Impact of Biomarkers on Pharmacokinetics and Pharmacodynamics of Direct Oral Anticoagulants

Pharmacokinetics Clinical Trial

Official title:

Impact of Biomarkers on Pharmacokinetics and Pharmacodynamics of Direct Oral Anticoagulants

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03161496
• Other study ID #: 2016[1236]
• Status: Recruiting
• Start date: June 6, 2017
• Est. completion date: December 2021

Study information

• Verified date: December 2020
• Source: Peking University First Hospital
• Contact: Qian Xiang, Ph.D
• Phone: +86 010 66110802
• Email: xiangqz[@]126.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1200
• Est. completion date: December 2021
• Est. primary completion date: October 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Accurate Medication
• Apixaban
• Dabigatran
• NOACs
• Novel Oral Anticoagulants
• Pharmacodynamics
• Pharmacogenomics
• Pharmacokinetics
• Rivaroxaban

Intervention

Genetic:
• detection of genotype
detection of genotype by next generation sequencing

Locations

Country	Name	City	State
China	Beijing Hospital	Beijing	Beijing
China	Beijing HuiLongGuan Hospital	Beijing	Beijing
China	Peking University First Hospital	Beijing	Beijing
China	The Third Hospital of Changsha	Changsha	Hunan
China	The Second Affiliated Hospital Of Chongqing Medical University	Chongqing	Chongqing
China	900 Hospital of the Joint Logistics Team (Original name: Fuzhou General Hospital of Nanjing Militray Command)	Fuzhou	Fujian
China	Fujian Medical University Union Hospital	Fuzhou	Fujian
China	Anhui Provincial Hospital(The First Affiliated Hospital Of USTC)	Hefei	Anhui
China	The affiliated hospital of Inner Mongolia medical university	Hohhot	Neimenggu
China	The First Affiliated Hospital of Nanchang University	Nanchang	Jiangxi
China	The Affiliated Hospital of Qingdao University	Qingdao	Shandong
China	Renji Hospital, School of Medicine, Shanghai Jiao Tong University	Shanghai	Shanghai
China	Shanghai Public Health Clinical Center	Shanghai	Shanghai
China	the First Affiliated Hospital of Liaoning University of Traditional Chinese Medicine	Shenyang	Liaoning
China	The Affiliated Hospital of Jiangnan University, or called Original Wuxi Third Hospital	Wuxi	Jiangsu
China	Wuxi People's Hospital	Wuxi	Jiangsu
China	The 7th People's Hospital of Zhengzhou	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
Cui Yimin

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of stroke or systemic embolic events (including TIA)	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.	At 1 year
Primary	Incidence of bleeding events	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.	At 1 year
Secondary	Genotype detected by next generation sequencing	Collect blood specimen before NOACs administration, then detect genotype of NOACs by next generation sequencing.	pre-dose of NOACs (rivaroxaban, apixaban, dabigatran)
Secondary	Level of anticoagulant activity assessed by anti-factor Xa activity	Before and after rivaroxaban and apixaban administration, record anti-factor Xa activity detected by blood coagulation tests.	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
Secondary	Level of anticoagulant activity assessed by anti-factor IIa activity	Before and after dabigatran administration, record anti-factor IIa activity detected by blood coagulation tests.	At baseline; at 2 hours, at 4 hours, at 8 hours, at 12 hours for Chinese healthy volunteers, at 72 hours for Chinese patients
Secondary	Expression level of miRNA	Before and after NOACs administration, detect the expression level of miRNA about pharmacodynamics.	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.
Secondary	Expression level of LncRNA	Before and after NOACs administration, detect the expression level of LncRNA about pharmacodynamics.	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.
Secondary	Incidence of stroke or systemic embolic events in the other observation times	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.	At 1 month, 6 months and 2 years (according the actual duration of NOACs taken in patiens)
Secondary	Incidence of bleeding events in the other observation times	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.	At 1 month, 6 months and 2 years (according the actual duration of NOACs taken in patiens)