Unique Clinical Study on DGF Using Paired Kidneys

使用配对肾脏进行 DGF 的独特临床研究

• 批准号: 8244441
• 负责人: WEIZHONG CAI
• 金额: $ 66.47万
• 依托单位: ANGION BIOMEDICA CORPORATION
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-02-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8244441
• 关键词: 3-Dimensional; Academic Medical Centers; Acute; Adult; Applications Grants; Attenuated; Biological Assay; Biological Markers; Biology; Cardiac Death; Cell Death; Cessation of life; Chronic; Chronic rejection of renal transplant; Clinical; Clinical Research; Clinical Trials; Collection; Country; Creatinine clearance measurement; Data; Development; Dialysis procedure; Dose; Dose-Limiting; Double-Blind Method; Drug Kinetics; Eligibility Determination; End stage renal failure; Enrollment; European Union; Evaluation; Exhibits; Experimental Models; Functional disorder; Funding; Genes; Grant; Growth Factor; Half-Life; Hemodialysis; Hepatocyte Growth Factor; Hour; Immune; Impairment; Incidence; Infusion procedures; Injury; Kidney; Kidney Transplantation; Length; Mediating; Medical; Modality; Modeling; Molecular Models; Morbidity - disease rate; Netherlands; Organ Donations; Outcome; Output; Patients; Phage Display; Pharmaceutical Preparations; Phase; Phase I Clinical Trials; Phase III Clinical Trials; Pilot Projects; Placebo Control; Placebos; Population; Population Study; Production; Protein Chemistry; Proteins; Proto-Oncogene Protein c-met; Randomized; Recruitment Activity; Renal Replacement Therapy; Renal function; Reperfusion Injury; Reperfusion Therapy; Reporting; Risk; Safety; Scheme; Site; Small Business Innovation Research Grant; Source; Specific qualifier value; Testing; Therapeutic; Time; Tissues; Toxic effect; Transplantation; United States National Institutes of Health; Urine; Variant; base; clinical application; clinical research site; cohort; cost; cost effective; delayed graft function; design; graft function; healthy volunteer; high risk; improved; in vivo; in vivo Model; kidney cell; meetings; mimetics; molecular modeling; mortality; pre-clinical; programs; public health relevance; renal ischemia; repaired; response; small molecule

DESCRIPTION: Renal transplantation is the most effective and cost-efficient form of renal replacement therapy for a burgeoning population that presents with end-stage renal disease. Although organ donation has become a national priority, the gap between the number of patients awaiting a kidney vs. the number of available kidneys continues to widen exponentially. In many countries within the European Union, utilization of "donation after cardiac death" (DCD) kidneys is steadily increasing, expanding the donor pool by >50%. Given the high incidence of cardiac deaths in this country, aggressive pursuit of the DCD kidney pool could potentially reduce waitlist periods to months, if not days. Risk for delayed graft function (DGF) with the attendant risks for increased recipient morbidity, chronic allograft nephropathy and increased medical costs has however tempered DCD kidney utilization in this country. Development of strategies that limit normothermic reperfusion injury, promote renal repair, reduce the incidence and/or duration of DGF and improve long-term outcome can greatly enhance acceptance and recruitment of DCD kidneys. Angion Biomedica is developing BB3, a small molecule hepatocyte growth factor mimetic that exhibits significant tissue protective activity in numerous models of acute renal injury. Importantly, this small molecule has completed clinical safety trials in both healthy volunteers and in patients with renal impairment. The present proposal is a pilot evaluation of safety and efficacy of intravenously administered BB3 in recipients of kidneys from DCD donors who are risk for developing DGF. This trial, to be conducted at Maastricht University Medical Center in the Netherlands, is unique in that it compares drug vs. placebo outcome in kidney recipients from the same donor with direct evaluation of function (creatinine clearance) in the graft. Results from this pilot study will form the basis of conducting a large multi-center Phase III trial evaluating efficacy and safety of BB3 in DCD kidney recipients at risk for DGF. Successful completion of these trials will more than likely change the kidney donor recruitment landscape here in the US. PUBLIC HEALTH RELEVANCE: The proposed study has significant clinical ramifications. A small molecule that improves post-transplantation function and outcome in higher risk donor kidneys can potentially increase the donor pool thereby reducing significantly the number of deaths in patients awaiting kidney transplant.

产品说明：肾移植是最有效和最具成本效益的形式肾脏替代治疗的新兴人口，提出了终末期肾病。虽然器官捐献已成为国家的优先事项，但等待肾脏的患者数量与可用肾脏数量之间的差距继续呈指数级扩大。在欧盟的许多国家，“心源性死亡后捐献”（DCD）肾脏的利用率稳步上升，使供体库扩大了50%以上。考虑到这个国家心脏病死亡的高发病率，积极追求DCD肾脏库可能会将等待时间缩短到几个月，如果不是几天的话。然而，移植肾功能延迟恢复（DGF）的风险以及随之而来的受体发病率增加、慢性移植肾肾病和医疗费用增加的风险已经缓和了该国DCD肾的利用。制定限制常温再灌注损伤、促进肾修复、减少DGF发生率和/或持续时间并改善长期结局的策略，可以大大提高DCD肾脏的接受和募集。Angion Biomedica正在开发BB 3，这是一种小分子肝细胞生长因子模拟物，在许多急性肾损伤模型中表现出显著的组织保护活性。重要的是，这种小分子已经在健康志愿者和肾损害患者中完成了临床安全性试验。本提案是一项初步评估静脉注射BB 3在DCD供体肾脏受者中的安全性和有效性，这些供体有发生DGF的风险。这项试验将在荷兰的马斯特里赫特大学医学中心进行，其独特之处在于，它通过直接评估移植物的功能（肌酐清除率），比较了来自同一供体的肾受体中药物与安慰剂的结局。这项初步研究的结果将构成进行大型多中心III期试验的基础，该试验评价BB 3在有DGF风险的DCD肾接受者中的疗效和安全性。这些试验的成功完成将很有可能改变美国肾脏捐献者的招募情况。 公共卫生相关性：拟议的研究具有重要的临床影响。改善高风险供体肾脏移植后功能和结果的小分子可能会增加供体库，从而显著减少等待肾移植患者的死亡人数。