<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/NCT04443920</url>
  </required_header>
  <id_info>
    <org_study_id>1372794</org_study_id>
    <nct_id>NCT04443920</nct_id>
  </id_info>
  <brief_title>Tranexamic Acid for Total Knee Arthroscopy</brief_title>
  <official_title>Comparison of the Effect of Two Common Regimens of Administration of Tranexamic Acid on Hemostasis and Clinical Outcome of Patients Undergoing Total Knee Arthroplasty</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The Miriam Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>The Miriam Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this investigation is to determine the most effective regimen of&#xD;
      administration of tranexamic acid to improve clinical outcome among patients undergoing total&#xD;
      knee arthroplasty.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Tranexamic acid (TXA) is synthetic lysine analog, which acts as anti-fibrinolytic agent by&#xD;
      preventing conversion of plasminogen in to plasmin. Various regimens of TXA administration&#xD;
      (routes, doses, timing) have been used to decrease perioperative blood loss and improve&#xD;
      clinical outcomes among patients undergoing different orthopedic surgeries. We are conducting&#xD;
      this prospective randomized placebo controlled trial to compare the effect of the two most&#xD;
      common regimens of TXA administration on hemostasis and clinical outcomes among patients&#xD;
      undergoing total knee arthroplasty. All recruited patients receive the first dose of 15mg/kg&#xD;
      of IV TXA prior to skin incision. The second dose of 15mg/kg IV TXA or identical placebo is&#xD;
      administered prior to the release of the tourniquet.&#xD;
&#xD;
      The assessment of hemostasis is performed using whole blood sample via viscoelastic testing&#xD;
      by rotational thromboelastography (ROTEM). A blood sample is collected in the preoperative&#xD;
      area and after the administration of each dose of TXA. Clinical data is collected until 90&#xD;
      days after surgery.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 29, 2019</start_date>
  <completion_date type="Actual">January 8, 2021</completion_date>
  <primary_completion_date type="Actual">October 7, 2020</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Assessment of changes in hemostasis via viscoelastic testing.</measure>
    <time_frame>intraoperative (min)</time_frame>
    <description>To compare the magnitude of lysis via lysis indexes.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Hematocrit</measure>
    <time_frame>postoperative day 1</time_frame>
    <description>The comparison of hematocrit recordings from preoperative period to the postoperative period</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of Hospitalization</measure>
    <time_frame>up to 7 days</time_frame>
    <description>Length of hospital stay from day of surgery to discharge from hospital.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The number of blood transfusions</measure>
    <time_frame>90 days</time_frame>
    <description>The number of blood products transfused after surgery</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hospital readmissions</measure>
    <time_frame>90 days</time_frame>
    <description>The occurrence of hospital readmissions following surgery</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">86</enrollment>
  <condition>Blood Loss, Surgical</condition>
  <arm_group>
    <arm_group_label>Tranexamic acid (TXA)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>All patients will receive 15 mg/kg Tranexamic acid (TXA) IV prior to skin incision. This arm will receive a second intravenous dose of 15 mg/kg of Tranexamic acid (TXA) before the release of the tourniquet. The medication is delivered from the pharmacy in a masked syringe labeled as &quot;study medication.&quot;</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo Normal Saline (NS)</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>All patients will receive 15 mg/kg Tranexamic acid (TXA) IV prior to skin incision. This arm will receive a second intravenous dose of placebo (Normal Saline) in the volume calculated to be equal to the volume of 15 mg/kg of TXA. The medication is delivered from the pharmacy in a masked syringe labeled as &quot;study medication.&quot;</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tranexamic acid (TXA)</intervention_name>
    <description>Randomly assigned [1:1 ratio] using a computer generated table of random numbers to 1 of the 2 intervention groups</description>
    <arm_group_label>Tranexamic acid (TXA)</arm_group_label>
    <other_name>Lysteda</other_name>
    <other_name>Cyklokapron</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo Normal Saline (NS)</intervention_name>
    <description>Randomly assigned [1:1 ratio] using a computer generated table of random numbers to 1 of the 2 intervention groups</description>
    <arm_group_label>Placebo Normal Saline (NS)</arm_group_label>
    <other_name>Sodium chloride</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        - Adult patients who are scheduled to undergo total knee arthroplasty will be approached to&#xD;
        participate.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Known allergy to TXA&#xD;
&#xD;
          -  History of venous or arterial thrombosis within 12 months&#xD;
&#xD;
          -  History of thromboembolic event within 12 months&#xD;
&#xD;
          -  Acute ischemic event (stroke, transient ischemic attack, myocardial infarction,&#xD;
             ischemic retinopathy) within 6 months&#xD;
&#xD;
          -  Known congenital thrombophilia&#xD;
&#xD;
        Relative Contraindications:&#xD;
&#xD;
          -  History of seizures&#xD;
&#xD;
          -  Impaired kidney function (Glomerular filtration rate &lt; 30 ml/min)&#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>Denis Snegovskikh, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Rhode Island Hospital; Brown University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Miriam Hospital</name>
      <address>
        <city>Providence</city>
        <state>Rhode Island</state>
        <zip>02903</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <results_reference>
    <citation>Pachauri A, Acharya KK, Tiwari AK. The effect of tranexamic acid on hemoglobin levels during total knee arthroplasty. Am J Ther. 2014 Sep-Oct;21(5):366-70. doi: 10.1097/MJT.0b013e318250f85a.</citation>
    <PMID>23917458</PMID>
  </results_reference>
  <results_reference>
    <citation>Aguilera X, Martinez-Zapata MJ, Bosch A, Urrutia G, Gonzalez JC, Jordan M, Gich I, Maymo RM, Martinez N, Monllau JC, Celaya F, Fernandez JA. Efficacy and safety of fibrin glue and tranexamic acid to prevent postoperative blood loss in total knee arthroplasty: a randomized controlled clinical trial. J Bone Joint Surg Am. 2013 Nov 20;95(22):2001-7. doi: 10.2106/JBJS.L.01182.</citation>
    <PMID>24257657</PMID>
  </results_reference>
  <results_reference>
    <citation>Kim TK, Chang CB, Kang YG, Seo ES, Lee JH, Yun JH, Lee SH. Clinical value of tranexamic acid in unilateral and simultaneous bilateral TKAs under a contemporary blood-saving protocol: a randomized controlled trial. Knee Surg Sports Traumatol Arthrosc. 2014 Aug;22(8):1870-8. doi: 10.1007/s00167-013-2492-1. Epub 2013 Apr 17.</citation>
    <PMID>23592025</PMID>
  </results_reference>
  <results_reference>
    <citation>Na HS, Shin HJ, Lee YJ, Kim JH, Koo KH, Do SH. The effect of tranexamic acid on blood coagulation in total hip replacement arthroplasty: rotational thromboelastographic (ROTEM(R)) analysis. Anaesthesia. 2016 Jan;71(1):67-75. doi: 10.1111/anae.13270. Epub 2015 Nov 12.</citation>
    <PMID>26559015</PMID>
  </results_reference>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>June 15, 2020</study_first_submitted>
  <study_first_submitted_qc>June 20, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 23, 2020</study_first_posted>
  <last_update_submitted>June 19, 2023</last_update_submitted>
  <last_update_submitted_qc>June 19, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 22, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Blood Loss, Surgical</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tranexamic Acid</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04443920
org study id: 1372794
nct id: NCT04443920
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this investigation is to determine the most effective regimen of
      administration of tranexamic acid to improve clinical outcome among patients undergoing total
      knee arthroplasty.
Tranexamic acid (TXA) is synthetic lysine analog, which acts as anti-fibrinolytic agent by
      preventing conversion of plasminogen in to plasmin. Various regimens of TXA administration
      (routes, doses, timing) have been used to decrease perioperative blood loss and improve
      clinical outcomes among patients undergoing different orthopedic surgeries. We are conducting
      this prospective randomized placebo controlled trial to compare the effect of the two most
      common regimens of TXA administration on hemostasis and clinical outcomes among patients
      undergoing total knee arthroplasty. All recruited patients receive the first dose of 15mg/kg
      of IV TXA prior to skin incision. The second dose of 15mg/kg IV TXA or identical placebo is
      administered prior to the release of the tourniquet.

