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

Study Description

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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.

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. 3500 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. 3500 randomly selected participants receive only Minimal care as described above.
3. 24000 participants receive usual care (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).

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

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	7000 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
Study Start Date :	February 2011
Estimated Primary Completion Date :	April 2018
Estimated Study Completion Date :	April 2018

Arms and Interventions

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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.

Outcome Measures

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Primary Outcome Measures :

1. Time to first major cardiovascular event [ Time Frame: 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 :

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

Eligibility Criteria

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Ages Eligible for Study:	50 Years to 79 Years (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

Iran, Islamic Republic of
Golestan Cohort Study Center
Gonbad, Golestan, Iran, Islamic Republic of

Sponsors and Collaborators

Tehran University of Medical Sciences

Golestan University of Medical Science

University of Birmingham

Investigators

Study Chair:	Reza Malekzadeh, M.D.	Digestive Disease Research Center

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications:

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.

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.

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.

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Responsible Party:	Tehran University of Medical Sciences
ClinicalTrials.gov Identifier:	NCT01271985 History of Changes
Other Study ID Numbers:	DDRC.89.17
First Posted:	January 7, 2011
Last Update Posted:	May 8, 2014
Last Verified:	May 2014

Keywords provided by Tehran University of Medical Sciences:

Cardiovascular Diseases; Drug Combinations; prevention and control	Aspirin; Antihypertensive Agents; Antilipemic Agents

Additional relevant MeSH terms:

Cardiovascular Diseases