Imapct of bioMarkers on Pharmacodynamics and Bleeding Risk of Direct Oral AntiCoagulants and Ticagrelor Study II
1 other identifier
observational
2,000
1 country
6
Brief Summary
Individual differences in drug efficacy and adverse reactions are common in the clinical application of drugs. Individual differences are caused by many factors, among which genetic factors account for more than 20%. Novel oral anticoagulant drugs (NOACs, including rivaroxaban, apixaban, edoxaban, dabigatran, etc.) and novel antiplatelet drug ticagrelor have the advantages of convenient use and no need for monitoring. But novel oral antithrombotic drugs also increase the risk of bleeding, and there is currently a lack of effective antagonists when antithrombosis is excessive or emergency surgery is required. At present, there are few studies on the causes of individual differences in novel antithrombotic drugs, and there is a lack of predictable biomarkers or drug genotypes, especially in China. Therefore, on the basis of previous studies on NOACs and ticagrelor individualized medication cohorts, this study plans to establish a validation cohort for novel antithrombotic drugs bleeding related biomarkers, conduct multi-omics testing and long-term follow-up, and explore markers related to pharmacodynamics of antithrombotic drugs, adverse bleeding reactions and clinical outcomes.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for all trials
Started Mar 2023
Longer than P75 for all trials
6 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 16, 2023
CompletedStudy Start
First participant enrolled
March 1, 2023
CompletedFirst Posted
Study publicly available on registry
March 10, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 1, 2027
March 10, 2023
March 1, 2023
3.8 years
February 16, 2023
March 1, 2023
Conditions
Outcome Measures
Primary Outcomes (12)
Incidence of new bleeding events
During the observation time, record the incidence of new bleeding events after NOACs(rivaroxaban, apixaban, edoxaban, dabigatran) or ticagrelor administration by telephone and out-patient clinic, including subcutaneous bleeding, gingival bleeding, gastrointestinal bleeding, intracranial hemorrhage, etc.
Within 1 month after enrollment
Incidence of new bleeding events
During the observation time, record the incidence of new 'bleeding events after NOACs(rivaroxaban, apixaban, edoxaban, dabigatran) or ticagrelor administration by telephone and out-patient clinic, including subcutaneous bleeding, gingival bleeding, gastrointestinal bleeding, intracranial hemorrhage, etc.
From 1 month to 6 months after enrollment
Incidence of new bleeding events
During the observation time, record the incidence of new bleeding events after NOACs(rivaroxaban, apixaban, edoxaban, dabigatran) or ticagrelor administration by telephone and out-patient clinic, including subcutaneous bleeding, gingival bleeding, gastrointestinal bleeding, intracranial hemorrhage, etc.
From 6 months to 1 year after enrollment
Incidence of new bleeding events
During the observation time, record the incidence of new bleeding events after NOACs(rivaroxaban, apixaban, edoxaban, dabigatran) or ticagrelor administration by telephone and out-patient clinic, including subcutaneous bleeding, gingival bleeding, gastrointestinal bleeding, intracranial hemorrhage, etc.
From 1 year to 2 years after enrollment
Incidence of new major cardiovascular events and all-cause death
During the observation time, record the new incidence of major cardiovascular events (MACEs) and all-cause death after NOACs(rivaroxaban, apixaban, edoxaban, dabigatran) or ticagrelor administration by telephone and out-patient clinic. MACEs including cardiac death, myocardial infarction (MI), stroke or transient cerebral thrombus (TIA), ischemic-driven coronary revascularization(PCI, CABG, thrombolysis, etc.), etc.
Within 1 month after enrollment
Incidence of new major cardiovascular events and all-cause death
During the observation time, record the new incidence of major cardiovascular events (MACEs) and all-cause death after NOACs(rivaroxaban, apixaban, edoxaban, dabigatran) or ticagrelor administration by telephone and out-patient clinic. MACEs including cardiac death, myocardial infarction (MI), stroke or transient cerebral thrombus (TIA), ischemic-driven coronary revascularization(PCI, CABG, thrombolysis, etc.), etc.
From 1 month to 6 months after enrollment
Incidence of new major cardiovascular events and all-cause death
During the observation time, record the new incidence of major cardiovascular events (MACEs) and all-cause death after NOACs(rivaroxaban, apixaban, edoxaban, dabigatran) or ticagrelor administration by telephone and out-patient clinic. MACEs including cardiac death, myocardial infarction (MI), stroke or transient cerebral thrombus (TIA), ischemic-driven coronary revascularization(PCI, CABG, thrombolysis, etc.), etc.
From 6 months to 1 year after enrollment
Incidence of new major cardiovascular events and all-cause death
During the observation time, record the new incidence of major cardiovascular events (MACEs) and all-cause death after NOACs(rivaroxaban, apixaban, edoxaban, dabigatran) or ticagrelor administration by telephone and out-patient clinic. MACEs including cardiac death, myocardial infarction (MI), stroke or transient cerebral thrombus (TIA), ischemic-driven coronary revascularization(PCI, CABG, thrombolysis, etc.), etc.
