Clinical trial NCT03894878: Association Between Genetic Variant Scores and Warfarin Effect
Official title: Association Between Risk Scores for Genetic Variants and Percentage of Time in Therapeutic Range for Participants With Atrial Fibrillation, Deep Vein Thrombosis, and/or Intracardiac Thrombosis Taking Warfarin
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Atrial Fibrillation
Deep Vein Thrombosis
Intracardiac Thrombus
Pulmonary Embolism
Venous Thromboembolic Disease
Keywords: Warfarin
Coumadin
Pharmacogenomics
Pharmacogenetics
Adverse Drug Reactions
Bleeding/hemorrhaging
Lead sponsor: Cipherome, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Santa Clara Valley Medical Center
First posted: 2019-03-29
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 1. Participants with a known disease that predisposes them to bleeding will be excluded, since it will be a confounder (trying to link abnormal genetic variant risk score to bleeding).
2. Participants taking medications or on a diet that increases bleeding propensity will also be excluded.
3. Pediatric participants will be excluded from this study, since atrial fibrillation and/or venous thromboembolism are rare in this cohort.

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.

Eligibility criteria: 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

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.

Primary outcomes:
measure: Percent time in therapeutic range during initial 12 weeks of warfarin
timeFrame: 12 weeks
Secondary outcomes:
measure: Time to reach therapeutic INR
timeFrame: 12 weeks
measure: INR ≥ 4.0 during first 12 weeks of warfarin therapy
timeFrame: 12 weeks
measure: Ischemic stroke
timeFrame: 12 weeks
measure: Major bleeding event during first 12 weeks of warfarin therapy
timeFrame: 12 weeks
measure: Clinically relevant non-major bleeding event during the first 12 weeks of warfarin therapy
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Santa Clara
country: United States
facility: Santa Clara Valley Medical Center
state: California
Study officials:
affiliation: Santa Clara Valley Medical Center
name: Clifford Wang, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Santa Clara Valley Medical Center
name: Dayani Nualles-Percy, MD
role: STUDY_DIRECTOR
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