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

Study Overview
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Brief Summary
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This 2-arm study recruited kidney transplant patients who were receiving standard care of calcineurin inhibitors (CNIs, tacrolimus or cyclosporine), CellCept (1.0-1.5 g twice daily) and corticosteroids. They were either randomized to continue this regimen, or CNI therapy was discontinued and replaced by sirolimus therapy (in combination with CellCept and corticosteroids). The effect of these 2 regimens on efficacy, safety and kidney function was evaluated. The anticipated time on study treatment was 1-2 years, and the target sample size was 100-500 individuals.

Official Title
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An Open Label, Randomized, Multicenter Study to Evaluate the Efficacy and Safety of Early Calcineurin Inhibitor Withdrawal in Recipients of Primary Renal Allografts Maintained Long-term on Mycophenolate Mofetil (MMF) (CellCept®) and Sirolimus (Rapamune®)

Conditions
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Kidney Transplantation

Intervention / Treatment
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* Drug: mycophenolate mofetil [CellCept]
* Drug: Corticosteroids
* Drug: Calcineurin inhibitors
* Drug: Sirolimus


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients 18-75 years of age Kidney transplant 30-180 days post-transplantation Receipt of cyclosporine or tacrolimus, CellCept, and corticosteroids for greater than 14 days prior to study entry No known contraindications to sirolimus Exclusion Criteria: Multiple organ transplant recipients or secondary kidney transplant recipients Corticosteroid-resistant rejection episode within 90 days prior to study entry or corticosteroid-sensitive rejection episode within 30 days prior to study entry More than 1 biopsy-proven episode of acute rejection prior to study entry Treated with sirolimus before the study Organ transplant or expected organ transplant, other than kidney History of malignancy in the last 5 years (except successfully treated localized non-melanotic skin cancer)

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 |
| --- | --- |
| Experimental: 1<br> | Drug: mycophenolate mofetil [CellCept]<br>* 1.0-1.5 g oral dose twice daily<br>Drug: Corticosteroids<br>* As prescribed<br>Drug: Sirolimus<br>* As prescribed<br>|
| Active Comparator: 2<br> | Drug: mycophenolate mofetil [CellCept]<br>* 1.0-1.5 g oral dose twice daily<br>Drug: Corticosteroids<br>* As prescribed<br>Drug: Calcineurin inhibitors<br>* As prescribed<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Percent Change in Glomerular Filtration Rate From Baseline to Month 12 | The primary efficacy endpoint was mean percent change in renal function from baseline to 12 months postrandomization, as measured by Glomerular Filtration Rate utilizing renal clearance of cold iothalamate. percent change= [(Glomerular Filtration Rate at Month 12-Glomerular Filtration Rate at baseline)/Glomerular Filtration Rate at baseline]*100 percent. | baseline to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Percent Change in Glomerular Filtration Rate From Baseline to Month 24 | A secondary efficacy endpoint was mean percent change in renal function from baseline to 24 months postrandomization, as measured by Glomerular Filtration Rate utilizing renal clearance of cold iothalamate. percent change= [(Glomerular Filtration Rate at Month 24-Glomerular Filtration Rate at baseline)/Glomerular Filtration Rate at baseline]*100 percent. | Baseline to 24 months | 
| Mean Percent Change in Serum Creatinine From Baseline to Months 6, 12, and 24 | Renal allograft function determined by mean percent change from baseline in serum creatinine by treatment group at 6, 12, and 24 months postrandomization. percent change= [(serum creatinine at Month t-serum creatinine at baseline)/serum creatinine at baseline]*100 percent, where t=6, 12, and 24 months postrandomization. | baseline, 6, 12, and 24 months | 
| Mean Percent Change in Calculated Creatinine Clearance From Baseline to Months 6, 12, and 24 | Renal allograft function determined by mean percent change from baseline in calculated creatinine clearance (Cockroft and Gault method) by treatment group at 6, 12, and 24 months postrandomization. percent change= [(calculated creatinine clearance at Month t - calculated creatinine clearance at baseline)/calculated creatinine clearance at baseline]*100 percent, where t=6, 12, and 24 months postrandomization | baseline 6, 12, and 24 months | 
| Mean Percent Change in Calculated Glomerular Filtration Rate From Baseline to Months 6, 12, and 24 (Nankivell Equation) | Renal allograft function determined by mean percent change from baseline in calculated Glomerular Filtration Rate (Nankivell equation) by treatment group at 6, 12, and 24 months postrandomization. percent change= [(calculated Glomerular Filtration Rate at Month t - calculated Glomerular Filtration Rate at baseline)/calculated Glomerular Filtration Rate at baseline]*100 percent, where t=6, 12, and 24 months postrandomization. | baseline, 6, 12, and 24 months |