<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/NCT03772730</url>
  </required_header>
  <id_info>
    <org_study_id>00008259</org_study_id>
    <nct_id>NCT03772730</nct_id>
  </id_info>
  <brief_title>Patient-Specific Precision Injury Signatures in Multiply Injured Orthopaedic Patients</brief_title>
  <acronym>PRECISE</acronym>
  <official_title>A Multi-Center, Prospective Observational Study to Evaluate the Use of Patient-Specific Precision Injury Signatures to Optimize Orthopaedic Interventions in Multiply Injured Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Major Extremity Trauma Research Consortium</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>United States Department of Defense</agency>
      <agency_class>U.S. Fed</agency_class>
    </collaborator>
  </sponsors>
  <source>Major Extremity Trauma Research Consortium</source>
  <oversight_info>
    <has_dmc>Yes</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>
      The purpose of this study is to evaluate the use of precision methods that quantify injury&#xD;
      and response to injury to predict how short-term clinical outcomes are affected by initial&#xD;
      and staged orthopaedic interventions in multiply injured patients (MIPs) who sustain major&#xD;
      orthopaedic trauma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      There is currently a knowledge gap regarding in the treatment of the severely injured MIP, as&#xD;
      clinicians are often challenged by when non-life threatening orthopaedic procedures should be&#xD;
      performed. Information to guide orthopaedic interventions in MIPs is based primarily on&#xD;
      resuscitation parameters and injury severity metrics.Lack of consensus among surgeons&#xD;
      regarding choices of orthopaedic interventions reflects the paucity of data to form treatment&#xD;
      decisions.&#xD;
&#xD;
      This study will define the key parameters affecting these decisions in a quantitative manner&#xD;
      by exploring the efficacy of a precision medicine approach to guide surgical decisions in&#xD;
      multiply injured patients (MIPs) with skeletal trauma. According to the National Institutes&#xD;
      of Health (NIH),36 precision medicine is &quot;an emerging approach for disease treatment and&#xD;
      prevention that takes into account individual variability in genes, environment, and&#xD;
      lifestyle for each person.&quot; This approach will allow clinicians and researchers to predict&#xD;
      more accurately which treatment and prevention strategies for a particular disease will work&#xD;
      in which groups of people. The application of precision medicine will bring to bear&#xD;
      evidence-based tools that can guide decisions facing the treating surgeons regarding the&#xD;
      optimal timing of definitive fracture surgery after injury, as well as defining the magnitude&#xD;
      of surgical intervention which may be pursued without engendering clinical complications.&#xD;
&#xD;
      Specific Aim 1: Define groups of patients based on Precision Injury Signatures (mechanical&#xD;
      and ischemic injury characteristics and immunologic response profile) that correspond to the&#xD;
      following short term clinical outcomes;&#xD;
&#xD;
        1. Multiple organ dysfunction&#xD;
&#xD;
        2. Nosocomial infection&#xD;
&#xD;
        3. Wound complications&#xD;
&#xD;
        4. Resource utilization (ICU/hospital LOS, days on mechanical ventilation, discharge&#xD;
           disposition)&#xD;
&#xD;
        5. Death&#xD;
&#xD;
      Hypothesis 1: Patients who develop complicated short term outcomes will demonstrate distinct&#xD;
      Precision Injury Signatures compared to patients who have uncomplicated outcomes for injuries&#xD;
      of similar magnitude.&#xD;
&#xD;
      Specific Aim 2: Evaluate the impact of timing and magnitude of orthopaedic surgical&#xD;
      interventions on progression of patient-specific physiologic and immunologic response.&#xD;
      Describe changes in physiologic and immunologic response after initial and staged orthopaedic&#xD;
      interventions.&#xD;
&#xD;
      Hypothesis 2: Immunologic and physiologic response to surgery will be a function of initial&#xD;
      Precision Injury Signature and timing/magnitude of orthopaedic surgical interventions.&#xD;
&#xD;
      Specific Aim 3: To develop surgical decision rules related to timing of definitive&#xD;
      orthopaedic intervention that optimize short term clinical outcomes.&#xD;
&#xD;
      Hypothesis 3a: Initial Precision Injury Signatures can be used to identify orthopaedic trauma&#xD;
      patients who are best treated with early definitive treatment or staged definitive&#xD;
      intervention.&#xD;
&#xD;
      Hypothesis 3b: Progression of Precision Injury Signatures can be used to determine optimal&#xD;
      timing and choices of definitive orthopaedic interventions.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">March 20, 2019</start_date>
  <completion_date type="Anticipated">June 30, 2023</completion_date>
  <primary_completion_date type="Actual">September 30, 2022</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>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Clinical outcomes recorded during 6month post injury medical record review</measure>
