Renal Transplantation in the Elderly - nEverOld Study

Graft Failure Clinical Trial

Official title:

Immunosuppression in Renal Transplantation in The Elderly: Time to Rethink. - nEverOld Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01631058
• Other study ID #: 26423
• Status: Recruiting
• Phase: Phase 4
• First received: June 21, 2012
• Last updated: December 3, 2015
• Start date: July 2012
• Est. completion date: June 2019

Study information

• Verified date: January 2013
• Source: University of Sao Paulo General Hospital
• Contact: Elias David-Neto, PhD
• Phone: +55 11 26618089
• Email: elias[@]cntt.com.br
• Is FDA regulated: No
• Health authority: Brazil: National Health Surveillance Agency
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: June 2019
• Est. primary completion date: July 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 60 Years and older

Eligibility

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.

Study Design

Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Renal Failure (CRF)
• Graft Failure
• Kidney Failure, Chronic
• Renal Insufficiency
• Renal Transplant Rejection
• Transplant; Failure, Kidney

Intervention

Drug:
• Everolimus
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.

Locations

Country	Name	City	State
Brazil	Clinical Hospital of the School of Medicine, University of Sao Paulo	Sao Paulo	SP
Brazil	Clinical Hospital of the School of Medicine, University of Sao Paulo	Sao Paulo	SP

Sponsors (1)

Lead Sponsor	Collaborator
University of Sao Paulo General Hospital

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluation 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.	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.	Yes
Secondary	Pharmacokinetic of Tacrolimus	Pharmacokinetic of Tacrolimus in the study population at days 7, 30, 60, 67, 90 and 180 post-transplant.	Days: 7, 30, 60, 67, 90, 180.	Yes
Secondary	Serious adverse events	Evaluate serious adverse events (as internationally defined by ICH-GCP).	Every year, for five years	Yes
Secondary	Biopsy	Biopsy proven acute rejection rated every year, for five years.	Every year, for five years	Yes
Secondary	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.	Days: 7, 30, 37, 60, 67, 90, 180. Months: 12, 18, 24, 36, 48, 60	No
Secondary	Bone density	Evaluation of bone density at month 12 post-transplant.	Month 12	No
Secondary	Vitamin D	Evaluation of vitamin D at months 2 and 12 post-transplant.	Months: 2, 12.	No
Secondary	Gonadal function	Evaluation of gonadal function at months 1 and 12 post-transplant.	Months: 1, 12.	No
Secondary	Quality of Life	Evaluate Quality of Life at months 1, 12, 18, 24, 36, 48 and 60 post-transplant in the study population.	Months: 1, 12, 18, 24, 36, 48, 60.	No
Secondary	Left Ventricular Mass (LVM)	Left Ventricular Mass (LVM) measured by echocardiography at the end of the first year.	Month: 12.	Yes
Secondary	Left Ventricle Ejection Fraction (LVEF)	Left Ventricle Ejection Fraction (LVEF) measured by echocardiography at the end of the first year.	Month: 12.	Yes
Secondary	Pharmacokinetic of Everolimus	Pharmacokinetic of Everolimus in the study population at days 7, 30, 60, 67, 90 and 180 post-transplant.	Days: 7, 30, 60, 67, 90, 180.	Yes
Secondary	Pharmacokinetic of Mycophenolate Sodium	Pharmacokinetic of Mycophenolate Sodium in the study population at days 7, 30, 60, 67, 90 and 180 post-transplant.	Days: 7, 30, 60, 67, 90, 180.	Yes