The Comparison of Tacrolimus and Sirolimus Immunosuppression Based Drug Regimens in Kidney Transplant Recipients

• GFR (iothalamate clearance) at other time points [ Time Frame: 24 months ] [ Designated as safety issue: No ]
• Other measures of renal function (serum creatinine, proteinuria and albuminuria) [ Time Frame: 24 months ] [ Designated as safety issue: No ]
• Acute rejection both early and after tacrolimus withdrawal [ Time Frame: 24 months ] [ Designated as safety issue: No ]
• Patient and graft survival [ Time Frame: 24 months after transplantation ] [ Designated as safety issue: No ]
• Complications-especially hypertension, diabetes, dyslipidemia [ Time Frame: 24 months ] [ Designated as safety issue: No ]

• GFR (iothalamate clearance) at other time points.
• Other measures of renal function (serum creatine, proteinuria and albuminuria).
• Acute rejection both early and after tacrolimus withdrawal.
• Patient and graft survival.
• Complications-esp. hypertension, diabetes, dyslipidemia.

This study was done to find out which treatment, tacrolimus or sirolimus, leads to better long-term kidney function in kidney transplant patients.

The aim of this study was to compare the complete avoidance of calcineurin inhibitors (CI) using a sirolimus-based immunosuppressive regimen to a tacrolimus-based regimen in kidney transplantation. This study was a prospective open-label trial randomizing patients to receive tacrolimus, mycophenolate mofetil and prednisone or sirolimus, mycophenolate mofetil and prednisone. All patients received antithymocyte globulin induction. All rejection episodes were proven by biopsy. The hypothesis was that CI free immunosuppression after kidney transplantation will lead to an increase in glomerular filtration rate (GFR) at one year after kidney transplantation.

• Drug: Anti-thymocyte globulin
  Thymoglobulin 1.5 mg/kg/d (days 0,1,2,4,6)
  Other Names:

  • Thymoglobulin
  • Atgam
• Drug: Mycophenolate mofetil
  Mycophenolate mofetil 750 mg p.o. b.i.d.- maintenance
  Other Name: CellCept
• Drug: Prednisone
  Prednisone 500 mg/day initially, tapered to 5 mg/day by day 92
  Other Names:

  • Deltasone
  • Liquid Pred
  • Meticorten
  • Orasone
  • Prednicen-M
  • Prednicot
  • Sterapred
  • Sterapred DS
• Drug: Tacrolimus
  Tacrolimus - maintain trough levels of 6-8 ng/ml (whole blood Imx assay)
  Other Names:

  • Prograf
  • Advagraf
  • Protopic
• Drug: Sirolimus
  Rapamycin 3 to 5 mg/day; adjust to the high-performance liquid chromatography (HPLC) blood level 15 to 20 ng ml
  Other Names:

  • Rapamune
  • Sirolimus

• Active Comparator: Tacrolimus
  Calcineurin inhibitor arm, consisting of treatment with tacrolimus, mycophenolate mofetil, and prednisone.
  Interventions:

  • Drug: Anti-thymocyte globulin
  • Drug: Mycophenolate mofetil
  • Drug: Prednisone
  • Drug: Tacrolimus
• Active Comparator: Sirolimus
  Calcineurin inhibitor-free arm, consisting of treatment with rapamycin, mycophenolate mofetil, and prednisone.
  Interventions:

  • Drug: Anti-thymocyte globulin
  • Drug: Mycophenolate mofetil
  • Drug: Prednisone
  • Drug: Sirolimus

• Dean PG, Grande JP, Sethi S, Park WD, Griffin MD, Cosio FG, Larson TS, Stegall MD. Kidney transplant histology after one year of continuous therapy with sirolimus compared with tacrolimus. Transplantation. 2008 Apr 27;85(8):1212-5.
• Larson TS, Dean PG, Stegall MD, Griffin MD, Textor SC, Schwab TR, Gloor JM, Cosio FG, Lund WJ, Kremers WK, Nyberg SL, Ishitani MB, Prieto M, Velosa JA. Complete avoidance of calcineurin inhibitors in renal transplantation: a randomized trial comparing sirolimus and tacrolimus. Am J Transplant. 2006 Mar;6(3):514-22.

Inclusion Criteria:

• Living and deceased donor kidney transplant recipients at the Mayo Clinic, Rochester, Minnesota

Exclusion Criteria:

• Patients with type 1 diabetes less than 50 years of age who receive a living donor kidney transplant followed by a pancreas transplant
• Pediatric patients (<18 years of age)
• Multi-organ transplants (e.g., kidney-pancreas, kidney-liver)
• ABO-incompatible or positive crossmatch recipients (ABO incompatibility is an immune system reaction that occurs when blood from two different and incompatible blood types are mixed together.)
• Patients with severe hyperlipidemia (serum cholesterol >350 mg/dl or serum triglycerides >500 mg/dl
• Patients with severe leukopenia (White Blood Cell count [WBC]<3000 10^3/ml)
• Patients unwilling to return to the transplant center for late follow-up visits
• Body mass index (BMI) ≥ 32 with incisional problems post transplant (as determined by renal transplant surgeon

• Wyeth is now a wholly owned subsidiary of Pfizer
• Genzyme
• Roche Pharma AG