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

This study is currently recruiting participants.
Verified September 2017 by Vera HM Deneer, St. Antonius Hospital
Sponsor:
ClinicalTrials.gov Identifier:
NCT01761786
First Posted: January 7, 2013
Last Update Posted: September 11, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborators:
Isala Klinieken, Zwolle
Meander Medical Center
UMC Utrecht
University Medical Center Groningen
OLVG
Onze Lieve Vrouw Hospital
Amphia Hospital
ZonMw: The Netherlands Organisation for Health Research and Development
Federico II University
Rijnstate Hospital
Dr. Nafiz Korez Sincan State Hospital
Information provided by (Responsible Party):
Vera HM Deneer, St. Antonius Hospital
  Purpose

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.


Condition Intervention Phase
Myocardial Infarction STEMI Genetic: CYP2C19 genotyping Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Screening
Official Title: 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).

Resource links provided by NLM:


Further study details as provided by Vera HM Deneer, St. Antonius Hospital:

Primary Outcome Measures:
  • 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.

  • 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.

  • 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.


Secondary Outcome Measures:
  • 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.

  • 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

  • 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

  • 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


Estimated Enrollment: 2700
Actual Study Start Date: June 2011
Estimated Study Completion Date: January 2019
Estimated Primary Completion Date: January 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   22 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01761786


Contacts
Contact: Jurrien M ten Berg, MD, PhD +31(0)88-3201121 jurtenberg@gmail.com
Contact: Thomas O Bergmeijer, MD +31(0)88-3205163 t.bergmeijer@antoniusziekenhuis.nl

Locations
Belgium
OLV Hospital Recruiting
Aalst, Belgium
Italy
University of Naples Federico II Recruiting
Naples, Italy
Contact: Carmine Morisco, MD         
Netherlands
Meander Medisch Centrum Recruiting
Amersfoort, Netherlands
OLVG Active, not recruiting
Amsterdam, Netherlands
Rijnstate Hospital Recruiting
Arnhem, Netherlands
Amphia Hospital Active, not recruiting
Breda, Netherlands
Catharina Ziekenhuis Withdrawn
Eindhoven, Netherlands
University Medical Center Groningen Recruiting
Groningen, Netherlands
St. Antonius Hospital Recruiting
Nieuwegein, Netherlands
Contact: Jurrien M ten Berg, MD, PhD, FESC, FACC       jurtenberg@gmail.com   
Principal Investigator: Jurrien M ten Berg, MD, PhD, FESC, FACC         
Sub-Investigator: Daniel MF Claassens, MD         
TweeSteden Ziekenhuis Withdrawn
Tilburg, Netherlands
University Medical Center Active, not recruiting
Utrecht, Netherlands
Isala Klinieken Recruiting
Zwolle, Netherlands
Turkey
Dr. Nafiz Korez Sincan State Hospital Recruiting
Ankara, Turkey
Sponsors and Collaborators
Vera HM Deneer
Isala Klinieken, Zwolle
Meander Medical Center
UMC Utrecht
University Medical Center Groningen
OLVG
Onze Lieve Vrouw Hospital
Amphia Hospital
ZonMw: The Netherlands Organisation for Health Research and Development
Federico II University
Rijnstate Hospital
Dr. Nafiz Korez Sincan State Hospital
Investigators
Principal Investigator: Jurrien M ten Berg, MD, PhD, FESC, FACC St. Antonius Hospital Nieuwegein, The Netherlands
Study Chair: Thomas O. Bergmeijer, MD St. Antonius Hospital Nieuwegein, The Netherlands
  More Information

Publications:

Responsible Party: Vera HM Deneer, PharmD, PhD, St. Antonius Hospital
ClinicalTrials.gov Identifier: NCT01761786     History of Changes
Other Study ID Numbers: PGxSTEMI06
First Submitted: September 19, 2012
First Posted: January 7, 2013
Last Update Posted: September 11, 2017
Last Verified: September 2017

Keywords provided by Vera HM Deneer, St. Antonius Hospital:
Platelet Aggregation Inhibitors
Myocardial Infarction
Thrombosis
Acute Coronary Syndrome
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Embolism and Thrombosis
Genetic Testing
Clopidogrel
Prasugrel
Ticagrelor
Purinergic P2Y Receptor Antagonists

Additional relevant MeSH terms:
Platelet Aggregation Inhibitors
Infarction
Myocardial Infarction
ST Elevation Myocardial Infarction
Ischemia
Pathologic Processes
Necrosis
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Ticagrelor
Purinergic P2Y Receptor Antagonists
Prasugrel Hydrochloride
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs