value, or other adverse medical event associated with the "Respiratory System" that appears or worsens in a subject during a clinical study, regardless of whether or not it is considered related to the procedure used as part of the protocol.	12 Month periods out to 5 years
Emergency Room Visits for Respiratory Symptoms	Proportion of Subjects with Emergency Room Visits for Respiratory Symptoms	12 Month periods out to 5 years
Emergency Room (ER) Visits for Respiratory Symptoms	Number of Emergency Room Visits for Respiratory Symptoms per subject per year.	12 Month periods out to 5 years
Hospitalizations for Respiratory Symptoms	Proportion of subjects with hospitalizations for respiratory symptoms.	12 Month periods out to 5 Years
Hospitalizations for Respiratory Symptoms	Number of Hospitalizations for Respiratory Symptoms per subject per year.	12 Month periods out to 5 years
Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1)	Pre-Bronchodilator FEV1 (% Predicted) percentage changes from Baseline to the Year 1, Year 2, Year 3, Year 4, and Year 5.	12 Month periods out to 5 years
Post-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1)	Post-Bronchodilator FEV1 (% Predicted) percentage changes from Baseline to the Year 1, Year 2, Year 3, Year 4, and Year 5.	12 Month periods out to 5 years

Collaborators and Investigators

• Sponsor: Boston Scientific Corporation

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: October 1, 2005
• Primary Completion (Actual): September 1, 2012
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: October 28, 2010
• First Submitted That Met QC Criteria: May 6, 2011
• First Posted (Estimate): May 9, 2011

Study Record Updates

• Last Update Posted (Estimate): September 26, 2016
• Last Update Submitted That Met QC Criteria: August 3, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Other Study ID Numbers: 10-01