Patients will be recruited who are receiving long term warfarin therapy for the treatment or prevention of venous or arterial thrombosis or embolism MedDRA version: 9.1 Level: LLT Classification code 10043566 Term: Thromboembolism
Conditions
Interventions
Product Name: Warfarin
Pharmaceutical Form: Tablet
INN or Proposed INN: warfarin sodium
CAS Number: 129066
Sponsors
Newcastle upon Tyne Hospitals NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patient being on warfarin for 9 months or more (so that percentage time in target range over the previous 6 months is not affected by the induction period of therapy where the correct maintenance dose is being established), and a target INR of 2.5. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Starting or stopping medication during the 6 months prior to study entry that might have interfered with warfarin, or having an illness during this time which might have affected warfarin dose, or having issues known to result in compliance with warfarin therapy being unreliable.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Vitamin K is necessary for the activation of clotting proteins normally needed to stop us from bleeding. Warfarin causes anticoagulation (blood-thinning) by inhibiting the vitamin K epoxide reductase (VKOR) enzyme responsible for the recycling of vitamin K in the liver. VKOR enzyme production is controlled by the vitamin K epoxide reductase gene (termed VKORC1). Some individuals can have mutations of the VKORC1 gene. These individuals produce VKOR enzyme with reduced activity. Vitamin K in the diet works in a directly opposite way to warfarin, counteracting the anticoagulation(blood thinning) response to warfarin. There are theoretical reasons, and a small amount of evidence to support that the antagonistic effect of dietary vitamin K might not be the same between patients with different genotypes. Our principal research objective is to assess this by exploring the inter-relationships between stability of anticoagulation control, dietary vitamin K intake and VKORC1 genotype.;Secondary Objective: Warfarin is metabolised, in part, by an enzyme called cytochrome P4502C9. There are 3 types of this enzyme, one with highest activity, one with medium activity, and one with low activity. By measuring the gene which controls this enzyme we will be able to look at the prevalence of CYP2C9 and VKORC1 polymorphisms in this large population. This will allow us to assess the contribution of both genes together, particularly having two genes giving enzymes of low activity, to how sensitive people are to warfarin and how stable their control of anticoagulation is.;Primary end point(s): . Weekly dietary intake of vitamin K will be assessed by asking a set of questions about their diet . Each participant will give a single blood sample (20 ml venous) for later VKORC1 and CYP2C9 genotyping. The former will be carried out using an established in-house PCR assay (Hatch et al. 2006), the latter by a published method (Kamali et al 2004). The percentage time each patient | — |
Countries
United Kingdom
Outcome results
None listed