Calcineurin Inhibitor (CNI) Versus Steroid Cessation in Renal Transplantation (CISTCERT)
Recruitment status was: Recruiting
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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||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.|
- To assess if superior graft function (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. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
- To compare the evolution of graft function (estimated GFR by means of modified MDRD formula)during the first 5 years post transplantation. [ Time Frame: 5 years ] [ Designated as safety issue: No ]
|Study Start Date:||October 2008|
|Estimated Study Completion Date:||April 2015|
|Estimated Primary Completion Date:||April 2010 (Final data collection date for primary outcome measure)|
Active Comparator: Cyclosporine
Simulect + cyclosporine + Myfortic + steroid stop at 3 months
Cyclosporine (Group 1):
basiliximab dose: 1x20 mg IV on Day 0 and 1x20 mg IV on Day 4
Cyclosporine: 8 mg/kg PO given before surgery, followed by 2x4 mg/kg/d. C-0h levels: month 1: 150-250 ng/ml; month 2: 100-200 ng/ml; month 3: withdrawal steroids: 100-150 ng/ml.
C-2h levels: month 1: 900-1100 ng/ml; month 2: 800-1000 ng/ml; month 3: withdrawal steroids: maintain level of 750 ng/ml
Enteric-coated mycophenolate(MPA):720mg PO pre-operatively followed by 1.44 g/day.
Steroids: pre-operatively: 250mg methylprednisolone IV; day 1:125mg IV.
Methylprednisolone:day 2-30:PO 12mg/d; day 31-60:tapered to 8mg/d ,day 61-90 :4mg/d; Month 3:stop
Active Comparator: Everolimus
Simulect + cyclosporine (decrease dose in one week at month 3 and replace by Everolimus (Certican)) + Myfortic + steroid maintenance
Everolimus (Group 2):
Basiliximab dose: idem as in group 1
Cyclosporine: first three months idem group 1; month 3: decreased dose by 50%, simultaneously initiate everolimus at a starting dose of 0.75 mg bid.
Once the everolimus blood levels range 6 - 12 ng/ml, cyclosporine will be stopped.
Enteric-coated mycophenolate (MPA) dosing idem as group 1.
Everolimus starting dose: 0.75 mg bid, trough levels: 6-12 ng/ml.
Steroid dosing: idem group 1, but maintained at 4 mg methylprednisolone after day 60.
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)
De novo kidney transplant recipients.
1.5 years inclusion+ follow-up during the first 5 years
Please refer to this study by its ClinicalTrials.gov identifier: NCT00903188
|Erasme University Hospital|
|Brussels, Belgium, 1070|
|University Hospital Brussels|
|Brussels, Belgium, 1090|
|University Hospital Antwerp|
|Edegem, Belgium, 2650|
|University Hospital, Ghent|
|Gent, Belgium, 9000|
|University Hospital of Liege|
|Liège, Belgium, 4000|
|Principal Investigator:||Jean-Louis Bosmans, MD/PhD||University Hospital Antwerp - Department Nephrology-Hypertension|