Impact of Biomarkers on Pharmacokinetics and Pharmacodynamics of Direct Oral Anticoagulants
- Conditions
- NOACsRivaroxabanApixabanPharmacokineticsPharmacodynamicsAccurate MedicationNovel Oral AnticoagulantsDabigatranPharmacogenomics
- Interventions
- Genetic: detection of genotype
- Registration Number
- NCT03161496
- Lead Sponsor
- Cui Yimin
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 1200
(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.
(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.
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description mutant genotype detection of genotype Through next generation sequencing, distinguish mutant genotype of NOACs wild genotype detection of genotype Through next generation sequencing, distinguish wild genotype of NOACs
- Primary Outcome Measures
Name Time Method Incidence of stroke or systemic embolic events (including TIA) 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 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.
- Secondary Outcome Measures
Name Time Method 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. Before and after NOACs administration, detect the expression level of miRNA about pharmacodynamics.
Genotype detected by next generation sequencing pre-dose of NOACs (rivaroxaban, apixaban, dabigatran) Collect blood specimen before NOACs administration, then detect genotype of NOACs by next generation sequencing.
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 Before and after rivaroxaban and apixaban administration, record anti-factor Xa activity detected by blood coagulation tests.
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 Before and after dabigatran administration, record anti-factor IIa activity detected by blood coagulation tests.
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) During the other 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.
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. Before and after NOACs administration, detect the expression level of LncRNA about pharmacodynamics.
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) During the other 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.
Trial Locations
- Locations (17)
The Third Hospital of Changsha
🇨🇳Changsha, Hunan, China
Wuxi People's Hospital
🇨🇳Wuxi, Jiangsu, China
Anhui Provincial Hospital（The First Affiliated Hospital Of USTC）
🇨🇳Hefei, Anhui, China
Beijing Hospital
🇨🇳Beijing, Beijing, China
Beijing HuiLongGuan Hospital
🇨🇳Beijing, Beijing, China
The Second Affiliated Hospital Of Chongqing Medical University
🇨🇳Chongqing, Chongqing, China
Fujian Medical University Union Hospital
🇨🇳Fuzhou, Fujian, China
900 Hospital of the Joint Logistics Team (Original name: Fuzhou General Hospital of Nanjing Militray Command)
🇨🇳Fuzhou, Fujian, China
The 7th People's Hospital of Zhengzhou
🇨🇳Zhengzhou, Henan, China
The Affiliated Hospital of Jiangnan University, or called Original Wuxi Third Hospital
🇨🇳Wuxi, Jiangsu, China
The First Affiliated Hospital of Nanchang University
🇨🇳Nanchang, Jiangxi, China
The affiliated hospital of Inner Mongolia medical university
🇨🇳Hohhot, Neimenggu, China
The Affiliated Hospital of Qingdao University
🇨🇳Qingdao, Shandong, China
the First Affiliated Hospital of Liaoning University of Traditional Chinese Medicine
🇨🇳Shenyang, Liaoning, China
Shanghai Public Health Clinical Center
🇨🇳Shanghai, Shanghai, China
Renji Hospital, School of Medicine, Shanghai Jiao Tong University
🇨🇳Shanghai, Shanghai, China
Peking University First Hospital
🇨🇳Beijing, Beijing, China