<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/NCT04497155</url>
  </required_header>
  <id_info>
    <org_study_id>HP-00082182</org_study_id>
    <nct_id>NCT04497155</nct_id>
  </id_info>
  <brief_title>Prehospital Norepinephrine and Early Mortality in Traumatic Shock</brief_title>
  <official_title>The Association of Norepinephrine Use in Pre-hospital Transport and Early Mortality in Hemorrhagic Shock</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Maryland, Baltimore</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Beaujon Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University Grenoble Alps</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Maryland, Baltimore</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The effect of early, prehospital norepinephrine use in patients with traumatic shock on&#xD;
      mortality is unknown. Recent existing observational evidence from single system data (US,&#xD;
      France, Japan) are conflicting. The investigators hypothesize that prehospital norepinephrine&#xD;
      is associated with decreased mortality when used in patients with traumatic shock.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Prehospital hypotension is associated with worse clinical outcomes in patients who sustain&#xD;
      traumatic injuries. Administration of vasoactive medications, including norepinephrine, is&#xD;
      not advocated in North American trauma systems due to the belief that vasopressors will&#xD;
      worsen clinical outcomes and increase mortality. However, in European trauma systems&#xD;
      prehospital vasopressor administration is included as part of the guidelines for the&#xD;
      management of hypotension and hemorrhagic shock. There are multiple physiologic explanations&#xD;
      for why prehospital vasopressor administration may be useful in patients with traumatic&#xD;
      shock, such as providing adequate blood pressure to maintain vital signs until arrival at the&#xD;
      trauma center, allowing adequate organ perfusion in the setting of low blood flow, and&#xD;
      supplementing decreased hormone production in the later stages of hemorrhagic shock.&#xD;
&#xD;
      The purpose of this retrospective study is to investigate if prehospital norepinephrine&#xD;
      administration is associated with decreased mortality in patients with traumatic shock. The&#xD;
      investigators will collect patient data from previously collected sources of information and&#xD;
      trauma databases from three separate locations: the TRAUMABase consortium in Paris, France;&#xD;
      TRENAU trauma database from Grenoble, France; and the R Adams Cowley Shock Trauma Center in&#xD;
      Baltimore, MD, USA. The investigators will perform statistical modeling to propensity score&#xD;
      match patients that received prehospital vasopressors with patients that did not receive&#xD;
      prehospital vasopressors and assess the association with 24-hour and 28-day mortality.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 1, 2013</start_date>
  <completion_date type="Actual">December 31, 2021</completion_date>
  <primary_completion_date type="Actual">December 31, 2018</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>Early mortality</measure>
    <time_frame>Admission to the trauma center to 24-hours after admission</time_frame>
    <description>Death within 24-hours of admission to the trauma center</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>28-day mortality</measure>
    <time_frame>Admission to the trauma center to 28-days after admission</time_frame>
    <description>Death occurring within 28-days from admission to the trauma center</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">2164</enrollment>
  <condition>Traumatic Shock</condition>
  <condition>Hemorrhagic Shock</condition>
  <condition>Traumatic Brain Injury</condition>
  <condition>Hypotension and Shock</condition>
  <arm_group>
    <arm_group_label>Prehospital norepinephrine</arm_group_label>
    <description>Trauma patients that received norepinephrine in the prehospital setting or in the resuscitation unit .</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Prehospital no norepinephrine</arm_group_label>
    <description>Trauma patients that did not receive norepinephrine in the prehospital setting or in the resuscitation unit.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Norepinephrine</intervention_name>
    <description>Trauma patients with prehospital or arrival to the trauma center hypotension, defined as a systolic blood pressure &lt;100 mmHg, that received norepinephrine during prehospital transport or in the resuscitation unit.</description>
    <arm_group_label>Prehospital norepinephrine</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        The study population will be collected from the previously collected trauma database at&#xD;
        three separate locations, as previously described. These databases are collected,&#xD;
        maintained, and managed by professional medical staff.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 18-90 years&#xD;
&#xD;
          -  Blunt traumatic mechanism of injury&#xD;
&#xD;
          -  Admitted to the trauma center from the scene of injury&#xD;
&#xD;
          -  Systolic blood pressure during prehospital transport or at admission to the trauma&#xD;
             center &lt;100 mmHg&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Penetrating mechanism of injury&#xD;
&#xD;
          -  No vital signs at the scene of injury&#xD;
&#xD;
          -  Prehospital cardiac arrest&#xD;
&#xD;
          -  Transferred to the trauma center from another hospital&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Tobias Gauss, MD</last_name>
    <role>Study Director</role>
    <affiliation>Hospital Beujon</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Pierre Bouzat, MD, PhD</last_name>
    <role>Study Director</role>
    <affiliation>University Grenoble Alps</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Justin E Richards, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>R Adams Cowley Shock Trauma Center</affiliation>
  </overall_official>
  <reference>
    <citation>Gupta B, Garg N, Ramachandran R. Vasopressors: Do they have any role in hemorrhagic shock? J Anaesthesiol Clin Pharmacol. 2017 Jan-Mar;33(1):3-8. doi: 10.4103/0970-9185.202185.</citation>
    <PMID>28413267</PMID>
  </reference>
  <reference>
    <citation>Beloncle F, Meziani F, Lerolle N, Radermacher P, Asfar P. Does vasopressor therapy have an indication in hemorrhagic shock? Ann Intensive Care. 2013 May 22;3(1):13. doi: 10.1186/2110-5820-3-13.</citation>
    <PMID>23697682</PMID>
  </reference>
  <results_reference>
    <citation>Gauss T, Gayat E, Harrois A, Raux M, Follin A, Daban JL, Cook F, Hamada S; TraumaBase Group; Prehospital Traumabase Group Ile de France, SAMU=Service d'Aide Medicale Urgente. Effect of early use of noradrenaline on in-hospital mortality in haemorrhagic shock after major trauma: a propensity-score analysis. Br J Anaesth. 2018 Jun;120(6):1237-1244. doi: 10.1016/j.bja.2018.02.032. Epub 2018 Apr 14.</citation>
    <PMID>29793591</PMID>
  </results_reference>
  <results_reference>
    <citation>Sims CA, Holena D, Kim P, Pascual J, Smith B, Martin N, Seamon M, Shiroff A, Raza S, Kaplan L, Grill E, Zimmerman N, Mason C, Abella B, Reilly P. Effect of Low-Dose Supplementation of Arginine Vasopressin on Need for Blood Product Transfusions in Patients With Trauma and Hemorrhagic Shock: A Randomized Clinical Trial. JAMA Surg. 2019 Nov 1;154(11):994-1003. doi: 10.1001/jamasurg.2019.2884.</citation>
    <PMID>31461138</PMID>
  </results_reference>
  <results_reference>
    <citation>Harrois A, Baudry N, Huet O, Kato H, Dupic L, Lohez M, Ziol M, Vicaut E, Duranteau J. Norepinephrine Decreases Fluid Requirements and Blood Loss While Preserving Intestinal Villi Microcirculation during Fluid Resuscitation of Uncontrolled Hemorrhagic Shock in Mice. Anesthesiology. 2015 May;122(5):1093-102. doi: 10.1097/ALN.0000000000000639.</citation>
    <PMID>25782753</PMID>
  </results_reference>
  <verification_date>January 2022</verification_date>
  <study_first_submitted>July 29, 2020</study_first_submitted>
  <study_first_submitted_qc>July 29, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 4, 2020</study_first_posted>
  <last_update_submitted>January 27, 2022</last_update_submitted>
  <last_update_submitted_qc>January 27, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">February 10, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Maryland, Baltimore</investigator_affiliation>
    <investigator_full_name>Justin Richards</investigator_full_name>
    <investigator_title>Associate Professor of Anesthesiology</investigator_title>
  </responsible_party>
  <keyword>hypotension</keyword>
  <keyword>norepinephrine</keyword>
  <keyword>traumatic shock</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Brain Injuries</mesh_term>
    <mesh_term>Brain Injuries, Traumatic</mesh_term>
    <mesh_term>Hypotension</mesh_term>
    <mesh_term>Shock</mesh_term>
    <mesh_term>Shock, Hemorrhagic</mesh_term>
    <mesh_term>Shock, Traumatic</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Norepinephrine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04497155
org study id: HP-00082182
nct id: NCT04497155
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
The effect of early, prehospital norepinephrine use in patients with traumatic shock on
      mortality is unknown. Recent existing observational evidence from single system data (US,
      France, Japan) are conflicting. The investigators hypothesize that prehospital norepinephrine
      is associated with decreased mortality when used in patients with traumatic shock.
Prehospital hypotension is associated with worse clinical outcomes in patients who sustain
      traumatic injuries. Administration of vasoactive medications, including norepinephrine, is
      not advocated in North American trauma systems due to the belief that vasopressors will
      worsen clinical outcomes and increase mortality. However, in European trauma systems
      prehospital vasopressor administration is included as part of the guidelines for the
      management of hypotension and hemorrhagic shock. There are multiple physiologic explanations
      for why prehospital vasopressor administration may be useful in patients with traumatic
      shock, such as providing adequate blood pressure to maintain vital signs until arrival at the
      trauma center, allowing adequate organ perfusion in the setting of low blood flow, and
      supplementing decreased hormone production in the later stages of hemorrhagic shock.

      The purpose of this retrospective study is to investigate if prehospital norepinephrine
      administration is associated with decreased mortality in patients with traumatic shock. The
      investigators will collect patient data from previously collected sources of information and
      trauma databases from three separate locations: the TRAUMABase consortium in Paris, France;
      TRENAU trauma database from Grenoble, France; and the R Adams Cowley Shock Trauma Center in
      Baltimore, MD, USA. The investigators will perform statistical modeling to propensity score
      match patients that received prehospital vasopressors with patients that did not receive
      prehospital vasopressors and assess the association with 24-hour and 28-day mortality.
observational model: Cohort
time perspective: Retrospective
measure: Early mortality
time frame: Admission to the trauma center to 24-hours after admission
description: Death within 24-hours of admission to the trauma center
measure: 28-day mortality
time frame: Admission to the trauma center to 28-days after admission
description: Death occurring within 28-days from admission to the trauma center
arm group label: Prehospital norepinephrine
description: Trauma patients that received norepinephrine in the prehospital setting or in the resuscitation unit .
arm group label: Prehospital no norepinephrine
description: Trauma patients that did not receive norepinephrine in the prehospital setting or in the resuscitation unit.
intervention type: Drug
intervention name: Norepinephrine
description: Trauma patients with prehospital or arrival to the trauma center hypotension, defined as a systolic blood pressure <100 mmHg, that received norepinephrine during prehospital transport or in the resuscitation unit.
arm group label: Prehospital norepinephrine
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 90 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Tobias Gauss, MD
role: Study Director
affiliation: Hospital Beujon
last name: Pierre Bouzat, MD, PhD
role: Study Director
affiliation: University Grenoble Alps
last name: Justin E Richards, MD
role: Principal Investigator
affiliation: R Adams Cowley Shock Trauma Center
citation: Gupta B, Garg N, Ramachandran R. Vasopressors: Do they have any role in hemorrhagic shock? J Anaesthesiol Clin Pharmacol. 2017 Jan-Mar;33(1):3-8. doi: 10.4103/0970-9185.202185.
PMID: 28413267
citation: Beloncle F, Meziani F, Lerolle N, Radermacher P, Asfar P. Does vasopressor therapy have an indication in hemorrhagic shock? Ann Intensive Care. 2013 May 22;3(1):13. doi: 10.1186/2110-5820-3-13.
PMID: 23697682
citation: Gauss T, Gayat E, Harrois A, Raux M, Follin A, Daban JL, Cook F, Hamada S; TraumaBase Group; Prehospital Traumabase Group Ile de France, SAMU=Service d'Aide Medicale Urgente. Effect of early use of noradrenaline on in-hospital mortality in haemorrhagic shock after major trauma: a propensity-score analysis. Br J Anaesth. 2018 Jun;120(6):1237-1244. doi: 10.1016/j.bja.2018.02.032. Epub 2018 Apr 14.
PMID: 29793591
citation: Sims CA, Holena D, Kim P, Pascual J, Smith B, Martin N, Seamon M, Shiroff A, Raza S, Kaplan L, Grill E, Zimmerman N, Mason C, Abella B, Reilly P. Effect of Low-Dose Supplementation of Arginine Vasopressin on Need for Blood Product Transfusions in Patients With Trauma and Hemorrhagic Shock: A Randomized Clinical Trial. JAMA Surg. 2019 Nov 1;154(11):994-1003. doi: 10.1001/jamasurg.2019.2884.
PMID: 31461138
citation: Harrois A, Baudry N, Huet O, Kato H, Dupic L, Lohez M, Ziol M, Vicaut E, Duranteau J. Norepinephrine Decreases Fluid Requirements and Blood Loss While Preserving Intestinal Villi Microcirculation during Fluid Resuscitation of Uncontrolled Hemorrhagic Shock in Mice. Anesthesiology. 2015 May;122(5):1093-102. doi: 10.1097/ALN.0000000000000639.
PMID: 25782753
responsible party type: Principal Investigator
investigator affiliation: University of Maryland, Baltimore
investigator full name: Justin Richards
investigator title: Associate Professor of Anesthesiology
mesh term: Brain Injuries
mesh term: Brain Injuries, Traumatic
mesh term: Hypotension
mesh term: Shock
mesh term: Shock, Hemorrhagic
mesh term: Shock, Traumatic
mesh term: Norepinephrine
sharing ipd: No