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

Phase 4

Completed

• Conditions: Myocardial Infarction; STEMI
• Interventions: Genetic: CYP2C19 genotyping

• Registration Number: NCT01761786
• Lead Sponsor: Vera HM Deneer

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 available

Study Timeline

• Study Start: 2011-06
• Study First Submitted: 2012-09-19
• Study First Submitted QC: 2013-01-03
• Study First Posted: 2013-01-07
• Primary Completion: 2019-04-04
• Study Completion: 2019-04-04
• Status Verified: 2019-05
• Last Update Submitted: 2019-05-08
• Last Update Posted: 2019-05-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 2700

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intervention group	CYP2C19 genotyping	CYP2C19 genotyping will be performed \<48h after PCI and antiplatelet treatment will be chosen based on genotyping results.

Primary Outcome Measures

Name	Time	Method
Net clinical benefit	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	1 year	The primary safety endpoint is the number of patients with PLATO major or minor bleeding at 1 year after PCI.
Pharmacoeconomics endpoint	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

Name	Time	Method
Secondary efficacy and safety endpoint	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
Drug endpoint	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
Net clinical benefit at 30 days	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 safety endpoint	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

Trial Locations

Locations (10)

Isala Klinieken; 🇳🇱 Zwolle, Netherlands

University of Naples Federico II; 🇮🇹 Naples, Italy

OLV Hospital; 🇧🇪 Aalst, Belgium

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