Clinical trial NCT00903188: Calcineurin Inhibitor (CNI) Versus Steroid Cessation in Renal Transplantation
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 type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Renal Transplantation
Keywords: Renal Transplantation
graft function
cardiovascular events
malignancy
cyclosporin
steroids
mycophenolate
everolimus
renal biopsies
pharmacokinetics
Lead sponsor: University Hospital, Antwerp
Sponsor class: OTHER
Collaborators: name: Novartis Pharmaceuticals
name: Erasme University Hospital
name: University Hospital, Ghent
name: University of Liege
name: Universitair Ziekenhuis Brussel
First posted: 2009-05-18
Enrollment: 152
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Eligibility criteria: 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

Primary outcomes:
measure: 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.
timeFrame: 1 year
Secondary outcomes:
measure: To compare the evolution of graft function (estimated GFR by means of modified MDRD formula)during the first 5 years post transplantation.
timeFrame: 5 years
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Erasme University Hospital
city: Brussels
country: Belgium
facility: University Hospital Brussels
city: Edegem
country: Belgium
facility: University Hospital Antwerp
city: Gent
country: Belgium
facility: University Hospital, Ghent
city: Liège
country: Belgium
facility: University Hospital of Liege
Study officials:
affiliation: University Hospital Antwerp - Department Nephrology-Hypertension
name: Jean-Louis Bosmans, MD/PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Pipeleers L, Abramowicz D, Broeders N, Lemoine A, Peeters P, Van Laecke S, Weekers LE, Sennesael J, Wissing KM, Geers C, Bosmans JL. 5-Year outcomes of the prospective and randomized CISTCERT study comparing steroid withdrawal to replacement of cyclosporine with everolimus in de novo kidney transplant patients. Transpl Int. 2021 Feb;34(2):313-326. doi: 10.1111/tri.13798. Epub 2020 Dec 31.