A Pharmacodynamic Study Comparing Prasugrel Versus Ticagrelor in Patients Undergoing PCI With CYP2C19 Loss-of-function:
2020年8月27日 更新者:University of Florida
A Pharmacodynamic Study Comparing Prasugrel Versus Ticagrelor in Patients With Coronary Artery Disease Undergoing PCI With CYP2C19 Loss-of-function Genotypes: A Feasibility Study With Point-of-care Pharmacodynamic and Genetic Testing
Numerous studies have shown that pharmacodynamics (PD) response profiles vary among clopidogrel treated patients and that individuals with reduced response have an increased risk of recurrent ischemic events.
There are multiple factors contributing to clopidogrel response variability, including genetic variations of the cytochrome P450 (CYP) 2C19 enzyme.
In particular, loss-of-function (LOF) alleles of the CYP2C19 enzyme reduce transformation of clopidogrel pro-drug into its active metabolite.
Thus, patients carrying LOF alleles have lower levels of clopidogrel's active metabolite as well as diminished platelet inhibition, which translates into an increased rate of adverse cardiovascular events, particularly in the setting of percutaneous coronary intervention (PCI).
Prasugrel and ticagrelor are novel generation P2Y12 receptor inhibitors characterized by greater PD potency and reduced ischemic event rates compared with clopidogrel, and are not affected by CYP2C19 LOF polymorphisms.
However, to date there are limited head-to-head PD comparisons between these two new P2Y12 receptors blockers, and there are no studies assessing on how these agents behave among CYP2C19 LOF carriers.
The aim of the present study is to compare the PD effects of prasugrel versus ticagrelor in patients undergoing PCI with CYP2C19 LOF alleles using the novel point-of-care genetic testing Spartan RX-CYP2C19 which permits accurate and rapid identification of CYP2C19 genetic status.
研究概览
详细说明
Clopidogrel is the most broadly utilized platelet P2Y12 receptor inhibitor.
However, numerous studies have shown that pharmacodynamics (PD) response profiles vary among clopidogrel treated patients and that individuals with reduced response have an increased risk of recurrent ischemic events.
There are multiple factors contributing to clopidogrel response variability.
Among these, genetic variations of the cytochrome P450 (CYP) 2C19 enzyme, a key contributor to clopidogrel metabolism, have been involved.
In particular, loss-of-function (LOF) alleles of the CYP2C19 enzyme reduce transformation of clopidogrel pro-drug into its active metabolite.
Thus, patients carrying LOF alleles have lower levels of clopidogrel's active metabolite as well as diminished platelet inhibition, which translates into an increased rate of adverse cardiovascular events, particularly in the setting of percutaneous coronary intervention (PCI).
Because of these findings, drug regulating authorities have provided a boxed warning on the product label of clopidogrel on the potential for reduced efficacy of clopidogrel among CYP2C19 LOF carriers and suggested considering alternative antiplatelet therapies for these individuals.
Prasugrel and ticagrelor are novel generation P2Y12 receptor inhibitors characterized by greater PD potency and reduced ischemic event rates compared with clopidogrel, and are not affected by CYP2C19 LOF polymorphisms.
However, to date there are limited head-to-head PD comparisons between these two new P2Y12 receptors blockers, and there are no studies assessing on how these agents behave among CYP2C19 LOF carriers.
Tailoring antiplatelet therapy according to results of genetic testing has been limited in real world clinical practice because of not having readily accessible results of individual's genetic makeup.
The aim of the present study is to compare the PD effects of prasugrel versus ticagrelor in patients undergoing PCI with CYP2C19 LOF alleles using the novel point-of-care genetic testing Spartan RX-CYP2C19 which permits accurate and rapid identification of CYP2C19 genetic status.
研究类型
介入性
注册 (实际的)
65
阶段
- 第四阶段
联系人和位置
本节提供了进行研究的人员的详细联系信息,以及有关进行该研究的地点的信息。
学习地点
-
-
Florida
-
Jacksonville、Florida、美国、32209
- University of Florida
-
-
参与标准
研究人员寻找符合特定描述的人,称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
18年 至 74年 (成人、年长者)
接受健康志愿者
不
有资格学习的性别
全部
描述
Inclusion criteria:
- Patients scheduled for left heart catheterization and undergoing PCI
- Age 18-75 years
- On aspirin (81mg) or aspirin (81mg) and clopidogrel (75mg/day)
- Presence of at least one 2C19 LOF allele
Exclusion criteria:
- Known allergies to aspirin, prasugrel, ticagrelor, or clopidogrel
- Age >75 years
- Weight <60kg
- Considered at high risk for bleeding
- History of ischemic or hemorrhagic stroke or transient ischemic attack
- Known severe hepatic dysfunction
- On treatment with oral anticoagulant therapy (Vitamin K antagonists, dabigatran, apixaban, rivaroxaban)
- Use of glycoprotein IIb/IIIa inhibitors (abciximab, eptifibatide, tirofiban)
- Blood dyscrasia or bleeding diathesis
- Platelet count <80x106/mL
- Hemoglobin <10 g/dL.
- Active bleeding or hemodynamic instability
- Creatinine Clearance <30 mL/minute
- Patients with sick sinus syndrome (SSS) or high degree AV block without pacemaker protection.
- Current treatment with drugs interfering with CYP3A4 metabolism (to avoid interaction with Ticagrelor): Ketoconazole, itraconazole, voriconazole, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir, and telithromizycin.
- Pregnant females* *Women of childbearing age must use reliable birth control (i.e. oral contraceptives) while participating in the study.
学习计划
本节提供研究计划的详细信息,包括研究的设计方式和研究的衡量标准。
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:随机化
- 介入模型:并行分配
- 屏蔽:无(打开标签)
武器和干预
参与者组/臂 |
干预/治疗 |
---|---|
有源比较器:Ticagrelor
The primary endpoint is the non-inferiority in platelet reactivity of prasugrel versus ticagrelor among CYP2C19 loss of function allele carriers.
|
Comparison of platelet reactivity between prasugrel and ticagrelor
其他名称:
|
实验性的:Prasugrel
The primary endpoint is the non-inferiority in platelet reactivity of prasugrel versus ticagrelor among CYP2C19 loss of function allele carriers.
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Comparison of platelet reactivity between prasugrel and ticagrelor
其他名称:
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研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
---|---|---|
Platelet Reactivity
大体时间:24 hours post loading dose
|
The primary endpoint is P2Y12 reaction unit (PRU) measured by the Verify Now P2Y12 assay 24hours/hospital discharge post randomization to prasugrel vs ticagrelor.
PRU is is an arbitrary unit of measure to assess ADP-induced platelet aggregation.
|
24 hours post loading dose
|
合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
出版物和有用的链接
负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查,以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始
2014年3月1日
初级完成 (实际的)
2019年4月22日
研究完成 (实际的)
2019年4月22日
研究注册日期
首次提交
2014年2月12日
首先提交符合 QC 标准的
2014年2月14日
首次发布 (估计)
2014年2月19日
研究记录更新
最后更新发布 (实际的)
2020年9月16日
上次提交的符合 QC 标准的更新
2020年8月27日
最后验证
2020年8月1日
更多信息
与本研究相关的术语
关键字
其他相关的 MeSH 术语
其他研究编号
- UFJ 2014-12
- IRB201702750 (其他标识符:UF IRB)
计划个人参与者数据 (IPD)
计划共享个人参与者数据 (IPD)?
不
药物和器械信息、研究文件
研究美国 FDA 监管的药品
不
研究美国 FDA 监管的设备产品
不
在美国制造并从美国出口的产品
不
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