Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   44334   clinical trials with a EudraCT protocol, of which   7366   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    Randomized, Controlled, Parallel-Group, Double-Blind Trial to Compare the Use of Deep or Standard Neuromuscular Blockade in Combination With Low or Standard Insufflation Pressures Using a 2x2 Factorial Design in Patients Undergoing Laparoscopic Cholecystectomy (Protocol No. MK-8616-076-03 also known as SCH 900616, P07982)

    Summary
    EudraCT number
    		 2012-001886-33
    Trial protocol
    		 DE   AT   FI   GB   IT  
    Global end of trial date
    29 Apr 2014

    Results information
    Results version number
    		 v2(current)
    This version publication date
    06 May 2016
    First version publication date
    02 May 2015
    Other versions
    		 v1
    Version creation reason

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    P07982
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01728584
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 Merck Registration number: P07982
    Sponsors
    Sponsor organisation name
    Merck Sharp & Dohme Corp.
    Sponsor organisation address
    2000 Galloping Hill Road, Kenilworth, NJ, United States, 07033
    Public contact
    Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com
    Scientific contact
    Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    29 Apr 2014
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    29 Apr 2014
    Global end of trial reached?
    Yes
    Global end of trial date
    29 Apr 2014
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Purpose of study is to compare use of deep or standard neuromuscular blockade (NMB) in combination with low or standard insufflation pressure in participants undergoing laparoscopic cholecystectomy. Primary hypothesis is that use of sustained deep NMB improves the surgeon's overall satisfaction with surgical conditions versus standard NMB. Inpatient surgery is performed on Day 1, and participant remains hospitalized for at least 24-48 hours after surgery, with follow-up visit/contact on Day 8. During procedure, surgeon could request modification to randomized treatment conditions (“rescue intervention”), if surgeon considered surgical conditions unacceptable. For participant on standard NMB, preferred rescue intervention was increase of NMB from standard to deep level; second option, if available, was to raise insufflation pressure from low to standard. If the participant was already on deep NMB, preferred option, if available, was to raise insufflation pressure from low to standard.
    Protection of trial subjects
    This study was conducted in conformance with Good Clinical Practice standards and applicable country and/or local statutes and regulations regarding ethical committee review, informed consent, and the protection of human subjects participating in biomedical research.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    28 Nov 2012
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Austria: 43
    Country: Number of subjects enrolled
    Finland: 11
    Country: Number of subjects enrolled
    Germany: 40
    Country: Number of subjects enrolled
    Italy: 20
    Country: Number of subjects enrolled
    United Kingdom: 13
    Worldwide total number of subjects
    127
    EEA total number of subjects
    127
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    112
    From 65 to 84 years
    15
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Participants were randomized to 4 arms based on combinations of NMB depth and insufflation pressure level. During procedure, blinded surgeon could request that unblinded anesthetist change the randomized treatment conditions (“rescue intervention”), if surgeon considered surgical conditions to be unacceptable.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind [1]
    Roles blinded
    		 Assessor, Subject
    Blinding implementation details
    The surgeon was blinded to random assignment. The anesthetist controlling the surgical conditions (depth of NMB, insufflation pressure level) was unblinded.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Standard NMB and Standard Insufflation Pressure
    Arm description
    		 Treatment condition for this reporting group is Standard NMB (depth of blockade at a targeted Train of Four [TOF] ratio of 10%)/Standard insufflation pressure (starting pressure of 12 mmHg).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Rocuronium
    Investigational medicinal product code
    Other name
    Esmeron® Injection (rocuronium bromide), Zemuron® Injection (rocuronium bromide)
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    NMB will be induced by intravenous (IV) administration of a bolus dose of 0.45 mg/kg rocuronium. NMB will be maintained using rocuronium infusion or additional bolus doses as needed for the management of NMB to the targeted depth according to the assigned treatment condition: Standard NMB - administration of neuromuscular blocking agent (NMBA) titrated to a depth of blockade at a targeted TOF ratio of 10% (range: TOF count 2-3 to TOF ratio of 20%); Deep NMB - administration of NMBA titrated to a targeted depth of 1-2 Post Tetanic Counts (PTCs) (range: 1-5 PTC).

    Investigational medicinal product name
    Carbon dioxide gas
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Medicinal gas, compressed
    Routes of administration
    Intraperitoneal use
    Dosage and administration details
    Insufflation (injection) of carbon dioxide will be used to induce pneumoperitoneum, which is presence of air or gas in the abdominal (peritoneal) cavity: Standard insufflation pressure - a starting pressure of 12 mmHg will be used; Low insufflation pressure - a starting pressure of 8 mmHg will be used.

    Investigational medicinal product name
    Sugammadex
    Investigational medicinal product code
    Other name
    sugammadex sodium injection, SCH 900616, Org 25969, Bridion®
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    NMB will be reversed with IV administration of 2 or 4 mg/kg sugammadex (depending on the depth of NMB) according to the approved label for sugammadex.

    Arm title
    		 Standard NMB and Low Insufflation Pressure
    Arm description
    		 Treatment condition for this reporting group is Standard NMB (depth of blockade at a targeted TOF ratio of 10%)/Low insufflation pressure (starting pressure of 8 mmHg).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Rocuronium
    Investigational medicinal product code
    Other name
    Esmeron® Injection (rocuronium bromide), Zemuron® Injection (rocuronium bromide)
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    NMB will be induced by IV administration of a bolus dose of 0.45 mg/kg rocuronium. NMB will be maintained using rocuronium infusion or additional bolus doses as needed for the management of NMB to the targeted depth according to the assigned treatment condition: Standard NMB - administration of NMBA titrated to a depth of blockade at a targeted TOF ratio of 10% (range: TOF count 2-3 to TOF ratio of 20%); Deep NMB - administration of NMBA titrated to a targeted depth of 1-2 PTCs (range: 1-5 PTC).

    Investigational medicinal product name
    Sugammadex
    Investigational medicinal product code
    Other name
    sugammadex sodium injection, SCH 900616, Org 25969, Bridion®
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    NMB will be reversed with IV administration of 2 or 4 mg/kg sugammadex (depending on the depth of NMB) according to the approved label for sugammadex.

    Investigational medicinal product name
    Carbon dioxide gas
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Medicinal gas, compressed
    Routes of administration
    Intraperitoneal use
    Dosage and administration details
    Insufflation (injection) of carbon dioxide will be used to induce pneumoperitoneum, which is presence of air or gas in the abdominal (peritoneal) cavity: Standard insufflation pressure - a starting pressure of 12 mmHg will be used; Low insufflation pressure - a starting pressure of 8 mmHg will be used.

    Arm title
    		 Deep NMB and Standard Insufflation Pressure
    Arm description
    		 Treatment condition for this reporting group is Deep NMB (depth of blockade of 1-2 PTCs)/Standard insufflation pressure (starting pressure of 12 mmHg).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Rocuronium
    Investigational medicinal product code
    Other name
    Esmeron® Injection (rocuronium bromide), Zemuron® Injection (rocuronium bromide)
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    NMB will be induced by IV administration of a bolus dose of 0.45 mg/kg rocuronium. NMB will be maintained using rocuronium infusion or additional bolus doses as needed for the management of NMB to the targeted depth according to the assigned treatment condition: Standard NMB - administration of NMBA titrated to a depth of blockade at a targeted TOF ratio of 10% (range: TOF count 2-3 to TOF ratio of 20%); Deep NMB - administration of NMBA titrated to a targeted depth of 1-2 PTCs (range: 1-5 PTC).

    Investigational medicinal product name
    Sugammadex
    Investigational medicinal product code
    Other name
    sugammadex sodium injection, SCH 900616, Org 25969, Bridion®
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    NMB will be reversed with IV administration of 2 or 4 mg/kg sugammadex (depending on the depth of NMB) according to the approved label for sugammadex.

    Investigational medicinal product name
    Carbon dioxide gas
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Medicinal gas, compressed
    Routes of administration
    Intraperitoneal use
    Dosage and administration details
    Insufflation (injection) of carbon dioxide will be used to induce pneumoperitoneum, which is presence of air or gas in the abdominal (peritoneal) cavity: Standard insufflation pressure - a starting pressure of 12 mmHg will be used; Low insufflation pressure - a starting pressure of 8 mmHg will be used.

    Arm title
    		 Deep NMB and Low Insufflation Pressure
    Arm description
    		 Treatment condition for this reporting group is Deep NMB (depth of blockade of 1-2 PTCs)/Low insufflation pressure (starting pressure of 8 mmHg).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Rocuronium
    Investigational medicinal product code
    Other name
    Esmeron® Injection (rocuronium bromide), Zemuron® Injection (rocuronium bromide)
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    NMB will be induced by IV administration of a bolus dose of 0.45 mg/kg rocuronium. NMB will be maintained using rocuronium infusion or additional bolus doses as needed for the management of NMB to the targeted depth according to the assigned treatment condition: Standard NMB - administration of NMBA titrated to a depth of blockade at a targeted TOF ratio of 10% (range: TOF count 2-3 to TOF ratio of 20%); Deep NMB - administration of NMBA titrated to a targeted depth of 1-2 PTCs (range: 1-5 PTC).

    Investigational medicinal product name
    Carbon dioxide gas
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Medicinal gas, compressed
    Routes of administration
    Intraperitoneal use
    Dosage and administration details
    Insufflation (injection) of carbon dioxide will be used to induce pneumoperitoneum, which is presence of air or gas in the abdominal (peritoneal) cavity: Standard insufflation pressure - a starting pressure of 12 mmHg will be used; Low insufflation pressure - a starting pressure of 8 mmHg will be used.

    Investigational medicinal product name
    Sugammadex
    Investigational medicinal product code
    Other name
    sugammadex sodium injection, SCH 900616, Org 25969, Bridion®
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    NMB will be reversed with IV administration of 2 or 4 mg/kg sugammadex (depending on the depth of NMB) according to the approved label for sugammadex.

    Notes
    [1] - The roles blinded appear to be inconsistent with a double blind trial.
    Justification: The surgeon, who made ratings of surgical conditions used for primary outcome measures and several other efficacy endpoints, was blinded to random assignment. The anesthetist controlling the surgical conditions was unblinded. A blinded safety assessor evaluated safety parameters, pain scores and analgesic medication use. Appropriate Sponsor personnel were blinded to random assignment.
    Number of subjects in period 1
    		Standard NMB and Standard Insufflation Pressure Standard NMB and Low Insufflation Pressure Deep NMB and Standard Insufflation Pressure Deep NMB and Low Insufflation Pressure
    Started
    36
    30
    31
    30
    Completed
    28
    30
    30
    29
    Not completed
    8
    0
    1
    1
         Physician decision
    4
    -
    1
    -
         Consent withdrawn by subject
    1
    -
    -
    -
         Adverse event, non-fatal
    1
    -
    -
    -
         Other reason (not specified)
    1
    -
    -
    1
         Screen failure
    1
    -
    -
    -

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Standard NMB and Standard Insufflation Pressure
    Reporting group description
    		 Treatment condition for this reporting group is Standard NMB (depth of blockade at a targeted Train of Four [TOF] ratio of 10%)/Standard insufflation pressure (starting pressure of 12 mmHg).

    Reporting group title
    Standard NMB and Low Insufflation Pressure
    Reporting group description
    		 Treatment condition for this reporting group is Standard NMB (depth of blockade at a targeted TOF ratio of 10%)/Low insufflation pressure (starting pressure of 8 mmHg).

    Reporting group title
    Deep NMB and Standard Insufflation Pressure
    Reporting group description
    		 Treatment condition for this reporting group is Deep NMB (depth of blockade of 1-2 PTCs)/Standard insufflation pressure (starting pressure of 12 mmHg).

    Reporting group title
    Deep NMB and Low Insufflation Pressure
    Reporting group description
    		 Treatment condition for this reporting group is Deep NMB (depth of blockade of 1-2 PTCs)/Low insufflation pressure (starting pressure of 8 mmHg).

    Reporting group values
    		 Standard NMB and Standard Insufflation Pressure Standard NMB and Low Insufflation Pressure Deep NMB and Standard Insufflation Pressure Deep NMB and Low Insufflation Pressure Total
    Number of subjects
    		 36 30 31 30 127
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0 0
        Children (2-11 years)
    		 0 0 0 0 0
        Adolescents (12-17 years)
    		 0 0 0 0 0
        Adults (18-64 years)
    		 28 29 29 26 112
        From 65-84 years
    		 8 1 2 4 15
        85 years and over
    		 0 0 0 0 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 46.1 ( 17.7 ) 39.1 ( 13.6 ) 43.5 ( 15.6 ) 46.7 ( 13.8 ) -
    Gender categorical
    Units: Subjects
        Female
    		 15 11 13 9 48
        Male
    		 21 19 18 21 79

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Standard NMB and Standard Insufflation Pressure
    Reporting group description
    		 Treatment condition for this reporting group is Standard NMB (depth of blockade at a targeted Train of Four [TOF] ratio of 10%)/Standard insufflation pressure (starting pressure of 12 mmHg).

    Reporting group title
    Standard NMB and Low Insufflation Pressure
    Reporting group description
    		 Treatment condition for this reporting group is Standard NMB (depth of blockade at a targeted TOF ratio of 10%)/Low insufflation pressure (starting pressure of 8 mmHg).

    Reporting group title
    Deep NMB and Standard Insufflation Pressure
    Reporting group description
    		 Treatment condition for this reporting group is Deep NMB (depth of blockade of 1-2 PTCs)/Standard insufflation pressure (starting pressure of 12 mmHg).

    Reporting group title
    Deep NMB and Low Insufflation Pressure
    Reporting group description
    		 Treatment condition for this reporting group is Deep NMB (depth of blockade of 1-2 PTCs)/Low insufflation pressure (starting pressure of 8 mmHg).

    Subject analysis set title
    Standard NMB
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Treatment condition for this reporting group is Standard NMB (depth of blockade at a targeted TOF ratio of 10%), whether in combination with Standard or Low insufflation pressure. Therefore, the included arms are Standard NMB/Standard insufflation pressure and Standard NMB/Low insufflation pressure.

    Subject analysis set title
    Deep NMB
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Treatment condition for this reporting group is Deep NMB (depth of blockade of 1-2 PTCs), whether in combination with Standard or Low insufflation pressure. Therefore, the included arms are Deep NMB/Standard insufflation pressure and Deep NMB/Low insufflation pressure.

    Subject analysis set title
    Standard Insufflation Pressure
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Treatment condition for this reporting group is Standard insufflation pressure (starting pressure of 12 mmHg), whether in combination with Standard or Deep NMB. Therefore, the included arms are Standard NMB/Standard insufflation pressure and Deep NMB/Standard insufflation pressure.

    Subject analysis set title
    Low Insufflation Pressure
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Treatment condition for this reporting group is Low insufflation pressure (starting pressure of 8 mmHg), whether in combination with Standard or Deep NMB. Therefore, the included arms are Standard NMB/Low insufflation pressure and Deep NMB/Low insufflation pressure.

    Subject analysis set title
    Standard NMB and Standard Insufflation Pressure
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Treatment condition for this reporting group is Standard NMB (depth of blockade at a targeted TOF ratio of 10%)/Standard insufflation pressure (starting pressure of 12 mmHg). Participants were included in arm corresponding to treatment actually received, which in case of rescue intervention was the post-intervention condition.

    Subject analysis set title
    Standard NMB and Low Insufflation Pressure
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Treatment condition for this reporting group is Standard NMB (depth of blockade at a targeted TOF ratio of 10%)/Low insufflation pressure (starting pressure of 8 mmHg). Participants were included in arm corresponding to treatment actually received, which in case of rescue intervention was the post-intervention condition.

    Subject analysis set title
    Deep NMB and Standard Insufflation Pressure
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Treatment condition for this reporting group is Deep NMB (depth of blockade of 1-2 PTCs)/Standard insufflation pressure (starting pressure of 12 mmHg). Participants were included in arm corresponding to treatment actually received, which in case of rescue intervention was the post-intervention condition.

    Subject analysis set title
    Deep NMB and Low Insufflation Pressure
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Treatment condition for this reporting group is Deep NMB (depth of blockade of 1-2 PTCs)/Low insufflation pressure (starting pressure of 8 mmHg). Participants were included in arm corresponding to treatment actually received, which in case of rescue intervention was the post-intervention condition.

    Primary: Score on surgeon's assessment of overall satisfaction with the surgical conditions: By depth of NMB (standard, deep) and insufflation pressure (standard, low)

    		 Close Top of page
    End point title
    		 Score on surgeon's assessment of overall satisfaction with the surgical conditions: By depth of NMB (standard, deep) and insufflation pressure (standard, low)
    End point description
    At the end of the procedure the surgeon responds to the following question, using an 11-point scale from 0 (poor, needed intervention) to 10 (excellent): "How satisfied were you overall with the surgical conditions related to anesthesia and pneumoperitoneum during the surgery you just performed?" If at any time the surgeon requests a rescue intervention, the overall assessment of surgical conditions should be rated as 0 (=poor, needed intervention). The surgeon will rate the surgical conditions according to his opinion but if a rescue intervention has been applied, that individual participant will be counted with a score of zero in the analysis. Population for analysis was randomized participants with available data who had NMB and pneumoperitoneum for laparoscopic surgery, and did not convert to open surgery before NMB and/or pressure application. Participants were included in the treatment arm to which they were randomized.
    End point type
    Primary
    End point timeframe
    End of surgery (Day 1)
    End point values
    		 Standard NMB Deep NMB Standard Insufflation Pressure Low Insufflation Pressure
    Number of subjects analysed
    60
    60
    60
    60
    Units: score on a scale
        least squares mean (confidence interval 95%)
    6.83 (5.97 to 7.69)
    7.92 (7.05 to 8.8)
    8.89 (8.05 to 9.72)
    5.87 (4.96 to 6.77)
    Statistical analysis title
    		 Comparison by NMB (standard, deep)
    Statistical analysis description
    Primary hypothesis – deep NMB improves surgeon’s overall satisfaction with the surgical conditions compared to standard NMB. Analysis of covariance (ANCOVA) model included factors depth of NMB, level of pressure, surgeon and body mass index (BMI).
    Comparison groups
    Standard NMB v Deep NMB
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.026
    Method
    		 ANCOVA
    Parameter type
    		 Difference in Least Squares (LS) Means
    Point estimate
    1.09
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.13
         upper limit
    		 2.04
    Statistical analysis title
    		 Comparison by pressure (standard, low)
    Statistical analysis description
    ANCOVA model included factors depth of NMB, level of pressure, surgeon and BMI.
    Comparison groups
    Low Insufflation Pressure v Standard Insufflation Pressure
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 Difference in LS Means
    Point estimate
    -3.02
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.99
         upper limit
    		 -2.05

    Primary: Score on surgeon's assessment of overall satisfaction with the surgical conditions: By treatment arm

    		 Close Top of page
    End point title
    		 Score on surgeon's assessment of overall satisfaction with the surgical conditions: By treatment arm
    End point description
    At the end of the procedure the surgeon responds to the following question, using an 11-point scale from 0 (poor, needed intervention) to 10 (excellent): "How satisfied were you overall with the surgical conditions related to anesthesia and pneumoperitoneum during the surgery you just performed?" If at any time the surgeon requests a rescue intervention, the overall assessment of surgical conditions should be rated as 0 (=poor, needed intervention). The surgeon will rate the surgical conditions according to his opinion but if a rescue intervention has been applied, that individual participant will be counted with a score of zero in the analysis. Population for analysis was randomized participants with available data who had NMB and pneumoperitoneum for laparoscopic surgery, and did not convert to open surgery before NMB and/or pressure application. Participants were included in the treatment arm to which they were randomized.
    End point type
    Primary
    End point timeframe
    End of surgery (Day 1)
    End point values
    		 Standard NMB and Standard Insufflation Pressure Standard NMB and Low Insufflation Pressure Deep NMB and Standard Insufflation Pressure Deep NMB and Low Insufflation Pressure
    Number of subjects analysed
    30
    30
    30
    30
    Units: score on a scale
        least squares mean (confidence interval 95%)
    8.65 (7.58 to 9.72)
    4.99 (3.88 to 6.11)
    9.09 (8.02 to 10.17)
    6.69 (5.57 to 7.8)
    Statistical analysis title
    		 Comparison by treatment arm
    Statistical analysis description
    ANCOVA model included factors depth of NMB, level of pressure, surgeon and BMI.
    Comparison groups
    Standard NMB and Standard Insufflation Pressure v Standard NMB and Low Insufflation Pressure
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Difference in Least Squares (LS) Means
    Point estimate
    3.66
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.3
         upper limit
    		 5.02
    Statistical analysis title
    		 Comparison by treatment arm
    Statistical analysis description
    ANCOVA model included factors depth of NMB, level of pressure, surgeon and BMI.
    Comparison groups
    Standard NMB and Standard Insufflation Pressure v Deep NMB and Standard Insufflation Pressure
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Difference in LS Means
    Point estimate
    -0.44
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.8
         upper limit
    		 0.91
    Statistical analysis title
    		 Comparison by treatment arm
    Statistical analysis description
    ANCOVA model included factors depth of NMB, level of pressure, surgeon and BMI.
    Comparison groups
    Standard NMB and Standard Insufflation Pressure v Deep NMB and Low Insufflation Pressure
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Difference in LS Means
    Point estimate
    1.96
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.57
         upper limit
    		 3.36
    Statistical analysis title
    		 Comparison by treatment arm
    Statistical analysis description
    ANCOVA model included factors depth of NMB, level of pressure, surgeon and BMI.
    Comparison groups
    Standard NMB and Low Insufflation Pressure v Deep NMB and Standard Insufflation Pressure
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Difference in LS Means
    Point estimate
    -4.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.42
         upper limit
    		 -2.78
    Statistical analysis title
    		 Comparison by treatment arm
    Statistical analysis description
    ANCOVA model included factors depth of NMB, level of pressure, surgeon and BMI.
    Comparison groups
    Standard NMB and Low Insufflation Pressure v Deep NMB and Low Insufflation Pressure
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Difference in LS Means
    Point estimate
    -1.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.01
         upper limit
    		 -0.38
    Statistical analysis title
    		 Comparison by treatment arm
    Statistical analysis description
    ANCOVA model included factors depth of NMB, level of pressure, surgeon and BMI.
    Comparison groups
    Deep NMB and Standard Insufflation Pressure v Deep NMB and Low Insufflation Pressure
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Difference in LS Means
    Point estimate
    2.41
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.08
         upper limit
    		 3.74

    Secondary: Participant's overall average pain score in the first 24 hours after administration of sugammadex: By depth of NMB (standard, deep) and insufflation pressure (standard, low)

    		 Close Top of page
    End point title
    		 Participant's overall average pain score in the first 24 hours after administration of sugammadex: By depth of NMB (standard, deep) and insufflation pressure (standard, low)
    End point description
    Participants rated pain at 1, 2, 4, 24 and 48 hours after the administration of sugammadex on day of surgery (Day 1), and daily from Day 3 to Day 8. Pain rating was made using an 11-point scale from 0 (no pain) to 10 (severe pain). Separate ratings were made for overall pain at rest, pain when provoked (e.g., due to participant transition from lying to sitting position) and shoulder pain at rest. The participant’s overall average pain score within 24 hours after sugammadex was the average of all pain assessments (including all 3 pain types assessed) at 1, 2, 4 and 24 hours after sugammadex dose. Population for analysis was randomized participants with available data who had NMB or pneumoperitoneum for laparoscopic surgery, or received sugammadex, and did not convert to open surgery before NMB and/or pressure. Participants were included in arm corresponding to treatment actually received, which in case of rescue intervention was the post-intervention condition.
    End point type
    Secondary
    End point timeframe
    Up to 24 hours after administration of sugammadex on Day 1
    End point values
    		 Standard NMB Deep NMB Standard Insufflation Pressure Low Insufflation Pressure
    Number of subjects analysed
    55
    65
    71
    49
    Units: score on a scale
        least squares mean (confidence interval 95%)
    2.48 (2.02 to 2.93)
    2.83 (2.39 to 3.28)
    2.74 (2.34 to 3.15)
    2.57 (2.07 to 3.07)
    Statistical analysis title
    		 Comparison by NMB (standard, deep)
    Statistical analysis description
    Analysis of variance (ANOVA) model included factors depth of NMB, level of pressure, gender and surgeon.
    Comparison groups
    Deep NMB v Standard NMB
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.148
    Method
    		 ANOVA
    Parameter type
    		 Difference in LS Means
    Point estimate
    0.35
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.13
         upper limit
    		 0.84
    Statistical analysis title
    		 Comparison by pressure (standard, low)
    Statistical analysis description
    Key secondary hypothesis – low insufflation pressure improves overall average pain score in first 24 hours compared to standard insufflation pressure. ANOVA model included factors depth of NMB, level of pressure, gender and surgeon.
    Comparison groups
    Low Insufflation Pressure v Standard Insufflation Pressure
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.494 [1]
    Method
    		 ANOVA
    Parameter type
    		 Difference in LS Means
    Point estimate
    -0.17
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.67
         upper limit
    		 0.33
    Notes
    [1] - To control for multiple testing, this difference was formally tested only if comparison of surgeon’s overall satisfaction with surgical conditions for deep versus standard NMB was significant at the 5% level, with greater satisfaction for deep NMB.

    Secondary: Participant's overall average pain score in the first 24 hours after administration of sugammadex: By treatment arm

    		 Close Top of page
    End point title
    		 Participant's overall average pain score in the first 24 hours after administration of sugammadex: By treatment arm
    End point description
    Participants rated pain at 1, 2, 4, 24 and 48 hours after the administration of sugammadex on day of surgery (Day 1), and daily from Day 3 to Day 8. Pain rating was made using an 11-point scale from 0 (no pain) to 10 (severe pain). Separate ratings were made for overall pain at rest, pain when provoked (e.g., due to participant transition from lying to sitting position) and shoulder pain at rest. The participant’s overall average pain score within 24 hours after sugammadex was the average of all pain assessments (including all 3 pain types assessed) at 1, 2, 4 and 24 hours after sugammadex dose. Population for analysis was randomized participants with available data who had NMB or pneumoperitoneum for laparoscopic surgery, or received sugammadex, and did not convert to open surgery before NMB and/or pressure. Participants were included in arm corresponding to treatment actually received, which in case of rescue intervention was the post-intervention condition.
    End point type
    Secondary
    End point timeframe
    Up to 24 hours after administration of sugammadex on Day 1
    End point values
    		 Standard NMB and Standard Insufflation Pressure Standard NMB and Low Insufflation Pressure Deep NMB and Standard Insufflation Pressure Deep NMB and Low Insufflation Pressure
    Number of subjects analysed
    32
    23
    39
    26
    Units: score on a scale
        least squares mean (confidence interval 95%)
    2.42 (1.9 to 2.93)
    2.62 (1.98 to 3.26)
    3.06 (2.56 to 3.57)
    2.57 (1.97 to 3.17)
    Statistical analysis title
    		 Comparison by treatment arm
    Statistical analysis description
    ANOVA model included factors treatment group, gender and surgeon.
    Comparison groups
    Standard NMB and Standard Insufflation Pressure v Standard NMB and Low Insufflation Pressure
    Number of subjects included in analysis
    55
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Difference in LS Means
    Point estimate
    -0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.92
         upper limit
    		 0.52
    Statistical analysis title
    		 Comparison by treatment arm
    Statistical analysis description
    ANOVA model included factors treatment group, gender and surgeon.
    Comparison groups
    Standard NMB and Standard Insufflation Pressure v Deep NMB and Standard Insufflation Pressure
    Number of subjects included in analysis
    71
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Difference in LS Means
    Point estimate
    -0.65
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.27
         upper limit
    		 -0.02
    Statistical analysis title
    		 Comparison by treatment arm
    Statistical analysis description
    ANOVA model included factors treatment group, gender and surgeon.
    Comparison groups
    Standard NMB and Standard Insufflation Pressure v Deep NMB and Low Insufflation Pressure
    Number of subjects included in analysis
    58
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Difference in LS Means
    Point estimate
    -0.15
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.84
         upper limit
    		 0.53
    Statistical analysis title
    		 Comparison by treatment arm
    Statistical analysis description
    ANOVA model included factors treatment group, gender and surgeon.
    Comparison groups
    Standard NMB and Low Insufflation Pressure v Deep NMB and Standard Insufflation Pressure
    Number of subjects included in analysis
    62
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Difference in LS Means
    Point estimate
    -0.45
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.15
         upper limit
    		 0.26
    Statistical analysis title
    		 Comparison by treatment arm
    Statistical analysis description
    ANOVA model included factors treatment group, gender and surgeon.
    Comparison groups
    Standard NMB and Low Insufflation Pressure v Deep NMB and Low Insufflation Pressure
    Number of subjects included in analysis
    49
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Difference in LS Means
    Point estimate
    0.05
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.69
         upper limit
    		 0.78
    Statistical analysis title
    		 Comparison by treatment arm
    Statistical analysis description
    ANOVA model included factors treatment group, gender and surgeon.
    Comparison groups
    Deep NMB and Standard Insufflation Pressure v Deep NMB and Low Insufflation Pressure
    Number of subjects included in analysis
    65
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Difference in LS Means
    Point estimate
    0.49
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.17
         upper limit
    		 1.16

    Secondary: Score on surgeon's assessment of overall satisfaction with the visibility of the surgical field: By depth of NMB (standard, deep)

    		 Close Top of page
    End point title
    		 Score on surgeon's assessment of overall satisfaction with the visibility of the surgical field: By depth of NMB (standard, deep)
    End point description
    At the end of the procedure the surgeon responds to the following question, using an 11-point scale from 0 (poor, unacceptable visibility) to 10 (excellent): "How satisfied were you overall with the visual field during the surgery you just performed?" If at any time the surgeon requests a rescue intervention, the surgeon will rate his overall satisfaction with the visibility of the surgical field according to his opinion, but if a rescue intervention has been applied, that individual patient will be counted with a score of zero in the analysis. Population for analysis was randomized participants with available data who had NMB and pneumoperitoneum for laparoscopic surgery, and did not convert to open surgery before NMB and/or pressure application. Participants were included in the treatment arm to which they were randomized.
    End point type
    Secondary
    End point timeframe
    End of surgery (Day 1)
    End point values
    		 Standard NMB Deep NMB
    Number of subjects analysed
    60
    60
    Units: score on a scale
        least squares mean (confidence interval 95%)
    6.88 (6.02 to 7.75)
    7.8 (6.92 to 8.68)
    Statistical analysis title
    		 Comparison by NMB (standard, deep)
    Statistical analysis description
    ANCOVA model included factors depth of NMB, level of pressure, surgeon and BMI.
    Comparison groups
    Deep NMB v Standard NMB
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.063 [2]
    Method
    		 ANCOVA
    Parameter type
    		 Difference in LS Means
    Point estimate
    0.91
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.05
         upper limit
    		 1.87
    Notes
    [2] - Not controlled for multiple testing.

    Secondary: Score on surgeon's assessment of the overall adequacy of muscle relaxation during surgery: By depth of NMB (standard, deep)

    		 Close Top of page
    End point title
    		 Score on surgeon's assessment of the overall adequacy of muscle relaxation during surgery: By depth of NMB (standard, deep)
    End point description
    At the end of the procedure the surgeon responds to the following question, using an 11-point scale from 0 (poor, unacceptable muscle relaxation, required intervention) to 10 (excellent): "How do you rate the overall adequacy of muscle relaxation during the surgery you just performed?" Population for analysis was randomized participants with available data who had NMB and pneumoperitoneum for laparoscopic surgery, and did not convert to open surgery before NMB and/or pressure application. Participants were included in the treatment arm to which they were randomized.
    End point type
    Secondary
    End point timeframe
    End of surgery (Day 1)
    End point values
    		 Standard NMB Deep NMB
    Number of subjects analysed
    60
    60
    Units: score on a scale
        least squares mean (confidence interval 95%)
    8.05 (7.56 to 8.54)
    8.87 (8.37 to 9.37)
    Statistical analysis title
    		 Comparison by NMB (standard, deep)
    Statistical analysis description
    ANCOVA model included factors depth of NMB, level of pressure, surgeon and BMI.
    Comparison groups
    Deep NMB v Standard NMB
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.004 [3]
    Method
    		 ANCOVA
    Parameter type
    		 Difference in LS Means
    Point estimate
    0.82
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.27
         upper limit
    		 1.37
    Notes
    [3] - Not controlled for multiple testing.

    Secondary: Score on surgeon's assessment of the overall adequacy of insufflation pressure during surgery: By depth of NMB (standard, deep)

    		 Close Top of page
    End point title
    		 Score on surgeon's assessment of the overall adequacy of insufflation pressure during surgery: By depth of NMB (standard, deep)
    End point description
    At the end of the procedure the surgeon responds to the following question, using an 11-point scale from 0 (poor, unacceptable insufflation pressure, required intervention) to 10 (excellent): "How do you rate the overall adequacy of insufflation pressure during the surgery you just performed?" Analysis population was randomized participants with available data who had NMB and pneumoperitoneum for laparoscopic surgery, and did not convert to open surgery before NMB and/or pressure application. Participants were included in the treatment arm to which they were randomized.
    End point type
    Secondary
    End point timeframe
    End of surgery (Day 1)
    End point values
    		 Standard NMB Deep NMB
    Number of subjects analysed
    60
    60
    Units: score on a scale
        least squares mean (confidence interval 95%)
    6.73 (6.01 to 7.45)
    7.86 (7.12 to 8.59)
    Statistical analysis title
    		 Comparison by NMB (standard, deep)
    Statistical analysis description
    ANCOVA model included factors depth of NMB, level of pressure, surgeon and BMI.
    Comparison groups
    Deep NMB v Standard NMB
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.006 [4]
    Method
    		 ANCOVA
    Parameter type
    		 Difference in LS Means
    Point estimate
    1.12
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.32
         upper limit
    		 1.92
    Notes
    [4] - Not controlled for multiple testing.

    Secondary: Number of times participant's movements or increased muscle tone interfered with the surgical conditions during laparoscopy: By depth of NMB (standard, deep)

    		 Close Top of page
    End point title
    		 Number of times participant's movements or increased muscle tone interfered with the surgical conditions during laparoscopy: By depth of NMB (standard, deep)
    End point description
    At the end of the procedure the surgeon responds to the following question: “How many times did patient's movements (coughing, bucking, hiccup) or increased muscle tone (resistance, difficulty to close fasciae or skin) interfere with your surgery?” Population for analysis was randomized participants with available data who had NMB and pneumoperitoneum for laparoscopic surgery, and did not convert to open surgery before NMB and/or pressure application. Participants were included in the treatment arm to which they were randomized.
    End point type
    Secondary
    End point timeframe
    During surgery, approximate duration of 1-2 hours (Day 1)
    End point values
    		 Standard NMB Deep NMB
    Number of subjects analysed
    60
    59
    Units: instances of occurrence that interfered
        least squares mean (confidence interval 95%)
    0.92 (0.33 to 1.52)
    0.32 (-0.29 to 0.92)
    Statistical analysis title
    		 Comparison by NMB (standard, deep)
    Statistical analysis description
    ANCOVA model included factors depth of NMB, level of pressure, surgeon and BMI.
    Comparison groups
    Deep NMB v Standard NMB
    Number of subjects included in analysis
    119
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.073 [5]
    Method
    		 ANCOVA
    Parameter type
    		 Difference in LS Means
    Point estimate
    -0.61
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.27
         upper limit
    		 0.06
    Notes
    [5] - Not controlled for multiple testing.

    Secondary: Score on surgeon's assessment of the effect participant's movements during surgery had on the overall surgical procedure: By depth of NMB (standard, deep)

    		 Close Top of page
    End point title
    		 Score on surgeon's assessment of the effect participant's movements during surgery had on the overall surgical procedure: By depth of NMB (standard, deep)
    End point description
    At the end of the procedure the surgeon responds to the following question, using an 11-point scale from 0 (extremely disruptive) to 10 (not disruptive): "How did the patient movements described above disrupt your surgical performance?" This refers to participant movements during surgery. Population for analysis was randomized participants with available data who had NMB and pneumoperitoneum for laparoscopic surgery, and did not convert to open surgery before NMB and/or pressure application. Participants were included in the treatment arm to which they were randomized.
    End point type
    Secondary
    End point timeframe
    End of surgery (Day 1)
    End point values
    		 Standard NMB Deep NMB
    Number of subjects analysed
    60
    60
    Units: score on a scale
        least squares mean (confidence interval 95%)
    9.21 (8.72 to 9.7)
    9.94 (9.45 to 10.44)
    Statistical analysis title
    		 Comparison by NMB (standard, deep)
    Statistical analysis description
    ANCOVA model included factors depth of NMB, level of pressure, surgeon and BMI.
    Comparison groups
    Deep NMB v Standard NMB
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.009 [6]
    Method
    		 ANCOVA
    Parameter type
    		 Difference in LS Means
    Point estimate
    0.74
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.19
         upper limit
    		 1.28
    Notes
    [6] - Not controlled for multiple testing.

    Secondary: Number of participants with rescue actions performed during surgery in order to improve insufficient surgical conditions: By treatment arm

    		 Close Top of page
    End point title
    		 Number of participants with rescue actions performed during surgery in order to improve insufficient surgical conditions: By treatment arm
    End point description
    During procedure, surgeon could request modification to randomized treatment conditions (“rescue intervention”), if surgeon considered surgical conditions unacceptable. For participant on standard NMB, preferred rescue intervention was increase of NMB from standard to deep level; second option, if available, was to raise insufflation pressure from low to standard. If the participant was already on deep NMB, preferred option, if available, was to raise insufflation pressure from low to standard. The anesthetist recorded any rescue actions performed. This measure presents number of participants: with any rescue action performed, with rescue change in depth of NMB, with rescue change in insufflation pressure level. Analysis included randomized participants with available data who had NMB and pneumoperitoneum for laparoscopic surgery, and did not convert to open surgery before NMB and/or pressure application. Participants were included in the treatment arm to which they were randomized.
    End point type
    Secondary
    End point timeframe
    During surgery, approximate duration of 1-2 hours (Day 1)
    End point values
    		 Standard NMB and Standard Insufflation Pressure Standard NMB and Low Insufflation Pressure Deep NMB and Standard Insufflation Pressure Deep NMB and Low Insufflation Pressure
    Number of subjects analysed
    31
    30
    31
    30
    Units: participants
        Number with rescue action performed
    0
    7
    0
    5
        Number with rescue change in depth of NMB
    0
    5
    0
    0
        Number with rescue change in pressure level
    0
    6
    0
    5
    No statistical analyses for this end point

    Secondary: Participant's daily assessment of overall pain at rest during post operative period: By treatment arm

    		 Close Top of page
    End point title
    		 Participant's daily assessment of overall pain at rest during post operative period: By treatment arm
    End point description
    Participants rated pain at 1, 2, 4, 24 and 48 hours after the administration of sugammadex on day of surgery (Day 1), and daily (in the morning) from Day 3 to Day 8. Pain rating was made using an 11-point scale from 0 (no pain) to 10 (severe pain). Separate ratings were made for overall pain at rest, pain when provoked (e.g., due to participant transition from lying to sitting position) and shoulder pain at rest. This measure summarizes the assessment of overall pain at rest for the study days following the surgery. Analysis population was randomized participants with available data who had NMB or pneumoperitoneum for laparoscopic surgery, or received sugammadex. Participants were included in arm corresponding to treatment actually received, which in case of rescue intervention was the post-intervention condition.
    End point type
    Secondary
    End point timeframe
    Days 2 to 8
    End point values
    		 Standard NMB and Standard Insufflation Pressure Standard NMB and Low Insufflation Pressure Deep NMB and Standard Insufflation Pressure Deep NMB and Low Insufflation Pressure
    Number of subjects analysed
    33
    23
    40
    26
    Units: score on a scale
    arithmetic mean (standard deviation)
        24 hours after sugammadex dose (n=29, 22, 38, 25)
    1.66 ( 1.45 )
    2.23 ( 2.09 )
    2.24 ( 1.62 )
    2.48 ( 2.2 )
        48 hours after sugammadex dose (n=27, 22, 33, 23)
    1.22 ( 1.45 )
    1.41 ( 1.68 )
    1.73 ( 1.53 )
    1.83 ( 1.64 )
        Day 3 (N=22, 20, 30, 17)
    0.86 ( 0.89 )
    1.65 ( 1.76 )
    1.87 ( 1.59 )
    2 ( 1.84 )
        Day 4 (N=28, 20, 37, 23)
    0.89 ( 1.23 )
    1.05 ( 1.5 )
    1.76 ( 1.55 )
    1.04 ( 1.46 )
        Day 5 (N=27, 21, 38, 24)
    0.89 ( 1.01 )
    1 ( 1.48 )
    1.45 ( 1.35 )
    0.92 ( 1.02 )
        Day 6 (N=27, 20, 35, 24)
    0.56 ( 0.75 )
    0.85 ( 1.39 )
    1.31 ( 1.55 )
    0.75 ( 0.9 )
        Day 7 (N=27, 21, 34, 22)
    0.48 ( 0.64 )
    0.95 ( 1.43 )
    1.18 ( 1.57 )
    0.59 ( 0.85 )
        Day 8 (N=28, 21, 35, 21)
    0.54 ( 0.79 )
    0.81 ( 1.29 )
    0.94 ( 1.24 )
    0.43 ( 0.75 )
    No statistical analyses for this end point

    Secondary: Participant's daily assessment of provoked pain during post operative period: By treatment arm

    		 Close Top of page
    End point title
    		 Participant's daily assessment of provoked pain during post operative period: By treatment arm
    End point description
    Participants rated pain at 1, 2, 4, 24 and 48 hours after the administration of sugammadex on day of surgery (Day 1), and daily (in the morning) from Day 3 to Day 8. Pain rating was made using an 11-point scale from 0 (no pain) to 10 (severe pain). Separate ratings were made for overall pain at rest, pain when provoked (e.g., due to participant transition from lying to sitting position) and shoulder pain at rest. This measure summarizes the assessment of provoked pain for the study days following the surgery. Population for analysis included randomized participants with available data who had NMB or pneumoperitoneum for laparoscopic surgery, or received sugammadex. Participants were included in arm corresponding to treatment actually received, which in case of rescue intervention was the post-intervention condition.
    End point type
    Secondary
    End point timeframe
    Days 2 to 8
    End point values
    		 Standard NMB and Standard Insufflation Pressure Standard NMB and Low Insufflation Pressure Deep NMB and Standard Insufflation Pressure Deep NMB and Low Insufflation Pressure
    Number of subjects analysed
    33
    23
    40
    26
    Units: score on a scale
    arithmetic mean (standard deviation)
        24 hours after sugammadex dose (n=29, 22, 38, 25)
    3.38 ( 2.37 )
    3.27 ( 2.76 )
    3.68 ( 1.92 )
    3.76 ( 2.47 )
        48 hours after sugammadex dose (n=27, 22, 33, 23)
    2.67 ( 1.96 )
    2.14 ( 2.19 )
    2.94 ( 2.08 )
    2.91 ( 1.83 )
        Day 3 (N=22, 20, 30, 17)
    2.23 ( 1.51 )
    2.5 ( 2.33 )
    2.97 ( 2.11 )
    3.24 ( 2.11 )
        Day 4 (N=28, 20, 37, 23)
    2.25 ( 1.69 )
    1.85 ( 1.95 )
    3.05 ( 2.17 )
    1.91 ( 1.56 )
        Day 5 (N=27, 21, 38, 24)
    1.93 ( 1.54 )
    1.9 ( 1.84 )
    2.58 ( 1.9 )
    1.71 ( 1.46 )
        Day 6 (N=27, 20, 35, 24)
    1.7 ( 1.59 )
    1.4 ( 1.82 )
    2.51 ( 2.06 )
    1.42 ( 1.28 )
        Day 7 (N=27, 21, 34, 22)
    1.37 ( 1.28 )
    1.52 ( 1.66 )
    2.21 ( 2.24 )
    1.23 ( 1.38 )
        Day 8 (N=28, 21, 35, 21)
    1.21 ( 1.34 )
    1.38 ( 1.75 )
    1.91 ( 2.02 )
    0.81 ( 1.08 )
    No statistical analyses for this end point

    Secondary: Participant's daily assessment of shoulder pain during post operative period: By treatment arm

    		 Close Top of page
    End point title
    		 Participant's daily assessment of shoulder pain during post operative period: By treatment arm
    End point description
    Participants rated pain at 1, 2, 4, 24 and 48 hours after the administration of sugammadex on day of surgery (Day 1), and daily (in the morning) from Day 3 to Day 8. Pain rating was made using an 11-point scale from 0 (no pain) to 10 (severe pain). Separate ratings were made for overall pain at rest, pain when provoked (e.g., due to participant transition from lying to sitting position) and shoulder pain at rest. This measure summarizes the assessment of shoulder pain for the study days following the surgery. Population for analysis was randomized participants with available data who had NMB or pneumoperitoneum for laparoscopic surgery, or received sugammadex. Participants were included in arm corresponding to treatment actually received, which in case of rescue intervention was the post-intervention condition
    End point type
    Secondary
    End point timeframe
    Days 2 to 8
    End point values
    		 Standard NMB and Standard Insufflation Pressure Standard NMB and Low Insufflation Pressure Deep NMB and Standard Insufflation Pressure Deep NMB and Low Insufflation Pressure
    Number of subjects analysed
    33
    23
    40
    26
    Units: score on a scale
    arithmetic mean (standard deviation)
        24 hours after sugammadex dose (n=29, 22, 38, 25)
    1 ( 1.71 )
    1.18 ( 2.15 )
    1.05 ( 1.66 )
    1.4 ( 2.33 )
        48 hours after sugammadex dose (n=27, 22, 33, 23)
    0.41 ( 0.97 )
    0.64 ( 1.22 )
    0.76 ( 1.23 )
    0.96 ( 2.12 )
        Day 3 (N=22, 20, 30, 17)
    0.18 ( 0.5 )
    0.8 ( 1.32 )
    0.67 ( 1.4 )
    0.88 ( 1.76 )
        Day 4 (N=28, 20, 37, 23)
    0.32 ( 1.09 )
    0.55 ( 1.23 )
    0.7 ( 1.6 )
    0.61 ( 1.27 )
        Day 5 (N=27, 21, 38, 24)
    0 ( 0 )
    0.43 ( 0.81 )
    0.68 ( 1.65 )
    0.25 ( 0.85 )
        Day 6 (N=27, 20, 35, 24)
    0 ( 0 )
    0.15 ( 0.37 )
    0.63 ( 1.55 )
    0.21 ( 0.83 )
        Day 7 (N=27, 21, 34, 22)
    0 ( 0 )
    0.14 ( 0.48 )
    0.68 ( 1.63 )
    0.23 ( 0.69 )
        Day 8 (N=28, 21, 35, 21)
    0.04 ( 0.19 )
    0.24 ( 0.44 )
    0.66 ( 1.49 )
    0.14 ( 0.36 )
    No statistical analyses for this end point

    Secondary: Number of participants using pain/analgesic medication during post operative period: By treatment arm

    		 Close Top of page
    End point title
    		 Number of participants using pain/analgesic medication during post operative period: By treatment arm
    End point description
    Post operative use of pain/analgesic medication by participant through Day 8 was recorded. Population for analysis was randomized participants with available data who had NMB or pneumoperitoneum for laparoscopic surgery, or received sugammadex. Participants were included in arm corresponding to treatment actually received, which in case of rescue intervention was the post-intervention condition.
    End point type
    Secondary
    End point timeframe
    Up to Day 8
    End point values
    		 Standard NMB and Standard Insufflation Pressure Standard NMB and Low Insufflation Pressure Deep NMB and Standard Insufflation Pressure Deep NMB and Low Insufflation Pressure
    Number of subjects analysed
    33
    23
    40
    26
    Units: participants using pain medication
        Within 3 hours post surgery
    31
    21
    37
    24
        3 to 24 hours post surgery
    26
    21
    38
    24
        24 to 48 hours post surgery
    26
    22
    35
    23
        Between 48 hours and end of Day 5
    27
    20
    29
    17
        On Day 6, 7 or 8
    19
    14
    25
    10
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Up to Day 8
    Adverse event reporting additional description
    Includes randomized participants with available data who had NMB or pneumoperitoneum for laparoscopic surgery, or received sugammadex. Participants were included in arm corresponding to treatment actually received, which in case of rescue intervention was the post-intervention condition.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    17.0
    Reporting groups
    Reporting group title
    Standard NMB and Standard Insufflation Pressure
    Reporting group description
    		 Treatment condition for this reporting group is Standard NMB (depth of blockade at a targeted TOF ratio of 10%)/Standard insufflation pressure (starting pressure of 12 mmHg).

    Reporting group title
    Deep NMB and Low Insufflation Pressure
    Reporting group description
    		 Treatment condition for this reporting group is Deep NMB (depth of blockade of 1-2 PTCs)/Low insufflation pressure (starting pressure of 8 mmHg).

    Reporting group title
    Deep NMB and Standard Insufflation Pressure
    Reporting group description
    		 Treatment condition for this reporting group is Deep NMB (depth of blockade of 1-2 PTCs)/Standard insufflation pressure (starting pressure of 12 mmHg).

    Reporting group title
    Standard NMB and Low Insufflation Pressure
    Reporting group description
    		 Treatment condition for this reporting group is Standard NMB (depth of blockade at a targeted TOF ratio of 10%)/Low insufflation pressure (starting pressure of 8 mmHg).

    Serious adverse events
    		 Standard NMB and Standard Insufflation Pressure Deep NMB and Low Insufflation Pressure Deep NMB and Standard Insufflation Pressure Standard NMB and Low Insufflation Pressure
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 33 (0.00%)
    2 / 26 (7.69%)
    1 / 40 (2.50%)
    1 / 23 (4.35%)
         number of deaths (all causes)
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    Injury, poisoning and procedural complications
    Procedural haemorrhage
         subjects affected / exposed
    0 / 33 (0.00%)
    0 / 26 (0.00%)
    1 / 40 (2.50%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Procedural pain
         subjects affected / exposed
    0 / 33 (0.00%)
    0 / 26 (0.00%)
    0 / 40 (0.00%)
    1 / 23 (4.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wound haemorrhage
         subjects affected / exposed
    0 / 33 (0.00%)
    1 / 26 (3.85%)
    0 / 40 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Haematoma
         subjects affected / exposed
    0 / 33 (0.00%)
    1 / 26 (3.85%)
    0 / 40 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Necrotising fasciitis
         subjects affected / exposed
    0 / 33 (0.00%)
    1 / 26 (3.85%)
    0 / 40 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 33 (0.00%)
    1 / 26 (3.85%)
    0 / 40 (0.00%)
    0 / 23 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Standard NMB and Standard Insufflation Pressure Deep NMB and Low Insufflation Pressure Deep NMB and Standard Insufflation Pressure Standard NMB and Low Insufflation Pressure
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    31 / 33 (93.94%)
    26 / 26 (100.00%)
    39 / 40 (97.50%)
    23 / 23 (100.00%)
    Investigations
    C-reactive protein increased
         subjects affected / exposed
    1 / 33 (3.03%)
    1 / 26 (3.85%)
    3 / 40 (7.50%)
    0 / 23 (0.00%)
         occurrences all number
    1
    1
    3
    0
    Oxygen saturation decreased
         subjects affected / exposed
    0 / 33 (0.00%)
    2 / 26 (7.69%)
    0 / 40 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Injury, poisoning and procedural complications
    Procedural nausea
         subjects affected / exposed
    3 / 33 (9.09%)
    3 / 26 (11.54%)
    4 / 40 (10.00%)
    1 / 23 (4.35%)
         occurrences all number
    3
    4
    5
    2
    Procedural pain
         subjects affected / exposed
    28 / 33 (84.85%)
    24 / 26 (92.31%)
    34 / 40 (85.00%)
    19 / 23 (82.61%)
         occurrences all number
    46
    42
    63
    34
    Procedural vomiting
         subjects affected / exposed
    0 / 33 (0.00%)
    2 / 26 (7.69%)
    1 / 40 (2.50%)
    1 / 23 (4.35%)
         occurrences all number
    0
    3
    1
    1
    Wound haemorrhage
         subjects affected / exposed
    2 / 33 (6.06%)
    1 / 26 (3.85%)
    3 / 40 (7.50%)
    4 / 23 (17.39%)
         occurrences all number
    2
    1
    3
    4
    Vascular disorders
    Hypertension
         subjects affected / exposed
    0 / 33 (0.00%)
    1 / 26 (3.85%)
    1 / 40 (2.50%)
    2 / 23 (8.70%)
         occurrences all number
    0
    1
    1
    2
    Nervous system disorders
    Headache
         subjects affected / exposed
    2 / 33 (6.06%)
    0 / 26 (0.00%)
    0 / 40 (0.00%)
    1 / 23 (4.35%)
         occurrences all number
    2
    0
    0
    1
    General disorders and administration site conditions
    Pain
         subjects affected / exposed
    3 / 33 (9.09%)
    2 / 26 (7.69%)
    3 / 40 (7.50%)
    3 / 23 (13.04%)
         occurrences all number
    3
    2
    4
    4
    Pyrexia
         subjects affected / exposed
    4 / 33 (12.12%)
    4 / 26 (15.38%)
    3 / 40 (7.50%)
    5 / 23 (21.74%)
         occurrences all number
    4
    5
    3
    5
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    2 / 33 (6.06%)
    1 / 26 (3.85%)
    1 / 40 (2.50%)
    0 / 23 (0.00%)
         occurrences all number
    2
    1
    1
    0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    3 / 33 (9.09%)
    2 / 26 (7.69%)
    4 / 40 (10.00%)
    4 / 23 (17.39%)
         occurrences all number
    3
    2
    5
    4
    Abdominal pain upper
         subjects affected / exposed
    2 / 33 (6.06%)
    1 / 26 (3.85%)
    1 / 40 (2.50%)
    1 / 23 (4.35%)
         occurrences all number
    2
    1
    2
    2
    Constipation
         subjects affected / exposed
    2 / 33 (6.06%)
    1 / 26 (3.85%)
    1 / 40 (2.50%)
    1 / 23 (4.35%)
         occurrences all number
    2
    1
    1
    1
    Nausea
         subjects affected / exposed
    11 / 33 (33.33%)
    3 / 26 (11.54%)
    8 / 40 (20.00%)
    3 / 23 (13.04%)
         occurrences all number
    11
    3
    8
    3
    Vomiting
         subjects affected / exposed
    5 / 33 (15.15%)
    3 / 26 (11.54%)
    6 / 40 (15.00%)
    2 / 23 (8.70%)
         occurrences all number
    6
    3
    6
    2
    Psychiatric disorders
    Sleep disorder
         subjects affected / exposed
    0 / 33 (0.00%)
    2 / 26 (7.69%)
    1 / 40 (2.50%)
    1 / 23 (4.35%)
         occurrences all number
    0
    2
    1
    1
    Renal and urinary disorders
    Urinary retention
         subjects affected / exposed
    3 / 33 (9.09%)
    0 / 26 (0.00%)
    0 / 40 (0.00%)
    2 / 23 (8.70%)
         occurrences all number
    3
    0
    0
    2
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    0 / 33 (0.00%)
    2 / 26 (7.69%)
    0 / 40 (0.00%)
    0 / 23 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Musculoskeletal pain
         subjects affected / exposed
    5 / 33 (15.15%)
    5 / 26 (19.23%)
    8 / 40 (20.00%)
    5 / 23 (21.74%)
         occurrences all number
    5
    5
    8
    5

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    08 Oct 2012
    Amendment 01: Primary reason for amendment was to revise definition of standard NMB, methodology for administration of rocuronium to maintain NMB and scoring instruction on surgical conditions questionnaire.
    10 Jun 2013
    Amendment 02: Primary reason for amendment was to allow prematurely discontinued subjects with missing outcome for the primary and/or key secondary endpoints to be replaced.
    06 Aug 2013
    Amendment 03: Primary reason for amendment was to revise two exclusion criteria.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Wed May 07 00:06:49 CEST 2025 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA