Stroke Minimization Through Additive Anti-atherosclerotic Agents in Routine Treatment

Study Overview
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Brief Summary
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The overarching objective of the Stroke Minimization through Additive Anti-atherosclerotic Agents in Routine Treatment (SMAART) trial is to assess whether a polypill containing fixed doses of (2/3) antihypertensives, a statin and antiplatelet therapy taken once daily orally would result in carotid intimal thickness regression-a surrogate marker of atherosclerosis, improved adherence, and tolerability compared with 'usual care' group on separate individual secondary preventive medications among Ghanaian first time stroke survivors. Our ultimate objective is to design of a future multi center, double-blinded, placebo-controlled, parallel-group, randomized trial comparing the clinical efficacy of the polypill strategy vs 'usual care' in the African context to derive locally relevant, high-quality evidence for routine deployment of polypill for CVD risk moderation among stroke survivors in LMICs. In this current study, we plan to recruit 120 recent ischemic stroke survivors randomized 1:1 to the polypill or usual care arms.

Official Title
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Stroke Minimization Through Additive Anti-atherosclerotic Agents in Routine Treatment

Conditions
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Atherosclerosis, Adherence, Medication, Tolerance

Intervention / Treatment
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* Drug: Polycap


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Above the age of 18 years; male or female Stroke/TIA diagnosis no greater than two months before enrollment. Ischemic strokes including lacunar, large-vessel atherosclerotic, cardio-embolic subtypes are eligible - Subjects with stroke may present with at least one of the following additional conditions: Documented diabetes mellitus or previous treatment with oral hypoglycemic or insulin; documented hypertension >140/90mmHg or previous treatment with anti-hypertensive medications; Mild to moderate renal dysfunction (eGFR 60-30ml/min/1.73m2); Prior myocardial infarction Legally competent to sign informed consent Exclusion Criteria: Unable to sign informed consent Contraindications to any of the components of the polypill Hemorrhagic stroke Severe cognitive impairment/dementia or severe global disability limiting the capacity of self-care Severe congestive cardiac failure (NYHA III-IV) Severe renal disease, eGFR <30ml/min/1.73m2), renal dialysis; awaiting renal transplant or transplant recipient Cancer diagnosis or treatment in past 2 years Need for oral anticoagulation at the time of randomization or planned in the future months Significant arrhythmias (including unresolved ventricular arrhythmias or atrial fibrillation) Nursing/pregnant mothers Do not agree to the filing, forwarding and use of his/her pseudonymized data.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: SMAART incorporates (i) a pilot randomized controlled trial and (ii) a human capital/institutional capacity building component. We propose a randomized, open label, blinded endpoint clinical trial with the intervention arm assigned to a polypill containing 2/3 antihypertensives, a moderate/high-intensity statin and Aspirin to be taken orally, once daily in the form of a hard capsule compared with the 'usual care' arm who will continue to take separate, individual secondary preventive medications as prescribed their physicians to assess CIMT changes as a robust intermediary outcome measure for CVD events, as well as adherence, tolerability, and risk factor control rates. Furthermore, a cadre of emerging investigators from Ghana will benefit from the rich learning environment to be created through the implementation of the RCT and the interactions (2 years) with experts from the Medical University of South Carolina.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Polypill<br>Assigned to a polypill containing 2/3 antihypertensives, a moderate/high-intensity statin and Aspirin to be taken orally, once daily in the form of a hard capsule | Drug: Polycap<br>* Assigned to a polypill containing 2/3 antihypertensives, a moderate/high-intensity statin and Aspirin to be taken orally, once daily in the form of a hard capsule<br>|
| No Intervention: Usual Care<br>Will continue to take separate, individual secondary preventive medications as prescribed | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Carotid Intimal Media Thickness | Thickness of the intima and media layers of the carotid arteries | Baseline and 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Morisky Adherence Scale Score | The Morisky Medication Adherence Scale (MMAS-8) is a validated assessment tool used to measure non-adherence in a variety of patient populations. The scale has been verified and substantiated by numerous studies on a global scale with over 110 versions and over 80 translations. The MMAS-8 is an 8-item structured, self-report measure. Total scores on the MMAS-8 range from 0 to 8, with scores of: 8 reflecting high adherence 7 or 6 reflecting medium adherence <6 reflecting low adherence. 0 is the worst and 8 is the best. | 12 months | 
| Hill-Bone Score | The Hill-Bone Compliance to High Blood Pressure Therapy Scale is a 14-item scale that assesses patient behaviors for three important behavioral domains of high blood pressure treatment. (the three sub-scales of the original scale): Appointment Keeping (3-items), Diet (2-items), Medication Adherence (9-items). The scale has a four point response format: (4) all the time, (3) most of time, (2) some of time, and (1) never. Items are assumed to be additive, and, when summed, the total score ranges from 14 (minimum) to 56. 14 is the worst and 56 is the best. | 12 months | 
| EQ-5D Quality-of-Life Score | The EQ-5D is a self-report survey that measures health-related quality of life. It consists of five dimensions: Mobility, Self-care, Usual activities, Pain/discomfort, Anxiety/depression. Each dimension has five response levels: No problems (Level 1) Slight Moderate Severe Extreme problems (Level 5) The EQ-5D also has a VAS scale from 0 (worst imaginable health state) to 100 (best imaginable health state). An individual records a score between 0 and 100 for their current overall health-related quality of life using the EQ VAS. | 12 months | 
| Treatment Satisfaction Questionnaire for Medication Score | The Treatment Satisfaction Questionnaire for Medication (TSQM) has scores that range from 0 to 100. Higher scores indicate higher patient satisfaction with medication. 0 is the worst, 100 is the best. The TSQM has 14 items and four domains: Effectiveness: Three items Side effects: Five items Convenience: Three items Global satisfaction: Three items The TSQM has a recall period of two to three weeks or since the last medication use. It was designed to assess patient treatment satisfaction in chronic diseases. | 12 months | 
| Montreal Cognitive Assessment Score | The Montreal Cognitive Assessment (MoCA) is a cognitive screening test that can detect dementia and mild cognitive impairment. The test consists of 11 questions that evaluate seven cognitive domains. The maximum score is 30. 26 or higher: Normal 18-25: Mild cognitive impairment 10-17: Moderate impairment Less than 10: Severe impairment. 0 is the worst, 30 is the best. | 12 months | 
| Modified Rankin Score | The Modified Rankin Score (mRS) is a 6 point disability scale with possible scores ranging from 0 to 5. A separate category of 6 is usually added for patients who expire. The Modified Rankin Score (mRS) is the most widely used outcome measure in stroke clinical trials. 0 is the best, 5 is the worst. | 12 months | 
| Hamilton Rating Scale for Depression Score | The Hamilton Rating Scale for Depression (HRSD) is a 21-item scale that is administered by a health care professional. The first 17 items are scored on either a 5-point or 3-point scale. The scale takes 15 to 20 minutes to complete and score. 0-7: No depression 8-16: Mild depression 17-23: Moderate depression 0 is the best, 23 is the worst. ≥24: Severe depression | 12 months |