Phase II Study of Heart Polypill Safety and Efficacy in Primary Prevention of Cardiovascular Disease - Full Text View

Sponsor:	Tehran University of Medical Sciences
Collaborator:	University of Birmingham
Information provided by:	Tehran University of Medical Sciences
ClinicalTrials.gov Identifier:	NCT00603590

Purpose

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.

Condition	Intervention	Phase
Cardiovascular Disease Hypertension Hyperlipidemia Heart Disease	Drug: Polypill Drug: Placebo drug	Phase II

Study Type:	Interventional
Study Design:	Prevention, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	Phase II Study of Heart Polypill in Primary Prevention of Cardiovascular Disease - Safety and Efficacy

Resource links provided by NLM:

MedlinePlus related topics: Blood Pressure Medicines Cholesterol Heart Diseases High Blood Pressure

U.S. FDA Resources

Further study details as provided by Tehran University of Medical Sciences:

Primary Outcome Measures:

Systolic Blood Pressure [ Time Frame: One year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Diastolic Blood Pressure [ Time Frame: One year ] [ Designated as safety issue: No ]
LDL Cholesterol [ Time Frame: One year ] [ Designated as safety issue: No ]

Enrollment:	475
Study Start Date:	November 2006
Study Completion Date:	July 2008
Primary Completion Date:	June 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Polypill: Experimental 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
Control: Placebo Comparator Identical placebo	Drug: Placebo drug Inactive tablet Once a day Identical in appearance to intervention drug

Eligibility

Ages Eligible for Study:	50 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00603590

Locations

Iran, Islamic Republic of, Golestan
Kalaleh Heart Study Center
Kalaleh, Golestan, Iran, Islamic Republic of

Sponsors and Collaborators

Tehran University of Medical Sciences

University of Birmingham

Investigators

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

More Information

Publications:

Rastegarpanah M, Malekzadeh F, Thomas GN, Mohagheghi A, Cheng KK, Marshall T. A new horizon in primary prevention of cardiovascular disease, can we prevent heart attack by "heart polypill"? Arch Iran Med. 2008 May;11(3):306-13. No abstract available.

Responsible Party:	Tehran University of Medical Sciences ( Reza Malekzadeh )
Study ID Numbers:	301/148, CCT-NAPN 15388
Study First Received:	January 1, 2008
Results First Received:	April 13, 2009
Last Updated:	September 22, 2009
ClinicalTrials.gov Identifier:	NCT00603590 History of Changes
Health Authority:	Iran: Ministry of Health

Keywords provided by Tehran University of Medical Sciences:

Cardiovascular disease
primary prevention
Polypill
efficacy
safety

ADR
Diabetes
Adherence
Compliance

Additional relevant MeSH terms:

Metabolic Diseases
Hyperlipidemias
Heart Diseases
Vascular Diseases

Cardiovascular Diseases
Dyslipidemias
Lipid Metabolism Disorders
Hypertension

ClinicalTrials.gov processed this record on February 04, 2010