Imapct of bioMarkers on Pharmacodynamics and Bleeding Risk of Direct Oral AntiCoagulants and Ticagrelor Study II

Bleeding Clinical Trial

Official title:

Imapct of bioMarkers on Pharmacodynamics and Bleeding Risk of Direct Oral AntiCoagulants and Ticagrelor Study II (IMPACT 2)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05764356
• Other study ID #: 2022CR67
• Status: Not yet recruiting
• Start date: March 2023
• Est. completion date: December 2027

Study information

• Verified date: March 2023
• Source: Peking University First Hospital
• Contact: Qian Xiang, Dr.
• Phone: +86-18610260623
• Email: xiangqz[@]pkufh.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 2000
• Est. completion date: December 2027
• Est. primary completion date: December 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

(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.

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Apixaban
• Biomarker
• Bleeding
• Dabigatran
• Hemorrhage
• NOACs
• Novel Oral Anticoagulants
• Pharmacodynamics
• Pharmacogenomics
• Rivaroxaban
• Ticagrelor

Intervention

Genetic:
• Detection of genotype and RNA profile in platelet and white blood cell
Detection of genotype by next generation sequencing Detection of RNA profile in platelet and white blood cell by RNA sequencing

Other:
• Indicators test related to coagulation function
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
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.

Locations

Country	Name	City	State
China	Peking University First Hospital	Beijing	Beijing
China	The Second Affiliated Hospital Of Chongqing Medical University	Chongqing	Chongqing
China	Anhui Provincial Hospital#The First Affiliated Hospital Of USTC#	Hefei	Anhui
China	Renji Hospital, School of Medicine, Shanghai Jiao Tong University	Shanghai	Shanghai
China	Zhongshan Hospital FuDan University	Shanghai	Shanghai
China	The 7th People's Hospital of Zhengzhou	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
Peking University First Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	Genotype detected by next generation sequencing	Collect blood specimen before NOACs administration, then detect genotype of NOACs by next generation sequencing.	Through study completion, collection only once
Secondary	Expression level of RNA in platelet and white blood cell	Before and after NOACs or ticagrelor administration, detect the 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).
Secondary	Anticoagulantion activity evaluation (for NOACs only)	Before and after NOACs administration, record anti-factor Xa activity(for rivaroxaban, apixaban, edoxaban) or anti-factor IIa activity (for dabigatran only) detected by blood coagulation tests.	Once each before administration, before and after administration at stable concentration (at least 48h for rivaroxaban, 72h for apixaban or edoxaban) .
Secondary	Platelet reactivity evaluation (for Ticagrelor only)	Before and after ticagrelor administration, record PRI detected by one or more following methods: 1)LTA; 2)VASP ELISA test; 3)TEG.	Once before administration and once after stable concentration.