The purpose of this trial is to evaluate the safety and efficacy of Sugammadex when administered according to actual body weight (ABW) as compared to ideal body weight (IBW) for the reversal of both moderate and deep neuromuscular blockade (NMB) induced by either Rocuronium or Vecuronium in morbidly obese participants. The primary hypothesis of this investigation is that, compared to obese participants dosed based on IBW, obese participants receiving Sugammadex according to ABW will demonstrate a faster time to recovery to a Train Of Four (TOF) ratio of ≥0.9 (i.e. faster NMB reversal), pooled across NMB depth and type of neuromuscular blocking agent (NMBA; Rocuronium or Vecuronium) administered.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
207
Following administration of NMBA (Rocuronium or Vecuronium) to achieve moderate NMB, participants received a single i.v. bolus of Sugammadex (2 mg/kg by ABW) for reversal of moderate NMB. Moderate NMB is defined as the reappearance of a second twitch (T2) in response to TOF stimulations.
Following administration of NMBA (Rocuronium or Vecuronium) to achieve moderate NMB, participants received a single i.v. bolus of Sugammadex (2 mg/kg by IBW) for reversal of moderate NMB. Moderate NMB is defined as the reappearance of T2 in response to TOF stimulations.
Following administration of NMBA (Rocuronium or Vecuronium) to achieve deep NMB, participants received a single i.v. bolus of Sugammadex (4 mg/kg by ABW) for reversal of deep NMB. Deep NMB is defined as no response to TOF stimulations (TOF=0) and a detection target of 1-2 post-tetanic counts (PTCs).
Following administration of NMBA (Rocuronium or Vecuronium) to achieve deep NMB, participants will receive a single i.v. bolus of Sugammadex (4 mg/kg by IBW) for reversal of deep NMB. Deep NMB is defined as no response to TOF stimulations (TOF=0) and a detection target of 1-2 post-tetanic counts (PTCs).
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), dosed according to participant ABW for reversal of moderate NMB. Moderate NMB is defined as the reappearance of T2 in response to TOF stimulations.
To achieve NMB, participants received steroidal NMBA Rocuronium Bromide or Vecuronium Bromide administered via i.v. infusion and dosed according to participant ABW. NMBAs were concomitant medications used per label as adjunct to general anesthesia.
University California / Davis ( Site 2001)
Sacramento, California, United States
Jackson Memorial Hospital/University of Miami ( Site 2007)
Miami, Florida, United States
University of Kansas Medical Center ( Site 2049)
Kansas City, Kansas, United States
William Beaumont Hospital - Royal Oak ( Site 2033)
Royal Oak, Michigan, United States
University Hospital- Columbia MO ( Site 2060)
Columbia, Missouri, United States
Robert Wood Johnson University Hospital ( Site 2037)
New Brunswick, New Jersey, United States
Mission Hospital - St. Joseph ( Site 2015)
Asheville, North Carolina, United States
Cleveland Clinic Foundation ( Site 2031)
Cleveland, Ohio, United States
Temple University Hospital ( Site 2004)
Philadelphia, Pennsylvania, United States
Vanderbilt University Medical Center ( Site 2032)
Nashville, Tennessee, United States
...and 14 more locations
Time to Recovery (TTR) of Participant Train Of Four (TOF) Ratio to ≥0.9: Primary Kaplan-Meier Analysis
The primary efficacy analysis of TTR of TOF ratio to ≥0.9 was performed by estimating event rates within each treatment group using the Kaplan-Meier method. TTR was monitored by applying electrical stimulations to the ulnar nerve every 15 seconds and assessing twitch response at the adductor pollicis muscle. T1 and T4 refer to magnitudes of the first and fourth twitches respectively, after nerve stimulation. The T4/T1 ratio (TOF; expressed as a decimal of up to 1.0) indicates the extent of recovery from NMB. A faster TTR of the TOF ratio to 0.9 indicates faster recovery from NMB. As specified by the protocol, analyses for this outcome measure were conducted in participants pooled by dosing method across depth of NMB (Sugammadex ABW \[2 mg/kg ABW plus 4 mg/kg ABW\] and Sugammadex IBW \[2 mg/kg IBW plus 4 mg/kg IBW\]) as well as in all randomized treatment arms separated by depth of NMB (Sugammadex 2 mg/kg ABW, Sugammadex 4 mg/kg ABW, Sugammadex 2 mg/kg IBW, and Sugammadex 4 mg/kg IBW).
Time frame: Up to 76 minutes
Percentage of Participants With Treatment-Emergent Sinus Bradycardia Events
The percentage of participants experiencing treatment-emergent bradycardia events were identified with continuous electrocardiogram (ECG) monitoring. Treatment-emergent sinus bradycardia is 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 be considered an adverse event (AE), as determined by investigator judgment. As specified by the protocol, analyses for this outcome measure were conducted in participants pooled by dosing method across depth of NMB (Sugammadex ABW \[2 mg/kg ABW plus 4 mg/kg ABW\] and Sugammadex IBW \[2 mg/kg IBW plus 4 mg/kg IBW\]) as well as in all randomized treatment arms separated by depth of NMB (Sugammadex 2 mg/kg ABW, Sugammadex 4 mg/kg ABW, Sugammadex 2 mg/kg IBW, and Sugammadex 4 mg/kg IBW).
Time frame: Up to 35 minutes
Percentage of Participants With Treatment-Emergent Sinus Tachycardia Events
The percentage of participants experiencing treatment-emergent sinus tachycardia events were 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 be considered an AE, as determined by investigator judgment. As specified by the protocol, analyses for this outcome measure were conducted in participants pooled by dosing method across depth of NMB (Sugammadex ABW \[2 mg/kg ABW plus 4 mg/kg ABW\] and Sugammadex IBW \[2 mg/kg IBW plus 4 mg/kg IBW\]) as well as in all randomized treatment arms separated by depth of NMB (Sugammadex 2 mg/kg ABW, Sugammadex 4 mg/kg ABW, Sugammadex 2 mg/kg IBW, and Sugammadex 4 mg/kg IBW).
Time frame: Up to 35 minutes
Percentage of Participants With Other Treatment-Emergent Cardiac Arrhythmia Events
The percentage of participants experiencing other treatment-emergent cardiac arrhythmia events were identified with continuous ECG monitoring. Other treatment-emergent cardiac arrhythmias are defined as new or worsening arrhythmias (e.g., atrial fibrillation, atrial tachyarrhythmia, ventricular fibrillation, or ventricular tachyarrhythmia), sustained for at least 1 minute after administration of study intervention. Worsening arrhythmia events may or may not be considered an AE, as determined by investigator judgment. As specified by the protocol, analyses for this outcome measure were conducted in participants pooled by dosing method across depth of NMB (Sugammadex ABW \[2 mg/kg ABW plus 4 mg/kg ABW\] and Sugammadex IBW \[2 mg/kg IBW plus 4 mg/kg IBW\]) as well as in all randomized treatment arms separated by depth of NMB (Sugammadex 2 mg/kg ABW, Sugammadex 4 mg/kg ABW, Sugammadex 2 mg/kg IBW, and Sugammadex 4 mg/kg IBW).
Time frame: Up to 35 minutes
Percentage of Participants Experiencing an Adverse Event (AE) After Administration of Study Intervention
The percentage of participants experiencing an AE following administration of study intervention was monitored. An AE is any unfavorable and unintended medical occurrence, symptom, or disease witnessed in a participant, regardless of whether or not a causal relationship with the study treatment can be demonstrated. Further, any worsening (i.e. any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of the study treatment is also considered an AE. As specified by the protocol, analyses for this outcome measure were conducted in participants pooled by dosing method across depth of NMB (Sugammadex ABW \[2 mg/kg ABW plus 4 mg/kg ABW\] and Sugammadex IBW \[2 mg/kg IBW plus 4 mg/kg IBW\]) as well as in all randomized treatment arms separated by depth of NMB (Sugammadex 2 mg/kg ABW, Sugammadex 4 mg/kg ABW, Sugammadex 2 mg/kg IBW, and Sugammadex 4 mg/kg IBW).
Time frame: Up to 7 days
Percentage of Participants Experiencing a Serious Adverse Event (SAE) After Administration of Study Intervention
The percentage of participants experiencing an SAE following administration of study intervention was monitored. An SAE is an adverse event that: results in death; is life threatening; results in persistent or significant disability or incapacity; results in or prolongs a hospitalization; is a congenital anomaly or birth defect; is a cancer; or may jeopardize the participant, potentially requiring medical or surgical intervention. As specified by the protocol, analyses for this outcome measure were conducted in participants pooled by dosing method across depth of NMB (Sugammadex ABW \[2 mg/kg ABW plus 4 mg/kg ABW\] and Sugammadex IBW \[2 mg/kg IBW plus 4 mg/kg IBW\]) as well as in all randomized treatment arms separated by depth of NMB (Sugammadex 2 mg/kg ABW, Sugammadex 4 mg/kg ABW, Sugammadex 2 mg/kg IBW, and Sugammadex 4 mg/kg IBW).
Time frame: Up to 7 days
Percentage of Participants Experiencing an Event of Clinical Interest (ECI) After Administration of Study Intervention
The percentage of participants experiencing an ECI following administration of study intervention was monitored. ECIs are 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. As specified by the protocol, analyses for this outcome measure were conducted in participants pooled by dosing method across depth of NMB (Sugammadex ABW \[2 mg/kg ABW plus 4 mg/kg ABW\] and Sugammadex IBW \[2 mg/kg IBW plus 4 mg/kg IBW\]) as well as in all randomized treatment arms separated by depth of NMB (Sugammadex 2 mg/kg ABW, Sugammadex 4 mg/kg ABW, Sugammadex 2 mg/kg IBW, and Sugammadex 4 mg/kg IBW).
