Liver Spare the Nephron (STN) Study - A Study of CellCept (Mycophenolate Mofetil) and Sirolimus in Recipients of a Liver Transplant

Study Overview
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Brief Summary
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This two-arm study will assess the efficacy and safety of a long-term calcineurin inhibitor-free maintenance regimen with CellCept and sirolimus in recipients of an orthotropic liver transplant. Patients will be randomized to receive either CellCept 1-1.5 g twice daily (BID) + tacrolimus + cyclosporine, or CellCept 1-1.5 g BID + sirolimus. The anticipated time on study treatment is 1 to 2 years, and the target sample size is 100 to 500 individuals.

Official Title
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A Randomized, Open-label Study of the Effect of a Long-term Calcineurin Inhibitor-free Maintenance Regimen With CellCept and Sirolimus on Preservation of Renal Function and Prevention of Acute Rejection in Recipients of an Orthotropic Liver Transplant

Conditions
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Liver Transplantation

Intervention / Treatment
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* Drug: mycophenolate mofetil [CellCept]
* Drug: Tacrolimus
* Drug: Cyclosporine
* Drug: Sirolimus


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients 18-74 years of age Single primary liver transplant from a deceased donor CellCept plus tacrolimus or cyclosporine from time of transplantation (within 72 hours) Patients with hepatitis C-positive status may be entered if they have had an intraoperative (back table) biopsy of the transplanted liver or will have a biopsy at the time of randomization. This is not required for patients negative for hepatitis C. Exclusion Criteria: Liver allograft from a living donor or a split liver Multiple organ transplant Dialysis therapy for >14 days from transplantation to randomization History of malignancy in the last 5 years (except hepatoma or non-melanoma skin cancer) Previous sirolimus therapy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 74 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: CellCept + CNI (tacrolimus or cyclosporine)<br> | Drug: mycophenolate mofetil [CellCept]<br>* 1-1.5 g orally or intravenously twice daily<br>Drug: Tacrolimus<br>* As prescribed, for 12 months<br>Drug: Cyclosporine<br>* As prescribed, for 12 months<br>|
| Active Comparator: CellCept + sirolimus<br> | Drug: mycophenolate mofetil [CellCept]<br>* 1-1.5 g orally or intravenously twice daily<br>Drug: Sirolimus<br>* 2-4 mg orally once daily for 9-11 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Glomerular Filtration Rate (GFR) at 12 Months Posttransplant | Mean percent change from baseline in estimated glomerular filtration rate (GFR) calculated by modification of diet in renal disease (MDRD)-6 variable equation at 12 months posttransplantation. MDRD-6 variables: serum creatinine, albumin and urea nitrogen, gender, age and ethnicity. | 12 months posttransplant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Glomerular Filtration Rate (GFR) at 6 Months Posttransplant | Mean percent change from baseline in estimated GFR calculated by modification of diet in renal disease (MDRD)-6 variable equation at 6 and 24 months posttransplantation. MDRD-6 variables: serum creatinine, albumin and urea nitrogen, gender, age and ethnicity. | 6 months posttransplant | 
| Change From Baseline in Glomerular Filtration Rate (GFR) at 24 Months Posttransplant | Mean percent change from baseline in estimated GFR calculated by modification of diet in renal disease (MDRD)-6 variable equation at 6 and 24 months posttransplantation. MDRD-6 variables: serum creatinine, albumin and urea nitrogen, gender, age and ethnicity. | 24 months posttransplant | 
| Change From Baseline in Creatinine Clearance | Mean percent change from baseline in calculated creatinine clearance (CL) at 6, 12, and 24 months posttransplantation | 6, 12, and 24 months posttransplantation |