A Polypill for Secondary Prevention of Ischemic Heart Disease

Fixed Combination Therapy for Secondary Prevention of Major Cardiovascular Events

Cardiovascular diseases (CVD) are the leading cause of mortality and morbidity worldwide. The most important aspect of CVD secondary prevention is adherence to guideline-indicated pharmacological therapy which globally remains low. In previous studies, a Polypill containing fixed dose combination of essential drugs have improved patient adherence to these drugs. The effect of such a strategy on pharmacological therapy uptake, cost-effectiveness, and CVD recurrence in our setting will be assessed in this study. Participants hospitalized in three referral hospitals in Isfahan, Iran because of an acute myocardial infarction (MI) (ST elevation MI (STEMI) or non-ST elevation MI (NSTEMI)) will be randomized to either receiving Polypill or usual care after MI. Patient recruitment will be carried out at the time of patient discharge from the hospitals.

Study Overview

• Status: Recruiting
• Conditions: ST Elevation Myocardial Infarction; Acute Myocardial Infarction; Non-ST Elevation Myocardial Infarction
• Intervention / Treatment: Drug: Polypill

• Study Type: Interventional
• Enrollment (Anticipated): 1200
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Masoumeh Sadeghi, Professor; Phone Number: 00989134091776; Email: sadeghimasoumeh@gmail.com
• Study Contact Backup: Name: Shervin Ghaffari Hoseini, MD,PhD; Email: shghaffari@yahoo.com

Study Locations

• Iran, Islamic Republic of
  • Isfahan, Iran, Islamic Republic of, 814651148
    • Recruiting
    • Chamran Cardiology Hospital
    • Contact: Maryam Kelardasht, MS; Phone Number: 00983136115313; Email: Kelardasht@yahoo.com
  • Isfahan, Iran, Islamic Republic of
    • Recruiting
    • Cardiovascular Research Institute
    • Contact: Safoora yazdekhasti; Phone Number: 00983136115208; Email: sfa.yazdekhasti@gmail.com
    • Sub-Investigator: Nizal Sarrafzadegan, Professor
    • Sub-Investigator: Shervin Gh Hoseini, MD, PhD
    • Sub-Investigator: Hamidreza Roohafza, MD
    • Sub-Investigator: Marjan Mansourian, PhD
    • Sub-Investigator: Jamshid Najafian, MD
    • Sub-Investigator: Alireza Nateghi Nateghi, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients hospitalized because of an acute myocardial infarction (STEMI/NSTEMI) and alive after discharge for at least 1 month
• signing informed consent
• clear indication of receiving all components of Polypill (aspirin, statin, ACE inhibitor/ARB, and beta blocker)
• living in Isfahan city or nearby areas so that they can attend follow-ups
• No mental illness limiting their self-care ability or Severe illness with an estimated lifespan of less than 3 years
• No history of adverse reaction or contraindication to any component of the Polypill
• Not having Secondary hyperlipidemia, serum creatinine ≥ 2, severe heart failure
• No plan for a procedure (CABG, PCI, or another surgical procedures) within following 6 months

Exclusion Criteria:

• Patient unlikely to complete trial
• Need to change or discontinue any of the four principal drugs of the Polypill to achieve better control of the disease or risk factors or because of adverse drug reactions (based on physician's idea)
• Severe illness with an estimated lifespan of less than 3 years

