Chronic Asthma, COPD
Conditions
Keywords
Adherence of inhaled medication, pharmaceutical intervention
Brief summary
Despite progress in pharmacological and non-pharmacological treatment in recent years, the burden of disease among asthma and COPD patients is high and patients may be frequently hospitalized due to exacerbations. Reasons for uncontrolled disease are manifold, but are frequently associated with poor inhalation technique and non-adherence to the prescribed treatment plan which may cause substantial mortality, morbidity, and cost to the healthcare system. In this respect, the study of causes for non-adherence and the development of measures to increase respectively maintain treatment adherence, particularly in chronic diseases, is of major clinical importance. The aim of this study was to investigate the impact of an acoustic reminder and a close supervision on adherence to inhaled medication and on course of disease and quality of life (Qol) in asthma and COPD patients. In this single-blinded trial, asthma and/or COPD patients were randomly assigned either to the intervention or the control group. Adherence to inhaled medication was monitored using electronic data capture devices, recording date and time of each inhalation device actuation. Follow-up was six months. Primary outcome was defined as time to next exacerbation. Secondary outcomes included number of exacerbations, number of exacerbations with hospitalization, taking/timing adherence, and Qol during follow-up. Adherence was measured using electronic data capture devices which saved date and time of each inhalative device actuation. Patients are randomly assigned to an intervention, respectively control group. Patients assigned to the intervention group will receive audio reminder and support calls in case medication is not been taken as prescribed or if rescue medication is used more frequently than prespecified in the study protocol. During the study, participants are assessed every two months.
Interventions
DEVICEElectronic Monitoring with audio reminders and additional support
Automated reminder: -Daily audio-reminder, generated by a smartphone. Support calls (only patients with Smartinhaler): * When the use of rescue medication doubles. * When inhaled medication was not inhaled as prescribed for more than two consecutive days. Feedback on adherence (only patients with POEMS): -At every clinical visit (after 2, 4 and 6 months).
Sponsors
University of Basel
Cantonal Hosptal, Baselland
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Inclusion: * Aged 18 years or older * Have an established asthma-diagnosis according to the Global Initiative for Asthma (GINA) guidelines and/or * Have an established COPD diagnosis according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines (severity GOLD I-IV based on the international GOLD-Criteria) \[46\] and * Are prescribed daily inhaled medication (controller medication for a daily maintenance treatment) * Had at least one exacerbation in the previous 12 months before study start * With a metered dose Inhaler (e.g. Ventolin®), Diskus (e.g.Seretide®), Turbohaler (e.g.Symbicort®), Aerolizer/Breezhaler (e.g.Onbrez®), HandiHaler (e.g. Spiriva®) or Ellipta (e.g Relvar®) Exclusion: * Suffering from malignancies and/or other severe diseases * Insufficient in the German language * Pregnant or lactating
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Next Asthma or COPD Exacerbation up to 182 Days | 182 days | The primary outcome of this study was time to next asthma or COPD exacerbation, defined as acute-onset worsening of the patient's condition beyond day-to-day variations requiring interaction with a healthcare provider. It was expressed as the number of exacerbations since the last visit with the exact period of exacerbation also including the number of exacerbations requiring hospitalisation. The first exacerbations during the study period served as reference to calculate the primary endpoint time to next exacerbation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Severe Exacerbations. | 180 days | Exacerbations with the need for hospitalization. |
| Adherence to Puff Inhalers | 180 days | Mean duration with Adherence to Puff Inhalers in the Target Range |
| Percentage of Days With Adherence to Dry Powder Capsules (Breezhaler and Handihaler) Assessed by POEMS | 180 days | percentage of days with Adherence to Dry Powder Capsules. Taking adherence = \[number of puffs inhaled during 24 hours / number of puffs prescribed during 24 hours) x 100. Correct taking adherence was considered when taking adherence was between 80-100%, based on previous studies. |
| Percentage of Days of Adherence | 180 days | percentage of days of Adherence for puff inhalers (metered dose inhalers, Turbohaler, Discus, Ellipta) assessed by Smartinhalers. |
| Percentage of Days With Timing Adherence | 180 days | percentage of days with timing Adherence for dry powder capsules (Breezhaler, Handihaler), assessed by POEMS |
| Number of Exacerbations. | 180 days | Number of exacerbations during the study period. |
| Percentage of Gaps for Dry Powder Capsules (Breezhaler, Handihaler), Assessed by POEMS. | 180 days | Percentage of Gaps = \[number of days without inhalation during the whole study period / number of days in same time period\] |
| Numbers of Days of the Longest Period of Time Without Inhalation During the Investigated Time Period | 180 days | Maximal gap length = number of consecutive days of the longest period of time without Inhalation during the investigated timeperiod.Assessed by Smartinhalers. |
| Number of Days of the Longest Period of Time Without Inhalation. | 180 days | Maximal gap length for dry powder capsules (Breezhaler, Handihaler), Assessed by POEMS = number of consecutive days of the longest period of time without inhalation. |
| Score of the St. George Respiratory Questionnaire | 180 days | Score of the St. George Respiratory Questionnaire. Quality of life was assessed using the St. George Respiratory Questionnaire. This is a questionnaire, which was developed for measuring impaired health and perceived well-being in patients with asthma and COPD. Each Subscore ranges from 0-100, higher scores indicate more limitations in one of the 4 domains. Subscore Symptoms (ranges from 0-100): higher scores indicate worse outcome Subscore Activity (ranges from 0-100): higher scores indicate worse outcome Subscore Impact (ranges from 0-100): higher scores indicate worse outcome Total Score (ranges from 0-100): higher scores indicate worse outcome. The total score is calculated as a weighted sum of the three subscores. Each questionnaire response has a unique empirically derived 'weight'. The lowest possible weight is zero and the highest is 100. |
| Percentage of Gaps in Puff Inhaler Use | 180 days | Percentage of Gaps in Puff Inhaler Use Gaps = \[number of days without inhalation during the whole study period / number of days in same time period\] x 100. |
Countries
Switzerland
Participant flow
Recruitment details
Patients from several hospitals in the Basel region and patients treated by pulmonologists in private practice are screened for eligibility. In addition, advertisement is made using posters, flyers, as well as on ad-screens. Advertisement is also placed in local newspapers. Enrolment started on January 2014 and will ended on September 2017.
Pre-assignment details
Prior to randomization, all participants take part in a training course before the baseline visit. The goal of the training course is to provide refresher training on inhalation techniques in order to ensure that all participants are at the same level of disease knowledge and use their medication correctly.
Participants by arm
| Arm | Count |
|---|---|
| Control Group Patients in the control group received a Smartinhaler/POEMS, which only records their adherence. The alarm function of the devices will be switched off, and these participants will not be reminded to take their inhalers. This group will not receive any calls, if they do not comply with the prescribed medication schedule or if they use their rescue medication too frequently. | 74 |
| Intervention Group Patients were randomly assigned either to the intervention or control group. The intervention consisted of an audio-reminder, generated by an app (in case of SmartInhaler devices) or in form of an alarm clock (for the POEMS), and directly transferred to the participant's smartphones. In addition, patients in the intervention group received support calls carried out by the pharmacist, when the use of rescue medication doubled respectively when the inhaled medication was not inhaled as prescribed for more than two consecutive days. Participants also received a feedback from the pharmacist on their adherence at each clinical visit, especially for the results of the POEMS.
Smartinhaler/POEMS with audio reminders and additional support calls: Patients assigned to the intervention group will receive a Smartinhaler/POEMS, which will contain an audio reminder function. If the alarm function is on, a ring tone will be generated, after the time predesigned for inhalation. If the use of | 75 |
| Total | 149 |
Baseline characteristics
| Characteristic | Control Group | Intervention Group | Total |
|---|---|---|---|
| Age, Continuous | 69.0 years STANDARD_DEVIATION 8.8 | 64.7 years STANDARD_DEVIATION 12.4 | 68.1 years STANDARD_DEVIATION 8.4 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Sex: Female, Male Female | 23 Participants | 29 Participants | 52 Participants |
| Sex: Female, Male Male | 51 Participants | 46 Participants | 97 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 84 | 0 / 81 |
| other Total, other adverse events | 0 / 84 | 0 / 81 |
| serious Total, serious adverse events | 0 / 84 | 0 / 81 |
Outcome results
Primary
Time to Next Asthma or COPD Exacerbation up to 182 Days
The primary outcome of this study was time to next asthma or COPD exacerbation, defined as acute-onset worsening of the patient's condition beyond day-to-day variations requiring interaction with a healthcare provider. It was expressed as the number of exacerbations since the last visit with the exact period of exacerbation also including the number of exacerbations requiring hospitalisation. The first exacerbations during the study period served as reference to calculate the primary endpoint time to next exacerbation.
Time frame: 182 days
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Intervention Group | Time to Next Asthma or COPD Exacerbation up to 182 Days | 172 days to first exacerbation |
| Control Group | Time to Next Asthma or COPD Exacerbation up to 182 Days | 161 days to first exacerbation |
Secondary
Adherence to Puff Inhalers
Mean duration with Adherence to Puff Inhalers in the Target Range
Time frame: 180 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention Group | Adherence to Puff Inhalers | 81.6 days in target range | Standard Deviation 14.2 |
| Control Group | Adherence to Puff Inhalers | 60.1 days in target range | Standard Deviation 30.3 |
Secondary
Number of Days of the Longest Period of Time Without Inhalation.
Maximal gap length for dry powder capsules (Breezhaler, Handihaler), Assessed by POEMS = number of consecutive days of the longest period of time without inhalation.
Time frame: 180 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention Group | Number of Days of the Longest Period of Time Without Inhalation. | 2.6 days | Standard Deviation 2.7 |
| Control Group | Number of Days of the Longest Period of Time Without Inhalation. | 5.9 days | Standard Deviation 5.2 |
Secondary
Number of Exacerbations.
Number of exacerbations during the study period.
Time frame: 180 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention Group | Number of Exacerbations. | 0.3 number of exacerbations | Standard Deviation 0.6 |
| Control Group | Number of Exacerbations. | 0.5 number of exacerbations | Standard Deviation 1 |
Secondary
Number of Severe Exacerbations.
Exacerbations with the need for hospitalization.
Time frame: 180 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention Group | Number of Severe Exacerbations. | 0.08 severe exacerbations | Standard Deviation 0.3 |
| Control Group | Number of Severe Exacerbations. | 0.08 severe exacerbations | Standard Deviation 0.4 |
Secondary
Numbers of Days of the Longest Period of Time Without Inhalation During the Investigated Time Period
Maximal gap length = number of consecutive days of the longest period of time without Inhalation during the investigated timeperiod.Assessed by Smartinhalers.
Time frame: 180 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention Group | Numbers of Days of the Longest Period of Time Without Inhalation During the Investigated Time Period | 1.6 days | Standard Deviation 2 |
| Control Group | Numbers of Days of the Longest Period of Time Without Inhalation During the Investigated Time Period | 11.6 days | Standard Deviation 25.6 |
Secondary
Percentage of Days of Adherence
percentage of days of Adherence for puff inhalers (metered dose inhalers, Turbohaler, Discus, Ellipta) assessed by Smartinhalers.
Time frame: 180 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention Group | Percentage of Days of Adherence | 68.9 % of days in target range | Standard Deviation 25 |
| Control Group | Percentage of Days of Adherence | 50.6 % of days in target range | Standard Deviation 32.5 |
Secondary
Percentage of Days With Adherence to Dry Powder Capsules (Breezhaler and Handihaler) Assessed by POEMS
percentage of days with Adherence to Dry Powder Capsules. Taking adherence = \[number of puffs inhaled during 24 hours / number of puffs prescribed during 24 hours) x 100. Correct taking adherence was considered when taking adherence was between 80-100%, based on previous studies.
