<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/NCT01728636</url>
  </required_header>
  <id_info>
    <org_study_id>STU00066949</org_study_id>
    <nct_id>NCT01728636</nct_id>
  </id_info>
  <brief_title>The Use of Tranexamic Acid to Reduce Perioperative Blood Loss During High Risk Spine Fusion Surgery</brief_title>
  <acronym>TXA</acronym>
  <official_title>The Use of Tranexamic Acid to Reduce Perioperative Blood Loss During High Risk Spine Fusion Surgery</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Northwestern University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Northwestern University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine if tranexamic acid reduces perioperative blood loss&#xD;
      and red blood cell transfusion during high risk spine surgery.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      There are conflicting studies in the literature reporting different efficacy outcomes for the&#xD;
      use of antifibrinolytics in spine fusion surgery. Several studies support the successful use&#xD;
      of tranexamic acid for major orthopedic procedures, but the patient populations studied for&#xD;
      spine surgery thus far have been small and highly variable, with less than clinically&#xD;
      significant results. If TXA if efficacious in reducing not only perioperative blood loss, but&#xD;
      RBC transfusion without an increase in thromboembolic events, then its use may be justified&#xD;
      for patients at risk for major blood transfusion.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 15, 2013</start_date>
  <completion_date type="Actual">December 30, 2017</completion_date>
  <primary_completion_date type="Actual">December 30, 2017</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Total Red Blood Cells Transfused in the Intraoperative Period</measure>
    <time_frame>Intraoperative period (approximately 12 hours)</time_frame>
    <description>Total red blood cells transfused in the intraoperative period in (mL). Total RBC equal packed red blood cells and cell saver infusion.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Additional Blood Products Transfused</measure>
    <time_frame>24 hours after skin incision</time_frame>
    <description>Total additional blood products (fresh frozen plasma, cryoprecipitate, and platelets) transfused in the perioperative period measured in units.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Post Operative Major Morbidity</measure>
    <time_frame>Time of surgery to date of discharge from hospital (average 7 days)</time_frame>
    <description>Number of participants who experienced arterial or venous thromboembolism, neurologic complications (including stroke, seizure,and delirium), infections, and pulmonary renal or cardiac adverse outcomes (demand ischemia, myocardial infarction or new arrhythmia) before another operative procedure or hospital discharge.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Estimated Intraoperative Blood Loss</measure>
    <time_frame>Incision to skin closure (approximately 10 hours)</time_frame>
    <description>Estimated Intraoperative blood loss in milliliters (mLs)</description>
  </other_outcome>
  <other_outcome>
    <measure>Total Tranexamic Acid Dose (mg)</measure>
    <time_frame>Intraoperative period</time_frame>
    <description>Total milligrams of intravenous tranexamic acid administered during the surgical procedure.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">61</enrollment>
  <condition>Curvature of Spine</condition>
  <arm_group>
    <arm_group_label>Tranexamic Acid</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tranexamic acid 10mg/kg loading dose given pre-incision and 1mg/kg/hr infusion throughout intraoperative period</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Normal saline placebo loading dose 0.5ml/kg and infusion at 0.5ml/kg/hr throughout operative course</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tranexamic Acid</intervention_name>
    <description>intravenous administration of bolus and infusion for duration of surgical procedure</description>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_label>Tranexamic Acid</arm_group_label>
    <other_name>Lysteda</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  age&gt;17 years&#xD;
&#xD;
          -  undergoing posterior spine fusion surgery for kyphoscoliosis with a &gt;80% chance of&#xD;
             major transfusion&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  age &lt; 18 years&#xD;
&#xD;
          -  non-English speaking&#xD;
&#xD;
          -  pregnancy&#xD;
&#xD;
          -  emergency procedures&#xD;
&#xD;
          -  surgery for tumor, trauma or infection&#xD;
&#xD;
          -  severe coronary artery disease&#xD;
&#xD;
          -  history of venous thromboembolism&#xD;
&#xD;
          -  history of cerebral vascular accident&#xD;
&#xD;
          -  history of renal insufficiency&#xD;
&#xD;
          -  allergy to tranexamic acid&#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>Louanne M Carabini, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Northwestern University Feinberg School of Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Northwestern Memorial Hospital</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Elgafy H, Bransford RJ, McGuire RA, Dettori JR, Fischer D. Blood loss in major spine surgery: are there effective measures to decrease massive hemorrhage in major spine fusion surgery? Spine (Phila Pa 1976). 2010 Apr 20;35(9 Suppl):S47-56. doi: 10.1097/BRS.0b013e3181d833f6.</citation>
    <PMID>20407351</PMID>
  </reference>
  <reference>
    <citation>Yang BP, Ondra SL, Chen LA, Jung HS, Koski TR, Salehi SA. Clinical and radiographic outcomes of thoracic and lumbar pedicle subtraction osteotomy for fixed sagittal imbalance. J Neurosurg Spine. 2006 Jul;5(1):9-17. doi: 10.3171/spi.2006.5.1.9.</citation>
    <PMID>16850951</PMID>
  </reference>
  <reference>
    <citation>Bernard AC, Davenport DL, Chang PK, Vaughan TB, Zwischenberger JB. Intraoperative transfusion of 1 U to 2 U packed red blood cells is associated with increased 30-day mortality, surgical-site infection, pneumonia, and sepsis in general surgery patients. J Am Coll Surg. 2009 May;208(5):931-7, 937.e1-2; discussion 938-9. doi: 10.1016/j.jamcollsurg.2008.11.019. Epub 2009 Mar 26.</citation>
    <PMID>19476865</PMID>
  </reference>
  <reference>
    <citation>Ferraris VA, Davenport DL, Saha SP, Austin PC, Zwischenberger JB. Surgical outcomes and transfusion of minimal amounts of blood in the operating room. Arch Surg. 2012 Jan;147(1):49-55. doi: 10.1001/archsurg.2011.790.</citation>
    <PMID>22250113</PMID>
  </reference>
  <reference>
    <citation>Henry D, Carless P, Fergusson D, Laupacis A. The safety of aprotinin and lysine-derived antifibrinolytic drugs in cardiac surgery: a meta-analysis. CMAJ. 2009 Jan 20;180(2):183-93. doi: 10.1503/cmaj.081109. Epub 2008 Dec 2.</citation>
    <PMID>19050037</PMID>
  </reference>
  <reference>
    <citation>Henry DA, Carless PA, Moxey AJ, O'Connell D, Stokes BJ, McClelland B, Laupacis A, Fergusson D. Anti-fibrinolytic use for minimising perioperative allogeneic blood transfusion. Cochrane Database Syst Rev. 2007 Oct 17;(4):CD001886. doi: 10.1002/14651858.CD001886.pub2.</citation>
    <PMID>17943760</PMID>
  </reference>
  <reference>
    <citation>Kagoma YK, Crowther MA, Douketis J, Bhandari M, Eikelboom J, Lim W. Use of antifibrinolytic therapy to reduce transfusion in patients undergoing orthopedic surgery: a systematic review of randomized trials. Thromb Res. 2009 Mar;123(5):687-96. doi: 10.1016/j.thromres.2008.09.015. Epub 2008 Nov 12.</citation>
    <PMID>19007970</PMID>
  </reference>
  <reference>
    <citation>CRASH-2 trial collaborators; Shakur H, Roberts I, Bautista R, Caballero J, Coats T, Dewan Y, El-Sayed H, Gogichaishvili T, Gupta S, Herrera J, Hunt B, Iribhogbe P, Izurieta M, Khamis H, Komolafe E, Marrero MA, Mejia-Mantilla J, Miranda J, Morales C, Olaomi O, Olldashi F, Perel P, Peto R, Ramana PV, Ravi RR, Yutthakasemsunt S. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial. Lancet. 2010 Jul 3;376(9734):23-32. doi: 10.1016/S0140-6736(10)60835-5. Epub 2010 Jun 14.</citation>
    <PMID>20554319</PMID>
  </reference>
  <reference>
    <citation>Elwatidy S, Jamjoom Z, Elgamal E, Zakaria A, Turkistani A, El-Dawlatly A. Efficacy and safety of prophylactic large dose of tranexamic acid in spine surgery: a prospective, randomized, double-blind, placebo-controlled study. Spine (Phila Pa 1976). 2008 Nov 15;33(24):2577-80. doi: 10.1097/BRS.0b013e318188b9c5.</citation>
    <PMID>19011538</PMID>
  </reference>
  <reference>
    <citation>Endres S, Heinz M, Wilke A. Efficacy of tranexamic acid in reducing blood loss in posterior lumbar spine surgery for degenerative spinal stenosis with instability: a retrospective case control study. BMC Surg. 2011 Nov 3;11:29. doi: 10.1186/1471-2482-11-29.</citation>
    <PMID>22047046</PMID>
  </reference>
  <reference>
    <citation>Gill JB, Chin Y, Levin A, Feng D. The use of antifibrinolytic agents in spine surgery. A meta-analysis. J Bone Joint Surg Am. 2008 Nov;90(11):2399-407. doi: 10.2106/JBJS.G.01179.</citation>
    <PMID>18978408</PMID>
  </reference>
  <reference>
    <citation>Tsutsumimoto T, Shimogata M, Ohta H, Yui M, Yoda I, Misawa H. Tranexamic acid reduces perioperative blood loss in cervical laminoplasty: a prospective randomized study. Spine (Phila Pa 1976). 2011 Nov 1;36(23):1913-8. doi: 10.1097/BRS.0b013e3181fb3a42.</citation>
    <PMID>21289587</PMID>
  </reference>
  <reference>
    <citation>Halpin RJ, Sugrue PA, Gould RW, Kallas PG, Schafer MF, Ondra SL, Koski TR. Standardizing care for high-risk patients in spine surgery: the Northwestern high-risk spine protocol. Spine (Phila Pa 1976). 2010 Dec 1;35(25):2232-8. doi: 10.1097/BRS.0b013e3181e8abb0.</citation>
    <PMID>21102298</PMID>
  </reference>
  <reference>
    <citation>Tzortzopoulou A, Cepeda MS, Schumann R, Carr DB. Antifibrinolytic agents for reducing blood loss in scoliosis surgery in children. Cochrane Database Syst Rev. 2008 Jul 16;(3):CD006883. doi: 10.1002/14651858.CD006883.pub2.</citation>
    <PMID>18646174</PMID>
  </reference>
  <reference>
    <citation>Dirkmann D, Gorlinger K, Gisbertz C, Dusse F, Peters J. Factor XIII and tranexamic acid but not recombinant factor VIIa attenuate tissue plasminogen activator-induced hyperfibrinolysis in human whole blood. Anesth Analg. 2012 Jun;114(6):1182-8. doi: 10.1213/ANE.0b013e31823b6683. Epub 2011 Nov 21.</citation>
    <PMID>22104068</PMID>
  </reference>
  <reference>
    <citation>Ozier Y, Bellamy L. Pharmacological agents: antifibrinolytics and desmopressin. Best Pract Res Clin Anaesthesiol. 2010 Mar;24(1):107-19. doi: 10.1016/j.bpa.2009.09.014.</citation>
    <PMID>20402174</PMID>
  </reference>
  <verification_date>January 2021</verification_date>
  <study_first_submitted>November 9, 2012</study_first_submitted>
  <study_first_submitted_qc>November 13, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 20, 2012</study_first_posted>
  <results_first_submitted>November 26, 2019</results_first_submitted>
  <results_first_submitted_qc>January 5, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">January 26, 2021</results_first_posted>
  <last_update_submitted>January 5, 2021</last_update_submitted>
  <last_update_submitted_qc>January 5, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">January 26, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Northwestern University</investigator_affiliation>
    <investigator_full_name>Louanne Carabini</investigator_full_name>
    <investigator_title>Assistant Professor of Anesthesiology &amp; Neurological Surgery</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Spinal Curvatures</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>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>July 6, 2015</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/36/NCT01728636/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Tranexamic Acid</title>
          <description>Tranexamic acid 10mg/kg loading dose given pre-incision and 1mg/kg/hr infusion throughout intraoperative period&#xD;
Tranexamic Acid: intravenous administration of bolus and infusion for duration of surgical procedure</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Normal saline placebo loading dose 0.5ml/kg and infusion at 0.5ml/kg/hr throughout operative course&#xD;
Tranexamic Acid: intravenous administration of bolus and infusion for duration of surgical procedure</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="31"/>
                <participants group_id="P2" count="30"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="31"/>
                <participants group_id="P2" count="30"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Tranexamic Acid</title>
          <description>Tranexamic acid 10mg/kg loading dose given pre-incision and 1mg/kg/hr infusion throughout intraoperative period&#xD;
Tranexamic Acid: intravenous administration of bolus and infusion for duration of surgical procedure</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Normal saline placebo loading dose 0.5ml/kg and infusion at 0.5ml/kg/hr throughout operative course&#xD;
Tranexamic Acid: intravenous administration of bolus and infusion for duration of surgical procedure</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="31"/>
            <count group_id="B2" value="30"/>
            <count group_id="B3" value="61"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="31"/>
                    <count group_id="B2" value="30"/>
                    <count group_id="B3" value="61"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="68" lower_limit="62" upper_limit="72"/>
                    <measurement group_id="B2" value="65" lower_limit="62" upper_limit="69"/>
                    <measurement group_id="B3" value="66" lower_limit="62" upper_limit="72"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="31"/>
                    <count group_id="B2" value="30"/>
                    <count group_id="B3" value="61"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="21"/>
                    <measurement group_id="B2" value="21"/>
                    <measurement group_id="B3" value="42"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race and Ethnicity Not Collected</title>
          <population>Race and Ethnicity were not collected from any participant.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                    <count group_id="B2" value="0"/>
                    <count group_id="B3" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="31"/>
                    <count group_id="B2" value="30"/>
                    <count group_id="B3" value="61"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="31"/>
                    <measurement group_id="B2" value="30"/>
                    <measurement group_id="B3" value="61"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Weight (kilogram)</title>
          <description>Weight measured in kilograms</description>
          <units>kilogram (kg)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="31"/>
                    <count group_id="B2" value="30"/>
                    <count group_id="B3" value="61"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="82.1" spread="18.9"/>
                    <measurement group_id="B2" value="72.9" spread="21.7"/>
                    <measurement group_id="B3" value="77" spread="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Height (cm)</title>
          <units>centimeters</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="31"/>
                    <count group_id="B2" value="30"/>
                    <count group_id="B3" value="61"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="165.9" spread="9.4"/>
                    <measurement group_id="B2" value="161.7" spread="11.6"/>
                    <measurement group_id="B3" value="163" spread="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Body Mass Index</title>
          <description>Body mass index calculated by: kg/m^2</description>
          <units>kg/m^2</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="31"/>
                    <count group_id="B2" value="30"/>
                    <count group_id="B3" value="61"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="31.2" lower_limit="24.3" upper_limit="33.8"/>
                    <measurement group_id="B2" value="26.4" lower_limit="22.7" upper_limit="30.8"/>
                    <measurement group_id="B3" value="29" lower_limit="22.7" upper_limit="33.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>ASA status</title>
          <description>American Society of Anesthesiologists Physical Status.&#xD;
Healthy person.&#xD;
Mild systemic disease.&#xD;
Severe systemic disease.&#xD;
Severe systemic disease that is a constant threat to life.&#xD;
A moribund person who is not expected to survive without the operation.&#xD;
A declared brain-dead person whose organs are being removed for donor purposes.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="31"/>
                    <count group_id="B2" value="30"/>
                    <count group_id="B3" value="61"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2" lower_limit="2" upper_limit="3"/>
                    <measurement group_id="B2" value="2" lower_limit="2" upper_limit="3"/>
                    <measurement group_id="B3" value="2" lower_limit="2" upper_limit="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Medical History (none)</title>
          <description>No contributory medical history.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="31"/>
                    <count group_id="B2" value="30"/>
                    <count group_id="B3" value="61"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>History of hypertension</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="31"/>
                    <count group_id="B2" value="30"/>
                    <count group_id="B3" value="61"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="21"/>
                    <measurement group_id="B3" value="34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>History of coronary artery disease</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="31"/>
                    <count group_id="B2" value="30"/>
                    <count group_id="B3" value="61"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>History of atrial fibrillation</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="31"/>
                    <count group_id="B2" value="30"/>
                    <count group_id="B3" value="61"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>History of peripheral vascular disease</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="31"/>
                    <count group_id="B2" value="30"/>
                    <count group_id="B3" value="61"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>History of diabetes melitus</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="31"/>
                    <count group_id="B2" value="30"/>
                    <count group_id="B3" value="61"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>History of asthma</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="31"/>
                    <count group_id="B2" value="30"/>
                    <count group_id="B3" value="61"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>History of obstructive sleep apnea</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="31"/>
                    <count group_id="B2" value="30"/>
                    <count group_id="B3" value="61"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Baseline Hemoglobin (g/dl)</title>
          <description>Hemoglobin measured as grams per deciliter/</description>
          <units>g/dl (grams per deciliter)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="31"/>
                    <count group_id="B2" value="30"/>
                    <count group_id="B3" value="61"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="10.6" spread="1.0"/>
                    <measurement group_id="B2" value="10.6" spread="1.4"/>
                    <measurement group_id="B3" value="10.6" spread="1.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Baseline hematocrit</title>
          <description>Baseline hematocrit in %.</description>
          <units>Percent</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="31"/>
                    <count group_id="B2" value="30"/>
                    <count group_id="B3" value="61"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="32.1" spread="2.9"/>
                    <measurement group_id="B2" value="31.9" spread="4"/>
                    <measurement group_id="B3" value="32" spread="3.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Baseline Platelets</title>
          <description>Baseline platelets x 10^5 cells/mm^3</description>
          <units>x 10^5 cells/mm^3</units>
          <param>Mean</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="31"/>
                    <count group_id="B2" value="30"/>
                    <count group_id="B3" value="61"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="136" lower_limit="120" upper_limit="149"/>
                    <measurement group_id="B2" value="133" lower_limit="112" upper_limit="146"/>
                    <measurement group_id="B3" value="135" lower_limit="112" upper_limit="149"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Baseline fibrinogen (mg/dL)</title>
          <description>Fibrinogen measured in miligrams per deciliter.</description>
          <units>miligrams per deciliter</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="31"/>
                    <count group_id="B2" value="30"/>
                    <count group_id="B3" value="61"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="272" lower_limit="222" upper_limit="321"/>
                    <measurement group_id="B2" value="268.5" lower_limit="239" upper_limit="347"/>
                    <measurement group_id="B3" value="270" lower_limit="222" upper_limit="347"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Preoperative risk of major transfusion</title>
          <description>The preoperative risk of receiving a major blood transfusion described as percent risk.&#xD;
0%= no preoperative risk- 100% high risk. Above 100%-600% very high risk.</description>
          <units>Percent</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="31"/>
                    <count group_id="B2" value="30"/>
                    <count group_id="B3" value="61"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="212" lower_limit="130" upper_limit="505"/>
                    <measurement group_id="B2" value="505" lower_limit="150" upper_limit="550"/>
                    <measurement group_id="B3" value="358" lower_limit="130" upper_limit="550"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Total number of vertebral levels</title>
          <description>Total number of vertebral levels operated upon.</description>
          <units>Vertebra levels</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="31"/>
                    <count group_id="B2" value="30"/>
                    <count group_id="B3" value="61"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="15" lower_limit="10" upper_limit="16"/>
                    <measurement group_id="B2" value="10" lower_limit="9" upper_limit="16"/>
                    <measurement group_id="B3" value="13" lower_limit="9" upper_limit="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Total Red Blood Cells Transfused in the Intraoperative Period</title>
        <description>Total red blood cells transfused in the intraoperative period in (mL). Total RBC equal packed red blood cells and cell saver infusion.</description>
        <time_frame>Intraoperative period (approximately 12 hours)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Tranexamic Acid</title>
            <description>Tranexamic acid 10mg/kg loading dose given pre-incision and 1mg/kg/hr infusion throughout intraoperative period&#xD;
Tranexamic Acid: intravenous administration of bolus and infusion for duration of surgical procedure</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Normal saline placebo loading dose 0.5ml/kg and infusion at 0.5ml/kg/hr throughout operative course&#xD;
Tranexamic Acid: intravenous administration of bolus and infusion for duration of surgical procedure</description>
          </group>
        </group_list>
        <measure>
          <title>Total Red Blood Cells Transfused in the Intraoperative Period</title>
          <description>Total red blood cells transfused in the intraoperative period in (mL). Total RBC equal packed red blood cells and cell saver infusion.</description>
          <units>milliliters</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="31"/>
                <count group_id="O2" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1140" lower_limit="560" upper_limit="1744"/>
                    <measurement group_id="O2" value="1460" lower_limit="1115" upper_limit="2650"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>.05</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Additional Blood Products Transfused</title>
        <description>Total additional blood products (fresh frozen plasma, cryoprecipitate, and platelets) transfused in the perioperative period measured in units.</description>
        <time_frame>24 hours after skin incision</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Tranexamic Acid</title>
            <description>Tranexamic acid 10mg/kg loading dose given pre-incision and 1mg/kg/hr infusion throughout intraoperative period&#xD;
Tranexamic Acid: intravenous administration of bolus and infusion for duration of surgical procedure</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Normal saline placebo loading dose 0.5ml/kg and infusion at 0.5ml/kg/hr throughout operative course&#xD;
Tranexamic Acid: intravenous administration of bolus and infusion for duration of surgical procedure</description>
          </group>
        </group_list>
        <measure>
          <title>Additional Blood Products Transfused</title>
          <description>Total additional blood products (fresh frozen plasma, cryoprecipitate, and platelets) transfused in the perioperative period measured in units.</description>
          <units>Units</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="31"/>
                <count group_id="O2" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1" lower_limit="1" upper_limit="4"/>
                    <measurement group_id="O2" value="2" lower_limit="0" upper_limit="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Post Operative Major Morbidity</title>
        <description>Number of participants who experienced arterial or venous thromboembolism, neurologic complications (including stroke, seizure,and delirium), infections, and pulmonary renal or cardiac adverse outcomes (demand ischemia, myocardial infarction or new arrhythmia) before another operative procedure or hospital discharge.</description>
        <time_frame>Time of surgery to date of discharge from hospital (average 7 days)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Tranexamic Acid</title>
            <description>Tranexamic acid 10mg/kg loading dose given pre-incision and 1mg/kg/hr infusion throughout intraoperative period&#xD;
Tranexamic Acid: intravenous administration of bolus and infusion for duration of surgical procedure</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Normal saline placebo loading dose 0.5ml/kg and infusion at 0.5ml/kg/hr throughout operative course&#xD;
Tranexamic Acid: intravenous administration of bolus and infusion for duration of surgical procedure</description>
          </group>
        </group_list>
        <measure>
          <title>Post Operative Major Morbidity</title>
          <description>Number of participants who experienced arterial or venous thromboembolism, neurologic complications (including stroke, seizure,and delirium), infections, and pulmonary renal or cardiac adverse outcomes (demand ischemia, myocardial infarction or new arrhythmia) before another operative procedure or hospital discharge.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="31"/>
                <count group_id="O2" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                    <measurement group_id="O2" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Estimated Intraoperative Blood Loss</title>
        <description>Estimated Intraoperative blood loss in milliliters (mLs)</description>
        <time_frame>Incision to skin closure (approximately 10 hours)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Tranexamic Acid</title>
            <description>Tranexamic acid 10mg/kg loading dose given pre-incision and 1mg/kg/hr infusion throughout intraoperative period&#xD;
Tranexamic Acid: intravenous administration of bolus and infusion for duration of surgical procedure</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Normal saline placebo loading dose 0.5ml/kg and infusion at 0.5ml/kg/hr throughout operative course&#xD;
Tranexamic Acid: intravenous administration of bolus and infusion for duration of surgical procedure</description>
          </group>
        </group_list>
        <measure>
          <title>Estimated Intraoperative Blood Loss</title>
          <description>Estimated Intraoperative blood loss in milliliters (mLs)</description>
          <units>Milliliters</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="31"/>
                <count group_id="O2" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1550" lower_limit="1200" upper_limit="3200"/>
                    <measurement group_id="O2" value="1600" lower_limit="1200" upper_limit="2500"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Total Tranexamic Acid Dose (mg)</title>
        <description>Total milligrams of intravenous tranexamic acid administered during the surgical procedure.</description>
        <time_frame>Intraoperative period</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Tranexamic Acid</title>
            <description>Tranexamic acid 10mg/kg loading dose given pre-incision and 1mg/kg/hr infusion throughout intraoperative period&#xD;
Tranexamic Acid: intravenous administration of bolus and infusion for duration of surgical procedure</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Normal saline placebo loading dose 0.5ml/kg and infusion at 0.5ml/kg/hr throughout operative course&#xD;
Tranexamic Acid: intravenous administration of bolus and infusion for duration of surgical procedure</description>
          </group>
        </group_list>
        <measure>
          <title>Total Tranexamic Acid Dose (mg)</title>
          <description>Total milligrams of intravenous tranexamic acid administered during the surgical procedure.</description>
          <units>milligrams</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="31"/>
                <count group_id="O2" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1408" lower_limit="1235" upper_limit="1685"/>
                    <measurement group_id="O2" value="0" lower_limit="0" upper_limit="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Post-Hoc</type>
        <title>Total Operating Room Time</title>
        <description>Total operating room time from incision to closure of incision in minutes.</description>
        <time_frame>Minutes</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Tranexamic Acid</title>
            <description>Tranexamic acid 10mg/kg loading dose given pre-incision and 1mg/kg/hr infusion throughout intraoperative period&#xD;
Tranexamic Acid: intravenous administration of bolus and infusion for duration of surgical procedure</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Normal saline placebo loading dose 0.5ml/kg and infusion at 0.5ml/kg/hr throughout operative course&#xD;
Tranexamic Acid: intravenous administration of bolus and infusion for duration of surgical procedure</description>
          </group>
        </group_list>
        <measure>
          <title>Total Operating Room Time</title>
          <description>Total operating room time from incision to closure of incision in minutes.</description>
          <units>Minutes</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="31"/>
                <count group_id="O2" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="602" lower_limit="522" upper_limit="653"/>
                    <measurement group_id="O2" value="576" lower_limit="526" upper_limit="690"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Start of surgery to discharge from the hospital ( approximately 7 days)</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Tranexamic Acid</title>
          <description>Tranexamic acid 10mg/kg loading dose given pre-incision and 1mg/kg/hr infusion throughout intraoperative period&#xD;
Tranexamic Acid: intravenous administration of bolus and infusion for duration of surgical procedure</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Normal saline placebo loading dose 0.5ml/kg and infusion at 0.5ml/kg/hr throughout operative course&#xD;
Tranexamic Acid: intravenous administration of bolus and infusion for duration of surgical procedure</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="31"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Composite outcome of postoperative adverse events</sub_title>
                <description>The events cannot be separated. Data was reported as composite outcome of postoperative morbidity including arterial or venous thromboembolic , renal or neurologic morbitity.</description>
                <counts group_id="E1" events="9" subjects_affected="9" subjects_at_risk="31"/>
                <counts group_id="E2" events="9" subjects_affected="9" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="31"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Luanne Carabini MD</name_or_title>
      <organization>Northwestern University</organization>
      <phone>312-695-0061</phone>
      <email>l-carabini@northwestern.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT01728636
org study id: STU00066949
nct id: NCT01728636
lead sponsor: 
has dmc: No
The purpose of this study is to determine if tranexamic acid reduces perioperative blood loss
      and red blood cell transfusion during high risk spine surgery.
There are conflicting studies in the literature reporting different efficacy outcomes for the
      use of antifibrinolytics in spine fusion surgery. Several studies support the successful use
      of tranexamic acid for major orthopedic procedures, but the patient populations studied for
      spine surgery thus far have been small and highly variable, with less than clinically
      significant results. If TXA if efficacious in reducing not only perioperative blood loss, but
      RBC transfusion without an increase in thromboembolic events, then its use may be justified
      for patients at risk for major blood transfusion.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Total Red Blood Cells Transfused in the Intraoperative Period
time frame: Intraoperative period (approximately 12 hours)
description: Total red blood cells transfused in the intraoperative period in (mL). Total RBC equal packed red blood cells and cell saver infusion.
measure: Additional Blood Products Transfused
time frame: 24 hours after skin incision
description: Total additional blood products (fresh frozen plasma, cryoprecipitate, and platelets) transfused in the perioperative period measured in units.
measure: Post Operative Major Morbidity
time frame: Time of surgery to date of discharge from hospital (average 7 days)
description: Number of participants who experienced arterial or venous thromboembolism, neurologic complications (including stroke, seizure,and delirium), infections, and pulmonary renal or cardiac adverse outcomes (demand ischemia, myocardial infarction or new arrhythmia) before another operative procedure or hospital discharge.
measure: Estimated Intraoperative Blood Loss
time frame: Incision to skin closure (approximately 10 hours)
description: Estimated Intraoperative blood loss in milliliters (mLs)
measure: Total Tranexamic Acid Dose (mg)
time frame: Intraoperative period
description: Total milligrams of intravenous tranexamic acid administered during the surgical procedure.
arm group label: Tranexamic Acid
arm group type: Experimental
description: Tranexamic acid 10mg/kg loading dose given pre-incision and 1mg/kg/hr infusion throughout intraoperative period
arm group label: Placebo
arm group type: Placebo Comparator
description: Normal saline placebo loading dose 0.5ml/kg and infusion at 0.5ml/kg/hr throughout operative course
intervention type: Drug
intervention name: Tranexamic Acid
description: intravenous administration of bolus and infusion for duration of surgical procedure
arm group label: Placebo
arm group label: Tranexamic Acid
other name: Lysteda
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Louanne M Carabini, MD
role: Principal Investigator
affiliation: Northwestern University Feinberg School of Medicine
facility: 
country: United States
citation: Elgafy H, Bransford RJ, McGuire RA, Dettori JR, Fischer D. Blood loss in major spine surgery: are there effective measures to decrease massive hemorrhage in major spine fusion surgery? Spine (Phila Pa 1976). 2010 Apr 20;35(9 Suppl):S47-56. doi: 10.1097/BRS.0b013e3181d833f6.
PMID: 20407351
citation: Yang BP, Ondra SL, Chen LA, Jung HS, Koski TR, Salehi SA. Clinical and radiographic outcomes of thoracic and lumbar pedicle subtraction osteotomy for fixed sagittal imbalance. J Neurosurg Spine. 2006 Jul;5(1):9-17. doi: 10.3171/spi.2006.5.1.9.
PMID: 16850951
citation: Bernard AC, Davenport DL, Chang PK, Vaughan TB, Zwischenberger JB. Intraoperative transfusion of 1 U to 2 U packed red blood cells is associated with increased 30-day mortality, surgical-site infection, pneumonia, and sepsis in general surgery patients. J Am Coll Surg. 2009 May;208(5):931-7, 937.e1-2; discussion 938-9. doi: 10.1016/j.jamcollsurg.2008.11.019. Epub 2009 Mar 26.
PMID: 19476865
citation: Ferraris VA, Davenport DL, Saha SP, Austin PC, Zwischenberger JB. Surgical outcomes and transfusion of minimal amounts of blood in the operating room. Arch Surg. 2012 Jan;147(1):49-55. doi: 10.1001/archsurg.2011.790.
PMID: 22250113
citation: Henry D, Carless P, Fergusson D, Laupacis A. The safety of aprotinin and lysine-derived antifibrinolytic drugs in cardiac surgery: a meta-analysis. CMAJ. 2009 Jan 20;180(2):183-93. doi: 10.1503/cmaj.081109. Epub 2008 Dec 2.
PMID: 19050037
citation: Henry DA, Carless PA, Moxey AJ, O'Connell D, Stokes BJ, McClelland B, Laupacis A, Fergusson D. Anti-fibrinolytic use for minimising perioperative allogeneic blood transfusion. Cochrane Database Syst Rev. 2007 Oct 17;(4):CD001886. doi: 10.1002/14651858.CD001886.pub2.
PMID: 17943760
citation: Kagoma YK, Crowther MA, Douketis J, Bhandari M, Eikelboom J, Lim W. Use of antifibrinolytic therapy to reduce transfusion in patients undergoing orthopedic surgery: a systematic review of randomized trials. Thromb Res. 2009 Mar;123(5):687-96. doi: 10.1016/j.thromres.2008.09.015. Epub 2008 Nov 12.
PMID: 19007970
citation: CRASH-2 trial collaborators; Shakur H, Roberts I, Bautista R, Caballero J, Coats T, Dewan Y, El-Sayed H, Gogichaishvili T, Gupta S, Herrera J, Hunt B, Iribhogbe P, Izurieta M, Khamis H, Komolafe E, Marrero MA, Mejia-Mantilla J, Miranda J, Morales C, Olaomi O, Olldashi F, Perel P, Peto R, Ramana PV, Ravi RR, Yutthakasemsunt S. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial. Lancet. 2010 Jul 3;376(9734):23-32. doi: 10.1016/S0140-6736(10)60835-5. Epub 2010 Jun 14.
PMID: 20554319
citation: Elwatidy S, Jamjoom Z, Elgamal E, Zakaria A, Turkistani A, El-Dawlatly A. Efficacy and safety of prophylactic large dose of tranexamic acid in spine surgery: a prospective, randomized, double-blind, placebo-controlled study. Spine (Phila Pa 1976). 2008 Nov 15;33(24):2577-80. doi: 10.1097/BRS.0b013e318188b9c5.
PMID: 19011538
citation: Endres S, Heinz M, Wilke A. Efficacy of tranexamic acid in reducing blood loss in posterior lumbar spine surgery for degenerative spinal stenosis with instability: a retrospective case control study. BMC Surg. 2011 Nov 3;11:29. doi: 10.1186/1471-2482-11-29.
PMID: 22047046
citation: Gill JB, Chin Y, Levin A, Feng D. The use of antifibrinolytic agents in spine surgery. A meta-analysis. J Bone Joint Surg Am. 2008 Nov;90(11):2399-407. doi: 10.2106/JBJS.G.01179.
PMID: 18978408
citation: Tsutsumimoto T, Shimogata M, Ohta H, Yui M, Yoda I, Misawa H. Tranexamic acid reduces perioperative blood loss in cervical laminoplasty: a prospective randomized study. Spine (Phila Pa 1976). 2011 Nov 1;36(23):1913-8. doi: 10.1097/BRS.0b013e3181fb3a42.
PMID: 21289587
citation: Halpin RJ, Sugrue PA, Gould RW, Kallas PG, Schafer MF, Ondra SL, Koski TR. Standardizing care for high-risk patients in spine surgery: the Northwestern high-risk spine protocol. Spine (Phila Pa 1976). 2010 Dec 1;35(25):2232-8. doi: 10.1097/BRS.0b013e3181e8abb0.
PMID: 21102298
citation: Tzortzopoulou A, Cepeda MS, Schumann R, Carr DB. Antifibrinolytic agents for reducing blood loss in scoliosis surgery in children. Cochrane Database Syst Rev. 2008 Jul 16;(3):CD006883. doi: 10.1002/14651858.CD006883.pub2.
PMID: 18646174
citation: Dirkmann D, Gorlinger K, Gisbertz C, Dusse F, Peters J. Factor XIII and tranexamic acid but not recombinant factor VIIa attenuate tissue plasminogen activator-induced hyperfibrinolysis in human whole blood. Anesth Analg. 2012 Jun;114(6):1182-8. doi: 10.1213/ANE.0b013e31823b6683. Epub 2011 Nov 21.
PMID: 22104068
citation: Ozier Y, Bellamy L. Pharmacological agents: antifibrinolytics and desmopressin. Best Pract Res Clin Anaesthesiol. 2010 Mar;24(1):107-19. doi: 10.1016/j.bpa.2009.09.014.
PMID: 20402174
responsible party type: Principal Investigator
investigator affiliation: Northwestern University
investigator full name: Louanne Carabini
investigator title: Assistant Professor of Anesthesiology & Neurological Surgery
mesh term: Spinal Curvatures
mesh term: Tranexamic Acid
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 