Research Project
8899253
? 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 ?Tm ? 2°C, Solvation rate in PBS at 37°C with the goal of maintaining resorption within 20% of nascent suture.
