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

NCT ID: NCT05764356

Last Updated: 2023-03-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Total Enrollment

2000 participants

Study Classification

OBSERVATIONAL

Study Start Date

2023-03-31

Study Completion Date

2027-12-31

Brief Summary

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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.

Detailed Description

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Conditions

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Novel Oral Anticoagulants NOACs Rivaroxaban Apixaban Edoxaban Dabigatran Ticagrelor Pharmacodynamics Pharmacogenomics RNA Profile Bleeding Biomarker

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Novel oral anticoagulants cohort

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

Intervention Type 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

Intervention Type 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.

Ticagrelor cohort

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

Intervention Type 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 platelet function

Intervention Type 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.

Interventions

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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

Intervention Type GENETIC

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.

Intervention Type OTHER

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.

Intervention Type OTHER

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Peking University First Hospital

OTHER

Sponsor Role lead

Responsible Party

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Cui Yimin

Prof.

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Anhui Provincial Hospital#The First Affiliated Hospital Of USTC#

Hefei, Anhui, China

Site Status

Peking University First Hospital

Beijing, Beijing Municipality, China

Site Status

The Second Affiliated Hospital Of Chongqing Medical University

Chongqing, Chongqing Municipality, China

Site Status

The 7th People's Hospital of Zhengzhou

Zhengzhou, Henan, China

Site Status

Renji Hospital, School of Medicine, Shanghai Jiao Tong University

Shanghai, Shanghai Municipality, China

Site Status

Zhongshan Hospital FuDan University

Shanghai, Shanghai Municipality, China

Site Status

Countries

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China

Central Contacts

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Qian Xiang, Dr.

Role: CONTACT

+86-18610260623

Facility Contacts

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Zhaoyi Yang, PhD

Role: primary

+86551-62283379 ext. 800

Qian Xiang, PhD

Role: primary

+86-18610260623

Na Wang, MS

Role: primary

+86-13594036081

Dongdong Yuan, MS

Role: primary

+86371-89905878

Mangmang Pan, MS

Role: primary

Xiaoyu Li

Role: primary

+8621-64041990 ext. 5062

Other Identifiers

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2022CR67

Identifier Type: -

Identifier Source: org_study_id

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