search
Back to results

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

Primary Purpose

Delayed Graft Function, Kidney Transplantation, Complement Activity

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Eculizumab
Normal Saline
Sponsored by
Heeger, Peter, M.D.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Delayed Graft Function focused on measuring Kidney Transplantation, Delayed Graft Function

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Yale - New Haven Hospital
  • Icahn School of Medicine at Mount Sinai
  • Montefiore Medical Center
  • University Hospitals Case Medical Center
  • Hospital of the University of Pennsylvania

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Eculizumab

Normal Saline

Arm Description

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

Administered at same volume and time as Experimental arm

Outcomes

Primary Outcome Measures

Hemodialysis
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 Outcome Measures

Estimated Glomerular Filtration Rate (GFR)
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
Number of dialysis sessions at 30 days and 8 weeks post-transplantation
Primary Non-function
The incidence of primary non-function (PNF) defined as the need for dialysis-dependency for more than 8 weeks
Graft Rejection
Incidence of graft rejection within 6 months
Patient Survival
Patient survival at 12 months post-transplantation
Graft Survival
Death censored graft survival at 12 months post-transplantation
Serum Creatinine
Change from baseline in serum creatinine and serum creatinine concentration at 24, 48 and 72 hours post-transplantation
Urine Output
Percentage of patients with total 24-hour urine output of more than 500 mL on post-transplantation days 2 and 3
Biomarkers
Absolute levels of biomarkers associated with acute renal injury
Qualified Delayed Graft Function (qDGF)
The incidence of qDGF defined as the requirement for dialysis for any reason in the first 7 days post-transplantation

Full Information

First Posted
August 7, 2013
Last Updated
February 23, 2018
Sponsor
Heeger, Peter, M.D.
Collaborators
Alexion, Icahn School of Medicine at Mount Sinai
search

1. Study Identification

Unique Protocol Identification Number
NCT01919346
Brief Title
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

2. Study Status

Record Verification Date
February 2018
Overall Recruitment Status
Terminated
Why Stopped
Based on results from Alexion PROTECT DGF study
Study Start Date
August 2013 (undefined)
Primary Completion Date
December 2017 (Actual)
Study Completion Date
December 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Heeger, Peter, M.D.
Collaborators
Alexion, Icahn School of Medicine at Mount Sinai

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Delayed Graft Function, Kidney Transplantation, Complement Activity
Keywords
Kidney Transplantation, Delayed Graft Function

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
21 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Eculizumab
Arm Type
Experimental
Arm Description
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
Arm Title
Normal Saline
Arm Type
Placebo Comparator
Arm Description
Administered at same volume and time as Experimental arm
Intervention Type
Drug
Intervention Name(s)
Eculizumab
Other Intervention Name(s)
Soliris
Intervention Type
Drug
Intervention Name(s)
Normal Saline
Primary Outcome Measure Information:
Title
Hemodialysis
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
Time Frame
7 days post-transplantation
Secondary Outcome Measure Information:
Title
Estimated Glomerular Filtration Rate (GFR)
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
Time Frame
6 months post-transplantation
Title
Hemodialysis
Description
Number of dialysis sessions at 30 days and 8 weeks post-transplantation
Time Frame
8 weeks post-transplantation
Title
Primary Non-function
Description
The incidence of primary non-function (PNF) defined as the need for dialysis-dependency for more than 8 weeks
Time Frame
8 weeks post-transplantation
Title
Graft Rejection
Description
Incidence of graft rejection within 6 months
Time Frame
6 months post-transplantation
Title
Patient Survival
Description
Patient survival at 12 months post-transplantation
Time Frame
12 months post-transplantation
Title
Graft Survival
Description
Death censored graft survival at 12 months post-transplantation
Time Frame
12 months post-transplantation
Title
Serum Creatinine
Description
Change from baseline in serum creatinine and serum creatinine concentration at 24, 48 and 72 hours post-transplantation
Time Frame
3 days post-transplantation
Title
Urine Output
Description
Percentage of patients with total 24-hour urine output of more than 500 mL on post-transplantation days 2 and 3
Time Frame
3 days post-transplantation
Title
Biomarkers
Description
Absolute levels of biomarkers associated with acute renal injury
Time Frame
6 months post-transplantation
Title
Qualified Delayed Graft Function (qDGF)
Description
The incidence of qDGF defined as the requirement for dialysis for any reason in the first 7 days post-transplantation
Time Frame
7 days post-transplantation

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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: 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 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Peter S Heeger, MD
Organizational Affiliation
Icahn School of Medicine at Mount Sinai
Official's Role
Principal Investigator
Facility Information:
Facility Name
Yale - New Haven Hospital
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06540
Country
United States
Facility Name
Icahn School of Medicine at Mount Sinai
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Montefiore Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Facility Name
University Hospitals Case Medical Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Hospital of the University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs