Anesthesia, General
Conditions
Brief summary
The purpose of the study is to compare the effectiveness, safety and pharmacokinetics of sugammadex in participants 65 and over with participants under 65. There is no hypothesis defined for the study.
Interventions
DRUGSugammadex
DRUGRocurium
intravenous (IV) single bolus dose of 0.6 mg.kg-1
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
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 to 3 * 18 years of age or older * Scheduled for elective surgical procedure under general anesthesia requiring neuromuscular block with the use of rocuronium * Scheduled for surgery in supine position * Given written informed consent
Exclusion criteria
* Participants in whom a difficult intubation is expected due to anatomical malformations * Participants known or suspected to have neuromuscular disorders impairing neuromuscular blockade and/or significant renal dysfunction * Participants known or suspected to have a (family) history of malignant hyperthermia * Participants known or suspected to have an allergy to narcotics, muscle relaxants or other medications used during surgery * Participants receiving medication known to interfere with neuromuscular blocking agents such as anticonvulsants, antibiotics and magnesium * Female participants who are pregnant or breast-feeding * Females participants of childbearing potential not using an acceptable method of birth control \[condom or diaphragm with spermicide, vasectomized partner (\> 6 months), intrauterine device (IUD), abstinence\] * Participants who had already participated in a Org 25969 trial including Protocol 19.4.305 * Participants who had participated in another clinical trial, not pre-approved by Organon, within 30 days of entering into Protocol 19.4.305
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Time From Start of Administration of Sugammadex to Recovery of the T4/T1 Ratio to 0.9 | up to 10 minutes from start of sugammadex | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Time From Start of Administration of Sugammadex to Recovery of the T4/T1 Ratio to 0.7 | up to 10 minutes from start of sugammadex | 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 0.7. 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 Administration of to Recovery of the T4/T1 Ratio to 0.8 | up to 10 minutes from start of sugammadex | 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 0.8. A higher T4/T1 ratio indicates a lower degree of neuromuscular blockade, with a value of 1.0 representing full recovery. |
| Participants Level of Consciousness Prior to Transfer to the Recovery Room After Extubation | Prior to Transfer to the Recovery Room After Extubation (up to 24 hours) | Participants level of consciousness was assessed post-extubation and prior to transfer to recovery room. The levels were reported as: awake and oriented; arousable with minimal stimulation; responsive only to tactile stimulation. The number of participants in each of the 3 categories was summarized. |
| Participants Level of Consciousness Prior to Discharge From Recovery Room | Prior to Discharge from Recovery Room (up to 24 hours) | Participants level of consciousness was assessed prior to discharge from the recovery room. The levels were reported as: awake and oriented; arousable with minimal stimulation; responsive only to tactile stimulation. The number of participants in each of the 3 categories was summarized. |
| Number of Participants With General Muscle Weakness Prior to Transfer to the Recovery Room After Extubation | Prior to Transfer to the Recovery Room After Extubation (up to 24 hours) | The number of participants experiencing general muscle weakness was assessed by the investigator as a measure of recovery from neuromuscular blockade post-extubation and prior to transfer to recovery room. A standardized examination form was used to determine the presence or absence of muscle weakness in various muscle groups and the overall assessments were reported as yes or no to general muscle weakness. Participants who were not cooperative with the examination were not included in the assessment. |
| Number of Participants With General Muscle Weakness Prior to Discharge From Recovery Room | Prior to Discharge from Recovery Room (up to 24 hours) | The number of participants experiencing general muscle weakness was assessed by the investigator as a measure of recovery from neuromuscular blockade prior to discharge from the recovery room. A standardized examination form was used to determine the presence or absence of muscle weakness in various muscle groups and the overall assessments were reported as yes or no to general muscle weakness. Participants who were not cooperative with the examination were not included in the assessment. |
| Number of Participants Who Can Perform a 5 Second Head Lift Prior to Transfer to the Recovery Room After Extubation | Prior to Transfer to the Recovery Room After Extubation (up to 24 hours) | Participants were asked to lift their head off the table while in a supine position post-extubation and prior to transfer to recovery room. The number of participants who could perform the 5 second head lift was summarized. Participants who were not cooperative with the examination were not included in the assessment. |
| Number of Participants Who Can Perform a 5 Second Head Lift Prior to Discharge From Recovery Room | Prior to Discharge from Recovery Room (up to 24 hours) | Participants were asked to lift their head off the table while in a supine position just prior to discharge from the recovery room. The number of participants who could perform the 5 second head lift was summarized. Participants who were not cooperative with the examination were not included in the assessment. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Participants 18 to 64 Years Old 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 T2 with an intravenous single bolus dose of 2.0 mg.kg-1 of sugammadex. | 48 |
| Participants 65 to 74 Years Old 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. | 62 |
| Participants 75 Years and Older 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. | 40 |
| Total | 150 |
Baseline characteristics
| Characteristic | Participants 18 to 64 Years Old | Participants 65 to 74 Years Old | Participants 75 Years and Older | Total |
|---|---|---|---|---|
| Age, Continuous | 45.5 Years STANDARD_DEVIATION 11.32 | 69.2 Years STANDARD_DEVIATION 2.53 | 80.1 Years STANDARD_DEVIATION 4.08 | 64.5 Years STANDARD_DEVIATION 15.41 |
| Sex: Female, Male Female | 29 Participants | 27 Participants | 24 Participants | 80 Participants |
| Sex: Female, Male Male | 19 Participants | 35 Participants | 16 Participants | 70 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 48 | 0 / 62 | 0 / 40 |
| other Total, other adverse events | 48 / 48 | 62 / 62 | 40 / 40 |
| serious Total, serious adverse events | 4 / 48 | 8 / 62 | 3 / 40 |
Outcome results
Primary
Mean Time From Start of Administration of Sugammadex to Recovery of the T4/T1 Ratio to 0.9
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.
Time frame: up to 10 minutes from start of sugammadex
Population: All participants that received study drug and had at least 1 post-baseline efficacy measurement. Missing data were imputed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Participants 18 to 64 Years Old | Mean Time From Start of Administration of Sugammadex to Recovery of the T4/T1 Ratio to 0.9 | 2.53 Minutes | Standard Deviation 1.35 |
| Participants 65 to 74 Years Old | Mean Time From Start of Administration of Sugammadex to Recovery of the T4/T1 Ratio to 0.9 | 2.92 Minutes | Standard Deviation 1.63 |
| Participants 75 Years and Older | Mean Time From Start of Administration of Sugammadex to Recovery of the T4/T1 Ratio to 0.9 | 3.93 Minutes | Standard Deviation 1.67 |
Secondary
Mean Time From Start of Administration of Sugammadex to Recovery of the T4/T1 Ratio to 0.7
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 0.7. A higher T4/T1 ratio indicates a lower degree of neuromuscular blockade, with a value of 1.0 representing full recovery.
Time frame: up to 10 minutes from start of sugammadex
Population: All participants that received study drug and had at least 1 post-baseline efficacy measurement. Missing data were imputed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Participants 18 to 64 Years Old | Mean Time From Start of Administration of Sugammadex to Recovery of the T4/T1 Ratio to 0.7 | 1.77 Minutes | Standard Deviation 0.78 |
| Participants 65 to 74 Years Old | Mean Time From Start of Administration of Sugammadex to Recovery of the T4/T1 Ratio to 0.7 | 2.10 Minutes | Standard Deviation 1.47 |
| Participants 75 Years and Older | Mean Time From Start of Administration of Sugammadex to Recovery of the T4/T1 Ratio to 0.7 | 2.68 Minutes | Standard Deviation 1.17 |
Secondary
Mean Time From Start of Administration of to Recovery of the T4/T1 Ratio to 0.8
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 0.8. A higher T4/T1 ratio indicates a lower degree of neuromuscular blockade, with a value of 1.0 representing full recovery.
Time frame: up to 10 minutes from start of sugammadex
Population: All participants that received study drug and had at least 1 post-baseline efficacy measurement. Missing data were imputed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Participants 18 to 64 Years Old | Mean Time From Start of Administration of to Recovery of the T4/T1 Ratio to 0.8 | 2.05 Minutes | Standard Deviation 0.98 |
| Participants 65 to 74 Years Old | Mean Time From Start of Administration of to Recovery of the T4/T1 Ratio to 0.8 | 2.38 Minutes | Standard Deviation 1.55 |
| Participants 75 Years and Older | Mean Time From Start of Administration of to Recovery of the T4/T1 Ratio to 0.8 | 3.10 Minutes | Standard Deviation 1.35 |
Secondary
Number of Participants Who Can Perform a 5 Second Head Lift Prior to Discharge From Recovery Room
Participants were asked to lift their head off the table while in a supine position just prior to discharge from the recovery room. The number of participants who could perform the 5 second head lift was summarized. Participants who were not cooperative with the examination were not included in the assessment.
Time frame: Prior to Discharge from Recovery Room (up to 24 hours)
Population: All participants that received study drug, had at least 1 post-baseline efficacy measurement and were determined to be cooperative.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants 18 to 64 Years Old | Number of Participants Who Can Perform a 5 Second Head Lift Prior to Discharge From Recovery Room | 46 Participants |
| Participants 65 to 74 Years Old | Number of Participants Who Can Perform a 5 Second Head Lift Prior to Discharge From Recovery Room | 58 Participants |
| Participants 75 Years and Older | Number of Participants Who Can Perform a 5 Second Head Lift Prior to Discharge From Recovery Room | 38 Participants |
Secondary
Number of Participants Who Can Perform a 5 Second Head Lift Prior to Transfer to the Recovery Room After Extubation
Participants were asked to lift their head off the table while in a supine position post-extubation and prior to transfer to recovery room. The number of participants who could perform the 5 second head lift was summarized. Participants who were not cooperative with the examination were not included in the assessment.
Time frame: Prior to Transfer to the Recovery Room After Extubation (up to 24 hours)
Population: All participants that received study drug, had at least 1 post-baseline efficacy measurement and were determined to be cooperative.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants 18 to 64 Years Old | Number of Participants Who Can Perform a 5 Second Head Lift Prior to Transfer to the Recovery Room After Extubation | 40 Participants |
| Participants 65 to 74 Years Old | Number of Participants Who Can Perform a 5 Second Head Lift Prior to Transfer to the Recovery Room After Extubation | 57 Participants |
| Participants 75 Years and Older | Number of Participants Who Can Perform a 5 Second Head Lift Prior to Transfer to the Recovery Room After Extubation | 31 Participants |
Secondary
Number of Participants With General Muscle Weakness Prior to Discharge From Recovery Room
The number of participants experiencing general muscle weakness was assessed by the investigator as a measure of recovery from neuromuscular blockade prior to discharge from the recovery room. A standardized examination form was used to determine the presence or absence of muscle weakness in various muscle groups and the overall assessments were reported as yes or no to general muscle weakness. Participants who were not cooperative with the examination were not included in the assessment.
Time frame: Prior to Discharge from Recovery Room (up to 24 hours)
Population: All participants that received study drug, had at least 1 post-baseline efficacy measurement and were determined to be cooperative.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants 18 to 64 Years Old | Number of Participants With General Muscle Weakness Prior to Discharge From Recovery Room | 0 Participants |
| Participants 65 to 74 Years Old | Number of Participants With General Muscle Weakness Prior to Discharge From Recovery Room | 0 Participants |
| Participants 75 Years and Older | Number of Participants With General Muscle Weakness Prior to Discharge From Recovery Room | 1 Participants |
Secondary
Number of Participants With General Muscle Weakness Prior to Transfer to the Recovery Room After Extubation
The number of participants experiencing general muscle weakness was assessed by the investigator as a measure of recovery from neuromuscular blockade post-extubation and prior to transfer to recovery room. A standardized examination form was used to determine the presence or absence of muscle weakness in various muscle groups and the overall assessments were reported as yes or no to general muscle weakness. Participants who were not cooperative with the examination were not included in the assessment.
