Accurate Medication, Pharmacodynamics, Pharmacogenomics, Pharmacokinetics, Ticagrelor
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%. 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.
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 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.
Exclusion criteria
(I)Chinese Healthy Volunteers * In accordance with the
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of major adverse cardiac events (MACE) | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. | Before and after ticagrelor administration, record the ADP aggregation rate detected by Light Transmittance Aggregometry(LTA). |
| Expression level of miRNA | At baseline, at 12 hours for Chinese healthy volunteers or at 48 hours for Chinese patients. | Before and after ticagrelor administration, detect the expression level of miRNA about pharmacodynamics. |
| Expression level of proteomics | At baseline, at 12 hours for Chinese healthy volunteers or at 48 hours for Chinese patients | Before and after ticagrelor administration, detect the expression level of proteomics about pharmacodynamics |
| Level of platelet reactivity assessed by PRI | At baseline, at 12 hours for Chinese healthy volunteers or at 48 hours for Chinese patients. | Before and after ticagrelor administration, record PRI detected by VerifyNow System. |
| 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) | During the other 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 in the other observation times | At 1 month, 6 months and 2 years (according the actual duration of ticagrelor taken in patiens) | During the other 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. |
| Expression level of LncRNA | At baseline, at 12 hours for Chinese healthy volunteers；at 48 hours for Chinese patients. | Before and after ticagrelor administration, detect the expression level of LncRNA about pharmacodynamics. |
| genotype detected by next generation sequencing | pre-dose of Ticagrelor | Collect blood specimen before ticagrelor administration, then detect genotype of Ticagrelor by next generation sequencing. |
Countries
China
Contacts
Primary ContactQian Xiang, Ph.D
Outcome results
None listed