Asthma
Conditions
Keywords
Adults, Severe persistent, AirDuo Digihaler, ProAir Digihaler
Brief summary
This trial is being completed to determine baseline inhalation parameters and patterns of use in patients receiving treatment with TEVA digital inhalers, to develop predictive models for asthma exacerbations and response to biologics using data collected from these devices. Enrolled participants will complete questionnaires along with other study specific procedures. Additionally, in-person and phone visits will be performed.
Detailed description
All participants were provided an AirDuo® Digihaler™ and ProAirDuo® Digihaler™, which the participants could choose to use or not. This trial did not restrict participants from using other asthma treatments in addition to or in lieu of the Digihalers.
Interventions
COMBINATION_PRODUCTAirDuo Digihaler
Participants will receive the AirDuo® Digihaler™ at a dose that is equivalent to the participants' current inhaled therapy dose. Most participants will likely require the high dose inhaler: 232/14 device. This medication will be administered twice daily. The study and treatment will last 1 year. Participants will also use a home spirometry device and smart device application (app) will be used to track medication usage and allow users to self-assess their respiratory symptoms on a daily basis.
COMBINATION_PRODUCTProAir Digihaler
Participants will receive the ProAir® Digihaler™ 90mcg at a dose that is equivalent to the participants' current inhaled therapy dose. Most participants will likely require the high dose inhaler: 232/14 device. The ProAir® Digihaler™ will be utilized up to six times per day as needed for acute asthma symptoms. The study and treatment will last 1 year.
Sponsors
University of Michigan
Teva Branded Pharmaceutical Products R&D, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
HEALTH_SERVICES_RESEARCH
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* A history of severe persistent asthma as defined by European Respiratory Society (ERS) and American Thoracic Society (ERS/ATS) criteria which includes the presence of poor asthma control on high dose inhaled corticosteroid (ICS) and a long-acting beta-agonist (CS/LABA) or the need for high dose ICS/LABA to maintain asthma control or oral steroids for maintenance therapy for more than 50% of the prior year. * Presence of current biologic use or planned initiation of biologics following study enrollment * Patients will be categorized on the basis of asthma control (Asthma Control Test (ACT)\< 19 will be considered poor asthma control). The study will cap the patients with good asthma control at 30% and will no longer enroll those patients once the strata have been fully enrolled. * Willingness to switch maintenance inhalers to AirDuo® Digihaler™ and to use ProAir® Digihaler™ for rescue therapy. Use of nebulized albuterol will be discouraged but not prohibited. * Can read and communicate in English and is familiar with and is willing to use his/her own smart device and download and use the study application * Ability to provide informed consent. * The patient must be willing and able to comply with study requirements and restrictions
Exclusion criteria
* Clinically important pulmonary disease other than asthma including Chronic obstructive pulmonary disease (COPD), bronchiectasis, pulmonary fibrosis, cystic fibrosis, or other lung disease * Any disorder that is either not stable or could in the opinion of the investigator affect the ability of the subject to safely participate in the study or could adversely affect study results. * History of human immunodeficiency virus or other immunodeficiency syndrome * Malignancy other than skin cancer that has occurred within the past year and that will impact survival thus limit participation in the clinical trial * History of chronic alcohol abuse or drug use * Any life-threatening diseases that will impact the patient's ability to complete the 12-month study period
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Number of Daily Doses AirDuo® Digihaler™. | up to 1 year | This outcome measured participant adherence to using the AirDuo® Digihaler™. All participants were provided the Digihaler, which they could choose to use or not. Subject-specific result was calculated as the sum total of doses for a given participant divided by their number of days of follow-up. |
| Mean Number of Daily Doses of ProAir® Digihaler™ | up to 1 year | This outcome measured participant adherence to using the ProAir® Digihaler™. All participants were provided the Digihaler device, which they could choose to use or not. Subject-specific result was calculated as the sum total of doses taken by participant divided by their number of days of follow-up. |
| Median Number of Daily Doses of AirDuo® Digihaler™ | up to 1 year | This outcome measured participant adherence to using the AirDuo® Digihaler™. All participants were provided the Digihaler, which they could choose to use or not. Subject-specific result was calculated as the 50th percentile value of all daily dose totals (or the average of two 50th percentile values if there was a tie) calculated over the number of days of follow-up. |
| Median Number of Daily Doses of ProAir® Digihaler™ | up to 1 year | This outcome measured participant adherence to using the ProAir® Digihaler™. All participants were provided the Digihaler, which they could choose to use or not. Subject-specific result was calculated as the 50th percentile value of all daily dose totals (or the average of two 50th percentile values if there was a tie) calculated over the number of days of follow-up. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Mean Peak Inspiratory Flow (PIF) | baseline up to 1 year | PIF is the maximum rate of airflow a person can inhale using an inhaler after a full breath. PIF was measured by the ProAir® Digihaler™ and AirDuo® Digihaler™. Results indicate the changes between the baseline and exacerbation measurements. |
| Change in Mean Forced Expiratory Volume in One Second (FEV1) | baseline up to 1 year | FEV1 was measured using the Go Spiro Spirometer. Results indicate the difference between the baseline and exacerbation measurements. |
| Change in Mean Inspiratory Time | baseline to 1 year | Inspiratory time was the total time taken to complete an inspiration (i.e., breathing in). Results were differences between the baseline and exacerbation measurements. |
| Maintenace Inhaler Adherence Rates | up to 1 year | This outcome measured participant adherence to using the AirDuo® Digihaler™. All participants were provided the Digihaler, which they could choose to use or not. Adherence rates were measured by the following: High (\>80% of puffs), moderate (50-80% of puffs), and low levels (\<50% of puffs) of adherence to maintenance inhalers over the course of the trial. |
| Participants Who Achieved Non-response, Partial Response, and Complete Response to Biologics | up to 1 year | All participants were provided the AirDuo® and ProAir® Digihalers, which they could choose to use or not. Responses were categorized as non-response, partial response, and complete response on the basis of five factors: a 50% reduction in exacerbations, any reduction in maintenance oral corticosteroids (OCS) dose, change of at least 10% in forced expiratory volume in one second (FEV1), improvement of 3 points in asthma control test (ACT) score, and patient perception of global improvement in asthma. Non-response indicated that a participant had no response to any of the 5 factors. Partial response indicated that a participant responded to at least 1 factor. Complete response indicated that a participant responded to all 5 factors. |
| Change in Mean Peak Inhalation Volume | baseline to 1 year | Peak inhalation volume is the maximum air volume a person can breathe in during a deep inhalation, serving as an indicator of lung capacity and respiratory function. Peak inhalation volume was measured by the digital inhaler at the end of inhalation. This measures the maximum volume that the participant was able to draw into their lungs. Larger numbers indicated healthier lungs. |
Other
| Measure | Time frame |
|---|---|
| Number of Exacerbations | up to 1 year |
| Mean Asthma Control Test (ACT) Score | up to 1 year |
| Number of Emergency Room Visits | up to 1 year |
| Number of Hospitalizations | up to 1 year |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AirDuo and ProAir This trial includes using the inhaler (AirDuo®) Digihaler™ and rescue inhalers (ProAir®) Digihaler™.
AirDuo Digihaler: Participants will receive the AirDuo® Digihaler™ at a dose that is equivalent to the participants' current inhaled therapy dose. Most participants will likely require the high dose inhaler: 232/14 device. This medication will be administered twice daily. The study and treatment will last 1 year.
Participants will also use a home spirometry device and smart device application (app) will be used to track medication usage and allow users to self-assess their respiratory symptoms on a daily basis.
ProAir Digihaler: Participants will receive the ProAir® Digihaler™ 90mcg at a dose that is equivalent to the participants' current inhaled therapy dose. Most participants will likely require the high dose inhaler: 232/14 device. The ProAir® Digihaler™ will be utilized up to six times per day as needed for acute asthma symptoms. The study and treatment will last 1 year. | 100 |
| Total | 100 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 1 |
| Overall Study | Lost to Follow-up | 11 |
| Overall Study | Withdrawal by Subject | 14 |
Baseline characteristics
| Characteristic | AirDuo and ProAir |
|---|---|
| Age, Continuous | 50.8 years STANDARD_DEVIATION 14.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 94 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 16 Participants |
| Race (NIH/OMB) More than one race | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 76 Participants |
| Region of Enrollment United States | 100 Participants |
| Sex: Female, Male Female | 66 Participants |
| Sex: Female, Male Male | 34 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 | 1 / 16 | 0 / 84 | 0 / 73 | 0 / 73 |
| other Total, other adverse events | 7 / 16 | 7 / 84 | 1 / 73 | 18 / 73 |
| serious Total, serious adverse events | 5 / 16 | 0 / 84 | 2 / 73 | 8 / 73 |
Outcome results
Primary
Mean Number of Daily Doses AirDuo® Digihaler™.
This outcome measured participant adherence to using the AirDuo® Digihaler™. All participants were provided the Digihaler, which they could choose to use or not. Subject-specific result was calculated as the sum total of doses for a given participant divided by their number of days of follow-up.
Time frame: up to 1 year
Population: Because the outcome measure concerned adherence, all participants were included in this outcome, regardless of whether they chose to use the AirDuo® Digihaler™.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ProAir® Digihaler | Mean Number of Daily Doses AirDuo® Digihaler™. | 0.99 doses per day | Standard Deviation 0.76 |
Primary
Mean Number of Daily Doses of ProAir® Digihaler™
This outcome measured participant adherence to using the ProAir® Digihaler™. All participants were provided the Digihaler device, which they could choose to use or not. Subject-specific result was calculated as the sum total of doses taken by participant divided by their number of days of follow-up.
Time frame: up to 1 year
Population: Because the outcome measure concerned adherence, all participants were included in this outcome, regardless of whether they chose to use the ProAir® Digihaler™.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ProAir® Digihaler | Mean Number of Daily Doses of ProAir® Digihaler™ | 0.55 doses per day | Standard Deviation 0.95 |
Primary
Median Number of Daily Doses of AirDuo® Digihaler™
This outcome measured participant adherence to using the AirDuo® Digihaler™. All participants were provided the Digihaler, which they could choose to use or not. Subject-specific result was calculated as the 50th percentile value of all daily dose totals (or the average of two 50th percentile values if there was a tie) calculated over the number of days of follow-up.
Time frame: up to 1 year
Population: Because the outcome measure concerned adherence, all participants were included in this outcome, regardless of whether they chose to use the AirDuo® Digihaler™.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ProAir® Digihaler | Median Number of Daily Doses of AirDuo® Digihaler™ | 0.99 doses per day |
Primary
Median Number of Daily Doses of ProAir® Digihaler™
This outcome measured participant adherence to using the ProAir® Digihaler™. All participants were provided the Digihaler, which they could choose to use or not. Subject-specific result was calculated as the 50th percentile value of all daily dose totals (or the average of two 50th percentile values if there was a tie) calculated over the number of days of follow-up.
Time frame: up to 1 year
Population: Because the outcome measure concerned adherence, all participants were included in this outcome, regardless of whether they chose to use the ProAir® Digihaler™.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ProAir® Digihaler | Median Number of Daily Doses of ProAir® Digihaler™ | 0.21 doses per day |
Secondary
Change in Mean Forced Expiratory Volume in One Second (FEV1)
FEV1 was measured using the Go Spiro Spirometer. Results indicate the difference between the baseline and exacerbation measurements.
Time frame: baseline up to 1 year
Population: Measurements were taken for those participants who experienced an exacerbation and compared to their baseline values. Home spirometry was not consistently used by all participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ProAir® Digihaler | Change in Mean Forced Expiratory Volume in One Second (FEV1) | Baseline | 66.07 Liters | Standard Deviation 20.34 |
| ProAir® Digihaler | Change in Mean Forced Expiratory Volume in One Second (FEV1) | Follow Up/Exacerbation | 68.43 Liters | Standard Deviation 19.47 |
Secondary
Change in Mean Inspiratory Time
Inspiratory time was the total time taken to complete an inspiration (i.e., breathing in). Results were differences between the baseline and exacerbation measurements.
Time frame: baseline to 1 year
Population: Measurements were taken for those participants who experienced an exacerbation and compared to their baseline values. Because the ProAir is a rescue inhaler, not all individuals used it, so the number of participants involved is smaller.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ProAir® Digihaler | Change in Mean Inspiratory Time | Baseline - AirDuo | 2002.99 Seconds | Standard Deviation 853.03 |
| ProAir® Digihaler | Change in Mean Inspiratory Time | Follow Up/Exacerbation - AirDuo | 1755.44 Seconds | Standard Deviation 692.41 |
| ProAir® Digihaler | Change in Mean Inspiratory Time | Baseline - ProAir | 2268.19 Seconds | Standard Deviation 919.78 |
| ProAir® Digihaler | Change in Mean Inspiratory Time | Follow Up/Exacerbation - ProAir | 1982.48 Seconds | Standard Deviation 756.34 |
Comparison: This analysis applies only to comparison of baseline and exacerbation for AirDuop-value: 0.0008t-test, 2 sided
Comparison: This analysis applies only to comparison of baseline and exacerbation for ProAirp-value: 0.0003t-test, 2 sided
Secondary
Change in Mean Peak Inhalation Volume
Peak inhalation volume is the maximum air volume a person can breathe in during a deep inhalation, serving as an indicator of lung capacity and respiratory function. Peak inhalation volume was measured by the digital inhaler at the end of inhalation. This measures the maximum volume that the participant was able to draw into their lungs. Larger numbers indicated healthier lungs.
