Adherence Study in COPD Patients

Study Overview
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Brief Summary
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A randomized clinical study to assess the impact of Symbicort® pMDI medication reminders on adherence in COPD patients

Detailed Description
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Chronic obstructive pulmonary disease (COPD) is a common disease with substantial associated morbidity and mortality. COPD is the third leading cause of death in the US and claimed 133,965 US lives in 2009. In 2011 12.7 million US adults were estimated to have COPD. However, approximately 24 million US adults have evidence of impaired lung function, indicating an under diagnosis of COPD. COPD also has a potentially harmful economic impact. In 2010, COPD resulted in over 10 million office visits, nearly 1.5 million emergency department visits, 700,000 hospitalizations, and 133,575 deaths in the US. In 2010, US total medical treatment costs attributed solely to COPD (i.e., excluding comorbidities) were estimated to be $32.1 billion with an additional $3.9 billion in COPD costs resulting from worker absenteeism. Even in industrialized countries such as the US, where anti-smoking initiatives have been relatively successful, the legacy of past smoking behavior in aging populations ensures that the COPD burden will unavoidably continue to climb over the next 20 to 30 years. Adherence rates for inhaled combination therapy is poor (average 3.9 refills per year). COPD patients with lower adherence tend to have higher overall healthcare costs, as demonstrated in a 24 month study of 33,816 patients in the US, which found: Patients continuing therapy had lower costs of care by $3764 compared with patients who had ceased to take their maintenance therapy. COPD patients with higher adherence to prescribed regimens experienced fewer hospitalizations and lower Medicare costs (-$2185) than those who exhibited lower adherence behaviors. Given the poor adherence with inhaled combination therapy seen in patients with COPD, and associated morbidity/mortality and economic costs, the present study is being conducted to see if medication reminders can be used to improve adherence in this population.

Official Title
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A Randomized Clinical Study to Assess the Impact of Symbicort® pMDI Medication Reminders on Adherence in COPD Patients

Conditions
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Chronic Obstructive Pulmonary Disease (COPD

Intervention / Treatment
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* Device: Arm 1: BreatheMate device with application
* Device: Arm 2: BreatheMate device without application


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For inclusion in the study subjects should fulfil the following criteria: Signed informed consent at Visit 1 prior to any study specific procedures Outpatient adults 40 years and older A diagnosis of COPD confirmed by a post-bronchodilator Forced Expiratory Volume in 1 second/Forced Vital Capacity (FEV1/FVC) <0.70 at some point in the past 3 years. Moderate to Very Severe COPD as defined by a post-bronchodilator FEV1 <80% of predicted on most recent spirometry. Had been on an ICS/LABA combination therapy of a brand and dose approved forCOPD, for at least 3 months prior to screening. Current or previous smoker with a smoking history equivalent to 10 or more pack years (1 pack year = 20 cigarettes smoked per day for 1 year). Willing to discontinue all medications containing both a LABA and an ICS and to begin Symbicort 160/4.5 μg, 2 inhalations bid. Must be willing to make a return visit, and complete all study assessments for the duration of study. Life expectancy >12 months. Must be willing to comply with all study procedures including being able to remove and attach device to the inhaler. Must be able and willing to read and write/respond using the electronic device provided. Exclusion Criteria: Patients should not enter the study if any of the following exclusion criteria are fulfilled: Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site). Previous randomization in the present study. Patients who have been randomized in a clinical study and received an investigational product within 30 days of Visit 1 (participation is defined as the completion of a treatment related visit). Current diagnosis of asthma. Known history of drug or alcohol abuse which, in the opinion of the Investigator, may interfere with subject's ability to participate or comply with the study. An acute exacerbation of COPD that required hospitalization or emergency room visit or treatment with systemic steroids and/or antibiotics during the 28 days before Visit 1. Patients who had a COPD exacerbation within 28 days of Visit 1 can be re-screened once. Re-screening can occur no earlier than 28 days from the last dose of systemic steroids and/or antibiotics and/or hospitalization, whichever is later. Enrolled patients that have a COPD exacerbation during the run-in period, defined as worsening symptoms which in the judgment of the Investigator requires treatment with systemic steroids and/or antibiotics and/or hospitalization. Patients who had a COPD exacerbation during the run-in period can be re-screened once. Re-screening can occur no earlier than 28 days from the last dose of systemic steroid and/or antibiotics and/or hospitalization, whichever is later. Any hospital admissions due to ischemic heart disease or heart failure within 3 months of study enrollment. Any significant disease or disorder (e.g., gastrointestinal, liver, renal, neurologic, musculoskeletal, endocrine, metabolic, infectious, psychiatric, major physical impairment) which, in the opinion of the Investigator, may either put the patient at risk because of participation in the study, or may influence the results of the study, or the patient's ability to participate in the study. History of lung or upper airway cancer and any other malignancy not in remission for 5 years or more, except for patients who have had basal cell carcinoma, or in situ carcinoma of the cervix provided that the patient is in remission and curative therapy was completed at least 12 months prior to the date informed consent was obtained. Use or planned use of systemic corticosteroids as a maintenance treatment (defined as daily or every other day treatment for 21 or more days) for inflammatory or immunologic conditions unrelated to their COPD. Planned hospitalization or surgical procedure requiring inpatient stay during the study. Pregnancy, breast-feeding or planned pregnancy during the study; fertile women not using acceptable contraceptive measures, as judged by the Investigator. Female subjects who are not post-menopausal or surgically sterile must have a negative urine pregnancy test (urine dipstick test only) prior to randomization and must comply with contraceptive methods. Any clinically relevant abnormal findings in physical examination or vital signs, which in the opinion of the Investigator, may put the patient at risk because of his/her participation in the study. Known or suspected hypersensitivity to the study therapy (Symbicort). Patients who are unable or unwilling to use mobile communication devices, or patients who plan to be away from home for a significant part of the study without access to cellular connectivity are excluded because of the challenges of collecting data and providing information to these patients who are unable to use the service. Patients with thoracic surgery within 6 months of Visit 1. Patients who have received a lung transplant or are currently active on the lung transplant waiting list.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 130 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: BreatheMate device and application<br>BreatheMate Bluetooth device that attaches to Symbicort pressurized Metered Dose Inhaler (pMDI) and cell phone with application that sends medication and refill reminders and reminders to complete a COPD questionnaire | Device: Arm 1: BreatheMate device with application<br>* The service known as 'BreatheMate' is a patient support tool that monitors daily Symbicort inhaler use. The BreatheMate service includes a bluetooth monitoring device that is attached to subjects' Symbicort pMDI inhaler which automatically detects and logs their maintenance medication use. Subjects will receive audio-visual daily reminders (beeps and flashes) on the BreatheMate Bluetooth device. The bluetooth device transmits this data to a cellular phone that is provided to all subjects in the study. Subjects in the intervention group will also receive audio-visual alerts (beeps, flashes) from the bluetooth device to take their medication.<br>|
