<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/NCT02229292</url>
  </required_header>
  <id_info>
    <org_study_id>2013-005473-52</org_study_id>
    <nct_id>NCT02229292</nct_id>
  </id_info>
  <brief_title>Prevention of Intraoperative Bleeding and Postoperative Swelling in Orthognathic Surgery Through the Use of Tranexamic Acid</brief_title>
  <acronym>TXA2014-15</acronym>
  <official_title>Prevention of Bleeding and Edema in Bimaxillary Orthognathic Surgery; the Effectiveness of Tranexamic Acid on Intraoperative Bleeding and Postoperative Swelling in Orthognathic Surgery.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hospital of South West Jutland</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Copenhagen</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Vestjydsk Ortopædisk Fond</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Hospital of South West Jutland</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Purpose of the study:&#xD;
&#xD;
        -  To evaluate the effect of tranexamic acid (TXA) of intraoperative blood loss in patients&#xD;
           subjected to bi-maxillary orthognathic surgery&#xD;
&#xD;
        -  To evaluate the potential effect of TXA on fibrin structure&#xD;
&#xD;
        -  To evaluate the potential effect of TXA of binding of plasminogen to fibrin&#xD;
&#xD;
        -  To evaluate the potential effect of TXA on postoperative edema formation.&#xD;
&#xD;
      Hypothesis:&#xD;
&#xD;
      H0: Intraoperative bleeding cannot be significantly reduced by preoperative administration of&#xD;
      tranexamic acid&#xD;
&#xD;
      H0,1: Postoperative edema cannot be significantly reduced by preoperative administration of&#xD;
      tranexamic acid&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study population consists of patients referred to simultaneous mandibular and maxillary&#xD;
      osteotomy at the Department of Oral and Maxillofacial Surgery, Hospital of South West Denmark&#xD;
      in 2014.&#xD;
&#xD;
      Hundred patients (50 men and 50 women) will be enrolled in the study. Reportedly, the mean&#xD;
      intraoperative blood loss in the placebo group is expected to be 436 ml with a standard&#xD;
      deviation of 208 ml. The difference in blood loss between the TXA-group and the placebo group&#xD;
      to be detected is 100 ml. The dropout frequency is estimated to 10%. To fulfil these&#xD;
      assumptions a minimum of 40 patients should be included in each group to reach a power of 0.8&#xD;
      and an alpha of 0.05. In order to accommodate an even gender distribution a block&#xD;
      randomization is performed resulting in the randomization of 100 patients.&#xD;
&#xD;
      The patients will be randomized to receive blindly either 10 ml tranexamic acid (100 mg/ml)&#xD;
      (Pfizer, Ballerup, Denmark) or 10 ml saline (9mg/ml) preoperatively. Intraoperative blood&#xD;
      loss will be determined by deducting the total volume of irrigation fluids from the volume of&#xD;
      the contents of the surgical suction device. Postoperative edema formation will be determined&#xD;
      by 3D surface scanning and volumetric analysis will be carried out in the &quot;Landmarker&quot;&#xD;
      software.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 19, 2014</start_date>
  <completion_date type="Actual">September 26, 2016</completion_date>
  <primary_completion_date type="Actual">September 26, 2016</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>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Intra-operative bleeding volume (ml)</measure>
    <time_frame>Within 10 minutes after ended surgery</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in hemostatic profile</measure>
    <time_frame>Baseline, 5.5 hours, 48 hours and 4 months postoperatively</time_frame>
    <description>Changes in the hemostatic profile measured through thrombelastography, thrombin generation test and fibrin structure analysis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in inflammatory profile</measure>
    <time_frame>Baseline, 5.5 hours, 48 hours and 4 months postoperatively</time_frame>
    <description>Changes in the inflammatory profile are investigated through measures of surface induced activation, inflammation and plasminogen binding.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Postoperative edema formation</measure>
    <time_frame>48 hours and 4 months postoperatively</time_frame>
    <description>The degree of postoperative swelling in connection with TXA /or not, is determined by non-invasive 3D face scans and quantified using the &quot;Landmarker&quot; software. Scans are carried out along with the 3rd and 4th blood samples, 48 hours and 4 months postoperatively.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">104</enrollment>
