CClinicalTrials.gg
Status unknownNCT03459560Updated Feb 10, 2021

Prevention of Cardiovascular Disease With Polypill Among Pars Cohort Participants

A Phase 3 interventional study of PolyPill in Cardiovascular Diseases, sponsored by Tehran University of Medical Sciences. Status unknown at 1 site in Iran, Islamic Republic of. Open to participants aged 50 Years to 79 Years. Per ClinicalTrials.gov, last updated 2021-02-10.

Sponsored by Tehran University of Medical Sciences · Phase 3, Interventional, and Prevention

The sponsor has not verified this record recently (last verified Jan 2021), so the status shown — last known as Active, not recruiting — may be out of date.
Phase
Phase 3
Study type
Interventional
Enrollment
4,415
Allocation
Randomized
Ages
50 Years to 79 Years
Sex
All
01

Study 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.

Read the 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).

02

Conditions studied

  • Cardiovascular Diseases

Keywords

  • fixed-dose combination therapy
  • Polypill
  • Prevention
  • Cardiovascular diseases
03

Who can participate

Ages eligible
50 Years to 79 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

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

Exclusion criteria

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
04

Study design

Phase
Phase 3
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Single (Outcomes assessor)
Enrollment
4,415 participants (actual)

Study arms

  • Experimental
    PolyPill

    Single daily dose of PolyPill and minimal care.

    Drug: PolyPill

  • No intervention
    Control

    Only minimal care

Interventions

  • DrugPolyPill

    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.

    Also known as: PolyPill-E, Polypill-V

05

What researchers measure

Primary outcomes

  1. Major Cardiovascular Events (MCVE)

    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.

    Time frame: 5 years

Secondary outcomes

  1. Number of Subjects Developing Adverse Events

    Number of participants who experience adverse effects to the PolyPill tablet leading to discontinuation

    Time frame: 5 years

  2. Compliance

    Compliance is measured by pill-count in participants of the intervention arm as percent pills taken

    Time frame: 5 years

  3. Non cardiovascular mortality

    Any death other than those due to CVDs during 5 years

    Time frame: 5 years

  4. Level of fasting blood sugar (mg/dL)

    Changes in fasting blood sugar after 5 years

    Time frame: 5 years

  5. Level of blood pressure (mmHg)

    Changes in blood pressure after 5 years

    Time frame: 5 years

  6. Level of total cholesterol (mg/dL)

    Changes in total cholesterol after 5 years

    Time frame: 5 years

  7. Level of HDL (mg/dL)

    Changes in HDL after 5 years

    Time frame: 5 years

  8. Level of LDL (mg/dL)

    Changes in LDL after 5 years

    Time frame: 5 years

  9. Level of triglycerides (mg/dL)

    Changes in triglycerides after 5 years

    Time frame: 5 years

06

Study locations

1 site
  • Pars Cohort Center
    Shiraz, Fars, Iran, Islamic Republic of
07

References and documents

Publications

  • 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. PubMed 31448738 ↗
  • 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. PubMed 20653798 ↗
  • 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. PubMed 25230980 ↗
  • 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. PubMed 21098469 ↗
  • 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. PubMed 17604490 ↗
  • 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. PubMed 21194270 ↗
  • 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. Erratum In: PLoS One. 2019 Nov 25;14(11):e0225924. doi: 10.1371/journal.pone.0225924. PubMed 21647425 ↗
  • 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. PubMed 22787067 ↗
  • 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. PubMed 19339045 ↗
  • 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. Erratum In: BMJ. 2003 Sep 13;327(7415):586. BMJ. 2006 Sep;60(9):823. PubMed 12829553 ↗
  • 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. Erratum In: Arch Iran Med. 2021 Feb 01;24(2):166. doi: 10.34172/aim.2021.26. PubMed 32894967 ↗

Individual participant data

Plan to share: No

08

Registry details

Key details

Study ID
NCT03459560
Lead sponsor
Tehran University of Medical Sciences
Collaborators
Shiraz University of Medical Sciences
Responsible party
Sponsor
First posted
Mar 9, 2018
Start date
Dec 20, 2015
Primary completion
Mar 20, 2022 (estimated)
Completion
Mar 20, 2022 (estimated)
Last update
Feb 10, 2021

Study contacts

Reza Malekzadeh, MD
study chair · Tehran University of Medical Sciences

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is status unknown, as verified in Jan 2021. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Start the discussion