Neuromuscular Blockade
Conditions
Brief summary
The objective of the trial is to determine the relationship within a participant between the time to manual detection of the reappearance of the fourth twitch (T4) measured using a peripheral nerve stimulator (PNS) and the time to recovery of the fourth twitch/first twitch (T4/T1) ratio to 0.9 measured using a Train Of Four (TOF)-Watch® SX, of 4.0 mg/kg sugammadex administered at 15 minutes after either a bolus dose of 0.6 mg/kg rocuronium or the last maintenance dose of 0.15 mg/kg rocuronium.
Detailed description
The TOF-Watch® SX has been used for neuromuscular monitoring in all clinical trials with sugammadex. In clinical practice however, a PNS is commonly used in many hospitals worldwide. A disadvantage of a PNS is that it is not objective monitoring like the TOF-Watch® SX, and it can detect only the number of twitches. In this trial, the relationship between the time to reappearance of T4 using PNS (i.e. Ministim® model MS-IV) and the time to recovery of the T4/T1 ratio to 0.9 using the TOF-Watch® SX was determined after a dose of 4.0 mg/kg sugammadex was administered 15 minutes after the last dose of rocuronium. Determining this relationship will enable the provision of advice on when it is safe to extubate participants after administration of 4.0 mg/kg sugammadex for reversing neuromuscular block while using a PNS. The time to reappearance of T4 was assessed by a blinded PNS-assessor. This assessor was blinded for the dose of sugammadex used and for the TOF results measured with the TOF-Watch® SX.
Interventions
DRUGsugammadex
Participants will receive an intubating dose of 0.6 mg/kg rocuronium, followed by one or more maintenance doses of 0.15 mg/kg rocuronium, if necessary. Fifteen minutes after the last dose of rocuronium, 1.0 or 4.0 mg/kg sugammadex will be randomly administered by intravenous (IV) bolus dose based on actual body weight.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
* American Society of Anesthesiologists (ASA) Class 1 or 2 or 3 * between the ages of 18 to 64 years, inclusive * scheduled for a surgical procedure under general anesthesia requiring neuromuscular relaxation with the use of rocuronium * scheduled for a surgical procedure in supine position * have given written informed consent
Exclusion criteria
* participants with a difficult intubation because of expected anatomical malformations * known or suspected to have neuromuscular disorders impairing neuromuscular blockade and/or significant hepatic and/or renal dysfunction * medical or physical condition that is expected to interfere with the proper conduct of simultaneous neuromuscular monitoring on both arms * known or suspected to have a (family) history of malignant hyperthermia * known or suspected to have arthritis or another disease that will cause the thumb not to move freely * known or suspected to have an allergy to narcotics, muscle relaxants or other medication used during general anesthesia * is receiving medication in a dose and/or at a time point known to interfere with neuromuscular blocking agents (NMBAs), such as antibiotics, anticonvulsants and Mg2+ * already participated in a sugammadex trial * participated in another clinical trial, not pre-approved, within prior 30 days * pregnant females * breast-feeding females
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time From Start of Administration of 4.0 mg/kg Sugammadex to Recovery of the T4/T1 Ratio to 0.9 Measured by a TOF-Watch® SX | Up to 4 minutes after administering sugammadex | 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. |
| Time From Start of Administration of 4.0 mg/kg Sugammadex to Reappearance of T4 Measured by a Peripheral Nerve Stimulator (PNS) | up to 2 minutes after administering sugammadex | 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. |
| Difference in Time Between Recovery of T4/T1 Ratio to 0.9 as Measured by TOF Watch® SX, and Reappearance of T4 as Measured by PNS, Within Participants, After Administration of 4.0 mg/kg Sugammadex | Up to 3 minutes after administering sugammadex | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Time From Start of Administration of 1.0 or 4.0 mg/kg Sugammadex to Recovery of the T4/T1 Ratio to 0.8 Measured by a TOF-Watch® SX | Up to 42 minutes after administering sugammadex | 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 0.8. A higher T4/T1 ratio indicates a lower degree of neuromuscular blockade, with a value of 1.0 representing full recovery. For participants treated with 1.0 mg/kg sugammadex the TOF-Watch® SX on the dominant forearm n =15, and on the non-dominant forearm n = 14. For participants treated with 4.0 mg/kg sugammadex the TOF-Watch® SX on the dominant forearm n =30, and on the non-dominant forearm n = 31. |
