Adherence Study in COPD Patients

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

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02864342

Enrollment

138

Registered

2016-08-12

Start date

2016-08-12

Completion date

2017-10-31

Last updated

2018-11-20

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Chronic Obstructive Pulmonary Disease (COPD

Keywords

chronic obstructive pulmonary disease, COPD, Respiratory, adherence, medication reminders

Brief summary

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

Detailed description

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.

Interventions

DEVICEArm 1: BreatheMate device with application

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.

DEVICEArm 2: BreatheMate device without application

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.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

40 Years to 130 Years

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
Mean Number of Adherent Sets of Symbicort Puffs Per Day Over the 26-Week Study Period	From baseline to end of treatment (EOT), (6 months).	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.

Secondary

Measure	Time frame	Description
Mean Clinical COPD Questionnaire (CCQ) Scores at Baseline, EOT, and Mean Change in Score Over the 26-Week Study Period.	From baseline to EOT (6 months).	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.
Mean Total and Domain Weekly CCQ Scores Over Each 2-Month Study Interval for the Intervention Group.	From baseline to EOT (6 months).	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.
Mean Number of Adherent Sets of Puffs Per Day for Each 2-Month Study Interval.	From baseline to EOT (6 months).	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.
Mean Number of Adherent Days Over the 26-Week Study Period.	From baseline to EOT (6 months).	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.
Mean Number of Symbicort Prescription Refills at Pharmacy Over the 26-Week Study Period.	From baseline to EOT (6 months).	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.

Countries

United States

Participant flow

Recruitment details

Subjects with chronic obstructive pulmonary disease (COPD) were recruited into 8 study sites in the United States from August 2016 to October 2017. The study evaluated the impact of medication reminders on adherence to Symbicort pressurized metered dose inhaler (pMDI) using a BreatheMate bluetooth device that monitored daily Symbicort inhaler use.

Pre-assignment details

Subjects who entered the study already on a stable dose of Symbicort were enrolled and randomized at Visit 1 followed by a 26-week treatment period. Subjects who converted to Symbicort were enrolled at Visit 1 and entered a 25-day run-in period after which they were randomized at Visit 2, followed by a 26-week treatment period.

Participants by arm

Arm	Count
Control Group All subjects took Symbicort pMDI budesonide/formoterol, 160/4.5 micrograms (mcg) x 2 actuations twice daily (BID), for oral inhalation from day 1 (baseline) of the treatment phase. Subjects randomized to the control group received Symbicort pMDI and a BreatheMate bluetooth monitoring device that monitored daily Symbicort inhaler use, as well as a study-supplied cellular phone that paired with the BreatheMate device to transmit data regarding Symbicort usage. Subjects in the control group did not receive any reminders to take their Symbicort or any feedback regarding medication compliance.	70
Intervention Group All subjects took Symbicort pMDI, budesonide/formoterol, 160/4.5 mcg x 2 actuations BID, for oral inhalation from day 1 (baseline) of the treatment phase. Subjects randomized to the intervention group received Symbicort pMDI, a BreatheMate bluetooth monitoring device that monitored daily Symbicort inhaler use, as well as a study-supplied cellular phone that paired with the BreatheMate device to transmit data regarding Symbicort usage. Subjects in the intervention group also received audio-visual daily reminders (beeps and flashes) to take their Symbicort on the BreatheMate Bluetooth monitoring device, and medication reminders from the cellular phone application.	67
Total	137

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	1	0
Overall Study	Death	0	1
Overall Study	Device Technology Issue	6	7
Overall Study	Did Not Start Treatment with Symbicort	0	1
Overall Study	Eligibility Criteria Deviation	2	3
Overall Study	Lost Device	1	0
Overall Study	Lost to Follow-up	1	5
Overall Study	Withdrawal by Subject	4	2

Baseline characteristics

Characteristic	Intervention Group	Total	Control Group
Age, Continuous	66.7 Years STANDARD_DEVIATION 8.72	66.7 Years STANDARD_DEVIATION 8.43	66.6 Years STANDARD_DEVIATION 8.21
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants	1 Participants	1 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	67 Participants	136 Participants	69 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	1 Participants	1 Participants
Race (NIH/OMB) Black or African American	14 Participants	25 Participants	11 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	1 Participants	1 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	2 Participants	2 Participants
Race (NIH/OMB) White	53 Participants	108 Participants	55 Participants
Sex: Female, Male Female	27 Participants	60 Participants	33 Participants
Sex: Female, Male Male	40 Participants	77 Participants	37 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 70	1 / 67
other Total, other adverse events	18 / 70	15 / 67
serious Total, serious adverse events	5 / 70	8 / 67

Outcome results

Primary

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.

Time frame: From baseline to end of treatment (EOT), (6 months).

Population: The FAS consisted of screened subjects who were randomized and took at least 1 inhalation of Symbicort during the treatment phase of the study.

Arm	Measure	Value (MEAN)	Dispersion
Control Group	Mean Number of Adherent Sets of Symbicort Puffs Per Day Over the 26-Week Study Period	1.3 Adherent sets of puffs / day	Standard Deviation 0.51
Intervention Group	Mean Number of Adherent Sets of Symbicort Puffs Per Day Over the 26-Week Study Period	1.6 Adherent sets of puffs / day	Standard Deviation 0.39

Comparison: The effect of medication reminders on Symbicort adherence was evaluated using a t-test. The equality of variances was also tested and as the variances were not equal, the Satterthwaite-t test was reported.p-value: <0.001Satterthwaite t-test

Secondary

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.