Approximately 80% of patients beginning hemodialysis (HD) in the United States use a catheter at treatment initiation, and 18.6% of all HD patients were using a catheter in 2017. However, the use of tunneled catheters for HD vascular access is associated with a relatively high incidence of complications such as poor flow and catheter dysfunction, with a catheter dysfunction rate of 0.5â3.42 episodes/1000 catheter-days. The most common catheter-related problems are infections (catheter-related bloodstream infections; CRBSI) and catheter thrombosis. Catheter dysfunction due to intraluminal thrombosis and fibrin sheath formation impairs the delivery of adequate dialysis and often requires salvage by instillation of a thrombolytic agent into the catheter lumen and/or catheter exchange. It leads to significant morbidity of the limbs involved, including pulmonary embolism, and post-thrombotic syndrome. Infections can be caused by biofouling and biofilm formation; rates vary from 0.25 to 6.5 per 1,000 catheter days, which results in significant morbidity. CRBSI can result in serious complications such as spine abscess, endocarditis, and death. CRBSI frequently requires hospitalization and sometimes even ICU stays. However, no available solutions to prevent catheter dysfunction can successfully prevent both thrombosis and infection. FFMD has developed a coating technology to create a tethered liquid perfluorocarbon (TLP) surface that reduces the complication rate with catheter use during HD by ameliorating thrombosis, biofilm formation, and infections [3]. In a two-step process, a thin layer of perfluorocarbon is chemically bound and tethered to the surface of the HD catheter and is then is coated with a mobile thin layer of liquid perfluorocarbon to yield a super-repellent TLP coating. Slippery perfluorocarbon coatings are unique because they remain stable under the clinically relevant blood flow seen in catheters and dialysis machines, resist thrombosis, and prevent biofouling. The objective of this phase I proposal is to obtain proof of concept that our TLP coating could reduce thrombogenicity and prevent biofilm formation in HD catheters. Once proof of concept has been obtained, we will progress to a Phase II application for cGMP manufacturing and FDA-recommended biocompatibility testing ready for premarket approval. Our goal is to improve patient outcomes by enhancing the long-term patency of HD catheters by reducing thrombosis and complications associated with CRBSI.
Public Health Relevance Statement: NARRATIVE Many patients undergoing hemodialysis require use of a catheter to secure vascular access, but complication rates are high due to infections and thrombosis; however, no available solutions successfully prevent both these complications. We developed a coating technology to reduce the complication rate with catheter use during hemodialysis by ameliorating thrombosis and infections. Our goal is to improve patient outcomes by enhancing the long-term patency of HD catheters by reducing complications.
Project Terms: Abscess; Adherence; Arteriovenous fistula; Bacterial Adhesion; biomaterial compatibility; Blood; Blood flow; Blood Vessels; Catheter-related bloodstream infection; Catheters; Cattle; Cessation of life; chemical binding; clinically relevant; Complication; cost; Cyclic GMP; Deposition; Devices; Dialysis procedure; Effectiveness; Endocarditis; Ensure; Environment; Fibrin; Fibrinolytic Agents; Fluorocarbons; Functional disorder; Goals; Gold; Hemodialysis; Hospitalization; Hospitals; Impairment; improved; In Vitro; Incidence; Infection; Institutes; Lead; Length; Licensing; Limb structure; Liquid substance; Measures; Medical; Medical Device; Microbial Biofilms; Modeling; Morbidity - disease rate; pathogen; Patient-Focused Outcomes; Patients; Peripheral; Peritoneal Dialysis; Phase; Physiological; Plasma Proteins; Postphlebitic Syndrome; prevent; Process; Property; Pulmonary Embolism; Roentgen Rays; Scanning Electron Microscopy; Secure; Serum; Small Business Innovation Research Grant; Spectrum Analysis; Surface; Technology; Testing; Thinness; thrombogenesis; Thrombosis; Thrombus; Treatment Cost; United States; Venous; Vertebral colum
