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.

本次提交包括两项申请（临床和统计数据协调中心）。我们提出 在美国进行一项大型（N= 1，100）、简单、实用的优效性试验- IMPROVE-AD -比较 药物治疗（MT）+胸主动脉腔内修复术（TEVAR）到MT+的策略 监测无并发症B型主动脉夹层（uTBAD）患者的恶化情况。监控将 包括临床指征TEVAR和/或在首次住院期间因恶化而进行的开放性修复 或者跟进这是第一个这种规模的试验，旨在建立对uTBAD管理的指导。审判 领导层由临床协调中心（CCC;杜克）的一组经验丰富的研究人员组成 临床研究所，达勒姆，北卡罗来纳州，贝勒医学院，休斯顿，得克萨斯州，和大学 华盛顿，西雅图，WA）统计和数据协调中心（SDCC;杜克临床研究所， 达勒姆，北卡罗来纳州）和一个多元化的，执行和指导委员会的专家在该领域代表临床医生， 试验者和病人的拥护者主动脉夹层（AD）是累及主动脉的最常见致死性事件 每百万人口中发生5至30例病例，导致美国每年有12，000人死亡。主动脉B型 夹层涉及整个降主动脉。根据20世纪60年代的证据， uTBAD是终身监测的医学治疗。这一战略已被证明具有不良的长期 25-50%的患者结局（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，开放性修复导致了关于使用前期TEVAR治疗uTBAD的争论。一个试点 欧洲试验（INSTEAD）在140例患者中比较了前期TEVAR与最佳药物治疗的结局 uTBAD患者尽管对全因死亡率的影响明显不足，但研究结果沿着 观察数据表明，药物治疗加预先TEVAR可能与降低所有- 原因和与疾病相关的死亡率。我们已完成的调查亦显示， 在uTBAD中最合适的治疗策略方面，医生之间的平衡。我们提出 一项集中、电话随访、远程血压监测的实用试验，一项临床相关试验， 分层主要终点（死亡率/与死亡相关的住院治疗），以及多学科团队， 研究人员和病人的拥护者。试验期为84个月，启动期为5个月。平均随访 最短为2.5年，最长为6年。改进-AD将 有88%的把握度检测到患者主要终点发生率相对降低25% 随机分配至前期MT + TEVAR组，与MT+恶化监测组相比，假设5年 MT中20%死亡和20%与药物相关的住院的累积发生率加上监测 恶化手臂