COPD, COPD Exacerbation Acute
Conditions
Keywords
COPD, Digihaler, Rescue Medication, Disease Management
Brief summary
A pilot study to explore the utilization of the TEVA ProAir Digihaler rescue medication use and inhalation parameters to identify disease deterioration to help in the management of COPD patients in clinical practice. The study is designed to follow a small sample size of patients with COPD, monitor and collect inhalation parameters from the Digihaler dashboard, and changes in symptom control as measured by the COPD Assessment Test (CAT) to identify potential inhalation parameter thresholds that could be applied to the management of patients with COPD in clinical practice.
Detailed description
The trial is an unblinded open label single center study designed to identify trends in Peak Inspiratory Flow (PIF) rates and Rescue Albuterol Inhaler usage (Inhalations) that associate with disease deterioration as defined by worsening of symptoms and reduced lung function in patients with COPD. The study will consist of a run-in period of approximately 2 weeks, a treatment period of 6 months and a follow-up period of 1 week. Twenty (20) patients with COPD requiring intermittent short acting beta agonist (SABA) rescue inhaler usage, but not requiring frequent SABA nebulizer rescue usage, will be enrolled. After signing informed consent, patients will undergo a screening evaluation. During the run-in period, patients will continue on their COPD maintenance treatments, while discontinuing all previously prescribed periodic use rescue medications. Upon completion of screening, all patients will be dispensed a ProAir Digihaler to be used exclusively as their rescue medication throughout the duration of the study. During the run-in period all rescue inhaler usage will be electronically monitored and patient data from the Digihaler Dashboard will be downloaded every other business day basis (Monday, Wednesday and Friday). At the completion of at least 2 weeks of run-in (with a minimum of at least 8 rescue inhaler usages) and with documentation of stable clinical status throughout run-in, the patient will return for baseline testing; including vital signs, health related quality of life and Anthonisen Exacerbation questionnaires, pre and post bronchodilator spirometry and 6-minute walk testing (see table/flow chart). Average Peak Inspiratory Flow (Baseline PIF) and average Number of Rescue Inhalations per day (Baseline Inhalations) will be determined from the Digihaler Dashboard Data downloads during run-in. In the event that the patient does not meet number of rescue inhaler usages or does not have a stable clinical status during run-in, an additional 2 weeks of run-in may be obtained. If at the end of the extended run-in period so that Baseline PIF and Baseline Inhalations cannot be determined or the patient continues to be clinically unstable, the patient will be discontinued from the study. If the patient has an upper respiratory tract infection or COPD exacerbation during run-in, they will also be discontinued from the study. Patients may be re-screened one time at a later date, when stable. Once run-in and baseline testing are complete, all patients will continue on their maintenance COPD medications and use the ProAir Digihaler rescue SABA exclusively for the next 6 months. Patients will be provided with paper forms of the CAT, BCSS and Anthonisen Exacerbation criteria, to be completed at home on a weekly basis and mailed to the research center upon completion). Throughout the treatment period, all rescue inhaler usage will be electronically transmitted to, monitored at and downloaded from the Digihaler Dashboard by the research center on every other business day basis (Monday, Wednesday and Friday). At the completion of each Digihaler Dashboard Data Download, comparisons of Daily PIF (average PIF of all rescue inhalations in a day) and Daily Inhalations (number of rescue inhalations in a day) to Baseline PIF and Baseline Inhalations will be made. All patients with Daily Inhalations exceeding Baseline Inhalations by ≥4 Inhalations per day and/or with a Daily PIF ≤80% of Baseline PIF for 2 consecutive days