Time frame: 180 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention Group | Percentage of Days With Adherence to Dry Powder Capsules (Breezhaler and Handihaler) Assessed by POEMS | 89.6 % of days in target range | Standard Deviation 9.8 |
| Control Group | Percentage of Days With Adherence to Dry Powder Capsules (Breezhaler and Handihaler) Assessed by POEMS | 80.2 % of days in target range | Standard Deviation 21.3 |
Secondary
Percentage of Days With Timing Adherence
percentage of days with timing Adherence for dry powder capsules (Breezhaler, Handihaler), assessed by POEMS
Time frame: 180 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention Group | Percentage of Days With Timing Adherence | 79.6 % of days in target range | Standard Deviation 12.9 |
| Control Group | Percentage of Days With Timing Adherence | 71.7 % of days in target range | Standard Deviation 22 |
Secondary
Percentage of Gaps for Dry Powder Capsules (Breezhaler, Handihaler), Assessed by POEMS.
Percentage of Gaps = \[number of days without inhalation during the whole study period / number of days in same time period\]
Time frame: 180 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention Group | Percentage of Gaps for Dry Powder Capsules (Breezhaler, Handihaler), Assessed by POEMS. | 4.6 % gaps | Standard Deviation 4.4 |
| Control Group | Percentage of Gaps for Dry Powder Capsules (Breezhaler, Handihaler), Assessed by POEMS. | 9.8 % gaps | Standard Deviation 8.9 |
Secondary
Percentage of Gaps in Puff Inhaler Use
Percentage of Gaps in Puff Inhaler Use Gaps = \[number of days without inhalation during the whole study period / number of days in same time period\] x 100.
Time frame: 180 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention Group | Percentage of Gaps in Puff Inhaler Use | 3.2 % of gaps | Standard Deviation 4.7 |
| Control Group | Percentage of Gaps in Puff Inhaler Use | 11.7 % of gaps | Standard Deviation 18.6 |
Secondary
Score of the St. George Respiratory Questionnaire
Score of the St. George Respiratory Questionnaire. Quality of life was assessed using the St. George Respiratory Questionnaire. This is a questionnaire, which was developed for measuring impaired health and perceived well-being in patients with asthma and COPD. Each Subscore ranges from 0-100, higher scores indicate more limitations in one of the 4 domains. Subscore Symptoms (ranges from 0-100): higher scores indicate worse outcome Subscore Activity (ranges from 0-100): higher scores indicate worse outcome Subscore Impact (ranges from 0-100): higher scores indicate worse outcome Total Score (ranges from 0-100): higher scores indicate worse outcome. The total score is calculated as a weighted sum of the three subscores. Each questionnaire response has a unique empirically derived 'weight'. The lowest possible weight is zero and the highest is 100.
Time frame: 180 days
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Intervention Group | Score of the St. George Respiratory Questionnaire | Subscore Activity | 45.2 score on a scale | Standard Deviation 19.3 |
| Intervention Group | Score of the St. George Respiratory Questionnaire | Total Score | 32.5 score on a scale | Standard Deviation 14.7 |
| Intervention Group | Score of the St. George Respiratory Questionnaire | Subscore Impact | 21.8 score on a scale | Standard Deviation 14.6 |
| Intervention Group | Score of the St. George Respiratory Questionnaire | Subscore Symptoms | 45.7 score on a scale | Standard Deviation 21.5 |
| Control Group | Score of the St. George Respiratory Questionnaire | Subscore Impact | 29.3 score on a scale | Standard Deviation 20.7 |
| Control Group | Score of the St. George Respiratory Questionnaire | Subscore Activity | 52.4 score on a scale | Standard Deviation 23.7 |
| Control Group | Score of the St. George Respiratory Questionnaire | Subscore Symptoms | 48.7 score on a scale | Standard Deviation 25.6 |
| Control Group | Score of the St. George Respiratory Questionnaire | Total Score | 39.6 score on a scale | Standard Deviation 20.3 |