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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00535496
First received: September 25, 2007
Last updated: March 13, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Neuromuscular Blockade
Drug: sugammadex
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • 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 [ Time Frame: Up to 4 minutes after administering sugammadex ] [ Designated as safety issue: No ]
    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.

  • Time From Start of Administration of 4.0 mg/kg Sugammadex to Reappearance of T4 Measured by a Peripheral Nerve Stimulator (PNS) [ Time Frame: up to 2 minutes after administering sugammadex ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: Up to 3 minutes after administering sugammadex ] [ Designated as safety issue: No ]
    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.


Other Outcome Measures:
  • 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 [ Time Frame: Up to 150 minutes after administering sugammadex ] [ Designated as safety issue: No ]
    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.

  • Time From Start of Administration of 1.0 or 4.0 mg/kg Sugammadex to Reappearance of T4 Measured by a TOF-Watch® SX [ Time Frame: Up to 7 minutes after administering sugammadex ] [ Designated as safety issue: No ]
    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.

  • Time From Start of Administration of 1.0 mg/kg Sugammadex to Reappearance of T4 Measured by a PNS [ Time Frame: Up to 5 minutes after administering sugammadex ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: Up to 42 minutes after administering sugammadex ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: Up to 42 minutes after administering sugammadex ] [ Designated as safety issue: No ]
    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.


Enrollment: 91
Study Start Date: September 2007
Study Completion Date: February 2008
Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
  • Bridion®
  • MK-8616
  • 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
  • Bridion®
  • MK-8616
  • 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
  • Bridion®
  • MK-8616
  • 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
  • Bridion®
  • MK-8616
  • SCH 900616

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.

  Eligibility

Ages Eligible for Study:   18 Years to 64 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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  More Information

Publications:
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00535496     History of Changes
Other Study ID Numbers: P05698, 19.4.313
Study First Received: September 25, 2007
Results First Received: May 1, 2013
Last Updated: March 13, 2014
Health Authority: Sweden: Medical Products Agency

Additional relevant MeSH terms:
Rocuronium
Neuromuscular Nondepolarizing Agents
Neuromuscular Blocking Agents
Neuromuscular Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 31, 2014