Kidney Transplantation for More Than One YearPhase 3EVATRANNCT04450953
The Effect of Eplerenone on the Evolution of Vasculopathy in Renal Transplant Patients.
A Phase 3 study testing Eplerenone 50mg/day (cross over design) and Period without eplerenone (cross over design) in people with Kidney Transplantation for More Than One Year and Patients with a Kidney Transplantation on Cyclosporine, run by Central Hospital, Nancy, France at 1 site in France.
Trial summary
Cardiovascular (CV) pathologies are the leading cause of death in kidney transplant patients.Arterial stiffness is a prognostic factor for CV mortality in kidney transplantation. Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Kidney Transplantation for More Than One Year, Patients with a Kidney Transplantation on Cyclosporine
- What is being tested?
- Eplerenone 50mg/day (cross over design) and Period without eplerenone (cross over design)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteFrance
- Study dates
- 12 Oct 2021to Nov 2025
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
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 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men or women ≥ 50 years of age;
- Patient who had a kidney transplant at least one year prior to inclusion;
- Patient on cyclosporine;
- Patient whose clinical-biological state has been stable for at least 3 months: no change in treatment with an impact on blood pressure (excluding immunosuppressive drug) for 3 months, no acute rejection diagnosed within 3 months;
- Patient with a glomerular filtration rate estimated according to the formula CKD-EPI ≥30mL/min/1.73m2;
- Patient with a peripheral PAS≥110mmHg, irrespective of the presence or not of an antihypertensive therapy (including ACE inhibitors or sartan) ;
- Patient with signed informed consent;
- Patient affiliated with or beneficiary of a social security system.
Who cannot join
- Patient with documented kalemia ≥ 5mmol/L in the last 15 days;
- Patient undergoing mineralocorticoid receptor antagonism or with a formal indication to receive this treatment;
- Bicarbonate blood level <20mmol/L with or without documented supplementation in the last 15 days.
- Indication for a combination of ACE inhibitor and sartan (each of which is authorized separately);
- Patient under another potassium sparing diuretics;
- Patient under digoxine;
Show all 20Show fewer
- Sodium polystyrene sulfonate contraindication;
- Known hypersensitivity or allergy to eplerenone and its excipients;
- Patient with severe hepatic impairment (Child-Pugh Class C);
- Patient under CYP3A4 inhibitor;
- know intolerance to Galactose, a Lapp lactase deficiency or galactose malabsorption syndrome;
- Patient participating in other interventional research;
- Woman with a desire of pregnancy within 15 months;
- Woman of childbearing age without effective contraception;
- Persons referred to in Articles L. 1121-5, L. 1121-7 and L1121-8 of the Public Health Code :
- Pregnant women, parturient women or nursing mothers ;
- Adult person subject to a legal protection measure (guardianship, curator, judicial safeguard);
- Adults person who is unable to give consent and who is not subject to a legal protection measure;
- Persons deprived of their liberty by a judicial or administrative decision;
- Persons subject to psychiatric care pursuant to articles L. 3212-1 and L. 3213-1.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
France1 site, 1 recruiting
- Recruiting
CHRU de Nancy
Vandœuvre-lès-Nancy, 54500
Sophie GIRERD, MD, (0) 3 83 15 73 22 ext. +33, s.girerd@chru-nancy.fr
About this study
Official title: A Randomized Crossover Clinical Trial Regarding the Blockage of the Mineralocorticoid Receptor Using Eplerenone on the Evolution of Arterial Stiffness in Kidney Patients One Year After Transplant
Cardiovascular (CV) pathologies are the leading cause of death in kidney transplant patients.Arterial stiffness is a prognostic factor for CV mortality in kidney transplantation. Despite a reduced CV risk in transplant kidney patients in comparison to patients in dialysis, CV mortality among kidney transplant patients is much higher than the general population.
After renal transplantation, the cardiac and vascular anomalies observed in chronic end-stage renal disease are partially improved because of restored normal kidney function and withdrawal from dialysis.
Read more
However, patients are exposed to immunosuppressive drugs, in particular calcineurin inhibitors, which can be associated with vascular toxicity, either directly or by promoting the appearance of hypertension, diabetes, or dyslipidemia.The pathophysiology of arterial stiffness in kidney transplantation is complex and multifactorial.
Calcineurin inhibitors are likely to play an important role in the persistence of increased arterial stiffness in transplant patients in whom renal function has been restored. Indeed, the discontinuation of anti-calcineurins in favour of other molecules .is associated with a decrease of arterial stiffness.
Preclinical work has shown that the vascular toxicity of cyclosporine is mediated by activation of the mineralocorticoid receptor in smooth muscle cells. The involvement of the mineralocorticoid receptor in the onset of arterial stiffness is also well demonstrated in non-transplanted subjects.
Blocking the mineralocorticoid receptor in patients under cyclosporine may reduce their arterial stiffness and in and consequently improve their CV prognosis.
Studies have show a good safety in kidney transplant patients. This pilot study proposes to examine, for the first time, the impact of treatment with a mineralocorticoid receptor antagonist on the evolution of arterial stiffness in renal transplant patients on calcineurin inhibitors.
- Conditions
- Kidney Transplantation for More Than One Year, Patients with a Kidney Transplantation on Cyclosporine
- Being tested
- Eplerenone 50mg/day (cross over design), Period without eplerenone (cross over design)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Eplerenone 50mg/day (cross over design)Drug
Eplerenone 50mg/day for 6 months followed
Period without eplerenone (cross over design)Other
6-month period without eplerenone
| Study group | Role | What they receive |
|---|---|---|
| Eplerenone group A (cross over design) | Active comparator | Patient will receive eplerenone 50mg/day taken orally for 6 months, followed by a 8 to 10 weeks wash-out period, then a 6-month period without eplerenone, until the end of the study. Receives: Drug: Eplerenone 50mg/day (cross over design); Other: Period without eplerenone (cross over design) |
| Eplerenone group B (cross over design) | Active comparator | Eplerenone-free for 6 months, followed by a 8 to 10 weeks wash-out period, then a 6-month period in which patients will receive eplerenone 50 mg/day as a single dose taken orally. Receives: Drug: Eplerenone 50mg/day (cross over design); Other: Period without eplerenone (cross over design) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evolution of pulse wave velocity (PWV in m/s) adjusted to the blood pressure
Measured: After 6 months of treatment with eplerenone
Secondary outcomes (21)
Evolution of Central Systolic Blood Pressure (CSPc)
Measured: After 6 months of treatment with eplerenone
Evolution of central Diastolic Blood Pressure (CDAb)
Measured: After 6 months of treatment with eplerenone
Evolution of Central Pulsed Pressure (CPp)
Measured: After 6 months of treatment with eplerenone
Evolution of Augmentation index (Aix in %)
Measured: After 6 months of treatment with eplerenone
Evolution peripheral systolic blood pressure (PASp in mmHg)
Measured: After 6 months of treatment with eplerenone
Evolution of peripheral diastolic blood pressure (PADp in mmHg)
Measured: After 6 months of treatment with eplerenone
Evolution of peripheral pulse pressure (PPp in mmHg)
Measured: After 6 months of treatment with eplerenone
Evolution of Intima-media thickness (in mm)
Measured: After 6 months of treatment with eplerenone
Evolution of left ventricular mass (LVM in g/m2)
Measured: After 6 months of treatment with eplerenone
Evolution of biological markers of oxidative stress (plasma Isoprostane)
Measured: After 6 months of treatment with eplerenone
Evolution of biological markers of oxidative stress (Malondialdehyde)
Measured: After 6 months of treatment with eplerenone
Evolution of Biological markers of endothelial dysfunction (endothelin)
Measured: After 6 months of treatment with eplerenone
Evolution of biological markers of endothelial dysfunction (soluble endothelium selectin (sE-selectin))
Measured: After 6 months of treatment with eplerenone
Evolution of biological markers of endothelial dysfunction (von Willebrand factor)
Measured: After 6 months of treatment with eplerenone
Evolution of graft function
measured by creatinine (in micromol/L) with estimation of glomerular filtration rate (eGFR in mL/min/1.73m2 ) according to the CKD-EPI formula.
Measured: After 6 months of treatment with eplerenone
Evolution of proteinuria
measured by the ratio proteinuria/creatinuria (in mg/g)
Measured: After 6 months of treatment with eplerenone
Percentage of patients with DFG ≥ 90, 60-89, 45-59, 30-44, 15-29 <15ml/min/1,73m2
Measured: After 6 months of treatment with eplerenone
Percentage of patient with ratio proteinuria/creatinuria (en mg/g) <500 ; 500-1000, 1000-2000, 2000-3000, >3000
Measured: After 6 months of treatment with eplerenone
hyperkalemia occurence ≥ 5.5 mmol/L
Measured: during 6 month of treatment with eplerenone
Number of hyperkalemia
number of hyperkalemias during hyperkalemia follow-up between 5 - 5.49; 5.5 - 6; >6mmol/L
Measured: during 6 month of treatment with eplerenone
increase of creatinine of more than 50%
Evaluation of risk of acute renal failure defined as an increase in creatinine of more than 50%
Measured: during 6 month of treatment with eplerenone
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jun 2020
- Study start12 Oct 2021
- Primary completionNov 2025 (estimated)
- Study completionNov 2025 (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 Kidney Transplantation for More Than One YearStudies of the same condition, open and under way.
- More trials run by Central Hospital, Nancy, FranceThe sponsor's other registered studies.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- * Arm A in which they will receive eplerenone 50mg/day taken orally for 6 months, followed by a 8 to 10 weeks wash-out period, then a 6-month period without eplerenone, until the end of the study. * arm B where they will be eplerenone-free for 6 months, followed by a 8 to 10 weeks wash-out period, then a 6-month period in which they will receive eplerenone 50 mg/day as a single dose taken orally.
- Masking
- None (open label)
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Central Hospital, Nancy, France
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Pr. Nicolas GIRERD, Central Hospital, Nancy, France
- Investigators
- Nicolas GIRERD, MD-Phd, Study chair, Central Hospital, Nancy, FranceSophie GIRERD, MD-PhD, Principal investigator, Central Hospital, Nancy, France
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04450953
- Sponsor's protocol ID
- 2019-004243-74
- Other IDs
- 2019
- Acronym
- EVATRAN
- Status last verified
- Feb 2025
- First submitted
- 25 Jun 2020
- Last updated
- 12 Feb 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Simon A, Girerd N, Jaisser F, Bozec E, Lepage X, Merckle L, Rossignol P, Frimat L, Girerd S. EVATRAN (The Effect of Eplerenone on the Evolution of Vasculopathy in Renal Transplant Patients): study protocol for a cross-over randomized controlled trial. Trials. 2025 Nov 7;26(1):479. doi: 10.1186/s13063-025-09187-w.
PubMed 41204172Natale P, Mooi PK, Palmer SC, Cross NB, Cooper TE, Webster AC, Masson P, Craig JC, Strippoli GF. Antihypertensive treatment for kidney transplant recipients. Cochrane Database Syst Rev. 2024 Jul 31;7(7):CD003598. doi: 10.1002/14651858.CD003598.pub3.
PubMed 39082471
Study at a glance
From the registry record, last updated by the sponsor on 12 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Crossover Clinical Trial Regarding the Blockage of the Mineralocorticoid Receptor Using Eplerenone on the Evolution of Arterial Stiffness in Kidney Patients One Year After Transplant
- ClinicalTrials.gov ID
- NCT04450953
- Acronym / sponsor ID
- EVATRAN / 2019-004243-74
- Conditions
- Kidney Transplantation for More Than One Year, Patients with a Kidney Transplantation on Cyclosporine
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- Central Hospital, Nancy, FranceUniversity, hospital or other
- Study start
- 12 Oct 2021 (actual)
- Primary completion
- Nov 2025 (estimated)
- Study completion
- Nov 2025 (estimated)
- First posted
- 30 Jun 2020 (actual)
- 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.
Cardiovascular (CV) pathologies are the leading cause of death in kidney transplant patients.Arterial stiffness is a prognostic factor for CV mortality in kidney transplantation. Despite a reduced CV risk in transplant kidney patients in comparison to patients in dialysis, CV mortality among kidney transplant patients is much higher than the general population.
After renal transplantation, the cardiac and vascular anomalies observed in chronic end-stage renal disease are partially improved because of restored normal kidney function and withdrawal from dialysis.
However, patients are exposed to immunosuppressive drugs, in particular calcineurin inhibitors, which can be associated with vascular toxicity, either directly or by promoting the appearance of hypertension, diabetes, or dyslipidemia.The pathophysiology of arterial stiffness in kidney transplantation is complex and multifactorial.
Calcineurin inhibitors are likely to play an important role in the persistence of increased arterial stiffness in transplant patients in whom renal function has been restored. Indeed, the discontinuation of anti-calcineurins in favour of other molecules .is associated with a decrease of arterial stiffness.
Preclinical work has shown that the vascular toxicity of cyclosporine is mediated by activation of the mineralocorticoid receptor in smooth muscle cells. The involvement of the mineralocorticoid receptor in the onset of arterial stiffness is also well demonstrated in non-transplanted subjects.
Blocking the mineralocorticoid receptor in patients under cyclosporine may reduce their arterial stiffness and in and consequently improve their CV prognosis.
Studies have show a good safety in kidney transplant patients. This pilot study proposes to examine, for the first time, the impact of treatment with a mineralocorticoid receptor antagonist on the evolution of arterial stiffness in renal transplant patients on calcineurin inhibitors.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- * Arm A in which they will receive eplerenone 50mg/day taken orally for 6 months, followed by a 8 to 10 weeks wash-out period, then a 6-month period without eplerenone, until the end of the study. * arm B where they will be eplerenone-free for 6 months, followed by a 8 to 10 weeks wash-out period, then a 6-month period in which they will receive eplerenone 50 mg/day as a single dose taken orally.
| Arm | Type | Receives |
|---|---|---|
| Eplerenone group A (cross over design) | Active comparator | Drug: Eplerenone 50mg/day (cross over design), Other: Period without eplerenone (cross over design)Patient will receive eplerenone 50mg/day taken orally for 6 months, followed by a 8 to 10 weeks wash-out period, then a 6-month period without eplerenone, until the end of the study. |
| Eplerenone group B (cross over design) | Active comparator | Drug: Eplerenone 50mg/day (cross over design), Other: Period without eplerenone (cross over design)Eplerenone-free for 6 months, followed by a 8 to 10 weeks wash-out period, then a 6-month period in which patients will receive eplerenone 50 mg/day as a single dose taken orally. |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Men or women ≥ 50 years of age;
- Patient who had a kidney transplant at least one year prior to inclusion;
- Patient on cyclosporine;
- Patient whose clinical-biological state has been stable for at least 3 months: no change in treatment with an impact on blood pressure (excluding immunosuppressive drug) for 3 months, no acute rejection diagnosed within 3 months;
- Patient with a glomerular filtration rate estimated according to the formula CKD-EPI ≥30mL/min/1.73m2;
Key exclusion criteria (20 listed)
- Patient with documented kalemia ≥ 5mmol/L in the last 15 days;
- Patient undergoing mineralocorticoid receptor antagonism or with a formal indication to receive this treatment;
- Bicarbonate blood level <20mmol/L with or without documented supplementation in the last 15 days.
