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Optimalization of Nephroprotection Using Agents Inhibiting Renin-Angiotensin-Aldosterone System

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00528385
Recruitment Status : Completed
First Posted : September 12, 2007
Last Update Posted : September 12, 2007
Information provided by:
Medical University of Gdansk

Brief Summary:
The main purpose of the study is find whether the addition of aldosterone antagonist, spironolactone to dual renin-angiotensin-aldosterone system blockade involving angiotensin converting enzyme inhibitor and AT-1 angiotensin II receptor blocker leads to the reduction of proteinuria, main prognostic marker of chronic kidney disease progression.

Condition or disease Intervention/treatment Phase
Chronic Kidney Disease Proteinuria Drug: Spironolactone (Spironol) 25 mg Not Applicable

Detailed Description:
The renin-angiotensin-aldosterone system (RAAS) plays an important role in the progression of chronic kidney diseases (CKD), and inhibition of the RAAS with angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II type 1 receptor blockers (ARB) may retard CKD progression. Dual pharmacological blockade of the RAAS with ACEI and ARB is recommended as a standard renoprotective management at least in patients with nondiabetic proteinuric CKD. However, neither ACEI nor ARB, even in high doses or in concomitant usage, abrogate the progression of CKD completely. Innovative approaches are needed to keep patients with CKD off dialysis. Additional blockade of the aldosterone pathway may prove to be such beneficial therapeutic concept.Aldosterone, a final effector of RAAS plays a significant role in the pathogenesis of CKD independently of angiotensin II through direct cellular action. This includes promoting an inflammatory response, endothelial dysfunction, and fibrosis by increasing plasminogen activator inhibitor (PAI-1) and transforming growth factor beta-1 (TGF-beta-1) expression and stimulation reactive oxygen species.A number of observations suggest nongenomic vasoconstrictor action of aldosterone leading to raise arterial and glomerular capillary pressure.Given these facts additional administration of aldosterone antagonist to combination treatment with ACEI and ARB, so called triple RAAS blockade may provide additional renal protection. To shed more light on this issue, we performed a randomised open controlled study to evaluate the influence of triple RAAS therapy on surrogate markers of kidney injury, i.e. proteinuria, markers of tubular involvement and kidney fibrosis.

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Study Type : Interventional  (Clinical Trial)
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Influence of Adding Aldosterone Receptor Blocker to Dual Renin-Angiotensin-Aldosterone System Blockade on Proteinuria
Study Start Date : March 2005

Resource links provided by the National Library of Medicine

Intervention Details:
  • Drug: Spironolactone (Spironol) 25 mg
    In the 8-weeks run-in period ACEI, cilazapril (5 mg), telmisartan (80 mg) and hydrochlorotiazyd (12.5 mg) were administered to achieve the target blood pressure below 130/80 mmHg. Next, they were randomly assigned to add (or not) 25 mg of spironolactone in two active treatment periods lasting 8 weeks each.

Primary Outcome Measures :
  1. Investigate the antiproteinuric effect of adding aldosterone antagonist, spironolactone to the combination therapy with angiotensin converting enzyme inhibitor and AT-1 receptor blocker in maximal recommended doses.

Secondary Outcome Measures :
  1. Investigate the effect of the study intervention on urine excretion of N-acetyl-β-D-glucosaminidase, alfa1-microglobulin and amino-terminal propeptide of type III procollagen.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • chronic kidney disease
  • stable proteinuria above 300 mg/24 hours (no variations above 25% in the last 6 months)
  • normal or slightly impaired stable renal function defined as serum creatinine level below 1.7 mg/dl (eGFR > 45 ml/min)

Exclusion Criteria:

  • nephrotic syndrome
  • steroids or other immunosuppressive treatment minimum during six months before the study
  • diabetes mellitus
  • potassium serum level > 5.1 mEq/L
  • albumin serum level < 2.0mg/dL
  • creatinine serum level >2 mg/dl
  • current diagnosis of heart failure New York Heart Association (NYHA) Class II-IV
  • clinically significant valvular heart disease or second or third degree heart block without a pacemaker
  • history of hypertensive encephalopathy, cerebrovascular accident or transient ischemic cerebral attack
  • history of myocardial infarction, unstable angina pectoris, coronary bypass surgery, or any percutaneous coronary intervention
  • history of malignancy including leukemia and lymphoma (but not basal cell skin carcinoma) within the past five years
  • pregnant or nursing women
  • any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of study drugs.
  • history of alcohol abuse
  • NSAID abuse (more than 2 doses per week)
  • known or suspected contraindications to the study medications, including history of allergy to ACE inhibitors, AT-1 receptor blockers and aldosterone antagonists

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00528385

Sponsors and Collaborators
Medical University of Gdansk
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Principal Investigator: Boleslaw Rutkowski, MD, PhD Department of Nephrology Transplantology and Internal Medicine. Medical University of Gdansk.
Publications automatically indexed to this study by Identifier (NCT Number):
Layout table for additonal information Identifier: NCT00528385    
Other Study ID Numbers: ST-4/RAAS/02
First Posted: September 12, 2007    Key Record Dates
Last Update Posted: September 12, 2007
Last Verified: September 2007
Keywords provided by Medical University of Gdansk:
Renin-Angiotensin-Aldosterone System
Aldosterone Antagonists
Additional relevant MeSH terms:
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Kidney Diseases
Renal Insufficiency, Chronic
Urologic Diseases
Renal Insufficiency
Urination Disorders
Urological Manifestations
Mineralocorticoid Receptor Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Diuretics, Potassium Sparing
Natriuretic Agents