Anti-T-Lymphocyte Globulin (ATG) in Renal Transplantation of Kidneys With a Non-Heart-Beating (NHB) Donor

Study Overview
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Brief Summary
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One of the greatest problems in renal transplantation is the shortage of donor kidneys. Kidneys of non-heart-beating donors (NHB) are a possible solution, but transplantation is accompanied with a high percentage of acute renal failure, caused by ischemia-reperfusion injury. The increased ischemia-reperfusion injury results in an increased immune activation, which can lead to more injury of the kidney and additional acute rejections. The hypothesis of this trial is that ischemia-reperfusion injury can be diminished by ATG. ATG could have additional favourable effects. To investigate this half of the patients is treated with additional ATG to the standard immunosuppressive treatment. Calcineurin inhibitors are not diminished during the first days after transplantation to investigate whether ATG has special effects on ischemia-reperfusion injury.

Official Title
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A Prospective, Randomized, Open, Multicenter Study to Evaluate the Efficacy and Tolerability of Induction Therapy With a Single High-Dose Anti-T-Lymphocyte Globulin (ATG) in Renal Transplant Patients With a Kidney From a Non-Heart-Beating Donor and Tacrolimus, Mycophenolate Mofetil, and Steroids as Basic Immunosuppression.

Conditions
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Renal Transplant Patients, Recipients of a Kidney From a Non-Heart-Beating Donor

Intervention / Treatment
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* Drug: ATG Fresenius


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Non-heart-beating-donors (Maastricht III/IV) Female patients of childbearing age agree to maintain effective birth control practice during the study. Exclusion Criteria: Pregnant or lactating women at the time of randomization. Patients and donors are ABO incompatible. Women having had >3 pregnancies (including abortions if no consistent data on PRA or anti-donor antibodies are available). Patients with hypersensibility to rabbit proteins, previous treatment with rabbit IgG, or known intolerance to any component of basal immunosuppression. Patients with leukocytes <3,000/mm3 and/or platelets <50,000/mm3 before initiation of transplant. Patients, who are HIV positive. Patients subjected to previous transplants or candidates for multiple transplants (e.g. SKP). Patients, who are unlikely to comply with the visit schedule in the protocol and patients who cannot communicate reliably with the investigator. Patients with pulmonary oedema or with other signs of overhydration.

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: ATG<br>One gift of ATG Fresenius (9 mg/kg body weight) intravenously during the transplantation procedure. ATG is given in addition to standard immunosuppressive treatment (tacrolimus/MMF/prednisolone) | Drug: ATG Fresenius<br>* One gift of ATG Fresenius (9 mg/kg body weight) intravenously during the transplantation procedure. ATG is given in addition to standard immunosuppressive treatment (tacrolimus/MMF/prednisolone)<br>|
| No Intervention: Control<br>Standard immunosuppressive treatment for renal transplantation including tacrolimus/MMF/prednisolone without ATG treatment. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of initial delayed graft function (defined as need for dialysis) |  | Within three months after transplantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of initial delayed graft failure |  | Within 3 months after transplantation | 
| Incidence of primary never-functioning grafts |  | Within 3 months after transplantation | 
| Incidence of acute rejections (biopsy proven) |  | Within 3 months after transplantation | 
| Renal function as determined by MDRD |  | At 1, 2, 3 months after transplantation | 
| Proteinuria |  | At 1, 2, 3 months after transplantation | 
| Percentage of patients with arterial hypertension |  | At 3 months after transplantation | 
| Percentage of patients with antihypertensive drugs (and the number of different classes of antihypertensive drugs) |  | At 3 months after transplantation | 
| Percentage of hyperlipidemic patients |  | At 3 months after transplantation | 
| Percentage of post transplant diabetes mellitus |  | During 3 months after transplantation | 
| Incidence of cytomegalovirus infection |  | During 3 months after transplantation | 
| Incidence of tumours/PTLD |  | At 3 months after transplantation | 
| Patient and graft survival |  | At 3 months after transplantation | 
| Incidence of other infections |  | During 3 months after transplantation | 
| Microalbuminuria |  | At 1, 2, 3 months after transplantation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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kidney, transplantation, non-heart-beating donor, delayed graft function, Antithymocyte globulin, ischemia-reperfusion damage