DOAC ADRs Retrospective Study on Genetic Variations

NCT04580589 | Completed

• 1 other identifier: C02-001 SC003
• Study Type: observational
• Target: 210
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Drug-Related Side Effects and Adverse Reactions; Treatment Failure

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (1)

• Thromboembolic events

  Within 1 year of DOAC therapy initiation

Other Outcomes (1)

• Discovery of novel genetic variants

  Within 1 year of DOAC therapy initiation

Study Arms (3)

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.

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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.

You may not qualify if:

• Failure to provide informed consent

Sponsors & Collaborators

• Cipherome, Inc.: lead
• Santa Clara Valley Medical Center: collaborator

Study Sites (1)

Santa Clara Valley Medical Center

Santa Clara, California, 95128, United States

Location

Related Publications (15)

• 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.

  PMID: 23831166 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.

  PMID: 17620536 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.

  PMID: 22224125 BACKGROUND

• 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.

  PMID: 22949490 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.

  PMID: 24319220 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.

  PMID: 30658513 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.

  PMID: 30455596 BACKGROUND

• 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.

  PMID: 28066243 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.

  PMID: 29457840 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.

  PMID: 27614009 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.

  PMID: 27261537 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.

  PMID: 30100750 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.

  PMID: 26432245 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.

  PMID: 20331949 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.

  PMID: 23425163 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Blood DNA sample

MeSH Terms

Conditions

Drug-Related Side Effects and Adverse Reactions

Condition Hierarchy (Ancestors)

Chemically-Induced Disorders

Study Officials

• Dayani Nualles-Percy, MD

  Santa Clara Valley Medical Center

  PRINCIPAL INVESTIGATOR

• Clifford Wang, MD

  Santa Clara Valley Medical Center

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: RETROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 2, 2020
• First Posted: October 8, 2020
• Study Start: February 1, 2021
• Primary Completion: October 31, 2022
• Study Completion: October 31, 2022
• Last Updated: February 16, 2023

Record last verified: 2023-02

Locations

US (1)