Phase II Study of Heart Polypill Safety and Efficacy in Primary Prevention of Cardiovascular Disease

Study Overview
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Brief Summary
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Cardiovascular is a major cause of mortality in Iran, accounting for 45.7% of deaths. In Golestan (North Eastern Iran) preliminary findings from follow-up of the Golestan Cohort are consistent with national figures: with 45% (at least 22 of 48 deaths) of all deaths attributed to cardiovascular events. Cardiovascular diseases will become an increasing problem as the Iranian population ages. In 2003 Law and Wald proposed prevention of cardiovascular disease using fixed-dose combination therapy combining antihypertensive, lipid lowering and antiplatelet drugs in a single preparation. They proposed that this treatment should be offered to all persons at high risk of cardiovascular disease whether or not they have elevated blood pressure or elevated serum lipid concentrations. This pilot study aims to investigate the safety and efficacy of fixed-dose combination therapy with two antihypertensive drugs, aspirin and atorvastatin in a population who would not currently be considered eligible for antihypertensive treatment or for lipid lowering treatment. Methods: This is a double-blind randomized controlled trial. The intervention group will be assigned to take a tablet consisting of a single daily tablet comprising Aspirin 81mg, Hydrochlorothiazide 12.5mg, Enalapril 2.5mg and Atorvastatin 20mg. The control group will be assigned to an identical placebo. The population studied includes men aged 50 to 80 (inclusive) and women aged 55 to 80 (inclusive) who are currently not eligible for or taking antihypertensive or lipid lowering therapy. Persons who are found at baseline to have blood pressure >160/100 mm Hg, total cholesterol >240mg/dL, existing cardiovascular disease or to be taking antihypertensive ore lipid lowering therapy are excluded. It is intended to randomize and follow up 500 subjects for 12 months. The primary outcome for the purpose of sample size calculation is change in systolic blood pressure. Additional outcomes include change in diastolic blood pressure, change in LDL cholesterol and occurrence of adverse events.

Official Title
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Phase II Study of Heart Polypill in Primary Prevention of Cardiovascular Disease - Safety and Efficacy

Conditions
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Cardiovascular Disease, Hypertension, Hyperlipidemia, Heart Disease

Intervention / Treatment
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* Drug: Polypill
* Drug: Placebo drug


Participation Criteria
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Eligibility Criteria
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Inclusion criteria All men over 50 to 80 and all women 55 to 80 who are resident in Kalaleh, Golestan, for at least one year. Exclusion criteria Existing cardiovascular disease (stroke, transient ischaemic attack, myocardial infarction or angina) Already taking antihypertensive drugs, aspirin or statins Already have clinical indications for treatment with antihypertensive drugs, aspirin or statins. Blood pressure >160/100 mm Hg Total Cholesterol > 240 mg/dL (or LDL >190 mg/dL) Probable diabetes: HbA1c >6.0 Contraindication to a component of the Polypill Contraindications to aspirin Previous history of allergy to aspirin History of peptic ulcer bleeding in whole life or endoscopic evidence of peptic ulcer within the past 3 months Contraindications to statins Liver failure Contraindications to further blood pressure lowering Systolic blood pressure ≤90 mm Hg or diastolic blood pressure ≤70 mm Hg Symptomatic postural hypotension Difference between mean seated BP and standing BP greater than 20 mm Hg Contraindications to thiazide Uric acid >8 for men and uric acid >6 for women / gout ( 10%) Creatinine >1.2 mg/dl Other predominant medical problem that may limit compliance with study treatment including: History of alcohol abuse: more than 60cc for women and more than 80cc for men History of drug abuse: IV drug abuser or eating or smoking more than 4 times a week Limiting psychiatric illness (eg: mania, schizophrenia, severe depression, psychosis or dementia) Limiting physical disability sufficient to prevent subject from walking Other life-threatening condition such as cancer

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Polypill<br>Fixed dose combination therapy with Aspirin 81mg, Hydrochlorothiazide 12.5mg, Enalapril 2.5mg and Atorvastatin 20mg | Drug: Polypill<br>* Fixed dose combination therapy - aspirin 81mg, hydrochlorothiazide 12.5mg, enalapril 2.5mg and atorvastatin 20mg Once daily<br>|
| Placebo Comparator: Control<br>Identical placebo | Drug: Placebo drug<br>* Inactive tablet Once a day Identical in appearance to intervention drug<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Systolic Blood Pressure | Systolic blood pressure. Mean of two seated measurements. | One year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diastolic Blood Pressure | Mean of two seated diastolic blood pressures | One year | 
| LDL Cholesterol | Serum LDL cholesterol | One year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cardiovascular disease, primary prevention, Polypill, efficacy, safety, ADR, Diabetes, Adherence, Compliance