Association Between Genetic Variant Scores and Warfarin Effect

Completed

• Conditions: Atrial Fibrillation; Deep Vein Thrombosis; Intracardiac Thrombus; Pulmonary Embolism; Venous Thromboembolic Disease

• Registration Number: NCT03894878
• Lead Sponsor: Cipherome, Inc.

Brief Summary

Study objective is to determine whether there is an association between genetic variant risk scores and clinical outcomes (percent time in therapeutic range, time to reach therapeutic international normalized ratio (INR), INR ≥ 4, bleeding event, ischemic stroke, death) in participants taking warfarin for atrial fibrillation, deep vein thrombosis (DVT), pulmonary embolism (PE), and/or intracardiac thrombosis.

Detailed Description

It is anticipated that next generation genomic sequencing will identify rare genetic variants in ethnically diverse populations, which otherwise would not have been detected using commercially available warfarin tests. Furthermore, retrospective review of clinical outcomes (percent time in therapeutic range, time to reach therapeutic international normalized ratio (INR), INR ≥ 4, major bleeding event, ischemic stroke) of study participants will determine the clinical utility of genetic variant risk scores. Study outcomes will provide guidance on future directions for optimizing dosing algorithms for warfarin that combine pharmacogenetic principles with clinical dosing.

Study Timeline

• Study Start: 2019-02-11
• Study First Submitted: 2019-03-27
• Study First Submitted QC: 2019-03-27
• Study First Posted: 2019-03-29
• Primary Completion: 2022-09-30
• Study Completion: 2022-09-30
• Status Verified: 2023-02
• Last Update Submitted: 2023-02-14
• Last Update Posted: 2023-02-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

1. Non-valvular atrial fibrillation
2. Deep venous thrombosis (DVT) and/or pulmonary embolism (PE) with no hypercoagulable condition
3. Non-valvular atrial fibrillation and DVT/PE (with no hypercoagulable condition)
4. Intracardiac thrombosis (i.e. apical thrombosis, atrial thrombosis, auricular thrombosis, mural thrombosis, and/or ventricular thrombosis)
5. Age 18-99 years
6. Signed informed consent

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Exclusion Criteria

1. Presence of a mechanical heart valve
2. Failure to provide signed informed consent
3. Known diseases that affects coagulation test results such as vitamin K deficiency, disseminated intravascular coagulopathy, Von Willebrand disease, hemophilia, liver failure, etc.

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Percent time in therapeutic range during initial 12 weeks of warfarin	12 weeks	Within the 12 weeks of treatment, this is the percentage of time that a given participant is within the therapeutic range (e.g. participant is in therapeutic range 75% of time/12 weeks of measurement)

Secondary Outcome Measures

Name	Time	Method
INR ≥ 4.0 during first 12 weeks of warfarin therapy	12 weeks	Time greater than the desired INR therapeutic range within the first 12 weeks of warfarin therapy
Ischemic stroke	12 weeks	Development of a clinical diagnosis of an ischemic stroke
Time to reach therapeutic INR	12 weeks	Time needed to achieve first INR within the range of 2 to 3, provided that subsequent INR ≥ 7 days later was also within the range of 2 to 3
Major bleeding event during first 12 weeks of warfarin therapy	12 weeks	Development of a major bleeding event during the first 12 weeks of warfarin therapy, diagnosed by a clinician
Clinically relevant non-major bleeding event during the first 12 weeks of warfarin therapy	12 weeks	Development of a clinically relevant non-major bleeding event during the first 12 weeks of warfarin therapy, diagnosed by a clinician

Trial Locations

Locations (1)

Santa Clara Valley Medical Center; 🇺🇸 Santa Clara, California, United States