Renal Transplantation in the Elderly - nEverOld Study

• ClinicalTrials.gov Identifier: NCT01631058
• Recruitment Status: Unknown
• First Posted: June 28, 2012
• Last Update Posted: December 4, 2015
• Sponsor: University of Sao Paulo General Hospital
• Information provided by (Responsible Party): University of Sao Paulo General Hospital

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Chronic Renal Failure (CRF); Graft Failure; Transplant; Failure, Kidney; Renal Transplant Rejection	Drug: Everolimus	Phase 4

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 90 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Immunosuppression in Renal Transplantation in The Elderly: Time to Rethink. - nEverOld Study
• Study Start Date: July 2012
• Actual Primary Completion Date: July 2014
• Estimated Study Completion Date: June 2019

Arms and Interventions

Arm

Intervention/treatment

Experimental: Everolimus; Number of patients: 45 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.

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.; Other Names: Certican (NOVARTIS); Myfortic (NOVARTIS); Prednisone (generic)

Outcome Measures

Primary Outcome Measures :

1. Evaluation of functional graft [ 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. ]
   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 Outcome Measures :

1. Pharmacokinetic of Tacrolimus [ Time Frame: Days: 7, 30, 60, 67, 90, 180. ]
   Pharmacokinetic of Tacrolimus in the study population at days 7, 30, 60, 67, 90 and 180 post-transplant.
2. Serious adverse events [ Time Frame: Every year, for five years ]
   Evaluate serious adverse events (as internationally defined by ICH-GCP).
3. Biopsy [ Time Frame: Every year, for five years ]
   Biopsy proven acute rejection rated every year, for five years.
4. Renal filtration markers [ Time Frame: Days: 7, 30, 37, 60, 67, 90, 180. Months: 12, 18, 24, 36, 48, 60 ]
   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. Bone density [ Time Frame: Month 12 ]
   Evaluation of bone density at month 12 post-transplant.
6. Vitamin D [ Time Frame: Months: 2, 12. ]
   Evaluation of vitamin D at months 2 and 12 post-transplant.
7. Gonadal function [ Time Frame: Months: 1, 12. ]
   Evaluation of gonadal function at months 1 and 12 post-transplant.
8. Quality of Life [ Time Frame: Months: 1, 12, 18, 24, 36, 48, 60. ]
   Evaluate Quality of Life at months 1, 12, 18, 24, 36, 48 and 60 post-transplant in the study population.
9. Left Ventricular Mass (LVM) [ Time Frame: Month: 12. ]
   Left Ventricular Mass (LVM) measured by echocardiography at the end of the first year.
10. Left Ventricle Ejection Fraction (LVEF) [ Time Frame: Month: 12. ]
    Left Ventricle Ejection Fraction (LVEF) measured by echocardiography at the end of the first year.
11. Pharmacokinetic of Everolimus [ Time Frame: Days: 7, 30, 60, 67, 90, 180. ]
    Pharmacokinetic of Everolimus in the study population at days 7, 30, 60, 67, 90 and 180 post-transplant.
12. Pharmacokinetic of Mycophenolate Sodium [ Time Frame: Days: 7, 30, 60, 67, 90, 180. ]
    Pharmacokinetic of Mycophenolate Sodium in the study population at days 7, 30, 60, 67, 90 and 180 post-transplant.

Eligibility Criteria

• Ages Eligible for Study: 60 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Contacts

Contact: Elias David-Neto, PhD; +55 11 26618089; elias@cntt.com.br

Locations

Brazil

Clinical Hospital of the School of Medicine, University of Sao Paulo; Recruiting

Sao Paulo, SP, Brazil, 05403900

Principal Investigator: Elias David-Neto, PhD

Sub-Investigator: Francine B. Lemos, PhD

Sub-Investigator: Nelson Z. Galante, PhD

Sub-Investigator: Fabiana Agena, MS

Sub-Investigator: William C Nahas, PhD

Sub-Investigator: Wilson Jacob-Filho, PhD

Sub-Investigator: Marcelo Altona, MD

Sub-Investigator: Daisa R David, PhD

Sub-Investigator: Flavio J Paula, PhD

Sub-Investigator: Paschoalina Romano, MS

Sub-Investigator: Persio AR Ebner, Biol

Sub-Investigator: Maria da Luz Fernandes, MS

Sub-Investigator: Veronica PC Coelho, PhD

Sub-Investigator: Venceslau A Coelho, MD

Sub-Investigator: Fabio Di Nizio, MD

Clinical Hospital of the School of Medicine, University of Sao Paulo; Recruiting

Sao Paulo, SP, Brazil, 05403900

Principal Investigator: Elias David-Neto, PhD

Sub-Investigator: Francine B. Lemos, PhD

Sub-Investigator: Nelson Z. Galante, PhD

Sub-Investigator: Fabiana Agena, MS

Sponsors and Collaborators

University of Sao Paulo General Hospital

Investigators

• Principal Investigator: Elias David-Neto, PhD; Clinical Hospital of the School of Medicine, University of Sao Paulo

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: University of Sao Paulo General Hospital
• ClinicalTrials.gov Identifier: NCT01631058
• Other Study ID Numbers: 26423
• First Posted: June 28, 2012
• Last Update Posted: December 4, 2015
• Last Verified: January 2013

Keywords provided by University of Sao Paulo General Hospital:

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

Additional relevant MeSH terms:

Renal Insufficiency; Kidney Failure, Chronic; Kidney Diseases; Urologic Diseases; Renal Insufficiency, Chronic; Prednisone; Everolimus; Lactitol; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Antineoplastic Agents, Hormonal; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Cathartics; Gastrointestinal Agents