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

Study Overview
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Brief Summary
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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).

Conditions
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CKD II-III

Intervention / Treatment
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* Drug: Eplerenone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 |