Novel Expandable Infusion Catheter for the Treatment of Acute Pulmonary Embolism

项目概要-Thrombolex，Inc.开发了一种血管内导管， 篮状输注肢体，以提高大血管中导管定向溶栓（CDT）的疗效。 临床前研究表明通过Bashir™施用重组组织纤溶酶原激活剂（rtPA） 血管内导管（BEC）比非扩张式CDT器械更大程度地减少血栓负荷。 BEC的成功商业化有可能减少溶栓药物的剂量 给大血管血栓形成患者使用，缩短输注时间， 与当前CDT设备相比，改善了短期和长期结果。多达90万美国人 肺栓塞（PE）或深静脉血栓形成的影响。1大血栓可引起突然的 肺动脉（PA）阻塞、右心室（RV）衰竭和心血管衰竭。而 CDT可降低RV/LV比值并改善RV功能，3目前的小直径导管可输送溶栓药物 血栓的横截面很小，尺寸减小≤ 30%。我们预计BEC的表现将优于 目前的CDT设备，并通过三种机制改善患者的结果：1）篮的扩张产生了一个 血栓内的大通道，恢复血流; 2）血栓溶解明显加速，这一大通道 通道，增加暴露于输注的溶栓和内源性纤溶药物的表面积， 其具有协同效应;4和3）该设备允许医疗团队测量PA压力并混合 静脉血氧饱和度监测溶栓，理想情况下减少溶栓的持续时间/剂量，从而减少 出血并发症而不牺牲疗效。在临床前猪研究中，我们证明了1） 扩张BEC可恢复血流，2）通过扩张篮输注rtPA可减少血栓体积 仅4小时后就减少>80%; 3）BEC不引起内皮损伤。FDA批准BEC用于 外周血管系统，但确定在批准用于PE之前需要进行进一步试验，因为 可膨胀篮是一种可能影响安全性或有效性的创新。10名患者的早期可行性研究 (EFS)正在进行中，在这里，我们提出了一个直接到第二阶段SBIR项目，以支持一个十个网站，为期两年的关键 125名患者的临床试验是迈向商业化的重要一步。瞄准的有效性进行评估 BEC输送的rtPA改善急性次大块PE患者的RV尺寸和功能。成功 标准：完全入组;主要/次要终点数据的采集和分析; 有效性：RV/LV比值降低≥ 20%; 510（k）提交。团队-包括Riyaz Bashir博士，Brian Firth博士， 咨询委员会和审判指导委员会包括Anthony Comerota博士、Kenneth Rosenfield和Akhilesh Sista。影响-本项目将提供疗效数据，以满足FDA的要求， 支持具有超大规模PE指示的510（k）申请。BEC的临床可用性 有可能提高生存率，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.