Time frame: Up to 7 days
Percentage of Participants With Prolonged (>10 Minutes) Time to Recovery (TTR) of the Train Of Four (TOF) Ratio to ≥0.9
Following administration of study intervention, the percentage of participants experiencing prolonged (\>10 minutes) recovery to a TOF ratio ≥0.9 was calculated. TTR was monitored by applying electrical stimulations to the ulnar nerve every 15 seconds and assessing twitch response at the adductor pollicis muscle. T1 and T4 refer to magnitudes of the first and fourth twitches respectively, after nerve stimulation. The T4/T1 ratio (TOF; expressed as a decimal of up to 1.0) indicates the extent of recovery from NMB. A faster TTR of the TOF ratio to 0.9 indicates faster recovery from NMB. As specified by the protocol, analyses for this outcome measure were conducted in participants pooled by dosing method across depth of NMB (Sugammadex ABW \[2 mg/kg ABW plus 4 mg/kg ABW\] and Sugammadex IBW \[2 mg/kg IBW plus 4 mg/kg IBW\]) as well as in all randomized treatment arms separated by depth of NMB (Sugammadex 2 mg/kg ABW, Sugammadex 4 mg/kg ABW, Sugammadex 2 mg/kg IBW, and Sugammadex 4 mg/kg IBW).
Time frame: Up to 76 minutes
Time to Recovery (TTR) of Participant Train of Four (TOF) Ratio to ≥0.9: Secondary Geometric Mean Analysis
The secondary efficacy analysis of TTR of participant TOF ratio to ≥0.9 was performed by estimating the geometric mean of TTR within each treatment group. TTR was monitored by applying electrical stimulations to the ulnar nerve every 15 seconds and assessing twitch response at the adductor pollicis muscle. T1 and T4 refer to magnitudes of the first and fourth twitches respectively, after nerve stimulation. The T4/T1 ratio (TOF; expressed as a decimal of up to 1.0) indicates the extent of recovery from NMB. A faster TTR of the TOF ratio to 0.9 indicates faster recovery from NMB. As specified by the protocol, analyses for this outcome measure were conducted in participants pooled by dosing method across depth of NMB (Sugammadex ABW \[2 mg/kg ABW plus 4 mg/kg ABW\] and Sugammadex IBW \[2 mg/kg IBW plus 4 mg/kg IBW\]) as well as in all randomized treatment arms separated by depth of NMB (Sugammadex 2 mg/kg ABW, Sugammadex 4 mg/kg ABW, Sugammadex 2 mg/kg IBW, and Sugammadex 4 mg/kg IBW).
Time frame: Up to 76 minutes
Time to Recovery (TTR) of Participant Train of Four (TOF) Ratio to ≥0.8: Geometric Mean Analysis
The efficacy analysis of TTR of participant TOF ratio to ≥0.8 was performed by estimating the geometric mean of TTR within each treatment group. TTR was monitored by applying electrical stimulations to the ulnar nerve every 15 seconds and assessing twitch response at the adductor pollicis muscle. T1 and T4 refer to magnitudes of the first and fourth twitches respectively, after nerve stimulation. The T4/T1 ratio (TOF; expressed as a decimal of up to 1.0) indicates the extent of recovery from NMB. A faster TTR of the TOF ratio to 0.8 indicates faster recovery from NMB. As specified by the protocol, analyses for this outcome measure were conducted in participants pooled by dosing method across depth of NMB (Sugammadex ABW \[2 mg/kg ABW plus 4 mg/kg ABW\] and Sugammadex IBW \[2 mg/kg IBW plus 4 mg/kg IBW\]) as well as in all randomized treatment arms separated by depth of NMB (Sugammadex 2 mg/kg ABW, Sugammadex 4 mg/kg ABW, Sugammadex 2 mg/kg IBW, and Sugammadex 4 mg/kg IBW).
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Time frame: Up to 69 minutes
Time to Recovery (TTR) of Participant Train of Four (TOF) Ratio to ≥0.7: Geometric Mean Analysis
The efficacy analysis of TTR of participant TOF ratio to ≥0.7 was performed by estimating the geometric mean of TTR within each treatment group. TTR was monitored by applying electrical stimulations to the ulnar nerve every 15 seconds and assessing twitch response at the adductor pollicis muscle. T1 and T4 refer to magnitudes of the first and fourth twitches respectively, after nerve stimulation. The T4/T1 ratio (TOF; expressed as a decimal of up to 1.0) indicates the extent of recovery from NMB. A faster TTR of the TOF ratio to 0.7 indicates faster recovery from NMB. As specified by the protocol, analyses for this outcome measure were conducted in participants pooled by dosing method across depth of NMB (Sugammadex ABW \[2 mg/kg ABW plus 4 mg/kg ABW\] and Sugammadex IBW \[2 mg/kg IBW plus 4 mg/kg IBW\]) as well as in all randomized treatment arms separated by depth of NMB (Sugammadex 2 mg/kg ABW, Sugammadex 4 mg/kg ABW, Sugammadex 2 mg/kg IBW, and Sugammadex 4 mg/kg IBW).
Time frame: Up to 61 minutes