EPLERENONE for Renal transplant

Inclusion criteria

• {"criterion_text":"- Men or women ≥ 18 years of age.\n- Patient affiliated to a social security scheme or beneficiary of such a scheme.\n- Person who has undergone a prior clinical examination suitable for the clinical trial.\n- Renal transplant patient for at least one year.\n- Patient on long-term ciclosporin or tacrolimus therapy.\n- Patient with a clinical and biological situation stable for at least three months: no change in treatment with a potential impact on blood pressure for 3 months (excluding immunosuppressive therapy) and no acute graft rejection diagnosed within 3 months\n- Patient with a GFR estimated according to the CKD-EPI formula ≥40ml/min/1.73m2 less than one month old.\n- Patient with peripheral SBP≥110mmHg, regardless of whether or not antihypertensive treatment (including ACE inhibitor or sartan) is being used.\n- With the following echocardiographic abnormalities on trans-thoracic echocardiography performed at inclusion: - Indexed LV mass > 88 g/m2 in women or > 102 g/m2 in men, - And/or Left atrial volume > 34 ml/m2.\n- Patient signed informed consent."}

Exclusion criteria

• {"criterion_text":"- Patient transplanted more than 5 years.\n- Patients treated with digoxin.\n- Left ventricular ejection fraction <40% on echocardiography at inclusion.\n- Planned ligature of the arteriovenous fistula in the coming year.\n- Known hypersensitivity or allergy to eplerenone and its excipients.\n- Patients with severe hepatic impairment (Child-Pugh class C).\n- Patient treated with a potent CYP3A4 inhibitor (e.g. itraconazole, ketoconazole, ritonavir, nelfinavir, clarithromycin, telithromycin and nefazodone).\n- Patients with known galactose intolerance, Lapp lactase deficiency or glucose or galactose malabsorption syndrome.\n- Patients with a contraindication to Kayexalate: history of hypersensitivity to polystyrene sulphonate resins, obstructive intestinal pathology or laxative treatment with sorbitol.\n- A woman of childbearing age without an effective contraceptive device : A woman is considered to be of childbearing age, i.e., fertile, from the onset of her first menstruation until she becomes menopausal, unless she is permanently sterile. An effective contraceptive method is considered to be: estrogen-progestogen hormonal contraception that inhibits ovulation, administered orally, intravaginally, or transdermally; or progestogen-only hormonal contraception that inhibits ovulation, administered orally, by injection, or implant; or intrauterine device (IUD) or hormonal IUD; or tubal ligation; or male partner with vasectomy; or sexual abstinence.\n- Women wishing to become pregnant within 12 months.\n- Patient in permanent atrial fibrillation.\n- Patient taking part in other therapeutic interventional research.\n- Pregnant woman, parturient or breast-feeding mother\n- Minor child (not emancipated)\n- An adult subject to a legal protection measure (guardianship, curatorship, safeguard of justice)\n- Persons deprived of their liberty by a judicial or administrative decision.\n- Patient unable to express consent.\n- Patient with valve disease grade 3 or higher.\n- A patient whose risk of mortality is considered to be very high in the following year.\n- Patients with documented kalaemia ≥ 5mmol/L in the month before or on long-term potassium chelating resins.\n- Blood bicarbonate level < 20mmol/L with or without documented supplementation in the month before.\n- Patient under mineralocorticoid receptor antagonist or with formal indication to receive this treatment.\n- Patient receiving another potassium-sparing diuretic.\n- Patients receiving a combination of ACE inhibitors and sartan."}

Primary endpoints

• {"endpoint_text":"- Hierarchized composite criterion evaluated at 36 weeks (win ratio method), including in order of priority: 1/ Death or hospitalization for heart failure or acute coronary syndrome, 2/ Variation in indexed left ventricular mass (LVMi) (with a precision of 5 g/m² allowing patients with a difference in variation LVMi between randomization and 36 weeks of less than 5 g/m² to be considered as tied), 3/Variation in indexed left atrial volume.","definition_or_measurement_approach":"Evaluated at 36 weeks using the win ratio method; hierarchical components are (1) death or hospitalization for heart failure or acute coronary syndrome, (2) change in indexed left ventricular mass (LVMi) with a 5 g/m² precision threshold for ties between baseline (randomization) and 36 weeks, (3) change in indexed left atrial volume."}

