Anesthesia, General, Neuromuscular Blockade
Conditions
Brief summary
The present trial is set up to evaluate the efficacy and safety of 4.0 mg.kg-1 sugammadex in Chinese and Caucasian subjects for registration purposes in China.
Interventions
DRUGSugammadex
After induction of anesthesia an intubation dose of 0.6 mg/kg rocuronium was to be administered. Maintenance doses of 0.1-0.2 mg/kg rocuronium intravenous (IV) could have been administered if necessary. At 1-2 PTC after the last administration of rocuronium, an IV single bolus dose of 4.0 mg/kg sugammadex was to be administered.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
-Subjects who are willing to provide informed consent; be between 18 and 64 years old; are American Society of Anaesthesiology (ASA) class 1-3 (extremes included); scheduled for elective surgery under general anesthesia, allowing stable neuromuscular monitoring, which requires neuromuscular blockade using rocuronium; be compliant with the dose/visit schedules, and use an accepted method of contraception (if applicable). For China only: Subjects of Chinese descent born in China, never emigrated out of China and have a Chinese home address. For Europe only: Subjects of Caucasian descent born in Europe, never emigrated out of Europe and have a European home address.
Exclusion criteria
-Subjects with expected difficult intubation, neuromuscular disorders affecting neuromuscular blockade, significant renal/hepatic dysfunction, use of a tourniquet, (family) history of malignant hyperthermia, allergy to general anesthesia medications, contraindication to study drugs, breast feeding, pregnant, participation in previous or new trials, a clinically significant condition that may interfere with the trial, or membership in the (family of) study/sponsor staff.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time From Start of Administration of Sugammadex to Recovery of the T4/T1 Ratio to 0.9 | Start of administration of sugammadex to recovery from neuromuscular blockade | 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. Nerve stimulation continued until the ratio of the magnitude of the fourth twitch (T4) to first twitch (T1) reached at least 0.9. The greater the T4/T1 ratio the greater the recovery from neuromuscular blockade, with a value of 1.0 representing full recovery. Analysis of recovery in Chinese subjects was the primary objective; Caucasian subjects and between-group analyses were secondary. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time From Start of Administration of Sugammadex to Recovery of the T4/T1 Ratio to 0.7 | Start of administration of sugammadex to recovery from neuromuscular blockade | 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. The greater the T4/T1 ratio the greater the recovery from neuromuscular blockade. |
| Time From Start of Administration of Sugammadex to Recovery of the T4/T1 Ratio to 0.8 | Start of administration of sugammadex to recovery from neuromuscular blockade | 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. The greater the T4/T1 ratio the greater the recovery from neuromuscular blockade. |
Participant flow
Pre-assignment details
Two subjects were screened but not enrolled (one Chinese subject and one Caucasian subject).
Participants by arm
| Arm | Count |
|---|---|
| Sugammadex in Chinese Subjects At 1-2 post-tetanic counts (PTC) after the last dose of rocuronium, 4.0 mg.kg-1 sugammadex was to be administered. Chinese subjects living in China. | 115 |
| Sugammadex in Caucasian Subjects At 1-2 post-tetanic counts (PTC) after the last dose of rocuronium, 4.0 mg.kg-1 sugammadex was to be administered. Caucasian subjects living in Europe. | 36 |
| Total | 151 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Administrative | 9 | 0 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Subject Withdrew Consent | 3 | 0 |
Baseline characteristics
| Characteristic | Sugammadex in Chinese Subjects | Sugammadex in Caucasian Subjects | Total |
|---|---|---|---|
| Age, Continuous | 47.9 years STANDARD_DEVIATION 10 | 47.2 years STANDARD_DEVIATION 11 | 47.7 years STANDARD_DEVIATION 10.2 |
| Sex: Female, Male Female | 66 Participants | 29 Participants | 95 Participants |
| Sex: Female, Male Male | 49 Participants | 7 Participants | 56 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 46 / 115 | 20 / 36 |
| serious Total, serious adverse events | 0 / 115 | 1 / 36 |
Outcome results
Primary
Time From Start of Administration of Sugammadex to Recovery of the 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. Nerve stimulation continued until the ratio of the magnitude of the fourth twitch (T4) to first twitch (T1) reached at least 0.9. The greater the T4/T1 ratio the greater the recovery from neuromuscular blockade, with a value of 1.0 representing full recovery. Analysis of recovery in Chinese subjects was the primary objective; Caucasian subjects and between-group analyses were secondary.
Time frame: Start of administration of sugammadex to recovery from neuromuscular blockade
Population: The Full Analysis Set (FAS) consisted of all subjects who received sugammadex and had at least one efficacy measurement. One treated Chinese subject did not have any efficacy data and was thus excluded from the FAS. Hence, 114 Chinese Asian and 36 European Caucasian subjects were included in the FAS.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Sugammadex in Chinese Subjects | Time From Start of Administration of Sugammadex to Recovery of the T4/T1 Ratio to 0.9 | 2.3 minutes |
| Sugammadex in Caucasian Subjects | Time From Start of Administration of Sugammadex to Recovery of the T4/T1 Ratio to 0.9 | 1.4 minutes |
95% CI: [30, 72]
Secondary
Time From Start of Administration of Sugammadex to Recovery of the T4/T1 Ratio to 0.7
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. The greater the T4/T1 ratio the greater the recovery from neuromuscular blockade.
Time frame: Start of administration of sugammadex to recovery from neuromuscular blockade
Population: The Full Analysis Set (FAS) consisted of all subjects who received sugammadex and had at least one efficacy measurement. One treated Chinese subject did not have any efficacy data and was thus excluded from the FAS. Hence, 114 Chinese Asian and 36 European Caucasian subjects were included in the FAS.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Sugammadex in Chinese Subjects | Time From Start of Administration of Sugammadex to Recovery of the T4/T1 Ratio to 0.7 | 1.6 minutes |
| Sugammadex in Caucasian Subjects | Time From Start of Administration of Sugammadex to Recovery of the T4/T1 Ratio to 0.7 | 1.1 minutes |
Secondary
Time From Start of Administration of Sugammadex to Recovery of the T4/T1 Ratio to 0.8
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. The greater the T4/T1 ratio the greater the recovery from neuromuscular blockade.
Time frame: Start of administration of sugammadex to recovery from neuromuscular blockade
Population: The Full Analysis Set (FAS) consisted of all subjects who received sugammadex and had at least one efficacy measurement. One treated Chinese subject did not have any efficacy data and was thus excluded from the FAS. Hence, 114 Chinese Asian and 36 European Caucasian subjects were included in the FAS.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Sugammadex in Chinese Subjects | Time From Start of Administration of Sugammadex to Recovery of the T4/T1 Ratio to 0.8 | 1.9 minutes |
| Sugammadex in Caucasian Subjects | Time From Start of Administration of Sugammadex to Recovery of the T4/T1 Ratio to 0.8 | 1.2 minutes |