SBIR-STTR Award

Catheter-related bloodstream infection (CRBSI) is a leading cause of healthcare-acquired infections (HAIs) and is associated with high mortality (12-25%) and cost ($9 billion in the US). Catheter-related thrombosis (CRT) is another common complication with central venous catheters (CVCs) that contributes to 41% of premature device removal before treatment is over. Although various coatings, including those with anti-thrombogenic or antimicrobial agents have been applied, the safety and clinical efficacy of these coatings to reduce the rates of CRBSI and/or CRT remains unsatisfactory, especially for extended implantation. LiquiGlide is investigating a new coating solution to overcome the limitations. Liquid-impregnated surface (LIS) provides a non-adherent, self-healing, and replenishable surface that other coatings cannot achieve. Formulating a LIS coating with parenteral nutrient ingredients that have been approved by FDA for intravenous administration, confirming their safety, we have developed a coated surface that significantly reduces thrombus formation and bacterial colonization. When the coating is applied on a vascular catheter, the parenteral nutrients can be replenished through the catheter lumen to increase the duration of efficacy, which is especially beneficial as occlusion and long-term CRBSI occur predominantly through the intralumenal pathway. In preliminary studies, we demonstrated the safety and patency of coated catheters in a swine model during an implantation with three replenishments. The objective of this proposal is to develop the LIS coating on a peripherally inserted central catheter (PICC) to eliminate occlusion and reduce infection in long-term implantation with a side-by-side comparison in a same animal. To achieve the objective, we will first apply the coating on a PICC, meeting the safety and durability requirements as a vascular implant. Then, the LIS-coated PICC will be evaluated in vitro to assess its ability to prevent thrombosis formation (>95% reduction) and achieve 100% elimination of occlusion (Aim 1) under simulated external flow and infusate injections. We will further demonstrate that the coated device has a broad spectrum anti-microbial resistance (Aim 2), targeting reducing both bacterial colonization and biofilm formation with >99% reduction with three typical microorganisms that commonly cause CRBSI. To evaluate the safety and anti-occlusion/anti-infection efficacy in vivo, we will perform a seven-animal study with a swine model, monitoring catheter patency and microorganism colonization on the devices during implantation and assessing explants for thrombus formation and microbial cultures/identification (Aim 3). The proposed phase I study will address challenges related to replenishable LIS-coated PICCs, achieving full occlusion elimination and significant CRBSI reduction. Upon achievement of the phase I milestones, the coated PICC will be ready for the next level of product development. The next phase will target at scaling-up the coating process with LiquiGlide in-house cGMP facility, preforming confirmatory preclinical investigation for regulatory submission, and being ready to product launch.

Public Health Relevance Statement:
PROJECT NARRATIVE Catheter-related bloodstream infection (CRBSI) and catheter-related thrombosis (CRT) are common complications of central venous catheters (CVCs) and are associated with high mortality, morbidity, and cost. The proposed project aims to apply a novel liquid-impregnated surface (LIS) coating on a peripherally inserted central catheter (PICC; a type of CVC) to eliminate these common complications and demonstrate the safety and the long-term efficacy of the coated devices using a swine model. The coating is formulated with an intravenous feeding ingredient that is replenishable through the catheter lumen for extended performance.

Project Terms:
Achievement; Achievement Attainment; Anatomy; Anatomic; Anatomic Sites; Anatomic structures; Anatomical Sciences; Animals; Biological Assay; Assay; Bioassay; Biologic Assays; Blood; Blood Reticuloendothelial System; Blood Chemical Analysis; Blood Chemical Analyses; blood chemistry; Blood Vessels; vascular; Candida albicans; C albicans; C. albicans; C.albicans; Cardiovascular system; Cardiovascular; Cardiovascular Body System; Cardiovascular Organ System; Heart Vascular; circulatory system; Complement Activation; complement pathway regulation; Complication; Diagnosis; intravenous administration; Electrophysiology (science); Electrophysiology; Neurophysiology / Electrophysiology; electrophysiological; Embolism; Embolus; Environment; Goals; Gram-Negative Bacteria; Gram-Positive Bacteria; Cyclic GMP; Guanosine Cyclic Monophosphate; cGMP; Hospitals; Human; Modern Man; Immune system; allergic/immunologic body system; allergic/immunologic organ system; In Vitro; Infection; Structure of jugular vein; Jugular Veins; Medical Device; Morbidity - disease rate; Morbidity; mortality; Oils; Intravenous Feeding; Intravenous Hyperalimentation; Parenteral Feedings; hyperalimentation; hyperalimentation therapy; Parenteral Nutrition; Patients; Blood Plasma; Plasma Serum; Reticuloendothelial System, Serum, Plasma; Plasma; Polymers; pressure; P aeruginosa; P. aeruginosa; Pseudomonas pyocyanea; Pseudomonas aeruginosa; Safety; Science; S aureus; S. aureus; Staph aureus; Staphylococcus aureus; thrombotic disease; thrombotic disorder; Thrombosis; Triglycerides; Triacylglycerol; Yeasts; Microbial Biofilms; biofilm; Catheters; Healthcare; health care; Thrombus; Treatment Cost; base; Blood specimen; Blood Sample; Peripheral; Surface; Clinical; premature; prematurity; Phase; Physiological; Physiologic; Evaluation; Blood Serum; Serum; fluid; liquid; Liquid substance; Venous; anti-microbial agent; anti-microbial drug; antimicrobial agent; antimicrobial drug; Investigation; Side; microorganism; Upper arm; meetings; copolymer; injection/infusion; Performance; microbial colonization; microbial; Nutrient; novel; Devices; Reporting; Device Removal; Sampling; surface coating; Membrum superius; Upper Limb; Upper Extremity; Thickness; Thick; preventing; prevent; Clotting; Coagulation; Coagulation Process; Address; Antimicrobial resistant; Resistance to antimicrobial; anti-microbial resistance; anti-microbial resistant; resistance to anti-microbial; resistant to anti-microbial; resistant to antimicrobial; Antimicrobial Resistance; Cytokine Activation; device development; instrument development; Device or Instrument Development; in vivo; Patient-Focused Outcomes; Patient outcome; Patient-Centered Outcomes; Monitor; Characteristics; Process; Allergic Reaction; Pathway interactions; pathway; pre-clinical; preclinical; cost; healing; Catheter-related bloodstream infection; clinical efficacy; scale up; antimicrobial; anti-microbial; Implant; implantation; FDA approved; product development; phase 1 study; Phase I Study; improved outcome; Injections; thrombogenesis; thrombogenicity; porcine model; pig model; piglet model; swine model