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)

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Anesthesia

Intervention / Treatment
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* Drug: Sugammadex
* Drug: Neostigmine
* Drug: Rocuronium


Participation Criteria
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Eligibility Criteria
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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;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sugammadex<br>4 mg/kg sugammadex | Drug: Sugammadex<br>* Participants received 4 mg/kg sugammadex at 1-2 Post Tetanic Counts (PTCs) or better after the last dose of rocuronium bromide.<br>* Other names: Bridion®;Drug: Rocuronium<br>* Participants received a single intubation bolus dose of 0.6 mg/kg rocuronium bromide, followed if necessary to maintain neuromuscular blockade by one or more single bolus dose(s) of 0.15 mg/kg rocuronium bromide.<br>* Other names: Esmeron®;|
| Active Comparator: Neostigmine<br>50 µg/kg neostigmine | Drug: Neostigmine<br>* Participants received 50 µg/kg neostigmine combined with 10 µg/kg glycopyrrolate after the last dose of rocuronium bromide as per standard of care.<br>* Other names: Prostigmin®;Drug: Rocuronium<br>* Participants received a single intubation bolus dose of 0.6 mg/kg rocuronium bromide, followed if necessary to maintain neuromuscular blockade by one or more single bolus dose(s) of 0.15 mg/kg rocuronium bromide.<br>* Other names: Esmeron®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Residual Neuromuscular Blockade Evidenced by T4/T1 Ratio at the Time of Tracheal Extubation | Neuromuscular function 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 with a TOF-Watch® SX. The magnitudes (heights) of the first and fourth twitches (T1 and T4) were used to calculate the T4/T1 ratio, where a higher T4/T1 ratio indicates a greater recovery from neuromuscular blockade, with a value of 1.0 indicating complete recovery. After anesthesia, when neuromuscular function was expected to be fully recovered, tracheal extubation was performed, at which time the T4/T1 ratio was measured, with any missing recovery times imputed. | Up to the first 24 hours after tracheal extubation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Post-operative Complications | Post-operative complications include any of the following: procedural pain, nausea, vomiting, incision-site pain, constipation, headache, pyrexia, dizziness and pruritus. | Up to 7 days after surgery | 
| Number of Participants With Evidence of Possible Interaction of Sugammadex With Endogenous Compounds or Exogenous Compounds Other Than Rocuronium Bromide | Evidence of adverse events due to a possible interaction of sugammadex with exogenous compounds or endogenous compounds other than rocuronium was recorded. | Up to 7 days after surgery | 
| Time From Start of Administration of Investigational Medicinal Product (IMP) to Recovery of the T4/T1 Ratio to 0.9 | Neuromuscular function was monitored by applying repetitive TOF electrical stimulations to the ulnar nerve every 15 seconds, and assessing T1 and T4 twitch response at the adductor pollicis muscle with a TOF-Watch® SX. Nerve stimulation was continued until the T4/T1 ratio, which indicates the extent of recovery from neuromuscular blockade, achieved a ratio of 0.9, with imputed data included. | Up to 1 hour after treatment | 
| Time From Start of Administration of IMP to Recovery of the T4/T1 Ratio to 0.8 | Neuromuscular function was monitored by applying repetitive TOF electrical stimulations to the ulnar nerve every 15 seconds, and assessing T1 and T4 twitch response at the adductor pollicis muscle with a TOF-Watch® SX. Nerve stimulation was continued until the T4/T1 ratio, which indicates the extent of recovery from neuromuscular blockade, achieved a ratio of 0.8, with imputed data included. | Up to 1 hour after treatment | 
| Time From Start of Administration of IMP to Recovery of the T4/T1 Ratio to 0.7 | Neuromuscular function was monitored by applying repetitive TOF electrical stimulations to the ulnar nerve every 15 seconds, and assessing T1 and T4 twitch response at the adductor pollicis muscle with a TOF-Watch® SX. Nerve stimulation was continued until the T4/T1 ratio, which indicates the extent of recovery from neuromuscular blockade, achieved a ratio of 0.7, with imputed data included. | Up to 1 hour after treatment |