Clinical trial NCT01631058: Renal Transplantation in the Elderly - nEverOld Study
Official title: Immunosuppression in Renal Transplantation in The Elderly: Time to Rethink. - nEverOld Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Chronic Renal Failure (CRF)
Graft Failure
Transplant; Failure, Kidney
Renal Transplant Rejection
Keywords: kidney transplantation
chronic renal failure
immunosuppressive therapy
elderly
pharmacokinetic
tacrolimus
everolimus
mycophenolate sodium
serious adverse events
biopsy
Cystatin C
metabolic effects
Left Ventricular Mass (LVM)
Left Ventricle Ejection Fraction
Lead sponsor: University of Sao Paulo General Hospital
Sponsor class: OTHER
First posted: 2012-06-28
Enrollment: 90
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* All renal (only) male and female recipients aged ≥ 60, years undergoing kidney transplantation from a living or deceased donor, including Expanded Criteria Donors (ECD).
* Panel Reactive Antibody (PRA) \< 30%.
* Patients who consented to participate in the study by signing the informed consent form before the transplant surgery to the 1st post-operative day).

Exclusion Criteria:

* Allergy to any of proposed medications
* Patients with any active infection including HBV, HCV and HIV.

Primary outcomes:
measure: Evaluation of functional graft
timeFrame: 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.
Secondary outcomes:
measure: Pharmacokinetic of Tacrolimus
timeFrame: Days: 7, 30, 60, 67, 90, 180.
measure: Serious adverse events
timeFrame: Every year, for five years
measure: Biopsy
timeFrame: Every year, for five years
measure: Renal filtration markers
timeFrame: Days: 7, 30, 37, 60, 67, 90, 180. Months: 12, 18, 24, 36, 48, 60
measure: Bone density
timeFrame: Month 12
measure: Vitamin D
timeFrame: Months: 2, 12.
measure: Gonadal function
timeFrame: Months: 1, 12.
measure: Quality of Life
timeFrame: Months: 1, 12, 18, 24, 36, 48, 60.
measure: Left Ventricular Mass (LVM)
timeFrame: Month: 12.
measure: Left Ventricle Ejection Fraction (LVEF)
timeFrame: Month: 12.
measure: Pharmacokinetic of Everolimus
timeFrame: Days: 7, 30, 60, 67, 90, 180.
measure: Pharmacokinetic of Mycophenolate Sodium
timeFrame: Days: 7, 30, 60, 67, 90, 180.
Other outcomes:
Locations:
city: Sao Paulo
country: Brazil
facility: Clinical Hospital of the School of Medicine, University of Sao Paulo
state: SP
city: Sao Paulo
country: Brazil
facility: Clinical Hospital of the School of Medicine, University of Sao Paulo
state: SP
Study officials:
affiliation: Clinical Hospital of the School of Medicine, University of Sao Paulo
name: Elias David-Neto, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Romano P, Agena F, de Almeida Rezende Ebner P, Massakazu Sumita N, Kamada Triboni AH, Ramos F, Dos Santos Garcia M, Coelho Duarte NJ, Brambate Carvalhinho Lemos F, Zocoler Galante N, David-Neto E. Longitudinal Pharmacokinetics of Mycophenolic Acid in Elderly Renal Transplant Recipients Compared to a Younger Control Group: Data from the nEverOld Trial. Eur J Drug Metab Pharmacokinet. 2019 Apr;44(2):189-199. doi: 10.1007/s13318-018-0506-6.