Maintenance Neoral Monotherapy Compared to Bitherapy in Renal Transplantation

Study Overview
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Brief Summary
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We have previously defined factors that predict the long term success of maintenance CsA monotherapy (CsAm) after kidney transplantation : donor age < 40 years, serum creatinine level at the initiation of CsAm £ 125 µmol/L, no rejection episode before CsAm initiation. We have also shown that the 8-year graft survival in 329 selected patients enrolled in maintenance CsA-m was 84 % (Hurault de Ligny et al, Transplantation, 2000 ; 69 : 1327-1332). These results were obtained with an old formulation of cyclosporin, azathioprine, steroid withdrawal over the first year and induction antibody. This prospective randomized multicentre study was designed to clarify whether maintenance Neoral + MMF or Neoral + AZA is better than a CsAm and wether Neoral + MMF is better than Neoral + AZA in low immunological risk cadaveric kidney transplant recipients.

Detailed Description
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Between july 1998 and january 2004 selected patients were randomly assigned equally within each centre to receive CsAm or bitherapy with equally CsA + MMF or CsA + AZA.

Official Title
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Efficacy and Safety of Maintenance Neoral Compared to Bitherapy Neoral-Imurel or Neoral-CellCept in Renal Transplantation

Conditions
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Kidney Transplantation

Intervention / Treatment
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* Drug: Cyclosporin A: C0: 75-125ng/ml-dose adapted in the 3 groups
* Drug: Group A: CsA + Azathioprine(1 to 2 mg/kg/day)
* Drug: Group B: CsA + CellCept(500 mg x 2/day)
* Drug: Group C: CsAm


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Primary cadaveric renal transplant with induction therapy, delayed Neoral, MMF and prednisone Steroid withdrawal >= 3 months before enrolment Bitherapy Neoral + CellCept Follow up time since transplantation : 11-24 months Recipient age >= 25 years Donor age <= 45 years Serum creatinine level <= 125 µmol/L and/or calculated creatinine clearance >= 50 ml/mn (CG formula) No or only one steroid-sensitive acute rejection episode during the first year post-transplantation PRA <= 25 % Written informed consent Exclusion Criteria: Living donor transplantation Recipient receiving tacrolimus Azathioprine intolerance Thrombopenia < 100 000/mm³ Neutropenia < 1500/mm³ Hemoglobinemia <= 8g/dl On going infection

Ages Eligible for Study
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Minimum Age: 25 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Cyclosporin A: C0: 75-125ng/ml-dose adapted in the 3 groups|nan|
|Drug: Group A: CsA + Azathioprine(1 to 2 mg/kg/day)|nan|
|Drug: Group B: CsA + CellCept(500 mg x 2/day)|nan|
|Drug: Group C: CsAm|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| to compare maintenance CsAm with dual therapy groups and within dual therapy MMF with AZA for : |  |  | 
| The incidence and the delay of occurrence of graft dysfunction episode defined as ³ 20 % increase in serum creatinine level (mean of three results obtained in the same laboratory) and requiring a graft biopsy. |  |  | 
| Causes of graft dysfunction episodes diagnosed by graft biopsy. |  |  | 
| The incidence of serious infections (HVZ, EBV, HPV genital infection, febrile UTI, pneumonitis...) |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare the three treatment groups for the following parameters : |  |  | 
| Incidence of therapeutic failure defined by biopsy proven acute rejection episode or CsA renal toxicity |  |  | 
| Graft function evaluated by serum creatinine level and calculated creatinine clearance (CG formula) |  |  | 
| Adverse events |  |  | 
| Patient and graft survival |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immunosuppression, Kidney transplantation, multicenter study