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

NCT ID: NCT01271985

Last Updated: 2019-01-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

8410 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-02-28

Study Completion Date

2019-01-31

Brief Summary

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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

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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)

Conditions

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Cardiovascular Diseases

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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PolyPill

PolyPill once daily and Minimal Care

Group Type ACTIVE_COMPARATOR

PolyPill

Intervention Type DRUG

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

Minimal care

Intervention Type OTHER

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

Minimal care

Minimal care.

Group Type ACTIVE_COMPARATOR

Minimal care

Intervention Type OTHER

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

Usual care

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

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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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

Intervention Type DRUG

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

Intervention Type OTHER

Other Intervention Names

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PolyPill 4-1 PolyPill 4-2

Eligibility Criteria

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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
Minimum Eligible Age

50 Years

Maximum Eligible Age

79 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Golestan University of Medical sciences

OTHER

Sponsor Role collaborator

University of Birmingham

OTHER

Sponsor Role collaborator

Tehran University of Medical Sciences

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Reza Malekzadeh, M.D.

Role: STUDY_CHAIR

Digestive Disease Research Center

Locations

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Golestan Cohort Study Center

Gonbad, Golestan Province, Iran

Site Status

Countries

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Iran

References

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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.

Reference Type BACKGROUND
PMID: 20653798 (View on PubMed)

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. No abstract available.

Reference Type BACKGROUND
PMID: 21098469 (View on PubMed)

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

Reference Type BACKGROUND
PMID: 19884824 (View on PubMed)

Malekzadeh F, Pourshams A, Marshall T. The preventive polypill--much promise, insufficient evidence. Arch Iran Med. 2007 Jul;10(3):430-1. No abstract available.

Reference Type BACKGROUND
PMID: 17604490 (View on PubMed)

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. No abstract available.

Reference Type BACKGROUND
PMID: 21194270 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21647425 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19339045 (View on PubMed)

Wald NJ, Law MR. A strategy to reduce cardiovascular disease by more than 80%. BMJ. 2003 Jun 28;326(7404):1419. doi: 10.1136/bmj.326.7404.1419.

Reference Type BACKGROUND
PMID: 12829553 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21276141 (View on PubMed)

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. No abstract available.

Reference Type BACKGROUND
PMID: 21130112 (View on PubMed)

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. No abstract available.

Reference Type BACKGROUND
PMID: 20021541 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21205325 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21194261 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20597569 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19104519 (View on PubMed)

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. doi: 10.1016/j.amjcard.2004.09.036.

Reference Type BACKGROUND
PMID: 15670547 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21107436 (View on PubMed)

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. doi: 10.1016/j.amepre.2007.04.007.

Reference Type BACKGROUND
PMID: 17673104 (View on PubMed)

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. No abstract available.

Reference Type BACKGROUND
PMID: 20304934 (View on PubMed)

Dagenais GR, Pais P, Gao P, Roshandel G, Malekzadeh R, Joseph P, Yusuf S. Fixed dose combination therapies in primary cardiovascular disease prevention in different groups: an individual participant meta-analysis. Heart. 2023 Aug 24;109(18):1372-1379. doi: 10.1136/heartjnl-2022-322278.

Reference Type DERIVED
PMID: 37258095 (View on PubMed)

Roshandel G, Khoshnia M, Poustchi H, Hemming K, Kamangar F, Gharavi A, Ostovaneh MR, Nateghi A, Majed M, Navabakhsh B, Merat S, Pourshams A, Nalini M, Malekzadeh F, Sadeghi M, Mohammadifard N, Sarrafzadegan N, Naemi-Tabiei M, Fazel A, Brennan P, Etemadi A, Boffetta P, Thomas N, Marshall T, Cheng KK, Malekzadeh R. Effectiveness of polypill for primary and secondary prevention of cardiovascular diseases (PolyIran): a pragmatic, cluster-randomised trial. Lancet. 2019 Aug 24;394(10199):672-683. doi: 10.1016/S0140-6736(19)31791-X.

Reference Type DERIVED
PMID: 31448738 (View on PubMed)

Other Identifiers

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DDRC.89.17

Identifier Type: -

Identifier Source: org_study_id

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