Surgical Procedures, Elective
Conditions
Brief summary
This study will compare the incidence of residual neuromuscular blockade in participants who undergo reversal of neuromuscular blockade with sugammadex compared to those who undergo reversal of neuromuscular blockade with usual care (neostigmine/glycopyrrolate).
Interventions
DRUGGlycopyrrolate
glycopyrrolate per usual practice
DRUGNeostigmine
neostigmine, per usual practice
DRUGSugammadex
sugammadex, intravenous (IV) bolus, 2 or 4 mg/kg depending on level of neuromuscular recovery
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
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 or 2 or 3 * Scheduled to undergo an elective abdominal surgical procedure under general anesthesia; and: * expected to undergo neuromuscular relaxation with rocuronium for endotracheal intubation; and * expected to require at least one maintenance dose of rocuronium; and * expected to require active reversal of neuromuscular blockade; and * expected to require clinical or subjective neuromuscular monitoring only; and * expected to recover in the PACU * Arm that is accessible for measuring the TOF ratio in the PACU * Sexually active female patient of child-bearing potential must agree to use a medically accepted method of contraception through seven days after receiving protocol-specified medication.
Exclusion criteria
* Anatomical malformations that may lead to difficult intubation * Neuromuscular disorder(s) that may affect neuromuscular blockade and/or trial assessments * Dialysis-dependent or has or is suspected of having severe renal insufficiency * Significant hepatic dysfunction * Family history of malignant hyperthermia * Cardiac pacemaker * Allergy to study treatments or its/their excipients, to opioids / opiates, sugammadex, muscle relaxants or their excipients, or other medication(s) used during general anesthesia * Toremifene before or within 24 hours of study drug administration * Scheduled for an overnight stay (or \>12 hours) in PACU * Expected transfer to an Intensive Care Unit after surgery * Pregnant, intention to become pregnant between randomization and the Day 30 pregnancy follow-up visit * Breast-feeding. * Investigational drug(s) within 30 days of randomization on this study * Participation in any other clinical trial within 30 days, inclusive, of signing the informed consent form of the current trial * Participant or family member is among the personnel of the investigational or Sponsor staff directly involved with this trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Residual Neuromuscular Blockade (NMB) as Defined by a Train-of-Four (TOF) Ratio <0.9 at Post Anesthesia Care Unit (PACU) Entry | At PACU entry on Day 1 | Neuromuscular functioning was monitored by applying four TOF electrical stimulations to the ulnar nerve and assessing twitch response at the adductor pollicis muscle. T1 and T4 refer to the magnitudes (height) of the first and fourth 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 NMB, with a higher ratio indicating greater recovery from NMB. A T4/T1 Ratio of \<0.9 is indicative of residual NMB. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time From Start of Study Drug Administration to Operating Room Discharge-ready | Day 1 | The time of operating room discharge readiness was determined by the surgical team based on clinical evaluations. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sugammadex Participants receive a single intravenous (IV) bolus dose of sugammadex, 2 or 4 mg/kg, depending on level of neuromuscular recovery | 74 |
| Neostigmine/Glycopyrrolate Participants receive a single IV bolus dose of neostigmine/glycopyrrolate (neostigmine total dose not to exceed 5 mg) per usual practice | 77 |
| Total | 151 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Randomized | Adverse Event | 1 | 1 |
| Randomized | Withdrawal by Subject | 1 | 0 |
| Treated | Lost to Follow-up | 0 | 2 |
Baseline characteristics
| Characteristic | Sugammadex | Neostigmine/Glycopyrrolate | Total |
|---|---|---|---|
| Age, Continuous | 56.4 years STANDARD_DEVIATION 12.8 | 57.0 years STANDARD_DEVIATION 12.7 | 56.7 years STANDARD_DEVIATION 12.7 |
| Sex: Female, Male Female | 27 Participants | 34 Participants | 61 Participants |
| Sex: Female, Male Male | 47 Participants | 43 Participants | 90 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 18 / 74 | 18 / 77 |
| serious Total, serious adverse events | 7 / 74 | 8 / 77 |
Outcome results
Primary
Incidence of Residual Neuromuscular Blockade (NMB) as Defined by a Train-of-Four (TOF) Ratio <0.9 at Post Anesthesia Care Unit (PACU) Entry
Neuromuscular functioning was monitored by applying four TOF electrical stimulations to the ulnar nerve and assessing twitch response at the adductor pollicis muscle. T1 and T4 refer to the magnitudes (height) of the first and fourth 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 NMB, with a higher ratio indicating greater recovery from NMB. A T4/T1 Ratio of \<0.9 is indicative of residual NMB.
Time frame: At PACU entry on Day 1
Population: The analysis population consisted of all randomized participants who received at least one dose of study drug (sugammadex or neostigmine/glycopyrrolate) and had a reliable TOF measurement at PACU entry.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sugammadex | Incidence of Residual Neuromuscular Blockade (NMB) as Defined by a Train-of-Four (TOF) Ratio <0.9 at Post Anesthesia Care Unit (PACU) Entry | 0 participants |
| Neostigmine/Glycopyrrolate | Incidence of Residual Neuromuscular Blockade (NMB) as Defined by a Train-of-Four (TOF) Ratio <0.9 at Post Anesthesia Care Unit (PACU) Entry | 33 participants |
Comparison: Sugammadex is the numerator and Neostigmine/Glycopyrrolate is the denominator.p-value: <0.000195% CI: [0, 0.059]Pearson's Chi-square test
Secondary
Time From Start of Study Drug Administration to Operating Room Discharge-ready
The time of operating room discharge readiness was determined by the surgical team based on clinical evaluations.
Time frame: Day 1
Population: The analysis population consisted of all randomized participants who received at least one dose of study drug (sugammadex or neostigmine/glycopyrrolate).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sugammadex | Time From Start of Study Drug Administration to Operating Room Discharge-ready | 15.02 minutes |
| Neostigmine/Glycopyrrolate | Time From Start of Study Drug Administration to Operating Room Discharge-ready | 18.05 minutes |
Comparison: Sugammadex is the numerator and neostigmine/glycopyrrolate is the denominator. Used log-transformed time intervals.p-value: 0.02195% CI: [0.71, 0.97]ANCOVA