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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

Tracking Information
First Submitted Date  ICMJE September 11, 2007
First Posted Date  ICMJE September 12, 2007
Last Update Posted Date September 12, 2007
Study Start Date  ICMJE March 2005
Primary Completion Date Not Provided
Current Primary Outcome Measures  ICMJE
 (submitted: September 11, 2007)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: September 11, 2007)
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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Optimalization of Nephroprotection Using Agents Inhibiting Renin-Angiotensin-Aldosterone System
Official Title  ICMJE Influence of Adding Aldosterone Receptor Blocker to Dual Renin-Angiotensin-Aldosterone System Blockade on Proteinuria
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.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Chronic Kidney Disease
  • Proteinuria
Intervention  ICMJE 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.
Study Arms  ICMJE Not Provided
Publications * 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:CD007004. doi: 10.1002/14651858.CD007004.pub4.

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Completed
Enrollment  ICMJE Not Provided
Original Enrollment  ICMJE Not Provided
Study Completion Date  ICMJE Not Provided
Primary Completion Date Not Provided
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 60 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT00528385
Other Study ID Numbers  ICMJE ST-4/RAAS/02
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Not Provided
Study Sponsor  ICMJE Medical University of Gdansk
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Boleslaw Rutkowski, MD, PhD Department of Nephrology Transplantology and Internal Medicine. Medical University of Gdansk.
PRS Account Medical University of Gdansk
Verification Date September 2007

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP