Asthma
Conditions
Brief summary
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%.
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.
Interventions
Bronchial Thermoplasty with the Alair System
Sponsors
Boston Scientific Corporation
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Severe Exacerbations | 12 month periods out to 5 Years | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Respiratory Adverse Events | 12 Month periods out to 5 years | 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. |
| Emergency Room Visits for Respiratory Symptoms | 12 Month periods out to 5 years | Proportion of Subjects with Emergency Room Visits for Respiratory Symptoms |
| Emergency Room (ER) Visits for Respiratory Symptoms | 12 Month periods out to 5 years | Number of Emergency Room Visits for Respiratory Symptoms per subject per year. |
| Severe Exacerbations | 12 Month periods out to 5 years | 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). |
| Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) | 12 Month periods out to 5 years | Pre-Bronchodilator FEV1 (% Predicted) percentage changes from Baseline to the Year 1, Year 2, Year 3, Year 4, and Year 5. |
| Post-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) | 12 Month periods out to 5 years | Post-Bronchodilator FEV1 (% Predicted) percentage changes from Baseline to the Year 1, Year 2, Year 3, Year 4, and Year 5. |
| Hospitalizations for Respiratory Symptoms | 12 Month periods out to 5 Years | Proportion of subjects with hospitalizations for respiratory symptoms. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Alair Group Subjects who underwent treatment with the Alair System in the AIR2 Trial (Protocol No. 04-02, NCT00231114). | 181 |
| Total | 181 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 13 |
| Overall Study | Physician Decision | 2 |
| Overall Study | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | Alair Group |
|---|---|
| Age, Continuous | 40.8 years STANDARD_DEVIATION 11.81 |
| amPEF (Peak Expiratory Flow) | 383.4 L/min (liters per minute) STANDARD_DEVIATION 104.65 |
| Asthma Quality of Life Questionnaire (AQLQ) Score | 4.32 Scores on a scale STANDARD_DEVIATION 1.15 |
| Height (cm) | 166.8 cm STANDARD_DEVIATION 8.94 |
| ICS Dose (Inhaled Corticosteroid dose) | 1943.9 mcg/day (micrograms/day) STANDARD_DEVIATION 722.39 |
| LABA Dose (Long-acting Beta Agonists) | 119.2 mcg/day STANDARD_DEVIATION 45.64 |
| OCS Dose (Oral corticosteroids) | 6.4 mg/day STANDARD_DEVIATION 1.97 |
| Post-Bronchodilator FEV1 (Forced Expiratory Volume in 1 second) | 86 % predicted STANDARD_DEVIATION 15.65 |
| Pre-Bronchodilator FEV1 (Forced Expiratory Volume in 1 second) | 77.8 % predicted STANDARD_DEVIATION 15.67 |
| Region of Enrollment Australia | 7 participants |
| Region of Enrollment Brazil | 54 participants |
| Region of Enrollment Canada | 34 participants |
| Region of Enrollment Netherlands | 5 participants |
| Region of Enrollment United Kingdom | 27 participants |
| Region of Enrollment United States | 54 participants |
| Sex: Female, Male Female | 102 Participants |
| Sex: Female, Male Male | 79 Participants |
| Weight (kg) | 81.9 kg STANDARD_DEVIATION 17.95 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 112 / 187 | 89 / 168 | 81 / 163 | 77 / 163 | 61 / 162 |
| serious Total, serious adverse events | 5 / 187 | 8 / 168 | 10 / 163 | 9 / 163 | 3 / 162 |
Outcome results
Primary
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).
Time frame: 12 month periods out to 5 Years
Population: Number of Subjects Completing Follow-up. 181 subjects completed 12 month follow-up; 165 subjects completed Year 2 follow-up; 162 subjects completed Year 3 follow-up; 159 subjects completed Year 4 follow-up; and 162 subjects completed Year 5 follow-up.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Alair Group | Severe Exacerbations | Year 1 | 30.9 Percentage subjects severe exacerbations |
| Alair Group | Severe Exacerbations | Year 2 | 23.6 Percentage subjects severe exacerbations |
| Alair Group | Severe Exacerbations | Year 3 | 34 Percentage subjects severe exacerbations |
| Alair Group | Severe Exacerbations | Year 4 | 36.5 Percentage subjects severe exacerbations |
| Alair Group | Severe Exacerbations | Year 5 | 21.6 Percentage subjects severe exacerbations |
Secondary
Emergency Room (ER) Visits for Respiratory Symptoms
Number of Emergency Room Visits for Respiratory Symptoms per subject per year.
Time frame: 12 Month periods out to 5 years
Population: Number of Subjects Completing Follow-up. 181 subjects completed 12 month follow-up; 165 subjects completed Year 2 follow-up; 162 subjects completed Year 3 follow-up; 159 subjects completed Year 4 follow-up; and 162 subjects completed Year 5 follow-up.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Alair Group | Emergency Room (ER) Visits for Respiratory Symptoms | Year 1 | 0.072 Number of events/subject/year |
| Alair Group | Emergency Room (ER) Visits for Respiratory Symptoms | Year 2 | 0.085 Number of events/subject/year |
| Alair Group | Emergency Room (ER) Visits for Respiratory Symptoms | Year 3 | 0.136 Number of events/subject/year |
| Alair Group | Emergency Room (ER) Visits for Respiratory Symptoms | Year 4 | 0.094 Number of events/subject/year |
| Alair Group | Emergency Room (ER) Visits for Respiratory Symptoms | Year 5 | 0.068 Number of events/subject/year |
Secondary
Emergency Room Visits for Respiratory Symptoms
Proportion of Subjects with Emergency Room Visits for Respiratory Symptoms
Time frame: 12 Month periods out to 5 years
Population: Number of Subjects Completing Follow-up. 181 subjects completed 12 month follow-up; 165 subjects completed Year 2 follow-up; 162 subjects completed Year 3 follow-up; 159 subjects completed Year 4 follow-up; and 162 subjects completed Year 5 follow-up.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Alair Group | Emergency Room Visits for Respiratory Symptoms | Year 1 | 5 Percentage subjects ER respir. symptoms |
| Alair Group | Emergency Room Visits for Respiratory Symptoms | Year 2 | 6.7 Percentage subjects ER respir. symptoms |
| Alair Group | Emergency Room Visits for Respiratory Symptoms | Year 3 | 8 Percentage subjects ER respir. symptoms |
| Alair Group | Emergency Room Visits for Respiratory Symptoms | Year 4 | 6.9 Percentage subjects ER respir. symptoms |
| Alair Group | Emergency Room Visits for Respiratory Symptoms | Year 5 | 5.6 Percentage subjects ER respir. symptoms |
Secondary
Hospitalizations for Respiratory Symptoms
Proportion of subjects with hospitalizations for respiratory symptoms.
Time frame: 12 Month periods out to 5 Years
Population: Number of Subjects Completing Follow-up. 181 subjects completed 12 month follow-up; 165 subjects completed Year 2 follow-up; 162 subjects completed Year 3 follow-up; 159 subjects completed Year 4 follow-up; and 162 subjects completed Year 5 follow-up.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Alair Group | Hospitalizations for Respiratory Symptoms | Year 4 | 5.7 Percentage of subjects hospitalized |
| Alair Group | Hospitalizations for Respiratory Symptoms | Year 1 | 3.3 Percentage of subjects hospitalized |
| Alair Group | Hospitalizations for Respiratory Symptoms | Year 2 | 4.2 Percentage of subjects hospitalized |
| Alair Group | Hospitalizations for Respiratory Symptoms | Year 3 | 6.2 Percentage of subjects hospitalized |
| Alair Group | Hospitalizations for Respiratory Symptoms | Year 5 | 1.9 Percentage of subjects hospitalized |
Secondary
Hospitalizations for Respiratory Symptoms
Number of Hospitalizations for Respiratory Symptoms per subject per year.
Time frame: 12 Month periods out to 5 years
Population: Number of Subjects Completing Follow-up. 181 subjects completed 12 month follow-up; 165 subjects completed Year 2 follow-up; 162 subjects completed Year 3 follow-up; 159 subjects completed Year 4 follow-up; and 162 subjects completed Year 5 follow-up.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Alair Group | Hospitalizations for Respiratory Symptoms | Year 2 | 0.061 Number of events/subjects/year |
| Alair Group | Hospitalizations for Respiratory Symptoms | Year 3 | 0.068 Number of events/subjects/year |
| Alair Group | Hospitalizations for Respiratory Symptoms | Year 1 | 0.039 Number of events/subjects/year |
| Alair Group | Hospitalizations for Respiratory Symptoms | Year 4 | 0.075 Number of events/subjects/year |
| Alair Group | Hospitalizations for Respiratory Symptoms | Year 5 | 0.025 Number of events/subjects/year |
Secondary
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.
