Precision Medicine Platform for Novel Oral Anticoagulants

Anticoagulant Adverse Reaction Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04056143
• Other study ID #: KMUHIRB-G(I)-20180026
• Secondary ID: 108-2622-B-037-0
• Status: Recruiting
• Start date: January 2, 2019
• Est. completion date: December 31, 2022

Study information

• Verified date: August 2021
• Source: Kaohsiung Medical University
• Contact: Hsiang-Chun Lee, MD, PhD
• Phone: 886-7-3121101
• Email: hclee[@]kmu.edu.tw
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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, CYP2C9*2, CYP2C9*3, 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 500
• Est. completion date: December 31, 2022
• Est. primary completion date: December 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

Inclusion Criteria:

• Long-term indication for use of dabigatran
• Long-term indication for use of rivaroxaban
• Long-term indication for use of apixaban
• Long-term indication for use of edoxaban

Exclusion Criteria:

• Any contraindication for use of anticoagulants
• Prisoners
• pregnancy
• mental disorders
• history of any mechanical or prosthetic valve replacement
• hemodialysis or other renal replacement therapy
• congenital coagulation abnormalities
• autoimmune diseases

Related Conditions & MeSH terms

• Anticoagulant Adverse Reaction

Intervention

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.

Locations

Country	Name	City	State
Taiwan	Kaohsiung Medical University Hospital	Kaohsiung

Sponsors (1)

Lead Sponsor	Collaborator
Kaohsiung Medical University

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of major bleeding events during any NOAC treatment	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.	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.
Primary	Number of minor bleeding events during any NOAC treatment	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.	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.
Primary	Number of thromboembolism events during any NOAC treatment	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.	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.