Improving Adherence to Statin Therapy Through a Medication Management Application

Study Overview
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Brief Summary
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Interventional study to compare standard of care vs standard of care plus the use of a medication therapy management smartphone app (mediteo m+, Mediteo GmbH, Heidelberg) in patients with atherosclerotic cardiovascular disease and indication to start high intensity statin therapy.

Detailed Description
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Patients with atherosclerotic cardiovascular disease and indication to start high intensity statin therapy will be recruited during hospital-stay or in the neurovascular outpatient clinic of the Neurology Department as well as in the Department of Cardiology and Vascular Medicine at the University Hospital Essen. Participants will be randomly allocated 1:1 to the intervention or control arm and all will receive a Low density Lipoprotein-Cholesterin (LDL-C) target and a statin-prescription as standard of care. All patients will be asked to take the prescribed statin in the evening and to provide LDL-C values measured by the family physician after 6 and 18 months. Additional blood will be collected after 6 and 18 months to control for cardiovascular risk-factors in the study center (LDL-C amongst others). In addition, the intervention group will receive free access to a study version of the medication management app mediteo m+ (Mediteo GmbH, Heidelberg). Installation of the app will be performed on the day of enrolment. After entering the medication, the app will remind the patient to take his or her statin therapy according to the therapy plan. Each intake has to be confirmed by the patient, either directly via the reminder notification or in the app. In addition, the app can be used to set reminders to go the family physician to take LDL-C values and to document the personal LDL-C values. The endpoint assessment will be performed in blinded manner.

Official Title
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Improving Adherence to Statin Therapy Through a Medication Management Application (STAPP)

Conditions
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Atherosclerosis

Intervention / Treatment
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* Other: Medication management app (mediteo m+, Mediteo GmbH, Heidelberg)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >18 years Atherosclerosis (neurovascular, cardiac or peripheral) with an indication to start a high intensity statin-therapy (equivalent to 40mg of atorvastatin or 20mg of rosuvastatin; start of statin therapy +/- 10 days of enrolment) Statin naivety LDL-C >100 mg/dl. No older than 21 days Exclusion Criteria: Inability to take medication independently or to use the mediteo m+ app independently (e.g. people in need of care, people with dementia) Patient has no own smartphone (no device provided for this study) Prior drug therapy to lower LDL-C within the last 30 days Active cancer (defined as a diagnosis of cancer within 6 months before enrolment, any treatment for cancer within the previous 6 months, or recurrent or metastatic cancer) or other severe concomitant disease with a life expectancy of <6 months Use of a digital therapy management application (including mediteo or mediteo m+) within the last month Participation in another interventional trial Pregnancy Inability or unwillingness to provide informed consent

Ages Eligible for Study
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Minimum Age: 18 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

