An Open, Single Centre, Randomised, Parallel Group Study to Investigate Three Different Immunosuppressive Regimens
Condition: Comparative Study; Immunosuppressive Agents
Study type: Interventional
Phase: Phase 4

Summary: 
      An open, single center, randomised study to investigate three different immunosuppressive
      regimens for de novo renal transplant recipients:

        1. st sirolimus / EC-MPS / tacrolimus regimen

           - After 3 months a protocol biopsy is performed. If no rejection is detected the
           calcineurin inhibitor (tacrolimus) is withdrawn.

        2. nd everolimus / EC-MPS / tacrolimus regimen

           - After 3 months a protocol biopsy is performed. If no rejection is detected the
           calcineurin inhibitor (tacrolimus) is withdrawn.

        3. rd tacrolimus / EC-MPS / prednisone regimen - After 3 months a protocol biopsy is
           performed. If no rejection is detected prednisone is withdrawn.
    

Detailed description: 
      This study is designed to show similar efficacy but a different adverse event profile between
      the three regimens. Its main purpose is to provide more information, if steroid free
      immunosuppressive treatment is a valuable alternative in the treatment of de novo kidney
      transplant recipients and that it is possible to withdraw calcineurin inhibitors after 3
      months in this steroid free protocol. A secondary rationale of the study is to compare
      sirolimus with everolimus directly to better differentiate these two mTOR-inhibitors in terms
      of compound-specific effects and class-effects. This should allow for early conclusions on
      the usage of these two mTOR-inhibitors in CNI-free regimens.

      Basis for this study are the following hypotheses regarding the first 6 months of treatment
      following kidney transplantation:

        -  Similar graft function in the three treatment groups after 6 months

        -  No difference in graft and patient survival in the three groups

        -  No differences in incidence of first, total number, type of acute rejections, and number
           of anti-rejection treatments in the three groups

        -  No differences in number of patients successfully withdrawn from calcineurin inhibitor
           in the sirolimus and everolimus arm, respectively

        -  A different adverse event profile with regard to the incidence of dyslipidemias,
           impaired fasting glucose, new onset diabetes mellitus, de novo post-transplant insulin
           dependency, histological signs of calcineurin inhibitor toxicity, and tubulointerstitial
           nephrotoxicity in the three groups. In addition to this the incidence of mTOR-inhibitor
           specific adverse events will be analysed.

      These hypotheses are the basis for the study objectives.
    

Intervention name(s): Rapamycin; Everolimus; Prednisone
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Add rapamycin de novo to tacrolimus and MMF; Add everolimus de novo to tacrolimus and MMF; Add prednisone de novo to tacrolimus and MMF
Other intervention name(s): Sirolimus
Intervention MeSH terms: Sirolimus; Prednisone; Everolimus
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Everolimus,; rapamycin,; prednisone,; tacrolimus,; MMF,; steroid-free,; protocol biopsy