<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/NCT01683006</url>
  </required_header>
  <id_info>
    <org_study_id>753/2009UH</org_study_id>
    <nct_id>NCT01683006</nct_id>
  </id_info>
  <brief_title>Influence of Skeletal Muscle Paralysis on Metabolism in Hypothermic Patients After Cardiac Arrest</brief_title>
  <official_title>Influence of Skeletal Muscle Paralysis on Metabolism in Hypothermic Patients After Cardiac Arrest</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Medical University of Vienna</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Medical University of Vienna</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the impact of muscle relaxing drugs on the energy&#xD;
      rate during hypothermia after cardiac arrest.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Mild hypothermia improves neurological outcome after cardiac arrest. Neuromuscular blockers&#xD;
      are in use, together with analgesia and sedation, during the cooling process in many centers&#xD;
      to prevent shivering. However, neuromuscular blockers are accused to be associated with&#xD;
      various side effects causing serious harm and/or leading to prolonged ICU stay. Furthermore,&#xD;
      the use of neuromuscular blockers may mask epileptic activity. Therefore, the advantages and&#xD;
      disadvantages of neuromuscular blockers during therapeutic hypothermia need to be&#xD;
      re-evaluated.&#xD;
&#xD;
      Aim of this study is to investigate if continuous application of neuromuscular blockers is&#xD;
      necessary to prevent shivering and thereby avoiding an increase in energy expenditure in&#xD;
      patients during therapeutic hypothermia and rewarming after cardiac arrest (initial 72h).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 2012</start_date>
  <completion_date type="Actual">November 2014</completion_date>
  <primary_completion_date type="Actual">May 2014</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Supportive Care</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change of resting energy expenditure compared to baseline at 33C°</measure>
    <time_frame>initial 72h after cardiac arrest at defined temperatures or timepoints: 1) 33°C 2) 34.5°C 3) 36 °C 4) 36.5 - 37.5 °C 5) after 48-72h</time_frame>
    <description>resting energy expenditure will be assessed with indirect calorimetry at different measurement time points:&#xD;
12-24 h after initiation of mild hypothermia (33C°)&#xD;
during warming up (at 34.5°C)&#xD;
during warming up (at 36°C)&#xD;
during warming up (at 36.5°C - 37.5°C)&#xD;
normal Temperature, after 48 - 72 h after initiation of mild hypothermia</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change of substrate oxidation rate (protein, fat and glucose) compared to baseline at 33C°</measure>
    <time_frame>initial 72h after cardiac arrest at defined temperatures or timepoints: 1) 33°C 2) 34.5°C 3) 36 °C 4) 36.5 - 37.5 °C 5) after 48-72h</time_frame>
    <description>substrate oxidation rates will be assessed with indirect calorimetry at different measurement time points:&#xD;
12-24 h after initiation of mild hypothermia (33C°)&#xD;
during warming up (at 34.5°C)&#xD;
during warming up (at 36°C)&#xD;
during warming up (at 36.5°C - 37.5°C)&#xD;
at normal Temperature, after 48 - 72 h after initiation of mild hypothermia</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Difference in resting energy expenditure between patients with favorable and unfavorable outcome</measure>
    <time_frame>initial 72h after cardiac arrest at defined temperatures or timepoints: 1) 33°C 2) 34.5°C 3) 36 °C 4) 36.5 - 37.5 °C 5) after 48-72h</time_frame>
    <description>resting energy expenditure will be assessed with indirect calorimetry at different measurement time points:&#xD;
12-24 h after initiation of mild hypothermia (33C°)&#xD;
during warming up (at 34.5°C)&#xD;
during warming up (at 36°C)&#xD;
during warming up (at 36.5°C - 37.5°C)&#xD;
normal Temperature, after 48 - 72 h after initiation of mild hypothermia</description>
  </other_outcome>
  <other_outcome>
    <measure>Difference in substrate metabolism between patients with favorable and unfavorable outcome</measure>
    <time_frame>initial 72h after cardiac arrest at defined temperatures or timepoints: 1) 33°C 2) 34.5°C 3) 36 °C 4) 36.5 - 37.5 °C 5) after 48-72h</time_frame>
    <description>substrate oxidation rates will be assessed with indirect calorimetry at different measurement time points:&#xD;
12-24 h after initiation of mild hypothermia (33C°)&#xD;
during warming up (at 34.5°C)&#xD;
during warming up (at 36°C)&#xD;
during warming up (at 36.5°C - 37.5°C)&#xD;
at normal Temperature, after 48 - 72 h after initiation of mild hypothermia</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">43</enrollment>
  <condition>Critical Illness</condition>
  <condition>Cardiac Arrest</condition>
  <arm_group>
    <arm_group_label>Neuromuscular blocker group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Continuous application of neuromuscular blockers during therapeutic hypothermia.&#xD;
Bolus application of placebo in case of shivering.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo group</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Continuous application of placebo during therapeutic hypothermia.&#xD;
Bolus application of neuromuscular blockers in case of shivering.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rocuronium</intervention_name>
    <description>Continuous application of Rocuronium (0.5 mg/kg body weight/hour).&#xD;
Bolus application of placebo in case of shivering.</description>
    <arm_group_label>Neuromuscular blocker group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Continuous application of placebo during therapeutic hypothermia.&#xD;
Bolus application of Rocuronium (0.5 mg/kg body weight) in case of shivering.</description>
    <arm_group_label>Placebo group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  All patients receiving mild therapeutic hypothermia after cardiac arrest of presumed&#xD;
             cardiopulmonary origin&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  age &lt; 18&#xD;
&#xD;
          -  cardiac arrest &gt;6 hours before admittance at the hospital&#xD;
&#xD;
          -  patients with known or clinically apparent pregnancy&#xD;
&#xD;
          -  patients who reach our hospital with a body temperature below 35°C&#xD;
&#xD;
          -  patients with known allergic reactions against rocuronium&#xD;
&#xD;
          -  patients with a history of myasthenia gravis&#xD;
&#xD;
          -  patients with obvious intoxication&#xD;
&#xD;
          -  wards of the state/prisoners&#xD;
&#xD;
          -  patients with known epileptic disease&#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_official>
    <last_name>Ulrike Holzinger, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Medical University of Vienna</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Medical University Vienna</name>
      <address>
        <city>Vienna</city>
        <zip>1090</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Austria</country>
  </location_countries>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>April 8, 2012</study_first_submitted>
  <study_first_submitted_qc>September 6, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 11, 2012</study_first_posted>
  <last_update_submitted>August 28, 2017</last_update_submitted>
  <last_update_submitted_qc>August 28, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 29, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Medical University of Vienna</investigator_affiliation>
    <investigator_full_name>Ulrike Holzinger</investigator_full_name>
    <investigator_title>MD, Assoc Prof</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Paralysis</mesh_term>
    <mesh_term>Heart Arrest</mesh_term>
    <mesh_term>Critical Illness</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rocuronium</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/NCT01683006
org study id: 753/2009UH
nct id: NCT01683006
lead sponsor: 
has dmc: No
The purpose of this study is to evaluate the impact of muscle relaxing drugs on the energy
      rate during hypothermia after cardiac arrest.
Mild hypothermia improves neurological outcome after cardiac arrest. Neuromuscular blockers
      are in use, together with analgesia and sedation, during the cooling process in many centers
      to prevent shivering. However, neuromuscular blockers are accused to be associated with
      various side effects causing serious harm and/or leading to prolonged ICU stay. Furthermore,
      the use of neuromuscular blockers may mask epileptic activity. Therefore, the advantages and
      disadvantages of neuromuscular blockers during therapeutic hypothermia need to be
      re-evaluated.

      Aim of this study is to investigate if continuous application of neuromuscular blockers is
      necessary to prevent shivering and thereby avoiding an increase in energy expenditure in
      patients during therapeutic hypothermia and rewarming after cardiac arrest (initial 72h).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Supportive Care
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change of resting energy expenditure compared to baseline at 33C°
time frame: initial 72h after cardiac arrest at defined temperatures or timepoints: 1) 33°C 2) 34.5°C 3) 36 °C 4) 36.5 - 37.5 °C 5) after 48-72h
description: resting energy expenditure will be assessed with indirect calorimetry at different measurement time points:
12-24 h after initiation of mild hypothermia (33C°)
during warming up (at 34.5°C)
during warming up (at 36°C)
during warming up (at 36.5°C - 37.5°C)
normal Temperature, after 48 - 72 h after initiation of mild hypothermia
measure: Change of substrate oxidation rate (protein, fat and glucose) compared to baseline at 33C°
time frame: initial 72h after cardiac arrest at defined temperatures or timepoints: 1) 33°C 2) 34.5°C 3) 36 °C 4) 36.5 - 37.5 °C 5) after 48-72h
description: substrate oxidation rates will be assessed with indirect calorimetry at different measurement time points:
12-24 h after initiation of mild hypothermia (33C°)
during warming up (at 34.5°C)
during warming up (at 36°C)
during warming up (at 36.5°C - 37.5°C)
at normal Temperature, after 48 - 72 h after initiation of mild hypothermia
measure: Difference in resting energy expenditure between patients with favorable and unfavorable outcome
time frame: initial 72h after cardiac arrest at defined temperatures or timepoints: 1) 33°C 2) 34.5°C 3) 36 °C 4) 36.5 - 37.5 °C 5) after 48-72h
description: resting energy expenditure will be assessed with indirect calorimetry at different measurement time points:
12-24 h after initiation of mild hypothermia (33C°)
during warming up (at 34.5°C)
during warming up (at 36°C)
during warming up (at 36.5°C - 37.5°C)
normal Temperature, after 48 - 72 h after initiation of mild hypothermia
measure: Difference in substrate metabolism between patients with favorable and unfavorable outcome
time frame: initial 72h after cardiac arrest at defined temperatures or timepoints: 1) 33°C 2) 34.5°C 3) 36 °C 4) 36.5 - 37.5 °C 5) after 48-72h
description: substrate oxidation rates will be assessed with indirect calorimetry at different measurement time points:
12-24 h after initiation of mild hypothermia (33C°)
during warming up (at 34.5°C)
during warming up (at 36°C)
during warming up (at 36.5°C - 37.5°C)
at normal Temperature, after 48 - 72 h after initiation of mild hypothermia
arm group label: Neuromuscular blocker group
arm group type: Active Comparator
description: Continuous application of neuromuscular blockers during therapeutic hypothermia.
Bolus application of placebo in case of shivering.
arm group label: Placebo group
arm group type: Placebo Comparator
description: Continuous application of placebo during therapeutic hypothermia.
Bolus application of neuromuscular blockers in case of shivering.
intervention type: Drug
intervention name: Rocuronium
description: Continuous application of Rocuronium (0.5 mg/kg body weight/hour).
Bolus application of placebo in case of shivering.
arm group label: Neuromuscular blocker group
intervention type: Drug
intervention name: Placebo
description: Continuous application of placebo during therapeutic hypothermia.
Bolus application of Rocuronium (0.5 mg/kg body weight) in case of shivering.
arm group label: Placebo group
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Ulrike Holzinger, MD
role: Principal Investigator
affiliation: Medical University of Vienna
facility: 
country: Austria
responsible party type: Principal Investigator
investigator affiliation: Medical University of Vienna
investigator full name: Ulrike Holzinger
investigator title: MD, Assoc Prof
mesh term: Paralysis
mesh term: Heart Arrest
mesh term: Critical Illness
mesh term: Rocuronium