<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/NCT03803111</url>
  </required_header>
  <id_info>
    <org_study_id>BIHKF-7162</org_study_id>
    <nct_id>NCT03803111</nct_id>
  </id_info>
  <brief_title>Effects of Iron Therapy and Exercise Training in Patients With Heart Failure and Iron Deficiency</brief_title>
  <acronym>IronEx</acronym>
  <official_title>A Randomized Trial on Sequential Effects of Iron Therapy and Exercise Training in Patients With Heart Failure and Iron Deficiency</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Herzzentrum Bremen</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Herzzentrum Bremen</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      It is the aim of the study to prove, if intravenous supplementation with ferric&#xD;
      carboxymaltose in iron-deficient patients with heart failure with reduced ejection fraction&#xD;
      (HFrEF) leads to better exercise training effects compared to exercise training without&#xD;
      previous iron supplementation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In patients with heart failure with reduced ejection fraction (HFrEF) exercise training (ET)&#xD;
      is recommended. In iron-deficient HFrEF patients iron supplementation by ferric&#xD;
      carboxymaltose (FCM) is recommended. Both treatment options (ET and iron supplementation)&#xD;
      affect oxidative metabolism.&#xD;
&#xD;
      In this study iron-deficient HFrEF patients are included and randomly assigned to two study&#xD;
      arms:&#xD;
&#xD;
      Study arm A: Intravenous iron supplementation with FCM, subsequent (after 2 months) ET&#xD;
      program.&#xD;
&#xD;
      Study arm B: ET program, subsequent (after 2 months) intravenous iron supplementation with&#xD;
      FCM.&#xD;
&#xD;
      Primary study endpoint is exercise capacity (Peak VO2). Secondary endpoints are 6-minute&#xD;
      walking distance, NYHA class, echocardiographic parameters and the combined endpoint&#xD;
      cardiovascular hospitalizations and death.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Sponsoring and Screening of first patients was not sufficient&#xD;
  </why_stopped>
  <start_date type="Actual">January 1, 2021</start_date>
  <completion_date type="Actual">March 15, 2022</completion_date>
  <primary_completion_date type="Actual">March 15, 2022</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Exercise capacity (Peak VO2)</measure>
    <time_frame>Change from baseline to 4 months</time_frame>
    <description>Peak VO2 is measured by spiroergometry</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>6 Minute walking distance</measure>
    <time_frame>Change from baseline to 4 months</time_frame>
    <description>To further assess exercise capacity</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>New York Heart Association class (class I, II, III, IV with class I = best status, and class IV = worst status)</measure>
    <time_frame>Improvement or deterioration of NYHA class from baseline to 4 months</time_frame>
    <description>To assess symptoms</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Echocardiographic ejection fraction of left ventricular function (measured in %, the lower the worse)</measure>
    <time_frame>Improvement or deterioration of ejection fraction from baseline to 4 months</time_frame>
    <description>Systolic and diastolic function, chamber diameters, strain analyses</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Combined endpoint cardiovascular hospitalizations and death</measure>
    <time_frame>After 2 and 4 months</time_frame>
    <description>To assess major events</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Heart Failure With Reduced Ejection Fraction</condition>
  <condition>Exercise Training</condition>
  <condition>Ferric Carboxymaltose</condition>
  <arm_group>
    <arm_group_label>Initial FCM</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Intravenous iron supplementation with FCM, subsequent (after 2 months) exercise training program</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Initial exercise</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Exercise training program, subsequent (after 2 months) intravenous iron supplementation with FCM</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Initial exercise training</intervention_name>
    <description>Initial exercise training program</description>
    <arm_group_label>Initial exercise</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Initial FCM</intervention_name>
    <description>Initial intravenous iron supplementation (FCM)</description>
    <arm_group_label>Initial FCM</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Subsequent FCM</intervention_name>
    <description>Subsequent intravenous iron Supplementation (FCM) after 2 months</description>
    <arm_group_label>Initial exercise</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Subsequent exercise training</intervention_name>
    <description>Subsequent exercise training program after 2 months</description>
    <arm_group_label>Initial FCM</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Heart failure with reduced ejection fraction ≤ 40%&#xD;
&#xD;
          -  New York Heart Failure Asssociation class II-III&#xD;
&#xD;
          -  Iron deficiency (ferritin &lt; 100 ng/ml or 100-299 ng/ml, if transferrin saturation &lt;&#xD;
             20%)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Planned cardiovascular interventions (such as bypass surgery or valve interventions)&#xD;
&#xD;
          -  Acute coronary Syndrome&#xD;
&#xD;
          -  Malignant rhythm disturbances&#xD;
&#xD;
          -  Acute or chronic infection&#xD;
&#xD;
          -  Reduced prognosis or exercise capacity by non-cardiac comorbidities&#xD;
&#xD;
          -  Missing informed consent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Bremer Institut für Herz- und Kreislaufforschung</name>
      <address>
        <city>Bremen</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>January 8, 2019</study_first_submitted>
  <study_first_submitted_qc>January 10, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 14, 2019</study_first_posted>
  <last_update_submitted>March 15, 2022</last_update_submitted>
  <last_update_submitted_qc>March 15, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 16, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Herzzentrum Bremen</investigator_affiliation>
    <investigator_full_name>Dr. Harm Wienbergen</investigator_full_name>
    <investigator_title>Head of the Bremen Institute for Heart and Circulation Research (BIHKF)</investigator_title>
  </responsible_party>
  <keyword>Heart Failure with Reduced Ejection Fraction</keyword>
  <keyword>Exercise Training Program</keyword>
  <keyword>Iron Deficiency</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Heart Failure</mesh_term>
    <mesh_term>Anemia, Iron-Deficiency</mesh_term>
    <mesh_term>Iron Deficiencies</mesh_term>
  </condition_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/NCT03803111
org study id: BIHKF-7162
nct id: NCT03803111
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
It is the aim of the study to prove, if intravenous supplementation with ferric
      carboxymaltose in iron-deficient patients with heart failure with reduced ejection fraction
      (HFrEF) leads to better exercise training effects compared to exercise training without
      previous iron supplementation.
In patients with heart failure with reduced ejection fraction (HFrEF) exercise training (ET)
      is recommended. In iron-deficient HFrEF patients iron supplementation by ferric
      carboxymaltose (FCM) is recommended. Both treatment options (ET and iron supplementation)
      affect oxidative metabolism.

      In this study iron-deficient HFrEF patients are included and randomly assigned to two study
      arms:

      Study arm A: Intravenous iron supplementation with FCM, subsequent (after 2 months) ET
      program.

      Study arm B: ET program, subsequent (after 2 months) intravenous iron supplementation with
      FCM.

      Primary study endpoint is exercise capacity (Peak VO2). Secondary endpoints are 6-minute
      walking distance, NYHA class, echocardiographic parameters and the combined endpoint
      cardiovascular hospitalizations and death.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Exercise capacity (Peak VO2)
time frame: Change from baseline to 4 months
description: Peak VO2 is measured by spiroergometry
measure: 6 Minute walking distance
time frame: Change from baseline to 4 months
description: To further assess exercise capacity
measure: New York Heart Association class (class I, II, III, IV with class I = best status, and class IV = worst status)
time frame: Improvement or deterioration of NYHA class from baseline to 4 months
description: To assess symptoms
measure: Echocardiographic ejection fraction of left ventricular function (measured in %, the lower the worse)
time frame: Improvement or deterioration of ejection fraction from baseline to 4 months
description: Systolic and diastolic function, chamber diameters, strain analyses
measure: Combined endpoint cardiovascular hospitalizations and death
time frame: After 2 and 4 months
description: To assess major events
arm group label: Initial FCM
arm group type: Experimental
description: Intravenous iron supplementation with FCM, subsequent (after 2 months) exercise training program
arm group label: Initial exercise
arm group type: Experimental
description: Exercise training program, subsequent (after 2 months) intravenous iron supplementation with FCM
intervention type: Behavioral
intervention name: Initial exercise training
description: Initial exercise training program
arm group label: Initial exercise
intervention type: Drug
intervention name: Initial FCM
description: Initial intravenous iron supplementation (FCM)
arm group label: Initial FCM
intervention type: Drug
intervention name: Subsequent FCM
description: Subsequent intravenous iron Supplementation (FCM) after 2 months
arm group label: Initial exercise
intervention type: Behavioral
intervention name: Subsequent exercise training
description: Subsequent exercise training program after 2 months
arm group label: Initial FCM
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: Germany
responsible party type: Principal Investigator
investigator affiliation: Herzzentrum Bremen
investigator full name: Dr. Harm Wienbergen
investigator title: Head of the Bremen Institute for Heart and Circulation Research (BIHKF)
mesh term: Heart Failure
mesh term: Anemia, Iron-Deficiency
mesh term: Iron Deficiencies