Neuromuscular Blockade
Conditions
Brief summary
This is a randomized, active-controlled, parallel-group, single-dose, multi-site, safety-assessor blinded study comparing sugammadex to neostigmine for reversal of neuromuscular blockade in Korean subjects undergoing elective surgical procedures under general anesthesia that require rocuronium for neuromuscular blockade. Study medication will be administered at reappearance of T2. Time to recovery will be measured from start of study medication administration to recovery of the T4/T1 ratio of 0.9. The primary hypothesis is that the time to recovery of the T4/T1 ratio of 0.9 is shorter with sugammadex than with neostigmine.
Interventions
DRUGsugammadex
sugammadex 2.0 mg/kg, single intravenous bolus dose administered within 10 seconds into a fast flowing venous infusion
DRUGneostigmine
neostigmine 50 mcg/kg (total dose not to exceed 5.0 mg) combined with glycopyrrolate 10 mcg/kg, single intravenous bolus dose administered within 10 seconds into a fast flowing venous infusion
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* American Society of Anesthesiologists Class 1 or 2 or 3 * \>=18 years of age and of either sex * scheduled for elective surgical procedure under general anesthesia requiring the use of rocuronium for endotracheal intubation and/or maintenance of neuromuscular blockade in a supine position allowing neuromuscular transmission monitoring and requiring reversal of neuromuscular blockade * Korean descent born in Korea, never emigrated out of Korea, and have a Korean home address
Exclusion criteria
* expected difficult intubation due to anatomic malformations * expected transfer to intensive care unit after surgery * neuromuscular disorders affecting neuromuscular blockade * significant hepatic or renal dysfunction * require use of pneumatic tourniquet during surgery * (family) history of malignant hyperthermia * allergy to cyclodextrins (including sugammadex) or other medication(s) used during general anesthesia; use of toremifene or fusidic acid within 24 hours of study drug administration; contraindication to use of neostigmine or glycopyrrolate
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time From Start of Study Drug Administration to Recovery of the T4/T1 Ratio to 0.9 | From Start of Study Drug Administration to Recovery of the T4/T1 Ratio to 0.9 (estimated from 2 minutes up to ~15 minutes) | Neuromuscular functioning was monitored by applying repetitive Train-Of-Four (TOF) electrical stimulations to the ulnar nerve every 15 seconds & assessing twitch response at the adductor pollicis muscle. T1 & T4 refer to the magnitudes (height) of the 1st & 4th twitches, respectively, after TOF nerve stimulation. The T4/T1 Ratio (expressed as a decimal of up to 1.0) indicates the extent of recovery from neuromuscular blockade. In this study, twitch responses were recorded until the T4/T1 Ratio reached \>= 0.9, the minimum acceptable ratio that indicated complete recovery. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sugammadex sugammadex 2 mg/kg | 60 |
| Neostigmine neostigmine 50 mcg/kg | 60 |
| Total | 120 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Administrative | 4 | 1 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 2 |
Baseline characteristics
| Characteristic | Sugammadex | Neostigmine | Total |
|---|---|---|---|
| Age, Continuous | 41.3 years STANDARD_DEVIATION 14 | 42.6 years STANDARD_DEVIATION 14 | 42.0 years STANDARD_DEVIATION 13.9 |
| Sex: Female, Male Female | 21 Participants | 23 Participants | 44 Participants |
| Sex: Female, Male Male | 39 Participants | 37 Participants | 76 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 36 / 60 | 42 / 60 |
| serious Total, serious adverse events | 2 / 60 | 2 / 60 |
Outcome results
Primary
Time From Start of Study Drug Administration 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 & assessing twitch response at the adductor pollicis muscle. T1 & T4 refer to the magnitudes (height) of the 1st & 4th twitches, respectively, after TOF nerve stimulation. The T4/T1 Ratio (expressed as a decimal of up to 1.0) indicates the extent of recovery from neuromuscular blockade. In this study, twitch responses were recorded until the T4/T1 Ratio reached \>= 0.9, the minimum acceptable ratio that indicated complete recovery.
Time frame: From Start of Study Drug Administration to Recovery of the T4/T1 Ratio to 0.9 (estimated from 2 minutes up to ~15 minutes)
Population: Full Analysis Set, defined as all participants who received randomized treatment and had at least one efficacy measurement.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Sugammadex | Time From Start of Study Drug Administration to Recovery of the T4/T1 Ratio to 0.9 | 1.77 minutes |
| Neostigmine | Time From Start of Study Drug Administration to Recovery of the T4/T1 Ratio to 0.9 | 14.80 minutes |
Comparison: To evaluate the efficacy of sugammadex compared to the efficacy of neostigmine, the ratio of the geometric means of time to recovery of the T4/T1 ratio to 0.9 was calculated using a 2-way ANOVA model adjusted for trial site.p-value: <0.000195% CI: [6.8, 9.6]ANOVA