| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT01422304 | Reversal of Neuromuscular Blockade With Sugammadex or Usual Care in Hip Fracture Surgery or Joint (Hip/Knee) Replacement (P07038) | PHASE3 | COMPLETED | 1,198 | — | — | Oct 12, 2011 | Sep 26, 2012 | Feb 12, 2021 | - | — |
| NCT01050543 | Comparison of Sugammadex With Neostigmine as Reversal Agents for Rocuronium at Reappearance of T2 (Study P06101) | PHASE3 | COMPLETED | 128 | — | — | Feb 1, 2010 | Aug 20, 2010 | Jul 2, 2017 | - | — |
| NCT00656799 | Dialysis of Sugammadex in Participants With Severe Renal Impairment (Study 19.4.333) (P05773) | PHASE3 | COMPLETED | 6 | — | — | Apr 1, 2008 | Jul 1, 2009 | Mar 10, 2015 | - | — |
| NCT00535496 | Relation Between TOF-Watch® SX and a Peripheral Nerve Stimulator After 4.0 mg.Kg-1 Sugammadex (P05698) | PHASE3 | COMPLETED | 91 | — | — | Sep 1, 2007 | Feb 1, 2008 | Mar 17, 2015 | - | — |
| NCT03519854 | Efficacy, Safety and Pharmacokinetics of Sugammadex (Org 25969; MK-8616) at 3 Different Time Points After 0.6 mg/kg Esmeron® in Male Participants (P05940; MK-8616-020). | PHASE2 | COMPLETED | 99 | — | — | Dec 1, 2002 | Jun 1, 2003 | Apr 2, 2019 | - | — |
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.
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.
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).
| Arm | Type | Description |
|---|---|---|
| Sugammadex | 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 sugammadex and placebo to neostigmine, and participants assigned to planned spontaneous recovery will receive sugammadex. Study drug will be administered after the last dose of rocuronium or vecuronium and after wound closure. |
| 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 | - |
| 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) |
| 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®. |
| Name | Type | Description |
|---|---|---|
| Sugammadex | DRUG | Sugammadex 4 mg/kg intravenously |
| 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%) |
| neostigmine | DRUG | neostigmine 50 mcg/kg (total dose not to exceed 5.0 mg) combined with glycopyrrolate 10 mcg/kg, single intravenous bolus dose administered within 10 seconds into a fast flowing venous infusion |
| Rocuronium | DRUG | After achieving stable anesthesia an IV single bolus dose of 0.6 mg/kg rocuronium was administered |
| Placebo | DRUG | 0.9% NaCl administered as a fast IV bolus dose (within 30 seconds). |
| Esmeron® | DRUG | Esmeron® administered at 0.6 mg/kg as a fast IV bolus (within 10 seconds), dosed according to participant actual body weight. |
Inclusion Criteria: * Must be American Society of Anesthesiologists (ASA) Class 1, 2, or 3 * Must be scheduled for a hip fracture surgery or joint (hip or knee) replacement surgery under general anesthesia including the use of rocuronium or vecuronium for neuromuscular blockade * Must be: * Curr...