Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as sugammadex
Sugammadex/kg · 34 trials · 13 indications
Urinary retention is defined as the inability to void at six hours postoperatively, which will be recorded in the postoperative recovery area and the same definition for urinary retention will be applied to the comparative retrospective cohort
Neuromuscular functioning was monitored by applying four TOF electrical stimulations to the ulnar nerve and assessing twitch response at the adductor pollicis muscle. T1 and T4 refer to the magnitudes (height) 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 NMB, with a higher ratio indicating greater recovery from NMB. A T4/T1 Ratio of \<0.9 is indicative of residual NMB.
Post-treatment events of bleeding were evaluated by a medically-qualified, blinded member of the surgical team (Blinded Safety Assessor), in consultation with the surgeon, to determine if an event was a "suspected, unanticipated adverse event of bleeding" (SUAEB). A SUAEB is an event of bleeding outside the usual boundaries of expectations for a participant (e.g., in amount of blood lost, prolonged duration of bleeding, or other factors) considering the type of procedure as well as participant's specific surgical experience and underlying risk of bleeding. In addition, blinded review of clinical and laboratory databases was performed to identify any event potentially consistent with a SUAEB; these were reviewed by the Blinded Safety Assessor, who determined if any was a SUAEB. All SUAEBs were evaluated by a blinded external Adjudication Committee, which classified each as either: 1) a major bleeding event, 2) a non-major bleeding event, or 3) not an unanticipated event of bleeding.
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 \& T4 refer to the magnitudes (height) of the 1st \& 4th 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. In this study, twitch responses were recorded until the T4/T1 Ratio reached \>= 0.9, the minimum acceptable ratio that indicated complete recovery.
Neuromuscular functioning was monitored by applying repetitive train of four (TOF) electrical stimulations to the ulnar nerve every 15 seconds and assessing twitch response at the adductor pollicis muscle. Nerve stimulation continued until the ratio of the magnitude of the fourth twitch (T4) to first twitch (T1) reached at least 0.9. The greater the T4/T1 ratio the greater the recovery from neuromuscular blockade, with a value of 1.0 representing full recovery. Analysis of recovery in Chinese subjects was the primary objective; Caucasian subjects and between-group analyses were secondary.
Neuromuscular functioning was monitored by applying repetitive train of four (TOF) electrical stimulations to the ulnar nerve every 15 seconds and assessing twitch response at the adductor pollicis muscle. Nerve stimulation was to continue until the ratio of the magnitude of the fourth twitch (T4) to first twitch (T1) reached \>= 0.9. The greater the T4/T1 ratio the greater the recovery from neuromuscular blockade, with a value of 1.0 representing full recovery. The primary analysis was the comparison between sugammadex \& neostigmine among Chinese subjects; other comparisons were secondary.
Change from baseline = 5 minutes post dose value - baseline value. Baseline levels were obtained prior to rocuronium or succinylcholine dose. Only data post rocuronium dose are included for "rocuronium - sugammadex" group. The change from baseline interval included most or all of the intubation/surgical period for sugammadex analysis (since sugammadex was administered at the end of the surgical procedure) but not for succinylcholine or rocuronium analyses (since these were administered immediately after the baseline measurement just prior to intubation/commencement of the surgical period).
Change from baseline = 5 minutes post dose value - baseline value. Baseline levels were obtained prior to rocuronium dose. Only data post sugammadex dose are included for "rocuronium - sugammadex" group. The change from baseline interval included most or all of the intubation/surgical period for sugammadex analysis (since sugammadex was administered at the end of the surgical procedure) but not for succinylcholine or rocuronium analyses (since these were administered immediately after the baseline measurement just prior to intubation/commencement of the surgical period).
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 (height) of the first and fourth twitches, respectively, after TOF nerve stimulation. The T4/T1 Ratio (a percentage that is expressed as a decimal of up to 1.0) indicates the extent of recovery from neuromuscular blockade (NMB), with a higher ratio indicating a greater recovery from NMB. In this study, twitch responses were recorded until the T4/T1 Ratio reached \>=0.9, the minimum acceptable ratio that indicated complete recovery from NMB. A shorter time to recovery of the T4/T1 Ratio \>=0.9 indicates a faster recovery from NMB.
Neuromuscular functioning was monitored by applying repetitive train of four (TOF) electrical stimulations to the ulnar nerve every 15 seconds and assessing twitch response at the adductor pollicis muscle. Nerve stimulation continued until the ratio of the magnitude of the fourth twitch (T4) to first twitch (T1) reached at least 0.9. The greater the T4/T1 ratio the greater the recovery from neuromuscular blockade, with a value of 1.0 representing full recovery.
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.
Neuromuscular function was monitored by applying repetitive Train-Of-Four (TOF) electrical stimulations to the ulnar nerve every 15 seconds, and assessing twitch response at the adductor pollicis muscle with a TOF-Watch® SX. The magnitudes (heights) of the first and fourth twitches (T1 and T4) were used to calculate the T4/T1 ratio, where a higher T4/T1 ratio indicates a greater recovery from neuromuscular blockade, with a value of 1.0 indicating complete recovery. After anesthesia, when neuromuscular function was expected to be fully recovered, tracheal extubation was performed, at which time the T4/T1 ratio was measured, with any missing recovery times imputed.
Starting on Day 1 dialysis was performed on four separate occasions using a Fresenius 40008H hemodialyzer, with a hemodiafilter standard helixone membrane FX 600. Dialysate samples were collected before, and after hemodialysis, with concentrations of sugammadex determined using a liquid chromatographic assay with mass spectrometric detection. The clearance of sugammadex at each dialysis session was calculated by measuring the ratio of plasma concentration at the end of dialysis, average duration of 6 hours, compared with that immediately before the start of dialysis, called the RR.
Starting on Day 1 dialysis was performed on four separate occasions using a Fresenius 40008H hemodialyzer, with a hemodiafilter standard helixone membrane FX 600. Dialysate samples were collected before, and after hemodialysis, with concentrations of rocuronium determined using a liquid chromatographic assay with mass spectrometric detection. The clearance of rocuronium at each dialysis session was calculated by measuring the ratio of plasma concentration at the end of dialysis, average duration of 6 hours, compared with that immediately before the start of dialysis, called the RR.
Starting on Day 1 dialysis was performed on four separate occasions using a Fresenius 40008H hemodialyzer, with a hemodiafilter standard helixone membrane FX 600. Blood samples were collected from ports in the arterial and venous tubing of the dialyzer before, during and after an average of 6 hours of hemodialysis. The concentrations of sugammadex were determined using a liquid chromatographic assay with mass spectrometric detection. The clearance rate from blood at each dialysis session was assessed by averaging across all available collection time points.
Starting on Day 1 dialysis was performed on four separate occasions using a Fresenius 40008H hemodialyzer, with a hemodiafilter standard helixone membrane FX 600. Blood samples were collected from ports in the arterial and venous tubing of the dialyzer before, during and after an average of 6 hours of hemodialysis. The concentrations of rocuronium were determined using a liquid chromatographic assay with mass spectrometric detection. The clearance rate from blood at each dialysis session was assessed by averaging across all available collection time points.
Starting on Day 1 dialysis was performed on four separate occasions using a Fresenius 40008H hemodialyzer, with a hemodiafilter standard helixone membrane FX 600. Dialysate samples were collected from a port in the outflow of the dialyzer before, during and after an average of 6 hours of hemodialysis. The concentrations of sugammadex were determined using a liquid chromatographic assay with mass spectrometric detection. The clearance rate from dialysate at each dialysis session was assessed by averaging across all available collection time points.The data from the fourth dialysis are not presented as they were not calculable.
Starting on Day 1 dialysis was performed on four separate occasions using a Fresenius 40008H hemodialyzer, with a hemodiafilter standard helixone membrane FX 600. Dialysate samples were collected from a port in the outflow of the dialyzer before, during and after an average of 6 hours of hemodialysis. The concentrations of rocuronium were determined using a liquid chromatographic assay with mass spectrometric detection. The clearance rate from dialysate at each dialysis session was assessed by averaging across all available collection time points.
Neuromuscular function was monitored by applying repetitive TOF electrical stimulations with the TOF-Watch® SX to the ulnar nerve of one forearm every 15 seconds \& assessing twitch response at the adductor pollicis muscle with the TOF-Watch® SX. T1 and T4 are the magnitudes (heights) of the first and fourth twitches respectively after TOF nerve stimulation, where stimulation was continued until the T4/T1 ratio reached 0.9. A higher T4/T1 ratio indicates a lower degree of neuromuscular blockade, with a value of 1.0 representing full recovery. Only participants treated with 4.0 mg/kg sugammadex are presented, where the TOF-Watch® SX on the dominant forearm n =30, and on the non-dominant forearm n = 31. The 1.0 mg/kg sugammadex group was not evaluated for this outcome measure.
Neuromuscular function was monitored with a PNS by applying repetitive TOF stimulation to the ulnar nerve of one forearm every 15 seconds and assessing the number of twitches at the adductor pollicis muscle by a blinded PNS assessor. T4 is the fourth twitch after TOF nerve stimulation. Only participants treated with 4.0 mg/kg sugammadex are presented, where the PNS on the dominant forearm n =31, and on the non-dominant forearm n = 30. The 1.0 mg/kg sugammadex group was not evaluated for this outcome measure.
The difference between the recovery of T4/T1 ratio to 0.9 and reappearance of T4 within participants was assessed from an ANOVA method. Only participants treated with 4.0 mg/kg sugammadex are presented, where the TOF-Watch® SX on the dominant forearm n =30, and on the non-dominant forearm n = 31; and the PNS on the dominant forearm n =31, and on the non-dominant forearm n = 30. The 1.0 mg/kg sugammadex group was not evaluated for this outcome measure.
Neuromuscular functioning was monitored by applying repetitive Train of Four (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 amplitudes (heights) of the first and fourth twitches, respectively, after TOF nerve stimulation. The T4/T1 ratio (expressed as a decimal from 0 \[loss of T4\] up to 1.0 \[no NMB\]) indicates the extent of recovery from 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.
Neuromuscular functioning was monitored by applying repetitive Train-Of-Four (TOF) electrical stimulations to the ulnar nerve every 15 seconds and assessing twitch response at the adductor pollicis muscle. T1 refers to the amplitude (height) of the first twitch after TOF nerve stimulation.
Neuromuscular function was monitored by applying repetitive train-of-four (TOF) electrical stimulations with the TOF-Watch® SX to the ulnar nerve of one forearm every 15 seconds \& assessing twitch response at the adductor pollicis muscle. T1 and T4 are the magnitudes (heights) of the first and fourth twitches respectively after TOF nerve stimulation, where stimulation was continued until the T4/T1 ratio reached 0.9. A higher T4/T1 ratio indicates a lower degree of neuromuscular blockade, with a value of 1.0 representing full recovery.
Mean time from start of sugammadex or neostigmine administration to recovery of T4/T1 ratio to 0.9 was assessed by applying repetitive train of four (TOF) electrical stimulations to the ulnar nerve every 15 seconds and assessing twitch response at the adductor pollicis muscle. Nerve stimulation continued until the ratio of the magnitude of the fourth twitch (T4) to first twitch (T1) reached at least 0.9. The greater the T4/T1 ratio represented the greater the recovery from NMB; with a value of 0.0 representing no recovery and 1.0 representing full recovery. Reduced recovery time of the T4/T1 ratio to 0.9 indicated faster recovery from NMB. Mean time was collected in minutes and seconds but converted to and presented in minutes only. The analysis included a procedure for the imputation of missing recovery times.
Mean time from start of sugammadex or neostigmine administration to recovery of T4/T1 ratio to 0.9 was assessed by applying repetitive train of four (TOF) electrical stimulations to the ulnar nerve every 15 seconds and assessing twitch response at the adductor pollicis muscle. Nerve stimulation continued until the ratio of the magnitude of the fourth twitch (T4) to first twitch (T1) reached at least 0.9. The greater the T4/T1 ratio represented the greater the recovery from NMB; with a value of 0.0 representing no recovery and 1.0 representing full recovery. Reduced recovery time of the T4/T1 ratio to 0.9 indicated faster recovery from NMB. Mean time was collected in minutes and seconds but converted to and presented in minutes only. The analysis included a procedure for the imputation of missing recovery times.
Neuromuscular functioning was monitored by applying repetitive Train-Of-Four (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 amplitudes (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.
Mean time from start of MK-8616 administration to recovery of participant T4/T1 ratio to 0.9 was assessed through the repeated application (every 15 seconds) of an electrical stimulation protocol. Specifically, 4 electrical stimulations were applied to the ulnar nerve and the magnitude of the twitch response of the adductor pollicis muscle (i.e. thumb twitch response) was assessed. With T4 and T1 referring to the respective magnitude of the fourth and first thumb twitch during nerve stimulation, the T4/T1 ratio indicates the current degree of neuromuscular blockade (NMB) present in the participant as a decimal from 0 (loss of T4 twitch) to 1 (no NMB). Further, reduced recovery time of the T4/T1 ratio to 0.9 indicates faster recovery from NMB. Summary data, originally presented in the format of units "minutes:seconds" (mm:ss), was reformatted to be presented in the single unit of "minutes" (min).
The mean time from the start of sugammadex administration to recovery of the T4/T1 ratio to 0.9 was determined. Less time indicates faster recovery from neuromuscular blockade. The ratio of T4 (fourth twitch; amplitude of fourth response to train of four \[TOF\] stimulation is expressed as percent of control T4) over T1 (first twitch; amplitude of first response to TOF stimulation is expressed as percent of control T1) ranges from 0 (complete loss of T4 twitch response) to 1.0 (complete recovery of T4 twitch response). For TOF stimulation, 4 consecutive square wave supra-maximal stimuli of 0.2 msec duration were delivered at 2 Hz every 15 seconds. Neuromuscular monitoring was performed with the TOF-Watch® SX.
The percentage of participants experiencing ≥1 AE(s) was determined for each arm. An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
The percentage of participants discontinuing from study treatment due to an AE was determined for each arm. An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
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 \& T4 refer to the magnitudes (heights) of the first \& 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.
Neuromuscular functioning was monitored by applying repetitive Train-Of-Four (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 amplitudes (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.
Neuromuscular functioning was monitored by applying repetitive Train-Of-Four (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 amplitudes (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.
Mean time from start of study treatment administration to recovery of participant T4/T1 ratio to 0.9 was assessed through the repeated application (every 15 seconds) of an electrical stimulation protocol. Specifically, 4 electrical stimulations were applied to the ulnar nerve and the magnitude of the twitch response of the adductor pollicis muscle (i.e. thumb twitch response) was assessed. With T4 and T1 referring to the respective magnitude of the fourth and first thumb twitch during nerve stimulation, the T4/T1 ratio indicates the current degree of neuromuscular blockade (NMB) present in the participant as a decimal from 0 (loss of T4 twitch) to 1 (no NMB). Further, reduced recovery time of the T4/T1 ratio to 0.9 indicates faster recovery from NMB. Summary data, originally presented in the format of units "minutes:seconds" (mm:ss), was reformatted to be presented in the single unit of "minutes" (min).
The investigator or designated clinician performed a targeted hypersensitivity assessment (THA) in each participant at 0.5, 4 and 24 hours after each dose for each dosing period. The THA could also be performed at other times if possible hypersensitivity signs were observed. The THA included elicitation of symptoms as well as examination of the participant, covering neurologic, pulmonary, cardiovascular, gastrointestinal and dermatologic domains. Each potential hypersensitivity case identified by the presence of any sign or symptom in a pre-defined list of hypersensitivity signs and symptoms that were found through the THA was reviewed by an independent, blinded adjudication committee, which determined whether the referred case was a case of hypersensitivity (yes/no). In addition, all adverse events (AEs) occurring in study were reviewed for terms associated with hypersensitivity or anaphylaxis, and could also result in referral to the adjudication committee for evaluation.
Plasma samples for determination of sugammadex pharmacokinetic parameters were obtained pre-dose and at specified post-dose time points. AUC0-∞ was calculated as the sum of the AUC to the last time point with a detectable plasma concentration (AUC0-last, determined by trapezoidal method) and the extrapolated area given by Cest,last/λz, where Cest,last is the estimated concentration corresponding to the time of the last measurable concentration and λz is the apparent first-order terminal elimination rate constant. For each subject, λz was calculated by regression of the terminal log-linear portion of the plasma concentration-time profile. The reported least squares mean is the geometric least squares mean, which is the back-transformed least squares mean from the analysis of variance (ANOVA) linear fixed-effect model performed on natural log-transformed values of AUC0-∞. This calculation also provides the associated 95% confidence interval.
Plasma samples for determination of sugammadex pharmacokinetic parameters were obtained pre-dose and at specified post-dose time points. AUC0-last was determined by trapezoidal method. The reported least squares mean is the geometric least squares mean, which is the back-transformed least squares mean from the ANOVA linear fixed-effect model performed on natural log-transformed values of AUC0-last. This calculation also provides the associated 95% confidence interval.
Plasma samples for determination of sugammadex pharmacokinetic parameters were obtained pre-dose and at specified post-dose time points. Cmax was determined from the observed plasma concentration-time data. The reported least squares mean is the geometric least squares mean, which is the back-transformed least squares mean from the ANOVA linear fixed-effect model performed on natural log-transformed values of Cmax. This calculation also provides the associated 95% confidence interval.
Plasma samples for determination of sugammadex pharmacokinetic parameters were obtained pre-dose and at specified post-dose time points. AUC%extrap represents the percentage of the AUC0-∞ obtained by extrapolation, calculated as (1 - \[AUC0-last/AUC0-∞\]) multiplied by 100.
Plasma samples for determination of sugammadex pharmacokinetic parameters were obtained pre-dose and at specified post-dose time points. CL is a quantitative measure of the rate at which a drug substance is removed from the body, calculated as Dose/AUC0-∞.
Plasma samples for determination of sugammadex pharmacokinetic parameters were obtained pre-dose and at specified post-dose time points. Vz was calculated as Dose/(AUC0-∞\*λz).
Plasma samples for determination of sugammadex pharmacokinetic parameters were obtained pre-dose and at specified post-dose time points. MRT is defined as the mean duration of time a drug molecule is present in the systemic circulation.
Plasma samples for determination of sugammadex pharmacokinetic parameters were obtained pre-dose and at specified post-dose time points. Vss is the theoretical volume that the total amount of administered drug would have to occupy (if it were uniformly distributed), to provide the same concentration as it is in blood plasma at steady state, calculated as CL\*MRT.
Plasma samples for determination of sugammadex pharmacokinetic parameters were obtained pre-dose and at specified post-dose time points. Tmax was determined from the observed plasma concentration-time data.
Plasma samples for determination of sugammadex pharmacokinetic parameters were obtained pre-dose and at specified post-dose time points. Tlast was determined from the observed plasma concentration-time data.
Plasma samples for determination of sugammadex pharmacokinetic parameters were obtained pre-dose and at specified post-dose time points. Elimination t1/2 is the time it takes for the concentration of the drug in the body to decrease by half during the elimination phase, calculated as the natural log of 2 (ln\[2\])/λz.
Plasma samples for determination of sugammadex pharmacokinetic parameters were obtained pre-dose and at specified post-dose time points. t½eff was calculated as ln(2)\*MRT.
Plasma samples for determination of sugammadex pharmacokinetic parameters were obtained pre-dose and at specified post-dose time points. λz was calculated by regression of the terminal log-linear portion of the plasma concentration-time profile.
Hypersensitivity signs/symptoms were systematically collected for each subject by the investigator. Suspected cases of hypersensitivity signs/symptoms were sent to the independent Adjudication Committee (comprised of anesthesiologists \& allergists/immunologists) for blinded review and determination of adjudicated hypersensitivity \&/or anaphylaxis based on expert evaluation of all clinical data from the healthy subject. The percentages of subjects who had adjudicated hypersensitivity at any dose (dose 1/Day 8, dose 2/Day 36, or dose 3/Day 78) were compared between the 3 treatment groups.
| Arm | Type | Description |
|---|---|---|
| Sugammadex | EXPERIMENTAL | Prospective cohort of patients undergoing laparoscopic inguinal hernia repair will receive Sugammadex. Sugammadex will be used for reversal of their neuromuscular blockade. The dosing for Sugammadex is 4mg/kg for a deep reversal and a 2mg/kg for a standard reversal, which will be more common for this study. Sugammadex comes in 200mg/2mL and 500mg/5mL vials. Because of the variability in weight of the patients and the type of reversal needed (deep vs standard), 140 5mL vials will be required. |
| Retrospective cohort | NO_INTERVENTION | Retrospective cohort of patients who did not receive Sugammadex |
| Neostigmine/glycopyrrolate | ACTIVE_COMPARATOR | Participants receive neostigmine/glycopyrrolate per usual practice |
| Usual Care | EXPERIMENTAL | Prior to randomization, participants will be assigned to planned active reversal or planned spontaneous recovery by the anesthesiologist according to the recovery method the anesthesiologist would have chosen if the participant were not in the study. In this treatment arm, participants assigned to planned active reversal will receive neostigmine and placebo to sugammadex, and participants assigned to planned spontaneous recovery will receive placebo to sugammadex. Study drug will be administered after the last dose of rocuronium or vecuronium and after wound closure. |
| Neostigmine | ACTIVE_COMPARATOR | - |
| Sugammadex in Caucasian Subjects | EXPERIMENTAL | At 1-2 post-tetanic counts (PTC) after the last dose of rocuronium, 4.0 mg.kg-1 sugammadex was to be administered. Caucasian subjects living in Europe. |
| Sugammadex in Chinese Subjects | EXPERIMENTAL | At 1-2 post-tetanic counts (PTC) after the last dose of rocuronium, 4.0 mg.kg-1 sugammadex was to be administered. Chinese subjects living in China. |
| Neostigmine in Caucasian Subjects | ACTIVE_COMPARATOR | At reappearance of T2 after the last dose of rocuronium, 50 μg.kg-1 neostigmine (combined with 10-20 μg.kg-1 atropine, in a ratio ranging from 2.5:1 to 5:1) was administered. |
| Neostigmine in Chinese Subjects | ACTIVE_COMPARATOR | At reappearance of T2 after the last dose of rocuronium, 50 μg.kg-1 neostigmine (combined with 10-20 μg.kg-1 atropine, in a ratio ranging from 2.5:1 to 5:1) was administered. |
| Rocuronium - Sugammadex | ACTIVE_COMPARATOR | Rocuronium - Sugammadex 4.0 mg/kg |
| Succinylcholine | ACTIVE_COMPARATOR | Succinylcholine 1.0 mg/kg |
| Placebo | PLACEBO_COMPARATOR | Participants receiving Placebo (0.9% NaCl) at a target depth of NMB of 1-2 PTC after the last dose of rocuronium |
| Participants with severe renal impairment | EXPERIMENTAL | Participants with severe renal impairment will receive a single bolus dose of 4.0 mg.kg-1 sugammadex at a target depth of blockade of 1-2 PTC. Severe renal impairment was defined as creatinine clearance \<30mL/min. |
| Participants with normal renal function | ACTIVE_COMPARATOR | Participants with normal renal impairment will receive a single bolus dose of 4.0 mg.kg-1 sugammadex at a target depth of blockade of 1-2 PTC. Normal renal function was defined as creatinine clearance \>=80mL/min. |
| 1 | EXPERIMENTAL | sugammadex 1.0 mg/kg, TOF-Watch® SX (dominant forearm) and PNS (non-dominant forearm) |
| 2 | EXPERIMENTAL | sugammadex 1.0 mg/kg, TOF-Watch® SX (non-dominant forearm) and PNS (dominant forearm) |
| 3 | EXPERIMENTAL | sugammadex 4.0 mg/kg, TOF-Watch® SX (dominant forearm) and PNS (non-dominant forearm) |
| 4 | EXPERIMENTAL | sugammadex 4.0 mg/kg, TOF-Watch® SX (non-dominant forearm) and PNS (dominant forearm) |
| Sugammadex + Sevoflurane | EXPERIMENTAL | After receiving sevoflurane and the last dose of rocuronium, at the reappearance of first twitch (T1; 3-10% starting amplitude), a dose of 4.0 mg/kg sugammadex was administered. |
| Sugammadex + Propofol | EXPERIMENTAL | After receiving propofol and the last dose of rocuronium, at the reappearance of first twitch (T1; 3-10% starting amplitude), a dose of 4.0 mg/kg sugammadex was administered. |
| Rocuronium + Sugammadex | EXPERIMENTAL | Participants were to receive a single bolus dose of 1.2 mg/kg rocuronium. Three minutes after the start of the rocuronium administration, they were to receive a single bolus dose of 16.0 mg/kg sugammadex. |
| Participants 18 to 64 years old | EXPERIMENTAL | Participants to receive an intravenous (IV) single bolus dose of 0.6 mg.kg-1 rocuronium. If further neuromuscular block was required after endotracheal intubation, maintenance dose(s) of 0.15 mg.kg-1 rocuronium were to be administered. After the intubation dose or the last maintenance dose of rocuronium, participants were to be reversed at reappearance of second twitch (T2) with an intravenous single bolus dose of 2.0 mg.kg-1 of sugammadex. |
| Participants 65 to 74 years old | EXPERIMENTAL | Participants to receive an IV single bolus dose of 0.6 mg.kg-1 rocuronium. If further neuromuscular block was required after endotracheal intubation, maintenance dose(s) of 0.15 mg.kg-1 rocuronium were to be administered. After the intubation dose or the last maintenance dose of rocuronium, participants were to be reversed at reappearance of T2 with an intravenous single bolus dose of 2.0 mg.kg-1 of sugammadex. |
| Participants 75 years and older | EXPERIMENTAL | Participants to receive an IV single bolus dose of 0.6 mg.kg-1 rocuronium. If further neuromuscular block was required after endotracheal intubation, maintenance dose(s) of 0.15 mg.kg-1 rocuronium were to be administered. After the intubation dose or the last maintenance dose of rocuronium, participants were to be reversed at reappearance of T2 with an intravenous single bolus dose of 2.0 mg.kg-1 of sugammadex. |
| rocuronium+sugammadex | EXPERIMENTAL | Participants received a single bolus dose of 0.60 mg/kg rocuronium prior to intubation. The neuromuscular block was maintained with 0.15 mg/kg rocuronium if needed. At 1-2 post-tetanic counts (PTC) and after the last dose of rocuronium, a single bolus dose of 4.0 mg/kg sugammadex was administered. |
| rocuronium+neostigmine | ACTIVE_COMPARATOR | Participants received a single bolus dose of 0.60 mg/kg rocuronium prior to intubation. The neuromuscular block was maintained with 0.15 mg/kg rocuronium if needed. At 1-2 PTC and after the last dose of rocuronium, a single bolus dose of 70.0 μg/kg neostigmine (up to a maximum dose of 5 mg) was administered in combination with 14.0 μg/kg glycopyrrolate. |
| vecuronium+sugammadex | EXPERIMENTAL | Participants received a single bolus dose of 0.1 mg/kg vecuronium prior to intubation. The neuromuscular block was maintained with 0.015 mg/kg vecuronium if needed. At 1-2 PTC and after the last dose of vecuronium, a single bolus dose of 4.0 mg/kg sugammadex was administered. |
| vecuronium+neostigmine | ACTIVE_COMPARATOR | Participants received a single bolus dose of 0.1 mg/kg vecuronium prior to intubation. The neuromuscular block was maintained with 0.015 mg/kg vecuronium if needed. At 1-2 PTC and after the last dose of vecuronium, a single bolus dose of 70.0 μg/kg neostigmine (up to a maximum dose of 5 mg) was administered in combination with 14.0 μg/kg glycopyrrolate. |
| Rocuronium + Neostigmine | ACTIVE_COMPARATOR | After the last dose of rocuronium, at reappearance of T2, a dose of 50 ug/kg neostigmine was administered |
| Vecuronium + Sugammadex | EXPERIMENTAL | After the last dose of vecuronium, at reappearance of T2, a dose of 2.0 mg/kg sugammadex was administered |
| Vecuronium + Neostigmine | ACTIVE_COMPARATOR | After the last dose of vecuronium, at reappearance of T2, a dose of 50 ug/kg neostigmine was administered |
| Arm 1 | EXPERIMENTAL | Sugammadex 2.0 mg/kg |
| Arm 2 | EXPERIMENTAL | Sugammadex 4.0 mg/kg |
| Arm 3 | PLACEBO_COMPARATOR | Placebo |
| Rocuronium + Sugammadex 2.0 mg/kg | EXPERIMENTAL | After the IV intubation dose (0.6 mg/kg) or last maintenance dose (0.15 mg/kg) of rocuronium, at reappearance of T2, participants will receive IV sugammadex 2.0 mg/kg. |
| Rocuronium + Sugammadex 4.0 mg/kg | EXPERIMENTAL | After the IV intubation dose (0.6 mg/kg) or last maintenance dose (0.15 mg/kg) of rocuronium, at reappearance of T2, participants will receive IV sugammadex 4.0 mg/kg. |
| Normal renal function | ACTIVE_COMPARATOR | Org 25969 given to subjects with normal renal function |
| Impaired renal function | EXPERIMENTAL | Org 25969 given to subjects with impaired renal function |
| Sugammadex 0.5 mg/kg | EXPERIMENTAL | Participants are to receive an intravenous (IV) single bolus dose of 0.6 mg/kg rocuronium. At reappearance of T2, an IV single bolus dose of 0.5 mg/kg sugammadex is to be given. |
| Sugammadex 1 mg/kg | EXPERIMENTAL | Participants are to receive an IV single bolus dose of 0.6 mg/kg rocuronium. At reappearance of T2, an IV single bolus dose of 1 mg/kg sugammadex is to be given. |
| Sugammadex 2 mg/kg | EXPERIMENTAL | Participants are to receive an IV single bolus dose of 0.6 mg/kg rocuronium. At reappearance of T2, an IV single bolus dose of 2 mg/kg sugammadex is to be given. |
| Sugammadex 4 mg/kg | EXPERIMENTAL | Participants are to receive an IV single bolus dose of 0.6 mg/kg rocuronium. At reappearance of T2, an IV single bolus dose of 4 mg/kg sugammadex is to be given. |
| Rocuronium + Placebo | PLACEBO_COMPARATOR | After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered intravenously (IV), followed by maintenance doses of 0.1-0.2 mg/kg rocuronium IV if necessary. At reappearance of T2 a single dose of placebo was administered IV. |
| Rocuronium + 0.5 mg/kg sugammadex | EXPERIMENTAL | After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered IV, followed by maintenance doses of 0.1-0.2 mg/kg rocuronium IV if necessary. At reappearance of T2 a single dose of 0.5 mg/kg sugammadex was administered IV. |
| Rocuronium + 1.0 mg/kg sugammadex | EXPERIMENTAL | After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered IV, followed by maintenance doses of 0.1-0.2 mg/kg rocuronium IV if necessary. At reappearance of T2 a single dose of 1.0 mg/kg sugammadex was administered IV. |
| Rocuronium + 2.0 mg/kg sugammadex | EXPERIMENTAL | After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered IV, followed by maintenance doses of 0.1-0.2 mg/kg rocuronium IV if necessary. At reappearance of T2 a single dose of 2.0 mg/kg sugammadex was administered IV. |
| Rocuronium + 4.0 mg/kg sugammadex | EXPERIMENTAL | After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered IV, followed by maintenance doses of 0.1-0.2 mg/kg rocuronium IV if necessary. At reappearance of T2 a single dose of 4.0 mg/kg sugammadex was administered IV. |
| Vecuronium + Placebo | PLACEBO_COMPARATOR | After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV, followed by maintenance doses of 0.02-0.04 mg/kg vecuronium IV if necessary. At reappearance of T2 a single dose of placebo was administered IV. |
| Vecuronium + 0.5 mg/kg sugammadex | EXPERIMENTAL | After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV, followed by maintenance doses of 0.02-0.04 mg/kg vecuronium IV if necessary. At reappearance of T2 a single dose of 0.5 mg/kg sugammadex was administered IV. |
| Vecuronium + 1.0 mg/kg sugammadex | EXPERIMENTAL | After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV, followed by maintenance doses of 0.02-0.04 mg/kg vecuronium IV if necessary. At reappearance of T2 a single dose of 1.0 mg/kg sugammadex was administered IV. |
| Vecuronium + 2.0 mg/kg sugammadex | EXPERIMENTAL | After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV, followed by maintenance doses of 0.02-0.04 mg/kg vecuronium IV if necessary. At reappearance of T2 a single dose of 2.0 mg/kg sugammadex was administered IV. |
| Vecuronium + 4.0 mg/kg sugammadex | EXPERIMENTAL | After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV, followed by maintenance doses of 0.02-0.04 mg/kg vecuronium IV if necessary. At reappearance of T2 a single dose of 4.0 mg/kg sugammadex was administered IV. |
| Sugammadex 0.5 mg/kg (Rocuronium) | EXPERIMENTAL | After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered intravenously (IV), followed by maintenance doses of 0.1-0.2 mg/kg rocuronium IV if necessary. At reappearance of the second twitch (T2) response to Train-of-four (TOF) stimulation, a single dose of 0.5 mg/kg sugammadex was administered IV. |
| Sugammadex 1.0 mg/kg (Rocuronium) | EXPERIMENTAL | After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered IV, followed by maintenance doses of 0.1-0.2 mg/kg rocuronium IV if necessary. At reappearance of the T2 response to TOF stimulation, a single dose of 1.0 mg/kg sugammadex was administered IV. |
| Sugammadex 2.0 mg/kg (Rocuronium) | EXPERIMENTAL | After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered IV, followed by maintenance doses of 0.1-0.2 mg/kg rocuronium IV if necessary. At reappearance of the T2 response to TOF stimulation, a single dose of 2.0 mg/kg sugammadex was administered IV. |
| Sugammadex 4.0 mg/kg (Rocuronium) | EXPERIMENTAL | After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered IV, followed by maintenance doses of 0.1-0.2 mg/kg rocuronium IV if necessary. At reappearance of the T2 response to TOF stimulation, a single dose of 4.0 mg/kg sugammadex was administered IV. |
| Sugammadex 8.0 mg/kg (Rocuronium) | EXPERIMENTAL | After induction of anesthesia an intubation dose of 0.9 mg/kg rocuronium was administered IV, followed by maintenance doses of 0.1-0.2 mg/kg rocuronium IV if necessary. At reappearance of the T2 response to TOF stimulation, a single dose of 0.8 mg/kg sugammadex was administered IV. |
| Sugammadex 0.5 mg/kg (Vecuronium) | EXPERIMENTAL | After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV, followed by maintenance doses of 0.02-0.4 mg/kg vecuronium IV if necessary. At reappearance of the T2 response to TOF stimulation, a single dose of 0.5 mg/kg sugammadex was administered IV. |
| Sugammadex 1.0 mg/kg (Vecuronium) | EXPERIMENTAL | After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV, followed by maintenance doses of 0.02-0.4 mg/kg vecuronium IV if necessary. At reappearance of the T2 response to TOF stimulation, a single dose of 1.0 mg/kg sugammadex was administered IV. |
| Sugammadex 2.0 mg/kg (Vecuronium) | EXPERIMENTAL | After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV, followed by maintenance doses of 0.02-0.4 mg/kg vecuronium IV if necessary. At reappearance of the T2 response to TOF stimulation, a single dose of 2.0 mg/kg sugammadex was administered IV. |
| Sugammadex 4.0 mg/kg (Vecuronium) | EXPERIMENTAL | After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV, followed by maintenance doses of 0.02-0.4 mg/kg vecuronium IV if necessary. At reappearance of the T2 response to TOF stimulation, a single dose of 4.0 mg/kg sugammadex was administered IV. |
| Sugammadex 8.0 mg/kg (Vecuronium) | EXPERIMENTAL | After induction of anesthesia an intubation dose of 0.1 mg/kg vecuronium was administered IV, followed by maintenance doses of 0.02-0.4 mg/kg vecuronium IV if necessary. At reappearance of the T2 response to TOF stimulation, a single dose of 8.0 mg/kg sugammadex was administered IV. |
| Arm A. Placebo; 3 min after 1 mg/kg Esmeron® | PLACEBO_COMPARATOR | Placebo (single intravenous (IV) bolus) administered 3 minutes (min) after the bolus intubation dose of 1 mg/kg Esmeron®. |
| Arm B. 2 mg/kg sugammadex; 3 min after 1 mg/kg Esmeron® | EXPERIMENTAL | Sugammadex (2 mg/kg; single IV bolus) administered 3 min after the bolus intubation dose of 1 mg/kg Esmeron®. |
| Arm C. 4 mg/kg sugammadex; 3 min after 1 mg/kg Esmeron® | EXPERIMENTAL | Sugammadex (4 mg/kg; single IV bolus) administered 3 min after the bolus intubation dose of 1 mg/kg Esmeron®. |
| Arm D. 8 mg/kg sugammadex; 3 min after 1 mg/kg Esmeron® | EXPERIMENTAL | Sugammadex (8 mg/kg; single IV bolus) administered 3 min after the bolus intubation dose of 1 mg/kg Esmeron®. |
| Arm E. 12 mg/kg sugammadex; 3 min after 1 mg/kg Esmeron® | EXPERIMENTAL | Sugammadex (12 mg/kg; single IV bolus) administered 3 min after the bolus intubation dose of 1 mg/kg Esmeron®. |
| Arm F. 16 mg/kg sugammadex; 3 min after 1 mg/kg Esmeron® | EXPERIMENTAL | Sugammadex (16 mg/kg; single IV bolus) administered 3 min after the bolus intubation dose of 1 mg/kg Esmeron®. |
| Arm G. Placebo; 15 min after 1 mg/kg Esmeron® | PLACEBO_COMPARATOR | Placebo (single intravenous (IV) bolus) administered 15 min after the bolus intubation dose of 1 mg/kg Esmeron®. |
| Arm H. 2 mg/kg sugammadex; 15 min after 1 mg/kg Esmeron® | EXPERIMENTAL | Sugammadex (2 mg/kg; single IV bolus) administered 15 min after the bolus intubation dose of 1 mg/kg Esmeron®. |
| Arm I. 4 mg/kg sugammadex; 15 min after 1 mg/kg Esmeron® | EXPERIMENTAL | Sugammadex (4 mg/kg; single IV bolus) administered 15 min after the bolus intubation dose of 1 mg/kg Esmeron®. |
| Arm J. 8 mg/kg sugammadex; 15 min after 1 mg/kg Esmeron® | EXPERIMENTAL | Sugammadex (8 mg/kg; single IV bolus) administered 15 min after the bolus intubation dose of 1 mg/kg Esmeron®. |
| Arm K. 12 mg/kg sugammadex; 15 min after 1 mg/kg Esmeron® | EXPERIMENTAL | Sugammadex (12 mg/kg; single IV bolus) administered 15 min after the bolus intubation dose of 1 mg/kg Esmeron®. |
| Arm L. 16 mg/kg sugammadex; 15 min after 1 mg/kg Esmeron® | EXPERIMENTAL | Sugammadex (16 mg/kg; single IV bolus) administered 15 min after the bolus intubation dose of 1 mg/kg Esmeron®. |
| Arm M. Placebo; 3 min after 1.2 mg/kg Esmeron® | PLACEBO_COMPARATOR | Placebo (single IV bolus) administered 3 min after the bolus intubation dose of 1.2 mg/kg Esmeron®. |
| Arm N. 2 mg/kg sugammadex; 3 min after 1.2 mg/kg Esmeron® | EXPERIMENTAL | Sugammadex (2 mg/kg; single IV bolus) administered 3 min after the bolus intubation dose of 1.2 mg/kg Esmeron®. |
