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NCT Number: NCT05764356

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

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.

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Key information

Conditions

Novel Oral Anticoagulants Apixaban Biomarker Bleeding Dabigatran Edoxaban Hemorrhage NOACs Pathologic Processes Pathological Conditions, Signs and Symptoms Pharmacodynamics Pharmacogenomics RNA Profile Rivaroxaban Ticagrelor

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Anhui Provincial Hospital#The First Affiliated Hospital Of USTC#, Hefei, Anhui, China

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Detection of genotype and RNA profile in platelet and white blood cell

Genetic

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

Indicators test related to coagulation function

Other

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

Other

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.

Primary outcomes

  1. Incidence of new bleeding events

    Time frame: Within 1 month after enrollment

    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.

  2. Incidence of new bleeding events

    Time frame: From 1 month to 6 months after enrollment

    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.

  3. Incidence of new bleeding events

    Time frame: From 6 months to 1 year after enrollment

    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.

  4. Incidence of new bleeding events

    Time frame: From 1 year to 2 years after enrollment

    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.

  5. Incidence of new major cardiovascular events and all-cause death

    Time frame: Within 1 month after enrollment

    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.

  6. Incidence of new major cardiovascular events and all-cause death

    Time frame: From 1 month to 6 months after enrollment

    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.

  7. Incidence of new major cardiovascular events and all-cause death

    Time frame: From 6 months to 1 year after enrollment

    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.

  8. Incidence of new major cardiovascular events and all-cause death

    Time frame: From 1 year to 2 years after enrollment

    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.

  9. Incidence of new thromboembolic events

    Time frame: Within 1 month after enrollment

    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.

  10. Incidence of new thromboembolic events

    Time frame: From 1 month to 6 months after enrollment

    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.

  11. Incidence of new thromboembolic events

    Time frame: From 6 months to 1 year after enrollment

    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.

  12. Incidence of new thromboembolic events

    Time frame: From 1 year to 2 years after enrollment

    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.

Secondary outcomes

  1. Genotype detected by next generation sequencing

    Time frame: Through study completion, collection only once

    Collect blood specimen before NOACs administration, then detect genotype of NOACs by next generation sequencing.

  2. Expression level of RNA in platelet and white blood cell

    Time frame: 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).

    Before and after NOACs or ticagrelor administration, detect the expression level of RNA in platelet and white blood cell .

  3. Anticoagulantion activity evaluation (for NOACs only)

    Time frame: Once each before administration, before and after administration at stable concentration (at least 48h for rivaroxaban, 72h for apixaban or edoxaban) .

    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.

  4. Platelet reactivity evaluation (for Ticagrelor only)

    Time frame: Once before administration and once after stable concentration.

    Before and after ticagrelor administration, record PRI detected by one or more following methods: 1)LTA; 2)VASP ELISA test; 3)TEG.

Study contacts

Contact information is provided by the study sponsor or research team.

Qian Xiang, Dr.

CONTACT

[email protected]

+86-18610260623

Sponsors and collaborators

Lead sponsor

Peking University First Hospital

Other

Registry information

Official study title

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

Important dates

Study start
2023
Primary completion
2026
Study completion
2027
First posted
Mar 10, 2023
Registry last updated
Mar 10, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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