Study to Evaluate the Safety and Efficacy of Switching Calcineurin Inhibitor to Everolimus After Kidney Transplantation in Adults

Study Overview
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Brief Summary
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The purpose of this study is to demonstrate the efficacy and safety in the use of everolimus, with its onset after 3 months of treatment with calcineurin inhibitor.

Detailed Description
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The patient who met the inclusion and exclusion criteria will be included in the study and randomized into two groups in the third month post transplant, they will be in use of tacrolimus, corticosteroids and Mycophenolate sodium. The group 1 will undergo a conversion from calcineurin inhibitor to Everolimus within 1 day (overnight), group 2 will be maintained with the initial immunosuppression. We will start Everolimus at 1 mg 2x/day and three days after the beginning we will adjust the dose by the serum levels, which will be kept in 6 to 10ng/dL. The doses of corticosteroids and Mycophenolate sodium will be retained. There will be performed renal biopsies at randomization and after 12 months. The glomerular filtration rate will be calculated monthly using the MDRD.

Official Title
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A Prospective, Open-label, Controlled, Randomized Study to Evaluate the Safety and Efficacy of Switching Calcineurin Inhibitor to Everolimus After 90 to 150 Days After Kidney Transplantation in Adults, Maintaining Corticosteroid and Mycophenolate Sodium Compared to Patients Who Will Maintain the Use of Calcineurin Inhibitor

Conditions
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Immunosuppression, Kidney Transplant

Intervention / Treatment
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* Drug: Everolimus
* Drug: calcineurin inhibitor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged from 18 to 65 years old First transplantation recipients PRA < 30% Living or cadaveric donor Stable renal function Patients not pregnant or breastfeeding , where pregnancy is defined as the woman status from conception to gestation conclusion, through a positive beta hCG test (>5mUI/mL) Provided written informed consent form Exclusion Criteria: Cadaveric donor with expanded criterion Multiple organs transplantation Kidney cold ischemia time > 24 hours Severe rejection episode - Banf >IIA Glomerular filtration rate < 35mL/min Presence of hard to treat dyslipidemia - severe hypercholesterolemia (>350mg/dL) or hypertriglyceridemia (>500mg/dL) Proteinuria > 800mg/24h Patients with history of malignancy of any organic system, treated or not, within 5 years, with or without evidence of local recurrence or metastases, other than localized basal cell carcinoma Female with childbearing potential without using a reliable contraceptive method.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Everolimus<br> | Drug: Everolimus<br>* Group will switch calcineurin inhibitor to everolimus within 1 day (overnight).<br>* Other names: Certican;|
| Active Comparator: calcineurin inhibitor<br> | Drug: calcineurin inhibitor<br>* Group will maintain their initial immunosuppression therapy with calcineurin inhibitor<br>* Other names: Tacrolimus, Cyclosporin, NeoOral, Prograf;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Creatinine Clearance at 24 months | The primary objective is to demonstrate the effectiveness and non-inferiority of treatment with everolimus, by assessing renal function, in comparison with the use of calcineurin inhibitor. | baseline and two years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Events | The secondary objective is to demonstrate the safety by comparing rejection episodes, graft loss, infection, cancer and death in the control group | baseline and two years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Kidney, Transplant, Immunosuppression, Everolimus, Graft function