<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/NCT02972294</url>
  </required_header>
  <id_info>
    <org_study_id>49RC16_0014</org_study_id>
    <nct_id>NCT02972294</nct_id>
  </id_info>
  <brief_title>HiFIT Study : Hip Fracture: Iron and Tranexamic Acid</brief_title>
  <acronym>HiFIT</acronym>
  <official_title>HiFIT Study: Interest of Intravenous Iron and Tranexamic Acid to Reduce Transfusion in Hip Fracture Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Angers</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Hospital, Angers</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>
      Fractures of the upper end of the femur, called commonly &quot;Hip fractures&quot; are very common,&#xD;
      with an incidence of approximately 1.6 million cases per year worldwide. This high incidence&#xD;
      is anticipated to grow rapidly in the next decades, driven by population aging. Anemia is&#xD;
      very frequent on admission for hip fracture, concerning up to 45% of the patients, with a&#xD;
      mean hemoglobin level of 12.5±0.2 g/dl. This high prevalence of anemia together with blood&#xD;
      losses, secondary to the fracture itself and surgery are responsible for a high rate of blood&#xD;
      transfusion (approximately 40-50% of the patients). However, both anemia and blood&#xD;
      transfusion are associated with poor outcome, including increased mortality, length of stay,&#xD;
      infection rate etc. In addition, blood is a scarce and expensive resource and its use should&#xD;
      be limited as much as possible. There is therefore a need to treat this anemia and/or to&#xD;
      prevent the decrease in hemoglobin. For this purpose, intravenous iron has been proposed.&#xD;
      Some non-randomized, mainly retrospective, studies have shown that perioperative intravenous&#xD;
      iron was able to reduce blood transfusion (i.e. the number of patients transfused and the&#xD;
      number of units per patient). Another way to reduce blood transfusion would be to reduce&#xD;
      perioperative bleeding. Tranexamic acid has proven to be efficient for this purpose both in&#xD;
      trauma patients and in elective surgery patients.The interest for perioperative blood&#xD;
      management has recently increased thanks to better recognition of the adverse effects of&#xD;
      blood transfusion, better understanding of iron metabolism, new intravenous iron drugs and a&#xD;
      renewed interest in former medications (i.e. tranexamic acid). HiFIT study therefore propose&#xD;
      a 2X2 factorial design for this study in order to answer questions vis-à-vis the interest of&#xD;
      iron and tranexamic acid to reduce blood transfusion in hip fracture patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Fractures of the upper end of the femur, called commonly &quot;Hip fractures&quot;are very common, with&#xD;
      an incidence of approximately 1.6 million cases per year worldwide. This high incidence is&#xD;
      anticipated to grow rapidly in the next decades, driven by population aging. Anemia is very&#xD;
      frequent on admission for hip fracture, concerning up to 45% of the patients, with a mean&#xD;
      hemoglobin level of 12.5±0.2 g/dl. This high prevalence of anemia together with blood losses,&#xD;
      secondary to the fracture itself and surgery are responsible for a high rate of blood&#xD;
      transfusion (approximately 40-50% of the patients). However, both anemia and blood&#xD;
      transfusion are associated with poor outcome, including increased mortality, length of stay,&#xD;
      infection rate etc. In addition, blood is a scarce and expensive resource and its use should&#xD;
      be limited as much as possible. There is therefore a need to treat this anemia and/or to&#xD;
      prevent the decrease in hemoglobin. For this purpose, intravenous iron has been proposed.&#xD;
      Some non-randomized, mainly retrospective, studies have shown that perioperative intravenous&#xD;
      iron was able to reduce blood transfusion (i.e. the number of patients transfused and the&#xD;
      number of units per patient). Indeed, a pooled analysis of 5 studies including 1,361 patients&#xD;
      suggests that intravenous iron could reduce perioperative transfusion in hip fracture&#xD;
      patients. However, there is no definitive data. Another way to reduce blood transfusion would&#xD;
      be to reduce perioperative bleeding. Tranexamic acid has proven to be efficient for this&#xD;
      purpose both in trauma patients and in elective surgery patients. However, there are only two&#xD;
      randomized studies investigating the interest of tranexamic acid in hip fractures, and they&#xD;
      are not conclusive probably owing to a lack of power. In addition, use of intravenous&#xD;
      tranexamic acid could be limited in this population of frail patients and topical use of&#xD;
      tranexamic acid, notably to prevent the intraoperative bleeding, appear to be an accurate and&#xD;
      sure alternative.&#xD;
&#xD;
      Although hip fracture is a very frequent pathology, with a high burden of care, few data are&#xD;
      available that focus on the management of perioperative anemia in this context. The interest&#xD;
      for perioperative blood management has recently increased thanks to better recognition of the&#xD;
      adverse effects of blood transfusion, better understanding of iron metabolism, new&#xD;
      intravenous iron drugs and a renewed interest in former medications (i.e. tranexamic acid).&#xD;
      hiFIT study therefore propose a 2X2 factorial design for this study in order to answer&#xD;
      questions vis-à-vis the interest of iron and tranexamic acid to reduce blood transfusion in&#xD;
      hip fracture patients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    1year inclusion hold due to PV new fact (Monofer hold for risk revaluation) DSMB Interim&#xD;
    analysis : 1treatment with important transfusion risk reduction/inclusions issues (COVID)/sites&#xD;
    change of practice if study continue=&gt;stop inclusions&#xD;
  </why_stopped>
  <start_date type="Actual">March 31, 2017</start_date>
  <completion_date type="Actual">September 16, 2021</completion_date>
  <primary_completion_date type="Actual">September 16, 2021</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>Factorial Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Proportion of patients who received a blood transfusion during their hospital stay following surgery</measure>
    <time_frame>From the day of surgery until hospital discharge (or until day 30 if patient is still hospitalized).</time_frame>
    <description>Proportion of patients who received a blood transfusion during their hospital stay following surgery</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients who received a blood transfusion after surgery</measure>
    <time_frame>From the day of surgery until Day 3, Day 7 and Day 30 post surgery.</time_frame>
    <description>Proportion of patients who received a blood transfusion during the month following surgery (including fresh frozen plasma and platelets)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of packed red blood cell units transfused per patient, as well as number of fresh frozen plasma and platelets units</measure>
    <time_frame>Till postoperative Day3, first week posteratively,and till hospital discharge (or one month if patients still hospitalised)</time_frame>
    <description>Number of packed red blood cell units transfused per patient, as well as number of fresh frozen plasma and platelets units</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hemoglobin concentration</measure>
    <time_frame>At inclusion and on days 3, 7 (or hospital discharge if it happens first) and 30.</time_frame>
    <description>Hemoglobin concentration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients with anemia (hemoglobin &lt;12 g/dL in women and &lt;13 g/dL in men)</measure>
    <time_frame>At inclusion and on days 3, 7, hospital discharge (if it happens before Day 30) and 30.</time_frame>
    <description>Proportion of patients with anemia (hemoglobin &lt;12 g/dL in women and &lt;13 g/dL in men)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Reticulocytes count</measure>
    <time_frame>On days 3, 7 (or hospital discharge if it happens first) and 30 post surgery</time_frame>
    <description>Reticulocytes count</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Perioperative blood loss (estimated according to a formula based on hematocrit variation).</measure>
    <time_frame>During surgery</time_frame>
    <description>Perioperative blood loss (estimated according to a formula based on hematocrit variation): (HtD0 - HtD3)*TBV + number of RPBC transfused unit x 200 ml. Ht = Haematocrit, TBV = total blood volume (70 mL/kg in men and 65 mL/kg in women)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Post operative Iron deficiency rate</measure>
    <time_frame>On Day 7 (or hospital discharge if it happens first) and Day 30.</time_frame>
    <description>Proportion of patients with Iron deficiency (defined as a ferritin &lt; 100 ng/ml or &lt; 300 ng/ml together with transferrin saturation &lt;20%), measurement of ferritin and transferrin saturation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of hospitalization days</measure>
    <time_frame>On Day 30 and Day 90 following surgery.</time_frame>
    <description>Number of hospitalization days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients at home</measure>
    <time_frame>On Day 30 and Day 90.</time_frame>
    <description>Proportion of patients returned at home (or at their previous place of living)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients able to walk a distance of ten feet without assistance</measure>
    <time_frame>On Day 30 and Day 90</time_frame>
    <description>Proportion of patients able to walk a distance of ten feet without assistance</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Variation of quality of life</measure>
    <time_frame>From inclusion to Day 30 and Day 90</time_frame>
    <description>Variation of EQ-5D score</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Variation of perceived quality of life</measure>
    <time_frame>From inclusion to Day 7 (or hospital discharge if it happens first) and Day 90.</time_frame>
    <description>Variation of perceived quality of life with a single overall item from PQOL scale</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Variation of IADL test</measure>
    <time_frame>From inclusion to Day 90.</time_frame>
