Comparison of Sugammadex With Neostigmine During Laparoscopic Cholecystectomy or Appendectomy (P05699)

NCT00724932 | Completed Phase 3 Results DMC

• 4 other identifiers: P0569919.4.318MK-8616-0022007-007951-14
• Study Type: interventional
• Target: 140
• Locations: 0 countries
• Sites: N/A

Brief Summary

The current trial was designed to demonstrate faster recovery from a neuromuscular blockade (NMB) induced by rocuronium after reversal at 1-2 Post Tetanic Count (PTC) by 4.0 mg.kg-1 sugammadex compared to 50 µg.kg-1 neostigmine at reappearance of second twitch (T2) in participants undergoing laparoscopic cholecystectomy or appendectomy under propofol anesthesia, to compare safety and to evaluate operating room and Post Anesthetic Care Unit (PACU) length of stay.

Conditions

Anesthesia, General

Outcome Measures

Primary Outcomes (1)

• Time From Start of Administration of Investigational Medicinal Product (IMP, 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 \& assessing twitch response at the adductor pollicis muscle. T1 and T4 refer to the magnitudes (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.

  From start of IMP administration to recovery of T4/T1 ratio to 0.9 (ranging from ~2 minutes to ~9 minutes)

Secondary Outcomes (4)

• Time From Start of Administration of IMP to Recovery of the T4/T1 Ratio to 0.7

  From start of IMP administration to recovery of T4/T1 Ratio to 0.7 (ranging from ~2 minutes to ~5 minutes)

• Time From Start of Administration of IMP to Recovery of the T4/T1 Ratio to 0.8

  From start of IMP administration to recovery of T4/T1 Ratio to 0.8 (ranging from ~2 minutes to ~6 minutes)

• Number of Participants Who Experienced Pre-treatment Serious Adverse Events (SAEs) and Post-treatment SAEs

  From signing of informed consent to end of trial (7 days after surgery)

• Number of Participants Who Experienced Pre-treatment Non-serious Adverse Events (AEs) and Post-treatment Non-serious AEs

  From signing of informed consent to end of trial (7 days after surgery)

Other Outcomes (29)

• Time From Start of Administration of IMP to Recovery of the T4/T1 Ratio to 0.5 and 0.6

  From start of IMP administration to recovery of T4/T1 Ratio to 0.5 and 0.6 (ranging from ~1 minute to ~4 minutes)

• Time From Start of Administration of the Last Dose of Rocuronium to Recovery of the T4/T1 Ratio to 0.5, 0.6, 0.7, 0.8 and 0.9

  From start of last dose of rocuronium to recovery of T4/T1 Ratio to 0.5, 0.6, 0.7, 0.8 and 0.9 (ranging from ~12 minutes to ~36 minutes)

• Time From Start of Administration of the Last Dose of Rocuronium to the Time of 1-2 PTC in the 4.0 mg.Kg-1 Sugammadex Group

  From last dose of rocuronium to 1-2 PTC (up to ~9 minutes)

Study Arms (2)

Sugammadex

EXPERIMENTAL

4.0 mg.kg-1 sugammadex at 1-2 PTC

Drug: Rocuronium; Drug: Sugammadex

Neostigmine

EXPERIMENTAL

50 µg.kg-1 neostigmine (with atropine in a ratio of 5:1 for neostigmine:atropine) at reappearance of T2

Drug: Rocuronium; Drug: Neostigmine; Drug: Atropine

Interventions

Rocuronium DRUG

Participants will receive an intravenous (i.v.) single bolus dose of 0.6 mg.kg-1 rocuronium. After this dose, maintenance doses of 0.1-0.2 mg.kg-1 rocuronium may be given.

Also known as: rocuronium bromide, Esmeron®

Neostigmine; Sugammadex

Sugammadex DRUG

After the last dose of rocuronium has been administered, participants will receive, according to the randomization, a single bolus dose of 4.0 mg.kg-1 sugammadex at 1-2 PTC.

Also known as: Org 25969, SCH 900616, MK-8616, Bridion®

Sugammadex

Neostigmine DRUG

After the last dose of rocuronium has been administered, participants will receive, according to the randomization, 50 μg.kg-1 neostigmine (with atropine in a ratio of 5:1 for neostigmine:atropine) at reappearance of T2.

Also known as: Prostigmin®

Neostigmine

Atropine DRUG

After the last dose of rocuronium has been administered, participants will receive, according to randomization, 10 μg.kg-1 atropine (with neostigmine in a ratio of 5:1 for neostigmine:atropine) at reappearance of T2.

Also known as: atropine sulfate

Neostigmine

Eligibility Criteria

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

You may qualify if:

• Participants of American Society of Anesthesiologists class 1-3
• Participants of age above or equal to the age of 18 years
• Participants who are scheduled to undergo a laparoscopic cholecystectomy or appendectomy under general anesthesia requiring neuromuscular relaxation with rocuronium, and if applicable, maintenance of neuromuscular blockade
• Participants who have given written informed consent

You may not qualify if:

• Participants in whom a difficult intubation because of anatomical malformations is expected
• Participants known or suspected to have neuromuscular disorders affecting NMB
• Participants known or suspected to have a significant renal dysfunction
• Participants known or suspected to have a severe hepatic dysfunction
• Participants known or suspected to have (family) history of malignant hyperthermia
• Participants known or suspected to have an allergy to opioids, muscle relaxants or other medication used during general anesthesia
• Participants in whom the use of neostigmine and/or atropine is contraindicated
• Female participants who are pregnant (pregnancy will be excluded for women both from medical history and by a human chorionic gonadotropin (hCG) test within 24h before surgery, except for women who are not of childbearing potential, i.e. at least 2 years menopausal or have undergone tubal ligation or a hysterectomy)
• Female participants who are breast-feeding
• Participants who participated in another clinical trial not pre-approved by the sponsor, within 30 days of entering into trial 19.4.318 (P05699)
• Participants who have already participated in a sugammadex trial

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (7)

• Suresh D, Carter JA, Whitehead JP, Goldhill DR, Flynn PJ. Cardiovascular changes at antagonism of atracurium. Effects of different doses of premixed neostigmine and glycopyrronium in a ratio of 5:1. Anaesthesia. 1991 Oct;46(10):877-80. doi: 10.1111/j.1365-2044.1991.tb09609.x.

  PMID: 1952007 BACKGROUND

• Caldwell JE. Reversal of residual neuromuscular block with neostigmine at one to four hours after a single intubating dose of vecuronium. Anesth Analg. 1995 Jun;80(6):1168-74. doi: 10.1097/00000539-199506000-00018.

  PMID: 7762847 BACKGROUND

• Irie T, Uekama K. Pharmaceutical applications of cyclodextrins. III. Toxicological issues and safety evaluation. J Pharm Sci. 1997 Feb;86(2):147-62. doi: 10.1021/js960213f.

  PMID: 9040088 BACKGROUND

• Apfel CC, Kranke P, Eberhart LH, Roos A, Roewer N. Comparison of predictive models for postoperative nausea and vomiting. Br J Anaesth. 2002 Feb;88(2):234-40. doi: 10.1093/bja/88.2.234.

  PMID: 11883387 BACKGROUND

• Apfel CC, Laara E, Koivuranta M, Greim CA, Roewer N. A simplified risk score for predicting postoperative nausea and vomiting: conclusions from cross-validations between two centers. Anesthesiology. 1999 Sep;91(3):693-700. doi: 10.1097/00000542-199909000-00022.

  PMID: 10485781 BACKGROUND

• Aldrete JA, Kroulik D. A postanesthetic recovery score. Anesth Analg. 1970 Nov-Dec;49(6):924-34. No abstract available.

  PMID: 5534693 BACKGROUND

• Geldner G, Niskanen M, Laurila P, Mizikov V, Hubler M, Beck G, Rietbergen H, Nicolayenko E. A randomised controlled trial comparing sugammadex and neostigmine at different depths of neuromuscular blockade in patients undergoing laparoscopic surgery. Anaesthesia. 2012 Sep;67(9):991-8. doi: 10.1111/j.1365-2044.2012.07197.x. Epub 2012 Jun 14.

  PMID: 22698066 RESULT

MeSH Terms

Interventions

Rocuronium; Sugammadex; Neostigmine; Atropine

Intervention Hierarchy (Ancestors)

Androstanols; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; gamma-Cyclodextrins; Cyclodextrins; Macrocyclic Compounds; Dextrins; Starch; Glucans; Polysaccharides; Carbohydrates; Phenylammonium Compounds; Quaternary Ammonium Compounds; Amines; Organic Chemicals; Onium Compounds; Atropine Derivatives; Tropanes; Azabicyclo Compounds; Aza Compounds; Belladonna Alkaloids; Solanaceous Alkaloids; Alkaloids; Heterocyclic Compounds; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring

Results Point of Contact

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

ClinicalTrialsDisclosure@merck.com

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: July 28, 2008
• First Posted: July 30, 2008
• Study Start: July 16, 2008
• Primary Completion: April 1, 2009
• Study Completion: May 3, 2009
• Last Updated: May 16, 2017
• Results First Posted: April 29, 2013

Record last verified: 2017-04