Time frame: baseline to 1 year
Population: Measurements were taken for those participants who experienced an exacerbation and compared to their baseline values. Because the ProAir is a rescue inhaler, not all individuals used it, so the number of participants involved is smaller.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ProAir® Digihaler | Change in Mean Peak Inhalation Volume | Baseline - AirDuo | 2436.48 milliliters | Standard Deviation 1328.27 |
| ProAir® Digihaler | Change in Mean Peak Inhalation Volume | Follow Up/Exacerbation - AirDuo | 2041.79 milliliters | Standard Deviation 803 |
| ProAir® Digihaler | Change in Mean Peak Inhalation Volume | Baseline - ProAir | 2147.69 milliliters | Standard Deviation 1201.34 |
| ProAir® Digihaler | Change in Mean Peak Inhalation Volume | Follow Up/Exacerbation - ProAir | 1833.74 milliliters | Standard Deviation 806.61 |
Comparison: This analysis applies only to comparison of baseline and exacerbation for AirDuop-value: 0.0019t-test, 2 sided
Comparison: This analysis applies only to comparison of baseline and exacerbation for ProAirp-value: 0.002t-test, 2 sided
Secondary
Change in Mean Peak Inspiratory Flow (PIF)
PIF is the maximum rate of airflow a person can inhale using an inhaler after a full breath. PIF was measured by the ProAir® Digihaler™ and AirDuo® Digihaler™. Results indicate the changes between the baseline and exacerbation measurements.
Time frame: baseline up to 1 year
Population: Measurements were taken for those participants who experienced an exacerbation and compared to their baseline values. Because the ProAir is a rescue inhaler, not all individuals used it, so the number of participants involved is smaller.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ProAir® Digihaler | Change in Mean Peak Inspiratory Flow (PIF) | Baseline - AirDuo | 103.41 Liters per minute | Standard Deviation 35.02 |
| ProAir® Digihaler | Change in Mean Peak Inspiratory Flow (PIF) | Follow Up/Exacerbation - AirDuo | 99.04 Liters per minute | Standard Deviation 29.58 |
| ProAir® Digihaler | Change in Mean Peak Inspiratory Flow (PIF) | Baseline - ProAir | 79.60 Liters per minute | Standard Deviation 27.08 |
| ProAir® Digihaler | Change in Mean Peak Inspiratory Flow (PIF) | Follow Up/Exacerbation - ProAir | 77.14 Liters per minute | Standard Deviation 23.61 |
Comparison: This analysis applies only to comparison of baseline and exacerbation for AirDuop-value: 0.04t-test, 2 sided
Comparison: This analysis applies only to comparison of baseline and exacerbation for ProAirp-value: 0.0965t-test, 2 sided
Secondary
Maintenace Inhaler Adherence Rates
This outcome measured participant adherence to using the AirDuo® Digihaler™. All participants were provided the Digihaler, which they could choose to use or not. Adherence rates were measured by the following: High (\>80% of puffs), moderate (50-80% of puffs), and low levels (\<50% of puffs) of adherence to maintenance inhalers over the course of the trial.
Time frame: up to 1 year
Population: Because the outcome measure concerned adherence, all participants were included in this outcome, regardless of whether they chose to use the AirDuo® Digihaler™.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ProAir® Digihaler | Maintenace Inhaler Adherence Rates | Moderate (50-80% of puffs) | 25 Participants |
| ProAir® Digihaler | Maintenace Inhaler Adherence Rates | Low levels (<50% of puffs) | 52 Participants |
| ProAir® Digihaler | Maintenace Inhaler Adherence Rates | High (>80% of puffs) | 23 Participants |
Secondary
Participants Who Achieved Non-response, Partial Response, and Complete Response to Biologics
All participants were provided the AirDuo® and ProAir® Digihalers, which they could choose to use or not. Responses were categorized as non-response, partial response, and complete response on the basis of five factors: a 50% reduction in exacerbations, any reduction in maintenance oral corticosteroids (OCS) dose, change of at least 10% in forced expiratory volume in one second (FEV1), improvement of 3 points in asthma control test (ACT) score, and patient perception of global improvement in asthma. Non-response indicated that a participant had no response to any of the 5 factors. Partial response indicated that a participant responded to at least 1 factor. Complete response indicated that a participant responded to all 5 factors.
Time frame: up to 1 year
Population: Because the outcome measure concerned response to biologics, all participants were included in this outcome, regardless of whether they chose to use either Digihaler or not.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ProAir® Digihaler | Participants Who Achieved Non-response, Partial Response, and Complete Response to Biologics | Non-response | 3 Participants |
| ProAir® Digihaler | Participants Who Achieved Non-response, Partial Response, and Complete Response to Biologics | Complete response | 15 Participants |
| ProAir® Digihaler | Participants Who Achieved Non-response, Partial Response, and Complete Response to Biologics | Partial response | 82 Participants |
Other Pre-specified
Mean Asthma Control Test (ACT) Score
Time frame: up to 1 year
Other Pre-specified
Number of Emergency Room Visits
Time frame: up to 1 year
Other Pre-specified
Number of Exacerbations
Time frame: up to 1 year
Other Pre-specified
Number of Hospitalizations
Time frame: up to 1 year