Eculizumab for Prevention of Delayed Graft Function in Deceased Donor Kidney Transplantation
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 21
- 试验地点
- 5
- 主要终点
- Hemodialysis
研究概览
简要总结
The purpose of this study is to evaluate the efficacy of Eculizumab in the prevention of Delayed Graft Function following deceased donor kidney transplantation. Based on experimental data and supportive observations in humans associating complement gene upregulation with ischemic reperfusion (IR) injury, it is hypothesized that C5 cleavage is a key step in the pathogenesis of ischemic reperfusion injury following transplantation. It is further hypothesized that Eculizumab, a humanized monoclonal antibody that blocks C5 cleavage in humans will be an effective prophylactic agent to prevent IR injury in high risk recipients. This trial is a prospective, randomized study to test the efficacy of eculizumab vs. placebo given once at the time of transplantation and once again 24 hours later in preventing delayed graft function in first adult recipients of deceased donor kidneys.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18 years or older
- •Weight > 40 kg
- •Male or Female
- •Recipient of first deceased donor kidney
- •Able to provide written informed consent
- •Transplant candidate as per site specific guidelines
- •Dialysis dependent renal failure (initiated more than 2 months prior to transplant)
- •Recipients of kidneys defined as:
- •Extended Criteria Donor (ECD) kidney with brain death: Kidney donors 60 years of age or older; or donors aged 50-59 years and have two of the following features: Hypertension, terminal serum creatinine > 1.5 mg/dL, or death from cerebrovascular accident (CVA), OR
- •Standard Criteria Donor (SCD) kidney with actual cold ischemia time (CIT) 18 - 40 hours
排除标准
- •Patient is planned to receive a multi-organ transplant
- •Kidney from donor < 6 years of age
- •Dual kidney transplant (from same donor, including en bloc)
- •Living donor kidney transplant
- •Recipients with donor-specific anti-HLA antibodies of more than 3,000 MFI
- •Participation in another investigational drug study
- •Recipient BMI > 40
- •ABO incompatible
- •DCD (donor with cardiac death) Donor
- •Women who are pregnant or breast-feeding
- •Women of child bearing potential who are unable or unwilling to use a medically acceptable form of contraception (defined as the use of oral, injected or implanted hormonal methods of contraception, intrauterine device (IUD)or intrauterine system (IUS), barrier methods of contraception (condom or occlusive cap with spermicidal foam/gel/film/cream/suppository)
- •Patients with HBsAg-positive status, HCV infection, or HIV infection
- •Patients with atypical hemolytic uremic syndrome (aHUS) or C3 glomerulonephritis (C3GN)
- •Active bacterial or other infection which is clinically significant in the opinion of the investigator
- •Patients with history of splenectomy
- •Patients with history of meningococcal disease
- •Patients allergic to or unable to tolerate Ciprofloxacin
- •Patients unable or unwilling to receive vaccination against meningitis prior to study drug administration
- •Patients with a known or suspected hereditary complement deficiency
- •Patients with a history of cancer (other than non melanoma skin cancers) within the last five years
- •Donors of more than 70 years of age
- •Subjects with a psychiatric or physical illness which in the opinion of the Investigator would interfere with their ability to participate in the study.
研究组 & 干预措施
Eculizumab
Eculizumab 1200 mg (diluted in Sodium Chloride (NaCl) to 5mg/mL, volume = 240 mL) will be given intraoperatively at the time of transplantation prior to reperfusion of the renal allograft and again at 900 mg (diluted in NaCl to 5mg/mL, volume = 180 mL) 12-24 hours post-transplantation
干预措施: Eculizumab (Drug)
Normal Saline
Administered at same volume and time as Experimental arm
干预措施: Normal Saline (Drug)
结局指标
主要结局
Hemodialysis
时间窗: 7 days post-transplantation
The need of at least one dialysis treatment during the first 7 days after transplantation excluding: (i) requirement for a single dialysis session indicated for hyperkalemia (ii) hyperacute rejection, renal arterial and/or venous thrombosis, obstructive uropathy, recurrence of primary disease, and early thrombotic microangiopathy
次要结局
- Estimated Glomerular Filtration Rate (GFR)(6 months post-transplantation)
- Hemodialysis(8 weeks post-transplantation)
- Primary Non-function(8 weeks post-transplantation)
- Graft Rejection(6 months post-transplantation)
- Patient Survival(12 months post-transplantation)
- Graft Survival(12 months post-transplantation)
- Biomarkers(6 months post-transplantation)
- Qualified Delayed Graft Function (qDGF)(7 days post-transplantation)
- Serum Creatinine(3 days post-transplantation)
- Urine Output(3 days post-transplantation)