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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
132
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.
CHU Nantes
Nantes, France
CHU Strasbourg - nouvel hôpital Civil
Strasbourg, France
CHRU Nancy - hôpital Brabois
Vandœuvre-lès-Nancy, France
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.
Time frame: at 36 weeks
Evolution of Nt-ProBNP concentration
Time frame: randomization, at 12 and 36 weeks
Evolution of collagen biomarkers (PICP )
Time frame: at 36 weeks
Evolution of Biological markers of endothelial dysfunction (endothelin)
Time frame: at 36 weeks
The occurrence of hyperkalaemia
hyperkalaemia between 5 - 5.49; 5.5 - 6; \>6mmol/L
Time frame: at 36 weeks
Proportion of creatinine increase > 50%
Assessment of the proportion of acute kidney injury (AKI), defined as a \>50% increase in serum creatinine from baseline.
Time frame: at 36 weeks
Evolution of parameters of systolic function (LVEF, strain)
Time frame: at 36 weeks
Evolution of parameters of remodeling (left ventricular volume)
Time frame: at 36 weeks
Evolution of parameters of filling pressures (E/e')
Time frame: at 36 weeks
Evolution of peripheral systolic blood pressure (mmHg)
Time frame: at 36 weeks
Evolution of peripheral diastolic blood pressure (mmHg)
Time frame: at 36 weeks
Evolution of peripheral pulse pressure (mmHg)
Time frame: at 36 weeks
Evolution of Graft function assessed with serum creatinine (micromol/L)
Graft function assessed with serum creatinine with estimation of glomerular filtration rate according to the CKD-EPI formula. The percentage of patients with GFR ≥ 90, 60-89, 45-59, 30-44, 15-29, \<15ml/min/1.73m2 will also be assessed.
Time frame: at 36 weeks
Evolution of proteinuria (mg/g)
Proteinuria measured by the proteinuria/creatininuria ratio. The percentage of patients with proteinuria/creatininuria ratio \<500; 500-1000, 1000-2000, 2000-3000, \>3000mg/g will also be assessed.
Time frame: at 36 weeks
Evolution of parameters of remodeling (left atrial volumes)
Time frame: at 36 weeks
Evolution of collagen biomarkers ( PIIINP)
Time frame: at 36 weeks
Evolution of Biological markers of endothelial dysfunction ( soluble endothelium selectin)
Time frame: at 36 weeks
Evolution of Biological markers of endothelial dysfunction (von Willebrand factor)
Time frame: at 36 weeks
Evolution of parameters of filling pressures (E-wave deceleration time).
Time frame: at 36 weeks
Evolution of parameters of filling pressures (Systolic Pulmonary Artery Pressure (PAPs)).
Time frame: at 36 weeks
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