PolyIran: Prevention of Cardiovascular Disease in Middle-aged and Elderly Iranians Using a Single PolyPill

Sponsor

Tehran University of Medical Sciences (Other)

Overall Status

Completed

CT.gov ID

NCT01271985

Collaborator

Golestan University of Medical Science (Other), University of Birmingham (Other)

8,410

Enrollment

Location

Arms

Actual Duration (Months)

88.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the effects of PolyPill tablet (a fixed dose combination of two anti-hypertensive medications, atorvastatin and aspirin) on primary and secondary prevention of cardiovascular disease in Iranian adults older than 50.

Condition or Disease	Intervention/Treatment	Phase
Cardiovascular Diseases	Drug: PolyPill Other: Minimal care	Phase 3

Detailed Description

Cardiovascular diseases (myocardial infarction and stroke) are the most common cause of death and disability in Iran and account for nearly half of all-cause mortality in Iranians. Therefore, prevention of cardiovascular diseases is a top priority in countries with limited health system budgets such as Iran.

Eighty seven to hundred percent of patients dying from Coronary Heart Disease (CHD) have at least one risk factor for cardiovascular diseases. Therefore, risk factor modification in middle-aged and old individuals might prevent death and is a main priority. Combination drug therapy has been proposed as a cost-effective measure to reduce modifiable risk factors for cardiovascular disease in aged people. It has been showed that combination drug therapy can potentially decrease ischemic heart events and strokes by 88 and 80 percent, respectively.

This is a study on subjects older than 50 enrolled in the Golestan Cohort Study. The study is designed as a pragmatic cluster randomized trial. The study comprises three arms as follows:

4234 randomly selected participants receive PolyPill tablets once daily and Minimal care (which consists of direct education and pamphlet on cardiovascular risk reduction, biannual follow-ups and BP measurements).
4177 randomly selected participants receive only Minimal care as described above.
Include remaining 24000 participants of rural participants of Golestan cohort, aged 50 and higher who receive the basic primary health care provided by the local physicians and Community Health Workers for the whole participants of Golestan Cohort study consistent with the current Iranian Health Care System guidelines. A random sample of 4395 subjects from this usual care arm were selected from this group as the third arm of the study and outcome ascertainment will be performed for this sample and will be used in the secondary comparison.

Arms #1 and #2 are compared via a 2-armed open-labeled cluster Randomized Controlled Trial. Comparisons between arm #3 and the other 2 arms are also performed.

Endpoints include major cardiovascular events (death and hospitalization)

Study Design

Study Type:

Interventional

Actual Enrollment :

8410 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

Fixed-dose Combination Therapy (PolyPill) in Primary and Secondary Prevention of Cardiovascular Disease in Middle-aged and Elderly Iranians

Actual Study Start Date :

Feb 1, 2011

Actual Primary Completion Date :

Jan 1, 2019

Actual Study Completion Date :

Jan 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: PolyPill PolyPill once daily and Minimal Care	Drug: PolyPill A combination tablet containing Aspirin 81 mg, enalapril 5 mg (or valsartan 40 mg), atorvastatin 20 mg and hydrochlorothiazide 12.5 mg taken once daily Other Names: PolyPill 4-1 PolyPill 4-2 Other: Minimal care Health education pamphlet on reducing cardiovascular risk factors, direct education on reducing cardiovascular risk factors provided by the study physician and the Community Health Worker, biannual follow-up and BP measurement
Active Comparator: Minimal care Minimal care.	Other: Minimal care Health education pamphlet on reducing cardiovascular risk factors, direct education on reducing cardiovascular risk factors provided by the study physician and the Community Health Worker, biannual follow-up and BP measurement
No Intervention: Usual care Basic primary health care provided by the local physicians and Community Health Workers consistent with the current Iranian Health Care System guidelines.

Arm

Intervention/Treatment

Active Comparator: PolyPill

PolyPill once daily and Minimal Care

Drug: PolyPill

A combination tablet containing Aspirin 81 mg, enalapril 5 mg (or valsartan 40 mg), atorvastatin 20 mg and hydrochlorothiazide 12.5 mg taken once daily

Other Names:

PolyPill 4-1

PolyPill 4-2

Other: Minimal care

Health education pamphlet on reducing cardiovascular risk factors, direct education on reducing cardiovascular risk factors provided by the study physician and the Community Health Worker, biannual follow-up and BP measurement

Active Comparator: Minimal care

Minimal care.

Other: Minimal care

No Intervention: Usual care

Basic primary health care provided by the local physicians and Community Health Workers consistent with the current Iranian Health Care System guidelines.

Outcome Measures

Primary Outcome Measures

Time to first major cardiovascular event [5 years]
Major cardiovascular events are defined as: Major coronary events include: sudden cardiac death, myocardial infarction, a diagnosis of angina, revascularization procedure Cerebrovascular accidents (CVA) including transient ischemic attacks (TIA) Hospitalization because of cardiovascular disease

Secondary Outcome Measures

Blood pressure [5 years]
Changes in blood pressure after 5 years
Fasting blood sugar, total cholesterol, HDL-C and LDL-C [5 years]
Changes in fasting blood sugar and lipid profile after 5 years
Number of Subjects Developing Adverse Events [5 years]
Number of participants who experience adverse effects to the PolyPill tablet leading to discontinuation.
Compliance [5 years]
Compliance is measured by pill-count in participants of the intervention arm as percent pills taken.
Rate of major cardiovascular events [5 years]
Number of major cardiovascular events (as described above) during 5 years

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years to 79 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

50-79 years old
Enrollment in the Golestan Cohort Study

Exclusion Criteria:

Hypersensitivity to any of PolyPill components:
Hypersensitivity to Non-steroidal anti-inflammatory agents
Hypersensitivity to statins
Hypersensitivity to hydrochlorothiazide or sulfonamides
Hypersensitivity to enalapril and valsartan
Past medical history of angioedema
Medical history of GI bleeding or peptic ulcer in the last 3 months
Pregnancy or lactation
Bleeding disorders such as hemophilia
Receiving anticoagulation therapy
Alcohol consumption greater than 40gr/week
Advanced liver disease
Uncontrolled seizures
Asthma with any of the following criteria present:
Daily symptoms
Asthmatic attacks waking the patient from sleep more than once a week
History of nasal polyps
Aspirin sensitive asthma
Presence of rhinitis symptoms not due to infection
Past medical history of gout
Serum creatinine values above 2 mg/dL or a Glomerular Filtration Rate (GFR) below 30 mL/min
Hemoglobin concentrations below 11 g/dL for males and 10 g/dL for females
BP < 90/60
Debilitating medical/mental disorders affecting medication compliance (including psychosis, disabilities, and blindness)
Past medical history of stroke