Efficacy and Safety of Enteric-coated Mycophenolate Sodium and Cyclosporine in Combination With and Without Steroids, in Adult Renal Transplant Recipients

Study Overview
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Brief Summary
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This study will investigate the efficacy and safety of a steroid avoidance regimen in comparison with steroid treatment in combination with an initially higher dose of enteric-coated mycophenolate sodium (EC-MPS) and cyclosporine microemulsion in de novo renal transplant recipients. Patients will be randomly allocated to receive either EC-MPS or steroids in combination with EC-MPS. Patients of both treatment groups will receive monoclonal antibody induction therapy and a perioperative bolus of steroids and cyclosporine.

Official Title
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A Multicenter Randomized Open Label Study to Assess Efficacy and Safety of a Steroid Avoidance Regimen in Comparison to a Treatment With Steroids, in Combination With Enteric-coated Mycophenolate Sodium (EC-MPS) 2.16 g/d for 6 Weeks and Cyclosporine Microemulsion, in de Novo Adult Renal Transplant Recipients

Conditions
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Renal Transplantation

Intervention / Treatment
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* Drug: Enteric-coated mycophenolate sodium (EC-MPS)
* Drug: Prednisone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Primary donor kidney transplant Panel reactive antibody (PRA) ≤ 20% Exclusion Criteria: Multi-organ transplantation including dual kidneys or previous transplant with any other organ different from kidney Non-heart beating donor or kidney from a non-compatible donor Other protocol-defined inclusion/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Without Steroids<br>Patients received Enteric-coated Mycophenolate Sodium (EC-MPS), administered orally 2 times a day for 6 months. Patients also received cyclosporine and a dose of methylprednisolone immediately after transplantation, but did not subsequently receive oral corticosteroids for the remainder of the study. | Drug: Enteric-coated mycophenolate sodium (EC-MPS)<br>* An initial dose of 1080 mg EC-MPS was administered immediately before transplantation. Then, during the first 6 weeks post-transplantation, EC-MPS was administered at a dose of 1080 mg twice a day 12 hours apart. From week 7 until the end of the study (month 6), EC-MPS was administered at standard dose of 720 mg twice a day.<br>* Other names: Myfortic;|
| Active Comparator: With Steroids<br>Patients received Enteric-coated Mycophenolate Sodium (EC-MPS), administered orally 2 times a day for 6 months. Patients also received cyclosporine and a dose of methylprednisolone immediately after transplantation, and subsequently continued to receive daily oral prednisone. | Drug: Enteric-coated mycophenolate sodium (EC-MPS)<br>* An initial dose of 1080 mg EC-MPS was administered immediately before transplantation. Then, during the first 6 weeks post-transplantation, EC-MPS was administered at a dose of 1080 mg twice a day 12 hours apart. From week 7 until the end of the study (month 6), EC-MPS was administered at standard dose of 720 mg twice a day.<br>* Other names: Myfortic;Drug: Prednisone<br>* Oral tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With the Occurrence of Treatment Failures at 6 Months Post-transplantation | Treatment failures defined as Biopsy Proven Acute Rejection (BPAR), graft loss, death or loss to follow-up. Only BPAR from other biopsies than the protocol defined biopsy at Month 3 are described. Acute rejection: an episode of acute renal dysfunction diagnosed as rejection on the basis of biopsy or clinical observations, treated with anti-rejection medication. BPAR: renal transplant biopsy finding of acute cellular or antibody mediated rejection. Graft loss: allograft will be presumed to be lost on the day the patient starts dialysis and is not able to subsequently be removed from dialysis. | 6 months post transplantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Number of Participants With BPAR, Clinical Acute Rejection (AR) and Treated AR at 6 Months | If a participant experienced several BPAR, only the rejection with highest grade is taken into account. Only events that occurred before study treatment discontinuation are taken into account. Only BPAR from other biopsies than the protocol defined biopsy at Month 3 are described. Acute rejection: an episode of acute renal dysfunction diagnosed as rejection on the basis of biopsy or clinical observations, treated with anti-rejection medication. BPAR: renal transplant biopsy finding of acute cellular or antibody mediated rejection. | Month 6 | 
| Number of Participants With Treatment Failure, BPAR, Clinical Acute Rejection (AR) and Treated AR at 3 Months | A treatment failure is a Biopsy Proven Acute Rejection (BPAR), a graft loss, a death, or a loss to follow-up. Only BPAR from other biopsies than the protocol defined biopsy at Month 3 are described. Acute rejection: an episode of acute renal dysfunction diagnosed as rejection on the basis of biopsy or clinical observations, treated with anti-rejection medication. BPAR: renal transplant biopsy finding of acute cellular or antibody mediated rejection. Graft loss: The allograft will be presumed lost on the day the patient starts dialysis and is not able to subsequently be removed from dialysis. | Month 3 | 
| Number of Participants With Subclinical Histological Rejections | The number of participants with subclinical histological rejections was determined by renal biopsy screening at 3 months in 125 patients, providing adequate samples for 112 biopsies. | Month 3 | 
| Number of Participants With Treatment Failure at 3 Months by Graft Recovery Status | The number of participants with treatment failure defined as a Biopsy Proven Acute Rejection (BPAR), a graft loss, a death, or a loss to follow-up at 3 months by graft recovery status. Delayed graft function is defined as the need for dialysis within the first 7 days post-transplantation, excluding the first post-transplantation day. Slow graft function is defined as a serum creatinine value > 250 µmol/L at day 5. | Month 3 | 
| Number of Participants Requiring Steroids in Non-steroid Treatment Group |  | Months 3 and 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Steroids avoidance,, enteric-coated mycophenolate sodium (EC-MPS),, de novo renal transplantation