Impact of Biomarkers on Pharmacokinetics and Pharmacodynamics of Direct Oral Anticoagulants

Cui Yimin

Status

Unknown

Conditions

Pharmacodynamics

Dabigatran

NOACs

Rivaroxaban

Apixaban

Pharmacogenomics

Accurate Medication

Novel Oral Anticoagulants

Pharmacokinetics

Treatments

Genetic: detection of genotype

Study type

Observational

Funder types

Other

Identifiers

NCT03161496

2016[1236]

Details and patient eligibility

About

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.

Enrollment

1,200 estimated patients

Sex

All

Ages

18+ years old

Volunteers

Accepts Healthy Volunteers

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 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.