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

2008年9月15日，代理卫生局局长史蒂文·加尔森指出， 静脉血栓栓塞症(VTE)导致至少10万美国人死亡 每年。因为其中许多死亡发生得很突然，所以最好的管理方法是预防。 在这项随机对照试验中，华盛顿大学的研究人员将测试 通过使用非营利性Web应用程序提高VTE预防的安全性和有效性 (www.WarfarinDosing.org)为每个人量身定做华法林的剂量 和/或临床资料。他们还提议测试美国科学院的建议 整形外科医生(AAOS)使用低水平抗凝(即目标国际 骨科患者预防VTE的归一化比(INR)和2.0。因此，总体上， 华法林预防DVT的遗传学-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。 华盛顿大学研究人员提议对1500名患者进行随机对照试验 在巴恩斯犹太医院接受全髋关节或膝关节置换手术。通过研究这种高- 多普勒超声对无症状深静脉血栓形成的危险人群及筛查 在手术后，拟议的试验将被适当地授权来阐明两部小说 预防VTE的策略。研究人员将使用2x2析因设计来随机化 患者：(1)华法林的药物遗传学剂量与临床剂量；以及(2)目标INR为2.5vs. &lt；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心脏病的风险 静脉血栓、非致命性大出血和血管死亡。尽管FDA已经批准了转基因 测试影响华法林剂量的变种，没有事先(或计划的)试验支持 确定此策略是否会影响结果。 目的2：确定目标INR为2.0的华法林治疗是否不逊于 目标INR为2.5，用于预防骨科患者的VTE。尽管美国大学 胸科医生(ACCP)建议目标INR为2.5，AAOS建议为2.0和 这些相互冲突的目标从未在初级VTE预防试验中进行过比较。

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.