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EPLErenone in CsA-Treated Recipients (EpleCsAT): Safety (EpleCsAT)

Primary Purpose

Chronic Kidney Insufficiency, Kidney Transplantation

Status
Unknown status
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Eplerenone
Sponsored by
CHU de Reims
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Kidney Insufficiency

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

All the patients that will be included in this trial have to fulfil all the following conditions:

  • more than 18-years old at the date of inclusion
  • a full legal capacity
  • belonging to a health care system
  • give their written consent
  • a functional kidney allograft for at least 1 year from the date of inclusion
  • be under cyclosporine A-treatment
  • impaired renal function estimated by the MDRD formula between 30 to 50mL/min/1.73m²

Exclusion Criteria:

All the patients that will be included in this trial have to fulfil no one of the following conditions:

  • serum potassium higher than or equal to 5mmol/L at the date of inclusion
  • one or more history of severe hyperkalemia (serum potassium higher than or equal to 6mmol/L) whatever the reason
  • currently under potassium exchange resin treatment like KAYEXALATE®
  • an acute rejection of the graft within the 6 months before the date of inclusion
  • an ongoing pregnancy or a lack of effective contraception during all the study
  • an uncontrolled high arterial blood pressure
  • an orthostatic hypotension
  • a systolic arterial blood pressure under or equal to 110mmHg
  • a heart failure within the past 3 months before the date of inclusion or a chronic heart failure (stages III or IV of the NYHA classification)
  • a severe hepatic failure (stage C of the Child-Pugh classification)
  • an allergy to one or more of the components of the speciality eplerenone - INSPRA®
  • an ongoing treatment with spironolactone - ALDACTONE® or eplerenone - INSPRA®
  • a contra-indicated association whose treatment could not be suspended during the study: potassium sparing diuretics, potassium salts, enzymatic inhibitors of CYP3A4 (like itraconazole, ketoconazole, ritonavir, nelfinavir, clarithromycine, telithromycine, nefazodone)
  • a malabsorption syndrome, an abnormality of galactose metabolism or a deficiency in galactase
  • an ongoing treatment with nonsteroidal anti-inflammatory or with lithium or another nephrotoxic agent
  • an ongoing treatment with a double-blockade of the Renin-Angiotensin-Aldosterone System by the association ACE-I (Angiotensin-Converting Enzyme Inhibitor) and ARB (Angiotensin Receptor Blocker)

Sites / Locations

  • Centre Hospitalier Universitaire de ReimsRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

A

Arm Description

Eplerenone

Outcomes

Primary Outcome Measures

Occurence of an adverse event requiring the discontinuation of eplerenone
Occurrence of an adverse event requiring the discontinuation of eplerenone: serum potassium higher than or equal to 6mmol/L and/or higher than or equal to 5.5mmol/L under 2 measuring spoons of KAYEXALATE® acidosis evidenced by serum alkaline reserve lower than or equal to 15mmol/L systemic hypotension evidenced by a systolic blood pressure lower than 100mHg orthostatic hypotension evidenced by a decrease of systolic blood pressure more than 20mmHg to the transition to upright posture within 3 minutes acute kidney failure evidenced by an increase of serum creatinine more than 30% from the starting value (at the date of inclusion) every other adverse event unscheduled by investigators, only if it requires the discontinuation of eplerenone

Secondary Outcome Measures

Full Information

First Posted
April 11, 2013
Last Updated
April 16, 2013
Sponsor
CHU de Reims
Collaborators
Institut National de la Santé Et de la Recherche Médicale, France
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1. Study Identification

Unique Protocol Identification Number
NCT01834768
Brief Title
EPLErenone in CsA-Treated Recipients (EpleCsAT): Safety
Acronym
EpleCsAT
Official Title
Study of the Safety of Eplerenone in Cyclosporine A-treated Transplant Recipients
Study Type
Interventional

2. Study Status

Record Verification Date
April 2013
Overall Recruitment Status
Unknown status
Study Start Date
February 2013 (undefined)
Primary Completion Date
April 2013 (Anticipated)
Study Completion Date
December 2013 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
CHU de Reims
Collaborators
Institut National de la Santé Et de la Recherche Médicale, France

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Kidney transplant recipients usually lose their graft by rejection or by immunosuppressive drugs toxicity. In kidney transplantation, calcineurin-inhibitors (including cyclosporine A) are widely used. Their renal toxicity could be divided between an acute toxicity (toxic arteriolopathy and toxic tubulopathy) and a chronic toxicity (hyaline arteriolopathy, interstitial fibrosis, tubular atrophy and glomerulosclerosis). Several animal models have shown the implication of the mineralocorticoid receptor (MR) activation in those toxic phenomenons. The use of a mineralocorticoid receptor antagonist is useful regarding to the renal function and kidney histological damages. Several antagonists are available in France but none is indicated in kidney transplantation. Eplerenone appears to be the most selective molecule of the mineralocorticoid receptor and to have less adverse anti-androgenic effects than others molecules. Its principal adverse events are hyperkalemia and orthostatic hypotension. Mineralocorticoid receptor antagonists, especially eplerenone, could be very useful in the prevention of the nephrotoxicity induced by calcineurin-inhibitors. Classically, eplerenone is contra-indicated in patients presenting with an impaired renal function, determined by a creatinine clearance under 50mL/min. Moreover, in France, a warning is especially notified for the association with cyclosporine A due to the fact that no study have been done in this context. The investigators study first the safety of the use of eplerenone in association with cyclosporine A in kidney transplant recipients. Then, if it is safe, the investigators will study its efficiency in a large randomized controlled trial.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Kidney Insufficiency, Kidney Transplantation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
31 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
A
Arm Type
Experimental
Arm Description
Eplerenone
Intervention Type
Drug
Intervention Name(s)
Eplerenone
Primary Outcome Measure Information:
Title
Occurence of an adverse event requiring the discontinuation of eplerenone
Description
Occurrence of an adverse event requiring the discontinuation of eplerenone: serum potassium higher than or equal to 6mmol/L and/or higher than or equal to 5.5mmol/L under 2 measuring spoons of KAYEXALATE® acidosis evidenced by serum alkaline reserve lower than or equal to 15mmol/L systemic hypotension evidenced by a systolic blood pressure lower than 100mHg orthostatic hypotension evidenced by a decrease of systolic blood pressure more than 20mmHg to the transition to upright posture within 3 minutes acute kidney failure evidenced by an increase of serum creatinine more than 30% from the starting value (at the date of inclusion) every other adverse event unscheduled by investigators, only if it requires the discontinuation of eplerenone
Time Frame
8 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: All the patients that will be included in this trial have to fulfil all the following conditions: more than 18-years old at the date of inclusion a full legal capacity belonging to a health care system give their written consent a functional kidney allograft for at least 1 year from the date of inclusion be under cyclosporine A-treatment impaired renal function estimated by the MDRD formula between 30 to 50mL/min/1.73m² Exclusion Criteria: All the patients that will be included in this trial have to fulfil no one of the following conditions: serum potassium higher than or equal to 5mmol/L at the date of inclusion one or more history of severe hyperkalemia (serum potassium higher than or equal to 6mmol/L) whatever the reason currently under potassium exchange resin treatment like KAYEXALATE® an acute rejection of the graft within the 6 months before the date of inclusion an ongoing pregnancy or a lack of effective contraception during all the study an uncontrolled high arterial blood pressure an orthostatic hypotension a systolic arterial blood pressure under or equal to 110mmHg a heart failure within the past 3 months before the date of inclusion or a chronic heart failure (stages III or IV of the NYHA classification) a severe hepatic failure (stage C of the Child-Pugh classification) an allergy to one or more of the components of the speciality eplerenone - INSPRA® an ongoing treatment with spironolactone - ALDACTONE® or eplerenone - INSPRA® a contra-indicated association whose treatment could not be suspended during the study: potassium sparing diuretics, potassium salts, enzymatic inhibitors of CYP3A4 (like itraconazole, ketoconazole, ritonavir, nelfinavir, clarithromycine, telithromycine, nefazodone) a malabsorption syndrome, an abnormality of galactose metabolism or a deficiency in galactase an ongoing treatment with nonsteroidal anti-inflammatory or with lithium or another nephrotoxic agent an ongoing treatment with a double-blockade of the Renin-Angiotensin-Aldosterone System by the association ACE-I (Angiotensin-Converting Enzyme Inhibitor) and ARB (Angiotensin Receptor Blocker)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Philippe RIEU
Email
prieu@chu-reims.fr
Facility Information:
Facility Name
Centre Hospitalier Universitaire de Reims
City
Reims
ZIP/Postal Code
51092
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Philippe RIEU, PhD, MD
Email
prieu@chu-reims.fr
First Name & Middle Initial & Last Name & Degree
Philippe RIEU, PhD, MD

12. IPD Sharing Statement

Citations:
PubMed Identifier
27088859
Citation
Bertocchio JP, Barbe C, Lavaud S, Toupance O, Nazeyrollas P, Jaisser F, Rieu P. Safety of Eplerenone for Kidney-Transplant Recipients with Impaired Renal Function and Receiving Cyclosporine A. PLoS One. 2016 Apr 18;11(4):e0153635. doi: 10.1371/journal.pone.0153635. eCollection 2016.
Results Reference
derived

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EPLErenone in CsA-Treated Recipients (EpleCsAT): Safety

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