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

Condition(s) targeted: Anesthesia, General

Intervention: Rocuronium (Drug); Sugammadex (Drug); Neostigmine (Drug); Atropine (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: Merck Sharp & Dohme Corp.

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.

Official title: A Multi-center, Randomized, Parallel-group, Comparative, Active-controlled, Safety-assessor Blinded Trial in Adult Subjects Comparing the Efficacy and Safety of Sugammadex (SCH 900616, ORG 25969) Administered at 1-2 PTC With Neostigmine Administered at Reappearance of T2 in Subjects Undergoing Laparoscopic Cholecystectomy or Appendectomy Under Propofol Anesthesia

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome: 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

Secondary outcome:

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

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

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

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

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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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

Related publications:

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.

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.

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

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. Review.

Apfel CC, Läärä 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.

Aldrete JA, Kroulik D. A postanesthetic recovery score. Anesth Analg. 1970 Nov-Dec;49(6):924-34.

Starting date: July 2008
Last updated: February 26, 2015