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

April 16, 2013 updated by: CHU de Reims

Study of the Safety of Eplerenone in Cyclosporine A-treated Transplant Recipients

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.

Study Overview

Status

Unknown

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

31

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

      • Reims, France, 51092
        • Recruiting
        • Centre Hospitalier Universitaire de Reims
        • Contact:
        • Principal Investigator:
          • Philippe RIEU, PhD, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: A
Eplerenone

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Occurence of an adverse event requiring the discontinuation of eplerenone
Time Frame: 8 weeks

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
8 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2013

Primary Completion (ANTICIPATED)

April 1, 2013

Study Completion (ANTICIPATED)

December 1, 2013

Study Registration Dates

First Submitted

April 11, 2013

First Submitted That Met QC Criteria

April 16, 2013

First Posted (ESTIMATE)

April 18, 2013

Study Record Updates

Last Update Posted (ESTIMATE)

April 18, 2013

Last Update Submitted That Met QC Criteria

April 16, 2013

Last Verified

April 1, 2013

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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