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.

项目概要 主动脉瓣狭窄 (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 – 如果未获得治疗，诊断后 3 年 中度至重度病例的护理标准。 有症状的 AS 是外科瓣膜修复或置换，这可能需要进行心脏直视手术。 “标准”护理受到重大限制的困扰，包括老年人的高发病率和死亡率（ 最常见的患者），以及无法接受手术的患者比例高得惊人（估计 40-50% 的患有严重症状的 AS 患者）。 经导管主动脉瓣置换术（TAVR）已被广泛应用于治疗中度或以上患者 传统主动脉瓣置换术的标准血管通路存在较高的并发症风险。 TAVR 是通过股动脉（“经股动脉”）进行的，但美国有 8-12% 的患者不符合资格 对于经股动脉 TAVR，因为他们的髂股动脉太小或病变太严重。 Robert J. Lederman 博士开创了从腹腔经腔静脉进入腹主动脉的创新方法 毗邻下腔静脉，为没有良好通路的患者提供完全经皮 TAVR 技术 然而，该程序使用了标签外的可渗透性镍钛诺导管封堵器装置，尽管如此。 使手术成为可能，与严重的出血并发症和手术难度有关。 市场上没有任何设备可以专门克服标签外使用的这些限制 镍钛合金封堵器认识到市场的这一缺陷，导致 NHLBI 进入直接进入第二阶段。 与 Transmural Systems LLC 签订合同 在第二阶段，Transmural 率先推出了专门设计的 Transcaval。 闭合装置 (TCD) 可最大限度地降低与这种创新的经腔 TAVR 手术相关的风险。 TCD经历了迭代设计开发，最终创建了一个成熟的设备，并经过验证 在台架模型测试以及急性和慢性动物研究中具有卓越的安全性和有效性。 在此 IIB 阶段，Transmural 准备在以下机构的支持下将其成熟的 TCD 推进到真正的临床环境： Robert Lederman 博士、Adam Greenbaum 博士、Vasilis Babaliaros 博士和 Toby Rogers 博士评估安全性。 和 TCD 的功效，Transmural Systems 将进行早期可行性研究 (EFS) 临床试验（目标 1) 将在进行关键临床试验（目标 2）之前通知任何必要的产品修改。 EFS 将在美国三个具有前瞻性思维的心脏病学机构举行，由专门从事以下领域的外科医生进行： Pivotal 研究将扩大到包括 Robert J. Lederman 博士的 20 个部位。 超适应症使用封堵器的经腔临床试验将成功完成拟议的临床试验。 Transmural Systems 将推出治疗 AS 的专用设备，简化闭合程序并实现 将经腔静脉技术应用于更广泛的不适合经股动脉入路的患者。