Impact of CYP2C19 Genotype-guided Clopidogrel and Ticagrelor Treatment on Platelet Function Test and Metabolomics Profile Among Coronary Artery Disease (CAD) Patients Undergoing Percutaneous Coronary Intervention (PCI)
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Platelet Reactivity
研究概览
简要总结
Several studies have shown that pharmacodynamic (PD) response varies between patients treated with clopidogrel and that individuals with reduced response have an increased risk of recurrent ischemic events, particularly in patients undergoing percutaneous coronary intervention. This is due to several factors influencing the response to clopidogrel, including genetic variations of the cytochrome P450 (CYP) 2C19 enzyme. Loss of function (LOF) carriers of the CYP2C19 gene are associated with the decreased generation of the active metabolite clopidogrel and decreased platelet inhibition, which translates to an increased rate of adverse cardiovascular events, particularly in the setting of percutaneous coronary intervention (PCI). Thus, drug regulatory authorities have cautioned about the decreased efficacy of clopidogrel among individuals with CYP2C19 LOF carriers and suggested using alternative therapies to inhibit p2Y12. Ticagrelor is a new generation P2Y12 receptor inhibitor with greater efficacy for PD and reduced rates of ischemic events compared with clopidogrel and are not affected by the CYP2C19 LOF polymorphism. However, in clinical practice, the genotype-guided selection strategy for the oral P2Y12 inhibitor has been limited despite intensive research efforts. This is due to the interaction of cardiovascular risk factors and molecular and biochemical complications that lead to poor response to platelet inhibitor therapy, which impedes physicians' ability to prescribe a more effective and personalized antiplatelet therapy. Therefore, we must move away from traditional approaches and use integrated systems biology study designs and disciplines to bridge the gap between genotype, phenotype, disease manifestation and/or recurrence. Pharmacometabolomics is a rapidly developing field that takes advantage of a systems pharmacology approach to probe the molecular pathways involved in drug response variability to understand metabolic changes and identify novel biomarkers that can be used to predict response more comprehensively. Using profiles of changes in metabolites can help establish drug exposure fingerprints and clarify the determinants of drug response. This study aims to investigate the Impact of pharmacogenetics-guided clopidogrel and ticagrelor treatment on platelet function test and its association with metabolomics in Coronary Artery Disease (CAD) patients undergoing PCI in Malaysia
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males or females.
- •Age more than 18 and below 80 years.
- •Patients with stable CAD planned for elective PCI.
- •Thienopyridine naive for at least two weeks before admission.
排除标准
- •Any urgent/emergent coronary angiography procedure that would not allow for genetic testing to be performed before PCI
- •Considered at high risk for bleeding
- •History of ischemic or hemorrhagic stroke or transient ischemic attack
- •. Current treatment with drugs interfering with CYP3A4 metabolism (to avoid interaction with Ticagrelor): ketoconazole, itraconazole, voriconazole, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir, and telithromycin
- •History of ACS within 12 months of screening or need for revascularization
- •Any acute or chronic unstable condition.
- •Liver disease.
- •Have increased bleeding risk, e.g., recent gastrointestinal bleed, uncontrolled high blood pressure, low platelet count.
- •History of intolerance or allergy to ticagrelor or clopidogrel
- •Patient on dialysis.
研究组 & 干预措施
Clopidogrel
The primary endpoint is the non-inferiority in platelet reactivity of clopidogrel versus ticagrelor among CYP2C19*2 or *3 allele carriers.
干预措施: Clopidogrel (Drug)
Clopidogrel
The primary endpoint is the non-inferiority in platelet reactivity of clopidogrel versus ticagrelor among CYP2C19*2 or *3 allele carriers.
干预措施: Ticagrelor (Drug)
Ticagrelor
The primary endpoint is the non-inferiority in platelet reactivity of clopidogrel versus ticagrelor among CYP2C19 CYP2C19*2 or *3 allele carriers.
干预措施: Clopidogrel (Drug)
Ticagrelor
The primary endpoint is the non-inferiority in platelet reactivity of clopidogrel versus ticagrelor among CYP2C19 CYP2C19*2 or *3 allele carriers.
干预措施: Ticagrelor (Drug)
结局指标
主要结局
Platelet Reactivity
时间窗: 4 hours post loading dose
The primary endpoint is a Platelet reactivity index (PRI) measured by the ELISA-Based Vasodilator-Associated Stimulated Phosphoprotein Phosphorylation Assay 4hours/hospital discharge post randomization to clopidogrel vs ticagrelor. Vasodilator-stimulated phosphoprotein (VASP) measurement is the most specific approach to evaluate the extent to which P2Y12 receptors are functionally blocked by a P2Y12 antagonist.
次要结局
- Participants With Major or Minor Bleeding(First dosing up to 30 days)
- Participants With Any Event From the Composite of All-cause Mortality, and MI(Randomization up to 30 days)
- Participants With MI Event(Randomization up to 30 days)
研究者
Mohammed Rezeq Akkaif
Principle investigator
Universiti Sains Malaysia