Pilot Study to Investigate a Steroid Free Immunosuppressive Regimen for Renal Transplant Recipients

Protocol synopsis Title An open, single centre, pilot study to investigate a steroid free immunosuppressive regimen for de novo renal transplant recipients followed by a two arm randomization to a calcineurin inhibitor containing and a calcineurin inhibitor free maintenance immunosuppression after three months. Study code Sterfree pilot study Project phase An open, single centre, one arm study followed by a 1:1 randomized, parallel group, comparative study after three months. Study objectives To obtain preliminary information on the efficacy and safety of a rapamycin / sodium-mycophenolate (Myfortic) / tacrolimus regimen in the absence of steroids for the prevention of acute rejection following renal transplantation. To compare a low dose tacrolimus / rapamycin / sodium-mycophenolate (Myfortic) regimen to a rapamycin / sodium-mycophenolate regimen in patients without evidence of acute rejection after three months.

Efficacy:

Primary endpoint

• Plasma creatinine (and creatinine clearance (Cockcroft)) Secondary endpoints
• Incidence of first acute rejections and total number of acute rejections
• Total number of anti-rejection treatments
• Patients successfully withdrawn from calcineurin inhibitor at three months
• Graft survival
• Patient survival

Safety:

• Graft survival
• Patient survival
• Protocol biopsies at 3 months( range: day 75 to 105) and 6 months (range day 165 to 195) sub clinical rejection
• Incidence of first acute biopsy proven rejection and total number of acute rejection episodes
• Total number of anti-rejection treatments
• Patients switched from assigned therapy due to rejection or side effects
• Patients needing steroids because of rejection
• Incidence of selected adverse events: tubulointerstitial nephrotoxicity (TOR inhibitor), leucopenia, thrombocytopenia, elevated fasting blood glucose, dyslipidemia, , electrolyte disturbances, de novo insulin dependency, gastrointestinal disorders (non infectious), neurotoxicity.
• Patients withdrawn due to adverse events

Long term patient follow up Patients will be followed up for graft and patient survival at 12, 24, and 36 months post-transplantation.

Inclusion criteria

• adult patients with end stage kidney disease suitable for primary renal transplantation or retransplantation
• patients receiving a graft from a living related, living unrelated or brain-death donor

Exclusion criteria

• patients with a low or high immunological risk constellation