Drug-Related Side Effects and Adverse Reactions Clinical Trial
— DARES1Official title:
Investigation of Genetic Variations on Patients With Adverse Events While on Direct Oral Anticoagulants (DOACs)
Verified date | February 2023 |
Source | Cipherome, Inc. |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Observational |
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.
Status | Completed |
Enrollment | 210 |
Est. completion date | October 31, 2022 |
Est. primary completion date | October 31, 2022 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | All |
Age group | 18 Years to 99 Years |
Eligibility | Inclusion Criteria: - 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. Control patients will be recruited from all adult patients who are on DOAC therapy. Exclusion Criteria: - Failure to provide informed consent |
Country | Name | City | State |
---|---|---|---|
United States | Santa Clara Valley Medical Center | Santa Clara | California |
Lead Sponsor | Collaborator |
---|---|
Cipherome, Inc. | Santa Clara Valley Medical Center |
United States,
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. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
Ing Lorenzini K, Daali Y, Fontana P, Desmeules J, Samer C. Rivaroxaban-Induced Hemorrhage Associated with ABCB1 Genetic Defect. Front Pharmacol. 2016 Dec 19;7:494. doi: 10.3389/fphar.2016.00494. eCollection 2016. — View Citation
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. — View Citation
Kirley K, Qato DM, Kornfield R, Stafford RS, Alexander GC. National trends in oral anticoagulant use in the United States, 2007 to 2011. Circ Cardiovasc Qual Outcomes. 2012 Sep 1;5(5):615-21. doi: 10.1161/CIRCOUTCOMES.112.967299. Epub 2012 Sep 4. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
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. Erratum In: Pharmgenomics Pers Med. 2018 Sep 26;11:167. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
* Note: There are 15 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | 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 | |
Primary | Major bleeding event during DOAC therapy | Reduction in hemoglobin of at least 2 g/dL
Blood loss requiring transfusion of at least 2 units of whole blood or erythrocytes Critical anatomical sites of bleeding: intramuscular with compartment syndrome, intracranial, intraspinal, retroperitoneal, intraocular, pericardial, and atraumatic intra-articular bleeding. Bleeding leading to death |
Within 1 year of DOAC therapy initiation | |
Primary | Clinically relevant non-major bleeding | Hospital admission for bleeding, or
Physician guided medical or surgical treatment for bleeding, or Change in antithrombotic therapy (including interruption or discontinuation of study drug). |
Within 1 year of DOAC therapy initiation | |
Secondary | 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 |
Status | Clinical Trial | Phase | |
---|---|---|---|
Active, not recruiting |
NCT03258151 -
Association of Genetic Polymorphisms With Docetaxel-based Chemotherapy Toxicities in Chinese Solid Tumor Patients
|
||
Recruiting |
NCT05202964 -
Compliance and Tolerance to Oral AntiBiotherapy in Osteoarticular Infections (OTABIO)
|
||
Completed |
NCT04597593 -
Association Between Genetic Variant Scores and DOACs (DARES2)
|
||
Recruiting |
NCT05096338 -
Mechanisms, Predictors, and Social Determinants of Cardiotoxicity in Prostate Cancer
|
||
Recruiting |
NCT05078190 -
Mechanisms, Predictors, and Social Determinants of Cardiotoxicity in Breast Cancer
|
||
Completed |
NCT02457039 -
Acupuncture Prevents Chemobrain in Breast Cancer Patients
|
N/A | |
Completed |
NCT02779530 -
CYP4A11 and CYP4F2 Gene Variants as Makers of Cardiovascular Adverse Events of Non-steroidal Anti-inflammatory Drugs
|
Phase 4 | |
Recruiting |
NCT03051880 -
Preventive Effect of EGF Cream for Cutaneous Adverse Event of EGFR Inhibitors
|
N/A | |
Recruiting |
NCT03047863 -
Therapeutic Effect of EGF Cream for Cutaneous Adverse Event of EGFR Inhibitors
|
N/A | |
Completed |
NCT02482025 -
The Secure Messaging for Medication Reconciliation Tool (SMMRT) Trial
|
N/A | |
Not yet recruiting |
NCT03147157 -
The Effect of Human Leukocyte Antigen Macthing on Guiding Tacrolimus Regimen After Liver Transplantation
|
N/A | |
Recruiting |
NCT03156348 -
Impact of Clinical Pharmacist on Adverse Drug Events in Older Adults
|
N/A | |
Recruiting |
NCT03501108 -
Discontinuation of Long-term Medications in Older People Entering Nursing Home Care
|
N/A | |
Recruiting |
NCT06427317 -
Routinely Collected Clinical Data and Evaluation of Antimicrobial Target Attainment
|
||
Completed |
NCT03227653 -
Neuropsychiatric Side Effects of Efavirenz in Children Living With HIV
|
||
Completed |
NCT03177174 -
Different Chemotherapy Protocols Combined With Intensity Modulated Radiation Therapy in Patients With Locally Advanced Nasopharyngeal Carcinoma
|
N/A | |
Recruiting |
NCT04077281 -
Improving Medication Prescribing-Related Outcomes for Vulnerable Elderly In Transitions
|
N/A | |
Not yet recruiting |
NCT05247814 -
Individual Risk Profiles for Adverse Drug Reactions in Geriatric Patients
|
||
Recruiting |
NCT03938597 -
Investigation of Serious Adverse Events Following Vaccination Against Yellow Fever: Emphasis on Genetic Basis and Biological Markers
|
||
Recruiting |
NCT06291688 -
Applying Mobile Healthcare Education to Improve Cutaneous Self-care Capability
|
N/A |