<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/NCT02188784</url>
  </required_header>
  <id_info>
    <org_study_id>Pro00054061</org_study_id>
    <secondary_id>2U10HL084904</secondary_id>
    <nct_id>NCT02188784</nct_id>
  </id_info>
  <brief_title>Oral Iron Repletion Effects On Oxygen Uptake in Heart Failure</brief_title>
  <acronym>IRONOUT</acronym>
  <official_title>Oral Iron Repletion Effects On Oxygen Uptake in Heart Failure</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Adrian Hernandez</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Heart, Lung, and Blood Institute (NHLBI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Duke University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine if oral iron (Fe) polysaccharide is superior to&#xD;
      oral placebo in improving functional capacity as measured by change in peak VO2 (oxygen&#xD;
      uptake) by CPET (Cardiopulmonary Exercise Testing) , of a broad population of patients with&#xD;
      HFrEF (Heart Failure with Reduced Ejection Fraction) and Fe deficiency at 16 weeks.&#xD;
&#xD;
      Hypothesis: In a broad population of HFrEF patients with Fe deficiency, compared to oral&#xD;
      placebo, therapy with oral Fe polysaccharide will be associated with improvement in&#xD;
      functional capacity at 16 weeks as assessed by CPET.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Therapeutic options to further improve functional capacity and symptoms in HF beyond&#xD;
      neurohormonal antagonism are limited. Studies have demonstrated impaired oxidative capacity&#xD;
      of skeletal muscle among HF patients, which may contribute to symptoms of breathlessness and&#xD;
      persistent fatigue.&#xD;
&#xD;
      In addition to its role in erythropoiesis, iron (Fe) plays a critical role in skeletal&#xD;
      muscle's oxygen (O2)-storage capacity (myoglobin) and systemic aerobic energy production. As&#xD;
      Fe deficiency is common in patients with symptomatic HF, repletion of iron stores may improve&#xD;
      submaximal exercise capacity among these patients beyond the effects on erythropoiesis.&#xD;
&#xD;
      While intravenous Fe repletion in HF patients with mild Fe-deficiency (i.e. Ferritin &lt;100 or&#xD;
      Ferritin 100-299 with transferrin saturation &lt;20%) with or without anemia global well-being&#xD;
      and functional status, oral Fe repletion has not been studied. Furthermore, the efficacy of&#xD;
      oral Fe to replete iron stores in a similar population and its impact on functional capacity,&#xD;
      measured objectively by peak VO2, remains unknown.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 3, 2014</start_date>
  <completion_date type="Actual">April 6, 2016</completion_date>
  <primary_completion_date type="Actual">April 6, 2016</primary_completion_date>
  <phase>Phase 3</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>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Peak VO2 (ml/Min) (VO2 =Oxygen Consumption)</measure>
    <time_frame>Baseline (BL) and Week 16</time_frame>
    <description>To determine if oral Fe (Iron) polysaccharide is superior to oral placebo in improving functional capacity as measured by change in peak VO2 by CPET (Cardiopulmonary Exercise Testing) , of a broad population of patients with HFrEF (Heart Failure with Reduced Ejection Fraction) and Fe deficiency at 16 weeks.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Sub-maximal Exercise Capacity as Assessed by the 6 Minute Walk Test (6MWT)</measure>
    <time_frame>Measured at BL, week 8 and week 16</time_frame>
    <description>To determine the impact of oral Fe repletion on Submaximal exercise capacity as measured by 6MWT</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Plasma NT-pro BNP</measure>
    <time_frame>Measured at Baseline and Week 16</time_frame>
    <description>To determine the impact of oral Fe repletion on Plasma N-terminal pro-B-type natriuretic peptide (NT-pro BNP)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Health Status: Kansas City Cardiomyopathy Questionnaire (KCCQ) - Clinical Summary Score</measure>
    <time_frame>Measured at Baseline, Week 8 and Week 16</time_frame>
    <description>To determine the impact of oral Fe repletion on Health Status: KCCQ.&#xD;
KCCQ is a 23-item, self administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life for patients with congestive heart failure. It is a predictive tool that tracks how patients are doing if they have weakened heart muscle due to prior heart attacks, heart valve problems, viral infections, or other causes.&#xD;
The KCCQs questions are used to calculate scores in ten domains. Physical Limitation, Symptom Stability, Frequency, Burden and Total Symptom. Social Limitation, Self-Efficacy, Quality of Life, and Clinical Summary. Overall summary: a combined measure of all the above.&#xD;
For each domain, the validity, reproducibility, responsiveness and interpretability have been independently established. Scores are transformed to a range of 0-100, in which higher scores reflect better health status.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in O2 Uptake Kinetics as Assessed by Mean Response Time From CPET</measure>
    <time_frame>Measured at BL week 16</time_frame>
    <description>To determine the impact of oral Fe repletion on O2 Uptake Kinetics as measured by CPET</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Ventilatory Efficiency Defined by Ve/VCO2</measure>
    <time_frame>Measured at BL week 16</time_frame>
    <description>Change from baseline in Ventilatory Efficiency defined by Ve/VCO2 (carbon dioxide output) as measured by CPET</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">225</enrollment>
  <condition>Chronic Heart Failure</condition>
  <arm_group>
    <arm_group_label>Polysaccharide iron complex 150 mg</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>oral Fe polysaccharide 150mg twice daily for 16 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo (for Polysaccharide Iron Complex 150 mg)</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Oral placebo twice a day for 16 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Polysaccharide Iron Complex 150 mg</intervention_name>
    <description>Oral Iron</description>
    <arm_group_label>Polysaccharide iron complex 150 mg</arm_group_label>
    <other_name>Feramax 150 mg</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo (for Polysaccharide Iron Complex)</intervention_name>
    <description>Sugar capsule designed to mimic Polysaccharide Iron Complex.</description>
    <arm_group_label>Placebo (for Polysaccharide Iron Complex 150 mg)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age &gt;18 years&#xD;
&#xD;
          2. Previous clinical diagnosis of heart failure with current New York Heart Association&#xD;
             (NYHA) Class II-IV symptoms LVEF≤0.40 within 2 years prior to consent, and ≥3 months&#xD;
             after a major change in cardiac status (i.e. CABG or CRT).&#xD;
&#xD;
          3. Serum ferritin between 15-100 ng/ml or serum ferritin between 100-299 ng/ml with&#xD;
             transferrin saturation &lt;20%&#xD;
&#xD;
          4. Hemoglobin 9.0-13.5 g/dL (males), 9-13.5 (females) at time of enrollment&#xD;
&#xD;
          5. Stable evidence-based medical therapy for HF (including beta-blocker and&#xD;
             ACE-inhibitor/ARB unless previously deemed intolerant, and diuretics as necessary)&#xD;
             with &lt;/= 100% change in dose for 30 days prior to randomization&#xD;
&#xD;
             a. Changes in diuretic dose guided by a patient-directed flexible dosing program are&#xD;
             considered stable medical therapy&#xD;
&#xD;
          6. Willingness to provide informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Presence of a neuromuscular, orthopedic or other non-cardiac condition that prevents&#xD;
             the patient from exercise testing on a bicycle/treadmill ergometer and/or inability to&#xD;
             achieve an RER ≥ 1.0 on screening/baseline CPET&#xD;
&#xD;
          2. Severe renal dysfunction (eGFR&lt; 20 ml/min/1.73m2)&#xD;
&#xD;
          3. Severe liver disease (ALT or AST &gt; 3x normal, alkaline phosphatase or bilirubin &gt;2x&#xD;
             normal)&#xD;
&#xD;
          4. Gastrointestinal conditions known to impair Fe absorption (i.e. inflammatory bowel&#xD;
             disease)&#xD;
&#xD;
          5. Known active infection as defined by current use of oral or intravenous antimicrobial&#xD;
             agents&#xD;
&#xD;
          6. Documented active gastrointestinal bleeding&#xD;
&#xD;
          7. Active malignancy other than non-melanoma skin cancers&#xD;
&#xD;
          8. Anemia with known cause other than Fe deficiency or chronic disease&#xD;
&#xD;
          9. Fe overload disorders (i.e. hemochromatosis or hemosiderosis)&#xD;
&#xD;
         10. History of erythropoietin, IV or oral Fe therapy, or blood transfusion in previous 3&#xD;
             months.&#xD;
&#xD;
         11. Current ventricular assist device&#xD;
&#xD;
         12. Anticipated cardiac transplantation within the next 4 months&#xD;
&#xD;
         13. Primary hypertrophic cardiomyopathy, infiltrative cardiomyopathy, acute myocarditis,&#xD;
             constrictive pericarditis or tamponade&#xD;
&#xD;
         14. Previous adverse reaction to study drug or other oral Fe preparation&#xD;
&#xD;
         15. Known or anticipated pregnancy in the next 4 months&#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>Adrian Hernandez, MD,MHS,FAHA</last_name>
    <role>Principal Investigator</role>
    <affiliation>Duke University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Emory University School of Medicine</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Johns Hopkins Hospital</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21287</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tufts Medical Center</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02111</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Massachusetts General Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Brigham and Women's Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Louis University Hospital</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington University School of Medicine</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duke University Medical Center</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27705</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospitals-Case Medical Center</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Metor Health System</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic Foundation</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lancaster General Hospital</name>
      <address>
        <city>Lancaster</city>
        <state>Pennsylvania</state>
        <zip>17603</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital of the University of Pennsylvania</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Thomas Jefferson University</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19107</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Utah Hospitals and Clinics</name>
      <address>
        <city>Murray</city>
        <state>Utah</state>
        <zip>84107</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The University of Vermont - Fletcher Allen Health Care</name>
      <address>
        <city>Burlington</city>
        <state>Vermont</state>
        <zip>05401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2017</verification_date>
  <study_first_submitted>July 10, 2014</study_first_submitted>
  <study_first_submitted_qc>July 11, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 14, 2014</study_first_posted>
  <results_first_submitted>December 30, 2016</results_first_submitted>
  <results_first_submitted_qc>April 5, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">May 15, 2017</results_first_posted>
  <last_update_submitted>June 9, 2017</last_update_submitted>
  <last_update_submitted_qc>June 9, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">July 11, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Duke University</investigator_affiliation>
    <investigator_full_name>Adrian Hernandez</investigator_full_name>
    <investigator_title>MD, MHS, FAHA: Associate Professor of Medicine;Director, Outcomes &amp; Health Services Research</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Heart Failure</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Iron</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>After the study results have been published, site-specific participant data will be shared with sites upon request. Sites are expected to follow their specific institutional policies regarding sharing results with their participants.</ipd_description>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Polysaccharide Iron Complex 150 mg</title>
          <description>oral Fe polysaccharide 150mg twice daily for 16 weeks&#xD;
Polysaccharide Iron Complex 150 mg: Oral Iron</description>
        </group>
        <group group_id="P2">
          <title>Placebo (for Polysaccharide Iron Complex 150 mg)</title>
          <description>Oral placebo twice a day for 16 weeks&#xD;
Placebo (for Polysaccharide Iron Complex): Sugar capsule designed to mimic Polysaccharide Iron Complex.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="111"/>
                <participants group_id="P2" count="114"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="102">Patients completing the protocol excluding death, lost to follow-up and withdrawn consent.</participants>
                <participants group_id="P2" count="101">Patients completing the protocol excluding death, lost to follow-up and withdrawn consent.</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
                <participants group_id="P2" count="13"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="9"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>All randomized patients</population>
      <group_list>
        <group group_id="B1">
          <title>Polysaccharide Iron Complex 150 mg</title>
          <description>oral Fe polysaccharide 150mg twice daily for 16 weeks&#xD;
Polysaccharide Iron Complex 150 mg: Oral Iron</description>
        </group>
        <group group_id="B2">
          <title>Placebo (for Polysaccharide Iron Complex 150 mg)</title>
          <description>Oral placebo twice a day for 16 weeks&#xD;
Placebo (for Polysaccharide Iron Complex): Sugar capsule designed to mimic Polysaccharide Iron Complex.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="111"/>
            <count group_id="B2" value="114"/>
            <count group_id="B3" value="225"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="61.8" spread="13.4"/>
                    <measurement group_id="B2" value="51.6" spread="12.5"/>
                    <measurement group_id="B3" value="61.7" spread="12.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="44"/>
                    <measurement group_id="B2" value="36"/>
                    <measurement group_id="B3" value="80"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="67"/>
                    <measurement group_id="B2" value="78"/>
                    <measurement group_id="B3" value="145"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="108"/>
                    <measurement group_id="B2" value="107"/>
                    <measurement group_id="B3" value="215"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="31"/>
                    <measurement group_id="B2" value="26"/>
                    <measurement group_id="B3" value="57"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="79"/>
                    <measurement group_id="B2" value="85"/>
                    <measurement group_id="B3" value="164"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="111"/>
                    <measurement group_id="B2" value="114"/>
                    <measurement group_id="B3" value="225"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Peak VO2 (ml/Min) (VO2 =Oxygen Consumption)</title>
        <description>To determine if oral Fe (Iron) polysaccharide is superior to oral placebo in improving functional capacity as measured by change in peak VO2 by CPET (Cardiopulmonary Exercise Testing) , of a broad population of patients with HFrEF (Heart Failure with Reduced Ejection Fraction) and Fe deficiency at 16 weeks.</description>
        <time_frame>Baseline (BL) and Week 16</time_frame>
        <population>All randomized patients with available change data</population>
        <group_list>
          <group group_id="O1">
            <title>Polysaccharide Iron Complex 150 mg</title>
            <description>oral Fe polysaccharide 150mg twice daily for 16 weeks&#xD;
Polysaccharide Iron Complex 150 mg: Oral Iron</description>
          </group>
          <group group_id="O2">
            <title>Placebo (for Polysaccharide Iron Complex 150 mg)</title>
            <description>Oral placebo twice a day for 16 weeks&#xD;
Placebo (for Polysaccharide Iron Complex): Sugar capsule designed to mimic Polysaccharide Iron Complex.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Peak VO2 (ml/Min) (VO2 =Oxygen Consumption)</title>
          <description>To determine if oral Fe (Iron) polysaccharide is superior to oral placebo in improving functional capacity as measured by change in peak VO2 by CPET (Cardiopulmonary Exercise Testing) , of a broad population of patients with HFrEF (Heart Failure with Reduced Ejection Fraction) and Fe deficiency at 16 weeks.</description>
          <population>All randomized patients with available change data</population>
          <units>mL/min</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="96"/>
                <count group_id="O2" value="95"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="28.04" spread="212.75"/>
                    <measurement group_id="O2" value="3.90" spread="190.24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.4570</p_value>
            <method>Regression, Linear</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>21.03</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-34.38</ci_lower_limit>
            <ci_upper_limit>76.43</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Sub-maximal Exercise Capacity as Assessed by the 6 Minute Walk Test (6MWT)</title>
        <description>To determine the impact of oral Fe repletion on Submaximal exercise capacity as measured by 6MWT</description>
        <time_frame>Measured at BL, week 8 and week 16</time_frame>
        <population>All randomized patients with available change data</population>
        <group_list>
          <group group_id="O1">
            <title>Polysaccharide Iron Complex 150 mg</title>
            <description>oral Fe polysaccharide 150mg twice daily for 16 weeks&#xD;
Polysaccharide Iron Complex 150 mg: Oral Iron</description>
          </group>
          <group group_id="O2">
            <title>Placebo (for Polysaccharide Iron Complex 150 mg)</title>
            <description>Oral placebo twice a day for 16 weeks&#xD;
Placebo (for Polysaccharide Iron Complex): Sugar capsule designed to mimic Polysaccharide Iron Complex.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Sub-maximal Exercise Capacity as Assessed by the 6 Minute Walk Test (6MWT)</title>
          <description>To determine the impact of oral Fe repletion on Submaximal exercise capacity as measured by 6MWT</description>
          <population>All randomized patients with available change data</population>
          <units>meters</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="111"/>
                <count group_id="O2" value="114"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>8 weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="101"/>
                    <count group_id="O2" value="97"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.65" spread="95.89"/>
                    <measurement group_id="O2" value="16.63" spread="83.20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>16 weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="97"/>
                    <count group_id="O2" value="97"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.76" spread="62.29"/>
                    <measurement group_id="O2" value="30.94" spread="77.33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Change from Baseline to Week 8</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.9487</p_value>
            <method>Regression, Linear</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-0.77</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-24.12</ci_lower_limit>
            <ci_upper_limit>22.59</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Change from Baseline to Week 16</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.1921</p_value>
            <method>Regression, Linear</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-12.67</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-31.71</ci_lower_limit>
            <ci_upper_limit>6.37</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Plasma NT-pro BNP</title>
        <description>To determine the impact of oral Fe repletion on Plasma N-terminal pro-B-type natriuretic peptide (NT-pro BNP)</description>
        <time_frame>Measured at Baseline and Week 16</time_frame>
        <population>All randomized patients with available change data</population>
        <group_list>
          <group group_id="O1">
            <title>Polysaccharide Iron Complex 150 mg</title>
            <description>oral Fe polysaccharide 150mg twice daily for 16 weeks&#xD;
Polysaccharide Iron Complex 150 mg: Oral Iron</description>
          </group>
          <group group_id="O2">
            <title>Placebo (for Polysaccharide Iron Complex 150 mg)</title>
            <description>Oral placebo twice a day for 16 weeks&#xD;
Placebo (for Polysaccharide Iron Complex): Sugar capsule designed to mimic Polysaccharide Iron Complex.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Plasma NT-pro BNP</title>
          <description>To determine the impact of oral Fe repletion on Plasma N-terminal pro-B-type natriuretic peptide (NT-pro BNP)</description>
          <population>All randomized patients with available change data</population>
          <units>pg/ml</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="98"/>
                <count group_id="O2" value="98"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="119.36" spread="1937.58"/>
                    <measurement group_id="O2" value="-70.88" spread="1256.49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.4296</p_value>
            <method>Regression, Linear</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>182.43</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-272.14</ci_lower_limit>
            <ci_upper_limit>637.0</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Health Status: Kansas City Cardiomyopathy Questionnaire (KCCQ) - Clinical Summary Score</title>
        <description>To determine the impact of oral Fe repletion on Health Status: KCCQ.&#xD;
KCCQ is a 23-item, self administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life for patients with congestive heart failure. It is a predictive tool that tracks how patients are doing if they have weakened heart muscle due to prior heart attacks, heart valve problems, viral infections, or other causes.&#xD;
The KCCQs questions are used to calculate scores in ten domains. Physical Limitation, Symptom Stability, Frequency, Burden and Total Symptom. Social Limitation, Self-Efficacy, Quality of Life, and Clinical Summary. Overall summary: a combined measure of all the above.&#xD;
For each domain, the validity, reproducibility, responsiveness and interpretability have been independently established. Scores are transformed to a range of 0-100, in which higher scores reflect better health status.</description>
        <time_frame>Measured at Baseline, Week 8 and Week 16</time_frame>
        <population>All randomized patients with available change data</population>
        <group_list>
          <group group_id="O1">
            <title>Polysaccharide Iron Complex 150 mg</title>
            <description>oral Fe polysaccharide 150mg twice daily for 16 weeks&#xD;
Polysaccharide Iron Complex 150 mg: Oral Iron</description>
          </group>
          <group group_id="O2">
            <title>Placebo (for Polysaccharide Iron Complex 150 mg)</title>
            <description>Oral placebo twice a day for 16 weeks&#xD;
Placebo (for Polysaccharide Iron Complex): Sugar capsule designed to mimic Polysaccharide Iron Complex.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Health Status: Kansas City Cardiomyopathy Questionnaire (KCCQ) - Clinical Summary Score</title>
          <description>To determine the impact of oral Fe repletion on Health Status: KCCQ.&#xD;
KCCQ is a 23-item, self administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life for patients with congestive heart failure. It is a predictive tool that tracks how patients are doing if they have weakened heart muscle due to prior heart attacks, heart valve problems, viral infections, or other causes.&#xD;
The KCCQs questions are used to calculate scores in ten domains. Physical Limitation, Symptom Stability, Frequency, Burden and Total Symptom. Social Limitation, Self-Efficacy, Quality of Life, and Clinical Summary. Overall summary: a combined measure of all the above.&#xD;
For each domain, the validity, reproducibility, responsiveness and interpretability have been independently established. Scores are transformed to a range of 0-100, in which higher scores reflect better health status.</description>
          <population>All randomized patients with available change data</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="111"/>
                <count group_id="O2" value="114"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 8</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="104"/>
                    <count group_id="O2" value="103"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.25" spread="16.91"/>
                    <measurement group_id="O2" value="0.58" spread="13.63"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 16</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="100"/>
                    <count group_id="O2" value="100"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.42" spread="16.05"/>
                    <measurement group_id="O2" value="4.11" spread="11.80"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Change from baseline to week 8</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.0722</p_value>
            <method>Regression, Linear</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>3.60</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.33</ci_lower_limit>
            <ci_upper_limit>7.52</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Change from baseline to week 16</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.6927</p_value>
            <method>Regression, Linear</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>0.71</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-2.83</ci_lower_limit>
            <ci_upper_limit>4.24</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in O2 Uptake Kinetics as Assessed by Mean Response Time From CPET</title>
        <description>To determine the impact of oral Fe repletion on O2 Uptake Kinetics as measured by CPET</description>
        <time_frame>Measured at BL week 16</time_frame>
        <population>All randomized patients with available change data</population>
        <group_list>
          <group group_id="O1">
            <title>Polysaccharide Iron Complex 150 mg</title>
            <description>oral Fe polysaccharide 150mg twice daily for 16 weeks&#xD;
Polysaccharide Iron Complex 150 mg: Oral Iron</description>
          </group>
          <group group_id="O2">
            <title>Placebo (for Polysaccharide Iron Complex 150 mg)</title>
            <description>Oral placebo twice a day for 16 weeks&#xD;
Placebo (for Polysaccharide Iron Complex): Sugar capsule designed to mimic Polysaccharide Iron Complex.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in O2 Uptake Kinetics as Assessed by Mean Response Time From CPET</title>
          <description>To determine the impact of oral Fe repletion on O2 Uptake Kinetics as measured by CPET</description>
          <population>All randomized patients with available change data</population>
          <units>seconds</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="71"/>
                <count group_id="O2" value="62"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.63" spread="13.31"/>
                    <measurement group_id="O2" value="-0.95" spread="13.29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.0643</p_value>
            <method>Regression, Linear</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>3.56</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.21</ci_lower_limit>
            <ci_upper_limit>7.33</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Ventilatory Efficiency Defined by Ve/VCO2</title>
        <description>Change from baseline in Ventilatory Efficiency defined by Ve/VCO2 (carbon dioxide output) as measured by CPET</description>
        <time_frame>Measured at BL week 16</time_frame>
        <population>All randomized patients with available change data</population>
        <group_list>
          <group group_id="O1">
            <title>Polysaccharide Iron Complex 150 mg</title>
            <description>oral Fe polysaccharide 150mg twice daily for 16 weeks&#xD;
Polysaccharide Iron Complex 150 mg: Oral Iron</description>
          </group>
          <group group_id="O2">
            <title>Placebo (for Polysaccharide Iron Complex 150 mg)</title>
            <description>Oral placebo twice a day for 16 weeks&#xD;
Placebo (for Polysaccharide Iron Complex): Sugar capsule designed to mimic Polysaccharide Iron Complex.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Ventilatory Efficiency Defined by Ve/VCO2</title>
          <description>Change from baseline in Ventilatory Efficiency defined by Ve/VCO2 (carbon dioxide output) as measured by CPET</description>
          <population>All randomized patients with available change data</population>
          <units>VE/VCO2 Slope</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="96"/>
                <count group_id="O2" value="95"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.48" spread="5.85"/>
                    <measurement group_id="O2" value="-1.31" spread="8.85"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.4006</p_value>
            <method>Regression, Linear</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>0.77</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1.04</ci_lower_limit>
            <ci_upper_limit>2.58</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Randomization to Week 16</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Polysaccharide Iron Complex 150 mg</title>
          <description>oral Fe polysaccharide 150mg twice daily for 16 weeks&#xD;
Polysaccharide Iron Complex 150 mg: Oral Iron</description>
        </group>
        <group group_id="E2">
          <title>Placebo (for Polysaccharide Iron Complex 150 mg)</title>
          <description>Oral placebo twice a day for 16 weeks&#xD;
Placebo (for Polysaccharide Iron Complex): Sugar capsule designed to mimic Polysaccharide Iron Complex.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 19.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="111"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="114"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title vocab="MedDRA (10.0)">Abdominal Pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="111"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="114"/>
              </event>
              <event>
                <sub_title vocab="MedDRA (10.0)">Gastrointestinal Pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="111"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="114"/>
              </event>
              <event>
                <sub_title>Melaena</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="111"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="114"/>
              </event>
              <event>
                <sub_title>Rectal Haemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="111"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="114"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Non-Cardiac Chest Pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="111"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="114"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bronchitis Viral</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="111"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="114"/>
              </event>
              <event>
                <sub_title>Gastroenteritis Viral</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="111"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="114"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="111"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="114"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="111"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="114"/>
              </event>
              <event>
                <sub_title>Streptococcal Sepsis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="111"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="114"/>
              </event>
              <event>
                <sub_title>Vestibular Neuronitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="111"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="114"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Abdominal Injury</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="111"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="114"/>
              </event>
              <event>
                <sub_title>Road Traffic Accident</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="111"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="114"/>
              </event>
              <event>
                <sub_title>Norovirus Test Positive</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="111"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="114"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Liver Function Test Abnormal</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="111"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="114"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperosmolar Hyperglycaemic State</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="111"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="114"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Musculoskeletal Chest Pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="111"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="114"/>