      The assessment of hemostasis is performed using whole blood sample via viscoelastic testing
      by rotational thromboelastography (ROTEM). A blood sample is collected in the preoperative
      area and after the administration of each dose of TXA. Clinical data is collected until 90
      days after surgery.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Assessment of changes in hemostasis via viscoelastic testing.
time frame: intraoperative (min)
description: To compare the magnitude of lysis via lysis indexes.
measure: Hematocrit
time frame: postoperative day 1
description: The comparison of hematocrit recordings from preoperative period to the postoperative period
measure: Length of Hospitalization
time frame: up to 7 days
description: Length of hospital stay from day of surgery to discharge from hospital.
measure: The number of blood transfusions
time frame: 90 days
description: The number of blood products transfused after surgery
measure: Hospital readmissions
time frame: 90 days
description: The occurrence of hospital readmissions following surgery
arm group label: Tranexamic acid (TXA)
arm group type: Active Comparator
description: All patients will receive 15 mg/kg Tranexamic acid (TXA) IV prior to skin incision. This arm will receive a second intravenous dose of 15 mg/kg of Tranexamic acid (TXA) before the release of the tourniquet. The medication is delivered from the pharmacy in a masked syringe labeled as "study medication."
arm group label: Placebo Normal Saline (NS)
arm group type: Placebo Comparator
description: All patients will receive 15 mg/kg Tranexamic acid (TXA) IV prior to skin incision. This arm will receive a second intravenous dose of placebo (Normal Saline) in the volume calculated to be equal to the volume of 15 mg/kg of TXA. The medication is delivered from the pharmacy in a masked syringe labeled as "study medication."
intervention type: Drug
intervention name: Tranexamic acid (TXA)
description: Randomly assigned [1:1 ratio] using a computer generated table of random numbers to 1 of the 2 intervention groups
arm group label: Tranexamic acid (TXA)
other name: Lysteda
other name: Cyklokapron
intervention type: Drug
intervention name: Placebo Normal Saline (NS)
description: Randomly assigned [1:1 ratio] using a computer generated table of random numbers to 1 of the 2 intervention groups
arm group label: Placebo Normal Saline (NS)
other name: Sodium chloride
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Denis Snegovskikh, MD
role: Principal Investigator
affiliation: Rhode Island Hospital; Brown University
facility: 
country: United States
citation: Pachauri A, Acharya KK, Tiwari AK. The effect of tranexamic acid on hemoglobin levels during total knee arthroplasty. Am J Ther. 2014 Sep-Oct;21(5):366-70. doi: 10.1097/MJT.0b013e318250f85a.
PMID: 23917458
citation: Aguilera X, Martinez-Zapata MJ, Bosch A, Urrutia G, Gonzalez JC, Jordan M, Gich I, Maymo RM, Martinez N, Monllau JC, Celaya F, Fernandez JA. Efficacy and safety of fibrin glue and tranexamic acid to prevent postoperative blood loss in total knee arthroplasty: a randomized controlled clinical trial. J Bone Joint Surg Am. 2013 Nov 20;95(22):2001-7. doi: 10.2106/JBJS.L.01182.
PMID: 24257657
citation: Kim TK, Chang CB, Kang YG, Seo ES, Lee JH, Yun JH, Lee SH. Clinical value of tranexamic acid in unilateral and simultaneous bilateral TKAs under a contemporary blood-saving protocol: a randomized controlled trial. Knee Surg Sports Traumatol Arthrosc. 2014 Aug;22(8):1870-8. doi: 10.1007/s00167-013-2492-1. Epub 2013 Apr 17.
PMID: 23592025
citation: Na HS, Shin HJ, Lee YJ, Kim JH, Koo KH, Do SH. The effect of tranexamic acid on blood coagulation in total hip replacement arthroplasty: rotational thromboelastographic (ROTEM(R)) analysis. Anaesthesia. 2016 Jan;71(1):67-75. doi: 10.1111/anae.13270. Epub 2015 Nov 12.
PMID: 26559015
responsible party type: Sponsor
mesh term: Blood Loss, Surgical
mesh term: Tranexamic Acid
sharing ipd: No