Current practice of immune suppressive standard therapy after renal transplantation in non-risk patients is a triple therapy consisting of steroids, a calcineurin inhibitor and MMF. The aim of this clinical trial is to combine a reduction of CNI using tacrolimus and a concept of not using steroids in order to establish an immunosuppressive regimen in immunologically non-risk patients that is efficient and causes as few side effects as possible.
In this triple arm, prospectively randomized multi centre phase IV study 200 patients per study arm will be investigated for 12 months. Based on the results of the Symphony study the low dose tacrolimus study arm will be modified to further improve efficacy (prevention of BPAR, best possible renal function) and safety (adverse event profile regarding infections, cardiovascular risk factors, malignant tumours) of immunosuppression. For this, CNI will be reduced and in addition the rate of steroid free patients after 1 week will be maximized to achieve a long lasting improved post surgical cardiovascular risk profile (in particular concerning de novo induction of diabetes mellitus and other adverse events caused by steroids). Safety should be increased without loss of efficacy of immunosuppression (measured in rejection rate and allograft loss rate) as compared to an immune suppressive therapy comprising steroids. Therefore, following the successful study arm of the Symphony study, immunosuppression in the first of the three study arms comprises a steroid in combination with Advagraf and CellCept in addition to a two dose induction therapy with Simulect (group A). The regimen of the second study arm is similar but discontinues steroids on day seven after transplantation (group B). Therapy of group three is similar to group B but Simulect is replaced by T-cell depleting polyclonal antibodies (Thymoglobulin) (group C).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
Control group. Therapy with Prednisolon.
No Prednisolon after 7 days
Induction therapy: rATG instead of Basiliximab. No Prednisolon.
Universitaetsklinikum Berlin
Berlin, Germany
Efficacy of immunosuppression measured in rejection rate confirmed by biopsy according to BANFF 97, modified 2005.
Time frame: one year after transplantation
Rate of patients with steroid-free immunosuppression
Rate of patients with steroid-free immunosuppression
patient and graft survival rate
patient and graft survival rate
graft function (calculated by the Cock- croft-Gault and MDRD-IV formula respectively calculated creatinine clearance by the Nankivell formula respectively cystatin C measurement)
graft function (calculated by the Cock- croft-Gault and MDRD-IV formula respectively calculated creatinine clearance by the Nankivell formula respectively cystatin C measurement)
Number of steroid-resistant rejections
Number of steroid-resistant rejections
blood pressure level and also amount and types of blood pressure medications
blood pressure level and also amount and types of blood pressure medications
Lipid levels and also amount and types of lipid-lowering medications
Lipid levels and also amount and types of lipid-lowering medications
body weight, relative weight gain [kg], BMI
body weight, relative weight gain \[kg\], BMI
infection rate, infection type and infection severity
infection rate, infection type and infection severity
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Universitaetsklinikum Bonn
Bonn, Germany
Klinikum Bremen-Mitte
Bremen, Germany
Universitaetsklinikum Koeln
Cologne, Germany
Kliniken der Stadt Köln gGmbH - Krankenhaus Köln-Merheim
Cologne, Germany
Carl Gustav Carus Universitätsklinikum
Dresden, Germany
Universitaetsklinikum Erlangen
Erlangen, Germany
Universitaetsklinikum Essen
Essen, Germany
Universitätsklinikum Frankfurt
Frankfurt am Main, Germany
Universitaetsklinikum Freiburg
Freiburg im Breisgau, Germany
...and 15 more locations
anemia requiring erythropoietin treatment
anemia requiring erythropoietin treatment
PTLD incidence
PTLD incidence
tumor incidence
tumor incidence
incidence of diabetes mellitus nd incidence of abnormal fasting blood sugar levels respectively incidence of impaired glucose tolerance, incidence of de novo insulin-requiring or oral-antidiabetic-requiring treatment over ≥30 days
incidence of diabetes mellitus (ADA criteria, venous blood glucose concentration on an empty stomach ≥7.0 mmol/l, pathologic OGTT) and incidence of abnormal fasting blood sugar levels respectively incidence of impaired glucose tolerance, incidence of de novo insulin-requiring or oral-antidiabetic-requiring treatment over ≥30 days
Time frame: 30 days
incidence of cataracts
incidence of cataracts
incidence of avascular necrosis
incidence of avascular necrosis
incidence of osteoporosis
incidence of osteoporosis (assessment of fracture rate, osteodensitometry)
Wound healing disorders
Wound healing disorders
incidence of chronic allograft nephropathy (CAN) (12-month histology)
incidence of chronic allograft nephropathy (CAN) (12-month histology)
incidence of CMV disease (qPCR >1000 copies/μL)
incidence of CMV disease (qPCR \>1000 copies/μL)
incidence of BKV disease (qPCR >1000 copies/μL)
incidence of BKV disease (qPCR \>1000 copies/μL)
incidence of EBV disease (qPCR >1000 copies/μL)
incidence of EBV disease (qPCR \>1000 copies/μL)