Development of Intrasaccular Flow Disrupters for Small and Ruptured Aneurysms

 描述（由申请人提供）：该2期SBIR项目的长期目标是为患有小型宽颈颅内动脉瘤的患者提供高效微创治疗选择。为了解决治疗小型宽颈动脉瘤的未满足的临床需求，Sequent Medical，Inc.，开发了Woven EndoBridge或WEB设备。WEB代表了这一重要动脉瘤亚组治疗的根本性变化;在其目前的形式下，根据先前的I期SBIR开发，WEB很容易放置在宽颈分叉动脉瘤中，并导致流入动脉瘤的快速停止，而不需要腔内支持装置或抗血小板治疗。最初的WEB已获得欧盟国家以及智利，阿根廷，哥伦比亚，澳大利亚和阿拉伯联合酋长国的监管批准，并已被放置在全球1500多个动脉瘤中，主要是中型动脉瘤;目前正在美国进行研究器械豁免（IDE）试验。目前的安全性和有效性数据非常有希望。尽管原始WEB取得了巨大的成功，但重要的问题，患者群体和市场仍然需要充分解决。由于放置当前WEB器械所需的入路导管相对较大，因此WEB器械在破裂和未破裂的小动脉瘤中的应用受到限制。目前的WEB器械需要的导管远大于用于治疗动脉瘤的内径为0.017”的标准微导管（017微导管）。在过去的两年中，Sequent工程团队在缩小下一代WEB设备的规模方面取得了快速进展。最新的WEB器械（单层（SL）和单层球形（SLS））可以通过定制的021微导管放置，这些微导管仍然太大，无法帮助治疗最常见尺寸的破裂动脉瘤。因此，我们在这里建议继续开发一种创新的WEB设备，用于治疗小型宽颈动脉瘤，包括破裂的动脉瘤。这将需要重新设计与017微导管配合使用的WEB器械（Aim 1），并在马约诊所与Kallmes博士一起在标准模型系统中重新测试该器械（Aim 2）。我们在原始WEB方面的经验相当于第一阶段的概念验证，证明WEB设备是可行的，具有很大的医疗用途;事实上，我们的原始工作很快就完成了，我们独立地进行了开发阶段，而不是等待第二阶段SBIR。因此，在对原始WEB器械（我们最初预期的II期）独立进行IDE的同时，我们现在提出了直接II期，以调整WEB用于任何形态动脉瘤的标准尺寸入路导管，从而显著扩展器械的预期效用。在第二阶段SBIR的成功结束时，我们将准备在IDE中研究新适应的WEB-017设备。值得注意的是，当前WEB模型的进展降低了开发这种新器械的监管和技术风险，这将为治疗小型宽颈动脉瘤提供突破。

 DESCRIPTION (provided by applicant): The long term goal of this Phase 2 SBIR program is to provide a highly effective, minimally-invasive treatment option for patients suffering from small, broad-necked intracranial aneurysms. To address the unmet clinical need for treating small broad-necked aneurysms, Sequent Medical, Inc., has developed the Woven EndoBridge, or WEB device. The WEB represents a fundamental change in the treatment of this important subset of aneurysms; in its current form, developed under a previous Phase 1 SBIR, the WEB is readily placed into broad-necked, bifurcation aneurysms and results in rapid cessation of flow into the aneurysm, without need for an intraluminal support device or antiplatelet therapy. The original WEB received regulatory approval for use in European Union countries as well as Chile, Argentina, Colombia, Australia and the United Arab Emirates and has been placed into more than 1500 aneurysms worldwide, mostly in medium-sized aneurysms; it is currently being studied under an Investigational Device Exemption (IDE) trial in the US. Current safety and efficacy data are highly promising. Notwithstanding the substantial success of the original WEB, important issues, patient groups, and markets remain to be fully addressed. Application of the WEB device to small aneurysms, both ruptured and unruptured, has been limited because of the relatively large-sized access catheters required to place the current WEB devices. The current WEB devices require catheters substantially larger than standard microcatheters of 0.017" inner diameter (017 microcatheters) used to treat aneurysms. Over the past two years, the Sequent engineering team has made rapid progress in down-sizing the profile of later-generation WEB devices. The newest WEB devices (Single Layer (SL) and Single Layer Spherical (SLS)) can be placed through customized 021 microcatheters, which are still too large to facilitate treatment of the most common sizes of ruptured aneurysms. Thus, we propose here to proceed with development of an innovative WEB device targeting treatment of small broad-necked aneurysm, including those that are ruptured. This will entail re-engineering the WEB device for use with 017 microcatheters (Aim 1) and retesting the device in a standard model system with Dr. Kallmes at the Mayo Clinic (Aim 2). Our experience with the original WEB stands as a Phase I-equivalent proof-of-concept that WEB devices are feasible and of great medical utility; indeed, our original work was so rapidly completed that we proceeded with development phases independently, rather than waiting for a Phase II SBIR. Thus, while independently pursuing an IDE on the original WEB device (our originally intended Phase II), we now propose a Direct Phase II to adapt the WEB for use in standard-sized access catheters in aneurysms of any morphology and thus markedly expand the anticipated utility of the device. At the successful conclusion of this Phase II SBIR, we will be poised to study the newly adapted WEB-017 device in an IDE. Notably, the progress of the current WEB model reduces the regulatory and technical risk for the development of this new device, which would provide a breakthrough in the treatment of small broad-necked aneurysms.