<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/NCT04402242</url>
  </required_header>
  <id_info>
    <org_study_id>2019_0051</org_study_id>
    <nct_id>NCT04402242</nct_id>
  </id_info>
  <brief_title>Impact of NOL Index Intraoperative Guided Remifentanil Analgesia</brief_title>
  <acronym>Eu-MultiNOL</acronym>
  <official_title>Impact of Nociceptive-Level (NOL) Intraoperative Guided Remifentanil Analgesia Versus Standard Clinical Care (SCC) for Elective Major Abdominal Surgery</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hopital Foch</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hopital Foch</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>
      The Physiological Monitoring Device (PMD-200™) system is comprised of a monitor and a&#xD;
      designated finger probe containing 4 sensors. The sensors included are Photoplethysmography&#xD;
      (PPG), Galvanic Skin Response (GSR), Accelerometer for movement (ACC) and Thermistor for&#xD;
      peripheral temperature (TMP).&#xD;
&#xD;
      The PMD-200 is intended to be used for assessing the nociception level in anesthetized&#xD;
      patients.&#xD;
&#xD;
      The purpose of the study is confirmation of a reduction in the dosage of remifentanil allowed&#xD;
      by the monitoring of nociception by the NOL which could open the way to a double control of&#xD;
      the administration of anesthetic agents: control of the administration of hypnotics by the&#xD;
      bispectral index (BIS) and control of the administration of opiate by the NOL.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The PMD-200 continuous pain monitor is intended to be used for assessing changes in pain&#xD;
      levels. The system monitors the physiological responses to pain using a relative pain index&#xD;
      from 0-100, called the Nociception Level (NOL®) index. In the NOL index, 0 represents no&#xD;
      nociception or pain and 100 represents high nociception or pain level.&#xD;
&#xD;
      The PMD-200 system consists of a monitor and a specific finger probe containing 4 sensors.&#xD;
      The sensors included are Photoplethysmography (PPG), Galvanic Skin Response (GSR),&#xD;
      Accelerometer for movement (ACC) and Thermistor for peripheral temperature (TMP).&#xD;
&#xD;
      The PMD-200™ is intended to be used for assessing the nociception level in anesthetized&#xD;
      patients. The device is European Conformity (CE) marked and commercially available.&#xD;
&#xD;
      Meier et al. recently published a randomized trial involving 80 patients for major abdominal&#xD;
      surgery, one group receiving routine care and the other NOL-guided analgesia. In the latter&#xD;
      group, the remifentanil concentration was reduced when NOL values were below 10 or increased&#xD;
      when NOL values were above 25 for at least 1 minute. In both groups, propofol was titrated to&#xD;
      have bispectral index values between 45 and 55. Remifentanil administration was reduced in&#xD;
      the NOL-guided group: 0.119 ± 0.033 vs 0.086 ± 0.032 μg.kg.min (p &lt; 0.001). In the NOL-&#xD;
      guided group, 2 out of 40 (5%) patients had hypotension (mean blood pressure less than 55 mm&#xD;
      Hg) compared to 11 out of 40 (28%) in the control group (p = 0.006) and 16 out of 40 (40%)&#xD;
      patients received vasoactive drugs vs 25 out of 40 (63%) (p = 0.044).&#xD;
&#xD;
      Previous results cover a small number of patients treated in a single center. The purpose of&#xD;
      this study is to confirm this result within a multicenter study involving a larger group of&#xD;
      patients. Confirmation of a reduction in the dosage of remifentanil allowed by the monitoring&#xD;
      of nociception by the NOL will open the way to a double control of the administration of&#xD;
      anesthetic agents: control of the administration of hypnotics by the bispectral index (BIS)&#xD;
      and control of the administration of opiate by the NOL.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">April 13, 2021</start_date>
  <completion_date type="Anticipated">May 2025</completion_date>
  <primary_completion_date type="Anticipated">May 2025</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>Randomized, multi-center, single blinded interventional study with 2 parallel groups: standard clinical care (SCC group, control group) and NOL-guided analgesia (NOL guided analgesia group, interventional group), stratified by site</intervention_model_description>
    <primary_purpose>Other</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Remifentanil consumption during maintenance</measure>
    <time_frame>surgery day (D0)</time_frame>
    <description>Remifentanil consumption during anesthesia maintenance in μg/kg/min</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Remifentanil consumption during induction</measure>
    <time_frame>surgery day (D0)</time_frame>
    <description>Remifentanil consumption during anesthesia induction in μg/kg/min</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Propofol consumption during induction</measure>
    <time_frame>surgery day (D0)</time_frame>
    <description>Propofol consumption during anesthesia induction in μg/kg/min</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Propofol consumption during maintenance</measure>
    <time_frame>surgery day (D0)</time_frame>
    <description>Propofol consumption during anesthesia maintenance in μg/kg/min</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients with intraoperative hemodynamic abnormality in the NOL index group compared to standard care group during induction</measure>
    <time_frame>surgery day (D0)</time_frame>
    <description>A hemodynamic abnormality is defined as:&#xD;
administration of a vasoactive agent (ephedrine, phenylephrine, norepinephrine, adrenaline, atropine)&#xD;
and/or average blood pressure &lt; 55 mmHg or &lt; 60 mmHg or &lt; 65 mmHg for any length of time&#xD;
an/or a systolic blood pressure &gt; 140 mmHg for any length of time&#xD;
and/or a heart rate &lt; 45 or &gt; 90 /min</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients with intraoperative hemodynamic abnormality in the NOL index group compared to standard care group during maintenance</measure>
    <time_frame>surgery day (D0)</time_frame>
    <description>Mean Blood pressure events during anesthesia inductio A hemodynamic abnormality is defined as:&#xD;
administration of a vasoactive agent (ephedrine, phenylephrine, norepinephrine, adrenaline, atropine)&#xD;
and/or average blood pressure &lt; 55 mmHg or &lt; 60 mmHg or &lt; 65 mmHg for any length of time&#xD;
an/or a systolic blood pressure &gt; 140 mmHg for any length of time&#xD;
and/or a heart rate &lt; 45 or &gt; 90 /min</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients with intraoperative anesthetic abnormality in the NOL index group compared to standard care group during induction</measure>
    <time_frame>surgery day (D0)</time_frame>
    <description>An anesthetic abnormality is defined as:&#xD;
a bispectral (BIS) index &lt; 40 or &gt; 60 for at least one minute&#xD;
and/or a Burst Suppression Ratio (BSR) index &gt; 10% during one minute&#xD;
and/or a NOL index &gt; 25 or &lt; 10 for at least 2 minutes</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients with intraoperative anesthetic abnormality in the NOL index group compared to standard care group during maintenance</measure>
    <time_frame>surgery day (D0)</time_frame>
    <description>An anesthetic abnormality is defined as:&#xD;
a bispectral (BIS) index &lt; 40 or &gt; 60 for at least one minute&#xD;
and/or a Burst Suppression Ratio (BSR) index &gt; 10% during one minute&#xD;
and/or a NOL index &gt; 25 or &lt; 10 for at least 2 minutes</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Wake up time</measure>
    <time_frame>surgery day (D0)</time_frame>
    <description>delay between the end of Propofol or Sugammadex/Neostigmine and extubation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Intensity of pain in PACU (post-anesthesia care unit)</measure>
    <time_frame>surgery day (D0)</time_frame>
    <description>Morphine consumption in PACU (post-anesthesia care unit)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">210</enrollment>
  <condition>Abdominal Surgery</condition>
  <arm_group>
    <arm_group_label>&quot;SCS&quot; Group</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>Receiving anesthesia according to routine standard care, with the use of the &quot;hidden&quot; NOL (used to compare the data at the end of anesthesia with those of the classic BIS - without monitoring of the anesthesia by the NOL (without adjustment of treatments ))</description>
  </arm_group>
  <arm_group>
    <arm_group_label>NOL Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Receiving anesthesia monitored by the NOL</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Bispectral index</intervention_name>
    <description>Anesthesia monitoring</description>
    <arm_group_label>&quot;SCS&quot; Group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Bispectral index + NOL index</intervention_name>
    <description>Anesthesia monitoring</description>
    <arm_group_label>NOL Group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age ≥ 18 years old&#xD;
&#xD;
          -  American Society of Anesthesiologists score (ASA) I, II or III stable&#xD;
&#xD;
          -  Laparotomy or laparoscopy for major, planned, digestive, urological or gynecological&#xD;
             surgery under total intravenous anesthesia (expected total duration &gt; 90 minutes)&#xD;
&#xD;
          -  Having sign an informed consent form prior to any study specific procedure&#xD;
&#xD;
          -  Being covered by a national health insurance&#xD;
&#xD;
        Non-Inclusion Criteria:&#xD;
&#xD;
          -  Pregnancy/lactation&#xD;
&#xD;
          -  Patient with antiarrhythmic agents&#xD;
&#xD;
          -  Patient with Central nervous system disorder&#xD;
&#xD;
          -  Patient with veinous approach difficulties&#xD;
&#xD;
          -  Patient at risk of difficult mask ventilation or difficult intubation&#xD;
&#xD;
          -  Concomitant use of any type of anesthesia other than general anesthesia (epidural&#xD;
             anesthesia, spinal anesthesia, wall block, pericatricial infiltration). Wall blocks&#xD;
             and pericatricial infiltrations are allowed if they are carried out at the end of the&#xD;
             intervention&#xD;
&#xD;
          -  Allergy or intolerance to any of the study drugs&#xD;
&#xD;
          -  Patient not understanding French language&#xD;
&#xD;
          -  Being deprived of liberty or under guardianship&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patient requiring the administration of succinylcholine&#xD;
&#xD;
          -  Patient with hemodynamic abnormality just before induction of anesthesia (mean&#xD;
             arterial pressure &lt; 65 mm Hg or &gt; 110 mm Hg, heart rate &lt; 45/min or &gt; 90/min&#xD;
&#xD;
          -  Concomitant use of any type of anesthesia other than general anesthesia (epidural&#xD;
             anesthesia, spinal anesthesia, wall block, pericatricial infiltration). Wall blocks&#xD;
             and pericatricial infiltrations are allowed if they are carried out at the end of the&#xD;
             intervention&#xD;
&#xD;
          -  Concomitant use of IV lidocaine or continuous ketamine (IV, SE) during anaesthesia&#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>Morgan LE GUEN, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Foch HOSPITAL</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Morgan LE GUEN, Dr</last_name>
    <phone>+33146252998</phone>
    <email>m.leguen@hopital-foch.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Elisabeth HULIER AMMAR, Dr</last_name>
    <phone>+33146251175</phone>
    <email>drci-promotion@hopital-foch.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Hôpital d'Instruction des Armées - Sainte-Anne</name>
      <address>
        <city>Toulon</city>
        <state>Provence-Alpes-Côte d'Azur</state>
        <zip>83800</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Julien Bordes, MD</last_name>
      <phone>06.81.49.81.77</phone>
      <email>julien.bordes@intradef.gouv.fr</email>
    </contact>
    <contact_backup>
      <last_name>Karine Michaud Grosbenoit</last_name>
      <phone>04.83.76.24.61</phone>
      <email>karine.dandrieux@intradef.gouv.fr</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Hopital d'Instruction des Armées de Bégin</name>
      <address>
        <city>Saint-Mandé</city>
        <state>Saint Mandé</state>
        <zip>94160</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Jean Pierre TOURTIER, PhD</last_name>
      <phone>0033767669549</phone>
      <email>jean-pierre.tourtier@intradef.gouv.fr</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Foch Hospital</name>
      <address>
        <city>Suresnes</city>
        <zip>92150</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Morgan LE GUEN, MD</last_name>
      <phone>+33146252989</phone>
      <email>m.leguen@hopital-foch.com</email>
    </contact>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <results_reference>
    <citation>Meijer FS, Martini CH, Broens S, Boon M, Niesters M, Aarts L, Olofsen E, van Velzen M, Dahan A. Nociception-guided versus Standard Care during Remifentanil-Propofol Anesthesia: A Randomized Controlled Trial. Anesthesiology. 2019 May;130(5):745-755. doi: 10.1097/ALN.0000000000002634.</citation>
    <PMID>30829658</PMID>
  </results_reference>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>April 20, 2020</study_first_submitted>
  <study_first_submitted_qc>May 22, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 26, 2020</study_first_posted>
  <last_update_submitted>June 13, 2023</last_update_submitted>
  <last_update_submitted_qc>June 13, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 15, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT04402242
org study id: 2019_0051
nct id: NCT04402242
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The Physiological Monitoring Device (PMD-200™) system is comprised of a monitor and a
      designated finger probe containing 4 sensors. The sensors included are Photoplethysmography
      (PPG), Galvanic Skin Response (GSR), Accelerometer for movement (ACC) and Thermistor for
      peripheral temperature (TMP).

      The PMD-200 is intended to be used for assessing the nociception level in anesthetized
      patients.

      The purpose of the study is confirmation of a reduction in the dosage of remifentanil allowed
      by the monitoring of nociception by the NOL which could open the way to a double control of
      the administration of anesthetic agents: control of the administration of hypnotics by the
      bispectral index (BIS) and control of the administration of opiate by the NOL.
The PMD-200 continuous pain monitor is intended to be used for assessing changes in pain
      levels. The system monitors the physiological responses to pain using a relative pain index
      from 0-100, called the Nociception Level (NOL®) index. In the NOL index, 0 represents no
      nociception or pain and 100 represents high nociception or pain level.

      The PMD-200 system consists of a monitor and a specific finger probe containing 4 sensors.
      The sensors included are Photoplethysmography (PPG), Galvanic Skin Response (GSR),
      Accelerometer for movement (ACC) and Thermistor for peripheral temperature (TMP).

      The PMD-200™ is intended to be used for assessing the nociception level in anesthetized
      patients. The device is European Conformity (CE) marked and commercially available.

      Meier et al. recently published a randomized trial involving 80 patients for major abdominal
      surgery, one group receiving routine care and the other NOL-guided analgesia. In the latter
      group, the remifentanil concentration was reduced when NOL values were below 10 or increased
      when NOL values were above 25 for at least 1 minute. In both groups, propofol was titrated to
      have bispectral index values between 45 and 55. Remifentanil administration was reduced in
      the NOL-guided group: 0.119 ± 0.033 vs 0.086 ± 0.032 μg.kg.min (p < 0.001). In the NOL-
      guided group, 2 out of 40 (5%) patients had hypotension (mean blood pressure less than 55 mm
      Hg) compared to 11 out of 40 (28%) in the control group (p = 0.006) and 16 out of 40 (40%)
      patients received vasoactive drugs vs 25 out of 40 (63%) (p = 0.044).

      Previous results cover a small number of patients treated in a single center. The purpose of
      this study is to confirm this result within a multicenter study involving a larger group of
      patients. Confirmation of a reduction in the dosage of remifentanil allowed by the monitoring
      of nociception by the NOL will open the way to a double control of the administration of
      anesthetic agents: control of the administration of hypnotics by the bispectral index (BIS)
      and control of the administration of opiate by the NOL.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Randomized, multi-center, single blinded interventional study with 2 parallel groups: standard clinical care (SCC group, control group) and NOL-guided analgesia (NOL guided analgesia group, interventional group), stratified by site
primary purpose: Other
masking: Single (Participant)
measure: Remifentanil consumption during maintenance
time frame: surgery day (D0)
description: Remifentanil consumption during anesthesia maintenance in μg/kg/min
measure: Remifentanil consumption during induction
time frame: surgery day (D0)
description: Remifentanil consumption during anesthesia induction in μg/kg/min
measure: Propofol consumption during induction
time frame: surgery day (D0)
description: Propofol consumption during anesthesia induction in μg/kg/min
measure: Propofol consumption during maintenance
time frame: surgery day (D0)
description: Propofol consumption during anesthesia maintenance in μg/kg/min
measure: Proportion of patients with intraoperative hemodynamic abnormality in the NOL index group compared to standard care group during induction
time frame: surgery day (D0)
description: A hemodynamic abnormality is defined as:
administration of a vasoactive agent (ephedrine, phenylephrine, norepinephrine, adrenaline, atropine)
and/or average blood pressure < 55 mmHg or < 60 mmHg or < 65 mmHg for any length of time
an/or a systolic blood pressure > 140 mmHg for any length of time
and/or a heart rate < 45 or > 90 /min
measure: Proportion of patients with intraoperative hemodynamic abnormality in the NOL index group compared to standard care group during maintenance
time frame: surgery day (D0)
description: Mean Blood pressure events during anesthesia inductio A hemodynamic abnormality is defined as:
administration of a vasoactive agent (ephedrine, phenylephrine, norepinephrine, adrenaline, atropine)
and/or average blood pressure < 55 mmHg or < 60 mmHg or < 65 mmHg for any length of time
an/or a systolic blood pressure > 140 mmHg for any length of time
and/or a heart rate < 45 or > 90 /min
measure: Proportion of patients with intraoperative anesthetic abnormality in the NOL index group compared to standard care group during induction
time frame: surgery day (D0)
description: An anesthetic abnormality is defined as:
a bispectral (BIS) index < 40 or > 60 for at least one minute
and/or a Burst Suppression Ratio (BSR) index > 10% during one minute
and/or a NOL index > 25 or < 10 for at least 2 minutes
measure: Proportion of patients with intraoperative anesthetic abnormality in the NOL index group compared to standard care group during maintenance
time frame: surgery day (D0)
description: An anesthetic abnormality is defined as:
a bispectral (BIS) index < 40 or > 60 for at least one minute
and/or a Burst Suppression Ratio (BSR) index > 10% during one minute
and/or a NOL index > 25 or < 10 for at least 2 minutes
measure: Wake up time
time frame: surgery day (D0)
description: delay between the end of Propofol or Sugammadex/Neostigmine and extubation
measure: Intensity of pain in PACU (post-anesthesia care unit)
time frame: surgery day (D0)
description: Morphine consumption in PACU (post-anesthesia care unit)
arm group label: "SCS" Group
arm group type: Sham Comparator
description: Receiving anesthesia according to routine standard care, with the use of the "hidden" NOL (used to compare the data at the end of anesthesia with those of the classic BIS - without monitoring of the anesthesia by the NOL (without adjustment of treatments ))
arm group label: NOL Group
arm group type: Experimental
description: Receiving anesthesia monitored by the NOL
intervention type: Device
intervention name: Bispectral index
description: Anesthesia monitoring
arm group label: "SCS" Group
intervention type: Device
intervention name: Bispectral index + NOL index
description: Anesthesia monitoring
arm group label: NOL Group
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Morgan LE GUEN, MD
role: Principal Investigator
affiliation: Foch HOSPITAL
last name: Morgan LE GUEN, Dr
phone: +33146252998
email: m.leguen@hopital-foch.com
last name: Elisabeth HULIER AMMAR, Dr
phone: +33146251175
email: drci-promotion@hopital-foch.com
facility: 
status: Not yet recruiting
contact: 
contact backup: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Recruiting
contact: 
country: France
citation: Meijer FS, Martini CH, Broens S, Boon M, Niesters M, Aarts L, Olofsen E, van Velzen M, Dahan A. Nociception-guided versus Standard Care during Remifentanil-Propofol Anesthesia: A Randomized Controlled Trial. Anesthesiology. 2019 May;130(5):745-755. doi: 10.1097/ALN.0000000000002634.
PMID: 30829658
responsible party type: Sponsor
sharing ipd: No