MethLock vs. heparin as dialysis catheter lock

目前约有25%的终末期肾病患者接受血液透析治疗。 通过隧道中心静脉导管进行透析(CVCD)。标准 这些导管的抗凝剂锁是肝素，它没有抗菌特性。这个 使用CVCDs的终末期肾病患者最大的风险是导管相关的血流感染； (CRBSI)，并经常进展为败血症。方法锁是一种导尿管锁，包括 亚甲蓝(一种抗菌物质)和柠檬酸钠(7%，一种抗凝剂)。体外培养； 对MethLock的研究表明，它对所有细菌都有杀菌作用，即使在 稀释的血液或培养液。此第一阶段和第二阶段拨款将支持多中心 MethLock与肝素作为导管锁定的安全性和有效性的随机试验 隧道CVCD。该协议已经得到了FDA的批准，并为用于 审判。主要终点是CRBSI(从外周提取的一致细菌培养物 血液和导管管腔)，以及因通畅失败而拔除导管(在演示之后 与基线治疗相比，透析过程中的流速至少下降了25%)。每个病人都会 被跟踪长达6个月，研究的规模(400名患者)将提供足够的数据来 证明与肝素相比，方法锁是否降低CRBSI的发生率，同时维持 导管的通畅度等于肝素。研究的终点是客观的，而且很容易定义 但尚未在CVCD或导管锁的全面临床试验中得到验证。在第一阶段，我们将 在一个透析中心(试点中心)实施该方案，以确定 试验，分析：患者登记的简易性，不良事件的识别速度，以及 我们定义的终点与工作人员对CVCDS的临床干预之间的总体相关性。 在第一阶段之后，我们将确定是否需要修改协议，如果需要，将请求 食品和药物管理局的方案修改。在第二阶段，我们将在以下几个方面实施该协议 并按照最初的建议或第一阶段后的修改完成研究。

Currently about 25% of patients on hemodialysis therapy for End Stage Renal Disease (ESRD) receive dialysis through tunneled central venous catheters for dialysis (CVCD). The standard anticoagulant lock for these catheters is heparin, which has no antibacterial properties. The greatest risk for ESRD patients using CVCDs access is catheter related bloodstream infection ; (CRBSI), with frequent progression to sepsis. MethLock ¿ is a catheter lock comprised of methylene blue (an antibacterial substance) and sodium citrate (7%, an anticoagulant). In vitro ; studies of MethLock have shown that it is bactericidal for all bacteria, even in the presence of diluted blood or culture medium. This Phase I and Phase II grant will support a multicenter randomized trial of the safety and effectiveness of MethLock versus heparin as a catheter lock in tunneled CVCD. The protocol has been approved by the FDA and an IDE granted for MethLock for the trial. The primary endpoints are CRBSI (concordant bacterial culture drawn from peripheral blood and the catheter lumen) and removal of the catheter for patency failure (after demonstration of at least 25% decrease in flow rate during dialysis versus a baseline treatment). Each patient will be followed for up to 6 months, and the size of the study (400 patients) will provide enough data to demonstrate whether MethLock decreases the incidence CRBSI versus heparin while maintaining patency of catheters equal to heparin. The endpoints of the study are objective and easily definable but have not been validated in a full-scale clinical trial of CVCD or catheter lock. In Phase Iwe will implement the protocol at one dialysis center (a "pilot" center) to determine the practicality of the trial, analyzing: the ease of patient enrollment, speed of identification of adverse events, and the general correlation between our defined endpoints and clinical interventions by staff on theCVCDs. After Phase I we will determine whether the protocol needs to be modified and if so will request protocol modifications from the FDA. In Phase II we will implement the protocol in a number of dialysis centers and complete the study as originally proposed or as modified after Phase I.