From 1 year to 2 years after enrollment
Incidence of new thromboembolic events
During the observation time, record the incidence of new thromboembolic events after NOACs(rivaroxaban, apixaban, edoxaban, dabigatran) or ticagrelor administration by telephone and out-patient clinic, including stroke or TIA, systemic embolism (SE), deep vein thrombosis (DVT), pulmonary embolism, left auricular thrombus, stent thrombosis, stent stenosis and stent endothelial hyperplasiastent, etc.
Within 1 month after enrollment
Incidence of new thromboembolic events
During the observation time, record the incidence of new thromboembolic events after NOACs(rivaroxaban, apixaban, edoxaban, dabigatran) or ticagrelor administration by telephone and out-patient clinic, including stroke or TIA, systemic embolism (SE), deep vein thrombosis (DVT), pulmonary embolism, left auricular thrombus, stent thrombosis, stent stenosis and stent endothelial hyperplasiastent, etc.
From 1 month to 6 months after enrollment
Incidence of new thromboembolic events
During the observation time, record the incidence of new thromboembolic events after NOACs(rivaroxaban, apixaban, edoxaban, dabigatran) or ticagrelor administration by telephone and out-patient clinic, including stroke or TIA, systemic embolism (SE), deep vein thrombosis (DVT), pulmonary embolism, left auricular thrombus, stent thrombosis, stent stenosis and stent endothelial hyperplasiastent, etc.
From 6 months to 1 year after enrollment
Incidence of new thromboembolic events
During the observation time, record the incidence of new thromboembolic events after NOACs(rivaroxaban, apixaban, edoxaban, dabigatran) or ticagrelor administration by telephone and out-patient clinic, including stroke or TIA, systemic embolism (SE), deep vein thrombosis (DVT), pulmonary embolism, left auricular thrombus, stent thrombosis, stent stenosis and stent endothelial hyperplasiastent, etc.
From 1 year to 2 years after enrollment
Secondary Outcomes (4)
Genotype detected by next generation sequencing
Through study completion, collection only once
Expression level of RNA in platelet and white blood cell
NOACs: Once each before administration, before and after administration at stable concentration (at least 48h for rivaroxaban, 72h for apixaban or edoxaban). Ticagrelor: Once before administration and once after stable concentration (at least 48h).
Anticoagulantion activity evaluation (for NOACs only)
Once each before administration, before and after administration at stable concentration (at least 48h for rivaroxaban, 72h for apixaban or edoxaban) .
Platelet reactivity evaluation (for Ticagrelor only)
Once before administration and once after stable concentration.
Study Arms (2)
Novel oral anticoagulants cohort
Ticagrelor cohort
Interventions
Detection of genotype by next generation sequencing Detection of RNA profile in platelet and white blood cell by RNA sequencing
Indicators test including prothrombin time (PT), activated partial thrombin time (APTT), thrombin time (TT), diluted TT (dTT), snake vein enzyme coagulation time (ECT), anti-XA or IIa activity, etc.
Indicators test related to platelet function. Platelet reactivity was measured by VASP. Platelet aggregation rate was measured by turbidimetric method. Platelet and fibrinolytic function were measured by thrombologram, etc.
Eligibility Criteria
Chinese Patients taking NOACs or ticagrelor#In accordance with anticoagulation indications of NOACs or with diagnosis of acute coronary syndrome (ACS)# received NOACs or ticagrelor in a month and intend to take NOACs or ticagrelor, or have received NOACs or ticagrelor for more than one week continuously#1000 patients for each cohort (NOACs or ticagrelor).
You may qualify if:
- (I) Chinese Patients taking NOACs
- 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.
- (II) Chinese Patients taking ticagrelor
- With diagnosis of acute coronary syndrome (ACS), included unstable angina, non ST segment elevation myocardial infarction and ST segment elevation myocardial infarction;
- More than 18 years of age, male or female;
- Never received ticagrelor in a month and intend to take ticagrelor or have received ticagrelor for more than one week continuously#
- sign informed consent.
You may not qualify if:
- 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 antithrombosis, 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (6)
Anhui Provincial Hospital#The First Affiliated Hospital Of USTC#
Hefei, Anhui, China
Peking University First Hospital
Beijing, Beijing Municipality, China
The Second Affiliated Hospital Of Chongqing Medical University
Chongqing, Chongqing Municipality, China
The 7th People's Hospital of Zhengzhou
Zhengzhou, Henan, China
Renji Hospital, School of Medicine, Shanghai Jiao Tong University
Shanghai, Shanghai Municipality, China
Zhongshan Hospital FuDan University
Shanghai, Shanghai Municipality, China
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- observational
- Observational Model
- COHORT
- Time Perspective
- PROSPECTIVE
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Prof.
Study Record Dates
First Submitted
February 16, 2023
First Posted
March 10, 2023
Study Start
March 1, 2023
Primary Completion (Estimated)
December 1, 2026
Study Completion (Estimated)
December 1, 2027
Last Updated
March 10, 2023
Record last verified: 2023-03