xml: <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/NCT06025162</url>
    </required_header>
    <id_info>
      <org_study_id>028.PHA.2022.D</org_study_id>
      <nct_id>NCT06025162</nct_id>
    </id_info>
    <brief_title>Evaluation of Chemical Venous Thromboembolism Prophylaxis in Trauma</brief_title>
    <official_title>Evaluation of Chemical Venous Thromboembolism Prophylaxis in Trauma</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Methodist Health System</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Methodist Health System</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        Venous thromboembolism (VTE) causes up to 100,000 deaths annually. Between 10%-30% of&#xD;
        patients die within one month of VTE diagnosis, while survivors remain at increased risk for&#xD;
        VTE recurrence or other complications like post-thrombotic syndrome or chronic pulmonary&#xD;
        hypertension in the following decade. Trauma patients have many risk factors that predispose&#xD;
        them to a VTE. During the first 48 hours after blunt trauma, patients are prothrombotic due&#xD;
        to the release of procoagulant factors, have excessive thrombin generation due to extensive&#xD;
        tissue and vascular injury, and have reduced circulation of endogenous anticoagulants like&#xD;
        protein C.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Trauma patients have many risk factors that predispose them to a VTE. During the first 48&#xD;
        hours after blunt trauma, patients are prothrombotic due to the release of procoagulant&#xD;
        factors, have excessive thrombin generation due to extensive tissue and vascular injury, and&#xD;
        have reduced circulation of endogenous anticoagulants like protein C. Trauma patients are&#xD;
        immobile for prolonged periods of time due to frequent surgical intervention and extended&#xD;
        sedation. Even when administered chemoprophylaxis, up to 15% of trauma patients develop&#xD;
        thromboses. Given the high rates of thromboses, one study validated certain risk factors for&#xD;
        VTE among trauma patients. This study categorized patients as high-risk or very high-risk of&#xD;
        VTE based on patient-specific factors. High-risk factors for VTE included a history of VTE,&#xD;
        repair or ligation of major venous injury, an abbreviated injury scale (AIS) &gt;2 for the head,&#xD;
        a Glasgow coma Scale (GCS) score &lt;8 for &gt;4 hours after trauma, and age ≥60 years. Very&#xD;
        high-risk factors for VTE consist of complex lower extremity fractures, pelvic fractures,&#xD;
        spinal cord injury with associated para- or quadriplegia, and age ≥75 years. The 2020 Western&#xD;
        Trauma Association guidelines recommend initiation of VTE prophylaxis with enoxaparin within&#xD;
        24 hours of admission in trauma patients, with special consideration for patients with active&#xD;
        bleeding, solid organ injury, traumatic brain injury (TBI), or spinal cord injury. Several&#xD;
        studies support this recommendation and correlate delays in VTE prophylaxis initiation and&#xD;
        interruption in therapy with increased risk of VTE.&#xD;
  &#xD;
        Recent evidence also highlights that the standard trauma VTE dosing strategy of 30 mg of&#xD;
        enoxaparin twice daily often fails to reach adequate target anti-Xa levels in trauma&#xD;
        patients. Thus, consideration of 0.5 mg/kg enoxaparin twice daily with adjustments based on&#xD;
        anti-Xa levels may be considered in patients at highest risk of VTE. This strategy may be&#xD;
        associated with improved outcomes while mitigating adverse effects like clinically&#xD;
        significant bleeding.&#xD;
  &#xD;
        Despite these recommendations, providers may choose to delay initiation of VTE prophylaxis&#xD;
        due to a patient's apparent bleeding risk. Trauma-induced coagulopathy is present in 20%-25%&#xD;
        of patients and is associated with a higher incidence of bleeding, increased transfusion&#xD;
        requirements, and elevated risk of multi-organ failure versus patients without this&#xD;
        coagulopathy. Additionally, chemical VTE prophylaxis with anticoagulants like LMWH may&#xD;
        increase bleeding possibility, especially in patients that are at risk for emergent surgical&#xD;
        intervention. Even so, current evidence supports that early initiation of VTE prophylaxis in&#xD;
        high-risk patients, as benefit outweighs bleed risk.&#xD;
  &#xD;
        Special trauma populations like TBI, spinal cord injury, and solid organ injury have been the&#xD;
        focus of recent studies evaluating bleeding risk after initiation of VTE prophylaxis. In one&#xD;
        study, TBI patients were at a significantly increased risk for VTE and substantial delays in&#xD;
        VTE prophylaxis initiation (7 days vs 1.5 days) versus non-TBI patients. Concern for&#xD;
