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

1/2 改善血管疾病的结果 - 主动脉夹层 (IMPROVE-AD)

• 批准号: 10663037
• 负责人: Panagiotis Kougias
• 金额: $ 152.84万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-21 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10663037
• 关键词: Abdominal Aortic Aneurysm; Acute; Address; Admission activity; Advocate; African American population; Ancillary Study; Aorta; Aortic Diseases; Aortic Rupture; Blood Pressure; Blood Pressure Monitors; Blood Vessels; Cessation of life; Chest; Clinical; Clinical Research; Clinical Trials; Cost Analysis; Creativeness; Data; Data Coordinating Center; Descending aorta; Deterioration; Dialysis procedure; Disease; Dissection; Elderly; Enrollment; Equipoise; European; Event; Fistula; Funding; Guidelines; Health; Hispanic; Hospital Costs; Hospital Mortality; Hospitalization; Hypertension; Image; Incidence; Individual; Industry; Injury; Intervention; Leadership; Medical; Medicine; Minority; Morbidity - disease rate; Multicenter Trials; Myocardial Infarction; National Heart, Lung, and Blood Institute; Operative Surgical Procedures; Organ; Outcome; Pain; Pain management; Paraparesis; Paraplegia; Participant; Patients; Population; Prevalence; Prevention; Quality of Life Assessment; Quality of life; Questionnaires; Randomized; Recommendation; Renal Replacement Therapy; Research Institute; Research Personnel; Risk; Safety; Spinal cord injury; Strategic vision; Stroke; Surveys; Syndrome; Telephone; Testing; Therapeutic; Time; Universities; Vascular Diseases; Washington; arm; clinically relevant; college; cost; cost effectiveness; design; experience; follow-up; gender disparity; health difference; hospital readmission; implementation research; improved; improved outcome; indexing; limb loss; mortality; multidisciplinary; patient oriented; pragmatic trial; primary endpoint; racial disparity; repaired; standard of care; treatment strategy

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.

此提交包括两个应用程序（临床和统计数据协调中心）。我们建议 在美国进行大型（n = 1,100），简单，务实，优越试验 - 改进 - 比较 医疗疗法策略（MT）加上前期胸腔内血管内主动脉修复（TEVAR）至MT Plus 监测将用于确定不复杂的B型主动脉夹层（UTBAD）患者。 包括临床指示的TEVAR和/或进行开放修复以确定指数住院期间 或跟进。这是旨在为UTBAD管理建立指导的第一次试验。试验 在临床协调中心（CCC; Duke）中，领导才能完成一群经验丰富的调查员。 北卡罗来纳州达勒姆市临床研究所，德克萨斯州休斯敦贝勒医学院和大学 华盛顿州西雅图的华盛顿）一个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（Durham））以及代表临床医生的现场专家的潜水员，执行和指导委员会， 审判者和患者拥护者。主动脉夹层（AD）是涉及主动脉的最常见致命事件 每年有5至30例人口中发生5至30例，每年在美国12,000例死亡。类型B主动脉 解剖涉及整个下降主动脉。根据1960年代的证据，主要策略 UTBAD是终身监测的医疗疗法。该策略已被证明长期很差 25-50％的患者（主动脉相关事件）的结果。 Tevar的出现是一种侵入性的替代品 但是，要开放维修，就使用前期Tevar来治疗UTBAD引起了争论。飞行员 欧洲试验（相反）将前期Tevar的结果与140的最佳药物疗法进行了比较 UTBAD患者。尽管全因死亡率大大不足，但这些发现以及 观察数据表明，医疗疗法加上前期Tevar可能与全能降低有关 原因和主动脉相关的死亡率。我们还从完成的调查中证明了 在UTBAD中最合适的治疗策略方面，从业者之间的平衡。我们建议 一项实用试验，包括集中的电话随访，远程血压监测，临床相关 分层初级终点（死亡 /主动脉相关住院）和多学科团队 调查人员和患者拥护者。试验持续时间为84个月，有5个月的初创企业。平均随访 为期4年，至少为2。5年，最高6年的个人及早入学。改进会 具有88％的功率可检测患者的主要终点事件的相对减少25％ 假设有5年 MT和监视的20％死亡和20％主动脉相关住院的累积事件 恶化臂。