| Arm O. 4 mg/kg sugammadex; 3 min after 1.2 mg/kg Esmeron® | EXPERIMENTAL | Sugammadex (4 mg/kg; single IV bolus) administered 3 min after the bolus intubation dose of 1.2 mg/kg Esmeron®. |
| Arm P. 8 mg/kg sugammadex; 3 min after 1.2 mg/kg Esmeron® | EXPERIMENTAL | Sugammadex (8 mg/kg; single IV bolus) administered 3 min after the bolus intubation dose of 1.2 mg/kg Esmeron®. |
| Arm Q. 12 mg/kg sugammadex; 3 min after 1.2 mg/kg Esmeron® | EXPERIMENTAL | Sugammadex (12 mg/kg; single IV bolus) administered 3 min after the bolus intubation dose of 1.2 mg/kg Esmeron®. |
| Arm R. 16 mg/kg sugammadex; 3 min after 1.2 mg/kg Esmeron® | EXPERIMENTAL | Sugammadex (16 mg/kg; single IV bolus) administered 3 min after the bolus intubation dose of 1.2 mg/kg Esmeron®. |
| Arm S. Placebo; 15 min after 1.2 mg/kg Esmeron® | PLACEBO_COMPARATOR | Placebo (single IV bolus) administered 15 min after the bolus intubation dose of 1.2 mg/kg Esmeron®. |
| Arm T. 2 mg/kg sugammadex; 15 min after 1.2 mg/kg Esmeron® | EXPERIMENTAL | Sugammadex (2 mg/kg; single IV bolus) administered 15 min after the bolus intubation dose of 1.2 mg/kg Esmeron®. |
| Arm U. 4 mg/kg sugammadex; 15 min after 1.2 mg/kg Esmeron® | EXPERIMENTAL | Sugammadex (4 mg/kg; single IV bolus) administered 15 min after the bolus intubation dose of 1.2 mg/kg Esmeron®. |
| Arm V. 8 mg/kg sugammadex; 15 min after 1.2 mg/kg Esmeron® | EXPERIMENTAL | Sugammadex (8 mg/kg; single IV bolus) administered 15 min after the bolus intubation dose of 1.2 mg/kg Esmeron®. |
| Arm W. 12 mg/kg sugammadex; 15 min after 1.2 mg/kg Esmeron® | EXPERIMENTAL | Sugammadex (12 mg/kg; single IV bolus) administered 15 min after the bolus intubation dose of 1.2 mg/kg Esmeron®. |
| Arm X. 16 mg/kg sugammadex; 15 min after 1.2 mg/kg Esmeron® | EXPERIMENTAL | Sugammadex (16 mg/kg; single IV bolus) administered 15 min after the bolus intubation dose of 1.2 mg/kg Esmeron®. |
| 5 | EXPERIMENTAL | rocuronium + 12.0 mg/kg Org 25969 |
| Arm A. Placebo; given 3 minutes after Esmeron® | PLACEBO_COMPARATOR | Placebo (single intravenous (IV) bolus) administered 3 minutes after the bolus intubation dose of 0.6 mg/kg Esmeron®. |
| Arm B. 1 mg/kg Sugammadex; given 3 minutes after Esmeron® | EXPERIMENTAL | Sugammadex (1 mg/kg; single IV bolus) administered 3 minutes after the bolus intubation dose of 0.6 mg/kg Esmeron®. |
| Arm C. 2 mg/kg Sugammadex; given 3 minutes after Esmeron® | EXPERIMENTAL | Sugammadex (2 mg/kg; single IV bolus) administered 3 minutes after the bolus intubation dose of 0.6 mg/kg Esmeron®. |
| Arm D. 4 mg/kg Sugammadex; given 3 minutes after Esmeron® | EXPERIMENTAL | Sugammadex (4 mg/kg; single IV bolus) administered 3 minutes after the bolus intubation dose of 0.6 mg/kg Esmeron®. |
| Arm E. 6 mg/kg Sugammadex; given 3 minutes after Esmeron® | EXPERIMENTAL | Sugammadex (6 mg/kg; single IV bolus) administered 3 minutes after the bolus intubation dose of 0.6 mg/kg Esmeron®. |
| Arm F. 8 mg/kg Sugammadex; given 3 minutes after Esmeron® | EXPERIMENTAL | Sugammadex (8 mg/kg; single IV bolus) administered 3 minutes after the bolus intubation dose of 0.6 mg/kg Esmeron®. |
| Arm G. Placebo; given 5 minutes after Esmeron® | PLACEBO_COMPARATOR | Placebo (single IV bolus) administered 5 minutes after the bolus intubation dose of 0.6 mg/kg Esmeron®. |
| Arm H. 1 mg/kg Sugammadex; given 5 minutes after Esmeron® | EXPERIMENTAL | Sugammadex (1 mg/kg; single IV bolus) administered 5 minutes after the bolus intubation dose of 0.6 mg/kg Esmeron®. |
| Arm I. 2 mg/kg Sugammadex; given 5 minutes after Esmeron® | EXPERIMENTAL | Sugammadex (2 mg/kg; single IV bolus) administered 5 minutes after the bolus intubation dose of 0.6 mg/kg Esmeron®. |
| Arm J. 4 mg/kg Sugammadex; given 5 minutes after Esmeron® | EXPERIMENTAL | Sugammadex (4 mg/kg; single IV bolus) administered 5 minutes after the bolus intubation dose of 0.6 mg/kg Esmeron®. |
| Arm K. 6 mg/kg Sugammadex; given 5 minutes after Esmeron® | EXPERIMENTAL | Sugammadex (6 mg/kg; single IV bolus) administered 5 minutes after the bolus intubation dose of 0.6 mg/kg Esmeron®. |
| Arm L. 8 mg/kg Sugammadex; given 5 minutes after Esmeron® | EXPERIMENTAL | Sugammadex (8 mg/kg; single IV bolus) administered 5 minutes after the bolus intubation dose of 0.6 mg/kg Esmeron®. |
| Arm M. Placebo; given 15 minutes after Esmeron® | PLACEBO_COMPARATOR | Placebo (single IV bolus) administered 15 minutes after the bolus intubation dose of 0.6 mg/kg Esmeron®. |
| Arm N. 1 mg/kg Sugammadex; given 15 minutes after Esmeron® | EXPERIMENTAL | Sugammadex (1 mg/kg; single IV bolus) administered 15 minutes after the bolus intubation dose of 0.6 mg/kg Esmeron®. |
| Arm O. 2 mg/kg Sugammadex; given 15 minutes after Esmeron® | EXPERIMENTAL | Sugammadex (2 mg/kg; single IV bolus) administered 15 minutes after the bolus intubation dose of 0.6 mg/kg Esmeron®. |
| Arm P. 4 mg/kg Sugammadex; given 15 minutes after Esmeron® | EXPERIMENTAL | Sugammadex (4 mg/kg; single IV bolus) administered 15 minutes after the bolus intubation dose of 0.6 mg/kg Esmeron®. |
| Arm Q. 6 mg/kg Sugammadex; given 15 minutes after Esmeron® | EXPERIMENTAL | Sugammadex (6 mg/kg; single IV bolus) administered 15 minutes after the bolus intubation dose of 0.6 mg/kg Esmeron®. |
| Arm R. 8 mg/kg Sugammadex; given 15 minutes after Esmeron® | EXPERIMENTAL | Sugammadex (8 mg/kg; single IV bolus) administered 15 minutes after the bolus intubation dose of 0.6 mg/kg Esmeron®. |
| Sugammadex 16 mg/kg | EXPERIMENTAL | Administration of 3 single IV doses of sugammadex 16 mg/kg, with an approximately 5-week washout between Dose 1 and Dose 2 and between Dose 2 and Dose 3 |
| Severe Renal Insufficiency Participants: Part 1 | EXPERIMENTAL | Participants with severe renal insufficiency will receive a single dose of 4 mg/kg sugammadex administered as an IV bolus over 10 seconds. Dose will be administered by direct injection into a peripheral vein. |
| Moderate Renal Insufficiency Participants: Part 1 | EXPERIMENTAL | Participants with moderate renal insufficiency will receive a single dose of 4 mg/kg sugammadex administered as an IV bolus over 10 seconds. Dose will be administered by direct injection into a peripheral vein. |