Time frame: Prior to Transfer to the Recovery Room After Extubation (up to 24 hours)
Population: All participants that received study drug, had at least 1 post-baseline efficacy measurement and were determined to be cooperative.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants 18 to 64 Years Old | Number of Participants With General Muscle Weakness Prior to Transfer to the Recovery Room After Extubation | 0 Participants |
| Participants 65 to 74 Years Old | Number of Participants With General Muscle Weakness Prior to Transfer to the Recovery Room After Extubation | 3 Participants |
| Participants 75 Years and Older | Number of Participants With General Muscle Weakness Prior to Transfer to the Recovery Room After Extubation | 1 Participants |
Secondary
Participants Level of Consciousness Prior to Discharge From Recovery Room
Participants level of consciousness was assessed prior to discharge from the recovery room. The levels were reported as: awake and oriented; arousable with minimal stimulation; responsive only to tactile stimulation. The number of participants in each of the 3 categories was summarized.
Time frame: Prior to Discharge from Recovery Room (up to 24 hours)
Population: All participants that received study drug and had at least 1 post-baseline efficacy measurement and had data available for endpoint
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Participants 18 to 64 Years Old | Participants Level of Consciousness Prior to Discharge From Recovery Room | Arousable with minimal stimulation | 3 Participants |
| Participants 18 to 64 Years Old | Participants Level of Consciousness Prior to Discharge From Recovery Room | Awake and oriented | 43 Participants |
| Participants 18 to 64 Years Old | Participants Level of Consciousness Prior to Discharge From Recovery Room | Responsive only to tactile stimulation | 0 Participants |
| Participants 65 to 74 Years Old | Participants Level of Consciousness Prior to Discharge From Recovery Room | Arousable with minimal stimulation | 2 Participants |
| Participants 65 to 74 Years Old | Participants Level of Consciousness Prior to Discharge From Recovery Room | Awake and oriented | 56 Participants |
| Participants 65 to 74 Years Old | Participants Level of Consciousness Prior to Discharge From Recovery Room | Responsive only to tactile stimulation | 0 Participants |
| Participants 75 Years and Older | Participants Level of Consciousness Prior to Discharge From Recovery Room | Awake and oriented | 36 Participants |
| Participants 75 Years and Older | Participants Level of Consciousness Prior to Discharge From Recovery Room | Responsive only to tactile stimulation | 0 Participants |
| Participants 75 Years and Older | Participants Level of Consciousness Prior to Discharge From Recovery Room | Arousable with minimal stimulation | 2 Participants |
Secondary
Participants Level of Consciousness Prior to Transfer to the Recovery Room After Extubation
Participants level of consciousness was assessed post-extubation and prior to transfer to recovery room. The levels were reported as: awake and oriented; arousable with minimal stimulation; responsive only to tactile stimulation. The number of participants in each of the 3 categories was summarized.
Time frame: Prior to Transfer to the Recovery Room After Extubation (up to 24 hours)
Population: All participants that received study drug, had at least 1 post-baseline efficacy measurement and had data available for endpoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Participants 18 to 64 Years Old | Participants Level of Consciousness Prior to Transfer to the Recovery Room After Extubation | Arousable with minimal stimulation | 21 Participants |
| Participants 18 to 64 Years Old | Participants Level of Consciousness Prior to Transfer to the Recovery Room After Extubation | Awake and oriented | 24 Participants |
| Participants 18 to 64 Years Old | Participants Level of Consciousness Prior to Transfer to the Recovery Room After Extubation | Responsive only to tactile stimulation | 2 Participants |
| Participants 65 to 74 Years Old | Participants Level of Consciousness Prior to Transfer to the Recovery Room After Extubation | Arousable with minimal stimulation | 22 Participants |
| Participants 65 to 74 Years Old | Participants Level of Consciousness Prior to Transfer to the Recovery Room After Extubation | Awake and oriented | 38 Participants |
| Participants 65 to 74 Years Old | Participants Level of Consciousness Prior to Transfer to the Recovery Room After Extubation | Responsive only to tactile stimulation | 1 Participants |
| Participants 75 Years and Older | Participants Level of Consciousness Prior to Transfer to the Recovery Room After Extubation | Awake and oriented | 21 Participants |
| Participants 75 Years and Older | Participants Level of Consciousness Prior to Transfer to the Recovery Room After Extubation | Responsive only to tactile stimulation | 2 Participants |
| Participants 75 Years and Older | Participants Level of Consciousness Prior to Transfer to the Recovery Room After Extubation | Arousable with minimal stimulation | 17 Participants |