A Clinical Trial to Assess the Efficacy and Safety of the Conversion to Everolimus

Study Overview
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Brief Summary
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The study hypotheses to be tested in this study are: Conversion to everolimus at 3 months post-transplantation is safe and effective; Accurate noninvasive molecular diagnostic tests can replace biopsy at 3 months pre-conversion (for the diagnosis of subclinical cellular and/or humoral rejection, tissue fibrosis and calcineurin inhibitor-induced nephrotoxicity) in kidney transplant recipients; Follow-up biopsy at 12 months post-conversion (for the diagnosis of tissue fibrosis) can be replaced with accurate noninvasive molecular diagnostic tests in kidney transplant recipients.

Official Title
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An Open-label Randomized Controlled Clinical Trial to Assess the Efficacy and Safety of the Conversion to Everolimus 3 Months After Kidney Transplantation.

Conditions
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Kidney Transplant Recipients

Intervention / Treatment
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* Drug: Tacrolimus
* Drug: Everolimus


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients undergoing their first living- or deceased-donor kidney transplant who maintain a functioning graft 3 months post-transplant; Older than 18 years; Panel-reactive antibodies lower than 20%; Baseline immunosuppression with tacrolimus, mycophenolate sodium (MPS) and prednisone at randomization at 3 months. Exclusion Criteria: eGFR < 35 mL/min at randomization; Urine protein-to-creatinine ratio > 0.8 at randomization; Episode of acute rejection with Banff histological classification > 1A in the first 3 months post-transplant; Cholesterol > 350 mg/dL or triglycerides > 400 mg/dL with therapy at randomization; Active infection at randomization; Chronic liver disease; Refusal to participate in the study; Contraindications to kidney biopsy; Biopsy findings at 3 months post-transplant including borderline rejection, cellular rejection or antibody-mediated rejection.

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Tacrolimus<br>The subjects included in the study will be clinically followed up for at least 12 months. The patients will be selected at 3 months post-transplant according to inclusion and exclusion criteria and randomized in a 1:1 ratio for conversion to everolimus or maintenance of tacrolimus therapy. Intervention arm: Tacrolimus | Drug: Tacrolimus<br>* TACROLIMUS (C0 = 5-10 ng/mL) + MPS 1440 mg + Pred<br>|
| Active Comparator: Everolimus<br>The subjects included in the study will be clinically followed up for at least 12 months. The patients will be selected at 3 months post-transplant according to inclusion and exclusion criteria and randomized in a 1:1 ratio for conversion to everolimus or maintenance of tacrolimus therapy. Intervention arm: Everolimus | Drug: Everolimus<br>* Everolimus (C0 = 6-10 ng/mL) + MPS 1440 mg + Pred<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate cumulative patient and graft survival at 12 months post conversion | Patient and graft survival will be evaluated one year after randomization by Kaplan-Meier analysis | one year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of estimated glomerular filtration rate 12 months post-conversion | - To assess the efficacy of conversion from tacrolimus to everolimus 12 months post-conversion by measuring the estimated glomerular filtration rate using the Modification of Diet in Renal Disease (MDRD) equation | one year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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everolimus, renal transplantation, tacrolimus, molecular evaluation