<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/NCT03251963</url>
  </required_header>
  <id_info>
    <org_study_id>100484</org_study_id>
    <nct_id>NCT03251963</nct_id>
  </id_info>
  <brief_title>Fixed Versus Weight-Based Enoxaparin Dosing in Thoracic Surgery Patients</brief_title>
  <official_title>Fixed Versus Weight-Based Enoxaparin Dosing in Thoracic Surgery Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Utah</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Michigan</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Utah</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of this research is to better understand how patient-level factors can be used to&#xD;
      predict the appropriate enoxaparin dose to maximize venous thromboembolism (VTE) risk&#xD;
      reduction and minimize bleeding.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      VTE encompasses deep venous thrombosis and pulmonary embolus and is the proximate cause of&#xD;
      death in over 100,000 hospitalized patients per year 4,5. To put this in better context, VTE&#xD;
      kills more people each year than the annual morbidity from motor vehicle crashes and breast&#xD;
      cancer combined-and one third of these deaths are known to occur after surgical procedures&#xD;
      34. &quot;Breakthrough&quot; VTE events occur in patients despite the receipt of guideline-compliant&#xD;
      chemical prophylaxis. These events can be frustrating for surgeons, can represent a resource&#xD;
      and financial burden for hospital systems, and most importantly, can be life or limb&#xD;
      threatening for patients.&#xD;
&#xD;
      Existing data from our group and others suggests that inadequate enoxaparin dosing,&#xD;
      quantified by aFXa levels, represents a plausible explanatory mechanism for &quot;breakthrough&quot;&#xD;
      VTE events that occur among thoracic surgery patients. This project will examine the&#xD;
      pharmacodynamics of fixed dose enoxaparin (40mg/day) after VATS-this dose and frequency were&#xD;
      the most commonly prescribed VTE chemical prophylaxis strategy in a recent survey of thoracic&#xD;
      surgeons 35. If inadequate aFXa levels are observed with fixed enoxaparin dosing, the study&#xD;
      will design, implement and test a weight-based dosing approach to optimize aFXa levels. The&#xD;
      study will also examine how alteration of enoxaparin dose magnitude affects peak aFXa levels&#xD;
      and risk for VTE and major bleeding events.&#xD;
&#xD;
      Aim 1: To evaluate peak steady-state aFXa levels in response to a fixed dose of enoxaparin&#xD;
      prophylaxis (40mg once daily) in VATS patients.&#xD;
&#xD;
      Rationale: Over 12% of thoracic surgery patients have &quot;breakthrough&quot; VTE events despite&#xD;
      receipt of fixed dose chemical prophylaxis 29. Fixed dose enoxaparin prophylaxis has been&#xD;
      shown to be inadequate for the majority of patients in other surgical subspecialties.&#xD;
&#xD;
      Hypothesis: Peak steady state aFXa levels will be within the accepted range (0.3-0.5 IU/mL)&#xD;
      in 40% of patients after VATS.&#xD;
&#xD;
      Aim 2: To compare the effect of fixed (40mg once daily) and weight-based (0.5mg/kg once&#xD;
      daily) enoxaparin prophylaxis on peak steady state aFXa levels after VATS.&#xD;
&#xD;
      Rationale: Our preliminary data shows a potential association between body weight and aFXa&#xD;
      levels in response to fixed dosing; this will be confirmed using a multi-center approach in&#xD;
      Aim #1. Body weight may be an important predictor of appropriate enoxaparin dose.&#xD;
&#xD;
      Hypothesis: Weight-based enoxaparin prophylaxis, when compared to fixed dose prophylaxis,&#xD;
      will increase the proportion of patients with in-range peak aFXa levels from 40% to 80%.&#xD;
&#xD;
      Aim 3: To examine rates of 90-day VTE and clinically relevant bleeding events in VATS&#xD;
      patients who receive fixed dose vs. weight-based enoxaparin prophylaxis.&#xD;
&#xD;
      Rationale: This observational Aim will allow us to better understand VTE and bleeding rates&#xD;
      after VATS. Since these are rare events it is impossible to power the study to detect&#xD;
      increases or decreases in risk between the dose groups. This study does provide a way to&#xD;
      demonstrate an unexpected, very large difference in risk.&#xD;
&#xD;
      Hypothesis: Rates of post-operative VTE and clinically relevant bleeding will be less than 2%&#xD;
      in each group.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 15, 2017</start_date>
  <completion_date type="Actual">July 27, 2019</completion_date>
  <primary_completion_date type="Actual">March 27, 2019</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Participants enrolled in months 1-6 of the study will all receive a fixed dose of enoxaparin. Patients enrolled in months 7-12 of the study will all receive a variable dose of enoxaparin.</intervention_model_description>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Patients With in Range Initial Peak Xa Level</measure>
    <time_frame>36 hours</time_frame>
    <description>Number of patients with in range initial peak Xa level</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Venous Thromboembolism Events or Death</measure>
    <time_frame>90 days</time_frame>
    <description>Any symptomatic venous thromboembolism events, including deep venous thrombosis or pulmonary embolus occurring within 90 days of surgery</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Bleeding Events</measure>
    <time_frame>90 days</time_frame>
    <description>Bleeding events requiring alteration in the course of care within 90 days of surgery</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">131</enrollment>
  <condition>Venous Thromboembolism</condition>
  <condition>Deep Venous Thrombosis</condition>
  <condition>Surgery</condition>
  <arm_group>
    <arm_group_label>Fixed Dose Enoxaparin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Eligible patients will be administered 40 mg enoxaparin daily and will have steady state peak and trough anti-Xa levels drawn after the third enoxaparin dose.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Variable Dose Enoxaparin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Eligible patients will be administered 0.5 mg/kg enoxaparin daily and will have steady state peak and trough anti-Xa levels drawn after the third enoxaparin dose.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fixed Dose Enoxaparin</intervention_name>
    <description>Eligible patients will be administered 40 mg enoxaparin daily and will have steady state peak and trough anti-Xa levels drawn after the third enoxaparin dose. For patients in-range (levels 0.3-0.5IUmL), no intervention will be undertaken. For patients out of range, enoxaparin dose will be adjusted according to an established dose adjustment algorithm. Repeat levels will be checked after the third administration of the new dose.</description>
    <arm_group_label>Fixed Dose Enoxaparin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Variable Dose Enoxaparin</intervention_name>
    <description>Eligible patients will be administered 0.5 mg/kg enoxaparin daily and will have steady state peak and trough anti-Xa levels drawn after the third enoxaparin dose. For patients in-range (levels 0.3-0.5IUmL), no intervention will be undertaken. For patients out of range, enoxaparin dose will be adjusted according to an established dose adjustment algorithm. Repeat levels will be checked after the third administration of the new dose.</description>
    <arm_group_label>Variable Dose Enoxaparin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  receiving Video-Assisted Thoracoscopic Surgery&#xD;
&#xD;
          -  able to have Enoxaparin initiated within 8 hours after procedure&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Contraindication to use of enoxaparin&#xD;
&#xD;
          -  Intracranial bleeding/stroke&#xD;
&#xD;
          -  Hematoma or bleeding disorder&#xD;
&#xD;
          -  Heparin-induced thrombocytopenia positive&#xD;
&#xD;
          -  Creatinine clearance less than or equal to 30 mL/min&#xD;
&#xD;
          -  Serum creatinine greater than 1.6 mg/dL&#xD;
&#xD;
          -  Epidural catheter&#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>Christopher Puccini, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Utah</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Utah</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>August 14, 2017</study_first_submitted>
  <study_first_submitted_qc>August 14, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 16, 2017</study_first_posted>
  <results_first_submitted>June 8, 2020</results_first_submitted>
  <results_first_submitted_qc>July 7, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">July 8, 2020</results_first_posted>
  <last_update_submitted>July 7, 2020</last_update_submitted>
  <last_update_submitted_qc>July 7, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 8, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Utah</investigator_affiliation>
    <investigator_full_name>Christopher Pannucci</investigator_full_name>
    <investigator_title>Assistant Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Thrombosis</mesh_term>
    <mesh_term>Thromboembolism</mesh_term>
    <mesh_term>Venous Thromboembolism</mesh_term>
    <mesh_term>Venous Thrombosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Enoxaparin</mesh_term>
    <mesh_term>Enoxaparin sodium</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>June 19, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/63/NCT03251963/Prot_SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Fixed Dose Enoxaparin</title>
          <description>Eligible patients will be administered 40 mg enoxaparin daily and will have steady state peak and trough anti-Xa levels drawn after the third enoxaparin dose.&#xD;
Fixed Dose Enoxaparin: Eligible patients will be administered 40 mg enoxaparin daily and will have steady state peak and trough anti-Xa levels drawn after the third enoxaparin dose. For patients in-range (levels 0.3-0.5IUmL), no intervention will be undertaken. For patients out of range, enoxaparin dose will be adjusted according to an established dose adjustment algorithm. Repeat levels will be checked after the third administration of the new dose.</description>
        </group>
        <group group_id="P2">
          <title>Weight Tiered Enoxaparin</title>
          <description>Eligible patients will be receive weight tiered daily enoxaparin. Patients &lt;70kg received 30mg, patients 70kg to 89.9kg received 40mg, and patients ≥90kg received 50mg.&#xD;
Variable Dose Enoxaparin: Patients &lt;70kg received 30mg, patients 70kg to 89.9kg received 40mg, and patients ≥90kg received 50mg. For patients in-range (levels 0.3-0.5IUmL), no intervention will be undertaken. For patients out of range, enoxaparin dose will be adjusted according to an established dose adjustment algorithm. Repeat levels will be checked after the third administration of the new dose.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="65"/>
                <participants group_id="P2" count="66"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="56"/>
                <participants group_id="P2" count="61"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>inappropriate Xa level timing</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>no peak Xa level drawn</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>bled prior to Xa level</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Group 1 65 plus Group 2 66 =131 total</population>
      <group_list>
        <group group_id="B1">
          <title>Fixed Dose Enoxaparin</title>
          <description>Eligible patients will be administered 40 mg enoxaparin daily and will have steady state peak and trough anti-Xa levels drawn after the third enoxaparin dose.&#xD;
Fixed Dose Enoxaparin: Eligible patients will be administered 40 mg enoxaparin daily and will have steady state peak and trough anti-Xa levels drawn after the third enoxaparin dose. For patients in-range (levels 0.3-0.5IUmL), no intervention will be undertaken. For patients out of range, enoxaparin dose will be adjusted according to an established dose adjustment algorithm. Repeat levels will be checked after the third administration of the new dose.</description>
        </group>
        <group group_id="B2">
          <title>Weight Tiered Enoxaparin</title>
          <description>Eligible patients will be receive weight tiered daily enoxaparin. Patients &lt;70kg received 30mg, patients 70kg to 89.9kg received 40mg, and patients ≥90kg received 50mg.&#xD;
Variable Dose Enoxaparin: Patients &lt;70kg received 30mg, patients 70kg to 89.9kg received 40mg, and patients ≥90kg received 50mg. For patients in-range (levels 0.3-0.5IUmL), no intervention will be undertaken. For patients out of range, enoxaparin dose will be adjusted according to an established dose adjustment algorithm. Repeat levels will be checked after the third administration of the new dose.</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="65"/>
            <count group_id="B2" value="66"/>
            <count group_id="B3" value="131"/>
          </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="32"/>
                    <measurement group_id="B2" value="33"/>
                    <measurement group_id="B3" value="65"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="33"/>
                    <measurement group_id="B2" value="33"/>
                    <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>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="60.9" spread="15.6"/>
                    <measurement group_id="B2" value="59.0" spread="16.8"/>
                    <measurement group_id="B3" value="60.0" spread="16.2"/>
                  </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="37"/>
                    <measurement group_id="B2" value="32"/>
                    <measurement group_id="B3" value="69"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="28"/>
                    <measurement group_id="B2" value="34"/>
                    <measurement group_id="B3" value="62"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</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>Asian</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>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="61"/>
                    <measurement group_id="B2" value="63"/>
                    <measurement group_id="B3" value="124"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</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_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="65"/>
                    <measurement group_id="B2" value="66"/>
                    <measurement group_id="B3" value="131"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Patients With in Range Initial Peak Xa Level</title>
        <description>Number of patients with in range initial peak Xa level</description>
        <time_frame>36 hours</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Fixed Dose Enoxaparin</title>
            <description>Eligible patients will be administered 40 mg enoxaparin daily and will have steady state peak and trough anti-Xa levels drawn after the third enoxaparin dose.&#xD;
Fixed Dose Enoxaparin: Eligible patients will be administered 40 mg enoxaparin daily and will have steady state peak and trough anti-Xa levels drawn after the third enoxaparin dose. For patients in-range (levels 0.3-0.5IUmL), no intervention will be undertaken. For patients out of range, enoxaparin dose will be adjusted according to an established dose adjustment algorithm. Repeat levels will be checked after the third administration of the new dose.</description>
          </group>
          <group group_id="O2">
            <title>Weight Tiered Enoxaparin</title>
            <description>Eligible patients will be receive weight tiered daily enoxaparin. Patients &lt;70kg received 30mg, patients 70kg to 89.9kg received 40mg, and patients ≥90kg received 50mg.&#xD;
Variable Dose Enoxaparin: Patients &lt;70kg received 30mg, patients 70kg to 89.9kg received 40mg, and patients ≥90kg received 50mg. For patients in-range (levels 0.3-0.5IUmL), no intervention will be undertaken. For patients out of range, enoxaparin dose will be adjusted according to an established dose adjustment algorithm. Repeat levels will be checked after the third administration of the new dose.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients With in Range Initial Peak Xa Level</title>
          <description>Number of patients with in range initial peak Xa level</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="56"/>
                <count group_id="O2" value="61"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="27"/>
                    <measurement group_id="O2" value="27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Venous Thromboembolism Events or Death</title>
        <description>Any symptomatic venous thromboembolism events, including deep venous thrombosis or pulmonary embolus occurring within 90 days of surgery</description>
        <time_frame>90 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Fixed Dose Enoxaparin</title>
            <description>Eligible patients will be administered 40 mg enoxaparin daily and will have steady state peak and trough anti-Xa levels drawn after the third enoxaparin dose.&#xD;
Fixed Dose Enoxaparin: Eligible patients will be administered 40 mg enoxaparin daily and will have steady state peak and trough anti-Xa levels drawn after the third enoxaparin dose. For patients in-range (levels 0.3-0.5IUmL), no intervention will be undertaken. For patients out of range, enoxaparin dose will be adjusted according to an established dose adjustment algorithm. Repeat levels will be checked after the third administration of the new dose.</description>
          </group>
          <group group_id="O2">
            <title>Weight Tiered Enoxaparin</title>
            <description>Eligible patients will be receive weight tiered daily enoxaparin. Patients &lt;70kg received 30mg, patients 70kg to 89.9kg received 40mg, and patients ≥90kg received 50mg.&#xD;
Variable Dose Enoxaparin: Patients &lt;70kg received 30mg, patients 70kg to 89.9kg received 40mg, and patients ≥90kg received 50mg. For patients in-range (levels 0.3-0.5IUmL), no intervention will be undertaken. For patients out of range, enoxaparin dose will be adjusted according to an established dose adjustment algorithm. Repeat levels will be checked after the third administration of the new dose.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Venous Thromboembolism Events or Death</title>
          <description>Any symptomatic venous thromboembolism events, including deep venous thrombosis or pulmonary embolus occurring within 90 days of surgery</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="65"/>
                <count group_id="O2" value="66"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Bleeding Events</title>
        <description>Bleeding events requiring alteration in the course of care within 90 days of surgery</description>
        <time_frame>90 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Fixed Dose Enoxaparin</title>
            <description>Eligible patients will be administered 40 mg enoxaparin daily and will have steady state peak and trough anti-Xa levels drawn after the third enoxaparin dose.&#xD;
Fixed Dose Enoxaparin: Eligible patients will be administered 40 mg enoxaparin daily and will have steady state peak and trough anti-Xa levels drawn after the third enoxaparin dose. For patients in-range (levels 0.3-0.5IUmL), no intervention will be undertaken. For patients out of range, enoxaparin dose will be adjusted according to an established dose adjustment algorithm. Repeat levels will be checked after the third administration of the new dose.</description>
          </group>
          <group group_id="O2">
            <title>Weight Tiered Enoxaparin</title>
            <description>Eligible patients will be receive weight tiered daily enoxaparin. Patients &lt;70kg received 30mg, patients 70kg to 89.9kg received 40mg, and patients ≥90kg received 50mg.&#xD;
Variable Dose Enoxaparin: Patients &lt;70kg received 30mg, patients 70kg to 89.9kg received 40mg, and patients ≥90kg received 50mg. For patients in-range (levels 0.3-0.5IUmL), no intervention will be undertaken. For patients out of range, enoxaparin dose will be adjusted according to an established dose adjustment algorithm. Repeat levels will be checked after the third administration of the new dose.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Bleeding Events</title>
          <description>Bleeding events requiring alteration in the course of care within 90 days of surgery</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="65"/>
                <count group_id="O2" value="66"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>90 days</time_frame>
      <desc>Symptomatic VTE was defined as any symptomatic deep vein thrombosis or pulmonary embolus with imaging confirmation. Screening duplex ultrasound was not performed, as suggested by current American College of Chest Physicians guidelines. Clinically relevant bleeding was defined as any bleeding that changed the course of care; this included bleeding requiring enoxaparin cessation, unexpected transfusion, or procedural (interventional radiology or operating room) intervention.</desc>
      <group_list>
        <group group_id="E1">
          <title>Fixed Dose Enoxaparin</title>
          <description>Eligible patients will be administered 40 mg enoxaparin daily and will have steady state peak and trough anti-Xa levels drawn after the third enoxaparin dose.&#xD;
Fixed Dose Enoxaparin: Eligible patients will be administered 40 mg enoxaparin daily and will have steady state peak and trough anti-Xa levels drawn after the third enoxaparin dose. For patients in-range (levels 0.3-0.5IUmL), no intervention will be undertaken. For patients out of range, enoxaparin dose will be adjusted according to an established dose adjustment algorithm. Repeat levels will be checked after the third administration of the new dose.</description>
        </group>
        <group group_id="E2">
          <title>Weight Tiered Enoxaparin</title>
          <description>Eligible patients will be receive weight tiered daily enoxaparin. Patients &lt;70kg received 30mg, patients 70kg to 89.9kg received 40mg, and patients ≥90kg received 50mg.&#xD;
Variable Dose Enoxaparin: Patients &lt;70kg received 30mg, patients 70kg to 89.9kg received 40mg, and patients ≥90kg received 50mg. For patients in-range (levels 0.3-0.5IUmL), no intervention will be undertaken. For patients out of range, enoxaparin dose will be adjusted according to an established dose adjustment algorithm. Repeat levels will be checked after the third administration of the new dose.</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="1" subjects_at_risk="65"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="66"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="65"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="66"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>90-day Death</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="65"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="66"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="65"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="66"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>DVT/PE</sub_title>
                <description>90 day symptomatic VTE</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="65"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="66"/>
              </event>
              <event>
                <sub_title>clinically relevant bleeding</sub_title>
                <description>90-day clinically relevant bleeding</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="65"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="66"/>
              </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>Christopher Pannucci</name_or_title>
      <organization>University of Utah</organization>
      <phone>801 581 2121</phone>
      <email>christopher.pannucci@hsc.utah.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/NCT03251963
org study id: 100484
nct id: NCT03251963
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
The aim of this research is to better understand how patient-level factors can be used to
      predict the appropriate enoxaparin dose to maximize venous thromboembolism (VTE) risk
      reduction and minimize bleeding.
VTE encompasses deep venous thrombosis and pulmonary embolus and is the proximate cause of
      death in over 100,000 hospitalized patients per year 4,5. To put this in better context, VTE
      kills more people each year than the annual morbidity from motor vehicle crashes and breast
      cancer combined-and one third of these deaths are known to occur after surgical procedures
      34. "Breakthrough" VTE events occur in patients despite the receipt of guideline-compliant
      chemical prophylaxis. These events can be frustrating for surgeons, can represent a resource
      and financial burden for hospital systems, and most importantly, can be life or limb
      threatening for patients.

      Existing data from our group and others suggests that inadequate enoxaparin dosing,
      quantified by aFXa levels, represents a plausible explanatory mechanism for "breakthrough"
      VTE events that occur among thoracic surgery patients. This project will examine the
      pharmacodynamics of fixed dose enoxaparin (40mg/day) after VATS-this dose and frequency were
      the most commonly prescribed VTE chemical prophylaxis strategy in a recent survey of thoracic
      surgeons 35. If inadequate aFXa levels are observed with fixed enoxaparin dosing, the study
      will design, implement and test a weight-based dosing approach to optimize aFXa levels. The
      study will also examine how alteration of enoxaparin dose magnitude affects peak aFXa levels
      and risk for VTE and major bleeding events.

      Aim 1: To evaluate peak steady-state aFXa levels in response to a fixed dose of enoxaparin
      prophylaxis (40mg once daily) in VATS patients.

