|- candidate number||1672|
|- NTR Number||NTR480|
|- Date ISRCTN created||27-jan-2006|
|- date ISRCTN requested||18-nov-2005|
|- Date Registered NTR||15-sep-2005|
|- Secondary IDs||N/A |
|- Public Title||Novel maintenance Immunosuppression
with Controlled systemic Exposure.
|- Scientific Title||Prospective, open label, randomized multicenter study to compare AUC-monitored withdrawal of either cyclosporine (Neoral) or mycophenolate mofetil (MMF) in stable renal transplant recipients on a triple regimen with Neoral, MMF and steroids.|
|- hypothesis||To compare the safety, efficacy, and impact on non-immune toxicity of AUC-controlled withdrawal of either cyclosporin (Neoral) or MMF (Cellcept) in stable renal transplant recipients currently on a triple maintenance regimen with Neoral, MMF, and steroids.|
|- Healt Condition(s) or Problem(s) studied||Renal transplant |
|- Inclusion criteria||1. Patients, 18 years or older, on maintenance therapy with Neoral, MMF and steroids;|
2. Informed consent.
|- 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 lymfoproliferative disease.
|- mec approval received||yes|
|- multicenter trial||yes|
|- Type||2 or more arms, randomized|
|- planned startdate ||1-jan-2003|
|- planned closingdate||1-jan-2005|
|- Target number of participants||100|
|- Interventions||Randomized, controlled, prospective multicenter study in stable renal transplant recipients, at least 6 months post-transplantation, who receive maintenance immunosuppressive treatment with cyclosporine (Neoral) b.i.d., mycophenolate mofetil (MMF) 1 gram b.i.d., and steroids.|
In elegible patients, systemic drug exposure (cyclosporine, MMF) will be measured by a 12-hours area under the time-blood concentration curve (AUC0-12) before randomization to one of the three study arms.
Patients will be randomized 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) cyclosporine will be dosed to reach the defined target AUC0-12 of 3250 ng.h/ml (range 3000-3500 ng.h/ml).
- In group C (cyclosporine withdrawal) MMF will be given at a fixed dose of 1000 mg b.i.d 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 b.i.d.
|- Primary outcome||1. Composite of Graft function, |
- incidence of acute rejection episodes;
2. Graft and patient survival.
|- Secondary outcome||Non-immune toxicity|
3. Gout, uric acid;
5. Nausea, dyspepsia, diarrhea;
7. Infections (clinically defined);
8. Post-transplant lympho-proliferative disease;
|- Trial web site||N/A|
|- status||inclusion stopped: follow-up|
|- CONTACT FOR PUBLIC QUERIES||MD. PhD. J.W. Fijter, de|
|- CONTACT for SCIENTIFIC QUERIES||MD. PhD. J.W. Fijter, de|
|- Sponsor/Initiator ||Leiden University Medical Center (LUMC)|
(Source(s) of Monetary or Material Support)
|Roche Nederland BV, Novartis Pharma B.V.|
|- Brief summary||N/A|
|- Main changes (audit trail)|
|- RECORD||15-sep-2005 - 23-jun-2008|