Clinical trial NCT02490904: Eplerenone in Patients Undergoing REnal Transplant (EPURE TRANSPLANT)
Official title: Double-blind Placebo-Controlled Randomized Clinical Trial of Mineralocorticoid Receptor Blockade With Eplerenone After Renal Transplantation : Effect on Graft Function at 3 Months.
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: End-stage Renal Disease
Keywords: Kidney transplantation
Eplerenone
Lead sponsor: Central Hospital, Nancy, France
Sponsor class: OTHER
First posted: 2015-07-07
Enrollment: 132
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Iohexol clearance
timeFrame: 3 months
Secondary outcomes:
measure: Proportion of dialysis dependency
timeFrame: 3 months
measure: Proportion of patients presenting a delayed graft function
timeFrame: 7 days post transplantation
measure: 24-hour proteinuria
timeFrame: 3 months
measure: Occurrence of hyperkalemia > 6 mmol/l
timeFrame: 7 days post transplant
measure: Length of initial hospital stay
timeFrame: 1 month
measure: Proportion of patients alive
timeFrame: 3 months 1 year, 3 years, 10 years
measure: serum creatinine
timeFrame: 3 months 1 year, 3 years, 10 years
measure: glomerular filtration rate
timeFrame: 3 months 1 year, 3 years, 10 years
measure: Proportion of patients with immediate renal recovery,
timeFrame: 7 days post transplant
measure: Iohexol clearance < 30 mL/min/1,73m²
timeFrame: 3 months
measure: 24-hour microalbuminuria
timeFrame: 3 months
measure: Proportion of patients with a slow renal recovery
timeFrame: 7 days post transplant
measure: Proportion of patients with biopsy-proven acute rejection
timeFrame: 3 months post transplant
Other outcomes:
Locations:
city: Besancon
country: France
facility: CHRU Besançon
city: Brest
country: France
facility: CHU Brest
city: Dijon
country: France
facility: CHU Dijon- Hôpital Bocage Central
city: Nancy
country: France
facility: CHRU de Nancy
city: Reims
country: France
facility: CHU Reims-Hôpital Maison Blanche
city: Saint-Étienne
country: France
facility: CHU Saint Etienne
city: Strasbourg
country: France
facility: NHC -CHRU Strasbourg
Study officials:
affiliation: CHRU de Nancy
name: Frédéric JAISSER, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: CHRU de NANCY
name: Sophie GIRERD, MD
role: STUDY_CHAIR
affiliation: CHRU de Nancy
name: Nicolas GIRERD, MD, PhD
role: STUDY_CHAIR
affiliation: CHRU de Nancy
name: Luc FRIMAT, MD, PhD
role: STUDY_CHAIR
affiliation: CHRU de Nancy
name: Patrick ROSSIGNOL, MD, PhD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.