Precision Medicine Platform for Novel Oral Anticoagulants

Sponsor

Kaohsiung Medical University (Other)

Overall Status

Recruiting

CT.gov ID

NCT04056143

Collaborator

(none)

500

Enrollment

Location

47.9

Anticipated Duration (Months)

10.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The anticoagulants have been developed with new generation for FDA-approved indications including treatment and prevention of venous, pulmonary, and systemic thromboembolism. While the prescription of new oral anticoagulants (NOAC) has increasingly and largely replaced warfarin in accordance of better efficacy and safety, there are still adverse effects, including incidental minor and major bleeding, and inefficacy in thrombosis prevention. The overarching goal of this study is to develop a Pharmacogenomics Platform that is specifically designed for NOACs, in order to optimize and personalize the prescription and to facilitate the precision medicine.

Condition or Disease	Intervention/Treatment	Phase
Anticoagulant Adverse Reaction	Diagnostic Test: Pharmacogenomics

Detailed Description

Pharmaceutical companies have developed new oral anticoagulants (NOACs) to replace warfarin for prevention of systemic thrombo-embolization and embolic stroke in patients with atrial fibrillation or other thromboembolism diseases. The sale of NOACs has been increasing globally as the prevalence of atrial fibrillation increases in countries with aging population. Patients with high thromboembolism risk are also at high risk for major bleeding. The conservative strategy is not good for that more patients on reduced dose of NOACs had stroke. The clinical dilemma is how to justify the efficacy of NOACs in stroke prevention without encountering the incidental major bleeding from side effects. In order to solve this dilemma, the comprehensive evaluation of risk for thromboembolism, risk of bleeding, and genetic background on related to drug pharmacokinetics and response is essential. The primary goal of this project is to combine the clinical data and genetic information to develop a drug response evaluation platform to facilitate personalized and precision medicine for NOACs prescription.

Pharmacogenomics elucidates the drug response and side effect on the basis of individual genetic background. This proposed project will enroll clinical patients who have atrial fibrillation and indications for the prescription of NOACs. The information will be collected for clinical demographics, medical history of embolic stroke, thromboembolism events, any bleeding events, and concurrent use of other medicines. Peak level of NOAC in use, and post-drug coagulation test will be performed. The above data will be integrated for the pharmacogenomic analysis with multiple genes (CES1, ABCB1, SLCO1B1, CYP2C92, CYP2C93, VKORC, CYP3A4, MMP-9, ALOX5AP, MTHFR, FGB and eNOs). The single nucleotide polymorphism (SNPs) of gene clusters will be derived from this clinical study. These output results will be used to optimize the gene-array product that is specifically-designed for NOACs prescription.

The NOACs-specific gene-array for a precision prescription will be developed to help physicians to choose the right NOAC and the best dose for individualized patients. This tool will maximize thromboembolism prevention from the NOACs prescription along with the minimization of NOACs side effects. The product will be commercialized with great potential for the global market.

Study Design

Study Type:

Observational

Anticipated Enrollment :

500 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Development of Precision Medicine Platform for Pharmacogenomics of Novel Oral Anticoagulants (NOACs)

Actual Study Start Date :

Jan 2, 2019

Anticipated Primary Completion Date :

Dec 31, 2021

Anticipated Study Completion Date :

Dec 31, 2022

Arms and Interventions

Arm	Intervention/Treatment
Dabigatran Subjects who are receiving long-term Dabigatran for certain clinical conditions, and without any contraindication are enrolled for this cohort group.	Diagnostic Test: Pharmacogenomics Subjects enrolled in this study are providing blood samples for completing a set of laboratory testing and pharmacogenomic analyses. They are requested to comply a Pharmacist interview and complete of assisted questionnaires. Other Names: Prothrombin time (PT), activated partial thromboplastin time (aPTT), Ecarin-based assay (for dabigatran), chromogenic anti-Xa assays (for rivaroxaban, apixaban, and edoxaban)
Rivaroxaban Subjects who are receiving long-term Rivaroxaban for certain clinical conditions, and without any contraindication are enrolled for this cohort group.	Diagnostic Test: Pharmacogenomics Subjects enrolled in this study are providing blood samples for completing a set of laboratory testing and pharmacogenomic analyses. They are requested to comply a Pharmacist interview and complete of assisted questionnaires. Other Names: Prothrombin time (PT), activated partial thromboplastin time (aPTT), Ecarin-based assay (for dabigatran), chromogenic anti-Xa assays (for rivaroxaban, apixaban, and edoxaban)
Apixaban Subjects who are receiving long-term Apixaban for certain clinical conditions, and without any contraindication are enrolled for this cohort group.	Diagnostic Test: Pharmacogenomics Subjects enrolled in this study are providing blood samples for completing a set of laboratory testing and pharmacogenomic analyses. They are requested to comply a Pharmacist interview and complete of assisted questionnaires. Other Names: Prothrombin time (PT), activated partial thromboplastin time (aPTT), Ecarin-based assay (for dabigatran), chromogenic anti-Xa assays (for rivaroxaban, apixaban, and edoxaban)
Edoxaban Subjects who are receiving long-term Edoxaban for certain clinical conditions, and without any contraindication are enrolled for this cohort group.	Diagnostic Test: Pharmacogenomics Subjects enrolled in this study are providing blood samples for completing a set of laboratory testing and pharmacogenomic analyses. They are requested to comply a Pharmacist interview and complete of assisted questionnaires. Other Names: Prothrombin time (PT), activated partial thromboplastin time (aPTT), Ecarin-based assay (for dabigatran), chromogenic anti-Xa assays (for rivaroxaban, apixaban, and edoxaban)

Outcome Measures

Primary Outcome Measures

Number of major bleeding events during any NOAC treatment [From date of enrollment until the date of first major bleeding events of any type or date of death, whichever came first, assessed up to 36 months.]
Any gastrointestinal, retroperitoneal, urinary tract, abnormal uterine bleeding, intracranial, intra-ocular or intra-spinal bleeding events that are noted in medical records or examination reports, or demonstrated by images studies including a computer tomography scan or a magnetic resonance imaging, or a sonography or an ophthalmoscope; or bleeding requiring surgery; or transfusion of ≥ 2 units (i.e. ≥ 500 mL) of packed red blood cells) or associated with a decrease in hemoglobin of ≥ 2.0 g/L episodes.
Number of minor bleeding events during any NOAC treatment [From date of enrollment until the date of first major bleeding events of any type or date of death, whichever came first, assessed up to 36 months.]
Any gastrointestinal, urinary tract, abnormal uterine, soft tissue, skin, conjunctival, nasopharyngeal, oral cavity bleeding events that are noted in medical records or examination reports, or demonstrated by images studies including an endoscopic examination, or a sonography or an ophthalmoscope; or requirement of blood transfusion of < 2 units (i.e. less than 500 mL) of packed red blood cells or associated with a decrease in hemoglobin of < 2.0 g/L episodes.
Number of thromboembolism events during any NOAC treatment [From date of enrollment until the date of first thromboembolism events of any type or date of death, whichever came first, assessed up to 36 months.]
Any clinical evident events of venous, pulmonary, or systemic thromboembolism that are noted in medical records or examination records, or demonstrated by images of an angiography, or a sonography, or a computer tomography scan, or an isotope phlebography.