- Indication for a combination of ACE inhibitor and sartan (each of which is authorized separately);
- Patient under another potassium sparing diuretics;
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 |
|---|---|---|
| Eplerenone 50mg/day (cross over design)Eplerenone 50mg/day for 6 months followed | Drug | Eplerenone group A (cross over design), Eplerenone group B (cross over design) |
| Period without eplerenone (cross over design)6-month period without eplerenone | Other | Eplerenone group A (cross over design), Eplerenone group B (cross over design) |
Primary outcome
Evolution of pulse wave velocity (PWV in m/s) adjusted to the blood pressure
Time frame: After 6 months of treatment with eplerenone
21 secondary outcomes
Evolution of Central Systolic Blood Pressure (CSPc)
Time frame: After 6 months of treatment with eplerenone
Evolution of central Diastolic Blood Pressure (CDAb)
Time frame: After 6 months of treatment with eplerenone
Evolution of Central Pulsed Pressure (CPp)
Time frame: After 6 months of treatment with eplerenone
Evolution of Augmentation index (Aix in %)
Time frame: After 6 months of treatment with eplerenone
Evolution peripheral systolic blood pressure (PASp in mmHg)
Time frame: After 6 months of treatment with eplerenone
Evolution of peripheral diastolic blood pressure (PADp in mmHg)
Time frame: After 6 months of treatment with eplerenone
Evolution of peripheral pulse pressure (PPp in mmHg)
Time frame: After 6 months of treatment with eplerenone
Evolution of Intima-media thickness (in mm)
Time frame: After 6 months of treatment with eplerenone
Evolution of left ventricular mass (LVM in g/m2)
Time frame: After 6 months of treatment with eplerenone
Evolution of biological markers of oxidative stress (plasma Isoprostane)
Time frame: After 6 months of treatment with eplerenone
Evolution of biological markers of oxidative stress (Malondialdehyde)
Time frame: After 6 months of treatment with eplerenone
Evolution of Biological markers of endothelial dysfunction (endothelin)
Time frame: After 6 months of treatment with eplerenone
Evolution of biological markers of endothelial dysfunction (soluble endothelium selectin (sE-selectin))
Time frame: After 6 months of treatment with eplerenone
Evolution of biological markers of endothelial dysfunction (von Willebrand factor)
Time frame: After 6 months of treatment with eplerenone
Evolution of graft function
Time frame: After 6 months of treatment with eplerenone
Evolution of proteinuria
Time frame: After 6 months of treatment with eplerenone
Percentage of patients with DFG ≥ 90, 60-89, 45-59, 30-44, 15-29 <15ml/min/1,73m2
Time frame: After 6 months of treatment with eplerenone
Percentage of patient with ratio proteinuria/creatinuria (en mg/g) <500 ; 500-1000, 1000-2000, 2000-3000, >3000
Time frame: After 6 months of treatment with eplerenone
hyperkalemia occurence ≥ 5.5 mmol/L
Time frame: during 6 month of treatment with eplerenone
Number of hyperkalemia
Time frame: during 6 month of treatment with eplerenone
increase of creatinine of more than 50%
Time frame: during 6 month of treatment with eplerenone
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Feb 2025.
- Derived from this study: PubMed 41204172Simon A, Girerd N, Jaisser F, Bozec E, Lepage X, Merckle L, Rossignol P, Frimat L, Girerd S. EVATRAN (The Effect of Eplerenone on the Evolution of Vasculopathy in Renal Transplant Patients): study protocol for a cross-over randomized controlled trial. Trials. 2025 Nov 7;26(1):479. doi: 10.1186/s13063-025-09187-w.
- Derived from this study: PubMed 39082471Natale P, Mooi PK, Palmer SC, Cross NB, Cooper TE, Webster AC, Masson P, Craig JC, Strippoli GF. Antihypertensive treatment for kidney transplant recipients. Cochrane Database Syst Rev. 2024 Jul 31;7(7):CD003598. doi: 10.1002/14651858.CD003598.pub3.
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.
Nicolas GIRERD, MD-Phd study chair
Central Hospital, Nancy, France
Sophie GIRERD, MD-PhD principal investigator
Central Hospital, Nancy, France
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Eplerenone 50mg/day (cross over design) and Period without eplerenone (cross over design) in people with Kidney Transplantation for More Than One Year and Patients with a Kidney Transplantation on Cyclosporine, run by Central Hospital, Nancy, France at 1 site in France.
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 8 inclusion and 20 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: looking for participants now, as of the sponsor's last update on 12 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Sophie GIRERD, MD-phD ((0) 3 83 15 73 22 ext. +33, s.girerd@chru-nancy.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Evolution of pulse wave velocity (PWV in m/s) adjusted to the blood pressure (time frame: After 6 months of treatment with eplerenone). 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 NCT04450953, 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 12 Feb 2025.