Anesthesia, General
Conditions
Brief summary
The primary purpose of the study is to determine the time-course of recovery to a T4/T1 ratio of 0.9 within 4 minutes after 4.0 mg.kg\^-1 Sugammadex is administered at least 15 minutes after the last administration of rocuronium in a wide range of surgical procedures and anesthetic regimens (routine use). Safety evaluation is part of the study.
Interventions
DRUGSugammadex
At least 15 minutes after the intubation dose or the last maintenance dose of rocuronium, an intravenous single bolus dose of 4.0 mg/kg Org 25969 was administered.
DRUGRocuronium
Each participant received an intravenous single bolus dose of 0.6 mg/kg rocuronium. If further neuromuscular block was required after endotracheal intubation, maintenance dose(s) of 0.15 mg/kg rocuronium was/were administered.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* American Society of Anesthesiologists (ASA) Class 1-3 participants who are scheduled to undergo an elective surgical procedure under general anesthesia requiring neuromuscular relaxation with the use of rocuronium.
Exclusion criteria
* Participants with neuromuscular disorders, significant renal dysfunction, malignant hyperthermia, allergy to medications used in general anesthesia and in whom difficult intubation is expected. * Participants taking medications known to interfere with neuromuscular blocking agents. * Participants who are of child-bearing potential, pregnant, and breast feeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time From Start of MK-8616 Administration to Recovery of the T4/T1 Ratio to 0.9 | Up to approximately 30 minutes following administration of study treatment | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time From Start of MK-8616 Administration to Recovery of the T4/T1 Ratio to 0.7 | Up to approximately 10 minutes following administration of study treatment | Mean time from start of MK-8616 administration to recovery of participant T4/T1 ratio to 0.7 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 0.7 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). |
| Time From Start of MK-8616 Administration to Recovery of the T4/T1 Ratio to 0.8 | Up to approximately 15 minutes following administration of study treatment | Mean time from start of MK-8616 administration to recovery of participant T4/T1 ratio to 0.8 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 0.8 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). |
| Clinical Assessment of Recovery - Participant's Level of Consciousness | Up to 24 hours | The quality of recovery was assessed by asking the participant 40 questions from a validated Quality of Recovery Questionnaire (QoR-40). Participants were assessed for level of consciousness (i.e., awake and oriented, arousable with minimal stimulation, responsive only to tactile stimulation), if applicable, by asking their name, if they are aware of where they are, and what day it is. Assessment 1 occurred prior to transfer to the recovery room after extubation and Assessment 2 occurred prior to discharge from the recovery room. |
| Clinical Assessments of Recovery - Participant Able to Perform 5-second Head Lift (5SHL) | Up to 24 hours | 5-second head lift test was assessment of the ability of the participant to lift the head for 5 seconds and was performed by a blinded safety assessor. Tests were repeated every 15 minutes until the participant could successfully perform the 5-second head-lift. Assessment 1 occurred prior to transfer to the recovery room after extubation and Assessment 2 occurred prior to discharge from the recovery room. |
| Clinical Assessments of Recovery - Check for General Muscle Weakness (GMW) | Up to 24 hours | General muscle weakness check was assessed by the investigator. The assessment of general muscle weakness was based on a scale from 0-10, with 0 representing total paralysis, 1 signifying extreme impairment, 9 for close to no impairment, and 10 for normal muscle strength. Scores of 3, 4, 5, etc. denoted increasing muscle strength in approximately 10% increments. Scores of 9 and lower were denoted as GMW. Assessment 1 occurred prior to transfer to the recovery room after extubation and assessment 2 occurred prior to discharge from the recovery room. |
Participant flow
Recruitment details
The trial was conducted in 19 trial sites in the United States.
Participants by arm
| Arm | Count |
|---|---|
| Sugammadex Each participant received an intravenous single bolus dose of 0.6 mg/kg rocuronium. If further neuromuscular block was required after endotracheal intubation, maintenance dose(s) of 0.15 mg/kg rocuronium was administered. At least 15 minutes after the intubation dose or the last maintenance dose of rocuronium, an intravenous single bolus dose of 4.0 mg/kg MK-8616 was administered. | 197 |
| Total | 197 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Lost to Follow-up | 3 |
| Overall Study | Participants did not receive treatment | 27 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Sugammadex |
|---|---|
| Age, Continuous | 53 Years STANDARD_DEVIATION 15 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants |
| Race (NIH/OMB) Black or African American | 18 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 172 Participants |
| Sex: Female, Male Female | 103 Participants |
| Sex: Female, Male Male | 94 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 197 |
| other Total, other adverse events | 187 / 197 |
| serious Total, serious adverse events | 8 / 197 |
Outcome results
Primary
Time From Start of MK-8616 Administration to Recovery of the T4/T1 Ratio to 0.9
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).
Time frame: Up to approximately 30 minutes following administration of study treatment
Population: The analysis population consisted of all treated participants had at least one post baseline T4/T1 ratio to 0.9 efficacy measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sugammadex | Time From Start of MK-8616 Administration to Recovery of the T4/T1 Ratio to 0.9 | 2.32 Minutes | Standard Deviation 2.15 |
Secondary
Clinical Assessment of Recovery - Participant's Level of Consciousness
The quality of recovery was assessed by asking the participant 40 questions from a validated Quality of Recovery Questionnaire (QoR-40). Participants were assessed for level of consciousness (i.e., awake and oriented, arousable with minimal stimulation, responsive only to tactile stimulation), if applicable, by asking their name, if they are aware of where they are, and what day it is. Assessment 1 occurred prior to transfer to the recovery room after extubation and Assessment 2 occurred prior to discharge from the recovery room.
Time frame: Up to 24 hours
Population: The analysis population consisted of all participants who received investigational product and had at least one post baseline efficacy measurement for the analysis endpoint.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Sugammadex | Clinical Assessment of Recovery - Participant's Level of Consciousness | Awake and oriented - Assessment 1 | 138 Participants |
| Sugammadex | Clinical Assessment of Recovery - Participant's Level of Consciousness | Awake and oriented - Assessment 2 | 184 Participants |
| Sugammadex | Clinical Assessment of Recovery - Participant's Level of Consciousness | Arousable with minimal stimulation - Assessment 1 | 51 Participants |
| Sugammadex | Clinical Assessment of Recovery - Participant's Level of Consciousness | Arousable with minimal stimulation - Assessment 2 | 12 Participants |
| Sugammadex | Clinical Assessment of Recovery - Participant's Level of Consciousness | Responsive only to tactile stimulation - Assess. 1 | 8 Participants |
| Sugammadex | Clinical Assessment of Recovery - Participant's Level of Consciousness | Responsive only to tactile stimulation - Assess. 2 | 0 Participants |
Secondary
Clinical Assessments of Recovery - Check for General Muscle Weakness (GMW)
General muscle weakness check was assessed by the investigator. The assessment of general muscle weakness was based on a scale from 0-10, with 0 representing total paralysis, 1 signifying extreme impairment, 9 for close to no impairment, and 10 for normal muscle strength. Scores of 3, 4, 5, etc. denoted increasing muscle strength in approximately 10% increments. Scores of 9 and lower were denoted as GMW. Assessment 1 occurred prior to transfer to the recovery room after extubation and assessment 2 occurred prior to discharge from the recovery room.
Time frame: Up to 24 hours
Population: The analysis population consisted of all participants who received investigational product and had at least one post baseline efficacy measurement for the analysis endpoint.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Sugammadex | Clinical Assessments of Recovery - Check for General Muscle Weakness (GMW) | GMW present during Assessment 1 | 4 Participants |
| Sugammadex | Clinical Assessments of Recovery - Check for General Muscle Weakness (GMW) | GMW present during Assessment 2 | 9 Participants |
Secondary
Clinical Assessments of Recovery - Participant Able to Perform 5-second Head Lift (5SHL)
5-second head lift test was assessment of the ability of the participant to lift the head for 5 seconds and was performed by a blinded safety assessor. Tests were repeated every 15 minutes until the participant could successfully perform the 5-second head-lift. Assessment 1 occurred prior to transfer to the recovery room after extubation and Assessment 2 occurred prior to discharge from the recovery room.
Time frame: Up to 24 hours
Population: The analysis population consisted of all participants who received investigational product and had at least one post baseline efficacy measurement for the analysis endpoint.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Sugammadex | Clinical Assessments of Recovery - Participant Able to Perform 5-second Head Lift (5SHL) | Able to perform 5SHL during Assessment 1 | 173 Participants |
| Sugammadex | Clinical Assessments of Recovery - Participant Able to Perform 5-second Head Lift (5SHL) | Able to perform 5SHL during Assessment 2 | 196 Participants |
Secondary
Time From Start of MK-8616 Administration to Recovery of the T4/T1 Ratio to 0.7
Mean time from start of MK-8616 administration to recovery of participant T4/T1 ratio to 0.7 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 0.7 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).
Time frame: Up to approximately 10 minutes following administration of study treatment
Population: The analysis population consisted of all treated participants had at least one post baseline T4/T1 ratio to 0.7 efficacy measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sugammadex | Time From Start of MK-8616 Administration to Recovery of the T4/T1 Ratio to 0.7 | 1.50 Minutes | Standard Deviation 1.07 |
Secondary
Time From Start of MK-8616 Administration to Recovery of the T4/T1 Ratio to 0.8
Mean time from start of MK-8616 administration to recovery of participant T4/T1 ratio to 0.8 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 0.8 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).
Time frame: Up to approximately 15 minutes following administration of study treatment
Population: The analysis population consisted of all treated participants had at least one post baseline T4/T1 ratio to 0.8 efficacy measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sugammadex | Time From Start of MK-8616 Administration to Recovery of the T4/T1 Ratio to 0.8 | 1.80 Minutes | Standard Deviation 1.37 |