<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/NCT03822793</url>
  </required_header>
  <id_info>
    <org_study_id>18CH052</org_study_id>
    <secondary_id>2018-004552-37</secondary_id>
    <secondary_id>2022-502532-38-01</secondary_id>
    <nct_id>NCT03822793</nct_id>
  </id_info>
  <brief_title>A Dose-response Study of Tranexamic Acid in Total Hip Arthroplasty</brief_title>
  <acronym>PRADO</acronym>
  <official_title>Dose Study of Tranexamic Acid in Total Hip Replacement to Reduce Post-operative Hemoglobin Loss: A Phase 2 Randomized Double-blind Monocentric Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Centre Hospitalier Universitaire de Saint Etienne</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Centre Hospitalier Universitaire de Saint Etienne</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>
      A single preoperative dose of tranexamic acid (TXA) reduces blood loss and red blood cell&#xD;
      transfusion in primary hip arthroplasty. Numerous regimens have been tested, ranging from&#xD;
      10mg/kg up to 3g. However the optimal dose to administer is unknown.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This dose-response study is a randomized double blind study with five groups of 30 patients&#xD;
      each. Patients will be randomized to placebo, tranexamic acid (TXA) 300 mg, tranexamic acid&#xD;
      (TXA) 500 mg, tranexamic acid (TXA) 1000 mg or tranexamic acid (TXA) 3000 mg. In addition a&#xD;
      pharmacokinetic/pharmacodynamic study will be performed to identify the contribution of&#xD;
      tranexamic acid (TXA) plasma concentration as a predictor of intra and postoperative D-Dimer&#xD;
      values.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Not yet recruiting</overall_status>
  <start_date type="Anticipated">August 2023</start_date>
  <completion_date type="Anticipated">December 2026</completion_date>
  <primary_completion_date type="Anticipated">December 2026</primary_completion_date>
  <phase>Phase 2</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>
    <masking_description>randomized double blind study</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>haemoglobin decrease in the perioperative period</measure>
    <time_frame>Day 8</time_frame>
    <description>Percentage of haemoglobin change in the perioperative period. It requires the sampling of haemoglobin before surgery and on the eighth postoperative day.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Evolution of the concentration of tranexamic acid</measure>
    <time_frame>Day 8</time_frame>
    <description>For tranexamic acid pharmacokinetics, the outcome measure is the sampling of tranexamic blood concentration.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evolution of the concentration of D-Dimer</measure>
    <time_frame>Day 8</time_frame>
    <description>For tranexamic acid pharmacodynamics, the outcome is the sampling of D-Dimer levels.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>allogenic red blood cell transfusion</measure>
    <time_frame>Day 8</time_frame>
    <description>For allogenic red blood cell transfusion, the outcome measure will be the percentage of patients that will receive the transfusion of at least one allogenic red blood cell unit in the perioperative period.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>severe anaemia</measure>
    <time_frame>Day 8</time_frame>
    <description>For severe anaemia (defined as a level of haemoglobin &lt;10 gram by deciliter), the outcome measure will be the percentage of patients that will have at least one value of haemoglobin &lt;10 gram by deciliter in the perioperative period.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>incidence of symptomatic thrombotic events and death</measure>
    <time_frame>Day 8</time_frame>
    <description>For the incidence of symptomatic thrombotic events and death, the outcome measure is a combined criteria of venous events (deep venous thrombosis or pulmonary embolism), arterial events (acute coronary syndrome, stroke or peripheral arterial thrombosis) and death.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>occurrence of a seizure</measure>
    <time_frame>Day 8</time_frame>
    <description>Upon the occurrence of a seizure, the endpoint is a clinical endpoint involving either the observation of a generalized tonic-clonic seizure or a partial seizure or absence with epilepsy confirmed by an electroencephalogram interpreted by a blind neurologist in the patient's inclusion group.</description>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Anticipated">150</enrollment>
  <condition>Arthropathy of Hip</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Patient will be included in this group by randomization and they will receive a perfusion of NaCl (sodium chloride 9%; placebo) intravenous over 10 minutes just before surgery.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 1: perfusion of 300 mg Exacyl</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patient will be included in the group 2 by randomization and they will receive a perfusion of 300 mg Exacyl (tranexamic acid) intravenous (IV) over 10 minutes just before surgery.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2: perfusion of 500 mg Exacyl</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patient will be included in the group 2 by randomization and they will receive a perfusion of 500 mg Exacyl (tranexamic acid) intravenous (IV) over 10 minutes just before surgery.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 3: perfusion of 1000 mg Exacyl</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patient will be included in the group 3 by randomization and they will receive a perfusion of 1000 mg Exacyl (tranexamic acid) intravenous (IV) over 10 minutes just before surgery.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 4: perfusion of 3000 mg Exacyl</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patient will be included in the group 4 by randomization and they will receive a perfusion of 3000 mg Exacyl (tranexamic acid) intravenous (IV) over 10 minutes just before surgery.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Patient will receive a perfusion of NaCl (sodium chloride 9%; placebo) intravenous over 10 minutes just before surgery.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Group 1: perfusion of 300 mg Exacyl</intervention_name>
    <description>Patient will receive a perfusion of 300 mg Exacyl (tranexamic acid) intravenous (IV) over 10 minutes just before surgery.</description>
    <arm_group_label>Group 1: perfusion of 300 mg Exacyl</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Group 2: perfusion of 500 mg Exacyl</intervention_name>
    <description>Patient will receive a perfusion of 500 mg Exacyl (tranexamic acid) intravenous (IV) over 10 minutes just before surgery.</description>
    <arm_group_label>Group 2: perfusion of 500 mg Exacyl</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Group 3: perfusion of 1000 mg Exacyl</intervention_name>
    <description>Patient will receive a perfusion of 1000 mg Exacyl (tranexamic acid) intravenous (IV) over 10 minutes just before surgery.</description>
    <arm_group_label>Group 3: perfusion of 1000 mg Exacyl</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Group 4: perfusion of 3000 mg Exacyl</intervention_name>
    <description>Patient will receive a perfusion of 3000 mg Exacyl (tranexamic acid) intravenous (IV) over 10 minutes just before surgery.</description>
    <arm_group_label>Group 4: perfusion of 3000 mg Exacyl</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patient requiring primary hip arthroplasty (less than 3 months)&#xD;
&#xD;
          -  Consent of the patient or a family member or the support person&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Contraindication to tranexamic acid&#xD;
&#xD;
          -  Contraindication to apixaban&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Patient receiving a curative anticoagulating treatment in the preoperative period&#xD;
&#xD;
          -  Bilateral or previous hip arthroplasty&#xD;
&#xD;
          -  Hemorrhagic surgery less than 2 weeks old&#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>Julien LANOISELEE, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>CHU Saint-Etienne</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Julien LANOISELEE, MD</last_name>
    <phone>(0)477828554</phone>
    <phone_ext>+33</phone_ext>
    <email>julien.lanoiselee@chu-st-etienne.fr</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Béatrice DEYGAS, CRA</last_name>
    <phone>(0)477127655</phone>
    <phone_ext>+33</phone_ext>
    <email>beatrice.deygas@chu-st-etienne.fr</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>CHU Saint-Etienne</name>
      <address>
        <city>Saint-Étienne</city>
        <country>France</country>
      </address>
    </facility>
    <investigator>
      <last_name>Julien LANOISELEE, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Paul ZUFFEREY, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Julie GALLAND-CARNESECCHI, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Jean-Yves BIEN, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Cédric DELZANNO, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Pierre LAMBERT, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Malik BAROUDI, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Zeina PRADES, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>December 31, 2018</study_first_submitted>
  <study_first_submitted_qc>January 29, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 30, 2019</study_first_posted>
  <last_update_submitted>June 19, 2023</last_update_submitted>
  <last_update_submitted_qc>June 19, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 22, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>tranexamic acid (TXA)</keyword>
  <keyword>arthroplasty</keyword>
  <keyword>hip</keyword>
  <keyword>Exacyl</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Joint Diseases</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tranexamic Acid</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/NCT03822793
org study id: 18CH052
secondary id: 2018-004552-37
secondary id: 2022-502532-38-01
nct id: NCT03822793
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
A single preoperative dose of tranexamic acid (TXA) reduces blood loss and red blood cell
      transfusion in primary hip arthroplasty. Numerous regimens have been tested, ranging from
      10mg/kg up to 3g. However the optimal dose to administer is unknown.
This dose-response study is a randomized double blind study with five groups of 30 patients
      each. Patients will be randomized to placebo, tranexamic acid (TXA) 300 mg, tranexamic acid
      (TXA) 500 mg, tranexamic acid (TXA) 1000 mg or tranexamic acid (TXA) 3000 mg. In addition a
      pharmacokinetic/pharmacodynamic study will be performed to identify the contribution of
      tranexamic acid (TXA) plasma concentration as a predictor of intra and postoperative D-Dimer
      values.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
masking description: randomized double blind study
measure: haemoglobin decrease in the perioperative period
time frame: Day 8
description: Percentage of haemoglobin change in the perioperative period. It requires the sampling of haemoglobin before surgery and on the eighth postoperative day.
