Adherence, Medication, Atherosclerosis, Tolerance
Conditions
Brief summary
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.
Interventions
DRUGPolycap
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
Sponsors
Kwame Nkrumah University Teaching Hospital
Northern California Institute of Research and Education
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Carotid Intimal Media Thickness | Baseline and 12 months | Thickness of the intima and media layers of the carotid arteries |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hill-Bone Score | 12 months | 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. |
| EQ-5D Quality-of-Life Score | 12 months | 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. |
| Treatment Satisfaction Questionnaire for Medication Score | 12 months | 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. |
| Morisky Adherence Scale Score | 12 months | 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. |
| Modified Rankin Score | 12 months | 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. |
| Hamilton Rating Scale for Depression Score | 12 months | 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 |
| Montreal Cognitive Assessment Score | 12 months | 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. |
Countries
Ghana
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Polypill 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
Polycap: 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 | 74 |
| Usual Care Will continue to take separate, individual secondary preventive medications as prescribed | 74 |
| Total | 148 |
Baseline characteristics
| Characteristic | Polypill | Usual Care | Total |
|---|---|---|---|
| Age, Continuous | 58.5 years STANDARD_DEVIATION 10.7 | 58.1 years STANDARD_DEVIATION 13.3 | 58.3 years STANDARD_DEVIATION 12.07 |
| Alcohol use, current | 8 Participants | 11 Participants | 19 Participants |
| Angiotensin converting enzyme inhibitor | 15 Participants | 16 Participants | 31 Participants |
| Angiotensin receptor blocker | 43 Participants | 43 Participants | 86 Participants |
| Antiplatelet Therapy (aspirin or clopidogrel) | 62 Participants | 66 Participants | 128 Participants |
| Atorvastatin at 40mg or 8mg daily | 55 Participants | 63 Participants | 118 Participants |
| BMI | 25.4 kg/m^2 STANDARD_DEVIATION 4.3 | 25.7 kg/m^2 STANDARD_DEVIATION 5.1 | 25.55 kg/m^2 STANDARD_DEVIATION 4.72 |
| Calcium channel blocker | 62 Participants | 58 Participants | 120 Participants |
| Cigarette Smoking | 0 Participants | 1 Participants | 1 Participants |
| Common CIMT (Carotid Intima-Media Thickness) | 1.00 mm STANDARD_DEVIATION 0.17 | 1.03 mm STANDARD_DEVIATION 0.16 | 1.02 mm STANDARD_DEVIATION 0.17 |
| Diabetes | 15 Participants | 21 Participants | 36 Participants |
| Diastolic Blood Pressure, mmHg | 92.0 mmHg STANDARD_DEVIATION 13.9 | 92.6 mmHg STANDARD_DEVIATION 14.6 | 92.3 mmHg STANDARD_DEVIATION 14.25 |
| Diuretics | 25 Participants | 29 Participants | 54 Participants |
| Educational Status None | 11 Participants | 15 Participants | 26 Participants |
| Educational Status Postgraduate | 0 Participants | 1 Participants | 1 Participants |
| Educational Status Primary | 42 Participants | 28 Participants | 70 Participants |
| Educational Status Secondary | 12 Participants | 18 Participants | 30 Participants |
| Educational Status Tertiary | 9 Participants | 12 Participants | 21 Participants |
| Employment Status Employed | 54 Participants | 45 Participants | 99 Participants |
| Employment Status Retired | 11 Participants | 10 Participants | 21 Participants |
| Employment Status Unemployed | 9 Participants | 19 Participants | 28 Participants |
| EQ-5D Quality-of-Life Score (Euro Quality of Life-5D) | 83.7 score on a scale STANDARD_DEVIATION 11.6 | 80.6 score on a scale STANDARD_DEVIATION 11.7 | 82.15 score on a scale STANDARD_DEVIATION 11.65 |
| Haemoglobin A % | 6.5 percent STANDARD_DEVIATION 1.7 | 7 percent STANDARD_DEVIATION 2.5 | 6.75 percent STANDARD_DEVIATION 2.14 |
| Hamilton Rating Scale for Depression Score | 5.6 score on a scale STANDARD_DEVIATION 4.36 | 6.8 score on a scale STANDARD_DEVIATION 4.13 | 6.2 score on a scale STANDARD_DEVIATION 4.25 |
| Hill-Bone Score | 50.4 score on a scale STANDARD_DEVIATION 1.81 | 50.1 score on a scale STANDARD_DEVIATION 1.76 | 50.25 score on a scale STANDARD_DEVIATION 1.79 |
| Hydralazine | 10 Participants | 8 Participants | 18 Participants |
| Hypertension | 74 Participants | 74 Participants | 148 Participants |
| Marital Status Cohabiting | 0 Participants | 1 Participants | 1 Participants |
| Marital Status Divorced | 2 Participants | 2 Participants | 4 Participants |
| Marital Status Married | 43 Participants | 47 Participants | 90 Participants |
| Marital Status Never married | 6 Participants | 5 Participants | 11 Participants |
| Marital Status Separated | 12 Participants | 5 Participants | 17 Participants |
