Comparison of Sugammadex (MK-8616/Org 25969) With Neostigmine Administered at 1-2 Post-tetanic Counts (PTCs) After Administration of Rocuronium or Vecuronium (19.4.302/P05945/MK-8616-025)

NCT00473694 | Completed Phase 3 Results DMC FDA Drug

• 3 other identifiers: P0594519.4.302MK-8616-025
• Study Type: interventional
• Target: 182
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of the trial is to demonstrate a faster recovery from neuromuscular block (NMB) induced with rocuronium or vecuronium after reversal by 4.0 mg/kg of Org 25969 compared with reversal by 70 μg/kg of neostigmine in combination with 14 μg/kg glycopyrrolate.

Conditions

Anesthesia, General

Outcome Measures

Primary Outcomes (2)

• Time From Start of Administration of Sugammadex or Neostigmine to Recovery of the T4/T1 Ratio to 0.9 After Neuromuscular Block (NMB) Induced by Rocuronium

  Mean time from start of sugammadex or neostigmine administration to recovery of T4/T1 ratio to 0.9 was assessed 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. Nerve stimulation continued until the ratio of the magnitude of the fourth twitch (T4) to first twitch (T1) reached at least 0.9. The greater the T4/T1 ratio represented the greater the recovery from NMB; with a value of 0.0 representing no recovery and 1.0 representing full recovery. Reduced recovery time of the T4/T1 ratio to 0.9 indicated faster recovery from NMB. Mean time was collected in minutes and seconds but converted to and presented in minutes only. The analysis included a procedure for the imputation of missing recovery times.

  Up to approximately 3 hours after administration of study drug

• Time From Start of Administration of Sugammadex or Neostigmine to Recovery of the T4/T1 Ratio to 0.9 After Neuromuscular Block (NMB) Induced by Vecuronium

  Mean time from start of sugammadex or neostigmine administration to recovery of T4/T1 ratio to 0.9 was assessed 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. Nerve stimulation continued until the ratio of the magnitude of the fourth twitch (T4) to first twitch (T1) reached at least 0.9. The greater the T4/T1 ratio represented the greater the recovery from NMB; with a value of 0.0 representing no recovery and 1.0 representing full recovery. Reduced recovery time of the T4/T1 ratio to 0.9 indicated faster recovery from NMB. Mean time was collected in minutes and seconds but converted to and presented in minutes only. The analysis included a procedure for the imputation of missing recovery times.

  Up to approximately 6 hours after administration of study drug

Secondary Outcomes (9)

• Time From Start of Administration of Sugammadex or Neostigmine to Recovery of the T4/T1 Ratio to 0.7 After Neuromuscular Block (NMB) Induced by Rocuronium

  Up to approximately 2 hours after administration of study drug

• Time From Start of Administration of Sugammadex or Neostigmine to Recovery of the T4/T1 Ratio to 0.7 After Neuromuscular Block (NMB) Induced by Vecuronium

  Up to approximately 4 hours after administration of study drug

• Time From Start of Administration of Sugammadex or Neostigmine to Recovery of the T4/T1 Ratio to 0.8 After Neuromuscular Block (NMB) Induced by Rocuronium

  Up to approximately 3 hours after administration of study drug

• Time From Start of Administration of Sugammadex or Neostigmine to Recovery of the T4/T1 Ratio to 0.8 After Neuromuscular Block (NMB) Induced by Vecuronium

  Up to approximately 5 hours after administration of study drug

• Number of Participants Awake and Oriented After Anesthesia (Clinical Assessment of Level of Consciousness)

  Up to 24 hours

Study Arms (4)

rocuronium+sugammadex

EXPERIMENTAL

Participants received a single bolus dose of 0.60 mg/kg rocuronium prior to intubation. The neuromuscular block was maintained with 0.15 mg/kg rocuronium if needed. At 1-2 post-tetanic counts (PTC) and after the last dose of rocuronium, a single bolus dose of 4.0 mg/kg sugammadex was administered.

Drug: sugammadex; Drug: rocuronium

rocuronium+neostigmine

ACTIVE COMPARATOR

Participants received a single bolus dose of 0.60 mg/kg rocuronium prior to intubation. The neuromuscular block was maintained with 0.15 mg/kg rocuronium if needed. At 1-2 PTC and after the last dose of rocuronium, a single bolus dose of 70.0 μg/kg neostigmine (up to a maximum dose of 5 mg) was administered in combination with 14.0 μg/kg glycopyrrolate.

Drug: neostigmine; Drug: rocuronium; Drug: glycopyrrolate

vecuronium+sugammadex

EXPERIMENTAL

Participants received a single bolus dose of 0.1 mg/kg vecuronium prior to intubation. The neuromuscular block was maintained with 0.015 mg/kg vecuronium if needed. At 1-2 PTC and after the last dose of vecuronium, a single bolus dose of 4.0 mg/kg sugammadex was administered.

Drug: sugammadex; Drug: vecuronium

vecuronium+neostigmine

ACTIVE COMPARATOR

Participants received a single bolus dose of 0.1 mg/kg vecuronium prior to intubation. The neuromuscular block was maintained with 0.015 mg/kg vecuronium if needed. At 1-2 PTC and after the last dose of vecuronium, a single bolus dose of 70.0 μg/kg neostigmine (up to a maximum dose of 5 mg) was administered in combination with 14.0 μg/kg glycopyrrolate.

Drug: neostigmine; Drug: vecuronium; Drug: glycopyrrolate

Interventions

sugammadex DRUG

Administered as an intravenous (IV) infusion

Also known as: Org 25969, MK-8616, BRIDION®

rocuronium+sugammadex; vecuronium+sugammadex

neostigmine DRUG

Administered as an IV infusion

Also known as: PROSTIGMIN®

rocuronium+neostigmine; vecuronium+neostigmine

vecuronium DRUG

Administered as an IV infusion

Also known as: NORCURON®

vecuronium+neostigmine; vecuronium+sugammadex

rocuronium DRUG

Administered as an IV infusion

Also known as: ZEMURON®

rocuronium+neostigmine; rocuronium+sugammadex

glycopyrrolate DRUG

Administered as an IV infusion

Also known as: ROBINUL®

rocuronium+neostigmine; vecuronium+neostigmine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• American Society of Anesthesiologists (ASA) Class 1 to 4
• years or older
• Scheduled to undergo an elective surgical procedure under general anesthesia requiring the use of rocuronium or vecuronium for endotracheal intubation and maintenance of neuromuscular block
• Scheduled for surgery in supine position
• Given written informed consent

You may not qualify if:

• Participants in whom a difficult intubation is expected due to anatomical malformations
• Known or suspected to have neuromuscular disorders impairing neuromuscular blockade and/or significant renal dysfunction
• Known or suspected to have a (family) history of malignant hyperthermia
• Known or suspected to have an allergy to narcotics, muscle relaxants, or other medications used during surgery
• Receiving medication known to interfere with neuromuscular blocking agents such as anticonvulsants, antibiotics, and magnesium (Mg2+)
• Participants in whom the use of neostigmine and/or glycopyrrolate may be contraindicated
• Female participants who are pregnant or breast-feeding
• Females participants of childbearing potential not using an acceptable method of birth control \[condom or diaphragm with spermicide, vasectomized partner (\> 6 months), IUD, abstinence\]
• Participants who had already participated in an Org 25969 trial
• Participants who had participated in another clinical trial, not pre-approved by Organon, within 30 days of entering into Protocol 19.4.302

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (2)

• Lemmens HJ, El-Orbany MI, Berry J, Morte JB Jr, Martin G. Reversal of profound vecuronium-induced neuromuscular block under sevoflurane anesthesia: sugammadex versus neostigmine. BMC Anesthesiol. 2010 Sep 1;10:15. doi: 10.1186/1471-2253-10-15.

  PMID: 20809967 RESULT

• Jones RK, Caldwell JE, Brull SJ, Soto RG. Reversal of profound rocuronium-induced blockade with sugammadex: a randomized comparison with neostigmine. Anesthesiology. 2008 Nov;109(5):816-24. doi: 10.1097/ALN.0b013e31818a3fee.

  PMID: 18946293 RESULT

Related Links

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

MeSH Terms

Interventions

Sugammadex; Neostigmine; Vecuronium Bromide; Rocuronium; Glycopyrrolate

Intervention Hierarchy (Ancestors)

gamma-Cyclodextrins; Cyclodextrins; Macrocyclic Compounds; Polycyclic Compounds; Dextrins; Starch; Glucans; Polysaccharides; Carbohydrates; Phenylammonium Compounds; Quaternary Ammonium Compounds; Amines; Organic Chemicals; Onium Compounds; Androstanols; Androstanes; Steroids; Fused-Ring Compounds; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 14, 2007
• First Posted: May 15, 2007
• Study Start: November 28, 2005
• Primary Completion: November 6, 2006
• Study Completion: January 29, 2007
• Last Updated: March 19, 2019
• Results First Posted: March 7, 2019

Record last verified: 2019-03