<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/NCT03250481</url>
  </required_header>
  <id_info>
    <org_study_id>HelsinkiUCHFin</org_study_id>
    <nct_id>NCT03250481</nct_id>
  </id_info>
  <brief_title>Responsiveness Index Versus the RASS Based Method for Adjusting Sedation in Critically Ill Patients</brief_title>
  <official_title>Responsiveness Index Versus the RASS Based Method for Adjusting Sedation in Critically Ill Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Helsinki University Central Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Helsinki University Central Hospital</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Systematic evaluation of pain, agitation and delirium in ICU-patients is recommended and deep&#xD;
      sedation should be avoided. Sedation is still monitored with clinical assessments, like RASS.&#xD;
      The Responsiveness Index (RI) is a recently described method for ICU sedation monitoring. It&#xD;
      is based on processed frontal EMG and reflects the interaction between a patient's conscious&#xD;
      state and the intensity and frequency of stimulations during treatment. RI has not been&#xD;
      randomly compared to RASS to titrate sedation to target at a clinically adequate sedation&#xD;
      state. In this open randomized controlled pilot study of 32 critically ill, mechanically&#xD;
      ventilated adult patients, investigators will evaluate the feasibility, safety and efficacy&#xD;
      of RI based sedation compared to standard RASS based titration of sedation. Investigators&#xD;
      hypothesize first that RI controlled sedation will be safe and, second that RI controlled&#xD;
      sedation will associate with increased number of ventilator free days alive in 30 days&#xD;
      without excess adverse events.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Sedation of intensive care patients is needed for patient's safety but deep sedation is&#xD;
      associated with adverse outcomes. Frontal electromyogram based Responsiveness Index (RI) aims&#xD;
      to quantify patient's arousal. RI monitoring together with staff education may have potential&#xD;
      to improve sedation quality. Investigators will evaluate the safety of RI based sedation&#xD;
      versus standard care using Richmond Agitation-Sedation Scale (RASS) for sedation.&#xD;
&#xD;
      Methods: randomized study, critically ill adult patients with mechanical ventilation and&#xD;
      administration of sedation to either RI- or RASS-guided sedation. Propofol (and midazolam&#xD;
      combined with if needed) as a hypnotic drug and oxycodone as an analgesic drug. Investigators&#xD;
      will follow standardized sedation protocol in both groups to achieve the predetermined target&#xD;
      sedation level: either RI 40-80 (RI-group) or RASS -3-0 (RASS group). RI measurement is&#xD;
      continuous in both groups, but blinded in the RASS group. Accordingly, RI group is blinded to&#xD;
      RASS assessments. State Entropy (SE) will register in both groups.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 2013</start_date>
  <completion_date type="Actual">August 28, 2017</completion_date>
  <primary_completion_date type="Actual">August 28, 2017</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>Treatment</primary_purpose>
    <masking>Single (Care Provider)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of patients with sedation or sedation monitoring related predetermined adverse events</measure>
    <time_frame>Up to 96 hours (starting when RI-monitoring begins)</time_frame>
    <description>Predetermined adverse events hypotension, hypertension, tachycardia, tachypnea, anxiety, unintended catheter removal, gas exchange deficiency, skin irritation caused by electrodes, hemodynamic instability</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Increased ventilator free days</measure>
    <time_frame>30 days</time_frame>
    <description>Time alive without mechanical ventilation</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">32</enrollment>
  <condition>Critical Illness</condition>
  <arm_group>
    <arm_group_label>'Sedation guidance with RASS-group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Sedation is guided with RASS. Targeted sedation level is RASS -3 - 0. Propofol: an initial rate of 2.4 mg/kg/h for one hour. Thereafter, the infusion rate of propofol is 0.8-4 mg/kg/h to reach or maintain the target RASS score. Propofol bolus of 20-40 mg is allowed. Oxycodone as 3-6 mg boluses for pain management. Other opiates are not allowed. Midazolam may given if the maximum dose of propofol is reached and pain management by oxycodone restricted achievement of the target sedation level. Midazolam will supply intravenously in boluses of 1-2 mg (based on the weight of the patient), starting at 3 boluses/h for the first hour. Dexmedetomidine and other sedatives are not allowed.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>'Sedation guidance with RI</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Sedation is guided with RI. Targeted sedation level is RI 40-80. Propofol: an initial rate of 2.4 mg/kg/h for one hour. Thereafter, the infusion rate of propofol is 0.8-4 mg/kg/h to reach or maintain the target RI score. Propofol bolus of 20-40 mg is allowed. Oxycodone as 3-6 mg boluses for pain management. Other opiates are not allowed. Midazolam may given if the maximum dose of propofol is reached and pain management by oxycodone restricted achievement of the target sedation level. Midazolam will supply intravenously in boluses of 1-2 mg (based on the weight of the patient), starting at 3 boluses/h for the first hour. Dexmedetomidine and other sedatives are not allowed.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Propofol</intervention_name>
    <description>Sedation targeted to RASS -3-0 or RI 20-40</description>
    <arm_group_label>'Sedation guidance with RASS-group</arm_group_label>
    <arm_group_label>'Sedation guidance with RI</arm_group_label>
    <other_name>Oxycodone</other_name>
    <other_name>Midazolame</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Intensive care patients&#xD;
&#xD;
          -  Need of mechanical ventilation and sedation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  contraindication to propofol or oxycodone&#xD;
&#xD;
          -  hypoxic or traumatic brain injury&#xD;
&#xD;
          -  intracranial hemorrhage&#xD;
&#xD;
          -  status epilepticus&#xD;
&#xD;
          -  drug overdose as admission diagnosis&#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>Johanna Wennervirta, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Helsinki and Helsinki University Hospital, PO Box 340, 00029 Helsinki, Finland</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>HelsinkiUCH</name>
      <address>
        <city>Helsinki</city>
        <country>Finland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Finland</country>
  </location_countries>
  <verification_date>August 2019</verification_date>
  <study_first_submitted>August 8, 2017</study_first_submitted>
  <study_first_submitted_qc>August 11, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 15, 2017</study_first_posted>
  <last_update_submitted>August 13, 2019</last_update_submitted>
  <last_update_submitted_qc>August 13, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">August 15, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Helsinki University Central Hospital</investigator_affiliation>
    <investigator_full_name>Ville Pettilä</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Sedation, Responsiveness Index, Electromyogram</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Critical Illness</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Oxycodone</mesh_term>
    <mesh_term>Propofol</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/NCT03250481
org study id: HelsinkiUCHFin
nct id: NCT03250481
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Systematic evaluation of pain, agitation and delirium in ICU-patients is recommended and deep
      sedation should be avoided. Sedation is still monitored with clinical assessments, like RASS.
      The Responsiveness Index (RI) is a recently described method for ICU sedation monitoring. It
      is based on processed frontal EMG and reflects the interaction between a patient's conscious
      state and the intensity and frequency of stimulations during treatment. RI has not been
      randomly compared to RASS to titrate sedation to target at a clinically adequate sedation
      state. In this open randomized controlled pilot study of 32 critically ill, mechanically
      ventilated adult patients, investigators will evaluate the feasibility, safety and efficacy
      of RI based sedation compared to standard RASS based titration of sedation. Investigators
      hypothesize first that RI controlled sedation will be safe and, second that RI controlled
      sedation will associate with increased number of ventilator free days alive in 30 days
      without excess adverse events.
Sedation of intensive care patients is needed for patient's safety but deep sedation is
      associated with adverse outcomes. Frontal electromyogram based Responsiveness Index (RI) aims
      to quantify patient's arousal. RI monitoring together with staff education may have potential
      to improve sedation quality. Investigators will evaluate the safety of RI based sedation
      versus standard care using Richmond Agitation-Sedation Scale (RASS) for sedation.

      Methods: randomized study, critically ill adult patients with mechanical ventilation and
      administration of sedation to either RI- or RASS-guided sedation. Propofol (and midazolam
      combined with if needed) as a hypnotic drug and oxycodone as an analgesic drug. Investigators
      will follow standardized sedation protocol in both groups to achieve the predetermined target
      sedation level: either RI 40-80 (RI-group) or RASS -3-0 (RASS group). RI measurement is
      continuous in both groups, but blinded in the RASS group. Accordingly, RI group is blinded to
      RASS assessments. State Entropy (SE) will register in both groups.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Care Provider)
measure: Number of patients with sedation or sedation monitoring related predetermined adverse events
time frame: Up to 96 hours (starting when RI-monitoring begins)
description: Predetermined adverse events hypotension, hypertension, tachycardia, tachypnea, anxiety, unintended catheter removal, gas exchange deficiency, skin irritation caused by electrodes, hemodynamic instability
measure: Increased ventilator free days
time frame: 30 days
description: Time alive without mechanical ventilation
arm group label: 'Sedation guidance with RASS-group
arm group type: Active Comparator
description: Sedation is guided with RASS. Targeted sedation level is RASS -3 - 0. Propofol: an initial rate of 2.4 mg/kg/h for one hour. Thereafter, the infusion rate of propofol is 0.8-4 mg/kg/h to reach or maintain the target RASS score. Propofol bolus of 20-40 mg is allowed. Oxycodone as 3-6 mg boluses for pain management. Other opiates are not allowed. Midazolam may given if the maximum dose of propofol is reached and pain management by oxycodone restricted achievement of the target sedation level. Midazolam will supply intravenously in boluses of 1-2 mg (based on the weight of the patient), starting at 3 boluses/h for the first hour. Dexmedetomidine and other sedatives are not allowed.
arm group label: 'Sedation guidance with RI
arm group type: Experimental
description: Sedation is guided with RI. Targeted sedation level is RI 40-80. Propofol: an initial rate of 2.4 mg/kg/h for one hour. Thereafter, the infusion rate of propofol is 0.8-4 mg/kg/h to reach or maintain the target RI score. Propofol bolus of 20-40 mg is allowed. Oxycodone as 3-6 mg boluses for pain management. Other opiates are not allowed. Midazolam may given if the maximum dose of propofol is reached and pain management by oxycodone restricted achievement of the target sedation level. Midazolam will supply intravenously in boluses of 1-2 mg (based on the weight of the patient), starting at 3 boluses/h for the first hour. Dexmedetomidine and other sedatives are not allowed.
intervention type: Drug
intervention name: Propofol
description: Sedation targeted to RASS -3-0 or RI 20-40
arm group label: 'Sedation guidance with RASS-group
arm group label: 'Sedation guidance with RI
other name: Oxycodone
other name: Midazolame
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Johanna Wennervirta, MD, PhD
role: Principal Investigator
affiliation: University of Helsinki and Helsinki University Hospital, PO Box 340, 00029 Helsinki, Finland
facility: 
country: Finland
responsible party type: Principal Investigator
investigator affiliation: Helsinki University Central Hospital
investigator full name: Ville Pettilä
investigator title: Professor
mesh term: Critical Illness
mesh term: Oxycodone
mesh term: Propofol