Clinical trial NCT04056143: Precision Medicine Platform for Novel Oral Anticoagulants
Official title: Development of Precision Medicine Platform for Pharmacogenomics of Novel Oral Anticoagulants (NOACs)
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Anticoagulant Adverse Reaction
Keywords: Thromboembolism
Oral anticoagulants
Adverse events
Pharmacogenomics
Precision Medicine
Lead sponsor: Kaohsiung Medical University
Sponsor class: OTHER
First posted: 2019-08-14
Enrollment: 500
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients who have one of the indications to use long-term anticoagulants, including atrial fibrillation, deep venous thrombosis, and pulmonary embolism.

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.

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, 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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of major bleeding events during any NOAC treatment
timeFrame: 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.
measure: Number of minor bleeding events during any NOAC treatment
timeFrame: 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.
measure: Number of thromboembolism events during any NOAC treatment
timeFrame: 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.
Secondary outcomes:
Other outcomes:
Locations:
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Hospital
Study officials:
affiliation: Kaohsiung Medical University
name: Hsiang-Chun Lee, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: