Patients with a kidney transplantation for more than one year and on cyclosporine MedDRA version: 20.0 Level: SOC Classification code 10047065 Term: Vascular disorders System Organ Class: 10047065 - Vascular disorders
Conditions
Interventions
Trade Name: INSPRA 25 mg or his generics
Product Name: Inspra 25 mg or his generics
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: EPLERENONE
CAS Number: 107724-20-9
Concentration unit
Sponsors
Centre Hospitalier Régional Universitaire de Nancy
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Male or female = 50 years of age ; • Patient who had a kidney transplant at least one year prior to inclusion; • Patient treated with cyclosporine; • 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; • Patient with a glomerular filtration rate estimated according to the formula CKD-EPI =30mL/min/1.73m2; • Patient with a peripheral PAS=110mmHg, irrespective of the presence or not of an antihypertensive therapy (including ACE inhibitors or sartan) • Patient who signed informed consent; • Patient affiliated with to beneficiary of a social security system. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 14 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 22
Exclusion criteria
Exclusion criteria: • Patient with documented kalemia = 5mmol/L in the last 15 days, • Bicarbonate blood level <20mmol/L with or without documented supplementation in the last 15 days, • Patient undergoing mineralocorticoid receptor antagonism or with a formal indication to receive this treatment; • Indication for a combination of ACE inhibitor and sartan or renin inhibitor (each of which is authorized separately); Patient undergoing digoxin medication, • Known hypersensitivity or allergy to eplerenone and its excipients; • Patient with severe hepatic impairment (Child-Pugh Class C); Patient treated with potent CYP3A4 inhibitor, Patient with known galactose intolerance, lactase Lapp deficiency, or glucose, galactose malabsorption syndrom, • Patient participating in other interventional research; • Female with a desire of pregnancy for the next 15 months; • Female of childbearing age without effective contraception; • Persons referred to in Articles L. 1121-5, L. 1121-7 and L1121-8 of the Public Health Code. - Pregnant women, parturient women or nursing mothers ; - Adult person subject to a legal protection measure (guardianship, curatorship, judicial safeguard); - Adults person who is unable to give consent and who is not subject to a legal protection measure; - Persons deprived of their liberty by a judicial or administrative decision; - Persons subject to psychiatric care pursuant to articles L. 3212-1 and L. 3213-
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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 Objective: To evaluate the impact of a 6 months administration of eplerenone among kidney transplant patients on cyclosporine : 1.the central blood pressure profile after 6 months of treatment 2.the peripheral blood pressure profile after 3 and 6 months of treatment 3.the carotid intima-media thickness after 6 months of treatment 4.left ventricular hypertrophy after 6 months of treatment 5.oxidative stress after 6 months of treatment 6.endothelial dysfunction after 6 months of treatment 7.the graft function throughout the course of treatment 8.the risk of life-threatening hyperkalaemia throughout the course of treatment 9.the risk of acute renal failure throughout the course of treatment ;Primary end point(s): Evolution of pulse wave velocity (PWV in m/s) adjusted to the blood pressure measured by Sphygmocor®, after 6 months of treatment with eplerenone.;Timepoint(s) of evaluation of this end point: 6 months after treatment with eplerenone | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary objectives will be the evaluation based on evolution after six months of treatment with eplerenone of: 1. 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. Peripheral systolic blood pressure (PASp in mmHg), peripheral diastolic blood pressure (PADp in mmHg), peripheral pulse pressure (PPp in mmHg) 3. Intima-media thickness (in mm) measured by Echotracking (ART.LAB, ESAOTE®) ; 4. Left ventricular mass (LVM in g/m2) measured by cardiac ultrasound; 5. Biological markers of oxidative stress (plasma Isoprostane and Malondialdehyde (MDA)) ; 6. 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, 3000. Each variable corresponding to criteria 1 to 4 will be evaluated by the difference in value between the start and end of treatment (absolute change), as well as the percentage change (relative change). Secondary Objectives 8 and 9 will be evaluated by : 8. the 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. the risk of acute renal failure defined as an increase in creatinine of more than 50%. ;Timepoint(s) of evaluation of this end point: The secondary objectives will be based on evolution after six months of treatment with eplerenone. | — |
Countries
France
Contacts
Public ContactStudy project manager
Centre Hospitalier Régional Universitaire de Nancy
Outcome results
None listed