Safety and Efficacy of Sugammadex (Org 25969, MK-8616) in Participants With or Having a Past History of Pulmonary Disease (19.4.308) (P05932) (MK-8616-017)

A Multicenter, Randomized, Parallel Group, Comparative, Safety-Assessor Blinded, Phase IIIa Trial in Adult Surgical Subjects Under General Anesthesia at Increased Risk for Pulmonary Complications

The purpose of the trial is to research the safety and to show faster recovery after administration of 2.0 mg/kg or 4.0 mg/kg sugammadex (Org 25969, MK-8616) given as a reversal agent for 0.6 mg/kg (0.15 mg/kg maintenance dose) rocuronium (Zemuron®) in participants diagnosed with or having a history of pulmonary disease. All drug administration will be via the intravenous (IV) route.

Study Overview

• Status: Completed
• Conditions: Anesthesia, General
• Intervention / Treatment: Drug: Sugammadex; Drug: Rocuronium

• Study Type: Interventional
• Enrollment (Actual): 86
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• American Society of Anesthesiologists (ASA) Class 1 to 3;
• Has been diagnosed with or having a past history of pulmonary disease;
• Is scheduled for elective surgical procedure under general anesthesia requiring neuromuscular block with the use of rocuronium;
• Is scheduled for surgery in supine position;
• Has given written informed consent;

Exclusion Criteria:

