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

• 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
• 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

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.

项目摘要 与导管相关的血液感染（CRBSI）是医疗保健获得感染（HAI）和 与高死亡率（12-25％）和成本（美国为90亿美元）有关。导管相关血栓形成（CRT）是 中央静脉导管（CVC）的另一个常见并发症，贡献了早产设备的41％ 在治疗结束之前去除。虽然各种涂层，包括具有抗直流电或 已经应用了抗菌剂，这些涂料的安全性和临床效率以降低 CRBSI和/或CRT仍然不令人满意，尤其是用于扩展植入。 Liquiglide正在研究 克服局限性的新涂料解决方案。液体浸渍的表面（LIS）提供了不粘附的， 其他涂料无法实现的自我修复和可复制的表面。配制与 肠胃外营养素已被FDA批准用于静脉内给药，证实了他们的 安全性，我们开发了一个涂层的表面，可显着降低血栓形成和细菌 殖民化。当涂层涂在血管导管上时，可以复制父母的营养 通过导管管腔增加效率的持续时间，这在遮挡和 长期CRBSI主要通过义内途径发生。在初步研究中，我们 在植入三个时，证明了猪模型中涂层导管的安全性和通知 补充。该提议的目的是在周围插入的中央开发LIS涂层 导管（PICC）消除与并排植入长期植入中的阻塞并减少感染 在同一动物中进行比较。为了实现目标，我们将首先将涂层应用于PICC，满足 作为血管植入物的安全性和耐用性要求。然后，将在体外评估LIS涂层的PICC 评估其预防血栓形成的能力（降低> 95％），并100％消除闭塞 （AIM 1）在模拟的外流和注射下。我们将进一步证明涂层设备 具有广谱抗微生物耐药性（AIM 2），靶向降低细菌定植和生物膜 通常会引起CRBSI的三种典型微生物，形成> 99％。评估 在体内的安全性和抗封闭性/抗感染效率，我们将通过猪模型进行七个动物研究， 监测植入和评估期间设备上的导管通畅性和微生物定植 外植体用于血栓形成和微生物培养/鉴定（AIM 3）。拟议的I阶段研究将 解决与可复制的LIS涂层PICC相关的挑战，实现了完全的遮挡消除和 显着降低CRBSI。在达到第一阶段里程碑后，涂层的PICC将准备好 产品开发的下一个水平。下一阶段将针对用液体缩放涂料工艺的目标 内部CGMP设施，预先提出确认临床前调查监管提交以及 准备发布产品。