Clinical trial NCT01919346: Eculizumab for Prevention of Delayed Graft Function (DGF) in Kidney Transplantation
Official title: Eculizumab for Prevention of Delayed Graft Function in Deceased Donor Kidney Transplantation
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Delayed Graft Function
Kidney Transplantation
Complement Activity
Keywords: Kidney Transplantation
Delayed Graft Function
Lead sponsor: Heeger, Peter, M.D.
Sponsor class: INDIV
Collaborators: name: Alexion Pharmaceuticals, Inc.
name: Icahn School of Medicine at Mount Sinai
First posted: 2013-08-09
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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.


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.

Primary outcomes:
measure: Hemodialysis
timeFrame: 7 days post-transplantation
Secondary outcomes:
measure: Estimated Glomerular Filtration Rate (GFR)
timeFrame: 6 months post-transplantation
measure: Hemodialysis
timeFrame: 8 weeks post-transplantation
measure: Primary Non-function
timeFrame: 8 weeks post-transplantation
measure: Graft Rejection
timeFrame: 6 months post-transplantation
measure: Patient Survival
timeFrame: 12 months post-transplantation
measure: Graft Survival
timeFrame: 12 months post-transplantation
measure: Serum Creatinine
timeFrame: 3 days post-transplantation
measure: Urine Output
timeFrame: 3 days post-transplantation
measure: Biomarkers
timeFrame: 6 months post-transplantation
measure: Qualified Delayed Graft Function (qDGF)
timeFrame: 7 days post-transplantation
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale - New Haven Hospital
state: Connecticut
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: New York
country: United States
facility: Montefiore Medical Center
state: New York
city: Cleveland
country: United States
facility: University Hospitals Case Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Peter S Heeger, MD
role: PRINCIPAL_INVESTIGATOR
References: