Clinical trial NCT00603590: Phase II Study of Heart Polypill Safety and Efficacy in Primary Prevention of Cardiovascular Disease
Official title: Phase II Study of Heart Polypill in Primary Prevention of Cardiovascular Disease - Safety and Efficacy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cardiovascular Disease
Hypertension
Hyperlipidemia
Heart Disease
Keywords: Cardiovascular disease
primary prevention
Polypill
efficacy
safety
ADR
Diabetes
Adherence
Compliance
Lead sponsor: Tehran University of Medical Sciences
Sponsor class: OTHER
Collaborators: name: University of Birmingham
First posted: 2008-01-29
Enrollment: 475
Sex: ALL
Minimum age (years): 50
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.


Eligibility 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

Primary outcomes:
measure: Systolic Blood Pressure
timeFrame: One year
Secondary outcomes:
measure: Diastolic Blood Pressure
timeFrame: One year
measure: LDL Cholesterol
timeFrame: One year
Other outcomes:
Locations:
city: Kalaleh
country: Iran, Islamic Republic of
facility: Kalaleh Heart Study Center
state: Golestan
Study officials:
affiliation: Tehran University of Medical Sciences
name: Reza Malekzadeh, M.D.
role: STUDY_CHAIR
affiliation: Tehran University of Medical Sciences
name: Fatemeh Malekzadeh, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Tehran University of Medical Sciences
name: Mansoor Rastegarpanah, Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Birmingham
name: Kar K Cheng, PhD
role: STUDY_CHAIR
affiliation: University of Birmingham
name: Tom P Marshall, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Tehran University of Medical Sciences
name: Akram Pourshams, PhD
role: STUDY_DIRECTOR
References:
citation: 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.