Association Between Genetic Variant Scores and Warfarin Effect

NCT ID: NCT03894878

Last Updated: 2023-02-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

200 participants

Study Classification

OBSERVATIONAL

Study Start Date

2019-02-11

Study Completion Date

2022-09-30

Brief Summary

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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

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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.

Conditions

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Atrial Fibrillation Deep Vein Thrombosis Intracardiac Thrombus Pulmonary Embolism Venous Thromboembolic Disease

Study Design

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Observational Model Type

COHORT

Study Time Perspective

RETROSPECTIVE

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

99 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Santa Clara Valley Medical Center

OTHER

Sponsor Role collaborator

Cipherome, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clifford Wang, MD

Role: PRINCIPAL_INVESTIGATOR

Santa Clara Valley Medical Center

Dayani Nualles-Percy, MD

Role: STUDY_DIRECTOR

Santa Clara Valley Medical Center

Locations

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Santa Clara Valley Medical Center

Santa Clara, California, United States

Site Status

Countries

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United States

References

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Colilla S, Crow A, Petkun W, Singer DE, Simon T, Liu X. Estimates of current and future incidence and prevalence of atrial fibrillation in the U.S. adult population. Am J Cardiol. 2013 Oct 15;112(8):1142-7. doi: 10.1016/j.amjcard.2013.05.063. Epub 2013 Jul 4.

Reference Type BACKGROUND
PMID: 23831166 (View on PubMed)

Wysowski DK, Nourjah P, Swartz L. Bleeding complications with warfarin use: a prevalent adverse effect resulting in regulatory action. Arch Intern Med. 2007 Jul 9;167(13):1414-9. doi: 10.1001/archinte.167.13.1414.

Reference Type BACKGROUND
PMID: 17620536 (View on PubMed)

Zareh M, Davis A, Henderson S. Reversal of warfarin-induced hemorrhage in the emergency department. West J Emerg Med. 2011 Nov;12(4):386-92. doi: 10.5811/westjem.2011.3.2051.

Reference Type BACKGROUND
PMID: 22224125 (View on PubMed)

Johnson JA, Caudle KE, Gong L, Whirl-Carrillo M, Stein CM, Scott SA, Lee MT, Gage BF, Kimmel SE, Perera MA, Anderson JL, Pirmohamed M, Klein TE, Limdi NA, Cavallari LH, Wadelius M. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Pharmacogenetics-Guided Warfarin Dosing: 2017 Update. Clin Pharmacol Ther. 2017 Sep;102(3):397-404. doi: 10.1002/cpt.668. Epub 2017 Apr 4.

Reference Type BACKGROUND
PMID: 28198005 (View on PubMed)

Cavallari LH, Perera MA. The future of warfarin pharmacogenetics in under-represented minority groups. Future Cardiol. 2012 Jul;8(4):563-76. doi: 10.2217/fca.12.31.

Reference Type BACKGROUND
PMID: 22871196 (View on PubMed)

https://www.bcbsks.com/CustomerService/Providers/MedicalPolicies/policies/policies/GeneticTesting_WarfarinDose_2017-09-01.pdf (Accessed July 22, 2019)

Reference Type BACKGROUND

Pirmohamed M, Burnside G, Eriksson N, Jorgensen AL, Toh CH, Nicholson T, Kesteven P, Christersson C, Wahlstrom B, Stafberg C, Zhang JE, Leathart JB, Kohnke H, Maitland-van der Zee AH, Williamson PR, Daly AK, Avery P, Kamali F, Wadelius M; EU-PACT Group. A randomized trial of genotype-guided dosing of warfarin. N Engl J Med. 2013 Dec 12;369(24):2294-303. doi: 10.1056/NEJMoa1311386. Epub 2013 Nov 19.

Reference Type BACKGROUND
PMID: 24251363 (View on PubMed)

Kimmel SE, French B, Kasner SE, Johnson JA, Anderson JL, Gage BF, Rosenberg YD, Eby CS, Madigan RA, McBane RB, Abdel-Rahman SZ, Stevens SM, Yale S, Mohler ER 3rd, Fang MC, Shah V, Horenstein RB, Limdi NA, Muldowney JA 3rd, Gujral J, Delafontaine P, Desnick RJ, Ortel TL, Billett HH, Pendleton RC, Geller NL, Halperin JL, Goldhaber SZ, Caldwell MD, Califf RM, Ellenberg JH; COAG Investigators. A pharmacogenetic versus a clinical algorithm for warfarin dosing. N Engl J Med. 2013 Dec 12;369(24):2283-93. doi: 10.1056/NEJMoa1310669. Epub 2013 Nov 19.

Reference Type BACKGROUND
PMID: 24251361 (View on PubMed)

Rosendaal FR, Cannegieter SC, van der Meer FJ, Briet E. A method to determine the optimal intensity of oral anticoagulant therapy. Thromb Haemost. 1993 Mar 1;69(3):236-9.

Reference Type BACKGROUND
PMID: 8470047 (View on PubMed)

Schulman S, Kearon C; Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost. 2005 Apr;3(4):692-4. doi: 10.1111/j.1538-7836.2005.01204.x.

Reference Type BACKGROUND
PMID: 15842354 (View on PubMed)

Lip GY. Intracardiac thrombus formation in cardiac impairment: the role of anticoagulant therapy. Postgrad Med J. 1996 Dec;72(854):731-8. doi: 10.1136/pgmj.72.854.731.

Reference Type BACKGROUND
PMID: 9015466 (View on PubMed)

Cregler LL. Antithrombotic therapy in left ventricular thrombosis and systemic embolism. Am Heart J. 1992 Apr;123(4 Pt 2):1110-4. doi: 10.1016/0002-8703(92)91069-d.

Reference Type BACKGROUND
PMID: 1553880 (View on PubMed)

Other Identifiers

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C01-001 SC001

Identifier Type: -

Identifier Source: org_study_id

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