Eculizumab for Prevention and Treatment of Kidney Graft Reperfusion Injury

Study Overview
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Brief Summary
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Study of eculizumab ability to correct the reperfusion injury of the kidney allograft.

Detailed Description
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Based on experimental data and supportive observations in humans associating complement gene upregulation with ischemic reperfusion injury, it is hypothesized that C5 cleavage is a key step in the pathogenesis of ischemic reperfusion injury following transplantation. It was further hypothesized that eculizumab, antibody that blocks C5 cleavage in humans will be an effective prophylactic agent to prevent ischemic reperfusion injury in high risk recipients. For testing this hypothesis, this study is a pilot prospective study to test the efficacy of eculizumab in preventing the development of reperfusion injury and contribute graft survival.

Official Title
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Study of Eculizumab for Prevention and Treatment Reperfusion Injury in Kidney Transplantation.

Conditions
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End-Stage Renal Disease, Kidney Failure, Graft Reperfusion Injury

Intervention / Treatment
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* Drug: eculizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age 1-80 weight - >6 kg male or female recipient of first kidney graft either from standard criteria deceased or live donor end stage renal disease or congenital nephrotic syndrome - Exclusion Criteria: Blood group (ABO) incompatible transplantation presence of donor-specific anti-human leukocyte antigen (HLA) antibodies multiorgan transplantation previous transplant patients infected with HIV, hepatitis C virus (HCV) or hepatitis B virus (HBV) patients with haemolytic-uraemic syndrome (HUS) -

Ages Eligible for Study
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Minimum Age: 12 Months
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: eculizumab<br>Eculizumab 1200 mg/m2 will be administered once, 1 hour before graft reperfusion | Drug: eculizumab<br>* Eculizumab 1200 mg/m2 will be administered once, 1 hour before graft reperfusion<br>* Other names: Soliris;|
| No Intervention: control<br>No intervention will be applied instead eculizumab infusion | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| speed of the graft warming | The speed of the graft surface warming in the range 15-20°C is accessed on the the infrared video record, taken during graft reperfusion by Nec Thermo Tracer. | at the time of engraftment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| graft morphology changes | Protocol biopsy will be obtained at one month and one year. Progression of allograft nephropathy will be compared between groups. | one year after transplantation | 
| One-year graft and patient survival, as well as rejection and infection rates will be calculated |  | one year after Tx | 
| primary graft function | initial graft function will be accessed daily during the first week post Tx and measured as follows: the rate of serum creatinine decrease expressed as percent per day, where 100% will be the creatinine on the day before; intragraft blood flow by Doppler indexes (acceleration, resistance) and blood flow velocity on the three levels - main, interlobar and arcuate arteries; | first week after Tx | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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eculizumab, kidney transplantation, reperfusion, rejection, infection