<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01691053</url>
  </required_header>
  <id_info>
    <org_study_id>MN0511_1</org_study_id>
    <secondary_id>2011-003179-12</secondary_id>
    <secondary_id>01KG1202</secondary_id>
    <nct_id>NCT01691053</nct_id>
  </id_info>
  <brief_title>Mineralocorticoid Receptor Antagonists in End Stage Renal Disease</brief_title>
  <acronym>MiREnDa</acronym>
  <official_title>Phase II Trial to Evaluate the Efficacy and Safety of Spironolactone in Hemodialysis Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Wuerzburg University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>German Federal Ministry of Education and Research</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Clinical Trial Center Wuerzburg (CTCW)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Wuerzburg University Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      End stage renal disease (ESRD) patients exhibit an extraordinarily high annual mortality.&#xD;
      Cardiovascular (CV) causes account for almost half of all-cause mortality. Increased left&#xD;
      ventricular mass (LVM) is a common finding in ESRD patients on dialysis and is an independent&#xD;
      predictor of survival. Yet, to date there is no established medical treatment to reduce CV&#xD;
      morbidity and mortality in ESRD patients on hemodialysis. Blockade of aldosterone action by&#xD;
      means of mineralocorticoid receptor antagonists (MRA) provides cardioprotection and improves&#xD;
      outcome in heart failure patients. Furthermore, the MRA spironolactone has recently been&#xD;
      shown to reduce LVM in patients with mild-to-moderate chronic kidney disease (CKD). The&#xD;
      investigators here hypothesize that spironolactone treatment is cardioprotective by reducing&#xD;
      LVM in ESRD patients on dialysis.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>December 2012</start_date>
  <completion_date type="Actual">March 28, 2018</completion_date>
  <primary_completion_date type="Actual">February 14, 2017</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Left Ventricular Mass Index</measure>
    <time_frame>9 months</time_frame>
    <description>as assessed by cardiac MRI</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Cardiac function parameters</measure>
    <time_frame>9 months</time_frame>
    <description>cardiac volumes, systolic and diastolic function, cardiac output as measured by cardiac MRI and echocardiography</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Office and 24h blood pressure</measure>
    <time_frame>9 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical measures of heart failure severity</measure>
    <time_frame>9 months</time_frame>
    <description>New York Heart Association (NYHA) functional class, 6 minute walk test</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vascular function</measure>
    <time_frame>9 months</time_frame>
    <description>Carotid intima meda thickness, pulse wave analysis, carotid artery distensibility, flow mediated dilatation of the brachial artery</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Biomarkers of heart failure, inflammation and fibrosis</measure>
    <time_frame>9 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of Life - Hospital Anxiety and Depression Scale (HADS)</measure>
    <time_frame>9 months</time_frame>
    <description>Quality of life will be measured by analyzing HADS</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cardiac death and/or hospitalization for heart failure</measure>
    <time_frame>9 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety measures</measure>
    <time_frame>9 months</time_frame>
    <description>Pre-dialysis potassium levels, frequency of hyperkalemic episodes (K&gt;6.5mmol/l), measurement of residual kidney function (if applicable)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of Life - Kidney Disease Quality of Life Instrument (KDQOL-SF36)</measure>
    <time_frame>9 months</time_frame>
    <description>Quality of life will be measured by analyzing KDQOL-SF36</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">118</enrollment>
  <condition>End Stage Renal Disease / Hemodialysis</condition>
  <arm_group>
    <arm_group_label>Spironolactone</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Spironolactone</intervention_name>
    <description>50mg once daily</description>
    <arm_group_label>Spironolactone</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age &gt;18 years&#xD;
&#xD;
          -  Hemodialysis treatment for at least 3 months&#xD;
&#xD;
          -  At least 3 dialysis sessions per week&#xD;
&#xD;
          -  Written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Contraindications for cardiac magnet resonance imaging (CMR)&#xD;
&#xD;
          -  Mineralocorticoid receptor antagonist treatment within the last 6 months&#xD;
&#xD;
          -  Estimated life expectancy &lt; 12 months as judged by the nephrologist&#xD;
&#xD;
          -  History of hyperkalemia, defined as pre-dialysis potassium &gt; 6.5 mmol/l occurring ≥ 3&#xD;
             times within the last 3 months prior to enrolment.&#xD;
&#xD;
          -  High risk to develop hyperkalemia defined as pre-dialysis potassium &gt; 6.0 mmol/l&#xD;
&#xD;
          -  Hypotension (systolic blood pressure &lt; 100 mmHg)&#xD;
&#xD;
          -  Planned kidney transplantation (living donor) within the prospected study duration&#xD;
