<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/NCT03759964</url>
  </required_header>
  <id_info>
    <org_study_id>CEHDF 1050</org_study_id>
    <nct_id>NCT03759964</nct_id>
  </id_info>
  <brief_title>Effects of Ferinject® on Anemia and Transfusion Rates After Cardiac Surgery</brief_title>
  <acronym>FCAACS</acronym>
  <official_title>Ferric Carboxymaltose (Ferinject®) Administered After Cardiac Surgery: (FCAACS) Effects On Correction Of Anemia And Transfusion Rates: A Prospective Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>St Joseph University, Beirut, Lebanon</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Vifor Pharma</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Saint-Joseph University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>St Joseph University, Beirut, Lebanon</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>
      Several studies using new forms of intravenous iron showed that it is effective in treating&#xD;
      perioperative anemia in orthopedic and digestive surgery. Effects of ferric carboxymaltose&#xD;
      have not been assessed in the settings of cardiac surgery.&#xD;
&#xD;
      This study will compare ferric carboxymaltose to placebo in a randomized trial design where&#xD;
      ferric carboxymaltose / placebo will be administered in the postoperative period (Day 1)&#xD;
      after cardiac surgery. A total sample size of 200 patients (100 per group) will be needed.&#xD;
&#xD;
      The FCAACS trial will assess the impact of administering intravenous iron (Ferric&#xD;
      carboxymaltose) after cardiac surgery with cardiopulmonary bypass (CPB) on the:&#xD;
&#xD;
        -  incidence of postoperative anemia&#xD;
&#xD;
        -  incidence of postoperative transfusion&#xD;
&#xD;
        -  incidence of complications related to intravenous iron&#xD;
&#xD;
      All the surgeries will be performed by the same surgical team and follow-up will be ensured&#xD;
      by the same Cardiac Surgery Unit (CSU) team according to department's standard protocols.&#xD;
&#xD;
      Participants in the Ferric carboxymaltose group will receive 1g of Ferric carboxymaltose&#xD;
      diluted in 100 mL of IV isotonic serum saline, whereas participants in the Placebo group will&#xD;
      receive 100 mL of IV Placebo&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Anemia is very common in the perioperative of major surgery affecting about 30% of patients&#xD;
      preoperatively and more than 80% postoperatively. Anemia is an independent risk factor of&#xD;
      morbi-mortality.&#xD;
&#xD;
      Iron deficiency is the first cause of anemia. Physiological reserves of iron are not&#xD;
      important, and the correction of anemia after hemorrhage is very slow. Hence, it takes 90&#xD;
      days to return to 80% of the basic Hb level after a blood donation of 500ml, and more than&#xD;
      150 days (almost 6 months), if one is deficient in iron. This is why iron is used to correct&#xD;
      anemia that occurs after bleeding. There are two routes for iron administration: oral and&#xD;
      intravenous.&#xD;
&#xD;
      Gastrointestinal absorption of iron is limited to 10-15 mg/d even when ingested doses are&#xD;
      increased. This absorption is decreased in the presence of an inflammatory state, which is&#xD;
      very common in the postoperative period.&#xD;
&#xD;
      The intravenous route allows the delivery of significantly higher doses of iron (up to 1000&#xD;
      mg in 1 infusion), without any limitation related to absorption. This is why it is&#xD;
      interesting to administer it perioperatively where the expected delays are short.&#xD;
&#xD;
      There are currently new intravenous iron formulations that have two advantages: a shorter&#xD;
      intravenous injection time and a higher maximum injectable dose per infusion. These new forms&#xD;
      are risk-free, with no serious allergy described so far in the literature.&#xD;
&#xD;
      Several studies using new forms of intravenous iron showed that it is effective in treating&#xD;
      perioperative anemia in orthopedic and digestive surgery. Effects of ferric carboxymaltose&#xD;
      have not been assessed in the settings of cardiac surgery.&#xD;
&#xD;
      To assess the impact of ferric carboxymaltose in cardiac surgery, it will be compared to&#xD;
      placebo in a randomized trial design, where ferric carboxymaltose / placebo will be&#xD;
      administered in the postoperative period. Ferric carboxymaltose / placebo will be an add-on&#xD;
      to the current treatment of patients in the postoperative period of cardiac surgery, the&#xD;
      group that will be receiving placebo reflects the current management of the patients in these&#xD;
      settings.&#xD;
&#xD;
      The FCAACS trial will assess the impact of administering intravenous iron (Ferric&#xD;
      carboxymaltose) after cardiac surgery with cardiopulmonary bypass (CPB) on the:&#xD;
&#xD;
        -  incidence of postoperative anemia&#xD;
&#xD;
        -  incidence of postoperative transfusion&#xD;
&#xD;
        -  incidence of complications related to intravenous iron&#xD;
&#xD;
      FCAACS will be a parallel group randomized trial, with a 2-group design and no crossover.&#xD;
      Allocation ratio will be 1/1, in an equivalence framework. A total sample size of 200&#xD;
      patients (100 per group) will be needed.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 15, 2018</start_date>
  <completion_date type="Actual">January 2, 2021</completion_date>
  <primary_completion_date type="Actual">December 9, 2020</primary_completion_date>
  <phase>Phase 4</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>
    <intervention_model_description>FCAACS will be a parallel group randomized trial, with a 2-group design and no crossover. Allocation ratio will be 1/1, in an equivalence framework.</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Triple (Participant, Care Provider, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in level of hemoglobin (g/dL) from preoperative until day 30 after surgery</measure>
    <time_frame>Preoperative (Day -2), Day 0 [CSU admission], Day 2 [CSU discharge], Day 5 [hospital discharge], Day 30</time_frame>
    <description>mean ± standard deviation, measured at 5 timepoints</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>change in Hematocrit from preoperative until day 30 after surgery (final value)</measure>
    <time_frame>Preoperative (Day -2), Day 0 [CSU admission], Day 2 [CSU discharge], Day 5 [hospital discharge], Day 30</time_frame>
    <description>mean ± standard deviation, measured at 5 timepoints</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Reticulocytes count from preoperative until day 30 after surgery (final value)</measure>
    <time_frame>Preoperative (Day -2), Day 2 [CSU discharge], Day 5 [hospital discharge], Day 30</time_frame>
    <description>measured at 4 timepoints</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Percentage of transferrin from preoperative until day 30 after surgery (final value)</measure>
    <time_frame>Preoperative (Day -2), Day 1 [CSU, before study drug], Day 5 [hospital discharge], Day 30</time_frame>
    <description>measured at 4 timepoints</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Ferritin from preoperative until day 30 after surgery (final value)</measure>
    <time_frame>Preoperative (Day -2), Day 1 [CSU, before study drug], Day 5 [hospital discharge], Day 30</time_frame>
    <description>measured at 4 timepoints</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of red cell packs transfused (final value)</measure>
    <time_frame>Day 1, Day 5,and Day 30</time_frame>
    <description>mean ± standard deviation, measured at 3 timepoints</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Total bleeding (mL) until drain removal (final value)</measure>
    <time_frame>From Day 0 until Day 2</time_frame>
    <description>mean ± standard deviation</description>
  </other_outcome>
  <other_outcome>
    <measure>Time to tracheal tube removal, measured in hours (final value)</measure>
    <time_frame>From Hour 0 until Hour 6 (on average, until tracheal tube removal)</time_frame>
    <description>mean ± standard deviation</description>
  </other_outcome>
  <other_outcome>
    <measure>Length of stay in the CSU measured in Days</measure>
    <time_frame>From Day 0 [CSU admission] until Day 2 [on overage, CSU discharge]</time_frame>
    <description>median and interquartile range</description>
  </other_outcome>
  <other_outcome>
    <measure>Surgical exploration for bleeding (Boolean, proportion)</measure>
    <time_frame>From Day 0 [CSU admission] until Day 2 [on overage, CSU discharge]</time_frame>
    <description>Proportion, with 95% confidence interval</description>
  </other_outcome>
  <other_outcome>
    <measure>Complications related to administration of Ferric carboxymaltose (proportion)</measure>
    <time_frame>From Day 0 until Day 30</time_frame>
    <description>Proportion, with 95% confidence interval</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">194</enrollment>
  <condition>Anemia, Iron Deficiency</condition>
  <arm_group>
    <arm_group_label>Ferric Carboxymaltose group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Ferric carboxymaltose group will receive 1g of Ferric carboxymaltose at day 1 following cardiac surgery</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo group</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo group will receive 100 mL of IV isotonic serum saline at day 1 following cardiac surgery</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ferric carboxymaltose</intervention_name>
    <description>1g of Ferric carboxymaltose diluted in 100 mL of IV isotonic serum saline at day 1 following surgery</description>
    <arm_group_label>Ferric Carboxymaltose group</arm_group_label>
    <other_name>Ferinject®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>100 mL of IV isotonic serum saline at day 1 following surgery</description>
    <arm_group_label>Placebo group</arm_group_label>
    <other_name>Serum saline</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult patients admitted for elective cardiac surgery under cardiopulmonary bypass,&#xD;
             with no exclusion criteria, and having signed an informed consent, will be enrolled in&#xD;
             the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients &lt; 18 years&#xD;
&#xD;
          -  Urgent surgery&#xD;
&#xD;
          -  Off-pump cardiac surgery&#xD;
&#xD;
          -  Redo cardiac surgery&#xD;
&#xD;
          -  Preoperative anemia (Hb &lt; 10g/l or Ht &lt; 30%)&#xD;
&#xD;
          -  Transfusion within 72h preoperatively&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  History of asthma or other specific allergies&#xD;
&#xD;
          -  History of allergy to iron&#xD;
&#xD;
          -  Acute infection&#xD;
&#xD;
          -  Hepatic insufficiency&#xD;
&#xD;
          -  Renal insufficiency (creatinine Clearance &lt; 30ml/min)&#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>Samia Madi-Jebara, Pr</last_name>
    <role>Principal Investigator</role>
    <affiliation>St Joseph University Beirut</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hotel Dieu de France Hospital</name>
      <address>
        <city>Beirut</city>
        <zip>166830</zip>
        <country>Lebanon</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Lebanon</country>
  </location_countries>
  <verification_date>October 2021</verification_date>
  <study_first_submitted>November 25, 2018</study_first_submitted>
  <study_first_submitted_qc>November 29, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 30, 2018</study_first_posted>
  <last_update_submitted>October 8, 2021</last_update_submitted>
  <last_update_submitted_qc>October 8, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">October 11, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>St Joseph University, Beirut, Lebanon</investigator_affiliation>
    <investigator_full_name>Samia Madi Jebara</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>cardiac surgery</keyword>
  <keyword>ferric carboxymaltose</keyword>
  <keyword>anemia</keyword>
  <keyword>transfusion</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anemia</mesh_term>
    <mesh_term>Anemia, Iron-Deficiency</mesh_term>
    <mesh_term>Iron Deficiencies</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03759964
org study id: CEHDF 1050
nct id: NCT03759964
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Several studies using new forms of intravenous iron showed that it is effective in treating
      perioperative anemia in orthopedic and digestive surgery. Effects of ferric carboxymaltose
      have not been assessed in the settings of cardiac surgery.

      This study will compare ferric carboxymaltose to placebo in a randomized trial design where
      ferric carboxymaltose / placebo will be administered in the postoperative period (Day 1)
      after cardiac surgery. A total sample size of 200 patients (100 per group) will be needed.

      The FCAACS trial will assess the impact of administering intravenous iron (Ferric
      carboxymaltose) after cardiac surgery with cardiopulmonary bypass (CPB) on the:

        -  incidence of postoperative anemia

        -  incidence of postoperative transfusion

        -  incidence of complications related to intravenous iron

      All the surgeries will be performed by the same surgical team and follow-up will be ensured
      by the same Cardiac Surgery Unit (CSU) team according to department's standard protocols.

      Participants in the Ferric carboxymaltose group will receive 1g of Ferric carboxymaltose
      diluted in 100 mL of IV isotonic serum saline, whereas participants in the Placebo group will
      receive 100 mL of IV Placebo
Anemia is very common in the perioperative of major surgery affecting about 30% of patients
      preoperatively and more than 80% postoperatively. Anemia is an independent risk factor of
      morbi-mortality.

      Iron deficiency is the first cause of anemia. Physiological reserves of iron are not
      important, and the correction of anemia after hemorrhage is very slow. Hence, it takes 90
      days to return to 80% of the basic Hb level after a blood donation of 500ml, and more than
      150 days (almost 6 months), if one is deficient in iron. This is why iron is used to correct
      anemia that occurs after bleeding. There are two routes for iron administration: oral and
      intravenous.

      Gastrointestinal absorption of iron is limited to 10-15 mg/d even when ingested doses are
      increased. This absorption is decreased in the presence of an inflammatory state, which is
      very common in the postoperative period.

      The intravenous route allows the delivery of significantly higher doses of iron (up to 1000
      mg in 1 infusion), without any limitation related to absorption. This is why it is
      interesting to administer it perioperatively where the expected delays are short.

      There are currently new intravenous iron formulations that have two advantages: a shorter
      intravenous injection time and a higher maximum injectable dose per infusion. These new forms
      are risk-free, with no serious allergy described so far in the literature.

      Several studies using new forms of intravenous iron showed that it is effective in treating
      perioperative anemia in orthopedic and digestive surgery. Effects of ferric carboxymaltose
      have not been assessed in the settings of cardiac surgery.

      To assess the impact of ferric carboxymaltose in cardiac surgery, it will be compared to
      placebo in a randomized trial design, where ferric carboxymaltose / placebo will be
      administered in the postoperative period. Ferric carboxymaltose / placebo will be an add-on
      to the current treatment of patients in the postoperative period of cardiac surgery, the
      group that will be receiving placebo reflects the current management of the patients in these
      settings.

      The FCAACS trial will assess the impact of administering intravenous iron (Ferric
      carboxymaltose) after cardiac surgery with cardiopulmonary bypass (CPB) on the:

        -  incidence of postoperative anemia

        -  incidence of postoperative transfusion

        -  incidence of complications related to intravenous iron

      FCAACS will be a parallel group randomized trial, with a 2-group design and no crossover.
      Allocation ratio will be 1/1, in an equivalence framework. A total sample size of 200
      patients (100 per group) will be needed.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: FCAACS will be a parallel group randomized trial, with a 2-group design and no crossover. Allocation ratio will be 1/1, in an equivalence framework.
primary purpose: Prevention
masking: Triple (Participant, Care Provider, Outcomes Assessor)
measure: Change in level of hemoglobin (g/dL) from preoperative until day 30 after surgery
time frame: Preoperative (Day -2), Day 0 [CSU admission], Day 2 [CSU discharge], Day 5 [hospital discharge], Day 30
description: mean ± standard deviation, measured at 5 timepoints
measure: change in Hematocrit from preoperative until day 30 after surgery (final value)
time frame: Preoperative (Day -2), Day 0 [CSU admission], Day 2 [CSU discharge], Day 5 [hospital discharge], Day 30
description: mean ± standard deviation, measured at 5 timepoints
measure: Change in Reticulocytes count from preoperative until day 30 after surgery (final value)
time frame: Preoperative (Day -2), Day 2 [CSU discharge], Day 5 [hospital discharge], Day 30
description: measured at 4 timepoints
measure: Change in Percentage of transferrin from preoperative until day 30 after surgery (final value)
time frame: Preoperative (Day -2), Day 1 [CSU, before study drug], Day 5 [hospital discharge], Day 30
description: measured at 4 timepoints
measure: Change in Ferritin from preoperative until day 30 after surgery (final value)
time frame: Preoperative (Day -2), Day 1 [CSU, before study drug], Day 5 [hospital discharge], Day 30
description: measured at 4 timepoints
measure: Number of red cell packs transfused (final value)
time frame: Day 1, Day 5,and Day 30
description: mean ± standard deviation, measured at 3 timepoints
measure: Total bleeding (mL) until drain removal (final value)
time frame: From Day 0 until Day 2
description: mean ± standard deviation
measure: Time to tracheal tube removal, measured in hours (final value)
time frame: From Hour 0 until Hour 6 (on average, until tracheal tube removal)
description: mean ± standard deviation
measure: Length of stay in the CSU measured in Days
time frame: From Day 0 [CSU admission] until Day 2 [on overage, CSU discharge]
description: median and interquartile range
measure: Surgical exploration for bleeding (Boolean, proportion)
time frame: From Day 0 [CSU admission] until Day 2 [on overage, CSU discharge]
description: Proportion, with 95% confidence interval
measure: Complications related to administration of Ferric carboxymaltose (proportion)
time frame: From Day 0 until Day 30
description: Proportion, with 95% confidence interval
arm group label: Ferric Carboxymaltose group
arm group type: Active Comparator
description: Ferric carboxymaltose group will receive 1g of Ferric carboxymaltose at day 1 following cardiac surgery
arm group label: Placebo group
arm group type: Placebo Comparator
description: Placebo group will receive 100 mL of IV isotonic serum saline at day 1 following cardiac surgery
intervention type: Drug
intervention name: Ferric carboxymaltose
description: 1g of Ferric carboxymaltose diluted in 100 mL of IV isotonic serum saline at day 1 following surgery
arm group label: Ferric Carboxymaltose group
other name: Ferinject®
intervention type: Drug
intervention name: Placebo
description: 100 mL of IV isotonic serum saline at day 1 following surgery
arm group label: Placebo group
other name: Serum saline
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Samia Madi-Jebara, Pr
role: Principal Investigator
affiliation: St Joseph University Beirut
facility: 
country: Lebanon
responsible party type: Principal Investigator
investigator affiliation: St Joseph University, Beirut, Lebanon
investigator full name: Samia Madi Jebara
investigator title: Professor
mesh term: Anemia
mesh term: Anemia, Iron-Deficiency
mesh term: Iron Deficiencies
sharing ipd: Undecided