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

Cardiovascular Diseases Clinical Trial

— PolyIran  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01271985
• Other study ID #: DDRC.89.17
• Status: Completed
• Phase: Phase 3
• Start date: February 2011
• Est. completion date: January 2019

Study information

• Verified date: January 2019
• Source: Tehran University of Medical Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8410
• Est. completion date: January 2019
• Est. primary completion date: January 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 79 Years

Eligibility

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

Related Conditions & MeSH terms

• Cardiovascular Diseases

Intervention

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:
• 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

Locations

Country	Name	City	State
Iran, Islamic Republic of	Golestan Cohort Study Center	Gonbad	Golestan

Sponsors (3)

Lead Sponsor	Collaborator
Tehran University of Medical Sciences	Golestan University of Medical Science, University of Birmingham

Country where clinical trial is conducted

Iran, Islamic Republic of, 

References & Publications (19)

Indian Polycap Study (TIPS), Yusuf S, Pais P, Afzal R, Xavier D, Teo K, Eikelboom J, Sigamani A, Mohan V, Gupta R, Thomas N. Effects of a polypill (Polycap) on risk factors in middle-aged individuals without cardiovascular disease (TIPS): a phase II, double-blind, randomised trial. Lancet. 2009 Apr 18;373(9672):1341-51. doi: 10.1016/S0140-6736(09)60611-5. Epub 2009 Mar 30. — View Citation

Lonn E, Bosch J, Teo KK, Pais P, Xavier D, Yusuf S. The polypill in the prevention of cardiovascular diseases: key concepts, current status, challenges, and future directions. Circulation. 2010 Nov 16;122(20):2078-88. doi: 10.1161/CIRCULATIONAHA.109.873232. Review. — View Citation

Lonn E, Yusuf S. Polypill: the evidence and the promise. Curr Opin Lipidol. 2009 Dec;20(6):453-9. doi: 10.1097/MOL.0b013e32833305a3. Review. — View Citation

Majed M, Moradmand Badie S. A pilot double-blind randomised placebo-controlled trial of the effects of fixed-dose combination therapy ('polypill') on cardiovascular risk factors. Arch Iran Med. 2011 Jan;14(1):78-80. doi: 011141/AIM.0020. — View Citation

Malekzadeh F, Marshall T, Pourshams A, Gharravi M, Aslani A, Nateghi A, Rastegarpanah M, Khoshnia M, Semnani S, Salahi R, Thomas GN, Larijani B, Cheng KK, Malekzadeh R. A pilot double-blind randomised placebo-controlled trial of the effects of fixed-dose combination therapy ('polypill') on cardiovascular risk factors. Int J Clin Pract. 2010 Aug;64(9):1220-7. doi: 10.1111/j.1742-1241.2010.02412.x. — View Citation

Malekzadeh F, Pourshams A, Marshall T. The preventive polypill--much promise, insufficient evidence. Arch Iran Med. 2007 Jul;10(3):430-1. — View Citation

PILL Collaborative Group, Rodgers A, Patel A, Berwanger O, Bots M, Grimm R, Grobbee DE, Jackson R, Neal B, Neaton J, Poulter N, Rafter N, Raju PK, Reddy S, Thom S, Vander Hoorn S, Webster R. An international randomised placebo-controlled trial of a four-component combination pill ("polypill") in people with raised cardiovascular risk. PLoS One. 2011;6(5):e19857. doi: 10.1371/journal.pone.0019857. Epub 2011 May 25. — View Citation

Relton C, Torgerson D, O'Cathain A, Nicholl J. Rethinking pragmatic randomised controlled trials: introducing the "cohort multiple randomised controlled trial" design. BMJ. 2010 Mar 19;340:c1066. doi: 10.1136/bmj.c1066. — View Citation

Rifai L, Khan BV. Do the current medical and economic times dictate the need for the "polypill"? J Clin Hypertens (Greenwich). 2009 Dec;11(12):775-6. doi: 10.1111/j.1751-7176.2009.00188.x. — View Citation

Robinson JG, Maheshwari N. A "poly-portfolio" for secondary prevention: a strategy to reduce subsequent events by up to 97% over five years. Am J Cardiol. 2005 Feb 1;95(3):373-8. — View Citation

Sanson-Fisher RW, Bonevski B, Green LW, D'Este C. Limitations of the randomized controlled trial in evaluating population-based health interventions. Am J Prev Med. 2007 Aug;33(2):155-61. Review. — View Citation

Sanz G, Fuster V. Fixed-dose combination therapy and secondary cardiovascular prevention: rationale, selection of drugs and target population. Nat Clin Pract Cardiovasc Med. 2009 Feb;6(2):101-10. doi: 10.1038/ncpcardio1419. Epub 2008 Dec 23. Review. — View Citation

Sarrafzadegan N, Talaei M, Sadeghi M, Kelishadi R, Oveisgharan S, Mohammadifard N, Sajjadieh AR, Kabiri P, Marshall T, Thomas GN, Tavasoli A. The Isfahan cohort study: rationale, methods and main findings. J Hum Hypertens. 2011 Sep;25(9):545-53. doi: 10.1038/jhh.2010.99. Epub 2010 Nov 25. — View Citation

Sepanlou SG, Kamangar F, Poustchi H, Malekzadeh R. Reducing the burden of chronic diseases: a neglected agenda in Iranian health care system, requiring a plan for action. Arch Iran Med. 2010 Jul;13(4):340-50. doi: 010134/AIM.0015. Review. — View Citation

Sepanlou SG, Poustchi H, Kamangar F, Malekzadeh R. Effectiveness and feasibility of lifestyle and low-cost pharmacologic interventions in the prevention of chronic diseases: a review. Arch Iran Med. 2011 Jan;14(1):46-53. doi: 011141/AIM.0010. Review. — View Citation

Soliman EZ, Mendis S, Dissanayake WP, Somasundaram NP, Gunaratne PS, Jayasingne IK, Furberg CD. A Polypill for primary prevention of cardiovascular disease: a feasibility study of the World Health Organization. Trials. 2011 Jan 5;12:3. doi: 10.1186/1745-6215-12-3. — View Citation

Wald DS, Wald NJ. Implementation of a simple age-based strategy in the prevention of cardiovascular disease: the Polypill approach. J Eval Clin Pract. 2012 Jun;18(3):612-5. doi: 10.1111/j.1365-2753.2011.01637.x. Epub 2011 Jan 30. — View Citation

Wald DS, Wald NJ. The Polypill in the prevention of cardiovascular disease. Prev Med. 2011 Jan;52(1):16-7. doi: 10.1016/j.ypmed.2010.11.015. Epub 2010 Dec 2. — View Citation

Wald NJ, Law MR. A strategy to reduce cardiovascular disease by more than 80%. BMJ. 2003 Jun 28;326(7404):1419. Erratum in: BMJ. 2006 Sep;60(9):823. BMJ. 2003 Sep 13;327(7415):586. — View Citation

* Note: There are 19 references in all — Click here to view all references

Outcome

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