      Rationale: Over 12% of thoracic surgery patients have "breakthrough" VTE events despite
      receipt of fixed dose chemical prophylaxis 29. Fixed dose enoxaparin prophylaxis has been
      shown to be inadequate for the majority of patients in other surgical subspecialties.

      Hypothesis: Peak steady state aFXa levels will be within the accepted range (0.3-0.5 IU/mL)
      in 40% of patients after VATS.

      Aim 2: To compare the effect of fixed (40mg once daily) and weight-based (0.5mg/kg once
      daily) enoxaparin prophylaxis on peak steady state aFXa levels after VATS.

      Rationale: Our preliminary data shows a potential association between body weight and aFXa
      levels in response to fixed dosing; this will be confirmed using a multi-center approach in
      Aim #1. Body weight may be an important predictor of appropriate enoxaparin dose.

      Hypothesis: Weight-based enoxaparin prophylaxis, when compared to fixed dose prophylaxis,
      will increase the proportion of patients with in-range peak aFXa levels from 40% to 80%.

      Aim 3: To examine rates of 90-day VTE and clinically relevant bleeding events in VATS
      patients who receive fixed dose vs. weight-based enoxaparin prophylaxis.

      Rationale: This observational Aim will allow us to better understand VTE and bleeding rates
      after VATS. Since these are rare events it is impossible to power the study to detect
      increases or decreases in risk between the dose groups. This study does provide a way to
      demonstrate an unexpected, very large difference in risk.

      Hypothesis: Rates of post-operative VTE and clinically relevant bleeding will be less than 2%
      in each group.
allocation: Non-Randomized
intervention model: Parallel Assignment
intervention model description: Participants enrolled in months 1-6 of the study will all receive a fixed dose of enoxaparin. Patients enrolled in months 7-12 of the study will all receive a variable dose of enoxaparin.
primary purpose: Other
masking: None (Open Label)
measure: Number of Patients With in Range Initial Peak Xa Level
time frame: 36 hours
description: Number of patients with in range initial peak Xa level
measure: Number of Participants With Venous Thromboembolism Events or Death
time frame: 90 days
description: Any symptomatic venous thromboembolism events, including deep venous thrombosis or pulmonary embolus occurring within 90 days of surgery
measure: Number of Participants With Bleeding Events
time frame: 90 days
description: Bleeding events requiring alteration in the course of care within 90 days of surgery
arm group label: Fixed Dose Enoxaparin
arm group type: Experimental
description: Eligible patients will be administered 40 mg enoxaparin daily and will have steady state peak and trough anti-Xa levels drawn after the third enoxaparin dose.
arm group label: Variable Dose Enoxaparin
arm group type: Experimental
description: Eligible patients will be administered 0.5 mg/kg enoxaparin daily and will have steady state peak and trough anti-Xa levels drawn after the third enoxaparin dose.
intervention type: Drug
intervention name: Fixed Dose Enoxaparin
description: Eligible patients will be administered 40 mg enoxaparin daily and will have steady state peak and trough anti-Xa levels drawn after the third enoxaparin dose. For patients in-range (levels 0.3-0.5IUmL), no intervention will be undertaken. For patients out of range, enoxaparin dose will be adjusted according to an established dose adjustment algorithm. Repeat levels will be checked after the third administration of the new dose.
arm group label: Fixed Dose Enoxaparin
intervention type: Drug
intervention name: Variable Dose Enoxaparin
description: Eligible patients will be administered 0.5 mg/kg enoxaparin daily and will have steady state peak and trough anti-Xa levels drawn after the third enoxaparin dose. For patients in-range (levels 0.3-0.5IUmL), no intervention will be undertaken. For patients out of range, enoxaparin dose will be adjusted according to an established dose adjustment algorithm. Repeat levels will be checked after the third administration of the new dose.
arm group label: Variable Dose Enoxaparin
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Christopher Puccini, MD
role: Principal Investigator
affiliation: University of Utah
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Utah
investigator full name: Christopher Pannucci
investigator title: Assistant Professor
mesh term: Thrombosis
mesh term: Thromboembolism
mesh term: Venous Thromboembolism
mesh term: Venous Thrombosis
mesh term: Enoxaparin
mesh term: Enoxaparin sodium
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 