Study Evaluating Sirolimus in Kidney Transplant Recipients

Study Overview
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Brief Summary
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The purpose of this study is to compare the kidney function in patients who have received a transplanted kidney and were treated with the combination of sirolimus, daclizumab, mycophenolate and corticosteroids versus transplanted patients treated with cyclosporine, mycophenolate and corticosteroids.

Official Title
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A Randomized Open-Label Study Comparing the Efficacy and Safety of Sirolimus Combined With Daclizumab, Mycophenolate and Corticosteroids vs Cyclosporine, Mycophenolate and Corticosteroids in Renal Allograft Recipients Receiving Kidneys From Older Donors

Conditions
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Graft vs Host Disease, Kidney Transplantation

Intervention / Treatment
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* Drug: sirolimus
* Drug: cyclosporine
* Drug: mycophenolate mofetil
* Drug: corticosteroids
* Drug: daclizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Kidney transplantation Donor must be at least 60 years old. Exclusion Criteria: Current systemic infection Unstable angina or treatment for serious arrhythmia. Cancer within the previous 5 years.

Ages Eligible for Study
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Minimum Age: 18 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>Sirolimus + Daclizumab + Mycophenolate + Corticosteroids | Drug: sirolimus<br>* 15 mg loading dose, followed by 5 mg/day to achieve target trough levels of 10-15 ng/mL at months 1-6, then 8-12 ng/mL at months 7-12<br>Drug: mycophenolate mofetil<br>* 1 g twice daily; may be reduced to 750 mg BID for adverse events, or to 500 mg BID for persisting adverse events<br>Drug: corticosteroids<br>* As per center practice. By day 8 prednisolone tapered to 20 mg/day; by day 30 to 15 mg/day; by day 60 to 10 mg/day; after 4 to 6 months to 5-7.5 mg/day<br>Drug: daclizumab<br>* IV: 1 mg/kg to a maximum of 100 mg/dose. 5 doses at 2, 4, 6, and 8 weeks after transplantation<br>|
| Active Comparator: 2<br>Cyclosporine + Mycophenolate + Corticosteroids | Drug: cyclosporine<br>* Initial dose of 10 mg/kg/day, then twice daily to achieve target trough levels of 300-400 ng/mL at weeks 0-4; 200-300 ng/mL at months 1-2; 150-250 ng/mL at months 2-3; 100-200 ng/mL at months 3-6; 75-150 ng/mL months 6-12<br>Drug: mycophenolate mofetil<br>* 1 g twice daily; may be reduced to 750 mg BID for adverse events, or to 500 mg BID for persisting adverse events<br>Drug: corticosteroids<br>* As per center practice. By day 8 prednisolone tapered to 20 mg/day; by day 30 to 15 mg/day; by day 60 to 10 mg/day; after 4 to 6 months to 5-7.5 mg/day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Creatinine Clearance Rate | Creatinine clearance is a measure of kidney function. Creatinine clearance rate is the volume of blood plasma that is cleared of creatinine by the kidneys per unit time. Creatinine clearance can be measured directly or estimated using established formulas. For this study, the creatinine clearance rate was calculated using the Nankivell formula. Normal values for healthy, young males are in the range of 100-135 ml/min and for females 90-125 ml/min. A low creatinine clearance indicates poor kidney function. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Acute Rejection | The diagnosis of acute rejection was made via kidney biopsy (Banff criteria). The Banff criteria are standardized diagnostic categories based on histological assessments (e.g., cell types and distributions). Biopsy was performed before initiation of anti-rejection therapy, or at least within 24 hours of the start of therapy. | 3 and 12 months | 
| Patient and Graft Survival | Graft survival is measured by graft loss which is defined as removal of the transplant. | 12 months | 
| Mean Creatinine Clearance Rate - 3 Months | Creatinine clearance is a measure of kidney function. Creatinine clearance rate is the volume of blood plasma that is cleared of creatinine by the kidneys per unit time. Creatinine clearance can be measured directly or estimated using established formulas. For this study, the creatinine clearance rate was calculated using the Nankivell formula. Normal values for healthy, young males are in the range of 100-135 ml/min and for females 90-125 ml/min. A low creatinine clearance indicates poor kidney function. | 3 months | 

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