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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2009 by University Hospital, Antwerp
Sponsor:
Collaborators:
Novartis Pharmaceuticals
Erasme University Hospital
University Hospital, Ghent
University Hospital of Liege
Universitair Ziekenhuis Brussel
Information provided by:
University Hospital, Antwerp
ClinicalTrials.gov Identifier:
NCT00903188
First received: May 15, 2009
Last updated: NA
Last verified: May 2009
History: No changes posted
  Purpose

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 Intervention Phase
Renal Transplantation
Drug: cyclosporine
Drug: Everolimus
Phase 4

Study Type: Interventional
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.

Resource links provided by NLM:


Further study details as provided by University Hospital, Antwerp:

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. [ Time Frame: 1 year ] [ Designated as safety issue: No ]

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. [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 152
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)
Arms Assigned Interventions
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

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00903188

Contacts
Contact: Jean-Louis Bosmans, MD/PhD +32/3/821 37 92 jeanlouis.bosmans@ua.ac.be

Locations
Belgium
Erasme University Hospital Recruiting
Brussels, Belgium, 1070
Contact: Daniel Abramowicz, MD/PhD    +32/2/555 35 32    dabram@ulb.ac.be   
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    jeanlouis.bosmans@ua.ac.be   
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    patrick.peeters@ugent.be   
Principal Investigator: Patrick Peeters, MD         
University Hospital of Liege Recruiting
Liège, Belgium, 4000
Contact: Catherine Bonvoisin, MD/PhD    +32/4/366 82 58    catherine.bonvoisin@chu.ulg.ac.be   
Principal Investigator: Catherine Bonvoisin, MD         
Sponsors and Collaborators
University Hospital, Antwerp
Novartis Pharmaceuticals
Erasme University Hospital
University Hospital, Ghent
University Hospital of Liege
Universitair Ziekenhuis Brussel
Investigators
Principal Investigator: Jean-Louis Bosmans, MD/PhD University Hospital Antwerp - Department Nephrology-Hypertension
  More Information

No publications provided

Responsible Party: Prof. Dr. Jean-Louis Bosmans, University Hospital Antwerp
ClinicalTrials.gov Identifier: NCT00903188     History of Changes
Other Study ID Numbers: 2007-005844-26
Study First Received: May 15, 2009
Last Updated: May 15, 2009
Health Authority: European Union: European Medicines Agency
Belgium: Federal Agency for Medicinal Products and Health Products

Keywords provided by University Hospital, Antwerp:
Renal Transplantation
graft function
cardiovascular events
malignancy
cyclosporin
steroids
mycophenolate
everolimus
renal biopsies
pharmacokinetics

Additional relevant MeSH terms:
Cyclosporins
Cyclosporine
Mycophenolic Acid
Mycophenolate mofetil
Everolimus
Sirolimus
Basiliximab
Methylprednisolone acetate
Prednisolone acetate
Methylprednisolone
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone hemisuccinate
Prednisolone phosphate
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Dermatologic Agents
Antirheumatic Agents
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on July 20, 2014