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.
Brief Title
Eculizumab for Prevention of Delayed Graft Function (DGF) in Kidney Transplantation
Categories
Completion Date
Completion Date Type
Actual
Conditions
Delayed Graft Function
Kidney Transplantation
Complement Activity
Eligibility Criteria
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.
* 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.
Inclusion Criteria
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
* 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
Gender
All
Gender Based
false
Keywords
Kidney Transplantation
Delayed Graft Function
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT01919346
Org Class
Indiv
Org Full Name
Heeger, Peter, M.D.
Org Study Id
13-0920
Overall Status
Terminated
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
Eculizumab for Prevention of Delayed Graft Function in Deceased Donor Kidney Transplantation
Primary Outcomes
Outcome Description
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
Outcome Measure
Hemodialysis
Outcome Time Frame
7 days post-transplantation
Secondary Outcomes
Outcome Description
Estimated GFR as determined from the 4-variable MDRD (Modified Diet in Renal Disease) equation on days 7, 30, 90 and 180 post-transplantation
Outcome Time Frame
6 months post-transplantation
Outcome Measure
Estimated Glomerular Filtration Rate (GFR)
Outcome Description
Number of dialysis sessions at 30 days and 8 weeks post-transplantation
Outcome Time Frame
8 weeks post-transplantation
Outcome Measure
Hemodialysis
Outcome Description
The incidence of primary non-function (PNF) defined as the need for dialysis-dependency for more than 8 weeks
Outcome Time Frame
8 weeks post-transplantation
Outcome Measure
Primary Non-function
Outcome Description
Incidence of graft rejection within 6 months
Outcome Time Frame
6 months post-transplantation
Outcome Measure
Graft Rejection
Outcome Description
Patient survival at 12 months post-transplantation
Outcome Time Frame
12 months post-transplantation
Outcome Measure
Patient Survival
Outcome Description
Death censored graft survival at 12 months post-transplantation
Outcome Time Frame
12 months post-transplantation
Outcome Measure
Graft Survival
Outcome Description
Change from baseline in serum creatinine and serum creatinine concentration at 24, 48 and 72 hours post-transplantation
Outcome Time Frame
3 days post-transplantation
Outcome Measure
Serum Creatinine
Outcome Description
Percentage of patients with total 24-hour urine output of more than 500 mL on post-transplantation days 2 and 3
Outcome Time Frame
3 days post-transplantation
Outcome Measure
Urine Output
Outcome Description
Absolute levels of biomarkers associated with acute renal injury
Outcome Time Frame
6 months post-transplantation
Outcome Measure
Biomarkers
Outcome Description
The incidence of qDGF defined as the requirement for dialysis for any reason in the first 7 days post-transplantation
Outcome Time Frame
7 days post-transplantation
Outcome Measure
Qualified Delayed Graft Function (qDGF)
Start Date
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Enver Akalin
Investigator Email
eakalin@montefiore.org
Investigator Phone
718-920-4815