Eplerenone, ACE Inhibition and Albuminuria

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Radboud University
ClinicalTrials.gov Identifier:
NCT00315016
First received: April 14, 2006
Last updated: May 25, 2012
Last verified: May 2012
  Purpose

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


Condition Intervention Phase
Diabetic Nephropathy
Drug: eplerenone
Drug: fosinopril
Drug: placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Eplerenone, ACE Inhibition and Albuminuria

Resource links provided by NLM:


Further study details as provided by Radboud University:

Primary Outcome Measures:
  • proteinuria [ Time Frame: 0, 4, 12, 24 and 30 weeks ] [ Designated as safety issue: No ]
  • blood pressure by home measurements [ Time Frame: 0, 4, 12, 24 and 30 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • serum potassium [ Time Frame: 0, 3, days, 2, 4, 12, 24 and 30 weeks ] [ Designated as safety issue: Yes ]
  • haemoglobin [ Time Frame: 0, 4, 12, 24 and 30 weeks ] [ Designated as safety issue: Yes ]
  • urinary excretion of CTGF, TGF-b, collagen IV [ Time Frame: 0, 4, 12, 24 and 30 weeks ] [ Designated as safety issue: No ]
  • inulin and PAH clearance [ Time Frame: 0, 24 and 30 weeks ] [ Designated as safety issue: No ]
  • Quality of Life [ Time Frame: 0, 4, 12, 24 and 30 weeks ] [ Designated as safety issue: Yes ]
  • plasma aldosterone, renin [ Time Frame: 0, 24 and 30 weeks ] [ Designated as safety issue: No ]
  • plasma angiotensins and bradykinins [ Time Frame: 0, 24 and 30 weeks ] [ Designated as safety issue: No ]

Enrollment: 30
Study Start Date: January 2007
Study Completion Date: July 2011
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: 1
placebo (double dummy)
Drug: placebo
placebo (double dummy)
Other Name: no other name
Active Comparator: 2
eplerenone
Drug: eplerenone
active comparator
Other Name: Eplerenone or INSPRA
Active Comparator: 3
doubling of fosinopril dose
Drug: fosinopril
doubling of fosinopril dose
Other Name: fosinopril or Newace

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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • documented diabetic renal disease with albuminuria >0.020 g/L, stable renal function (i.e. increase of serum creatinine <25% / 6 months), creatinine clearance > 40 ml/min/1.73 m2 , in spite of maximal ACE-inhibition (40 mg fosinopril/day)
  • blood pressure < 140/90 mm Hg ( at baseline)
  • serum potassium < 5.0 mmol/l (at baseline).

Exclusion Criteria:

  • use of NSAID's or immunosuppressive drugs
  • use of ARBs, intolerance for ACE inhibition.
  • use of diuretics that increase potassium such as triamterene, spironolactone or eplerenone
  • pregnancy
  • rash or cough on one on the drugs
  • severe heart disease or instable angina
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00315016

Locations
Netherlands
Jeroen Bosch Hospital
's-Hertogenbosch, Noord Brabant, Netherlands
University Medical Center Nijmegen St Radboud
Nijmegen, Netherlands, 6525 GA
Sponsors and Collaborators
Radboud University
Investigators
Principal Investigator: Jacob Deinum, MD University Medical Center Nijmegen St Radboud, The Netherlands
  More Information

No publications provided

Responsible Party: Radboud University
ClinicalTrials.gov Identifier: NCT00315016     History of Changes
Other Study ID Numbers: IRG 2005-316
Study First Received: April 14, 2006
Last Updated: May 25, 2012
Health Authority: Netherlands: Medicines Evaluation Board (MEB)

Keywords provided by Radboud University:
albuminuria
eplerenone
ACE inhibition
renal function
endothelial function

Additional relevant MeSH terms:
Albuminuria
Diabetic Nephropathies
Kidney Diseases
Proteinuria
Urination Disorders
Urologic Diseases
Urological Manifestations
Signs and Symptoms
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases
Fosinopril
Eplerenone
Spironolactone
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Aldosterone Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Diuretics
Natriuretic Agents

ClinicalTrials.gov processed this record on July 22, 2014