will be DEFINED as at risk. For each at risk event, the patient will be contacted, their health status reviewed, and CAT and Anthonisen Exacerbation questionnaires will be administered. Based on symptoms, patients may also be advised to seek additional medical care. All patients will be contacted on a monthly basis, irrespective of risk findings and seen in person every 3 months. All medication usage (including ProAir Digihaler medication usage), changes in medical care, healthcare contacts and usage, and any adverse events will be recorded. All office records for the intervening time period will be reviewed and Information for any non-office healthcare contacts and usage will be requested to provide detailed clinical information for comparison to Digihaler usage records. At months 3 and 6 on treatment, all subjects will return to the research center, where vital signs, Anthonisen Exacerbation and CAT questionnaires, and post bronchodilator spirometry will be assessed. All medication usage (including ProAir Digihaler medication usage), changes in medical care, healthcare contacts and usage, and any adverse events will be recorded. All office records for the intervening time period will be reviewed and Information for any non-office healthcare contacts and usage will be requested to provide detailed clinical information for comparison to Digihaler usage records. Three (3) new ProAir Digihalers will be dispensed at month 3. Throughout the treatment period, all rescue inhaler usage will be electronically monitored and downloaded from the Digihaler Dashboard by the research center on an every other business day basis (Monday, Wednesday and Friday). At the completion of each Digihaler Dashboard Data Download, comparisons of Daily PIF (average PIF of all rescue inhalations in a day) and Daily Inhalations (number of rescue inhalations in a day) to Baseline PIF and Baseline Inhalations will be made. All patients with Daily Inhalations exceeding Baseline Inhalations by ≥4 Inhalations per day and/or with a Daily PIF ≤80% of Baseline PIF for 2 consecutive days will be DEFINED as at risk. For each at risk event, the patient will be contacted, their health status reviewed, and CAT and Anthonisen Exacerbation questionnaires will be administered. Based on symptoms, patients may also be advised to seek additional medical care. At the conclusion of the 6-month treatment period the patients will return to the research center for a final visit, returning all study medication not previously returned. The patient will be advised to resume usage of their prior rescue inhaler medication at that time. A telephone call will be made to the patient 1 week after their final in-person visit, to assess vital status and any adverse events that may have occurred subsequent to discontinuing the ProAir Digihaler.
Interventions
DRUGProAir Digihaler
Monitor parameters transmitted from the Proair Digihaler to the Digihaler Dashboard, including peak inspiratory Flow, inspiratory volume and frequency of rescue use
DEVICEDigihaler
Monitor parameters transmitted from the Proair Digihaler to the Digihaler Dashboard, including peak inspiratory Flow, inspiratory volume and frequency of rescue use
Sponsors
Teva Branded Pharmaceutical Products R&D, Inc.
Pulmonary Research Institute of Southeast Michigan
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
45 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Documented history of COPD by ATS/GOLD criteria 2. Age \> 45 years 3. Patient willing and able to: 1. participate in the study, including all scheduled visits 2. demonstrate the ability to use the ProAir Digihaler, including transfer of Digihaler data via blue-tooth to a smart device 3. perform all required testing, including spirometry and walk tests 4. complete all home questionnaires and participate in all telephone contacts 5. switch current rescue inhaler/device to ProAir Digihaler 4. Baseline spirometry consistent with COPD (post bronchodilator FEV1 \< 80% predicted, FEV1/FVC \<70%) 5. Use of albuterol inhaler as primary device for administration of rescue therapy 6. Reported use of rescue inhaler at least twice (4 inhalations) a week in the previous 6 months 7. Access to smartphone with blue-tooth and cellular/internet access
