Tumor Embolization Using A Novel Catheter With Integrated Flow Regulation

使用具有集成流量调节功能的新型导管进行肿瘤栓塞

• 批准号: 8976952
• 负责人: Michael Patrick Allen
• 金额: $ 22.19万
• 依托单位: EMBOLX, INC.
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-25 至 2016-05-24
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8976952
• 关键词: Anatomy; Animal Testing; Animals; Arterial Embolization; Arteries; Balloon Occlusion; Blood; Blood Circulation; Blood Vessels; Blood flow; Bypass; Calibration; Caring; Catheters; Chemoembolization; Clinical Research; Colorectal Cancer; Data; Development; Device or Instrument Development; Devices; Diagnosis; Distal; Dose; Drops; Excision; Family suidae; Goals; Hand; Housing; Infusion procedures; Injection of therapeutic agent; Investigation; Life; Liver; Malignant Neoplasms; Malignant neoplasm of liver; Marketing; Measurement; Mediating; Methods; Modeling; Neoplasm Metastasis; Outcome; Patients; Pharmaceutical Preparations; Physicians; Prevalence; Primary Neoplasm; Primary carcinoma of the liver cells; Procedures; Quality of life; Radioactivity; Reflux; Regulation; Reproducibility; Research; Safety; Signal Transduction; Site; Specific qualifier value; Staging; Standardization; Systolic Pressure; Techniques; Test Result; Testing; Therapeutic Embolization; Toxic effect; Transplantation; United States National Institutes of Health; Visual; antitumor agent; artery occlusion; base; chemotherapy; improved; novel; pressure; prevent; public health relevance; response; simulation; standard of care; tumor; Anatomy; Animal Testing; Animals; Arterial Embolization; Arteries; Balloon Occlusion; Blood; Blood Circulation; Blood Vessels; Blood flow; Bypass; Calibration; Caring; Catheters; Chemoembolization; Clinical Research; Colorectal Cancer; Data; Development; Device or Instrument Development; Devices; Diagnosis; Distal; Dose; Drops; Excision; Family suidae; Goals; Hand; Housing; Infusion procedures; Injection of therapeutic agent; Investigation; Life; Liver; Malignant Neoplasms; Malignant neoplasm of liver; Marketing; Measurement; Mediating; Methods; Modeling; Neoplasm Metastasis; Outcome; Patients; Pharmaceutical Preparations; Physicians; Prevalence; Primary Neoplasm; Primary carcinoma of the liver cells; Procedures; Quality of life; Radioactivity; Reflux; Regulation; Reproducibility; Research; Safety; Signal Transduction; Site; Specific qualifier value; Staging; Standardization; Systolic Pressure; Techniques; Test Result; Testing; Therapeutic Embolization; Toxic effect; Transplantation; United States National Institutes of Health; Visual; antitumor agent; artery occlusion; base; chemotherapy; improved; novel; pressure; prevent; public health relevance; response; simulation; standard of care; tumor

