Study Evaluating of Calcineurin Inhibitor and Sirolimus (Rapamune) Treatment in Liver Transplant Recipients

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the sirolimus conversion regimen as compared with the calcineurin inhibitor continuation regimen with regards to renal function in stable liver transplant subjects.

Official Title
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A Randomized, Open-Label, Comparative Evaluation of Conversion From Calcineurin Inhibitor Treatment to Sirolimus Treatment Versus Continued Calcineurin Inhibitor Treatment in Liver Allograft Recipients Undergoing Maintenance Therapy

Conditions
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Liver Transplantation

Intervention / Treatment
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* Drug: Sirolimus (Rapamune)
* Drug: Cyclosporine or Tacrolimus


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age greater than 13 years (age greater than 18 years as required by some local regulations). Receiving immunosuppressive therapy with calcineurin inhibitors (CI) +/- corticosteroids +/- antimetabolite. 6 to 144 months after orthotopic liver transplantation. Cockcroft-Gault GFR values ≥40 mL/min and ≤90mL/min at screening Exclusion Criteria: History of nonhepatic transplantation Evidence of systemic infection (sepsis, bacteremia, pneumonia etc). Known or suspected malignancy < 5 years before random assignment.

Ages Eligible for Study
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Minimum Age: 13 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: A<br> | Drug: Sirolimus (Rapamune)<br> <br> |
| Active Comparator: B<br> | Drug: Cyclosporine or Tacrolimus<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline Adjusted Mean in Glomerular Filtration Rate (GFR) | GFR is an index of kidney function. GFR was calculated using Cockcroft-Gault method. A normal GFR is >90 mL/min, higher values indicate better function. Change=adjusted mean of 12 months minus baseline. Mean adjusted for baseline GFR, with antimetabolite therapy status and hepatitis C status as fixed effects. | Baseline and 12 months | 
| Patient and Graft Survival | Endpoint was a composite assessment of patient and graft survival. Patients categorized as graft survival or graft loss. Graft loss defined as pure graft loss (requiring retransplant) or death (with a functioning graft), if the event occurred in the first 12 months after randomization. Patients with missing graft data were counted as graft losses. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With a Biopsy Confirmed Acute Rejection | Overall event rate is determined as yes or no. | 12 months | 
| Mean Serum Creatinine | Observed mean values for serum creatinine. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Liver, Transplant