The Effect of Eplerenone on the Evolution of Vasculopathy in Renal Transplant Patients. (EVATRAN)

Overview

Sponsor-declared trial summary

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

12 Oct 2021 → 14 Oct 2025

Decision date (initial)

2024-08-07

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

CHRU of Nancy

External identifiers

EU CT number

2024-513808-34-00

EudraCT number

2019-004243-74

ClinicalTrials.gov

NCT04450953

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To evaluate the impact of a six month administration of eplerenone on arterial stiffness, among stable kidney transplant patients on cyclosporine, transplanted for at least one year

Secondary objectives 9

1. To evaluate the impact of a 6 months administration of eplerenone among kidney transplant patients on cyclosporine on the central blood pressure profile after 6 months of treatment
2. To evaluate the impact of a 6 months administration of eplerenone among kidney transplant patients on cyclosporine on the peripheral blood pressure profile after 3 and 6 months of treatment
3. To evaluate the impact of a 6 months administration of eplerenone among kidney transplant patients on cyclosporine on the carotid intima-media thickness after 6 months of treatment
4. To evaluate the impact of a 6 months administration of eplerenone among kidney transplant patients on cyclosporine on left ventricular hypertrophy after 6 months of treatment
5. To evaluate the impact of a 6 months administration of eplerenone among kidney transplant patients on cyclosporine oxydative stress after 6 months of treatment
6. To evaluate the impact of a 6 months administration of eplerenone among kidney transplant patients on cyclosporine on endothelial dysfunction after 6 months of treatment
7. To evaluate the impact of a 6 months administration of eplerenone among kidney transplant patients on cyclosporine on the graft function throughout the course of treatment
8. To evaluate the impact of a 6 months administration of eplerenone among kidney transplant patients on cyclosporine on the risk of life-threatening hyperkalaemia throughout the course of treatment
9. To evaluate the impact of a 6 months administration of eplerenone among kidney transplant patients on cyclosporine on the risk of acute renal failure throughout the course of treatment

Conditions and MedDRA coding

kidney transplantation

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Male or female ≥ 50 years of age
2. Patient who had a kidney transplant at least one year prior to inclusion
3. Patient treated with cyclosporine
4. Patient whose clinical-biological state has been stable for at least 3 months: no change in treatment with an impact on blood pressure (excluding immunosuppressive drug) for 3 months, no acute rejection diagnosed within 3 months
5. Patient with a glomerular filtration rate estimated according to the formula CKD-EPI ≥30mL/min/1.73m2
6. Patient with a peripheral PAS≥110mmHg, irrespective of the presence or not of an antihypertensive therapy (including ACE inhibitors or sartan)
7. Patient who signed informed consent
8. Patient affiliated with to beneficiary of a social security system

Exclusion criteria 19

1. Patient with documented kalemia ≥ 5mmol/L in the last 15 days
2. Bicarbonate blood level <20mmol/L with or without documented supplementation in the last 15 days,
3. Patient undergoing mineralocorticoid receptor antagonism or with a formal indication to receive this treatment
4. Patients receiving potassium sparing diuretics
5. Patients treated with a combination of ACEi and ARBs (each of which is authorized separately);
6. Patient undergoing digoxin medication
7. Known hypersensitivity or allergy to eplerenone and its excipients
8. Patient with severe hepatic impairment (Child-Pugh Class C)
9. Patient treated with potent CYP3A4 inhibitor (p.e. itraconazole, ketoconazole, ritonavir, nelfinavir, clarithromycine, télithromycine et nefazodone)
10. Patient with known galactose intolerance, lactase Lapp deficiency, or glucose, galactose malabsorption syndrom
11. Contraindication to Sodium polystyrène sulfonate (potassium binder) administration : Intestinal obstructive disease and sorbitol laxative treatment
12. Patient participating in other interventional research
13. Female with a desire of pregnancy for the next 15 months
14. Female of childbearing age without effective contraception
15. Pregnant women, parturient women or nursing mothers
16. Adult person subject to a legal protection measure (guardianship, curatorship, judicial safeguard)
17. Adults person who is unable to give consent and who is not subject to a legal protection measure
18. Persons deprived of their liberty by a judicial or administrative decision
19. persons subject to psychiatric care pursuant to articles L. 3212-1 and L. 3213-1

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Evolution of pulse wave velocity (PWV in m/s) adjusted to the blood pressure measured by Sphygmocor®, after 6 months of treatment with eplerenone

Secondary endpoints 9

1. Evolution after 6 months of treatment of central Systolic Blood Pressure (CSPc), Central Diastolic Blood Pressure (CDAb), Central Pulsed Pressure (CPp), Index of Increase (Aix in %), measured by Sphygmocor® (Atcor medical) applanation tonometry
2. Evolution after six months of treatment of Peripheral systolic blood pressure (PASp in mmHg), peripheral diastolic blood pressure (PADp in mmHg), peripheral pulse pressure (PPp in mmHg)
3. Evolution after six months of treatment of intima-media thickness (in mm) measured by Echotracking (ART.LAB, ESAOTE®)
4. Evolution after six months of treatment of left ventricular mass (LVM in g/m2) measured by cardiac ultrasound
5. Evolution after 6 months of treatment of biological markers of oxidative stress (plasma Isoprostane and Malondialdehyde (MDA))
6. Evolution after 6 months of treatment of biological markers of endothelial dysfunction (endothelin, soluble endothelium selectin (sE-selectin), von Willebrand factor )
7. Graft function measured by blood creatinine (in micromol/L) with estimation of glomerular filtration rate (DFGe in mL/min/1.73m2 ) according to the CKD-EPI formula as well asproteinuria measured by the ratio proteinuria/creatininuria (in mg/g). The percentage of patients with DFG ≥ 90, 60-89, 45-59, 30-44, 15-29, <15ml/min/1.73m2 will also be evaluated, as well as the percentage of patients with ratio proteinuria/creatininuria <500; 500-1000, 1000-2000, 2000-3000, >3000 at 6 months
8. Occurrence of hyperkalemia ≥ 5.5 mmol/L and the number of hyperkalemias during hyperkalemia follow-up between 5 - 5.49; 5.5 - 6; >6mmol/L
9. Risk of acute renal failure defined as an increase in creatinine of more than 50%.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

CHRU De Nancy

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 · 1 investigational sites

By country

Investigational sites

Country notifications

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

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.

Application history

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