Exclusion criteria
1. Allergy, contraindication or inability to use albuterol sulfate 2. Frequent use of a nebulizer as rescue therapy (\>1 time per day) 3. Current diagnosis of asthma 4. Unstable medical condition that could prevent the completion of the research trial 5. Pregnancy, planning to become pregnant or breast feeding 6. Failure to use rescue inhaler during Run-in period (minimum of at least 8 rescue inhaler inhalations over the 2 weeks) 7. Exacerbations that require discontinuation from study (during run-in period)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PIF Alerts and COPD Exacerbations | 6 months | Presence of a Peak Inspiratory Flow (PIF) alert prior to a COPD Exacerbation Peak Inspiratory Flow (PIF) is the maximal inspiratory flow achieved during each patient inhalation of the Digihaler dry powder inhaler. PIF is automatically measured by the Digihaler dry powder inhaler during every inspiration of medication by a subject. Inspiratory flow is used to inhale respiratory medications into the lungs. A low inspiratory flow rate has been considered to place a COPD patient at risk for reducing medication inhalation and for other adverse outcomes. An acute fall in a patient's PIF may also be a marker of an impending change in a patient's condition. All acute COPD exacerbations were assessed by patient history, diaries and direct patient interviews. If a COPD Exacerbation had occurred, PIF measurements in the prior 2 weeks were assessed to determine if a PIF Alert, defined as a 20% fall in PIF from baseline for a minimum of 2 consecutive days, had occurred in the 2 weeks prior. |
| Low PIF Alerts and Worsening CAT Score | 6 months | Presence of a Low Peak Inspiratory Flow (PIF) alert, defined by an 20% reduction in PIF from baseline for a minimum of 2 consecutive days occurring in the 2 weeks prior to a worsening of a subject COPD Assessment Test Score (CAT, score range 0-40, clinically important difference defined as a change in CAT score of 2 or more over time with an increase in value identifying worsening disease). Peak Inspiratory Flow (PIF) is the maximal inspiratory flow achieved during each patient inhalation of the Digihaler dry powder inhaler. PIF is automatically measured and recorded by the Digihaler device during every inspiration of medication with the device. All PIF measures in the 2 weeks prior to any worsening of CAT were assessed and a PIF alert was identified as being present if PIF fell by ≥20% from baseline on 2 or more consecutive days in the 2 weeks prior to a worsening of CAT score event. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rescue SABA Puff Use Alerts and COPD Exacerbations | 6 months | Presence of a Rescue SABA Puff Use Alert, defined as an increase of 2 or more rescue inhaler puffs per day above baseline for 2 or more days in the 2 weeks prior to any COPD exacerbation. Rescue SABA Puff use is the counted and recorded use of the DIgihaler inhaler device each time the subject uses of the Digihaler device. |
| Low IV Alerts and COPD Exacerbations | 6 months | Presence of a Low Inhalation Volume (IV) alert, defined by a 20% fall in IV from baseline for 2 or more days in the 2 weeks prior to any COPD exacerbation. IV is the volume of air inhaled and measured during each patient inhalation use of the Digihaler device. |
Countries
United States
Participant flow
Recruitment details
Recruitment initiated May 19, 2021. Study completed June 20, 2022. The study was conducted at a single clinical research center, the Pulmonary Research Institute of Southeast Michigan.
Pre-assignment details
27 subjects were recruited and consented to enroll 20 subjects for 6 months of observation. 7 participants failed during run-in: 4 due to COPD exacerbation during run-in, 1 did not meet FEV1 entry criteria and 2 withdrew during run-in unrelated to study participation. All 20 participants enrolled in the study completed the study and were included in all analysis.Post study, subjects were stratified based on the occurrence of a COPD exacerbation during the study and analyzed accordingly.