| Marital Status Widow or widower | 11 Participants | 14 Participants | 25 Participants |
| Methyldopa | 1 Participants | 2 Participants | 3 Participants |
| Mineralocortcoid receptor blocker | 7 Participants | 7 Participants | 14 Participants |
| Modified Rankin Score | 2.6 score on a scale STANDARD_DEVIATION 0.97 | 2.74 score on a scale STANDARD_DEVIATION 0.85 | 2.67 score on a scale STANDARD_DEVIATION 0.91 |
| Monthly Income 0-100, US $ | 7 Participants | 11 Participants | 18 Participants |
| Monthly Income 101-250 | 37 Participants | 37 Participants | 74 Participants |
| Monthly Income 250-500 | 27 Participants | 24 Participants | 51 Participants |
| Monthly Income >500 | 3 Participants | 2 Participants | 5 Participants |
| Montreal Cognitive Assessment Score | 16.0 score on a scale STANDARD_DEVIATION 6.7 | 16.2 score on a scale STANDARD_DEVIATION 5.78 | 16.1 score on a scale STANDARD_DEVIATION 6.26 |
| Morisky Adherence Scale Score | 6.7 score on a scale STANDARD_DEVIATION 0.51 | 6.7 score on a scale STANDARD_DEVIATION 0.37 | 6.7 score on a scale STANDARD_DEVIATION 0.45 |
| NIHSS Score | 2.9 score on a scale STANDARD_DEVIATION 3.4 | 2.4 score on a scale STANDARD_DEVIATION 2.8 | 2.65 score on a scale STANDARD_DEVIATION 2.66 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 74 Participants | 74 Participants | 148 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Ghana | 74 Participants | 74 Participants | 148 Participants |
| Sex: Female, Male Female | 38 Participants | 36 Participants | 74 Participants |
| Sex: Female, Male Male | 36 Participants | 38 Participants | 74 Participants |
| Stroke subtype Large vessel disease | 20 Participants | 16 Participants | 36 Participants |
| Stroke subtype Small vessel disease | 11 Participants | 23 Participants | 34 Participants |
| Stroke subtype Undetermined | 43 Participants | 35 Participants | 78 Participants |
| Systolic Blood Pressure, mmHg | 161.3 mmHg STANDARD_DEVIATION 17.2 | 160.4 mmHg STANDARD_DEVIATION 18 | 160.85 mmHg STANDARD_DEVIATION 17.6 |
| Treatment Satisfaction Questionnaire for Medication Score | 53.5 score on a scale STANDARD_DEVIATION 2.8 | 52.7 score on a scale STANDARD_DEVIATION 2.8 | 53.1 score on a scale STANDARD_DEVIATION 2.8 |
| Urban Residence | 42 Participants | 37 Participants | 79 Participants |
| Waist-to-hip Ratio | 92.2 cm STANDARD_DEVIATION 10.3 | 90.6 cm STANDARD_DEVIATION 12.1 | 91.4 cm STANDARD_DEVIATION 11.24 |
| β blocker | 12 Participants | 10 Participants | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 5 / 74 | 2 / 74 |
| other Total, other adverse events | 5 / 74 | 7 / 74 |
| serious Total, serious adverse events | 3 / 74 | 0 / 74 |
Outcome results
Primary
Carotid Intimal Media Thickness
Thickness of the intima and media layers of the carotid arteries
Time frame: Baseline and 12 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Polypill | Carotid Intimal Media Thickness | -0.017 mm |
| Usual Care | Carotid Intimal Media Thickness | -0.092 mm |
Secondary
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.
Time frame: 12 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Polypill | EQ-5D Quality-of-Life Score | 7.63 score on a scale |
| Usual Care | EQ-5D Quality-of-Life Score | 10.23 score on a scale |
Secondary
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
Time frame: 12 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Polypill | Hamilton Rating Scale for Depression Score | -3.51 score on a scale |
| Usual Care | Hamilton Rating Scale for Depression Score | -4.06 score on a scale |
Secondary
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.
Time frame: 12 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Polypill | Hill-Bone Score | -0.51 score on a scale |
| Usual Care | Hill-Bone Score | -1.11 score on a scale |
Secondary
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.
Time frame: 12 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Polypill | Modified Rankin Score | -0.92 score on a scale |
| Usual Care | Modified Rankin Score | -0.89 score on a scale |
Secondary
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.
Time frame: 12 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Polypill | Montreal Cognitive Assessment Score | 5.17 score on a scale |
| Usual Care | Montreal Cognitive Assessment Score | 5.39 score on a scale |
Secondary
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.
Time frame: 12 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Polypill | Morisky Adherence Scale Score | -0.19 score on a scale |
| Usual Care | Morisky Adherence Scale Score | -0.14 score on a scale |
Secondary
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.
Time frame: 12 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Polypill | Treatment Satisfaction Questionnaire for Medication Score | -10.92 score on a scale |
| Usual Care | Treatment Satisfaction Questionnaire for Medication Score | -6.72 score on a scale |