<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/NCT03285087</url>
  </required_header>
  <id_info>
    <org_study_id>17200062</org_study_id>
    <nct_id>NCT03285087</nct_id>
  </id_info>
  <brief_title>Risk Prediction of Dexmedetomidine-associated Hemodynamic Instability</brief_title>
  <acronym>DEXSEDATION</acronym>
  <official_title>Risk Prediction and Consequences of Dexmedetomidine-associated Hemodynamic Instability in Intubated Mechanically Ventilated Intensive Care Unit Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assiut University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Assiut University</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Hypotension and bradycardia have been commonly associated with dexmedetomidine therapy,&#xD;
      occurring in 13% to 68% and 1% to 42% of patients, respectively. The variability in reported&#xD;
      incidence may be partially attributed to inconsistent definitions and study populations. The&#xD;
      significance of this hemodynamic instability is not only highlighted by its high incidence&#xD;
      but also the need for corrective interventions. In one study, hemodynamic instability&#xD;
      requiring clinical intervention occurred in nearly one third of ICU patients receiving&#xD;
      dexmedetomidine. Moreover, patients who experienced dexmedetomidine-associated hypotension&#xD;
      had a higher mortality rate than those who did not.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Dexmedetomidine is specific for the α-2a receptor, especially at lower concentrations,&#xD;
      resulting in both vasodilation and a blunting of the sympathetic response. Due to these&#xD;
      mechanistic considerations, patients who are dependent upon adrenergic tone to maintain blood&#xD;
      pressure are more prone to its' hemodynamic instability. This is especially true in those who&#xD;
      are receiving dexmedetomidine in the settings of hypovolemia, traumatic spinal cord injury,&#xD;
      or general anesthetic administration. The use of dexmedetomidine in these patient populations&#xD;
      may explain the high rate of hypotension reported in a recent study in trauma patients where&#xD;
      almost 50% of patients had a spinal cord injury.&#xD;
&#xD;
      Although hemodynamic instability may negatively impact outcomes in the ICU, specific risk&#xD;
      factors for the development of clinically significant hemodynamic instability in patients&#xD;
      receiving dexmedetomidine are poorly characterized in the current literature. Although&#xD;
      previous studies in focused populations have implicated dexmedetomidine dosing strategies,&#xD;
      including initial loading infusions and titration frequency, the degree to which alternative&#xD;
      patient-specific factors or concurrent interventions impact the risk of hemodynamic&#xD;
      instability remains incompletely understood.&#xD;
&#xD;
      The aim of this study will be to determine the risk factors of dexmedetomidine-associated&#xD;
      hemodynamic instability in critically ill trauma patients and the effect of this hemodynamic&#xD;
      instability on different body systems.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Suspended</overall_status>
  <why_stopped>
    dexmedetomidine is unavailable in this time&#xD;
  </why_stopped>
  <start_date type="Anticipated">June 2021</start_date>
  <completion_date type="Anticipated">August 2022</completion_date>
  <primary_completion_date type="Anticipated">August 2022</primary_completion_date>
  <phase>Phase 2/Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>The primary end point will be the occurrence of at least 1 episode of clinically significant hemodynamic instability during dexmedetomidine therapy defined as systolic blood pressure (SBP) &lt; 80 mm Hg, diastolic blood pressure (DBP) &lt;50 mm Hg, or heart rate &lt;50 beats per minute (bpm) To qualify as an event, the hemodynamic variable had to remain below the specified threshold for at least 2 consecutive readings (≥30 minutes of recorded hemodynamic instability). The cumulative incidence of hemodynamic instability events during dexmedetomidine sedation will be plotted and Cox proportional hazards models will be constructed to determine hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk factors of hemodynamic instability during dexmedetomidine therapy.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>Open label</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of hemodynamic instability events during dexmedetomidine</measure>
    <time_frame>24 hours</time_frame>
    <description>The primary end point will be the occurrence of at least 1 episode of clinically significant hemodynamic instability during dexmedetomidine therapy defined as systolic blood pressure (SBP) &lt; 80 mm Hg, diastolic blood pressure (DBP) &lt;50 mm Hg, or heart rate &lt;50 beats per minute (bpm) To qualify as an event, the hemodynamic variable had to remain below the specified threshold for at least 2 consecutive readings (≥30 minutes of recorded hemodynamic instability). The cumulative incidence of hemodynamic instability events during dexmedetomidine sedation will be plotted and Cox proportional hazards models will be constructed to determine hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk factors of hemodynamic instability during dexmedetomidine therapy.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">250</enrollment>
  <condition>Sedation</condition>
  <arm_group>
    <arm_group_label>DEX 0.2 μg/kg/h</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will receive dexmedetomidine for sedation with initial maintenance dose rate of 0.2 μg/kg/h. The dose will be increased in 0.1 μg/kg/h increments to achieve target Richmond Agitation Sedation Scale (RASS) levels of -2 to zero and with a maximum dose of 1.4 μg/kg/h for 24 hours.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>DEX 0.2 μg/kg/h.</intervention_name>
    <description>DEX 0.2 μg/kg/h. The dose will be increased in 0.1 μg/kg/h increments to achieve target Richmond Agitation Sedation Scale (RASS) levels of -2 to zero and with a maximum dose of 1.4 μg/kg/h for 24 hours.</description>
    <arm_group_label>DEX 0.2 μg/kg/h</arm_group_label>
    <other_name>Precedex</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult patients (18-65 years old)&#xD;
&#xD;
          -  admitted to Intensive care units in Assiut university Hospital&#xD;
&#xD;
          -  requiring endotracheal intubation, mechanical ventilation and light to moderate&#xD;
             sedation&#xD;
&#xD;
          -  of an estimated duration not less than 24h.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of coronary care unit admission.&#xD;
&#xD;
          -  Severe traumatic brain injury.&#xD;
&#xD;
          -  Low baseline arterial blood pressure defined as SBP &lt;100 mm Hg or mean arterial blood&#xD;
             pressure (MAP) &lt;70 mm Hg in the 60 minutes preceding dexmedetomidine initiation.&#xD;
&#xD;
          -  Slow baseline heart rate was &lt;70 bpm in the 60 minutes preceding dexmedetomidine&#xD;
             initiation.&#xD;
&#xD;
          -  Spinal cord injury.&#xD;
&#xD;
          -  Patients who have a cardiac pacemaker or automatic implantable cardioverter&#xD;
             defibrillator.&#xD;
&#xD;
          -  Patients who are admitted with a primary diagnosis of substance withdrawal.&#xD;
&#xD;
          -  Pregnant females.&#xD;
&#xD;
          -  Patients who are incarcerated.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Hala S Abdelghaffar, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Professor of anesthesia, faculty of medicine, Assiut university, Egypt</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Hala S Abdelghaffar, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Professor of anesthesia, faculty of medicine, Assiut university, Assiut, Egypy</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Assiut university main hospital, Trauma ICU</name>
      <address>
        <city>Assiut</city>
        <state>Assiut Governorate</state>
        <zip>715715</zip>
        <country>Egypt</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Egypt</country>
  </location_countries>
  <verification_date>January 2021</verification_date>
  <study_first_submitted>September 14, 2017</study_first_submitted>
  <study_first_submitted_qc>September 14, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 15, 2017</study_first_posted>
  <last_update_submitted>January 12, 2021</last_update_submitted>
  <last_update_submitted_qc>January 12, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">January 14, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Assiut University</investigator_affiliation>
    <investigator_full_name>Hala Saad Abdel-Ghaffar</investigator_full_name>
    <investigator_title>Assisstant professor in anesthesia and intensive care, Faculty of medicine, Assiut university, Egypt.</investigator_title>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dexmedetomidine</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/NCT03285087
org study id: 17200062
nct id: NCT03285087
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
Hypotension and bradycardia have been commonly associated with dexmedetomidine therapy,
      occurring in 13% to 68% and 1% to 42% of patients, respectively. The variability in reported
      incidence may be partially attributed to inconsistent definitions and study populations. The
      significance of this hemodynamic instability is not only highlighted by its high incidence
      but also the need for corrective interventions. In one study, hemodynamic instability
      requiring clinical intervention occurred in nearly one third of ICU patients receiving
      dexmedetomidine. Moreover, patients who experienced dexmedetomidine-associated hypotension
      had a higher mortality rate than those who did not.
Dexmedetomidine is specific for the α-2a receptor, especially at lower concentrations,
      resulting in both vasodilation and a blunting of the sympathetic response. Due to these
      mechanistic considerations, patients who are dependent upon adrenergic tone to maintain blood
      pressure are more prone to its' hemodynamic instability. This is especially true in those who
      are receiving dexmedetomidine in the settings of hypovolemia, traumatic spinal cord injury,
      or general anesthetic administration. The use of dexmedetomidine in these patient populations
      may explain the high rate of hypotension reported in a recent study in trauma patients where
      almost 50% of patients had a spinal cord injury.

      Although hemodynamic instability may negatively impact outcomes in the ICU, specific risk
      factors for the development of clinically significant hemodynamic instability in patients
      receiving dexmedetomidine are poorly characterized in the current literature. Although
      previous studies in focused populations have implicated dexmedetomidine dosing strategies,
      including initial loading infusions and titration frequency, the degree to which alternative
      patient-specific factors or concurrent interventions impact the risk of hemodynamic
      instability remains incompletely understood.

      The aim of this study will be to determine the risk factors of dexmedetomidine-associated
      hemodynamic instability in critically ill trauma patients and the effect of this hemodynamic
      instability on different body systems.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: The primary end point will be the occurrence of at least 1 episode of clinically significant hemodynamic instability during dexmedetomidine therapy defined as systolic blood pressure (SBP) < 80 mm Hg, diastolic blood pressure (DBP) <50 mm Hg, or heart rate <50 beats per minute (bpm) To qualify as an event, the hemodynamic variable had to remain below the specified threshold for at least 2 consecutive readings (≥30 minutes of recorded hemodynamic instability). The cumulative incidence of hemodynamic instability events during dexmedetomidine sedation will be plotted and Cox proportional hazards models will be constructed to determine hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk factors of hemodynamic instability during dexmedetomidine therapy.
primary purpose: Treatment
masking: None (Open Label)
masking description: Open label
measure: Incidence of hemodynamic instability events during dexmedetomidine
time frame: 24 hours
description: The primary end point will be the occurrence of at least 1 episode of clinically significant hemodynamic instability during dexmedetomidine therapy defined as systolic blood pressure (SBP) < 80 mm Hg, diastolic blood pressure (DBP) <50 mm Hg, or heart rate <50 beats per minute (bpm) To qualify as an event, the hemodynamic variable had to remain below the specified threshold for at least 2 consecutive readings (≥30 minutes of recorded hemodynamic instability). The cumulative incidence of hemodynamic instability events during dexmedetomidine sedation will be plotted and Cox proportional hazards models will be constructed to determine hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk factors of hemodynamic instability during dexmedetomidine therapy.
arm group label: DEX 0.2 μg/kg/h
arm group type: Experimental
description: Patients will receive dexmedetomidine for sedation with initial maintenance dose rate of 0.2 μg/kg/h. The dose will be increased in 0.1 μg/kg/h increments to achieve target Richmond Agitation Sedation Scale (RASS) levels of -2 to zero and with a maximum dose of 1.4 μg/kg/h for 24 hours.
intervention type: Drug
intervention name: DEX 0.2 μg/kg/h.
description: DEX 0.2 μg/kg/h. The dose will be increased in 0.1 μg/kg/h increments to achieve target Richmond Agitation Sedation Scale (RASS) levels of -2 to zero and with a maximum dose of 1.4 μg/kg/h for 24 hours.
arm group label: DEX 0.2 μg/kg/h
other name: Precedex
criteria: 
gender: All
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: No
last name: Hala S Abdelghaffar, MD
role: Principal Investigator
affiliation: Professor of anesthesia, faculty of medicine, Assiut university, Egypt
last name: Hala S Abdelghaffar, MD
role: Principal Investigator
affiliation: Professor of anesthesia, faculty of medicine, Assiut university, Assiut, Egypy
facility: 
country: Egypt
responsible party type: Principal Investigator
investigator affiliation: Assiut University
investigator full name: Hala Saad Abdel-Ghaffar
investigator title: Assisstant professor in anesthesia and intensive care, Faculty of medicine, Assiut university, Egypt.
mesh term: Dexmedetomidine
sharing ipd: No