Prevention of Cardiovascular Disease With Polypill Among Pars Cohort Participants

NCT ID: NCT03459560

Last Updated: 2021-02-10

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

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

4415 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-12-20

Study Completion Date

2022-03-20

Brief Summary

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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

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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).

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

SINGLE

Outcome Assessors

Study Groups

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PolyPill

Single daily dose of PolyPill and minimal care.

Group Type EXPERIMENTAL

PolyPill

Intervention Type DRUG

After the baseline enrollment and excluding non-eligible participants, we randomized villages to Polypill and control arms. Follow-ups are scheduled for 1, 3, and 6 months after the initial enrollment in the Polypill arm and every six months thereafter. For the minimal care arm, the follow-ups are arranged every six months.

Control

Only minimal care

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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PolyPill

After the baseline enrollment and excluding non-eligible participants, we randomized villages to Polypill and control arms. Follow-ups are scheduled for 1, 3, and 6 months after the initial enrollment in the Polypill arm and every six months thereafter. For the minimal care arm, the follow-ups are arranged every six months.

Intervention Type DRUG

Other Intervention Names

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PolyPill-E, Polypill-V

Eligibility Criteria

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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
Minimum Eligible Age

50 Years

Maximum Eligible Age

79 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Shiraz University of Medical Sciences

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, MD

Role: STUDY_CHAIR

Tehran University of Medical Sciences

Locations

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Pars Cohort Center

Shiraz, Fars, Iran

Site Status

Countries

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Iran

References

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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 BACKGROUND
PMID: 31448738 (View on PubMed)

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)

Ostovaneh MR, Poustchi H, Hemming K, Marjani H, Pourshams A, Nateghi A, Majed M, Navabakhsh B, Khoshnia M, Jaafari E, Mohammadifard N, Malekzadeh F, Merat S, Sadeghi M, Naemi M, Etemadi A, Thomas GN, Sarrafzadegan N, Cheng KK, Marshall T, Malekzadeh R. Polypill for the prevention of cardiovascular disease (PolyIran): study design and rationale for a pragmatic cluster randomized controlled trial. Eur J Prev Cardiol. 2015 Dec;22(12):1609-17. doi: 10.1177/2047487314550803. Epub 2014 Sep 17.

Reference Type BACKGROUND
PMID: 25230980 (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)

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)

Yusuf S, Pais P, Sigamani A, Xavier D, Afzal R, Gao P, Teo KK. Comparison of risk factor reduction and tolerability of a full-dose polypill (with potassium) versus low-dose polypill (polycap) in individuals at high risk of cardiovascular diseases: the Second Indian Polycap Study (TIPS-2) investigators. Circ Cardiovasc Qual Outcomes. 2012 Jul 1;5(4):463-71. doi: 10.1161/CIRCOUTCOMES.111.963637. Epub 2012 Jul 10.

Reference Type BACKGROUND
PMID: 22787067 (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)

Malekzadeh F, Gandomkar A, Poustchi H, Etemadi A, Roshandel G, Attar A, Abtahi F, Sadeghi Boogar S, Mohammadkarimi V, Fattahi MR, Mohagheghi A, Malekzadeh R, Sepanlou SG. Effectiveness of polypill for primary and secondary prevention of cardiovascular disease: a pragmatic cluster-randomised controlled trial (PolyPars). Heart. 2024 Jun 25;110(14):940-946. doi: 10.1136/heartjnl-2023-323614.

Reference Type DERIVED
PMID: 38485210 (View on PubMed)

Malekzadeh F, Gandomkar A, Malekzadeh Z, Poustchi H, Moghadami M, Fattahi MR, Moini M, Anushiravani A, Mortazavi R, Sadeghi Boogar S, Mohammadkarimi V, Abtahi F, Merat S, Sepanlou SG, Malekzadeh R. Effectiveness of Polypill for Prevention of Cardiovascular Disease (PolyPars): Protocol of a Randomized Controlled Trial. Arch Iran Med. 2020 Aug 1;23(8):548-556. doi: 10.34172/aim.2020.58.

Reference Type DERIVED
PMID: 32894967 (View on PubMed)

Other Identifiers

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MOH-700/107

Identifier Type: -

Identifier Source: org_study_id

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