DOAC ADRs Retrospective Study

Drug-Related Side Effects and Adverse Reactions Clinical Trial

Official title:

Investigation of Genetic Variations on Patients With Adverse Drug Events While on Direct Oral Anticoagulants (DOACs)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04247919
• Other study ID #: C02-001 SC002
• Status: Terminated
• Start date: January 10, 2020
• Est. completion date: July 24, 2020

Study information

• Verified date: March 2021
• Source: Cipherome, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This retrospective study's objective is to evaluate if Cipherome's algorithm could have predicted the serious adverse drug reactions (ADRs) experienced by patients while on direct oral anti-coagulants (DOACs).

Description:

Using the latest next generation sequencing tools, this study will evaluate adverse drug reactions (ADRs) (e.g., major bleeding or treatment failure) in study participants while on direct oral anticoagulants (DOACs). A web-based program will analyze the data obtain from sequencing, and generate a drug safety score (DSS). The DSS risk score will be compared with pre-specified serious ADRs associated with DOAC therapy. A secondary analysis will involve discovery of novel variants that arise from our analysis and may potentially affect the outcome of DOAC treatment.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: July 24, 2020
• Est. primary completion date: July 24, 2020
• 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 a serious adverse drug reaction while taking a DOAC and is able to provide informed consent.

Exclusion Criteria:

• Failure to provide informed consent

Related Conditions & MeSH terms

• Drug-Related Side Effects and Adverse Reactions

Locations

Country	Name	City	State
United States	Santa Clara Valley Medical Center	San Jose	California

Sponsors (2)

Lead Sponsor	Collaborator
Cipherome, Inc.	Santa Clara Valley Medical Center

Country where clinical trial is conducted

United States, 

References & Publications (13)

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. Review. — 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). pii: E7. doi: 10.3390/jpm9010007. Review. — 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. Epub 2012 Sep 4. — View Citation

Sennesael AL, Larock AS, Douxfils J, Elens L, Stillemans G, Wiesen M, Taubert M, Dogné 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. — 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 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants with a Major Bleeding Event	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 led to death	Within 90 days of DOAC therapy initiation
Primary	Number of Participants with a Clinically Relevant Non-major Bleeding Event	Acute or subacute clinically overt bleed that does not meet the criteria for a major bleed but prompts a clinical response, in that it leads to at least one of the following: A hospital admission for bleeding, or A physician guided medical or surgical treatment for bleeding, or A change in antithrombotic therapy (including interruption or discontinuation of study drug).	Within 90 days of DOAC therapy initiation
Primary	Number of Deaths Reported	Death at any time	Through study completion, an average of 1 year
Secondary	Number of Participants with a Thromboembolic Event	Deep vein thrombosis, pulmonary embolism, ischemic stroke, transient ischemic attack, arterial thrombosis, or other thromboembolic event.	Within 90 days of DOAC therapy initiation