Novel Expandable Infusion Catheter for the Treatment of Acute Pulmonary Embolism

项目摘要-血栓公司已经开发出一种具有可扩展螺旋的血管内导管 一篮子输液肢体，以提高大血管导管定向溶栓(CDT)的疗效。 临床前研究表明通过巴希尔™给药重组组织型纤溶酶原激活剂(RtPA) 与不可膨胀的CDT装置相比，血管内导管(BEC)可以更大程度地减少血栓负担。 BEC的成功商业化有可能减少溶栓剂的剂量 用于大血管血栓形成的患者，缩短输液时间，并显著 与目前的CDT设备相比，改善了短期和长期结果。多达90万美国人 每年受到肺栓塞(PE)或深静脉血栓形成的影响。大血栓可突然产生 肺动脉(PA)阻塞，右心室(RV)衰竭，以及心血管衰竭。而当 CDT可降低RV/LV比值，改善RV功能。3目前的小口径导管可提供溶栓剂 仅对血栓的一小段横截面进行处理，并将其大小减少≤30%。我们预计BEC将会跑赢大盘 目前的CDT设备并通过三种机制改善患者预后：1)篮子的扩大创建了 血栓内的大通道，恢复血液流动；2)血栓溶解明显加速 渠道，增加暴露于注入的溶栓和内源性纤溶剂的表面积， 具有协同效应；4和3)该设备允许医疗团队测量PA压力和混合 静脉氧气监测溶栓情况，理想情况下可缩短溶栓时间/剂量，从而减少 在不牺牲疗效的情况下出现出血并发症。在临床前猪研究中，我们证明了1) 扩张BEC可以恢复血流，2)通过扩张篮子输注rtPA可以减少血栓体积。 仅4小时后80%，3)BEC未造成内皮损伤。FDA批准BEC用于 在清除供在PE中使用之前，需要对外周血管进行进一步的测试，因为 可伸缩篮子是一种可能影响安全性或有效性的创新。一项10例患者早期可行性研究 (EFS)正在进行中，在此我们建议一个直接转到第二阶段的SBIR项目，以支持一个为期两年的十个站点的关键项目 对125名患者进行试验，作为迈向商业化的关键一步。瞄准。评估……的有效性 BEC-rtPA改善急性亚大面积PE患者右室大小和功能的作用成功 标准：全面注册；获取和分析有关主要/次要终端的数据；演示 疗效：³减少20%的RV/LV比率；510(K)提交。团队-包括Riyaz Bashir博士，Brian Firth博士， 和Marvin Woodall先生；咨询委员会和试验指导委员会成员包括Anthony Comerota博士，Kenneth 罗森菲尔德和阿克希莱什·西斯塔。影响-该项目将提供疗效数据，以满足FDA的要求和 支持具有亚大规模PE指示的510(K)应用程序。BEC的临床可用性具有 有可能提高存活率，减少出血并发症，并减少急性PE的长期影响。

PROJECT SUMMARY—Thrombolex, Inc. has developed an intravascular catheter with an expandable spiral basket of infusion limbs to improve the efficacy of catheter-directed thrombolysis (CDT) in large vessels. Preclinical studies indicate administration of recombinant tissue plasminogen activator (rtPA) via the Bashir™ Endovascular Catheter (BEC) reduces thrombus burden to a greater degree than non-expandable CDT devices. Successful commercialization of the BEC has the potential to reduce the dose of thrombolytic agents administered to patients with large vessel thrombosis, shorten the duration of infusion, and substantially improve short- and long-term outcomes compared to current CDT devices. Up to 900,000 Americans are affected by pulmonary embolism (PE) or deep vein thrombosis each year.1 Large thrombi can produce a sudden obstruction of the pulmonary arteries (PA), failure of the right ventricle (RV), and cardiovascular collapse. While CDT reduces RV/LV ratio and improves RV function,3 the current small diameter catheters deliver thrombolytics to only a small cross-section of a thrombus and reduce its size by ≤ 30%. We expect the BEC will outperform current CDT devices and improve patient outcomes by three mechanisms: 1) expansion of the basket creates a large channel within the thrombus, restoring blood flow; 2) thrombolysis is markedly accelerated by this large channel, increasing the surface area exposed to both the infused thrombolytic and endogenous fibrinolytics, which has a synergistic effect;4 and 3) the device allows the medical team to measure PA pressure and mixed venous O2 sat to monitor thrombolysis and ideally reduce the duration/dose of thrombolysis, thereby reducing bleeding complications without sacrificing efficacy. In preclinical porcine studies, we demonstrated that 1) expanding the BEC restores blood flow, 2) infusion of rtPA via the expanded basket reduced thrombus volume by >80% after only 4 hours, and 3) the BEC did not cause endothelial damage. FDA cleared the BEC for use in the peripheral vasculature but determined further testing is needed prior to clearance for use in PE since the expandable basket is an innovation that could affect safety or effectiveness. A 10-patient Early Feasibility Study (EFS) is underway, and here we propose a Direct-to-Phase II SBIR project to support a ten-site, two-year pivotal trial with 125 patients as an essential step in toward commercialization. Aim. To evaluate the effectiveness of BEC-delivered rtPA in improving RV size and function in patients with acute submassive PE. Success Criteria: Full enrollment; acquisition and analysis of data on primary/secondary endpoints; demonstration of efficacy: ³ 20% reduction in RV/LV ratio; 510(k) submission. Team – Includes Dr. Riyaz Bashir, Dr. Brian Firth, and Mr. Marvin Woodall; Advisory Board and trial Steering Committee include Drs. Anthony Comerota, Kenneth Rosenfield, and Akhilesh Sista. Impact – This project will provide efficacy data to satisfy FDA requirements and support a 510(k) application with an indication for submassive PE. Clinical availability of the BEC has the potential to improve survival, reduce complications from bleeding, and reduce long-term effects of acute PE.