Clinical trial NCT05764356: Imapct of bioMarkers on Pharmacodynamics and Bleeding Risk of Direct Oral AntiCoagulants and Ticagrelor Study II
Official title: Imapct of bioMarkers on Pharmacodynamics and Bleeding Risk of Direct Oral AntiCoagulants and Ticagrelor Study II (IMPACT 2)
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Novel Oral Anticoagulants
NOACs
Rivaroxaban
Apixaban
Edoxaban
Dabigatran
Ticagrelor
Pharmacodynamics
Pharmacogenomics
RNA Profile
Bleeding
Biomarker
Lead sponsor: Peking University First Hospital
Sponsor class: OTHER
First posted: 2023-03-10
Enrollment: 2000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 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).

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of new bleeding events
timeFrame: Within 1 month after enrollment
measure: Incidence of new bleeding events
timeFrame: From 1 month to 6 months after enrollment
measure: Incidence of new bleeding events
timeFrame: From 6 months to 1 year after enrollment
measure: Incidence of new bleeding events
timeFrame: From 1 year to 2 years after enrollment
measure: Incidence of new major cardiovascular events and all-cause death
timeFrame: Within 1 month after enrollment
measure: Incidence of new major cardiovascular events and all-cause death
timeFrame: From 1 month to 6 months after enrollment
measure: Incidence of new major cardiovascular events and all-cause death
timeFrame: From 6 months to 1 year after enrollment
measure: Incidence of new major cardiovascular events and all-cause death
timeFrame: From 1 year to 2 years after enrollment
measure: Incidence of new thromboembolic events
timeFrame: Within 1 month after enrollment
measure: Incidence of new thromboembolic events
timeFrame: From 1 month to 6 months after enrollment
measure: Incidence of new thromboembolic events
timeFrame: From 6 months to 1 year after enrollment
measure: Incidence of new thromboembolic events
timeFrame: From 1 year to 2 years after enrollment
Secondary outcomes:
measure: Genotype detected by next generation sequencing
timeFrame: Through study completion, collection only once
measure: Expression level of RNA in platelet and white blood cell
timeFrame: 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).
measure: Anticoagulantion activity evaluation (for NOACs only)
timeFrame: Once each before administration, before and after administration at stable concentration (at least 48h for rivaroxaban, 72h for apixaban or edoxaban) .
measure: Platelet reactivity evaluation (for Ticagrelor only)
timeFrame: Once before administration and once after stable concentration.
Other outcomes:
Locations:
city: Hefei
country: China
facility: Anhui Provincial Hospital#The First Affiliated Hospital Of USTC#
state: Anhui
city: Beijing
country: China
facility: Peking University First Hospital
state: Beijing
city: Chongqing
country: China
facility: The Second Affiliated Hospital Of Chongqing Medical University
state: Chongqing
city: Zhengzhou
country: China
facility: The 7th People's Hospital of Zhengzhou
state: Henan
city: Shanghai
country: China
facility: Renji Hospital, School of Medicine, Shanghai Jiao Tong University
state: Shanghai
city: Shanghai
country: China
facility: Zhongshan Hospital FuDan University
state: Shanghai
Study officials:
References: