<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/NCT02252523</url>
  </required_header>
  <id_info>
    <org_study_id>CHU-210</org_study_id>
    <secondary_id>2013-004697-10</secondary_id>
    <nct_id>NCT02252523</nct_id>
  </id_info>
  <brief_title>Dexmedetomidine-based Sedation in Neurocritical Care Patients</brief_title>
  <official_title>Feasibility of Dexmedetomidine-based Sedation in Neurocritical Care Patients : a Pilot Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Clermont-Ferrand</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Orion Corporation, Orion Pharma</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University Hospital, Clermont-Ferrand</source>
  <brief_summary>
    <textblock>
      This will be an open, prospective pilot study with pharmacological analysis. This study is&#xD;
      designed to assess the efficacity and safety of dexmedetomidine-based sedation in two&#xD;
      subgroups of neurocritically ill patients requiring mechanical ventilation for more than 48&#xD;
      hours. Those with or at risk for intracranial hypertension requiring deep sedation and those&#xD;
      requiring a light to moderate sedation for early neurological evaluation.&#xD;
&#xD;
      The main objective is to assess the feasability of dexmedetomidine infusion in terms of&#xD;
      efficacy and safety (especially cardiovascular tolerance) in brain-injured patients admitted&#xD;
      to intensive care unit and requiring sedation and mechanical ventilation for a predictable&#xD;
      duration greater than or equal to 48 hours. Secondary objectives include the study of&#xD;
      hemodynamic parameters evolution, dose-response relationship, blood (+/- cerebrospinal fluid)&#xD;
      drug concentration, opioates and co-hypnotic consumption.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A written informed consent will be obtained from patients next-of-kin, before study&#xD;
      enrollment according to inclusion and exclusion criterias. All consecutive brain-injured&#xD;
      patients (traumatic brain injury, subarachnoid or intracerebral hemorrhage, postoperative&#xD;
      neurosurgical procedure) admitted to our neurocritical care unit, older than 18 years and&#xD;
      requiring sedation and analgesia for mechanical ventilation longer than 48 hours, will be&#xD;
      eligible for the study. Depending on the absence or presence of lesion which may increase&#xD;
      intracranial pressure, patients will be included in the &quot;light to moderate&quot; sedation subgroup&#xD;
      (MLS) or in the &quot;deep&quot; sedation subgroup (DS).&#xD;
&#xD;
      In the MLS subgroup (RASS 0/-3), sedation and analgesia will be drived by propofol and&#xD;
      opiates. Once the goals of sedation achieved with usual hypnotic, dexmedetomidine will be&#xD;
      initiated at a dose of 0.5 μg/kg/h, and then gradually increased or decreased by increments&#xD;
      of 0.1 μ g / kg / h all hours to a maximum dose of 1.4 μg/kg/h, depending on the target&#xD;
      sedation achievement. Propofol will be discontinued at study drug initiation. Dexmedetomidine&#xD;
      infusion will bemaintained at least during 48 hours, evaluation of the efficacy and safety&#xD;
      will be continuous during this period.&#xD;
&#xD;
      After these first 48 hours, in the absence of neurological worsening requiring a deep&#xD;
      sedation and if sedation's levels will are achieved with dexmedetomidine alone (ie without&#xD;
      requirement of propofol continuous administration) , it will be maintained untill withdrawal&#xD;
      of mechanical ventilation. Otherwise, study drug will discontinued and propofol will be&#xD;
      restarted.&#xD;
&#xD;
      In the DS subgroup, &quot;deep&quot; sedation (RASS -4/-5) will be achieved by propofol infusion. If&#xD;
      sedation level are not achieved with the maximum recommended propofol dose (5mg/kg/h),&#xD;
      midazolam will be started to reach target sedation level with a maximum dose of 0.15mg/kg/h.&#xD;
      Once the goals of sedation will be achieved a dexmedetomidine infusion will be initiated at a&#xD;
      dose of 0.5 μg/kg/h and then gradually titrated by increase of 0.1 μg/kg/h every hour up to&#xD;
      the maximum patient-tolerated dose (maximum dose of 1.4 μg/kg/h). Conventional hypnotic doses&#xD;
      will be adjusted according to the sedation target. In parallel to dexmedetomidine titration,&#xD;
      midazolam first and then propofol will be decreased. The study drug will be maintained at the&#xD;
      maximum patient-tolerated dose for a total of 48 hours during which the efficacy and safety&#xD;
      will be assessed continuously. After this period, dexmedetomidine will be discontinued.&#xD;
      According to the patient's neurological evolution, either sedation objectives will remain&#xD;
      identical (RASS -4/-5), or sedation will be decreased. Conventional hypnotic will be used&#xD;
      again to achieve these objectives.&#xD;
&#xD;
      The expected result of this study is to confirm that the administration of dexmedetomidine is&#xD;
      effective and safe for &quot;light to moderate&quot; and &quot;deep&quot; sedation of brain-injured patients&#xD;
      admitted to intensive care unit. In addition, this feasibility study could provide legitimacy&#xD;
      if the results are conclusive, to conduct a prospective multicenter randomized controlled&#xD;
      trial on the potential benefits of dexmedetomidine in neurocritical ill patients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>April 2014</start_date>
  <completion_date type="Anticipated">April 2015</completion_date>
  <primary_completion_date type="Anticipated">April 2015</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Hemodynamic events</measure>
    <time_frame>at day 1</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Adverse effects other than hemodynamic event</measure>
    <time_frame>at day 1</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Premature discontinuation of dexmedetomidine infusion</measure>
    <time_frame>at day 1</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Delirium assessed by CAM- ICU scale</measure>
    <time_frame>at day 1</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Withdrawal syndrome at dexmedetomidine discontinuation</measure>
    <time_frame>at day 1</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Level of sedation assessed by the RASS scale from dexmedetomidine initation</measure>
    <time_frame>at day 1</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dose of dexmedetomidine necessary to achieve the objectives of sedation</measure>
    <time_frame>at day 1</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effective plasma concentration</measure>
    <time_frame>at day 1</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">66</enrollment>
  <condition>Acute Brain Injuries</condition>
  <arm_group>
    <arm_group_label>DEXMEDETOMIDINE</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dexmedetomidine</intervention_name>
    <arm_group_label>DEXMEDETOMIDINE</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Brain-injured patients (traumatic brain injury, subarachnoid or intracerebral&#xD;
             hemorrhage, postoperative neurosurgical procedure)&#xD;
&#xD;
          -  Older than 18 years&#xD;
&#xD;
          -  Requiring sedation and analgesia for mechanical ventilation longer than 48 hours&#xD;
&#xD;
          -  Written informed consent obtained from patients next-of-kin, before study enrollment&#xD;
&#xD;
          -  Depending on the absence or presence of lesion which may increase intracranial&#xD;
             pressure, patients will be included in the &quot;light to moderate&quot; sedation subgroup or in&#xD;
             the &quot;deep&quot; sedation subgroup&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  - Heart rate &lt; 45 bpm,&#xD;
&#xD;
          -  Uncontrolled shock or cardiac failure,&#xD;
&#xD;
          -  High-grade AV block,&#xD;
&#xD;
          -  Acute ischemic neurological injury,&#xD;
&#xD;
          -  Severe liver failure,&#xD;
&#xD;
          -  Drug overdose and prior enrollment in a trial with any experimental drug in the last&#xD;
             30 days,&#xD;
&#xD;
          -  Need for ongoing neuromuscular blockade except for tracheal intubation,&#xD;
&#xD;
          -  Pregnancy/lactation,&#xD;
&#xD;
          -  Known allergic reaction to dexmedetomidine,&#xD;
&#xD;
          -  Uncontrolled diabetes.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Patrick LACARIN</last_name>
    <phone>04 73 75 11 95</phone>
    <email>placarin@chu-clermontferrand.fr</email>
  </overall_contact>
  <location>
    <facility>
      <name>CHU Clermont-Ferrand</name>
      <address>
        <city>Clermont-Ferrand</city>
        <zip>63003</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Patrick LACARIN</last_name>
      <phone>04 73 75 11 95</phone>
      <email>placarin@chu-clermontferrand.fr</email>
    </contact>
    <investigator>
      <last_name>Jean-Michel CONSTANTIN</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>September 2014</verification_date>
  <study_first_submitted>September 26, 2014</study_first_submitted>
  <study_first_submitted_qc>September 26, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 30, 2014</study_first_posted>
  <last_update_submitted>September 26, 2014</last_update_submitted>
  <last_update_submitted_qc>September 26, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 30, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Feasibility study</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Brain Injuries</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dexmedetomidine</mesh_term>
  </intervention_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/NCT02252523
org study id: CHU-210
secondary id: 2013-004697-10
nct id: NCT02252523
lead sponsor: 
collaborator: 
This will be an open, prospective pilot study with pharmacological analysis. This study is
      designed to assess the efficacity and safety of dexmedetomidine-based sedation in two
      subgroups of neurocritically ill patients requiring mechanical ventilation for more than 48
      hours. Those with or at risk for intracranial hypertension requiring deep sedation and those
      requiring a light to moderate sedation for early neurological evaluation.

      The main objective is to assess the feasability of dexmedetomidine infusion in terms of
      efficacy and safety (especially cardiovascular tolerance) in brain-injured patients admitted
      to intensive care unit and requiring sedation and mechanical ventilation for a predictable
      duration greater than or equal to 48 hours. Secondary objectives include the study of
      hemodynamic parameters evolution, dose-response relationship, blood (+/- cerebrospinal fluid)
      drug concentration, opioates and co-hypnotic consumption.
A written informed consent will be obtained from patients next-of-kin, before study
      enrollment according to inclusion and exclusion criterias. All consecutive brain-injured
      patients (traumatic brain injury, subarachnoid or intracerebral hemorrhage, postoperative
      neurosurgical procedure) admitted to our neurocritical care unit, older than 18 years and
      requiring sedation and analgesia for mechanical ventilation longer than 48 hours, will be
      eligible for the study. Depending on the absence or presence of lesion which may increase
      intracranial pressure, patients will be included in the "light to moderate" sedation subgroup
      (MLS) or in the "deep" sedation subgroup (DS).

      In the MLS subgroup (RASS 0/-3), sedation and analgesia will be drived by propofol and
      opiates. Once the goals of sedation achieved with usual hypnotic, dexmedetomidine will be
      initiated at a dose of 0.5 μg/kg/h, and then gradually increased or decreased by increments
      of 0.1 μ g / kg / h all hours to a maximum dose of 1.4 μg/kg/h, depending on the target
      sedation achievement. Propofol will be discontinued at study drug initiation. Dexmedetomidine
      infusion will bemaintained at least during 48 hours, evaluation of the efficacy and safety
      will be continuous during this period.

      After these first 48 hours, in the absence of neurological worsening requiring a deep
      sedation and if sedation's levels will are achieved with dexmedetomidine alone (ie without
      requirement of propofol continuous administration) , it will be maintained untill withdrawal
      of mechanical ventilation. Otherwise, study drug will discontinued and propofol will be
      restarted.

      In the DS subgroup, "deep" sedation (RASS -4/-5) will be achieved by propofol infusion. If
      sedation level are not achieved with the maximum recommended propofol dose (5mg/kg/h),
      midazolam will be started to reach target sedation level with a maximum dose of 0.15mg/kg/h.
      Once the goals of sedation will be achieved a dexmedetomidine infusion will be initiated at a
      dose of 0.5 μg/kg/h and then gradually titrated by increase of 0.1 μg/kg/h every hour up to
      the maximum patient-tolerated dose (maximum dose of 1.4 μg/kg/h). Conventional hypnotic doses
      will be adjusted according to the sedation target. In parallel to dexmedetomidine titration,
      midazolam first and then propofol will be decreased. The study drug will be maintained at the
      maximum patient-tolerated dose for a total of 48 hours during which the efficacy and safety
      will be assessed continuously. After this period, dexmedetomidine will be discontinued.
      According to the patient's neurological evolution, either sedation objectives will remain
      identical (RASS -4/-5), or sedation will be decreased. Conventional hypnotic will be used
      again to achieve these objectives.

      The expected result of this study is to confirm that the administration of dexmedetomidine is
      effective and safe for "light to moderate" and "deep" sedation of brain-injured patients
      admitted to intensive care unit. In addition, this feasibility study could provide legitimacy
      if the results are conclusive, to conduct a prospective multicenter randomized controlled
      trial on the potential benefits of dexmedetomidine in neurocritical ill patients.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Hemodynamic events
time frame: at day 1
measure: Adverse effects other than hemodynamic event
time frame: at day 1
measure: Premature discontinuation of dexmedetomidine infusion
time frame: at day 1
measure: Delirium assessed by CAM- ICU scale
time frame: at day 1
measure: Withdrawal syndrome at dexmedetomidine discontinuation
time frame: at day 1
measure: Level of sedation assessed by the RASS scale from dexmedetomidine initation
time frame: at day 1
measure: Dose of dexmedetomidine necessary to achieve the objectives of sedation
time frame: at day 1
measure: Effective plasma concentration
time frame: at day 1
arm group label: DEXMEDETOMIDINE
arm group type: Experimental
intervention type: Drug
intervention name: Dexmedetomidine
arm group label: DEXMEDETOMIDINE
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Patrick LACARIN
phone: 04 73 75 11 95
email: placarin@chu-clermontferrand.fr
facility: 
status: Recruiting
contact: 
investigator: 
country: France
responsible party type: Sponsor
mesh term: Brain Injuries
mesh term: Dexmedetomidine