EPLErenone in CsA-Treated Recipients (EpleCsAT): Safety

NCT01834768 | Unknown Phase 2 DMC

• 1 other identifier: PA11020
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

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.

Conditions

Chronic Kidney Insufficiency; Kidney Transplantation

Outcome Measures

Primary Outcomes (1)

• 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

  8 weeks

Study Arms (1)

A

EXPERIMENTAL

Eplerenone

Drug: Eplerenone

Interventions

Eplerenone DRUG

A

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All the patients that will be included in this trial have to fulfil all the following conditions:
• a full legal capacity
• belonging to a health care system
• give their written consent
• be under cyclosporine A-treatment
• impaired renal function estimated by the MDRD formula between 30 to 50mL/min/1.73m²

You may not qualify if:

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

Sponsors & Collaborators

• CHU de Reims: lead
• Institut National de la Santé Et de la Recherche Médicale, France: collaborator

Study Sites (1)

Centre Hospitalier Universitaire de Reims

Reims, 51092, France

RECRUITING

Related Publications (1)

• 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.

  PMID: 27088859 DERIVED

MeSH Terms

Conditions

Renal Insufficiency, Chronic

Interventions

Eplerenone

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Lactones; Organic Chemicals; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Central Study Contacts

Philippe RIEU

CONTACT

prieu@chu-reims.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 11, 2013
• First Posted: April 18, 2013
• Study Start: February 1, 2013
• Primary Completion: April 1, 2013
• Study Completion: December 1, 2013
• Last Updated: April 18, 2013

Record last verified: 2013-04

Locations

FR (1)