Variability in Response to Warfarin in Children- Version 1.0

• Research type

  Research Study

• Full title

  Inter-individual Variability in response to Warfarin in Children: Analysis of Environmental and Pharmacogenetic Factors

• IRAS ID

  6571

• Sponsor organisation

  Newcastle upon Tyne Hospitals NHS Foundation Trust

• Eudract number

  2008-005395-27

• ISRCTN Number

  N/A

• Clinicaltrials.gov Identifier

  N/A

• Research summary

  Warfarin is a blood-thinning (anticoagulant) drug that is commonly used in children with heart defects to prevent or treat blood clots (thrombosis). Anticoagulation response to warfarin is notoriously unpredictable because of the large differences in dose requirements between children. Overdosing with warfarin can lead to haemorrhage and under-dosing to recurrent thrombosis, both of which are potentially fatal. Regular monitoring of a childs?? anticoagulation status is therefore necessary to ensure efficacy and safety of therapy. However, this is costly to the heath service and inconvenient to the child as it requires frequent blood tests.Studies in adults have shown that sensitivity to warfarin is flunced by genetic and environmental factors. However it is not known to what extent such factors flunce warfarin dose requirement in children.Uncertainty of response renders currently used dosing regimens for children inaccurate as they fail to take into account genetic and environmental factors which can potentially have a major flunce upon warfarin dose requirement. Children anticoagulated with warfarin from four sites in the UK (Newcastle, Birmingham, Manchester and Glasgow) and one site in Canada (Toronto) will take part in the proposed study. A single blood sample will be taken from each child for later genotyping of the genes which express enzymes that mediate the pharmacological action of warfarin and for the measurement of plasma warfarin and vitamin K concentrations. Patient demographics, including age and body size will be recorded. We will use the analyses results to develop a personalised warfarin dosing regimen that will predict warfarin dose requirement more accurately in newly diagnosed patients based upon the patient's genetic and demongraphic features. A more individualised approach to anticoagulation therapy could reduce the complications of warfarin therapy and the frequency of monitoring. Improving the safety of warfarin therapy will improve the quality of life of children who are anticoagulated with warfarin.This research is funded by The Royal College of Pathologists and Baxter Healthcare as an educational fellowship.

• REC name

  North East - Newcastle & North Tyneside 2 Research Ethics Committee

• REC reference

  08/H0907/157

• Date of REC Opinion

  21 Jan 2009

• REC opinion

  Further Information Favourable Opinion