Secondary endpoints

• {"endpoint_text":"- Evolution o f parameters of systolic function (LVEF, strain), remodeling (left ventricular and atrial volumes) and filling pressures (E/e', deceleration time, PAPs) at 36 weeks","definition_or_measurement_approach":"Assessed at 36 weeks by echocardiography: LVEF, strain, ventricular and left atrial volumes, E/e', deceleration time, pulmonary artery pressures (PAPs)."}
• {"endpoint_text":"- Evolution of peripheral systolic blood pressure (pSBP in mmHg), peripheral diastolic blood pressure (pDBP in mmHg), peripheral pulse pressure (pPP in mmHg) at 36 weeks","definition_or_measurement_approach":"Peripheral blood pressure parameters measured at baseline and at 36 weeks (pSBP, pDBP, pPP in mmHg)."}
• {"endpoint_text":"- Evolution of Nt-ProBNP concentration at randomisation, 12 and 36 weeks.","definition_or_measurement_approach":"Nt‑ProBNP measured at randomisation, week 12, and week 36."}
• {"endpoint_text":"- Evolution of collagen biomarkers (PICP and PIIINP) performed at randomisation, at 12 weeks and at 36 weeks","definition_or_measurement_approach":"Collagen biomarkers PICP and PIIINP measured at randomisation, week 12, and week 36."}
• {"endpoint_text":"- Evolution of Biological markers of endothelial dysfunction (endothelin, soluble endothelium selectin (sE-selectin), von Willebrand factor) performed at randomization, at 12 weeks, at 36 weeks","definition_or_measurement_approach":"Endothelial dysfunction biomarkers (endothelin, sE‑selectin, von Willebrand factor) measured at randomisation, week 12, and week 36."}
• {"endpoint_text":"- Graft function assessed with serum creatinine (micromol/L) with estimation of glomerular filtration rate (eGFR in mL/min/1.73m2) according to the CKD-EPI formula, as well as proteinuria measured by the proteinuria/creatininuria ratio (mg/g). The percentage of patients with GFR ≥ 90, 60-89, 45-59, 30-44, 15-29, <15ml/min/1,73m2 will also be assessed, as well as the percentage of patients with proteinuria/creatininuria ratio <500; 500-1000, 1000-2000, 2000-3000, >3000mg/g at 36Weeks","definition_or_measurement_approach":"Serum creatinine and eGFR (CKD‑EPI) and proteinuria/creatininuria ratio measured, with categorical breakdowns of eGFR and proteinuria assessed at 36 weeks."}
• {"endpoint_text":"- The occurrence of hyperkalaemia between 5 - 5.49; 5.5 - 6; >6mmol/L during 36 weeks follow-up","definition_or_measurement_approach":"Incidence of hyperkalaemia graded by serum potassium thresholds (5–5.49; 5.5–6; >6 mmol/L) during 36-week follow-up."}
• {"endpoint_text":"- The risk of acute renal failure defined by an increase in creatinine > 50% during follow-up for 36 weeks","definition_or_measurement_approach":"Acute renal failure defined as >50% increase in serum creatinine during 36-week follow-up."}
• {"endpoint_text":"- The echocardiographic characteristics: parameters of systolic function (LVEF, strain), remodeling (ventricular and left atrial volumes), and filling pressures (E/e', deceleration time, PAPs).","definition_or_measurement_approach":"Echocardiographic parameters measured as secondary endpoints (LVEF, strain, ventricular and left atrial volumes, E/e', deceleration time, PAPs) at specified timepoints."}

France

Earliest CTIS Part Ii Submission Date

04-02-2025

Latest Decision Or Authorization Date

07-03-2025

Processing Time Days

31

Number Of Sites

3

Number Of Participants

132

Primary sponsor

Full Name

CHRU De Nancy

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France

Third parties

• {"country":"France","full_name":"French Ministry of Health (PHRC IR 2019)","duties_or_roles":"Monetary support (PHRC IR 2019)","organisation_type":"Government"}