1/2 IMPRoving Outcomes in Vascular DisEase - Aortic Dissection (IMPROVE-AD)

本申请包括两项申请(临床和统计数据协调中心)。我们建议 在美国进行一项大型(N=1,100)、简单、务实、优势的试验-改善-AD-比较 内科治疗(MT)加胸主动脉腔内修补术(TEVAR)对内科治疗加胸主动脉腔内修复术的影响 无并发症的B型主动脉夹层患者病情恶化的监测。监视将会 包括临床显示TEVAR和/或在指标住院期间因恶化而实施的开放修复 或者跟进。这是第一次进行这种规模的试验，旨在建立关于uTBAD管理的指导方针。这场审判 领导层由临床协调中心(CCC；Duke)的一组经验丰富的调查人员组成 临床研究所，北卡罗来纳州达勒姆，贝勒医学院，休斯顿，德克萨斯州，和华盛顿大学 华盛顿州西雅图华盛顿)统计和数据协调中心(SDCC；杜克临床研究所， 北卡罗来纳州达勒姆)和代表临床医生的该领域多样化的执行和指导专家委员会， 试验者和耐心倡导者。主动脉夹层(AD)是涉及主动脉的最常见的致命事件。 在美国，每年每百万人口中就有5到30个病例发生，导致12,000人死亡。B型主动脉 夹层涉及整个降主动脉。根据20世纪60年代的证据，主要战略是 UTBAD是一种终身监测的医学疗法。事实证明，这一战略的长期效果很差。 25%-50%的患者的预后(与主动脉相关的事件)。TEVAR作为一种侵入性较小的替代方案的出现 然而，开放修复导致了关于使用预先TEVAR治疗uTBAD的争论。飞行员 相反，欧洲试验(改为)在140名患者中比较了预先使用TEVAR和最佳药物治疗的结果 UTBAD患者。尽管对全因死亡率的控制力度明显不足，但研究结果以及 观察数据表明，药物治疗加预先TEVAR可能与ALL-ALL- 原因和与主动脉相关的死亡率。我们还从我们完成的调查中证明，有 在utbad最适当的治疗策略方面，从业者之间保持平衡。我们建议 一项具有集中化、电话跟踪、远程血压监测的务实试验，具有临床相关性 分级主要终点(死亡率/与主动脉相关的住院)和多学科团队 调查人员和患者权益倡导者。试用期为84个月，启动5个月。平均随访率 四年，最低为2.5年，提前入学的最长为6年。改进-AD将 有88%的能力检测到患者主要终点的发生率相对降低25% 随机接受预先MT加TEVAR，与MT加监测病情恶化相比，假设为5年 MT中20%的死亡和20%的与主动脉相关的住院的累积发生率加上对 恶化的手臂。

This submission comprises two applications (Clinical and Statistical Data Coordinating Centers). We propose to conduct a large (N=1,100), simple, pragmatic, superiority trial in the US - IMPROVE-AD – comparing a strategy of medical therapy (MT) plus upfront thoracic endovascular aortic repair (TEVAR) to MT plus surveillance for deterioration in patients with uncomplicated type B aortic dissection (uTBAD). Surveillance will include clinically indicated TEVAR and/or open repair performed for deterioration during index hospitalization or follow up. This is the first trial of this size designed to establish guidance on uTBAD management. The trial leadership is comprised of an experienced group of investigators in a Clinical Coordination Center (CCC; Duke Clinical Research Institute, Durham, NC, Baylor College of Medicine, Houston, TX, and University of Washington, Seattle, WA) a Statistical and Data Coordination Center (SDCC; Duke Clinical Research Institute, Durham, NC) and a diverse, Executive and Steering Committee of experts in the field representing clinicians, trialists, and patient advocates. Aortic dissection (AD) is the most common fatal event involving the aorta occurring in 5 to 30 cases per million of population resulting in 12,000 deaths in the US annually. Type B aortic dissections involve the entire descending aorta. Based on evidence from the 1960s, the main strategy for uTBAD is medical therapy with lifelong surveillance. This strategy has been shown to have poor long-term outcome in 25-50% of patients (aortic related events). The emergence of TEVAR as a less invasive alternative to open repair, however, has resulted in debate over the use of upfront TEVAR to treat uTBAD. A pilot European trial (INSTEAD) compared the outcomes of upfront TEVAR to optimal medical therapy in 140 patients with uTBAD. Despite being significantly underpowered for all-cause mortality, the findings, along with observational data suggest that medical therapy plus upfront TEVAR may be associated with decreased all- cause and aortic-related mortality. We have also demonstrated from our completed surveys that there is equipoise among practitioners with respect to the most appropriate treatment strategy in uTBAD. We propose a pragmatic trial with centralized, telephone follow-up, remote blood pressure monitoring, a clinically relevant hierarchical primary endpoint (mortality / aortic-related hospitalization), and multi-disciplinary teams of investigators and patient advocates. The trial duration is 84 months with 5-month start-up. Average follow-up is 4 year with a minimum of 2.5 years and maximum of 6 years for individuals enrolled early. IMPROVE-AD will have 88% power to detect a 25% relative reduction in the incidence of the primary endpoint for patients randomized to upfront MT plus TEVAR compared to MT plus surveillance for deterioration, assuming a 5 year cumulative incidence of 20% death and 20% aortic-related hospitalization in the MT plus surveillance for deterioration arm.