Novel Oral AnticoagulantsNCT03161496
Impact of Biomarkers on Pharmacokinetics and Pharmacodynamics of Direct Oral Anticoagulants
An observational study of Novel Oral Anticoagulants and NOACs, run by Cui Yimin at 17 sites in China.
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… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Novel Oral Anticoagulants, NOACs, Rivaroxaban
- What is being tested?
- detection of genotype
- How many people
- 1,200 participants
- Where
- 17 sitesChina
- Study dates
- 6 Jun 2017to Dec 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
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
Who may be able to join
- (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;
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- 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.
Who cannot join
- (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.
Trial locations and contacts
17 sites in 1 country.
17 sites in 1 country
China17 sites, 8 recruiting
- Recruiting
Peking University First Hospital
Beijing, Beijing Municipality, 100034
Qian Xiang, Ph.D, +86 010 66110802, xiangqz@126.com
- Recruiting
Beijing Hospital
Beijing, Beijing Municipality, 100730
Yatong Zhang, MS, +86-010-85133637, zyt2002888@qq.com
- Active, not recruiting
Beijing HuiLongGuan Hospital
Beijing, Beijing Municipality
- Active, not recruiting
The Third Hospital of Changsha
Changsha, Hunan
- Recruiting
The Second Affiliated Hospital Of Chongqing Medical University
Chongqing, Chongqing Municipality, 400010
Na Wang, MS, +86-13594036081, 182429490@qq.com
- Active, not recruiting
Fujian Medical University Union Hospital
Fuzhou, Fujian, 350000
- Recruiting
900 Hospital of the Joint Logistics Team (Original name: Fuzhou General Hospital of Nanjing Militray Command)
Fuzhou, Fujian
Zhihong Liu, liuzh827@sina.cn
- Recruiting
Anhui Provincial Hospital（The First Affiliated Hospital Of USTC）
Hefei, Anhui, 230001
Zhaoyi Yang, PhD, +86-0551-62283379-800, young2382@163.com
- Recruiting
The affiliated hospital of Inner Mongolia medical university
Hohhot, Neimenggu
Jianjun Sun, PhD, sunjian8840@sina.com
- Active, not recruiting
The First Affiliated Hospital of Nanchang University
Nanchang, Jiangxi, 330006
- Active, not recruiting
The Affiliated Hospital of Qingdao University
Qingdao, Shandong
- Active, not recruiting
Shanghai Public Health Clinical Center
Shanghai, Shanghai Municipality, 201508
- Recruiting
Renji Hospital, School of Medicine, Shanghai Jiao Tong University
Shanghai, Shanghai Municipality
Mangmang Pan, MS, panmangmang@renjj.com
- Active, not recruiting
the First Affiliated Hospital of Liaoning University of Traditional Chinese Medicine
Shenyang, Liaoning, 110032
- Withdrawn
Wuxi People's Hospital
Wuxi, Jiangsu, 214023
- Active, not recruiting
The Affiliated Hospital of Jiangnan University, or called Original Wuxi Third Hospital
Wuxi, Jiangsu
- Recruiting
The 7th People's Hospital of Zhengzhou
Zhengzhou, Henan
Dongdong Yuan, MS, 0371-89905878, 44676878@qq.com
About this study
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
- Being tested
- detection of genotype
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
detection of genotypeGenetic
detection of genotype by next generation sequencing
| Study group | Role | What they receive |
|---|---|---|
| wild genotype | Through next generation sequencing, distinguish wild genotype of NOACs Receives: Genetic: detection of genotype | |
| mutant genotype | Through next generation sequencing, distinguish mutant genotype of NOACs Receives: Genetic: detection of genotype |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: At 1 year
Secondary outcomes (7)
Genotype detected by next generation sequencing
Collect blood specimen before NOACs administration, then detect genotype of NOACs by next generation sequencing.
Measured: pre-dose of NOACs (rivaroxaban, apixaban, dabigatran)
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.
Measured: 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
Before and after dabigatran administration, record anti-factor IIa activity detected by blood coagulation tests.
Measured: 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
Before and after NOACs administration, detect the expression level of miRNA about pharmacodynamics.
Measured: 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
Before and after NOACs administration, detect the expression level of LncRNA about pharmacodynamics.
Measured: 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.
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.
Measured: At 1 month, 6 months and 2 years (according the actual duration of NOACs taken in patiens)
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.
Measured: At 1 month, 6 months and 2 years (according the actual duration of NOACs taken in patiens)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 May 2017
- Study start6 Jun 2017
- Primary completionOct 2021 (estimated)
- Study completionDec 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Novel Oral AnticoagulantsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 1,200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Cui Yimin
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Cui Yimin, Peking University First Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03161496
- Sponsor's protocol ID
- 2016[1236]
- Status last verified
- Dec 2020
- First submitted
- 9 May 2017
- Last updated
- 22 Dec 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 37203300Zhang 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.
PubMed 36578040Liu 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.
PubMed 35935625
Study at a glance
From the registry record, last updated by the sponsor on 22 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Biomarkers on Pharmacokinetics and Pharmacodynamics of Direct Oral Anticoagulants
- ClinicalTrials.gov ID
- NCT03161496
- Acronym / sponsor ID
- 2016[1236]
- Conditions
- Novel Oral Anticoagulants, NOACs, Rivaroxaban, Apixaban, Dabigatran, Pharmacokinetics
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 1,200 participants (estimated)
- Lead sponsor
- Cui YiminUniversity, hospital or other
- Study start
- 6 Jun 2017 (actual)
- Primary completion
- Oct 2021 (estimated)
- Study completion
- Dec 2021 (estimated)
- First posted
- 19 May 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| wild genotype | – | Genetic: detection of genotypeThrough next generation sequencing, distinguish wild genotype of NOACs |
| mutant genotype | – | Genetic: detection of genotypeThrough next generation sequencing, distinguish mutant genotype of NOACs |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- 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
Key inclusion criteria (9 listed)
- (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
Key exclusion criteria (8 listed)
- (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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| detection of genotypedetection of genotype by next generation sequencing | Genetic | mutant genotype, wild genotype |
Primary outcome
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.
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.
7 secondary outcomes
Genotype detected by next generation sequencing
Time frame: pre-dose of NOACs (rivaroxaban, apixaban, dabigatran)
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
Level of anticoagulant activity assessed by anti-factor IIa activity
Time frame: 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
Time frame: 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
Time frame: 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.
Incidence of stroke or systemic embolic events in the other observation times
Time frame: At 1 month, 6 months and 2 years (according the actual duration of NOACs taken in patiens)
Incidence of bleeding events in the other observation times
Time frame: At 1 month, 6 months and 2 years (according the actual duration of NOACs taken in patiens)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Dec 2020.
- Derived from this study: PubMed 37203300Xiang 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.
- Derived from this study: PubMed 36578040Zhang 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.
- Derived from this study: PubMed 35935625Liu 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
17 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Novel Oral Anticoagulants and NOACs, run by Cui Yimin at 17 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 22 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Qian Xiang, Ph.D (+86 010 66110802, xiangqz@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of stroke or systemic embolic events (including TIA) (time frame: At 1 year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03161496, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Dec 2020.