Contact information
Type
Scientific
Primary contact
Dr J.W. Fijter, de
ORCID ID
Contact details
Leiden University Medical Center
Department of Nephrology
C3-P22
P.O. Box 9600
Leiden
2300 RC
Netherlands
+31 (0)71 5262169
jwdefijter@lumc.nl
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
N/A
Study information
Scientific title
Added 26/08/09: Prospective, open label, randomised multicentre study to compare Area Under the Curve (AUC)-monitored withdrawal of either cyclosporin (Neoral®) or mycophenolate mofetil (MMF) (CellCept®) in stable renal transplant recipients on a triple regimen with cyclosporin, MMF and steroids.
Acronym
NICE
Study hypothesis
To compare the safety, efficacy, and impact on non-immune toxicity of AUC-controlled withdrawal of either cyclosporine or MMF in stable renal transplant recipients currently on a triple maintenance regimen with cyclosporin, MMF and steroids.
Ethics approval
Received from local medical ethics committee
Study design
Multicentre randomised open label active controlled parallel group trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Condition
Renal transplant
Intervention
Randomised, controlled, prospective multicentre study in stable renal transplant recipients, at least 6 months post-transplantation, who receive maintenance immunosuppressive treatment with cyclosporin bid, MMF 1 g bid, and steroids.
In eligible patients, systemic drug exposure (cyclosporin, MMF) will be measured by a 12-hour area under the time-blood concentration curve (AUC0-12) before randomisation to one of the three study arms.
Patients will be randomised 1:1:1 with stratification for the occurrence of previous acute rejection episodes.
Group A will continue on their current treatment regimen aiming at C2 levels of 700 ng/ml, (range: 600-800 ng/ml). In this group AUC-values will be blinded to the clinicians and evaluated retrospectively.
In group B (MMF withdrawal) cyclosporin will be dosed to reach the defined target AUC0-12 of 3250 ng.h/ml (range 3000-3500 ng.h/ml).
In group C (cyclosporin withdrawal) MMF will be given at a fixed dose of 1000 mg bid at the start of the study period. After cessation of the cyclosporine AUC will be measured to adjust the dose to reach the defined MPA-AUC0-12 target of 75 mg.h/ml (range 60-90 ng.h/ml). For safety reasons the minimal dose will be 500 mg bid.
Intervention type
Drug
Phase
Not Specified
Drug names
Cyclosporin (Neoral®), mycophenolate mofetil (MMF) (CellCept®)
Primary outcome measures
1. Composite of Graft function
2. Incidence of acute rejection episodes
3. Graft and patient survival
Secondary outcome measures
1. Non-immune toxicity
2. Hypertension
3. Hyperlipedimia
4. Gout, uric acid
5. Magnesium
6. Nausea, dyspepsia, diarrhea
7. Anemia/Leukopenia/Thrombopenia
8. Infections (clinically defined)
9. Post-transplant lympho-proliferative disease
10. Malignancy
Overall trial start date
01/01/2003
Overall trial end date
01/01/2005
Reason abandoned
Eligibility
Participant inclusion criteria
1. Patients, 18 years or older, on maintenance therapy with cyclosporin, MMF and steroids
2. Informed consent
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
100
Participant exclusion criteria
1. Calculated creatinine clearance 20 ml/min
2. Multi-organ recipients
3. Patients with an (historic) PRA >60%
4. Vascular type rejection in the past
5. Patients with more than two acute rejection episodes in the past
6. Third renal transplant or more
7. Patients receiving other investigational drugs than MMF in combination with Neoral
8. Metastatic neoplasms, post-transplant lymphoproliferative disease
Recruitment start date
01/01/2003
Recruitment end date
01/01/2005
Locations
Countries of recruitment
Netherlands
Trial participating centre
Leiden University Medical Center
Leiden
2300 RC
Netherlands
Funders
Funder type
Industry
Funder name
Roche Nederland BV (Netherlands)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Novartis Pharma BV (Netherlands)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary