<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/NCT03303651</url>
  </required_header>
  <id_info>
    <org_study_id>20170824</org_study_id>
    <nct_id>NCT03303651</nct_id>
  </id_info>
  <brief_title>Monitor-Guided Analgesia During General Anesthesia - Part I</brief_title>
  <acronym>MOGADA</acronym>
  <official_title>Investigation of the Effect of Opioid Titration Guided by Analgesia Indices During General Anesthesia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Universitätsklinikum Hamburg-Eppendorf</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Universitätsklinikum Hamburg-Eppendorf</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This prospective randomized clinical trial evaluates the effects of a monitor-guided opioid&#xD;
      analgesia during general anesthesia. To date no standard-monitoring device exists to&#xD;
      specifically reflect the analgesic component of general anesthesia. Quality and safety of&#xD;
      general anesthesia are of major clinical importance and should be improved by limiting the&#xD;
      opioid analgesic's dosage to the minimum amount needed. The study compares the effects of&#xD;
      monitoring nociception during general anesthesia with different innovative techniques in&#xD;
      comparison to routine clinical practice.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This prospective randomized clinical study aims to investigate the effects of a&#xD;
      monitor-guided opioid analgesia during general anesthesia by different monitoring systems in&#xD;
      comparison to routine clinical practice. Many surgical procedures require general anesthesia.&#xD;
      The main components of general anesthesia are hypnosis and analgesia, and anesthesiologists&#xD;
      usually combine a hypnotic drug with an opioid analgesic.&#xD;
&#xD;
      Until today, however, there is no standard-monitoring of nociception to specifically reflect&#xD;
      the analgesic component of general anesthesia. In clinical practice the opioid dosage is&#xD;
      chosen by clinical judgment of the attending anesthesiologist based upon changes of heart&#xD;
      rate, blood pressure, pupil size, lacrimation and sweating of the patient.&#xD;
&#xD;
      On the one hand, underdosage of opioids can cause nociception leading to an increased&#xD;
      sympathetic tone, increase of plasma levels of stress hormones, nociceptive movements as well&#xD;
      as increase postoperative pain. On the other hand, overdosage of opioids can lead to drug&#xD;
      side effects such as nausea and vomiting, hemodynamic instability, an increase in recovery&#xD;
      times, immunosuppression and an increase in postoperative pain by&#xD;
      opioid-induced-hyperalgesia. Quality and safety of general anesthesia are of major clinical&#xD;
      importance and can be improved by limiting the administration of opioid analgesics to the&#xD;
      optimal individual dose needed. In the last years, different analgesia monitoring devices&#xD;
      have been developed for monitoring nociception. The present study evaluates the effects of&#xD;
      the administration of opioids during general anesthesia guided by three different monitoring&#xD;
      systems in comparison to routine clinical practice. After institutional approval by the&#xD;
      Ethics committee of the Medical Board of the City of Hamburg, Germany and obtaining patients'&#xD;
      written informed consent the investigators randomize elective patients with major abdominal&#xD;
      surgery for open radical prostatectomy into one of four treatment groups.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 16, 2017</start_date>
  <completion_date type="Actual">January 26, 2018</completion_date>
  <primary_completion_date type="Actual">December 5, 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>
    <intervention_model_description>Participants are assigned to intervention groups by chance</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
    <masking_description>Participants are not informed about the group assignement (intervention takes place in general anesthesia). Outcome assessors are persons without knowledge on former treatment in intervention/control group.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Intraoperative opioid consumption</measure>
    <time_frame>1 day</time_frame>
    <description>Compares the amount of intraoperative opioid administration (sufentanil) per minute of general anesthesia and per kg bodyweight between groups.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to extubation</measure>
    <time_frame>1 day</time_frame>
    <description>Postoperative recovery time: Time interval between end of operation and tracheal extubation of the patient.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to fit-for-discharge</measure>
    <time_frame>1 day</time_frame>
    <description>Postoperative recovery time: Time interval between postoperative tracheal extubation and the patient reaching fit-for-discharge criteria from the PACU to the ward.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Postoperative pain level</measure>
    <time_frame>1 day</time_frame>
    <description>Postoperative pain level measured with the highest score in numeric pain rating scale (NRS).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Postoperative opioid administration</measure>
    <time_frame>1 day</time_frame>
    <description>Amount of postoperative opioid administration (piritramid) in the postanesthesia care unit (PACU). Piritramid is given if NRS score is &gt; 3.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient satisfaction</measure>
    <time_frame>2-21 days</time_frame>
    <description>Patient satisfaction with the general anesthesia and pain management evaluated by a numeric rating scale.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Release of stress hormones</measure>
    <time_frame>1 day</time_frame>
    <description>Amount of perioperative plasma level of cortisol and ACTH.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">48</enrollment>
  <condition>Pain</condition>
  <condition>Pain, Postoperative</condition>
  <condition>Nociceptive Pain</condition>
  <condition>Opioid Use</condition>
  <condition>Analgesia</condition>
  <arm_group>
    <arm_group_label>PPI (Pain Pupillary Index)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Opioid administration guided by Pain Pupillary Index (PPI) derived from Videopupillometry performed with the device AlgiScan manufactured by IDMed, Marseille, France. The device measures the degree of pupillary reflex dilation (PRD) following an electric nociceptive stimulation. It automatically increases the intensity of the electric stimulation from 10 to 60 milliampere depending on the degree of PRD and afterwards displays the PPI. The numerical index ranges from 0 to 10. A low PPI score indicates a deep analgesia, a high PPI score indicates an insufficient or light analgesia. A PPI score of 2 or 3 is supposed to represent an optimal level of analgesia according to the manufacturer. 5 µg sufentanil will be administered every 5 minutes if PPI score is calculated more than 3.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SPI (Surgical Pleth Index)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Opioid administration (sufentanil) guided by by Surgical Pleth Index (SPI) derived from photoplethysmography performed by the device CARESCAPE B650 Patient Monitor from the manufacturer GE (General Electrics) Healthcare, Helsinki, Finland. Included in the monitoring system is a software that continuously calculates the SPI from normalized heart rate and pulse wave amplitude derived from finger plethysmography. The numerical index ranges between 0 (low sympathetic tone) and 100 (high sympathetic tone). A SPI score between 20 and 50 has been proposed as the target range to guide analgesics (15 - 17). 5 µg Sufentanil will be administered every 5 minutes if SPI score is calculated more than 50.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>NOL (Nociception Level)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Opioid administration (sufentanil) guided by Nociception Level (NOL) derived from finger photoplethysmography performed with the analgesia monitoring device PMD200 manufactured by Medasense, Ramat Gan, Israel. The device continuously calculates the NOL with a multi-parametric approach from pulse rate, pulse rate variability, pulse wave amplitude, skin conductance level, skin conductance fluctuations, skin temperature and finger motion. The composite algorithm of the device analyses the data and the numerical index NOL is presented on a scale from 0 (no pain) to 100 (extreme pain) (18). A NOL score between 10 and 25 has been proposed as the target range to guide analgesics. 5 µg Sufentanil will be administered every 5 minutes if NOL score is calculated more than 25.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Opioid administration (sufentanil) guided according to standard clinical practice of the attending anesthesiologist based upon changes of heart rate, blood pressure, lacrimation and sweating of the patient.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Opioid administration in intervention groups</intervention_name>
    <description>Elective surgery in radical open abdominal prostatectomy. Opioid titration is guided by analgesia indices during general anesthesia in the experimental arms.</description>
    <arm_group_label>NOL (Nociception Level)</arm_group_label>
    <arm_group_label>PPI (Pain Pupillary Index)</arm_group_label>
    <arm_group_label>SPI (Surgical Pleth Index)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Opioid administration in control group</intervention_name>
    <description>Elective surgery in radical open abdominal prostatectomy. Opioid titration is guided by clinical signs in the control group.</description>
    <arm_group_label>Control</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Radical open abdominal prostatectomy scheduled in the operation theater where the&#xD;
             study is conducted&#xD;
&#xD;
          -  &gt; 18 years&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Chronic pain therapy, e.g. out-of-hospital opioid therapy&#xD;
&#xD;
          -  Beta blocker and digitalis therapy&#xD;
&#xD;
          -  Eye disease with affection of pupil reactivity&#xD;
&#xD;
          -  Pacemaker therapy&#xD;
&#xD;
          -  Higher degrees of cardiac arrhythmias, e.g. atrial fibrillation&#xD;
&#xD;
          -  Pre-operative medication with steroids&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Rainer Nitzschke, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Anesthesiology; Center of Anesthesiology and Intensive Care Medicine, Hamburg Eppendorf University Medical Center</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Sandra Funcke, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Anesthesiology; Center of Anesthesiology and Intensive Care Medicine, Hamburg Eppendorf University Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Department of Anesthesiology; Center of Anesthesiology and Intensive Care Medicine, Hamburg Eppendorf University Medical Center</name>
      <address>
        <city>Hamburg</city>
        <zip>20257</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>April 2018</verification_date>
  <study_first_submitted>August 28, 2017</study_first_submitted>
  <study_first_submitted_qc>October 2, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 6, 2017</study_first_posted>
  <last_update_submitted>April 24, 2018</last_update_submitted>
  <last_update_submitted_qc>April 24, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">April 25, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Analgesia, Monitoring, Opioid, Sufentanil, Sevoflurane</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pain, Postoperative</mesh_term>
    <mesh_term>Nociceptive Pain</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Analgesics, Opioid</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>All data will be anonymized before publication.</ipd_description>
  </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/NCT03303651
org study id: 20170824
nct id: NCT03303651
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This prospective randomized clinical trial evaluates the effects of a monitor-guided opioid
      analgesia during general anesthesia. To date no standard-monitoring device exists to
      specifically reflect the analgesic component of general anesthesia. Quality and safety of
      general anesthesia are of major clinical importance and should be improved by limiting the
      opioid analgesic's dosage to the minimum amount needed. The study compares the effects of
      monitoring nociception during general anesthesia with different innovative techniques in
      comparison to routine clinical practice.
This prospective randomized clinical study aims to investigate the effects of a
      monitor-guided opioid analgesia during general anesthesia by different monitoring systems in
      comparison to routine clinical practice. Many surgical procedures require general anesthesia.
      The main components of general anesthesia are hypnosis and analgesia, and anesthesiologists
      usually combine a hypnotic drug with an opioid analgesic.

      Until today, however, there is no standard-monitoring of nociception to specifically reflect
      the analgesic component of general anesthesia. In clinical practice the opioid dosage is
      chosen by clinical judgment of the attending anesthesiologist based upon changes of heart
      rate, blood pressure, pupil size, lacrimation and sweating of the patient.

      On the one hand, underdosage of opioids can cause nociception leading to an increased
      sympathetic tone, increase of plasma levels of stress hormones, nociceptive movements as well
      as increase postoperative pain. On the other hand, overdosage of opioids can lead to drug
      side effects such as nausea and vomiting, hemodynamic instability, an increase in recovery
      times, immunosuppression and an increase in postoperative pain by
      opioid-induced-hyperalgesia. Quality and safety of general anesthesia are of major clinical
      importance and can be improved by limiting the administration of opioid analgesics to the
      optimal individual dose needed. In the last years, different analgesia monitoring devices
      have been developed for monitoring nociception. The present study evaluates the effects of
      the administration of opioids during general anesthesia guided by three different monitoring
      systems in comparison to routine clinical practice. After institutional approval by the
      Ethics committee of the Medical Board of the City of Hamburg, Germany and obtaining patients'
      written informed consent the investigators randomize elective patients with major abdominal
      surgery for open radical prostatectomy into one of four treatment groups.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Participants are assigned to intervention groups by chance
primary purpose: Treatment
masking: Double (Participant, Outcomes Assessor)
masking description: Participants are not informed about the group assignement (intervention takes place in general anesthesia). Outcome assessors are persons without knowledge on former treatment in intervention/control group.
measure: Intraoperative opioid consumption
time frame: 1 day
description: Compares the amount of intraoperative opioid administration (sufentanil) per minute of general anesthesia and per kg bodyweight between groups.
measure: Time to extubation
time frame: 1 day
description: Postoperative recovery time: Time interval between end of operation and tracheal extubation of the patient.
measure: Time to fit-for-discharge
time frame: 1 day
description: Postoperative recovery time: Time interval between postoperative tracheal extubation and the patient reaching fit-for-discharge criteria from the PACU to the ward.
measure: Postoperative pain level
time frame: 1 day
description: Postoperative pain level measured with the highest score in numeric pain rating scale (NRS).
measure: Postoperative opioid administration
time frame: 1 day
description: Amount of postoperative opioid administration (piritramid) in the postanesthesia care unit (PACU). Piritramid is given if NRS score is > 3.
measure: Patient satisfaction
time frame: 2-21 days
description: Patient satisfaction with the general anesthesia and pain management evaluated by a numeric rating scale.
measure: Release of stress hormones
time frame: 1 day
description: Amount of perioperative plasma level of cortisol and ACTH.
arm group label: PPI (Pain Pupillary Index)
arm group type: Experimental
description: Opioid administration guided by Pain Pupillary Index (PPI) derived from Videopupillometry performed with the device AlgiScan manufactured by IDMed, Marseille, France. The device measures the degree of pupillary reflex dilation (PRD) following an electric nociceptive stimulation. It automatically increases the intensity of the electric stimulation from 10 to 60 milliampere depending on the degree of PRD and afterwards displays the PPI. The numerical index ranges from 0 to 10. A low PPI score indicates a deep analgesia, a high PPI score indicates an insufficient or light analgesia. A PPI score of 2 or 3 is supposed to represent an optimal level of analgesia according to the manufacturer. 5 µg sufentanil will be administered every 5 minutes if PPI score is calculated more than 3.
arm group label: SPI (Surgical Pleth Index)
arm group type: Experimental
description: Opioid administration (sufentanil) guided by by Surgical Pleth Index (SPI) derived from photoplethysmography performed by the device CARESCAPE B650 Patient Monitor from the manufacturer GE (General Electrics) Healthcare, Helsinki, Finland. Included in the monitoring system is a software that continuously calculates the SPI from normalized heart rate and pulse wave amplitude derived from finger plethysmography. The numerical index ranges between 0 (low sympathetic tone) and 100 (high sympathetic tone). A SPI score between 20 and 50 has been proposed as the target range to guide analgesics (15 - 17). 5 µg Sufentanil will be administered every 5 minutes if SPI score is calculated more than 50.
arm group label: NOL (Nociception Level)
arm group type: Experimental
description: Opioid administration (sufentanil) guided by Nociception Level (NOL) derived from finger photoplethysmography performed with the analgesia monitoring device PMD200 manufactured by Medasense, Ramat Gan, Israel. The device continuously calculates the NOL with a multi-parametric approach from pulse rate, pulse rate variability, pulse wave amplitude, skin conductance level, skin conductance fluctuations, skin temperature and finger motion. The composite algorithm of the device analyses the data and the numerical index NOL is presented on a scale from 0 (no pain) to 100 (extreme pain) (18). A NOL score between 10 and 25 has been proposed as the target range to guide analgesics. 5 µg Sufentanil will be administered every 5 minutes if NOL score is calculated more than 25.
arm group label: Control
arm group type: Active Comparator
description: Opioid administration (sufentanil) guided according to standard clinical practice of the attending anesthesiologist based upon changes of heart rate, blood pressure, lacrimation and sweating of the patient.
intervention type: Procedure
intervention name: Opioid administration in intervention groups
description: Elective surgery in radical open abdominal prostatectomy. Opioid titration is guided by analgesia indices during general anesthesia in the experimental arms.
arm group label: NOL (Nociception Level)
arm group label: PPI (Pain Pupillary Index)
arm group label: SPI (Surgical Pleth Index)
intervention type: Procedure
intervention name: Opioid administration in control group
description: Elective surgery in radical open abdominal prostatectomy. Opioid titration is guided by clinical signs in the control group.
arm group label: Control
criteria: 
gender: Male
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Rainer Nitzschke, MD
role: Principal Investigator
affiliation: Department of Anesthesiology; Center of Anesthesiology and Intensive Care Medicine, Hamburg Eppendorf University Medical Center
last name: Sandra Funcke, MD
role: Principal Investigator
affiliation: Department of Anesthesiology; Center of Anesthesiology and Intensive Care Medicine, Hamburg Eppendorf University Medical Center
facility: 
country: Germany
responsible party type: Sponsor
mesh term: Pain, Postoperative
mesh term: Nociceptive Pain
mesh term: Analgesics, Opioid
sharing ipd: No
ipd description: All data will be anonymized before publication.