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Completed

NCT Number: NCT01761786

Cost-effectiveness of Genotype Guided Treatment With Antiplatelet Drugs in STEMI Patients: 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.

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Key information

Conditions

Myocardial Infarction Acute Coronary Syndrome Cardiovascular Diseases Embolism and Thrombosis Heart Diseases Infarction Ischemia Myocardial Ischemia Necrosis Pathologic Processes Pathological Conditions, Signs and Symptoms ST Elevation Myocardial Infarction STEMI Thrombosis Vascular Diseases

Age range

22 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

OLV Hospital, Aalst, Belgium

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

CYP2C19 genotyping

Genetic

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.

Primary outcomes

  1. 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.

  2. 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.

  3. 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 outcomes

  1. 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.

  2. 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

  3. 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

  4. 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

Sponsors and collaborators

Lead sponsor

Vera HM Deneer

Other

Collaborators

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

Registry information

Official study 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).

Important dates

Study start
2011
Primary completion
2019
Study completion
2019
First posted
Jan 7, 2013
Registry last updated
May 10, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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