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Polypill; Polypill group will receive a fixed dose combinations of aspirin (81mg), atorvastatin (40mg), metoprolol (50 mg), and Valsartan (40 mg), prescribed once daily by moth for 34 months	Drug: Polypill; fixed dose combination of aspirin (81mg), atorvastatin (40mg), metoprolol (50 mg), and Valsartan (40 mg); Other Names: Polypill-S
No Intervention: Control; The usual care arm will receive regular drug order at the time of discharge from the hospital.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
A composite clinical outcome of major adverse cardiovascular events (MACE)	MACE includes cardiac death, fatal/nonfatal MI or stroke, hospitalization due to acute coronary syndrome/acute cerebrovascular accident, revascularization procedures, development or worsening of HF, and development of persistent new AF.	from time of randomization up to 34 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
cost-effectiveness of Polypill treatment compared with usual care	The analysis will be done on direct and indirect costs of treatment. Direct costs will be assessed from perspective of health care system. Current Iranian public medical tariffs will be the base of calculations. The incremental cost effectiveness ratio (ICER) will be calculated for primary outcomes.	up to 34 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
drug related adverse events	assessed by a questionnaire filled by the responsible physician	1 month
drug related adverse events	assessed by a questionnaire filled by the responsible physician	4 months
drug related adverse events	assessed by a questionnaire filled by the responsible physician	10 months
drug related adverse events	assessed by a questionnaire filled by the responsible physician	22 months
drug related adverse events	assessed by a questionnaire filled by the responsible physician	34 months
patient satisfaction with drug consumption	Satisfaction Questionnaire for Medication (TSQM)	1 month
patient satisfaction with drug consumption	Satisfaction Questionnaire for Medication (TSQM)	4 months
patient satisfaction with drug consumption	Satisfaction Questionnaire for Medication (TSQM)	10 months
patient satisfaction with drug consumption	Satisfaction Questionnaire for Medication (TSQM)	22 months
patient satisfaction with drug consumption	Satisfaction Questionnaire for Medication (TSQM)	34 months
health related quality of life	Validated Persian version of the EuroQol-5D (EQ-5D)	1 month
health related quality of life	Validated Persian version of the EuroQol-5D (EQ-5D)	4 months
health related quality of life	Validated Persian version of the EuroQol-5D (EQ-5D)	10 months
health related quality of life	Validated Persian version of the EuroQol-5D (EQ-5D)	22 months
health related quality of life	Validated Persian version of the EuroQol-5D (EQ-5D)	34 months
changes in systolic blood pressure from baseline	average readings of systolic blood pressure measured two times (at least 3 min apart) at sitting position	baseline and 1 month
changes in systolic blood pressure from baseline	average readings of systolic blood pressure measured two times (at least 3 min apart) at sitting position	baseline and 4 months
changes in systolic blood pressure from baseline	average readings of systolic blood pressure measured two times (at least 3 min apart) at sitting position	baseline and 10 months
changes in systolic blood pressure from baseline	average readings of systolic blood pressure measured two times (at least 3 min apart) at sitting position	baseline and 22 months
changes in systolic blood pressure from baseline	average readings of systolic blood pressure measured two times (at least 3 min apart) at sitting position	baseline and 34 months
change in serum LDL from baseline	fasting Low Density Lipoprotein Cholesterol (LDL-C)	baseline and 1 month
change in serum LDL from baseline	fasting Low Density Lipoprotein Cholesterol (LDL-C)	baseline and 4 months
change in serum LDL from baseline	fasting Low Density Lipoprotein Cholesterol (LDL-C)	baseline and 10 months
change in serum LDL from baseline	fasting Low Density Lipoprotein Cholesterol (LDL-C)	baseline and 22 months
change in serum LDL from baseline	fasting Low Density Lipoprotein Cholesterol (LDL-C)	baseline and 34 months
patient adherence to Aspirin at the final visit	patient is adherent if achieves a score of more than 6 from validated Persian version of Morisky-Medication Adherence Scale (8 item) Questionnaire (MMAS-8) (score: 0 to 8) and more than 85% of pills prescribed over last 3 months are consumed (pill count method)	34 months
patient adherence to Atorvastatin at the final visit	MMAS-8 questionnaire and pill count	34 months
patient adherence to Metoprolol at the final visit	MMAS-8 questionnaire and pill count	34 months
patient adherence to valsartan at the final visit	MMAS-8 questionnaire and pill count	34 months
patient adherence to Aspirin, Atorvastatin, Metoprolol, Valsartan	MMAS-8 questionnaire and pill count	1 month
patient adherence to Aspirin, Atorvastatin, Metoprolol, Valsartan	MMAS-8 questionnaire and pill count	4 months
patient adherence to Aspirin, Atorvastatin, Metoprolol, Valsartan	MMAS-8 questionnaire and pill count	10 months
patient adherence to Aspirin, Atorvastatin, Metoprolol, Valsartan	MMAS-8 questionnaire and pill count	22 months

Collaborators and Investigators

• Sponsor: Isfahan University of Medical Sciences
• Collaborators: Tehran University of Medical Sciences
• Investigators: Principal Investigator: Masoumeh Sadeghi, professor, Isfahan Cardiovascular Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran

Study record dates

Study Major Dates

• Study Start (Actual): May 20, 2019
• Primary Completion (Anticipated): August 1, 2023
• Study Completion (Anticipated): August 1, 2024

Study Registration Dates

• First Submitted: May 17, 2018
• First Submitted That Met QC Criteria: May 17, 2018
• First Posted (Actual): May 30, 2018

Study Record Updates

• Last Update Posted (Actual): October 14, 2020
• Last Update Submitted That Met QC Criteria: October 11, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: Cardiovascular disease; cost effectiveness; fixed dose combination therapy
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction; ST Elevation Myocardial Infarction; Non-ST Elevated Myocardial Infarction
• Other Study ID Numbers: Persian Polypill

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Sharing Time Frame: 1 year after study completion
• IPD Sharing Access Criteria: Requests will be assessed by a responsible panel after signing a data access agrement.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No