Asthma
Conditions
Keywords
Asthma
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).
Interventions
DEVICEAlair System
Treatment of airways with the Alair System
Sponsors
Boston Scientific Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Integrated Asthma Quality of Life Questionnaire (AQLQ) Score (Change From Baseline) | Baseline, 12 Months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total Symptom Score (Change From Baseline) | Baseline, 12 Months | 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. |
| Number of Puffs of Rescue Medication Used (Change From Baseline) | Baseline, 12 Months | 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. |
| Percent Days Rescue Medication Used (Change From Baseline) | Baseline, 12 Months | 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. |
| Asthma Control Questionnaire (ACQ) Score (Change From Baseline) | Baseline, 12 Months | 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. |
| Morning Peak Expiratory Flow (amPEF) (Change From Baseline) | Baseline, 12 Months | 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. |
| Pre-Bronchodilator FEV1 (Percent Predicted) (Change From Baseline) | Baseline, 12 Months | 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. |
| Post-Bronchodilator FEV1 (Percent Predicted) (Change From Baseline) | Baseline, 12 Months | 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. |
| Percent Symptom-Free Days (Change From Baseline) | Baseline, 12 Months | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With Severe Exacerbations Requiring Systemic Corticosteroids | Baseline, 12 Months | 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. |
| Unscheduled Physician Office Visits for Respiratory Symptoms | 12 Months | — |
| Emergency Room Visits for Respiratory Symptoms | 12 Months | — |
| Hospitalizations for Respiratory Symptoms | 12 Months | — |
| Rate of Severe Exacerbations Requiring Systemic Corticosteroids | Baseline, 12 Months | 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. |
| Days Lost From Work/School/Other Activities Due to Asthma | 12 Months | — |
Countries
Australia, Brazil, Canada, Denmark, Netherlands, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Alair Alair treatment plus conventional therapy with inhaled corticosteroids and long acting β2-agonists. | 190 |
| Sham Sham bronchoscopy plus conventional therapy with inhaled corticosteroids and long acting β2-agonists. | 98 |
| Total | 288 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Post-Treatment Period | Lost to Follow-up | 6 | 1 |
| Post-Treatment Period | Physician Decision | 1 | 0 |
| Post-Treatment Period | Withdrawal by Subject | 1 | 0 |
| Randomized | Withdrawal by Subject | 6 | 3 |
| Treatment Period | Death: Motor Vehicle Accident | 1 | 0 |
Baseline characteristics
| Characteristic | Alair | Sham | Total |
|---|---|---|---|
| Age, Continuous | 40.7 years STANDARD_DEVIATION 11.89 | 40.6 years STANDARD_DEVIATION 11.85 | 40.65 years STANDARD_DEVIATION 11.86 |
| Region of Enrollment Australia | 7 participants | 6 participants | 13 participants |
| Region of Enrollment Brazil | 55 participants | 29 participants | 84 participants |
| Region of Enrollment Canada | 36 participants | 17 participants | 53 participants |
| Region of Enrollment Netherlands | 5 participants | 2 participants | 7 participants |
| Region of Enrollment United Kingdom | 28 participants | 15 participants | 43 participants |
| Region of Enrollment United States | 59 participants | 29 participants | 88 participants |
| Sex: Female, Male Female | 109 Participants | 60 Participants | 169 Participants |
| Sex: Female, Male Male | 81 Participants | 38 Participants | 119 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 176 / 190 | 82 / 98 | 157 / 187 | 86 / 98 |
| serious Total, serious adverse events | 19 / 190 | 4 / 98 | 12 / 187 | 10 / 98 |
Outcome results
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.
Time frame: Baseline, 12 Months
Population: Intent-to-Treat (ITT) population. Consists of all randomized subjects who were administered at least one bronchoscopy.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alair | Integrated Asthma Quality of Life Questionnaire (AQLQ) Score (Change From Baseline) | 1.35 Units on a scale | Standard Deviation 1.1 |
| Sham | Integrated Asthma Quality of Life Questionnaire (AQLQ) Score (Change From Baseline) | 1.16 Units on a scale | Standard Deviation 1.23 |
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.
Time frame: Baseline, 12 Months
Population: Intent-to-Treat (ITT) population. Consists of all randomized subjects who were administered at least one bronchoscopy.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alair | Asthma Control Questionnaire (ACQ) Score (Change From Baseline) | -0.82 Units on a scale | Standard Deviation 0.95 |
| Sham | Asthma Control Questionnaire (ACQ) Score (Change From Baseline) | -0.77 Units on a scale | Standard Deviation 1.08 |
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.
Time frame: Baseline, 12 Months
Population: Intent-to-Treat (ITT) population. Consists of all randomized subjects who were administered at least one bronchoscopy.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alair | Morning Peak Expiratory Flow (amPEF) (Change From Baseline) | 27.8 L/Min | Standard Deviation 49.78 |
| Sham | Morning Peak Expiratory Flow (amPEF) (Change From Baseline) | 22.3 L/Min | Standard Deviation 51.54 |
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.
