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

Medical University of Vienna24 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

Conditions

CKD II-III

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 99 Years

Medical Language ↔ Plain English

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)

Outcomes

Primary Outcomes

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.

Time frame: 1 year