Use of Sugammadex at the End of Case in Routine Anesthesia (MK-8616-023)

A Multicenter, Open Label, Phase IIIa Trial to Evaluate the Efficacy and Safety of Org 25969 When Used at the End of a Surgical Procedure to Reverse the Neuromuscular Block Induced by Rocuronium Following Routine Anesthesia

The primary purpose of the study is to determine the time-course of recovery to a T4/T1 ratio of 0.9 within 4 minutes after 4.0 mg.kg^-1 Sugammadex is administered at least 15 minutes after the last administration of rocuronium in a wide range of surgical procedures and anesthetic regimens (routine use). Safety evaluation is part of the study.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 224
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• American Society of Anesthesiologists (ASA) Class 1-3 participants who are scheduled to undergo an elective surgical procedure under general anesthesia requiring neuromuscular relaxation with the use of rocuronium.

Exclusion criteria:

• Participants with neuromuscular disorders, significant renal dysfunction, malignant hyperthermia, allergy to medications used in general anesthesia and in whom difficult intubation is expected.
• Participants taking medications known to interfere with neuromuscular blocking agents.
• Participants who are of child-bearing potential, pregnant, and breast feeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Sugammadex; Each participant received an intravenous single bolus dose of 0.6 mg/kg rocuronium. If further neuromuscular block was required after endotracheal intubation, maintenance dose(s) of 0.15 mg/kg rocuronium was administered. At least 15 minutes after the intubation dose or the last maintenance dose of rocuronium, an intravenous single bolus dose of 4.0 mg/kg MK-8616 was administered.

Drug: Sugammadex; At least 15 minutes after the intubation dose or the last maintenance dose of rocuronium, an intravenous single bolus dose of 4.0 mg/kg Org 25969 was administered.; Other Names: Org 25969; MK-8616; Drug: Rocuronium; Each participant received an intravenous single bolus dose of 0.6 mg/kg rocuronium. If further neuromuscular block was required after endotracheal intubation, maintenance dose(s) of 0.15 mg/kg rocuronium was/were administered.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time From Start of MK-8616 Administration to Recovery of the T4/T1 Ratio to 0.9	Mean time from start of MK-8616 administration to recovery of participant T4/T1 ratio to 0.9 was assessed through the repeated application (every 15 seconds) of an electrical stimulation protocol. Specifically, 4 electrical stimulations were applied to the ulnar nerve and the magnitude of the twitch response of the adductor pollicis muscle (i.e. thumb twitch response) was assessed. With T4 and T1 referring to the respective magnitude of the fourth and first thumb twitch during nerve stimulation, the T4/T1 ratio indicates the current degree of neuromuscular blockade (NMB) present in the participant as a decimal from 0 (loss of T4 twitch) to 1 (no NMB). Further, reduced recovery time of the T4/T1 ratio to 0.9 indicates faster recovery from NMB. Summary data, originally presented in the format of units "minutes:seconds" (mm:ss), was reformatted to be presented in the single unit of "minutes" (min).	Up to approximately 30 minutes following administration of study treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time From Start of MK-8616 Administration to Recovery of the T4/T1 Ratio to 0.7	Mean time from start of MK-8616 administration to recovery of participant T4/T1 ratio to 0.7 was assessed through the repeated application (every 15 seconds) of an electrical stimulation protocol. Specifically, 4 electrical stimulations were applied to the ulnar nerve and the magnitude of the twitch response of the adductor pollicis muscle (i.e. thumb twitch response) was assessed. With T4 and T1 referring to the respective magnitude of the fourth and first thumb twitch during nerve stimulation, the T4/T1 ratio indicates the current degree of neuromuscular blockade (NMB) present in the participant as a decimal from 0 (loss of T4 twitch) to 1 (no NMB). Further, reduced recovery time of the T4/T1 ratio to 0.7 indicates faster recovery from NMB. Summary data, originally presented in the format of units "minutes:seconds" (mm:ss), was reformatted to be presented in the single unit of "minutes" (min).	Up to approximately 10 minutes following administration of study treatment
Time From Start of MK-8616 Administration to Recovery of the T4/T1 Ratio to 0.8	Mean time from start of MK-8616 administration to recovery of participant T4/T1 ratio to 0.8 was assessed through the repeated application (every 15 seconds) of an electrical stimulation protocol. Specifically, 4 electrical stimulations were applied to the ulnar nerve and the magnitude of the twitch response of the adductor pollicis muscle (i.e. thumb twitch response) was assessed. With T4 and T1 referring to the respective magnitude of the fourth and first thumb twitch during nerve stimulation, the T4/T1 ratio indicates the current degree of neuromuscular blockade (NMB) present in the participant as a decimal from 0 (loss of T4 twitch) to 1 (no NMB). Further, reduced recovery time of the T4/T1 ratio to 0.8 indicates faster recovery from NMB. Summary data, originally presented in the format of units "minutes:seconds" (mm:ss), was reformatted to be presented in the single unit of "minutes" (min).	Up to approximately 15 minutes following administration of study treatment
Clinical Assessment of Recovery - Participant's Level of Consciousness	The quality of recovery was assessed by asking the participant 40 questions from a validated Quality of Recovery Questionnaire (QoR-40). Participants were assessed for level of consciousness (i.e., awake and oriented, arousable with minimal stimulation, responsive only to tactile stimulation), if applicable, by asking their name, if they are aware of where they are, and what day it is. Assessment 1 occurred prior to transfer to the recovery room after extubation and Assessment 2 occurred prior to discharge from the recovery room.	Up to 24 hours
Clinical Assessments of Recovery - Participant Able to Perform 5-second Head Lift (5SHL)	5-second head lift test was assessment of the ability of the participant to lift the head for 5 seconds and was performed by a blinded safety assessor. Tests were repeated every 15 minutes until the participant could successfully perform the 5-second head-lift. Assessment 1 occurred prior to transfer to the recovery room after extubation and Assessment 2 occurred prior to discharge from the recovery room.	Up to 24 hours
Clinical Assessments of Recovery - Check for General Muscle Weakness (GMW)	General muscle weakness check was assessed by the investigator. The assessment of general muscle weakness was based on a scale from 0-10, with 0 representing total paralysis, 1 signifying extreme impairment, 9 for close to no impairment, and 10 for normal muscle strength. Scores of 3, 4, 5, etc. denoted increasing muscle strength in approximately 10% increments. Scores of 9 and lower were denoted as GMW. Assessment 1 occurred prior to transfer to the recovery room after extubation and assessment 2 occurred prior to discharge from the recovery room.	Up to 24 hours

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Hudson ME, Rietbergen H, Chelly JE. Sugammadex is effective in reversing rocuronium in the presence of antibiotics. BMC Anesthesiol. 2014 Aug 15;14:69. doi: 10.1186/1471-2253-14-69. eCollection 2014.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): October 27, 2005
• Primary Completion (Actual): May 22, 2006
• Study Completion (Actual): May 22, 2006

Study Registration Dates

• First Submitted: March 1, 2006
• First Submitted That Met QC Criteria: March 1, 2006
• First Posted (Estimate): March 3, 2006

Study Record Updates

• Last Update Posted (Actual): March 27, 2019
• Last Update Submitted That Met QC Criteria: March 15, 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; Rocuronium
• Other Study ID Numbers: P05943 (Other Identifier: Schering-Plough Protocol Number); 19.4.311 (Other Identifier: Organon Protocol Number); MK-8616-023 (Other Identifier: Merck Protocol Number)

Plan for Individual participant data (IPD)

Study Data/Documents

1. CSR Synopsis