We propose a novel and price competitive Tunneled Dialysis Catheter (TDC) made from a proprietary polymeric formulation to effectively reduce TDC dysfunction via long-term nitric oxide (NO) release, particularly during the period of AVF maturation in incident hemodialysis and TDC dependent patients. Preliminary studies with polymer materials used to prepare existing commercial TDCs, suggests that the proposed device will possess: (a) microbicidal (b) anti-platelet/anti-thrombosis and (c) anti-smooth-muscle cell-proliferation activities to target all the current effector arms of TDC dysfunction: infection thrombosis/fibrin sheath formation, and central venous stenosis. In addition, it is anticipated tha the device's shelf life can be extended well beyond the unprecedented 2-4 months at 37?C (already demonstrated) while maintaining anti-TDC dysfunction properties for over 3-4 weeks at body temperatures (37?C). Currently, over 80% (88,200) of incident hemodialysis (HD) patients start HD using a TDC, and the overall prevalence rate of TDCs is over 20%. In 2010, 83,000 patients were admitted to hospitals for TDC related bacteremia or sepsis, and each central line-associated bloodstream nosocomial infection adds ca. $47,000 to the cost of care and a 14.6 d increase in length of stay. Current heparin, silver impregnated, or antibiotic coated TDCs are either expensive, non-effective, or suffer from mechanical breakdown after prolonged use. The proposed device will be processed and assembled in the US at almost half the cost of current heparin or silver coated TDCs, and potentially have a significant clinical impact on the 5 fold increase in mortality in patients starting HD with a TDC as opposed to an AV fistula or graft. To continue the development of our product, we propose: (1) to examine in vitro NO release profiles and biological activity of dual lumen 11.5Fr carbosil/polyurethane prototype dual lumen catheters for effective biofilm prevention (Staphylococcus aureus, and Staphylococcus epidermidis);(2) to optimize the polymeric formulation to allow for 3 months of shelf life after proper sterilization while maintaining antimicrobial and antithrombotic properties;and (3) to obtain an in vivo "proof-of-principle" understanding to gauge the product's clinical effectiveness in terms of infection, thrombosis and CVS reduction using a pig model. This combined collaborative approach between a respected academic laboratory which is a world leader in the local delivery and release of NO (Meyerhoff laboratory) and an innovative and productive translational research group with large animal expertise (Dr. Roy-Chaudhury's Dialysis Vascular Access Research Group) will effectively bring the technology, business, and clinical needs together, to develop an innovative solution to the TDC problem. This technology has been optioned by Biocrede Inc. via the Office of Tech Transfer at the University of Michigan.
Tunneled Dialysis Catheter (TDC) dysfunction is a major clinical problem resulting in a 5-fold increase in mortality in patients starting hemodialysis witha TDC versus AV fistula or graft, due to complications resulting from infection, thrombosis that clot TDC lumens, and central venous stenosis (CVS). Current immobilized heparin, silver impregnated or antibiotic ointment coated TDCs are either expensive and not fully effective, or suffer from mechanical breakdown after prolonged use. We propose a novel long term nitric oxide release TDC that will allow at least 28 days of antiseptic, anti-platelet/anti-thrombosis, an anti- CVS activity to provide off-the-shelf storage for more than 3 months even at 37?C to improve the quality of life and survival rate of hemodialysis patients.
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