measure: Evolution of the concentration of tranexamic acid
time frame: Day 8
description: For tranexamic acid pharmacokinetics, the outcome measure is the sampling of tranexamic blood concentration.
measure: Evolution of the concentration of D-Dimer
time frame: Day 8
description: For tranexamic acid pharmacodynamics, the outcome is the sampling of D-Dimer levels.
measure: allogenic red blood cell transfusion
time frame: Day 8
description: For allogenic red blood cell transfusion, the outcome measure will be the percentage of patients that will receive the transfusion of at least one allogenic red blood cell unit in the perioperative period.
measure: severe anaemia
time frame: Day 8
description: For severe anaemia (defined as a level of haemoglobin <10 gram by deciliter), the outcome measure will be the percentage of patients that will have at least one value of haemoglobin <10 gram by deciliter in the perioperative period.
measure: incidence of symptomatic thrombotic events and death
time frame: Day 8
description: For the incidence of symptomatic thrombotic events and death, the outcome measure is a combined criteria of venous events (deep venous thrombosis or pulmonary embolism), arterial events (acute coronary syndrome, stroke or peripheral arterial thrombosis) and death.
measure: occurrence of a seizure
time frame: Day 8
description: Upon the occurrence of a seizure, the endpoint is a clinical endpoint involving either the observation of a generalized tonic-clonic seizure or a partial seizure or absence with epilepsy confirmed by an electroencephalogram interpreted by a blind neurologist in the patient's inclusion group.
arm group label: Placebo
arm group type: Placebo Comparator
description: Patient will be included in this group by randomization and they will receive a perfusion of NaCl (sodium chloride 9%; placebo) intravenous over 10 minutes just before surgery.
arm group label: Group 1: perfusion of 300 mg Exacyl
arm group type: Experimental
description: Patient will be included in the group 2 by randomization and they will receive a perfusion of 300 mg Exacyl (tranexamic acid) intravenous (IV) over 10 minutes just before surgery.
arm group label: Group 2: perfusion of 500 mg Exacyl
arm group type: Experimental
description: Patient will be included in the group 2 by randomization and they will receive a perfusion of 500 mg Exacyl (tranexamic acid) intravenous (IV) over 10 minutes just before surgery.
arm group label: Group 3: perfusion of 1000 mg Exacyl
arm group type: Experimental
description: Patient will be included in the group 3 by randomization and they will receive a perfusion of 1000 mg Exacyl (tranexamic acid) intravenous (IV) over 10 minutes just before surgery.
arm group label: Group 4: perfusion of 3000 mg Exacyl
arm group type: Experimental
description: Patient will be included in the group 4 by randomization and they will receive a perfusion of 3000 mg Exacyl (tranexamic acid) intravenous (IV) over 10 minutes just before surgery.
intervention type: Drug
intervention name: Placebo
description: Patient will receive a perfusion of NaCl (sodium chloride 9%; placebo) intravenous over 10 minutes just before surgery.
arm group label: Placebo
intervention type: Drug
intervention name: Group 1: perfusion of 300 mg Exacyl
description: Patient will receive a perfusion of 300 mg Exacyl (tranexamic acid) intravenous (IV) over 10 minutes just before surgery.
arm group label: Group 1: perfusion of 300 mg Exacyl
intervention type: Drug
intervention name: Group 2: perfusion of 500 mg Exacyl
description: Patient will receive a perfusion of 500 mg Exacyl (tranexamic acid) intravenous (IV) over 10 minutes just before surgery.
arm group label: Group 2: perfusion of 500 mg Exacyl
intervention type: Drug
intervention name: Group 3: perfusion of 1000 mg Exacyl
description: Patient will receive a perfusion of 1000 mg Exacyl (tranexamic acid) intravenous (IV) over 10 minutes just before surgery.
arm group label: Group 3: perfusion of 1000 mg Exacyl
intervention type: Drug
intervention name: Group 4: perfusion of 3000 mg Exacyl
description: Patient will receive a perfusion of 3000 mg Exacyl (tranexamic acid) intravenous (IV) over 10 minutes just before surgery.
arm group label: Group 4: perfusion of 3000 mg Exacyl
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Julien LANOISELEE, MD
role: Principal Investigator
affiliation: CHU Saint-Etienne
last name: Julien LANOISELEE, MD
phone: (0)477828554
phone ext: +33
email: julien.lanoiselee@chu-st-etienne.fr
last name: Béatrice DEYGAS, CRA
phone: (0)477127655
phone ext: +33
email: beatrice.deygas@chu-st-etienne.fr
facility: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
country: France
responsible party type: Sponsor
mesh term: Joint Diseases
mesh term: Tranexamic Acid
sharing ipd: No