<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/NCT02233101</url>
  </required_header>
  <id_info>
    <org_study_id>RUSH2233</org_study_id>
    <nct_id>NCT02233101</nct_id>
  </id_info>
  <brief_title>Oral vs. Intravenous TXA Study Proposal: TJA</brief_title>
  <official_title>Oral vs. Intravenous TXA Study Proposal: TJA</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Rush University Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Rush University Medical Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Purpose: Examine oral and intravenous Tranexamic Acid (TXA) to determine whether or not the&#xD;
      different routes of drug administration are equivalent in terms of post-operative reduction&#xD;
      in hemoglobin, number of transfusions, and post-operative blood loss following TJA surgery.&#xD;
&#xD;
      Hypothesis: Oral and intravenous TXA are equivalent routes of drug administration.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Purpose: Examine oral and intravenous Tranexamic Acid (TXA) to determine whether or not the&#xD;
      different routes of drug administration are equivalent in terms of post-operative reduction&#xD;
      in hemoglobin, number of transfusions, and post-operative blood loss following TJA surgery.&#xD;
&#xD;
      Hypothesis: Oral and intravenous TXA are equivalent routes of drug administration.&#xD;
&#xD;
      Background/Scientific review:&#xD;
&#xD;
      Total hip or knee arthroplasty is associated with the risk of moderate to significant blood&#xD;
      loss. Techniques such as the use of antifibrinolytics or desmopressin, or normovolaemic&#xD;
      haemodilution have been used to reduce the need for allogeneic blood transfusion. Tranexamic&#xD;
      acid (TXA) has been used to reduce blood loss and transfusion requirement for total hip and&#xD;
      knee arthroplasty, with good results. Approximately one-third of patients undergoing total&#xD;
      joint replacement surgery require one to three units of blood postoperatively. Tranexamic&#xD;
      acid is a synthetic antifibrinolytic agent that has been successfully used intravenously to&#xD;
      control bleeding after total joint replacement. The use of TXA has been shown to&#xD;
      significantly reduce the need for blood products during total joint replacement1-4.&#xD;
&#xD;
      There are only a few studies directly comparing outcomes following the use of intravenous&#xD;
      tranexamic acid (IVTA) and oral tranexamic acid (OTA) in arthroplasty surgery. In the&#xD;
      randomized study by Zohar et al5. OTA (n = 20) was associated with significant allogeneic&#xD;
      blood sparing com- pared with controls (n = 20), but not when compared with short- and&#xD;
      long-term IVTA regimens. A recent randomized trial comparing OTA (n = 26) with placebo (n =&#xD;
      20) reported significant reductions in blood drained at 24 hours, and in the fall of both Hb&#xD;
      and Hct in the OTA group, without any significant difference in the requirement of&#xD;
      transfusion6.&#xD;
&#xD;
      Study Design: Prospective, randomized, single-blinded study&#xD;
&#xD;
      Treatment Groups:&#xD;
&#xD;
        1. Intravenous TXA Group - 1 gram IV bolus 10 minutes prior to incision&#xD;
&#xD;
        2. Oral TXA Group - 3 tablets (1950 mg) oral 2 hours prior to incision&#xD;
&#xD;
      Demographics/Patient Specifics: Age, Sex, ASA score, Weight, Height, Estimated&#xD;
      intra-operative blood loss, Intra-operative fluids (crystalloid, colloid), Operative time,&#xD;
      Hospitalization days, BMI, Pre-operative PT/INR, Pre-operative PTT, Pre-operative platelet&#xD;
      count&#xD;
&#xD;
      Outcome Measurements:&#xD;
&#xD;
        1. Post-operative reduction in Hgb - Measure pre-operative Hgb levels and post-operative&#xD;
           days 0, 1, 2, and 3 Hgb levels. Among the studies presented, they used different time&#xD;
           points to determine the reduction in Hgb. They either used the post-operative 12-hour&#xD;
           Hgb, post-operative day 4 Hgb, or the lowest Hgb during the hospitalization. Because we&#xD;
           rarely have patients stay until post-operative day 4, we will have to make our measure&#xD;
           off a different time period. We have patients get discharged as early as post-operative&#xD;
           day 1, so we'll probably have to use the post-operative day 1 Hgb level. We feel a Hgb&#xD;
           level difference of &gt;1 g/dL is clinically significant.&#xD;
&#xD;
        2. Post-operative reduction in Hematocrit - Measure pre-operative and post-operative days&#xD;
           0, 1, 2, and 3 Hematocrit levels&#xD;
&#xD;
        3. Number of units transfused&#xD;
&#xD;
        4. Number of patients transfused&#xD;
&#xD;
        5. Cost comparison - Cost differences resulted from differences in the blood transfusion&#xD;
           rate, length of hospital stay, and management of complications as well as from the cost&#xD;
           of the TXA itself&#xD;
&#xD;
        6. Complications&#xD;
&#xD;
             1. DVT or PE&#xD;
&#xD;
             2. Return to the OR within 30 days&#xD;
&#xD;
             3. Re-admission within 30 days&#xD;
&#xD;
             4. Superficial infection&#xD;
&#xD;
             5. Deep infection&#xD;
&#xD;
             6. Periprosthetic fracture&#xD;
&#xD;
             7. Cerebrovascular accident or Transient ischemic attack&#xD;
&#xD;
             8. Dislocation&#xD;
&#xD;
      Risks/Benefits&#xD;
&#xD;
      The use of Tranexamic Acid is a standard of care used everyday in both primary and revision&#xD;
      surgeries, this includes both oral and intravenous forms of Tranexamic Acid. TXA side effects&#xD;
      include of nausea, vomiting and/or diarrhea. Gastrointestinal upset could occur with Oral&#xD;
      tranexamic acid.&#xD;
&#xD;
      The only risk involved is the potential for breach of confidentiality and/or privacy. Below&#xD;
      is a description of the procedure for maintaining confidentiality. There is no direct benefit&#xD;
      to the participants in this study.&#xD;
&#xD;
      Procedures for Maintaining Confidentiality&#xD;
&#xD;
      A breach of confidentiality and/or privacy is a risk of this study. To prevent this, all&#xD;
      collected data will be stored electronically in password-protected files to protect patient&#xD;
      identity and information. All information will be collected and reviewed by the research team&#xD;
      only. Data will be maintained on a password-protected computer that will be accessible only&#xD;
      to the study team. No patient identifiers will be maintained in the database.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>June 2014</start_date>
  <completion_date type="Actual">August 2015</completion_date>
  <primary_completion_date type="Actual">August 2015</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants Who Required Blood Transfusion</measure>
    <time_frame>during or within 24 hours after surgery</time_frame>
    <description>Patient hemoglobin will be measured during and after surgery for the first 24 hours to determine if a blood transfusion is indicated.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Other Complications</measure>
    <time_frame>participants will be followed for the duration of hospital stay, an expected average of no more than 30 days</time_frame>
    <description>Any other complications listed below:&#xD;
DVT or PE&#xD;
Return to the OR within 30 days&#xD;
Re-admission within 30 days&#xD;
Superficial infection&#xD;
Deep infection&#xD;
Periprosthetic fracture&#xD;
Cerebrovascular accident or Transient ischemic attack&#xD;
Dislocation</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">167</enrollment>
  <condition>Blood Loss After Primary Total Joint Arthroplasty</condition>
  <condition>Need for Blood Transfusion After Total Joint Arthroplasty</condition>
  <arm_group>
    <arm_group_label>Oral Tranexamic Acid</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients will receive either oral or intravenous Tranexamic Acid</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Intravenous Tranexamic Acid</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients will receive either oral or intravenous Tranexamic Acid</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oral Tranexamic Acid</intervention_name>
    <description>patients will receive 1950mg of oral prior to surgery to help reduce blood loss during total joint replacement</description>
    <arm_group_label>Oral Tranexamic Acid</arm_group_label>
    <other_name>TXA</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Intravenous Tranexamic Acid</intervention_name>
    <description>Patients will receive 1950mg of intravenous Tranexamic Acid prior to total joint arthroplasty and blood loss or need for transfusion within 24 hours post operative</description>
    <arm_group_label>Intravenous Tranexamic Acid</arm_group_label>
    <other_name>TXA</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Any patient scheduled for a primary TKA or cementless THA with epidural/spinal&#xD;
             anesthesia&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Allergy to TXA, acquired disturbances of color vision, refusal of blood products,&#xD;
             pre-op use of anticoagulant therapy within five days before surgery, a history of&#xD;
             arterial or venous thromboembolic disease (such as DVT, PE, CVA, TIA), pregnancy,&#xD;
             breastfeeding, major comorbidities (such as severe ischemic heart disease [New York&#xD;
             Heart Association Class III or IV], previous myocardial infarction, severe pulmonary&#xD;
             disease, renal impairment, or hepatic failure), patients who decline to participate,&#xD;
             any patient undergoing a revision TKA, THA or BHR&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Craig J Della Valle, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Rush University Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Rush University Medical Center</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2017</verification_date>
  <study_first_submitted>June 26, 2014</study_first_submitted>
  <study_first_submitted_qc>September 3, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 8, 2014</study_first_posted>
  <results_first_submitted>March 20, 2017</results_first_submitted>
  <results_first_submitted_qc>March 20, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">April 28, 2017</results_first_posted>
  <last_update_submitted>October 23, 2017</last_update_submitted>
  <last_update_submitted_qc>October 23, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">November 28, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hemorrhage</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>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Oral Tranexamic Acid</title>
          <description>Patients will receive either oral or intravenous Tranexamic Acid&#xD;
Oral Tranexamic Acid: patients will receive 1950mg of oral prior to surgery to help reduce blood loss during total joint replacement</description>
        </group>
        <group group_id="P2">
          <title>Intravenous Tranexamic Acid</title>
          <description>Patients will receive either oral or intravenous Tranexamic Acid&#xD;
Intravenous Tranexamic Acid: Patients will receive 1950mg of intravenous Tranexamic Acid prior to total joint arthroplasty and blood loss or need for transfusion within 24 hours post operative</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="86"/>
                <participants group_id="P2" count="81"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="74"/>
                <participants group_id="P2" count="80"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Oral Tranexamic Acid</title>
          <description>Patients will receive either oral or intravenous Tranexamic Acid&#xD;
Oral Tranexamic Acid: patients will receive 1950mg of oral prior to surgery to help reduce blood loss during total joint replacement</description>
        </group>
        <group group_id="B2">
          <title>Intravenous Tranexamic Acid</title>
          <description>Patients will receive either oral or intravenous Tranexamic Acid&#xD;
Intravenous Tranexamic Acid: Patients will receive 1950mg of intravenous Tranexamic Acid prior to total joint arthroplasty and blood loss or need for transfusion within 24 hours post operative</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="86"/>
            <count group_id="B2" value="81"/>
            <count group_id="B3" value="167"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="52"/>
                    <measurement group_id="B2" value="49"/>
                    <measurement group_id="B3" value="101"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="34"/>
                    <measurement group_id="B2" value="32"/>
                    <measurement group_id="B3" value="66"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="61" lower_limit="37" upper_limit="87"/>
                    <measurement group_id="B2" value="58" lower_limit="30" upper_limit="85"/>
                    <measurement group_id="B3" value="60" lower_limit="30" upper_limit="87"/>
                  </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>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="48"/>
                    <measurement group_id="B2" value="48"/>
                    <measurement group_id="B3" value="96"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="38"/>
                    <measurement group_id="B2" value="33"/>
                    <measurement group_id="B3" value="71"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="86"/>
                    <measurement group_id="B2" value="81"/>
                    <measurement group_id="B3" value="167"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants Who Required Blood Transfusion</title>
        <description>Patient hemoglobin will be measured during and after surgery for the first 24 hours to determine if a blood transfusion is indicated.</description>
        <time_frame>during or within 24 hours after surgery</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Oral Tranexamic Acid</title>
            <description>Patients will receive either oral or intravenous Tranexamic Acid&#xD;
Oral Tranexamic Acid: patients will receive 1950mg of oral prior to surgery to help reduce blood loss during total joint replacement</description>
          </group>
          <group group_id="O2">
            <title>Intravenous Tranexamic Acid</title>
            <description>Patients will receive either oral or intravenous Tranexamic Acid&#xD;
Intravenous Tranexamic Acid: Patients will receive 1950mg of intravenous Tranexamic Acid prior to total joint arthroplasty and blood loss or need for transfusion within 24 hours post operative</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Who Required Blood Transfusion</title>
          <description>Patient hemoglobin will be measured during and after surgery for the first 24 hours to determine if a blood transfusion is indicated.</description>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="74"/>
                <count group_id="O2" value="80"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Other Complications</title>
        <description>Any other complications listed below:&#xD;
DVT or PE&#xD;
Return to the OR within 30 days&#xD;
Re-admission within 30 days&#xD;
Superficial infection&#xD;
Deep infection&#xD;
Periprosthetic fracture&#xD;
Cerebrovascular accident or Transient ischemic attack&#xD;
Dislocation</description>
        <time_frame>participants will be followed for the duration of hospital stay, an expected average of no more than 30 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Oral Tranexamic Acid</title>
            <description>Patients will receive either oral or intravenous Tranexamic Acid&#xD;
Oral Tranexamic Acid: patients will receive 1950mg of oral prior to surgery to help reduce blood loss during total joint replacement</description>
          </group>
          <group group_id="O2">
            <title>Intravenous Tranexamic Acid</title>
            <description>Patients will receive either oral or intravenous Tranexamic Acid&#xD;
Intravenous Tranexamic Acid: Patients will receive 1950mg of intravenous Tranexamic Acid prior to total joint arthroplasty and blood loss or need for transfusion within 24 hours post operative</description>
          </group>
        </group_list>
        <measure>
          <title>Other Complications</title>
          <description>Any other complications listed below:&#xD;
DVT or PE&#xD;
Return to the OR within 30 days&#xD;
Re-admission within 30 days&#xD;
Superficial infection&#xD;
Deep infection&#xD;
Periprosthetic fracture&#xD;
Cerebrovascular accident or Transient ischemic attack&#xD;
Dislocation</description>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="74"/>
                <count group_id="O2" value="80"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Oral Tranexamic Acid</title>
          <description>Patients will receive either oral or intravenous Tranexamic Acid&#xD;
Oral Tranexamic Acid: patients will receive 1950mg of oral prior to surgery to help reduce blood loss during total joint replacement</description>
        </group>
        <group group_id="E2">
          <title>Intravenous Tranexamic Acid</title>
          <description>Patients will receive either oral or intravenous Tranexamic Acid&#xD;
Intravenous Tranexamic Acid: Patients will receive 1950mg of intravenous Tranexamic Acid prior to total joint arthroplasty and blood loss or need for transfusion within 24 hours post operative</description>
        </group>
      </group_list>
      <serious_events>
        <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="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="81"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="81"/>
              </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="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="81"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE 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>Craig J. Della Valle, MD</name_or_title>
      <organization>Rush University Medical Center</organization>
      <phone>312-432-2350</phone>
      <email>craigdellavalle@rushortho.com</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/NCT02233101
org study id: RUSH2233
nct id: NCT02233101
lead sponsor: 
has dmc: No
Purpose: Examine oral and intravenous Tranexamic Acid (TXA) to determine whether or not the
      different routes of drug administration are equivalent in terms of post-operative reduction
      in hemoglobin, number of transfusions, and post-operative blood loss following TJA surgery.

      Hypothesis: Oral and intravenous TXA are equivalent routes of drug administration.
Purpose: Examine oral and intravenous Tranexamic Acid (TXA) to determine whether or not the
      different routes of drug administration are equivalent in terms of post-operative reduction
      in hemoglobin, number of transfusions, and post-operative blood loss following TJA surgery.

      Hypothesis: Oral and intravenous TXA are equivalent routes of drug administration.

      Background/Scientific review:

      Total hip or knee arthroplasty is associated with the risk of moderate to significant blood
      loss. Techniques such as the use of antifibrinolytics or desmopressin, or normovolaemic
      haemodilution have been used to reduce the need for allogeneic blood transfusion. Tranexamic
      acid (TXA) has been used to reduce blood loss and transfusion requirement for total hip and
      knee arthroplasty, with good results. Approximately one-third of patients undergoing total
      joint replacement surgery require one to three units of blood postoperatively. Tranexamic
      acid is a synthetic antifibrinolytic agent that has been successfully used intravenously to
      control bleeding after total joint replacement. The use of TXA has been shown to
      significantly reduce the need for blood products during total joint replacement1-4.

      There are only a few studies directly comparing outcomes following the use of intravenous
      tranexamic acid (IVTA) and oral tranexamic acid (OTA) in arthroplasty surgery. In the
      randomized study by Zohar et al5. OTA (n = 20) was associated with significant allogeneic
      blood sparing com- pared with controls (n = 20), but not when compared with short- and
      long-term IVTA regimens. A recent randomized trial comparing OTA (n = 26) with placebo (n =
      20) reported significant reductions in blood drained at 24 hours, and in the fall of both Hb
      and Hct in the OTA group, without any significant difference in the requirement of
      transfusion6.

      Study Design: Prospective, randomized, single-blinded study

      Treatment Groups:

        1. Intravenous TXA Group - 1 gram IV bolus 10 minutes prior to incision

        2. Oral TXA Group - 3 tablets (1950 mg) oral 2 hours prior to incision

      Demographics/Patient Specifics: Age, Sex, ASA score, Weight, Height, Estimated
      intra-operative blood loss, Intra-operative fluids (crystalloid, colloid), Operative time,
      Hospitalization days, BMI, Pre-operative PT/INR, Pre-operative PTT, Pre-operative platelet
      count

      Outcome Measurements:

        1. Post-operative reduction in Hgb - Measure pre-operative Hgb levels and post-operative
           days 0, 1, 2, and 3 Hgb levels. Among the studies presented, they used different time
           points to determine the reduction in Hgb. They either used the post-operative 12-hour
           Hgb, post-operative day 4 Hgb, or the lowest Hgb during the hospitalization. Because we
           rarely have patients stay until post-operative day 4, we will have to make our measure
           off a different time period. We have patients get discharged as early as post-operative
           day 1, so we'll probably have to use the post-operative day 1 Hgb level. We feel a Hgb
           level difference of >1 g/dL is clinically significant.

        2. Post-operative reduction in Hematocrit - Measure pre-operative and post-operative days
           0, 1, 2, and 3 Hematocrit levels

        3. Number of units transfused

        4. Number of patients transfused

        5. Cost comparison - Cost differences resulted from differences in the blood transfusion
           rate, length of hospital stay, and management of complications as well as from the cost
           of the TXA itself

        6. Complications

             1. DVT or PE

             2. Return to the OR within 30 days

             3. Re-admission within 30 days

             4. Superficial infection

             5. Deep infection

             6. Periprosthetic fracture

             7. Cerebrovascular accident or Transient ischemic attack

             8. Dislocation

      Risks/Benefits

      The use of Tranexamic Acid is a standard of care used everyday in both primary and revision
      surgeries, this includes both oral and intravenous forms of Tranexamic Acid. TXA side effects
      include of nausea, vomiting and/or diarrhea. Gastrointestinal upset could occur with Oral
      tranexamic acid.

      The only risk involved is the potential for breach of confidentiality and/or privacy. Below
      is a description of the procedure for maintaining confidentiality. There is no direct benefit
      to the participants in this study.

      Procedures for Maintaining Confidentiality

      A breach of confidentiality and/or privacy is a risk of this study. To prevent this, all
      collected data will be stored electronically in password-protected files to protect patient
      identity and information. All information will be collected and reviewed by the research team
      only. Data will be maintained on a password-protected computer that will be accessible only
      to the study team. No patient identifiers will be maintained in the database.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Number of Participants Who Required Blood Transfusion
time frame: during or within 24 hours after surgery
description: Patient hemoglobin will be measured during and after surgery for the first 24 hours to determine if a blood transfusion is indicated.
measure: Other Complications
time frame: participants will be followed for the duration of hospital stay, an expected average of no more than 30 days
description: Any other complications listed below:
DVT or PE
Return to the OR within 30 days
Re-admission within 30 days
Superficial infection
Deep infection
Periprosthetic fracture
Cerebrovascular accident or Transient ischemic attack
Dislocation
arm group label: Oral Tranexamic Acid
arm group type: Active Comparator
description: Patients will receive either oral or intravenous Tranexamic Acid
arm group label: Intravenous Tranexamic Acid
arm group type: Active Comparator
description: Patients will receive either oral or intravenous Tranexamic Acid
intervention type: Drug
intervention name: Oral Tranexamic Acid
description: patients will receive 1950mg of oral prior to surgery to help reduce blood loss during total joint replacement
arm group label: Oral Tranexamic Acid
other name: TXA
intervention type: Drug
intervention name: Intravenous Tranexamic Acid
description: Patients will receive 1950mg of intravenous Tranexamic Acid prior to total joint arthroplasty and blood loss or need for transfusion within 24 hours post operative
arm group label: Intravenous Tranexamic Acid
other name: TXA
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Craig J Della Valle, MD
role: Principal Investigator
affiliation: Rush University Medical Center
facility: 
country: United States
responsible party type: Sponsor
mesh term: Hemorrhage
mesh term: Tranexamic Acid
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 