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Medication management app<br>Standard of care (statin prescription, targeted monitoring of individual LDL-C values by primary care physician) + medication management app and follow-up visits at our institution at 6 and 18 months | Other: Medication management app (mediteo m+, Mediteo GmbH, Heidelberg)<br>* Free access to a study version of the medication management app mediteo m+ for reminders and documentation of statin therapy in addition to usual care<br>|
| No Intervention: Standard of care<br>Statin prescription, targeted monitoring of individual LDL-C values by primary care physician and follow-up visits at our institution at 6 and 18 months | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relative change in LDL-C | Relative change in LDL-C (mg/dl) after 6 months measured by study site (or according to the value measured by the family physician, if the value measured by the study site is not available after 6 months) as compared to baseline-value | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Modified Rankin Scale (mRS)-Score after 6 months | Change in mRS [0 to 6, higher scores indicating worse outcome] after 6 months | 6 months | 
| Proportion of available LDL-C values measured by the family physician after 6 months | Proportion of available LDL-C values measured by the family physician after 6 months | 6 months | 
| Relative change in high density lipoprotein-cholesterol (HDL-C) after 6 months | Relative change in HDL-C (mg/dl) after 6 months as compared to baseline-value | 6 months | 
| Relative change in total cholesterol after 6 months | Relative change in total cholesterol (mg/dl) after 6 months as compared to baseline-value | 6 months | 
| Relative change in hemoglobin A1C (HbA1c) after 6 months | Relative change in HbA1c (%) after 6 months as compared to baseline-value | 6 months | 
| Relative change in high-sensitivity C-reactive protein (hsCRP) after 6 months | Relative change in hsCRP (mg/dl) after 6 months as compared to baseline-value | 6 months | 
| Relative change in Lipoprotein (a) after 6 months | Relative change in Lipoprotein (a) (mg/dl) after 6 months as compared to baseline-value | 6 months | 
| Relative change in glutamic oxaloacetic transaminase (GOT) after 6 months | Relative change in GOT (U/l) after 6 months as compared to baseline-value | 6 months | 
| Relative change in glutamate-pyruvate transaminase (GPT) | Relative change in GPT (U/l) after 6 months as compared to baseline-value | 6 months | 
| Relative change in creatine kinase (CK) after 6 months | Relative change in CK (U/l) after 6 months as compared to baseline-value | 6 months | 
| Adherence to statin therapy as measured by the German version of the Medication Adherence Report Scale (MARS-D) after 6 months | Adherence to statin therapy after 6 months as measured by the German version of the Medication Adherence Report Scale as measured by MARS-D, range 5-25, higher scores indicating better adherence | 6 months | 
| Adherence to statin therapy as measured by the German version of the A14 scale after 6 months | Measured by the German version of the A14 scale, range 0 - 56, lower scores indicating better adherence | 6 months | 
| Change in Quality of life score EQ-5D-5L after 6 months | Change in Quality of life score EQ-5D-5L is a standardised measure of health status developed by the EuroQol Group including 5 dimensions, 5 levels and the EQ visual analogue scale [VAS] from 0 to 100 with higher values indicating higher quality of life | 6 months | 
| Change in Beliefs about Medicines Questionnaire (BMQ) after 6 months | The BMQ consists of two sections assessing personal beliefs about the necessity of prescribed medication (5 items) and concerns (5 items). Scores range from 5 to 25 with higher scores indicating a higher degree of necessity/concern. | 6 months | 
| Incidence of major vascular events after 6 months | Incidence of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina or urgent coronary revascularization therapy after 6 months | 6 months | 
| Change in highest degree of extracranial stenosis after 6 months | Change in highest degree of extracranial stenosis (%) as determined by carotid ultrasound using North American Carotid Endarterectomy Trial (NASCET) criteria after 6 months | 6 months | 
| Change in maximum height of largest carotid plaque after 6 months | Change in maximum height of largest carotid plaque (mm) on carotid ultrasound after 6 months | 6 months | 
| Change in longitudinal area of largest carotid plaque after 6 months | Change in longitudinal area of largest carotid plaque [mm2] on carotid ultrasound after 6 months | 6 months | 
| Change in cross-sectional area of largest carotid plaque after 6 months | Change in cross-sectional area of largest carotid plaque [mm2] on carotid ultrasound after 6 months | 6 months | 
| Relative change in LDL-C after 18 months | Relative change in LDL-C (mg/dl) after 18 months measured by study site (or according to the value measured by the family physician, if the value measured by the study site is not available) as compared to baseline-value | 18 months | 
| Modified Rankin Scale (mRS)-Score after 18 months | Change in mRS [0 to 6, higher scores indicating worse outcome] after 18 months | 18 months | 
| Proportion of available LDL-C values measured by the family physician after 18 months | Proportion of available LDL-C values measured by the family physician after 18 months | 18 months | 
| Relative change in high density lipoprotein-cholesterol (HDL-C) after 18 months | Relative change in HDL-C (mg/dl) after 18 months as compared to baseline-value | 18 months | 
| Relative change in total cholesterol after 18 months | Relative change in total cholesterol (mg/dl) after 18 months as compared to baseline-value | 18 months | 
| Relative change in hemoglobin A1C (HbA1c) after 18 months | Relative change in HbA1c (%) after 18 months as compared to baseline-value | 18 months | 
| Relative change in high-sensitivity C-reactive protein (hsCRP) after 18 months | Relative change in hsCRP (mg/dl) after 18 months as compared to baseline-value | 18 months | 
| Relative change in Lipoprotein (a) after 18 months | Relative change in Lipoprotein (a) (mg/dl) after 18 months as compared to baseline-value | 18 months | 
| Relative change in glutamic oxaloacetic transaminase (GOT) after 18 months | Relative change in GOT (U/l) after 18 months as compared to baseline-value | 18 months | 
| Relative change in glutamate-pyruvate transaminase (GPT) after 18 months | Relative change in GPT (U/l) after18 months as compared to baseline-value | 18 months | 
| Relative change in creatine kinase (CK) after 18 months | Relative change in CK (U/l) after 18 months as compared to baseline-value | 18 months | 
| Adherence to statin therapy as measured by the German version of the Medication Adherence Report Scale (MARS-D) after 18 months | Adherence to statin therapy after 18 months as measured by the German version of the Medication Adherence Report Scale as measured by MARS-D, range 5-25, higher scores indicating better adherence | 18 months | 
| Adherence to statin therapy as measured by the German version of the A14 scale after 18 months | Measured by the German version of the A14 scale, range 0 - 56, lower scores indicating better adherence | 18 months | 
| Change in Quality of life score EQ-5D-5L after 18 months | Change in Quality of life score EQ-5D-5L is a standardised measure of health status developed by the EuroQol Group including 5 dimensions, 5 levels and the EQ visual analogue scale [VAS] from 0 to 100 with higher values indicating higher quality of life | 18 months | 
| Change in Beliefs about Medicines Questionnaire (BMQ) after 18 months | The BMQ consists of two sections assessing personal beliefs about the necessity of prescribed medication (5 items) and concerns (5 items). Scores range from 5 to 25 with higher scores indicating a higher degree of necessity/concern. | 18 months | 
| Incidence of major vascular events after 18 months | Incidence of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina or urgent coronary revascularization therapy after 18 months | 18 months | 
| Change in highest degree of extracranial stenosis after 18 months | Change in highest degree of extracranial stenosis (%) as determined by carotid ultrasound using North American Carotid Endarterectomy Trial (NASCET) criteria after 18 months | 18 months | 
| Change in maximum height of largest carotid plaque after 18 months | Change in maximum height of largest carotid plaque (mm) on carotid ultrasound after 18 months | 18 months | 
| Change in longitudinal area of largest carotid plaque after 18 months | Change in longitudinal area of largest carotid plaque [mm2] on carotid ultrasound after 18 months | 18 months | 
| Change in cross-sectional area of largest carotid plaque after 18 months | Change in cross-sectional area of largest carotid plaque [mm2] on carotid ultrasound after 18 months | 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Smartphone Application, Medication Therapy Management