Relation Between TOF-Watch® SX and a Peripheral Nerve Stimulator After 4.0 mg.Kg-1 Sugammadex (P05698)

Comparison of the T4/T1 Ratio Measured by Means of the TOF Watch® SX With the Reappearance of T4 Measured by Means of a Peripheral Nerve Stimulator in Adult Subjects Receiving 4.0 mg.Kg-1 Sugammadex at 15 Minutes After Rocuronium

The objective of the trial is to determine the relationship within a participant between the time to manual detection of the reappearance of the fourth twitch (T4) measured using a peripheral nerve stimulator (PNS) and the time to recovery of the fourth twitch/first twitch (T4/T1) ratio to 0.9 measured using a Train Of Four (TOF)-Watch® SX, of 4.0 mg/kg sugammadex administered at 15 minutes after either a bolus dose of 0.6 mg/kg rocuronium or the last maintenance dose of 0.15 mg/kg rocuronium.

Study Overview

• Status: Completed
• Conditions: Neuromuscular Blockade
• Intervention / Treatment: Drug: sugammadex

Detailed Description

The TOF-Watch® SX has been used for neuromuscular monitoring in all

clinical trials with sugammadex. In clinical practice however, a PNS is commonly

used in many hospitals worldwide. A disadvantage of a PNS is that it is not objective monitoring like the TOF-Watch® SX, and it can detect only the number of twitches. In this trial, the relationship between the time to reappearance of T4 using PNS (i.e. Ministim® model MS-IV) and the time to recovery of the T4/T1 ratio to 0.9 using the TOF-Watch® SX was determined after a dose of 4.0 mg/kg sugammadex was administered 15 minutes after the last dose of rocuronium. Determining this relationship will enable the provision of advice on when it is safe to extubate participants after administration of 4.0 mg/kg sugammadex for reversing neuromuscular block while using a PNS. The time to reappearance of T4 was assessed by a blinded PNS-assessor. This assessor was blinded for the dose of sugammadex used and for the TOF results measured with the TOF-Watch® SX.

• Study Type: Interventional
• Enrollment (Actual): 91
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• American Society of Anesthesiologists (ASA) Class 1 or 2 or 3
• between the ages of 18 to 64 years, inclusive
• scheduled for a surgical procedure under general anesthesia requiring

neuromuscular relaxation with the use of rocuronium

• scheduled for a surgical procedure in supine position
• have given written informed consent

Exclusion Criteria:

• participants with a difficult intubation because of expected anatomical

malformations

• known or suspected to have neuromuscular disorders impairing

neuromuscular blockade and/or significant hepatic and/or renal

dysfunction

• medical or physical condition that is expected to interfere

with the proper conduct of simultaneous neuromuscular monitoring on

both arms

• known or suspected to have a (family) history of malignant

hyperthermia

• known or suspected to have arthritis or another disease that will

cause the thumb not to move freely

• known or suspected to have an allergy to narcotics, muscle

relaxants or other medication used during general anesthesia

• is receiving medication in a dose and/or at a time point known to

interfere with neuromuscular blocking agents (NMBAs), such as antibiotics, anticonvulsants and Mg2+

• already participated in a sugammadex trial
• participated in another clinical trial, not pre-approved, within prior 30 days
• pregnant females
• breast-feeding females

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

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; sugammadex 1.0 mg/kg, TOF-Watch® SX (dominant forearm) and PNS (non-dominant forearm)	Drug: sugammadex; Participants will receive an intubating dose of 0.6 mg/kg rocuronium, followed by one or more maintenance doses of 0.15 mg/kg rocuronium, if necessary. Fifteen minutes after the last dose of rocuronium, 1.0 or 4.0 mg/kg sugammadex will be randomly administered by intravenous (IV) bolus dose based on actual body weight.; Other Names: Org 25969; MK-8616; Bridion®; SCH 900616
Experimental: 2; sugammadex 1.0 mg/kg, TOF-Watch® SX (non-dominant forearm) and PNS (dominant forearm)	Drug: sugammadex; Participants will receive an intubating dose of 0.6 mg/kg rocuronium, followed by one or more maintenance doses of 0.15 mg/kg rocuronium, if necessary. Fifteen minutes after the last dose of rocuronium, 1.0 or 4.0 mg/kg sugammadex will be randomly administered by intravenous (IV) bolus dose based on actual body weight.; Other Names: Org 25969; MK-8616; Bridion®; SCH 900616
Experimental: 3; sugammadex 4.0 mg/kg, TOF-Watch® SX (dominant forearm) and PNS (non-dominant forearm)	Drug: sugammadex; Participants will receive an intubating dose of 0.6 mg/kg rocuronium, followed by one or more maintenance doses of 0.15 mg/kg rocuronium, if necessary. Fifteen minutes after the last dose of rocuronium, 1.0 or 4.0 mg/kg sugammadex will be randomly administered by intravenous (IV) bolus dose based on actual body weight.; Other Names: Org 25969; MK-8616; Bridion®; SCH 900616
Experimental: 4; sugammadex 4.0 mg/kg, TOF-Watch® SX (non-dominant forearm) and PNS (dominant forearm)	Drug: sugammadex; Participants will receive an intubating dose of 0.6 mg/kg rocuronium, followed by one or more maintenance doses of 0.15 mg/kg rocuronium, if necessary. Fifteen minutes after the last dose of rocuronium, 1.0 or 4.0 mg/kg sugammadex will be randomly administered by intravenous (IV) bolus dose based on actual body weight.; Other Names: Org 25969; MK-8616; Bridion®; SCH 900616

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time From Start of Administration of 4.0 mg/kg Sugammadex to Recovery of the T4/T1 Ratio to 0.9 Measured by a TOF-Watch® SX	Neuromuscular function was monitored by applying repetitive TOF electrical stimulations with the TOF-Watch® SX to the ulnar nerve of one forearm every 15 seconds & assessing twitch response at the adductor pollicis muscle with the TOF-Watch® SX. T1 and T4 are the magnitudes (heights) of the first and fourth twitches respectively after TOF nerve stimulation, where stimulation was continued until the T4/T1 ratio reached 0.9. A higher T4/T1 ratio indicates a lower degree of neuromuscular blockade, with a value of 1.0 representing full recovery. Only participants treated with 4.0 mg/kg sugammadex are presented, where the TOF-Watch® SX on the dominant forearm n =30, and on the non-dominant forearm n = 31. The 1.0 mg/kg sugammadex group was not evaluated for this outcome measure.	Up to 4 minutes after administering sugammadex
Time From Start of Administration of 4.0 mg/kg Sugammadex to Reappearance of T4 Measured by a Peripheral Nerve Stimulator (PNS)	Neuromuscular function was monitored with a PNS by applying repetitive TOF stimulation to the ulnar nerve of one forearm every 15 seconds and assessing the number of twitches at the adductor pollicis muscle by a blinded PNS assessor. T4 is the fourth twitch after TOF nerve stimulation. Only participants treated with 4.0 mg/kg sugammadex are presented, where the PNS on the dominant forearm n =31, and on the non-dominant forearm n = 30. The 1.0 mg/kg sugammadex group was not evaluated for this outcome measure.	up to 2 minutes after administering sugammadex
Difference in Time Between Recovery of T4/T1 Ratio to 0.9 as Measured by TOF Watch® SX, and Reappearance of T4 as Measured by PNS, Within Participants, After Administration of 4.0 mg/kg Sugammadex	The difference between the recovery of T4/T1 ratio to 0.9 and reappearance of T4 within participants was assessed from an ANOVA method. Only participants treated with 4.0 mg/kg sugammadex are presented, where the TOF-Watch® SX on the dominant forearm n =30, and on the non-dominant forearm n = 31; and the PNS on the dominant forearm n =31, and on the non-dominant forearm n = 30. The 1.0 mg/kg sugammadex group was not evaluated for this outcome measure.	Up to 3 minutes after administering sugammadex

