Prevention of Cardiovascular Disease With Polypill Among Pars Cohort Participants

Phase 3

• Conditions: Cardiovascular Diseases
• Interventions: Drug: PolyPill

• Registration Number: NCT03459560
• Lead Sponsor: Tehran University of Medical Sciences

Brief Summary

The purpose of this study is to determine the effects of a fixed dose combination of enalapril (or valsartan), with hydrochlorthiazide, atorvastatin and acetylsalicylic acid (PolyPill) on primary and secondary prevention of cardiovascular disease in participants of Pars Cohort of Iran.

Detailed Description

Cardiovascular diseases (CVDs) are the most common causes 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 CVDs have at least one risk factor for cardiovascular diseases. Therefore, risk factor modification 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. It has been showed that combination drug therapy can potentially decrease ischemic heart events and strokes by 88 and 80 percent, respectively.

The study is designed as a pragmatic cluster randomized controlled trial. The purpose of this study is to determine the effects of a fixed dose combination of either enalapril or valsartan, with hydrochlorthiazide, atorvastatin and acetylsalicylic acid (PolyPill) on primary and secondary prevention of cardiovascular disease in Iranian adults older than 50. Two formulations of Polypill tablets were used. The first formulation (Polypill-E) contained enalapril 5 mg. If participants developed cough, they were switched by a trained physician to Polypill-V, containing valsartan 40 mg instead of enalapril.

The investigators have previously tested the same combination in a different setting in Golestan, Northeast of Iran. The results of the study were published in the Lancet. The current study enrolls participants of Pars Cohort running in Fars province, southern Iran, aged above 50. A total of 4415 participants (91 clusters) were recruited following inclusion and exclusion criteria. The study comprises two arms as follows:

2200 randomly selected participants receive PolyPill tablets once daily and minimal care (which consists of direct education and pamphlet on cardiovascular risk reduction).

2215 randomly selected participants receive only minimal care as described above.

Endpoints include major cardiovascular events (MCVE).

Study Timeline

• Study Start: 2015-12-20
• Study First Submitted: 2018-03-03
• Study First Submitted QC: 2018-03-03
• Study First Posted: 2018-03-09
• Status Verified: 2021-01
• Last Update Submitted: 2021-02-05
• Last Update Posted: 2021-02-10
• Primary Completion: 2022-03-20
• Study Completion: 2022-03-20

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 4415

Inclusion Criteria

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

Exclusion Criteria

1. Not consenting to participate in the study

2. 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

3. Past medical history of angioedema

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

5. Pregnancy or lactation

6. Bleeding disorders such as hemophilia

7. Receiving regular anticoagulation therapy

8. Alcohol consumption greater than 40gr/week

9. Advanced liver disease

10. Uncontrolled seizures

11. 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

12. Past medical history of gout

13. Serum creatinine values above 2 mg/dL

14. Glomerular Filtration Rate (GFR) below 30 mL/min

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

16. BP < 90/60 mmHg

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

18. Past medical history of stroke

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
PolyPill	PolyPill	Single daily dose of PolyPill and minimal care.

Primary Outcome Measures

Name	Time	Method
Major Cardiovascular Events (MCVE)	5 years	the first occurrence of acute coronary syndrome (non-fatal myocardial infarction and unstable angina), fatal myocardial infarction, sudden cardiac death, new-onset heart failure, coronary artery revascularization procedures, transient ischemic attack, cerebrovascular accidents (fatal or non-fatal), and hospitalization due to any of the mentioned conditions.

Secondary Outcome Measures

Name	Time	Method
Level of blood pressure (mmHg)	5 years	Changes in blood pressure after 5 years
Level of total cholesterol (mg/dL)	5 years	Changes in total cholesterol after 5 years
Level of HDL (mg/dL)	5 years	Changes in HDL after 5 years
Level of LDL (mg/dL)	5 years	Changes in LDL after 5 years
Level of triglycerides (mg/dL)	5 years	Changes in triglycerides after 5 years
Level of fasting blood sugar (mg/dL)	5 years	Changes in fasting blood sugar 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
Non cardiovascular mortality	5 years	Any death other than those due to CVDs during 5 years

Trial Locations

Locations (1)

Pars Cohort Center; 🇮🇷 Shiraz, Fars, Iran, Islamic Republic of