Eplerenone, ACE Inhibition and Albuminuria

Diabetic Nephropathy Clinical Trial

Official title:

Eplerenone, ACE Inhibition and Albuminuria

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00315016
• Other study ID #: IRG 2005-316
• Status: Completed
• Phase: Phase 2
• First received: April 14, 2006
• Last updated: May 25, 2012
• Start date: January 2007
• Est. completion date: July 2011

Study information

• Verified date: May 2012
• Source: Radboud University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: Medicines Evaluation Board (MEB)
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: July 2011
• Est. primary completion date: July 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Albuminuria
• Diabetic Nephropathies
• Diabetic Nephropathy

Intervention

Drug:
• eplerenone
active comparator
• fosinopril
doubling of fosinopril dose
• placebo
placebo (double dummy)

Locations

Country	Name	City	State
Netherlands	Jeroen Bosch Hospital	's-Hertogenbosch	Noord Brabant
Netherlands	University Medical Center Nijmegen St Radboud	Nijmegen

Sponsors (1)

Lead Sponsor	Collaborator
Radboud University

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	proteinuria		0, 4, 12, 24 and 30 weeks	No
Primary	blood pressure by home measurements		0, 4, 12, 24 and 30 weeks	No
Secondary	serum potassium		0, 3, days, 2, 4, 12, 24 and 30 weeks	Yes
Secondary	haemoglobin		0, 4, 12, 24 and 30 weeks	Yes
Secondary	urinary excretion of CTGF, TGF-b, collagen IV		0, 4, 12, 24 and 30 weeks	No
Secondary	inulin and PAH clearance		0, 24 and 30 weeks	No
Secondary	Quality of Life		0, 4, 12, 24 and 30 weeks	Yes
Secondary	plasma aldosterone, renin		0, 24 and 30 weeks	No
Secondary	plasma angiotensins and bradykinins		0, 24 and 30 weeks	No