Impact of Biomarkers on Pharmacokinetics and Pharmacodynamics of Direct Oral Anticoagulants
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 1,200
- 试验地点
- 17
- 主要终点
- Incidence of stroke or systemic embolic events (including TIA)
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%. Novel oral anticoagulants-NOACs (include rivaroxaban, apixaban, dabigatran and so on) have advantages of convenient use and no need of monitoring, compared with the traditional vitamin K antagonist. With lack of predicted biomarkers, especially the research data of Chinese, it has the important significance in studying individual differences of NOACs in the anticoagulant 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 NOACs and provide scientific basis for accurate medication guide for people to use NOACs.
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 NOACs;
- •Sign informed consent of the research;
- •Complete to collect indexes of pharmacodynamics and pharmacogenomics in the cycle with control drug.
- •(II)Chinese Patients
- •In accordance with anticoagulation indications of NOACs, include prevention of thrombosis in non valvular atrial fibrillation, prevention and treatment of deep vein thrombosis / pulmonary embolism and prevention of thrombosis after knee / hip replacement;
- •More than 18 years of age, male or female;
- •Never received NOACs in a month and intend to take NOACs or have received NOACs 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 NOACs;
- •(II)Chinese Patients
- •With history of immunodeficiency disease, including positive HIV index;
- •Positive Hepatitis B surface antigen (HBsAg) and HCV index;
- •Combined therapy of CYP3A4 strong inhibitors and P-gp inhibitors (e.g., systemic pyrrole antifungal agents such as ketoconazole, itraconazole, voriconazole and posaconazole; human immunodeficiency virus (HIV) - protease inhibitors such as ritonavir), CYP3A4 strong inducers and P-gp inducers (e.g., rifampicin, phenytoin, phenobarbital, carbamazepine, St. John's Wort, etc.) in 14 days before treatment with NOACs;
- •Severe liver dysfunction and abnormal renal function;
- •Include contraindications of NOACs, 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 stroke or systemic embolic events (including TIA)
时间窗: At 1 year
During the observation time, record the incidence of stroke or systemic embolic events (including TIA) after NOACs(rivaroxaban, apixaban, dabigatran) administration by telephone or out-patient clinic.
Incidence of bleeding events
时间窗: At 1 year
During the observation time, record the incidence of bleeding events after NOACs(rivaroxaban, apixaban, dabigatran) administration by telephone and out-patient clinic, including subcutaneous bleeding, gingival bleeding, gastrointestinal bleeding, intracranial hemorrhage, etc.
次要结局
- Expression level of miRNA(At baseline; at 2 or 3 hours, at 4 hours (only for dabigatran), at 8 or 9 hours, at 12 hours for Chinese healthy volunteers, at 48 or 72 hours for Chinese patients.)
- Genotype detected by next generation sequencing(pre-dose of NOACs (rivaroxaban, apixaban, dabigatran))
- Level of anticoagulant activity assessed by anti-factor Xa activity(At baseline; at 3 hours, at 8 or 9 hours, at 12 hours for Chinese healthy volunteers, at 48 or 72 hours for Chinese patients)
- Level of anticoagulant activity assessed by anti-factor IIa activity(At baseline; at 2 hours, at 4 hours, at 8 hours, at 12 hours for Chinese healthy volunteers, at 72 hours for Chinese patients)
- Incidence of bleeding events in the other observation times(At 1 month, 6 months and 2 years (according the actual duration of NOACs taken in patiens))
- Expression level of LncRNA(At baseline; at 2 or 3 hours, at 4 hours (only for dabigatran), at 8 or 9 hours, at 12 hours for Chinese healthy volunteers, at 48 or 72 hours for Chinese patients.)
- Incidence of stroke or systemic embolic events in the other observation times(At 1 month, 6 months and 2 years (according the actual duration of NOACs taken in patiens))
研究者
Cui Yimin
Director of pharmacy，M.D & Ph.D
Peking University First Hospital