    <description>Variation of IADL test</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Death rate from all causes</measure>
    <time_frame>From inclusion to Day 90</time_frame>
    <description>Death rate from all causes</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of adverse events including the following clinical complications: Vascular events, Heart failure; Renal failure; Infectious complications; Anaphylactic reaction; Transfusion-related complications</measure>
    <time_frame>From inclusion to Day 90</time_frame>
    <description>Rate of adverse events including the following clinical complications: Vascular events, Heart failure; Renal failure; Infectious complications; Anaphylactic reaction; Transfusion-related complications</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Strength assessed by the Hand Grip Strength test</measure>
    <time_frame>On day 7 (or hospital discharge if it happens first)</time_frame>
    <description>Maximum strength of the hand and forearm muscles assessed by the Hand Grip Strength test</description>
  </other_outcome>
  <other_outcome>
    <measure>Muscular fatigability assessed by the Hand Grip Strength test</measure>
    <time_frame>On day 7 (or hospital discharge if it happens first)</time_frame>
    <description>Muscular fatigability between the first attempt and the third attempt of the Hand Grip Strength test (variation of the maximum strength measured at the first and the third atempt)</description>
  </other_outcome>
  <other_outcome>
    <measure>Level of locomotion and balance assessed by the Timed &quot; Up and Go &quot; test.</measure>
    <time_frame>On day 7 (or hospital discharge if it happens first)</time_frame>
    <description>Level of locomotion and balance assessed by the Timed &quot; Up and Go &quot; test,</description>
  </other_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">419</enrollment>
  <condition>Hip Fractures Pathologic</condition>
  <condition>Anemia</condition>
  <arm_group>
    <arm_group_label>TXA + IIM</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The patients randomized to this arm will have iron isomaltoside 1000 and tranexamic acid</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo TXA + IIM</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The patients randomized to this arm will have iron isomaltoside 1000 and Placebos tranexamic acid</description>
  </arm_group>
  <arm_group>
    <arm_group_label>TXA + Placebo IIM</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The patients randomized to this arm will have Placebos iron isomaltoside 1000 and tranexamic acid</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo TXA + Placebo IIM</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The patients randomized to this arm will have Placebos iron isomaltoside 1000 and Placebos tranexamic acid</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Iron Isomaltoside 1000</intervention_name>
    <description>Iron Isomaltoside 1000 will be use. Blinding procedure will be put in place for the administration of the treatment</description>
    <arm_group_label>Placebo TXA + IIM</arm_group_label>
    <arm_group_label>TXA + IIM</arm_group_label>
    <other_name>monofer</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tranexamic Acid</intervention_name>
    <description>Tranexamic acid will be use.</description>
    <arm_group_label>TXA + IIM</arm_group_label>
    <arm_group_label>TXA + Placebo IIM</arm_group_label>
    <other_name>exacyl</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebos iron isomaltoside 1000</intervention_name>
    <description>placebo of Iron Isomaltoside 1000 correspond to a saline solution. Blinding procedure will be put in place for the administration of this treatment</description>
    <arm_group_label>Placebo TXA + Placebo IIM</arm_group_label>
    <arm_group_label>TXA + Placebo IIM</arm_group_label>
    <other_name>saline serum</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebos tranexamic acid</intervention_name>
    <description>placebo of tranexamic acid correspond to a saline solution.</description>
    <arm_group_label>Placebo TXA + IIM</arm_group_label>
    <arm_group_label>Placebo TXA + Placebo IIM</arm_group_label>
    <other_name>saline serum</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age ≥ 18 years,&#xD;
&#xD;
          -  Osteoporotic Fractures of the upper end of the femur requiring surgical repair.&#xD;
&#xD;
          -  Preoperative hemoglobin between 9.5 and 13 g/dl.&#xD;
&#xD;
          -  Patient or relative signed informed consent or inclusion thanks to urgent inclusion&#xD;
             procedure&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Bone marrow disease or ongoing treatment (such as chemotherapy), which could interfere&#xD;
             with bone marrow erythropoiesis,&#xD;
&#xD;
          -  Known allergy or counter-indication to iron and/or to tranexamic acid,&#xD;
&#xD;
          -  Uncontrolled arterial hypertension,&#xD;
&#xD;
          -  Recent iron infusion (within one week),&#xD;
&#xD;
          -  Blood transfusion within one week before inclusion or preoperative blood transfusion&#xD;
             already scheduled,&#xD;
&#xD;
          -  Any patient who cannot be transfused or has refused consent for a blood transfusion,&#xD;
&#xD;
          -  Bedridden or very dependent patient (equivalent to GIR 1 or 2 class).&#xD;
&#xD;
          -  Non-affiliation to French health care coverage,&#xD;
&#xD;
          -  Adult patient protected under the law (guardianship),&#xD;
&#xD;
          -  Pregnancy.&#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>Sigismond SL Lasocki, PU-PH</last_name>
    <role>Study Director</role>
    <affiliation>UNIVERSITE HOSPITAL, ANGERS</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>CHU Angers - DEPARTEMENT D'ANESTHESIE REANIMATION</name>
      <address>
        <city>Angers</city>
        <zip>49000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinique de L'Anjou- Anesthesie Reanimation</name>
      <address>
        <city>Angers</city>
        <zip>49000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>HIA Clermont-Tonnerre</name>
      <address>
        <city>Brest</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chu Grenoble - Departement D'Anesthesie Reanimation</name>
      <address>
        <city>Grenoble</city>
        <zip>38043</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHD Vendée</name>
      <address>
        <city>La Roche-sur-Yon</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Lille</name>
      <address>
        <city>Lille</city>
        <zip>59037</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospices Civils Lyon</name>
      <address>
        <city>Lyon</city>
        <zip>69002</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ramsay Santé, Clinique de la Sauvegarde</name>
      <address>
        <city>Lyon</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chu Montpellier - Departement D'Anesthesie Reanimation</name>
      <address>
        <city>Montpellier</city>
        <zip>34295</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chu Nantes- Service de Reanimation Chirurgicale</name>
      <address>
        <city>Nantes</city>
        <zip>44093</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chu Poitiers - Service D'Anesthesie Reanimation</name>
      <address>
        <city>Poitiers</city>
        <zip>86000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chu Rennes - Service D'Anesthesie Reanimation</name>
      <address>
        <city>Rennes</city>
        <zip>35033</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medipôle</name>
      <address>
        <city>Villeurbanne</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>July 2022</verification_date>
  <study_first_submitted>November 21, 2016</study_first_submitted>
  <study_first_submitted_qc>November 21, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 23, 2016</study_first_posted>
  <last_update_submitted>July 28, 2022</last_update_submitted>
  <last_update_submitted_qc>July 28, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 2, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>iron isomaltoside</keyword>
  <keyword>tranexamic acid</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fractures, Bone</mesh_term>
    <mesh_term>Hip Fractures</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Iron</mesh_term>
    <mesh_term>Tranexamic Acid</mesh_term>
    <mesh_term>Iron isomaltoside 1000</mesh_term>
    <mesh_term>Ferric Compounds</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/NCT02972294
org study id: 49RC16_0014
nct id: NCT02972294
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Fractures of the upper end of the femur, called commonly "Hip fractures" are very common,
      with an incidence of approximately 1.6 million cases per year worldwide. This high incidence
      is anticipated to grow rapidly in the next decades, driven by population aging. Anemia is
      very frequent on admission for hip fracture, concerning up to 45% of the patients, with a
      mean hemoglobin level of 12.5±0.2 g/dl. This high prevalence of anemia together with blood
      losses, secondary to the fracture itself and surgery are responsible for a high rate of blood
      transfusion (approximately 40-50% of the patients). However, both anemia and blood
      transfusion are associated with poor outcome, including increased mortality, length of stay,
      infection rate etc. In addition, blood is a scarce and expensive resource and its use should
      be limited as much as possible. There is therefore a need to treat this anemia and/or to
      prevent the decrease in hemoglobin. For this purpose, intravenous iron has been proposed.
      Some non-randomized, mainly retrospective, studies have shown that perioperative intravenous
      iron was able to reduce blood transfusion (i.e. the number of patients transfused and the
      number of units per patient). Another way to reduce blood transfusion would be to reduce
      perioperative bleeding. Tranexamic acid has proven to be efficient for this purpose both in
      trauma patients and in elective surgery patients.The interest for perioperative blood
      management has recently increased thanks to better recognition of the adverse effects of
      blood transfusion, better understanding of iron metabolism, new intravenous iron drugs and a
      renewed interest in former medications (i.e. tranexamic acid). HiFIT study therefore propose
      a 2X2 factorial design for this study in order to answer questions vis-à-vis the interest of
      iron and tranexamic acid to reduce blood transfusion in hip fracture patients.
Fractures of the upper end of the femur, called commonly "Hip fractures"are very common, with
      an incidence of approximately 1.6 million cases per year worldwide. This high incidence is
      anticipated to grow rapidly in the next decades, driven by population aging. Anemia is very
      frequent on admission for hip fracture, concerning up to 45% of the patients, with a mean
      hemoglobin level of 12.5±0.2 g/dl. This high prevalence of anemia together with blood losses,
      secondary to the fracture itself and surgery are responsible for a high rate of blood
      transfusion (approximately 40-50% of the patients). However, both anemia and blood
      transfusion are associated with poor outcome, including increased mortality, length of stay,
      infection rate etc. In addition, blood is a scarce and expensive resource and its use should
      be limited as much as possible. There is therefore a need to treat this anemia and/or to
      prevent the decrease in hemoglobin. For this purpose, intravenous iron has been proposed.
      Some non-randomized, mainly retrospective, studies have shown that perioperative intravenous
      iron was able to reduce blood transfusion (i.e. the number of patients transfused and the
      number of units per patient). Indeed, a pooled analysis of 5 studies including 1,361 patients
      suggests that intravenous iron could reduce perioperative transfusion in hip fracture
      patients. However, there is no definitive data. Another way to reduce blood transfusion would
      be to reduce perioperative bleeding. Tranexamic acid has proven to be efficient for this
      purpose both in trauma patients and in elective surgery patients. However, there are only two
      randomized studies investigating the interest of tranexamic acid in hip fractures, and they
      are not conclusive probably owing to a lack of power. In addition, use of intravenous
      tranexamic acid could be limited in this population of frail patients and topical use of
      tranexamic acid, notably to prevent the intraoperative bleeding, appear to be an accurate and
      sure alternative.

      Although hip fracture is a very frequent pathology, with a high burden of care, few data are
      available that focus on the management of perioperative anemia in this context. The interest
      for perioperative blood management has recently increased thanks to better recognition of the
      adverse effects of blood transfusion, better understanding of iron metabolism, new
      intravenous iron drugs and a renewed interest in former medications (i.e. tranexamic acid).
      hiFIT study therefore propose a 2X2 factorial design for this study in order to answer
      questions vis-à-vis the interest of iron and tranexamic acid to reduce blood transfusion in
      hip fracture patients.
allocation: Randomized
intervention model: Factorial Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Proportion of patients who received a blood transfusion during their hospital stay following surgery
time frame: From the day of surgery until hospital discharge (or until day 30 if patient is still hospitalized).
description: Proportion of patients who received a blood transfusion during their hospital stay following surgery
measure: Proportion of patients who received a blood transfusion after surgery
time frame: From the day of surgery until Day 3, Day 7 and Day 30 post surgery.
description: Proportion of patients who received a blood transfusion during the month following surgery (including fresh frozen plasma and platelets)
measure: Number of packed red blood cell units transfused per patient, as well as number of fresh frozen plasma and platelets units
time frame: Till postoperative Day3, first week posteratively,and till hospital discharge (or one month if patients still hospitalised)
description: Number of packed red blood cell units transfused per patient, as well as number of fresh frozen plasma and platelets units
measure: Hemoglobin concentration
time frame: At inclusion and on days 3, 7 (or hospital discharge if it happens first) and 30.
description: Hemoglobin concentration
measure: Proportion of patients with anemia (hemoglobin <12 g/dL in women and <13 g/dL in men)
time frame: At inclusion and on days 3, 7, hospital discharge (if it happens before Day 30) and 30.
description: Proportion of patients with anemia (hemoglobin <12 g/dL in women and <13 g/dL in men)
measure: Reticulocytes count
time frame: On days 3, 7 (or hospital discharge if it happens first) and 30 post surgery
description: Reticulocytes count
measure: Perioperative blood loss (estimated according to a formula based on hematocrit variation).
time frame: During surgery
description: Perioperative blood loss (estimated according to a formula based on hematocrit variation): (HtD0 - HtD3)*TBV + number of RPBC transfused unit x 200 ml. Ht = Haematocrit, TBV = total blood volume (70 mL/kg in men and 65 mL/kg in women)
measure: Post operative Iron deficiency rate
time frame: On Day 7 (or hospital discharge if it happens first) and Day 30.
description: Proportion of patients with Iron deficiency (defined as a ferritin < 100 ng/ml or < 300 ng/ml together with transferrin saturation <20%), measurement of ferritin and transferrin saturation
measure: Number of hospitalization days
time frame: On Day 30 and Day 90 following surgery.
description: Number of hospitalization days
measure: Proportion of patients at home
time frame: On Day 30 and Day 90.
description: Proportion of patients returned at home (or at their previous place of living)
measure: Proportion of patients able to walk a distance of ten feet without assistance
time frame: On Day 30 and Day 90
description: Proportion of patients able to walk a distance of ten feet without assistance
measure: Variation of quality of life
time frame: From inclusion to Day 30 and Day 90
description: Variation of EQ-5D score
measure: Variation of perceived quality of life
time frame: From inclusion to Day 7 (or hospital discharge if it happens first) and Day 90.
description: Variation of perceived quality of life with a single overall item from PQOL scale
measure: Variation of IADL test
time frame: From inclusion to Day 90.
description: Variation of IADL test
measure: Death rate from all causes
time frame: From inclusion to Day 90
description: Death rate from all causes
measure: Rate of adverse events including the following clinical complications: Vascular events, Heart failure; Renal failure; Infectious complications; Anaphylactic reaction; Transfusion-related complications
time frame: From inclusion to Day 90
description: Rate of adverse events including the following clinical complications: Vascular events, Heart failure; Renal failure; Infectious complications; Anaphylactic reaction; Transfusion-related complications
measure: Strength assessed by the Hand Grip Strength test
time frame: On day 7 (or hospital discharge if it happens first)
description: Maximum strength of the hand and forearm muscles assessed by the Hand Grip Strength test
measure: Muscular fatigability assessed by the Hand Grip Strength test
time frame: On day 7 (or hospital discharge if it happens first)
description: Muscular fatigability between the first attempt and the third attempt of the Hand Grip Strength test (variation of the maximum strength measured at the first and the third atempt)
measure: Level of locomotion and balance assessed by the Timed " Up and Go " test.
time frame: On day 7 (or hospital discharge if it happens first)
description: Level of locomotion and balance assessed by the Timed " Up and Go " test,
arm group label: TXA + IIM
arm group type: Experimental
description: The patients randomized to this arm will have iron isomaltoside 1000 and tranexamic acid
arm group label: Placebo TXA + IIM
arm group type: Experimental
description: The patients randomized to this arm will have iron isomaltoside 1000 and Placebos tranexamic acid
arm group label: TXA + Placebo IIM
arm group type: Experimental
description: The patients randomized to this arm will have Placebos iron isomaltoside 1000 and tranexamic acid
arm group label: Placebo TXA + Placebo IIM
arm group type: Experimental
description: The patients randomized to this arm will have Placebos iron isomaltoside 1000 and Placebos tranexamic acid
intervention type: Drug
intervention name: Iron Isomaltoside 1000
description: Iron Isomaltoside 1000 will be use. Blinding procedure will be put in place for the administration of the treatment
arm group label: Placebo TXA + IIM
arm group label: TXA + IIM
other name: monofer
intervention type: Drug
intervention name: Tranexamic Acid
description: Tranexamic acid will be use.
arm group label: TXA + IIM
arm group label: TXA + Placebo IIM
other name: exacyl
intervention type: Drug
intervention name: Placebos iron isomaltoside 1000
description: placebo of Iron Isomaltoside 1000 correspond to a saline solution. Blinding procedure will be put in place for the administration of this treatment
arm group label: Placebo TXA + Placebo IIM
arm group label: TXA + Placebo IIM
other name: saline serum
intervention type: Drug
intervention name: Placebos tranexamic acid
description: placebo of tranexamic acid correspond to a saline solution.
arm group label: Placebo TXA + IIM
arm group label: Placebo TXA + Placebo IIM
other name: saline serum
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Sigismond SL Lasocki, PU-PH
role: Study Director
affiliation: UNIVERSITE HOSPITAL, ANGERS
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country: France
responsible party type: Sponsor
mesh term: Fractures, Bone
mesh term: Hip Fractures
mesh term: Iron
mesh term: Tranexamic Acid
mesh term: Iron isomaltoside 1000
mesh term: Ferric Compounds
sharing ipd: No