  <condition>Intraoperative Bleeding</condition>
  <condition>Postoperative Edema</condition>
  <arm_group>
    <arm_group_label>Tranexamic acid</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>The active comparator consists of an intravenously administered bolus injection of 10ml of 100mg/ml tranexamic (1g in total) given as a single dose, after the onset of anesthesia, prior to surgery.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Saline</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>The placebo consists of an intravenously administered bolus injection of 10 ml of 9mg/ml sodium chloride given as a single dose after the onset of anesthesia, prior to surgery.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tranexamic Acid</intervention_name>
    <description>Active group:&#xD;
Undergoes elective bi-maxillary orthognathic surgery consisting of a (un)/segmented LeFort I osteotomy combined with a bilateral sagittal split osteotomy, under the influence of 10ml tranexamic acid (100mg/ml) administered iv. prior to the onset of the surgical procedure.</description>
    <arm_group_label>Tranexamic acid</arm_group_label>
    <other_name>Tranexamsyre &quot;Pfizer&quot;, D.SP.NR.: 22646, ATC code: B 02 AA 02</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Saline</intervention_name>
    <description>Placebo group:&#xD;
Undergoes elective bi-maxillary orthognathic surgery consisting of a (un)/segmented LeFort I osteotomy combined with a bilateral sagittal split osteotomy, under the influence of 10ml sodium chloride (9mg/ml) administered iv. prior to the onset of the surgical procedure.</description>
    <arm_group_label>Saline</arm_group_label>
    <other_name>Natriumklorid &quot;B. Braun&quot;, D.SP.NR.: 6856, ATC code: V 07 AB</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients must be 18 years or older&#xD;
&#xD;
          -  Patients must be eligible for elective bi-maxillary orthognathic surgery&#xD;
&#xD;
          -  No severe reduction of kidney function&#xD;
&#xD;
          -  No known medical conditions&#xD;
&#xD;
          -  Signed informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Hypersensitivity to tranexamic acid&#xD;
&#xD;
          -  A medical history of acute venous thrombosis and/or arterial thrombosis&#xD;
&#xD;
          -  The presence of fibrinolytic conditions as a result of disseminated intravascular&#xD;
             coagulation, with the exception of a predominant activation of the fibrinolytic system&#xD;
             with acute severe bleeding.&#xD;
&#xD;
          -  Severe kidney deficiency&#xD;
&#xD;
          -  Cramps in the medical history&#xD;
&#xD;
          -  Intake of Omega-3 fatty acids, Gingko Biloba, ginger and garlic supplements within 3&#xD;
             months of surgery.&#xD;
&#xD;
          -  Pregnancy (female participants will be tested on the day of surgery)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jesper J Olsen, DDS</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospital of South West Jutland</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hospital of South West Denmark</name>
      <address>
        <city>Esbjerg</city>
        <zip>6700</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <reference>
    <citation>Song G, Yang P, Hu J, Zhu S, Li Y, Wang Q. The effect of tranexamic acid on blood loss in orthognathic surgery: a meta-analysis of randomized controlled trials. Oral Surg Oral Med Oral Pathol Oral Radiol. 2013 May;115(5):595-600. doi: 10.1016/j.oooo.2012.09.085. Epub 2012 Dec 20.</citation>
    <PMID>23260768</PMID>
  </reference>
  <verification_date>March 2017</verification_date>
  <study_first_submitted>August 28, 2014</study_first_submitted>
  <study_first_submitted_qc>August 28, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 1, 2014</study_first_posted>
  <last_update_submitted>March 9, 2017</last_update_submitted>
  <last_update_submitted_qc>March 9, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">March 10, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Hospital of South West Jutland</investigator_affiliation>
    <investigator_full_name>Jesper Jared Olsen</investigator_full_name>
    <investigator_title>DDS</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hemorrhage</mesh_term>
    <mesh_term>Blood Loss, Surgical</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>
  <!-- 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/NCT02229292
org study id: 2013-005473-52
nct id: NCT02229292
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
Purpose of the study:

        -  To evaluate the effect of tranexamic acid (TXA) of intraoperative blood loss in patients
           subjected to bi-maxillary orthognathic surgery

        -  To evaluate the potential effect of TXA on fibrin structure

        -  To evaluate the potential effect of TXA of binding of plasminogen to fibrin

        -  To evaluate the potential effect of TXA on postoperative edema formation.

      Hypothesis:

      H0: Intraoperative bleeding cannot be significantly reduced by preoperative administration of
      tranexamic acid

      H0,1: Postoperative edema cannot be significantly reduced by preoperative administration of
      tranexamic acid
The study population consists of patients referred to simultaneous mandibular and maxillary
      osteotomy at the Department of Oral and Maxillofacial Surgery, Hospital of South West Denmark
      in 2014.

      Hundred patients (50 men and 50 women) will be enrolled in the study. Reportedly, the mean
      intraoperative blood loss in the placebo group is expected to be 436 ml with a standard
      deviation of 208 ml. The difference in blood loss between the TXA-group and the placebo group
      to be detected is 100 ml. The dropout frequency is estimated to 10%. To fulfil these
      assumptions a minimum of 40 patients should be included in each group to reach a power of 0.8
      and an alpha of 0.05. In order to accommodate an even gender distribution a block
      randomization is performed resulting in the randomization of 100 patients.

      The patients will be randomized to receive blindly either 10 ml tranexamic acid (100 mg/ml)
      (Pfizer, Ballerup, Denmark) or 10 ml saline (9mg/ml) preoperatively. Intraoperative blood
      loss will be determined by deducting the total volume of irrigation fluids from the volume of
      the contents of the surgical suction device. Postoperative edema formation will be determined
      by 3D surface scanning and volumetric analysis will be carried out in the "Landmarker"
      software.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Intra-operative bleeding volume (ml)
time frame: Within 10 minutes after ended surgery
measure: Change in hemostatic profile
time frame: Baseline, 5.5 hours, 48 hours and 4 months postoperatively
description: Changes in the hemostatic profile measured through thrombelastography, thrombin generation test and fibrin structure analysis.
measure: Change in inflammatory profile
time frame: Baseline, 5.5 hours, 48 hours and 4 months postoperatively
description: Changes in the inflammatory profile are investigated through measures of surface induced activation, inflammation and plasminogen binding.
measure: Postoperative edema formation
time frame: 48 hours and 4 months postoperatively
description: The degree of postoperative swelling in connection with TXA /or not, is determined by non-invasive 3D face scans and quantified using the "Landmarker" software. Scans are carried out along with the 3rd and 4th blood samples, 48 hours and 4 months postoperatively.
arm group label: Tranexamic acid
arm group type: Active Comparator
description: The active comparator consists of an intravenously administered bolus injection of 10ml of 100mg/ml tranexamic (1g in total) given as a single dose, after the onset of anesthesia, prior to surgery.
arm group label: Saline
arm group type: Placebo Comparator
description: The placebo consists of an intravenously administered bolus injection of 10 ml of 9mg/ml sodium chloride given as a single dose after the onset of anesthesia, prior to surgery.
intervention type: Drug
intervention name: Tranexamic Acid
description: Active group:
Undergoes elective bi-maxillary orthognathic surgery consisting of a (un)/segmented LeFort I osteotomy combined with a bilateral sagittal split osteotomy, under the influence of 10ml tranexamic acid (100mg/ml) administered iv. prior to the onset of the surgical procedure.
arm group label: Tranexamic acid
other name: Tranexamsyre "Pfizer", D.SP.NR.: 22646, ATC code: B 02 AA 02
intervention type: Drug
intervention name: Saline
description: Placebo group:
Undergoes elective bi-maxillary orthognathic surgery consisting of a (un)/segmented LeFort I osteotomy combined with a bilateral sagittal split osteotomy, under the influence of 10ml sodium chloride (9mg/ml) administered iv. prior to the onset of the surgical procedure.
arm group label: Saline
other name: Natriumklorid "B. Braun", D.SP.NR.: 6856, ATC code: V 07 AB
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Jesper J Olsen, DDS
role: Principal Investigator
affiliation: Hospital of South West Jutland
facility: 
country: Denmark
citation: Song G, Yang P, Hu J, Zhu S, Li Y, Wang Q. The effect of tranexamic acid on blood loss in orthognathic surgery: a meta-analysis of randomized controlled trials. Oral Surg Oral Med Oral Pathol Oral Radiol. 2013 May;115(5):595-600. doi: 10.1016/j.oooo.2012.09.085. Epub 2012 Dec 20.
PMID: 23260768
responsible party type: Principal Investigator
investigator affiliation: Hospital of South West Jutland
investigator full name: Jesper Jared Olsen
investigator title: DDS
mesh term: Hemorrhage
mesh term: Blood Loss, Surgical
mesh term: Tranexamic Acid