        intracranial hemorrhage (ICH) progression was most likely found to cause delays in VTE&#xD;
        prophylaxis in this high-risk population despite the overall low incidence of this finding.15&#xD;
        In patients with intracranial bleeding, two studies identified that initiation of VTE&#xD;
        prophylaxis 24 hours after stable computerized tomography (CT) imaging did not increase risk&#xD;
        of ICH progression while decreasing overall incidence of VTE. For patients with blunt solid&#xD;
        organ injury, initiation of VTE prophylaxis within 48 hours of injury was not associated with&#xD;
        an escalation in bleeding events, but delaying prophylaxis beyond 72 hours correlated with in&#xD;
        increased risk for VTE. VTE prophylaxis initiation within 48 hours of non-operative spinal&#xD;
        cord injury was also found to significantly reduce VTE incidence versus initiation beyond 48&#xD;
        hours.&#xD;
  &#xD;
        In 2020, Methodist Dallas Medical Center's (MDMC's) pharmacy department developed a guideline&#xD;
        for VTE prophylaxis in trauma patients. This document was designed to improve patient&#xD;
        outcomes by providing evidence to assist providers when initiating patients on chemical VTE&#xD;
        prophylaxis and support the safe and efficacious use of weight-based VTE prophylaxis regimens&#xD;
        in patients at high-risk of VTE. The guideline's algorithm first recommends assessing for&#xD;
        contraindications for chemical VTE prophylaxis (like ongoing hemorrhagic shock). After&#xD;
        assessing contraindications and creatinine clearance, the document provided guidance on LMWH&#xD;
        dosing strategies, suggested patient populations for weight-based prophylaxis regimens, and&#xD;
        recommended timeframes for initiation of VTE prophylaxis based on injury type. Patient&#xD;
        outcomes have not been assessed since the implementation of MDMC-specific VTE prophylaxis&#xD;
        trauma guidelines.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Enrolling by invitation</overall_status>
    <start_date type="Actual">July 21, 2023</start_date>
    <completion_date type="Anticipated">August 31, 2024</completion_date>
    <primary_completion_date type="Anticipated">August 31, 2024</primary_completion_date>
    <study_type>Observational</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <observational_model>Cohort</observational_model>
      <time_perspective>Retrospective</time_perspective>
    </study_design_info>
    <primary_outcome>
      <measure>Episodes of clinically significant bleeding after VTE prophylaxis initiation</measure>
      <time_frame>&quot;48 Hours&quot;</time_frame>
      <description>High-risk factors for VTE included a history of VTE, repair or ligation of major venous injury, an abbreviated injury scale (AIS) &gt;2 for the head, a Glasgow coma Scale (GCS) score &lt;8 for &gt;4 hours after trauma, and age ≥60 years. Very high-risk factors for VTE consist of complex lower extremity fractures, pelvic fractures, spinal cord injury with associated para- or quadriplegia, and age ≥75 years.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Time to clinically significant bleeding after VTE prophylaxis initiation</measure>
      <time_frame>&quot;48 Hours&quot;</time_frame>
      <description>During the first 48 hours after blunt trauma, patients are prothrombotic due to the release of procoagulant factors, have excessive thrombin generation due to extensive tissue and vascular injury, and have reduced circulation of endogenous anticoagulants like protein C.5,6 Trauma patients are immobile for prolonged periods of time due to frequent surgical intervention and extended sedation.</description>
    </primary_outcome>
    <number_of_groups>1</number_of_groups>
    <enrollment type="Anticipated">100</enrollment>
    <condition>Thromboembolism, Venous</condition>
    <arm_group>
      <arm_group_label>LMWH dosing strategies</arm_group_label>
      <description>MDMC's trauma VTE prophylaxis guideline will be used to classify patients into two treatment arms (&quot;weight-based&quot; or &quot;standard dose&quot;) based on their dose of enoxaparin at 48 hours post-VTE prophylaxis initiation</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>enoxaparin</intervention_name>
      <description>dose of enoxaparin at 48 hours post-VTE prophylaxis initiation</description>
      <arm_group_label>LMWH dosing strategies</arm_group_label>
      <other_name>Accessing for contraindication for chemical VTE prophylaxis</other_name>
    </intervention>
    <eligibility>
      <study_pop>
        <textblock>
          This is a retrospective observational cohort study involving patients admitted to the&#xD;
          trauma service at Methodist Dallas Medical Center between October 1, 2021 and March 31,&#xD;
          2022.&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Non-Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  ≥18 years of age&#xD;
