GENETICS-InFORMATICS TRIAL (GIFT) OF WARFARIN TO PREVENT DVT

2008年9月15日，代理卫生部长，医学博士，公共卫生硕士史蒂文·加尔森指出， 静脉血栓栓塞事件（VTE）导致至少10万美国人死亡 每年.由于许多死亡是突然发生的，最好的管理是预防。 在这项随机对照试验中，华盛顿大学的研究人员将测试策略， 通过使用非营利网络应用程序提高静脉血栓栓塞预防的安全性和有效性 （www.WarfarinDosing.org）根据每个人的药物遗传学特点调整华法林的剂量。 和/或临床特征。他们还提议测试美国科学院的推荐 骨科医生（AAOS）使用低水平抗凝（即，a目标国际 标准化比值（INR）< 2.0），用于预防骨科患者的VTE。因此， 遗传信息学试验（GIFT）的目的是阐明 提高华法林治疗安全性和有效性的新策略。 华盛顿大学的研究人员建议对1500名患者进行随机对照试验 在巴恩斯犹太医院做全髋关节或膝关节置换手术。通过研究这个高- 多普勒超声筛查无症状下肢深静脉血栓的高危人群 术后，拟议的试验将有适当的把握度来阐明两个新的 预防VTE的策略。研究人员将使用2 x 2析因设计来随机化 患者：（1）华法林的药物遗传学与临床给药;和（2）目标INR为2.5与 < 2.0。该提案有两个具体目标： 目的1：确定基于药物遗传学的华法林治疗如何影响非致死性 VTE、非致死性大出血和血管性死亡。虽然FDA已经批准了基因 测试影响华法林剂量的变异，没有先前（或计划）的试验具有把握度， 确定该策略是否会影响结果。 目的2：确定目标INR < 2.0的华法林治疗是否非劣于 在骨科患者中预防VTE的目标INR为2.5。虽然美国大学 胸科医生（ACCP）建议目标INR为2.5，AAOS建议< 2.0， 这些相互冲突的目标从未在一级预防VTE的试验中进行过比较。

On September 15, 2008, acting Surgeon General, Steven Galson, MD MPH, noted that venous thromboembolic events (VTE) contribute to the death of at least 100,000 Americans each year. Because many of these deaths occur suddenly, the best management is prevention. In this randomized, controlled trial, Washington University researchers will test strategies to improve the safety and effectiveness of VTE prevention by using a non-profit web application (www.WarfarinDosing.org) to tailor the dose of warfarin to each person's pharmacogenetic and/or clinical profile. They also propose to test the recommendation of the American Academy of Orthopedic Surgeons (AAOS) to use low levels of anticoagulation (i.e., a target International Normalized Ratio (INR) < 2.0) for VTE prevention in orthopedic patients. Thus, the overall objective of the Genetics-InFormatics Trial (GIFT) of Warfarin to Prevent DVT is to elucidate novel strategies to improve the safety and effectiveness of warfarin therapy. Washington University researchers propose a randomized controlled trial of 1500 patients having total hip or knee replacement surgery at Barnes-Jewish Hospital. By studying this high- risk population and screening for asymptomatic deep venous thrombosis by Doppler ultrasound post-operatively, the proposed trial will be appropriately powered to elucidate two novel strategies to prevent VTE. The researchers will use a 2 x 2 factorial design to randomize patients to: (1) pharmacogenetic vs. clinical dosing of warfarin; and (2) to a target INR of 2.5 vs. < 2.0. The proposal has two specific aims: Aim 1: To determine how pharmacogenetic-based warfarin therapy affects risk of non-fatal VTE, non-fatal major hemorrhage, and vascular death. Although the FDA has approved genetic testing for variants that affect warfarin dose, no prior (or planned) trial has been powered to determine whether this strategy affects outcomes. Aim 2: To determine whether warfarin therapy with a target INR of < 2.0 is non-inferior to a target INR of 2.5 at preventing VTE in orthopedic patients. Although the American College of Chest Physician (ACCP) recommends a target INR of 2.5, the AAOS recommends < 2.0 and these conflicting goals have never been compared in a trial of primary VTE prevention.