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

2/2 血管疾病的改善结果 - 主动脉夹层 (IMPROVE-AD)

• 批准号: 10663555
• 负责人: Sean M O'Brien
• 金额: $ 82.05万
• 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 2030-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10663555
• 关键词: Abdominal Aortic Aneurysm; Acute; Address; Admission activity; Advocate; Ancillary Study; Aorta; Aortic Diseases; Aortic Rupture; Blood Pressure; Blood Pressure Monitors; Blood Vessels; Cessation of life; Chest; Clinical; Clinical Data; Clinical Research; Clinical Trials; Clinical Trials Data Monitoring Committees; Collaborations; Collection; Companions; Computers; Cost Analysis; Creativeness; Data; Data Collection; Data Coordinating Center; Data Reporting; Descending aorta; Deterioration; Dialysis procedure; Disease; Dissection; Electronics; Enrollment; Equipoise; European; Event; Fistula; Funding; Guidelines; Hospitalization; Hypertension; Image; Incidence; Individual; Industry; Injury; Intervention; Leadership; Medical; Medicine; Monitor; Morbidity - disease rate; Multicenter Trials; National Heart, Lung, and Blood Institute; Operative Surgical Procedures; Outcome; Pain management; Paraparesis; Paraplegia; Participant; Patients; Phase; Policies; Population; Preparation; Prevalence; Prevention; Procedures; Process; Publications; Qualifying; Quality Control; Quality of Life Assessment; Quality of life; Questionnaires; Randomized; Recommendation; Renal Replacement Therapy; Reporting; Research Design; Research Institute; Research Personnel; Safety; Site; Spinal cord injury; Statistical Data Interpretation; Strategic vision; Stroke; Surveys; Syndrome; System; Telephone; Testing; Therapeutic; Training; Universities; Vascular Diseases; Washington; Work; arm; clinically relevant; college; cost effectiveness; data integrity; data management; data sharing; design; electronic data; experience; follow-up; gender disparity; health difference; improved; improved outcome; indexing; mortality; multidisciplinary; patient oriented; pragmatic trial; primary endpoint; protocol development; racial disparity; repaired; standard of care; tool; 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.

本次提交包括两个应用程序（临床和统计数据协调中心）。 在美国进行一项大型（N=1,100）、简单、务实、优越性试验 - IMPROVE-AD – 比较 药物治疗（MT）加前期胸主动脉腔内修复术（TEVAR）策略改为 MT 加 对无并发症的 B 型主动脉夹层患者的病情恶化进行监测（uTBAD 监测）。 包括临床指示的 TEVAR 和/或因住院期间病情恶化而进行的开放式修复 这是此类规模的首次试验，旨在建立 uTBAD 管理指南。 领导层由临床协调中心（CCC；杜克大学）经验丰富的研究人员小组组成 北卡罗来纳州达勒姆临床研究所、德克萨斯州休斯顿贝勒医学院和德克萨斯大学 华盛顿州西雅图）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）以及由该领域专家组成的多元化执行和指导委员会，代表： 主动脉夹层（AD）是涉及主动脉的最常见的致命事件。 在美国，每百万人口中有 5 至 30 例发生，导致 12,000 人死亡。 根据 20 世纪 60 年代的证据，解剖涉及整个降主动脉。 uTBAD 是一种终身监测的药物治疗，这一策略已被证明长期效果不佳。 25-50% 患者的结果（主动脉相关事件） TEVAR 作为一种侵入性较小的替代方案的出现。 然而，开放式修复引发了关于使用前期 TEVAR 治疗 uTBAD A 试点的争论。 欧洲试验 (INSTEAD) 对 140 名患者进行了前期 TEVAR 与最佳药物治疗的结果进行了比较 尽管 uTBAD 患者的全因死亡率明显不足，但研究结果以及 观察数据表明，药物治疗加前期 TEVAR 可能与降低总体疗效有关。 我们还从已完成的调查中证明，存在与主动脉相关的死亡率。 我们建议从业者就 uTBAD 中最合适的治疗策略达成平衡。 一项务实的试验，包括集中、电话随访、远程血压监测、临床相关 分级主要终点（死亡率/主动脉相关住院治疗）和多学科团队 试验持续时间为 84 个月，平均随访时间为 5 个月。 提前注册的个人为期 4 年，最短 2.5 年，最长 6 年。 有 88% 的功效检测到患者主要终点的发生率相对降低 25% 随机分配至前期 MT 加 TEVAR 与 MT 加恶化监测进行比较（假设 5 年） MT 加监测中 20% 死亡和 20% 主动脉相关住院的累积发生率 恶化臂。