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Safety of Sugammadex for the Reversal of Neuromuscular Blockade in American Society of Anesthesiologists (ASA) Class 3 or 4 Participants (MK-8616-145)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03346057
Recruitment Status : Completed
First Posted : November 17, 2017
Results First Posted : October 8, 2020
Last Update Posted : October 8, 2020
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme LLC

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Reversal of Neuromuscular Blockade
Interventions Drug: Sugammadex 2 mg/kg
Drug: Sugammadex 4 mg/kg
Drug: Sugammadex 16 mg/kg
Drug: Neostigmine + Glycopyrrolate
Drug: Rocuronium
Drug: Vecuronium
Enrollment 344
Recruitment Details  
Pre-assignment 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.
Arm/Group Title Sugammadex 2 mg/kg Sugammadex 4 mg/kg Sugammadex 16 mg/kg Neostigmine + Glycopyrrolate
Hide Arm/Group Description Sugammadex 2 mg/kg administered as a single intravenous (IV) dose Sugammadex 4 mg/kg administered as a single IV dose Sugammadex 16 mg/kg administered as a single IV dose 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
Period Title: Overall Study
Started 111 112 68 53
Treated 105 107 68 51
Completed 104 104 67 51
Not Completed 7 8 1 2
Reason Not Completed
Death             1             2             0             0
Lost to Follow-up             0             2             1             0
Ineligible For Study - Not Treated             0             1             0             0
Renal Insufficiency - Not Treated             1             0             0             0
Physician Decision             3             2             0             2
Randomization Mistake - Not Treated             1             1             0             0
Withdrawal by Subject             1             0             0             0
Arm/Group Title Sugammadex 2 mg/kg Sugammadex 4 mg/kg Sugammadex 16 mg/kg Neostigmine + Glycopyrrolate Total
Hide Arm/Group Description Sugammadex 2 mg/kg administered as a single intravenous (IV) dose Sugammadex 4 mg/kg administered as a single IV dose Sugammadex 16 mg/kg administered as a single IV dose 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 Total of all reporting groups
Overall Number of Baseline Participants 111 112 68 53 344
Hide Baseline Analysis Population Description
All randomized participants
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 111 participants 112 participants 68 participants 53 participants 344 participants
69.5  (10.7) 67.8  (12.1) 69.4  (10.0) 66.6  (10.9) 68.5  (11.1)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 111 participants 112 participants 68 participants 53 participants 344 participants
Female
50
  45.0%
41
  36.6%
29
  42.6%
15
  28.3%
135
  39.2%
Male
61
  55.0%
71
  63.4%
39
  57.4%
38
  71.7%
209
  60.8%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 111 participants 112 participants 68 participants 53 participants 344 participants
Hispanic or Latino
2
   1.8%
6
   5.4%
0
   0.0%
2
   3.8%
10
   2.9%
Not Hispanic or Latino
109
  98.2%
105
  93.8%
67
  98.5%
51
  96.2%
332
  96.5%
Unknown or Not Reported
0
   0.0%
1
   0.9%
1
   1.5%
0
   0.0%
2
   0.6%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 111 participants 112 participants 68 participants 53 participants 344 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
2
   1.8%
0
   0.0%
0
   0.0%
0
   0.0%
2
   0.6%
Black or African American
3
   2.7%
9
   8.0%
2
   2.9%
3
   5.7%
17
   4.9%
White
106
  95.5%
103
  92.0%
66
  97.1%
50
  94.3%
325
  94.5%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Participant Stratifications   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 111 participants 112 participants 68 participants 53 participants 344 participants
Rocuronium, ASA Class 3
50
  45.0%
49
  43.8%
51
  75.0%
25
  47.2%
175
  50.9%
Rocuronium, ASA Class 4
15
  13.5%
18
  16.1%
17
  25.0%
8
  15.1%
58
  16.9%
Vecuronium, ASA Class 3
29
  26.1%
31
  27.7%
0
   0.0%
14
  26.4%
74
  21.5%
Vecuronium, ASA Class 4
11
   9.9%
11
   9.8%
0
   0.0%
5
   9.4%
27
   7.8%
Missing
6
   5.4%
3
   2.7%
0
   0.0%
1
   1.9%
10
   2.9%
[1]
Measure Description: Participants were stratified by neuromuscular blockade agent (NMBA, rocuronium or vecuronium) and American Society of Anesthesiologists (ASA) Class which ranges from ASA 1 (Normal healthy patient) to ASA 6 (Declared brain-dead patient whose organs are being removed for donor purposes). Higher ASA class with other factors (surgery type, frailty, and deconditioning) help predict greater perioperative risk. Participants were graded as ASA 3 if participants had severe systematic disease and as ASA 4 if participants had severe systematic disease that was a constant threat to the life.
1.Primary Outcome
Title Percentage of Participants With Treatment-Emergent Sinus Bradycardia Events
Hide Description The percentage of participants experiencing treatment-emergent sinus bradycardia events was identified with continuous electrocardiogram (ECG) monitoring. Treatment-emergent sinus bradycardia were defined as a heart rate <60 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.
Time Frame Up to approximately 35 minutes post-administration
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study intervention
Arm/Group Title Sugammadex 2 mg/kg Sugammadex 4 mg/kg Sugammadex 16 mg/kg Neostigmine + Glycopyrrolate
Hide Arm/Group Description:
Sugammadex 2 mg/kg administered as a single intravenous (IV) dose
Sugammadex 4 mg/kg administered as a single IV dose
Sugammadex 16 mg/kg administered as a single IV dose
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
Overall Number of Participants Analyzed 105 107 68 51
Measure Type: Number
Unit of Measure: Percentage of participants
1.0 1.9 7.4 7.8
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sugammadex 2 mg/kg, Neostigmine + Glycopyrrolate
Comments 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
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.026
Comments [Not Specified]
Method Stratified Miettinen & Nurminen method
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimated Difference in percentage
Estimated Value -6.7
Confidence Interval (2-Sided) 95%
-17.5 to -0.8
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Sugammadex 4 mg/kg, Neostigmine + Glycopyrrolate
Comments Miettinen & Nurminen method stratified by NMBA and ASA was used to provide estimated between-treatment difference, 95% confidence interval, and p-value
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.058
Comments [Not Specified]
Method Stratified Miettinen & Nurminen method
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimated Difference in percentage
Estimated Value -6.2
Confidence Interval (2-Sided) 95%
-17.3 to 0.2
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Sugammadex 16 mg/kg, Neostigmine + Glycopyrrolate
Comments Miettinen & Nurminen method stratified by NMBA and ASA was used to provide estimated between-treatment difference, 95% confidence interval, and p-value
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.730
Comments [Not Specified]
Method Stratified Miettinen & Nurminen method
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimated Difference in percentage
Estimated Value -2.0
Confidence Interval (2-Sided) 95%
-17.8 to 8.6
Estimation Comments [Not Specified]
2.Primary Outcome
Title Percentage of Participants With Treatment-Emergent Sinus Tachycardia Events
Hide 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.
Time Frame Up to approximately 35 minutes post-administration
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study intervention
Arm/Group Title Sugammadex 2 mg/kg Sugammadex 4 mg/kg Sugammadex 16 mg/kg Neostigmine + Glycopyrrolate
Hide Arm/Group Description:
Sugammadex 2 mg/kg administered as a single intravenous (IV) dose
Sugammadex 4 mg/kg administered as a single IV dose
Sugammadex 16 mg/kg administered as a single IV dose
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
Overall Number of Participants Analyzed 105 107 68 51
Measure Type: Number
Unit of Measure: Percentage of participants
6.7 9.3 8.8 21.6
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sugammadex 2 mg/kg, Neostigmine + Glycopyrrolate
Comments Miettinen & Nurminen method stratified by NMBA and ASA was used to provide estimated between-treatment difference, 95% confidence interval, and p-value
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.007
Comments [Not Specified]
Method Stratified Miettinen & Nurminen method
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimated Difference in percentage
Estimated Value -14.9
Confidence Interval (2-Sided) 95%
-28.8 to -4.0
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Sugammadex 4 mg/kg, Neostigmine + Glycopyrrolate
Comments Miettinen & Nurminen method stratified by NMBA and ASA was used to provide estimated between-treatment difference, 95% confidence interval, and p-value
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.036
Comments [Not Specified]
Method Stratified Miettinen & Nurminen method
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimated Difference in percentage
Estimated Value -12.2
Confidence Interval (2-Sided) 95%
-26.1 to -0.8
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Sugammadex 16 mg/kg, Neostigmine + Glycopyrrolate
Comments Miettinen & Nurminen method stratified by NMBA and ASA was used to provide estimated between-treatment difference, 95% confidence interval, and p-value
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.158
Comments [Not Specified]
Method Stratified Miettinen & Nurminen method
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimated Difference in percentage
Estimated Value -9.9
Confidence Interval (2-Sided) 95%
-27.6 to 3.6
Estimation Comments [Not Specified]
3.Primary Outcome
Title Percentage of Participants With Other Treatment-Emergent Cardiac Arrhythmia Events
Hide 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.
