An exploratory study of the efficacy and safety of a regimen consisted of Everolimus plus low tacrolimus for the immunosuppression in renal transplantation in the elderly. To evaluate the pharmacokinetics of immunosuppressants that have been little studied in this population. To evaluate whether the polymorphism of the genes that determine the expression of metabolizing enzymes and transporters of xenobiotics interfere in the elderly, also in the younger population, absorption and metabolism of immunosuppressants. To evaluate the potential minimization of immunosuppression in this population refers to how does the re-population of peripheral lymphocytes, in this age group, after the use of lymphocyte-depleting agents such as thymoglobulin and subsequently maintained with two regimes. Clarify which markers of renal filtration exist today, cystatin C and serum creatinine, is the right to monitor renal function in elderly transplanted.
Objectives: The objective of this study is to evaluate the safety and efficacy of everolimus (EVL) combined with low dose of Tacrolimus in comparison with Mycophenolate Sodium (MPS) combined with standard dose of Tacrolimus as immunosuppressive therapy for elderly recipients of kidney transplantation. Comparison between the two study arms of: Primary Objective: 1\. Composite efficacy failure demonstrated by graft loss and/or death with functional graft and/or GFR (Glomerular Filtration Rate determined by EDTA-Cr51) \< 50 ml/min at the end of first year after transplantation and every year until the fifth year. Secondary Objectives: 1. Pharmacokinetic study of immunosuppressive drugs (Tacrolimus, Everolimus and Mycophenolate Sodium) in the study population at days 7, 30, 60, 67, 90 and 180 post-transplant. 2. Serious adverse events (as internationally defined by ICH-GCP) every year, for five years. 3. Biopsy proven acute rejection rated every year, for five years. 4. Identify which of the renal filtration markers existing today, Cystatin C or Serum Creatinine, is more adequate to monitor renal function in elderly transplant and to develop abbreviated equations for eGFR from day 7 on. 5. Evaluation of other metabolic effects (bone density at month 12 post-transplant; vitamin D at months 2 and 12 post-transplant; and gonadal function at months 1 and 12 post-transplant) and Quality of Life at months 1, 12, 18, 24, 36, 48 and 60 post-transplant in the study population. 6. Left Ventricular Mass (LVM) and Left Ventricle Ejection Fraction (LVEF) measured by echocardiography at the end of the first year.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
90
This is a 5-years prospective, randomized, exploratory, single-center, parallel group trial that includes renal transplanted elderly patients (≥ 60 years old) randomized between months 1 and 3 after transplantation to be maintained under MPS/TAC regimen or be switched to EVL/low-TAC. Everolimus: initial dose of 1 mg BID. Doses will be adjusted in order to maintain Everolimus whole blood trough concentrations between 3-8 ng/ml. Tacrolimus: initial dose of 0.1 mg/kg/day. Doses will be adjusted in order to maintain Tacrolimus whole blood trough concentrations between 2- 4 ng/ml thereafter. Corticosteroids: as clinical practice.
Clinical Hospital of the School of Medicine, University of Sao Paulo
São Paulo, São Paulo, Brazil
RECRUITINGClinical Hospital of the School of Medicine, University of Sao Paulo
São Paulo, São Paulo, Brazil
RECRUITINGEvaluation of functional graft
Composite efficacy failure demonstrated by graft loss and/or death with functional graft and/or GFR (Glomerular Filtration Rate determined by EDTA-Cr51) \< 50 ml/min at the end of first year after transplantation and every year until the fifth year.
Time frame: The study is planned to analyze all patients at the end of the fifth year after transplantation. However, an interim analysis will be done at the end of each year.
Pharmacokinetic of Tacrolimus
Pharmacokinetic of Tacrolimus in the study population at days 7, 30, 60, 67, 90 and 180 post-transplant.
Time frame: Days: 7, 30, 60, 67, 90, 180.
Serious adverse events
Evaluate serious adverse events (as internationally defined by ICH-GCP).
Time frame: Every year, for five years
Biopsy
Biopsy proven acute rejection rated every year, for five years.
Time frame: Every year, for five years
Renal filtration markers
Identify which of the renal filtration markers existing today, Cystatin C or Serum Creatinine, is more adequate to monitor renal function in elderly transplant and to develop abbreviated equations for eGFR from day 7 on.
Time frame: Days: 7, 30, 37, 60, 67, 90, 180. Months: 12, 18, 24, 36, 48, 60
Bone density
Evaluation of bone density at month 12 post-transplant.
Time frame: Month 12
Vitamin D
Evaluation of vitamin D at months 2 and 12 post-transplant.
Time frame: Months: 2, 12.
Gonadal function
Evaluation of gonadal function at months 1 and 12 post-transplant.
Time frame: Months: 1, 12.
Quality of Life
Evaluate Quality of Life at months 1, 12, 18, 24, 36, 48 and 60 post-transplant in the study population.
Time frame: Months: 1, 12, 18, 24, 36, 48, 60.
Left Ventricular Mass (LVM)
Left Ventricular Mass (LVM) measured by echocardiography at the end of the first year.
Time frame: Month: 12.
Left Ventricle Ejection Fraction (LVEF)
Left Ventricle Ejection Fraction (LVEF) measured by echocardiography at the end of the first year.
Time frame: Month: 12.
Pharmacokinetic of Everolimus
Pharmacokinetic of Everolimus in the study population at days 7, 30, 60, 67, 90 and 180 post-transplant.
Time frame: Days: 7, 30, 60, 67, 90, 180.
Pharmacokinetic of Mycophenolate Sodium
Pharmacokinetic of Mycophenolate Sodium in the study population at days 7, 30, 60, 67, 90 and 180 post-transplant.
Time frame: Days: 7, 30, 60, 67, 90, 180.
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