CYP2C19 Genotype-GUided Dual Antiplatelet theRapy in pAtieNts Treated With New Generation Drug Eluting stEnts (the GUARANTEE Study)
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 4,009
- 试验地点
- 11
- 主要终点
- Occurrence of main adverse cardiovascular and cerebrovascular events (MACCE)
研究概览
简要总结
The aim of this study is to assess the efficacy and safety of the CYP2C19 genotype guided antiplatelet treatment strategy, using clopidogrel in non-carriers of a CYP2C19*2 or *3 allele and ticagrelor in carriers of a CYP2C19*2 or *3 allele in patients treated with new generation drug eluting stents.
详细描述
Background: P2Y12 receptor inhibitors are crucial for the management of patients undergoing coronary stenting. Although large-scale trials have shown that ticagrelor is superior to clopidogrel in terms of platelet inhibition and reduction of major adverse cardiovascular events (MACE), clopidogrel remains the most commonly used P2Y12 receptor inhibitor due to its lower price and bleeding risk. Despite the combined use of aspirin and clopidogrel, a substantial portion of patients after coronary stenting are at increased risk for adverse cardiovascular events including death, myocardial infarction, and stent thrombosis. This phenomenon may be due to the so-called clopidogrel resistance. Cytochrome P450 2C19 (CYP2C19) polymorphism plays a crucial role in the clopidogrel resistance. CYP2C19 is responsible, in part, for converting the clopidogrel prodrug into an active metabolite that irreversibly binds to the P2Y12 receptor thus inhibiting ADP-induced platelet aggregation. CYP2C19*2 and *3, which encounter loss function, have been demonstrated to be the most common genetic variants resulting in clopidogrel resistance.
Methods: Patients who undergo coronary stenting will be randomized to a prospective CYP2C19 genotype-guided antiplatelet therapy arm versus a conventional therapy arm. Venous blood collection will be completed immediately after randomization in all patients eligible for the study. The genotype results involving CYP2C19*2 and *3 allele variants will be obtained within 48 hours only in the genotyping arm. CYP2C19 *2 or *3 reduced function allele patients will receive ticagrelor 90 mg bid, whereas non-*2 or -*3 CYP2C19 patients will receive clopidogrel 75 mg once daily. The conventional therapy arm will receive either clopidogrel or ticagrelor, according to the clinical and procedural characteristics of patients. The dual antiplatelet therapy will last for at least one year in the both arms. The primary endpoints will be evaluated at one-year follow-up.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient ≥18 years of age
- •Patient presents with acute coronary syndrome (ACS) or stable coronary artery disease (SCAD)
- •Patient has a percutaneous coronary intervention (PCI) indication and the new generation drug eluting stent(s) is successfully implanted
排除标准
- •Patient unable to receive 12 months of dual anti-platelet therapy
- •Patient developing procedure-related complications such as stent thrombosis, coronary dissection, coronary perforation, cardiac tamponade or no-reflow during PCI
- •Contraindicated or allergic to clopidogrel or ticagrelor
- •Patient or physician refusal to enroll in the study
- •Patient having received thrombolytic therapy within the previous 24 hours
- •Physician has known the patient's CYP2C19 genotype
- •Anticipated discontinuation of dual anti-platelet therapy within the 12-month follow-up period, example for elective surgery
- •History of intracranial hemorrhage
- •Patient has a history of bleeding diathesis or coagulopathy
- •Patient has an active pathological bleeding, such as active gastrointestinal (GI) bleeding
- •Patient is pregnant, breastfeeding, or planning to become pregnant within 12 months
- •Patient is receiving chronic oral anticoagulation therapy (i.e., vitamin K antagonist, direct thrombin inhibitor, Factor Xa inhibitor)
- •Patient with cardiogenic shock or mechanical circulatory assist devices placed
- •Patient with LVEF <30%
- •Patient with active liver diseases
- •Patient with severe renal insufficiency (eGFR <30ml/min/1.73m2 based on simplified MDRD equation or CrCl <30ml/min based on Cockcroft-Gault equation)
- •Patient has a malignancy or a life expectancy of less than one year
- •Platelet count <100 000/μL, or hematocrit <32% or >52%, or white blood cell count <3000/μL
结局指标
主要结局
Occurrence of main adverse cardiovascular and cerebrovascular events (MACCE)
时间窗: 1 year
MACCE will include all-cause death, non-fatal stroke, non-fatal myocardial infarction (MI) and ischemia driven revascularization at one-year follow-up.
次要结局
未报告次要终点
研究者
Yujie Zhou
Professor
Beijing Anzhen Hospital