Comparison of Sugammadex (Org 25969) With Neostigmine as Reversal Agents for Rocuronium or Vecuronium at Reappearance of T2 (P05960)

Study Overview
=================
Brief Summary
-----------------
The purpose of this study was to demonstrate in adult participants faster recovery from a neuromuscular block induced by either rocuronium or vecuronium after reversal at reappearance of T2 (the amplitude of the first response of second twitch to train of four (TOF) stimulation, expressed as percentage of control first twitch, T1) by 2.0 mg/kg sugammadex (Org 25969) compared to 50 ug/kg neostigmine.

Official Title
-----------------
A Multi -Center Randomized Parallel Group Comparative Active Controlled Safety Assessor Blinded Phase 3a Pivotal Trial in Adult Subjects Comparing Org 25969 With Neostigmine as Reversal Agents of a Neuromuscular Block Induced by Rocuronium or Vecuronium at Reappearance of T2

Conditions
-----------------
Anesthesia, General

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Is of American Society of Anesthesiologists (ASA) 1 - 4; Is above or equal to the age of 18; Scheduled for surgical procedures with a general anesthesia with the use of rocuronium or vecuronium for endotracheal intubation and maintenance of neuromuscular block; Scheduled for surgical procedure in supine position; Given written informed consent. Exclusion Criteria: Participants in whom a difficult intubation because of anatomical malformations was expected; Is known or suspected to have neuromuscular disorders impairing neuromuscular block (NMB) and/or significant renal dysfunction; Is known or suspected to have a (family) history of malignant hyperthermia; Is known or suspected to have an allergy to narcotics, muscle relaxants or other medication used during general anesthesia; Is receiving medication in a dose and/or at a time point known to interfere with neuromuscular blocking agents such as antibiotics, anticonvulsants and Mg2+; Participants in whom the use of neostigmine and/or glycopyrrolate may be contraindicated; Had already participated in a sugammadex trial; Had participated in another clinical trial, not pre-approved by NV Organon, within 30 days of entering into P05960. Females who are pregnant: Females of childbearing potential not using any method of birth control: condom or using only hormonal contraception as birth control; Females who were breast-feeding.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rocuronium + Sugammadex<br>After the last dose of rocuronium, at reappearance of T2, a dose of 2.0 mg/kg sugammadex was administered | Drug: Sugammadex<br>* After the last dose of rocuronium or vecuronium, at reappearance of T2, a dose of 2.0 mg/kg sugammadex was to be administered<br>* Other names: Org 25969;|
| Active Comparator: Rocuronium + Neostigmine<br>After the last dose of rocuronium, at reappearance of T2, a dose of 50 ug/kg neostigmine was administered | Drug: Neostigmine<br>* After the last dose of rocuronium or vecuronium, at reappearance of T2, a dose of 50 ug/kg neostigmine was to be administered<br>* Other names: premix neostigmine/glycopyrrolate;|
| Experimental: Vecuronium + Sugammadex<br>After the last dose of vecuronium, at reappearance of T2, a dose of 2.0 mg/kg sugammadex was administered | Drug: Sugammadex<br>* After the last dose of rocuronium or vecuronium, at reappearance of T2, a dose of 2.0 mg/kg sugammadex was to be administered<br>* Other names: Org 25969;|
| Active Comparator: Vecuronium + Neostigmine<br>After the last dose of vecuronium, at reappearance of T2, a dose of 50 ug/kg neostigmine was administered | Drug: Neostigmine<br>* After the last dose of rocuronium or vecuronium, at reappearance of T2, a dose of 50 ug/kg neostigmine was to be administered<br>* Other names: premix neostigmine/glycopyrrolate;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time From Start of Administration of Sugammadex or Neostigmine 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 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 of up to 1.0) indicates the extent of recovery from neuromuscular blockade (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. | Day 1: From start of sugammadex or neostigmine administration to recovery of T4/T1 ratio to 0.9 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time From Start of Administration of Sugammadex or Neostigmine 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 of up to 1.0) 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. | Day 1: From start of sugammadex or neostigmine administration to recovery of T4/T1 ratio to 0.7 | 
| Time From Start of Administration of Sugammadex or Neostigmine 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 of up to 1.0) 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. | Day 1: From start of sugammadex or neostigmine administration to recovery of T4/T1 ratio to 0.8 | 
| Number of Participants With Clinical Signs of Recovery Assessed by Level of Consciousness, Head Lift and Muscle Weakness, Prior to Transfer to the Recovery Room After Extubation | After anesthesia and prior to transfer to the recovery room after extubation, neuromuscular recovery was assessed by monitoring every 15 minutes the following clinical signs of recovery: level of consciousness (i.e., awake and oriented, arousable with minimal stimulation, responsive only to tactile stimulation); 5-second head lift test (ability to lift the head for 5 seconds); and general muscle weakness | Day 1 | 
| Number of Participants With Clinical Signs of Recovery Assessed by Level of Consciousness, Head Lift and Muscle Weakness, Prior to Discharge From the Recovery Room | Just prior to discharge from the recovery room, neuromuscular recovery was assessed by monitoring every 15 minutes the following clinical signs of recovery: level of consciousness (i.e., awake and oriented, arousable with minimal stimulation, responsive only to tactile stimulation); 5-second head lift test (ability to lift the head for 5 seconds); and general muscle weakness | Day 1 |