&#xD;
          -  Any acute illness within the last 4 weeks precluding a study participation as judged&#xD;
             by the nephrologist&#xD;
&#xD;
          -  Non-amenorrheic women with child bearing potential without reliable contraception,&#xD;
             pregnancy/lactation&#xD;
&#xD;
          -  Allergy/hypersensitivity to spironolactone&#xD;
&#xD;
          -  Non-compliance suspected or demonstrated&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Christoph Wanner, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital Wuerzburg</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Fabian Hammer, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital Wuerzburg</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Vera Krane, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital Wuerzburg</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Hospital Erlangen-Nürnberg</name>
      <address>
        <city>Erlangen</city>
        <zip>91054</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Frankfurt</name>
      <address>
        <city>Frankfurt</city>
        <zip>60590</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Wuerzburg</name>
      <address>
        <city>Wuerzburg</city>
        <zip>97080</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>August 2019</verification_date>
  <study_first_submitted>September 19, 2012</study_first_submitted>
  <study_first_submitted_qc>September 21, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 24, 2012</study_first_posted>
  <last_update_submitted>August 1, 2019</last_update_submitted>
  <last_update_submitted_qc>August 1, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">August 6, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>End stage renal disease</keyword>
  <keyword>Hemodialysis</keyword>
  <keyword>Spironolactone</keyword>
  <keyword>Left ventricular hypertrophy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Kidney Diseases</mesh_term>
    <mesh_term>Kidney Failure, Chronic</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Spironolactone</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01691053
org study id: MN0511_1
secondary id: 2011-003179-12
secondary id: 01KG1202
nct id: NCT01691053
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
End stage renal disease (ESRD) patients exhibit an extraordinarily high annual mortality.
      Cardiovascular (CV) causes account for almost half of all-cause mortality. Increased left
      ventricular mass (LVM) is a common finding in ESRD patients on dialysis and is an independent
      predictor of survival. Yet, to date there is no established medical treatment to reduce CV
      morbidity and mortality in ESRD patients on hemodialysis. Blockade of aldosterone action by
      means of mineralocorticoid receptor antagonists (MRA) provides cardioprotection and improves
      outcome in heart failure patients. Furthermore, the MRA spironolactone has recently been
      shown to reduce LVM in patients with mild-to-moderate chronic kidney disease (CKD). The
      investigators here hypothesize that spironolactone treatment is cardioprotective by reducing
      LVM in ESRD patients on dialysis.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Left Ventricular Mass Index
time frame: 9 months
description: as assessed by cardiac MRI
measure: Cardiac function parameters
time frame: 9 months
description: cardiac volumes, systolic and diastolic function, cardiac output as measured by cardiac MRI and echocardiography
measure: Office and 24h blood pressure
time frame: 9 months
measure: Clinical measures of heart failure severity
time frame: 9 months
description: New York Heart Association (NYHA) functional class, 6 minute walk test
measure: Vascular function
time frame: 9 months
description: Carotid intima meda thickness, pulse wave analysis, carotid artery distensibility, flow mediated dilatation of the brachial artery
measure: Biomarkers of heart failure, inflammation and fibrosis
time frame: 9 months
measure: Quality of Life - Hospital Anxiety and Depression Scale (HADS)
time frame: 9 months
description: Quality of life will be measured by analyzing HADS
measure: Cardiac death and/or hospitalization for heart failure
time frame: 9 months
measure: Safety measures
time frame: 9 months
description: Pre-dialysis potassium levels, frequency of hyperkalemic episodes (K>6.5mmol/l), measurement of residual kidney function (if applicable)
measure: Quality of Life - Kidney Disease Quality of Life Instrument (KDQOL-SF36)
time frame: 9 months
description: Quality of life will be measured by analyzing KDQOL-SF36
arm group label: Spironolactone
arm group type: Active Comparator
arm group label: Placebo
arm group type: Placebo Comparator
intervention type: Drug
intervention name: Spironolactone
description: 50mg once daily
arm group label: Spironolactone
intervention type: Drug
intervention name: Placebo
description: Placebo
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Christoph Wanner, MD
role: Principal Investigator
affiliation: University Hospital Wuerzburg
last name: Fabian Hammer, MD, PhD
role: Principal Investigator
affiliation: University Hospital Wuerzburg
last name: Vera Krane, MD
role: Principal Investigator
affiliation: University Hospital Wuerzburg
facility: 
facility: 
facility: 
country: Germany
responsible party type: Sponsor
mesh term: Kidney Diseases
mesh term: Kidney Failure, Chronic
mesh term: Spironolactone