Efficacy and Safety of Everolimus in de Novo Kidney Transplant Recipients of ECD or AKI Donors

Study Overview
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Brief Summary
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Single center, open-label randomized-control trial Population: de novo 48 kidney transplant recipients (age 18-75 years) from ECD/AKI donors Compare: everolimus with low dose CNI and prednisolone versus standard immunosuppressive regimen Objective: To evaluate efficacy of everolimus with low dose CNI in de novo kidney transplant recipients of ECD/AKI donors Primary endpoint: Mean eGFR (CKD-EPI) at 12 months post-transplantation

Detailed Description
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Secondary Endpoints: To assess renal function by means of eGFR (Cockcrault and Gault formula), at -Month 6 and 12 post-transplantation To assess incidence of the individual composite endpoints including BPAR, graft loss and death at Month 6 and 12 post-transplantation To assess the incidence and duration of renal replacement therapy To assess the incidence of chronic allograft nephropathy (IF/TA) at Month 12 To assess renal function by means of serum creatinine at Month 6 and 12 post-transplantation To compare the overall safety and tolerability (incidence of AEs and SAEs, infections, discontinuations due to AEs, lab abnormalities, wound and surgical complications) at Month 6 and 12 post-transplantation Definition of ECD Brain-dead donor > 60 years old or Donor age > 50 years old with two of the following criteria; History of HT Terminal SCr. ≥ 1.5 mg/dL Death from cerebrovascular accident Definition of AKI donor Brain-dead donor with an increase of SCr. ≥ 0.3 mg/dL from baseline

Official Title
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A 12 Month, Single-center, Open-label, Randomized-controlled Trial to Investigate Efficacy, Safety and Tolerability of Everolimus in Combination With Cyclosporine A and Corticosteroid in de Novo Transplant Recipients of Expanded Criteria Donor Kidneys or Acute Kidney Injury

Conditions
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Transplantation of Kidney, Expanded Criteria Donor, ECD

Intervention / Treatment
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* Drug: Everolimus + low dose cyclosporin A + prednisolone
* Drug: Standard immunosupressive regimen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-75 years Recipients of first DDKT from ECD or AKI donors Patient willing to participate in the study Exclusion Criteria: Multi-organ recipients Organ donation after Cardiac Death (DCD). PRA > 20 % or with historical peak PRA > 50% Patients who lost first graft due to immunological reason within the first year post-transplantation. ABO incompatible transplants or positive cross-match Patients with chronic inflammatory bowel disease. Severe allergy requiring acute treatment, or any known hypersensitivity to everolimus, thymoglobulin Thrombocytopenia (platelet < 75,000/mm3), ANC < 1,500 /mm3 or leucopenia (leucocytes < 2,500/mm3), or Hb < 6 g/dL Chronic active HCV, HIV, or HBsAg positive History of malignancy during the last five years, except squamous or basal cell carcinoma of the skin. Ongoing infection requiring treatment with a systemic antibiotic. Patient with severe hypercholesterolemia (> 300 mg/dL) or hypertriglyceridemia (> 600 mg/dL) that cannot be controlled Evidence of severe liver disease. Severe restrictive or obstructive pulmonary disorders. Pregnant or nursing (lactating) women. Patient who refuse to participate into the study or would like to withdraw from the study.

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A: investigation arm<br>De novo kidney transplantation form ECD/AKI donor with Everolimus + low dose cyclosporinA + prednisolone as immunosuppressive regimen | Drug: Everolimus + low dose cyclosporin A + prednisolone<br> <br> |
| Other: B: control arm<br>De novo kidney transplantation form ECD/AKI donor with standard immunosuppressive regimen | Drug: Standard immunosupressive regimen<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| eGFR (CKD-EPI) |  | 12 months post kidney transplantation | 

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