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| Name | Class |
|---|---|
| Santa Clara Valley Medical Center | OTHER |
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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.
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.
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| Measure | Description | Time Frame |
|---|---|---|
| Percent time in therapeutic range during initial 12 weeks of warfarin | 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) | 12 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Time to reach therapeutic INR | 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 | 12 weeks |
| INR ≥ 4.0 during first 12 weeks of warfarin therapy |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Clifford Wang, MD | Santa Clara Valley Medical Center | Principal Investigator |
| Dayani Nualles-Percy, MD | Santa Clara Valley Medical Center | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Santa Clara Valley Medical Center | Santa Clara | California | 95128 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23831166 | Background | 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. | |
| 17620536 | Background | 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. |
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| ID | Term |
|---|---|
| D001281 | Atrial Fibrillation |
| D020246 | Venous Thrombosis |
| D011655 | Pulmonary Embolism |
| D064420 | Drug-Related Side Effects and Adverse Reactions |
| D006470 | Hemorrhage |
| ID | Term |
|---|---|
| D001145 | Arrhythmias, Cardiac |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D010335 | Pathologic Processes |
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Sample collection:
One 3 mL venous blood sample will be taken from each study participant and collected in EDTA tubes on the day of the one-time study visit, when the participant is reporting to the SCVH&HS laboratory to undergo INR testing per Anticoagulation Clinic protocol.
This 3 mL venous blood sample will be taken from each study participant, in addition to the standard of care blood draw for INR. Each sample tube will be labeled with the protocol study number, along with the date and time of collection.
Time greater than the desired INR therapeutic range within the first 12 weeks of warfarin therapy
| 12 weeks |
| Ischemic stroke | Development of a clinical diagnosis of an ischemic stroke | 12 weeks |
| Major bleeding event during first 12 weeks of warfarin therapy | Development of a major bleeding event during the first 12 weeks of warfarin therapy, diagnosed by a clinician | 12 weeks |
| Clinically relevant non-major bleeding event during the first 12 weeks of warfarin therapy | Development of a clinically relevant non-major bleeding event during the first 12 weeks of warfarin therapy, diagnosed by a clinician | 12 weeks |
| 22224125 | Background | 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. |
| 28198005 | Background | 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. |
| 22871196 | Background | 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. |
| Background | https://www.bcbsks.com/CustomerService/Providers/MedicalPolicies/policies/policies/GeneticTesting_WarfarinDose_2017-09-01.pdf (Accessed July 22, 2019) |
| 24251363 | 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. |
| 24251361 | Background | 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. |
| 8470047 | Background | 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. |
| 15842354 | Background | 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. |
| 9015466 | Background | 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. |
| 1553880 | Background | 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. |
| D013568 |
| Pathological Conditions, Signs and Symptoms |
| D013927 | Thrombosis |
| D016769 | Embolism and Thrombosis |
| D014652 | Vascular Diseases |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D004617 | Embolism |
| D064419 | Chemically-Induced Disorders |