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

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ClinicalTrials.gov Identifier: NCT01761786
Recruitment Status : Completed
First Posted : January 7, 2013
Last Update Posted : May 10, 2019
Sponsor:
Collaborators:
Isala
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
Information provided by (Responsible Party):
Vera HM Deneer, St. Antonius Hospital

Tracking Information
First Submitted Date  ICMJE September 19, 2012
First Posted Date  ICMJE January 7, 2013
Last Update Posted Date May 10, 2019
Actual Study Start Date  ICMJE June 2011
Actual Primary Completion Date April 4, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 7, 2017)
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: January 3, 2013)
  • Net clinical benefit [ Time Frame: 30 days ]
    The primary endpoint is the number of patients who either died, developed a recurrent myocardial infarction (MI), developed definite stent thrombosis, stroke or non-CABG related PLATO major bleeding at 30 days after PCI.
  • 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 non-CABG related 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.
Change History Complete list of historical versions of study NCT01761786 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 7, 2017)
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: January 3, 2013)
  • Secondary efficacy endpoint. [ Time Frame: 30 days ]
    Secondary efficacy endpoints are the number of patients who either died, died from cardiovascular death, from cerebrovascular death, developed recurrent MI, definite stent thrombosis, probable stent thrombosis, possible stent thrombosis, underwent urgent target vessel revascularisation (TVR), hospitalization for ACS, developed stroke or the number op patients with combinations of these endpoints at 30 days after PCI.
  • Secondary efficacy endpoint [ Time Frame: 1 year ]
    Secondary efficacy endpoints are the number of patients who either died, died from cardiovascular death, from cerebrovascular death, developed recurrent MI, definite stent thrombosis, probable stent thrombosis, possible stent thrombosis, underwent urgent target vessel revascularisation (TVR), hospitalization for ACS, developed stroke or the number op patients with combinations of these endpoints at 1 year after PCI.
  • Secondary safety endpoint [ Time Frame: 1 year ]
    Secondary safety endpoints are the number of patients with (non-)CABG-related major bleeding, major bleeding, minor bleeding, life threatening bleeding, fatal bleeding, intracranial bleeding, bleed requiring transfusion or the number of patients with combinations of these endpoints at 1 after PCI.
  • Drug endpoint [ Time Frame: 1 year ]
    The number of patients in whom the antiplatelet drug is prematurely discontinued or switched to an other drug at 1 year after PCI
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Cost-effectiveness of Genotype Guided Treatment With Antiplatelet Drugs in STEMI Patients: Optimization of Treatment (POPular Genetics)
Official Title  ICMJE 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).
Brief Summary

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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Myocardial Infarction
  • STEMI
Intervention  ICMJE 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.
Study Arms  ICMJE
  • 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.
    Intervention: Genetic: CYP2C19 genotyping
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 3, 2013)
2700
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE April 4, 2019
Actual Primary Completion Date April 4, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 22 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   Italy,   Netherlands
Removed Location Countries Turkey
 
Administrative Information
NCT Number  ICMJE NCT01761786
Other Study ID Numbers  ICMJE PGxSTEMI08
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Vera HM Deneer, St. Antonius Hospital
Study Sponsor  ICMJE Vera HM Deneer
Collaborators  ICMJE
  • Isala
  • 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
Investigators  ICMJE
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
PRS Account St. Antonius Hospital
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP