Anesthesia, Neuromuscular Blockade
Conditions
Brief summary
The current trial was designed to demonstrate faster recovery in participants undergoing elective surgeries requiring profound neuromuscular blockade induced by rocuronium to a fourth twitch/first twitch (T4/T1) ratio of 0.9, after reversal of a target depth of neuromuscular blockade (NMB) of 1-2 Post Tetanic Count (PTC) by 4.0 mg.kg-1 Sugammadex compared to Placebo, to evaluate the safety of 4.0 mg.kg-1 Sugammadex and to evaluate the Operating Room (OR) and Post Anesthetic Care Unit (PACU) length of stay for these participants.
Interventions
DRUGSugammadex
At a target depth of NMB of 1-2 PTC after the last dose of rocuronium, a bolus dose of 4.0 mg.kg-1 sugammadex (volume based on the actual body weight of the participant) will be administered, within 10 seconds into a fast running venous infusion.
At a target depth of NMB of 1-2 PTC after the last dose of rocuronium, a bolus dose of placebo (0.9% NaCl, volume based on the actual body weight of the participant) will be administered, within 10 seconds into a fast running 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
* Male or female participants * American Society of Anesthesiologists (ASA) class 1, 2 or 3 * Age \>=18 years * Scheduled to undergo a surgery requiring profound NMB such as cardiovascular, gynaecologic, neurologic and thoracic surgical procedures under general anesthesia requiring neuromuscular relaxation with rocuronium for endotracheal intubation and if applicable maintenance of NMB in a position allowing neuromuscular monitoring * Given written informed consent
Exclusion criteria
* Participants known or suspected to have neuromuscular disorders affecting NMB
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time From Start of Administration of Investigational Medicinal Product (IMP, Sugammadex or Placebo) to Recovery of the Fourth Twitch/First Twitch (T4/T1) Ratio to 0.9 | From Start of IMP Administration to Recovery of the T4/T1 Ratio to 0.9 (estimated from ~2 minutes up to ~90 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 and T4 refer to the magnitudes (height) of the first and fourth twitches, respectively, after TOF nerve stimulation. The T4/T1 Ratio (a percentage that is expressed as a decimal of up to 1.0) indicates the extent of recovery from neuromuscular blockade (NMB), with a higher ratio indicating a greater recovery from NMB. In this study, twitch responses were recorded until the T4/T1 Ratio reached \>=0.9, the minimum acceptable ratio that indicated complete recovery from NMB. A shorter time to recovery of the T4/T1 Ratio \>=0.9 indicates a faster recovery from NMB. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time From Start of Administration of IMP to Recovery of the T4/T1 Ratio to 0.7 | From Start of IMP Administration to Recovery of the T4/T1 Ratio to 0.7 (estimated from ~1 minute up to ~70 minutes) | Neuromuscular functioning was monitored by applying repetitive TOF electrical stimulations to the ulnar nerve every 15 seconds & 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 (a percentage that is expressed as a decimal of up to 1.0) indicates the extent of recovery from NMB, with a higher ratio indicating a greater recovery from NMB. |
| Time From Start of Administration of IMP to Recovery of the T4/T1 Ratio to 0.8 | From Start of IMP Administration to Recovery of the T4/T1 Ratio to 0.8 (estimated from ~2 minutes up to ~80 minutes) | Neuromuscular functioning was monitored by applying repetitive TOF electrical stimulations to the ulnar nerve every 15 seconds & 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 (a percentage that is expressed as a decimal of up to 1.0) indicates the extent of recovery from NMB, with a higher ratio indicating a greater recovery from NMB. |
Participant flow
Recruitment details
Participants were recruited from 10 sites in Germany from November 2008 to May 2009.
Participants by arm
| Arm | Count |
|---|---|
| Sugammadex Participants receiving 4.0 mg.kg-1 Sugammadex at a target depth of NMB of 1-2 PTC after the last dose of rocuronium. | 69 |
| Placebo Participants receiving Placebo (0.9% NaCl) at a target depth of NMB of 1-2 PTC after the last dose of rocuronium. | 68 |
| Total | 137 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Not Treated | 1 | 2 |
Baseline characteristics
| Characteristic | Sugammadex | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 57 years STANDARD_DEVIATION 17 | 57 years STANDARD_DEVIATION 14 | 57 years STANDARD_DEVIATION 16 |
| Sex: Female, Male Female | 21 Participants | 25 Participants | 46 Participants |
| Sex: Female, Male Male | 48 Participants | 43 Participants | 91 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 44 / 69 | 48 / 68 |
| serious Total, serious adverse events | 4 / 69 | 4 / 68 |
Outcome results
Primary
Time From Start of Administration of Investigational Medicinal Product (IMP, Sugammadex or Placebo) to Recovery of the 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 & 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 (a percentage that is expressed as a decimal of up to 1.0) indicates the extent of recovery from neuromuscular blockade (NMB), with a higher ratio indicating a greater recovery from NMB. In this study, twitch responses were recorded until the T4/T1 Ratio reached \>=0.9, the minimum acceptable ratio that indicated complete recovery from NMB. A shorter time to recovery of the T4/T1 Ratio \>=0.9 indicates a faster recovery from NMB.
Time frame: From Start of IMP Administration to Recovery of the T4/T1 Ratio to 0.9 (estimated from ~2 minutes up to ~90 minutes)
Population: The Intent-to-Treat (ITT) Population consisted of all participants who received either Sugammadex or Placebo and had at least one efficacy measurement. Imputed recovery times were used in cases of missing times.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Sugammadex | Time From Start of Administration of Investigational Medicinal Product (IMP, Sugammadex or Placebo) to Recovery of the Fourth Twitch/First Twitch (T4/T1) Ratio to 0.9 | 2.2 minutes |
| Placebo | Time From Start of Administration of Investigational Medicinal Product (IMP, Sugammadex or Placebo) to Recovery of the Fourth Twitch/First Twitch (T4/T1) Ratio to 0.9 | 89.8 minutes |
Secondary
Time From Start of Administration of IMP 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 & 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 (a percentage that is expressed as a decimal of up to 1.0) indicates the extent of recovery from NMB, with a higher ratio indicating a greater recovery from NMB.
Time frame: From Start of IMP Administration to Recovery of the T4/T1 Ratio to 0.7 (estimated from ~1 minute up to ~70 minutes)
Population: The ITT Population consisted of all participants who received either Sugammadex or Placebo and had at least one efficacy measurement. Imputed recovery times were used in cases of missing times.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Sugammadex | Time From Start of Administration of IMP to Recovery of the T4/T1 Ratio to 0.7 | 1.6 minutes |
| Placebo | Time From Start of Administration of IMP to Recovery of the T4/T1 Ratio to 0.7 | 70.1 minutes |
Secondary
Time From Start of Administration of IMP 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 & 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 (a percentage that is expressed as a decimal of up to 1.0) indicates the extent of recovery from NMB, with a higher ratio indicating a greater recovery from NMB.
Time frame: From Start of IMP Administration to Recovery of the T4/T1 Ratio to 0.8 (estimated from ~2 minutes up to ~80 minutes)
Population: The ITT Population consisted of all participants who received either Sugammadex or Placebo and had at least one efficacy measurement. Imputed recovery times were used in cases of missing times.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Sugammadex | Time From Start of Administration of IMP to Recovery of the T4/T1 Ratio to 0.8 | 1.8 minutes |
| Placebo | Time From Start of Administration of IMP to Recovery of the T4/T1 Ratio to 0.8 | 78.8 minutes |