Anesthesia, General
Conditions
Brief summary
The current trial was designed to demonstrate faster recovery from a neuromuscular blockade (NMB) induced by rocuronium after reversal at 1-2 Post Tetanic Count (PTC) by 4.0 mg.kg-1 sugammadex compared to 50 µg.kg-1 neostigmine at reappearance of second twitch (T2) in participants undergoing laparoscopic cholecystectomy or appendectomy under propofol anesthesia, to compare safety and to evaluate operating room and Post Anesthetic Care Unit (PACU) length of stay.
Detailed description
In those surgical procedures where a neuromuscular block is desired for intubation and/or avoid unwanted muscular activity, anesthesiologists may use a more profound NMB until the end of surgery, e.g. in open abdominal procedures or during laparoscopic procedures in order to improve surgical conditions. Reversal with sugammadex at a dose of 4.0 mg.kg-1 at 1-2 PTC after an intubation dose of 0.6 mg.kg-1 or maintenance dosing rocuronium has been found to be both safe and efficacious in previous clinical trials but has never been investigated exclusively in participants undergoing laparoscopic cholecystectomy or appendectomy. With sugammadex profound muscle relaxation may now be provided right up to the end of the surgical procedure. This may lead to improved Patient Outcomes, such as improvement in the time from end of surgery to the discharge to the PACU. In this multi-center, randomized, parallel-group, active-controlled, safety-assessor blinded trial such benefits will be further investigated.
Interventions
DRUGRocuronium
Participants will receive an intravenous (i.v.) single bolus dose of 0.6 mg.kg-1 rocuronium. After this dose, maintenance doses of 0.1-0.2 mg.kg-1 rocuronium may be given.
DRUGSugammadex
After the last dose of rocuronium has been administered, participants will receive, according to the randomization, a single bolus dose of 4.0 mg.kg-1 sugammadex at 1-2 PTC.
DRUGNeostigmine
After the last dose of rocuronium has been administered, participants will receive, according to the randomization, 50 μg.kg-1 neostigmine (with atropine in a ratio of 5:1 for neostigmine:atropine) at reappearance of T2.
DRUGAtropine
After the last dose of rocuronium has been administered, participants will receive, according to randomization, 10 μg.kg-1 atropine (with neostigmine in a ratio of 5:1 for neostigmine:atropine) at reappearance of T2.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants of American Society of Anesthesiologists class 1-3 * Participants of age above or equal to the age of 18 years * Participants who are scheduled to undergo a laparoscopic cholecystectomy or appendectomy under general anesthesia requiring neuromuscular relaxation with rocuronium, and if applicable, maintenance of neuromuscular blockade * Participants who have given written informed consent
Exclusion criteria
* Participants in whom a difficult intubation because of anatomical malformations is expected * Participants known or suspected to have neuromuscular disorders affecting NMB * Participants known or suspected to have a significant renal dysfunction * Participants known or suspected to have a severe hepatic dysfunction * Participants known or suspected to have (family) history of malignant hyperthermia * Participants known or suspected to have an allergy to opioids, muscle relaxants or other medication used during general anesthesia * Participants in whom the use of neostigmine and/or atropine is contraindicated * Female participants who are pregnant (pregnancy will be excluded for women both from medical history and by a human chorionic gonadotropin (hCG) test within 24h before surgery, except for women who are not of childbearing potential, i.e. at least 2 years menopausal or have undergone tubal ligation or a hysterectomy) * Female participants who are breast-feeding * Participants who participated in another clinical trial not pre-approved by the sponsor, within 30 days of entering into trial 19.4.318 (P05699) * Participants who have already participated in a sugammadex trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time From Start of Administration of Investigational Medicinal Product (IMP, Sugammadex or Neostigmine) to Recovery of the Fourth Twitch/First Twitch (T4/T1) Ratio to 0.9 | From start of IMP administration to recovery of T4/T1 ratio to 0.9 (ranging from ~2 minutes to ~9 minutes) | Neuromuscular functioning was monitored by applying repetitive Train-Of-Four (TOF) electrical stimulations to the ulnar nerve every 15 seconds & assessing twitch response at the adductor pollicis muscle. T1 and T4 refer to the magnitudes (heights) of the first and fourth twitches, respectively, after TOF nerve stimulation. The T4/T1 Ratio (expressed as a decimal of up to 1.0) indicates the extent of recovery from neuromuscular blockade (NMB). In this study, twitch responses were recorded until the T4/T1 Ratio reached \>= 0.9, the minimum acceptable ratio that indicated recovery from NMB. A faster time to recovery of the T4/T1 Ratio to 0.9 indicates a faster recovery from NMB. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time From Start of Administration of IMP to Recovery of the T4/T1 Ratio to 0.7 | From start of IMP administration to recovery of T4/T1 Ratio to 0.7 (ranging from ~2 minutes to ~5 minutes) | Neuromuscular functioning was monitored by applying repetitive TOF electrical stimulations to the ulnar nerve every 15 seconds & assessing twitch response at the adductor pollicis muscle. T1 and T4 refer to the magnitudes (heights) of the first and fourth twitches, respectively, after TOF nerve stimulation. The T4/T1 Ratio (expressed as a decimal of up to 1.0). A faster time to recovery of the T4/T1 Ratio to 0.7 indicates a faster recovery from NMB. |
| Time From Start of Administration of IMP to Recovery of the T4/T1 Ratio to 0.8 | From start of IMP administration to recovery of T4/T1 Ratio to 0.8 (ranging from ~2 minutes to ~6 minutes) | Neuromuscular functioning was monitored by applying repetitive TOF electrical stimulations to the ulnar nerve every 15 seconds & assessing twitch response at the adductor pollicis muscle. T1 and T4 refer to the magnitudes (heights) of the first and fourth twitches, respectively, after TOF nerve stimulation. The T4/T1 Ratio (expressed as a decimal of up to 1.0). A faster time to recovery of the T4/T1 Ratio to 0.8 indicates a faster recovery from NMB. |
| Number of Participants Who Experienced Pre-treatment Serious Adverse Events (SAEs) and Post-treatment SAEs | From signing of informed consent to end of trial (7 days after surgery) | An SAE is defined as any untoward medical occurrence that at any dose: results in death; is life-threatening; requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; or is a congenital anomaly/birth defect. Participants were monitored for occurrence SAEs for up to 7 days after last dose IMP. Pre-treatment refers to the period from signing of the informed consent up to start of IMP administration. Post-treatment refers to the period from start of IMP administration to 7 days after IMP administration. |
| Number of Participants Who Experienced Pre-treatment Non-serious Adverse Events (AEs) and Post-treatment Non-serious AEs | From signing of informed consent to end of trial (7 days after surgery) | An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body, whether or not considered related to the use of the product. Participants were monitored for occurrence AEs for up to 7 days after last dose IMP. Pre-treatment refers to the period from signing of the informed consent up to start of IMP administration. Post-treatment refers to the period from start of IMP administration to 7 days after IMP administration. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Mean Diastolic Blood Pressure | At screening, pre-rocuronium, pre-IMP, at 2, 5, 10, and 30 minutes post-IMP, and at the post-anesthetic visit (the day after surgery) | Diastolic Blood Pressure was measured at screening, before start of rocuronium administration, before start of IMP administration, at 2, 5, 10, 30 minutes post-IMP administration, and at the post-anesthetic visit (the day after surgery). |
| Mean Heart Rate | At screening, pre-rocuronium, pre-IMP, at 2, 5, 10, and 30 minutes post-IMP, and at the post-anesthetic visit (the day after surgery) | Heart Rate was measured at screening, before start of rocuronium administration, before start of IMP administration, at 2, 5, 10, 30 minutes post-IMP administration, and at the post-anesthetic visit (the day after surgery). |
| Number of Participants Who Had Physical Examinations | At screening (within 7 days prior to surgery) and at the post-anesthetic visit (the day after surgery) | Physical examinations were to be conducted at screening (within 7 days prior to surgery) and at the post-anesthetic visit (the day after surgery). |
| Number of Participants With Train-of-Four- (TOF-) Watch® SX and Arm Board Related Adverse Events | From induction of anesthesia to recovery from NMB (up to ~3 hours) | Events were to be collected for the entire period of neuromuscular transmission monitoring and were defined as an occurrence that resulted or could have resulted in: death; a serious deterioration in the state of health of a user; an occurrence which might, if it recurred, lead to death or serious deterioration in health; inaccuracy as well as any inadequacy in the labeling or instructions which could cause misuse or incorrect maintenance or adjustment which might lead to a death or serious deterioration in health; an examination of the medical device or the information supplied with the medical device indicated some factor with the potential for an incident involving death or serious deterioration in health; malfunction or deterioration in characteristics and/or performance of a medical device, which might lead to death, or serious deterioration in health; technical/medical recalls involving risk of death or serious deterioration in the state of health of the user. |
| Number of Participants With Reoccurrence of Neuromuscular Blockade Based on the Train-of-Four- (TOF-) Watch® SX Recording (i.e. a Decline in T4/T1 Ratio From >=0.9 to <0.8 in at Least Three Consecutive TOF Values) | Up to 30 minutes after IMP administration | Neuromuscular functioning was monitored by applying repetitive TOF electrical stimulations to the ulnar nerve every 15 seconds and assessing twitch response at the adductor pollicis muscle. T1 and T4 refer to the magnitudes (heights) of the 1st and 4th twitches, respectively, after TOF stimulation. The T4/T1 Ratio is expressed as a decimal of up to 1.0. A higher ratio indicates greater recovery from NMB. A decline in the T4/T1 ratio from \>=0.9 (indicating a recovery from NMB) to \<0.8 for at least three consecutive TOF values was considered to be a reoccurrence of NMB. |
| Number of Participants With Clinical Evidence of Reoccurrence of Neuromuscular Blockade or Residual Neuromuscular Blockade (Routine Oxygen Saturation by Pulse Oximetry and Breath Frequency Measurement) | Up to 24 hours after IMP administration | Clinical evidence of reoccurrence of NMB or residual NMB was assessed by oxygen saturation (by pulse oximetry) and breath frequency measurements as per routine practice after anesthesia and neuromuscular monitoring. |
| Number of Participants With Events Due to a Possible Interaction of Sugammadex With Endogenous Compounds or With Exogenous Compounds Other Than Rocuronium | Up to 7 days after IMP administration | Any evidence of events due to a possible interaction of sugammadex with endogenous compounds or with exogenous compounds other than rocuronium, was to be recorded. |
| Monitoring of Clinical Signs of Recovery According to Routine Anesthetic Procedures at the Trial Sites | Up to PACU discharge (up to ~4.5 hours) | The monitoring of clinical signs of recovery was to be conducted based on the routine anesthetic procedures at each site. |
| Number of Female Participants or Partners of Male Participants Who Became Pregnant During Study | Up to 30 days after IMP administration | Thirty days after administration of IMP, female participants of childbearing potential were asked whether they became pregnant during the trial and male participants were asked whether their partner (if of childbearing potential) became pregnant during the trial. |
| Time From Operating Room Admission to Operating Room Discharge Ready | From Operating Room admission to Operating Room discharge ready (up to ~3 hours) | The time of Operating Room admission was defined as the time at which the participant was physically placed into the Operating Room. The time of Operating Room discharge ready was defined as time at which the participant had T4/T1 ratio of ≥0.9 and the participant's wound dressing was in place. |
| Time From Operating Room Admission to Actual Operating Room Discharge | From Operating Room admission to actual Operating Room discharge (up to ~3 hours) | The time of Operating Room admission was defined as the time at which the participant was physically placed into the Operating Room. The time of Operating Room discharge was defined as the actual time the participant was discharged from the Operating Room. |
| Time From Operating Room Discharge Ready to Actual Operating Room Discharge | From Operating Room discharge ready to actual Operating Room discharge (up to ~5 minutes) | The time of Operating Room discharge ready was defined as time at which the participant had T4/T1 ratio of \>=0.9 and the participant's wound dressing was in place. The time of Operating Room discharge was defined as the actual time the participant was discharged from the Operating Room. |
| Time From Start of Administration of IMP to Recovery of the T4/T1 Ratio to 0.5 and 0.6 | From start of IMP administration to recovery of T4/T1 Ratio to 0.5 and 0.6 (ranging from ~1 minute to ~4 minutes) | Neuromuscular functioning was monitored by applying repetitive TOF electrical stimulations to the ulnar nerve every 15 seconds & assessing twitch response at the adductor pollicis muscle. T1 and T4 refer to the magnitudes (heights) of the first and fourth twitches, respectively, after TOF nerve stimulation. The T4/T1 Ratio (expressed as a decimal of up to 1.0). Faster times to recovery of the T4/T1 Ratios to 0.5 and 0.6 indicate faster recoveries from NMB. |
| Time From Start of IMP Administration to Tracheal Extubation | From start of IMP administration to tracheal extubation (up to ~21 minutes) | The time of IMP administration was defined as the actual time at which IMP administration was started. The time of tracheal extubation was defined as the actual time at which the participant was extubated. |
| Time From Start of IMP Administration to Operating Room Discharge Ready | From start of IMP administration to Operating Room discharge ready (up to ~21 minutes) | The time of IMP administration was defined as the actual time at which IMP administration was started. The time of Operating Room discharge ready was defined as time at which the participant had T4/T1 ratio of \>=0.9 and the participant's wound dressing was in place. |
| Time From Start of IMP Administration to Actual Operating Room Discharge | From start of IMP administration to actual Operating Room discharge (up to ~26 minutes) | The time of IMP administration was defined as the actual time at which IMP administration was started. The time of Operating Room discharge was defined as the actual time at which the participant was discharged from the Operating Room. |
| Time From Tracheal Extubation to Operating Room Discharge Ready | From tracheal extubation to Operating Room discharge ready (up to ~1 minute) | The time of tracheal extubation was defined as the actual time at which the participant was extubated. The time of Operating Room discharge ready was defined as time at which the participant had T4/T1 ratio of \>=0.9 and the participant's wound dressing was in place. |
| Time From Tracheal Extubation to Actual Operating Room Discharge | From tracheal extubation to actual OR discharge (up to ~5 minutes) | The time of tracheal extubation was defined as the actual time at which the participant was extubated. The time of Operating Room discharge was defined as the actual time at which the participant was discharged from the Operating Room. |
| Time From Operating Room Discharge Ready to Post Anesthetic Care Unit (PACU) Discharge Ready | From Operating Room discharge ready to PACU discharge ready (up to ~33 minutes) | The time of Operating Room discharge ready was defined as time at which the participant had T4/T1 ratio of \>=0.9 and the participant's wound dressing was in place. The time of PACU discharge ready was defined as the time at which the participant had a Modified Aldrete Score \>=9. The Modified Aldrete Score was to be assessed at PACU arrival, at 5, 15, 30, 45, 60 minutes after PACU arrival and every 15 minutes thereafter (if applicable) until the participant was ready to be discharged from the PACU. The Modified Aldrete Postoperative Recovery Score (range = 0-10) is calculated based on scores of 0 to 2 each for Activity, Respiration, Circulation, Consciousness and Oxygen Saturation, with a higher score indicating increased postoperative recovery. |