Time frame: 12 Month periods out to 5 years
Population: Number of Subjects Completing Follow-up. 181 subjects completed 12 month follow-up; 165 subjects completed Year 2 follow-up; 162 subjects completed Year 3 follow-up; 159 subjects completed Year 4 follow-up; and 162 subjects completed Year 5 follow-up.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Alair Group | Post-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) | Year 1 | -2.8 Percentage of change from Baseline | Standard Deviation 10.67 |
| Alair Group | Post-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) | Year 2 | -5.4 Percentage of change from Baseline | Standard Deviation 11.51 |
| Alair Group | Post-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) | Year 3 | -4 Percentage of change from Baseline | Standard Deviation 12.88 |
| Alair Group | Post-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) | Year 4 | -3.7 Percentage of change from Baseline | Standard Deviation 11.65 |
| Alair Group | Post-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) | Year 5 | -3.8 Percentage of change from Baseline | Standard Deviation 11.95 |
Secondary
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.
Time frame: 12 Month periods out to 5 years
Population: Number of Subjects Completing Follow-up. 181 subjects completed 12 month follow-up; 165 subjects completed Year 2 follow-up; 162 subjects completed Year 3 follow-up; 159 subjects completed Year 4 follow-up; and 162 subjects completed Year 5 follow-up.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Alair Group | Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) | Year 1 | -1.4 Percentage of change from Baseline | Standard Deviation 14.82 |
| Alair Group | Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) | Year 2 | -4.6 Percentage of change from Baseline | Standard Deviation 15.36 |
| Alair Group | Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) | Year 3 | -2.7 Percentage of change from Baseline | Standard Deviation 15.33 |
| Alair Group | Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) | Year 4 | -1.2 Percentage of change from Baseline | Standard Deviation 14.6 |
| Alair Group | Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) | Year 5 | -1.2 Percentage of change from Baseline | Standard Deviation 16.33 |
Secondary
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.
Time frame: 12 Month periods out to 5 years
Population: Number of Subjects Completing Follow-up. 181 subjects completed 12 month follow-up; 165 subjects completed Year 2 follow-up; 162 subjects completed Year 3 follow-up; 159 subjects completed Year 4 follow-up; and 162 subjects completed Year 5 follow-up.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Alair Group | Respiratory Adverse Events | Year 1 | 72.9 Percentage subjects with respiratory AE |
| Alair Group | Respiratory Adverse Events | Year 2 | 58.8 Percentage subjects with respiratory AE |
| Alair Group | Respiratory Adverse Events | Year 3 | 58 Percentage subjects with respiratory AE |
| Alair Group | Respiratory Adverse Events | Year 4 | 54.7 Percentage subjects with respiratory AE |
| Alair Group | Respiratory Adverse Events | Year 5 | 47.5 Percentage subjects with respiratory AE |
Secondary
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.
Time frame: 12 Month periods out to 5 years
Population: Number of Subjects Completing Follow-up. 181 subjects completed 12 month follow-up; 165 subjects completed Year 2 follow-up; 162 subjects completed Year 3 follow-up; 159 subjects completed Year 4 follow-up; and 162 subjects completed Year 5 follow-up.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Alair Group | Respiratory Adverse Events | Year 1 | 2.022 Number of events/number of subject/Year |
| Alair Group | Respiratory Adverse Events | Year 2 | 1.218 Number of events/number of subject/Year |
| Alair Group | Respiratory Adverse Events | Year 3 | 1.247 Number of events/number of subject/Year |
| Alair Group | Respiratory Adverse Events | Year 4 | 1.176 Number of events/number of subject/Year |
| Alair Group | Respiratory Adverse Events | Year 5 | 0.778 Number of events/number of subject/Year |
Secondary
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).
Time frame: 12 Month periods out to 5 years
Population: Number of Subjects Completing Follow-up. 181 subjects completed 12 month follow-up; 165 subjects completed Year 2 follow-up; 162 subjects completed Year 3 follow-up; 159 subjects completed Year 4 follow-up; and 162 subjects completed Year 5 follow-up.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Alair Group | Severe Exacerbations | Year 1 | 0.486 Number of events/Number of subjects/Year |
| Alair Group | Severe Exacerbations | Year 2 | 0.406 Number of events/Number of subjects/Year |
| Alair Group | Severe Exacerbations | Year 3 | 0.549 Number of events/Number of subjects/Year |
| Alair Group | Severe Exacerbations | Year 4 | 0.560 Number of events/Number of subjects/Year |
| Alair Group | Severe Exacerbations | Year 5 | 0.309 Number of events/Number of subjects/Year |