Comparison of Sugammadex (Org 25969) With Neostigmine as Reversal Agents for Rocuronium or Vecuronium at Reappearance of T2 (P05960)

NCT00451217 | Completed Phase 3 Results

• 3 other identifiers: P0596019.4.301MK-8616-033
• Study Type: interventional
• Target: 198
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study was to demonstrate in adult participants faster recovery from a neuromuscular block induced by either rocuronium or vecuronium after reversal at reappearance of T2 (the amplitude of the first response of second twitch to train of four (TOF) stimulation, expressed as percentage of control first twitch, T1) by 2.0 mg/kg sugammadex (Org 25969) compared to 50 ug/kg neostigmine.

Conditions

Anesthesia, General

Outcome Measures

Primary Outcomes (1)

• Time From Start of Administration of Sugammadex or Neostigmine to Recovery of the Fourth Twitch/First Twitch (T4/T1) Ratio to 0.9.

  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 and T4 refer to the amplitudes (heights) of the first and fourth twitches, respectively, after TOF nerve stimulation. The T4/T1 Ratio (expressed as a decimal of up to 1.0) indicates the extent of recovery from neuromuscular blockade (NMB). In this study, twitch responses were recorded until the T4/T1 Ratio reached \>= 0.9, the minimum acceptable ratio that indicated recovery from NMB. A faster time to recovery of the T4/T1 Ratio to 0.9 indicates a faster recovery from NMB.

  Day 1: From start of sugammadex or neostigmine administration to recovery of T4/T1 ratio to 0.9

Secondary Outcomes (4)

• Time From Start of Administration of Sugammadex or Neostigmine to Recovery of the T4/T1 Ratio to 0.7

  Day 1: From start of sugammadex or neostigmine administration to recovery of T4/T1 ratio to 0.7

• Time From Start of Administration of Sugammadex or Neostigmine to Recovery of the T4/T1 Ratio to 0.8

  Day 1: From start of sugammadex or neostigmine administration to recovery of T4/T1 ratio to 0.8

• Number of Participants With Clinical Signs of Recovery Assessed by Level of Consciousness, Head Lift and Muscle Weakness, Prior to Transfer to the Recovery Room After Extubation

  Day 1

• Number of Participants With Clinical Signs of Recovery Assessed by Level of Consciousness, Head Lift and Muscle Weakness, Prior to Discharge From the Recovery Room

  Day 1

Study Arms (4)

Rocuronium + Sugammadex

EXPERIMENTAL

After the last dose of rocuronium, at reappearance of T2, a dose of 2.0 mg/kg sugammadex was administered

Drug: Sugammadex

Rocuronium + Neostigmine

ACTIVE COMPARATOR

After the last dose of rocuronium, at reappearance of T2, a dose of 50 ug/kg neostigmine was administered

Drug: Neostigmine

Vecuronium + Sugammadex

EXPERIMENTAL

After the last dose of vecuronium, at reappearance of T2, a dose of 2.0 mg/kg sugammadex was administered

Drug: Sugammadex

Vecuronium + Neostigmine

ACTIVE COMPARATOR

After the last dose of vecuronium, at reappearance of T2, a dose of 50 ug/kg neostigmine was administered

Drug: Neostigmine

Interventions

Sugammadex DRUG

After the last dose of rocuronium or vecuronium, at reappearance of T2, a dose of 2.0 mg/kg sugammadex was to be administered

Also known as: Org 25969

Rocuronium + Sugammadex; Vecuronium + Sugammadex

Neostigmine DRUG

After the last dose of rocuronium or vecuronium, at reappearance of T2, a dose of 50 ug/kg neostigmine was to be administered

Also known as: premix neostigmine/glycopyrrolate

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:

• Is of American Society of Anesthesiologists (ASA) 1 - 4;
• Is above or equal to the age of 18;
• Scheduled for surgical procedures with a general anesthesia with the use of rocuronium or vecuronium for endotracheal intubation and maintenance of neuromuscular block;
• Scheduled for surgical procedure in supine position;
• Given written informed consent.

You may not qualify if:

• Participants in whom a difficult intubation because of anatomical malformations was expected;
• Is known or suspected to have neuromuscular disorders impairing neuromuscular block (NMB) and/or significant renal dysfunction;
• Is known or suspected to have a (family) history of malignant hyperthermia;
• Is 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 such as antibiotics, anticonvulsants and Mg2+;
• Participants in whom the use of neostigmine and/or glycopyrrolate may be contraindicated;
• Had already participated in a sugammadex trial;
• Had participated in another clinical trial, not pre-approved by NV Organon, within 30 days of entering into P05960.
• Females who are pregnant:
• Females of childbearing potential not using any method of birth control: condom or using only hormonal contraception as birth control;
• Females who were breast-feeding.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (2)

• Khuenl-Brady KS, Wattwil M, Vanacker BF, Lora-Tamayo JI, Rietbergen H, Alvarez-Gomez JA. Sugammadex provides faster reversal of vecuronium-induced neuromuscular blockade compared with neostigmine: a multicenter, randomized, controlled trial. Anesth Analg. 2010 Jan 1;110(1):64-73. doi: 10.1213/ane.0b013e3181ac53c3. Epub 2009 Aug 27.

  PMID: 19713265 RESULT

• Blobner M, Eriksson LI, Scholz J, Motsch J, Della Rocca G, Prins ME. Reversal of rocuronium-induced neuromuscular blockade with sugammadex compared with neostigmine during sevoflurane anaesthesia: results of a randomised, controlled trial. Eur J Anaesthesiol. 2010 Oct;27(10):874-81. doi: 10.1097/EJA.0b013e32833d56b7.

  PMID: 20683334 DERIVED

Related Links

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

MeSH Terms

Interventions

Sugammadex; Neostigmine; 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; 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: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 22, 2007
• First Posted: March 23, 2007
• Study Start: November 17, 2005
• Primary Completion: March 6, 2006
• Study Completion: March 6, 2006
• Last Updated: March 4, 2019
• Results First Posted: February 18, 2019

Record last verified: 2019-02