Aortic stenosis (AS) is a common and lethal cardiac valve disease with an average survival time of only 2 ? 3 years after diagnosis if no treatment is obtained. The standard of care for moderate to severe cases of symptomatic AS is surgical valve repair or replacement, which can necessitate open heart surgery. This ?gold standard? of care is plagued by substantial limitations, including high morbidity and mortality in the elderly (the most common patient), and an alarmingly high percentage of patients who cannot undergo surgery (estimated at 40 ? 50% of patients with severe symptomatic AS). Transcatheter aortic valve replacement (TAVR) has been widely adopted to treat patients at intermediate or high risk of complications from conventional surgical aortic valve replacement. The standard vascular access for TAVR is through the femoral arteries (trans-femoral), but between 8-12% of patients in the USA are not eligible for trans-femoral TAVR because their iliofemoral arteries are too small or too diseased. Dr. Robert J. Lederman has pioneered innovative transcaval access to the abdominal aorta from the adjoining inferior vena cava, to provide a fully percutaneous technique for TAVR in patients without good access options. However, the procedures have used permeable nitinol duct occluder devices off-label, which, despite making the procedure possible, are associated with significant bleeding complications and procedural difficulty. There is no device on the market that is built to specifically overcome these limitations in off-label use of nitinol occluders. The recognition of this deficient in the market led the NHLBI to enter into a direct-to-Phase II contract with Transmural Systems LLC. In Phase II, Transmural has pioneered a purpose-built Transcaval Closure Device (TCD) that will minimize risks associated with this innovative transcaval TAVR procedure. The TCD has undergone iterative design development, leading to the creation of a mature device with demonstrated excellence in safety and efficacy in bench model tests and in acute and chronic animal studies. In this Phase IIB, Transmural is prepared to advance its mature TCD to a true clinical setting with support of Dr. Robert Lederman, Dr. Adam Greenbaum, Dr. Vasilis Babaliaros and Dr. Toby Rogers. To assess the safety and efficacy of the TCD, Transmural Systems will conduct an Early Feasibility Study (EFS) clinical trial (Aim 1) that will inform any necessary product modification before conductance of a Pivotal clinical trial (Aim 2). The EFS will occur at three forward-thinking cardiology institutes in the US by surgeons who specialize in transcaval-access TAVR. The Pivotal study will expand to include the 20 sites from Dr. Robert J. Lederman?s transcaval clinical trial of off-label use occluders. Successful completion of the proposed clinical trials will poise Transmural Systems to market a purpose-built device to treat AS, simplifying the closure procedure and enabling the application of the transcaval technique to a wider range of patients ineligible for trans-femoral access.
The goal of this project is to finalize Transmural Systems? transcaval closure device and perform early feasibility and pivotal clinical trials in patients undergoing caval-aortic (transcaval) access for Transcatheter Aortic Valve Replacement (TAVR). Transmural Systems? purpose built device will provide an urgently needed life-saving option for patients with symptomatic AS who are deemed nonsurgical candidates and cannot undergo alternative TAVR procedures.