Participants by arm
| Arm | Count |
|---|---|
| Subjects With COPD Exacerbations All subjects meeting inclusion exclusion criteria who had an exacerbation during the study | 11 |
| Subjects With no COPD Exacerbation All subjects meeting inclusion exclusion criteria who did not have an exacerbation during the study | 9 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 4 |
| Overall Study | Did not meet FEV1 criteria | 1 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Subjects With COPD Exacerbations | Subjects With no COPD Exacerbation | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 5 Participants | 4 Participants | 9 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 5 Participants | 11 Participants |
| Age, Continuous | 66 years | 67 years | 67 years |
| Baseline PIF | 73.6 L/min STANDARD_DEVIATION 23.2 | 66.2 L/min STANDARD_DEVIATION 18.3 | 70.3 L/min STANDARD_DEVIATION 21 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Region of Enrollment United States | 11 participants | 9 participants | 20 participants |
| Sex: Female, Male Female | 9 Participants | 3 Participants | 12 Participants |
| Sex: Female, Male Male | 2 Participants | 6 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 27 |
| other Total, other adverse events | 16 / 27 |
| serious Total, serious adverse events | 3 / 27 |
Outcome results
Primary
Low PIF Alerts and Worsening CAT Score
Presence of a Low Peak Inspiratory Flow (PIF) alert, defined by an 20% reduction in PIF from baseline for a minimum of 2 consecutive days occurring in the 2 weeks prior to a worsening of a subject COPD Assessment Test Score (CAT, score range 0-40, clinically important difference defined as a change in CAT score of 2 or more over time with an increase in value identifying worsening disease). Peak Inspiratory Flow (PIF) is the maximal inspiratory flow achieved during each patient inhalation of the Digihaler dry powder inhaler. PIF is automatically measured and recorded by the Digihaler device during every inspiration of medication with the device. All PIF measures in the 2 weeks prior to any worsening of CAT were assessed and a PIF alert was identified as being present if PIF fell by ≥20% from baseline on 2 or more consecutive days in the 2 weeks prior to a worsening of CAT score event.
Time frame: 6 months
Population: All worsening of CAT score events
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| COPD Exacerbation | Low PIF Alerts and Worsening CAT Score | 3 Low PIF Alert |
Primary
PIF Alerts and COPD Exacerbations
Presence of a Peak Inspiratory Flow (PIF) alert prior to a COPD Exacerbation Peak Inspiratory Flow (PIF) is the maximal inspiratory flow achieved during each patient inhalation of the Digihaler dry powder inhaler. PIF is automatically measured by the Digihaler dry powder inhaler during every inspiration of medication by a subject. Inspiratory flow is used to inhale respiratory medications into the lungs. A low inspiratory flow rate has been considered to place a COPD patient at risk for reducing medication inhalation and for other adverse outcomes. An acute fall in a patient's PIF may also be a marker of an impending change in a patient's condition. All acute COPD exacerbations were assessed by patient history, diaries and direct patient interviews. If a COPD Exacerbation had occurred, PIF measurements in the prior 2 weeks were assessed to determine if a PIF Alert, defined as a 20% fall in PIF from baseline for a minimum of 2 consecutive days, had occurred in the 2 weeks prior.
Time frame: 6 months
Population: This was an observational study with one treatment arm using a single study drug during the 6 months of study. All acute COPD exacerbation events meeting Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria for an acute COPD exacerbation were assessed to determine if a PIF alert was present prior to the event. All subjects/ events were assessed as a treatment outcome (not a treatment arm).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| COPD Exacerbation | PIF Alerts and COPD Exacerbations | 2 Low PIF Alert |
Secondary
Low IV Alerts and COPD Exacerbations
Presence of a Low Inhalation Volume (IV) alert, defined by a 20% fall in IV from baseline for 2 or more days in the 2 weeks prior to any COPD exacerbation. IV is the volume of air inhaled and measured during each patient inhalation use of the Digihaler device.
Time frame: 6 months
Population: All acute COPD exacerbation events meeting Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria for an acute COPD exacerbation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| COPD Exacerbation | Low IV Alerts and COPD Exacerbations | 4 Low IV Alert |
Secondary
Rescue SABA Puff Use Alerts and COPD Exacerbations
Presence of a Rescue SABA Puff Use Alert, defined as an increase of 2 or more rescue inhaler puffs per day above baseline for 2 or more days in the 2 weeks prior to any COPD exacerbation. Rescue SABA Puff use is the counted and recorded use of the DIgihaler inhaler device each time the subject uses of the Digihaler device.
Time frame: 6 months
Population: All acute COPD exacerbation events meeting Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria for an acute COPD exacerbation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| COPD Exacerbation | Rescue SABA Puff Use Alerts and COPD Exacerbations | 0 Rescue SABA Puff Use Alert |