CKD II-III Clinical Trial
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).
| Status | Recruiting |
| Enrollment | 24 |
| Est. completion date | December 31, 2021 |
| Est. primary completion date | December 31, 2020 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years to 99 Years |
| Eligibility |
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) |
| Country | Name | City | State |
|---|---|---|---|
| Austria | Medical University of Vienna | Vienna |
| Lead Sponsor | Collaborator |
|---|---|
| Medical University of Vienna |
Austria,
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. Epub 2006 Jul 19. — View 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. Review. — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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 |