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

Primary Purpose

Chronic Kidney Disease, Proteinuria

Status
Completed
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Spironolactone (Spironol) 25 mg
Sponsored by
Medical University of Gdansk
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Kidney Disease focused on measuring Proteinuria, Renin-Angiotensin-Aldosterone System, Aldosterone Antagonists

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

    Outcomes

    Primary Outcome Measures

    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

    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.

    Full Information

    First Posted
    September 11, 2007
    Last Updated
    September 11, 2007
    Sponsor
    Medical University of Gdansk
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00528385
    Brief Title
    Optimalization of Nephroprotection Using Agents Inhibiting Renin-Angiotensin-Aldosterone System
    Official Title
    Influence of Adding Aldosterone Receptor Blocker to Dual Renin-Angiotensin-Aldosterone System Blockade on Proteinuria
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    September 2007
    Overall Recruitment Status
    Completed
    Study Start Date
    March 2005 (undefined)
    Primary Completion Date
    undefined (undefined)
    Study Completion Date
    undefined (undefined)

    3. Sponsor/Collaborators

    Name of the Sponsor
    Medical University of Gdansk

    4. Oversight

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Chronic Kidney Disease, Proteinuria
    Keywords
    Proteinuria, Renin-Angiotensin-Aldosterone System, Aldosterone Antagonists

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Not Applicable
    Interventional Study Model
    Crossover Assignment
    Masking
    None (Open Label)
    Allocation
    Randomized

    8. Arms, Groups, and Interventions

    Intervention Type
    Drug
    Intervention Name(s)
    Spironolactone (Spironol) 25 mg
    Intervention Description
    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 Measure Information:
    Title
    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 Measure Information:
    Title
    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.

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    60 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    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
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Boleslaw Rutkowski, MD, PhD
    Organizational Affiliation
    Department of Nephrology Transplantology and Internal Medicine. Medical University of Gdansk.
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    33107592
    Citation
    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.
    Results Reference
    derived

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

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