| Time From Operating Room Discharge Ready to Actual PACU Discharge | From Operating Room discharge ready to actual PACU discharge (up to ~4.5 hours) | The time of Operating Room discharge ready was defined as time at which the participant had T4/T1 ratio of \>=0.9 and the participant's wound dressing was in place. The time of PACU discharge was defined as the actual time the participant was discharged from the PACU. |
| Time From Actual Operating Room Discharge to PACU Discharge Ready | From actual Operating Room discharge to PACU discharge ready (up to ~30 minutes) | The time of Operating Room discharge was defined as the actual time the participant was discharged from the Operating Room. The time of PACU discharge ready was defined as the time at which the participant had a Modified Aldrete Score \>=9. The Modified Aldrete Score was to be assessed at PACU arrival, at 5, 15, 30, 45, 60 minutes after PACU arrival and every 15 minutes thereafter (if applicable) until the participant was ready to be discharged from the PACU. The Modified Aldrete Postoperative Recovery Score (range = 0-10) is calculated based on scores of 0 to 2 each for Activity, Respiration, Circulation, Consciousness and Oxygen Saturation, with a higher score indicating increased postoperative recovery. |
| Time From Actual Operating Room Discharge to Actual PACU Discharge | From actual Operating Room discharge to actual PACU discharge (up to ~4.4 hours) | The time of Operating Room discharge was defined as the actual time the participant was discharged from the Operating Room. The time of PACU discharge was defined as the actual time the participant was discharged from the PACU. |
| Time From PACU Admit to PACU Discharge Ready | From PACU admit to PACU discharge ready (up to ~25 minutes) | The time of PACU admit was defined as the actual time the participant was admitted to the PACU. The time of PACU discharge ready was defined as the time at which the participant had a Modified Aldrete Score \>=9. The Modified Aldrete Score was to be assessed at PACU arrival, at 5, 15, 30, 45, 60 minutes after PACU arrival and every 15 minutes thereafter (if applicable) until the participant was ready to be discharged from the PACU. The Modified Aldrete Postoperative Recovery Score (range = 0-10) is calculated based on scores of 0 to 2 each for Activity, Respiration, Circulation, Consciousness and Oxygen Saturation, with a higher score indicating increased postoperative recovery. |
| Time From PACU Admit to Actual PACU Discharge | From PACU admit to actual PACU discharge (up to ~4.3 hours) | The time of PACU admit was defined as the actual time the participant was admitted to the PACU. The time of PACU discharge was defined as the actual time the participant was discharged from the PACU. |
| Time From Start of IMP Administration to T4/T1 Ratio of <=0.60, >0.60 - <=0.70, >0.70 - <=0.80, >0.80 - <0.90 and >=0.90 | From start of IMP administration to recovery of the T4/T1 ratio to the designated value (ranging from ~1 minute to ~10 minutes) | The time of IMP administration was defined as the actual time at which IMP administration was started. |
| Time From Start of Administration of the Last Dose of Rocuronium to Recovery of the T4/T1 Ratio to 0.5, 0.6, 0.7, 0.8 and 0.9 | From start of last dose of rocuronium to recovery of T4/T1 Ratio to 0.5, 0.6, 0.7, 0.8 and 0.9 (ranging from ~12 minutes to ~36 minutes) | Neuromuscular functioning was monitored by applying repetitive TOF electrical stimulations to the ulnar nerve every 15 seconds & assessing twitch response at the adductor pollicis muscle. T1 and T4 refer to the magnitudes (heights) of the first and fourth twitches, respectively, after TOF nerve stimulation. The T4/T1 Ratio (expressed as a decimal of up to 1.0). A faster time to recovery of the T4/T1 Ratio indicates a faster recovery from NMB. |
| Time From Start of Administration of the Last Dose of Rocuronium to the Time of 1-2 PTC in the 4.0 mg.Kg-1 Sugammadex Group | From last dose of rocuronium to 1-2 PTC (up to ~9 minutes) | The time of 1-2 PTC refers to when 1-2 twitches are generated after tetanic stimulation. Time to 1-2 PTC is the time point of the last single twitch \>0 or baseline (in case of noise or direct stimulation) within the sequence of a PTC measurement. 1-2 PTC was the target depth of NMB at which sugammadex was to be administered. |
| Time From Start of Administration of the Last Dose of Rocuronium to the Time of Reappearance of T2 in the 50 μg.Kg-1 Neostigmine Group | From last dose of rocuronium to reappearance of T2 (up to ~26 minutes) | The time of reappearance of T2 refers to when the second twitch reappears after TOF stimulation. Reappearance of T2 was the target depth of NMB at which neostigmine was to be administered. |
| Mean Systolic Blood Pressure | At screening, pre-rocuronium, pre-IMP, at 2, 5, 10, and 30 minutes post-IMP, and at the post-anesthetic visit (the day after surgery) | Systolic Blood Pressure was measured at screening, before start of rocuronium administration, before start of IMP administration, at 2, 5, 10, 30 minutes post-IMP administration, and at the post-anesthetic visit (the day after surgery). |
Participant flow
Recruitment details
Participants were recruited from 10 sites in Germany, Russia, Finland and the United Kingdom between July 2008 and March 2009.
Participants by arm
| Arm | Count |
|---|---|
| Sugammadex Participants receiving 4.0 mg.kg-1 sugammadex at 1-2 PTC | 66 |
| Neostigmine Participants receiving 50 µg.kg-1 neostigmine (with atropine in a ratio of 5:1 for neostigmine:atropine) at reappearance of T2 | 67 |
| Total | 133 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Not treated | 4 | 3 |
Baseline characteristics
| Characteristic | Sugammadex | Neostigmine | Total |
|---|---|---|---|
| Age, Continuous | 51 years STANDARD_DEVIATION 16 | 51 years STANDARD_DEVIATION 14 | 51 years STANDARD_DEVIATION 15 |
| Sex: Female, Male Female | 49 Participants | 43 Participants | 92 Participants |
| Sex: Female, Male Male | 17 Participants | 24 Participants | 41 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 64 / 66 | 63 / 67 |
| serious Total, serious adverse events | 5 / 66 | 6 / 67 |
Outcome results
Primary
Time From Start of Administration of Investigational Medicinal Product (IMP, Sugammadex or Neostigmine) to Recovery of the Fourth Twitch/First Twitch (T4/T1) Ratio to 0.9
Neuromuscular functioning was monitored by applying repetitive Train-Of-Four (TOF) electrical stimulations to the ulnar nerve every 15 seconds & assessing twitch response at the adductor pollicis muscle. T1 and T4 refer to the magnitudes (heights) of the first and fourth twitches, respectively, after TOF nerve stimulation. The T4/T1 Ratio (expressed as a decimal of up to 1.0) indicates the extent of recovery from neuromuscular blockade (NMB). In this study, twitch responses were recorded until the T4/T1 Ratio reached \>= 0.9, the minimum acceptable ratio that indicated recovery from NMB. A faster time to recovery of the T4/T1 Ratio to 0.9 indicates a faster recovery from NMB.
Time frame: From start of IMP administration to recovery of T4/T1 ratio to 0.9 (ranging from ~2 minutes to ~9 minutes)
Population: The Intent-To-Treat (ITT) Population consisted of all randomized participants who received IMP and had at least one efficacy measurement. Imputed recovery times were used in cases of missing times.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Sugammadex | Time From Start of Administration of Investigational Medicinal Product (IMP, Sugammadex or Neostigmine) to Recovery of the Fourth Twitch/First Twitch (T4/T1) Ratio to 0.9 | 2.4 minutes |
| Neostigmine | Time From Start of Administration of Investigational Medicinal Product (IMP, Sugammadex or Neostigmine) to Recovery of the Fourth Twitch/First Twitch (T4/T1) Ratio to 0.9 | 8.4 minutes |
Comparison: To evaluate the efficacy of sugammadex compared to neostigmine, the ratio of the geometric means of time to recovery of the T4/T1 ratio to 0.9 was calculated using a two-way analysis of variance (ANOVA) model adjusted for treatment group and trial site.p-value: <0.000195% CI: [2.8, 4.1]ANOVA
Secondary
Number of Participants Who Experienced Pre-treatment Non-serious Adverse Events (AEs) and Post-treatment Non-serious AEs
An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body, whether or not considered related to the use of the product. Participants were monitored for occurrence AEs for up to 7 days after last dose IMP. Pre-treatment refers to the period from signing of the informed consent up to start of IMP administration. Post-treatment refers to the period from start of IMP administration to 7 days after IMP administration.
Time frame: From signing of informed consent to end of trial (7 days after surgery)
Population: The AST Population consisted of all randomized participants who received IMP.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sugammadex | Number of Participants Who Experienced Pre-treatment Non-serious Adverse Events (AEs) and Post-treatment Non-serious AEs | Pre-treatment non-serious AE | 38 participants |
| Sugammadex | Number of Participants Who Experienced Pre-treatment Non-serious Adverse Events (AEs) and Post-treatment Non-serious AEs | Post-treatment non-serious AE | 65 participants |
| Neostigmine | Number of Participants Who Experienced Pre-treatment Non-serious Adverse Events (AEs) and Post-treatment Non-serious AEs | Pre-treatment non-serious AE | 34 participants |
| Neostigmine | Number of Participants Who Experienced Pre-treatment Non-serious Adverse Events (AEs) and Post-treatment Non-serious AEs | Post-treatment non-serious AE | 65 participants |
Secondary
Number of Participants Who Experienced Pre-treatment Serious Adverse Events (SAEs) and Post-treatment SAEs
An SAE is defined as any untoward medical occurrence that at any dose: results in death; is life-threatening; requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; or is a congenital anomaly/birth defect. Participants were monitored for occurrence SAEs for up to 7 days after last dose IMP. Pre-treatment refers to the period from signing of the informed consent up to start of IMP administration. Post-treatment refers to the period from start of IMP administration to 7 days after IMP administration.
Time frame: From signing of informed consent to end of trial (7 days after surgery)
Population: The All-Subjects-Treated (AST) Population consisted of all randomized participants who received IMP.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sugammadex | Number of Participants Who Experienced Pre-treatment Serious Adverse Events (SAEs) and Post-treatment SAEs | Pre-treatment SAE | 1 participants |
| Sugammadex | Number of Participants Who Experienced Pre-treatment Serious Adverse Events (SAEs) and Post-treatment SAEs | Post-treatment SAE | 4 participants |
| Neostigmine | Number of Participants Who Experienced Pre-treatment Serious Adverse Events (SAEs) and Post-treatment SAEs | Pre-treatment SAE | 0 participants |
| Neostigmine | Number of Participants Who Experienced Pre-treatment Serious Adverse Events (SAEs) and Post-treatment SAEs | Post-treatment SAE | 6 participants |
Secondary
Time From Start of Administration of IMP to Recovery of the T4/T1 Ratio to 0.7
Neuromuscular functioning was monitored by applying repetitive TOF electrical stimulations to the ulnar nerve every 15 seconds & assessing twitch response at the adductor pollicis muscle. T1 and T4 refer to the magnitudes (heights) of the first and fourth twitches, respectively, after TOF nerve stimulation. The T4/T1 Ratio (expressed as a decimal of up to 1.0). A faster time to recovery of the T4/T1 Ratio to 0.7 indicates a faster recovery from NMB.
Time frame: From start of IMP administration to recovery of T4/T1 Ratio to 0.7 (ranging from ~2 minutes to ~5 minutes)
Population: The ITT Population consisted of all randomized participants who received IMP and had at least one efficacy measurement. Imputed recovery times were used in cases of missing recovery times.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Sugammadex | Time From Start of Administration of IMP to Recovery of the T4/T1 Ratio to 0.7 | 1.6 minutes |
| Neostigmine | Time From Start of Administration of IMP to Recovery of the T4/T1 Ratio to 0.7 | 4.1 minutes |
Comparison: To evaluate the efficacy of sugammadex compared to neostigmine, the ratio of the geometric means of time to recovery of the T4/T1 ratio to 0.7 was calculated using a two-way ANOVA model adjusted for treatment group and trial site.p-value: <0.000195% CI: [2.1, 2.8]ANOVA
Secondary
Time From Start of Administration of IMP to Recovery of the T4/T1 Ratio to 0.8
Neuromuscular functioning was monitored by applying repetitive TOF electrical stimulations to the ulnar nerve every 15 seconds & assessing twitch response at the adductor pollicis muscle. T1 and T4 refer to the magnitudes (heights) of the first and fourth twitches, respectively, after TOF nerve stimulation. The T4/T1 Ratio (expressed as a decimal of up to 1.0). A faster time to recovery of the T4/T1 Ratio to 0.8 indicates a faster recovery from NMB.
Time frame: From start of IMP administration to recovery of T4/T1 Ratio to 0.8 (ranging from ~2 minutes to ~6 minutes)
Population: The ITT Population consisted of all randomized participants who received IMP and had at least one efficacy measurement. Imputed recovery times were used in cases of missing recovery times.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Sugammadex | Time From Start of Administration of IMP to Recovery of the T4/T1 Ratio to 0.8 | 1.9 minutes |
| Neostigmine | Time From Start of Administration of IMP to Recovery of the T4/T1 Ratio to 0.8 | 5.6 minutes |
Comparison: To evaluate the efficacy of sugammadex compared to neostigmine, the ratio of the geometric means of time to recovery of the T4/T1 ratio to 0.8 was calculated using a two-way ANOVA model adjusted for treatment group and trial site.p-value: <0.000195% CI: [2.5, 3.4]ANOVA
Other Pre-specified
Mean Diastolic Blood Pressure
Diastolic Blood Pressure was measured at screening, before start of rocuronium administration, before start of IMP administration, at 2, 5, 10, 30 minutes post-IMP administration, and at the post-anesthetic visit (the day after surgery).
Time frame: At screening, pre-rocuronium, pre-IMP, at 2, 5, 10, and 30 minutes post-IMP, and at the post-anesthetic visit (the day after surgery)
Population: The AST Population consisted of all randomized participants who received IMP.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sugammadex | Mean Diastolic Blood Pressure | Screening | 80.9 mm Hg | Standard Deviation 9.9 |
| Sugammadex | Mean Diastolic Blood Pressure | Pre-rocuronium | 58.2 mm Hg | Standard Deviation 11.6 |
| Sugammadex | Mean Diastolic Blood Pressure | Pre-IMP | 72.8 mm Hg | Standard Deviation 12.1 |
| Sugammadex | Mean Diastolic Blood Pressure | 2 minutes post-IMP (N=65, N=65) | 73.4 mm Hg | Standard Deviation 11.8 |
| Sugammadex | Mean Diastolic Blood Pressure | 5 minutes post-IMP | 72.4 mm Hg | Standard Deviation 11.4 |
| Sugammadex | Mean Diastolic Blood Pressure | 10 minutes post-IMP (N=66, N=66) | 71.8 mm Hg | Standard Deviation 12.8 |
| Sugammadex | Mean Diastolic Blood Pressure | 30 minutes post-IMP (N=65, N=66) | 74.3 mm Hg | Standard Deviation 10.9 |
| Sugammadex | Mean Diastolic Blood Pressure | Post-anesthetic visit (N=66, N=66) | 76.7 mm Hg | Standard Deviation 9.4 |
| Neostigmine | Mean Diastolic Blood Pressure | Post-anesthetic visit (N=66, N=66) | 75.2 mm Hg | Standard Deviation 10.8 |
| Neostigmine | Mean Diastolic Blood Pressure | Screening | 82.8 mm Hg | Standard Deviation 9.4 |
| Neostigmine | Mean Diastolic Blood Pressure | 5 minutes post-IMP | 69.2 mm Hg | Standard Deviation 13.5 |
| Neostigmine | Mean Diastolic Blood Pressure | Pre-rocuronium | 58.3 mm Hg | Standard Deviation 10.1 |
| Neostigmine | Mean Diastolic Blood Pressure | 30 minutes post-IMP (N=65, N=66) | 73.1 mm Hg | Standard Deviation 13.5 |
| Neostigmine | Mean Diastolic Blood Pressure | Pre-IMP | 72.5 mm Hg | Standard Deviation 12.8 |
| Neostigmine | Mean Diastolic Blood Pressure | 10 minutes post-IMP (N=66, N=66) | 68.7 mm Hg | Standard Deviation 14.9 |
| Neostigmine | Mean Diastolic Blood Pressure | 2 minutes post-IMP (N=65, N=65) | 72.6 mm Hg | Standard Deviation 11.8 |
Other Pre-specified
Mean Heart Rate
Heart Rate was measured at screening, before start of rocuronium administration, before start of IMP administration, at 2, 5, 10, 30 minutes post-IMP administration, and at the post-anesthetic visit (the day after surgery).
Time frame: At screening, pre-rocuronium, pre-IMP, at 2, 5, 10, and 30 minutes post-IMP, and at the post-anesthetic visit (the day after surgery)
Population: The AST Population consisted of all randomized participants who received IMP.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sugammadex | Mean Heart Rate | Screening | 72.9 beats per minute | Standard Deviation 11 |
| Sugammadex | Mean Heart Rate | Pre-rocuronium | 63.4 beats per minute | Standard Deviation 13.4 |
| Sugammadex | Mean Heart Rate | Pre-IMP | 68.3 beats per minute | Standard Deviation 11 |
| Sugammadex | Mean Heart Rate | 2 minutes post-IMP (N=65, N=65) | 66.0 beats per minute | Standard Deviation 12.4 |
| Sugammadex | Mean Heart Rate | 5 minutes post-IMP | 64.9 beats per minute | Standard Deviation 12.3 |
| Sugammadex | Mean Heart Rate | 10 minutes post-IMP (N=66, N=66) | 67.3 beats per minute | Standard Deviation 12.4 |
| Sugammadex | Mean Heart Rate | Post-anesthetic visit (N=66, N=66) | 72.7 beats per minute | Standard Deviation 11.7 |
| Sugammadex | Mean Heart Rate | 30 minutes post-IMP (N=65, N=66) | 73.1 beats per minute | Standard Deviation 12.2 |
| Neostigmine | Mean Heart Rate | 30 minutes post-IMP (N=65, N=66) | 65.1 beats per minute | Standard Deviation 11.2 |
| Neostigmine | Mean Heart Rate | Screening | 74.6 beats per minute | Standard Deviation 11.4 |
| Neostigmine | Mean Heart Rate | 5 minutes post-IMP | 57.1 beats per minute | Standard Deviation 10.8 |
| Neostigmine | Mean Heart Rate | Pre-rocuronium | 63.6 beats per minute | Standard Deviation 12.4 |
| Neostigmine | Mean Heart Rate | Post-anesthetic visit (N=66, N=66) | 71.9 beats per minute | Standard Deviation 71.9 |
| Neostigmine | Mean Heart Rate | Pre-IMP | 68.0 beats per minute | Standard Deviation 12.3 |
| Neostigmine | Mean Heart Rate | 10 minutes post-IMP (N=66, N=66) | 56.3 beats per minute | Standard Deviation 11.4 |
| Neostigmine | Mean Heart Rate | 2 minutes post-IMP (N=65, N=65) | 65.3 beats per minute | Standard Deviation 12.4 |
Other Pre-specified
Mean Systolic Blood Pressure
Systolic Blood Pressure was measured at screening, before start of rocuronium administration, before start of IMP administration, at 2, 5, 10, 30 minutes post-IMP administration, and at the post-anesthetic visit (the day after surgery).
Time frame: At screening, pre-rocuronium, pre-IMP, at 2, 5, 10, and 30 minutes post-IMP, and at the post-anesthetic visit (the day after surgery)
Population: The AST Population consisted of all randomized participants who received IMP.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sugammadex | Mean Systolic Blood Pressure | Pre-IMP | 122.1 mm Hg | Standard Deviation 16.5 |
| Sugammadex | Mean Systolic Blood Pressure | 10 minutes post-IMP (N=66, N=66) | 124.0 mm Hg | Standard Deviation 17.8 |
| Sugammadex | Mean Systolic Blood Pressure | 2 minutes post-IMP (N=65, N=65) | 122.5 mm Hg | Standard Deviation 18.8 |
| Sugammadex | Mean Systolic Blood Pressure | 30 minutes post-IMP (N=65, N=66) | 132.9 mm Hg | Standard Deviation 17.4 |
| Sugammadex | Mean Systolic Blood Pressure | Pre-rocuronium | 98.2 mm Hg | Standard Deviation 13.9 |
| Sugammadex | Mean Systolic Blood Pressure | Post-anesthetic visit (N=66, N=66) | 127.3 mm Hg | Standard Deviation 16.6 |
| Sugammadex | Mean Systolic Blood Pressure | 5 minutes post-IMP | 122.6 mm Hg | Standard Deviation 17.7 |
| Sugammadex | Mean Systolic Blood Pressure | Screening | 132.7 mm Hg | Standard Deviation 17.7 |
| Neostigmine | Mean Systolic Blood Pressure | Pre-IMP | 121.3 mm Hg | Standard Deviation 18.8 |
| Neostigmine | Mean Systolic Blood Pressure | Screening | 133.9 mm Hg | Standard Deviation 19.1 |
| Neostigmine | Mean Systolic Blood Pressure | Pre-rocuronium | 101.6 mm Hg | Standard Deviation 18.2 |
| Neostigmine | Mean Systolic Blood Pressure | 2 minutes post-IMP (N=65, N=65) | 122.5 mm Hg | Standard Deviation 20.4 |
| Neostigmine | Mean Systolic Blood Pressure | 5 minutes post-IMP | 118.0 mm Hg | Standard Deviation 22.3 |
| Neostigmine | Mean Systolic Blood Pressure | 10 minutes post-IMP (N=66, N=66) | 119.3 mm Hg | Standard Deviation 23.7 |
| Neostigmine | Mean Systolic Blood Pressure | 30 minutes post-IMP (N=65, N=66) | 131.7 mm Hg | Standard Deviation 23 |
| Neostigmine | Mean Systolic Blood Pressure | Post-anesthetic visit (N=66, N=66) | 125.4 mm Hg | Standard Deviation 17.1 |
Other Pre-specified
Monitoring of Clinical Signs of Recovery According to Routine Anesthetic Procedures at the Trial Sites
The monitoring of clinical signs of recovery was to be conducted based on the routine anesthetic procedures at each site.
Time frame: Up to PACU discharge (up to ~4.5 hours)
Population: The AST Population consisted of all randomized participants who received IMP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sugammadex | Monitoring of Clinical Signs of Recovery According to Routine Anesthetic Procedures at the Trial Sites | NA participants |
| Neostigmine | Monitoring of Clinical Signs of Recovery According to Routine Anesthetic Procedures at the Trial Sites | NA participants |
Other Pre-specified
Number of Female Participants or Partners of Male Participants Who Became Pregnant During Study
Thirty days after administration of IMP, female participants of childbearing potential were asked whether they became pregnant during the trial and male participants were asked whether their partner (if of childbearing potential) became pregnant during the trial.
Time frame: Up to 30 days after IMP administration
Population: The AST Population consisted of all randomized participants who received IMP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sugammadex | Number of Female Participants or Partners of Male Participants Who Became Pregnant During Study | 0 participants |
| Neostigmine | Number of Female Participants or Partners of Male Participants Who Became Pregnant During Study | 0 participants |
Other Pre-specified
Number of Participants Who Had Physical Examinations
Physical examinations were to be conducted at screening (within 7 days prior to surgery) and at the post-anesthetic visit (the day after surgery).
Time frame: At screening (within 7 days prior to surgery) and at the post-anesthetic visit (the day after surgery)
Population: The AST Population consisted of all randomized participants who received IMP. As there was no specific physical examination case report form used in this study, data on whether or not a physical examination was conducted were not recorded.
Other Pre-specified
Number of Participants With Clinical Evidence of Reoccurrence of Neuromuscular Blockade or Residual Neuromuscular Blockade (Routine Oxygen Saturation by Pulse Oximetry and Breath Frequency Measurement)
Clinical evidence of reoccurrence of NMB or residual NMB was assessed by oxygen saturation (by pulse oximetry) and breath frequency measurements as per routine practice after anesthesia and neuromuscular monitoring.
Time frame: Up to 24 hours after IMP administration
Population: The AST Population consisted of all randomized participants who received IMP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sugammadex | Number of Participants With Clinical Evidence of Reoccurrence of Neuromuscular Blockade or Residual Neuromuscular Blockade (Routine Oxygen Saturation by Pulse Oximetry and Breath Frequency Measurement) | 1 participants |
| Neostigmine | Number of Participants With Clinical Evidence of Reoccurrence of Neuromuscular Blockade or Residual Neuromuscular Blockade (Routine Oxygen Saturation by Pulse Oximetry and Breath Frequency Measurement) | 0 participants |
Other Pre-specified
Number of Participants With Events Due to a Possible Interaction of Sugammadex With Endogenous Compounds or With Exogenous Compounds Other Than Rocuronium
Any evidence of events due to a possible interaction of sugammadex with endogenous compounds or with exogenous compounds other than rocuronium, was to be recorded.
Time frame: Up to 7 days after IMP administration
Population: The AST Population consisted of all randomized participants who received sugammadex. Participants who received neostigmine were excluded from this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sugammadex | Number of Participants With Events Due to a Possible Interaction of Sugammadex With Endogenous Compounds or With Exogenous Compounds Other Than Rocuronium | 0 participants |
Other Pre-specified
Number of Participants With Reoccurrence of Neuromuscular Blockade Based on the Train-of-Four- (TOF-) Watch® SX Recording (i.e. a Decline in T4/T1 Ratio From >=0.9 to <0.8 in at Least Three Consecutive TOF Values)
Neuromuscular functioning was monitored by applying repetitive TOF electrical stimulations to the ulnar nerve every 15 seconds and assessing twitch response at the adductor pollicis muscle. T1 and T4 refer to the magnitudes (heights) of the 1st and 4th twitches, respectively, after TOF stimulation. The T4/T1 Ratio is expressed as a decimal of up to 1.0. A higher ratio indicates greater recovery from NMB. A decline in the T4/T1 ratio from \>=0.9 (indicating a recovery from NMB) to \<0.8 for at least three consecutive TOF values was considered to be a reoccurrence of NMB.
Time frame: Up to 30 minutes after IMP administration
Population: The ITT Population consisted of all randomized participants who received IMP and had at least one efficacy measurement.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sugammadex | Number of Participants With Reoccurrence of Neuromuscular Blockade Based on the Train-of-Four- (TOF-) Watch® SX Recording (i.e. a Decline in T4/T1 Ratio From >=0.9 to <0.8 in at Least Three Consecutive TOF Values) | 0 participants |
| Neostigmine | Number of Participants With Reoccurrence of Neuromuscular Blockade Based on the Train-of-Four- (TOF-) Watch® SX Recording (i.e. a Decline in T4/T1 Ratio From >=0.9 to <0.8 in at Least Three Consecutive TOF Values) | 0 participants |
Other Pre-specified
Number of Participants With Train-of-Four- (TOF-) Watch® SX and Arm Board Related Adverse Events
Events were to be collected for the entire period of neuromuscular transmission monitoring and were defined as an occurrence that resulted or could have resulted in: death; a serious deterioration in the state of health of a user; an occurrence which might, if it recurred, lead to death or serious deterioration in health; inaccuracy as well as any inadequacy in the labeling or instructions which could cause misuse or incorrect maintenance or adjustment which might lead to a death or serious deterioration in health; an examination of the medical device or the information supplied with the medical device indicated some factor with the potential for an incident involving death or serious deterioration in health; malfunction or deterioration in characteristics and/or performance of a medical device, which might lead to death, or serious deterioration in health; technical/medical recalls involving risk of death or serious deterioration in the state of health of the user.
Time frame: From induction of anesthesia to recovery from NMB (up to ~3 hours)
Population: The AST Population consisted of all randomized participants who received IMP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sugammadex | Number of Participants With Train-of-Four- (TOF-) Watch® SX and Arm Board Related Adverse Events | 0 participants |
| Neostigmine | Number of Participants With Train-of-Four- (TOF-) Watch® SX and Arm Board Related Adverse Events | 0 participants |
Other Pre-specified
Time From Actual Operating Room Discharge to Actual PACU Discharge
The time of Operating Room discharge was defined as the actual time the participant was discharged from the Operating Room. The time of PACU discharge was defined as the actual time the participant was discharged from the PACU.
Time frame: From actual Operating Room discharge to actual PACU discharge (up to ~4.4 hours)
Population: The ITT Population consisted of all randomized participants who received IMP and had at least one efficacy measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sugammadex | Time From Actual Operating Room Discharge to Actual PACU Discharge | 264 minutes | Standard Deviation 347 |
| Neostigmine | Time From Actual Operating Room Discharge to Actual PACU Discharge | 207 minutes | Standard Deviation 284 |
Other Pre-specified
Time From Actual Operating Room Discharge to PACU Discharge Ready
The time of Operating Room discharge was defined as the actual time the participant was discharged from the Operating Room. The time of PACU discharge ready was defined as the time at which the participant had a Modified Aldrete Score \>=9. The Modified Aldrete Score was to be assessed at PACU arrival, at 5, 15, 30, 45, 60 minutes after PACU arrival and every 15 minutes thereafter (if applicable) until the participant was ready to be discharged from the PACU. The Modified Aldrete Postoperative Recovery Score (range = 0-10) is calculated based on scores of 0 to 2 each for Activity, Respiration, Circulation, Consciousness and Oxygen Saturation, with a higher score indicating increased postoperative recovery.
Time frame: From actual Operating Room discharge to PACU discharge ready (up to ~30 minutes)
Population: The ITT Population consisted of all randomized participants who received IMP and had at least one efficacy measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sugammadex | Time From Actual Operating Room Discharge to PACU Discharge Ready | 24 minutes | Standard Deviation 28 |
| Neostigmine | Time From Actual Operating Room Discharge to PACU Discharge Ready | 29 minutes | Standard Deviation 40 |
Other Pre-specified
Time From Operating Room Admission to Actual Operating Room Discharge
The time of Operating Room admission was defined as the time at which the participant was physically placed into the Operating Room. The time of Operating Room discharge was defined as the actual time the participant was discharged from the Operating Room.
Time frame: From Operating Room admission to actual Operating Room discharge (up to ~3 hours)
Population: The ITT Population consisted of all randomized participants who received IMP and had at least one efficacy measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sugammadex | Time From Operating Room Admission to Actual Operating Room Discharge | 158 minutes | Standard Deviation 47 |
| Neostigmine | Time From Operating Room Admission to Actual Operating Room Discharge | 169 minutes | Standard Deviation 58 |
Other Pre-specified
Time From Operating Room Admission to Operating Room Discharge Ready
The time of Operating Room admission was defined as the time at which the participant was physically placed into the Operating Room. The time of Operating Room discharge ready was defined as time at which the participant had T4/T1 ratio of ≥0.9 and the participant's wound dressing was in place.
Time frame: From Operating Room admission to Operating Room discharge ready (up to ~3 hours)
Population: The ITT Population consisted of all randomized participants who received IMP and had at least one efficacy measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sugammadex | Time From Operating Room Admission to Operating Room Discharge Ready | 154 minutes | Standard Deviation 46 |
| Neostigmine | Time From Operating Room Admission to Operating Room Discharge Ready | 165 minutes | Standard Deviation 55 |
Other Pre-specified
Time From Operating Room Discharge Ready to Actual Operating Room Discharge
The time of Operating Room discharge ready was defined as time at which the participant had T4/T1 ratio of \>=0.9 and the participant's wound dressing was in place. The time of Operating Room discharge was defined as the actual time the participant was discharged from the Operating Room.
Time frame: From Operating Room discharge ready to actual Operating Room discharge (up to ~5 minutes)
Population: The ITT Population consisted of all randomized participants who received IMP and had at least one efficacy measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sugammadex | Time From Operating Room Discharge Ready to Actual Operating Room Discharge | 4 minutes | Standard Deviation 5 |
| Neostigmine | Time From Operating Room Discharge Ready to Actual Operating Room Discharge | 5 minutes | Standard Deviation 6 |
Other Pre-specified
Time From Operating Room Discharge Ready to Actual PACU Discharge
The time of Operating Room discharge ready was defined as time at which the participant had T4/T1 ratio of \>=0.9 and the participant's wound dressing was in place. The time of PACU discharge was defined as the actual time the participant was discharged from the PACU.
Time frame: From Operating Room discharge ready to actual PACU discharge (up to ~4.5 hours)
Population: The ITT Population consisted of all randomized participants who received IMP and had at least one efficacy measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sugammadex | Time From Operating Room Discharge Ready to Actual PACU Discharge | 268 minutes | Standard Deviation 348 |
| Neostigmine | Time From Operating Room Discharge Ready to Actual PACU Discharge | 210 minutes | Standard Deviation 283 |
Other Pre-specified
Time From Operating Room Discharge Ready to Post Anesthetic Care Unit (PACU) Discharge Ready
The time of Operating Room discharge ready was defined as time at which the participant had T4/T1 ratio of \>=0.9 and the participant's wound dressing was in place. The time of PACU discharge ready was defined as the time at which the participant had a Modified Aldrete Score \>=9. The Modified Aldrete Score was to be assessed at PACU arrival, at 5, 15, 30, 45, 60 minutes after PACU arrival and every 15 minutes thereafter (if applicable) until the participant was ready to be discharged from the PACU. The Modified Aldrete Postoperative Recovery Score (range = 0-10) is calculated based on scores of 0 to 2 each for Activity, Respiration, Circulation, Consciousness and Oxygen Saturation, with a higher score indicating increased postoperative recovery.
Time frame: From Operating Room discharge ready to PACU discharge ready (up to ~33 minutes)
Population: The ITT Population consisted of all randomized participants who received IMP and had at least one efficacy measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sugammadex | Time From Operating Room Discharge Ready to Post Anesthetic Care Unit (PACU) Discharge Ready | 28 minutes | Standard Deviation 27 |
| Neostigmine | Time From Operating Room Discharge Ready to Post Anesthetic Care Unit (PACU) Discharge Ready | 33 minutes | Standard Deviation 40 |
Other Pre-specified
Time From PACU Admit to Actual PACU Discharge
The time of PACU admit was defined as the actual time the participant was admitted to the PACU. The time of PACU discharge was defined as the actual time the participant was discharged from the PACU.
Time frame: From PACU admit to actual PACU discharge (up to ~4.3 hours)
Population: The ITT Population consisted of all randomized participants who received IMP and had at least one efficacy measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sugammadex | Time From PACU Admit to Actual PACU Discharge | 260 minutes | Standard Deviation 347 |
| Neostigmine | Time From PACU Admit to Actual PACU Discharge | 203 minutes | Standard Deviation 284 |
Other Pre-specified
Time From PACU Admit to PACU Discharge Ready
The time of PACU admit was defined as the actual time the participant was admitted to the PACU. The time of PACU discharge ready was defined as the time at which the participant had a Modified Aldrete Score \>=9. The Modified Aldrete Score was to be assessed at PACU arrival, at 5, 15, 30, 45, 60 minutes after PACU arrival and every 15 minutes thereafter (if applicable) until the participant was ready to be discharged from the PACU. The Modified Aldrete Postoperative Recovery Score (range = 0-10) is calculated based on scores of 0 to 2 each for Activity, Respiration, Circulation, Consciousness and Oxygen Saturation, with a higher score indicating increased postoperative recovery.
Time frame: From PACU admit to PACU discharge ready (up to ~25 minutes)
Population: The ITT Population consisted of all randomized participants who received IMP and had at least one efficacy measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sugammadex | Time From PACU Admit to PACU Discharge Ready | 20 minutes | Standard Deviation 28 |
| Neostigmine | Time From PACU Admit to PACU Discharge Ready | 25 minutes | Standard Deviation 40 |
Other Pre-specified
Time From Start of Administration of IMP to Recovery of the T4/T1 Ratio to 0.5 and 0.6
Neuromuscular functioning was monitored by applying repetitive TOF electrical stimulations to the ulnar nerve every 15 seconds & assessing twitch response at the adductor pollicis muscle. T1 and T4 refer to the magnitudes (heights) of the first and fourth twitches, respectively, after TOF nerve stimulation. The T4/T1 Ratio (expressed as a decimal of up to 1.0). Faster times to recovery of the T4/T1 Ratios to 0.5 and 0.6 indicate faster recoveries from NMB.
Time frame: From start of IMP administration to recovery of T4/T1 Ratio to 0.5 and 0.6 (ranging from ~1 minute to ~4 minutes)
Population: The ITT Population consisted of all randomized participants who received IMP and had at least one efficacy measurement. No imputation was done for missing times to recovery of the T4/T1 ratio to 0.5 and 0.6.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Sugammadex | Time From Start of Administration of IMP to Recovery of the T4/T1 Ratio to 0.5 and 0.6 | Recovery of T4/T1 Ratio to 0.5 | 1.3 minutes |
| Sugammadex | Time From Start of Administration of IMP to Recovery of the T4/T1 Ratio to 0.5 and 0.6 | Recovery of T4/T1 Ratio to 0.6 | 1.5 minutes |
| Neostigmine | Time From Start of Administration of IMP to Recovery of the T4/T1 Ratio to 0.5 and 0.6 | Recovery of T4/T1 Ratio to 0.5 | 2.8 minutes |
| Neostigmine | Time From Start of Administration of IMP to Recovery of the T4/T1 Ratio to 0.5 and 0.6 | Recovery of T4/T1 Ratio to 0.6 | 3.4 minutes |
Other Pre-specified
Time From Start of Administration of the Last Dose of Rocuronium to Recovery of the T4/T1 Ratio to 0.5, 0.6, 0.7, 0.8 and 0.9
Neuromuscular functioning was monitored by applying repetitive TOF electrical stimulations to the ulnar nerve every 15 seconds & assessing twitch response at the adductor pollicis muscle. T1 and T4 refer to the magnitudes (heights) of the first and fourth twitches, respectively, after TOF nerve stimulation. The T4/T1 Ratio (expressed as a decimal of up to 1.0). A faster time to recovery of the T4/T1 Ratio indicates a faster recovery from NMB.
Time frame: From start of last dose of rocuronium to recovery of T4/T1 Ratio to 0.5, 0.6, 0.7, 0.8 and 0.9 (ranging from ~12 minutes to ~36 minutes)
Population: The ITT Population consisted of all randomized participants who received IMP and had at least one efficacy measurement. No imputation was done for missing times from administration of last dose of rocuronium to recovery of the T4/T1 ratio to 0.5, 0.6, 0.7, 0.8 and 0.9.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Sugammadex | Time From Start of Administration of the Last Dose of Rocuronium to Recovery of the T4/T1 Ratio to 0.5, 0.6, 0.7, 0.8 and 0.9 | Recovery of T4/T1 ratio to 0.6 | 11.9 minutes |
| Sugammadex | Time From Start of Administration of the Last Dose of Rocuronium to Recovery of the T4/T1 Ratio to 0.5, 0.6, 0.7, 0.8 and 0.9 | Recovery of T4/T1 ratio to 0.8 | 12.5 minutes |
| Sugammadex | Time From Start of Administration of the Last Dose of Rocuronium to Recovery of the T4/T1 Ratio to 0.5, 0.6, 0.7, 0.8 and 0.9 | Recovery of T4/T1 ratio to 0.7 | 12.1 minutes |
| Sugammadex | Time From Start of Administration of the Last Dose of Rocuronium to Recovery of the T4/T1 Ratio to 0.5, 0.6, 0.7, 0.8 and 0.9 | Recovery of T4/T1 ratio to 0.9 (N=65, N=61) | 13.3 minutes |
| Sugammadex | Time From Start of Administration of the Last Dose of Rocuronium to Recovery of the T4/T1 Ratio to 0.5, 0.6, 0.7, 0.8 and 0.9 | Recovery of T4/T1 ratio to 0.5 | 11.7 minutes |
| Neostigmine | Time From Start of Administration of the Last Dose of Rocuronium to Recovery of the T4/T1 Ratio to 0.5, 0.6, 0.7, 0.8 and 0.9 | Recovery of T4/T1 ratio to 0.9 (N=65, N=61) | 35.2 minutes |
| Neostigmine | Time From Start of Administration of the Last Dose of Rocuronium to Recovery of the T4/T1 Ratio to 0.5, 0.6, 0.7, 0.8 and 0.9 | Recovery of T4/T1 ratio to 0.5 | 30.0 minutes |
| Neostigmine | Time From Start of Administration of the Last Dose of Rocuronium to Recovery of the T4/T1 Ratio to 0.5, 0.6, 0.7, 0.8 and 0.9 | Recovery of T4/T1 ratio to 0.6 | 30.7 minutes |
| Neostigmine | Time From Start of Administration of the Last Dose of Rocuronium to Recovery of the T4/T1 Ratio to 0.5, 0.6, 0.7, 0.8 and 0.9 | Recovery of T4/T1 ratio to 0.7 | 31.6 minutes |
| Neostigmine | Time From Start of Administration of the Last Dose of Rocuronium to Recovery of the T4/T1 Ratio to 0.5, 0.6, 0.7, 0.8 and 0.9 | Recovery of T4/T1 ratio to 0.8 | 33.2 minutes |
Other Pre-specified
Time From Start of Administration of the Last Dose of Rocuronium to the Time of 1-2 PTC in the 4.0 mg.Kg-1 Sugammadex Group
The time of 1-2 PTC refers to when 1-2 twitches are generated after tetanic stimulation. Time to 1-2 PTC is the time point of the last single twitch \>0 or baseline (in case of noise or direct stimulation) within the sequence of a PTC measurement. 1-2 PTC was the target depth of NMB at which sugammadex was to be administered.
Time frame: From last dose of rocuronium to 1-2 PTC (up to ~9 minutes)
Population: The ITT Population consisted of all randomized participants who received sugammadex and had at least one efficacy measurement. The participants who received neostigmine were not included in this analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Sugammadex | Time From Start of Administration of the Last Dose of Rocuronium to the Time of 1-2 PTC in the 4.0 mg.Kg-1 Sugammadex Group | 8.9 minutes |
Other Pre-specified
Time From Start of Administration of the Last Dose of Rocuronium to the Time of Reappearance of T2 in the 50 μg.Kg-1 Neostigmine Group
The time of reappearance of T2 refers to when the second twitch reappears after TOF stimulation. Reappearance of T2 was the target depth of NMB at which neostigmine was to be administered.
Time frame: From last dose of rocuronium to reappearance of T2 (up to ~26 minutes)
Population: The ITT Population consisted of all randomized participants who received neostigmine and had at least one efficacy measurement. The participants who received sugammadex were not included in this analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Sugammadex | Time From Start of Administration of the Last Dose of Rocuronium to the Time of Reappearance of T2 in the 50 μg.Kg-1 Neostigmine Group | 25.6 minutes |
Other Pre-specified
Time From Start of IMP Administration to Actual Operating Room Discharge
The time of IMP administration was defined as the actual time at which IMP administration was started. The time of Operating Room discharge was defined as the actual time at which the participant was discharged from the Operating Room.
Time frame: From start of IMP administration to actual Operating Room discharge (up to ~26 minutes)
Population: The ITT Population consisted of all randomized participants who received IMP and had at least one efficacy measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sugammadex | Time From Start of IMP Administration to Actual Operating Room Discharge | 19 minutes | Standard Deviation 9 |
| Neostigmine | Time From Start of IMP Administration to Actual Operating Room Discharge | 26 minutes | Standard Deviation 13 |
Other Pre-specified
Time From Start of IMP Administration to Operating Room Discharge Ready
The time of IMP administration was defined as the actual time at which IMP administration was started. The time of Operating Room discharge ready was defined as time at which the participant had T4/T1 ratio of \>=0.9 and the participant's wound dressing was in place.
Time frame: From start of IMP administration to Operating Room discharge ready (up to ~21 minutes)
Population: The ITT Population consisted of all randomized participants who received IMP and had at least one efficacy measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sugammadex | Time From Start of IMP Administration to Operating Room Discharge Ready | 15 minutes | Standard Deviation 8 |
| Neostigmine | Time From Start of IMP Administration to Operating Room Discharge Ready | 21 minutes | Standard Deviation 11 |
Other Pre-specified
Time From Start of IMP Administration to T4/T1 Ratio of <=0.60, >0.60 - <=0.70, >0.70 - <=0.80, >0.80 - <0.90 and >=0.90
The time of IMP administration was defined as the actual time at which IMP administration was started.
Time frame: From start of IMP administration to recovery of the T4/T1 ratio to the designated value (ranging from ~1 minute to ~10 minutes)
Population: The ITT Population consisted of all randomized participants who received IMP and had at least one efficacy measurement. Data not collected. In Protocol Amendment 2, this outcome measure was removed.
Other Pre-specified
Time From Start of IMP Administration to Tracheal Extubation
The time of IMP administration was defined as the actual time at which IMP administration was started. The time of tracheal extubation was defined as the actual time at which the participant was extubated.
Time frame: From start of IMP administration to tracheal extubation (up to ~21 minutes)
Population: The ITT Population consisted of all randomized participants who received IMP and had at least one efficacy measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sugammadex | Time From Start of IMP Administration to Tracheal Extubation | 14 minutes | Standard Deviation 8 |
| Neostigmine | Time From Start of IMP Administration to Tracheal Extubation | 21 minutes | Standard Deviation 11 |
Other Pre-specified
Time From Tracheal Extubation to Actual Operating Room Discharge
The time of tracheal extubation was defined as the actual time at which the participant was extubated. The time of Operating Room discharge was defined as the actual time at which the participant was discharged from the Operating Room.
Time frame: From tracheal extubation to actual OR discharge (up to ~5 minutes)
Population: The ITT Population consisted of all randomized participants who received IMP and had at least one efficacy measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sugammadex | Time From Tracheal Extubation to Actual Operating Room Discharge | 5 minutes | Standard Deviation 7 |
| Neostigmine | Time From Tracheal Extubation to Actual Operating Room Discharge | 5 minutes | Standard Deviation 6 |
Other Pre-specified
Time From Tracheal Extubation to Operating Room Discharge Ready
The time of tracheal extubation was defined as the actual time at which the participant was extubated. The time of Operating Room discharge ready was defined as time at which the participant had T4/T1 ratio of \>=0.9 and the participant's wound dressing was in place.
Time frame: From tracheal extubation to Operating Room discharge ready (up to ~1 minute)
Population: The ITT Population consisted of all randomized participants who received IMP and had at least one efficacy measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sugammadex | Time From Tracheal Extubation to Operating Room Discharge Ready | 1 minutes | Standard Deviation 6 |
| Neostigmine | Time From Tracheal Extubation to Operating Room Discharge Ready | 0 minutes | Standard Deviation 6 |