Cost-effectiveness of Genotype Guided Treatment With Antiplatelet Drugs in STEMI Patients: Optimization of Treatment (POPular Genetics)

May 8, 2019 updated by: Vera HM Deneer

Cost-effectiveness of CYP2C19 Genotype Guided Treatment With Antiplatelet Drugs in Patients With ST-segment-elevation Myocardial Infarction Undergoing Immediate PCI With Stent Implantation: Optimization of Treatment (POPular Genetics).

Rationale: the use of antiplatelet drugs (i.e. clopidogrel, ticagrelor or prasugrel) is crucial in the treatment of patients undergoing percutaneous coronary intervention (PCI) with stent implantation to prevent atherothrombotic events. Ticagrelor and prasugrel are more effective in preventing atherothrombotic events, but with a higher risk of bleeding complications, compared to clopidogrel. Clopidogrel is converted into its active metabolite by CYP2C19. Carriers of the non functional CYP2C19*2 and *3 alleles have an impaired CYP2C19 capacity, making clopidogrel less effective. For these subjects ticagrelor or prasugrel is an alternative.

Objective: to assess the efficacy, safety and cost-effectiveness of the CYP2C19 genotype guided antiplatelet treatment strategy, using clopidogrel in non-carriers of a CYP2C19*2 or *3 allele and ticagrelor or prasugrel in carriers of a CYP2C19*2 or *3 allele in STEMI patients.

Intervention: the intervention group will be genotyped for CYP2C19*2 and *3 allele variants within 48 hours after primary PCI. Carriers will receive either ticagrelor (90 mg twice daily) or prasugrel (10 mg once daily or 5 mg once daily if the patient is older than age 75 or has a body weight less than 60 kg), according to local standards. Non-carriers will be treated with clopidogrel (75 mg once daily). The control group receives either ticagrelor or prasugrel, according to local standards at the same dosage as the CYP2C19*2 or *3 carriers in the intervention group. The antiplatelet drug will be continued for one year after PCI. The follow-up duration will be one year using follow-up questionnaires.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

2700

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Aalst, Belgium
        • OLV Hospital
  • Italy
      • Naples, Italy
        • University of Naples Federico II
  • Netherlands
      • Amersfoort, Netherlands
        • Meander Medisch Centrum
      • Amsterdam, Netherlands
        • OLVG
      • Arnhem, Netherlands
        • Rijnstate Hospital
      • Breda, Netherlands
        • Amphia Hospital
      • Groningen, Netherlands
        • University Medical Center Groningen
      • Nieuwegein, Netherlands
        • St. Antonius Hospital
      • Utrecht, Netherlands
        • University Medical Center
      • Zwolle, Netherlands
        • Isala Klinieken

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

22 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • more than 21 years of age with symptoms of acute myocardial infarction of more than 30 minutes but less than 12 hours
  • performed primary PCI with stenting for STEMI

Exclusion Criteria:

  • unable to give informed consent or have a life expectancy of less than one year
  • active malignancy with increase in bleeding risk, in the investigator's opinion
  • women who are known to be pregnant or who have given birth within the past 90 days or who are breastfeeding
  • having received thrombolytic therapy within the previous 24 hours or oral anticoagulants during the previous 7 days
  • severe renal function impairment needing dialysis
  • confirmed or persistent severe hypertension (Systolic Blood Pressure (SBP) > 180 mmHg and/or Diastolic Blood Pressure (DBP) >110 mmHg) at randomization
  • contraindication to anticoagulation or at increased bleeding risk, at the investigator's opinion
  • cardiogenic shock (SBP ≤ 80mmHg for >30 mins) or Intra-Aortic Balloon Pump (IABP) placed
  • history of major surgery, severe trauma, fracture or organ biopsy within 90 days prior to randomisation
  • clinically significant out of range values for platelet count or haemoglobin level at screening, in the investigator's opinion.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: Control group
CYP2C19 genotyping will be performed after end of study. Patients will be treated with prasugrel or ticagrelor, according to local protocol.
Active Comparator: Intervention group
CYP2C19 genotyping will be performed <48h after PCI and antiplatelet treatment will be chosen based on genotyping results.
Genetic: CYP2C19 genotyping
CYP2C19 genotyping will be performed in the intervention group. In patients with *1/*1 genotype (Extensive Metabolizer) clopidogrel will be prescribed. All patients who are carrier of a loss-to-function (*2 or *3) gene allel and all patients randomized to the control group will be prescribed prasugrel or ticagrelor, according to local protocol.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Net clinical benefit
Time Frame: 1 year
The primary endpoint is the number of patients who either died, developed a recurrent myocardial infarction (MI), developed definite stent thrombosis, stroke or PLATO major bleeding at 1 year after PCI.
1 year
Safety endpoint
Time Frame: 1 year
The primary safety endpoint is the number of patients with PLATO major or minor bleeding at 1 year after PCI.
1 year
Pharmacoeconomics endpoint
Time Frame: 1 year
The primary endpoints in terms of pharmacoeconomics are quality of life, direct medical costs e.g. costs for blood transfusions, drugs, hospitalization and non-medical costs e.g. costs incurred due to sickness absence.
1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Net clinical benefit at 30 days
Time Frame: 30 days
The number of patients who either died, developed a recurrent myocardial infarction (MI), developed definite stent thrombosis, stroke or PLATO major bleeding at 30 days after PCI.
30 days
Secondary efficacy and safety endpoint
Time Frame: 30 days and 1 year
both efficacy and safety will be studied in more detail, using the items of the primary endpoint (death, recurrent myocardial infarction, stentthrombosis, stroke, PLATO major bleeding) as separate parameters and in different combinations, adding cardiovascular and cerebrovascular death, probable and possible stent thrombosis, urgent target vessel revascularization (uTVR) and hospital admission for acute coronary syndrome (ACS) to the efficacy analysis, and (non-)CABG-related bleeding, major-, minor-, life threatening-, fatal-, intracranial and bleeding requiring transfusion to the bleeding analysis, both for 30 days and 1 year follow-up
30 days and 1 year
Secondary safety endpoint
Time Frame: 30 days and 1 year
Number of patients with bleeding events in 1 year follow up, not only using PLATO bleeding classification, but also, TIMI and BARC bleeding classifications to make the study comparable to previous and future publications
30 days and 1 year
Drug endpoint
Time Frame: 30 days and 1 year
Comparing the number of patients switching from the recommended P2Y12 inhibitor to a different P2Y12 inhibitor and the number of patients who discontinue the P2Y12 inhibitor early in both the control and genotype group
30 days and 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Vera HM Deneer

Collaborators

Federico II University
University Medical Center Groningen
UMC Utrecht
Onze Lieve Vrouw Hospital
ZonMw: The Netherlands Organisation for Health Research and Development
Rijnstate Hospital
OLVG
Isala
Meander Medical Center
Amphia Hospital

Investigators

  • Principal Investigator: Jurrien M ten Berg, MD, PhD, FESC, FACC, St. Antonius Hospital Nieuwegein, the Netherlands
  • Study Chair: Daniel MF Claassens, MD, St. Antonius Hospital Nieuwegein, the Netherlands

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 1, 2011

Primary Completion (Actual)

April 4, 2019

Study Completion (Actual)

April 4, 2019

Study Registration Dates

First Submitted

September 19, 2012

First Submitted That Met QC Criteria

January 3, 2013

First Posted (Estimate)

January 7, 2013

Study Record Updates

Last Update Posted (Actual)

May 10, 2019

Last Update Submitted That Met QC Criteria

May 8, 2019

Last Verified

May 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PGxSTEMI08

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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