Comparing Everolimus and Sirolimus in Renal Transplant Recipients

Study Overview
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Brief Summary
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This study is being done to compare the effectiveness and safety of two different kidney transplant immunosuppression drugs, Zortress (the study drug) and Rapamune (which is used in the current standard immunosuppression regimen).

Detailed Description
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Zortress is FDA approved, is used as standard of care at some other institutions, and may also be given as standard of care if it is believed to be the best immunosuppression regimen for a particular kidney transplant recipient. The rationale for testing Zortress vs. Rapamune is to determine which of these drugs is more effective in preventing chronic rejection of the transplanted kidney. Because these two drugs are related to each other there is no current literature addressing the replacement of Rapamune with Zortress in an immunosuppression regimen, therefore the goal of this study is to compare these two immunosuppression drugs.

Official Title
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A Prospective, Randomized, Single Center Pilot Study Comparing Patient and Graft Survival, Adverse Events and Tolerability of Zortress® (Everolimus) Versus Rapamune® (Sirolimus) in Combination With Low Dose Neoral® (Cyclosporine) Dosed by C2 Monitoring, in Deceased and Living Donor Renal Transplant Recipients Under a Thymoglobulin® (Antithymocyte Globulin) and Rapid Steroid Induction Protocol.

Conditions
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Renal Failure

Intervention / Treatment
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* Drug: Everolimus
* Drug: Sirolimus


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must give written informed consent before any assessment is performed. Primary renal transplant recipients between ages 18 and 75 years of age. Females capable of becoming pregnant must have a negative pregnancy test prior to transplantation and practice an effective form of birth control for the duration of the study and 12 weeks after discontinuation of the study drug if applicable. Exclusion Criteria: Total cholesterol > 300 mg/dl or triglycerides > 400 mg/dl despite lipid lowering therapy Pre-existing bone marrow suppression (White Blood Cell count of < 3000, platelets < 100,000) Active infection (Hepatitis B Virus, HIV) Malignancy (except for adequately treated squamous or basal cell skin carcinoma) unless patient has written clearance from an Oncologist or if patient has had no malignancy for at least 2 years prior to the transplant Allergy or intolerance to Zortress, Rapamune, cyclosporine, or Anti-thymocyte globulin

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Zortress (Everolimus)<br>Zortress will be started on day of transplant and initially dosed at 0.75 mg twice a day (12 hours apart) dosed simultaneously with Neoral. | Drug: Everolimus<br>* 0.75mg twice a day, Orally, starting on day of transplant<br>* Other names: Zortress;|
| Active Comparator: Rapamune (Sirolimus)<br>Rapamune will be dosed on day of transplant at 5 mg/d, decreasing to 3 mg/d. | Drug: Sirolimus<br>* 5mg, Orally, starting on day of transplant; decreasing to 3mg<br>* Other names: Rapamune;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Composite Endpoint of Graft Survival (Non-death Censored) and Biopsy Proven Acute Rejection at 1 Year | The primary objective of this pilot study will be to determine equivalency of Zortress® as compared to Rapamune® when used in our de novo immunosuppression regimen following renal transplantation. The primary endpoint will be a composite endpoint of graft survival (non-death censored) and biopsy proven acute rejection at 1 year. The primary outcome of immunosuppressive protection would be studied in our Thymoglobulin and rapid steroid discontinuation protocol, with half-dose Neoral as described above. | 1 Year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Kidney, Kidney transplant, Renal failure, End Stage Renal Disease, kidney transplant recipient