Calcineurin Inhibitor (CNI) Versus Steroid Cessation in Renal Transplantation (CISTCERT)
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
|Contact: Jean-Louis Bosmans, MD/PhD||+32/3/821 37 firstname.lastname@example.org|
|Erasme University Hospital||Recruiting|
|Brussels, Belgium, 1070|
|Contact: Daniel Abramowicz, MD/PhD +32/2/555 35 32 email@example.com|
|Principal Investigator: Daniel Abramowicz, MD/PhD|
|University Hospital Brussels||Recruiting|
|Brussels, Belgium, 1090|
|Contact: Jacques Sennesael, MD/PhD +32/2/477 60 55 Jacques.Sennesael@uzbrussel.be|
|Principal Investigator: Jacques Sennesael, MD|
|University Hospital Antwerp||Recruiting|
|Edegem, Belgium, 2650|
|Contact: Jean-Louis Bosmans, MD/PhD +32/3/821 37 92 firstname.lastname@example.org|
|Contact: Angelika Jurgens, Study Coord. +32/3/821 34 21 Angelika.Jurgens@uza.be|
|Principal Investigator: Jean-Louis Bosmans, MD/PhD|
|University Hospital, Ghent||Recruiting|
|Gent, Belgium, 9000|
|Contact: Patrick Peeters, MD/PhD +32/9/332 45 13 email@example.com|
|Principal Investigator: Patrick Peeters, MD|
|University Hospital of Liege||Recruiting|
|Liège, Belgium, 4000|
|Contact: Catherine Bonvoisin, MD/PhD +32/4/366 82 58 firstname.lastname@example.org|
|Principal Investigator: Catherine Bonvoisin, MD|
|Principal Investigator:||Jean-Louis Bosmans, MD/PhD||University Hospital Antwerp - Department Nephrology-Hypertension|