 DESCRIPTION (provided by applicant): The objective of this proposal is to develop and test a microcatheter that creates a partial arterial occlusion during injection of embolic agents into tumors in the liver and thereby improve efficacy and reproducibility of the method. In the US over 30,000 people will be diagnosed with primary liver cancer and over 140,000 people will be diagnosed with colorectal cancer each year, of which 75% will metastasize to the liver. Embolization therapy, or the transvascular injection of drug and/or embolic agents directly into the tumor vasculature using a microcatheter, was established as a standard of care for intermediate stage hepatocellular carcinoma in 2006. However, clinical study results are remarkably inconsistent. Embolx aims to develop a delivery microcatheter, including a balloon, comprised of longitudinal channels that regulate anterograde arterial flow into the tumor and one-way valves that prevent retrograde flow. The proposed device will allow pressure measurement in the vascular compartment distal to the occlusion and enable a quantitative pressure- mediated endpoint. When the occlusion balloon is inflated at the site of injection, the pressure distal to the balloon immediately drops, causing distal hepatoenteric arteries to reverse direction, thereby producing hepatofugal flow which provides anterograde protection. We hypothesize that this device will eliminate reflux of embolic agents into proximal arterial branches, reduce or eliminate anterograde bypass of embolic agents into distal hepatoenteric arteries and maintain a controlled flow rate of blood into the tumor, thereby delaying pressure elevation and enabling improved embolic distribution. Further, isolation of the arterial space distal to the occlusion from the general circulation enables a pressure measurement to be a reliable signal of endpoint and support standardization of the method. If the proposed aims are achieved, this development will open a new channel of investigation leading to a change in the paradigm of embolization therapy and improve outcomes and quality of life for patients living with cancers. In Specific Aim #1, the device development includes, a detailed multi-variable flow simulation (Task 1), development of the catheter (Task 2), and development of the partial occlusion balloon (Task 3). At the completion of this Aim, the fully functional device is ready for testing and device assembly of Specific Aim #2, wherein 30 devices are tested for functionality, most importantly, anterograde flow, retrograde retention and catheter over-the-wire trackability in a tortuous vasculature anatomy fixture. Following completion of testing, 30 devices will be assembled and packaged in a class 10,000 clean room and E-beam sterilized for animal testing. In Specific Aim #3, the device will be tested in the porcine liver model. The goals of the animal studies are to establish: (1) safety, (2) pressure drop distal to the occlusion balloon (3) flow reversal of the gastroenteric artery and (4) elimination of retrograde reflux. At the conclusion of these studies, we hope to have a functional, validated microcatheter device, ready for advanced animal testing, FDA submission, clinical studies and market introduction.

 描述（由适用提供）：该提案的目的是开发和测试微型导管，该微型导体在将栓塞剂注入肝脏中的肿瘤期间会产生部分人伪影，从而提高该方法的效率和可重复性。在美国，将有30,000多人被诊断出患有原发性肝癌，每年将被诊断出14万人被诊断出患有大肠癌，其中75％将转移到肝脏。在2006年，建立了栓塞疗法，或使用微量导管直接将药物和/或栓塞剂直接进入肿瘤脉管系统中的药物和/或栓塞剂。但是，临床研究结果非常不一致。 Embolx的目的是开发递送微导管，包括一个气球，该球囊由纵向通道组成，该纵向通道调节顺行动动脉流入肿瘤和单向阀，以防止逆行流动。所提出的装置将允许在阻塞远端的血管室中进行压力测量，并实现定量压力介导的终点。当注射部位闭塞气囊膨胀时，气球远端的压力立即掉落，导致肝远端动脉逆转方向，从而产生肝流动流，从而提供前进保护。我们假设该设备将消除栓塞剂在近端伪影分支中的反射X，减少或消除栓塞剂的顺行绕过肝远端动脉的地下旁路，并将血液流动流入肿瘤中，从而延迟压力升高并实现改善的栓塞分布。此外，从一般循环中闭塞远端的伪像的分离使压力测量成为可靠的端点信号，并支持该方法的标准化。如果实现了拟议的目标，这种发展将开放新的投资渠道，从而改变栓塞疗法的范式，并改善癌症患者的结局和生活质量。在特定的目标＃1中，设备开发包括一个详细的多变量流仿真（任务1），导管的开发（任务2）以及部分闭塞气囊的开发（任务3）。该目标完成时，功能齐全的设备已准备就绪 特定目标2的测试和设备组装，其中30个设备的功能测试，最重要的是，在曲折的血管解剖结构固定装置中，在曲折的脉管结构中，逆行保留和导管的超线跟踪性。测试完成后，将在10,000级清洁室组装并打包30个设备，并进行电子束进行消毒以进行动物测试。在特定的目标＃3中，将在猪肝模型中测试该设备。动物研究的目标是建立：（1）安全性，（2）胃肠道动脉逆转的闭塞球囊（3）的压力下降和（4）消除逆行反射x。结束 这些研究，我们希望有一个功能性的，经过验证的微型导管设备，准备进行高级动物测试，FDA提交，临床研究和市场介绍。