Anesthesia, General
Conditions
Brief summary
The objective of the trial was to show equivalence in recovery from neuromuscular block after a single dose of 4.0 mg/kg sugammadex, administered at first twitch (T1) 3-10% after continuous infusion of rocuronium, between participants receiving maintenance anesthesia using propofol and participants receiving sevoflurane, to investigate the safety and to compare the plasma levels of rocuronium in participants after continuous infusion of rocuronium and before the administration of sugammadex, under either propofol or sevoflurane anesthesia.
Interventions
DRUGSugammadex
Single dose 4.0 mg/kg sugammadex, administered at T1 3-10% after continuous infusion of rocuronium
DRUGRocuronium
Single bolus dose 0.6 mg/kg rocuronium and continuous infusion rocuronium
DRUGSevoflurane
Sevoflurane IV administered for induction and maintenance of anesthesia, based on randomization.
DRUGPropofol
Propofol IV administered for induction and maintenance of anesthesia, based on randomization.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Participants at least 20 years but under 65 years of age; * Participants of American Society of Anesthesiologists (ASA) class 1-3; * Participants scheduled for a surgical procedure under general anesthesia requiring neuromuscular relaxation with the use of a neuromuscular blocking agent (NMBA) with an anticipated duration of surgery between 2 and 5 hours; * Participants scheduled for a surgical procedure in supine position; * Participants who had given written informed consent.
Exclusion criteria
* Participants in whom difficult intubation was expected because of anatomical malformations; * Participants known or suspected to have neuromuscular disorders affecting NMB and/or significant renal dysfunction. In Germany, this also included serum creatinine and blood urea nitrogen outside local reference ranges; * Participants known or suspected to have a (family) history of malignant hyperthermia; * Participants known or suspected to have an allergy to medications used during general anesthesia; * Participants receiving medication interfering with NMBAs, such as antibiotics, anticonvulsants and Mg\^2+; based on the dose and time of administration; * Pregnant or lactating females; * Female participants of childbearing potential not using any birth control or using only hormonal contraception as birth control; * Participants who had already participated in trial CT 19.4.312, or in another trial with sugammadex; * Participants who had participated in another clinical trial, not pre-approved by Organon, within 30 days of entering into CT 19.4.312.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Time From Start Administration of Sugammadex to Recovery of Fourth Twitch/First Twitch (T4/T1) Ratio to 0.9 | Up to 3 minutes after sugammadex administration | 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. |
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 3 minutes after sugammadex administration | Neuromuscular functioning was monitored by applying repetitive 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. A faster time to recovery of the T4/T1 ratio to 0.7 indicates a faster recovery from NMB. |
| Mean Time From Start of Administration of Sugammadex to Recovery of the T4/T1 Ratio to 0.8 | Up to 3 minutes after sugammadex administration | Neuromuscular functioning was monitored by applying repetitive 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. A faster time to recovery of the T4/T1 ratio to 0.8 indicates a faster recovery from NMB. |
Participant flow
Recruitment details
Participants who had a surgical procedure using a general anesthesia (with sevoflurane or propofol) and rocuronium for endotracheal intubation and maintenance of neuromuscular block (NMB) were enrolled in this study.
Pre-assignment details
Out of 52 randomized participants, 51 received treatment.
Participants by arm
| Arm | Count |
|---|---|
| Sugammadex + Sevoflurane 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. | 26 |
| Sugammadex + Propofol 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. | 25 |
| Total | 51 |
Baseline characteristics
| Characteristic | Sugammadex + Sevoflurane | Sugammadex + Propofol | Total |
|---|---|---|---|
| Age, Continuous | 49.8 Years STANDARD_DEVIATION 12.4 | 50.4 Years STANDARD_DEVIATION 8.3 | 50.1 Years STANDARD_DEVIATION 10.5 |
| Sex: Female, Male Female | 17 Participants | 18 Participants | 35 Participants |
| Sex: Female, Male Male | 9 Participants | 7 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 26 | 0 / 25 |
| other Total, other adverse events | 21 / 26 | 21 / 25 |
| serious Total, serious adverse events | 0 / 26 | 0 / 25 |
Outcome results
Primary
Mean Time From Start Administration of Sugammadex to Recovery of Fourth Twitch/First Twitch (T4/T1) Ratio to 0.9
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.
Time frame: Up to 3 minutes after sugammadex administration
Population: All randomized participants who received sugammadex and had at least one efficacy measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sugammadex + Sevoflurane | Mean Time From Start Administration of Sugammadex to Recovery of Fourth Twitch/First Twitch (T4/T1) Ratio to 0.9 | 1.45 minutes | Standard Deviation 0.45 |
| Sugammadex + Propofol | Mean Time From Start Administration of Sugammadex to Recovery of Fourth Twitch/First Twitch (T4/T1) Ratio to 0.9 | 1.32 minutes | Standard Deviation 0.4 |
Secondary
Mean Time From Start of Administration of Sugammadex to Recovery of the T4/T1 Ratio to 0.7
Neuromuscular functioning was monitored by applying repetitive 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. A faster time to recovery of the T4/T1 ratio to 0.7 indicates a faster recovery from NMB.
Time frame: Up to 3 minutes after sugammadex administration
Population: All randomized participants who received sugammadex and had at least one efficacy measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sugammadex + Sevoflurane | Mean Time From Start of Administration of Sugammadex to Recovery of the T4/T1 Ratio to 0.7 | 1.07 minutes | Standard Deviation 0.25 |
| Sugammadex + Propofol | Mean Time From Start of Administration of Sugammadex to Recovery of the T4/T1 Ratio to 0.7 | 1.02 minutes | Standard Deviation 0.28 |
Secondary
Mean Time From Start of Administration of Sugammadex to Recovery of the T4/T1 Ratio to 0.8
Neuromuscular functioning was monitored by applying repetitive 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. A faster time to recovery of the T4/T1 ratio to 0.8 indicates a faster recovery from NMB.
Time frame: Up to 3 minutes after sugammadex administration
Population: All randomized participants who received sugammadex and had at least one efficacy measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sugammadex + Sevoflurane | Mean Time From Start of Administration of Sugammadex to Recovery of the T4/T1 Ratio to 0.8 | 1.20 minutes | Standard Deviation 0.35 |
| Sugammadex + Propofol | Mean Time From Start of Administration of Sugammadex to Recovery of the T4/T1 Ratio to 0.8 | 1.12 minutes | Standard Deviation 0.3 |