Study of Genetic Factors Other Than CYP2C9 and VKORC1 That Influence Warfarin Dose Requirements in a South-east Asian Population

NCT01050920 | Unknown

• 1 other identifier: PK03/32/09
• Study Type: observational
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Warfarin is a commonly used anti-coagulant, but has a narrow therapeutic index and wide inter-individual and inter-ethnic variation in dose requirements. Several genetic and non-genetic factors have been identified that could influence warfarin dose requirements. However, current known predictive factors could only explain about 50-60% of warfarin dose variability. Inter-ethnic differences in genetic influences on warfarin dose requirements also exist. We hypothesize that genetic factors other than CYP2C9 and VKORC1 may influence warfarin dosing and serve to further optimize warfarin dosing.

Conditions

Cancer

Outcome Measures

Primary Outcomes (1)

• To identify genetic variants other than CYP2C9 and VKORC1 that may influence warfarin dose requirements in a multi-ethnic population in Singapore.

Study Arms (1)

Blood Collection

Biological: Blood collection

Interventions

Blood collection BIOLOGICAL

Blood Collection

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Germline DNA will be genotyped for variants in genes in the anti-coagulation pathway, including CYP4F2, GGCX and EPHX1. The germline DNA was previously collected from a warfarin study (C/00/510, NUH, C/00/535, TTSH, PI-Dr Goh Boon Cher). Samples were anonymized, and data analysis will be done without patient identifiers. Germline DNA previously collected from 279 patients who were on maintenance warfarin dose will be genotyped. The clinical data that has been collected and will be used for the study include: gender, race, age, body weight, maintenance warfarin dose, serum albumin, two consecutive stable INR values, and indications for warfarin use.

You may qualify if:

• patients receiving maintenance warfarin therapy with a stable therapeutic international normalized ratio (INR) between 2 and 3 for at least 3 months,
• patients recruited from the anticoagulation clinics at the National University Hospital and Tan Tock Seng Hospital in Singapore between June 2002 and June 2004 for a previous genotyping study (C/00/510, NUH; C/00/535, TTSH, PI-Dr Goh Boon Cher).

You may not qualify if:

• patients below 21 years old, or
• patients with liver disease, malabsorption or chronic diarrheal diseases, or
• patients taking drugs that may potentially interact with warfarin.
• Dietary advice to avoid foods that may interfere with warfarin pharmacokinetics will be given to patients during warfarin therapy.

Sponsors & Collaborators

• National University Hospital, Singapore: lead

Study Sites (1)

National University Hospital

Singapore, 119074, Singapore

RECRUITING

Related Publications (2)

• Hirsh J, Fuster V, Ansell J, Halperin JL; American Heart Association/American College of Cardiology Foundation. American Heart Association/American College of Cardiology Foundation guide to warfarin therapy. J Am Coll Cardiol. 2003 May 7;41(9):1633-52. doi: 10.1016/s0735-1097(03)00416-9. No abstract available.

  PMID: 12742309 BACKGROUND

• Poller L, Taberner DA. Dosage and control of oral anticoagulants: an international collaborative survey. Br J Haematol. 1982 Jul;51(3):479-85. doi: 10.1111/j.1365-2141.1982.tb02805.x.

  PMID: 7104231 BACKGROUND

MeSH Terms

Conditions

Neoplasms

Interventions

Blood Specimen Collection

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Central Study Contacts

Soo Chin Lee, MBBS, MRCP

CONTACT

65 6772 4629; soo_chin_lee@nuhs.edu.sg

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: January 15, 2010
• First Posted: January 18, 2010
• Study Start: September 1, 2013
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: January 22, 2014

Record last verified: 2014-01

Locations

SG (1)