Renal Transplantation in the Elderly

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2013 by University of Sao Paulo General Hospital
Sponsor:
Information provided by (Responsible Party):
University of Sao Paulo General Hospital
ClinicalTrials.gov Identifier:
NCT01631058
First received: June 21, 2012
Last updated: June 20, 2013
Last verified: January 2013
  Purpose

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 Intervention Phase
Chronic Renal Failure (CRF)
Graft Failure
Transplant; Failure, Kidney
Renal Transplant Rejection
Drug: Everolimus
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Immunosuppression in Renal Transplantation in The Elderly: Time to Rethink.

Resource links provided by NLM:


Further study details as provided by University of Sao Paulo General Hospital:

Primary Outcome Measures:
  • 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. ] [ Designated as safety issue: Yes ]
    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:
  • Pharmacokinetic of Tacrolimus [ Time Frame: Days: 7, 30, 60, 67, 90, 180. ] [ Designated as safety issue: Yes ]
    Pharmacokinetic of Tacrolimus in the study population at days 7, 30, 60, 67, 90 and 180 post-transplant.

  • Serious adverse events [ Time Frame: Every year, for five years ] [ Designated as safety issue: Yes ]
    Evaluate serious adverse events (as internationally defined by ICH-GCP).

  • Biopsy [ Time Frame: Every year, for five years ] [ Designated as safety issue: Yes ]
    Biopsy proven acute rejection rated every year, for five years.

  • Renal filtration markers [ Time Frame: Days: 7, 30, 37, 60, 67, 90, 180. Months: 12, 18, 24, 36, 48, 60 ] [ Designated as safety issue: No ]
    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.

  • Bone density [ Time Frame: Month 12 ] [ Designated as safety issue: No ]
    Evaluation of bone density at month 12 post-transplant.

  • Vitamin D [ Time Frame: Months: 2, 12. ] [ Designated as safety issue: No ]
    Evaluation of vitamin D at months 2 and 12 post-transplant.

  • Gonadal function [ Time Frame: Months: 1, 12. ] [ Designated as safety issue: No ]
    Evaluation of gonadal function at months 1 and 12 post-transplant.

  • Quality of Life [ Time Frame: Months: 1, 12, 18, 24, 36, 48, 60. ] [ Designated as safety issue: No ]
    Evaluate Quality of Life at months 1, 12, 18, 24, 36, 48 and 60 post-transplant in the study population.

  • Left Ventricular Mass (LVM) [ Time Frame: Month: 12. ] [ Designated as safety issue: Yes ]
    Left Ventricular Mass (LVM) measured by echocardiography at the end of the first year.

  • Left Ventricle Ejection Fraction (LVEF) [ Time Frame: Month: 12. ] [ Designated as safety issue: Yes ]
    Left Ventricle Ejection Fraction (LVEF) measured by echocardiography at the end of the first year.

  • Pharmacokinetic of Everolimus [ Time Frame: Days: 7, 30, 60, 67, 90, 180. ] [ Designated as safety issue: Yes ]
    Pharmacokinetic of Everolimus in the study population at days 7, 30, 60, 67, 90 and 180 post-transplant.

  • Pharmacokinetic of Mycophenolate Sodium [ Time Frame: Days: 7, 30, 60, 67, 90, 180. ] [ Designated as safety issue: Yes ]
    Pharmacokinetic of Mycophenolate Sodium in the study population at days 7, 30, 60, 67, 90 and 180 post-transplant.


Estimated Enrollment: 90
Study Start Date: July 2012
Estimated Study Completion Date: June 2019
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)

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

Ages Eligible for Study:   60 Years and older
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01631058

Contacts
Contact: Elias David Neto, MD +55 11 26618089 elias.david.neto@attglobal.net

Locations
Brazil
Clinical Hospital of the School of Medicine, University of Sao Paulo Recruiting
Sao Paulo, SP, Brazil, 05403900
Principal Investigator: Elias David Neto, MD         
Sub-Investigator: Francine Brambate Lemos, MD         
Sponsors and Collaborators
University of Sao Paulo General Hospital
Investigators
Principal Investigator: Elias David Neto, MD Clinical Hospital of the School of Medicine, University of Sao Paulo
  More Information

No publications provided

Responsible Party: University of Sao Paulo General Hospital
ClinicalTrials.gov Identifier: NCT01631058     History of Changes
Other Study ID Numbers: 26423
Study First Received: June 21, 2012
Last Updated: June 20, 2013
Health Authority: Brazil: National Health Surveillance Agency

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:
Kidney Failure, Chronic
Renal Insufficiency
Renal Insufficiency, Chronic
Kidney Diseases
Urologic Diseases
Everolimus
Sirolimus
Tacrolimus
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Antifungal Agents
Anti-Infective Agents
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on July 26, 2014