Resorbable Antimicrobial Envelope to Prevent Infection of Implanted Cardiac Devices

可吸收抗菌包膜可防止植入心脏装置感染

基本信息

批准号：
10649672
负责人：
Glenn Brunner
金额：
$ 99.35万
依托单位：
N8 MEDICAL, INC.
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-01 至 2025-06-14
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10649672
关键词：
2019-nCoV Acute Address Anti-Bacterial Agents Anti-Infective Agents Anti-Inflammatory Agents Antibiotic Prophylaxis Antibiotic Resistance Antibiotics Antifungal Agents Articulation Bacteria Biological Assay Candida Candida albicans Cardiovascular system Cephalosporins Characteristics Chlorhexidine Chronic Clinical Coagulase Defibrillators Devices Dose Effectiveness Electronics Electrospinning Excision Food and Drug Administration Device Approval Frequencies Generations Genus staphylococcus Gluconates Glycolates Goals Growth Health Implant In Vitro Industrial Product Infection Infection prevention Infectious Agent Intervention Label Life Mechanics Medical Medical Care Costs Medical Device Membrane Methods Microbial Biofilms Minocycline Morbidity - disease rate New Zealand Operative Surgical Procedures Oryctolagus cuniculus Pacemakers Patient-Focused Outcomes Patients Permeability Phase Polymers Preparation Procedures Production Property Pseudomonas Pseudomonas aeruginosa Public Health Recommendation Resistance Resistance development Rifampin Risk Reduction Safety Secure Side Skin Small Business Innovation Research Grant Sterilization Surface Surgical Wound Infection Testing Textiles Vancomycin Virus antimicrobial antimicrobial peptide bacterial resistance biodegradable polymer biomaterial compatibility caprolactone cardiac device cardiac implant cardiac resynchronization therapy clinical practice cost cost effective cytotoxicity design efficacy study efficacy validation fabrication fungus genotoxicity immunoregulation implantation improved in vitro testing in vivo in vivo evaluation infection rate large scale production liver injury manufacture methicillin resistant Staphylococcus aureus microbial mortality novel pathogen poly(lactide)preclinical study prevent product development prototype renal damage safety study systemic toxicity

项目摘要

PROJECT SUMMARY Infections related to the implantation of cardiovascular implantable electronic devices (CIEDs) occur in 20% of the interventions and are associated with a 2-fold increase in mortality rate. While pre-operative antibiotic prophylaxis is currently used in clinical practice, targeting the infectious agents locally is recommended to reduce the risk of antibiotic resistance. The use of an antibacterial envelope (TYRX, Medtronic), made of a polymer mesh coated with two antibacterial agents (minocycline and rifampin), has been shown to reduce by 40% major CIED infections. Despite these positive results, the product has several drawbacks. The envelope has variable effectiveness against coagulase-negative Staphylococci and lacks effectiveness against fungi or biofilms. Moreover, several methicillin-resistant Staphylococcus aureus (MRSA) strains have developed resistance against it. Therefore, an antibacterial and antimycotic resorbable envelope that fully eradicates CIED-related infections remains an unmet clinical need. N8 Medical is developing a new bioresorbable polymeric CIED envelope that incorporates a proprietary ceragenin, a novel class of anti-infective agents that do not engender resistance. The new compound is a synthetic non-peptide compound that mimics the activity of the body’s endogenous antimicrobial peptides (AMPs) and it confers efficacy against difficult to eradicate strains, such as MRSA and fungi. N8 Medical’s CIED Envelope is the first surgical envelope to prevent fungal colonization of cardiac devices while providing superior inhibition of bacterial growth. Upon implantation of the CIED within the N8 Medical device, the envelope physically secures and stabilizes the implanted pacemaker and releases the ceragenin to eliminate infection-causing pathogens during the period before being fully resorbed by the body within 8-12 weeks. This SBIR Phase II project builds on the results of a Phase I project that provided preliminary validation of the efficacy of the envelope in vitro and in vivo and confirmed its potential broader spectrum of activity compared to TYRX. The goal of this Phase II project is to perform pivotal preclinical studies required to obtain an IDE and FDA device approval through a De Novo application. The project is articulated in three aims over 2 years. First, industrial product development will improve the fabrication method to assure the commercial viability of the envelope (Aim 1). The final design will then be validated in GLP pivotal safety (Aim 2) and efficacy (Aim 3) studies. Comprehensive biocompatibility tests (including cytotoxicity, sensitization, pyrogenicity, and genotoxicity assays), and in vivo acute and sub-chronic and chronic systemic toxicity will be assessed. The high efficacy of N8 Medical’s CIED Envelope in eradicating resistant bacterial strains, fungi, and biofilms, will lead to better patient outcomes in terms of morbidity and mortality, reduced infection-related complications, and reduction in the need for additional interventions.

项目概要 20% 的患者发生与植入心血管植入式电子设备 (CIED) 相关的感染术前使用抗生素时，干预措施会导致死亡率增加 2 倍。目前在临床实践中使用预防措施，建议局部针对传染源以减少使用由聚合物制成的抗菌包膜（TYRX，美敦力）。涂有两种抗菌剂（米诺环素和利福平）的网片已被证明可减少 40% 的主要细菌尽管有这些积极的结果，但该产品仍有一些缺点。对凝固酶阴性葡萄球菌有效，但对真菌或生物膜缺乏效力。此外，一些耐甲氧西林金黄色葡萄球菌（MRSA）菌株已产生耐药性因此，一种抗菌和抗真菌的可吸收包膜可以完全根除 CIED 相关的细菌。 N8 Medical 正在开发一种新型生物可吸收聚合物 CIED。包膜中含有专有的角藻素，这是一类新型抗感染剂，不会产生这种新化合物是一种合成的非肽化合物，可以模仿人体的活性。内源性抗菌肽（AMP），它对难以根除的菌株具有功效，例如 MRSA 和真菌 N8 Medical 的 CIED 包膜是第一个防止真菌定植的手术包膜。心脏装置，同时在植入 CIED 后提供对细菌生长的卓越抑制。 N8 医疗设备，物理外壳固定并稳定植入的起搏器并释放角藻蛋白在被人体完全吸收之前消除引起感染的病原体该 SBIR 第二阶段项目以提供初步结果的第一阶段项目的结果为基础。验证了包膜的体外和体内功效，并证实了其潜在的广谱性与 TYRX 相比，该二期项目的目标是进行关键的临床前研究。通过 De Novo 申请获得 IDE 和 FDA 设备批准该项目明确了三个目标。首先，工业产品开发将改进制造方法，以确保商业化。最终设计将在 GLP 关键安全性（目标 2）和功效中进行验证。（目标 3）综合生物相容性测试（包括细胞毒性、致敏性、热原性和遗传毒性测定），并将评估体内急性、亚慢性和慢性全身毒性。 N8 Medical 的 CIED Envelope 在根除耐药菌株、真菌和生物膜方面的功效，将导致改善患者的发病率和死亡率，减少感染相关并发症，以及减少额外干预的需要。