Peri-operative rATG-perfusion of Solid Transplants

Study Overview
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Brief Summary
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The increasing demand for organ transplantation and the shortage of available organs limit the success of organ transplantation programs. Consequently, acceptance of expanded criteria donor (ECD) organs with the consequences of higher risk of unfavorable transplantation outcome has become an increasing reality. Among the most prominent characteristics distinguishing ECD from Standard Criteria Donors (SCD) are risk factors including brain death (BD) or prolonged cold ischemia time (CI) amplifying ischemia reperfusion injury (IRI). Currently there are no standard regimens to improve the quality of ECD organs. Therefore, donor organ treatment might be a promising approach to substantially improve organ quality. It will be investigated whether the application of the peri-operative perfusion of kidneys and livers with the polyclonal antibody rabbit antithymocyte globulin (rATG) ameliorates IRI. This trial is designed as a parallel armed randomized controlled trial.

Official Title
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Reduction of Ischemic-reperfusion Injury by Ex-vivo ATG-perfusion of Kidneys and Livers Prior Organ Transplantation

Conditions
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Organ Preservation Solutions

Intervention / Treatment
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* Biological: organ perfusion with rabbit anti-thymocyte globulin (rATG)
* Other: organ perfusion with saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients receiving a kidney or liver transplant from deceased donors Exclusion Criteria: Hepatitis C Virus/Human Immunodeficiency Virus, undergoing re-transplantation or under a public guardian

Ages Eligible for Study
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Minimum Age: 18 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: AP-KTx/LTx<br>Transplant recipients receiving an rATG-perfused kidney or liver | Biological: organ perfusion with rabbit anti-thymocyte globulin (rATG)<br> <br> |
| Placebo Comparator: CP-KTx/LTx<br>Transplant recipients receiving a control-perfused kidney or liver. | Other: organ perfusion with saline<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Graft function | Graft function from baseline defined as serum creatinine (KTx arm) and aspartate transaminase (LTx arm). | Day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Graft function - creatinine | Graft function from baseline defined as serum creatinine (mg/dL) for the KTx arm. | Days 1-7 post transplantation, month 3, month 6, month 12 | 
| Graft function - glomeralur filtration rate | Graft function from baseline defined as glomerular filtration rate (ml/min/1.73M2) for the KTx arm. | Days 1-7 post transplantation, month 3, month 6, month 12 | 
| Graft function - serum urea | Graft function from baseline defined as serum urea (mg/dL) for the KTx arm. | Days 1-7 post transplantation, month 3, month 6, month 12 | 
| Graft function - aspartate transaminase | Graft function from baseline defined as aspartate transaminase (mg/dL) for LTx arm. | Days 1-7 post transplantation, month 3, month 6, month 12 | 
| Graft function - alanine transaminase | Graft function from baseline defined as alanine transaminase (mg/dL) for LTx arm. | Days 1-7 post transplantation, month 3, month 6, month 12 | 
| Graft function - total serum bilirubin | Graft function from baseline defined as total serum bilirubin (mg/dL) for LTx arm. | Days 1-7 post transplantation, month 3, month 6, month 12 | 
| Graft function - gamma-glutamyl transpeptidase | Graft function from baseline defined as gamma-glutamyl transpeptidase (mg/dL) for LTx arm. | Days 1-7 post transplantation, month 3, month 6, month 12 | 
| Graft function - alkaline phosphatase | Graft function from baseline defined as alkaline phosphatase (mg/dL) for LTx arm. | Days 1-7 post transplantation, month 3, month 6, month 12 | 
| Graft function - quick value | Graft function from baseline defined as quick value (%) for LTx arm. | Days 1-7 post transplantation, month 3, month 6, month 12 | 
| Patient age - recipient | Recipient age (years). | Day zero, at the time point of transplantation | 
| Patient age - donor | Donor age (years). | Day zero, at the time point of transplantation | 
| BMI - recipient | Recipient BMI (weight (lb) / [height (in)]2 x 703). | Day zero, at the time point of transplantation | 
| BMI - donor | Donor BMI (weight (lb) / [height (in)]2 x 703). | Day zero, at the time point of transplantation | 
| Sex - recipient | Recipient sex. | Day zero, at the time point of transplantation | 
| Sex - donor | Donor sex. | Day zero, at the time point of transplantation | 
| Cold ischemia time | Cold ischemia time (hours) from cross-clamping until start of anastomosis. | during transplantation | 
| Warm ischemia time | Warm ischemia time (hours) is the time from start of anastomosis until reperfusion. | during transplantation | 
| Panel-reactive antibodies | Presence of panel-reactive antibodies (%) in KTx recipients. | Day zero, at the time point of transplantation | 
| Hospital stay | Hospital stay (days) after transplantation | after transplantation | 
| ICU stay | Intensive care unit stay (days) after transplantation | after transplantation | 
| Mortality | Death rate in the investigated groups. | up to 12 month | 
| Graft loss | Graft loss rate in the investigated groups. | up to 12 month | 
| HLA missmatch | Human leukocyte antigen mismatches in KTx recipients. | Day zero, at the time point of transplantation | 
| Delayed graft function | Development of delayed graft function (requirement of dialysis within the first 7 post operative days) in KTx recipients. | after transplantation | 
| Experimental analysis of perioperative taken biopsies | mRNA Expression of pro-inflammatory and anti-inflammatory cytokine/chemokine pattern in biopsies will be analysed to evaluate immunactivation of the organ | Peri-operatively (zero hour biopsy) | 
| Experimental analysis of peripheral blood monunuclear cells | Leukocyte-composition and activation pattern will be analysed from peripheral blood via flow cytometry of the recipient and the donor | prior transplantation, days 1-7 post transplantation, month 3, month 6, month 12 for lymphocyte expression analysis of peripheral blood |