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

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2013 by St. Antonius Hospital
Sponsor:
Collaborators:
Isala Klinieken
Meander Medical Center
UMC Utrecht
TweeSteden Ziekenhuis Tilburg
Catharina Ziekenhuis Eindhoven
ZonMw: The Netherlands Organisation for Health Research and Development
Information provided by (Responsible Party):
Vera HM Deneer, St. Antonius Hospital
ClinicalTrials.gov Identifier:
NCT01761786
First received: September 19, 2012
Last updated: January 11, 2013
Last verified: January 2013
  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 and *3 allele and ticagrelor or prasugrel in carriers of a CYP2C19*2 and *3 allele in STEMI patients.

Intervention: the intervention group will be genotyped for CYP2C19*2 and *3 allele variants within 48 hours after 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 75 years or has a body weight < 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
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
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 St. Antonius Hospital:

Primary Outcome Measures:
  • Net clinical benefit [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    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:
  • Secondary efficacy endpoint. [ Time Frame: 30 days ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    The number of patients in whom the antiplatelet drug is prematurely discontinued or switched to an other drug at 1 year after PCI


Estimated Enrollment: 2700
Study Start Date: June 2011
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: September 2014 (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

Ages Eligible for Study:   22 Years and older
Genders Eligible for Study:   Both
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 needing Intra-Aortic Balloon Pump (IABP)
  • 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 at screening, in the investigator's opinion.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01761786

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

Locations
Netherlands
Meander Medisch Centrum Active, not recruiting
Amersfoort, Netherlands
Catharina Ziekenhuis Not yet recruiting
Eindhoven, 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: Paul Janssen, MD         
TweeSteden Ziekenhuis Active, not recruiting
Tilburg, Netherlands
University Medical Center Recruiting
Utrecht, Netherlands
Contact: F.W. Asselbergs, MD, PhD         
Isala Klinieken Recruiting
Zwolle, Netherlands
Sponsors and Collaborators
Vera HM Deneer
Isala Klinieken
Meander Medical Center
UMC Utrecht
TweeSteden Ziekenhuis Tilburg
Catharina Ziekenhuis Eindhoven
ZonMw: The Netherlands Organisation for Health Research and Development
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: PGxSTEMI05
Study First Received: September 19, 2012
Last Updated: January 11, 2013
Health Authority: Netherlands: Dutch Health Care Inspectorate
Netherlands: Medical Ethics Review Committee (METC)
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Netherlands: ZonMw, Netherlands Organisation for Health Research and Development

Keywords provided by 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:
Infarction
Myocardial Infarction
Ischemia
Pathologic Processes
Necrosis
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Platelet Aggregation Inhibitors
Purinergic P2Y Receptor Antagonists
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 18, 2014