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（由申请方提供）：目前，约25%接受终末期肾病（ESRD）血液透析治疗的患者通过隧道中心静脉透析导管（CVCD）接受透析。这些导管的标准抗凝剂锁是肝素，其没有抗菌特性。使用CVCD通路的ESRD患者的最大风险是导管相关血流感染（CRBSI），经常进展为败血症。MethLock（TM）是一种由亚甲蓝（抗菌物质）和柠檬酸钠（7%，抗凝剂）组成的导管锁。MethLock的体外研究表明，它对所有细菌都具有杀菌作用，即使在稀释的血液或培养基中也是如此。这项I期和II期拨款申请将支持一项多中心随机试验，评估MethLock与肝素作为隧道CVCD中导管锁的安全性和有效性。该方案已获得FDA批准，并为MethLock的试验授予IDE。主要终点是CRBSI（从外周血和导管腔中采集的一致细菌培养物）和因通畅性失败而取出导管（在证明透析期间的流速与基线治疗相比至少降低25%后）。将对每例患者进行长达6个月的随访，研究规模（400例患者）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。本研究的终点客观且易于定义，但尚未在CVCD或导管锁定的全面临床试验中得到验证。在I期，我们将在一个透析中心（“试点”中心）实施方案，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工作人员对CVCD进行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，将要求FDA修改方案。在II期，我们将在一些透析中心实施方案，并按照最初拟定或I期后修改的方案完成研究。