  &#xD;
            -  Admitted to the trauma service between October 1,2021 and March 31, 2022&#xD;
  &#xD;
            -  Weight ≥50 kg&#xD;
  &#xD;
            -  Received chemical VTE prophylaxis with LMWH for at least 48 hours&#xD;
  &#xD;
            -  At &quot;high risk&quot; or &quot;very high risk&quot; of VTE8&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Death, discharge, or hospice within 48 hours of admission&#xD;
  &#xD;
            -  Documented heparin allergy (heparin-induced thrombocytopenia)&#xD;
  &#xD;
            -  Indication for therapeutic anticoagulation, either prior to admission or during&#xD;
               hospitalization&#xD;
  &#xD;
            -  Prisoners&#xD;
  &#xD;
            -  &lt;18 years of age&#xD;
  &#xD;
            -  Pregnancy&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>120 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Tamara Reiter, PharmD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Methodist Health System</affiliation>
    </overall_official>
    <location>
      <facility>
        <name>Methodist Dallas Medical Center Pharmacy</name>
        <address>
          <city>Dallas</city>
          <state>Texas</state>
          <zip>75203</zip>
          <country>United States</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>December 20, 2022</study_first_submitted>
    <study_first_submitted_qc>September 1, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 6, 2023</study_first_posted>
    <last_update_submitted>September 1, 2023</last_update_submitted>
    <last_update_submitted_qc>September 1, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 6, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Thromboembolism</mesh_term>
      <mesh_term>Venous Thromboembolism</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Enoxaparin</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06025162
  org study id: 028.PHA.2022.D
  nct id: NCT06025162
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  Venous thromboembolism (VTE) causes up to 100,000 deaths annually. Between 10%-30% of
        patients die within one month of VTE diagnosis, while survivors remain at increased risk for
        VTE recurrence or other complications like post-thrombotic syndrome or chronic pulmonary
        hypertension in the following decade. Trauma patients have many risk factors that predispose
        them to a VTE. During the first 48 hours after blunt trauma, patients are prothrombotic due
        to the release of procoagulant factors, have excessive thrombin generation due to extensive
        tissue and vascular injury, and have reduced circulation of endogenous anticoagulants like
        protein C.
  Trauma patients have many risk factors that predispose them to a VTE. During the first 48
        hours after blunt trauma, patients are prothrombotic due to the release of procoagulant
        factors, have excessive thrombin generation due to extensive tissue and vascular injury, and
        have reduced circulation of endogenous anticoagulants like protein C. Trauma patients are
        immobile for prolonged periods of time due to frequent surgical intervention and extended
        sedation. Even when administered chemoprophylaxis, up to 15% of trauma patients develop
        thromboses. Given the high rates of thromboses, one study validated certain risk factors for
        VTE among trauma patients. This study categorized patients as high-risk or very high-risk of
        VTE based on patient-specific factors. High-risk factors for VTE included a history of VTE,
        repair or ligation of major venous injury, an abbreviated injury scale (AIS) >2 for the head,
        a Glasgow coma Scale (GCS) score <8 for >4 hours after trauma, and age ≥60 years. Very
        high-risk factors for VTE consist of complex lower extremity fractures, pelvic fractures,
        spinal cord injury with associated para- or quadriplegia, and age ≥75 years. The 2020 Western
        Trauma Association guidelines recommend initiation of VTE prophylaxis with enoxaparin within
        24 hours of admission in trauma patients, with special consideration for patients with active
        bleeding, solid organ injury, traumatic brain injury (TBI), or spinal cord injury. Several
        studies support this recommendation and correlate delays in VTE prophylaxis initiation and
        interruption in therapy with increased risk of VTE.
  
        Recent evidence also highlights that the standard trauma VTE dosing strategy of 30 mg of
        enoxaparin twice daily often fails to reach adequate target anti-Xa levels in trauma
        patients. Thus, consideration of 0.5 mg/kg enoxaparin twice daily with adjustments based on
        anti-Xa levels may be considered in patients at highest risk of VTE. This strategy may be
        associated with improved outcomes while mitigating adverse effects like clinically
        significant bleeding.
