Enteric-coated Mycophenolate Sodium (EC-MPS) With Reduced-dose Tacrolimus Versus EC-MPS With Standard-dose Tacrolimus in Stable Kidney Transplant Recipients

Study Overview
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Brief Summary
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This study introduces a new optimization immunosuppressive regimen associating tacrolimus at a reduced dose and enteric-coated mycophenolate sodium at an increased dose in order to slow down renal function worsening and to prevent the progression of chronic allograft nephropathy, while maintaining the same efficacy, in maintenance renal transplant recipients.

Official Title
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A Multicenter, National, Open-label, Prospective, Randomized Study to Evaluate Efficacy and Tolerability of Enteric-coated Mycophenolate Sodium 1440 mg/Day With Tacrolimus Reduced Dose Versus Enteric-coated Mycophenolate Sodium 720 mg/Day With Tacrolimus Standard Dose, in Maintenance, Stable, Adult, Kidney Transplant Recipients

Conditions
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Kidney Diseases

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Primary or secondary kidney transplant Treatment with mycophenolic acid (MMF 1 g/d or EC-MPS 720 mg/d) and tacrolimus (trough concentration [C0] ≥ 5.5 ng/mL) Creatinine clearance ≥ 30 mL/min and < 60 mL/min and stable renal function Exclusion Criteria: Multi-organ recipients or previous transplant with any other organ different from kidney Biopsy proven acute rejection or treated acute rejection within the last 3 months. Prescription of mycophenolate mofetil 1 g/d or mycophenolate sodium 720 mg/d due to adverse event occurrence when higher doses were administered Other protocol-defined inclusion/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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 |
| --- | --- |
| Active Comparator: Standard dose EC-MPS<br>Patients received 720 mg/day (360 mg twice a day (bid) orally) Enteric-coated mycophenolate sodium (EC-MPS) and tacrolimus dose (twice a day orally) adjusted to maintain the trough blood level (C0) contained between 5.5 and 10 ng/mL. The randomization was stratified on 1 factor: treatment with or without steroids. Prednisone (or oral equivalent) was administrated to patients as before entering the study and as per center's standard practice, but at a dose of at least 5 mg/day. | Drug: Enteric-coated mycophenolate sodium (EC-MPS)<br> <br> * Other names: Myfortic;Drug: Tacrolimus<br> <br> * Other names: Prograf;Drug: Corticosteroids<br>* At a dose of at least 5 mg/day.<br>* Other names: Prednisone;|
| Experimental: High EC-MPS<br>Patients received 1440 mg/day (720 mg twice a day (bid) orally) Enteric-coated mycophenolate sodium (EC-MPS) and tacrolimus dose (twice a day orally) tapered to reach a trough blood level target contained between 2 and 4.5 ng/mL within 15 days after randomization at the most. The randomization was stratified on 1 factor: treatment with or without steroids. Prednisone (or oral equivalent) was administrated to patients as before entering the study and as per center's standard practice, but at a dose of at least 5 mg/day. | Drug: Enteric-coated mycophenolate sodium (EC-MPS)<br> <br> * Other names: Myfortic;Drug: Tacrolimus<br> <br> * Other names: Prograf;Drug: Corticosteroids<br>* At a dose of at least 5 mg/day.<br>* Other names: Prednisone;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Renal Function Assessed by Change in Estimated Glomerular Filtration Rate(eGFR) | Change in estimated glomerular filtration rate from baseline to Month 6 calculated by using abbreviated Modification of Diet in Renal Disease (MDRD) formula. Modification of Diet in Renal Disease (MDRD) formula is: GFR [mL/min/1.73m^2] = 186.3*(C^-1.154)*(A^-0.203)*G*R where -C is the serum concentration of creatinine [mg/dL], -A is patient age at sample collection date [years], -G=0.742 when gender is female, otherwise G=1, -R=1.21 when race is black, otherwise R=1. | Baseline and Month 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Renal Function at 3 Months Assessed by Change in Estimated Glomerular Filtration Rate (eGFR) | Change in estimated glomerular filtration rate from baseline to Month 3 calculated by using abbreviated MDRD formula. Modification of Diet in Renal Disease (MDRD) formula is: GFR [mL/min/1.73m^2] = 186.3*(C^-1.154)*(A^-0.203)*G*R where -C is the serum concentration of creatinine [mg/dL], -A is patient age at sample collection date [years], -G=0.742 when gender is female, otherwise G=1, -R=1.21 when race is black, otherwise R=1. | Baseline and 3 months | 
| Number of Participants With Treatment Failure Parameters (Biopsy-Proven Acute Rejection (BPAR), Graft Loss, Death, or Loss to Follow-up) at 6 Months | A biopsy-proven acute rejection (BPAR) is defined as a biopsy graded IA, IB, IIA, IIB, or III based on the Banff 1997 classification.The allograft was presumed lost on the day the patient started dialysis and was not able to subsequently be removed from dialysis. If the patient went through a graft nephrectomy, then the day of nephrectomy was the day of graft loss. | 6 months | 
| Number of Participants With Graft and Patient Survivals at 6 Months | Graft survival was defined as the number of patients with no graft loss. The allograft was presumed lost on the day the patient started dialysis and was not able to subsequently be removed from dialysis. If the patient went through a graft nephrectomy, then the day of nephrectomy was the day of graft loss. Patient survival was defined as the number of patients alive with or without a functioning graft. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dose optimization, immune suppressive regimen, enteric-coated mycophenolate sodium, EC-MPS, renal transplantation, kidney, transplant, maintenance patients, Renal transplantation in maintenance