              </event>
              <event>
                <sub_title>Rhabdomyolysis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="111"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="114"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Skin Cancer</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="111"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="114"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Alcohol Withdrawal Syndrome</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="111"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="114"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertensive Crisis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="111"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="114"/>
              </event>
              <event>
                <sub_title>Temporal Arteritis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="111"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="114"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>2</frequency_threshold>
        <default_vocab>MedDRA 19.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="18" subjects_at_risk="111"/>
                <counts group_id="E2" subjects_affected="24" subjects_at_risk="114"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal Discomfort</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="111"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="114"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="8" subjects_affected="6" subjects_at_risk="111"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="114"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="111"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="114"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="111"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="114"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="111"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="114"/>
              </event>
              <event>
                <sub_title>Non-Cardiac Chest Pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="111"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="114"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="111"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="114"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Gout</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="111"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="114"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="111"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="114"/>
              </event>
              <event>
                <sub_title>Musculoskeletal Chest Pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="111"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="114"/>
              </event>
              <event>
                <sub_title>Pain in Extremity</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="111"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="114"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="111"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="114"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="111"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="114"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>To minimize the probability of inaccurate data in published materials, it is the policy of The Heart Failure Network (HFN) that all data and text considered for all papers, and all abstracts for presentation at scientific meetings, be submitted to the Publication &amp; Presentation Subcommittee, the NHLBI Project Officer and the Coordinating Center for review and approval prior to presentation or publication.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Adrian Hernandez</name_or_title>
      <organization>Duke Clinical Research Institute</organization>
      <phone>919-668-7515</phone>
      <email>adrian.hernandez@duke.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT02188784
org study id: Pro00054061
secondary id: 2U10HL084904
nct id: NCT02188784
lead sponsor: 
collaborator: 
has dmc: Yes
The purpose of this study is to determine if oral iron (Fe) polysaccharide is superior to
      oral placebo in improving functional capacity as measured by change in peak VO2 (oxygen
      uptake) by CPET (Cardiopulmonary Exercise Testing) , of a broad population of patients with
      HFrEF (Heart Failure with Reduced Ejection Fraction) and Fe deficiency at 16 weeks.

      Hypothesis: In a broad population of HFrEF patients with Fe deficiency, compared to oral
      placebo, therapy with oral Fe polysaccharide will be associated with improvement in
      functional capacity at 16 weeks as assessed by CPET.
Therapeutic options to further improve functional capacity and symptoms in HF beyond
      neurohormonal antagonism are limited. Studies have demonstrated impaired oxidative capacity
      of skeletal muscle among HF patients, which may contribute to symptoms of breathlessness and
      persistent fatigue.

      In addition to its role in erythropoiesis, iron (Fe) plays a critical role in skeletal
      muscle's oxygen (O2)-storage capacity (myoglobin) and systemic aerobic energy production. As
      Fe deficiency is common in patients with symptomatic HF, repletion of iron stores may improve
      submaximal exercise capacity among these patients beyond the effects on erythropoiesis.

      While intravenous Fe repletion in HF patients with mild Fe-deficiency (i.e. Ferritin <100 or
      Ferritin 100-299 with transferrin saturation <20%) with or without anemia global well-being
      and functional status, oral Fe repletion has not been studied. Furthermore, the efficacy of
      oral Fe to replete iron stores in a similar population and its impact on functional capacity,
      measured objectively by peak VO2, remains unknown.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Change in Peak VO2 (ml/Min) (VO2 =Oxygen Consumption)
time frame: Baseline (BL) and Week 16
description: To determine if oral Fe (Iron) polysaccharide is superior to oral placebo in improving functional capacity as measured by change in peak VO2 by CPET (Cardiopulmonary Exercise Testing) , of a broad population of patients with HFrEF (Heart Failure with Reduced Ejection Fraction) and Fe deficiency at 16 weeks.
measure: Change From Baseline in Sub-maximal Exercise Capacity as Assessed by the 6 Minute Walk Test (6MWT)
time frame: Measured at BL, week 8 and week 16
description: To determine the impact of oral Fe repletion on Submaximal exercise capacity as measured by 6MWT
measure: Change in Plasma NT-pro BNP
time frame: Measured at Baseline and Week 16
description: To determine the impact of oral Fe repletion on Plasma N-terminal pro-B-type natriuretic peptide (NT-pro BNP)
measure: Change in Health Status: Kansas City Cardiomyopathy Questionnaire (KCCQ) - Clinical Summary Score
time frame: Measured at Baseline, Week 8 and Week 16
description: To determine the impact of oral Fe repletion on Health Status: KCCQ.
KCCQ is a 23-item, self administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life for patients with congestive heart failure. It is a predictive tool that tracks how patients are doing if they have weakened heart muscle due to prior heart attacks, heart valve problems, viral infections, or other causes.
The KCCQs questions are used to calculate scores in ten domains. Physical Limitation, Symptom Stability, Frequency, Burden and Total Symptom. Social Limitation, Self-Efficacy, Quality of Life, and Clinical Summary. Overall summary: a combined measure of all the above.
For each domain, the validity, reproducibility, responsiveness and interpretability have been independently established. Scores are transformed to a range of 0-100, in which higher scores reflect better health status.
measure: Change From Baseline in O2 Uptake Kinetics as Assessed by Mean Response Time From CPET
time frame: Measured at BL week 16
description: To determine the impact of oral Fe repletion on O2 Uptake Kinetics as measured by CPET
measure: Change From Baseline in Ventilatory Efficiency Defined by Ve/VCO2
time frame: Measured at BL week 16
description: Change from baseline in Ventilatory Efficiency defined by Ve/VCO2 (carbon dioxide output) as measured by CPET
arm group label: Polysaccharide iron complex 150 mg
arm group type: Active Comparator
description: oral Fe polysaccharide 150mg twice daily for 16 weeks
arm group label: Placebo (for Polysaccharide Iron Complex 150 mg)
arm group type: Placebo Comparator
description: Oral placebo twice a day for 16 weeks
intervention type: Drug
intervention name: Polysaccharide Iron Complex 150 mg
description: Oral Iron
arm group label: Polysaccharide iron complex 150 mg
other name: Feramax 150 mg
intervention type: Drug
intervention name: Placebo (for Polysaccharide Iron Complex)
description: Sugar capsule designed to mimic Polysaccharide Iron Complex.
arm group label: Placebo (for Polysaccharide Iron Complex 150 mg)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Adrian Hernandez, MD,MHS,FAHA
role: Principal Investigator
affiliation: Duke University
facility: 
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country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: Duke University
investigator full name: Adrian Hernandez
investigator title: MD, MHS, FAHA: Associate Professor of Medicine;Director, Outcomes & Health Services Research
mesh term: Heart Failure
mesh term: Iron
sharing ipd: Yes
ipd description: After the study results have been published, site-specific participant data will be shared with sites upon request. Sites are expected to follow their specific institutional policies regarding sharing results with their participants.
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 