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

2024-517408-12-00 Therapeutic confirmatory (Phase III) Ongoing, recruiting

Start 28 Nov 2024 · Status Ongoing, recruiting · 1 EU/EEA countries · 7 sites

Overview

Sponsor-declared trial summary

Phase Therapeutic confirmatory (Phase III)
Status Ongoing, recruiting
Participants planned 132
Countries 1
Sites 7

Patient in end-stage renal disease candidate for a kidney transplant

To determine the impact of Eplerenone vs. placebo for 4 days before and immediately after transplantation on renal function assessed by glomerular filtration rate at 3 months post-kidney transplantation, a variable strongly associated with long-term graft survival.

Key facts

Sponsor
CHRU De Nancy
Participant type
Patients
Age range
18-64 years, 65+ years
Gender
Male and Female
Therapeutic area
Diseases [C] - Cardiovascular Diseases [C14]
Trial duration
28 Nov 2024 → ongoing
Decision date (initial)
2024-11-28
Transition trial
Yes
Low-intervention
No
Rare-disease indication
No
Vulnerable population
No

External identifiers

EU CT number
2024-517408-12-00
EudraCT number
2015-000956-29
ClinicalTrials.gov
NCT02490904

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To determine the impact of Eplerenone vs. placebo for 4 days before and immediately after transplantation on renal function assessed by glomerular filtration rate at 3 months post-kidney transplantation, a variable strongly associated with long-term graft survival.

Secondary objectives 7

  1. To determine the impact of Eplerenone vs. placebo during 4 days (immediately before and after transplantation) on the necessity of dialysis or filtration glomerular rate <30 ml/min/1.73m² at 3 months after kidney transplantation
  2. To determine the impact of Eplerenone vs. placebo during 4 days (immediately before and after transplantation) on the delay to graft recovery
  3. To determine the impact of Eplerenone vs. placebo during 4 days (immediately before and after transplantation) on proteinuria at 3 months after kidney transplantation
  4. To determine the impact of Eplerenone vs. placebo during 4 days (immediately before and after transplantation) on the occurrence of hyperkalemia > 6 mmol/L in the first week post-transplantation
  5. To determine the impact of Eplerenone vs. placebo during 4 days (immediately before and after transplantation) on the duration of initial hospitalization following the transplantation
  6. To determine the impact of Eplerenone vs. placebo during 4 days (immediately before and after transplantation) : graft function, graft survival, and patient survival evaluated at 1 year, 3 years, and 10 years post-transplantation
  7. To determine the impact of Eplerenone vs. placebo during 4 days (immediately before and after transplantation) on the incidence of acute rejection within the first 3 months post-transplant

Conditions and MedDRA coding

Patient in end-stage renal disease candidate for a kidney transplant

VersionLevelCodeTermSystem organ class
21.0 PT 10038533 Renal transplant 100000004865

Study design 1 period

#TitleAllocationBlindingRoles blindedArms
1 Randomized perdiod
Patient randomized with follow up to 3 months post randomization with primary outcome assessment, and fand follow-up at 1, 3 and 10 years after kidney transplantation.
 Randomised Controlled Double [{"id":89979,"code":1,"name":"Subject"},{"id":89981,"code":4,"name":"Analyst"},{"id":89980,"code":2,"name":"Investigator"}] Eplerenone group: Eplerenone administration within 2 hours prior to patient departure to the operating room and for 4 days after kidney
transplantation.
Placebo group: Placebo administration within 2 hours prior to patient departure to the operatingroom and for 4 days after kidney transplantation

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

  1. Patients older than 18 years of age
  2. Informed consent
  3. 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
  4. Chronic hemodialysis
  5. Affiliated to a social security system

Exclusion criteria 15

  1. Multiple organ transplantation (kidney and liver, kidney and heart, kidney and pancreas, kidney and lung, kidney and intestine)
  2. Hypersensitivity to lactose
  3. HLA desensitization prior to renal transplantation
  4. Pregnant woman or woman without effective contraception
  5. Patient under judicial protection
  6. Patient under legal guardianship
  7. Participation in another biomedical study
  8. Patient receiving a graft from a donor under mineralocorticoid receptor antagonist treatment (spironolactone or eplerenone)
  9. Peritoneal dialysis
  10. Preemptive transplantation
  11. Hypersensitivity or known allergy to Eplerenone or one of its excipients
  12. Patients with severe hepatic insufficiency (class Child-Pugh C)
  13. Patient receiving powerful CYP3A4 inhibitors (for example itraconazole, ketoconazole, ritonavir, nelfinavir, clarithromycin, telithromycyn and nefazodone)
  14. Hypersensitivity or known allergy to iodinated contrast agents (iohexol)
  15. Demonstrated thyrotoxicosis