| Time From Start of Administration of 1.0 mg/kg Sugammadex to Recovery of the T4/T1 Ratio to 0.9 Measured by a TOF-Watch® SX | Up to 150 minutes after administering sugammadex | 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 1.0 mg/kg sugammadex are presented where the TOF-Watch® SX on the dominant forearm n =15, and on the non-dominant forearm n = 14. The 4.0 mg/kg sugammadex group was not evaluated for this outcome measure. |
| Time From Start of Administration of 1.0 or 4.0 mg/kg Sugammadex to Recovery of the T4/T1 Ratio to 0.7 Measured by a TOF-Watch® SX | Up to 42 minutes after administering sugammadex | 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 0.7. A higher T4/T1 ratio indicates a lower degree of neuromuscular blockade, with a value of 1.0 representing full recovery. For participants treated with 1.0 mg/kg sugammadex the TOF-Watch® SX on the dominant forearm n =15, and on the non-dominant forearm n = 14. For participants treated with 4.0 mg/kg sugammadex the TOF-Watch® SX on the dominant forearm n =30, and on the non-dominant forearm n = 31. |
| Time From Start of Administration of 1.0 or 4.0 mg/kg Sugammadex to Reappearance of T4 Measured by a TOF-Watch® SX | Up to 7 minutes after administering sugammadex | 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. T4 is the fourth twitch after TOF nerve stimulation. For participants treated with 1.0 mg/kg sugammadex the TOF-Watch® SX on the dominant forearm n =15, and on the non-dominant forearm n = 14. For participants treated with 4.0 mg/kg sugammadex the TOF-Watch® SX on the dominant forearm n =30, and on the non-dominant forearm n = 31. |
| Time From Start of Administration of 1.0 mg/kg Sugammadex to Reappearance of T4 Measured by a PNS | Up to 5 minutes after administering sugammadex | Neuromuscular function was monitored by applying repetitive TOF stimulations manually to the ulnar nerve of one forearm every 15 seconds & the number of twitches collected manually at the adductor pollicis muscle with the PNS by a blinded PNS assessor. T4 is the fourth twitch after TOF nerve stimulation. Only participants treated with 1.0 mg/kg sugammadex are presented, where the PNS on the dominant forearm n =15, and on the non-dominant forearm n = 14. The 4.0 mg/kg sugammadex group was not evaluated for this outcome measure. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sugammadex 1.0 mg/kg Participants received an intubating dose of 0.6 mg/kg rocuronium, followed by one or more maintenance doses of 0.15 mg/kg rocuronium, if necessary. Fifteen minutes after the last dose of rocuronium, 1.0 mg/kg sugammadex was administered by intravenous (IV) bolus dose based on actual body weight. | 29 |
| Sugammadex 4.0 mg/kg Participants received an intubating dose of 0.6 mg/kg rocuronium, followed by one or more maintenance doses of 0.15 mg/kg rocuronium, if necessary. Fifteen minutes after the last dose of rocuronium, 4.0 mg/kg sugammadex was administered by intravenous (IV) bolus dose based on actual body weight. | 61 |
| Total | 90 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 | 0 | 0 |
| Overall Study | Not treated with sugammadex | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Sugammadex 1.0 mg/kg | Sugammadex 4.0 mg/kg | Total |
|---|---|---|---|
| Age, Continuous | 43 years STANDARD_DEVIATION 11 | 42 years STANDARD_DEVIATION 13 | 42 years STANDARD_DEVIATION 12 |
| Sex: Female, Male Female | 16 Participants | 40 Participants | 56 Participants |
| Sex: Female, Male Male | 13 Participants | 21 Participants | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 24 / 29 | 53 / 61 |
| serious Total, serious adverse events | 0 / 29 | 3 / 61 |
Outcome results
Primary
Difference in Time Between Recovery of T4/T1 Ratio to 0.9 as Measured by TOF Watch® SX, and Reappearance of T4 as Measured by PNS, Within Participants, After Administration of 4.0 mg/kg Sugammadex
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.
Time frame: Up to 3 minutes after administering sugammadex
Population: The ITT population: all randomized participants who received 4.0 mg/kg sugammadex, and had at least one efficacy measurement. As dominant and non-dominant forearms were aimed at preventing bias; their differences were not analyzed. One participant who did not reach a T4/T1 ratio of 0.9 was not analyzed. The 1.0 mg/kg group was not evaluated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sugammadex 4.0 mg/kg | Difference in Time Between Recovery of T4/T1 Ratio to 0.9 as Measured by TOF Watch® SX, and Reappearance of T4 as Measured by PNS, Within Participants, After Administration of 4.0 mg/kg Sugammadex | 0.8 Minutes | 95% Confidence Interval 0.6 |
Primary
Time From Start of Administration of 4.0 mg/kg Sugammadex to Reappearance of T4 Measured by a Peripheral Nerve Stimulator (PNS)
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.
Time frame: up to 2 minutes after administering sugammadex
Population: The ITT population consisting of all randomized participants who received 4.0 mg/kg sugammadex, and had at least one efficacy measurement. As dominant and non-dominant forearms were aimed at preventing bias, their differences were not analyzed. Participants treated with 1.0 mg/kg were not evaluated for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sugammadex 4.0 mg/kg | Time From Start of Administration of 4.0 mg/kg Sugammadex to Reappearance of T4 Measured by a Peripheral Nerve Stimulator (PNS) | 0.8 Minutes | Standard Deviation 0.3 |
Primary
Time From Start of Administration of 4.0 mg/kg Sugammadex to Recovery of the T4/T1 Ratio to 0.9 Measured by a TOF-Watch® SX
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.
Time frame: Up to 4 minutes after administering sugammadex
Population: The Intent-To-Treat (ITT) population: randomized, received 4.0 mg/kg sugammadex, and had at least one efficacy measurement. As dominant and non-dominant forearms were aimed at preventing bias, their differences were not analyzed. One participant who did not reach a T4/T1 ratio of 0.9 was not analyzed.The 1.0 mg/kg group was not evaluated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sugammadex 4.0 mg/kg | Time From Start of Administration of 4.0 mg/kg Sugammadex to Recovery of the T4/T1 Ratio to 0.9 Measured by a TOF-Watch® SX | 1.5 Minutes | Standard Deviation 0.7 |
Other Pre-specified
Time From Start of Administration of 1.0 mg/kg Sugammadex to Reappearance of T4 Measured by a PNS
Neuromuscular function was monitored by applying repetitive TOF stimulations manually to the ulnar nerve of one forearm every 15 seconds & the number of twitches collected manually at the adductor pollicis muscle with the PNS by a blinded PNS assessor. T4 is the fourth twitch after TOF nerve stimulation. Only participants treated with 1.0 mg/kg sugammadex are presented, where the PNS on the dominant forearm n =15, and on the non-dominant forearm n = 14. The 4.0 mg/kg sugammadex group was not evaluated for this outcome measure.
Time frame: Up to 5 minutes after administering sugammadex
Population: The ITT population consisting of all randomized participants who received 1.0 mg/kg sugammadex, and had at least one efficacy measurement. As dominant and non-dominant forearms were aimed at preventing bias, their differences were not analyzed. Participants treated with 4.0 mg/kg were not evaluated for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sugammadex 4.0 mg/kg | Time From Start of Administration of 1.0 mg/kg Sugammadex to Reappearance of T4 Measured by a PNS | 1.7 Minutes | Standard Deviation 1.1 |
Other Pre-specified
Time From Start of Administration of 1.0 mg/kg Sugammadex to Recovery of the T4/T1 Ratio to 0.9 Measured by a TOF-Watch® SX
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 1.0 mg/kg sugammadex are presented where the TOF-Watch® SX on the dominant forearm n =15, and on the non-dominant forearm n = 14. The 4.0 mg/kg sugammadex group was not evaluated for this outcome measure.
Time frame: Up to 150 minutes after administering sugammadex
Population: The ITT population: randomized participants who received 1.0 mg/kg sugammadex, and had at least one efficacy measurement. As dominant and non-dominant forearms were aimed at preventing bias, their differences were not analyzed. One participant was not analyzed as the time of recovery was judged unreliable. The 4.0 mg/kg group was not evaluated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sugammadex 4.0 mg/kg | Time From Start of Administration of 1.0 mg/kg Sugammadex to Recovery of the T4/T1 Ratio to 0.9 Measured by a TOF-Watch® SX | 17.2 Minutes | Standard Deviation 28.6 |
Other Pre-specified
Time From Start of Administration of 1.0 or 4.0 mg/kg Sugammadex to Reappearance of T4 Measured by a TOF-Watch® SX
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. T4 is the fourth twitch after TOF nerve stimulation. For participants treated with 1.0 mg/kg sugammadex the TOF-Watch® SX on the dominant forearm n =15, and on the non-dominant forearm n = 14. For participants treated with 4.0 mg/kg sugammadex the TOF-Watch® SX on the dominant forearm n =30, and on the non-dominant forearm n = 31.
Time frame: Up to 7 minutes after administering sugammadex
Population: The ITT population consisting of all randomized participants who received 1.0 or 4.0 mg/kg sugammadex, and had at least one efficacy measurement. As dominant and non-dominant forearms were aimed at preventing bias, their differences were not analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sugammadex 4.0 mg/kg | Time From Start of Administration of 1.0 or 4.0 mg/kg Sugammadex to Reappearance of T4 Measured by a TOF-Watch® SX | 2.1 Minutes | Standard Deviation 1.6 |
| Sugammadex 4.0 mg/kg | Time From Start of Administration of 1.0 or 4.0 mg/kg Sugammadex to Reappearance of T4 Measured by a TOF-Watch® SX | 0.8 Minutes | Standard Deviation 0.2 |
Other Pre-specified
Time From Start of Administration of 1.0 or 4.0 mg/kg Sugammadex to Recovery of the T4/T1 Ratio to 0.7 Measured by a TOF-Watch® SX
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 0.7. A higher T4/T1 ratio indicates a lower degree of neuromuscular blockade, with a value of 1.0 representing full recovery. For participants treated with 1.0 mg/kg sugammadex the TOF-Watch® SX on the dominant forearm n =15, and on the non-dominant forearm n = 14. For participants treated with 4.0 mg/kg sugammadex the TOF-Watch® SX on the dominant forearm n =30, and on the non-dominant forearm n = 31.
Time frame: Up to 42 minutes after administering sugammadex
Population: The ITT population consisting of all randomized participants who received 1.0 or 4.0 mg/kg sugammadex, and had at least one efficacy measurement. As dominant and non-dominant forearms were aimed at preventing bias, their differences were not analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sugammadex 4.0 mg/kg | Time From Start of Administration of 1.0 or 4.0 mg/kg Sugammadex to Recovery of the T4/T1 Ratio to 0.7 Measured by a TOF-Watch® SX | 7.6 Minutes | Standard Deviation 10.2 |
| Sugammadex 4.0 mg/kg | Time From Start of Administration of 1.0 or 4.0 mg/kg Sugammadex to Recovery of the T4/T1 Ratio to 0.7 Measured by a TOF-Watch® SX | 1.1 Minutes | Standard Deviation 0.9 |
Other Pre-specified
Time From Start of Administration of 1.0 or 4.0 mg/kg Sugammadex to Recovery of the T4/T1 Ratio to 0.8 Measured by a TOF-Watch® SX
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 0.8. A higher T4/T1 ratio indicates a lower degree of neuromuscular blockade, with a value of 1.0 representing full recovery. For participants treated with 1.0 mg/kg sugammadex the TOF-Watch® SX on the dominant forearm n =15, and on the non-dominant forearm n = 14. For participants treated with 4.0 mg/kg sugammadex the TOF-Watch® SX on the dominant forearm n =30, and on the non-dominant forearm n = 31.
Time frame: Up to 42 minutes after administering sugammadex
Population: The ITT population consisting of all randomized participants who received 1.0 or 4.0 mg/kg sugammadex, and had at least one efficacy measurement. As dominant and non-dominant forearms were aimed at preventing bias, their differences were not analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sugammadex 4.0 mg/kg | Time From Start of Administration of 1.0 or 4.0 mg/kg Sugammadex to Recovery of the T4/T1 Ratio to 0.8 Measured by a TOF-Watch® SX | 9.9 Minutes | Standard Deviation 11.4 |
| Sugammadex 4.0 mg/kg | Time From Start of Administration of 1.0 or 4.0 mg/kg Sugammadex to Recovery of the T4/T1 Ratio to 0.8 Measured by a TOF-Watch® SX | 1.3 Minutes | Standard Deviation 1.4 |