This study aims to evaluate the in vivo effectiveness of the Arteriovenous Fistula Eligibility (AFE) Systemâ¢, a small temporary wearable rotary blood pump system that rapidly and persistently dilates peripheral veins prior to arteriovenous fistula (AVF) surgery. Successful commercialization of the AFE System would enable the creation of AVF vascular access sites in hemodialysis patients who are currently ineligible because of inadequate vein diameter, improve the rate of AVF maturation after AVF surgery, reduce the time required for AVF maturation, prolong primary and secondary AVF patency rates, and reduce the use of hemodialysis catheters and grafts. Flow Forward Medical, Inc. has developed a working prototype of the AFE System, including the blood pump, inflow and outflow catheters, and rack-mounted controller. The device has demonstrated excellent hydrodynamic performance and minimal blood damage. Recent pilot in vivo studies in an ovine forelimb model demonstrated an 86% increase in mean cephalic vein diameter over 6 - 11 days of AFE System treatment with no untoward effects on cardiovascular function. After 6 weeks of maturation, AVFs that were made with veins pre-treated with the AFE System had mean inflow brachial artery diameters that were 28% larger in diameter, mean outflow cephalic vein diameters that were 52% larger in diameter, and blood flows that were 4X greater than control AVFs made with untreated veins. The objective of this proposed Phase I program is to complete a larger study evaluating cephalic vein diameter before and after AFE System treatment and comparing the maturation of AVFs made using AFE System-treated veins and untreated veins in a newly developed ovine model. Analysis during the treatment period will include measurements of AFE System blood flow and treated cephalic vein diameter. Analysis during the six week AVF maturation period will include weekly measurements of AVF inflow artery and outflow vein diameter by angiography and AVF blood flow by ultrasound. Analysis at the terminal end point will include histologic analysis of the AVFs with morphometry. Based upon the success of Phase I, Phase II of the program will include a GLP animal study with a commercial version of the AFE System and preparations for a US clinical trial.
Public Health Relevance Statement: PROJECT NARRATIVE There are over 425,000 patients with end-stage renal disease in the US who depend on hemodialysis. Creating effective and reliable vascular access sites that can connect patients to hemodialysis machines remains a major unmet clinical need. Hemodialysis patients who use an arteriovenous fistula (AVF) for vascular access live longer, healthier lives and cost less to care for. However, about 40% of hemodialysis patients in the US are ineligible for AVF surgery, mostly due to inadequate vein diameter, and must use arteriovenous grafts and catheters for hemodialysis access, subjecting them to higher failure rates, more complications, and higher costs. For those patients who have adequate peripheral veins and are eligible for AVF surgery, more than 50% will experience maturation failure, with a substantial number of those AVFs being subsequently abandoned prior to regular use. Prior studies have shown much higher rates of successful maturation after AVF surgery for patients with larger initial vein diameters. Flow Forward Medicalâs AFE System is designed to rapidly and persistently dilate peripheral veins, enabling nearly all hemodialysis patients to be eligible for an AVF and reducing their subsequent risk of AVF failure.
Project Terms: Address; Angiography; Animals; Area; Arteries; Arteriovenous fistula; base; Biological; Blood; Blood flow; Blood Pressure; blood pump; Blood Vessels; brachial artery; Caliber; Cardiovascular Physiology; Caring; Catheters; cell injury; cephalic vein; Clinical; Clinical Trials; commercialization; Contralateral; cost; design; Device Designs; Devices; Dose; Effectiveness; Eligibility Determination; End stage renal failure; Erythrocytes; Evaluation; experience; Failure; Forelimb; good laboratory practice; Government; Hemodialysis; Hemoglobin; Heparin; Histologic; Histology; Hyperplasia; improved; In Vitro; in vivo; Investigation; Lead; Maintenance; Measurement; Medical; Medical Device; Modeling; Morphology; morphometry; nitinol; Obstruction; Operative Surgical Procedures; Patient Care; Patients; Performance; Peripheral; Persons; Phase; Physicians; Plasma; Platelet Count measurement; Preparation; Procedures; programs; prototype; Pump; repaired; Research; Risk; Secure; shear stress; Sheep; Site; Stenosis; success; Superior vena cava structure; Surface; System; Techniques; Thrombosis; Thrombus; Time; treatment duration; Ultrasonography; Vascular Fistula; Ve
