Rocuronium Plus Sugammadex Versus Succinylcholine Alone in Participants Undergoing Short Surgical Procedures (19.4.319)(P05700 AM2)(COMPLETED)

A Multi-center, Randomized, Parallel Group, Comparative, Active Controlled, Safety Assessor Blinded Trial in Adult Subjects Comparing Rocuronium Plus Sugammadex Versus Succinylcholine Alone in Subjects Undergoing Short Surgical Procedures in Out-patient Surgicenters

A multi-center, randomized, parallel group, comparative, active controlled, safety assessor blinded trial in adult subjects comparing rocuronium plus sugammadex versus succinylcholine alone in subjects undergoing short surgical procedures in out-patient surgicenters. The primary objective was to evaluate changes in plasma potassium levels after treatment with rocuronium, sugammadex, or succinylcholine in adult subjects scheduled for short surgical procedures in out-patient surgicenters.

Study Overview

• Status: Completed
• Conditions: Neuromuscular Blockade
• Intervention / Treatment: Drug: rocuronium; Drug: sugammadex; Drug: succinylcholine

• Study Type: Interventional
• Enrollment (Actual): 161
• 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:

• Male or female subjects >=18 years of age;
• ASA Class 1-3;
• Subjects with a Body Mass Index (BMI) of < 35 kg/m^2 ;
• Subjects scheduled to undergo an elective short procedure with general anesthesia requiring neuromuscular relaxation and endotracheal intubation in outpatient surgicenters;
• Subjects scheduled to undergo an elective surgical procedure expected to last 1.5 hours or less (from end of intubation to end of suturing/stapling of skin);
• Subjects who are scheduled to undergo an elective surgical procedures that allows access to the arm for TOF-Watch® SX monitoring;
• Subjects who have given written informed consent.

Exclusion Criteria:

• Subjects known to have ischemic heart disease or a history of myocardial infarction;
• Subjects in whom a difficult intubation is expected because of anatomical malformations;
• Subjects with medical conditions and/or undergoing surgical procedures that are not compatible with the use of the TOF-Watch SX (e.g., injuries to the thumbs/distal forearms, bilateral ulnar nerve damage or subjects with cardiac pacemakers);
• Subjects known or suspected to have neuromuscular disorders impairing neuromuscular blockade (e.g., subjects with myasthenia gravis);
• Subjects who would require the use of pneumatic tourniquet during the surgical procedure;
• Subjects known or suspected to have significant renal dysfunction (e.g., creatinine clearance < 30 mL per min);
• Subjects known or suspected to have significant hepatic dysfunction;
• Subjects known or suspected to have a (family) history of malignant hyperthermia;
• Subjects known or suspected to be hypersensitive to sugammadex or other cyclodextrins or rocuronium or any of its excipients;
• Subjects known or suspected to have an allergy to opiates/opioids, muscle relaxants, or other medications used during general anesthesia;
• Subjects for whom a pre-established need for post operative intensive care admission and/or hospital admission is expected;
• Subjects for whom an intra operative IV administration of fluids that contain potassium is expected;
• Female subjects who are pregnant;
• Female subjects who are breast-feeding;
• Subjects who have participated in a previous sugammadex trial;
• Subjects who have participated in another investigational drug trial within 30 days before entering into clinical trial (CT) 19.4.319 (P05700) unless pre-approved by the sponsor.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Rocuronium - Sugammadex; Rocuronium - Sugammadex 4.0 mg/kg	Drug: rocuronium; A single bolus intubation dose of 0.6 mg/kg rocuronium will be administered following induction of anesthesia and if required, single bolus dose(s) of 0.15 mg/kg rocuronium will be administered to maintain the neuromuscular block.; Other Names: Zemuron® Injection (rocuronium bromide); Drug: sugammadex; At the end of the surgical procedure at a target depth of neuromuscular blockade of at least 1-2 Post-Tetanic Count (PTC), 4.0 mg/kg of sugammadex will be administered.; Other Names: Bridion; sugammadex sodium injection; SCH 900916; