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    Clinical Trial Results:
    A Phase 4 Randomized, Active-Comparator Controlled Clinical Trial to Study the Safety of Sugammadex (MK-8616) for the Reversal of Neuromuscular Blockade Induced by Either Rocuronium Bromide or Vecuronium Bromide in American Society of Anesthesiologists (ASA) Class 3 or 4 Subjects

    Summary
    EudraCT number
    		 2017-000187-15
    Trial protocol
    		 AT   DK  
    Global end of trial date
    04 Sep 2019

    Results information
    Results version number
    		 v1(current)
    This version publication date
    10 Sep 2020
    First version publication date
    10 Sep 2020
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    8616-145
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03346057
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 Merck Protocol Number: MK-8616-145
    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
    04 Sep 2019
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    04 Sep 2019
    Global end of trial reached?
    Yes
    Global end of trial date
    04 Sep 2019
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The purpose of this trial is to evaluate the safety of sugammadex for the reversal of neuromuscular blockade (NMB) induced by neuromuscular blockade agents (NMBA) rocuronium or vecuronium in adult American Society of Anesthesiologists (ASA) Physical Status Class 3 and 4 participants. The primary objectives of the study are to characterize the incidence of treatment emergent sinus bradycardia, treatment emergent sinus tachycardia, or other treatment emergent cardiac arrhythmias after administration of sugammadex and to evaluate the general safety of sugammadex in a population of ASA Class 3 and 4 participants in a surgical setting
    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
    20 Dec 2017
    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: 52
    Country: Number of subjects enrolled
    Denmark: 38
    Country: Number of subjects enrolled
    Germany: 114
    Country: Number of subjects enrolled
    United States: 140
    Worldwide total number of subjects
    344
    EEA total number of subjects
    204
    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
    218
    85 years and over
    14

    Subject disposition

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    Recruitment
    Recruitment details
    		 Male and female participants with a body mass index (BMI) of <40 kg/m2, of American Society of Anesthesiologists (ASA) Class 3 or 4, and a planned surgical procedure requiring Neuromuscular Blockade (NMB) with either rocuronium or vecuronium were recruited.

    Pre-assignment
    Screening details
    		 Of 344 participants randomized to the study, 331 received at least one dose of study treatment (All Treated Population) and were evaluable for all safety analysis.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Sugammadex 2 mg/kg
    Arm description
    		 Sugammadex 2 mg/kg administered as a single intravenous (IV) dose
    Arm type
    		 Experimental

    Investigational medicinal product name
    Sugammadex
    Investigational medicinal product code
    Other name
    MK-8616, Bridion
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous bolus use
    Dosage and administration details
    Following administration of NMBA (Rocuronium or Vecuronium) to achieve moderate NMB, participants received a single i.v. bolus of Sugammadex 2 mg/kg for reversal of moderate NMB. Moderate block is a level of NMB in which peripheral nerve stimulation elicits one to four muscle twitches.

    Investigational medicinal product name
    Vecuronium
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    To achieve NMB, participants received steroidal NMBA Vecuronium Bromide administered via IV infusion and dosed according to participant body weight. NMBAs were concomitant medications used per label and at Investigator's discretion as an adjunct to general anesthesia.

    Investigational medicinal product name
    Rocuronium
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    To achieve NMB, participants received steroidal NMBA Rocuronium Bromide administered via IV infusion and dosed according to participant body weight. NMBAs were concomitant medications used per label and at Investigator's discretion as an adjunct to general anesthesia.

    Arm title
    		 Sugammadex 4 mg/kg
    Arm description
    		 Sugammadex 4 mg/kg administered as a single IV dose
    Arm type
    		 Experimental

    Investigational medicinal product name
    Sugammadex
    Investigational medicinal product code
    Other name
    MK-8616, Bridion
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous bolus use
    Dosage and administration details
    Following administration of NMBA (Rocuronium or Vecuronium) to achieve deep NMB, participants received a single i.v. bolus of Sugammadex 4 mg/kg for reversal of deep NMB. Deep block is a level of NMB in which peripheral nerve stimulation elicits no muscle twitches and high-frequency muscle stimulation elicits minimal levels of muscle contraction.

    Investigational medicinal product name
    Rocuronium
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    To achieve NMB, participants received steroidal NMBA Rocuronium Bromide administered via IV infusion and dosed according to participant body weight. NMBAs were concomitant medications used per label and at Investigator's discretion as an adjunct to general anesthesia.

    Investigational medicinal product name
    Vecuronium
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    To achieve NMB, participants received steroidal NMBA Vecuronium Bromide administered via IV infusion and dosed according to participant body weight. NMBAs were concomitant medications used per label and at Investigator's discretion as an adjunct to general anesthesia.

    Arm title
    		 Sugammadex 16 mg/kg
    Arm description
    		 Sugammadex 16 mg/kg administered as a single IV dose
    Arm type
    		 Experimental

    Investigational medicinal product name
    Sugammadex
    Investigational medicinal product code
    Other name
    MK-8616, Bridion
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous bolus use
    Dosage and administration details
    Following administration of NMBA (Rocuronium) to achieve deep NMB, participants received a single i.v. bolus of Sugammadex 16 mg/kg for reversal of deep NMB. Deep block is a level of NMB in which peripheral nerve stimulation elicits no muscle twitches and high-frequency muscle stimulation elicits minimal levels of muscle contraction.

    Investigational medicinal product name
    Rocuronium
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    To achieve NMB, participants received steroidal NMBA Rocuronium Bromide administered via IV infusion and dosed according to participant body weight. NMBAs were concomitant medications used per label and at Investigator's discretion as an adjunct to general anesthesia.

    Arm title
    		 Neostigmine + Glycopyrrolate
    Arm description
    		 Neostigmine 50 μg/kg (up to 5 mg maximum dose) plus glycopyrrolate 10 μg/kg (up to 1 mg maximum dose) administered as a single IV dose
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Neostigmine + Glycopyrrolate
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous bolus use
    Dosage and administration details
    Following administration of NMBA (Rocuronium or Vecuronium) to achieve moderate NMB, participants received a single i.v. bolus of Neostigmine (50 µg/kg; 5 mg maximum) and Glycopyrrolate (10 µg/kg; 1 mg maximum) for reversal of moderate NMB. Moderate block is a level of NMB in which peripheral nerve stimulation elicits one to four muscle twitches.

    Investigational medicinal product name
    Vecuronium
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    To achieve NMB, participants received steroidal NMBA Vecuronium Bromide administered via IV infusion and dosed according to participant body weight. NMBAs were concomitant medications used per label and at Investigator's discretion as an adjunct to general anesthesia.

    Investigational medicinal product name
    Rocuronium
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    To achieve NMB, participants received steroidal NMBA Rocuronium Bromide administered via IV infusion and dosed according to participant body weight. NMBAs were concomitant medications used per label and at Investigator's discretion as an adjunct to general anesthesia.

    Number of subjects in period 1
    		Sugammadex 2 mg/kg Sugammadex 4 mg/kg Sugammadex 16 mg/kg Neostigmine + Glycopyrrolate
    Started
    111
    112
    68
    53
    Treated
    105
    107
    68
    51
    Completed
    104
    104
    67
    51
    Not completed
    7
    8
    1
    2
         Adverse event, serious fatal
    1
    2
    -
    -
         Physician decision
    3
    2
    -
    2
         Consent withdrawn by subject
    1
    -
    -
    -
         Renal Insufficiency - Not Treated
    1
    -
    -
    -
         Randomization Mistake - Not Treated
    1
    1
    -
    -
         Lost to follow-up
    -
    2
    1
    -
         Ineligible For Study - Not Treated
    -
    1
    -
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Sugammadex 2 mg/kg
    Reporting group description
    		 Sugammadex 2 mg/kg administered as a single intravenous (IV) dose

    Reporting group title
    Sugammadex 4 mg/kg
    Reporting group description
    		 Sugammadex 4 mg/kg administered as a single IV dose

    Reporting group title
    Sugammadex 16 mg/kg
    Reporting group description
    		 Sugammadex 16 mg/kg administered as a single IV dose

    Reporting group title
    Neostigmine + Glycopyrrolate
    Reporting group description
    		 Neostigmine 50 μg/kg (up to 5 mg maximum dose) plus glycopyrrolate 10 μg/kg (up to 1 mg maximum dose) administered as a single IV dose

    Reporting group values
    		 Sugammadex 2 mg/kg Sugammadex 4 mg/kg Sugammadex 16 mg/kg Neostigmine + Glycopyrrolate Total
    Number of subjects
    		 111 112 68 53 344
    Age categorical
    Units: Subjects
        In utero
        Preterm newborn infants (gestational age < 37 wks)
        Newborns (0-27 days)
        Infants and toddlers (28 days-23 months)
        Children (2-11 years)
        Adolescents (12-17 years)
        Adults (18-64 years)
        From 65-84 years
        85 years and over
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 69.5 ( 10.7 ) 67.8 ( 12.1 ) 69.4 ( 10.0 ) 66.6 ( 10.9 ) -
    Sex: Female, Male
    Units:
        Female
    		 50 41 29 15 135
        Male
    		 61 71 39 38 209
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0 0 0
        Asian
    		 0 0 0 0 0
        Native Hawaiian or Other Pacific Islander
    		 2 0 0 0 2
        Black or African American
    		 3 9 2 3 17
        White
    		 106 103 66 50 325
        More than one race
    		 0 0 0 0 0
        Unknown or Not Reported
    		 0 0 0 0 0
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 2 6 0 2 10
        Not Hispanic or Latino
    		 109 105 67 51 332
        Unknown or Not Reported
    		 0 1 1 0 2
    Participant Stratifications
    Units: Subjects
        Rocuronium, ASA Class 3
    		 50 49 51 25 175
        Rocuronium, ASA Class 4
    		 15 18 17 8 58
        Vecuronium, ASA Class 3
    		 29 31 0 14 74
        Vecuronium, ASA Class 4
    		 11 11 0 5 27
        Missing
    		 6 3 0 1 10

    End points

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    End points reporting groups
    Reporting group title
    Sugammadex 2 mg/kg
    Reporting group description
    		 Sugammadex 2 mg/kg administered as a single intravenous (IV) dose

    Reporting group title
    Sugammadex 4 mg/kg
    Reporting group description
    		 Sugammadex 4 mg/kg administered as a single IV dose

    Reporting group title
    Sugammadex 16 mg/kg
    Reporting group description
    		 Sugammadex 16 mg/kg administered as a single IV dose

    Reporting group title
    Neostigmine + Glycopyrrolate
    Reporting group description
    		 Neostigmine 50 μg/kg (up to 5 mg maximum dose) plus glycopyrrolate 10 μg/kg (up to 1 mg maximum dose) administered as a single IV dose

    Primary: Percentage of Participants With Treatment-Emergent Sinus Bradycardia Events

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    End point title
    		 Percentage of Participants With Treatment-Emergent Sinus Bradycardia Events
    End point description
    The percentage of participants experiencing treatment-emergent sinus bradycardia events was identified with continuous electrocardiogram (ECG) monitoring. Treatment-emergent sinus bradycardia defined as a heart rate <60 beats per minute (bpm) that has also decreased more than 20% compared to participant baseline heart rate value, sustained for at least 1 minute after administration of study intervention. Treatment-emergent sinus bradycardia events may or may not have been considered an adverse event (AE), as determined by investigator judgment. All randomized participants who received at least one dose of study intervention were analyzed.
    End point type
    Primary
    End point timeframe
    Up to approximately 35 minutes post-administration
    End point values
    		 Sugammadex 2 mg/kg Sugammadex 4 mg/kg Sugammadex 16 mg/kg Neostigmine + Glycopyrrolate
    Number of subjects analysed
    105
    107
    68
    51
    Units: Percentage of participants
        number (not applicable)
    1.0
    1.9
    7.4
    7.8
    Statistical analysis title
    		 Estimated Difference in percentage of participants
    Statistical analysis description
    Miettinen & Nurminen method stratified by neuromuscular blocking agent (NMBA) and American Society of Anesthesiologists (ASA) class was used to provide estimated between-treatment difference, 95% confidence interval, and p-value
    Comparison groups
    Sugammadex 2 mg/kg v Neostigmine + Glycopyrrolate
    Number of subjects included in analysis
    156
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.026
    Method
    		 Stratified Miettinen & Nurminen method
    Parameter type
    		 Estimated Difference in percentage
    Point estimate
    -6.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -17.5
         upper limit
    		 -0.8
    Statistical analysis title
    		 Estimated Difference in percentage of participants
    Statistical analysis description
    Miettinen & Nurminen method stratified by NMBA and ASA was used to provide estimated between-treatment difference, 95% confidence interval, and p-value
    Comparison groups
    Sugammadex 4 mg/kg v Neostigmine + Glycopyrrolate
    Number of subjects included in analysis
    158
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.058
    Method
    		 Stratified Miettinen & Nurminen method
    Parameter type
    		 Estimated Difference in percentage
    Point estimate
    -6.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -17.3
         upper limit
    		 0.2
    Statistical analysis title
    		 Estimated Difference in percentage of participants
    Statistical analysis description
    Miettinen & Nurminen method stratified by NMBA and ASA was used to provide estimated between-treatment difference, 95% confidence interval, and p-value
    Comparison groups
    Sugammadex 16 mg/kg v Neostigmine + Glycopyrrolate
    Number of subjects included in analysis
    119
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.73
    Method
    		 Stratified Miettinen & Nurminen method
    Parameter type
    		 Estimated Difference in percentage
    Point estimate
    -2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -17.8
         upper limit
    		 8.6

    Primary: Percentage of Participants With Treatment-Emergent Sinus Tachycardia Events

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    End point title
    		 Percentage of Participants With Treatment-Emergent Sinus Tachycardia Events
    End point description
    The percentage of participants experiencing treatment-emergent sinus tachycardia events was identified with continuous ECG monitoring. Treatment-emergent sinus tachycardia is defined as a heart rate ≥100 bpm that has also increased more than 20% compared to participant baseline heart rate value, sustained for at least 1 minute after administration of study intervention. Treatment-emergent sinus tachycardia events may or may not have been considered an AE, as determined by investigator judgment. All randomized participants who received at least one dose of study intervention were analyzed.
    End point type
    Primary
    End point timeframe
    Up to approximately 35 minutes post-administration
    End point values
    		 Sugammadex 2 mg/kg Sugammadex 4 mg/kg Sugammadex 16 mg/kg Neostigmine + Glycopyrrolate
    Number of subjects analysed
    105
    107
    68
    51
    Units: Percentage of participants
        number (not applicable)
    6.7
    9.3
    8.8
    21.6
    Statistical analysis title
    		 Estimated Difference in percentage of participants
    Statistical analysis description
    Miettinen & Nurminen method stratified by NMBA and ASA was used to provide estimated between-treatment difference, 95% confidence interval, and p-value
    Comparison groups
    Sugammadex 2 mg/kg v Neostigmine + Glycopyrrolate
    Number of subjects included in analysis
    156
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.007
    Method
    		 Stratified Miettinen & Nurminen method
    Parameter type
    		 Estimated Difference in percentage
    Point estimate
    -14.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -28.8
         upper limit
    		 -4
    Statistical analysis title
    		 Estimated Difference in percentage of participants
    Statistical analysis description
    Miettinen & Nurminen method stratified by NMBA and ASA was used to provide estimated between-treatment difference, 95% confidence interval, and p-value
    Comparison groups
    Sugammadex 4 mg/kg v Neostigmine + Glycopyrrolate
    Number of subjects included in analysis
    158
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.036
    Method
    		 Stratified Miettinen & Nurminen method
    Parameter type
    		 Estimated Difference in percentage
    Point estimate
    -12.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -26.1
         upper limit
    		 -0.8
    Statistical analysis title
    		 Estimated Difference in percentage of participants
    Statistical analysis description
    Miettinen & Nurminen method stratified by NMBA and ASA was used to provide estimated between-treatment difference, 95% confidence interval, and p-value
    Comparison groups
    Sugammadex 16 mg/kg v Neostigmine + Glycopyrrolate
    Number of subjects included in analysis
    119
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.158
    Method
    		 Stratified Miettinen & Nurminen method
    Parameter type
    		 Estimated Difference in percentage
    Point estimate
    -9.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -27.6
         upper limit
    		 3.6

    Primary: Percentage of Participants With Other Treatment-Emergent Cardiac Arrhythmia Events

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    End point title
    		 Percentage of Participants With Other Treatment-Emergent Cardiac Arrhythmia Events
    End point description
    The percentage of participants experiencing other treatment-emergent cardiac arrhythmia events was identified with continuous ECG monitoring. Other treatment-emergent cardiac arrhythmias were defined as new or worsening arrhythmias (e.g., atrial fibrillation, atrial tachycardia, ventricular fibrillation, or ventricular tachyarrhythmia), sustained for at least 1 minute after administration of study intervention. Worsening arrhythmia events may or may not have been considered an AE, as determined by investigator judgment. All randomized participants who received at least one dose of study intervention were analyzed.
    End point type
    Primary
    End point timeframe
    Up to approximately 35 minutes post-administration
    End point values
    		 Sugammadex 2 mg/kg Sugammadex 4 mg/kg Sugammadex 16 mg/kg Neostigmine + Glycopyrrolate
    Number of subjects analysed
    105
    107
    68
    51
    Units: Percentage of participants
        number (not applicable)
    1.0
    0.0
    1.5
    2.0
    Statistical analysis title
    		 Estimated Difference in percentage of participants
    Statistical analysis description
    Miettinen & Nurminen method stratified by NMBA and ASA was used to provide estimated between-treatment difference, 95% confidence interval, and p-value
    Comparison groups
    Sugammadex 2 mg/kg v Neostigmine + Glycopyrrolate
    Number of subjects included in analysis
    156
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.637
    Method
    		 Stratified Miettinen & Nurminen method
    Parameter type
    		 Estimated Difference in percentage
    Point estimate
    -0.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -9.4
         upper limit
    		 4
    Statistical analysis title
    		 Estimated Difference in percentage of participants
    Statistical analysis description
    Miettinen & Nurminen method stratified by NMBA and ASA was used to provide estimated between-treatment difference, 95% confidence interval, and p-value
    Comparison groups
    Sugammadex 4 mg/kg v Neostigmine + Glycopyrrolate
    Number of subjects included in analysis
    158
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.134
    Method
    		 Stratified Miettinen & Nurminen method
    Parameter type
    		 Estimated Difference in percentage
    Point estimate
    -2.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -10.6
         upper limit
    		 1.5
    Statistical analysis title
    		 Estimated Difference in percentage of participants
    Statistical analysis description
    Miettinen & Nurminen method stratified by NMBA and ASA was used to provide estimated between-treatment difference, 95% confidence interval, and p-value
    Comparison groups
    Sugammadex 16 mg/kg v Neostigmine + Glycopyrrolate
    Number of subjects included in analysis
    119
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.577
    Method
    		 Stratified Miettinen & Nurminen method
    Parameter type
    		 Estimated Difference in percentage
    Point estimate
    -1.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -14.7
         upper limit
    		 5.8

    Primary: Percentage of Participants Experiencing an Adverse Event (AE) Up To 7 Days After Administration of Study Intervention

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    End point title
    		 Percentage of Participants Experiencing an Adverse Event (AE) Up To 7 Days After Administration of Study Intervention
    End point description
    As per the protocol primary analysis, the percentage of participants experiencing an AE up to 7 days after administration of study intervention was reported. An AE was defined as any untoward medical occurrence in a participant which did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of the Sponsor’s product was also an AE. All randomized participants who received at least one dose of study intervention were analyzed.
    End point type
    Primary
    End point timeframe
    Up to 7 days
    End point values
    		 Sugammadex 2 mg/kg Sugammadex 4 mg/kg Sugammadex 16 mg/kg Neostigmine + Glycopyrrolate
    Number of subjects analysed
    105
    107
    68
    51
    Units: Percentage of participants
        number (not applicable)
    94.3
    88.8
    92.6
    88.2
    Statistical analysis title
    		 Estimated Difference in percentage of participants
    Statistical analysis description
    Miettinen & Nurminen method stratified by NMBA and ASA was used to provide estimated between-treatment difference and 95% confidence interval
    Comparison groups
    Sugammadex 2 mg/kg v Neostigmine + Glycopyrrolate
    Number of subjects included in analysis
    156
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Estimated Difference in percentage
    Point estimate
    6.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.6
         upper limit
    		 18.5
    Statistical analysis title
    		 Estimated Difference in percentage of participants
    Statistical analysis description
    Miettinen & Nurminen method stratified by NMBA and ASA was used to provide estimated between-treatment difference and 95% confidence interval
    Comparison groups
    Sugammadex 4 mg/kg v Neostigmine + Glycopyrrolate
    Number of subjects included in analysis
    158
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Estimated Difference in percentage
    Point estimate
    0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -9.3
         upper limit
    		 13.1
    Statistical analysis title
    		 Estimated Difference in percentage of participants
    Statistical analysis description
    Miettinen & Nurminen method stratified by NMBA and ASA was used to provide estimated between-treatment difference and 95% confidence interval
    Comparison groups
    Sugammadex 16 mg/kg v Neostigmine + Glycopyrrolate
    Number of subjects included in analysis
    119
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Estimated Difference in percentage
    Point estimate
    2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -8.4
         upper limit
    		 17.7

    Primary: Percentage of Participants Experiencing a Serious Adverse Event (SAE) Up To 7 Days After Administration of Study Intervention

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    End point title
    		 Percentage of Participants Experiencing a Serious Adverse Event (SAE) Up To 7 Days After Administration of Study Intervention
    End point description
    As per the protocol primary analysis, the percentage of participants experiencing an SAE up to 7 days after administration of study intervention was reported. An SAE was an adverse event that: resulted in death; was life threatening; resulted in persistent or significant disability or incapacity; resulted in or prolonged an existing inpatient hospitalization; was a congenital anomaly or birth defect; was an other important medical event, was a cancer; or was associated with an overdose. All randomized participants who received at least one dose of study intervention were analyzed.
    End point type
    Primary
    End point timeframe
    Up to 7 days
    End point values
    		 Sugammadex 2 mg/kg Sugammadex 4 mg/kg Sugammadex 16 mg/kg Neostigmine + Glycopyrrolate
    Number of subjects analysed
    105
    107
    68
    51
    Units: Percentage of Participants
        number (not applicable)
    11.4
    7.5
    10.3
    5.9
    Statistical analysis title
    		 Estimated Difference in percentage of participants
    Statistical analysis description
    Miettinen & Nurminen method stratified by NMBA and ASA was used to provide estimated between-treatment difference and 95% confidence interval
    Comparison groups
    Sugammadex 2 mg/kg v Neostigmine + Glycopyrrolate
    Number of subjects included in analysis
    156
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Estimated Difference in percentage
    Point estimate
    5.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.5
         upper limit
    		 14.3
    Statistical analysis title
    		 Estimated Difference in percentage of participants
    Statistical analysis description
    Miettinen & Nurminen method stratified by NMBA and ASA was used to provide estimated between-treatment difference and 95% confidence interval
    Comparison groups
    Sugammadex 4 mg/kg v Neostigmine + Glycopyrrolate
    Number of subjects included in analysis
    158
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Estimated Difference in percentage
    Point estimate
    1.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -9.2
         upper limit
    		 9.3
    Statistical analysis title
    		 Estimated Difference in percentage of participants
    Statistical analysis description
    Miettinen & Nurminen method stratified by NMBA and ASA was used to provide estimated between-treatment difference and 95% confidence interval
    Comparison groups
    Sugammadex 16 mg/kg v Neostigmine + Glycopyrrolate
    Number of subjects included in analysis
    119
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Estimated Difference in percentage
    Point estimate
    0.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -15.1
         upper limit
    		 12.7

    Primary: Percentage of Participants Experiencing an Event of Clinical Interest (ECI) Up To 7 Days After Administration of Study Intervention

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    End point title
    		 Percentage of Participants Experiencing an Event of Clinical Interest (ECI) Up To 7 Days After Administration of Study Intervention
    End point description
    As per the protocol primary analysis, the percentage of participants experiencing an ECI up to 7 days after administration of study intervention was reported. ECIs were a discrete set of both AEs and SAEs, specifically designated as such for the trial. For the purposes of this investigation, ECIs included 1) drug-induced liver injury; 2) clinically-relevant arrhythmias, inclusive of bradycardia and tachycardia defined as events necessitating intervention, as determined by investigator judgment; and 3) instances of hypersensitivity and/or anaphylaxis adjudicated by an external expert Adjudication Committee. All randomized participants who received at least one dose of study intervention were analyzed. A participant could have experienced more than one type of ECI.
    End point type
    Primary
    End point timeframe
    Up to 7 days
    End point values
    		 Sugammadex 2 mg/kg Sugammadex 4 mg/kg Sugammadex 16 mg/kg Neostigmine + Glycopyrrolate
    Number of subjects analysed
    105
    107
    68
    51
    Units: Percentage of participants
    number (not applicable)
        With one or more ECIs
    1.9
    5.6
    7.4
    3.9
        Adjudicated Hypersensitivity
    0.0
    0.0
    0.0
    0.0
        Adjudicated Anaphylaxis
    0.0
    0.0
    0.0
    0.0
        Clinically Relevant Bradycardia
    0.0
    2.8
    0.0
    2.0
        Clinically Relevant Tachycardia
    1.9
    1.9
    5.9
    0.0
        Other Clinically Relevant Cardiac Arrhythmia
    0.0
    0.9
    1.5
    2.0
        Drug Induced Liver Injury
    0.0
    0.0
    0.0
    0.0
    Statistical analysis title
    		 Estimated Difference in percentage of participants
    Statistical analysis description
    The percentage of participants experiencing one or more ECIs was compared between the Sugammadex 2 mg/kg arm and the Neostigmine plus Glycopyrrolate arm. Miettinen & Nurminen method stratified by NMBA and ASA was used to provide estimated between-treatment difference and 95% confidence interval
    Comparison groups
    Sugammadex 2 mg/kg v Neostigmine + Glycopyrrolate
    Number of subjects included in analysis
    156
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Estimated Difference in percentage
    Point estimate
    -2.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -11.8
         upper limit
    		 3.8
    Statistical analysis title
    		 Estimated Difference in percentage of participants
    Statistical analysis description
    The percentage of participants experiencing one or more ECIs was compared between the Sugammadex 4 mg/kg arm and the Neostigmine plus Glycopyrrolate arm. Miettinen & Nurminen method stratified by NMBA and ASA was used to provide estimated between-treatment difference and 95% confidence interval
    Comparison groups
    Sugammadex 4 mg/kg v Neostigmine + Glycopyrrolate
    Number of subjects included in analysis
    158
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Estimated Difference in percentage
    Point estimate
    1.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -8.1
         upper limit
    		 8.4
    Statistical analysis title
    		 Estimated Difference in percentage of participants
    Statistical analysis description
    The percentage of participants experiencing one or more ECIs was compared between the Sugammadex 16 mg/kg arm and the Neostigmine plus Glycopyrrolate arm. Miettinen & Nurminen method stratified by NMBA and ASA was used to provide estimated between-treatment difference and 95% confidence interval
    Comparison groups
    Sugammadex 16 mg/kg v Neostigmine + Glycopyrrolate
    Number of subjects included in analysis
    119
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Estimated Difference in percentage
    Point estimate
    1.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -13.5
         upper limit
    		 11.1

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Up to approximately 21 days.
    Adverse event reporting additional description
    All-Cause Mortality reported for all randomized participants (N = 344: Sugammadex 2 mg/kg: n = 111, Sugammadex 4 mg/kg: n = 112, Sugammadex 16 mg/kg: n = 68, and Neostigmine + Glycopyrrolate: n = 53). Serious AEs and Other AEs were reported for all randomized participants who received at least 1 dose of study treatment.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    22.1
    Reporting groups
    Reporting group title
    Sugammadex 2 mg/kg
    Reporting group description
    		 Sugammadex 2 mg/kg administered as a single intravenous (IV) dose

    Reporting group title
    Sugammadex 4 mg/kg
    Reporting group description
    		 Sugammadex 4 mg/kg administered as a single intravenous (IV) dose

    Reporting group title
    Sugammadex 16 mg/kg
    Reporting group description
    		 Sugammadex 16 mg/kg administered as a single intravenous (IV) dose

    Reporting group title
    Neostigmine + Glycopyrrolate
    Reporting group description
    		 Neostigmine 50 μg/kg (up to 5 mg maximum dose) plus glycopyrrolate 10 μg/kg (up to 1 mg maximum dose) administered as a single IV dose

    Serious adverse events
    		 Sugammadex 2 mg/kg Sugammadex 4 mg/kg Sugammadex 16 mg/kg Neostigmine + Glycopyrrolate
    Total subjects affected by serious adverse events
         subjects affected / exposed
    16 / 105 (15.24%)
    12 / 107 (11.21%)
    9 / 68 (13.24%)
    4 / 51 (7.84%)
         number of deaths (all causes)
    1
    2
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    Investigations
    C-reactive protein increased
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 107 (0.00%)
    1 / 68 (1.47%)
    0 / 51 (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
    Haemoglobin decreased
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 107 (0.00%)
    1 / 68 (1.47%)
    0 / 51 (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
    Injury, poisoning and procedural complications
    Abdominal wound dehiscence
         subjects affected / exposed
    2 / 105 (1.90%)
    0 / 107 (0.00%)
    0 / 68 (0.00%)
    1 / 51 (1.96%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Accidental overdose
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 107 (0.00%)
    0 / 68 (0.00%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anastomotic leak
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 107 (0.93%)
    0 / 68 (0.00%)
    0 / 51 (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
    Fascial rupture
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 107 (0.00%)
    0 / 68 (0.00%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal stoma necrosis
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 107 (0.00%)
    0 / 68 (0.00%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Incision site pain
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 107 (0.00%)
    1 / 68 (1.47%)
    0 / 51 (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
    Post procedural haematoma
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 107 (0.93%)
    0 / 68 (0.00%)
    0 / 51 (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
    Postoperative delirium
         subjects affected / exposed
    1 / 105 (0.95%)
    1 / 107 (0.93%)
    0 / 68 (0.00%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Postoperative ileus
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 107 (0.00%)
    0 / 68 (0.00%)
    1 / 51 (1.96%)
         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
    Procedural pain
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 107 (0.00%)
    0 / 68 (0.00%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary retention postoperative
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 107 (0.93%)
    0 / 68 (0.00%)
    0 / 51 (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 graft occlusion
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 107 (0.00%)
    0 / 68 (0.00%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Hypotension
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 107 (0.00%)
    0 / 68 (0.00%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lymphocele
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 107 (0.93%)
    0 / 68 (0.00%)
    0 / 51 (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
    Cardiac disorders
    Acute myocardial infarction
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 107 (0.00%)
    1 / 68 (1.47%)
    0 / 51 (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
    Atrial fibrillation
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 107 (0.93%)
    0 / 68 (0.00%)
    0 / 51 (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
    Cardiac arrest
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 107 (0.00%)
    1 / 68 (1.47%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 107 (0.93%)
    0 / 68 (0.00%)
    0 / 51 (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 / 1
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 107 (0.00%)
    0 / 68 (0.00%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial ischaemia
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 107 (0.93%)
    0 / 68 (0.00%)
    0 / 51 (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
    Tachycardia
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 107 (0.00%)
    0 / 68 (0.00%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Heparin-induced thrombocytopenia
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 107 (0.00%)
    1 / 68 (1.47%)
    0 / 51 (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
    General disorders and administration site conditions
    Catheter site haemorrhage
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 107 (0.00%)
    0 / 68 (0.00%)
    1 / 51 (1.96%)
         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
    Dehiscence
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 107 (0.00%)
    0 / 68 (0.00%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hernia
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 107 (0.00%)
    0 / 68 (0.00%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Impaired healing
         subjects affected / exposed
    2 / 105 (1.90%)
    0 / 107 (0.00%)
    0 / 68 (0.00%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Ileus
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 107 (0.00%)
    0 / 68 (0.00%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Impaired gastric emptying
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 107 (0.93%)
    0 / 68 (0.00%)
    0 / 51 (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
    Small intestinal obstruction
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 107 (0.00%)
    0 / 68 (0.00%)
    1 / 51 (1.96%)
         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
    Vomiting
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 107 (0.00%)
    1 / 68 (1.47%)
    0 / 51 (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
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 107 (0.93%)
    0 / 68 (0.00%)
    0 / 51 (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
    Dyspnoea
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 107 (0.00%)
    1 / 68 (1.47%)
    0 / 51 (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
    Hypoxia
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 107 (0.93%)
    0 / 68 (0.00%)
    0 / 51 (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