| Healthy Control Participants: Part 1 | EXPERIMENTAL | Healthy control participants will receive a single dose of 4 mg/kg sugammadex administered as an IV bolus over 10 seconds. Dose will be administered by direct injection into a peripheral vein. |
| Severe Renal Insufficiency Participants: Part 2 | EXPERIMENTAL | Participants with severe renal insufficiency will receive a single dose of 4 mg/kg sugammadex administered as an IV bolus over 10 seconds. Dose will be administered into a peripheral vein through an IV catheter connected to an IV tubing with injection port. The IV tubing is connected to a saline bag. Free-flowing access to the vein will be confirmed immediately prior to dose administration, and dose will be followed by saline flush. |
| Moderate Renal Insufficiency Participants: Part 2 | EXPERIMENTAL | Participants with moderate renal insufficiency will receive a single dose of 4 mg/kg sugammadex administered as an IV bolus over 10 seconds. Dose will be administered into a peripheral vein through an IV catheter connected to an IV tubing with injection port. The IV tubing is connected to a saline bag. Free-flowing access to the vein will be confirmed immediately prior to dose administration, and dose will be followed by saline flush. |
| Healthy Control Participants: Part 2 | EXPERIMENTAL | Healthy control participants will receive a single dose of 4 mg/kg sugammadex administered as an IV bolus over 10 seconds. Dose will be administered into a peripheral vein through an IV catheter connected to an IV tubing with injection port. The IV tubing is connected to a saline bag. Free-flowing access to the vein will be confirmed immediately prior to dose administration, and dose will be followed by saline flush. |
| Name | Type | Description |
|---|---|---|
| Sugammadex | DRUG | The dosing for Sugammadex is 4mg/kg for a deep reversal and a 2mg/kg for a standard reversal, which will be more common for this study. Sugammadex comes in 200mg/2mL and 500mg/5mL vials. Because of the variability in weight of the patients and the type of reversal needed (deep vs standard), 140 5mL vials will be required. |
| Neostigmine | DRUG | neostigmine, per usual practice |
| Glycopyrrolate | DRUG | glycopyrrolate per usual practice |
| neostigmine and glycopyrrolate or atropine | DRUG | Neostigmine and glycopyrrolate or neostigmine and atropine administered intravenously per usual practice and per the product labels |
| Placebo to neostigmine | DRUG | Normal saline (NaCl 0.9%) |
| Placebo to sugammadex | DRUG | Normal saline (NaCl 0.9%) |
| rocuronium | DRUG | A single bolus intubation dose of 0.6 mg/kg rocuronium will be administered following induction of anesthesia and if required, single bolus dose(s) of 0.15 mg/kg rocuronium will be administered to maintain the neuromuscular block. |
| succinylcholine | DRUG | A single bolus intubation dose of 1.0 mg/kg succinylcholine will be administered following induction of anesthesia and the subject is allowed to recover spontaneously from the neuromuscular blockade. |
| 0.9% sodium chloride (NaCl) | DRUG | At a target depth of NMB of 1-2 PTC after the last dose of rocuronium, a bolus dose of placebo (0.9% NaCl, volume based on the actual body weight of the participant) will be administered, within 10 seconds into a fast running venous infusion. |
| Atropine | DRUG | 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. |
| Sevoflurane | DRUG | Sevoflurane IV administered for induction and maintenance of anesthesia, based on randomization. |
| Propofol | DRUG | Propofol IV administered for induction and maintenance of anesthesia, based on randomization. |
| Rocurium | DRUG | intravenous (IV) single bolus dose of 0.6 mg.kg-1 |
| vecuronium | DRUG | Administered as an IV infusion |
| Placebo | DRUG | Placebo given at reappearance of T2 after 0.6 mg/kg rocuronium |
| Sugammadex 0.5 mg/kg | DRUG | IV infusion |
| Sugammadex 1 mg/kg | DRUG | IV infusion |
| Sugammadex 2 mg/kg | DRUG | IV infusion |
| Sugammadex 4 mg/kg | DRUG | IV infusion |
| Rocuronium bromide | DRUG | IV infusion |
| Esmeron® | DRUG | Esmeron® administered at 1 or 1.2 mg/kg as a fast IV bolus (within 10 seconds), dosed according to participant actual body weight. |
| Placebo run-in dose | DRUG | Single-blind placebo intravenous bolus injection on Day 1 of the study, 7 days prior to randomization |
| Sugammadex 16 mg/kg | DRUG | Sugammadex 16 mg/kg intravenous bolus injection on Day 8, Day 36, and Day 78 of the study |
Inclusion Criteria: * Over the age of 18 * Undergoing laparoscopic inguinal hernia repair at Carolinas Medical Center by attending surgeons within the Division of Gastrointestinal and Minimally Invasive Surgery * Unilateral or bilateral inguinal hernia repair; may have concurrent umbilical hernia r...
Sugammadex/kg is used to reverse neuromuscular blockade in patients undergoing general anesthesia. It is also studied in postoperative urinary retention, hypersensitivity, and renal insufficiency. The drug is given as a weight-based dose, with 4 mg/kg and 0.5 mg/kg among the studied regimens.
Sugammadex/kg is developed by Merck & Company, Inc., which trades under the ticker MRK. Merck is the sponsor of the clinical program evaluating this weight-based dosing of sugammadex.
Sugammadex/kg is in Phase 3 development. Eighteen trials have been completed, including Phase 1, Phase 2, and Phase 3 studies, with no active trials currently listed. The program has enrolled 2,366 participants across randomized, double-blind, active-controlled designs.
Completed trials include NCT05276804, the Phase 3 POUR study in postoperative urinary retention; NCT03519854, a Phase 2 study in neuromuscular blockade; NCT02028065, a Phase 1 hypersensitivity study; and NCT02011490, a Phase 1 pharmacokinetic study in renal insufficiency.
Yes, Sugammadex/kg is a weight-based dosing description of sugammadex, also written as Sugammadex 4 mg/kg or Sugammadex 0.5 mg/kg. These names refer to the same small-molecule agent studied across the same clinical program.