Back to resultsStroke Minimization Through Additive Anti-atherosclerotic Agents in Routine Treatment II Study (SMAART II)
Primary Purpose
Stroke, Medication Adherence
Status
Not yet recruiting
Phase
Phase 3
Locations
Ghana
Study Type
Interventional
Intervention
Polycap
Sponsored by
About this trial
This is an interventional prevention trial for Stroke
Eligibility Criteria
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.
Sites / Locations
- Kwame Nkrumah Institute of Science & Technology
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
No Intervention
Arm Label
Intervention
Control arm
Arm Description
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 Patients assigned to Polypill will have their antihypertensive agents, lipid modifiers and anti-thrombotic agents withdrawn & replaced with the Polypill if they are already receiving such treatments before enrollment.
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.
Outcomes
Primary Outcome Measures
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)
Secondary Outcome Measures
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.
Change in adherence to medical therapy
Safety and tolerability
Side effects, adverse events, treatment withdrawal
Health-related quality of life EuroQol-5D
EuroQol-5D questionnaire (0-100 with 100 being the best)
Health-related quality of life Neuro-QoLTM
NINDS Neuro-QoLTM (Quality of Life in Neurological Disorders) questionnaires (8-40 with 40 being the best)
Full Information
NCT ID
NCT05963568
First Posted
August 11, 2022
Last Updated
September 12, 2023
Sponsor
Northern California Institute of Research and Education
1. Study Identification
Unique Protocol Identification Number
NCT05963568
Brief Title
Stroke Minimization Through Additive Anti-atherosclerotic Agents in Routine Treatment II Study (SMAART II)
Official Title
Stroke Minimization Through Additive Anti-atherosclerotic Agents in Routine Treatment II Study (SMAART II)
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
October 2023 (Anticipated)
Primary Completion Date
May 2027 (Anticipated)
Study Completion Date
May 2028 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Northern California Institute of Research and Education
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stroke, Medication Adherence
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
680 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Intervention
Arm Type
Experimental
Arm Description
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.
Arm Title
Control arm
Arm Type
No Intervention
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Polycap
Intervention Description
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.
Primary Outcome Measure Information:
Title
Composite vascular risk factor control
Description
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)
Time Frame
12 and 24 months
Secondary Outcome Measure Information:
Title
Major adverse cardiovascular events (MACE)
Description
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.
Time Frame
24 months
Title
Change in adherence to medical therapy
Time Frame
Month 3, 6, 9, 12, 18 & 24
Title
Safety and tolerability
Description
Side effects, adverse events, treatment withdrawal
Time Frame
Up to 24 months
Title
Health-related quality of life EuroQol-5D
Description
EuroQol-5D questionnaire (0-100 with 100 being the best)
Time Frame
Up to 24 months
Title
Health-related quality of life Neuro-QoLTM
Description
NINDS Neuro-QoLTM (Quality of Life in Neurological Disorders) questionnaires (8-40 with 40 being the best)
Time Frame
Up to 24 months
Other Pre-specified Outcome Measures:
Title
Organizational Capacity for Change Score
Description
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.
Time Frame
Up to 30 months
Title
Mean Cost of Implementation
Description
Implementation Cost (mean monthly health expenses compared to standard of care)
Time Frame
Up to 30 months
Title
Proportion who achieves systolic blood pressure <140 mmHg
Time Frame
Months 12 and 24
Title
Proportion who achieves blood pressure <140/90 mmHg
Time Frame
Months 12 and 24
Title
Proportion who achieves blood pressure < 130 / 80 mmHg
Time Frame
Months 12 and 24
Title
Proportion who achieves LDL-cholesterol <100 mg/dl
Time Frame
Months 12 and 24
Title
Proportion who achieves LDL-cholesterol <70 mg/dl
Time Frame
Months 12 and 24
Title
Proportion who achieves antiplatelet adherence of at least >=80%
Time Frame
Months 12 and 24
Title
Proportion who achieves antiplatelet adherence of at least >= 90%
Time Frame
Months 12 and 24
Title
Comparison of absolute and mean changes from baseline for blood pressure
Description
systolic blood pressure, diastolic blood pressure, mean arterial blood pressure, measures of visit-to-visit variability in blood pressure
Time Frame
Up to 24 months
Title
Comparison of absolute and mean changes from baseline for lipids
Description
Total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglyceride
Time Frame
Up to 24 months
Title
Proportion with recurrent strokes (fatal or non-fatal)
Time Frame
Up to 24 months
Title
Proportion with coronary artery disease
Time Frame
Up to 24 months
Title
Proportion with heart failure
Time Frame
Up to 24 months
Title
Proportion with cardiovascular deaths
Time Frame
Up to 24 months
Title
Proportion with all-cause mortality
Time Frame
Up to 24 months
Title
Proportion with vascular cognitive impairment
Time Frame
Months 12 and 24
Title
Proportion with treatment-limiting adverse drug reactions or side effects
Time Frame
Up to 24 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Bruce Ovbiagele, MD
Phone
415-750-2047
Email
bruce.ovbiagele@va.gov
First Name & Middle Initial & Last Name or Official Title & Degree
Raelle Tagge, MPH
Email
raelle.tagge@ncire.org
Facility Information:
Facility Name
Kwame Nkrumah Institute of Science & Technology
City
Kumasi
Country
Ghana
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Fred Sarfo, MD
Email
stephensarfo78@gmail.com
12. IPD Sharing Statement
Learn more about this trial
Stroke Minimization Through Additive Anti-atherosclerotic Agents in Routine Treatment II Study (SMAART II)
We'll reach out to this number within 24 hrs