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

华法林预防 DVT 的遗传学-信息学试验（礼物）

• 批准号: 7699646
• 负责人: BRIAN F GAGE
• 金额: $ 74.86万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-10 至 2014-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7699646
• 关键词: 18 year old; Academic Medical Centers; Academy; Adverse event; Affect; Algorithms; American; American College of Physicians; Anticoagulant therapy; Anticoagulants; Anticoagulation; Area; Blood Clot; Blood Vessels; Blood coagulation; Caring; Cessation of life; Chest; Clinical; Coagulation Process; Conflict (Psychology); Deep Vein Thrombosis; Disease; Doppler Ultrasound; Dose; Effectiveness; Enrollment; Event; FDA approved; Genes; Genetic; Genetic Polymorphism; Genetic screening method; Genotype; Goals; Grant; Guidelines; Health; Healthcare; Hemorrhage; Hip region structure; Hospitals; Human; Inferior; Informatics; International Normalized Ratio; Internet; Intervention; Label; Measures; Medicine; Meta-Analysis; Metabolism; Operative Surgical Procedures; Orthopedics; Outcome; Participant; Patients; Personal Genetic Information; Persons; Pharmaceutical Preparations; Pharmacogenetics; Phase III Clinical Trials; Physicians; Pilot Projects; Population; Population Heterogeneity; Prevention; Prophylactic treatment; Protocols documentation; Publishing; Pulmonary Embolism; Randomized; Randomized Controlled Clinical Trials; Randomized Controlled Trials; Recommendation; Recurrence; Relative (related person); Replacement Arthroplasty; Research Personnel; Risk; Safety; Sample Size; Screening procedure; Services; Study Section; Surgeon; Testing; Therapeutic; Thromboembolism; Time; United States; Universities; Variant; Venous; Vitamin K; Warfarin; Warfarin Sodium; Washington; Wood material; Writing; base; college; design; falls; follower of religion Jewish; high risk; improved; knee replacement arthroplasty; novel strategies; prevent; public health relevance

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: On September 15, 2008, Acting Surgeon General Steven Galson, MD, MPH noted that blood clots (deep venous thrombosis and pulmonary embolism) contribute to the death of at least 100,000 Americans each year. Because many of these deaths occur suddenly where treatment is impossible, the best treatment is prevention. In this grant, Washington University researchers develop strategies to improve the safety and effectiveness of clot prevention by customizing blood thinners to each person's genetic and clinical profile.

描述（由申请人提供）：2008年9月15日，代理外科医生Steven Galson（医学博士、公共卫生硕士）指出，静脉血栓栓塞事件（VTE）每年导致至少10万美国人死亡。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通过使用非营利网络应用程序（www.WarfarinDosing.org）来测试提高VTE预防的安全性和有效性的策略，以根据每个人的药物遗传学和/或临床特征定制华法林的剂量。他们还建议测试美国骨科医生学会（AAOS）关于使用低水平抗凝剂的建议（即，目标国际标准化比率（INR）< 2.0）用于骨科患者的VTE预防。因此，华法林预防DVT的遗传学信息学试验（GIFT）的总体目标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提出了一项随机对照试验，1500例患者在巴恩斯犹太医院接受全髋关节或膝关节置换手术。通过研究该高危人群并在术后通过多普勒超声筛查无症状深静脉血栓形成，拟定试验将具有适当的把握度，以阐明预防VTE的两种新策略。研究人员将使用2 × 2析因设计将患者随机分为：（1）华法林的药物遗传学与临床剂量;（2）目标INR为2.5与< 2.0。该提案有两个具体目标：目标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的风险。尽管FDA已经批准了对影响华法林剂量的变异进行基因检测，但没有先前（或计划中）的试验能够确定这种策略是否会影响结果。目标二：确定目标INR < 2.0的华法林治疗在预防骨科患者VTE方面是否非劣效于目标INR 2.5。尽管美国胸科医师学会（ACCP）建议INR目标值为2.5，但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。公共卫生相关性：2008年9月15日，代理外科医生Steven Galson，医学博士，公共卫生硕士指出，血栓（深静脉血栓形成和肺栓塞）每年导致至少10万美国人死亡。由于许多死亡是突然发生的，无法治疗，因此最好的治疗方法是预防。在这项资助中，华盛顿大学的研究人员开发了一种策略，通过根据每个人的遗传和临床特征定制血液稀释剂来提高血栓预防的安全性和有效性。