Eplerenone in Patients Undergoing REnal Transplant (EPURE TRANSPLANT) (EPURE)

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: End-stage Renal Disease
• Intervention / Treatment: Drug: Eplerenone; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 132
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Besancon, France
    • CHRU Besançon
  • Brest, France
    • CHU Brest
  • Dijon, France
    • CHU Dijon- Hôpital Bocage Central
  • Nancy, France
    • CHRU de Nancy
  • Reims, France
    • CHU Reims-Hôpital Maison Blanche
  • Saint-Étienne, France
    • CHU Saint Etienne
  • Strasbourg, France
    • NHC -CHRU Strasbourg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Central Hospital, Nancy, France
• Investigators: Principal Investigator: Frédéric JAISSER, MD, CHRU de Nancy; Study Chair: Sophie GIRERD, MD, CHRU de Nancy; Study Chair: Nicolas GIRERD, MD, PhD, CHRU de Nancy; Study Chair: Luc FRIMAT, MD, PhD, CHRU de Nancy; Study Chair: Patrick ROSSIGNOL, MD, PhD, CHRU de Nancy

Publications and helpful links

General Publications

• Hasegawa T, Nishiwaki H, Ota E, Levack WM, Noma H. Aldosterone antagonists for people with chronic kidney disease requiring dialysis. Cochrane Database Syst Rev. 2021 Feb 15;2(2):CD013109. doi: 10.1002/14651858.CD013109.pub2.
• Girerd S, Frimat L, Ducloux D, Le Meur Y, Mariat C, Moulin B, Mousson C, Rieu P, Dali-Youcef N, Merckle L, Lepage X, Rossignol P, Girerd N, Jaisser F. EPURE Transplant (Eplerenone in Patients Undergoing Renal Transplant) study: study protocol for a randomized controlled trial. Trials. 2018 Oct 30;19(1):595. doi: 10.1186/s13063-018-2956-1.

Study record dates

Study Major Dates

• Study Start (Actual): October 19, 2016
• Primary Completion (Actual): November 9, 2021
• Study Completion (Estimated): August 1, 2031

Study Registration Dates

• First Submitted: July 1, 2015
• First Submitted That Met QC Criteria: July 6, 2015
• First Posted (Estimated): July 7, 2015

Study Record Updates

• Last Update Posted (Estimated): June 19, 2023
• Last Update Submitted That Met QC Criteria: June 16, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Kidney transplantation; Eplerenone
• Additional Relevant MeSH Terms: Pathologic Processes; Kidney Diseases; Urologic Diseases; Disease Attributes; Renal Insufficiency; Renal Insufficiency, Chronic; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Failure, Chronic; Physiological Effects of Drugs; Antihypertensive Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Natriuretic Agents; Diuretics; Hormone Antagonists; Mineralocorticoid Receptor Antagonists; Diuretics, Potassium Sparing; Eplerenone
• Other Study ID Numbers: 2015-000956-29