<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/NCT03003390</url>
  </required_header>
  <id_info>
    <org_study_id>1302011506</org_study_id>
    <secondary_id>1R21HD089131-01A1</secondary_id>
    <nct_id>NCT03003390</nct_id>
  </id_info>
  <brief_title>Catheter-Related Early Thromboprophylaxis With Enoxaparin (CRETE) Trial</brief_title>
  <acronym>CRETE</acronym>
  <official_title>Prevention of Central Venous Catheter-associated Thrombosis in Critically Ill Children: A Multicenter Phase 2b Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Yale University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>St. Louis Children's Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Dell Children's Medical Center of Central Texas</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Children's Hospital and Health System Foundation, Wisconsin</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Weill Medical College of Cornell University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Maria Fareri Children's Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Rochester Golisano Children's Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Yale 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>
      The purpose of this phase 2a, multi-center, randomized controlled study, is to explore the&#xD;
      efficacy of early prophylaxis against catheter-associated deep venous thrombosis (CADVT) in&#xD;
      critically ill children.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Critical illness and the presence of a central venous catheter (CVC) are the most important&#xD;
      risk factors for deep venous thrombosis (DVT) in children. Catheter-associated thrombosis&#xD;
      (CADVT) is highly prevalent and associated with poor outcomes in critically ill children.&#xD;
      Yet, based on underpowered pediatric trials, prophylaxis against CADVT is not recommended in&#xD;
      children. The recommendation to provide prophylaxis against thrombosis in critically ill&#xD;
      adults should not be applied to children because the hemostatic system and co-morbidities&#xD;
      vastly differ between age groups. Pivotal trials are urgently needed to determine whether&#xD;
      prophylaxis can prevent CADVT and its complications in critically ill children. However, the&#xD;
      timing and extent of reduction in thrombin generation, the biochemical goal of prophylaxis,&#xD;
      needed to prevent CADVT in children are unclear. The goal of this application is to explore&#xD;
      the efficacy of early prophylaxis against CADVT in critically ill children. Aim 1 is to&#xD;
      obtain preliminary evidence on the effect of early prophylaxis on the incidence of CADVT in&#xD;
      critically ill children. Based on the natural history of CADVT, we hypothesize that among&#xD;
      critically ill children, prophylaxis administered &lt;24 hours after catheter insertion&#xD;
      decreases the incidence of ultrasound-diagnosed CADVT compared with no prophylaxis. In this&#xD;
      phase 2a trial, children admitted to the intensive care unit with a newly inserted central&#xD;
      venous catheter will receive enoxaparin adjusted according to anti-Xa activity, a control&#xD;
      group will not receive enoxaparin adjusted according to anti-Xa activity. Enoxaparin has&#xD;
      become the &quot;standard&quot; pediatric anticoagulant for prophylaxis despite the absence of&#xD;
      conclusive data. We will use Bayesian approach to determine whether further trials are&#xD;
      warranted. Aim 2 is to evaluate the effect of an anti-Xa activity-directed prophylactic&#xD;
      strategy on thrombin generation in critically ill children. We hypothesize that among&#xD;
      critically ill children, standard prophylactic dose of enoxaparin adjusted by anti-Xa&#xD;
      activity reduces thrombin generation to &lt;700 nanomolar-minute (nM.min), as measured by&#xD;
      endogenous thrombin potential (ETP). In non-critically ill adults, prophylactic dose of&#xD;
      enoxaparin proven to prevent DVT reduces ETP to &lt;700 nM.min. Endogenous thrombin potential is&#xD;
      the best available measure of thrombin generation. We will measure endogenous thrombin&#xD;
      potential and anti-Xa activity at multiple time points then examine their relationship in all&#xD;
      children enrolled in the phase 2a trial. The proposed research challenges the current&#xD;
      paradigm on prophylaxis against CADVT in children. High quality evidence is needed to prevent&#xD;
      CADVT and its complications in this vulnerable population.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Met protocol defined stopping rule for futility&#xD;
  </why_stopped>
  <start_date type="Actual">April 5, 2017</start_date>
  <completion_date type="Actual">August 16, 2019</completion_date>
  <primary_completion_date type="Actual">August 16, 2019</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Eligible subjects will be randomized 1:1 to treatment or control.</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants With Central Venous Catheter (CVC)- Associated Deep Vein Thrombosis (DVT)</measure>
    <time_frame>Up to removal of CVC, an average of 6 days</time_frame>
    <description>Thrombus in the central vein where the CVC was inserted that is clinically suspected then confirmed radiologically, an incidental radiologic finding, or diagnosed with the study-related active surveillance ultrasound</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Endogenous Thrombin Potential</measure>
    <time_frame>Day of, day after and day 4 after insertion of the CVC</time_frame>
    <description>An established measure of coagulation status and is the best method to measure thrombin generation. It directly measures the amount of thrombin generation over time capturing the effects of natural (i.e., subject's coagulation status) and pharmacological (e.g., enoxaparin) pro- and anticoagulants. Endogenous thrombin potential is measured using thrombin generation assay.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number With Other Thromboembolic Events</measure>
    <time_frame>Up to removal of CVC, an average of 6 days</time_frame>
    <description>Thrombus in the deep vein of any extremity or PE that is clinically suspected then confirmed radiologically, an incidental radiologic finding, excluding DVT diagnosed with the study-related active surveillance ultrasound</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of Stay in the Pediatric Intensive Care Unit in Days</measure>
    <time_frame>Up to day of discharge from the pediatric intensive care unit, an average of 10 days</time_frame>
    <description>Duration of stay in the pediatric intensive care unit from the day of enrollment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of Stay in the Hospital</measure>
    <time_frame>Up to day of discharge from the hospital, an average of 18 days</time_frame>
    <description>Duration of stay in the hospital from the day of enrollment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number With Clinically Relevant Bleeding</measure>
    <time_frame>Up to 30 hours after the last enoxaparin dose</time_frame>
    <description>Bleeding that is fatal, associated with a decrease in hemoglobin by ≥2 g/dl in 24 hours, requires medical or surgical intervention to restore hemostasis, or is in the retroperitoneum, pulmonary, intracranial or central nervous system as defined by International Society of Thrombosis and Haemostasis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number With Laboratory Confirmed Heparin-induced Thrombocytopenia</measure>
    <time_frame>Up to removal of CVC, an average of 6 days</time_frame>
    <description>Heparin-induced thrombocytopenia that is diagnosed with a positive serotonin release assay</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Mortality</measure>
    <time_frame>Up to day of discharge from the hospital, average of 18 days</time_frame>
    <description>In-hospital mortality during the subject's admission</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Enrolled Eligible Children</measure>
    <time_frame>Up to 24 hours after insertion of CVC</time_frame>
    <description>Number of eligible children enrolled in the study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to 1st Dose of Enoxaparin</measure>
    <time_frame>Up to 48 hours after insertion of CVC</time_frame>
    <description>Time to first dose of enoxaparin</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Target Anti-Xa Activity</measure>
    <time_frame>Up to removal of CVC, an average of 6 days</time_frame>
    <description>Time from insertion of the CVC to time that anti-Xa activity was within 0.2-0.5 IU/mL.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Missed Doses of Enoxaparin</measure>
    <time_frame>Up to removal of CVC, an average of 6 days</time_frame>
    <description>Number of doses of enoxaparin that were not administered. This outcome measure was only applicable to the enoxaparin arm.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Children With Ultrasound</measure>
    <time_frame>Up to 24 hours after removal of CVC</time_frame>
    <description>Number of children in whom ultrasound was not performed.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">51</enrollment>
  <condition>Deep Venous Thrombosis</condition>
  <arm_group>
    <arm_group_label>Prophylaxis with enoxaparin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A clinical nurse will administer enoxaparin subcutaneously &lt;24 hours after insertion of the central venous catheter and then give enoxaparin subcutaneously every 12 hours until the removal of the catheter.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control arm</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Participants randomized to the control arm will receive no 'placebo' intervention.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Enoxaparin</intervention_name>
    <description>The clinical nurse will give enoxaparin subcutaneously every 12 hours at the currently used starting dose of 0.75 mg/kg for children ≤2 months old or 0.5 mg/kg (maximum of 40 mg) for older children. The 1st dose will be given &lt;24 hours after insertion of the catheter. Doses will be adjusted to target an anti-Xa level of 0.2-0.5 IU/mL.</description>
    <arm_group_label>Prophylaxis with enoxaparin</arm_group_label>
    <other_name>Lovenox</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria&#xD;
&#xD;
          1. Untunneled CVC inserted in the internal jugular or femoral vein within the past 24&#xD;
             hours&#xD;
&#xD;
          2. Child anticipated to stay in the pediatric intensive care unit ≥48 hours&#xD;
&#xD;
          3. CVC anticipated to be required for ≥24 hours&#xD;
&#xD;
          4. &gt;36 weeks corrected gestational age to &lt;18 years old&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
          1. Coagulopathy (i.e., international normalized ratio &gt;2.0, activated partial&#xD;
             thromboplastin time &gt;50 seconds or platelet count &lt;50,000/mm3)&#xD;
&#xD;
          2. Known bleeding disorder&#xD;
&#xD;
          3. Clinically relevant bleeding as defined by the International Society on Thrombosis and&#xD;
             Hemostasis (i.e., Hb decreased ≥2 g/dl in 24 hours, required medical or surgical&#xD;
             intervention to restore hemostasis, or in a critical organ system [i.e.,&#xD;
             retroperitoneum, pulmonary, intracranial or central nervous system])&#xD;
&#xD;
          4. &lt;60 days from a clinically relevant bleeding as defined above&#xD;
&#xD;
          5. &lt;7 days after trauma or surgery&#xD;
&#xD;
          6. Anticipated surgery within 48 hours after insertion of the CVC&#xD;
&#xD;
          7. Renal failure (i.e., creatinine clearance &lt;30 mL/min)&#xD;
&#xD;
          8. Presence of epidural catheter&#xD;
&#xD;
          9. Currently taking an antithrombotic agent (e.g., low molecular weight heparin (LMWH),&#xD;
             unfractionated heparin (UFH) at therapeutic doses, Coumadin or aspirin)&#xD;
&#xD;
         10. Radiologically documented DVT at the site of insertion of the CVC in the previous 6&#xD;
             weeks&#xD;
&#xD;
         11. Known hypersensitivity to heparin or its components, including pork products&#xD;
&#xD;
         12. History of heparin-induced thrombocytopenia (HIT) (i.e., positive serotonin release&#xD;
             assay)&#xD;
&#xD;
         13. Currently pregnant&#xD;
&#xD;
         14. Currently lactating&#xD;
&#xD;
         15. Prior enrollment in the study&#xD;
&#xD;
         16. Limitation of care&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>17 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>E. Vincent S Faustino, MD, MHS</last_name>
    <role>Principal Investigator</role>
    <affiliation>Associate Professor of Pediatrics, Yale School of Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Yale University Yale New Haven Health</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06520</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Louis Children's Hospital-Washington University School of Medicine-</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Weill Cornell Medicine</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Rochester Medical Center-Golisano Children's Hospital-</name>
      <address>
        <city>Rochester</city>
        <state>New York</state>
        <zip>14642</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Maria Fareri Children's Hospital</name>
      <address>
        <city>Valhalla</city>
        <state>New York</state>
        <zip>10595</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospital of Wisconsin/Medical College of Wisconsin</name>
      <address>
        <city>Milwaukee</city>
        <state>Wisconsin</state>
        <zip>53226</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2020</verification_date>
  <study_first_submitted>December 19, 2016</study_first_submitted>
  <study_first_submitted_qc>December 21, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 28, 2016</study_first_posted>
  <results_first_submitted>June 17, 2020</results_first_submitted>
  <results_first_submitted_qc>July 10, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">July 13, 2020</results_first_posted>
  <last_update_submitted>July 10, 2020</last_update_submitted>
  <last_update_submitted_qc>July 10, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 13, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>child</keyword>
  <keyword>critical illness</keyword>
  <keyword>venous thromboembolism</keyword>
  <keyword>enoxaparin</keyword>
  <keyword>thrombin generation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Thrombosis</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>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>August 25, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/90/NCT03003390/ICF_000.pdf</document_url>
    </provided_document>
    <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>August 22, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/90/NCT03003390/Prot_SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>One participant in the enoxaparin group was enrolled during a single arm phase and not included in the analysis.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Prophylaxis With Enoxaparin</title>
          <description>A clinical nurse will administer enoxaparin subcutaneously &lt;24 hours after insertion of the central venous catheter and then give enoxaparin subcutaneously every 12 hours until the removal of the catheter.&#xD;
Enoxaparin: The clinical nurse will give enoxaparin subcutaneously every 12 hours at the currently used starting dose of 0.75 mg/kg for children ≤2 months old or 0.5 mg/kg (maximum of 40 mg) for older children. The 1st dose will be given &lt;24 hours after insertion of the catheter. Doses will be adjusted to target an anti-Xa level of 0.2-0.5 IU/mL.</description>
        </group>
        <group group_id="P2">
          <title>Control Arm</title>
          <description>Participants randomized to the control arm will receive no 'placebo' intervention.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="27"/>
                <participants group_id="P2" count="24"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="23"/>
                <participants group_id="P2" count="24"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Parent refused intervention</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Prophylaxis With Enoxaparin</title>
          <description>A clinical nurse will administer enoxaparin subcutaneously &lt;24 hours after insertion of the central venous catheter and then give enoxaparin subcutaneously every 12 hours until the removal of the catheter.&#xD;
Enoxaparin: The clinical nurse will give enoxaparin subcutaneously every 12 hours at the currently used starting dose of 0.75 mg/kg for children ≤2 months old or 0.5 mg/kg (maximum of 40 mg) for older children. The 1st dose will be given &lt;24 hours after insertion of the catheter. Doses will be adjusted to target an anti-Xa level of 0.2-0.5 IU/mL.</description>
        </group>
        <group group_id="B2">
          <title>Control Arm</title>
          <description>Participants randomized to the control arm will receive no 'placebo' intervention.</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="27"/>
            <count group_id="B2" value="24"/>
            <count group_id="B3" value="51"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;1 year old</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="24"/>
                  </measurement_list>
                </category>
                <category>
                  <title>1-13 years old</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="23"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;13 years old</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="4"/>
                  </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="16"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="28"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="22"/>
                    <measurement group_id="B2" value="19"/>
                    <measurement group_id="B3" value="41"/>
                  </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>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="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="13"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="37"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</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>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>Size of Central Venous Catheter (CVC)</title>
          <description>The size of the CVC may affect the risk of CVC-associated DVT. Larger diameter of the CVC, i.e. higher F, particular relative to the size of the central vein has been associated with higher risk of DVT. The size of the CVC was determined by the clinical team.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>3 French (F)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>4 F</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>5 F</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>7 F</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Number of Lumens of CVC</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Site of Insertion of CVC</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Left Femoral</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Right Internal Jugular</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Right Femoral</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Central Venous Catheter (CVC)- Associated Deep Vein Thrombosis (DVT)</title>
        <description>Thrombus in the central vein where the CVC was inserted that is clinically suspected then confirmed radiologically, an incidental radiologic finding, or diagnosed with the study-related active surveillance ultrasound</description>
        <time_frame>Up to removal of CVC, an average of 6 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Prophylaxis With Enoxaparin</title>
            <description>A clinical nurse will administer enoxaparin subcutaneously &lt;24 hours after insertion of the central venous catheter and then give enoxaparin subcutaneously every 12 hours until the removal of the catheter.&#xD;
Enoxaparin: The clinical nurse will give enoxaparin subcutaneously every 12 hours at the currently used starting dose of 0.75 mg/kg for children ≤2 months old or 0.5 mg/kg (maximum of 40 mg) for older children. The 1st dose will be given &lt;24 hours after insertion of the catheter. Doses will be adjusted to target an anti-Xa level of 0.2-0.5 IU/mL.</description>
          </group>
          <group group_id="O2">
            <title>Control Arm</title>
            <description>Participants randomized to the control arm will receive no 'placebo' intervention.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Central Venous Catheter (CVC)- Associated Deep Vein Thrombosis (DVT)</title>
          <description>Thrombus in the central vein where the CVC was inserted that is clinically suspected then confirmed radiologically, an incidental radiologic finding, or diagnosed with the study-related active surveillance ultrasound</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="23"/>
                <count group_id="O2" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                    <measurement group_id="O2" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <param_type>Posterior probabilities</param_type>
            <param_value>0.09</param_value>
            <ci_n_sides>2-Sided</ci_n_sides>
            <other_analysis_desc>Using informative priors of B(1, 1) on the enoxaparin arm and B(18, 82) on the usual care arm, the risks of CADVT were 0.32 (95% CrI: 0.16, 0.51) in the enoxaparin arm and 0.25 (95% CrI: 0.18, 0.33) in the usual care arm. The posterior probability that the absolute difference in the risk of CADVT was lower by 0.06 in the enoxaparin arm was 9.1%. Using minimally informative priors, the risk ratio of CADVT with enoxaparin was 0.55 (95% CrI: 0.24, 1.11).</other_analysis_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Endogenous Thrombin Potential</title>
        <description>An established measure of coagulation status and is the best method to measure thrombin generation. It directly measures the amount of thrombin generation over time capturing the effects of natural (i.e., subject's coagulation status) and pharmacological (e.g., enoxaparin) pro- and anticoagulants. Endogenous thrombin potential is measured using thrombin generation assay.</description>
        <time_frame>Day of, day after and day 4 after insertion of the CVC</time_frame>
        <population>The numbers analyzed on the day after CVC insertion and four days after CVC insertion differ from the overall number of participants. Participants were excluded if the CVC was removed or if blood was not drawn.</population>
        <group_list>
          <group group_id="O1">
            <title>Prophylaxis With Enoxaparin</title>
            <description>A clinical nurse will administer enoxaparin subcutaneously &lt;24 hours after insertion of the central venous catheter and then give enoxaparin subcutaneously every 12 hours until the removal of the catheter.&#xD;
Enoxaparin: The clinical nurse will give enoxaparin subcutaneously every 12 hours at the currently used starting dose of 0.75 mg/kg for children ≤2 months old or 0.5 mg/kg (maximum of 40 mg) for older children. The 1st dose will be given &lt;24 hours after insertion of the catheter. Doses will be adjusted to target an anti-Xa level of 0.2-0.5 IU/mL.</description>
          </group>
          <group group_id="O2">
            <title>Control Arm</title>
            <description>Participants randomized to the control arm will receive no 'placebo' intervention.</description>
          </group>
        </group_list>
        <measure>
          <title>Endogenous Thrombin Potential</title>
          <description>An established measure of coagulation status and is the best method to measure thrombin generation. It directly measures the amount of thrombin generation over time capturing the effects of natural (i.e., subject's coagulation status) and pharmacological (e.g., enoxaparin) pro- and anticoagulants. Endogenous thrombin potential is measured using thrombin generation assay.</description>
          <population>The numbers analyzed on the day after CVC insertion and four days after CVC insertion differ from the overall number of participants. Participants were excluded if the CVC was removed or if blood was not drawn.</population>
          <units>Nanomolar-minute (nM.min)</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="27"/>
                <count group_id="O2" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day of CVC Insertion</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="27"/>
                    <count group_id="O2" value="24"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="919.7" lower_limit="418.71" upper_limit="1150.77"/>
                    <measurement group_id="O2" value="1035.6" lower_limit="800.22" upper_limit="1455.05"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day After CVC Insertion</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="24"/>
                    <count group_id="O2" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="851.19" lower_limit="627.31" upper_limit="995.98"/>
                    <measurement group_id="O2" value="896.58" lower_limit="433.9" upper_limit="1331.03"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 4 After CVC Insertion</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="20"/>
                    <count group_id="O2" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="826.97" lower_limit="0" upper_limit="1131.7"/>
                    <measurement group_id="O2" value="969.89" lower_limit="605.35" upper_limit="1302.95"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.22</p_value>
            <method>Linear mixed effects model</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number With Other Thromboembolic Events</title>
        <description>Thrombus in the deep vein of any extremity or PE that is clinically suspected then confirmed radiologically, an incidental radiologic finding, excluding DVT diagnosed with the study-related active surveillance ultrasound</description>
        <time_frame>Up to removal of CVC, an average of 6 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Prophylaxis With Enoxaparin</title>
            <description>A clinical nurse will administer enoxaparin subcutaneously &lt;24 hours after insertion of the central venous catheter and then give enoxaparin subcutaneously every 12 hours until the removal of the catheter.&#xD;
Enoxaparin: The clinical nurse will give enoxaparin subcutaneously every 12 hours at the currently used starting dose of 0.75 mg/kg for children ≤2 months old or 0.5 mg/kg (maximum of 40 mg) for older children. The 1st dose will be given &lt;24 hours after insertion of the catheter. Doses will be adjusted to target an anti-Xa level of 0.2-0.5 IU/mL.</description>
          </group>
          <group group_id="O2">
            <title>Control Arm</title>
            <description>Participants randomized to the control arm will receive no 'placebo' intervention.</description>
          </group>
        </group_list>
        <measure>
          <title>Number With Other Thromboembolic Events</title>
          <description>Thrombus in the deep vein of any extremity or PE that is clinically suspected then confirmed radiologically, an incidental radiologic finding, excluding DVT diagnosed with the study-related active surveillance ultrasound</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="27"/>
                <count group_id="O2" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>1.00</p_value>
            <method>Fisher Exact</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Length of Stay in the Pediatric Intensive Care Unit in Days</title>
        <description>Duration of stay in the pediatric intensive care unit from the day of enrollment</description>
        <time_frame>Up to day of discharge from the pediatric intensive care unit, an average of 10 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Prophylaxis With Enoxaparin</title>
            <description>A clinical nurse will administer enoxaparin subcutaneously &lt;24 hours after insertion of the central venous catheter and then give enoxaparin subcutaneously every 12 hours until the removal of the catheter.&#xD;
Enoxaparin: The clinical nurse will give enoxaparin subcutaneously every 12 hours at the currently used starting dose of 0.75 mg/kg for children ≤2 months old or 0.5 mg/kg (maximum of 40 mg) for older children. The 1st dose will be given &lt;24 hours after insertion of the catheter. Doses will be adjusted to target an anti-Xa level of 0.2-0.5 IU/mL.</description>
          </group>
          <group group_id="O2">
            <title>Control Arm</title>
            <description>Participants randomized to the control arm will receive no 'placebo' intervention.</description>
          </group>
        </group_list>
        <measure>
          <title>Length of Stay in the Pediatric Intensive Care Unit in Days</title>
          <description>Duration of stay in the pediatric intensive care unit from the day of enrollment</description>
          <units>days</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="27"/>
                <count group_id="O2" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12" lower_limit="6" upper_limit="22"/>
                    <measurement group_id="O2" value="8" lower_limit="4" upper_limit="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.31</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Length of Stay in the Hospital</title>
        <description>Duration of stay in the hospital from the day of enrollment</description>
        <time_frame>Up to day of discharge from the hospital, an average of 18 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Prophylaxis With Enoxaparin</title>
            <description>A clinical nurse will administer enoxaparin subcutaneously &lt;24 hours after insertion of the central venous catheter and then give enoxaparin subcutaneously every 12 hours until the removal of the catheter.&#xD;
Enoxaparin: The clinical nurse will give enoxaparin subcutaneously every 12 hours at the currently used starting dose of 0.75 mg/kg for children ≤2 months old or 0.5 mg/kg (maximum of 40 mg) for older children. The 1st dose will be given &lt;24 hours after insertion of the catheter. Doses will be adjusted to target an anti-Xa level of 0.2-0.5 IU/mL.</description>
          </group>
          <group group_id="O2">
            <title>Control Arm</title>
            <description>Participants randomized to the control arm will receive no 'placebo' intervention.</description>
          </group>
        </group_list>
        <measure>
          <title>Length of Stay in the Hospital</title>
          <description>Duration of stay in the hospital from the day of enrollment</description>
          <units>days</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="27"/>
                <count group_id="O2" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16" lower_limit="6" upper_limit="35"/>
                    <measurement group_id="O2" value="16" lower_limit="7" upper_limit="23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.58</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number With Clinically Relevant Bleeding</title>
        <description>Bleeding that is fatal, associated with a decrease in hemoglobin by ≥2 g/dl in 24 hours, requires medical or surgical intervention to restore hemostasis, or is in the retroperitoneum, pulmonary, intracranial or central nervous system as defined by International Society of Thrombosis and Haemostasis</description>
        <time_frame>Up to 30 hours after the last enoxaparin dose</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Prophylaxis With Enoxaparin</title>
            <description>A clinical nurse will administer enoxaparin subcutaneously &lt;24 hours after insertion of the central venous catheter and then give enoxaparin subcutaneously every 12 hours until the removal of the catheter.&#xD;
Enoxaparin: The clinical nurse will give enoxaparin subcutaneously every 12 hours at the currently used starting dose of 0.75 mg/kg for children ≤2 months old or 0.5 mg/kg (maximum of 40 mg) for older children. The 1st dose will be given &lt;24 hours after insertion of the catheter. Doses will be adjusted to target an anti-Xa level of 0.2-0.5 IU/mL.</description>
          </group>
          <group group_id="O2">
            <title>Control Arm</title>
            <description>Participants randomized to the control arm will receive no 'placebo' intervention.</description>
          </group>
        </group_list>
        <measure>
          <title>Number With Clinically Relevant Bleeding</title>
          <description>Bleeding that is fatal, associated with a decrease in hemoglobin by ≥2 g/dl in 24 hours, requires medical or surgical intervention to restore hemostasis, or is in the retroperitoneum, pulmonary, intracranial or central nervous system as defined by International Society of Thrombosis and Haemostasis</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="27"/>
                <count group_id="O2" value="24"/>
              </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>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>1.00</p_value>
            <method>Fisher Exact</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number With Laboratory Confirmed Heparin-induced Thrombocytopenia</title>
        <description>Heparin-induced thrombocytopenia that is diagnosed with a positive serotonin release assay</description>
        <time_frame>Up to removal of CVC, an average of 6 days</time_frame>
        <population>None of the participants experienced this outcome; hence, a statistical analysis was not performed.</population>
        <group_list>
          <group group_id="O1">
            <title>Prophylaxis With Enoxaparin</title>
            <description>A clinical nurse will administer enoxaparin subcutaneously &lt;24 hours after insertion of the central venous catheter and then give enoxaparin subcutaneously every 12 hours until the removal of the catheter.&#xD;
Enoxaparin: The clinical nurse will give enoxaparin subcutaneously every 12 hours at the currently used starting dose of 0.75 mg/kg for children ≤2 months old or 0.5 mg/kg (maximum of 40 mg) for older children. The 1st dose will be given &lt;24 hours after insertion of the catheter. Doses will be adjusted to target an anti-Xa level of 0.2-0.5 IU/mL.</description>
          </group>
          <group group_id="O2">
            <title>Control Arm</title>
            <description>Participants randomized to the control arm will receive no 'placebo' intervention.</description>
          </group>
        </group_list>
        <measure>
          <title>Number With Laboratory Confirmed Heparin-induced Thrombocytopenia</title>
          <description>Heparin-induced thrombocytopenia that is diagnosed with a positive serotonin release assay</description>
          <population>None of the participants experienced this outcome; hence, a statistical analysis was not performed.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="27"/>
                <count group_id="O2" value="24"/>
              </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>
        <type>Secondary</type>
        <title>Number of Mortality</title>
        <description>In-hospital mortality during the subject's admission</description>
        <time_frame>Up to day of discharge from the hospital, average of 18 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Prophylaxis With Enoxaparin</title>
            <description>A clinical nurse will administer enoxaparin subcutaneously &lt;24 hours after insertion of the central venous catheter and then give enoxaparin subcutaneously every 12 hours until the removal of the catheter.&#xD;
Enoxaparin: The clinical nurse will give enoxaparin subcutaneously every 12 hours at the currently used starting dose of 0.75 mg/kg for children ≤2 months old or 0.5 mg/kg (maximum of 40 mg) for older children. The 1st dose will be given &lt;24 hours after insertion of the catheter. Doses will be adjusted to target an anti-Xa level of 0.2-0.5 IU/mL.</description>
          </group>
          <group group_id="O2">
            <title>Control Arm</title>
            <description>Participants randomized to the control arm will receive no 'placebo' intervention.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Mortality</title>
          <description>In-hospital mortality during the subject's admission</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="27"/>
                <count group_id="O2" value="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.43</p_value>
            <method>Fisher Exact</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Enrolled Eligible Children</title>
        <description>Number of eligible children enrolled in the study.</description>
        <time_frame>Up to 24 hours after insertion of CVC</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Eligible Children</title>
            <description>Children eligible to participate in this study.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Enrolled Eligible Children</title>
          <description>Number of eligible children enrolled in the study.</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="164"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="51"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to 1st Dose of Enoxaparin</title>
        <description>Time to first dose of enoxaparin</description>
        <time_frame>Up to 48 hours after insertion of CVC</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Prophylaxis With Enoxaparin</title>
            <description>Participants in the treatment arm received enoxaparin.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to 1st Dose of Enoxaparin</title>
          <description>Time to first dose of enoxaparin</description>
          <units>hours from insertion of CVC</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="27"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="21.1" lower_limit="14.7" upper_limit="23.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Target Anti-Xa Activity</title>
        <description>Time from insertion of the CVC to time that anti-Xa activity was within 0.2-0.5 IU/mL.</description>
        <time_frame>Up to removal of CVC, an average of 6 days</time_frame>
        <population>This outcome measure is only applicable to subjects in the enoxaparin arm because the control arm did not receive enoxaparin for which anti-Xa activity is used to titrate the dose. Only 12 participants in the enoxaparin arm achieved the target anti-Xa activity.</population>
        <group_list>
          <group group_id="O1">
            <title>Prophylaxis With Enoxaparin</title>
            <description>Children were treated with enoxaparin</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Target Anti-Xa Activity</title>
          <description>Time from insertion of the CVC to time that anti-Xa activity was within 0.2-0.5 IU/mL.</description>
          <population>This outcome measure is only applicable to subjects in the enoxaparin arm because the control arm did not receive enoxaparin for which anti-Xa activity is used to titrate the dose. Only 12 participants in the enoxaparin arm achieved the target anti-Xa activity.</population>
          <units>hours from insertion of CVC</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="70.4" lower_limit="47.4" upper_limit="92.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Missed Doses of Enoxaparin</title>
        <description>Number of doses of enoxaparin that were not administered. This outcome measure was only applicable to the enoxaparin arm.</description>
        <time_frame>Up to removal of CVC, an average of 6 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Prophylaxis With Enoxaparin</title>
            <description>children were treated with enoxaparin</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Missed Doses of Enoxaparin</title>
          <description>Number of doses of enoxaparin that were not administered. This outcome measure was only applicable to the enoxaparin arm.</description>
          <units>Doses of enoxaparin</units>
          <param>Number</param>
          <units_analyzed>Doses</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="27"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>Doses</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="272"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Children With Ultrasound</title>
        <description>Number of children in whom ultrasound was not performed.</description>
        <time_frame>Up to 24 hours after removal of CVC</time_frame>
        <group_list>
          <group group_id="O1">
            <title>All Enrolled Children</title>
            <description>All children who participated in the study</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Children With Ultrasound</title>
          <description>Number of children in whom ultrasound was not performed.</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="51"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="47"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From hospital admission to day of discharge for death, up to 60 days.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Prophylaxis With Enoxaparin</title>
          <description>A clinical nurse will administer enoxaparin subcutaneously &lt;24 hours after insertion of the central venous catheter and then give enoxaparin subcutaneously every 12 hours until the removal of the catheter.&#xD;
Enoxaparin: The clinical nurse will give enoxaparin subcutaneously every 12 hours at the currently used starting dose of 0.75 mg/kg for children ≤2 months old or 0.5 mg/kg (maximum of 40 mg) for older children. The 1st dose will be given &lt;24 hours after insertion of the catheter. Doses will be adjusted to target an anti-Xa level of 0.2-0.5 IU/mL.</description>
        </group>
        <group group_id="E2">
          <title>Control Arm</title>
          <description>Participants randomized to the control arm will receive no 'placebo' intervention.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Non-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="5" subjects_at_risk="27"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="27"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Cardiac arrest</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="27"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>acute kidney injury</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="27"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>3</frequency_threshold>
        <default_assessment>Non-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="9" subjects_at_risk="27"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="27"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Oral hemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="27"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Edema trunk</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="27"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>General disorders and administration site conditions - Other, specify</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="27"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Tracheitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="27"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="27"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Acidosis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="27"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Hypernatremia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="27"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Hypoalbuminemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="27"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Hypocalcemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="27"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Hypoglycemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="27"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="27"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Hypophosphatemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="27"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Seizure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="27"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Hematuria</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="27"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Aspiration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="27"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="27"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="27"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Thromboembolic event</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="27"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
              </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>Dr. E. Vincent S Faustino</name_or_title>
      <organization>Yale University</organization>
      <phone>203-785-4651</phone>
      <email>vince.faustino@yale.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/NCT03003390
org study id: 1302011506
secondary id: 1R21HD089131-01A1
nct id: NCT03003390
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this phase 2a, multi-center, randomized controlled study, is to explore the
      efficacy of early prophylaxis against catheter-associated deep venous thrombosis (CADVT) in
      critically ill children.
Critical illness and the presence of a central venous catheter (CVC) are the most important
      risk factors for deep venous thrombosis (DVT) in children. Catheter-associated thrombosis
      (CADVT) is highly prevalent and associated with poor outcomes in critically ill children.
      Yet, based on underpowered pediatric trials, prophylaxis against CADVT is not recommended in
      children. The recommendation to provide prophylaxis against thrombosis in critically ill
      adults should not be applied to children because the hemostatic system and co-morbidities
      vastly differ between age groups. Pivotal trials are urgently needed to determine whether
      prophylaxis can prevent CADVT and its complications in critically ill children. However, the
      timing and extent of reduction in thrombin generation, the biochemical goal of prophylaxis,
      needed to prevent CADVT in children are unclear. The goal of this application is to explore
      the efficacy of early prophylaxis against CADVT in critically ill children. Aim 1 is to
      obtain preliminary evidence on the effect of early prophylaxis on the incidence of CADVT in
      critically ill children. Based on the natural history of CADVT, we hypothesize that among
      critically ill children, prophylaxis administered <24 hours after catheter insertion
      decreases the incidence of ultrasound-diagnosed CADVT compared with no prophylaxis. In this
      phase 2a trial, children admitted to the intensive care unit with a newly inserted central
      venous catheter will receive enoxaparin adjusted according to anti-Xa activity, a control
      group will not receive enoxaparin adjusted according to anti-Xa activity. Enoxaparin has
      become the "standard" pediatric anticoagulant for prophylaxis despite the absence of
      conclusive data. We will use Bayesian approach to determine whether further trials are
      warranted. Aim 2 is to evaluate the effect of an anti-Xa activity-directed prophylactic
      strategy on thrombin generation in critically ill children. We hypothesize that among
      critically ill children, standard prophylactic dose of enoxaparin adjusted by anti-Xa
      activity reduces thrombin generation to <700 nanomolar-minute (nM.min), as measured by
      endogenous thrombin potential (ETP). In non-critically ill adults, prophylactic dose of
      enoxaparin proven to prevent DVT reduces ETP to <700 nM.min. Endogenous thrombin potential is
      the best available measure of thrombin generation. We will measure endogenous thrombin
      potential and anti-Xa activity at multiple time points then examine their relationship in all
      children enrolled in the phase 2a trial. The proposed research challenges the current
      paradigm on prophylaxis against CADVT in children. High quality evidence is needed to prevent
      CADVT and its complications in this vulnerable population.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Eligible subjects will be randomized 1:1 to treatment or control.
primary purpose: Prevention
masking: None (Open Label)
measure: Number of Participants With Central Venous Catheter (CVC)- Associated Deep Vein Thrombosis (DVT)
time frame: Up to removal of CVC, an average of 6 days
description: Thrombus in the central vein where the CVC was inserted that is clinically suspected then confirmed radiologically, an incidental radiologic finding, or diagnosed with the study-related active surveillance ultrasound
measure: Endogenous Thrombin Potential
time frame: Day of, day after and day 4 after insertion of the CVC
description: An established measure of coagulation status and is the best method to measure thrombin generation. It directly measures the amount of thrombin generation over time capturing the effects of natural (i.e., subject's coagulation status) and pharmacological (e.g., enoxaparin) pro- and anticoagulants. Endogenous thrombin potential is measured using thrombin generation assay.
measure: Number With Other Thromboembolic Events
time frame: Up to removal of CVC, an average of 6 days
description: Thrombus in the deep vein of any extremity or PE that is clinically suspected then confirmed radiologically, an incidental radiologic finding, excluding DVT diagnosed with the study-related active surveillance ultrasound
measure: Length of Stay in the Pediatric Intensive Care Unit in Days
time frame: Up to day of discharge from the pediatric intensive care unit, an average of 10 days
description: Duration of stay in the pediatric intensive care unit from the day of enrollment
measure: Length of Stay in the Hospital
time frame: Up to day of discharge from the hospital, an average of 18 days
description: Duration of stay in the hospital from the day of enrollment
measure: Number With Clinically Relevant Bleeding
time frame: Up to 30 hours after the last enoxaparin dose
description: Bleeding that is fatal, associated with a decrease in hemoglobin by ≥2 g/dl in 24 hours, requires medical or surgical intervention to restore hemostasis, or is in the retroperitoneum, pulmonary, intracranial or central nervous system as defined by International Society of Thrombosis and Haemostasis
measure: Number With Laboratory Confirmed Heparin-induced Thrombocytopenia
time frame: Up to removal of CVC, an average of 6 days
description: Heparin-induced thrombocytopenia that is diagnosed with a positive serotonin release assay
measure: Number of Mortality
time frame: Up to day of discharge from the hospital, average of 18 days
description: In-hospital mortality during the subject's admission
measure: Number of Enrolled Eligible Children
time frame: Up to 24 hours after insertion of CVC
description: Number of eligible children enrolled in the study.
measure: Time to 1st Dose of Enoxaparin
time frame: Up to 48 hours after insertion of CVC
description: Time to first dose of enoxaparin
measure: Time to Target Anti-Xa Activity
time frame: Up to removal of CVC, an average of 6 days
description: Time from insertion of the CVC to time that anti-Xa activity was within 0.2-0.5 IU/mL.
measure: Number of Missed Doses of Enoxaparin
time frame: Up to removal of CVC, an average of 6 days
description: Number of doses of enoxaparin that were not administered. This outcome measure was only applicable to the enoxaparin arm.
measure: Number of Children With Ultrasound
time frame: Up to 24 hours after removal of CVC
description: Number of children in whom ultrasound was not performed.
arm group label: Prophylaxis with enoxaparin
arm group type: Experimental
description: A clinical nurse will administer enoxaparin subcutaneously <24 hours after insertion of the central venous catheter and then give enoxaparin subcutaneously every 12 hours until the removal of the catheter.
arm group label: Control arm
arm group type: No Intervention
description: Participants randomized to the control arm will receive no 'placebo' intervention.
intervention type: Drug
intervention name: Enoxaparin
description: The clinical nurse will give enoxaparin subcutaneously every 12 hours at the currently used starting dose of 0.75 mg/kg for children ≤2 months old or 0.5 mg/kg (maximum of 40 mg) for older children. The 1st dose will be given <24 hours after insertion of the catheter. Doses will be adjusted to target an anti-Xa level of 0.2-0.5 IU/mL.
arm group label: Prophylaxis with enoxaparin
other name: Lovenox
criteria: 
gender: All
minimum age: N/A
maximum age: 17 Years
healthy volunteers: No
last name: E. Vincent S Faustino, MD, MHS
role: Principal Investigator
affiliation: Associate Professor of Pediatrics, Yale School of Medicine
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country: United States
responsible party type: Sponsor
mesh term: Thrombosis
mesh term: Venous Thrombosis
mesh term: Enoxaparin
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