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van CCT (UK)

Eplerenone, Sodium restriction, hydroChlorothiazide, and ACE-inhibition in Proteinuria Evaluated.

- candidate number6783
- NTR NumberNTR2133
- ISRCTNISRCTN wordt niet meer aangevraagd.
- Date ISRCTN created
- date ISRCTN requested
- Date Registered NTR4-dec-2009
- Secondary IDsNL30907.042.09 METC
- Public TitleEplerenone, Sodium restriction, hydroChlorothiazide, and ACE-inhibition in Proteinuria Evaluated.
- Scientific TitleEplerenone, Sodium restriction, hydroChlorothiazide, and ACE-inhibition in Proteinuria Evaluated.
- hypothesisObjectives:
1. To investigate the added effects of eplerenone on top of ACEi, with and without dietary sodium restriction, on residual albuminuria, hypertension, and tubular injury markers, in patients with diabetic nephropathy;
2. To investigate whether the renoprotective effects of eplerenone added to ACEi outweigh the renoprotective effects of the diuretic hydrochlorothiazide added to ACEi, in patients with diabetic nephropathy;
3. To investigate whether the benefits of eplerenone on top of ACEi are the result of the diuretic actions (potentiating the efficacy of ACEi) or secondary to the direct antifibrotic properties of eplerenone.
- Healt Condition(s) or Problem(s) studiedHypertension, Proteinuria , Diabetes Mellitus, Albuminuria, Kidney disease, Aldosteron blockade
- Inclusion criteria1. Diabetic nephropathy;
2. Diabetes mellitus type II;
3. Proteinuria <3.0 g/24h;
4. Stable creatinine clearance > 30 mL/min;
5. Age ≥ 18 years.
- Exclusion criteria1. Diabetes mellitus type I;
2. Myocardial infarction or other cardiovascular event within the last 3 months prior to entry into the study;
3. Kidney disease other than caused by diabetes mellitus or hypertension;
4. Uncontrollable hypertension after the run- in period (>180/100 mmHg);
5. Serum potassium > 6.0 mmol/L;
6. Incompliance with regard to study medication or diet;
7. Unable to give informed consent;
8. Contraindication for the use of lisinopril or eplerenone.
- mec approval receivedyes
- multicenter trialno
- randomisedyes
- masking/blindingDouble
- controlPlacebo
- groupCrossover
- Type2 or more arms, randomized
- Studytypeintervention
- planned startdate 1-feb-2010
- planned closingdate1-feb-2012
- Target number of participants27
- InterventionsCombinations of:
1. Lisinopril 40 mg/d;
2. Hydrochlorothiazide 50 mg/d;
3. Eplerenone 25-50 mg/d;
4. Normal diet;
5. Sodium restricted diet.

Patients will be randomised into 4 groups, alike the DiNaMo study (the ESCAPE study is an addendum to the DiNaMo study). The ESCAPE study consists of 2 study periods of 6 weeks each, in which patients are treated with lisinopril 40 mg once daily and eplerenone 25-50 mg once daily. This is combined with a low sodium diet during 1 period, and a normal diet during the other period. The antiproteinuric effect of these regimens will be compared with the regimens of the DiNaMo study (which contains placebo, and hydrochlorothiazide, on top of lisinopril 40 mg/d and diet intervention).
- Primary outcome1. Albuminuria;
2. Blood pressure.
- Secondary outcome1. Tubular injury markers;
2. Extracellular fluid volume.
- TimepointsPatients visit the outpatient clinic at the 42th day of each study period for assessment of the endpoints (blood pressure, proteinuria) and safety parameters (potassium). At the 14th day of each period potassium levels are checked, as well as dietary compliance (urinary sodium excretion).
- Trial web siteN/A
- statusplanned
- Sponsor/Initiator University Medical Center Groningen (UMCG)
- Funding
(Source(s) of Monetary or Material Support)
University Medical Center Groningen (UMCG)
- PublicationsN/A
- Brief summaryN/A
- Main changes (audit trail)In many diabetic nephropathy patients loss of renal function occurs despite treatment with angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB), which is therapy of choice. Aldosterone, that besides sodium and water retention promotes renal inflammation and fibrosis, increases during ACEi and ARB ("aldosterone escape") which may explain the incomplete renoprotection during these therapies. Aldosterone levels can further increase when the antihypertensive and antiproteinuric effects of ACEi or ARB are potentiated by volume depletion with dietary sodium restriction and/or diuretic treatment.
Mineralocorticoid receptor blockers (MRB; i.e. spironolactone and eplerenone) inhibit the harmful effects of aldosterone, and MRB added to ACEi or ARB effectively reduce proteinuria, hypertension, and renal function decline.
Whether the added benefits of MRB on top of ACEi or ARB result from either the diuretic or the antifibrotic properties of MRB, is unknown. Furthermore, very few studies in renal patients investigated the protective effects of eplerenone, which is a relatively new but promising agent since it acts selectively and therefore has the benefit over spironolactone (a non-selective MRB) of less/no antiandrogenic and progestational side effects.
Therefore we aim to study: 1. whether the renoprotective effects of ACEi, with and without volume depletion measures, can be improved by the addition of eplerenone, 2. whether the renoprotective effects of eplerenone added to ACEi outweigh the renoprotective effects of the diuretic hydrochlorothiazide added to ACEi; in patients with diabetic nephropathy.
- RECORD4-dec-2009 - 10-jun-2010

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