MethLock vs. heparin as dialysis catheter lock

描述（由申请人提供）：目前约有25%的终末期肾病（ESRD）患者通过中心静脉导管透析（CVCD）接受血液透析治疗。这些导管的标准抗凝剂是肝素，它没有抗菌特性。使用CVCDs的ESRD患者的最大风险是导管相关血流感染（CRBSI），并经常发展为败血症。MethLock（tm）是一种导管锁，由亚甲蓝（一种抗菌物质）和柠檬酸钠（7%，一种抗凝剂）组成。对MethLock的体外研究表明，它对所有细菌都有杀菌作用，即使在稀释的血液或培养基中也是如此。该I期和II期资助申请将支持一项多中心随机试验，研究MethLock与肝素作为导管锁在隧道性心血管疾病中的安全性和有效性。该方案已经获得了FDA的批准，MethLock也获得了IDE的批准。主要终点是CRBSI（从外周血和导管腔中提取的一致性细菌培养物）和因通畅失败而移除导管（在证明透析期间流速比基线治疗至少降低25%之后）。每位患者将被随访长达6个月，该研究的规模（400例患者）将提供足够的数据来证明MethLock是否降低了与肝素相比CRBSI的发生率，同时维持了与肝素相同的导管通畅。该研究的终点是客观且易于定义的，但尚未在cvd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（一个“试点”中心）实施该方案，以确定试验的实用性，分析：患者入组的难易程度，不良事件的识别速度，以及我们定义的终点与cvcd工作人员临床干预之间的一般相关性。在第一阶段之后，我们将确定是否需要修改方案，如果需要，我们将向FDA申请修改方案。在第二阶段，我们将在一些透析中心实施该方案，并按照最初的建议或在第一阶段后修改的方法完成研究。

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.