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

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 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.

Study Overview

• Status: Completed
• Conditions: Hypertension; Cardiovascular Disease; Heart Disease; Hyperlipidemia
• Intervention / Treatment: Drug: Polypill; Drug: Placebo drug

• Study Type: Interventional
• Enrollment (Actual): 475
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Tehran University of Medical Sciences
• Collaborators: University of Birmingham
• Investigators: 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

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start: November 1, 2006
• Primary Completion (ACTUAL): June 1, 2008
• Study Completion (ACTUAL): July 1, 2008

Study Registration Dates

• First Submitted: January 1, 2008
• First Submitted That Met QC Criteria: January 28, 2008
• First Posted (ESTIMATE): January 29, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): October 2, 2009
• Last Update Submitted That Met QC Criteria: September 22, 2009
• Last Verified: September 1, 2009

More Information

Terms related to this study

• Keywords: Cardiovascular disease; Diabetes; Adherence; safety; efficacy; Compliance; primary prevention; Polypill; ADR
• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Dyslipidemias; Heart Diseases; Cardiovascular Diseases; Hyperlipidemias
• Other Study ID Numbers: 301/148; CCT-NAPN 15388