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

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ClinicalTrials.gov Identifier: NCT00603590
Recruitment Status : Completed
First Posted : January 29, 2008
Results First Posted : June 23, 2009
Last Update Posted : October 2, 2009
University of Birmingham
Information provided by:
Tehran University of Medical Sciences

Brief Summary:

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.


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.

Condition or disease Intervention/treatment Phase
Cardiovascular Disease Hypertension Hyperlipidemia Heart Disease Drug: Polypill Drug: Placebo drug Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 475 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Phase II Study of Heart Polypill in Primary Prevention of Cardiovascular Disease - Safety and Efficacy
Study Start Date : November 2006
Actual Primary Completion Date : June 2008
Actual Study Completion Date : July 2008

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Polypill
Fixed dose combination therapy with Aspirin 81mg, Hydrochlorothiazide 12.5mg, Enalapril 2.5mg and Atorvastatin 20mg
Drug: Polypill
Fixed dose combination therapy - aspirin 81mg, hydrochlorothiazide 12.5mg, enalapril 2.5mg and atorvastatin 20mg Once daily

Placebo Comparator: Control
Identical placebo
Drug: Placebo drug
Inactive tablet Once a day Identical in appearance to intervention drug

Primary Outcome Measures :
  1. Systolic Blood Pressure [ Time Frame: One year ]
    Systolic blood pressure. Mean of two seated measurements.

Secondary Outcome Measures :
  1. Diastolic Blood Pressure [ Time Frame: One year ]
    Mean of two seated diastolic blood pressures

  2. LDL Cholesterol [ Time Frame: One year ]
    Serum LDL cholesterol

Information from the National Library of Medicine

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Ages Eligible for Study:   50 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00603590

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Iran, Islamic Republic of
Kalaleh Heart Study Center
Kalaleh, Golestan, Iran, Islamic Republic of
Sponsors and Collaborators
Tehran University of Medical Sciences
University of Birmingham
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Study Chair: Reza Malekzadeh, M.D. Tehran University of Medical Sciences
Principal Investigator: Fatemeh Malekzadeh, M.D. Tehran University of Medical Sciences
Principal Investigator: Mansoor Rastegarpanah, Ph.D. Tehran University of Medical Sciences
Study Chair: Kar K Cheng, PhD University of Birmingham
Principal Investigator: Tom P Marshall, PhD University of Birmingham
Study Director: Akram Pourshams, PhD Tehran University of Medical Sciences
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Responsible Party: Reza Malekzadeh, Tehran University of Medical Sciences
ClinicalTrials.gov Identifier: NCT00603590    
Other Study ID Numbers: 301/148
CCT-NAPN 15388
First Posted: January 29, 2008    Key Record Dates
Results First Posted: June 23, 2009
Last Update Posted: October 2, 2009
Last Verified: September 2009
Keywords provided by Tehran University of Medical Sciences:
Cardiovascular disease
primary prevention
Additional relevant MeSH terms:
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Cardiovascular Diseases
Heart Diseases
Lipid Metabolism Disorders
Metabolic Diseases