    Pneumonia aspiration
         subjects affected / exposed
    2 / 105 (1.90%)
    0 / 107 (0.00%)
    0 / 68 (0.00%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    1 / 105 (0.95%)
    1 / 107 (0.93%)
    0 / 68 (0.00%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 107 (0.00%)
    0 / 68 (0.00%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 107 (0.00%)
    1 / 68 (1.47%)
    0 / 51 (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
    Subcutaneous emphysema
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 107 (0.00%)
    0 / 68 (0.00%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Haematuria
         subjects affected / exposed
    0 / 105 (0.00%)
    2 / 107 (1.87%)
    0 / 68 (0.00%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary bladder haemorrhage
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 107 (0.00%)
    1 / 68 (1.47%)
    0 / 51 (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
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 107 (0.00%)
    1 / 68 (1.47%)
    0 / 51 (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
    Gallbladder abscess
         subjects affected / exposed
    0 / 105 (0.00%)
    0 / 107 (0.00%)
    1 / 68 (1.47%)
    0 / 51 (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
    Post procedural infection
         subjects affected / exposed
    1 / 105 (0.95%)
    0 / 107 (0.00%)
    0 / 68 (0.00%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Purulent discharge
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 107 (0.93%)
    0 / 68 (0.00%)
    0 / 51 (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
    Metabolism and nutrition disorders
    Hyperkalaemia
         subjects affected / exposed
    0 / 105 (0.00%)
    1 / 107 (0.93%)
    0 / 68 (0.00%)
    0 / 51 (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
    		 Sugammadex 2 mg/kg Sugammadex 4 mg/kg Sugammadex 16 mg/kg Neostigmine + Glycopyrrolate
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    89 / 105 (84.76%)
    89 / 107 (83.18%)
    60 / 68 (88.24%)
    41 / 51 (80.39%)
    Injury, poisoning and procedural complications
    Incision site pain
         subjects affected / exposed
    25 / 105 (23.81%)
    31 / 107 (28.97%)
    19 / 68 (27.94%)
    9 / 51 (17.65%)
         occurrences all number
    26
    31
    19
    9
    Postoperative hypertension
         subjects affected / exposed
    1 / 105 (0.95%)
    3 / 107 (2.80%)
    4 / 68 (5.88%)
    1 / 51 (1.96%)
         occurrences all number
    1
    3
    4
    1
    Procedural nausea
         subjects affected / exposed
    4 / 105 (3.81%)
    2 / 107 (1.87%)
    5 / 68 (7.35%)
    4 / 51 (7.84%)
         occurrences all number
    4
    2
    5
    4
    Procedural pain
         subjects affected / exposed
    58 / 105 (55.24%)
    56 / 107 (52.34%)
    31 / 68 (45.59%)
    27 / 51 (52.94%)
         occurrences all number
    66
    67
    38
    31
    Vascular disorders
    Hypertension
         subjects affected / exposed
    6 / 105 (5.71%)
    6 / 107 (5.61%)
    1 / 68 (1.47%)
    0 / 51 (0.00%)
         occurrences all number
    8
    6
    1
    0
    Hypotension
         subjects affected / exposed
    6 / 105 (5.71%)
    8 / 107 (7.48%)
    5 / 68 (7.35%)
    4 / 51 (7.84%)
         occurrences all number
    6
    8
    6
    4
    Cardiac disorders
    Bradycardia
         subjects affected / exposed
    4 / 105 (3.81%)
    4 / 107 (3.74%)
    1 / 68 (1.47%)
    3 / 51 (5.88%)
         occurrences all number
    4
    4
    1
    3
    Sinus tachycardia
         subjects affected / exposed
    2 / 105 (1.90%)
    3 / 107 (2.80%)
    5 / 68 (7.35%)
    1 / 51 (1.96%)
         occurrences all number
    2
    3
    5
    1
    Tachycardia
         subjects affected / exposed
    5 / 105 (4.76%)
    8 / 107 (7.48%)
    3 / 68 (4.41%)
    4 / 51 (7.84%)
         occurrences all number
    5
    8
    3
    5
    Nervous system disorders
    Headache
         subjects affected / exposed
    3 / 105 (2.86%)
    5 / 107 (4.67%)
    2 / 68 (2.94%)
    4 / 51 (7.84%)
         occurrences all number
    4
    5
    2
    4
    Hypoaesthesia
         subjects affected / exposed
    3 / 105 (2.86%)
    3 / 107 (2.80%)
    2 / 68 (2.94%)
    3 / 51 (5.88%)
         occurrences all number
    3
    3
    2
    3
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    2 / 105 (1.90%)
    6 / 107 (5.61%)
    2 / 68 (2.94%)
    2 / 51 (3.92%)
         occurrences all number
    2
    6
    2
    2
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    7 / 105 (6.67%)
    7 / 107 (6.54%)
    6 / 68 (8.82%)
    2 / 51 (3.92%)
         occurrences all number
    7
    7
    6
    2
    Diarrhoea
         subjects affected / exposed
    2 / 105 (1.90%)
    6 / 107 (5.61%)
    0 / 68 (0.00%)
    1 / 51 (1.96%)
         occurrences all number
    2
    6
    0
    2
    Nausea
         subjects affected / exposed
    17 / 105 (16.19%)
    19 / 107 (17.76%)
    13 / 68 (19.12%)
    7 / 51 (13.73%)
         occurrences all number
    18
    20
    14
    8
    Vomiting
         subjects affected / exposed
    4 / 105 (3.81%)
    6 / 107 (5.61%)
    3 / 68 (4.41%)
    2 / 51 (3.92%)
         occurrences all number
    4
    6
    3
    4
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    2 / 105 (1.90%)
    2 / 107 (1.87%)
    0 / 68 (0.00%)
    3 / 51 (5.88%)
         occurrences all number
    2
    2
    0
    3
    Hypoxia
         subjects affected / exposed
    4 / 105 (3.81%)
    4 / 107 (3.74%)
    4 / 68 (5.88%)
    0 / 51 (0.00%)
         occurrences all number
    6
    4
    4
    0
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    3 / 105 (2.86%)
    8 / 107 (7.48%)
    4 / 68 (5.88%)
    2 / 51 (3.92%)
         occurrences all number
    3
    8
    4
    2
    Metabolism and nutrition disorders
    Hypokalaemia
         subjects affected / exposed
    6 / 105 (5.71%)
    3 / 107 (2.80%)
    4 / 68 (5.88%)
    1 / 51 (1.96%)
         occurrences all number
    6
    3
    4
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    13 Jul 2018
    The major change in amendment 1 was to provide flexibility to trial sites.

    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.

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