<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/NCT03034577</url>
  </required_header>
  <id_info>
    <org_study_id>2016.343</org_study_id>
    <nct_id>NCT03034577</nct_id>
  </id_info>
  <brief_title>Deep Neuromuscular Block for Laparoscopic Surgery</brief_title>
  <acronym>DEEPBLOCK</acronym>
  <official_title>A Randomized Trial of Deep Neuromuscular Blockade Reversed With Sugammadex Versus Moderate Neuromuscular Block Reversed With Neostigmine, on Postoperative Quality of Recovery</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Melbourne</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Melbourne Health</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Peter MacCallum Cancer Centre, Australia</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Royal Hospital For Women</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Northpark Private Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Melbourne</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>
      Trial summary: deep neuromuscular block is proposed as a technique to improve operative&#xD;
      conditions for laparoscopy. Early clinical data would suggest that there may also be patient&#xD;
      benefits beyond the operative period related to lower intra-abdominal pressure, and improved&#xD;
      surgical exposure. In order to safely conduct deep neuromuscular blockade, it is essential to&#xD;
      use Sugammadex to reverse the neuromuscular block. Conventional practice is to provide&#xD;
      moderate neuromuscular block and reverse with neostigmine. It is not possible to safely&#xD;
      reverse deep neuromuscular block using neostogmine, as the majority of block must have worn&#xD;
      off for neostigmine to be effective. in order to identify whether deep neuromuscular block&#xD;
      improves quality of recovery after surgery, the investigators will conduct a randomised trial&#xD;
      of deep versus moderate neuromuscular block, whilst minimising variance in other anaesthetic&#xD;
      techniques and drugs used. the outcome measured will be the post-operative quality of&#xD;
      recovery over multiple time periods using the Postoperative Quality of Recovery Scale&#xD;
      (PostopQRS). 350 patients will be enrolled over 4 centres.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Objectives&#xD;
&#xD;
      1. To identify whether the rate/quality of recovery is affected by deep neuromuscular block&#xD;
      (DNB) and reversal with sugammadex versus light/moderate neuromuscular block reversed with&#xD;
      neostigmine and couple with desflurane or sevoflurane in patients undergoing operative&#xD;
      gynecological or abdominal laparoscopic surgery of at least 1-hour duration.&#xD;
&#xD;
      Hypothesis&#xD;
&#xD;
      1. The technique of deep neuromuscular block and reversal with sugammadex will result in&#xD;
      improved quality of recovery, including cognition, compared to the current standard of care&#xD;
      technique using light/moderate neuromuscular block reversed with neostigmine in patients&#xD;
      undergoing operative gynecological or abdominal laparoscopic surgery of at least 1-hour&#xD;
      duration.&#xD;
&#xD;
      Background:&#xD;
&#xD;
      Importance and assessment of quality of recovery&#xD;
&#xD;
      Recovery following general anesthesia is a complex issue confounded by the type of surgery,&#xD;
      inflammation, different anesthetic drugs and techniques, patient co-morbidities, and&#xD;
      differing patient and clinician perceptions of what constitutes good recovery.&#xD;
&#xD;
      Recovery is not a single entity but rather covers many aspects or domains such as&#xD;
      physiological recovery, pain and nausea, emotion and mood, return to normal life or work&#xD;
      activities, and cognitive function. It is an entity that is difficult to quantify, which then&#xD;
      makes it difficult to study in a systematic manner. For anesthesiologists, poor recovery is&#xD;
      often relayed by the surgeon days or weeks after the event, and it is usually categorized as&#xD;
      an adverse outcome.&#xD;
&#xD;
      Research tools such as the Aldrete or the QoR scales, focus on early physiological recovery,&#xD;
      or the immediate perioperative period. These recovery scores are not sensitive enough to&#xD;
      measure the rate of recovery (change over time), and have not been designed for repeated&#xD;
      measures. They are also inadequate to identify poor cognitive recovery.&#xD;
&#xD;
      In 2007, an international group of anesthesiologists and neuropsychologists formed an&#xD;
      advisory board to create a new quality of recovery scale. The aim was to produce a tool that&#xD;
      was simple to perform, but sensitive enough to detect change in multiple domains of recovery&#xD;
      over time. The initial validation experiment included over 700 patients, and this work has&#xD;
      been published in Anesthesiology. It is called the Postoperative Quality Recovery Scale&#xD;
      (PostopQRS). Six domains of recovery are identified: physiological, nociceptive (pain and&#xD;
      nausea) emotive (anxiety and depression), functional recovery (return of activities of daily&#xD;
      living), cognitive recovery, and an overall patient perspective domain including&#xD;
      satisfaction. The scale is completed prior to surgery to provide baseline values, and then&#xD;
      repeated at user-defined intervals. From some of the subsequent discriminant validation&#xD;
      studies, time points have included early and late measures such as 15 minutes, 40 minutes, 1&#xD;
      and 3 days, and 3 months after the completion of anesthesia (typically defined as after the&#xD;
      last surgical stimulation). Recovery is broadly defined as return to baseline values or&#xD;
      better, except for the cognitive domain where a tolerance factor is included to allow for&#xD;
      normal performance variability, such that patients are allowed to perform a little worse than&#xD;
      baseline as still be scored as recovered. Because repeated tests tend to have a learning&#xD;
      effect, the cognitive domain uses parallel forms, and only a small learning has been shown.&#xD;
&#xD;
      One of the most important benefits of the PostopQRS scale is that it enables recovery to be&#xD;
      quantified and measured. This makes it possible to compare different interventions with the&#xD;
      express purpose of developing clinical interventions to improve quality of recovery. The&#xD;
      PostopQRS offers a tool to provide the recovery process to be examined. There are no other&#xD;
      tools in existence that provide a comprehensive, sensitive assessment of the multiple aspects&#xD;
      or domains of recovery, and is yet relatively simple to perform. Validation studies have been&#xD;
      performed and show good discriminative ability (5-8). Ease of use is facilitated by using a&#xD;
      web based data entry system and the ability to use the telephone to conduct surveys after&#xD;
      discharge form hospital. Telephone survey has been shown to be equivalent to face to face&#xD;
      interviews using the PostopQRS. Further, the PostopQRS allows users to drill down to identify&#xD;
      which recovery domain is affected for individuals in real time as well as for group audit.&#xD;
&#xD;
      Quality of recovery after operative laparoscopy&#xD;
&#xD;
      The majority of the literature compares different operative techniques with outcome measures&#xD;
      aimed at specific complications or length of stay. Few studies include quality of recovery or&#xD;
      quality of life measures as secondary endpoints. However, for potential benefits relating to&#xD;
      the use of sugammadex, there are a few studies primarily centered around deep neuromuscular&#xD;
      block (DNB) facilitating low intraabdominal inflation pressures. Most outcomes relate to&#xD;
      operative conditions with little data on patient centered outcomes especially after&#xD;
      discharge. The inclusion of sugammadex is to permit the use of DNB, and most comparative&#xD;
      groups (of moderate block) are reversed with neostigmine.&#xD;
&#xD;
      It has been shown that more patients can be operated on with low intraabdominal pressure with&#xD;
      DNB, and that operative conditions are rated as better in more patients with DNB, though it&#xD;
      is not absolute and there are frequent crossovers. That is, there are patients with moderate&#xD;
      block and low pressure, and equally patients with DNB requiring high inflation pressures. The&#xD;
      very few data on patient centered outcomes show reduced pain and nausea after DNB, but lack&#xD;
      of evidence of benefit for other recovery outcomes. This paucity of data has been stressed by&#xD;
      review articles and editorials that DNB is associated with a modest effect on improving&#xD;
      operating conditions but very little data to identify recovery benefits.&#xD;
&#xD;
      Sugammadex is an effective drug to reduce deep neuromuscular blockade&#xD;
&#xD;
      There is no clinical question that sugammadex is highly effective in reversing neuromuscular&#xD;
      blockade with rocuronium or vecuronium. This has been the subject of a Cochrane review which&#xD;
      included 18 randomized trials, showing that sugammadex can reverse blockade with rocuronium&#xD;
      or vecuronium independent on the depth of block, and superiority to neostigmine. This aspect&#xD;
      of sugammadex does not require further study. This translates to a low incidence of residual&#xD;
      blockade in the PACU compared to neostigmine reversal. The &quot;safety&quot; benefit to using&#xD;
      sugammadex has been proven, but this does not necessarily translate into better outcomes.&#xD;
      Sugammadex, however, is an enabling drug to facilitate deep neuromuscular blockade, allowing&#xD;
      the anesthesiologist to continue that block until the end of surgery and reliably reverse the&#xD;
      block. This is just not possible with neostigmine reversal, as one must wait until a train of&#xD;
      four count of at least 2 twitches (or TOF ratio &gt; 0.7) to safely reverse the block with&#xD;
      neostigmine.&#xD;
&#xD;
      Sugammadex is not a single intervention&#xD;
&#xD;
      The role of sugammadex as a single intervention can only be applied when reversing&#xD;
      neuromuscular block, when the block is moderate and a TOF 0.7 is achieved, with the outcome&#xD;
      restricted to reversal of blockade.&#xD;
&#xD;
      When sugammadex is used as a tool to facilitate deep muscular block, the intervention is&#xD;
      principally the DNB rather than sugammadex. In any randomized trial comparing sugammadex with&#xD;
      neostigmine for reversal of DNB, the extra time that anesthesia is continued in the&#xD;
      neostigmine group will be a confounder on post-operative outcomes. In a study comparing&#xD;
      sugammadex vs. neostigmine to reverse DNB, the anesthetic time in the neostigmine group was&#xD;
      almost double that of the sugammadex group (47 vs 95 min). This markedly increased anesthetic&#xD;
      duration was due to the time taken for the TOF ratio to exceed 0.9 and facilitate safe&#xD;
      extubation. It is therefore not possible to examine the issue of deep neuromuscular block and&#xD;
      unbundle sugammadex from the anesthetic technique required.&#xD;
&#xD;
      Outcomes and confounders when assessing post-operative quality of recovery There are a few&#xD;
      data assessing the impact of anesthetic drugs rather than surgical techniques or different&#xD;
      operations on the post-operative quality recovery. It is very likely that different&#xD;
      anesthetic drugs may independently contribute to changes in post-operative quality of&#xD;
      recovery, over and above the use of deep neuromuscular block for laparoscopic surgery.&#xD;
&#xD;
      The two most commonly used anesthetic drugs are propofol and sevoflurane. Both are relatively&#xD;
      short acting drugs, but have a wide variation of offset, particularly with more prolonged&#xD;
      anesthesia, and patient factors such as morbid obesity. Desflurane is a volatile agent which&#xD;
      is very short acting, and more importantly has highly predictable offset, which is&#xD;
      independent of patient factors such as obesity or of operation duration. In patients&#xD;
      receiving moderate neuromuscular block and reversal with neostigmine, the use of desflurane&#xD;
      lead to earlier response to command and return of airway reflexed compared to sevoflurane.&#xD;
&#xD;
      The investigators research group is currently conducting research into different anesthetic&#xD;
      techniques. Previously, the investigators studied effect of desflurane vs. propofol in&#xD;
      patients undergoing cardiac surgery, and showed less cognitive dysfunction one week after&#xD;
      surgery but not at three months after surgery with desflurane. The investigators have&#xD;
      recently concluded but not published a pilot study investigating propofol sedation vs.&#xD;
      desflurane general anesthesia to supplement spinal anesthesia for total hip replacement. The&#xD;
      participant numbers are too small for meaningful statistical analysis, but there is a trend&#xD;
      towards improved recovery and better cognitive recovery in the desflurane group (absolute&#xD;
      difference 15% and OR 2.3). What is interesting, though, is that the early differences were&#xD;
      negligible, and the trend occurred at 1 month and 3 months after surgery.&#xD;
&#xD;
      In this study, the investigators wish to primarily investigate the effect of the role of DNB,&#xD;
      and to reduce the potential for confounding from different anesthetic techniques, we will&#xD;
      standardize the anesthetic to use the shortest acting anesthetic bundle, and use desflurane&#xD;
      coupled with short acting opiates and multimodal analgesia in patients undergoing operative&#xD;
      gynecological or abdominal laparoscopic surgery of at least 1-hour duration.&#xD;
&#xD;
      Clinical significance&#xD;
&#xD;
      Quality of recovery is an emerging field within anesthesia of great importance. Although&#xD;
      large outcome studies are very important in anesthesia, there is a changing focus from&#xD;
      &quot;mortality and morbidity studies&quot;, to quality of recovery. The reason is that the frequency&#xD;
      of mortality is now very low with the result that few interventions will further reduce&#xD;
      mortality and in any event very large numbers will be required to demonstrate any&#xD;
      improvements in surgery and anesthesia with mortality as an outcome. However early data on&#xD;
      the PostopQRS as well as clinical reports indicate that the quality of recovery is often poor&#xD;
      in many patients, and yet these are not identified by the treating anesthesiologist. There&#xD;
      are implications for the individual patient, for the practice of anesthesia, and for the&#xD;
      community (such as safe return to work or to driving).&#xD;
&#xD;
      If providing deep neuromuscular block does lead to improved quality outcomes, then it is&#xD;
      essential to use sugammadex to reverse the block. There may be benefits (such as cognitive&#xD;
      recovery) that may be worsened by drugs such as neostigmine and avoidance of neostigmine may&#xD;
      be a mechanism of improving recovery. The coupling of drugs with similar offset times may&#xD;
      further lead to improved quality of recovery.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 16, 2017</start_date>
  <completion_date type="Actual">April 1, 2019</completion_date>
  <primary_completion_date type="Actual">February 15, 2019</primary_completion_date>
  <phase>Phase 4</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 (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of Patients Recovered Cognitively at 1 Week</measure>
    <time_frame>1 week</time_frame>
    <description>The primary outcome will be the cognitive domain at 1 week after surgery, when it is expected that most of the acute inflammation will have resolved, and analgesia requirements minimal.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of Patients Recovered in All Domains of the Postoperative Quality of Recovery Scale at 3 Months After the Operation</measure>
    <time_frame>3 months</time_frame>
    <description>Recovery for all domains and within domains of the PostopQRS scale at the other time points of measurement (15 minutes, 40 minutes 1 day, 3 days, 1 and 2 weeks, and 3 months following cessation of anesthesia). The domains of recovery are physiological, nociceptive, emotive activities of daily living, cognitive and overall patient perspective.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Full Reversal of Neuromuscular Blockade Prior to Extubation</measure>
    <time_frame>6 hours</time_frame>
    <description>Compliance with protocol to ensure deep block or light/moderate block, using the train of four ratio and post tetanic count</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Anesthesia From Induction to Cessation of the Anesthetic</measure>
    <time_frame>Up to 6 hours</time_frame>
    <description>Duration of Anesthesia from induction to cessation of the anesthetic up to 6 hours</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Categorized by Level of Surgical Satisfaction</measure>
    <time_frame>2 hours</time_frame>
    <description>Overall surgical satisfaction using a 1-5 Likert scale (1 = very unacceptable, 2 = unacceptable, 3 = acceptable, 4 = good, 5 = excellent).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Hospital Length of Stay</measure>
    <time_frame>3 days</time_frame>
    <description>Duration of hospital length of stay following their procedure until hospital discharge</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">350</enrollment>
  <condition>Laparoscopy</condition>
  <condition>Anesthesia Recovery Period</condition>
  <arm_group>
    <arm_group_label>ModNMB</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Moderate Neuromuscular block: participants will receive moderate neuromuscular blockade with rocuronium aiming for TOF 0-2 twitches, with neostigmine reversal when the TOF at least 3 twitches. The depth of neuromuscular block may be reduced after completion of the majority of surgical excision to TOF 3 or more&#xD;
Neostigmine</description>
  </arm_group>
  <arm_group>
    <arm_group_label>DeepNB</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Deep Neuromuscular block: participants will receive DNB aiming for a post tetanic count of 1-2, which will be maintained until removal of the laparoscopic ports, with reversal using sugammadex</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sugammadex</intervention_name>
    <description>Reversal of neuromuscular block Sugammadex dosage will be adjusted to body weight and PTC/TOF count at the time of reversal, and not administered until PTC at least 1. Dosage will be 4mg/kg if TOF = 0 and PTC ≥ 1; and 2 mg/kg if TOF ≥1.</description>
    <arm_group_label>DeepNB</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Neostigmine</intervention_name>
    <description>Neostigmine 50 micrograms/kg coupled with atropine 20 micrograms/kg or glycopyrrolate 5 micrograms/kg, to a maximum dose of neostigmine of 5.0 mg. The neostigmine should not be administered until the TOF has at least 3 twitches present.</description>
    <arm_group_label>ModNMB</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Adult participants&#xD;
&#xD;
          2. operative gynecological or abdominal surgery&#xD;
&#xD;
          3. receiving general anesthesia&#xD;
&#xD;
          4. Operation expected to exceed1 hour duration&#xD;
&#xD;
          5. Participants must speak sufficient English to answer the survey questions&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Participants undergoing diagnostic laparoscopy only&#xD;
&#xD;
          2. Participants &lt;18 years of age&#xD;
&#xD;
          3. Current pregnancy&#xD;
&#xD;
          4. Known allergy to rocuronium, neostigmine or sugammadex, or desflurane&#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>Colin Royse, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Melbourne</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Northpark Private Hospital</name>
      <address>
        <city>Bundoora</city>
        <state>Victoria</state>
        <zip>3083</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Melbourne Health</name>
      <address>
        <city>Parkville</city>
        <state>Victoria</state>
        <zip>3050</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Royal Womens Hospital</name>
      <address>
        <city>Parkville</city>
        <state>Victoria</state>
        <zip>3050</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Victorian Comprehensive Cancer Centre</name>
      <address>
        <city>Parkville</city>
        <state>Victoria</state>
        <zip>3050</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
  </location_countries>
  <verification_date>April 2020</verification_date>
  <study_first_submitted>January 17, 2017</study_first_submitted>
  <study_first_submitted_qc>January 26, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 27, 2017</study_first_posted>
  <results_first_submitted>July 1, 2019</results_first_submitted>
  <results_first_submitted_qc>September 25, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">October 21, 2019</results_first_posted>
  <last_update_submitted>April 13, 2020</last_update_submitted>
  <last_update_submitted_qc>April 13, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">April 22, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Melbourne</investigator_affiliation>
    <investigator_full_name>Colin Royse</investigator_full_name>
    <investigator_title>Professor of Anesthesia</investigator_title>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neostigmine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>November 24, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/77/NCT03034577/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>June 17, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/77/NCT03034577/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>In the period from June 2017 until November 2018, 350 patients were enrolled across 4 hospital sites (100 patients from the Royal Melbourne Hospital, 98 from the Peter MacCallum Cancer Centre, 88 from the Royal Women's Hospital and 64 from North Park Private Hospital).</recruitment_details>
      <pre_assignment_details>No participants were excluded from the study prior to surgical procedure</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Moderate Neuromuscular Blockade Reversed With Neostigmine</title>
          <description>The initial dosage of a moderate block was 0.6mg/kg of rocuronium, with repeat dosage of 0.15mg/kg given if the TOF &gt; 2.&#xD;
Once the TOF had 2 twitches, 50mcg/kg Neostigmine coupled with 20mcg/kg of atropine or 5mcg/kg of glycopyrrolate was administered for the reversal of a moderate block with a maximum dosage of 5.0mg of neostigmine.&#xD;
Extubation occurred when the TOF = 4 with no visible fade.</description>
        </group>
        <group group_id="P2">
          <title>Deep Neuromuscular Blockade Reversed With Sugammadex</title>
          <description>The initial dosage of deep block was 1.2mg/kg with repeat dosages of 0.15mg/kg until PTC ≤ 2.&#xD;
Sugammadex dosage was adjusted to body weight and PTC/TOF count at the time of reversal, and not administered until PTC at least 1. The dosage was 4mg/kg when TOF=0 and PTC ≥ 1; and 2 mg/kg if TOF ≥1.&#xD;
Extubation occurred when the TOF=4 with no visible fade.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="175"/>
                <participants group_id="P2" count="175"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="144"/>
                <participants group_id="P2" count="140"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="31"/>
                <participants group_id="P2" count="35"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="9"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="25"/>
                <participants group_id="P2" count="26"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Moderate Neuromuscular Blockade Reversed With Neostigmine</title>
          <description>The initial dosage of a moderate block was 0.6mg/kg of rocuronium, with repeat dosage of 0.15mg/kg given if the TOF &gt; 2.&#xD;
Once the TOF had 2 twitches, 50mcg/kg Neostigmine coupled with 20mcg/kg of atropine or 5mcg/kg of glycopyrrolate was administered for the reversal of a moderate block with a maximum dosage of 5.0mg of neostigmine.&#xD;
Extubation occurred when the TOF = 4 with no visible fade.</description>
        </group>
        <group group_id="B2">
          <title>Deep Neuromuscular Blockade Reversed With Sugammadex</title>
          <description>The initial dosage of deep block was 1.2mg/kg with repeat dosages of 0.15mg/kg until PTC ≤ 2.&#xD;
Sugammadex dosage was adjusted to body weight and PTC/TOF count at the time of reversal, and not administered until PTC at least 1. The dosage was 4mg/kg when TOF=0 and PTC ≥ 1; and 2 mg/kg if TOF ≥1.&#xD;
Extubation occurred when the TOF=4 with no visible fade.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="175"/>
            <count group_id="B2" value="175"/>
            <count group_id="B3" value="350"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="175"/>
                    <count group_id="B2" value="175"/>
                    <count group_id="B3" value="350"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="54.6" spread="16.3"/>
                    <measurement group_id="B2" value="54.4" spread="15.5"/>
                    <measurement group_id="B3" value="54.5" spread="15.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="175"/>
                    <count group_id="B2" value="175"/>
                    <count group_id="B3" value="350"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="102"/>
                    <measurement group_id="B2" value="79"/>
                    <measurement group_id="B3" value="181"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="73"/>
                    <measurement group_id="B2" value="96"/>
                    <measurement group_id="B3" value="169"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race and Ethnicity Not Collected</title>
          <population>Race and Ethnicity were not collected from any participant.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                    <count group_id="B2" value="0"/>
                    <count group_id="B3" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Australia</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="175"/>
                    <count group_id="B2" value="175"/>
                    <count group_id="B3" value="350"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="175"/>
                    <measurement group_id="B2" value="175"/>
                    <measurement group_id="B3" value="350"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>ASA Status</title>
          <description>ASA physical status classification system ASA I = healthy person ASA II = mild systemic disease ASA III = severe systemic disease</description>
          <population>Missing data Moderate block = 7 Deep block = 3</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="168"/>
                    <count group_id="B2" value="172"/>
                    <count group_id="B3" value="340"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>ASA I</title>
                  <measurement_list>
                    <measurement group_id="B1" value="24"/>
                    <measurement group_id="B2" value="30"/>
                    <measurement group_id="B3" value="54"/>
                  </measurement_list>
                </category>
                <category>
                  <title>ASA II</title>
                  <measurement_list>
                    <measurement group_id="B1" value="99"/>
                    <measurement group_id="B2" value="104"/>
                    <measurement group_id="B3" value="203"/>
                  </measurement_list>
                </category>
                <category>
                  <title>ASA III</title>
                  <measurement_list>
                    <measurement group_id="B1" value="45"/>
                    <measurement group_id="B2" value="38"/>
                    <measurement group_id="B3" value="83"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>BMI</title>
          <description>Body mass index</description>
          <units>kg/m^2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="175"/>
                    <count group_id="B2" value="175"/>
                    <count group_id="B3" value="350"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="29.5" spread="6.0"/>
                    <measurement group_id="B2" value="28.8" spread="6.1"/>
                    <measurement group_id="B3" value="29.2" spread="6.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Education</title>
          <description>Years in full-time education</description>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="175"/>
                    <count group_id="B2" value="175"/>
                    <count group_id="B3" value="350"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="13.5" spread="4.0"/>
                    <measurement group_id="B2" value="13.3" spread="3.4"/>
                    <measurement group_id="B3" value="13.4" spread="3.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Alcohol consumption</title>
          <description>Standard units consumed per week</description>
          <units>units/week</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="175"/>
                    <count group_id="B2" value="175"/>
                    <count group_id="B3" value="350"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4.8" spread="8.1"/>
                    <measurement group_id="B2" value="3.9" spread="6.3"/>
                    <measurement group_id="B3" value="4.3" spread="7.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Previous smoker</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="175"/>
                    <count group_id="B2" value="175"/>
                    <count group_id="B3" value="350"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="85"/>
                    <measurement group_id="B2" value="86"/>
                    <measurement group_id="B3" value="171"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Current Smoker</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="175"/>
                    <count group_id="B2" value="175"/>
                    <count group_id="B3" value="350"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="24"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Employment</title>
          <description>Currently employed</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="175"/>
                    <count group_id="B2" value="175"/>
                    <count group_id="B3" value="350"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="93"/>
                    <measurement group_id="B2" value="114"/>
                    <measurement group_id="B3" value="207"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Surgical access</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="175"/>
                    <count group_id="B2" value="175"/>
                    <count group_id="B3" value="350"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Laparoscopic surgery</title>
                  <measurement_list>
                    <measurement group_id="B1" value="125"/>
                    <measurement group_id="B2" value="131"/>
                    <measurement group_id="B3" value="256"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Robotic-assisted</title>
                  <measurement_list>
                    <measurement group_id="B1" value="50"/>
                    <measurement group_id="B2" value="44"/>
                    <measurement group_id="B3" value="94"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Out-patient</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="175"/>
                    <count group_id="B2" value="175"/>
                    <count group_id="B3" value="350"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Anaesthetic technique</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="175"/>
                    <count group_id="B2" value="175"/>
                    <count group_id="B3" value="350"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>General anaesthesia</title>
                  <measurement_list>
                    <measurement group_id="B1" value="164"/>
                    <measurement group_id="B2" value="164"/>
                    <measurement group_id="B3" value="328"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Spinal anaesthesia</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="20"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Regional block</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Patients Recovered Cognitively at 1 Week</title>
        <description>The primary outcome will be the cognitive domain at 1 week after surgery, when it is expected that most of the acute inflammation will have resolved, and analgesia requirements minimal.</description>
        <time_frame>1 week</time_frame>
        <population>There were 31 participants who did not complete the cognitive assessment at 1 week in the moderate neuromuscular blockade group, whereas there were 35 participants who did not complete the cognitive assessment at 1 week in the deep neuromuscular blockade group</population>
        <group_list>
          <group group_id="O1">
            <title>Moderate Neuromuscular Blockade Reversed With Neostigmine</title>
            <description>The initial dosage of a moderate block was 0.6mg/kg of rocuronium, with repeat dosage of 0.15mg/kg given if the TOF &gt; 2.&#xD;
Once the TOF had 2 twitches, 50mcg/kg Neostigmine coupled with 20mcg/kg of atropine or 5mcg/kg of glycopyrrolate was administered for the reversal of a moderate block with a maximum dosage of 5.0mg of neostigmine.&#xD;
Extubation occurred when the TOF = 4 with no visible fade.</description>
          </group>
          <group group_id="O2">
            <title>Deep Neuromuscular Blockade Reversed With Sugammadex</title>
            <description>The initial dosage of deep block was 1.2mg/kg with repeat dosages of 0.15mg/kg until PTC ≤ 2.&#xD;
Sugammadex dosage was adjusted to body weight and PTC/TOF count at the time of reversal, and not administered until PTC at least 1. The dosage was 4mg/kg when TOF=0 and PTC ≥ 1; and 2 mg/kg if TOF ≥1.&#xD;
Extubation occurred when the TOF=4 with no visible fade.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Patients Recovered Cognitively at 1 Week</title>
          <description>The primary outcome will be the cognitive domain at 1 week after surgery, when it is expected that most of the acute inflammation will have resolved, and analgesia requirements minimal.</description>
          <population>There were 31 participants who did not complete the cognitive assessment at 1 week in the moderate neuromuscular blockade group, whereas there were 35 participants who did not complete the cognitive assessment at 1 week in the deep neuromuscular blockade group</population>
          <units>percentage of patients recovered</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="144"/>
                <count group_id="O2" value="140"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="91.8"/>
                    <measurement group_id="O2" value="92.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Patients Recovered in All Domains of the Postoperative Quality of Recovery Scale at 3 Months After the Operation</title>
        <description>Recovery for all domains and within domains of the PostopQRS scale at the other time points of measurement (15 minutes, 40 minutes 1 day, 3 days, 1 and 2 weeks, and 3 months following cessation of anesthesia). The domains of recovery are physiological, nociceptive, emotive activities of daily living, cognitive and overall patient perspective.</description>
        <time_frame>3 months</time_frame>
        <population>Recovery in all domains of the Postoperative Quality of Recovery Scale at 3 months after the operation</population>
        <group_list>
          <group group_id="O1">
            <title>Moderate Neuromuscular Blockade Reversed With Neostigmine</title>
            <description>The initial dosage of a moderate block was 0.6mg/kg of rocuronium, with repeat dosage of 0.15mg/kg given if the TOF &gt; 2.&#xD;
Once the TOF had 2 twitches, 50mcg/kg Neostigmine coupled with 20mcg/kg of atropine or 5mcg/kg of glycopyrrolate was administered for the reversal of a moderate block with a maximum dosage of 5.0mg of neostigmine.&#xD;
Extubation occurred when the TOF = 4 with no visible fade.</description>
          </group>
          <group group_id="O2">
            <title>Deep Neuromuscular Blockade Reversed With Sugammadex</title>
            <description>The initial dosage of deep block was 1.2mg/kg with repeat dosages of 0.15mg/kg until PTC ≤ 2.&#xD;
Sugammadex dosage was adjusted to body weight and PTC/TOF count at the time of reversal, and not administered until PTC at least 1. The dosage was 4mg/kg when TOF=0 and PTC ≥ 1; and 2 mg/kg if TOF ≥1.&#xD;
Extubation occurred when the TOF=4 with no visible fade.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Patients Recovered in All Domains of the Postoperative Quality of Recovery Scale at 3 Months After the Operation</title>
          <description>Recovery for all domains and within domains of the PostopQRS scale at the other time points of measurement (15 minutes, 40 minutes 1 day, 3 days, 1 and 2 weeks, and 3 months following cessation of anesthesia). The domains of recovery are physiological, nociceptive, emotive activities of daily living, cognitive and overall patient perspective.</description>
          <population>Recovery in all domains of the Postoperative Quality of Recovery Scale at 3 months after the operation</population>
          <units>percentage of patients recovered</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="175"/>
                <count group_id="O2" value="175"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="75.7"/>
                    <measurement group_id="O2" value="73"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Full Reversal of Neuromuscular Blockade Prior to Extubation</title>
        <description>Compliance with protocol to ensure deep block or light/moderate block, using the train of four ratio and post tetanic count</description>
        <time_frame>6 hours</time_frame>
        <population>Full reversal prior to extubation (4 twitches and TOF ratio &gt;0.9)</population>
        <group_list>
          <group group_id="O1">
            <title>Moderate Neuromuscular Blockade Reversed With Neostigmine</title>
            <description>The initial dosage of a moderate block was 0.6mg/kg of rocuronium, with repeat dosage of 0.15mg/kg given if the TOF &gt; 2.&#xD;
Once the TOF had 2 twitches, 50mcg/kg Neostigmine coupled with 20mcg/kg of atropine or 5mcg/kg of glycopyrrolate was administered for the reversal of a moderate block with a maximum dosage of 5.0mg of neostigmine.&#xD;
Extubation occurred when the TOF = 4 with no visible fade.</description>
          </group>
          <group group_id="O2">
            <title>Deep Neuromuscular Blockade Reversed With Sugammadex</title>
            <description>The initial dosage of deep block was 1.2mg/kg with repeat dosages of 0.15mg/kg until PTC ≤ 2.&#xD;
Sugammadex dosage was adjusted to body weight and PTC/TOF count at the time of reversal, and not administered until PTC at least 1. The dosage was 4mg/kg when TOF=0 and PTC ≥ 1; and 2 mg/kg if TOF ≥1.&#xD;
Extubation occurred when the TOF=4 with no visible fade.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Full Reversal of Neuromuscular Blockade Prior to Extubation</title>
          <description>Compliance with protocol to ensure deep block or light/moderate block, using the train of four ratio and post tetanic count</description>
          <population>Full reversal prior to extubation (4 twitches and TOF ratio &gt;0.9)</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="175"/>
                <count group_id="O2" value="175"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="158"/>
                    <measurement group_id="O2" value="161"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of Anesthesia From Induction to Cessation of the Anesthetic</title>
        <description>Duration of Anesthesia from induction to cessation of the anesthetic up to 6 hours</description>
        <time_frame>Up to 6 hours</time_frame>
        <population>Duration of Anesthesia from induction to cessation of the anesthetic</population>
        <group_list>
          <group group_id="O1">
            <title>Moderate Neuromuscular Blockade Reversed With Neostigmine</title>
            <description>The initial dosage of a moderate block was 0.6mg/kg of rocuronium, with repeat dosage of 0.15mg/kg given if the TOF &gt; 2.&#xD;
Once the TOF had 2 twitches, 50mcg/kg Neostigmine coupled with 20mcg/kg of atropine or 5mcg/kg of glycopyrrolate was administered for the reversal of a moderate block with a maximum dosage of 5.0mg of neostigmine.&#xD;
Extubation occurred when the TOF = 4 with no visible fade.</description>
          </group>
          <group group_id="O2">
            <title>Deep Neuromuscular Blockade Reversed With Sugammadex</title>
            <description>The initial dosage of deep block was 1.2mg/kg with repeat dosages of 0.15mg/kg until PTC ≤ 2.&#xD;
Sugammadex dosage was adjusted to body weight and PTC/TOF count at the time of reversal, and not administered until PTC at least 1. The dosage was 4mg/kg when TOF=0 and PTC ≥ 1; and 2 mg/kg if TOF ≥1.&#xD;
Extubation occurred when the TOF=4 with no visible fade.</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Anesthesia From Induction to Cessation of the Anesthetic</title>
          <description>Duration of Anesthesia from induction to cessation of the anesthetic up to 6 hours</description>
          <population>Duration of Anesthesia from induction to cessation of the anesthetic</population>
          <units>minutes</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="175"/>
                <count group_id="O2" value="175"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="165.4" spread="88.8"/>
                    <measurement group_id="O2" value="164" spread="96"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants Categorized by Level of Surgical Satisfaction</title>
        <description>Overall surgical satisfaction using a 1-5 Likert scale (1 = very unacceptable, 2 = unacceptable, 3 = acceptable, 4 = good, 5 = excellent).</description>
        <time_frame>2 hours</time_frame>
        <population>Surgical operating conditions</population>
        <group_list>
          <group group_id="O1">
            <title>Moderate Neuromuscular Blockade Reversed With Neostigmine</title>
            <description>The initial dosage of a moderate block was 0.6mg/kg of rocuronium, with repeat dosage of 0.15mg/kg given if the TOF &gt; 2.&#xD;
Once the TOF had 2 twitches, 50mcg/kg Neostigmine coupled with 20mcg/kg of atropine or 5mcg/kg of glycopyrrolate was administered for the reversal of a moderate block with a maximum dosage of 5.0mg of neostigmine.&#xD;
Extubation occurred when the TOF = 4 with no visible fade.</description>
          </group>
          <group group_id="O2">
            <title>Deep Neuromuscular Blockade Reversed With Sugammadex</title>
            <description>The initial dosage of deep block was 1.2mg/kg with repeat dosages of 0.15mg/kg until PTC ≤ 2.&#xD;
Sugammadex dosage was adjusted to body weight and PTC/TOF count at the time of reversal, and not administered until PTC at least 1. The dosage was 4mg/kg when TOF=0 and PTC ≥ 1; and 2 mg/kg if TOF ≥1.&#xD;
Extubation occurred when the TOF=4 with no visible fade.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Categorized by Level of Surgical Satisfaction</title>
          <description>Overall surgical satisfaction using a 1-5 Likert scale (1 = very unacceptable, 2 = unacceptable, 3 = acceptable, 4 = good, 5 = excellent).</description>
          <population>Surgical operating conditions</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="166"/>
                <count group_id="O2" value="165"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Excellent</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="104"/>
                    <measurement group_id="O2" value="94"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Good</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="38"/>
                    <measurement group_id="O2" value="48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Acceptable</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20"/>
                    <measurement group_id="O2" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Unacceptable</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Very Unacceptable</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of Hospital Length of Stay</title>
        <description>Duration of hospital length of stay following their procedure until hospital discharge</description>
        <time_frame>3 days</time_frame>
        <population>Duration of hospital length of stay following their procedure until hospital discharge</population>
        <group_list>
          <group group_id="O1">
            <title>Moderate Neuromuscular Blockade Reversed With Neostigmine</title>
            <description>Moderate Neuromuscular block: participants will receive moderate neuromuscular blockade with rocuronium aiming for TOF 0-2 twitches, with neostigmine reversal when the TOF at least 3 twitches. The depth of neuromuscular block may be reduced after completion of the majority of surgical excision to TOF 3 or more&#xD;
Neostigmine&#xD;
Neostigmine: Neostigmine 50 micrograms/kg coupled with atropine 20 micrograms/kg or glycopyrrolate 5 micrograms/kg, to a maximum dose of neostigmine of 5.0 mg. The neostigmine should not be administered until the TOF has at least 3 twitches present.</description>
          </group>
          <group group_id="O2">
            <title>Deep Neuromuscular Blockade Reversed With Sugammadex</title>
            <description>Deep Neuromuscular block: participants will receive DNB aiming for a post tetanic count of 1-2, which will be maintained until removal of the laparoscopic ports, with reversal using sugammadex&#xD;
Sugammadex: Reversal of neuromuscular block Sugammadex dosage will be adjusted to body weight and PTC/TOF count at the time of reversal, and not administered until PTC at least 1. Dosage will be 4mg/kg if TOF = 0 and PTC ≥ 1; and 2 mg/kg if TOF ≥1.</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Hospital Length of Stay</title>
          <description>Duration of hospital length of stay following their procedure until hospital discharge</description>
          <population>Duration of hospital length of stay following their procedure until hospital discharge</population>
          <units>days</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="175"/>
                <count group_id="O2" value="175"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.6" spread="3.5"/>
                    <measurement group_id="O2" value="1.8" spread="1.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>3 months</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Moderate Neuromuscular Blockade Reversed With Neostigmine</title>
          <description>The initial dosage of a moderate block was 0.6mg/kg of rocuronium, with repeat dosage of 0.15mg/kg given if the TOF &gt; 2.&#xD;
Once the TOF had 2 twitches, 50mcg/kg Neostigmine coupled with 20mcg/kg of atropine or 5mcg/kg of glycopyrrolate was administered for the reversal of a moderate block with a maximum dosage of 5.0mg of neostigmine.&#xD;
Extubation occurred when the TOF = 4 with no visible fade.</description>
        </group>
        <group group_id="E2">
          <title>Deep Neuromuscular Blockade Reversed With Sugammadex</title>
          <description>The initial dosage of deep block was 1.2mg/kg with repeat dosages of 0.15mg/kg until PTC ≤ 2.&#xD;
Sugammadex dosage was adjusted to body weight and PTC/TOF count at the time of reversal, and not administered until PTC at least 1. The dosage was 4mg/kg when TOF=0 and PTC ≥ 1; and 2 mg/kg if TOF ≥1.&#xD;
Extubation occurred when the TOF=4 with no visible fade.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="175"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="175"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="175"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="175"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="175"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Prof Colin Royse</name_or_title>
      <organization>The University of Melbourne</organization>
      <phone>+61408467548</phone>
      <email>Colin.Royse@unimelb.edu.au</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03034577
org study id: 2016.343
nct id: NCT03034577
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Trial summary: deep neuromuscular block is proposed as a technique to improve operative
      conditions for laparoscopy. Early clinical data would suggest that there may also be patient
      benefits beyond the operative period related to lower intra-abdominal pressure, and improved
      surgical exposure. In order to safely conduct deep neuromuscular blockade, it is essential to
      use Sugammadex to reverse the neuromuscular block. Conventional practice is to provide
      moderate neuromuscular block and reverse with neostigmine. It is not possible to safely
      reverse deep neuromuscular block using neostogmine, as the majority of block must have worn
      off for neostigmine to be effective. in order to identify whether deep neuromuscular block
      improves quality of recovery after surgery, the investigators will conduct a randomised trial
      of deep versus moderate neuromuscular block, whilst minimising variance in other anaesthetic
      techniques and drugs used. the outcome measured will be the post-operative quality of
      recovery over multiple time periods using the Postoperative Quality of Recovery Scale
      (PostopQRS). 350 patients will be enrolled over 4 centres.
Objectives

      1. To identify whether the rate/quality of recovery is affected by deep neuromuscular block
      (DNB) and reversal with sugammadex versus light/moderate neuromuscular block reversed with
      neostigmine and couple with desflurane or sevoflurane in patients undergoing operative
      gynecological or abdominal laparoscopic surgery of at least 1-hour duration.

      Hypothesis

      1. The technique of deep neuromuscular block and reversal with sugammadex will result in
      improved quality of recovery, including cognition, compared to the current standard of care
      technique using light/moderate neuromuscular block reversed with neostigmine in patients
      undergoing operative gynecological or abdominal laparoscopic surgery of at least 1-hour
      duration.

      Background:

      Importance and assessment of quality of recovery

      Recovery following general anesthesia is a complex issue confounded by the type of surgery,
      inflammation, different anesthetic drugs and techniques, patient co-morbidities, and
      differing patient and clinician perceptions of what constitutes good recovery.

      Recovery is not a single entity but rather covers many aspects or domains such as
      physiological recovery, pain and nausea, emotion and mood, return to normal life or work
      activities, and cognitive function. It is an entity that is difficult to quantify, which then
      makes it difficult to study in a systematic manner. For anesthesiologists, poor recovery is
      often relayed by the surgeon days or weeks after the event, and it is usually categorized as
      an adverse outcome.

      Research tools such as the Aldrete or the QoR scales, focus on early physiological recovery,
      or the immediate perioperative period. These recovery scores are not sensitive enough to
      measure the rate of recovery (change over time), and have not been designed for repeated
      measures. They are also inadequate to identify poor cognitive recovery.

      In 2007, an international group of anesthesiologists and neuropsychologists formed an
      advisory board to create a new quality of recovery scale. The aim was to produce a tool that
      was simple to perform, but sensitive enough to detect change in multiple domains of recovery
      over time. The initial validation experiment included over 700 patients, and this work has
      been published in Anesthesiology. It is called the Postoperative Quality Recovery Scale
      (PostopQRS). Six domains of recovery are identified: physiological, nociceptive (pain and
      nausea) emotive (anxiety and depression), functional recovery (return of activities of daily
      living), cognitive recovery, and an overall patient perspective domain including
      satisfaction. The scale is completed prior to surgery to provide baseline values, and then
      repeated at user-defined intervals. From some of the subsequent discriminant validation
      studies, time points have included early and late measures such as 15 minutes, 40 minutes, 1
      and 3 days, and 3 months after the completion of anesthesia (typically defined as after the
      last surgical stimulation). Recovery is broadly defined as return to baseline values or
      better, except for the cognitive domain where a tolerance factor is included to allow for
      normal performance variability, such that patients are allowed to perform a little worse than
      baseline as still be scored as recovered. Because repeated tests tend to have a learning
      effect, the cognitive domain uses parallel forms, and only a small learning has been shown.

      One of the most important benefits of the PostopQRS scale is that it enables recovery to be
      quantified and measured. This makes it possible to compare different interventions with the
      express purpose of developing clinical interventions to improve quality of recovery. The
      PostopQRS offers a tool to provide the recovery process to be examined. There are no other
      tools in existence that provide a comprehensive, sensitive assessment of the multiple aspects
      or domains of recovery, and is yet relatively simple to perform. Validation studies have been
      performed and show good discriminative ability (5-8). Ease of use is facilitated by using a
      web based data entry system and the ability to use the telephone to conduct surveys after
      discharge form hospital. Telephone survey has been shown to be equivalent to face to face
      interviews using the PostopQRS. Further, the PostopQRS allows users to drill down to identify
      which recovery domain is affected for individuals in real time as well as for group audit.

      Quality of recovery after operative laparoscopy

      The majority of the literature compares different operative techniques with outcome measures
      aimed at specific complications or length of stay. Few studies include quality of recovery or
      quality of life measures as secondary endpoints. However, for potential benefits relating to
      the use of sugammadex, there are a few studies primarily centered around deep neuromuscular
      block (DNB) facilitating low intraabdominal inflation pressures. Most outcomes relate to
      operative conditions with little data on patient centered outcomes especially after
      discharge. The inclusion of sugammadex is to permit the use of DNB, and most comparative
      groups (of moderate block) are reversed with neostigmine.

      It has been shown that more patients can be operated on with low intraabdominal pressure with
      DNB, and that operative conditions are rated as better in more patients with DNB, though it
      is not absolute and there are frequent crossovers. That is, there are patients with moderate
      block and low pressure, and equally patients with DNB requiring high inflation pressures. The
      very few data on patient centered outcomes show reduced pain and nausea after DNB, but lack
      of evidence of benefit for other recovery outcomes. This paucity of data has been stressed by
      review articles and editorials that DNB is associated with a modest effect on improving
      operating conditions but very little data to identify recovery benefits.

      Sugammadex is an effective drug to reduce deep neuromuscular blockade

      There is no clinical question that sugammadex is highly effective in reversing neuromuscular
      blockade with rocuronium or vecuronium. This has been the subject of a Cochrane review which
      included 18 randomized trials, showing that sugammadex can reverse blockade with rocuronium
      or vecuronium independent on the depth of block, and superiority to neostigmine. This aspect
      of sugammadex does not require further study. This translates to a low incidence of residual
      blockade in the PACU compared to neostigmine reversal. The "safety" benefit to using
      sugammadex has been proven, but this does not necessarily translate into better outcomes.
      Sugammadex, however, is an enabling drug to facilitate deep neuromuscular blockade, allowing
      the anesthesiologist to continue that block until the end of surgery and reliably reverse the
      block. This is just not possible with neostigmine reversal, as one must wait until a train of
      four count of at least 2 twitches (or TOF ratio > 0.7) to safely reverse the block with
      neostigmine.

      Sugammadex is not a single intervention

      The role of sugammadex as a single intervention can only be applied when reversing
      neuromuscular block, when the block is moderate and a TOF 0.7 is achieved, with the outcome
      restricted to reversal of blockade.

      When sugammadex is used as a tool to facilitate deep muscular block, the intervention is
      principally the DNB rather than sugammadex. In any randomized trial comparing sugammadex with
      neostigmine for reversal of DNB, the extra time that anesthesia is continued in the
      neostigmine group will be a confounder on post-operative outcomes. In a study comparing
      sugammadex vs. neostigmine to reverse DNB, the anesthetic time in the neostigmine group was
      almost double that of the sugammadex group (47 vs 95 min). This markedly increased anesthetic
      duration was due to the time taken for the TOF ratio to exceed 0.9 and facilitate safe
      extubation. It is therefore not possible to examine the issue of deep neuromuscular block and
      unbundle sugammadex from the anesthetic technique required.

      Outcomes and confounders when assessing post-operative quality of recovery There are a few
      data assessing the impact of anesthetic drugs rather than surgical techniques or different
      operations on the post-operative quality recovery. It is very likely that different
      anesthetic drugs may independently contribute to changes in post-operative quality of
      recovery, over and above the use of deep neuromuscular block for laparoscopic surgery.

      The two most commonly used anesthetic drugs are propofol and sevoflurane. Both are relatively
      short acting drugs, but have a wide variation of offset, particularly with more prolonged
      anesthesia, and patient factors such as morbid obesity. Desflurane is a volatile agent which
      is very short acting, and more importantly has highly predictable offset, which is
      independent of patient factors such as obesity or of operation duration. In patients
      receiving moderate neuromuscular block and reversal with neostigmine, the use of desflurane
      lead to earlier response to command and return of airway reflexed compared to sevoflurane.

      The investigators research group is currently conducting research into different anesthetic
      techniques. Previously, the investigators studied effect of desflurane vs. propofol in
      patients undergoing cardiac surgery, and showed less cognitive dysfunction one week after
      surgery but not at three months after surgery with desflurane. The investigators have
      recently concluded but not published a pilot study investigating propofol sedation vs.
      desflurane general anesthesia to supplement spinal anesthesia for total hip replacement. The
      participant numbers are too small for meaningful statistical analysis, but there is a trend
      towards improved recovery and better cognitive recovery in the desflurane group (absolute
      difference 15% and OR 2.3). What is interesting, though, is that the early differences were
      negligible, and the trend occurred at 1 month and 3 months after surgery.

      In this study, the investigators wish to primarily investigate the effect of the role of DNB,
      and to reduce the potential for confounding from different anesthetic techniques, we will
      standardize the anesthetic to use the shortest acting anesthetic bundle, and use desflurane
      coupled with short acting opiates and multimodal analgesia in patients undergoing operative
      gynecological or abdominal laparoscopic surgery of at least 1-hour duration.

      Clinical significance

      Quality of recovery is an emerging field within anesthesia of great importance. Although
      large outcome studies are very important in anesthesia, there is a changing focus from
      "mortality and morbidity studies", to quality of recovery. The reason is that the frequency
      of mortality is now very low with the result that few interventions will further reduce
      mortality and in any event very large numbers will be required to demonstrate any
      improvements in surgery and anesthesia with mortality as an outcome. However early data on
      the PostopQRS as well as clinical reports indicate that the quality of recovery is often poor
      in many patients, and yet these are not identified by the treating anesthesiologist. There
      are implications for the individual patient, for the practice of anesthesia, and for the
      community (such as safe return to work or to driving).

      If providing deep neuromuscular block does lead to improved quality outcomes, then it is
      essential to use sugammadex to reverse the block. There may be benefits (such as cognitive
      recovery) that may be worsened by drugs such as neostigmine and avoidance of neostigmine may
      be a mechanism of improving recovery. The coupling of drugs with similar offset times may
      further lead to improved quality of recovery.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: Percentage of Patients Recovered Cognitively at 1 Week
time frame: 1 week
description: The primary outcome will be the cognitive domain at 1 week after surgery, when it is expected that most of the acute inflammation will have resolved, and analgesia requirements minimal.
measure: Percentage of Patients Recovered in All Domains of the Postoperative Quality of Recovery Scale at 3 Months After the Operation
time frame: 3 months
description: Recovery for all domains and within domains of the PostopQRS scale at the other time points of measurement (15 minutes, 40 minutes 1 day, 3 days, 1 and 2 weeks, and 3 months following cessation of anesthesia). The domains of recovery are physiological, nociceptive, emotive activities of daily living, cognitive and overall patient perspective.
measure: Number of Participants With Full Reversal of Neuromuscular Blockade Prior to Extubation
time frame: 6 hours
description: Compliance with protocol to ensure deep block or light/moderate block, using the train of four ratio and post tetanic count
measure: Duration of Anesthesia From Induction to Cessation of the Anesthetic
time frame: Up to 6 hours
description: Duration of Anesthesia from induction to cessation of the anesthetic up to 6 hours
measure: Number of Participants Categorized by Level of Surgical Satisfaction
time frame: 2 hours
description: Overall surgical satisfaction using a 1-5 Likert scale (1 = very unacceptable, 2 = unacceptable, 3 = acceptable, 4 = good, 5 = excellent).
measure: Duration of Hospital Length of Stay
time frame: 3 days
description: Duration of hospital length of stay following their procedure until hospital discharge
arm group label: ModNMB
arm group type: Active Comparator
description: Moderate Neuromuscular block: participants will receive moderate neuromuscular blockade with rocuronium aiming for TOF 0-2 twitches, with neostigmine reversal when the TOF at least 3 twitches. The depth of neuromuscular block may be reduced after completion of the majority of surgical excision to TOF 3 or more
Neostigmine
arm group label: DeepNB
arm group type: Active Comparator
description: Deep Neuromuscular block: participants will receive DNB aiming for a post tetanic count of 1-2, which will be maintained until removal of the laparoscopic ports, with reversal using sugammadex
intervention type: Drug
intervention name: Sugammadex
description: Reversal of neuromuscular block Sugammadex dosage will be adjusted to body weight and PTC/TOF count at the time of reversal, and not administered until PTC at least 1. Dosage will be 4mg/kg if TOF = 0 and PTC ≥ 1; and 2 mg/kg if TOF ≥1.
arm group label: DeepNB
intervention type: Drug
intervention name: Neostigmine
description: Neostigmine 50 micrograms/kg coupled with atropine 20 micrograms/kg or glycopyrrolate 5 micrograms/kg, to a maximum dose of neostigmine of 5.0 mg. The neostigmine should not be administered until the TOF has at least 3 twitches present.
arm group label: ModNMB
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Colin Royse, MD
role: Principal Investigator
affiliation: University of Melbourne
facility: 
facility: 
facility: 
facility: 
country: Australia
responsible party type: Principal Investigator
investigator affiliation: University of Melbourne
investigator full name: Colin Royse
investigator title: Professor of Anesthesia
mesh term: Neostigmine
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 