TABA for SAVE-FistulaS: A Pivotal Study of SelfWrap-Assisted ArterioVEnous FistulaS

PROJECT SUMMARY/ABSTRACT Arteriovenous fistulas (AVFs), surgical connections of autogenous arteries and veins, are considered the gold standard for hemodialysis (HD), the primary mode of survival for half a million Americans with failed kidneys (progressive chronic kidney disease, CKD) and millions more globally. However, 39% of the AVFs created in the United States fail to ever be used for dialysis, and 50% are abandoned within 12 months, greatly contributing to 1- and 5-year HD mortality rates of 21% and 60%, respectively. The reason for such high AVF failure rates is that veins are thinner-walled and far more compliant than arteries, not equipped for the high pressure, high flow, pulsatile environment of the arterial circulation. Veins drastically expand as a result, causing injury to the protective inner endothelial lining of the vessel that leads to migration and proliferation of vascular smooth muscle cells (VSMCs), or neointimal hyperplasia (NH), causing occlusion, lack of blood flow, and loss of patency. This problem of veins failing to successfully adapt or arterialize from surgeries connecting veins to arteries is termed the ‘Achilles heel’ of vascular surgery because the problem is so pervasive and incorrigible, greatly impacting morbidity and mortality for over 5 million new patients each year undergoing AVF creation, arteriovenous graft (AVG) creation, peripheral artery bypass grafting (PABG), or coronary artery bypass grafting (CABG) surgery. To address this underlying physiological problem, VenoStent has developed the SelfWrap Bioabsorbable Perivascular Wrap (i.e. SelfWrap), a wrap that goes around the vein at the time of the vein-to-artery connection surgery to provide optimal mechanical support and help it successfully arterialize, with a first indication for AVFs. SelfWrap is comprised of finely-tuned, bioabsorbable, thermo-responsive smart polymers and its geometric features are optimally configured to help the vein adapt favorably to the arterial circulation. The net result of this device impact has been a significant reduction in NH in three different chronic large animal models: a diseased rabbit bypass grafting model at 90 days (funded by the NIH STTR Phase I Award), ovine AVFs at 90,180, and 365 days (funded by NSF SBIR Phase II), and in ovine AVGs at 60 days. Most importantly, the clinical benefit of the SelfWrap device has been demonstrated in a 20-patient Initial Feasibility Study, where very high maturation rates, low intervention rates, high catheter removal rates, and high patency were achieved. These clinical and preclinical results awarded VenoStent Breakthrough Device Designation from FDA in 2022. This proposal evaluates the safety and effectiveness of SelfWrap in CKD patients referred for creation of a new AVF in a pivotal study. Successful completion of this pivotal trial, with a significant improvement in the primary outcome and no significant safety concerns using SelfWrap, would provide the evidence needed for FDA approval of this Breakthrough Device. This could potentially revolutionize the field of vascular surgery, improving the quality and length of life for millions of patients each year that undergo AVF, AVG, PABG, or CABG surgery.