Clinical trial NCT01050920: Study of Genetic Factors Other Than CYP2C9 and VKORC1 That Influence Warfarin Dose Requirements in a South-east Asian Population
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Cancer
Lead sponsor: National University Hospital, Singapore
Sponsor class: OTHER
First posted: 2010-01-18
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
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.

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.


Eligibility criteria: Inclusion Criteria:

* 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).

Exclusion Criteria:

* 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.

Primary outcomes:
measure: To identify genetic variants other than CYP2C9 and VKORC1 that may influence warfarin dose requirements in a multi-ethnic population in Singapore.
Secondary outcomes:
Other outcomes:
Locations:
city: Singapore
country: Singapore
facility: National University Hospital
Study officials:
References:
citation: 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.
citation: 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.