MethLock vs. heparin as dialysis catheter lock

目前，约25%的终末期肾病（ESRD）患者接受血液透析治疗 通过隧道式中心静脉透析导管（CVCD）接受透析。标准 用于这些导管的抗凝剂锁是肝素，其没有抗菌特性。的 使用CVCD通路的ESRD患者的最大风险是导管相关血流感染; （CRBSI），经常进展为脓毒症。MethLock <$是一种导管锁，由 亚甲蓝（抗菌物质）和柠檬酸钠（7%，抗凝剂）。体外; 对MethLock的研究表明，它对所有细菌都有杀菌作用，即使在存在 稀释的血液或培养基。第一阶段和第二阶段赠款将支持多中心 一项比较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该方案已获得FDA批准，MethLock获得IDE， 庭审主要终点是CRBSI（从外周血中采集的一致细菌培养物）。 血液和导管腔）和因通畅性失败而移除导管（在演示之后 与基线治疗相比，透析期间流速降低至少25%）。每例患者将 随访长达6个月，研究规模（400例患者）将提供足够的数据， 证明与肝素相比，MethLock是否能降低CRBSI的发生率， 导管的通畅性与肝素相同。研究的终点是客观的，易于定义 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， 在一个透析中心（“试点”中心）实施方案，以确定 试验，分析：患者入组的难易程度，不良事件的识别速度， 我们定义的终点与工作人员对CVCD进行的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，我们将要求 FDA的方案修改。在第二阶段，我们将在一些国家实施该议定书， 透析中心，并按照最初拟定或I期后修改的方案完成研究。

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.