<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/NCT01719770</url>
  </required_header>
  <id_info>
    <org_study_id>RELAX1</org_study_id>
    <nct_id>NCT01719770</nct_id>
  </id_info>
  <brief_title>Skeletal Muscle Paralysis in Hypothermic Patients After Cardiac Arrest</brief_title>
  <acronym>RELAX</acronym>
  <official_title>Requirement of Skeletal Muscle Paralysis in Hypothermic Patients After Cardiac Arrest - a Pilot Study</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>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <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. Since neuromuscular blockers are accused to be associated with various&#xD;
      side effects causing serious harm and/or leading to prolong ICU stay. So economical use seems&#xD;
      to be reasonable. Furthermore, the use of neuromuscular blockers may mask epileptic activity.&#xD;
      Therefore, post hypoxic seizures might remain undetected.&#xD;
&#xD;
      Aim of this study is to investigate if a continuous application of neuromuscular blockers is&#xD;
      necessary to prevent shivering and thereby avoid the counter regulation to achieve the target&#xD;
      temperature as soon as possible in mild hypothermic therapy after cardiac arrest.&#xD;
&#xD;
      A single center (university hospital) study. Randomized, double blinded, double dummy study&#xD;
      design. Eligible are all adult patients after successful resuscitation due to cardiac arrest&#xD;
      of presumed cardiac origin.&#xD;
&#xD;
      All patients receiving mild therapeutic hypothermia after cardiac arrest of presumed&#xD;
      cardiopulmonary origin will be included.&#xD;
&#xD;
      Patients &lt;18 years, cardiac arrest &gt;6 hours before admittance at the hospital, patients with&#xD;
      known or clinically apparent pregnancy, patients who reach our hospital with a body&#xD;
      temperature below 35°C, patients with known allergic reactions against rocuronium, patients&#xD;
      with a history of myasthenia gravis, patients with obvious intoxication, wards of the&#xD;
      state/prisoners and patients with known epileptic disease will be excluded.&#xD;
&#xD;
      Primary outcome:&#xD;
&#xD;
      Shivering episodes will be scored with the Shivering Assessment Scale.&#xD;
&#xD;
      Secondary outcome:&#xD;
&#xD;
      Total doses of rocuronium, time to target core temperature of 33°C, dissipated energy and&#xD;
      total energy needed during the cooling period will be compared between the two groups.&#xD;
&#xD;
      Changes in basal metabolism and depth of relaxation will be ascertained. Furthermore, serum&#xD;
      levels of midazolam, fentanyl, rocuronium and stress hormones will be measured.&#xD;
&#xD;
      Train-of-four will be performed to assess the depth of relaxation. Sedation will be monitored&#xD;
      via bispectral index; measurement of metabolic activity will be evaluated using indirect&#xD;
      calorimetry. Additionally, EEG will be performed to detect epileptiform activities. Blood&#xD;
      will be drawn to measure levels of midazolam, fentanyl and rocuronium.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>November 2010</start_date>
  <completion_date type="Actual">April 2015</completion_date>
  <primary_completion_date type="Actual">October 2013</primary_completion_date>
  <phase>Phase 3</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>Treatment</primary_purpose>
    <masking>Double (Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of shivering episodes</measure>
    <time_frame>during cooling period (mild therapeutic hypothermia will be performed for 24 hours after cooling initiation, rewarming with 0,4°C per hour until a body core temperature of 36°C is reached); total time of approximately 31 hours</time_frame>
    <description>Shivering episodes will be detected according to the Shivering Assessment Scale</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Elapsed time to target temperature</measure>
    <time_frame>Time from starting the cooling procedure until target temperature is reached - approximately 4 hours after cooling initiation</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dissipated energy to reach the target temperature</measure>
    <time_frame>Time from starting the cooling procedure until target temperature is reached - approximately 4 hours after cooling initiation</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in basal metabolism due to shivering or elevated stress levels</measure>
    <time_frame>during the first 72 hours after cardiac arrest</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Depth of relaxation</measure>
    <time_frame>during cooling and rewarming period, which will be approximately 30 hours up to 48 hours after initiation of cooling</time_frame>
    <description>via train of four measurement</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in serum levels of midazolam, fentanyl and rocuronium</measure>
    <time_frame>within the first 48 hours of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of necessary boli of rocuronium</measure>
    <time_frame>during colling period (mild therapeutic hypothermia will be performed for 24 hours after cooling initiation, rewarming with 0,4°C per hour until a body core temperature of 36°C is reached); total time of approximately 31 hours</time_frame>
    <description>In case of a shivering episode, a bolus of rocuronium will be administered (0,25mg/kg)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Cardiac Arrest With Successful Resuscitation</condition>
  <condition>Hypothermia</condition>
  <condition>Skeletal Muscle Relaxant Overdose</condition>
  <arm_group>
    <arm_group_label>Rocuronium</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Continuous infusion of rocuronium with 0,25mg/kg (blinded) for 29 hours after initiation of mild therapeutic hypothermia</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Continuous infusion of sodium-chloride (placebo) and rocuronium bolus (0,25mg/kg)in case of shivering episode (blinded)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>rocuronium</intervention_name>
    <description>continuous application of rocuronium 0,25mg/kg/h (blinded), in case of shivering episode bolus sodium-chloride (blinded)</description>
    <arm_group_label>Rocuronium</arm_group_label>
    <other_name>Esmeron</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>placebo</intervention_name>
    <description>continuous infusion of sodium-chloride (blinded), in case of shivering episode application of rocuronium 0,25mg/kg (blinded)</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>sodium-chloride</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  all patients receiving mild therapeutic hypothermia after cardiac arrest&#xD;
&#xD;
          -  cardiac arrest due to cardiopulmonary origin&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  patients younger than 18 years&#xD;
&#xD;
          -  traumatic cardiac arrest&#xD;
&#xD;
          -  cardiac arrest due to exsanguination, strangulation, smoke inhalation, drug overdose,&#xD;
             electrocution, hanging or drowning&#xD;
&#xD;
          -  known or clinically apparent pregnancy&#xD;
&#xD;
          -  no treatment with mild therapeutic hypothermia because of an AND order&#xD;
&#xD;
          -  terminal illness&#xD;
&#xD;
          -  a body core temperature below 35°C at hospital admission&#xD;
&#xD;
          -  known allergic reaction against rocuronium&#xD;
&#xD;
          -  history of myasthenia gravis&#xD;
&#xD;
          -  obvious intoxication&#xD;
&#xD;
          -  ward of the state or prisoner&#xD;
&#xD;
          -  known epileptic disease&#xD;
&#xD;
          -  cardiac arrest &gt;6 hours prior to hospital admission&#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>Heidrun Losert, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Medical University Vienna, Department of Emergency Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Medical University of Vienna, Department of Emergency Medicine</name>
      <address>
        <city>Vienna</city>
        <zip>1190</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Austria</country>
  </location_countries>
  <verification_date>April 2015</verification_date>
  <study_first_submitted>July 6, 2011</study_first_submitted>
  <study_first_submitted_qc>October 30, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 1, 2012</study_first_posted>
  <last_update_submitted>April 30, 2015</last_update_submitted>
  <last_update_submitted_qc>April 30, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">May 1, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Medical University of Vienna</investigator_affiliation>
    <investigator_full_name>Heidrun Losert</investigator_full_name>
    <investigator_title>Priv. Doz. Dr. Heidrun Losert</investigator_title>
  </responsible_party>
  <keyword>cardiac arrest</keyword>
  <keyword>therapeutic hypothermia</keyword>
  <keyword>skeletal muscle paralysis</keyword>
  <keyword>shivering</keyword>
  <keyword>serum drug levels</keyword>
  <keyword>basal metabolism</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Paralysis</mesh_term>
    <mesh_term>Muscle Hypotonia</mesh_term>
    <mesh_term>Heart Arrest</mesh_term>
    <mesh_term>Hypothermia</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/NCT01719770
org study id: RELAX1
nct id: NCT01719770
lead sponsor: 
has dmc: Yes
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. Since neuromuscular blockers are accused to be associated with various
      side effects causing serious harm and/or leading to prolong ICU stay. So economical use seems
      to be reasonable. Furthermore, the use of neuromuscular blockers may mask epileptic activity.
      Therefore, post hypoxic seizures might remain undetected.

      Aim of this study is to investigate if a continuous application of neuromuscular blockers is
      necessary to prevent shivering and thereby avoid the counter regulation to achieve the target
      temperature as soon as possible in mild hypothermic therapy after cardiac arrest.

      A single center (university hospital) study. Randomized, double blinded, double dummy study
      design. Eligible are all adult patients after successful resuscitation due to cardiac arrest
      of presumed cardiac origin.

      All patients receiving mild therapeutic hypothermia after cardiac arrest of presumed
      cardiopulmonary origin will be included.

      Patients <18 years, cardiac arrest >6 hours before admittance at the hospital, patients with
      known or clinically apparent pregnancy, patients who reach our hospital with a body
      temperature below 35°C, patients with known allergic reactions against rocuronium, patients
      with a history of myasthenia gravis, patients with obvious intoxication, wards of the
      state/prisoners and patients with known epileptic disease will be excluded.

      Primary outcome:

      Shivering episodes will be scored with the Shivering Assessment Scale.

      Secondary outcome:

      Total doses of rocuronium, time to target core temperature of 33°C, dissipated energy and
      total energy needed during the cooling period will be compared between the two groups.

      Changes in basal metabolism and depth of relaxation will be ascertained. Furthermore, serum
      levels of midazolam, fentanyl, rocuronium and stress hormones will be measured.

      Train-of-four will be performed to assess the depth of relaxation. Sedation will be monitored
      via bispectral index; measurement of metabolic activity will be evaluated using indirect
      calorimetry. Additionally, EEG will be performed to detect epileptiform activities. Blood
      will be drawn to measure levels of midazolam, fentanyl and rocuronium.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Care Provider, Investigator)
measure: Number of shivering episodes
time frame: during cooling period (mild therapeutic hypothermia will be performed for 24 hours after cooling initiation, rewarming with 0,4°C per hour until a body core temperature of 36°C is reached); total time of approximately 31 hours
description: Shivering episodes will be detected according to the Shivering Assessment Scale
measure: Elapsed time to target temperature
time frame: Time from starting the cooling procedure until target temperature is reached - approximately 4 hours after cooling initiation
measure: Dissipated energy to reach the target temperature
time frame: Time from starting the cooling procedure until target temperature is reached - approximately 4 hours after cooling initiation
measure: Changes in basal metabolism due to shivering or elevated stress levels
time frame: during the first 72 hours after cardiac arrest
measure: Depth of relaxation
time frame: during cooling and rewarming period, which will be approximately 30 hours up to 48 hours after initiation of cooling
description: via train of four measurement
measure: Changes in serum levels of midazolam, fentanyl and rocuronium
time frame: within the first 48 hours of treatment
measure: Number of necessary boli of rocuronium
time frame: during colling period (mild therapeutic hypothermia will be performed for 24 hours after cooling initiation, rewarming with 0,4°C per hour until a body core temperature of 36°C is reached); total time of approximately 31 hours
description: In case of a shivering episode, a bolus of rocuronium will be administered (0,25mg/kg)
arm group label: Rocuronium
arm group type: Active Comparator
description: Continuous infusion of rocuronium with 0,25mg/kg (blinded) for 29 hours after initiation of mild therapeutic hypothermia
arm group label: Placebo
arm group type: Placebo Comparator
description: Continuous infusion of sodium-chloride (placebo) and rocuronium bolus (0,25mg/kg)in case of shivering episode (blinded)
intervention type: Drug
intervention name: rocuronium
description: continuous application of rocuronium 0,25mg/kg/h (blinded), in case of shivering episode bolus sodium-chloride (blinded)
arm group label: Rocuronium
other name: Esmeron
intervention type: Other
intervention name: placebo
description: continuous infusion of sodium-chloride (blinded), in case of shivering episode application of rocuronium 0,25mg/kg (blinded)
arm group label: Placebo
other name: sodium-chloride
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Heidrun Losert, MD
role: Principal Investigator
affiliation: Medical University Vienna, Department of Emergency Medicine
facility: 
country: Austria
responsible party type: Principal Investigator
investigator affiliation: Medical University of Vienna
investigator full name: Heidrun Losert
investigator title: Priv. Doz. Dr. Heidrun Losert
mesh term: Paralysis
mesh term: Muscle Hypotonia
mesh term: Heart Arrest
mesh term: Hypothermia
mesh term: Rocuronium