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

Phase 3
Completed
Conditions
Anesthesia, General
Interventions
Registration Number
NCT00724932
Lead Sponsor
Merck Sharp & Dohme LLC
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.

Detailed Description

In those surgical procedures where a neuromuscular block is desired for intubation and/or avoid unwanted muscular activity, anesthesiologists may use a more profound NMB until the end of surgery, e.g. in open abdominal procedures or during laparoscopic procedures in order to improve surgical conditions. Reversal with sugammadex at a dose of 4.0 mg.kg-1 at 1-2 PTC after an intubation dose of 0.6 mg.kg-1 or maintenance dosing rocuronium has been found to be both safe and efficacious in previous clinical trials but has never been investigated exclusively in participants undergoing laparoscopic cholecystectomy or appendectomy.

With sugammadex profound muscle relaxation may now be provided right up to the end of the surgical procedure. This may lead to improved Patient Outcomes, such as improvement in the time from end of surgery to the discharge to the PACU. In this multi-center, randomized, parallel-group, active-controlled, safety-assessor blinded trial such benefits will be further investigated.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
140
Inclusion Criteria
  • 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
Exclusion Criteria
  • 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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
SugammadexRocuronium4.0 mg.kg-1 sugammadex at 1-2 PTC
SugammadexSugammadex4.0 mg.kg-1 sugammadex at 1-2 PTC
NeostigmineRocuronium50 µg.kg-1 neostigmine (with atropine in a ratio of 5:1 for neostigmine:atropine) at reappearance of T2
NeostigmineNeostigmine50 µg.kg-1 neostigmine (with atropine in a ratio of 5:1 for neostigmine:atropine) at reappearance of T2
NeostigmineAtropine50 µg.kg-1 neostigmine (with atropine in a ratio of 5:1 for neostigmine:atropine) at reappearance of T2
Primary Outcome Measures
NameTimeMethod
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 0.9From start of IMP administration to recovery of T4/T1 ratio to 0.9 (ranging from ~2 minutes to ~9 minutes)

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.

Secondary Outcome Measures
NameTimeMethod
Number of Participants Who Experienced Pre-treatment Non-serious Adverse Events (AEs) and Post-treatment Non-serious AEsFrom signing of informed consent to end of trial (7 days after surgery)

An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body, whether or not considered related to the use of the product. Participants were monitored for occurrence AEs for up to 7 days after last dose IMP. Pre-treatment refers to the period from signing of the informed consent up to start of IMP administration. Post-treatment refers to the period from start of IMP administration to 7 days after IMP administration.

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

Neuromuscular functioning was monitored by applying repetitive 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). A faster time to recovery of the T4/T1 Ratio to 0.7 indicates a faster recovery from NMB.

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

Neuromuscular functioning was monitored by applying repetitive 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). A faster time to recovery of the T4/T1 Ratio to 0.8 indicates a faster recovery from NMB.

Number of Participants Who Experienced Pre-treatment Serious Adverse Events (SAEs) and Post-treatment SAEsFrom signing of informed consent to end of trial (7 days after surgery)

An SAE is defined as any untoward medical occurrence that at any dose: results in death; is life-threatening; requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; or is a congenital anomaly/birth defect.

Participants were monitored for occurrence SAEs for up to 7 days after last dose IMP. Pre-treatment refers to the period from signing of the informed consent up to start of IMP administration. Post-treatment refers to the period from start of IMP administration to 7 days after IMP administration.

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