Stroke Minimization Through Additive Anti-atherosclerotic Agents in Routine Treatment II Study (SMAART II)

Study Overview
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Brief Summary
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The overall objective of the Stroke Minimization through Additive Anti-atherosclerotic Agents in Routine Treatment II (SMAART-II) is to deploy a hybrid study design to firstly, demonstrate the efficacy of a polypill (Polycap ®) containing fixed doses of antihypertensives, a statin, and antiplatelet therapy taken as two capsules, once daily orally in reducing composite vascular risk over 24 months vs. usual care among 500 recent stroke patients encountered at 12 hospitals in Ghana. Secondly, SMAART II seeks to develop an implementation strategy for routine integration and policy adoption of this polypill for post-stroke cardiovascular risk reduction in an under-resourced system burdened by suboptimal care and outcomes.

Official Title
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Stroke Minimization Through Additive Anti-atherosclerotic Agents in Routine Treatment II Study (SMAART II)

Conditions
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Stroke, Medication Adherence

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 Ischemic stroke 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 antihypertensive 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br>Patients allocated to the experimental arm will receive Two (2) (Polycap ®) taken orally once a day. A capsule of Polycap ® contains 100mg of Aspirin, 20mg of simvastatin, 12.5mg hydrochlorothiazide, 5mg of ramipril and 50mg of atenolol. Patients assigned to Polypill will have their antihypertensive agents, lipid modifiers and anti-thrombotic agents withdrawn & replaced with the Polypill if they are already receiving such treatments before enrollment. | Drug: Polycap<br>* Patients allocated to the experimental arm will receive Two (2) (Polycap ®) taken orally once a day. A capsule of Polycap ® contains 100mg of Aspirin, 20mg of simvastatin, 12.5mg hydrochlorothiazide, 5mg of ramipril and 50mg of atenolol. Patients assigned to Polypill will have their antihypertensive agents, lipid modifiers and anti-thrombotic agents withdrawn and replaced with the Polypill if they are already receiving such treatments before enrollment.<br>|
| No Intervention: Control arm<br>Patients allocated to the usual care arm will receive standard of care therapies for secondary prevention with drugs and doses left at the discretion of the treating physicians. Since our focus is to isolate the effect of the polypill strategy itself & create equipoise, at study inception providers for patients in both study arms will receive a brief one-time (Skype-based) training & a one time email synopsis on guideline recommended biomarker targets after stroke. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite vascular risk factor control | Proportion of people who have 0, 1, 2 and 3 of the following: systolic BP <140 mm Hg, LDL-cholesterol <100mg/dl, antiplatelet adherence by pill count >90%) at month 12 and month 24 (sustainment of effect) | 12 and 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major adverse cardiovascular events (MACE) | MACE to be assessed include recurrent stroke: fatal/severely disabling stroke or non-fatal stroke; coronary artery disease: acute STEMI/NSTEMI, sudden cardiac deaths. MACE will be confirmed by a blinded adjudication committee by reviewing available clinical notes supported by investigations for example CT scans, EKGs, troponin tests, death certificates or verbal autopsy if death occurs outside hospital. | 24 months | 
| Change in adherence to medical therapy |  | Month 3, 6, 9, 12, 18 & 24 | 
| Safety and tolerability | Side effects, adverse events, treatment withdrawal | Up to 24 months | 
| Health-related quality of life EuroQol-5D | EuroQol-5D questionnaire (0-100 with 100 being the best) | Up to 24 months | 
| Health-related quality of life Neuro-QoLTM | NINDS Neuro-QoLTM (Quality of Life in Neurological Disorders) questionnaires (8-40 with 40 being the best) | Up to 24 months |