Association Between Genetic Variant Scores and Warfarin Effect

NCT03894878 | Completed

• 1 other identifier: C01-001 SC001
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

Study objective is to determine whether there is an association between genetic variant risk scores and clinical outcomes (percent time in therapeutic range, time to reach therapeutic international normalized ratio (INR), INR ≥ 4, bleeding event, ischemic stroke, death) in participants taking warfarin for atrial fibrillation, deep vein thrombosis (DVT), pulmonary embolism (PE), and/or intracardiac thrombosis.

Conditions

Atrial Fibrillation; Deep Vein Thrombosis; Intracardiac Thrombus; Pulmonary Embolism; Venous Thromboembolic Disease

Keywords

Warfarin; Coumadin; Pharmacogenomics; Pharmacogenetics; Adverse Drug Reactions; Bleeding/hemorrhaging

Outcome Measures

Primary Outcomes (1)

• Percent time in therapeutic range during initial 12 weeks of warfarin

  Within the 12 weeks of treatment, this is the percentage of time that a given participant is within the therapeutic range (e.g. participant is in therapeutic range 75% of time/12 weeks of measurement)

  12 weeks

Secondary Outcomes (5)

• Time to reach therapeutic INR

  12 weeks

• INR ≥ 4.0 during first 12 weeks of warfarin therapy

  12 weeks

• Ischemic stroke

  12 weeks

• Major bleeding event during first 12 weeks of warfarin therapy

  12 weeks

• Clinically relevant non-major bleeding event during the first 12 weeks of warfarin therapy

  12 weeks

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

1. Participants with a known disease that predisposes them to bleeding will be excluded, since it will be a confounder (trying to link abnormal genetic variant risk score to bleeding). 2. Participants taking medications or on a diet that increases bleeding propensity will also be excluded. 3. Pediatric participants will be excluded from this study, since atrial fibrillation and/or venous thromboembolism are rare in this cohort.

You may qualify if:

• Non-valvular atrial fibrillation
• Deep venous thrombosis (DVT) and/or pulmonary embolism (PE) with no hypercoagulable condition
• Non-valvular atrial fibrillation and DVT/PE (with no hypercoagulable condition)
• Intracardiac thrombosis (i.e. apical thrombosis, atrial thrombosis, auricular thrombosis, mural thrombosis, and/or ventricular thrombosis)
• Age 18-99 years
• Signed informed consent

You may not qualify if:

• Presence of a mechanical heart valve
• Failure to provide signed informed consent
• Known diseases that affects coagulation test results such as vitamin K deficiency, disseminated intravascular coagulopathy, Von Willebrand disease, hemophilia, liver failure, etc.

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 (12)

• 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

• Johnson JA, Caudle KE, Gong L, Whirl-Carrillo M, Stein CM, Scott SA, Lee MT, Gage BF, Kimmel SE, Perera MA, Anderson JL, Pirmohamed M, Klein TE, Limdi NA, Cavallari LH, Wadelius M. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Pharmacogenetics-Guided Warfarin Dosing: 2017 Update. Clin Pharmacol Ther. 2017 Sep;102(3):397-404. doi: 10.1002/cpt.668. Epub 2017 Apr 4.

  PMID: 28198005 BACKGROUND

• Cavallari LH, Perera MA. The future of warfarin pharmacogenetics in under-represented minority groups. Future Cardiol. 2012 Jul;8(4):563-76. doi: 10.2217/fca.12.31.

  PMID: 22871196 BACKGROUND

• https://www.bcbsks.com/CustomerService/Providers/MedicalPolicies/policies/policies/GeneticTesting_WarfarinDose_2017-09-01.pdf (Accessed July 22, 2019)

  BACKGROUND

• Pirmohamed M, Burnside G, Eriksson N, Jorgensen AL, Toh CH, Nicholson T, Kesteven P, Christersson C, Wahlstrom B, Stafberg C, Zhang JE, Leathart JB, Kohnke H, Maitland-van der Zee AH, Williamson PR, Daly AK, Avery P, Kamali F, Wadelius M; EU-PACT Group. A randomized trial of genotype-guided dosing of warfarin. N Engl J Med. 2013 Dec 12;369(24):2294-303. doi: 10.1056/NEJMoa1311386. Epub 2013 Nov 19.

  PMID: 24251363 BACKGROUND

• Kimmel SE, French B, Kasner SE, Johnson JA, Anderson JL, Gage BF, Rosenberg YD, Eby CS, Madigan RA, McBane RB, Abdel-Rahman SZ, Stevens SM, Yale S, Mohler ER 3rd, Fang MC, Shah V, Horenstein RB, Limdi NA, Muldowney JA 3rd, Gujral J, Delafontaine P, Desnick RJ, Ortel TL, Billett HH, Pendleton RC, Geller NL, Halperin JL, Goldhaber SZ, Caldwell MD, Califf RM, Ellenberg JH; COAG Investigators. A pharmacogenetic versus a clinical algorithm for warfarin dosing. N Engl J Med. 2013 Dec 12;369(24):2283-93. doi: 10.1056/NEJMoa1310669. Epub 2013 Nov 19.

  PMID: 24251361 BACKGROUND

• Rosendaal FR, Cannegieter SC, van der Meer FJ, Briet E. A method to determine the optimal intensity of oral anticoagulant therapy. Thromb Haemost. 1993 Mar 1;69(3):236-9.

  PMID: 8470047 BACKGROUND

• Schulman S, Kearon C; Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost. 2005 Apr;3(4):692-4. doi: 10.1111/j.1538-7836.2005.01204.x.

  PMID: 15842354 BACKGROUND

• Lip GY. Intracardiac thrombus formation in cardiac impairment: the role of anticoagulant therapy. Postgrad Med J. 1996 Dec;72(854):731-8. doi: 10.1136/pgmj.72.854.731.

  PMID: 9015466 BACKGROUND

• Cregler LL. Antithrombotic therapy in left ventricular thrombosis and systemic embolism. Am Heart J. 1992 Apr;123(4 Pt 2):1110-4. doi: 10.1016/0002-8703(92)91069-d.

  PMID: 1553880 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Sample collection: One 3 mL venous blood sample will be taken from each study participant and collected in EDTA tubes on the day of the one-time study visit, when the participant is reporting to the SCVH\&HS laboratory to undergo INR testing per Anticoagulation Clinic protocol. This 3 mL venous blood sample will be taken from each study participant, in addition to the standard of care blood draw for INR. Each sample tube will be labeled with the protocol study number, along with the date and time of collection.

MeSH Terms

Conditions

Atrial Fibrillation; Venous Thrombosis; Pulmonary Embolism; Drug-Related Side Effects and Adverse Reactions; Hemorrhage

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Thrombosis; Embolism and Thrombosis; Vascular Diseases; Lung Diseases; Respiratory Tract Diseases; Embolism; Chemically-Induced Disorders

Study Officials

• Clifford Wang, MD

  Santa Clara Valley Medical Center

  PRINCIPAL INVESTIGATOR

• Dayani Nualles-Percy, MD

  Santa Clara Valley Medical Center

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: March 27, 2019
• First Posted: March 29, 2019
• Study Start: February 11, 2019
• Primary Completion: September 30, 2022
• Study Completion: September 30, 2022
• Last Updated: February 16, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)