Eplerenone: The intervention group will receive standard treatment according to usual care, coupled with eplerenone for 36 weeks from randomization. Start of treatment with eplerenone at the initial dose of 25 mg/day, then adjusted according to clinical and biological tolerance: 12.5 mg/day (i.e., 25 mg/48h), 25 mg/day, and 50 mg/day.
Study summary
The main objective of this research is to evaluate the effect, for 36 weeks, of eplerenone on abnormalities observed on cardiac ultrasound in patients with kidney transplantation for at least one year, under cyclosporine or tacrolimus. The intervention group will receive the usual standard treatment coupled with eplerenone for 36 weeks from randomization, while the control group will only receive the standard treatment. The main hypothesis is that anticalcineurins (cyclosporin or tacrolimus) lead to activation of the MR of vascular smooth muscle cells, vasoconstriction and vascular inflammation, which contributes to the persistence or recurrence of heart abnormalities in these patients after the initial post-transplant phase. The administration of eplerenone could antagonize this hyperactivation, reduce the cardiovascular effects of anticalcineurins and thus ultimately improve the cardiovascular prognosis of transplant patients.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Inclusion Criteria:
* Male or female with 18 years old or older.
* Transplant patient for at least one year.
* Patient on long-term cyclosporine or tacrolimus.
* Patient whose clinical situation has been stable for at least 3 months, without major treatment modification and without an episode of acute rejection.
* Patient with renal function with a GFR (glomerular filtration rate) greater than or equal to 40 ml/min/1.73m2.
* Patient with systolic blood pressure greater than or equal to 110 mmHg, with or without antihypertensive treatment.
* Patient with the following echocardiographic abnormalities at baseline : an left ventricular mass \> to 88 g/m2 in females or \> to 102 g/m2 in males and/or left atrial volume \> 34 ml/m2.
Exclusion Criteria:
* Kidney transplant recipient more than 5 years post-transplantation.
* Patient with permanent atrial fibrillation.
* Patient with valvular heart disease (grade ≥ 3).
* Patient considered to be at very high risk of mortality within the next year.
* Patient with documented serum potassium ≥ 5.0 mmol/L within the previous month or receiving long-term potassium-binding resin therapy.
* Patient with documented serum bicarbonate \< 20 mmol/L within the previous month, with or without bicarbonate supplementation.
* Patient receiving treatment with a mineralocorticoid receptor antagonist or having a formal indication for such treatment.
* Patient receiving another potassium-sparing diuretic.
* Patient receiving combined treatment with an ACE inhibitor and an angiotensin receptor blocker (each agent being permitted individually).
* Patient receiving digoxin therapy.
* Left ventricular ejection fraction (LVEF) \< 40% on the baseline echocardiographic assessment.
* Planned closure of an existing arteriovenous fistula within the following year.
* Known hypersensitivity or allergy to eplerenone or any of its excipients.
* Patient with severe hepatic impairment (Child-Pugh class C).
* Patient currently receiving treatment with a strong CYP3A4 inhibitor (e.g., itraconazole, ketoconazole, ritonavir, nelfinavir, clarithromycin, telithromycin, or nefazodone).
* Patient with known galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption syndrome.
* Patient with a contraindication to Kayexalate®: history of hypersensitivity to polystyrene sulfonate resins, obstructive bowel disease, or concomitant treatment with sorbitol-containing laxatives.
* Woman of childbearing potential not using an effective method of contraception or planning to become pregnant within the next 12 months.
* Patient participating in another interventional clinical study involving modifications to therapeutic management.
Primary outcome measure(s)
Hierarchical composite endpoint (win ratio) : 1/ Death or hospitalization for heart failure or acute coronary syndrome, 2/ Variation in indexed left ventricular mass, 3/Variation in indexed left atrial volume. — at 36 weeks
Trial sites (3)
Facility
City
Region
Status
CHU Nantes
Nantes
France
CHU Strasbourg - nouvel hôpital Civil
Strasbourg
France
CHRU Nancy - hôpital Brabois
Vandœuvre-lès-Nancy
France
More Central Hospital, Nancy, France trials in France
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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