Eplerenone in Patients Undergoing REnal Transplant (EPURE TRANSPLANT)

Study Overview
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Brief Summary
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Assess the impact of eplerenone (initiated within 2 hours prior to patient departure to the operating room and administered for 4 days during the post-operative period) on graft function evaluated by the measurement of glomerular filtration rate at 3 months - variable strongly associated with long-term graft survival.

Official Title
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Double-blind Placebo-Controlled Randomized Clinical Trial of Mineralocorticoid Receptor Blockade With Eplerenone After Renal Transplantation : Effect on Graft Function at 3 Months.

Conditions
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End-stage Renal Disease

Intervention / Treatment
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* Drug: Eplerenone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients older than 18 years of age Informed consent Candidate for a single or a dual kidney transplantation from an expanded criteria deceased donor ( 60 years or older or age between 50 and 59 with 2 of the 3 following criteria: cardiovascular death, history of hypertension, serum creatinine above 130µmol/L), regardless of machine perfusion and graft rank Chronic hemodialysis Affiliated to a social security system Exclusion Criteria: Multiple organ transplantation (kidney and liver, kidney and heart, kidney and pancreas, kidney and lung, kidney and intestine) Patient receiving a graft from a donor under mineralocorticoid receptor antagonist treatment (spironolactone or eplerenone) Peritoneal dialysis Preemptive transplantation Hypersensitivity or known allergy to Eplerenone or one of its excipients Patients with severe hepatic insufficiency (class Child-Pugh C) Patient receiving powerful CYP3A4 inhibitors (for example itraconazole, ketoconazole, ritonavir, nelfinavir, clarithromycin, telithromycyn and nefazodone) Hypersensitivity or known allergy to iodinated contrast agents (iohexol) Demonstrated thyrotoxicosis Hypersensitivity to lactose HLA desensitization prior to renal transplantation Pregnant woman or woman without effective contraception Patient under judicial protection Patient under legal guardianship Participation in another biomedical study

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Eplerenone group<br>Eplerenone administration within 2 hours prior to patient departure to the operating room and for 4 days after kidney transplantation. | Drug: Eplerenone<br>* Double-blinded Eplerenone administered for 4 days at 25mg every 12 hours<br>|
| Placebo Comparator: Placebo group<br>Placebo administration within 2 hours prior to patient departure to the operatingroom and for 4 days after kidney transplantation | Drug: Placebo<br>* Double-blinded Placebo administered for 4 days at 25mg every 12 hours<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Iohexol clearance | Graft function at 3 months evaluated by GFR using iohexol clearance | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of dialysis dependency |  | 3 months | 
| Proportion of patients presenting a delayed graft function | The proportion of patients with a delayed graft function defined by the need for one or more dialysis sessions during the 7 days following transplantation | 7 days post transplantation | 
| 24-hour proteinuria |  | 3 months | 
| Occurrence of hyperkalemia > 6 mmol/l |  | 7 days post transplant | 
| Length of initial hospital stay | between transplantation and discharge | 1 month | 
| Proportion of patients alive | vital status collected through the national database of organ recipients | 3 months 1 year, 3 years, 10 years | 
| serum creatinine | using the enzymatic method | 3 months 1 year, 3 years, 10 years | 
| glomerular filtration rate | estimation using the CKD-EPI formula (in mL/min/1.73m2) | 3 months 1 year, 3 years, 10 years | 
| Proportion of patients with immediate renal recovery, | The proportion of patients with an immediate renal recovery is defined by a serum creatinine lower than 30 mg/L at 7 days post-transplant | 7 days post transplant | 
| Iohexol clearance < 30 mL/min/1,73m² |  | 3 months | 
| 24-hour microalbuminuria |  | 3 months | 
| Proportion of patients with a slow renal recovery | The proportion of patients with slow renal recovery is defined by serum creatinine above 30 mg/L at 7 days post-transplant without the need for dialysis | 7 days post transplant | 
| Proportion of patients with biopsy-proven acute rejection | Proportion of patients with biopsy-proven acute rejection in the first three month after transplantation | 3 months post transplant | 

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