Time frame: Baseline, 12 Months
Population: Intent-to-Treat (ITT) population. Consists of all randomized subjects who were administered at least one bronchoscopy.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alair | Number of Puffs of Rescue Medication Used (Change From Baseline) | -6.0 Puffs/7 Days | Standard Deviation 16.67 |
| Sham | Number of Puffs of Rescue Medication Used (Change From Baseline) | -4.3 Puffs/7 Days | Standard Deviation 12.19 |
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.
Time frame: Baseline, 12 Months
Population: Intent-to-Treat (ITT) population. Consists of all randomized subjects who were administered at least one bronchoscopy.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alair | Percent Days Rescue Medication Used (Change From Baseline) | -24.0 Percent Change | Standard Deviation 33.51 |
| Sham | Percent Days Rescue Medication Used (Change From Baseline) | -22.0 Percent Change | Standard Deviation 36.14 |
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.
Time frame: Baseline, 12 Months
Population: Intent-to-Treat (ITT) population. Consists of all randomized subjects who were administered at least one bronchoscopy.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alair | Percent Symptom-Free Days (Change From Baseline) | 24.4 Percent Change | Standard Deviation 36.16 |
| Sham | Percent Symptom-Free Days (Change From Baseline) | 21.0 Percent Change | Standard Deviation 35.48 |
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.
Time frame: Baseline, 12 Months
Population: Intent-to-Treat (ITT) population. Consists of all randomized subjects who were administered at least one bronchoscopy.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alair | Post-Bronchodilator FEV1 (Percent Predicted) (Change From Baseline) | -2.8 Percent Change | Standard Deviation 10.74 |
| Sham | Post-Bronchodilator FEV1 (Percent Predicted) (Change From Baseline) | -2.4 Percent Change | Standard Deviation 8.33 |
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.
Time frame: Baseline, 12 Months
Population: Intent-to-Treat (ITT) population. Consists of all randomized subjects who were administered at least one bronchoscopy.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alair | Pre-Bronchodilator FEV1 (Percent Predicted) (Change From Baseline) | -1.4 Percent Change | Standard Deviation 14.71 |
| Sham | Pre-Bronchodilator FEV1 (Percent Predicted) (Change From Baseline) | -0.1 Percent Change | Standard Deviation 13.8 |
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.
Time frame: Baseline, 12 Months
Population: Intent-to-Treat (ITT) population. Consists of all randomized subjects who were administered at least one bronchoscopy.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alair | Total Symptom Score (Change From Baseline) | -1.7 Units on a scale | Standard Deviation 2.32 |
| Sham | Total Symptom Score (Change From Baseline) | -1.6 Units on a scale | Standard Deviation 2.64 |
Other Pre-specified
Days Lost From Work/School/Other Activities Due to Asthma
Time frame: 12 Months
Population: Intent-to-Treat (ITT) population. Consists of all randomized subjects who were administered at least one bronchoscopy.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alair | Days Lost From Work/School/Other Activities Due to Asthma | 1.32 Days/Subject/Year | Standard Deviation 0.36 |
| Sham | Days Lost From Work/School/Other Activities Due to Asthma | 3.9 Days/Subject/Year | Standard Deviation 1.6 |
Other Pre-specified
Emergency Room Visits for Respiratory Symptoms
Time frame: 12 Months
Population: Intent-to-Treat (ITT) population. Consists of all randomized subjects who were administered at least one bronchoscopy.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alair | Emergency Room Visits for Respiratory Symptoms | 0.07 Events/Subject/Year | Standard Deviation 0.03 |
| Sham | Emergency Room Visits for Respiratory Symptoms | 0.43 Events/Subject/Year | Standard Deviation 0.2 |
Other Pre-specified
Hospitalizations for Respiratory Symptoms
Time frame: 12 Months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alair | Hospitalizations for Respiratory Symptoms | 0.04 Events/Subject/Year |
| Sham | Hospitalizations for Respiratory Symptoms | 0.13 Events/Subject/Year |
Other Pre-specified
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.
Time frame: Baseline, 12 Months
Population: Intent-to-Treat (ITT) population. Consists of all randomized subjects who were administered at least one bronchoscopy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alair | Percentage of Subjects With Severe Exacerbations Requiring Systemic Corticosteroids | 26.3 Percent of Subjects |
| Sham | Percentage of Subjects With Severe Exacerbations Requiring Systemic Corticosteroids | 39.8 Percent of Subjects |
Other Pre-specified
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.
Time frame: Baseline, 12 Months
Population: Intent-to-Treat (ITT) population. Consists of all randomized subjects who were administered at least one bronchoscopy.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alair | Rate of Severe Exacerbations Requiring Systemic Corticosteroids | 0.48 Events/Subject/Year | Standard Deviation 0.07 |
| Sham | Rate of Severe Exacerbations Requiring Systemic Corticosteroids | 0.70 Events/Subject/Year | Standard Deviation 0.12 |
Other Pre-specified
Unscheduled Physician Office Visits for Respiratory Symptoms
Time frame: 12 Months
Population: Intent-to-Treat (ITT) population. Consists of all randomized subjects who were administered at least one bronchoscopy.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alair | Unscheduled Physician Office Visits for Respiratory Symptoms | 0.28 Events/Subject/Year | Standard Deviation 0.05 |
| Sham | Unscheduled Physician Office Visits for Respiratory Symptoms | 0.36 Events/Subject/Year | Standard Deviation 0.09 |