Impact of Biomarkers on Pharmacokinetics and Pharmacodynamics of Ticagrelor
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 400
- 试验地点
- 7
- 主要终点
- Incidence of major adverse cardiac events (MACE)
研究概览
简要总结
It is general that there are many factors for individual differences of drugs in clinical application, of which genetic factors accounted for more than 20%. Ticagrelor is a new-type receptor antagonist of P2Y12 and it is not affected by the influence of CYP2C19 polymorphism. With lack of predicted biomarkers, especially the research data of Chinese, it has the important significance in studying individual differences of ticagrelor in the antiplatelet efficacy and safety, through the pharmacogenomics research.
The aim of this study is to determine the polymorphism of drug metabolizing enzymes, drug transporters and drug target genes in Chinese population. By detecting the gene polymorphism, we intend to study the pharmacokinetic/ pharmacodynamics/ pharmacogenomics (PK-PD-PG) correlation of ticagrelor and provide scientific basis for accurate medication guide for people to use ticagrelor.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •(I)Chinese Healthy Volunteers
- •In accordance with the inclusion criteria for each bioequivalence trial of ticagrelor;
- •Sign informed consent of the research;
- •Complete to collect indexes of pharmacodynamics and pharmacogenomics in the cycle with control drug.
- •(II)Chinese Patients
- •With diagnosis of acute coronary syndrome (ACS), included unstable angina, non ST segment elevation myocardial infarction and ST segment elevation myocardial infarction;
- •More than 18 years of age, male or female;
- •Never received ticagrelor in a month and intend to take ticagrelor or have received ticagrelor for more than one week continuously；
- •sign informed consent.
排除标准
- •(I)Chinese Healthy Volunteers
- •In accordance with the exclusion criteria for each bioequivalence trial of ticagrelor;
- •(II)Chinese Patients
- •With history of immunodeficiency disease, including positive HIV index;
- •Positive Hepatitis B surface antigen (HBsAg) and HCV index;
- •Combined therapy of CYP3A potent inhibitors (e.g., ketoconazole, itraconazole, voriconazole, telithromycin, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, Atazanavir, etc.), CYP3A substrate of narrow therapy window (e.g., cyclosporine, quinidine, etc.) and potent inducers of CYP3A (e.g., rifampin, phenytoin, carbamazepine, etc.) in 14 days before treatment with ticagrelor;
- •Severe liver dysfunction and abnormal renal function;
- •Uncontrolled hypertension, or systolic blood pressure > 180mmHg or diastolic pressure > 110mmHg during screening;
- •Include contraindications of ticagrelor, such as hypersensitivity, active bleeding, moderate or severe liver disease, previous history of intracranial hemorrhage, gastrointestinal hemorrhage in the past 6 months and major operation within 30 days.
结局指标
主要结局
Incidence of major adverse cardiac events (MACE)
时间窗: At 1 year
During the observation time, record the incidence of MACE after ticagrelor administration by telephone or outpatient clinic , including myocardial infarction, cardiac death, stent stenosis, stent thrombosis, ect.
Incidence of bleeding events
时间窗: At 1 year
During the observation time, record the incidence of bleeding events after ticagrelor administration by telephone or outpatient clinic, including subcutaneous bleeding, gingival bleeding, gastrointestinal bleeding, intracranial hemorrhage, etc.
次要结局
- Expression level of miRNA(At baseline, at 12 hours for Chinese healthy volunteers or at 48 hours for Chinese patients.)
- Expression level of proteomics(At baseline, at 12 hours for Chinese healthy volunteers or at 48 hours for Chinese patients)
- genotype detected by next generation sequencing(pre-dose of Ticagrelor)
- Level of platelet reactivity assessed by ADP aggregation rate(At baseline, at 12 hours for Chinese healthy volunteers or at 48 hours for Chinese patients.)
- Level of platelet reactivity assessed by PRI(At baseline, at 12 hours for Chinese healthy volunteers or at 48 hours for Chinese patients.)
- Expression level of LncRNA(At baseline, at 12 hours for Chinese healthy volunteers；at 48 hours for Chinese patients.)
- Incidence of MACEs in the other observation times(At 1 month, 6 months and 2 years (according the actual duration of ticagrelor taken in patiens))
- Incidence of bleeding events in the other observation times(At 1 month, 6 months and 2 years (according the actual duration of ticagrelor taken in patiens))
研究者
Cui Yimin
Director of pharmacy，M.D & Ph.D
Peking University First Hospital