Chronic Renal Failure (CRF)Phase 4NCT01631058
Renal Transplantation in the Elderly - nEverOld Study
A Phase 4 study testing Everolimus in people with Chronic Renal Failure (CRF) and Graft Failure, run by University of Sao Paulo General Hospital at 2 sites in Brazil.
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. Read more about this study
- Who is it for?
- Ages 60 years and older
- Conditions the study is for
- Chronic Renal Failure (CRF), Graft Failure, Transplant; Failure, Kidney
- What is being tested?
- Everolimus
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 2 sitesBrazil
- Study dates
- Jul 2012to Jun 2019
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 60 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- Allergy to any of proposed medications
- Patients with any active infection including HBV, HCV and HIV.
Trial locations and contacts
2 sites in 1 country.
Brazil2 sites, 2 recruiting
- Recruiting
Clinical Hospital of the School of Medicine, University of Sao Paulo
São Paulo, São Paulo, 05403900
Elias David-Neto, PhD
Francine B. Lemos, PhD
- Recruiting
Clinical Hospital of the School of Medicine, University of Sao Paulo
São Paulo, São Paulo, 05403900
Elias David-Neto, PhD
Francine B. Lemos, PhD
About this study
Official title: Immunosuppression in Renal Transplantation in The Elderly: Time to Rethink. - nEverOld Study
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.
Read more
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.
Read the 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:
- 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:
- 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.
- Serious adverse events (as internationally defined by ICH-GCP) every year, for five years.
- Biopsy proven acute rejection rated every year, for five years.
- 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.
- 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.
- Left Ventricular Mass (LVM) and Left Ventricle Ejection Fraction (LVEF) measured by echocardiography at the end of the first year.
- Conditions
- Chronic Renal Failure (CRF), Graft Failure, Transplant; Failure, Kidney, Renal Transplant Rejection
- Being tested
- Everolimus
- 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
- Medical subject headings
- Kidney Failure, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EverolimusDrug
Also called Certican (NOVARTIS), Myfortic (NOVARTIS), Prednisone (generic)
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.
| Study group | Role | What they receive |
|---|---|---|
| Everolimus | Experimental | 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. Receives: Drug: Everolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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 (12)
Pharmacokinetic of Tacrolimus
Pharmacokinetic of Tacrolimus in the study population at days 7, 30, 60, 67, 90 and 180 post-transplant.
Measured: Days: 7, 30, 60, 67, 90, 180.
Serious adverse events
Evaluate serious adverse events (as internationally defined by ICH-GCP).
Measured: Every year, for five years
Biopsy
Biopsy proven acute rejection rated every year, for five years.
Measured: 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.
Measured: 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.
Measured: Month 12
Vitamin D
Evaluation of vitamin D at months 2 and 12 post-transplant.
Measured: Months: 2, 12.
Gonadal function
Evaluation of gonadal function at months 1 and 12 post-transplant.
Measured: 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.
Measured: 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.
Measured: Month: 12.
Left Ventricle Ejection Fraction (LVEF)
Left Ventricle Ejection Fraction (LVEF) measured by echocardiography at the end of the first year.
Measured: Month: 12.
Pharmacokinetic of Everolimus
Pharmacokinetic of Everolimus in the study population at days 7, 30, 60, 67, 90 and 180 post-transplant.
Measured: 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.
Measured: Days: 7, 30, 60, 67, 90, 180.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jun 2012 (estimated)
- Study startJul 2012
- Primary completionJul 2014
- Study completionJun 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Chronic Renal Failure (CRF)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Sao Paulo General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Elias David-Neto, PhD, Principal investigator, Clinical Hospital of the School of Medicine, University of Sao Paulo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01631058
- Sponsor's protocol ID
- 26423
- Status last verified
- Jan 2013
- First submitted
- 21 Jun 2012
- Last updated
- 4 Dec 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Freitas GRR, Fernandes MDL, Agena F, Lemos FBC, de Paula FJ, Coelho V, David-Neto E, Galante NZ. Effects of two immunosuppression regimens on T-lymphocyte subsets in elderly kidney transplant recipients. Front Immunol. 2024 Sep 20;15:1405855. doi: 10.3389/fimmu.2024.1405855. eCollection 2024.
PubMed 39372414Romano 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.
PubMed 30229398
Study at a glance
From the registry record, last updated by the sponsor on 4 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Immunosuppression in Renal Transplantation in The Elderly: Time to Rethink. - nEverOld Study
- ClinicalTrials.gov ID
- NCT01631058
- Acronym / sponsor ID
- 26423
- 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
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- University of Sao Paulo General HospitalUniversity, hospital or other
- Study start
- Jul 2012
- Primary completion
- Jul 2014 (actual)
- Study completion
- Jun 2019 (estimated)
- First posted
- 28 Jun 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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:
- 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.
- Serious adverse events (as internationally defined by ICH-GCP) every year, for five years.
- Biopsy proven acute rejection rated every year, for five years.
- 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.
- 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.
- Left Ventricular Mass (LVM) and Left Ventricle Ejection Fraction (LVEF) measured by echocardiography at the end of the first year.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Everolimus | Experimental | Drug: EverolimusNumber 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. |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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).
Key exclusion criteria (2 listed)
- Allergy to any of proposed medications
- Patients with any active infection including HBV, HCV and HIV.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EverolimusAlso: Certican (NOVARTIS), Myfortic (NOVARTIS), Prednisone (generic)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. | Drug | Everolimus |
Primary outcome
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.
12 secondary outcomes
Pharmacokinetic of Tacrolimus
Time frame: Days: 7, 30, 60, 67, 90, 180.
Serious adverse events
Time frame: Every year, for five years
Biopsy
Time frame: 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
Bone density
Time frame: Month 12
Vitamin D
Time frame: Months: 2, 12.
Gonadal function
Time frame: Months: 1, 12.
Quality of Life
Time frame: Months: 1, 12, 18, 24, 36, 48, 60.
Left Ventricular Mass (LVM)
Time frame: Month: 12.
Left Ventricle Ejection Fraction (LVEF)
Time frame: Month: 12.
Pharmacokinetic of Everolimus
Time frame: Days: 7, 30, 60, 67, 90, 180.
Pharmacokinetic of Mycophenolate Sodium
Time frame: Days: 7, 30, 60, 67, 90, 180.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Dec 2015.
- Derived from this study: PubMed 39372414Freitas GRR, Fernandes MDL, Agena F, Lemos FBC, de Paula FJ, Coelho V, David-Neto E, Galante NZ. Effects of two immunosuppression regimens on T-lymphocyte subsets in elderly kidney transplant recipients. Front Immunol. 2024 Sep 20;15:1405855. doi: 10.3389/fimmu.2024.1405855. eCollection 2024.
- Derived from this study: PubMed 30229398Romano 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.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Elias David-Neto, PhD principal investigator
Clinical Hospital of the School of Medicine, University of Sao Paulo
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Everolimus in people with Chronic Renal Failure (CRF) and Graft Failure, run by University of Sao Paulo General Hospital at 2 sites in Brazil.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 4 Dec 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Elias David-Neto, PhD (+55 11 26618089, elias@cntt.com.br), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01631058, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Dec 2015; AzTrials last refreshed its copy on 30 Oct 2026.