MethLock vs. heparin as dialysis catheter lock

MethLock 与肝素作为透析导管锁

• 批准号: 6935046
• 负责人: STEPHEN R ASH
• 金额: $ 10万
• 依托单位: ASH ACCESS TECHNOLOGY, INC.
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-01 至 2006-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6935046
• 关键词: antibacterial agents; anticoagulants; blood circulation; blood disorder; cardiovascular disorder prevention; catheterization; chemoprevention; chronic renal failure; clinical research; clinical trial phase III; drug screening /evaluation; hemodialysis; hemodynamics; heparin; human subject; human therapy evaluation; infection; patient oriented research; postoperative complications; septicemia

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.

描述（由申请人提供）：目前约有25％的血液透析治疗患者用于末期肾脏疾病（ESRD）通过隧道的透析中心静脉导管接受透析（CVCD）。这些导管的标准抗凝锁是肝素，该肝素没有抗菌特性。使用CVCD进入的ESRD患者的最大风险是导管相关的血液感染（CRBSI），并且经常进展为败血症。 Methlock（TM）是由甲基蓝（一种抗菌物质）和柠檬酸钠（7％，抗凝剂）组成的导管锁。甲锁的体外研究表明，即使存在稀释的血液或培养基，它也对所有细菌都是杀菌性的。 I阶段和第二阶段赠款的应用将支持甲基锁对肝素作为隧道CVCD中导管锁的安全性和有效性的多中心随机试验。该协议已获得FDA的批准，并授予了IDE进行ime锁进行试验。主要终点是CRBSI（从外周血和导管管腔中得出的一致细菌培养物）和导管的去除以进行通畅失败（证明透析期间至少降低了25％的流量下降25％，而基线治疗中的流量降低了25％）。每位患者最多可持续6个月，研究的大小（400名患者）将提供足够的数据，以证明MECH锁是否降低了CRBSI与肝素的发病率是否降低了导管的标准，同时保持了等于肝素。该研究的终点是客观的，易于定义，但在CVCD或导管锁的全尺度临床试验中尚未得到验证。在第一阶段，我们将在一个透析中心（一个“试点”中心）上实施该方案，以确定试验的实用性，分析：患者入学率的易度性，不良事件的识别速度以及我们确定的终点和员工在CVCD上的终端点和临床干预之间的一般相关性。第一阶段之后，我们将确定是否需要修改协议，以及是否需要从FDA请求修改协议。在第二阶段，我们将在许多透析中心中实施该方案，并按照最初提出的或修改。