Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Impact of Biomarkers on Pharmacokinetics and Pharmacodynamics of Direct Oral Anticoagulants

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03161496
Recruitment Status : Recruiting
First Posted : May 19, 2017
Last Update Posted : October 10, 2019
Sponsor:
Information provided by (Responsible Party):
Cui Yimin, Peking University First Hospital

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.


Condition or disease Intervention/treatment
Novel Oral Anticoagulants NOACs Rivaroxaban Apixaban Dabigatran Pharmacokinetics Pharmacodynamics Pharmacogenomics Accurate Medication Genetic: detection of genotype

Layout table for study information
Study Type : Observational
Estimated Enrollment : 1200 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Impact of Biomarkers on Pharmacokinetics and Pharmacodynamics of Direct Oral Anticoagulants
Actual Study Start Date : June 6, 2017
Estimated Primary Completion Date : October 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Blood Thinners

Group/Cohort Intervention/treatment
wild genotype
Through next generation sequencing, distinguish wild genotype of NOACs
Genetic: detection of genotype
detection of genotype by next generation sequencing

mutant genotype
Through next generation sequencing, distinguish mutant genotype of NOACs
Genetic: detection of genotype
detection of genotype by next generation sequencing




Primary Outcome Measures :
  1. Incidence of stroke or systemic embolic events (including TIA) [ Time Frame: 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.

  2. Incidence of bleeding events [ Time Frame: 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 Outcome Measures :
  1. Genotype detected by next generation sequencing [ Time Frame: pre-dose of NOACs (rivaroxaban, apixaban, dabigatran) ]
    Collect blood specimen before NOACs administration, then detect genotype of NOACs by next generation sequencing.

  2. Level of anticoagulant activity assessed by anti-factor Xa activity [ Time Frame: 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.

  3. Level of anticoagulant activity assessed by anti-factor IIa activity [ Time Frame: At baseline; at 2 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.

  4. Expression level of miRNA [ Time Frame: At baseline; at 2 or 3 hours, at 8or 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.

  5. Expression level of LncRNA [ Time Frame: At baseline; at 2 or 3 hours, at 8or 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03161496


Contacts
Layout table for location contacts
Contact: Qian Xiang, Ph.D +86 010 66110802 xiangqz@126.com

Locations
Layout table for location information
China, Anhui
Anhui Provincial Hospital(The First Affiliated Hospital Of USTC) Recruiting
Hefei, Anhui, China, 230001
Contact: Zhaoyi Yang, PhD    +86-0551-62283379-800    young2382@163.com   
China, Beijing
Peking University First Hospital Recruiting
Beijing, Beijing, China, 100034
Contact: Qian Xiang, Ph.D    +86 010 66110802    xiangqz@126.com   
Beijing Hospital Recruiting
Beijing, Beijing, China, 100730
Contact: Yatong Zhang, MS    +86-010-85133637    zyt2002888@qq.com   
Beijing HuiLongGuan Hospital Active, not recruiting
Beijing, Beijing, China
China, Chongqing
The Second Affiliated Hospital Of Chongqing Medical University Recruiting
Chongqing, Chongqing, China, 400010
Contact: Na Wang, MS    +86-13594036081    182429490@qq.com   
China, Fujian
Fujian Medical University Union Hospital Active, not recruiting
Fuzhou, Fujian, China, 350000
Fuzhou General Hospital of Nanjing Militray Command Recruiting
Fuzhou, Fujian, China
Contact: Taotao Hu, BS       412456139@qq.com   
China, Henan
The 7th People's Hospital of Zhengzhou Recruiting
Zhengzhou, Henan, China
Contact: Dongdong Yuan, MS    0371-89905878    44676878@qq.com   
China, Hunan
The Third Hospital of Changsha Active, not recruiting
Changsha, Hunan, China
China, Jiangsu
Wuxi People's Hospital Withdrawn
Wuxi, Jiangsu, China, 214023
Wuxi third people's hospital Enrolling by invitation
Wuxi, Jiangsu, China
China, Jiangxi
The First Affiliated Hospital of Nanchang University Active, not recruiting
Nanchang, Jiangxi, China, 330006
China, Liaoning
the First Affiliated Hospital of Liaoning University of Traditional Chinese Medicine Active, not recruiting
Shenyang, Liaoning, China, 110032
China, Neimenggu
The affiliated hospital of Inner Mongolia medical university Recruiting
Hohhot, Neimenggu, China
Contact: Jianjun Sun, PhD       sunjian8840@sina.com   
China, Shandong
The Affiliated Hospital of Qingdao University Active, not recruiting
Qingdao, Shandong, China
China, Shanghai
Shanghai Public Health Clinical Center Active, not recruiting
Shanghai, Shanghai, China, 201508
Renji Hospital, Medical College of Shanghai Jiaotong University Recruiting
Shanghai, Shanghai, China
Contact: Mangmang Pan, BS         
Sponsors and Collaborators
Cui Yimin

Layout table for additonal information
Responsible Party: Cui Yimin, Director of pharmacy,M.D & Ph.D, Peking University First Hospital
ClinicalTrials.gov Identifier: NCT03161496     History of Changes
Other Study ID Numbers: 2016[1236]
First Posted: May 19, 2017    Key Record Dates
Last Update Posted: October 10, 2019
Last Verified: October 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Anticoagulants