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

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.

Study Overview

• Status: Completed
• Conditions: Anesthesia, General
• Intervention / Treatment: Drug: Sugammadex; Drug: Rocuronium; Drug: Succinylcholine

• Study Type: Interventional
• Enrollment (Actual): 115
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rocuronium + Sugammadex; Participants were to receive a single bolus dose of 1.2 mg/kg rocuronium. Three minutes after the start of the rocuronium administration, they were to receive a single bolus dose of 16.0 mg/kg sugammadex.	Drug: Sugammadex; Single bolus intravenous (IV) dose of 16.0 mg/kg sugammadex; Other Names: Org 25969; MK-8616; Drug: Rocuronium; Single bolus IV dose of 1.2 mg/kg rocuronium; Other Names: Zemuron®
Active Comparator: Succinylcholine; Participants were to receive a single bolus dose of 1.0 mg/kg succinylcholine and allowed to recovery spontaneously from neuromuscular blockade.	Drug: Succinylcholine; Single bolus IV dose of 1.0 mg/kg succinylcholine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 15 minutes after administration of rocuronium + sugammadex or succinylcholine

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Recovery of T1 to 90% of Baseline Value From Start of Rocuronium + Sugammadex or Succinylcholine Administration	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.	Up to 20 minutes after administration of rocuronium + sugammadex or succinylcholine
Level of Consciousness: Number of Participants Awake and Oriented	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.	Up to 24 hours after administration of rocuronium + sugammadex or succinylcholine
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.	Up to 24 hours after administration of rocuronium + sugammadex or succinylcholine
Level of Consciousness: Number of Participants Responsive Only to Tactile Stimulation	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.	Up to 24 hours after administration of rocuronium + sugammadex or succinylcholine
Number of Participants Able to Perform 5-Second Head Lift	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.	Up to 24 hours after administration of rocuronium + sugammadex or succinylcholine
Number of Participants Experiencing General Muscle Weakness	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.	Up to 24 hours after administration of rocuronium + sugammadex or succinylcholine

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Lee C, Jahr JS, Candiotti KA, Warriner B, Zornow MH, Naguib M. Reversal of profound neuromuscular block by sugammadex administered three minutes after rocuronium: a comparison with spontaneous recovery from succinylcholine. Anesthesiology. 2009 May;110(5):1020-5. doi: 10.1097/ALN.0b013e31819dabb0.

Helpful Links

• Click here to access a synopsis of the study results.

Study record dates

Study Major Dates

• Study Start (Actual): February 10, 2006
• Primary Completion (Actual): August 22, 2006
• Study Completion (Actual): September 9, 2006

Study Registration Dates

• First Submitted: May 15, 2007
• First Submitted That Met QC Criteria: May 15, 2007
• First Posted (Estimate): May 16, 2007

Study Record Updates

• Last Update Posted (Actual): April 11, 2019
• Last Update Submitted That Met QC Criteria: March 28, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Peripheral Nervous System Agents; Neuromuscular Agents; Neuromuscular Nondepolarizing Agents; Neuromuscular Blocking Agents; Neuromuscular Depolarizing Agents; Rocuronium; Succinylcholine
• Other Study ID Numbers: P05946 (Other Identifier: Schering-Plough Protocol Number); 19.4.303 (Other Identifier: Organon Protocol Number); MK-8616-026 (Other Identifier: Merck Protocol Number)

Plan for Individual participant data (IPD)

Study Data/Documents

1. CSR Synopsis

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No