<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/NCT03231085</url>
  </required_header>
  <id_info>
    <org_study_id>9769</org_study_id>
    <secondary_id>2016-005065-31</secondary_id>
    <nct_id>NCT03231085</nct_id>
  </id_info>
  <brief_title>Comparison of the Rate of Preoperative Haemoglobin After Administration of Epoetin Alpha Associated With an Oral Medical Supplementation Versus Intravenous Before Surgery of Craniosynostosis at the Child</brief_title>
  <acronym>IRON KID</acronym>
  <official_title>Comparison of the Rate of Preoperative Haemoglobin After Administration of Epoetin Alpha Associated With an Oral Medical Supplementation Versus Intravenous Before Surgery of Craniosynostosis at the Child</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Montpellier</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Hospital, Montpellier</source>
  <oversight_info>
    <has_dmc>Yes</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>
      Oral iron is commonly used in conjunction with EPO preoperatively for hemorrhagic surgeries&#xD;
      in children and especially in the surgery of craniosynostosis. The bioavailability of oral&#xD;
      iron is low and compliance with treatment is inconsistent. The aim of this study is to&#xD;
      evaluate whether the use of ferric carboxymaltose by injection, which has a much better&#xD;
      bioavailability, would make it possible to increase the preoperative hemoglobin level more&#xD;
      effectively and thus reduce the risk of perioperative blood transfusion .&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Prospective study, randomized in two parallel groups (martial treatment versus venous&#xD;
      injection) and stratified by center (Montpellier, Nice, Angers).&#xD;
&#xD;
      The number of subjects required is 100 patients, or 50 per group.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">October 31, 2017</start_date>
  <completion_date type="Anticipated">June 2024</completion_date>
  <primary_completion_date type="Anticipated">October 2023</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Care Provider)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Variation from reference in hemoglobin rate at the day before surgery</measure>
    <time_frame>Hemoglobin rate change from reference day (right before treatment) to one day before surgery (from 22 days to 5 weeks maximum)</time_frame>
    <description>Variation of hemoglobin rate between reference value (collected right before the implementation of treatment) and preoperative hemoglobin rate (collected one day before surgery)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Variation from reference in hemoglobin rate at the day before surgery depending on the reference iron status</measure>
    <time_frame>Reference day (right before treatment) and one day before surgery (from 22 days to 5 weeks maximum)</time_frame>
    <description>Variation of hemoglobin rate between reference value (collected right before the implementation of treatment) and preoperative hemoglobin rate (collected one day before surgery) depending on the reference iron status</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Variation from reference in hemoglobin rate at the day before surgery depending on the inflammatory state of patient evaluated by CRP rate before treatment</measure>
    <time_frame>Reference day (right before treatment) and one day before surgery (from 22 days to 5 weeks maximum)</time_frame>
    <description>Variation of hemoglobin rate between reference value (collected right before the implementation of treatment) and preoperative hemoglobin rate (collected one day before surgery) depending on the CRP rate before treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frequency of EPO treatment discontinuation at the end of 2nd injection</measure>
    <time_frame>15 days before surgery</time_frame>
    <description>Number of patient stopping EPO injections at the end of 2nd injection</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Variation from reference in iron status at the day before surgery</measure>
    <time_frame>Reference day (right before treatment) and one day before surgery (from 22 days to 5 weeks maximum)</time_frame>
    <description>Changes in iron status between reference day (right before the implementation of treatment) and preoperative iron status (one day before surgery)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of adverse events due to experimental treatments</measure>
    <time_frame>from treatment administration to end of patient follow-up</time_frame>
    <description>Comparision of adverse event du to experimental treatments (ferric carboxymaltose versus ferrous fumarate)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Compliance of oral iron treatment</measure>
    <time_frame>At the end of oral iron treatment</time_frame>
    <description>Evaluated by visual analogic scale (0 the minimum to 10 the maximum)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of blood transfusion in perioperative phase and during 3 days following surgery</measure>
    <time_frame>Perioperative phase and during 3 days following surgery</time_frame>
    <description>Number of transfused patients among all patients</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of packed red blood cells transfused in perioperative phase and during 3 days following</measure>
    <time_frame>Perioperative phase and during 3 days following surgery</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Volume of packed red blood cells transfused</measure>
    <time_frame>Perioperative phase and during 3 days following surgery</time_frame>
    <description>Volume in mL/kg</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total perioperative blood loss</measure>
    <time_frame>Perioperative phase and during 3 days following surgery</time_frame>
    <description>Expressed in red blood cell mass</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cost of oral ferrous fumarate treatment compared to ferric carboxymaltose treatment</measure>
    <time_frame>At the end of patient folllow-up (6 months after surgery)</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Craniosynostosis</condition>
  <arm_group>
    <arm_group_label>Ferrous fumarate or ferrostrane</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>The oral treatment should begin 21 days before surgery.&#xD;
Recommended Dosage ferrous fumarate according to the SPC in force:&#xD;
5 to 8 kg: 2 cd rases / d or 200mg of ferrous fumarate&#xD;
8 to 10 kg: 3 cd rases / d or 300mg of ferrous fumarate&#xD;
10 to 12kg: 4 cd rases / d or 400mg of ferrous fumarate&#xD;
Ferrostrane ® (syrup) Laboratory TEOFARMA SRL Either 34mg of iron per teaspoon&#xD;
Recommended dosage according to the SPC in force:&#xD;
Infant 5 to 8 kg (about 1 to 6 months): 2 teaspoons a day,&#xD;
Infant from 8 to 12 kg (about 6 to 30 months): 3 teaspoons a day.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Ferric carboxymaltose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The single intravenous treatment the day of the inclusion. Dosage according to: 15mg / kg iron (to dilute in 3 ml / kg of Nacl 0.9% (SSI), to pass in 15 minutes.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ferrous fumarate or ferrostrane</intervention_name>
    <description>Young children operated with craniosynostosis and treated with EPO and ferrous fumarate or ferostrane per os or intravenous ferric carboxymaltose.</description>
    <arm_group_label>Ferric carboxymaltose</arm_group_label>
    <arm_group_label>Ferrous fumarate or ferrostrane</arm_group_label>
    <other_name>Intravenous ferric carboxymaltose.</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Craniosynostosis Surgery&#xD;
&#xD;
          -  Age: between 4 and 24 months inclusive&#xD;
&#xD;
          -  Weight: less than 12kg&#xD;
&#xD;
          -  Hemoglobin: 10 g / dl ≤ Hb 14 ≤ g / dl&#xD;
&#xD;
          -  Affiliated patients or beneficiaries of a Social Security scheme&#xD;
&#xD;
          -  Signature of the consent of the patient's parents&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Generalized infection&#xD;
&#xD;
          -  Time for consultation of anesthesia with respect to the date of surgery greater than 5&#xD;
             weeks or less than 22 days.&#xD;
&#xD;
          -  Initial biological assessment dating more than 3 months before the consultation of&#xD;
             anesthesia&#xD;
&#xD;
          -  Parents do not understand French&#xD;
&#xD;
          -  BMI greater than 20 kg.m-2&#xD;
&#xD;
          -  Contraindications to EPO&#xD;
&#xD;
          -  Contraindications to ferric carboxymaltose and to ferrous fumarate&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>4 Months</minimum_age>
    <maximum_age>24 Months</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Philippe PIRAT, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department d'Anesthésie reanimation Lapeyronie</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Philippe PIRAT, MD</last_name>
    <phone>0467338256</phone>
    <email>p-pirat@chu-montpellier.fr</email>
  </overall_contact>
  <location>
    <facility>
      <name>University Hospital of Angers</name>
      <address>
        <city>Angers</city>
        <zip>49100</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sigismond LASOCKI, PU-PH</last_name>
      <email>silasocki@chu-angers.fr</email>
    </contact>
    <contact_backup>
      <last_name>Laurent COLBUS, MD</last_name>
      <email>lacolbus@chu-angers.fr</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>University Hospital of Montpellier</name>
      <address>
        <city>Montpellier</city>
        <zip>34295</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sophie Bringuier, PharmaD</last_name>
      <phone>0467338256</phone>
      <email>s-bringuierbranchereau@chu-montpellier.fr</email>
    </contact>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>December 2021</verification_date>
  <study_first_submitted>June 27, 2017</study_first_submitted>
  <study_first_submitted_qc>July 24, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 27, 2017</study_first_posted>
  <last_update_submitted>December 22, 2021</last_update_submitted>
  <last_update_submitted_qc>December 22, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">December 23, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Craniosynostosis</keyword>
  <keyword>hemoglobin</keyword>
  <keyword>iron peros</keyword>
  <keyword>iron intravenous</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Craniosynostoses</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ferrous fumarate</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT03231085
org study id: 9769
secondary id: 2016-005065-31
nct id: NCT03231085
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Oral iron is commonly used in conjunction with EPO preoperatively for hemorrhagic surgeries
      in children and especially in the surgery of craniosynostosis. The bioavailability of oral
      iron is low and compliance with treatment is inconsistent. The aim of this study is to
      evaluate whether the use of ferric carboxymaltose by injection, which has a much better
      bioavailability, would make it possible to increase the preoperative hemoglobin level more
      effectively and thus reduce the risk of perioperative blood transfusion .
Prospective study, randomized in two parallel groups (martial treatment versus venous
      injection) and stratified by center (Montpellier, Nice, Angers).

      The number of subjects required is 100 patients, or 50 per group.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Care Provider)
measure: Variation from reference in hemoglobin rate at the day before surgery
time frame: Hemoglobin rate change from reference day (right before treatment) to one day before surgery (from 22 days to 5 weeks maximum)
description: Variation of hemoglobin rate between reference value (collected right before the implementation of treatment) and preoperative hemoglobin rate (collected one day before surgery)
measure: Variation from reference in hemoglobin rate at the day before surgery depending on the reference iron status
time frame: Reference day (right before treatment) and one day before surgery (from 22 days to 5 weeks maximum)
description: Variation of hemoglobin rate between reference value (collected right before the implementation of treatment) and preoperative hemoglobin rate (collected one day before surgery) depending on the reference iron status
measure: Variation from reference in hemoglobin rate at the day before surgery depending on the inflammatory state of patient evaluated by CRP rate before treatment
time frame: Reference day (right before treatment) and one day before surgery (from 22 days to 5 weeks maximum)
description: Variation of hemoglobin rate between reference value (collected right before the implementation of treatment) and preoperative hemoglobin rate (collected one day before surgery) depending on the CRP rate before treatment
measure: Frequency of EPO treatment discontinuation at the end of 2nd injection
time frame: 15 days before surgery
description: Number of patient stopping EPO injections at the end of 2nd injection
measure: Variation from reference in iron status at the day before surgery
time frame: Reference day (right before treatment) and one day before surgery (from 22 days to 5 weeks maximum)
description: Changes in iron status between reference day (right before the implementation of treatment) and preoperative iron status (one day before surgery)
measure: Occurrence of adverse events due to experimental treatments
time frame: from treatment administration to end of patient follow-up
description: Comparision of adverse event du to experimental treatments (ferric carboxymaltose versus ferrous fumarate)
measure: Compliance of oral iron treatment
time frame: At the end of oral iron treatment
description: Evaluated by visual analogic scale (0 the minimum to 10 the maximum)
measure: Rate of blood transfusion in perioperative phase and during 3 days following surgery
time frame: Perioperative phase and during 3 days following surgery
description: Number of transfused patients among all patients
measure: Number of packed red blood cells transfused in perioperative phase and during 3 days following
time frame: Perioperative phase and during 3 days following surgery
measure: Volume of packed red blood cells transfused
time frame: Perioperative phase and during 3 days following surgery
description: Volume in mL/kg
measure: Total perioperative blood loss
time frame: Perioperative phase and during 3 days following surgery
description: Expressed in red blood cell mass
measure: Cost of oral ferrous fumarate treatment compared to ferric carboxymaltose treatment
time frame: At the end of patient folllow-up (6 months after surgery)
arm group label: Ferrous fumarate or ferrostrane
arm group type: Active Comparator
description: The oral treatment should begin 21 days before surgery.
Recommended Dosage ferrous fumarate according to the SPC in force:
5 to 8 kg: 2 cd rases / d or 200mg of ferrous fumarate
8 to 10 kg: 3 cd rases / d or 300mg of ferrous fumarate
10 to 12kg: 4 cd rases / d or 400mg of ferrous fumarate
Ferrostrane ® (syrup) Laboratory TEOFARMA SRL Either 34mg of iron per teaspoon
Recommended dosage according to the SPC in force:
Infant 5 to 8 kg (about 1 to 6 months): 2 teaspoons a day,
Infant from 8 to 12 kg (about 6 to 30 months): 3 teaspoons a day.
arm group label: Ferric carboxymaltose
arm group type: Experimental
description: The single intravenous treatment the day of the inclusion. Dosage according to: 15mg / kg iron (to dilute in 3 ml / kg of Nacl 0.9% (SSI), to pass in 15 minutes.
intervention type: Drug
intervention name: Ferrous fumarate or ferrostrane
description: Young children operated with craniosynostosis and treated with EPO and ferrous fumarate or ferostrane per os or intravenous ferric carboxymaltose.
arm group label: Ferric carboxymaltose
arm group label: Ferrous fumarate or ferrostrane
other name: Intravenous ferric carboxymaltose.
criteria: 
gender: All
minimum age: 4 Months
maximum age: 24 Months
healthy volunteers: No
last name: Philippe PIRAT, MD
role: Principal Investigator
affiliation: Department d'Anesthésie reanimation Lapeyronie
last name: Philippe PIRAT, MD
phone: 0467338256
email: p-pirat@chu-montpellier.fr
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
country: France
responsible party type: Sponsor
mesh term: Craniosynostoses
mesh term: Ferrous fumarate
sharing ipd: No