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time From Start of Administration of 1.0 mg/kg Sugammadex to Recovery of the T4/T1 Ratio to 0.9 Measured by a TOF-Watch® SX	Neuromuscular function was monitored by applying repetitive TOF electrical stimulations with the TOF-Watch® SX to the ulnar nerve of one forearm every 15 seconds & assessing twitch response at the adductor pollicis muscle with the TOF-Watch® SX. T1 and T4 are the magnitudes (heights) of the first and fourth twitches respectively after TOF nerve stimulation, where stimulation was continued until the T4/T1 ratio reached 0.9. A higher T4/T1 ratio indicates a lower degree of neuromuscular blockade, with a value of 1.0 representing full recovery. Only participants treated with 1.0 mg/kg sugammadex are presented where the TOF-Watch® SX on the dominant forearm n =15, and on the non-dominant forearm n = 14. The 4.0 mg/kg sugammadex group was not evaluated for this outcome measure.	Up to 150 minutes after administering sugammadex
Time From Start of Administration of 1.0 or 4.0 mg/kg Sugammadex to Reappearance of T4 Measured by a TOF-Watch® SX	Neuromuscular function was monitored by applying repetitive TOF electrical stimulations with the TOF-Watch® SX to the ulnar nerve of one forearm every 15 seconds & assessing twitch response at the adductor pollicis muscle with the TOF-Watch® SX. T4 is the fourth twitch after TOF nerve stimulation. For participants treated with 1.0 mg/kg sugammadex the TOF-Watch® SX on the dominant forearm n =15, and on the non-dominant forearm n = 14. For participants treated with 4.0 mg/kg sugammadex the TOF-Watch® SX on the dominant forearm n =30, and on the non-dominant forearm n = 31.	Up to 7 minutes after administering sugammadex
Time From Start of Administration of 1.0 mg/kg Sugammadex to Reappearance of T4 Measured by a PNS	Neuromuscular function was monitored by applying repetitive TOF stimulations manually to the ulnar nerve of one forearm every 15 seconds & the number of twitches collected manually at the adductor pollicis muscle with the PNS by a blinded PNS assessor. T4 is the fourth twitch after TOF nerve stimulation. Only participants treated with 1.0 mg/kg sugammadex are presented, where the PNS on the dominant forearm n =15, and on the non-dominant forearm n = 14. The 4.0 mg/kg sugammadex group was not evaluated for this outcome measure.	Up to 5 minutes after administering sugammadex
Time From Start of Administration of 1.0 or 4.0 mg/kg Sugammadex to Recovery of the T4/T1 Ratio to 0.8 Measured by a TOF-Watch® SX	Neuromuscular function was monitored by applying repetitive TOF electrical stimulations with the TOF-Watch® SX to the ulnar nerve of one forearm every 15 seconds & assessing twitch response at the adductor pollicis muscle with the TOF-Watch® SX. T1 and T4 are the magnitudes (heights) of the first and fourth twitches respectively after TOF nerve stimulation, where stimulation was continued until the T4/T1 ratio reached 0.8. A higher T4/T1 ratio indicates a lower degree of neuromuscular blockade, with a value of 1.0 representing full recovery. For participants treated with 1.0 mg/kg sugammadex the TOF-Watch® SX on the dominant forearm n =15, and on the non-dominant forearm n = 14. For participants treated with 4.0 mg/kg sugammadex the TOF-Watch® SX on the dominant forearm n =30, and on the non-dominant forearm n = 31.	Up to 42 minutes after administering sugammadex
Time From Start of Administration of 1.0 or 4.0 mg/kg Sugammadex to Recovery of the T4/T1 Ratio to 0.7 Measured by a TOF-Watch® SX	Neuromuscular function was monitored by applying repetitive TOF electrical stimulations with the TOF-Watch® SX to the ulnar nerve of one forearm every 15 seconds & assessing twitch response at the adductor pollicis muscle with the TOF-Watch® SX. T1 and T4 are the magnitudes (heights) of the first and fourth twitches respectively after TOF nerve stimulation, where stimulation was continued until the T4/T1 ratio reached 0.7. A higher T4/T1 ratio indicates a lower degree of neuromuscular blockade, with a value of 1.0 representing full recovery. For participants treated with 1.0 mg/kg sugammadex the TOF-Watch® SX on the dominant forearm n =15, and on the non-dominant forearm n = 14. For participants treated with 4.0 mg/kg sugammadex the TOF-Watch® SX on the dominant forearm n =30, and on the non-dominant forearm n = 31.	Up to 42 minutes after administering sugammadex

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Drobnik L, Sparr HJ, Thorn SE, Khuenl-Brady KS, Rietbergen H, Prins ME, Ullman J. A randomized simultaneous comparison of acceleromyography with a peripheral nerve stimulator for assessing reversal of rocuronium-induced neuromuscular blockade with sugammadex. Eur J Anaesthesiol. 2010 Oct;27(10):866-73. doi: 10.1097/EJA.0b013e32833b1b85.

Study record dates

Study Major Dates

• Study Start: September 1, 2007
• Primary Completion (Actual): January 1, 2008
• Study Completion (Actual): February 1, 2008

Study Registration Dates

• First Submitted: September 25, 2007
• First Submitted That Met QC Criteria: September 25, 2007
• First Posted (Estimate): September 26, 2007

Study Record Updates

• Last Update Posted (Estimate): March 17, 2015
• Last Update Submitted That Met QC Criteria: February 26, 2015
• Last Verified: February 1, 2015

More Information

Terms related to this study

• Other Study ID Numbers: P05698; 19.4.313