Comparison of Recovery From Rocuronium 1.2 mg/kg Followed by Sugammadex (Org 25969) 16 mg/kg at 3 Minutes With Recovery From Succinylcholine 1.0 mg/kg (19.4.303)(P05946)(MK-8616-026)

A Multicenter, Randomized, Parallel Group, Comparative, Active-Controlled, Safety-Assessor Blinded, Phase IIIa, Trial, in Adult Subjects Comparing Recovery From 1.2 mg.Kg-1 Rocuronium Followed by 16 mg.Kg-1 Org 25969 at 3 Minutes With Recovery From 1.0 mg.Kg-1 Succinylcholine

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00474253

Enrollment

115

Registered

2007-05-16

Start date

2006-02-10

Completion date

2006-09-09

Last updated

2019-04-11

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Anesthesia, General

Brief summary

The purpose of the trial is to demonstrate a faster recovery from neuromuscular block induced by 1.2 mg/kg rocuronium after reversal at 3 minutes by 16.0 mg/kg of sugammadex compared with recovery after a neuromuscular block induced by 1.0 mg/kg succinylcholine.

Interventions

DRUGSugammadex

Single bolus intravenous (IV) dose of 16.0 mg/kg sugammadex

DRUGSuccinylcholine

Single bolus IV dose of 1.0 mg/kg succinylcholine

DRUGRocuronium

Single bolus IV dose of 1.2 mg/kg rocuronium

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

Inclusion criteria

* American Society of Anesthesiologists (ASA) Class 1 or 2 physical status; * 18 to 65 years of age (inclusive); * Scheduled for elective surgical procedure under general anesthesia requiring a short duration of neuromuscular block with the use of rocuronium or succinylcholine and requiring endotracheal intubation; * Scheduled for surgery in supine position; * Body mass index (BMI) \< 30; * Given written informed consent.

Exclusion criteria

* Has ischemic heart disease or history of myocardial infarction within the last year; * May experience difficult intubation due to anatomical malformations; * Known or suspected to have neuromuscular disorders impairing neuromuscular blockade and/or significant renal dysfunction; * Known or suspected family history of malignant hyperthermia; * Known or suspected allergy to narcotics, muscle relaxants, midazolam, anesthetics or other medications used during surgery; * Is receiving medication known to interfere with neuromuscular blocking agents such as anticonvulsants, antibiotics and Mg2+; * Individuals in whom the use of neostigmine and/or glycopyrrolate may be contraindicated; * Females who are pregnant or breast-feeding; * Females of childbearing potential who are not using an acceptable method of birth control \[condom or diaphragm with spermicide, vasectomized partner (\> 6 months), IUD, abstinence\]; * Has already participated in a sugammadex trial including Protocol 19.4.303.

Design outcomes

Primary

Measure	Time frame	Description
Time to Recovery of T1 to 10% of Baseline Value From Start of Rocuronium + Sugammadex or Succinylcholine Administration	Up to 15 minutes after administration of rocuronium + sugammadex or succinylcholine	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 refers to the amplitude (height) of the first twitch after TOF nerve stimulation.

Secondary

Measure	Time frame	Description
Level of Consciousness: Number of Participants Awake and Oriented	Up to 24 hours after administration of rocuronium + sugammadex or succinylcholine	The number of participants who were awake and oriented was assessed as part of an overall assessment of the clinical level of consciousness. The clinical level of consciousness was used as a measure of recovery from neuromuscular blockade at two time points: prior to transfer to the recovery room after extubation and prior to discharge from the recovery room. Attempts were made to arouse participants every 15 minutes with mild prodding, mild shaking, and asking questions regarding name, location, and day of the week. The assessment ended once the participant was awake and fully orientated.
Level of Consciousness: Number of Participants Arousable With Minimal Stimulation	Up to 24 hours after administration of rocuronium + sugammadex or succinylcholine	The number of participants aroused with minimal stimulation was assessed as part of an overall assessment of level of consciousness. The level of consciousness was used as a measure of recovery from neuromuscular blockade at two time points: prior to transfer to the recovery room after extubation and prior to discharge from the recovery room. Attempts were made to arouse participants every 15 minutes with mild prodding, mild shaking, and asking questions regarding name, location, and day of the week. The assessment ended once the participant was awake and fully orientated.
Time to Recovery of T1 to 90% of Baseline Value From Start of Rocuronium + Sugammadex or Succinylcholine Administration	Up to 20 minutes after administration of rocuronium + sugammadex or succinylcholine	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 refers to the amplitude (height) of the first twitch after TOF nerve stimulation.
Number of Participants Able to Perform 5-Second Head Lift	Up to 24 hours after administration of rocuronium + sugammadex or succinylcholine	The number of participants who were able to lift their head for 5 seconds was assessed as a measure of recovery following neuromuscular blockade at two time points: prior to transfer to the recovery room after extubation and prior to discharge from the recovery room. The assessment was performed every 15 minutes until the first successful 5-second head lift was achieved.
Number of Participants Experiencing General Muscle Weakness	Up to 24 hours after administration of rocuronium + sugammadex or succinylcholine	The number of participants experiencing general muscle weakness was assessed by the investigator as a measure of recovery from neuromuscular blockade at two time points: prior to transfer to the recovery room after extubation and prior to discharge from the recovery room. The assessments were performed every 15 minutes until the absence of general muscle weakness. A standardized examination form was used to determine the presence or absence of muscle weakness in various muscle groups.
Level of Consciousness: Number of Participants Responsive Only to Tactile Stimulation	Up to 24 hours after administration of rocuronium + sugammadex or succinylcholine	The number of participants responsive only to tactile stimulation was assessed as part of an overall assessment of the level of consciousness. The level of consciousness was used as a measure of recovery from neuromuscular blockade at two time points: prior to transfer to the recovery room after extubation and prior to discharge from the recovery room. Attempts were made to arouse participants every 15 minutes with mild prodding, mild shaking, and asking questions regarding name, location, and day of the week. The assessment ended once the participant was awake and fully orientated.

Participant flow

Participants by arm

Arm	Count
Rocuronium + Sugammadex Participants received a single bolus IV dose of 1.2 mg/kg rocuronium to induce neuromuscular block. This was followed by a single bolus IV dose of sugammadex 16.0 mg/kg 3 minutes after the start of rocuronium administration, to reverse the neuromuscular block.	56
Succinylcholine Participants received a single bolus IV dose of 1.0 mg/kg succinylcholine to induce neuromuscular block. They were allowed to recovery spontaneously from the neuromuscular block.	54
Total	110

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Discharged prior to study completion	0	1
Overall Study	Lost to Follow-up	1	0
Overall Study	Withdrew consent	2	0
Overall Study	Withdrew due to surgery-related issues	0	3

Baseline characteristics

Characteristic	Rocuronium + Sugammadex	Succinylcholine	Total
Age, Continuous	42 Years STANDARD_DEVIATION 13	41 Years STANDARD_DEVIATION 13	42 Years STANDARD_DEVIATION 13
Sex: Female, Male Female	33 Participants	31 Participants	64 Participants
Sex: Female, Male Male	23 Participants	23 Participants	46 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 56	0 / 54
other Total, other adverse events	51 / 56	50 / 54
serious Total, serious adverse events	0 / 56	1 / 54

Outcome results

Primary

Time to Recovery of T1 to 10% of Baseline Value From Start of Rocuronium + Sugammadex or Succinylcholine 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 refers to the amplitude (height) of the first twitch after TOF nerve stimulation.

Time frame: Up to 15 minutes after administration of rocuronium + sugammadex or succinylcholine

Population: All participants who received study treatment and had at least one post-baseline efficacy assessment

Arm	Measure	Value (MEAN)	Dispersion
Rocuronium + Sugammadex	Time to Recovery of T1 to 10% of Baseline Value From Start of Rocuronium + Sugammadex or Succinylcholine Administration	4.35 Minutes	Standard Deviation 0.72
Succinylcholine	Time to Recovery of T1 to 10% of Baseline Value From Start of Rocuronium + Sugammadex or Succinylcholine Administration	7.15 Minutes	Standard Deviation 1.55

Secondary

Level of Consciousness: Number of Participants Arousable With Minimal Stimulation

The number of participants aroused with minimal stimulation was assessed as part of an overall assessment of level of consciousness. The level of consciousness was used as a measure of recovery from neuromuscular blockade at two time points: prior to transfer to the recovery room after extubation and prior to discharge from the recovery room. Attempts were made to arouse participants every 15 minutes with mild prodding, mild shaking, and asking questions regarding name, location, and day of the week. The assessment ended once the participant was awake and fully orientated.