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 主动脉瓣狭窄（AS）是一种常见的致死性心脏瓣膜疾病，平均生存时间仅为2 - 确诊后3年，如果未接受治疗。中度至重度病例的护理标准 症状性AS是外科瓣膜修复或置换，这可能需要心脏直视手术。这个“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），以及无法接受手术的患者比例高得惊人（估计 40 - 50%的重度症状性AS患者）。 经导管主动脉瓣置换术（TAVR）已被广泛用于治疗中度或重度患者。 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（“经股动脉”），但美国有8-12%的患者不符合条件 因为髂股动脉太小或病变太严重。 Robert J. Lederman博士开创了创新性的经腔静脉进入腹主动脉， 毗邻下腔静脉，为无良好入路的患者提供完全经皮TAVR技术 选项.然而，这些手术使用了标签外的可渗透镍钛合金导管封堵器，尽管 使手术成为可能，与严重的出血并发症和手术困难有关。 市场上没有专门克服标签外使用这些限制的器械 镍钛合金封堵器。认识到这一不足的市场导致NHLBI进入直接到第二阶段 联系我们联系我们在第二阶段，Astruural率先推出了一种专门建造的Transcaval 闭合装置（TCD）将最大限度地降低与这种创新性经腔TAVR手术相关的风险。的 TCD经过反复的设计开发，最终形成了一种成熟的器械， 在实验室模型试验以及急性和慢性动物研究中具有卓越的安全性和有效性。 在这个IIB期研究中，Aureural准备在以下支持下将其成熟的TCD推向真正的临床环境： 博士罗伯特·莱德曼，亚当·格林鲍姆博士，瓦西里斯·巴巴利亚罗斯博士和托比·罗杰斯博士。及其安全 和有效性的TCD，脑电系统将进行早期可行性研究（EFS）的临床试验（目的 1)这将通知任何必要的产品修改之前进行的初步临床试验（目标2）。 EFS将在美国三个前瞻性心脏病研究所进行，由专门从事以下方面的外科医生进行： 经腔静脉TAVR。这项研究将扩大到包括罗伯特·J·莱德曼博士的20个研究中心。 超说明书使用封堵器的经腔静脉临床试验。成功完成拟议的临床试验将平衡 医疗系统公司将销售一种专门用于治疗AS的设备，简化了闭合程序， 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。