CLOSURE DEVICE FOR TRANSCAVAL ACCESS TO THE ABDOMINAL AORTA

用于经腔进入腹主动脉的闭合装置

• 批准号: 9980469
• 负责人: Nasser Rafiee
• 金额: $ 99.63万
• 依托单位: TRANSMURAL SYSTEMS, LLC
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-06-01 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9980469
• 关键词: Acute; Adopted; Affect; Age; Animals; Aortic Valve Stenosis; Apical; Arteries; Asia; Award; Axilla; Blood Vessels; Cardiac; Cardiac Surgery procedures; Cardiology; Chronic; Clinical; Clinical Protocols; Clinical Trials; Collaborations; Conduct Clinical Trials; Consensus; Contracts; Development; Device Designs; Devices; Diagnosis; Disease; Duct (organ) structure; Elderly; Engineering; Family suidae; Feasibility Studies; Feedback; Goals; Gold; Heart Valve Diseases; Hemorrhage; Hemostatic function; Hospitals; Individual; Inferior vena cava structure; Institutes; Investigation; Label; Length of Stay; Letters; Life; Mind; Modeling; Modification; Morbidity - disease rate; National Heart, Lung, and Blood Institute; Operative Surgical Procedures; Patients; Permeability; Phase; Physicians; Positioning Attribute; Prevalence; Procedures; Protocols documentation; Quality of life; Research; Route; Running; Safety; Savings; Site; Small Business Innovation Research Grant; Surgeon; Surgical Valves; Survival Rate; System; Techniques; Testing; Thinking; Time; United States Food and Drug Administration; Validation; Woman; abdominal aorta; aged; aortic valve replacement; base; cardiovascular disorder therapy; commercialization; comorbidity; design; experience; experimental study; femoral artery; first-in-human; high risk; improved; in vivo; innovation; iterative design; men; mortality; nitinol; novel; off-label use; pre-clinical; repaired; risk minimization; standard care; standard of care; surgical risk; verification and validation

Project Summary Aortic stenosis (AS) is a common and lethal cardiac valve disease with an average survival time of only 2 – 3 years after diagnosis if no treatment is obtained. The standard of care for moderate to severe cases of symptomatic AS is surgical valve repair or replacement, which can necessitate open heart surgery. This “gold standard” of care is plagued by substantial limitations, including high morbidity and mortality in the elderly (the most common patient), and an alarmingly high percentage of patients who cannot undergo surgery (estimated at 40 – 50% of patients with severe symptomatic AS). Transcatheter aortic valve replacement (TAVR) has been widely adopted to treat patients at intermediate or high risk of complications from conventional surgical aortic valve replacement. The standard vascular access for TAVR is through the femoral arteries ("trans-femoral"), but between 8-12% of patients in the USA are not eligible for trans-femoral TAVR because their iliofemoral arteries are too small or too diseased. Dr. Robert J. Lederman has pioneered innovative transcaval access to the abdominal aorta from the adjoining inferior vena cava, to provide a fully percutaneous technique for TAVR in patients without good access options. However, the procedures have used permeable nitinol duct occluder devices off-label, which, despite making the procedure possible, are associated with significant bleeding complications and procedural difficulty. There is no device on the market that is built to specifically overcome these limitations in off-label use of nitinol occluders. The recognition of this deficient in the market led the NHLBI to enter into a direct-to-Phase II contract with Transmural Systems LLC. In Phase II, Transmural has pioneered a purpose-built Transcaval Closure Device (TCD) that will minimize risks associated with this innovative transcaval TAVR procedure. The TCD has undergone iterative design development, leading to the creation of a mature device with demonstrated excellence in safety and efficacy in bench model tests and in acute and chronic animal studies. In this Phase IIB, Transmural is prepared to advance its mature TCD to a true clinical setting with support of Dr. Robert Lederman, Dr. Adam Greenbaum, Dr. Vasilis Babaliaros and Dr. Toby Rogers. To assess the safety and efficacy of the TCD, Transmural Systems will conduct an Early Feasibility Study (EFS) clinical trial (Aim 1) that will inform any necessary product modification before conductance of a Pivotal clinical trial (Aim 2). The EFS will occur at three forward-thinking cardiology institutes in the US by surgeons who specialize in transcaval-access TAVR. The Pivotal study will expand to include the 20 sites from Dr. Robert J. Lederman’s transcaval clinical trial of off-label use occluders. Successful completion of the proposed clinical trials will poise Transmural Systems to market a purpose-built device to treat AS, simplifying the closure procedure and enabling the application of the transcaval technique to a wider range of patients ineligible for trans-femoral access.

项目摘要 主动脉狭窄（AS）是一种常见且致命的心脏瓣膜疾病，平均生存时间仅为2 - 诊断后3年，如果没有获得治疗。中度至重度病例的护理标准 有症状的手术瓣膜修复或置换，这必然可以打开心脏手术。这个“黄金 护理的标准”受到重大​​局限性的困扰，包括较早的发病率和死亡率（ 最常见的患者），并且无法接受手术的患者比例令人震惊（估计） 在40％至50％的严重症状患者中）。 经导管主动脉瓣置换（TAVR）已被广泛采用，以治疗中级或 常规手术主动脉瓣更换的高风险。标准血管通道 TAVR通过股动脉（“跨妇女”），但美国8-12％的患者不合格 对于跨女性tavr而言，因为它们的股毛动脉太小或太病了。 罗伯特·J·莱德曼（Robert J. 毗邻下腔静脉，为TAVR提供完全经皮的技术 选项。但是，这些程序已使用可渗透的硝基醇管封闭式设备，该设备在标签之外，该设备要求 使程序成为可能，与严重的出血并发症和程序上的困难有关。 市场上没有构建的设备可以专门克服标签外使用这些限制 奈蒂醇阻塞。对市场不足的认识导致NHLBI进入直接阶段II 与透壁系统有限责任公司合同。在第二阶段，透壁启动了专门建造的经诊所 闭合设备（TCD）将最大程度地减少与此创新的Transcaval TAVR程序相关的风险。 TCD经历了迭代设计开发，导致创建一个成熟的设备，并证明 基准模型测试以及急性和慢性动物研究的安全性和效率卓越。 在此阶段IIB中，透壁准备将其成熟的TCD推向真正的临床环境 Robert Lederman博士，Adam Greenbaum博士，Vasilis Babaliaros博士和Toby Rogers博士。评估安全性 TCD的便利性，透壁系统将进行早期可行性研究（EFS）临床试验（AIM 1）将在电导临床试验之前通知任何必要的产品修改（AIM 2）。 EFS将在美国的外科医生在美国的三个前瞻性心脏病学上发生 transcaval-access tavr。关键研究将扩展到包括Robert J. Lederman博士的20个地点 标签外使用阻塞器的跨诊所临床试验。成功完成拟议的临床试验将毒化 跨壁系统销售专门建造的设备，以简化封闭过程并启用 跨诊断技术应用于不符合跨妇女通道的更广泛范围的患者。