  
        Despite these recommendations, providers may choose to delay initiation of VTE prophylaxis
        due to a patient's apparent bleeding risk. Trauma-induced coagulopathy is present in 20%-25%
        of patients and is associated with a higher incidence of bleeding, increased transfusion
        requirements, and elevated risk of multi-organ failure versus patients without this
        coagulopathy. Additionally, chemical VTE prophylaxis with anticoagulants like LMWH may
        increase bleeding possibility, especially in patients that are at risk for emergent surgical
        intervention. Even so, current evidence supports that early initiation of VTE prophylaxis in
        high-risk patients, as benefit outweighs bleed risk.
  
        Special trauma populations like TBI, spinal cord injury, and solid organ injury have been the
        focus of recent studies evaluating bleeding risk after initiation of VTE prophylaxis. In one
        study, TBI patients were at a significantly increased risk for VTE and substantial delays in
        VTE prophylaxis initiation (7 days vs 1.5 days) versus non-TBI patients. Concern for
        intracranial hemorrhage (ICH) progression was most likely found to cause delays in VTE
        prophylaxis in this high-risk population despite the overall low incidence of this finding.15
        In patients with intracranial bleeding, two studies identified that initiation of VTE
        prophylaxis 24 hours after stable computerized tomography (CT) imaging did not increase risk
        of ICH progression while decreasing overall incidence of VTE. For patients with blunt solid
        organ injury, initiation of VTE prophylaxis within 48 hours of injury was not associated with
        an escalation in bleeding events, but delaying prophylaxis beyond 72 hours correlated with in
        increased risk for VTE. VTE prophylaxis initiation within 48 hours of non-operative spinal
        cord injury was also found to significantly reduce VTE incidence versus initiation beyond 48
        hours.
  
        In 2020, Methodist Dallas Medical Center's (MDMC's) pharmacy department developed a guideline
        for VTE prophylaxis in trauma patients. This document was designed to improve patient
        outcomes by providing evidence to assist providers when initiating patients on chemical VTE
        prophylaxis and support the safe and efficacious use of weight-based VTE prophylaxis regimens
        in patients at high-risk of VTE. The guideline's algorithm first recommends assessing for
        contraindications for chemical VTE prophylaxis (like ongoing hemorrhagic shock). After
        assessing contraindications and creatinine clearance, the document provided guidance on LMWH
        dosing strategies, suggested patient populations for weight-based prophylaxis regimens, and
        recommended timeframes for initiation of VTE prophylaxis based on injury type. Patient
        outcomes have not been assessed since the implementation of MDMC-specific VTE prophylaxis
        trauma guidelines.
  observational model: Cohort
  time perspective: Retrospective
  measure: Episodes of clinically significant bleeding after VTE prophylaxis initiation
  time frame: "48 Hours"
  description: High-risk factors for VTE included a history of VTE, repair or ligation of major venous injury, an abbreviated injury scale (AIS) >2 for the head, a Glasgow coma Scale (GCS) score <8 for >4 hours after trauma, and age ≥60 years. Very high-risk factors for VTE consist of complex lower extremity fractures, pelvic fractures, spinal cord injury with associated para- or quadriplegia, and age ≥75 years.
  measure: Time to clinically significant bleeding after VTE prophylaxis initiation
  time frame: "48 Hours"
  description: During the first 48 hours after blunt trauma, patients are prothrombotic due to the release of procoagulant factors, have excessive thrombin generation due to extensive tissue and vascular injury, and have reduced circulation of endogenous anticoagulants like protein C.5,6 Trauma patients are immobile for prolonged periods of time due to frequent surgical intervention and extended sedation.
  arm group label: LMWH dosing strategies
  description: MDMC's trauma VTE prophylaxis guideline will be used to classify patients into two treatment arms ("weight-based" or "standard dose") based on their dose of enoxaparin at 48 hours post-VTE prophylaxis initiation
  intervention type: Drug
  intervention name: enoxaparin
  description: dose of enoxaparin at 48 hours post-VTE prophylaxis initiation
  arm group label: LMWH dosing strategies
  other name: Accessing for contraindication for chemical VTE prophylaxis
  study pop: 
  sampling method: Non-Probability Sample
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 120 Years
  healthy volunteers: No
  last name: Tamara Reiter, PharmD
  role: Principal Investigator
  affiliation: Methodist Health System
  facility: 
  country: United States
  responsible party type: Sponsor
  mesh term: Thromboembolism
  mesh term: Venous Thromboembolism
  mesh term: Enoxaparin
  sharing ipd: No