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| Name | Class |
|---|---|
| Santa Clara Valley Medical Center | OTHER |
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The purpose of this study is to see if the participant's genetic profile and clinical factors (age, drug dose, etc.) affect drug outcomes (i.e. serious bleeding) that the participant may have experienced since taking the drug (direct oral anticoagulant) for preventing blood clots from forming in the blood vessels.
Genes can have variants or mutations that can increase the participant's risk for bleeding when receiving a direct oral anticoagulant (DOACs). The investigators will be studying participants on DOACs who have had bleeding and also participants who are on DOACs who did not have bleeding (control group). The goal of the study is to determine the accuracy of Cipherome's Drug Safety Score (DSS) in it's ability to predict adverse drug reactions (ADRs). A DSS score ranges from 0 to 1, with scores less than 0.3 correlated with a higher risk of ADRs and scores more than 0.7 correlated with a lower risk of ADRs. The participant's DSS score will be compared with the actual clinical outcome using a statistical test to determine the accuracy of the DSS.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Adverse Drug Reaction on DOAC | Participants on Direct Oral Anti-coagulants (DOACs) who experience major bleeding or clinically relevant non-major bleeding per International Society of Thrombosis and Haemostasis criteria. This is an observational study, so there will be no intervention. | ||
| Treatment Failure on DOAC | Participants on Direct Oral Anti-coagulants (DOACs) who experience treatment failure (e.g., recurrent MI, systemic embolism, ischemic stroke, etc.). This is an observational study, so there will be no intervention. | ||
| Case Control | Participants on Direct Oral Anti-coagulants (DOACs) who experience neither major bleeding or treatment failure. |
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| Measure | Description | Time Frame |
|---|---|---|
| Major bleeding event during DOAC therapy |
| Within 1 year of DOAC therapy initiation |
| Clinically relevant non-major bleeding |
| Within 1 year of DOAC therapy initiation |
| Measure | Description | Time Frame |
|---|---|---|
| Thromboembolic events | Thromboembolic events including, but not limited to: deep vein thrombosis, pulmonary embolism, ischemic stroke, transient ischemic attack, arterial thrombosis, or other thromboembolic event | Within 1 year of DOAC therapy initiation |
| Measure | Description | Time Frame |
|---|---|---|
| Discovery of novel genetic variants | To discover novel pharmacogenomic variants associated with DOAC metabolism. The investigators will be conducting whole genome sequencing to determine novel variants found in individuals with major bleeding or treatment failures. | Within 1 year of DOAC therapy initiation |
Inclusion Criteria:
Exclusion Criteria:
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Any adult patient 18 years and older, who experienced major bleeding, clinically relevant non major bleeding or treatment failure while taking a DOAC during the study time frame and is able to provide informed consent.
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| Name | Affiliation | Role |
|---|---|---|
| Dayani Nualles-Percy, MD | Santa Clara Valley Medical Center | Principal Investigator |
| Clifford Wang, 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 |
|---|---|
| D064420 | Drug-Related Side Effects and Adverse Reactions |
| ID | Term |
|---|---|
| D064419 | Chemically-Induced Disorders |
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Blood DNA sample
| 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. |
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| 24319220 | Background | Bauer KA. Pros and cons of new oral anticoagulants. Hematology Am Soc Hematol Educ Program. 2013;2013:464-70. doi: 10.1182/asheducation-2013.1.464. |
| 30658513 | Background | Kanuri SH, Kreutz RP. Pharmacogenomics of Novel Direct Oral Anticoagulants: Newly Identified Genes and Genetic Variants. J Pers Med. 2019 Jan 17;9(1):7. doi: 10.3390/jpm9010007. |
| 30455596 | Background | Sennesael AL, Larock AS, Douxfils J, Elens L, Stillemans G, Wiesen M, Taubert M, Dogne JM, Spinewine A, Mullier F. Rivaroxaban plasma levels in patients admitted for bleeding events: insights from a prospective study. Thromb J. 2018 Nov 12;16:28. doi: 10.1186/s12959-018-0183-3. eCollection 2018. |
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| 29457840 | Background | Ueshima S, Hira D, Kimura Y, Fujii R, Tomitsuka C, Yamane T, Tabuchi Y, Ozawa T, Itoh H, Ohno S, Horie M, Terada T, Katsura T. Population pharmacokinetics and pharmacogenomics of apixaban in Japanese adult patients with atrial fibrillation. Br J Clin Pharmacol. 2018 Jun;84(6):1301-1312. doi: 10.1111/bcp.13561. Epub 2018 Apr 16. |
| 27614009 | Background | Shi J, Wang X, Nguyen JH, Bleske BE, Liang Y, Liu L, Zhu HJ. Dabigatran etexilate activation is affected by the CES1 genetic polymorphism G143E (rs71647871) and gender. Biochem Pharmacol. 2016 Nov 1;119:76-84. doi: 10.1016/j.bcp.2016.09.003. Epub 2016 Sep 8. |
| 27261537 | Background | Dimatteo C, D'Andrea G, Vecchione G, Paoletti O, Cappucci F, Tiscia GL, Buono M, Grandone E, Testa S, Margaglione M. Pharmacogenetics of dabigatran etexilate interindividual variability. Thromb Res. 2016 Aug;144:1-5. doi: 10.1016/j.thromres.2016.05.025. Epub 2016 May 26. |
| 30100750 | Background | Sychev DA, Levanov AN, Shelekhova TV, Bochkov PO, Denisenko NP, Ryzhikova KA, Mirzaev KB, Grishina EA, Gavrilov MA, Ramenskaya GV, Kozlov AV, Bogoslovsky T. The impact of ABCB1 (rs1045642 and rs4148738) and CES1 (rs2244613) gene polymorphisms on dabigatran equilibrium peak concentration in patients after total knee arthroplasty. Pharmgenomics Pers Med. 2018 Jul 25;11:127-137. doi: 10.2147/PGPM.S169277. eCollection 2018. |
| 26432245 | Background | 1000 Genomes Project Consortium; Auton A, Brooks LD, Durbin RM, Garrison EP, Kang HM, Korbel JO, Marchini JL, McCarthy S, McVean GA, Abecasis GR. A global reference for human genetic variation. Nature. 2015 Oct 1;526(7571):68-74. doi: 10.1038/nature15393. |
| 20331949 | Background | Beckman MG, Hooper WC, Critchley SE, Ortel TL. Venous thromboembolism: a public health concern. Am J Prev Med. 2010 Apr;38(4 Suppl):S495-501. doi: 10.1016/j.amepre.2009.12.017. |
| 23425163 | Background | Schulman S, Kearon C, Kakkar AK, Schellong S, Eriksson H, Baanstra D, Kvamme AM, Friedman J, Mismetti P, Goldhaber SZ; RE-MEDY Trial Investigators; RE-SONATE Trial Investigators. Extended use of dabigatran, warfarin, or placebo in venous thromboembolism. N Engl J Med. 2013 Feb 21;368(8):709-18. doi: 10.1056/NEJMoa1113697. |