Eplerenone, ACE Inhibition and Albuminuria
Condition: Diabetic Nephropathy
MeSH terms: Diabetic Nephropathies; Albuminuria
Study type: Interventional
Phase: Phase 2

Summary: 
      The purpose of this study is to determine whether eplerenone is more effective than doubling
      the dose of ACE inhibitor in reducing urinary protein (albumin) loss in diabetes mellitus
    

Detailed description: 
      In patients with proteinuric renal diseases renal function almost invariably deteriorates,
      independent from the original renal disease. It has been demonstrated that the rapidity of
      renal function deterioration is determined by blood pressure and proteinuria1. Treatment
      modalities that lower proteinuria in general tend to attenuate the deterioration of renal
      function. As such, ACE-inhibitors have been proven to be of particular value in the treatment
      of patients with proteinuria, since these drugs consistently lower proteinuria. More
      recently, similar antiproteinuric effects have been described for the angiotensin receptor
      blockers (ARBs). Theoretically, ACE inhibitors may have advantages over ARBs because they are
      supposed to increase bradykinin levels. Bradykinin has also been implicated in the
      development of nephropathy in mice. About its role in human diabetic nephropathy few if any
      data exist. The effect of ACE inhibition or ARBs is not complete, since addition of either
      drug to the other may further improve albuminuria. This may be explained by insufficient
      dosage of single drug therapy or because of an escape phenomenon. The latter has been amply
      described for ACE inhibitors. Especially with chronic ACE inhibition angiotensin II levels
      may be near normal. This may lead to persistent angiotensin II effects, among which
      aldosterone stimulation.

      Even though most investigators have emphasized the role of the renin-angiotensin system in
      progressive renal injury, aldosterone has received little attention. However, its profibrotic
      effects make aldosterone a potentially important player in the field, even more so because
      the escape of aldosterone during treatment with ACE-inhibitors or ARBs. Moreover, in addition
      to these theoretical considerations, evidence is emerging that mineralocorticoid receptor
      blockade with spironolactone added to ACE-inhibitors or ARBs indeed has an additive,
      favourable effect on proteinuria. These findings warrant a search for the value of such
      agents in albuminuria and exploration of the mechanisms by which mineralocorticoid blockade
      may exert its beneficial effects.

      Primary aim:

      1. To study whether the combination of eplerenone and a standard dose of ACE-inhibition has
      an additive effect on albuminuria in patients with albuminuric nephropathy compared to ACE-I
      alone, or double dose of ACE-inhibitor.
    

Intervention name(s): eplerenone; fosinopril; placebo
Intervention type(s): Drug; Drug; Drug
Intervention description(s): active comparator; doubling of fosinopril dose; placebo (double dummy)
Other intervention name(s): Eplerenone or INSPRA; fosinopril or Newace; no other name
Intervention MeSH terms: Eplerenone; Fosinopril
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: albuminuria; eplerenone; ACE inhibition; renal function; endothelial function