Eplerenone, ACE Inhibition and Albuminuria

NCT ID: NCT00315016

Last Updated: 2012-05-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-01-31
• Study Completion Date: 2011-07-31

Brief 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.

Conditions

Diabetic Nephropathy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

1

placebo (double dummy)

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

placebo (double dummy)

2

eplerenone

Group Type: ACTIVE_COMPARATOR

eplerenone

Intervention Type: DRUG

active comparator

3

doubling of fosinopril dose

Group Type: ACTIVE_COMPARATOR

fosinopril

Intervention Type: DRUG

doubling of fosinopril dose

Interventions

eplerenone

active comparator

Intervention Type: DRUG

fosinopril

doubling of fosinopril dose

Intervention Type: DRUG

placebo

placebo (double dummy)

Intervention Type: DRUG

Other Intervention Names

Eplerenone or INSPRA; fosinopril or Newace; no other name

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Radboud University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jacob Deinum, MD

Role: PRINCIPAL_INVESTIGATOR

University Medical Center Nijmegen St Radboud, The Netherlands

Locations

Jeroen Bosch Hospital

's-Hertogenbosch, North Brabant, Netherlands

University Medical Center Nijmegen St Radboud

Nijmegen, , Netherlands

Countries

Netherlands

References

Chung EY, Ruospo M, Natale P, Bolignano D, Navaneethan SD, Palmer SC, Strippoli GF. Aldosterone antagonists in addition to renin angiotensin system antagonists for preventing the progression of chronic kidney disease. Cochrane Database Syst Rev. 2020 Oct 27;10(10):CD007004. doi: 10.1002/14651858.CD007004.pub4.

Reference Type: DERIVED

PMID: 33107592 (View on PubMed)

Other Identifiers

IRG 2005-316

Identifier Type: -

Identifier Source: org_study_id