Comparing 4.0 mg.Kg-1 Sugammadex With Placebo in the Reversal of Profound Neuromuscular Blockade (P05767)

Study Overview
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Brief Summary
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The current trial was designed to demonstrate faster recovery in participants undergoing elective surgeries requiring profound neuromuscular blockade induced by rocuronium to a fourth twitch/first twitch (T4/T1) ratio of 0.9, after reversal of a target depth of neuromuscular blockade (NMB) of 1-2 Post Tetanic Count (PTC) by 4.0 mg.kg-1 Sugammadex compared to Placebo, to evaluate the safety of 4.0 mg.kg-1 Sugammadex and to evaluate the Operating Room (OR) and Post Anesthetic Care Unit (PACU) length of stay for these participants.

Official Title
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A Randomized, Safety-assessor Blinded Trial Comparing 4.0 mg.Kg-1 Sugammadex With Placebo in Adult Subjects Scheduled for Surgery Requiring Profound Neuromuscular Blockade

Conditions
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Anesthesia, Neuromuscular Blockade

Intervention / Treatment
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* Drug: Sugammadex
* Drug: 0.9% sodium chloride (NaCl)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female participants American Society of Anesthesiologists (ASA) class 1, 2 or 3 Age >=18 years Scheduled to undergo a surgery requiring profound NMB such as cardiovascular, gynaecologic, neurologic and thoracic surgical procedures under general anesthesia requiring neuromuscular relaxation with rocuronium for endotracheal intubation and if applicable maintenance of NMB in a position allowing neuromuscular monitoring Given written informed consent Exclusion Criteria: Participants known or suspected to have neuromuscular disorders affecting NMB

Ages Eligible for Study
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Minimum Age: 18 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>Participants receiving 4.0 mg.kg-1 Sugammadex at a target depth of NMB of 1-2 PTC after the last dose of rocuronium | Drug: Sugammadex<br>* At a target depth of NMB of 1-2 PTC after the last dose of rocuronium, a bolus dose of 4.0 mg.kg-1 sugammadex (volume based on the actual body weight of the participant) will be administered, within 10 seconds into a fast running venous infusion.<br>* Other names: Bridion®;|
| Placebo Comparator: Placebo<br>Participants receiving Placebo (0.9% NaCl) at a target depth of NMB of 1-2 PTC after the last dose of rocuronium | Drug: 0.9% sodium chloride (NaCl)<br>* At a target depth of NMB of 1-2 PTC after the last dose of rocuronium, a bolus dose of placebo (0.9% NaCl, volume based on the actual body weight of the participant) will be administered, within 10 seconds into a fast running venous infusion.<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time From Start of Administration of Investigational Medicinal Product (IMP, Sugammadex or Placebo) 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 (height) of the first and fourth twitches, respectively, after TOF nerve stimulation. The T4/T1 Ratio (a percentage that is expressed as a decimal of up to 1.0) indicates the extent of recovery from neuromuscular blockade (NMB), with a higher ratio indicating a greater recovery from NMB. In this study, twitch responses were recorded until the T4/T1 Ratio reached >=0.9, the minimum acceptable ratio that indicated complete recovery from NMB. A shorter time to recovery of the T4/T1 Ratio >=0.9 indicates a faster recovery from NMB. | From Start of IMP Administration to Recovery of the T4/T1 Ratio to 0.9 (estimated from  2 minutes up to  90 minutes) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time From Start of Administration of IMP to Recovery of the T4/T1 Ratio to 0.7 | 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 (height) of the first and fourth twitches, respectively, after TOF nerve stimulation. The T4/T1 Ratio (a percentage that is expressed as a decimal of up to 1.0) indicates the extent of recovery from NMB, with a higher ratio indicating a greater recovery from NMB. | From Start of IMP Administration to Recovery of the T4/T1 Ratio to 0.7 (estimated from  1 minute up to  70 minutes) | 
| Time From Start of Administration of IMP to Recovery of the T4/T1 Ratio to 0.8 | 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 (height) of the first and fourth twitches, respectively, after TOF nerve stimulation. The T4/T1 Ratio (a percentage that is expressed as a decimal of up to 1.0) indicates the extent of recovery from NMB, with a higher ratio indicating a greater recovery from NMB. | From Start of IMP Administration to Recovery of the T4/T1 Ratio to 0.8 (estimated from  2 minutes up to  80 minutes) |