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A pharmacogenomic approach to coumarin anticoagulant therapy

Objective

The effectiveness of treatment with oral anticoagulants in the prevention of thrombotic disorders is well established, but these drugs are potentially dangerous because of their narrow therapeutic index. In Europe three coumarins are used: warfarin, acenocoumarol, and phenprocoumon. Genetic factors that have been recently demonstrated to change the pharmacokinetics and pharmacodynamics of coumarins are the presence of polymorphisms in the genes encoding for CYP2C9 and VKOR (vitamin K epoxide reductase complex). Polymorphisms in these genes are associated with increased risk for severe overanticoagulation and bleedings. A clinical trial will be performed in seven European countries to determine whether knowledge of the genotype of patients at the start of coumarin treatment will increase the safety of use of these compounds and whether such gene testing is cost-effective. Patients will be randomized to receive treatment with a coumarin either dosed with an algorithm that does not include information on their genotype, or with an algorithm that does contain this information. The primary outcome will be time within therapeutic INR range. Secondary outcomes include INR>4 and bleedings.

Field of science

  • /medical and health sciences/basic medicine/pharmacology and pharmacy/pharmacokinetics

Call for proposal

FP7-HEALTH-2007-B
See other projects for this call

Funding Scheme

CP-FP - Small or medium-scale focused research project

Coordinator

UNIVERSITEIT UTRECHT
Address
Heidelberglaan 8
3584 CS Utrecht
Netherlands
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 658 185
Administrative Contact
Rinske De Kok-Baan (Ms.)

Participants (11)

ACADEMISCH ZIEKENHUIS LEIDEN
Netherlands
EU contribution
€ 73 680
Address
Albinusdreef 2
2333 ZA Leiden
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Guillaine De Blecourt (Ms.)
ERASMUS UNIVERSITAIR MEDISCH CENTRUM ROTTERDAM
Netherlands
EU contribution
€ 11 510,10
Address
Dr Molewaterplein 40
3015 GD Rotterdam
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Jenny Klomps (Ms.)
UNIVERSITAET ULM
Germany
EU contribution
€ 154 858
Address
Helmholtzstrasse 16
89081 Ulm
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Frank Gleixner
UNIVERSITY OF NEWCASTLE UPON TYNE
United Kingdom
EU contribution
€ 388 696
Address
Kings Gate
NE1 7RU Newcastle Upon Tyne
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Nicola Place (Ms.)
THE UNIVERSITY OF LIVERPOOL
United Kingdom
EU contribution
€ 488 072
Address
Brownlow Hill 765 Foundation Building
L69 7ZX Liverpool
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Jane Cloke (Dr.)
LGC LIMITED
United Kingdom
EU contribution
€ 161 452
Address
Queens Road
TW11 0LY Teddington
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Rita Barallon (Dr.)
UNIVERSITE PARIS-SUD

Participation ended

France
Address
Rue Georges Clemenceau 15
91405 Orsay Cedex
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Laurent Becquemont (Prof.)
UPPSALA UNIVERSITET
Sweden
EU contribution
€ 309 541
Address
Von Kraemers Alle 4
751 05 Uppsala
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Anette Mc Loughlin (Ms.)
DIMOKRITIO PANEPISTIMIO THRAKIS
Greece
EU contribution
€ 224 904
Address
Panepistimioupoli Rectorate Building
69100 Komotini
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Evangelos Manolopoulos (Prof.)
ALLGEMEIN OFFENTLICHES KRANKENHAUS DER ELISABETHINEN
Austria
EU contribution
€ 54 810
Address
Fadingerstrasse 1
4010 Linz
Activity type
Research Organisations
Administrative Contact
Elisabeth Haschke-Becher (Mrs.)
ERASMUS UNIVERSITEIT ROTTERDAM
Netherlands
EU contribution
€ 19 182,90
Address
Burgemeester Oudlaan 50
3062 PA Rotterdam
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Robert Speek (Mr.)