Precision Medicine Platform for Novel Oral Anticoagulants

August 30, 2021 updated by: Hsiang-Chun Lee, Kaohsiung Medical University

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Observational

Enrollment (Anticipated)

500

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Hsiang-Chun Lee, MD, PhD
  • Phone Number: 2293 886-7-3121101
  • Email: hclee@kmu.edu.tw

Study Locations

  • Taiwan
      • Kaohsiung, Taiwan, 807
        • Recruiting
        • Kaohsiung Medical University Hospital
        • Contact:
          • Hsiang-Chun Lee, MD, PhD
          • Phone Number: 2293 886-7-3121101
          • Email: hclee@kmu.edu.tw

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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.

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of major bleeding events during any NOAC treatment
Time Frame: 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.
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.
Number of minor bleeding events during any NOAC treatment
Time Frame: 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.
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.
Number of thromboembolism events during any NOAC treatment
Time Frame: 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.
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Kaohsiung Medical University

Investigators

  • Principal Investigator: Hsiang-Chun Lee, MD, PhD, Kaohsiung Medical University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 2, 2019

Primary Completion (Anticipated)

December 31, 2021

Study Completion (Anticipated)

December 31, 2022

Study Registration Dates

First Submitted

July 30, 2019

First Submitted That Met QC Criteria

August 12, 2019

First Posted (Actual)

August 14, 2019

Study Record Updates

Last Update Posted (Actual)

September 2, 2021

Last Update Submitted That Met QC Criteria

August 30, 2021

Last Verified

August 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • KMUHIRB-G(I)-20180026
  • 108-2622-B-037-003 -CC1 (Other Grant/Funding Number: Taiwan Ministry of Science and Technology)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Anticoagulant Adverse Reaction

Clinical Trials on Pharmacogenomics

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Tanzania

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe