Comparison of Sugammadex Administered at 1-2 Post Tetanic Counts (PTCs) or Better With Neostigmine Administered as Per Standard of Care to Reverse Rocuronium-Induced Neuromuscular Blockade in Adults Undergoing Elective Open Abdominal Procedure (19.4.334) (P05774)

Condition(s) targeted: Anesthesia

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

Phase: Phase 3

Status: Completed

Sponsored by: Merck Sharp & Dohme Corp.

The primary purpose of this study is to compare the incidence of residual neuromuscular blockade at the time of tracheal extubation after reversal of rocuronium bromide-induced neuromuscular blockade by 4 mg/kg sugammadex with that of 50 µg/kg neostigmine. Residual neuromuscular blockade is defined as the fourth twitch to first twitch (T4/T1) ratio of < 0. 90.

Official title: A Multi-center, Randomized, Parallel Group, Comparative, Active Controlled, Safety-assessor Blinded, Anesthesiologist-TOF-Watch® SX Blinded Trial Comparing T4/T1 Ratio at Time of Tracheal Extubation Using 4 mg/kg Sugammadex Administered at 1-2 PTCs or Better After the Last Dose of Rocuronium Bromide to 50 µg/kg Neostigmine Administered as Per Standard of Care in Adult Subjects Undergoing Elective Open Abdominal Procedures Requiring Neuromuscular Blockade Reversal

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

Primary outcome: Residual Neuromuscular Blockade Evidenced by T4/T1 Ratio at the Time of Tracheal Extubation

Secondary outcome:

Number of Participants With Post-operative Complications

Number of Participants With Evidence of Possible Interaction of Sugammadex With Endogenous Compounds or Exogenous Compounds Other Than Rocuronium Bromide

Time From Start of Administration of Investigational Medicinal Product (IMP) to Recovery of the T4/T1 Ratio to 0.9

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

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

Detailed description: Undetected residual neuromuscular blockade is common in the post-anesthesia care unit (PACU). In fact, 16%-42% of patients receiving intermediate-acting muscle relaxants in the operating room have T4/T1 ratios <0. 7-0. 8 in the PACU. Respiratory and pharyngeal muscle function can be adversely affected during minimal neuromuscular blockade. Studies in awake volunteers and surgical patients have demonstrated that T4/T1 ratios of 0. 7

- 0. 9 are associated with impaired airway protective reflexes, upper airway obstruction, a

decreased hypoxic ventilatory response, and post-operative hypoxemia. The incidence and severity of residual neuromuscular blockade at the time of tracheal extubation will be evaluated to determine how these influence the length of stay in the operating room and PACU.

Minimum age: 18 Years. Maximum age: 65 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- male or females who are >= 18 and <= 65 years of age

- classified by the American Society of Anesthesiologists (ASA) as Class 1 or 2 or 3;

- Body Mass Index (BMI) of <35 kg/m^2;

- is scheduled to undergo an elective open abdominal surgical procedure under general

anesthesia requiring neuromuscular relaxation using rocuronium bromide (maintenance of neuromuscular blockade if required) for endotracheal intubation and requiring neuromuscular blockade reversal;

- is scheduled to undergo a surgical procedure in a position that does not interfere

with the use of TOF-Watch® SX;

- is scheduled to undergo an elective open abdominal procedure expected to last <=4

hours (from start of skin incision to end of last stitch of the skin);

- have given written informed consent.

Exclusion Criteria:

- participants for whom a difficult intubation is expected because of anatomical

malformations;

- is known or suspected to have neuromuscular disorders that may impair neuromuscular

blockade;

- is known or suspected to have significant renal dysfunction (e. g., creatinine

clearance < 30 mL/min) ;

- is known or suspected to have significant hepatic dysfunction;

- is known or suspected to have a (family) history of malignant hyperthermia;

- is known or suspected to have an allergy to opioids, muscle relaxants or other

medications used during general anesthesia;

- participants for whom the use of neostigmine and/or glycopyrrolate may be

contraindicated;

- participants for whom a pre-established need for postoperative intensive care

admission is expected;

- pregnant or breast-feeding females;

- have participated in a previous sugammadex clinical trial;

Starting date: May 2008
Last updated: February 24, 2015