Impact of Biomarkers on Pharmacokinetics and Pharmacodynamics of Direct Oral Anticoagulants

NCT03161496 | Unknown

• 1 other identifier: 2016[1236]
• Study Type: observational
• Target: 1,200
• Locations: 1 country
• Sites: 17

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.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (7)

• Genotype detected by next generation sequencing

  pre-dose of NOACs (rivaroxaban, apixaban, dabigatran)

• 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

• 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

• 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.

• 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.

Study Arms (2)

wild genotype

Through next generation sequencing, distinguish wild genotype of NOACs

Genetic: detection of genotype

mutant genotype

Through next generation sequencing, distinguish mutant genotype of NOACs

Genetic: detection of genotype

Interventions

detection of genotype GENETIC

detection of genotype by next generation sequencing

mutant genotype; wild genotype

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

(I)Chinese Healthy Volunteers：In accordance with the criteria of each bioequivalence trial of NOACs；150-200 cases for each drug (II)Chinese Patients：In accordance with anticoagulation indications of NOACs，never received NOACs in a month and intend to take NOACs or have received NOACs for more than one week continuously；200 cases for each drug

You may qualify if:

• (I)Chinese Healthy Volunteers
• 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.

You may not qualify if:

• (I)Chinese Healthy Volunteers
• (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.

Sponsors & Collaborators

• Cui Yimin: lead

Study Sites (17)

Anhui Provincial Hospital（The First Affiliated Hospital Of USTC）

Hefei, Anhui, 230001, China

RECRUITING

Peking University First Hospital

Beijing, Beijing Municipality, 100034, China

RECRUITING

Beijing Hospital

Beijing, Beijing Municipality, 100730, China

RECRUITING

Beijing HuiLongGuan Hospital

Beijing, Beijing Municipality, China

ACTIVE NOT RECRUITING

The Second Affiliated Hospital Of Chongqing Medical University

Chongqing, Chongqing Municipality, 400010, China

RECRUITING

Fujian Medical University Union Hospital

Fuzhou, Fujian, 350000, China

ACTIVE NOT RECRUITING

900 Hospital of the Joint Logistics Team (Original name: Fuzhou General Hospital of Nanjing Militray Command)

Fuzhou, Fujian, China

RECRUITING

The 7th People's Hospital of Zhengzhou

Zhengzhou, Henan, China

RECRUITING

The Third Hospital of Changsha

Changsha, Hunan, China

ACTIVE NOT RECRUITING

Wuxi People's Hospital

Wuxi, Jiangsu, 214023, China

WITHDRAWN

The Affiliated Hospital of Jiangnan University, or called Original Wuxi Third Hospital

Wuxi, Jiangsu, China

ACTIVE NOT RECRUITING

The First Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, 330006, China

ACTIVE NOT RECRUITING

the First Affiliated Hospital of Liaoning University of Traditional Chinese Medicine

Shenyang, Liaoning, 110032, China

ACTIVE NOT RECRUITING

The affiliated hospital of Inner Mongolia medical university

Hohhot, Neimenggu, China

RECRUITING

The Affiliated Hospital of Qingdao University

Qingdao, Shandong, China

ACTIVE NOT RECRUITING

Shanghai Public Health Clinical Center

Shanghai, Shanghai Municipality, 201508, China

ACTIVE NOT RECRUITING

Renji Hospital, School of Medicine, Shanghai Jiao Tong University

Shanghai, Shanghai Municipality, China

RECRUITING

Related Publications (3)

• Xiang Q, Wang Z, Mu G, Xie Q, Liu Z, Zhou S, Zhang H, Wang Z, Jiang J, Hu K, Zhang Y, Zhao Z, Yuan D, Guo L, Wu T, Zhang J, Wang N, Xiang J, Gu Z, Sun J, Cui Y. Genetic variants influenced the risk of bleeding and pharmacodynamics of rivaroxaban in patients with nonvalvular atrial fibrillation: A multicentre prospective cohort study. Clin Transl Med. 2023 May;13(5):e1263. doi: 10.1002/ctm2.1263.

  PMID: 37203300 DERIVED

• Zhang H, Zhang Z, Liu Z, Mu G, Xie Q, Zhou S, Wang Z, Cao Y, Tan Y, Wei X, Yuan D, Xiang Q, Cui Y. Circulating miR-320a-3p and miR-483-5p level associated with pharmacokinetic-pharmacodynamic profiles of rivaroxaban. Hum Genomics. 2022 Dec 28;16(1):72. doi: 10.1186/s40246-022-00445-5.

  PMID: 36578040 DERIVED

• Liu Z, Mu G, Xie Q, Zhang H, Jiang J, Xiang Q, Cui Y. Hemoclot Thrombin Inhibitor Assay and Expected Peak-Trough Levels of Dabigatran: A Multicenter Study. Front Cardiovasc Med. 2022 Jul 22;9:894888. doi: 10.3389/fcvm.2022.894888. eCollection 2022.

  PMID: 35935625 DERIVED

Central Study Contacts

Qian Xiang, Ph.D

CONTACT

+86 010 66110802; xiangqz@126.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director of pharmacy，M.D & Ph.D

Study Record Dates

• First Submitted: May 9, 2017
• First Posted: May 19, 2017
• Study Start: June 6, 2017
• Primary Completion: October 1, 2021
• Study Completion: December 1, 2021
• Last Updated: December 22, 2020

Record last verified: 2020-12

Locations

CN (17)