    <time_frame>6 months post injury</time_frame>
    <description>Number of occurrences of multiple organ dysfunction, nosocomial infection, wound complications, resource utilization and death as noted in medical record review.</description>
  </primary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">320</enrollment>
  <condition>Pelvic, Acetabular, Femur, or Diaphyseal Tibial Operative Orthopaedic Injuries</condition>
  <arm_group>
    <arm_group_label>Group 1</arm_group_label>
    <description>Multiply injured patients having at least one operative orthopaedic injury to the pelvis, acetabulum, femur, or diaphyseal tibia with planned definitive fixation to occur prior to discharge.</description>
  </arm_group>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Blood&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Adult (18-55) patients sustaining multiple injuries, including at least one qualifying&#xD;
        orthopaedic injury to the pelvis, acetabulum, femur, or diaphyseal tibia.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Adult ages 18 years old to 55 years old inclusive;&#xD;
&#xD;
          2. Direct admission to hospital from scene of injury, or if transferred, admitted no more&#xD;
             than 6 hours from injury&#xD;
&#xD;
          3. Full trauma activation with either direct admission to Intensive Care Unit (ICU) or&#xD;
             other higher level of care, or taken directly to surgery and admitted to ICU after&#xD;
             surgery;&#xD;
&#xD;
          4. Sustaining at least one operative orthopaedic injury to the pelvis, acetabulum, femur,&#xD;
             or diaphyseal tibia with planned definitive fixation to occur prior to discharge.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Non-survivable head trauma.&#xD;
&#xD;
          2. Signs of severe traumatic brain injury indicated by a GCS of &lt; 7 at the time of&#xD;
             admission and no improvement in the GCS by the time of consent.&#xD;
&#xD;
          3. Spinal cord injury with likely permanent neurologic deficits&#xD;
&#xD;
          4. Pre-existing organ dysfunction or failure prior to their injury, including but not&#xD;
             limited to end-stage renal disease, liver failure, congestive heart failure, or severe&#xD;
             COPD requiring home oxygen.&#xD;
&#xD;
          5. Qualifying orthopaedic injury primarily a periarticular fracture (tibial pilon or&#xD;
             plateau) with planned delay to definitive fixation for soft tissue reasons.&#xD;
&#xD;
          6. Primary blood draw could not be obtained within 3 hours of presentation&#xD;
&#xD;
          7. Patient is pregnant&#xD;
&#xD;
          8. Patient is a prisoner/incarcerated&#xD;
&#xD;
          9. Patient or legally authorized representative (LAR) unable to provide consent prior to&#xD;
             48 hour blood draw.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Todd McKinley, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Indiana University/Methodist Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Miami Ryder Trauma Center</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33101</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Methodist Hospital/Indiana University</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Kentucky Medical Center</name>
      <address>
        <city>Lexington</city>
        <state>Kentucky</state>
        <zip>40536</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Maryland, R Adams Cowley Shock Trauma Center</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Carolinas Medical Center</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>28232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Pittsburgh Medical Center</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UT Health: The University of Texas Health Science Center at Houston Medical School</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Washington Harborview Medical Center</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>December 7, 2018</study_first_submitted>
  <study_first_submitted_qc>December 10, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 11, 2018</study_first_posted>
  <last_update_submitted>January 4, 2023</last_update_submitted>
  <last_update_submitted_qc>January 4, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 5, 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>Wounds and Injuries</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03772730
org study id: 00008259
nct id: NCT03772730
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to evaluate the use of precision methods that quantify injury
      and response to injury to predict how short-term clinical outcomes are affected by initial
      and staged orthopaedic interventions in multiply injured patients (MIPs) who sustain major
      orthopaedic trauma.
There is currently a knowledge gap regarding in the treatment of the severely injured MIP, as
      clinicians are often challenged by when non-life threatening orthopaedic procedures should be
      performed. Information to guide orthopaedic interventions in MIPs is based primarily on
      resuscitation parameters and injury severity metrics.Lack of consensus among surgeons
      regarding choices of orthopaedic interventions reflects the paucity of data to form treatment
      decisions.

      This study will define the key parameters affecting these decisions in a quantitative manner
      by exploring the efficacy of a precision medicine approach to guide surgical decisions in
      multiply injured patients (MIPs) with skeletal trauma. According to the National Institutes
      of Health (NIH),36 precision medicine is "an emerging approach for disease treatment and
      prevention that takes into account individual variability in genes, environment, and
      lifestyle for each person." This approach will allow clinicians and researchers to predict
      more accurately which treatment and prevention strategies for a particular disease will work
      in which groups of people. The application of precision medicine will bring to bear
      evidence-based tools that can guide decisions facing the treating surgeons regarding the
      optimal timing of definitive fracture surgery after injury, as well as defining the magnitude
      of surgical intervention which may be pursued without engendering clinical complications.

      Specific Aim 1: Define groups of patients based on Precision Injury Signatures (mechanical
      and ischemic injury characteristics and immunologic response profile) that correspond to the
      following short term clinical outcomes;

        1. Multiple organ dysfunction

        2. Nosocomial infection

        3. Wound complications

        4. Resource utilization (ICU/hospital LOS, days on mechanical ventilation, discharge
           disposition)

        5. Death

      Hypothesis 1: Patients who develop complicated short term outcomes will demonstrate distinct
      Precision Injury Signatures compared to patients who have uncomplicated outcomes for injuries
      of similar magnitude.

      Specific Aim 2: Evaluate the impact of timing and magnitude of orthopaedic surgical
      interventions on progression of patient-specific physiologic and immunologic response.
      Describe changes in physiologic and immunologic response after initial and staged orthopaedic
      interventions.

      Hypothesis 2: Immunologic and physiologic response to surgery will be a function of initial
      Precision Injury Signature and timing/magnitude of orthopaedic surgical interventions.

      Specific Aim 3: To develop surgical decision rules related to timing of definitive
      orthopaedic intervention that optimize short term clinical outcomes.

      Hypothesis 3a: Initial Precision Injury Signatures can be used to identify orthopaedic trauma
      patients who are best treated with early definitive treatment or staged definitive
      intervention.

      Hypothesis 3b: Progression of Precision Injury Signatures can be used to determine optimal
      timing and choices of definitive orthopaedic interventions.
observational model: Cohort
time perspective: Prospective
measure: Clinical outcomes recorded during 6month post injury medical record review
time frame: 6 months post injury
description: Number of occurrences of multiple organ dysfunction, nosocomial infection, wound complications, resource utilization and death as noted in medical record review.
arm group label: Group 1
description: Multiply injured patients having at least one operative orthopaedic injury to the pelvis, acetabulum, femur, or diaphyseal tibia with planned definitive fixation to occur prior to discharge.
Blood
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: No
last name: Todd McKinley, MD
role: Principal Investigator
affiliation: Indiana University/Methodist Hospital
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Wounds and Injuries