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、艾滋病和车辆死亡的总和。金属下腔静脉滤器(IVC)已被证明在高危人群中有效地将PE降低到约1-2%；然而，它们在部署后会带来高昂的成本，即昂贵的回收程序和长期的并发症，如腔静脉穿透和末端器官穿孔。我们的建议是开发第一个完全可吸收的下腔静脉滤器，通过导管插入以捕获血栓 对于暂时禁止使用抗凝剂的高危患者，在5周的预防性期间防止它们进入肺部。在血栓溶解后，过滤器 24周后就消失在二氧化碳和水中。其价值主张是无需进行滤器取出手术即可预防PE，并可减轻金属IVC滤器所特有的危及生命的长期并发症。用于此类预防的IVC过滤器市场一直在以每年26%的速度增长，预计2015年将达到5.5亿美元。这一第二阶段SBIR的重点是通过一项关键的大型动物研究来推进完全可吸收的IVC过滤器和输送系统，以追求FDA的批准。第一阶段的可行性是通过与MD Anderson癌症中心合作进行了3年的体外和体内测试，并通过在领先的同行评议医学杂志(J VASc Interv Radiol)上发表的3篇论文来验证的。这些研究已经在大型动物身上证明了初步的安全性和有效性，在这些动物中，过滤器提供了足够的强度来在推荐的预防时间内捕获血栓。FDA在提交前的一次会议上审查了这里提出的研究方案，他们在会上声称它是“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，可以获得批准/批准。目标1：制造输送系统-设计、台架测试和改进导管输送系统，目标是：高可靠性-过滤器固定在指定的下腔静脉区域(±5 mm)时100%的部署成功，易于使用-过滤器部署的最少步骤(理想情况下，用于扩张和释放的≤3)。目标2：进行关键动物研究-在MD Anderson进行的一项由FDA审查、IACUC批准的研究中，将可吸收的下腔静脉滤器部署到16只动物中，以评估安全性和有效性，目标如下：滤器在10周内完好无损，迁移≤ 5 mm，栓塞≤2 0%，PE≤2 0%，死亡≤10%，治愈率≥81%(8个月以上无并发症)。目的3：评估过滤器的毒性潜力-测定过滤器聚合物的物理化学变化：TM和结晶度以评估缝合阶段的变化，目标是ΔTM≤2°C，在PBS中的溶剂化速率在37°C，目标是将吸收保持在新生缝合线的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.