Study of Everolimus in de Novo Renal Transplant Recipients

Study Overview
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Brief Summary
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In the present study, the investigators propose a conversion scheme with 50% reduction in CNI dosage until adjustment of everolimus dosage, in order to reach a trough blood level of 6-10 ng/mL, thus avoiding overimmunosuppression or alternatively breakthrough rejection episodes. The hypothesis of this study is to demonstrate that the therapeutic regimen with Myfortic® and Certican® significantly improves renal function compared with the standard regimen of CNI.

Official Title
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Evaluation of the Early Conversion From a Calcineurin Inhibitor-based Immunosuppressive Regimen to Everolimus in de Novo Renal Transplant Recipients, a Multicenter Experience

Conditions
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End Stage Renal Failure With Renal Transplant

Intervention / Treatment
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* Drug: Everolimus


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Renal transplant patients Age between 18 and 85 years Recipients of living or deceased donors Donor under the age of 85 years Panel Reactivity Antibodies (PRA) over or equal to 30% 4-5 months post-transplant CNI-based immunosuppressive regimen Stable graft function (creatinine lower than 2.0 mg/dl) No currently acute rejection Proteinuria lower than 800mg/d No laboratory or physical clinically significant signs presented for the last 2 months before screening. Exclusion Criteria: Recipient of multiple organs Recipient with a history of focal segmental glomerulosclerosis or membranous glomerulonephritis Presence of uncontrolled hypercholesterolemia (≥350 mg/dL)hypertriglyceridemia (over or equal to 500 mg/dL) Patients with eGFR lower than 40 ml/min/1.73m2 Evidence of acute rejection within 2 months before screening Thrombocytopenia (lower than 75,000/mm3) Neutropenia (lower than 1,500/mm3) Leukocytopenia (lower than 2500/mm3) Anemia (hemoglobin lower than 6.0g/dL) Severe liver disease (including transaminases or bilirubin equal or over 3 times normal) Proteinuria over 800mg/dL Systemic infection or pneumonia (active infection) Positive for Hepatitis B, Hepatitis C or HIV.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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 |
| --- | --- |
| No Intervention: Control<br>35 patients using Cyclosporin or Tacrolimus (C0=100-200/5-10ng/mL)+ Myfortic® 1440mg/dia + Steroids. Medications will be administered orally, twice a day | |
| Active Comparator: Intervention<br>35 randomized Patients Converted to Certican® (Everolimus C0=6-10 ng/mL) + Myfortic® 1440mg/day + Steroids. On the day of conversion (day 1), 2 mg everolimus will be introduced in the morning and at night, as morning dose of CsA or Tac will be maintained and evening dose of CsA or Tac will be reduced by 50%. In two days, 2 mg everolimus will be associated with 50% of CsA or Tac original dosage, both in the morning and evening. After that, everolimus dose will be adjusted to achieve a C0 target level of 6-10 ng/mL. Once target levels of everolimus are met, the CNI drug will be suspended. | Drug: Everolimus<br>* On the day of conversion (day 1), 2 mg everolimus will be introduced in the morning and at night, as morning dose of CsA or Tac will be maintained and evening dose of CsA or Tac will be reduced by 50%. In two days, 2 mg everolimus will be associated with 50% of CsA or Tac original dosage, both in the morning and evening. After that, everolimus dose will be adjusted to achieve a C0 target level of 6-10 ng/mL. Once target levels of everolimus are met, the CNI drug will be suspended.<br>* Other names: Certican;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in estimated glomerular filtration rate (eGFR) | The eGFR will be calculated by Cockcroft-Gault, CKD-EPI and MDRD equations, firstly 4-5 months after transplantation (baseline), and then 6 and 12 months after conversion to everolimus (Certican ®) and suspension of CNI, associated with Myfortic ® (mycophenolate sodium enteric-coated - MSEC). | 4-5 months after transplantation (baseline), and then 6 and 12 months after conversion to everolimus | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| graft acute rejection | incidence of acute biopsy-proven rejection and clinical acute rejection (without biopsy), graft loss, death with a functioning graft, and loss of follow up at 6 and 12 months after conversion; | 6 and 12 months after conversion | 
| Laboratory results and clinical alterations | analyzing the incidence of anemia, thrombocytopenia, leukopenia, gastrointestinal side effects, pneumonitis, oral ulcers, edema, proteinuria, and any other adverse events, as well as the need of drug withdrawal | 3, 6 and 12 months after conversion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immunosuppression, Chronic Kidney Disease, Renal Transplant