BEST-CLI Trial-DCC

BEST-CLI 试用-DCC

基本信息

批准号：
8371073
负责人：
SUSAN FERA ASSMANN
金额：
$ 122.89万
依托单位：
NEW ENGLAND RESEARCH INSTITUTES, INC.
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-09-17 至 2018-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8371073
关键词：
Abbreviations Academic Medical Centers Accounting Address Aging Am 80 Amputation Ankle Annual Reports Area Atherosclerosis Blood Vessels Boston Bypass Canada Cardiology Case Report Form Clinical Clinical Data Clinical Trials Clinical Trials Design Code Collaborations Communities Conflict of Interest Consent Forms Contracts Cost Effectiveness Analysis Data Data Coordinating Center Databases Diabetes Mellitus Disease Disease-Free Survival Documentation Enrollment Ensure Equipoise Event General Hospitals Healed Hospitals Institutional Review Boards Intervention Interventional radiology Ischemia Leadership Leg Ulcer Limb structure Living Costs Maintenance Manuals Manuscripts Massachusetts Medicine Monitor New England North America Notification Operative Surgical Procedures Pain Pain in lower limb Participant Patients Pattern Peripheral arterial disease Platelet Factor 4 Population Preparation Prevalence Prosthesis Protocols documentation Qualifying Quality of life Randomized Recruitment Activity Reporting Research Research Institute Research Personnel Rest Safety Site Smoker Surgeon Surveys System Target Populations Techniques Testing Thrombectomy Time Tissues Training Validation Veins Venous Woman Work abstracting base cohort comparative effectiveness cost cost effective cost effectiveness data management design diabetic effectiveness trial experience follow-up functional status hazard healing health economics indexing innovation instrument limb amputation meetings mortality novel operation payment prevent programs public health relevance radiologist randomized trial response thrombolysis web site

项目摘要

DESCRIPTION (provided by applicant): This resubmission is comprised of three applications (Clinical and Data Coordinating Centers (CCC, DCC) and Cost-Effectiveness Analysis Core). We propose to conduct a large (N=2100) simple, superiority trial in the US and Canada - BEST - comparing best open surgery to best endovascular revascularization to prevent mortality, limb-amputation or further revascularization in a target limb with critical limb ischemia (CLI), meeting the current mandate for assessing comparative effectiveness. Trial leadership is comprised of a closely integrated and highly experienced group of investigators based at a CCC (Brigham and Women's Hospital, BWH , Boston University Medical Center, BUMC, and Massachusetts Hospital, MGH, Boston, MA), a DCC (New England Research Institutes, Inc., Watertown, MA) and an Executive Committee of experts in the field. The Health Economics Group at BWH will work closely with the DCC to address assessment of quality of life and cost-effectiveness (C-E). The trial will be conducted at approximately 120 sites in the U.S. and Canada, builds upon prior feasibility data and endeavors to address limitations of current research in this area. Peripheral artery disease prevalence is 15-20% over 70 years, with higher rates in smokers and diabetics. In the subset with CLI, 40% require limb amputation and annual mortality exceeds 20%. With the advent of endovascular techniques for revascularization, we demonstrate from our completed surveys that there is current equipoise among practitioners with respect to best therapy in the majority of CLI cases. The BEST trial will provide, for the first time, urgently needed clinical guidance for CLI management in the context of C-E by using: a pragmatic design, including a range of established techniques; a novel primary endpoint - MALE (major adverse limb event including limb amputation or major re-intervention, bypass graft/graft revision or thrombectomy/thrombolysis) - free survival; multi-disciplinary recruitment of vascular surgeons and interventional cardiologists and radiologists; and an innovative, cost-efficient C-E approach. Additional endpoints include other clinical event rates, functional status and QOL and C-E, all using standard definitions and instruments. 140 eligible centers in North America will be approached to ensure 120 are initiated and 80 sites each recruit 1 subject/month over 27 months accrual. Trial duration is 4.25 yrs - 2.25 yrs accrual and 2.0 yrs minimum follow-up. Two cohorts will be studied: All-Vein (N=1620) and Prosthetic Conduit (N=480). Within each cohort, the trial is stratified on 2 factors (4 strata): tissue loss vs. isolated rest pain and infrainguinl with/without significant infrapopliteal occlusive disease. In the All-Vein cohort, BEST has 85% power to detect an EVT vs. OPEN hazard ratio of 1.25 in the primary endpoint (MALE-free survival) with crossover rates accounted for, as well as 2% loss to follow-up. In the Prosthetic Conduit cohort, there is 80% power to detect a hazard ratio of 0.70 for the primary endpoint. This resubmission fully addresses all prior reviewer concerns, to successfully and efficiently execute a trial that will provide important information for the CLI community. PUBLIC HEALTH RELEVANCE: With the aging of the US population and increasing diabetes, there is an increase in ischemic leg pain and open leg ulcers, frequently requiring amputation. The results of the BEST trial (including 2,100 participants in North America) will provide clinical guidance on the most cost-effective ways to reduce leg pain, heal leg ulcers and prevent disabling amputation, by testing a range of surgical and endovascular techniques. (End of Abstract)

描述（由申请人提供）：此次重新提交由三个申请组成（临床和数据协调中心（CCC、DCC）和成本效益分析核心）。我们建议在美国和加拿大进行一项大型（N=2100）简单、优越性试验 - BEST - 比较最佳开放手术与最佳血管内血运重建术，以预防严重肢体缺血的目标肢体的死亡、截肢或进一步血运重建（ CLI），满足当前评估比较有效性的任务。试验领导层由紧密结合且经验丰富的研究人员小组组成，他们分别来自 CCC（Brigham 妇女医院、BWH、波士顿大学医学中心、BUMC 和马萨诸塞州医院、MGH，马萨诸塞州波士顿）、DCC（新英格兰研究中心） Institutes, Inc.（马萨诸塞州沃特敦）和该领域专家执行委员会。 BWH 的健康经济学小组将与 DCC 密切合作，对生活质量和成本效益 (C-E) 进行评估。该试验将在美国和加拿大约 120 个地点进行，以先前的可行性数据为基础，并努力解决该领域当前研究的局限性。 70 年间，外周动脉疾病的患病率为 15-20%，其中吸烟者和糖尿病患者的患病率更高。在患有 CLI 的子集中，40% 需要截肢，年死亡率超过 20%。随着血管内血运重建技术的出现，我们从已完成的调查中证明，目前从业者对于大多数 CLI 病例的最佳治疗方法持均衡态度。 BEST 试验将首次为 C-E 背景下的 CLI 管理提供急需的临床指导，方法是：务实的设计，包括一系列已建立的技术；新的主要终点 - MALE（主要不良肢体事件，包括肢体截肢或重大再干预、旁路移植/移植翻修或血栓切除术/溶栓）-无生存期；多学科招募血管外科医生、介入心脏病专家和放射科医生；以及创新的、具有成本效益的 C-E 方法。其他终点包括其他临床事件发生率、功能状态以及 QOL 和 C-E，所有这些都使用标准定义和工具。将联系北美 140 个符合条件的中心，以确保启动 120 个中心，并且每个中心 80 个中心在 27 个月的时间内每月招募 1 名受试者。试验期限为 4.25 年 - 累积期 2.25 年，最短随访期 2.0 年。将研究两个队列：全静脉 (N=1620) 和假体导管 (N=480)。在每个队列中，试验根据 2 个因素（4 个层次）进行分层：组织损失与孤立性静息痛以及有/无明显腘下闭塞性疾病的腹股沟下痛。在全静脉队列中，BEST 在主要终点（无 MALE 生存）中检测 EVT 与 OPEN 风险比为 1.25 的功效为 85%（考虑交叉率），以及 2% 的失访率。在假体导管队列中，有 80% 的功效检测到主要终点的风险比为 0.70。这次重新提交完全解决了之前审稿人的所有担忧，成功有效地执行了将为 CLI 社区提供重要信息的试验。公共卫生相关性：随着美国人口的老龄化和糖尿病的增加，缺血性腿部疼痛和开放性腿部溃疡的情况有所增加，经常需要截肢。 BEST 试验（包括北美 2,100 名参与者）的结果将通过测试一系列手术和血管内技术，为减轻腿部疼痛、治愈腿部溃疡和防止致残性截肢的最具成本效益的方法提供临床指导。（摘要完）