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Genetics informatics trial (GIFT) of warfarin to prevent deep vein thrombosis (DVT): rationale and study design

The Pharmacogenomics Journal volume 12, pages 417–424 (2012)Cite this article

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Abstract

The risk of venous thromboembolism (VTE) is higher after the total hip or knee replacement surgery than after almost any other surgical procedure; warfarin sodium is commonly prescribed to reduce this peri-operative risk. Warfarin has a narrow therapeutic window with high inter-individual dose variability and can cause hemorrhage. The genetics-informatics trial (GIFT) of warfarin to prevent deep vein thrombosis (DVT) is a 2 × 2 factorial-design, randomized controlled trial designed to compare the safety and effectiveness of warfarin-dosing strategies. GIFT will answer two questions: (1) does pharmacogenetic (PGx) dosing reduce the rate of adverse events in orthopedic patients; and (2) is a lower target international normalized ratio (INR) non-inferior to a higher target INR in orthopedic participants? The composite primary endpoint of the trial is symptomatic and asymptomatic VTE (identified on screening ultrasonography), major hemorrhage, INR⩾4, and death.

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Acknowledgements

This research is funded by the NIH (R01 HL097036). We thank the NIH, FDA and CMS whose constructive criticism improved the trial design. We appreciate the comments of Gerald Moskowitz, PhD, on an earlier draft of the manuscript.

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Authors and Affiliations

  1. Department of Internal Medicine, Washington University, St Louis, MO, USA

    E J Do, P Lenzini, C S Eby & B F Gage

  2. Department of Pathology, Washington University, St Louis, MO, USA

    C S Eby

  3. Hospital for Special Surgery, New York, NY, USA

    A R Bass

  4. Department of Pathology, University of Utah, Salt Lake City, UT, USA

    G A McMillin

  5. Intermountain Medical Center, Salt Lake City, UT, USA

    S M Stevens, S C Woller & J L Anderson

  6. Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA

    R C Pendleton & P Proctor

  7. Department of Orthopedic Surgery, Washington University, St Louis, MO, USA

    R M Nunley

  8. Cardiovascular Division, Washington University, St Louis, MO, USA

    V Davila-Roman

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Do, E., Lenzini, P., Eby, C. et al. Genetics informatics trial (GIFT) of warfarin to prevent deep vein thrombosis (DVT): rationale and study design. Pharmacogenomics J 12, 417–424 (2012). https://doi.org/10.1038/tpj.2011.18

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