A single-center, randomized, open-label, 12 months study, with two parallel group to compare the efficacy of everolimus combination + tacrolimus in regression of left ventricular hypertrophy vs tacrolimus + mycophenolate mofetil in renal transplant patients in the maintenance phase

INTERVENTION: Trade Name: Certican Pharmaceutical Form: Tablet INN or Proposed INN: EVEROLIMUS CAS Number: 159351‐69‐6 Current Sponsor code: RAD001 Other descriptive name: RAD001 Concentration unit: µg/l microgram(s)/litre Concentration type: range Concentration number: 3‐8 CONDITION: Left ventricular hypertrophy in renal transplant patients in the maintenance phase . ; MedDRA version: 19.0 Level: PT Classification code 10049773 Term: Left ventricular hypertrophy System Organ Class: 10007541 ‐ Cardiac disorders Therapeutic area: Diseases [C] ‐ Cardiovascular Diseases [C14] PRIMARY OUTCOME: Main Objective: To demonstrate that immunosuppressant combination based on tacrolimus + everolimus in stable renal transplant patients (> 12 months after transplant) achieves a greater reduction of left ventricular hypertrophy (LVH) compared to the “standard” combination based on tacrolimus + mycophenolate mofetil Primary end point(s): The primary endpoint is the measurement of left ventricular hypertrophy (LVH) in the two treatment groups by Cardio‐NMR, through the calculation of left ventricular mass indexed (LVMI) defined as:; LVMI > 91 g/m2 (men); LVMI > 78 g/m2 (women) Secondary Objective: To determine that the study combination improves cardiovascular profile by evaluating the improvement of pulse wave velocity,blood pressure, the measurement of intra‐aortic pressure and determination of major cardiovascular events; To demonstrate that the study combination improves kidney function by measuring serum creatinine, calculated GFR and clearance of iohexol; To compare the CV and immunological profile in the two treatment groups using the following biomarkers: HbA1c, troponin I, NT‐proBNP, CRP, FGF23 and development of donor specific antibodies (DSA). Markers related to myocardial fibrosis and arterial stiffness are also assessed: MMP‐2, ‐9, PIINP, CITP; To compare efficacy between the two treatment groups assessing: BPAR, graft loss, death and loss to follow up.; To assess the safety of the combination by evaluating adverse events (AEs), Diabetes Mellitus and lipid profile Timepoint(s) of evaluation of this end point: MONTH 12 SECONDARY OUTCOME: Secondary end point(s): ‐ Clinical measurements: weight, height, BMI, waist circumference.; ‐ Pulse Wave Velocity (PWV).; ‐ Measurement of blood pressure (ABPM).; ‐ Study Pharmacokinetics (PK) tacrolimus + everolimus group; ‐ Major cardiovascular events (MACE).; ‐ Cardiovascular Biomarkers (CV).; ‐ Renal function (Clearance).; ‐ Acute rejection ‐ proven by biopsy (BPAR).; ‐ Graft survival.; ‐ Survival of the patient.; ‐ Loss of follow‐up. Timepoint(s) of evaluation of this end point: MONTH 12 INCLUSION CRITERIA: ‐Patient’s signed informed consent prior to any study‐related procedure. ‐ Adult patients (> 18 years), renal transplant recipients of more than 1 year of evolution. ‐ Patients receiving maintenance immunosuppression with tacrolimus delayed release (Envarsus®) and MMF / MPA. ‐Patients with Left Ventricular Hypertrophy detected by Cardio‐NMR. ‐Subjects with glomerular filtration rate >30 ml/min (calculated by CKD‐EPI) and stable in the last two analytical determinations (variation <20%). ‐No known contraindications to the use of Mtor inhibitors (previous intolerance, deep vein thrombosis , pulmonary embolism, proteinuria > 0.5 g/day) ‐Patients with Hb levels = 11 gr/dl. ‐Patients with blood pressure <140/90 mmHg in the hospital visits or <135/85 mmHg at home. 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 20 F.1.3 Elderly