- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04580589
DOAC ADRs Retrospective Study on Genetic Variations (DARES1)
February 14, 2023 updated by: Cipherome, Inc.
Investigation of Genetic Variations on Patients With Adverse Events While on Direct Oral Anticoagulants (DOACs)
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.
Study Overview
Status
Completed
Detailed Description
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.
Study Type
Observational
Enrollment (Actual)
210
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Jane Chiang, MD
- Phone Number: 1007 4082431460
- Email: jane.chiang@cipherome.com
Study Contact Backup
- Name: Kenneth J Park, PharmD
- Phone Number: 8175040116
- Email: kenneth.park@cipherome.com
Study Locations
-
-
California
-
Santa Clara, California, United States, 95128
- Santa Clara Valley Medical Center
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 99 years (Adult, Older Adult)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
All
Sampling Method
Non-Probability Sample
Study Population
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.
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Observational Models: Case-Control
- Time Perspectives: Retrospective
Cohorts and Interventions
Group / Cohort |
---|
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Major bleeding event during DOAC therapy
Time Frame: Within 1 year of DOAC therapy initiation
|
|
Within 1 year of DOAC therapy initiation
|
Clinically relevant non-major bleeding
Time Frame: Within 1 year of DOAC therapy initiation
|
|
Within 1 year of DOAC therapy initiation
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Thromboembolic events
Time Frame: Within 1 year of DOAC therapy initiation
|
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
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Discovery of novel genetic variants
Time Frame: Within 1 year of DOAC therapy initiation
|
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
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: Dayani Nualles-Percy, MD, Santa Clara Valley Medical Center
- Study Director: Clifford Wang, MD, Santa Clara Valley Medical Center
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
February 1, 2021
Primary Completion (Actual)
October 31, 2022
Study Completion (Actual)
October 31, 2022
Study Registration Dates
First Submitted
October 2, 2020
First Submitted That Met QC Criteria
October 2, 2020
First Posted (Actual)
October 8, 2020
Study Record Updates
Last Update Posted (Actual)
February 16, 2023
Last Update Submitted That Met QC Criteria
February 14, 2023
Last Verified
February 1, 2023
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- C02-001 SC003
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
UNDECIDED
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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