CISTCERT: Calcineurin Inhibitor (CNI) Versus Steroid Cessation in Renal Transplantation

Sponsor

University Hospital, Antwerp (Other)

Overall Status

Unknown status

CT.gov ID

NCT00903188

Collaborator

Novartis Pharmaceuticals (Industry), Erasme University Hospital (Other), University Hospital, Ghent (Other), University of Liege (Other), Universitair Ziekenhuis Brussel (Other)

152

Enrollment

Locations

Arms

Duration (Months)

30.4

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Renal Transplantation	Drug: cyclosporine Drug: Everolimus	Phase 4

Detailed Description

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

Study Design

Study Type:

Interventional

Anticipated Enrollment :

152 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (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.

Study Start Date :

Oct 1, 2008

Anticipated Primary Completion Date :

Apr 1, 2010

Anticipated Study Completion Date :

Apr 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Cyclosporine Simulect + cyclosporine + Myfortic + steroid stop at 3 months	Drug: cyclosporine 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 Other Names: Neoral Myfortic Solumedrol Medrol Simulect
Active Comparator: Everolimus Simulect + cyclosporine (decrease dose in one week at month 3 and replace by Everolimus (Certican)) + Myfortic + steroid maintenance	Drug: Everolimus 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. Other Names: Certican Neoral Myfortic Solumedrol Medrol Simulect

Arm

Intervention/Treatment

Active Comparator: Cyclosporine

Simulect + cyclosporine + Myfortic + steroid stop at 3 months

Drug: cyclosporine

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

Other Names:

Neoral

Myfortic

Solumedrol

Medrol

Simulect

Active Comparator: Everolimus

Simulect + cyclosporine (decrease dose in one week at month 3 and replace by Everolimus (Certican)) + Myfortic + steroid maintenance

Drug: Everolimus

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.

Other Names:

Certican

Neoral

Myfortic

Solumedrol

Medrol

Simulect

Outcome Measures

Primary Outcome Measures

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. [1 year]

Secondary Outcome Measures

To compare the evolution of graft function (estimated GFR by means of modified MDRD formula)during the first 5 years post transplantation. [5 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Erasme University Hospital	Brussels	Belgium	1070
2	University Hospital Brussels	Brussels	Belgium	1090
3	University Hospital Antwerp	Edegem	Belgium	2650
4	University Hospital, Ghent	Gent	Belgium	9000
5	University Hospital of Liege	Liège	Belgium	4000