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

• 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
• 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

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.

项目摘要 与植入心血管植入电子设备（CIEDS）有关的感染发生在20％ 干预措施，与死亡率增加2倍。而术前抗生素 预防目前用于临床实践中，针对当地的传染剂以减少 抗生素抗性的风险。由聚合物制成的抗菌包膜（Tyrx，Medtronic）的使用 涂有两种抗菌剂（minocycline和Rifampin）的网眼已显示可降低40％ 凝结感染。尽管有这些积极的结果，但该产品仍有几个缺点。信封具有可变 针对凝固酶阴性葡萄球菌的有效性，缺乏针对真菌或生物膜的有效性。 此外，几种耐甲氧西林金黄色葡萄球菌（MRSA）菌株已经发展出抗性 反对它。因此，完全放射性相关的抗菌和抗魔法可吸收包膜 感染仍然是未满足的临床需求。 N8 Medical正在开发一种新的生物烘焙聚合物CIED 包含专有Ceragenin的信封，这是一种新型的反感染剂，不产生 反抗。新化合物是一种合成的非肽化合物，模仿了人体的活性 内源性抗菌胡椒（AMPS），它承认对难以放射素菌株的有效性，例如 MRSA和真菌。 N8 Medical的Cied信封是第一个防止真菌定植的手术信封 心脏设备在提供细菌生长的良好抑制作用的同时。在植入中心后 N8医疗设备，信封可以物理固定并稳定植入的起搏器并释放 在完全被身体吸收之前 在8-12周内。这个SBIR II期项目基于提供初步的I期项目的结果 验证信封在体外和体内的效率，并确认其潜在的广播频谱 与Tyrx相比。该第二阶段项目的目标是进行需要的关键临床前研究 通过从头申请获得IDE和FDA设备批准。该项目以三个目标阐明 超过2年。首先，工业产品开发将改善制造方法以确保广告 信封的可行性（AIM 1）。然后，最终设计将在GLP关键安全性（AIM 2）中进行验证，并放松 （目标3）研究。全面的生物相容性测试（包括细胞毒性，致敏性，热源性和 将评估遗传毒性评估）以及体内急性和亚基和慢性全身毒性。高 N8 Medical的CIED信封在根除抗性细菌菌株，真菌和生物膜中的功效将导致 在发病率和死亡率，感染相关并发症降低以及 减少需要其他干预措施的需求。