Calcineurin Inhibitor (CNI) Versus Steroid Cessation in Renal Transplantation

Impact of Cyclosporine or Steroid Withdrawal at 3 Months Post Transplantation on Graft Function, Patient Survival and Cardiovascular Surrogate Markers the First 5 Years After Renal Transplantation.

This study intends to determine whether steroid withdrawal or calcineurin inhibitor withdrawal is superior for graft function and graft survival. Secondary endpoints for this study are: incidence of tumors and cardiovascular events.

The primary objective: To assess if superior graft function (glomerular filtration rate (GFR) difference of 10 ml/min) will be achieved at 1 year after transplantation in cohorts of de novo kidney transplant patients treated with Myfortic-everolimus plus steroids compared to Myfortic-cyclosporine.

Methodology:

• A 5-year, multicentre, prospective, randomized, open-label, controlled study

  • Group 1: Simulect + cyclosporine + Myfortic + steroid stop at 3 months
  • Group 2: Simulect + cyclosporine (decrease dose in one week at month 3 and replace by everolimus) + Myfortic + steroid maintenance.

• In both groups MPA AUC monitoring will be done at 5-7 days and at 3 months, to ensure sufficient MPA protection.

Sample size calculations:

A total of 152 patients will be randomized (76 patients per group)

Population:

De novo kidney transplant recipients.

Study duration:

1.5 years inclusion+ follow-up during the first 5 years

Inclusion Criteria:

• Male or female recipients of a de novo kidney transplant, aged above 18 years
• Women of childbearing potential must have a negative serum or urine pregnancy test with sensitivity equal to at least 50 mIU/ml
• Patients must be capable of understanding the purpose and risks of the study, and must sign an informed consent form

Exclusion Criteria:

• Multiple organ transplantation (e.g., Kidney-pancreas, kidney-heart, kidney- liver,...)
• Transplantation of a patient who got another organ transplant previously
• Recipients of a HLA-identical living-related renal transplant
• Patients with PRA > 30%, patients who have lost a first graft from rejection within two years after transplantation, and African European patients.
• Patients with primary renal disease at risk for recurrence: FSGS, MPGN, HUS
• Pregnant or lactating women
• WBC < 2.5 x 109/l (IU), platelet count < 100 x 109/l (IU), or Hb < 6 g/dl at the time of entry into the study
• Active peptic ulcer
• Severe diarrhea or other gastrointestinal disorder, which might interfere with their ability to absorb oral medication, including diabetic patients with previously diagnosed diabetic gastroenteropathy
• Known HIV-1 or HTLV-1 positive tests
• The use of investigational drugs or other immunosuppressive drugs, as those specified in this protocol
• Patients receiving bile acid sequestrants
• Psychological illness or condition, interfering with the patient's compliance or ability to understand the requirements of the study