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 |
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Recruitment Status :
Completed
First Posted : January 7, 2013
Last Update Posted : May 10, 2019
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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 or disease | Intervention/treatment | Phase |
|---|---|---|
| Myocardial Infarction STEMI | Genetic: CYP2C19 genotyping | Phase 4 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 2700 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Single (Outcomes Assessor) |
| Primary Purpose: | Treatment |
| 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). |
| Actual Study Start Date : | June 2011 |
| Actual Primary Completion Date : | April 4, 2019 |
| Actual Study Completion Date : | April 4, 2019 |
| Arm | Intervention/treatment |
|---|---|
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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.
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Active Comparator: Intervention group
CYP2C19 genotyping will be performed <48h after PCI and antiplatelet treatment will be chosen based on genotyping results.
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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. |
- 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.
- 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
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| Ages Eligible for Study: | 22 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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.
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
| Belgium | |
| OLV Hospital | |
| Aalst, Belgium | |
| Italy | |
| University of Naples Federico II | |
| Naples, Italy | |
| Netherlands | |
| Meander Medisch Centrum | |
| Amersfoort, Netherlands | |
| OLVG | |
| Amsterdam, Netherlands | |
| Rijnstate Hospital | |
| Arnhem, Netherlands | |
| Amphia Hospital | |
| Breda, Netherlands | |
| University Medical Center Groningen | |
| Groningen, Netherlands | |
| St. Antonius Hospital | |
| Nieuwegein, Netherlands | |
| University Medical Center | |
| Utrecht, Netherlands | |
| Isala Klinieken | |
| Zwolle, Netherlands | |
| 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 automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Vera HM Deneer, PharmD, PhD, St. Antonius Hospital |
| ClinicalTrials.gov Identifier: | NCT01761786 |
| Other Study ID Numbers: |
PGxSTEMI08 |
| First Posted: | January 7, 2013 Key Record Dates |
| Last Update Posted: | May 10, 2019 |
| Last Verified: | May 2019 |
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Myocardial Infarction Thrombosis Acute Coronary Syndrome Myocardial Ischemia Heart Diseases Cardiovascular Diseases Vascular Diseases |
Embolism and Thrombosis Genetic Testing Clopidogrel Prasugrel Ticagrelor Platelet Aggregation Inhibitors Purinergic P2Y Receptor Antagonists |
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Myocardial Infarction Infarction Ischemia Pathologic Processes Necrosis |
Myocardial Ischemia Heart Diseases Cardiovascular Diseases Vascular Diseases |