Sugammadex After Continuous Infusion of Rocuronium During Sevoflurane and Propofol Anesthesia (P05949; MK-8616-028)

Study Overview
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Brief Summary
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The objective of the trial was to show equivalence in recovery from neuromuscular block after a single dose of 4.0 mg/kg sugammadex, administered at first twitch (T1) 3-10% after continuous infusion of rocuronium, between participants receiving maintenance anesthesia using propofol and participants receiving sevoflurane, to investigate the safety and to compare the plasma levels of rocuronium in participants after continuous infusion of rocuronium and before the administration of sugammadex, under either propofol or sevoflurane anesthesia.

Official Title
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A Multi -Center, Randomized, Parallel Group, Safety Assessor Blinded Trial Comparing Efficacy and Safety of 4.0 mg.Kg-1 Sugammadex , Administered at T1 3-10% After Continuous Infusion of Rocuronium, and Pharmacokinetics of Rocuronium, Between Subjects Receiving Maintenance Anesthesia Using Propofol and Subjects Receiving Maintenance Anesthesia Using Sevoflurane

Conditions
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Anesthesia, General

Intervention / Treatment
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* Drug: Sugammadex
* Drug: Rocuronium
* Drug: Sevoflurane
* Drug: Propofol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants at least 20 years but under 65 years of age; Participants of American Society of Anesthesiologists (ASA) class 1-3; Participants scheduled for a surgical procedure under general anesthesia requiring neuromuscular relaxation with the use of a neuromuscular blocking agent (NMBA) with an anticipated duration of surgery between 2 and 5 hours; Participants scheduled for a surgical procedure in supine position; Participants who had given written informed consent. Exclusion Criteria: Participants in whom difficult intubation was expected because of anatomical malformations; Participants known or suspected to have neuromuscular disorders affecting NMB and/or significant renal dysfunction. In Germany, this also included serum creatinine and blood urea nitrogen outside local reference ranges; Participants known or suspected to have a (family) history of malignant hyperthermia; Participants known or suspected to have an allergy to medications used during general anesthesia; Participants receiving medication interfering with NMBAs, such as antibiotics, anticonvulsants and Mg^2+; based on the dose and time of administration; Pregnant or lactating females; Female participants of childbearing potential not using any birth control or using only hormonal contraception as birth control; Participants who had already participated in trial CT 19.4.312, or in another trial with sugammadex; Participants who had participated in another clinical trial, not pre-approved by Organon, within 30 days of entering into CT 19.4.312.

Ages Eligible for Study
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Minimum Age: 20 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 + Sevoflurane<br>After receiving sevoflurane and the last dose of rocuronium, at the reappearance of first twitch (T1; 3-10% starting amplitude), a dose of 4.0 mg/kg sugammadex was administered. | Drug: Sugammadex<br>* Single dose 4.0 mg/kg sugammadex, administered at T1 3-10% after continuous infusion of rocuronium<br>* Other names: MK-8616;Drug: Rocuronium<br>* Single bolus dose 0.6 mg/kg rocuronium and continuous infusion rocuronium<br>* Other names: Rocuronium Bromide;Drug: Sevoflurane<br>* Sevoflurane IV administered for induction and maintenance of anesthesia, based on randomization.<br>* Other names: Ultane®;|
| Experimental: Sugammadex + Propofol<br>After receiving propofol and the last dose of rocuronium, at the reappearance of first twitch (T1; 3-10% starting amplitude), a dose of 4.0 mg/kg sugammadex was administered. | Drug: Sugammadex<br>* Single dose 4.0 mg/kg sugammadex, administered at T1 3-10% after continuous infusion of rocuronium<br>* Other names: MK-8616;Drug: Rocuronium<br>* Single bolus dose 0.6 mg/kg rocuronium and continuous infusion rocuronium<br>* Other names: Rocuronium Bromide;Drug: Propofol<br>* Propofol IV administered for induction and maintenance of anesthesia, based on randomization.<br>* Other names: Diprivan®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Time From Start Administration of Sugammadex to Recovery of 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 and assessing twitch response at the adductor pollicis muscle. T1 and T4 refer to the amplitudes (heights) of the first and fourth twitches, respectively, after TOF nerve stimulation. The T4/T1 ratio (expressed as a decimal from 0 [loss of T4] up to 1.0 [no NMB]) indicates the extent of recovery from 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. | Up to 3 minutes after sugammadex administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Time From Start of Administration of Sugammadex 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 and assessing twitch response at the adductor pollicis muscle. T1 and T4 refer to the amplitudes (heights) of the first and fourth twitches, respectively, after TOF nerve stimulation. The T4/T1 ratio (expressed as a decimal from 0 [loss of T4] up to 1.0 [no NMB]) indicates the extent of recovery from NMB. A faster time to recovery of the T4/T1 ratio to 0.7 indicates a faster recovery from NMB. | Up to 3 minutes after sugammadex administration | 
| Mean Time From Start of Administration of Sugammadex 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 and assessing twitch response at the adductor pollicis muscle. T1 and T4 refer to the amplitudes (heights) of the first and fourth twitches, respectively, after TOF nerve stimulation. The T4/T1 ratio (expressed as a decimal from 0 [loss of T4] up to 1.0 [no NMB]) indicates the extent of recovery from NMB. A faster time to recovery of the T4/T1 ratio to 0.8 indicates a faster recovery from NMB. | Up to 3 minutes after sugammadex administration |