MethLock vs. heparin as dialysis catheter lock

描述(申请人提供)：目前，约25%的终末期肾病(ESRD)血液透析患者通过隧道中心静脉导管透析(CVCD)进行透析。这些导管的标准抗凝剂锁是肝素，它没有抗菌特性。对于使用CVCDs通路的终末期肾病患者来说，最大的风险是导管相关性血流感染(CRBSI)，并经常进展为脓毒症。方法Lock(Tm)是一种由亚甲蓝(抗菌物质)和柠檬酸钠(7%，抗凝剂)组成的导尿管锁。体外研究表明，MethLock对所有细菌都有杀菌作用，即使是在稀释的血液或培养液中也是如此。这项第一阶段和第二阶段的赠款申请将支持一项多中心随机试验，以比较在隧道CVCD中使用MethLock和肝素作为导管锁的安全性和有效性。该协议已经得到FDA的批准，并获得了用于该试验的集成开发环境的批准。主要终点是CRBSI(从外周血液和导管管腔中提取一致的细菌培养)和因通畅失败而拔除导管(在证明透析期间流量与基线治疗相比至少减少25%后)。每名患者将接受长达6个月的跟踪调查，这项研究的规模(400名患者)将提供足够的数据来证明，与肝素相比，MethLock是否降低了CRBSI的发生率，同时保持导管的通畅性与肝素相同。这项研究的终点是客观的，很容易定义，但尚未在CVCD或导管锁定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，以确定试验的实用性，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在CVCD上进行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方案，如果需要，将向FDA请求修改方案。在第二阶段，我们将在一些透析中心实施该方案，并按照最初的提议或第一阶段后的修改完成研究。

DESCRIPTION (provided by applicant): Currently about 25% of patients on hemodialysis therapy for End Stage Renal Disease (ESRD) receives 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(tm) 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 application will support a multi-center 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 I we 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 the CVCDs. 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.