Clinical trial NCT01832558: The EPOCH Study (Eplerenone on Top of ACE Inhibition in Chronic Kidney Disease Patients With Hypertension)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: CKD II-III
Lead sponsor: Medical University of Vienna
Sponsor class: OTHER
First posted: 2013-04-16
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: 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)

Primary outcomes:
measure: 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.
timeFrame: 1 year
Secondary outcomes:
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Medical University of Vienna
Study officials:
References:
citation: 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.
citation: 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.