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）：该重新提交由三个应用程序（临床和数据协调中心（CCC，DCC）和成本效益分析核心）组成。我们建议在美国和加拿大进行大型（n = 2100）的简单，优势试验 - 最佳 - 将最佳的开放手术与最佳血管内血运重建进行比较，以防止具有关键的肢体缺血（CLI）的目标肢体死亡率，肢体吸收或进一步的血运重建，并符合当前评估比较有效性的授权。试验领导者由CCC（BUMC BUMC的BRIGHAM and and Hospital，BWH，波士顿大学医学中心）和马萨诸塞州MGH，MGH，马萨诸塞州MGH，MGH（新英格兰研究机构，新英格兰研究机构，Inc。，MA）和该领域的执行委员会组成，由CCC（BRIGHAM and妇女医院，BWH，波士顿大学医学中心）和马萨诸塞州MGH，MGH，马萨诸塞州MGH，马萨诸塞州MGH，马萨诸塞州MGH）组成，由CCC（BRIGHAM and and Hospital，BWH，波士顿大学医学中心）和马萨诸塞州医院，马萨诸塞州，马萨诸塞州MGH）组成。 BWH的卫生经济学集团将与DCC紧密合作，以解决对生活质量和成本效益（C-E）的评估。该试验将在美国和加拿大的大约120个地点进行，基于先前的可行性数据，并努力解决该领域当前研究的局限性。在70年内，周围动脉疾病的患病率为15-20％，吸烟者和糖尿病患者率高。在带有CLI的子集中，40％需要肢体截肢，年死亡率超过20％。随着血管口血管内技术的出现，我们从完整的调查中证明，在大多数CLI病例中，从业人员目前在从业人员中有目前的设备。最好的试验将首次通过使用：务实设计（包括一系列既定技术）在C-E的背景下首次提供CLI管理的临床指南；一个新的主要终点 - 男性（包括肢体截肢或重新干预，旁路移植/移植物修订或血栓切除术/血栓分解）的男性（包括肢体截肢或重新干预） - 自由存活；血管外科医生和介入心脏病学家和放射科医生的多学科招募；以及一种创新，具有成本效益的C-E方法。其他终点包括其他使用标准定义和仪器，包括其他临床事件率，功能状态以及QOL和C-E。将接触北美140个合格的中心，以确保启动120个，并在27个月内应计为1个招募1个主题/月。试验持续时间为4.25年-2.25年应计和2.0年的最低随访。将研究两个队列：All-Vein（n = 1620）和假体导管（n = 480）。在每个队列中，对2个因素（4个层）进行了分层：组织损失与孤立的休息疼痛和非副州非脑闭塞性疾病的外静脉疼痛和非纹理性疼痛。在全静脉队列中，Best具有85％的功率，可在主要终点（无男性生存率）中检测到EVT与开放危险比为1.25，分频率占了2％的损失。在假肢导管队列中，有80％的功率可以检测主要终点的危险比为0.70。该重新提交完全解决了所有先前的审阅者的关注，以成功有效地执行将为CLI社区提供重要信息的试验。公共卫生相关性：随着美国人群的衰老和糖尿病的增加，缺血性腿部疼痛和开放腿溃疡会增加，经常需要截肢。最佳试验的结果（包括北美的2100名参与者）将通过测试一系列手术和血管内技术来提供最具成本效益的方法，以减轻腿部疼痛，治愈腿部溃疡和防止截肢的方式提供临床指导。（抽象的结尾）