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. Iohexol clearance at 3 months

Secondary endpoints 7

  1. Proportion of dialysis dependency at 3 months
  2. Proportion of patients presenting a delayed graft function at 7 days post transplantation
  3. 24-hour proteinuria and 24-hour microalbuminuria at 3 months
  4. Occurrence of hyperkalemia > 6 mmol/l at 7 days post transplantation
  5. Length of initial hospital stay
  6. Proportion of patients alive and glomerular filtration rate at 3 months 1 year, 3 years, 10 years post transplantation
  7. Proportion of patients with biopsy-proven acute rejection at 3 months post tranplantation

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

INSPRA 50 mg, comprimé pelliculé

PRD10029058 · Product

Active substance
Eplerenone
Pharmaceutical form
FILM-COATED TABLET
Route of administration
ORAL USE
Max daily dose
50 mg milligram(s)
Max total dose
200 mg milligram(s)
Max treatment duration
4 Day(s)
Authorisation status
Authorised
ATC code
C03DA04 — -
Marketing authorisation
34009 390 994 6 0
MA holder
VIATRIS UP
MA country
France
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
Yes
Modification description
Change in the dosage form of 50 mg film-coated eplerenone tablets to capsules (see attached document for the manufacturing process of 25 mg eplerenone)

Placebo 1

Gélules de lactose monohydraté additionné de carmin de cochenille

N/A · Product

Other product name
N/A
Pharmaceutical form
N/A
ATC code
N/A — N/A
Marketing authorisation
N/A
MA holder
N/A
MA country
Iceland
Paediatric formulation
No

Auxiliary 1

OMNIPAQUE 300 mg d'I/ml, solution injectable

PRD315643 · Product

Active substance
Iohexol
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
INTRAVENOUS
Max daily dose
3235000 µg microgram(s)
Max total dose
3235000 µg microgram(s)
Max treatment duration
1 Day(s)
Authorisation status
Authorised
ATC code
V08AB02 — IOHEXOL
Marketing authorisation
34009 326 815 7 0
MA holder
GE HEALTHCARE SAS
MA country
France
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

CHRU De Nancy

18 Total trials 13 Recruiting 3 Ended
Academic / Non-commercial
Sponsor organisation
CHRU De Nancy
Address
Co N°34, 29 Avenue Du Mal De Lattre De Tassigny, Bp 60034 29 Avenue Du Mal De Lattre De Tassigny Bp 60034
City
Nancy Cedex
Postcode
54035
Country
France

Scientific contact point

Organisation
CHRU De Nancy
Contact name
Sophie GIRERD

Public contact point

Organisation
CHRU De Nancy
Contact name
Sophie GIRERD

Locations

1 EU/EEA country · 7 investigational sites

By country

CountryMS statusPlanned subjectsSites
France Ongoing, recruiting 132 7
Rest of world — 0 —

Investigational sites

France

7 sites · Ongoing, recruiting
Centre Hospitalier Universitaire De Dijon
Nephrologie, 14 Rue Paul Gaffarel, 21000, Dijon
Centre Hospitalier Regional Et Universitaire De Brest
Néphrologie-Transplantation, Boulevard Tanguy Prigent, 29200, Brest
CHU Besancon
Néphrologie-Transplantation, 3 Boulevard Alexandre Fleming, 25000, Besancon
Assistance Publique Hopitaux De Paris
Néphrologie-Transplantation, 51 Avenue Du Mal De Lattre De Tassigny, 94010, Creteil Cedex
Centre Hospitalier Universitaire Reims
Néphrologie-Transplantation, 45 Rue Cognacq Jay, 51100, Reims
CHRU De Nancy
Néphrologie, Rue Du Morvan, 54500, Vandoeuvre Les Nancy
Les Hopitaux Universitaires De Strasbourg
Néphrologie-Transplantation, 1 Place De L Hopital, 67000, Strasbourg

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Country Trial startTrial end Recruitment startRecruitment end Early termination
France 2024-11-28 2024-11-28

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

TypeTitleVersion
Protocol (for publication) D1_Protocole_2024-517408-12-00 8
Recruitment arrangements (for publication) Aspect evalue et autorise sous directive 1
Subject information and informed consent form (for publication) L1_SIS and ICF_adulte_ genetique 4
Subject information and informed consent form (for publication) L1_SIS and ICF_adulte_etude principal 4
Summary of Product Characteristics (SmPC) (for publication) G2_SmPC_INSPRA 50 mg 1
Synopsis of the protocol (for publication) D1_Protocole synopsis_2024-517408-12-00 8

Application history

1 submissions — initial application plus substantial / non-substantial modifications

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2024-10-17 France Acceptable
2024-11-27
 2024-11-28

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