Resorbable Inferior Vena Cava Filter

 描述（由申请人提供）：肺栓塞（PE）是第三大死亡原因，每年夺去至少10万美国人的生命-超过乳腺癌，艾滋病和交通工具死亡的总和。金属下腔静脉（IVC）滤器已被证明可有效降低风险人群的PE至约1-2%;然而，它们具有沉重的展开后代价，即昂贵的回收程序和长期并发症，如腔静脉穿透和终末器官穿刺。我们的建议是开发第一个完全可吸收的下腔静脉过滤器，通过导管插入捕获血栓 并在5周的预防期内防止其进入肺部，用于暂时禁忌抗凝剂的高危患者。在血液凝块溶解之后，过滤器 24周后消失为二氧化碳和水。价值主张是预防PE而无需滤器取出手术，并缓解金属IVC滤器特有的危及生命的长期并发症。用于此类预防用途的IVC过滤器市场每年增长26%，预计2015年将达到5.5亿美元。该II期SBIR的重点是通过一项关键的大型动物研究推进完全可吸收的IVC滤器和输送系统，以获得FDA批准。与MD安德森癌症中心合作，通过3年的体外和体内试验确立了I期可行性，并通过领先的同行评审医学杂志（J Vasc IntervRadiol）上的3篇出版物进行了验证。这些研究已经证明了在大型动物中的初步安全性和有效性，其中滤器提供了足够的强度以在推荐的预防性持续时间内捕获血栓。FDA已在提交前会议上对本文提出的研究方案进行了审查，他们声称该方案是“全面的”和“经过深思熟虑的”。FDA进一步声称，在完成拟议的动物研究（2年）和约100名患者的小型多中心临床试验（1年）后，可以获得许可/批准。目标1：制造输送系统-设计、台架试验和改进导管输送系统，目标是：高可靠性-滤器锚定在指定IVC区域（± 5 mm）时100%成功展开，易于使用-滤器展开步骤最少（理想情况下扩张和释放≤ 3）。目标二：进行活体动物研究-在MD安德森进行的FDA审查、IACUC批准的研究中，在16只动物中展开可吸收IVC滤器，以评估安全性和有效性，目标如下：10周内滤器完好，移位≤ 5 mm，栓塞≤ 20%，PE ≤ 20%，死亡≤ 10%，医疗成功率≥ 81%（滤器展开8个月内无并发症）。目标3：评价滤器的潜在毒性-确定滤器聚合物的物理化学变化：Tm和结晶度，以评估缝线阶段的变化，目标是ΔTm ≤ 2°C，37°C下PBS中的溶剂化率，目标是将吸收保持在新生缝线的20%以内。

 DESCRIPTION (provided by applicant): Pulmonary embolism (PE) is the 3rd leading cause of death, claiming the lives of at least 100,000 Americans annually - more than breast cancer, AIDS, and vehicle fatalities combined. Metallic Inferior Vena Cava (IVC) filters have been proven effective in reducing PE to about 1-2% in at risk populations; however, they come with a heavy post deployment price, namely the expensive retrieval procedure and long term complications such as caval penetration and end organ puncture. Our proposal is the development of the first totally absorbable IVC filter inserted via catheter to capture blood clots and prevent their passage to the lungs for the prophylactic period of 5 weeks for at risk patients temporarily contraindicated to anticoagulants. Following the dissolution of blood clots, the filter vanishes into mere CO2 and H2O by 24 weeks. The value proposition is the prevention of PE without requiring filter removal surgeries, and alleviation of life-threatening, long term complications characteristic of metallic IVC filters. The IVC filter market for such prophylactic use has been growing 26% annually, expected to reach $550M in 2015. This Phase II SBIR is focused on advancing a totally absorbable IVC filter and delivery system through a pivotal large animal study in the pursuit of FDA clearance. Phase I feasibility has been established through 3 years of in-vitro and in-vivo testing in collaboration with MD Anderson Cancer Center and validated through 3 publications in a leading peer-reviewed medical journal (J Vasc Interv Radiol). These studies have demonstrated preliminary safety and efficacy in large animals where the filter provided sufficient strength to capture thrombus for the recommended prophylactic duration. The study protocol proposed herein has been reviewed by the FDA at a Pre-Submission meeting where they claimed it was "comprehensive" and "well thought out". The FDA further claimed that clearance/approval can be obtained following the completion of the proposed animal studies (2 years) and a small, multicenter clinical trial of about 100 patients (1 year). Aim 1: Manufacture Delivery System - design, bench test, and refine catheter delivery system with goals: High reliability - 100% deployment success where filter is anchored to designated IVC region (± 5mm), Easy-to use - minimal number of steps for filter deployment (ideally ≤ 3 for dilation and release). Aim 2: Conduct Pivotal Animal Study - deploy absorbable IVC filters into 16 animals under a FDA-reviewed, IACUC-approved study at MD Anderson to assess safety and efficacy with the following goals: Filter intact through 10 weeks, migration ≤ 5mm, embolization ≤ 20%, PE ≤ 20%, death ≤ 10%, Medical success ≥ 81% (filter deployment without complications over 8 months). Aim 3: Evaluate Toxicity Potential of Filter - determine changes in the physical chemistry of filter polymer: Tm and crystallinity to assess change in the suture phase with the goal of ΔTm ≤ 2°C, Solvation rate in PBS at 37°C with the goal of maintaining resorption within 20% of nascent suture.