<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/NCT01678625</url>
  </required_header>
  <id_info>
    <org_study_id>EH12-158</org_study_id>
    <nct_id>NCT01678625</nct_id>
  </id_info>
  <brief_title>Electromyographic Assessment of Onset and Recovery of Neuromuscular Blockade</brief_title>
  <official_title>Electromyographic Assessment of Onset and Recovery of Neuromuscular Blockade</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>NorthShore University HealthSystem</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>T4 Analytics</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>NorthShore University HealthSystem</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Residual neuromuscular blockade (weakness) is a common occurrence in the postanesthesia care&#xD;
      unit when muscle relaxant drugs have been used in the operating room. The only method of&#xD;
      reliably detecting the presence of neuromuscular blockade is through the use of quantitative&#xD;
      neuromuscular monitors. These devices measure and quantify the degree of muscle weakness and&#xD;
      display the results on a screen. When using train-of-four (TOF) nerve stimulation, the ratio&#xD;
      of the fourth muscle contraction (twitch) to the first twitch will be displayed; when this&#xD;
      ratio is 90% (or 0.9) or greater, full recovery of muscle strength is present, and the&#xD;
      endotracheal tube can be removed. At the present time, there is only one&#xD;
      commercially-available quantitative monitor available in the United States -the TOF-Watch. It&#xD;
      is not used by many clinicians because it requires experience to obtain accurate results, is&#xD;
      expensive, and is subject to interference by factors in the operating room. The aim of this&#xD;
      investigation is to examine a new quantitative monitor (the T4-EMG (EMG = electromyography)&#xD;
      that may not be subject to the same limitations as the TOF-Watch AMG (AMG =&#xD;
      acceleromyography). In order to study the accuracy of this new device, the T4-EMG will be&#xD;
      compared to the current &quot;clinical gold standard&quot;, the TOF-Watch.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The aim of this investigation is to examine a new prototype of a quantitative monitoring&#xD;
      instrument that will meet these requirements. Patients undergoing surgery under general&#xD;
      anesthesia will be monitored with a new EMG device (T4-EMG) from induction of anesthesia&#xD;
      until recovery of neuromuscular blockade. Continuous data will be recorded onto an interfaced&#xD;
      computer from the T4-EMG monitor during this time period. At the same time, continuous&#xD;
      neuromuscular data will be recorded onto the computer from an AMG device (TOF-Watch, the&#xD;
      &quot;established standard&quot; for clinical use) which is attached to the same arm. The applicability&#xD;
      (ease of use, equipment need, etc.), repeatability (precision or internal consistency), and&#xD;
      performance (agreement with established standard, bias) of the T4-EMG compared to the AMG&#xD;
      will be determined during onset and recovery of neuromuscular blockade.&#xD;
&#xD;
      44 patients presenting for elective surgical procedures with an expected duration greater&#xD;
      than 60 minutes will be enrolled in this study. ASA I to III patients requiring neuromuscular&#xD;
      blockade in the operating room will be eligible for enrollment. Anesthetic management will be&#xD;
      standardized.&#xD;
&#xD;
      Upon arrival to the operating room, neuromuscular monitoring surface electrodes will be&#xD;
      applied. All monitoring will be conducted while the patient is under general anesthesia for&#xD;
      the surgical procedure. Surface electrodes (non-invasive EKG electrodes) will be placed on&#xD;
      the cleansed skin over the ulnar nerve of the available arm near the wrist. The electrodes&#xD;
      will be connected by leads to a peripheral nerve stimulator (TOF-Watch). When the nerve&#xD;
      stimulator is activated, the response to stimulation will be measured simultaneously by the&#xD;
      AMG (TOF-Watch-acceleration of contraction of the adductor pollicis-thumb) and the EMG&#xD;
      (T4-EMG-electrical activity of the adductor pollicis-thumb) devices. Therefore, the TOF-Watch&#xD;
      will serve as nerve stimulator for both study groups. The transducer of the AMG device will&#xD;
      be placed on the thumb of the corresponding hand. A 75-150g preload (via the Hand adapter)&#xD;
      will be applied as per standard recommendations. After induction of anesthesia, but before&#xD;
      administration of rocuronium, calibration, supramaximal stimulation, and stable baseline will&#xD;
      be achieved for the TOF-Watch as suggested by the GCRP guidelines.&#xD;
&#xD;
      The T4-EMG will be placed on the same arm as the AMG device, with sensing electrodes attached&#xD;
      to the surface of the thenar eminence (base of the thumb). A second sensing lead, used to&#xD;
      detect the delivery of an electrical stimulating pulse, will be placed over the stimulating&#xD;
      leads of the AMG device. This sensing lead will only be used to trigger data acquisition in&#xD;
      the T4-EMG, and has no direct connection to the patient, nor any electrical feedback&#xD;
      connection that alters the function of the AMG. After a satisfactory level of stimulation and&#xD;
      response has been obtained for the TOF-Watch, the T4-EMG device will be turned on, and the&#xD;
      impedance of the thenar sensing leads will be measured. The trigger sense will be engaged,&#xD;
      and further baseline stimuli will be delivered via the AMG (TOF-Watch). Data simultaneously&#xD;
      collected from the thenar sensing leads will be inspected on the T4-EMG display, and fine&#xD;
      adjustment of electrode positioning and stimulus intensity may be made to optimize the evoked&#xD;
      myoelectric response from the patient. At the conclusion of the setup procedure, all settings&#xD;
      of the AMG and the T4-EMG will be held constant for the remainder of the surgery.&#xD;
&#xD;
      After these baseline data are collected (average time 5 minutes), the neuromuscular blocking&#xD;
      agent (NMBA) will be administered. Data relating to onset (a TOF ratio decreases from 1.0 to&#xD;
      0.3 or less on the AMG device display), maintenance (the TOF ratio is less than 0.3 and&#xD;
      constant on the AMG device display), and reversal (an increase in the TOF ratio from 0.1 to&#xD;
      0.9 or above) will be recorded. Monitoring will continue until full recovery of neuromuscular&#xD;
      function is noted (a TOF ratio of at least 0.9 or greater on the AMG device display). At this&#xD;
      time, the anesthesia agents will be turned off and the patient awakened and extubated.&#xD;
      Patients' trachea may extubated before achieving a TOF ratio of 0.9 if they awaken before&#xD;
      this time, as per usual clinical routine determined by the clinician.&#xD;
&#xD;
      For the first 34 patients, the TOF-Watch is used as the nerve stimulator for both the AMG&#xD;
      (TOF-Watch) and EMG (T4-EMG) groups. The ability of the T4-EMG device to sense/measure TOF&#xD;
      ratios is the primary aim of the study (in comparison to the &quot;clinical gold standard&quot;&#xD;
      TOF-Watch). However, the prototype T4-EMG (as well as the commercial device to be developed)&#xD;
      will also contain a nerve stimulator (as do all qualitative and quantitative monitors). On a&#xD;
      subset of patients monitored by the TOF-Watch (10 patients), the stand-alone T4-EMG device&#xD;
      (single unit containing both the nerve stimulator and sensing/monitoring components) will be&#xD;
      connected to the same arm and operated independently of the TOF-Watch. Its stimulating&#xD;
      electrodes will be placed on the surface of the arm adjacent to the TOF-Watch electrodes;&#xD;
      sensing leads will be placed on the thenar eminence as in the protocol described above. The&#xD;
      T4-EMG will be set up independently of the TOF-Watch, with its own stimulator adjustment&#xD;
      being made according to the same protocol as the TOF-Watch adjustment. The T4-EMG will be&#xD;
      operated to stimulate and record at times selected by the anesthesiologist that do not&#xD;
      conflict with operation of the TOF-Watch or interfere with other patient care activities.&#xD;
      Evoked muscle response data will be displayed by the T4-EMG, but amplitude ratios will not be&#xD;
      computed and it will not be used for direct patient care. The purpose is to demonstrate that&#xD;
      the device elicits and records evoked muscle responses from surgical patients and to assess&#xD;
      usability: this is in contrast to the main protocol where the T4-EMG is triggered by the&#xD;
      TOF-Watch and where comparison of recorded responses is the goal.&#xD;
&#xD;
      The primary endpoint in the first 33 patients will be an analysis of the agreement between&#xD;
      the AMG (clinical &quot;gold standard&quot;) and EMG devices during neuromuscular recovery. Data will&#xD;
      be compared between the two devices at AMG-derived TOF ratios values of 0.7, 0.8, 0.9, and&#xD;
      1.0 (if achieved) during recovery of neuromuscular function. Bias and limits of agreement&#xD;
      will be calculated at each TOF value.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Company making the device no longer in existence. Did not finish supplying data to research&#xD;
    team&#xD;
  </why_stopped>
  <start_date>June 2012</start_date>
  <completion_date type="Actual">December 2013</completion_date>
  <primary_completion_date type="Actual">December 2013</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Train-of-four (TOF)ratio</measure>
    <time_frame>TOF ratios will be measured for the duration of the operation, approximately 3 hours</time_frame>
    <description>Train-of-four ratios during recovery of neuromuscular blockade will be compared between the AMG and EMG devices (at a TOF ratio of 0.6, 0.7, 0.8, and 0.9.)</description>
  </primary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">30</enrollment>
  <condition>Residual Neuromuscular Blockade</condition>
  <arm_group>
    <arm_group_label>Acceleromyography group</arm_group_label>
    <description>Train-of-four ratio calculation (TOF-Watch-SX-Bluestar enterprise)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Electromyography group</arm_group_label>
    <description>Train-of-four ratio calculation (T4-EMG)</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Train-of-four ratio calculation (T4-EMG)</intervention_name>
    <description>TOF ratios will be compared between the EMG and AMG groups</description>
    <arm_group_label>Acceleromyography group</arm_group_label>
    <arm_group_label>Electromyography group</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Patients presenting for elective surgical procedures under general anesthesia with an&#xD;
        expected duration greater than 60 minutes will be enrolled in this study.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  American Society of Anesthesiologists Status I to III patients requiring neuromuscular&#xD;
             blockade in the operating room will be eligible for enrollment&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  1) presence of an underlying neuromuscular disease; 2) use of drugs known to interfere&#xD;
             with neuromuscular transmission (antiseizure medications, anticholinesterases,&#xD;
             magnesium sulfate); 3) presence of renal or hepatic disease; or 4) procedures&#xD;
             preventing access to at least one of the upper extremities.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Glenn S. Murphy, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>NorthShore University HealthSystem</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>NorthShore University HealthSystem</name>
      <address>
        <city>Evanston</city>
        <state>Illinois</state>
        <zip>60201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2019</verification_date>
  <study_first_submitted>August 28, 2012</study_first_submitted>
  <study_first_submitted_qc>August 30, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 5, 2012</study_first_posted>
  <last_update_submitted>September 12, 2019</last_update_submitted>
  <last_update_submitted_qc>September 12, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">September 13, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>NorthShore University HealthSystem</investigator_affiliation>
    <investigator_full_name>Glenn Murphy</investigator_full_name>
    <investigator_title>Director, Clinical Research</investigator_title>
  </responsible_party>
  <keyword>Residual neuromuscular blockade</keyword>
  <keyword>Train-of-four</keyword>
  <keyword>Acceleromyography</keyword>
  <keyword>Electromyography</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Delayed Emergence from Anesthesia</mesh_term>
  </condition_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/NCT01678625
org study id: EH12-158
nct id: NCT01678625
lead sponsor: 
collaborator: 
has dmc: No
Residual neuromuscular blockade (weakness) is a common occurrence in the postanesthesia care
      unit when muscle relaxant drugs have been used in the operating room. The only method of
      reliably detecting the presence of neuromuscular blockade is through the use of quantitative
      neuromuscular monitors. These devices measure and quantify the degree of muscle weakness and
      display the results on a screen. When using train-of-four (TOF) nerve stimulation, the ratio
      of the fourth muscle contraction (twitch) to the first twitch will be displayed; when this
      ratio is 90% (or 0.9) or greater, full recovery of muscle strength is present, and the
      endotracheal tube can be removed. At the present time, there is only one
      commercially-available quantitative monitor available in the United States -the TOF-Watch. It
      is not used by many clinicians because it requires experience to obtain accurate results, is
      expensive, and is subject to interference by factors in the operating room. The aim of this
      investigation is to examine a new quantitative monitor (the T4-EMG (EMG = electromyography)
      that may not be subject to the same limitations as the TOF-Watch AMG (AMG =
      acceleromyography). In order to study the accuracy of this new device, the T4-EMG will be
      compared to the current "clinical gold standard", the TOF-Watch.
The aim of this investigation is to examine a new prototype of a quantitative monitoring
      instrument that will meet these requirements. Patients undergoing surgery under general
      anesthesia will be monitored with a new EMG device (T4-EMG) from induction of anesthesia
      until recovery of neuromuscular blockade. Continuous data will be recorded onto an interfaced
      computer from the T4-EMG monitor during this time period. At the same time, continuous
      neuromuscular data will be recorded onto the computer from an AMG device (TOF-Watch, the
      "established standard" for clinical use) which is attached to the same arm. The applicability
      (ease of use, equipment need, etc.), repeatability (precision or internal consistency), and
      performance (agreement with established standard, bias) of the T4-EMG compared to the AMG
      will be determined during onset and recovery of neuromuscular blockade.

      44 patients presenting for elective surgical procedures with an expected duration greater
      than 60 minutes will be enrolled in this study. ASA I to III patients requiring neuromuscular
      blockade in the operating room will be eligible for enrollment. Anesthetic management will be
      standardized.

      Upon arrival to the operating room, neuromuscular monitoring surface electrodes will be
      applied. All monitoring will be conducted while the patient is under general anesthesia for
      the surgical procedure. Surface electrodes (non-invasive EKG electrodes) will be placed on
      the cleansed skin over the ulnar nerve of the available arm near the wrist. The electrodes
      will be connected by leads to a peripheral nerve stimulator (TOF-Watch). When the nerve
      stimulator is activated, the response to stimulation will be measured simultaneously by the
      AMG (TOF-Watch-acceleration of contraction of the adductor pollicis-thumb) and the EMG
      (T4-EMG-electrical activity of the adductor pollicis-thumb) devices. Therefore, the TOF-Watch
      will serve as nerve stimulator for both study groups. The transducer of the AMG device will
      be placed on the thumb of the corresponding hand. A 75-150g preload (via the Hand adapter)
      will be applied as per standard recommendations. After induction of anesthesia, but before
      administration of rocuronium, calibration, supramaximal stimulation, and stable baseline will
      be achieved for the TOF-Watch as suggested by the GCRP guidelines.

      The T4-EMG will be placed on the same arm as the AMG device, with sensing electrodes attached
      to the surface of the thenar eminence (base of the thumb). A second sensing lead, used to
      detect the delivery of an electrical stimulating pulse, will be placed over the stimulating
      leads of the AMG device. This sensing lead will only be used to trigger data acquisition in
      the T4-EMG, and has no direct connection to the patient, nor any electrical feedback
      connection that alters the function of the AMG. After a satisfactory level of stimulation and
      response has been obtained for the TOF-Watch, the T4-EMG device will be turned on, and the
      impedance of the thenar sensing leads will be measured. The trigger sense will be engaged,
      and further baseline stimuli will be delivered via the AMG (TOF-Watch). Data simultaneously
      collected from the thenar sensing leads will be inspected on the T4-EMG display, and fine
      adjustment of electrode positioning and stimulus intensity may be made to optimize the evoked
      myoelectric response from the patient. At the conclusion of the setup procedure, all settings
      of the AMG and the T4-EMG will be held constant for the remainder of the surgery.

      After these baseline data are collected (average time 5 minutes), the neuromuscular blocking
      agent (NMBA) will be administered. Data relating to onset (a TOF ratio decreases from 1.0 to
      0.3 or less on the AMG device display), maintenance (the TOF ratio is less than 0.3 and
      constant on the AMG device display), and reversal (an increase in the TOF ratio from 0.1 to
      0.9 or above) will be recorded. Monitoring will continue until full recovery of neuromuscular
      function is noted (a TOF ratio of at least 0.9 or greater on the AMG device display). At this
      time, the anesthesia agents will be turned off and the patient awakened and extubated.
      Patients' trachea may extubated before achieving a TOF ratio of 0.9 if they awaken before
      this time, as per usual clinical routine determined by the clinician.

      For the first 34 patients, the TOF-Watch is used as the nerve stimulator for both the AMG
      (TOF-Watch) and EMG (T4-EMG) groups. The ability of the T4-EMG device to sense/measure TOF
      ratios is the primary aim of the study (in comparison to the "clinical gold standard"
      TOF-Watch). However, the prototype T4-EMG (as well as the commercial device to be developed)
      will also contain a nerve stimulator (as do all qualitative and quantitative monitors). On a
      subset of patients monitored by the TOF-Watch (10 patients), the stand-alone T4-EMG device
      (single unit containing both the nerve stimulator and sensing/monitoring components) will be
      connected to the same arm and operated independently of the TOF-Watch. Its stimulating
      electrodes will be placed on the surface of the arm adjacent to the TOF-Watch electrodes;
      sensing leads will be placed on the thenar eminence as in the protocol described above. The
      T4-EMG will be set up independently of the TOF-Watch, with its own stimulator adjustment
      being made according to the same protocol as the TOF-Watch adjustment. The T4-EMG will be
      operated to stimulate and record at times selected by the anesthesiologist that do not
      conflict with operation of the TOF-Watch or interfere with other patient care activities.
      Evoked muscle response data will be displayed by the T4-EMG, but amplitude ratios will not be
      computed and it will not be used for direct patient care. The purpose is to demonstrate that
      the device elicits and records evoked muscle responses from surgical patients and to assess
      usability: this is in contrast to the main protocol where the T4-EMG is triggered by the
      TOF-Watch and where comparison of recorded responses is the goal.

      The primary endpoint in the first 33 patients will be an analysis of the agreement between
      the AMG (clinical "gold standard") and EMG devices during neuromuscular recovery. Data will
      be compared between the two devices at AMG-derived TOF ratios values of 0.7, 0.8, 0.9, and
      1.0 (if achieved) during recovery of neuromuscular function. Bias and limits of agreement
      will be calculated at each TOF value.
observational model: Case-Control
time perspective: Prospective
measure: Train-of-four (TOF)ratio
time frame: TOF ratios will be measured for the duration of the operation, approximately 3 hours
description: Train-of-four ratios during recovery of neuromuscular blockade will be compared between the AMG and EMG devices (at a TOF ratio of 0.6, 0.7, 0.8, and 0.9.)
arm group label: Acceleromyography group
description: Train-of-four ratio calculation (TOF-Watch-SX-Bluestar enterprise)
arm group label: Electromyography group
description: Train-of-four ratio calculation (T4-EMG)
intervention type: Device
intervention name: Train-of-four ratio calculation (T4-EMG)
description: TOF ratios will be compared between the EMG and AMG groups
arm group label: Acceleromyography group
arm group label: Electromyography group
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Glenn S. Murphy, MD
role: Principal Investigator
affiliation: NorthShore University HealthSystem
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: NorthShore University HealthSystem
investigator full name: Glenn Murphy
investigator title: Director, Clinical Research
mesh term: Delayed Emergence from Anesthesia