The EPOCH Study (Eplerenone on Top of ACE Inhibition in Chronic Kidney Disease Patients With Hypertension)

In a prospective single centre placebo-controlled trial over ten weeks, 24 CKD II-III patients (eGFR 30-89 ml/min per 1.73 m2) with DM II will be randomized to enalapril 20mg per day after a two week run-in phase. Thereafter, patients will either receive eplerenone 25mg (n=12) or a placebo (n=12) for eight weeks. Eplerenone will be increased to 50mg under close monitoring of serum potassium levels. Employing a novel mass-spectrometry ( MS)-based method, quantification of up to 10 different Ang metabolites (Ang I, Ang II, Ang 1-7, Ang 1-9, Ang 2-10, Ang 1-5, Ang 2-7, Ang 3-7, Ang 3-8 and Ang 2-8) will be performed simultaneously out of blood sera (after run-in phase and after 10 weeks).

Study Overview

• Status: Unknown
• Conditions: CKD II-III
• Intervention / Treatment: Drug: Placebo; Drug: Eplerenone

• Study Type: Interventional
• Enrollment (Anticipated): 24
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Recruiting
    • Medical University of Vienna
    • Contact: Marcus Saemann, MD; Phone Number: 01/40400/55930; Email: marcus.saemann@meduniwien.ac.at
    • Sub-Investigator: Johannes Kovarik, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• CKD II to III and diabetes mellitus type 2
• CKD will be defined according to estimated glomerular filtration rate (eGFR) with the MDRD formula
• eGFR between 30 and 89 ml/min
• albumin excretion rates > 300 mg/24 hours (UACR > 300 mg/gram) or > 200 mg/g if already receiving any RAS blockade Patients should be hypertonic stage I or II according to the European guidelines (Chobanian et al. JAMA 2003)

Exclusion Criteria:

• Age < 18 years
• UACR > 3500mg/g
• severe hypertension
• pregnancy
• unwilling or inability to sign the informed consent
• coronary heart disease
• systolic blood pressure < 130 mmHg
• additional RAS interfering drugs (ACEis, ARBs, direct renin inhibitors)
• 25-hydroxy vitamin D levels below 16.6±8.3 pg/ml
• 1,25-dihydroxy vitamin D 33.1±15.5 pg/ml

Intolerance to eplerenon or an excipient of it:

tablettcore: Lactose-Monohydrat Mikrokristalline Cellulose (E 460) Croscarmellose-sodium (E 468) Hypromellose (E 464) Sodiumdodecylsulfat Talkum (E 553b) Magnesiumstearat (E 470b)

filmcoat

Opadry, yellow:

Hypromellose (E 464) Titandioxid (E 171) Macrogol 400 Polysorbat 80 (E 433) Yellow ironoxide (E 172) Red ironoxide (E 172)

• Patients with Serumpotassium > 5,0 mmol/l at start of the treatment
• Patients with severe renal insufficiency (eGFR <30ml/min./1.73 m2)
• Patients with severe liver insufficiency (Child-Pugh class C)
• Patients taking potassium saving diuretics, potassium supplements or strong CYP3A4-inhibitors (z. B. Itraconazol, Ketoconazol, Ritonavir, Nelfinavir, Clarithromycin, Telithromycin und Nefazodon)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Eplerenone; Eplerenone 25-50mg daily additionally to standard ACE-inhibition with enalapril 20mg daily	Drug: Eplerenone
Placebo Comparator: Placebo; Placebo additionally to standard ACE-inhibition with enalapril 20mg daily	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Angiotensin levels (pg/ml) of CKD II-III patients with DM II with eplerenone additional to enalapril in comparison to patients who receive a placebo on top of enalapril therapy.	1 year

Collaborators and Investigators

• Sponsor: Medical University of Vienna

Publications and helpful links

General Publications

• Epstein M, Williams GH, Weinberger M, Lewin A, Krause S, Mukherjee R, Patni R, Beckerman B. Selective aldosterone blockade with eplerenone reduces albuminuria in patients with type 2 diabetes. Clin J Am Soc Nephrol. 2006 Sep;1(5):940-51. doi: 10.2215/CJN.00240106. Epub 2006 Jul 19.
• Shavit L, Lifschitz MD, Epstein M. Aldosterone blockade and the mineralocorticoid receptor in the management of chronic kidney disease: current concepts and emerging treatment paradigms. Kidney Int. 2012 May;81(10):955-968. doi: 10.1038/ki.2011.505. Epub 2012 Feb 15.

Study record dates

Study Major Dates

• Study Start: November 1, 2012
• Primary Completion (Anticipated): December 31, 2020
• Study Completion (Anticipated): December 31, 2021

Study Registration Dates

• First Submitted: April 8, 2013
• First Submitted That Met QC Criteria: April 15, 2013
• First Posted (Estimate): April 16, 2013

Study Record Updates

• Last Update Posted (Actual): June 19, 2020
• Last Update Submitted That Met QC Criteria: June 17, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Antihypertensive Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Natriuretic Agents; Diuretics; Hormone Antagonists; Mineralocorticoid Receptor Antagonists; Diuretics, Potassium Sparing; Eplerenone
• Other Study ID Numbers: EudraCT: 2012-002175-34