Time Frame Up to approximately 35 minutes post-administration
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study intervention
Arm/Group Title Sugammadex 2 mg/kg Sugammadex 4 mg/kg Sugammadex 16 mg/kg Neostigmine + Glycopyrrolate
Hide Arm/Group Description:
Sugammadex 2 mg/kg administered as a single intravenous (IV) dose
Sugammadex 4 mg/kg administered as a single IV dose
Sugammadex 16 mg/kg administered as a single IV dose
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
Overall Number of Participants Analyzed 105 107 68 51
Measure Type: Number
Unit of Measure: Percentage of participants
1.0 0.0 1.5 2.0
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sugammadex 2 mg/kg, Neostigmine + Glycopyrrolate
Comments Miettinen & Nurminen method stratified by NMBA and ASA was used to provide estimated between-treatment difference, 95% confidence interval, and p-value
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.637
Comments [Not Specified]
Method Stratified Miettinen & Nurminen method
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimated Difference in percentage
Estimated Value -0.9
Confidence Interval (2-Sided) 95%
-9.4 to 4.0
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Sugammadex 4 mg/kg, Neostigmine + Glycopyrrolate
Comments Miettinen & Nurminen method stratified by NMBA and ASA was used to provide estimated between-treatment difference, 95% confidence interval, and p-value
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.134
Comments [Not Specified]
Method Stratified Miettinen & Nurminen method
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimated Difference in percentage
Estimated Value -2.1
Confidence Interval (2-Sided) 95%
-10.6 to 1.5
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Sugammadex 16 mg/kg, Neostigmine + Glycopyrrolate
Comments Miettinen & Nurminen method stratified by NMBA and ASA was used to provide estimated between-treatment difference, 95% confidence interval, and p-value
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.577
Comments [Not Specified]
Method Stratified Miettinen & Nurminen method
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimated Difference in percentage
Estimated Value -1.7
Confidence Interval (2-Sided) 95%
-14.7 to 5.8
Estimation Comments [Not Specified]
4.Primary Outcome
Title Percentage of Participants Experiencing an Adverse Event (AE) Up To 7 Days After Administration of Study Intervention
Hide 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.
Time Frame Up to 7 days
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study intervention
Arm/Group Title Sugammadex 2 mg/kg Sugammadex 4 mg/kg Sugammadex 16 mg/kg Neostigmine + Glycopyrrolate
Hide Arm/Group Description:
Sugammadex 2 mg/kg administered as a single intravenous (IV) dose
Sugammadex 4 mg/kg administered as a single IV dose
Sugammadex 16 mg/kg administered as a single IV dose
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
Overall Number of Participants Analyzed 105 107 68 51
Measure Type: Number
Unit of Measure: Percentage of participants
94.3 88.8 92.6 88.2
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sugammadex 2 mg/kg, Neostigmine + Glycopyrrolate
Comments Miettinen & Nurminen method stratified by NMBA and ASA was used to provide estimated between-treatment difference and 95% confidence interval
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimated Difference in percentage
Estimated Value 6.2
Confidence Interval (2-Sided) 95%
-2.6 to 18.5
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Sugammadex 4 mg/kg, Neostigmine + Glycopyrrolate
Comments Miettinen & Nurminen method stratified by NMBA and ASA was used to provide estimated between-treatment difference and 95% confidence interval
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimated Difference in percentage
Estimated Value 0.5
Confidence Interval (2-Sided) 95%
-9.3 to 13.1
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Sugammadex 16 mg/kg, Neostigmine + Glycopyrrolate
Comments Miettinen & Nurminen method stratified by NMBA and ASA was used to provide estimated between-treatment difference and 95% confidence interval
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimated Difference in percentage
Estimated Value 2.0
Confidence Interval (2-Sided) 95%
-8.4 to 17.7
Estimation Comments [Not Specified]
5.Primary Outcome
Title Percentage of Participants Experiencing a Serious Adverse Event (SAE) Up To 7 Days After Administration of Study Intervention
Hide 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.
Time Frame Up to 7 days
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study intervention
Arm/Group Title Sugammadex 2 mg/kg Sugammadex 4 mg/kg Sugammadex 16 mg/kg Neostigmine + Glycopyrrolate
Hide Arm/Group Description:
Sugammadex 2 mg/kg administered as a single intravenous (IV) dose
Sugammadex 4 mg/kg administered as a single IV dose
Sugammadex 16 mg/kg administered as a single IV dose
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
Overall Number of Participants Analyzed 105 107 68 51
Measure Type: Number
Unit of Measure: Percentage of Participants
11.4 7.5 10.3 5.9
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sugammadex 2 mg/kg, Neostigmine + Glycopyrrolate
Comments Miettinen & Nurminen method stratified by NMBA and ASA was used to provide estimated between-treatment difference and 95% confidence interval
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimated Difference in percentage
Estimated Value 5.6
Confidence Interval (2-Sided) 95%
-5.5 to 14.3
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Sugammadex 4 mg/kg, Neostigmine + Glycopyrrolate
Comments Miettinen & Nurminen method stratified by NMBA and ASA was used to provide estimated between-treatment difference and 95% confidence interval
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimated Difference in percentage
Estimated Value 1.5
Confidence Interval (2-Sided) 95%
-9.2 to 9.3
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Sugammadex 16 mg/kg, Neostigmine + Glycopyrrolate
Comments Miettinen & Nurminen method stratified by NMBA and ASA was used to provide estimated between-treatment difference and 95% confidence interval
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimated Difference in percentage
Estimated Value 0.9
Confidence Interval (2-Sided) 95%
-15.1 to 12.7
Estimation Comments [Not Specified]
6.Primary Outcome
Title Percentage of Participants Experiencing an Event of Clinical Interest (ECI) Up To 7 Days After Administration of Study Intervention
Hide 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. A participant could have experienced more than one type of ECI.
Time Frame Up to 7 days
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study intervention
Arm/Group Title Sugammadex 2 mg/kg Sugammadex 4 mg/kg Sugammadex 16 mg/kg Neostigmine + Glycopyrrolate
Hide Arm/Group Description:
Sugammadex 2 mg/kg administered as a single intravenous (IV) dose
Sugammadex 4 mg/kg administered as a single IV dose
Sugammadex 16 mg/kg administered as a single IV dose
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
Overall Number of Participants Analyzed 105 107 68 51
Measure Type: Number
Unit of Measure: Percentage of Participants
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
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sugammadex 2 mg/kg, Neostigmine + Glycopyrrolate
Comments 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
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimated Difference in percentage
Estimated Value -2.1
Confidence Interval (2-Sided) 95%
-11.8 to 3.8
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Sugammadex 4 mg/kg, Neostigmine + Glycopyrrolate
Comments 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
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimated Difference in percentage
Estimated Value 1.8
Confidence Interval (2-Sided) 95%
-8.1 to 8.4
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Sugammadex 16 mg/kg, Neostigmine + Glycopyrrolate
Comments 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
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimated Difference in percentage
Estimated Value 1.1
Confidence Interval (2-Sided) 95%
-13.5 to 11.1
Estimation Comments [Not Specified]
Time Frame Up to approximately 21 days post treatment
Adverse Event Reporting 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.
 
Arm/Group Title Sugammadex 2 mg/kg Sugammadex 4 mg/kg Sugammadex 16 mg/kg Neostigmine + Glycopyrrolate
Hide Arm/Group Description Sugammadex 2 mg/kg administered as a single intravenous (IV) dose Sugammadex 4 mg/kg administered as a single IV dose Sugammadex 16 mg/kg administered as a single IV dose 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
All-Cause Mortality
Sugammadex 2 mg/kg Sugammadex 4 mg/kg Sugammadex 16 mg/kg Neostigmine + Glycopyrrolate
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/111 (0.90%)      2/112 (1.79%)      0/68 (0.00%)      0/53 (0.00%)    
Hide Serious Adverse Events
Sugammadex 2 mg/kg Sugammadex 4 mg/kg Sugammadex 16 mg/kg Neostigmine + Glycopyrrolate
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   16/105 (15.24%)      12/107 (11.21%)      9/68 (13.24%)      4/51 (7.84%)    
Blood and lymphatic system disorders         
Heparin-induced thrombocytopenia  1  0/105 (0.00%)  0 0/107 (0.00%)  0 1/68 (1.47%)  1 0/51 (0.00%)  0
Cardiac disorders         
Acute myocardial infarction  1  0/105 (0.00%)  0 0/107 (0.00%)  0 1/68 (1.47%)  1 0/51 (0.00%)  0
Atrial fibrillation  1  0/105 (0.00%)  0 1/107 (0.93%)  1 0/68 (0.00%)  0 0/51 (0.00%)  0
Cardiac arrest  1  1/105 (0.95%)  1 0/107 (0.00%)  0 1/68 (1.47%)  1 0/51 (0.00%)  0
Cardiac failure  1  0/105 (0.00%)  0 1/107 (0.93%)  1 0/68 (0.00%)  0 0/51 (0.00%)  0
Myocardial infarction  1  1/105 (0.95%)  1 0/107 (0.00%)  0 0/68 (0.00%)  0 0/51 (0.00%)  0
Myocardial ischaemia  1  0/105 (0.00%)  0 1/107 (0.93%)  1 0/68 (0.00%)  0 0/51 (0.00%)  0
Tachycardia  1  1/105 (0.95%)  1 0/107 (0.00%)  0 0/68 (0.00%)  0 0/51 (0.00%)  0
Gastrointestinal disorders         
Ileus  1  1/105 (0.95%)  2 0/107 (0.00%)  0 0/68 (0.00%)  0 0/51 (0.00%)  0
Impaired gastric emptying  1  0/105 (0.00%)  0 1/107 (0.93%)  1 0/68 (0.00%)  0 0/51 (0.00%)  0
Small intestinal obstruction  1  0/105 (0.00%)  0 0/107 (0.00%)  0 0/68 (0.00%)  0 1/51 (1.96%)  1
Vomiting  1  0/105 (0.00%)  0 0/107 (0.00%)  0 1/68 (1.47%)  1 0/51 (0.00%)  0
General disorders         
Catheter site haemorrhage  1  0/105 (0.00%)  0 0/107 (0.00%)  0 0/68 (0.00%)  0 1/51 (1.96%)  1
Dehiscence  1  1/105 (0.95%)  1 0/107 (0.00%)  0 0/68 (0.00%)  0 0/51 (0.00%)  0
Hernia  1  1/105 (0.95%)  1 0/107 (0.00%)  0 0/68 (0.00%)  0 0/51 (0.00%)  0
Impaired healing  1  2/105 (1.90%)  2 0/107 (0.00%)  0 0/68 (0.00%)  0 0/51 (0.00%)  0
Infections and infestations         
Bronchitis  1  0/105 (0.00%)  0 0/107 (0.00%)  0 1/68 (1.47%)  1 0/51 (0.00%)  0
Gallbladder abscess  1  0/105 (0.00%)  0 0/107 (0.00%)  0 1/68 (1.47%)  1 0/51 (0.00%)  0
Post procedural infection  1  1/105 (0.95%)  1 0/107 (0.00%)  0 0/68 (0.00%)  0 0/51 (0.00%)  0
Purulent discharge  1  0/105 (0.00%)  0 1/107 (0.93%)  1 0/68 (0.00%)  0 0/51 (0.00%)  0
Injury, poisoning and procedural complications         
Abdominal wound dehiscence  1  2/105 (1.90%)  2 0/107 (0.00%)  0 0/68 (0.00%)  0 1/51 (1.96%)  1
Accidental overdose  1  1/105 (0.95%)  1 0/107 (0.00%)  0 0/68 (0.00%)  0 0/51 (0.00%)  0
Anastomotic leak  1  0/105 (0.00%)  0 1/107 (0.93%)  1 0/68 (0.00%)  0 0/51 (0.00%)  0
Fascial rupture  1  1/105 (0.95%)  1 0/107 (0.00%)  0 0/68 (0.00%)  0 0/51 (0.00%)  0
Gastrointestinal stoma necrosis  1  1/105 (0.95%)  1 0/107 (0.00%)  0 0/68 (0.00%)  0 0/51 (0.00%)  0
Incision site pain  1  0/105 (0.00%)  0 0/107 (0.00%)  0 1/68 (1.47%)  1 0/51 (0.00%)  0
Post procedural haematoma  1  0/105 (0.00%)  0 1/107 (0.93%)  1 0/68 (0.00%)  0 0/51 (0.00%)  0
Postoperative delirium  1  1/105 (0.95%)  1 1/107 (0.93%)  1 0/68 (0.00%)  0 0/51 (0.00%)  0
Postoperative ileus  1  0/105 (0.00%)  0 0/107 (0.00%)  0 0/68 (0.00%)  0 1/51 (1.96%)  1
Procedural pain  1  1/105 (0.95%)  1 0/107 (0.00%)  0 0/68 (0.00%)  0 0/51 (0.00%)  0
Urinary retention postoperative  1  0/105 (0.00%)  0 1/107 (0.93%)  1 0/68 (0.00%)  0 0/51 (0.00%)  0
Vascular graft occlusion  1  1/105 (0.95%)  1 0/107 (0.00%)  0 0/68 (0.00%)  0 0/51 (0.00%)  0
Investigations         
C-reactive protein increased  1  0/105 (0.00%)  0 0/107 (0.00%)  0 1/68 (1.47%)  1 0/51 (0.00%)  0
Haemoglobin decreased  1  0/105 (0.00%)  0 0/107 (0.00%)  0 1/68 (1.47%)  1 0/51 (0.00%)  0
Metabolism and nutrition disorders         
Hyperkalaemia  1  0/105 (0.00%)  0 1/107 (0.93%)  1 0/68 (0.00%)  0 0/51 (0.00%)  0
Renal and urinary disorders         
Haematuria  1  0/105 (0.00%)  0 2/107 (1.87%)  2 0/68 (0.00%)  0 0/51 (0.00%)  0
Urinary bladder haemorrhage  1  0/105 (0.00%)  0 0/107 (0.00%)  0 1/68 (1.47%)  1 0/51 (0.00%)  0
Respiratory, thoracic and mediastinal disorders         
Chronic obstructive pulmonary disease  1  0/105 (0.00%)  0 1/107 (0.93%)  1 0/68 (0.00%)  0 0/51 (0.00%)  0
Dyspnoea  1  0/105 (0.00%)  0 0/107 (0.00%)  0 1/68 (1.47%)  1 0/51 (0.00%)  0
Hypoxia  1  0/105 (0.00%)  0 1/107 (0.93%)  1 0/68 (0.00%)  0 0/51 (0.00%)  0
Pneumonia aspiration  1  2/105 (1.90%)  2 0/107 (0.00%)  0 0/68 (0.00%)  0 0/51 (0.00%)  0
Pneumothorax  1  1/105 (0.95%)  1 1/107 (0.93%)  1 0/68 (0.00%)  0 0/51 (0.00%)  0
Respiratory failure  1  1/105 (0.95%)  1 0/107 (0.00%)  0 0/68 (0.00%)  0 0/51 (0.00%)  0
Skin and subcutaneous tissue disorders         
Rash  1  0/105 (0.00%)  0 0/107 (0.00%)  0 1/68 (1.47%)  1 0/51 (0.00%)  0
Subcutaneous emphysema  1  1/105 (0.95%)  1 0/107 (0.00%)  0 0/68 (0.00%)  0 0/51 (0.00%)  0
Vascular disorders         
Hypotension  1  1/105 (0.95%)  1 0/107 (0.00%)  0 0/68 (0.00%)  0 0/51 (0.00%)  0
Lymphocele  1  0/105 (0.00%)  0 1/107 (0.93%)  1 0/68 (0.00%)  0 0/51 (0.00%)  0
1
Term from vocabulary, MedDRA 22.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Sugammadex 2 mg/kg Sugammadex 4 mg/kg Sugammadex 16 mg/kg Neostigmine + Glycopyrrolate
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   89/105 (84.76%)      89/107 (83.18%)      60/68 (88.24%)      41/51 (80.39%)    
Cardiac disorders         
Bradycardia  1  4/105 (3.81%)  4 4/107 (3.74%)  4 1/68 (1.47%)  1 3/51 (5.88%)  3
Sinus tachycardia  1  2/105 (1.90%)  2 3/107 (2.80%)  3 5/68 (7.35%)  5 1/51 (1.96%)  1
Tachycardia  1  5/105 (4.76%)  5 8/107 (7.48%)  8 3/68 (4.41%)  3 4/51 (7.84%)  5
Gastrointestinal disorders         
Constipation  1  7/105 (6.67%)  7 7/107 (6.54%)  7 6/68 (8.82%)  6 2/51 (3.92%)  2
Diarrhoea  1  2/105 (1.90%)  2 6/107 (5.61%)  6 0/68 (0.00%)  0 1/51 (1.96%)  2
Nausea  1  17/105 (16.19%)  18 19/107 (17.76%)  20 13/68 (19.12%)  14 7/51 (13.73%)  8
Vomiting  1  4/105 (3.81%)  4 6/107 (5.61%)  6 3/68 (4.41%)  3 2/51 (3.92%)  4
General disorders         
Asthenia  1  2/105 (1.90%)  2 6/107 (5.61%)  6 2/68 (2.94%)  2 2/51 (3.92%)  2
Injury, poisoning and procedural complications         
Incision site pain  1  25/105 (23.81%)  26 31/107 (28.97%)  31 19/68 (27.94%)  19 9/51 (17.65%)  9
Postoperative hypertension  1  1/105 (0.95%)  1 3/107 (2.80%)  3 4/68 (5.88%)  4 1/51 (1.96%)  1
Procedural nausea  1  4/105 (3.81%)  4 2/107 (1.87%)  2 5/68 (7.35%)  5 4/51 (7.84%)  4
Procedural pain  1  58/105 (55.24%)  66 56/107 (52.34%)  67 31/68 (45.59%)  38 27/51 (52.94%)  31
Metabolism and nutrition disorders         
Hypokalaemia  1  6/105 (5.71%)  6 3/107 (2.80%)  3 4/68 (5.88%)  4 1/51 (1.96%)  1
Nervous system disorders         
Headache  1  3/105 (2.86%)  4 5/107 (4.67%)  5 2/68 (2.94%)  2 4/51 (7.84%)  4
Hypoaesthesia  1  3/105 (2.86%)  3 3/107 (2.80%)  3 2/68 (2.94%)  2 3/51 (5.88%)  3
Psychiatric disorders         
Insomnia  1  3/105 (2.86%)  3 8/107 (7.48%)  8 4/68 (5.88%)  4 2/51 (3.92%)  2
Respiratory, thoracic and mediastinal disorders         
Cough  1  2/105 (1.90%)  2 2/107 (1.87%)  2 0/68 (0.00%)  0 3/51 (5.88%)  3
Hypoxia  1  4/105 (3.81%)  6 4/107 (3.74%)  4 4/68 (5.88%)  4 0/51 (0.00%)  0
Vascular disorders         
Hypertension  1  6/105 (5.71%)  8 6/107 (5.61%)  6 1/68 (1.47%)  1 0/51 (0.00%)  0
Hypotension  1  6/105 (5.71%)  6 8/107 (7.48%)  8 5/68 (7.35%)  6 4/51 (7.84%)  4
1
Term from vocabulary, MedDRA 22.1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results. Sponsor review can be expedited to meet publication timelines.
Results Point of Contact
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Name/Title: Senior Vice President, Global Clinical Development
Organization: Merck Sharp & Dohme Corp.
Phone: 1-800-672-6372
EMail: ClinicalTrialsDisclosure@merck.com
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Responsible Party: Merck Sharp & Dohme LLC
ClinicalTrials.gov Identifier: NCT03346057    
Other Study ID Numbers: 8616-145
2017-000187-15 ( EudraCT Number )
MK-8616-145 ( Other Identifier: Merck Protocol Number )
First Submitted: November 15, 2017
First Posted: November 17, 2017
Results First Submitted: August 24, 2020
Results First Posted: October 8, 2020
Last Update Posted: October 8, 2020