Prevention of Cardiovascular Disease With Polypill Among Pars Cohort Participants

Cardiovascular Diseases Clinical Trial

Official title:

Effectiveness of Polypill for Primary Prevention of Cardiovascular Disease (PolyPars): Study Design and Rationale for a Pragmatic Cluster Randomized Controlled Trial

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03459560
• Other study ID #: MOH-700/107
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: December 20, 2015
• Est. completion date: March 20, 2022

Study information

• Verified date: January 2021
• 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 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.

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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 4415
• Est. completion date: March 20, 2022
• Est. primary completion date: March 20, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 79 Years

Eligibility

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

Related Conditions & MeSH terms

• Cardiovascular Diseases

Intervention

Drug:
• 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.

Locations

Country	Name	City	State
Iran, Islamic Republic of	Pars Cohort Center	Shiraz	Fars

Sponsors (2)

Lead Sponsor	Collaborator
Tehran University of Medical Sciences	Shiraz University of Medical Sciences

Country where clinical trial is conducted

Iran, Islamic Republic of, 

References & Publications (10)

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

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

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. — 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. Erratum in: PLoS One. 2019 Nov 25;14(11):e0225924. — View Citation

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. — 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. 2003 Sep 13;327(7415):586. BMJ. 2006 Sep;60(9):823. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	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	Non cardiovascular mortality	Any death other than those due to CVDs during 5 years	5 years
Secondary	Level of fasting blood sugar (mg/dL)	Changes in fasting blood sugar after 5 years	5 years
Secondary	Level of blood pressure (mmHg)	Changes in blood pressure after 5 years	5 years
Secondary	Level of total cholesterol (mg/dL)	Changes in total cholesterol after 5 years	5 years
Secondary	Level of HDL (mg/dL)	Changes in HDL after 5 years	5 years
Secondary	Level of LDL (mg/dL)	Changes in LDL after 5 years	5 years
Secondary	Level of triglycerides (mg/dL)	Changes in triglycerides after 5 years	5 years