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

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 who would not currently be considered eligible for antihypertensive treatment or for lipid lowering treatment.

Methods:

This is a double-blind randomised 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 randomise 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 occurence of adverse events.

Study Type: Interventional

Study Design: Prevention, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: June 2008

Intervention(s) in this Clinical Trial

• Drug: Polypill
  • Fixed dose combination therapy - aspirin 81mg, hydrochlorothiazide 12.5mg, enalapril 2.5mg and atorvastatin 20mg Once daily
• Drug: Placebo drug
  • Inactive tablet Once a day Identical in appearance to intervention drug

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Polypill
  • Fixed dose combination therapy with Aspirin 81mg, Hydrochlorothiazide 12.5mg, Enalapril 2.5mg and Atorvastatin 20mg
• Placebo Comparator: Control
  • Identical placebo

Primary Measures

• Systolic Blood Pressure
  • Time Frame: One year
    Safety Issue?: No

Secondary Measures

• Diastolic Blood Pressure
  • Time Frame: One year
    Safety Issue?: No
• LDL Cholesterol
  • Time Frame: One year
    Safety Issue?: No

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 50 Years

Maximum Age for this Clinical Trial: 80 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Sponsor: Tehran University of Medical Sciences

Overall Clinical Trial Officials and Contacts

Reza Malekzadeh, M.D. Study Chair Tehran University of Medical Sciences  

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00603590

Study ID Number: 301/148

ClinicalTrials.gov Identifier: NCT00603590

Health Authority: Iran: Ministry of Health