EUropean Pharmacogenetics of AntiCoagulant Therapy - Warfarin

Summary

Rationale:

The narrow therapeutic range and wide inter-patient variability in dose requirement make anticoagulation response to coumarin derivatives unpredictable. As a result, patients require frequent monitoring to avert adverse effects and maintain therapeutic efficacy. Polymorphisms in cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase complex 1 (VKORC1) jointly account for about 40% of the inter-individual variability in dose requirements. To date, several pharmacogenetic guided dosing algorithms for coumarin derivatives, predominately for warfarin, have been developed. However, the potential benefit of these dosing algorithms in terms of their safety and clinical utility has not been adequately investigated in randomised settings. Objective:

To determine whether a dosing algorithm containing genetic information increases the time within therapeutic INR range during anticoagulation therapy with each of warfarin, acenocoumarol and phenprocoumon compared to a dosing regimen that does not contain this information. Secondary outcomes of the study include cost effectiveness, number of thromboembolic and bleeding events, time to reach stable dose and number of supratherapeutic INR peaks.

Conditions

• Venous Thromboembolism
• Atrial Fibrillation

Interventions

OTHER

Genotype-guided dosing algorithm

Loading and monitoring dose according to genotype-guided dosing algorithm

OTHER

Standard care

Standard care

Sponsors & Collaborators

• Utrecht University

  collaborator OTHER

• Leiden University Medical Center

  collaborator OTHER

• Erasmus Medical Center

  collaborator OTHER

• University of Ulm

  collaborator OTHER

• Newcastle University

  collaborator OTHER

• University of Liverpool

  collaborator OTHER

• LGC Limited

  collaborator INDUSTRY

• Uppsala University

  collaborator OTHER

• Democritus University of Thrace

  collaborator OTHER

• Elisabethinen Hospital

  collaborator OTHER

• Utrecht Institute for Pharmaceutical Sciences

  lead OTHER

Principal Investigators

• Munir Pirmohamed, MD PhD · University of Liverpool

Study Design

Allocation

RANDOMIZED

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2011-01-31

Primary Completion

2013-10-31

Completion

2013-10-31

Countries

• Sweden
• United Kingdom

Study Locations