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

Phase 3

Completed

• Conditions: Cardiovascular Diseases
• Interventions: Other: Minimal care; Drug: PolyPill

• Registration Number: NCT01271985
• Lead Sponsor: Tehran University of Medical Sciences

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.

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.

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.

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:

1. 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).

2. 4177 randomly selected participants receive only Minimal care as described above.

3. 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 Timeline

• Study First Submitted: 2010-12-14
• Study First Submitted QC: 2011-01-05
• Study First Posted: 2011-01-07
• Study Start: 2011-02
• Status Verified: 2019-01
• Primary Completion: 2019-01
• Study Completion: 2019-01
• Last Update Submitted: 2019-01-17
• Last Update Posted: 2019-01-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 8410

Inclusion Criteria

• 50-79 years old
• Enrollment in the Golestan Cohort Study

Exclusion Criteria

1. Hypersensitivity to any of PolyPill components:

   1. Hypersensitivity to Non-steroidal anti-inflammatory agents
   2. Hypersensitivity to statins
   3. Hypersensitivity to hydrochlorothiazide or sulfonamides
   4. Hypersensitivity to enalapril and valsartan

2. Past medical history of angioedema

3. Medical history of GI bleeding or peptic ulcer in the last 3 months

4. Pregnancy or lactation

5. Bleeding disorders such as hemophilia

6. Receiving anticoagulation therapy

7. Alcohol consumption greater than 40gr/week

8. Advanced liver disease

9. Uncontrolled seizures

10. Asthma with any of the following criteria present:

    1. Daily symptoms
    2. Asthmatic attacks waking the patient from sleep more than once a week
    3. History of nasal polyps
    4. Aspirin sensitive asthma
    5. Presence of rhinitis symptoms not due to infection

11. Past medical history of gout

12. Serum creatinine values above 2 mg/dL or a Glomerular Filtration Rate (GFR) below 30 mL/min

13. Hemoglobin concentrations below 11 g/dL for males and 10 g/dL for females

14. BP < 90/60

15. Debilitating medical/mental disorders affecting medication compliance (including psychosis, disabilities, and blindness)

16. Past medical history of stroke

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Minimal care	Minimal care	Minimal care.
PolyPill	PolyPill	PolyPill once daily and Minimal Care
PolyPill	Minimal care	PolyPill once daily and Minimal Care

Primary Outcome Measures

Name	Time	Method
Time to first major cardiovascular event	5 years	Major cardiovascular events are defined as: 1. Major coronary events include: sudden cardiac death, myocardial infarction, a diagnosis of angina, revascularization procedure; 2. Cerebrovascular accidents (CVA) including transient ischemic attacks (TIA); 3. Hospitalization because of cardiovascular disease

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

Golestan Cohort Study Center; 🇮🇷 Gonbad, Golestan, Iran, Islamic Republic of