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Eculizumab for Prevention of Delayed Graft Function (DGF) in Kidney Transplantation

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01919346
Recruitment Status : Terminated (Based on results from Alexion PROTECT DGF study)
First Posted : August 9, 2013
Last Update Posted : February 27, 2018
Sponsor:
Collaborators:
Alexion Pharmaceuticals
Icahn School of Medicine at Mount Sinai
Information provided by (Responsible Party):
Heeger, Peter, M.D.

Tracking Information
First Submitted Date  ICMJE August 7, 2013
First Posted Date  ICMJE August 9, 2013
Last Update Posted Date February 27, 2018
Study Start Date  ICMJE August 2013
Actual Primary Completion Date December 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 7, 2013)
Hemodialysis [ Time Frame: 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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 11, 2014)
  • Estimated Glomerular Filtration Rate (GFR) [ Time Frame: 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
  • Hemodialysis [ Time Frame: 8 weeks post-transplantation ]
    Number of dialysis sessions at 30 days and 8 weeks post-transplantation
  • Primary Non-function [ Time Frame: 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 [ Time Frame: 6 months post-transplantation ]
    Incidence of graft rejection within 6 months
  • Patient Survival [ Time Frame: 12 months post-transplantation ]
    Patient survival at 12 months post-transplantation
  • Graft Survival [ Time Frame: 12 months post-transplantation ]
    Death censored graft survival at 12 months post-transplantation
  • Serum Creatinine [ Time Frame: 3 days post-transplantation ]
    Change from baseline in serum creatinine and serum creatinine concentration at 24, 48 and 72 hours post-transplantation
  • Urine Output [ Time Frame: 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 [ Time Frame: 6 months post-transplantation ]
    Absolute levels of biomarkers associated with acute renal injury
  • Qualified Delayed Graft Function (qDGF) [ Time Frame: 7 days post-transplantation ]
    The incidence of qDGF defined as the requirement for dialysis for any reason in the first 7 days post-transplantation
Original Secondary Outcome Measures  ICMJE
 (submitted: August 7, 2013)
  • Estimated Glomerular Filtration Rate (GFR) [ Time Frame: 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
  • Hemodialysis [ Time Frame: 8 weeks post-transplantation ]
    Number of dialysis sessions in the 8 weeks post-transplantation period
  • Primary Non-function [ Time Frame: 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 [ Time Frame: 6 months post-transplantation ]
    Incidence of graft rejection within 6 months
  • Patient Survival [ Time Frame: 12 months post-transplantation ]
    Patient survival at 12 months post-transplantation
  • Graft Survival [ Time Frame: 12 months post-transplantation ]
    Death censored graft survival at 12 months post-transplantation
  • Serum Creatinine [ Time Frame: 3 days post-transplantation ]
    Change from baseline in serum creatinine and serum creatinine concentration at 24, 48 and 72 hours post-transplantation
  • Urine Output [ Time Frame: 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 [ Time Frame: 6 months post-transplantation ]
    Absolute levels of biomarkers (Ngal, Kim-1, IL-18) associated with acute renal injury
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Eculizumab for Prevention of Delayed Graft Function (DGF) in Kidney Transplantation
Official Title  ICMJE Eculizumab for Prevention of Delayed Graft Function in Deceased Donor Kidney Transplantation
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE
  • Delayed Graft Function
  • Kidney Transplantation
  • Complement Activity
Intervention  ICMJE
  • Drug: Eculizumab
    Other Name: Soliris
  • Drug: Normal Saline
Study Arms  ICMJE
  • Experimental: 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
    Intervention: Drug: Eculizumab
  • Placebo Comparator: Normal Saline
    Administered at same volume and time as Experimental arm
    Intervention: Drug: Normal Saline
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: February 23, 2018)
21
Original Estimated Enrollment  ICMJE
 (submitted: August 7, 2013)
24
Actual Study Completion Date  ICMJE December 2017
Actual Primary Completion Date December 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01919346
Other Study ID Numbers  ICMJE 13-0920
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Heeger, Peter, M.D.
Study Sponsor  ICMJE Heeger, Peter, M.D.
Collaborators  ICMJE
  • Alexion Pharmaceuticals
  • Icahn School of Medicine at Mount Sinai
Investigators  ICMJE
Principal Investigator: Peter S Heeger, MD Icahn School of Medicine at Mount Sinai
PRS Account Heeger, Peter, M.D.
Verification Date February 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP