Accurate Medication, Apixaban, Dabigatran, NOACs, Novel Oral Anticoagulants, Pharmacodynamics, Pharmacogenomics, Pharmacokinetics, Rivaroxaban
Conditions
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.
Interventions
GENETICdetection of genotype
detection of genotype by next generation sequencing
Sponsors
Cui Yimin
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
(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.
Exclusion criteria
(I)Chinese Healthy Volunteers * In accordance with the
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
China
Contacts
Primary ContactQian Xiang, Ph.D
Outcome results
None listed