• Is expected to have a difficult intubation due to anatomical malformations;
• Has known or suspected of having neuromuscular disorders impairing neuromuscular blockade and/or significant renal dysfunction;
• Has known or suspected of having a (family) history of malignant hyperthermia;
• Has known or suspected of having an allergy to narcotics, muscle relaxants or other medications used during surgery;
• Is receiving medication known to interfere with neuromuscular blocking agents such as anticonvulsants, antibiotics and Mg2+;
• Is a female who is pregnant or breast-feeding;
• Is a female of childbearing potential not using an acceptable method of birth control [condom or diaphragm with spermicide, vasectomized partner (> 6 months), IUD, abstinence] or using only hormonal contraception as birth control;
• Has already participated in a sugammadex trial including Protocol 19.4.308;
• Has participated in another clinical trial, not pre-approved by Organon, within 30 days of entering into Protocol 19.4.308.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rocuronium + Sugammadex 2.0 mg/kg; After the IV intubation dose (0.6 mg/kg) or last maintenance dose (0.15 mg/kg) of rocuronium, at reappearance of T2, participants will receive IV sugammadex 2.0 mg/kg.	Drug: Sugammadex; Sugammadex solution for injection.; Other Names: Org 25969, MK-8616, Bridion®; Drug: Rocuronium; Rocuronium bromide solution for injection.; Other Names: Zemuron®
Experimental: Rocuronium + Sugammadex 4.0 mg/kg; After the IV intubation dose (0.6 mg/kg) or last maintenance dose (0.15 mg/kg) of rocuronium, at reappearance of T2, participants will receive IV sugammadex 4.0 mg/kg.	Drug: Sugammadex; Sugammadex solution for injection.; Other Names: Org 25969, MK-8616, Bridion®; Drug: Rocuronium; Rocuronium bromide solution for injection.; Other Names: Zemuron®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time From Start of Sugammadex Administration to Recovery of T4/T1 Ratio to 0.9 in Participants With or Having a Past History of Pulmonary Disease	The mean time from the start of sugammadex administration to recovery of the T4/T1 ratio to 0.9 was determined. Less time indicates faster recovery from neuromuscular blockade. The ratio of T4 (fourth twitch; amplitude of fourth response to train of four [TOF] stimulation is expressed as percent of control T4) over T1 (first twitch; amplitude of first response to TOF stimulation is expressed as percent of control T1) ranges from 0 (complete loss of T4 twitch response) to 1.0 (complete recovery of T4 twitch response). For TOF stimulation, 4 consecutive square wave supra-maximal stimuli of 0.2 msec duration were delivered at 2 Hz every 15 seconds. Neuromuscular monitoring was performed with the TOF-Watch® SX.	Up to 90 minutes
Percentage of Participants Experiencing ≥1 Adverse Event(s) (AE)	The percentage of participants experiencing ≥1 AE(s) was determined for each arm. An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.	Up to 7 days
Percentage of Participants Discontinuing Study Treatment Due to an Adverse Event (AE)	The percentage of participants discontinuing from study treatment due to an AE was determined for each arm. An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.	Up to 7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time From Start of Sugammadex Administration to Recovery of T4/T1 Ratio to 0.7 in Participants With or Having a Past History of Pulmonary Disease	The mean time from the start of sugammadex administration to recovery of the T4/T1 ratio to 0.7 was determined. Less time indicates faster recovery from neuromuscular blockade. The ratio of T4 (fourth twitch; amplitude of fourth response to train of four [TOF] stimulation is expressed as percent of control T4) over T1 (first twitch; amplitude of first response to TOF stimulation is expressed as percent of control T1) ranges from 0 (complete loss of T4 twitch response) to 1.0 (complete recovery of T4 twitch response). For TOF stimulation, 4 consecutive square wave supra-maximal stimuli of 0.2 msec duration were delivered at 2 Hz every 15 seconds. Neuromuscular monitoring was performed with the TOF-Watch® SX.	Up to 90 minutes
Time From Start of Sugammadex Administration to Recovery of T4/T1 Ratio to 0.8 in Participants With or Having a Past History of Pulmonary Disease	The mean time from the start of sugammadex administration to recovery of the T4/T1 ratio to 0.8 was determined. Less time indicates faster recovery from neuromuscular blockade. The ratio of T4 (fourth twitch; amplitude of fourth response to train of four [TOF] stimulation is expressed as percent of control T4) over T1 (first twitch; amplitude of first response to TOF stimulation is expressed as percent of control T1) ranges from 0 (complete loss of T4 twitch response) to 1.0 (complete recovery of T4 twitch response). For TOF stimulation, 4 consecutive square wave supra-maximal stimuli of 0.2 msec duration were delivered at 2 Hz every 15 seconds. Neuromuscular monitoring was performed with the TOF-Watch® SX.	Up to 90 minutes
Level of Consciousness Assessment 1: Prior to Transfer to the Recovery Room Following Extubation	The level of consciousness prior to transfer to the recovery room was determined by the clinician for each participant. Each participants was assigned 1 of 3 potential levels of consciousness: 1) awake and oriented; 2) arousable with minimal stimulation; or 3) responsive only to tactile stimulation.	Up to 6 hours (prior to transfer to the recovery room after extubation)
Level of Consciousness Assessment 2: Prior to Discharge From the Recovery Room	The level of consciousness prior to discharge from the recovery room was determined by the clinician for each participant. Each participants was assigned 1 of 3 potential levels of consciousness: 1) awake and oriented; 2) arousable with minimal stimulation; or 3) responsive only to tactile stimulation.	Up to 6 hours (prior to discharge from the recovery room)
Five-Second Head Lift Assessment 1: Prior to Transfer to the Recovery Room Following Extubation	The ability of each cooperative (based on clinician determination) participant to perform a 5-second head lift was determined by the clinician. Participants were rated as either able or not able to complete the head lift task.	Up to 6 hours (prior to transfer to the recovery room after extubation)
Five-Second Head Lift Assessment 2: Prior to Discharge From the Recovery Room	The ability of each cooperative (based on clinician determination) participant to perform a 5-second head lift was determined by the clinician. Participants were rated as either able or not able to complete the head lift task.	Up to 6 hours (prior to discharge from the recovery room)
General Muscle Weakness Assessment 1: Prior to Transfer to the Recovery Room Following Extubation	Each cooperative (based on clinician determination) participant was assessed by a clinician to determine if there was muscle weakness. Participants were rated as having or not having muscle weakness by the clinician.	Up to 6 hours (prior to transfer to the recovery room after extubation)
General Muscle Weakness Assessment 2: Prior to Discharge From the Recovery Room	Each cooperative (based on clinician determination) participant was assessed by a clinician to determine if there was muscle weakness. Participants were rated as having or not having muscle weakness by the clinician.	Up to 6 hours (prior to discharge from the recovery room)

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Amao R, Zornow MH, Cowan RM, Cheng DC, Morte JB, Allard MW. Use of sugammadex in patients with a history of pulmonary disease. J Clin Anesth. 2012 Jun;24(4):289-97. doi: 10.1016/j.jclinane.2011.09.006.

Helpful Links

• Click here to access a synopsis of the study results.

Study record dates

Study Major Dates

• Study Start (Actual): October 27, 2005
• Primary Completion (Actual): August 21, 2006
• Study Completion (Actual): September 9, 2006

Study Registration Dates

• First Submitted: May 17, 2007
• First Submitted That Met QC Criteria: May 17, 2007
• First Posted (Estimate): May 21, 2007

Study Record Updates

• Last Update Posted (Actual): April 12, 2019
• Last Update Submitted That Met QC Criteria: April 10, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Peripheral Nervous System Agents; Neuromuscular Agents; Neuromuscular Nondepolarizing Agents; Neuromuscular Blocking Agents; Rocuronium
• Other Study ID Numbers: P05932 (Other Identifier: Schering-Plough Protocol Number); 19.4.308 (Other Identifier: Organon Protocol Number); MK-8616-017 (Other Identifier: Merck Protocol Number)

Plan for Individual participant data (IPD)

Study Data/Documents

1. CSR Synopsis