A replenishable LIS coating that eliminates occlusion and reduces infection on vascular catheters

可补充的 LIS 涂层可消除血管导管的闭塞并减少感染

基本信息

批准号：
10544076
负责人：
Zheng Zhang
金额：
$ 32.28万
依托单位：
LIQUIGLIDE, INC.
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-01 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10544076
关键词：
Achievement Address Allergic Reaction Anatomy Animals Antimicrobial Resistance Biological Assay Blood Blood Chemical Analysis Blood Vessels Blood specimen Candida albicans Cardiovascular system Catheter-related bloodstream infection Catheters Characteristics Clinical Coagulation Process Complement Activation Complication Cyclic GMP Cytokine Activation Device Removal Device or Instrument Development Devices Diagnosis Electrophysiology (science)Embolism Environment Evaluation FDA approved Goals Gram-Negative Bacteria Gram-Positive Bacteria Healthcare Hospitals Human Immune system Implant In Vitro Infection Injections Investigation Liquid substance Medical Device Microbial Biofilms Monitor Morbidity - disease rate Nutrient Oils Parenteral Nutrition Pathway interactions Patient-Focused Outcomes Patients Performance Peripheral Phase Physiological Plasma Polymers Process Pseudomonas aeruginosa Reporting Safety Sampling Science Serum Side Staphylococcus aureus Structure of jugular vein Surface Thick Thrombosis Thrombus Treatment Cost Triglycerides Upper Extremity Upper arm Venous Yeasts antimicrobial antimicrobial drug base clinical efficacy copolymer cost healing implantation improved outcome in vivo injection/infusion intravenous administration meetings microbial microbial colonization microorganism mortality novel phase 1 study porcine model pre-clinical premature pressure prevent product development scale up surface coating thrombogenesis

项目摘要

PROJECT SUMMARY 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.

项目概要导管相关血流感染 (CRBSI) 是医疗保健获得性感染 (HAIs) 和与高死亡率（12-25%）和费用（美国 90 亿美元）相关。中心静脉导管 (CVC) 的另一种常见并发症，导致 41% 的装置过早出现尽管有各种涂层，包括具有抗血栓形成或抗凝血作用的涂层，但在治疗结束之前应将其去除。抗菌剂的应用，这些涂层的安全性和临床功效，以降低感染率 CRBSI 和/或 CRT 仍然不能令人满意，特别是 LiquiGlide 正在研究延长植入。新的涂层解决方案克服了液体浸渍表面（LIS）的局限性。配制 LIS 涂层无法实现的自修复和可补充表面。经 FDA 批准用于静脉注射的肠外营养成分，确认其为了安全，我们开发了一种涂层表面，可显着减少血栓形成和细菌当将涂层涂在血管导管上时，可以补充肠外营养物质。通过导管腔以增加疗效的持续时间，这对于闭塞和在初步研究中，长期 CRBSI 主要通过腔内途径发生。证明了在猪模型中植入三个涂层导管的安全性和通畅性该提案的目的是在外周插入的中心上开发 LIS 涂层。并排植入导管（PICC）可消除闭塞并减少长期植入时的感染为了实现这一目标，我们首先将涂层涂在 PICC 上，以满足要求。然后，对 LIS 涂层 PICC 进行体外评估，以评估其作为血管植入物的安全性和耐久性要求。评估其预防血栓形成（减少>95%）并实现100%消除闭塞的能力（目标 1）在模拟外部流动和输液注射下我们将进一步证明涂层装置。具有广谱抗微生物耐药性（目标 2），旨在减少细菌定植和生物膜三种通常引起 CRBSI 的典型微生物的形成率降低了 >99%。体内安全性和抗闭塞/抗感染功效，我们将用猪模型进行七种动物研究，在植入和评估过程中监测导管的通畅性和设备上的微生物定植外植体用于血栓形成和微生物培养/鉴定（目标 3）。解决与可补充的 LIS 涂层 PICC 相关的挑战，实现完全闭塞消除和在实现第一阶段里程碑后，涂层 PICC 将为 CRBSI 显着减少做好准备。下一阶段的产品开发目标是扩大 LiquiGlide 的涂层工艺。内部 cGMP 设施，为监管提交进行确认性临床前调查，并正在准备推出产品。