Complement Activity, Delayed Graft Function, Kidney Transplantation
Conditions
Keywords
Kidney Transplantation, Delayed Graft Function
Brief summary
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.
Interventions
DRUGEculizumab
DRUGNormal Saline
Sponsors
Alexion Pharmaceuticals, Inc.
Icahn School of Medicine at Mount Sinai
Heeger, Peter, M.D.
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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: 1. 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 2. Standard Criteria Donor (SCD) kidney with actual cold ischemia time (CIT) 18 - 40 hours
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hemodialysis | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hemodialysis | 8 weeks post-transplantation | Number of dialysis sessions at 30 days and 8 weeks post-transplantation |
| Primary Non-function | 8 weeks post-transplantation | The incidence of primary non-function (PNF) defined as the need for dialysis-dependency for more than 8 weeks |
| Graft Rejection | 6 months post-transplantation | Incidence of graft rejection within 6 months |
| Patient Survival | 12 months post-transplantation | Patient survival at 12 months post-transplantation |
| Estimated Glomerular Filtration Rate (GFR) | 6 months post-transplantation | Estimated GFR as determined from the 4-variable MDRD (Modified Diet in Renal Disease) equation on days 7, 30, 90 and 180 post-transplantation |
| Serum Creatinine | 3 days post-transplantation | Change from baseline in serum creatinine and serum creatinine concentration at 24, 48 and 72 hours post-transplantation |
| Urine Output | 3 days post-transplantation | Percentage of patients with total 24-hour urine output of more than 500 mL on post-transplantation days 2 and 3 |
| Biomarkers | 6 months post-transplantation | Absolute levels of biomarkers associated with acute renal injury |
| Qualified Delayed Graft Function (qDGF) | 7 days post-transplantation | The incidence of qDGF defined as the requirement for dialysis for any reason in the first 7 days post-transplantation |
| Graft Survival | 12 months post-transplantation | Death censored graft survival at 12 months post-transplantation |
Countries
United States
Outcome results
None listed