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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Stroke; Medication Adherence
• Intervention / Treatment: Drug: Polycap

• Study Type: Interventional
• Enrollment (Estimated): 680
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Raelle Tagge, MPH; Email: raelle.tagge@ncire.org
• Study Contact Backup: Name: Bruce Ovbiagele, MD; Phone Number: 415-750-2047; Email: bruce.ovbiagele@va.gov

Study Locations

• Ghana
  • Kumasi, Ghana
    • Kwame Nkrumah Institute of Science & Technology
    • Contact: Fred Sarfo, MD; Email: stephensarfo78@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention; 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; 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.
No Intervention: Control arm; 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?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Organizational Capacity for Change Score	Adoption i.e. Organizational Capacity for Change (OCC Scale Score comparison) with stratification by level of healthcare delivery. The measure is a 32-item multidimensional scale that evaluates an organization's capacity to upgrade or revise existing organizational competencies, while cultivating new competencies that enable the organization to survive and prosper. It comprises different aspects of leadership, employee behavior, and an organizational infrastructure supporting organizational change. Items are rated on a 5-point Likert scale. OCC has a Cronbach α of 0.87.	Up to 30 months
Mean Cost of Implementation	Implementation Cost (mean monthly health expenses compared to standard of care)	Up to 30 months
Proportion who achieves systolic blood pressure <140 mmHg		Months 12 and 24
Proportion who achieves blood pressure <140/90 mmHg		Months 12 and 24
Proportion who achieves blood pressure < 130 / 80 mmHg		Months 12 and 24
Proportion who achieves LDL-cholesterol <100 mg/dl		Months 12 and 24
Proportion who achieves LDL-cholesterol <70 mg/dl		Months 12 and 24
Proportion who achieves antiplatelet adherence of at least >=80%		Months 12 and 24
Proportion who achieves antiplatelet adherence of at least >= 90%		Months 12 and 24
Comparison of absolute and mean changes from baseline for blood pressure	systolic blood pressure, diastolic blood pressure, mean arterial blood pressure, measures of visit-to-visit variability in blood pressure	Up to 24 months
Comparison of absolute and mean changes from baseline for lipids	Total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglyceride	Up to 24 months
Proportion with recurrent strokes (fatal or non-fatal)		Up to 24 months
Proportion with coronary artery disease		Up to 24 months
Proportion with heart failure		Up to 24 months
Proportion with cardiovascular deaths		Up to 24 months
Proportion with all-cause mortality		Up to 24 months
Proportion with vascular cognitive impairment		Months 12 and 24
Proportion with treatment-limiting adverse drug reactions or side effects		Up to 24 months

Collaborators and Investigators

• Sponsor: Northern California Institute of Research and Education

Publications and helpful links

General Publications

• Sarfo FS, Wahab K, Matuja SS, Adebayo PB, Adoukonou T, Tagge R, Ovbiagele B. Stroke minimization through additive anti-atherosclerotic agents in routine treatment (SMAART) II: Rationale for a multi-country polypill phase 3 trial in sub-Saharan Africa. Equity Neurosci. 2026 Apr;2(1):100020. doi: 10.1016/j.neuros.2026.100020. Epub 2026 Jan 22.

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): September 1, 2028

Study Registration Dates

• First Submitted: August 11, 2022
• First Submitted That Met QC Criteria: July 19, 2023
• First Posted (Actual): July 27, 2023

Study Record Updates

• Last Update Posted (Actual): June 5, 2026
• Last Update Submitted That Met QC Criteria: June 4, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Behavior; Treatment Adherence and Compliance; Health Behavior; Patient Compliance; Patient Acceptance of Health Care; Stroke; Medication Adherence
• Other Study ID Numbers: 22-37310

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No