| Placebo Comparator: BreatheMate device without application<br>BreatheMate Bluetooth device that attaches to Symbicort pressurized Metered Dose Inhaler (pMDI) and cell phone without any reminders or alerts. | Device: Arm 2: BreatheMate device without application<br>* The service known as 'BreatheMate' is a patient support tool that monitors daily Symbicort inhaler use. The BreatheMate service includes a bluetooth monitoring device that is attached to subjects' Symbicort pMDI inhaler which automatically detects and logs their maintenance medication use. The functionality of audio-visual daily reminders (beeps and flashes) is deactivated for this control group. The BreatheMate service also includes a cellular phone that will display whether the Bluetooth monitoring device is paired and communicating with the cellular phone. The Bluetooth device will transmit data regarding medication usage to the cellular phone.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Number of Adherent Sets of Symbicort Puffs Per Day Over the 26-Week Study Period | The mean number of adherent sets of Symbicort puffs per day for each group, over an average of 26 weeks was calculated. An adherent set of puffs was defined as exactly 2 sets of 2 Symbicort puffs per day. The 2 puffs that constitute a set must have been taken within 60 minutes of each other. A mean of 2.00 sets would be equal to 100% adherence (2 sets of 2 puffs). Subjects who did not take exactly 2 sets of 2 puffs on any given day throughout their device time on study were considered non-adherent for that day. | From baseline to end of treatment (EOT), (6 months). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Clinical COPD Questionnaire (CCQ) Scores at Baseline, EOT, and Mean Change in Score Over the 26-Week Study Period. | The CCQ is a 10-item measure of a subject's COPD symptoms, divided into 3 domains (Symptoms: Items 1, 2, 5 and 6; Functional State: Items 7, 8, 9, and 10; and Mental State: Items 3 and 4). Individual items within the CCQ were equally weighted. The total score was calculated by adding the scores of the 10 items and dividing that number by 10 (=number of items). In addition, individual domain scores were calculated. The total CCQ score and each of the 3 domain scores range from 0 (very good health status) to 6 (extremely poor health status). CCQ data was collected for all subjects at baseline and EOT visits. The mean CCQ total and domain scores at both baseline and 26 weeks (EOT) are presented along with the mean change from baseline at EOT or week 26. A positive change indicates worsening symptoms and a higher value is indicative of a poorer health status. | From baseline to EOT (6 months). | 
| Mean Total and Domain Weekly CCQ Scores Over Each 2-Month Study Interval for the Intervention Group. | The CCQ is a 10-item measure of a subject's COPD symptoms, divided into 3 domains (Symptoms: Items 1, 2, 5 and 6; Functional State: Items 7, 8, 9, and 10; and Mental State: Items 3 and 4). Individual items within the CCQ were equally weighted. The total score was calculated by adding the scores of the 10 items and dividing that number by 10 (=number of items). Individual domain scores were also calculated. The total CCQ score and each of the 3 domain scores range from 0 (very good health status) to 6 (extremely poor health status). Subjects in the intervention group took the CCQ weekly throughout the study. The 26-week treatment period was broken down into 3, 2-month intervals: Interval 1: from study day 1 to study day 63 (inclusive), Interval 2: study day 64 to study day 126 (inclusive), Interval 3: study day 127 to EOT (inclusive). The last week of each 2-month interval was used to represent that interval and results are presented for the total CCQ score and the 3 domain scores. | From baseline to EOT (6 months). | 
| Mean Number of Adherent Sets of Puffs Per Day for Each 2-Month Study Interval. | The mean number of adherent sets of Symbicort puffs per day was calculated for each subject, for each of the 3, 2-month study intervals. Interval 1: from study day 1 to study day 63 (inclusive); Interval 2: study day 64 to study day 126 (inclusive); Interval 3: study day 127 to EOT (inclusive). A set is 2 puffs taken on the same calendar day, with the 2 puffs taken within 60 minutes of each other. The mean number of sets of Symbicort puffs per day was determined only for the days during device time on study for each subject. | From baseline to EOT (6 months). | 
| Mean Number of Adherent Days Over the 26-Week Study Period. | The total number of adherent days was defined as the number of treatment days a subject took 2 sets of 2 puffs of Symbicort and the inhalations in a puff set were within 60 minutes of each other. Subjects who did not take exactly 2 sets of 2 puffs on any given day throughout their device time on study were considered non-adherent for that day. The total number of adherent days for each subject was counted over the 26 week treatment period and the mean number of adherent days per group is presented. | From baseline to EOT (6 months). | 
| Mean Number of Symbicort Prescription Refills at Pharmacy Over the 26-Week Study Period. | The total number of Symbicort prescriptions filled at a pharmacy during the 26-week treatment period was counted per subject. The mean number of Symbicort 30-day prescription refills per subject was then calculated and presented per group. | From baseline to EOT (6 months). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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chronic obstructive pulmonary disease, COPD, Respiratory, adherence, medication reminders