<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/NCT03287336</url>
  </required_header>
  <id_info>
    <org_study_id>IND134701</org_study_id>
    <secondary_id>UL1TR001876</secondary_id>
    <secondary_id>KL2TR001877</secondary_id>
    <secondary_id>K23HL141640</secondary_id>
    <nct_id>NCT03287336</nct_id>
  </id_info>
  <brief_title>Prevention of Postpartum Hemorrhage With Tranexamic Acid</brief_title>
  <official_title>Prevention of Postpartum Hemorrhage: Identifying Pregnant Women at Risk and Determining the Safe and Effective Use of Tranexamic Acid Using State-of-the-art Pharmacokinetic/Pharmacodynamics Modeling</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>George Washington University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institutes of Health (NIH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Heart, Lung, and Blood Institute (NHLBI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>George Washington University</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>
      Postpartum hemorrhage is a significant contributor to maternal morbidity and mortality and is&#xD;
      worldwide. TXA has recently been proven to reduce mortality when given to women in setting of&#xD;
      diagnosed PPH. US obstetricians and anesthesiologists are hesitant to use TXA in the&#xD;
      peripartum period especially for prevention of PPH due to uncertainty of an optimal dose and&#xD;
      safety profile. The purpose of this study is to characterize the pharmacokinetics of TXA when&#xD;
      given prophylactically at time of delivery. In addition investigators will determine the&#xD;
      pharmacodynamics of TXA in the peripartum period.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Conduct a prospective, open-label, dose finding PK study in 30 pregnant 3rd trimester women&#xD;
      scheduled for non-emergent cesarean section who are at risk for hemorrhage. Three doses of&#xD;
      the drug will be administered in an escalating fashion by cohort with the lowest dose first.&#xD;
      A maximum of 1 gram will be administered. TXA serum levels at several time points after&#xD;
      delivery will be assayed. A PK model will be constructed for determining the optimal TXA dose&#xD;
      administered at parturition.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">January 2, 2018</start_date>
  <completion_date type="Anticipated">November 1, 2023</completion_date>
  <primary_completion_date type="Anticipated">September 1, 2023</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <intervention_model_description>Three doses of Tranexamic acid (5 mg/kg, 10 mg/kg, and 15 mg/kg) will be used in a dose escalation fashion by cohort with the lowest dose first.</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Pharmacokinetics of Tranexamic Acid</measure>
    <time_frame>Different time points ranging from surgery (T0) to 1 day postpartum.</time_frame>
    <description>Serum Assay of TXA in blood and breast milk to determine clearance.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacodynamics of Tranexamic acid</measure>
    <time_frame>Different time points ranging from surgery (T0) to 1 day postpartum.</time_frame>
    <description>Pharmacodynamics: maximum lysis (ML) and other coagulation markers such as d-dimer and plasmin-anti-plasmin complexes</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Estimated blood loss</measure>
    <time_frame>During surgery</time_frame>
    <description>Intraoperative blood loss</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety parameters</measure>
    <time_frame>During surgery, after surgery while in hospital, 2 weeks and 6 weeks postpartum</time_frame>
    <description>Safety parameters such as adverse events and serious adverse events</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Postpartum Hemorrhage</condition>
  <arm_group>
    <arm_group_label>Cohort 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dose of Tranexamic acid 5mg/kg will be administered.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dose of Tranexamic acid 10 mg/kg will be administered.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dose of Tranexamic acid 15 mg/kg will be administered.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tranexamic Acid</intervention_name>
    <description>Tranexamic acid dosage (5 mg/kg, 10 mg/kg and 15 mg/kg) administered in a dose escalating fashion by cohort with the lowest dose first.</description>
    <arm_group_label>Cohort 1</arm_group_label>
    <arm_group_label>Cohort 2</arm_group_label>
    <arm_group_label>Cohort 3</arm_group_label>
    <other_name>TXA; Cyklokapron</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Women who are undergoing medically indicated cesarean section at greater than 34+0&#xD;
             weeks gestation or women undergoing elective cesarean section at 39+0 weeks gestation&#xD;
             in accordance with recommendations from the American Congress of Obstetricians and&#xD;
             Gynecologists&#xD;
&#xD;
          -  Pregnant women with normal serum creatinine (serum creatinine &lt; 0.9)&#xD;
&#xD;
          -  Women between the ages of 18 and 50 years old&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients younger than 18 or older than 50&#xD;
&#xD;
          -  women with active thrombotic or thromboembolic disease&#xD;
&#xD;
          -  Women with a history of arterial or venous thromboembolic event&#xD;
&#xD;
          -  Women with inherited thrombophilia or preexisting conditions that predisposes them to&#xD;
             thromboembolic events (i.e. lupus, antiphospholipid syndrome)&#xD;
&#xD;
          -  Women with a subarachnoid hemorrhage&#xD;
&#xD;
          -  Women with acquired defective color vision&#xD;
&#xD;
          -  history of seizure disorder&#xD;
&#xD;
          -  known renal dysfunction&#xD;
&#xD;
          -  multiple gestations (Twin or triplet pregnancies)&#xD;
&#xD;
          -  Hypersensitivity to Tranexamic acid or anti-fibrinolytic therapy&#xD;
&#xD;
          -  History of liver dysfunction&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <gender_description>Pregnant women in 3rd trimester of pregnancy</gender_description>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>49 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Homa Ahmadzia, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>George Washington University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>James Slota</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20037</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>June 27, 2017</study_first_submitted>
  <study_first_submitted_qc>September 18, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 19, 2017</study_first_posted>
  <last_update_submitted>October 17, 2022</last_update_submitted>
  <last_update_submitted_qc>October 17, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 19, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>George Washington University</investigator_affiliation>
    <investigator_full_name>Homa Ahmadzia</investigator_full_name>
    <investigator_title>PI</investigator_title>
  </responsible_party>
  <keyword>tranexamic acid</keyword>
  <keyword>postpartum hemorrhage</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Postpartum Hemorrhage</mesh_term>
    <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>
  <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/NCT03287336
org study id: IND134701
secondary id: UL1TR001876
secondary id: KL2TR001877
secondary id: K23HL141640
nct id: NCT03287336
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
Postpartum hemorrhage is a significant contributor to maternal morbidity and mortality and is
      worldwide. TXA has recently been proven to reduce mortality when given to women in setting of
      diagnosed PPH. US obstetricians and anesthesiologists are hesitant to use TXA in the
      peripartum period especially for prevention of PPH due to uncertainty of an optimal dose and
      safety profile. The purpose of this study is to characterize the pharmacokinetics of TXA when
      given prophylactically at time of delivery. In addition investigators will determine the
      pharmacodynamics of TXA in the peripartum period.
Conduct a prospective, open-label, dose finding PK study in 30 pregnant 3rd trimester women
      scheduled for non-emergent cesarean section who are at risk for hemorrhage. Three doses of
      the drug will be administered in an escalating fashion by cohort with the lowest dose first.
      A maximum of 1 gram will be administered. TXA serum levels at several time points after
      delivery will be assayed. A PK model will be constructed for determining the optimal TXA dose
      administered at parturition.
allocation: Non-Randomized
intervention model: Sequential Assignment
intervention model description: Three doses of Tranexamic acid (5 mg/kg, 10 mg/kg, and 15 mg/kg) will be used in a dose escalation fashion by cohort with the lowest dose first.
primary purpose: Prevention
masking: Single (Outcomes Assessor)
measure: Pharmacokinetics of Tranexamic Acid
time frame: Different time points ranging from surgery (T0) to 1 day postpartum.
description: Serum Assay of TXA in blood and breast milk to determine clearance.
measure: Pharmacodynamics of Tranexamic acid
time frame: Different time points ranging from surgery (T0) to 1 day postpartum.
description: Pharmacodynamics: maximum lysis (ML) and other coagulation markers such as d-dimer and plasmin-anti-plasmin complexes
measure: Estimated blood loss
time frame: During surgery
description: Intraoperative blood loss
measure: Safety parameters
time frame: During surgery, after surgery while in hospital, 2 weeks and 6 weeks postpartum
description: Safety parameters such as adverse events and serious adverse events
arm group label: Cohort 1
arm group type: Experimental
description: Dose of Tranexamic acid 5mg/kg will be administered.
arm group label: Cohort 2
arm group type: Experimental
description: Dose of Tranexamic acid 10 mg/kg will be administered.
arm group label: Cohort 3
arm group type: Experimental
description: Dose of Tranexamic acid 15 mg/kg will be administered.
intervention type: Drug
intervention name: Tranexamic Acid
description: Tranexamic acid dosage (5 mg/kg, 10 mg/kg and 15 mg/kg) administered in a dose escalating fashion by cohort with the lowest dose first.
arm group label: Cohort 1
arm group label: Cohort 2
arm group label: Cohort 3
other name: TXA; Cyklokapron
criteria: 
gender: Female
gender based: Yes
gender description: Pregnant women in 3rd trimester of pregnancy
minimum age: 18 Years
maximum age: 49 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Homa Ahmadzia, MD
role: Principal Investigator
affiliation: George Washington University
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: George Washington University
investigator full name: Homa Ahmadzia
investigator title: PI
mesh term: Postpartum Hemorrhage
mesh term: Hemorrhage
mesh term: Tranexamic Acid
sharing ipd: No