CLOSURE DEVICE FOR TRANSCAVAL ACCESS TO THE ABDOMINAL AORTA

项目摘要 主动脉瓣狭窄(AS)是一种常见的致命性心脏瓣膜疾病，平均生存时间仅为2天。 如果没有得到治疗，则在诊断后3年。对中到重度病例的护理标准 有症状的是外科瓣膜修复或替换，这可能需要进行心脏直视手术。这是“黄金” 标准护理受到实质性限制的困扰，包括老年人的高发病率和死亡率( 最常见的患者)，以及不能接受手术的患者比例高得惊人(估计 在有严重症状的AS患者中有40%-50%)。 经导管主动脉瓣置换术(TAVR)已被广泛应用于治疗中老年患者 传统外科主动脉瓣置换术并发症风险高。标准的血管通路 TAVR是通过股动脉(“经股”)进行的，但在美国有8%-12%的患者不符合条件 对于经股动脉TAVR，因为他们的髂股动脉太小或太多病变。 罗伯特·J·莱德曼博士开创了从腹主动脉经下腔静脉进入腹主动脉的创新途径。 与下腔静脉毗邻，为没有良好通路的患者提供一种完全经皮TAVR的技术 选择。然而，该程序使用了标签外的透气性镍钛合金导管封堵器，尽管 使手术成为可能，都与严重的出血并发症和手术困难有关。 市场上没有专门为克服标签外使用这些限制而设计的设备 镍钛合金封堵器。认识到这一市场缺陷的NHLBI进入了直接到第二阶段 与TransmWall Systems LLC签订合同。在第二阶段，TransWall率先推出了一款专门建造的TransCaval 闭合装置(TCD)，将最大限度地减少与这种创新的跨腔静脉TAVR手术相关的风险。这个 TCD经历了迭代的设计开发，导致创建了一个成熟的设备，并展示了 在台架模型试验以及急性和慢性动物研究中表现出卓越的安全性和有效性。 在这个IIB阶段，TransWall准备在以下支持下将其成熟的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。以评估其安全性 和TCD的有效性，跨壁系统将进行早期可行性研究(EFS)临床试验(AIM 1)这将在关键临床试验(目标2)导通之前通知任何必要的产品修改。 EFS将在美国的三个具有前瞻性的心脏病研究所由专门从事 经下腔静脉入路TAVR这项关键的研究将扩大到包括罗伯特·J·莱德曼博士的20个地点 非标签式封堵器的跨腔静脉临床试验。成功完成拟议的临床试验将保持平衡 TransWall Systems将推出一种专门设计的设备来治疗AS，从而简化关闭程序并使 将经下腔静脉技术应用于更多不符合经股动脉入路条件的患者。

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.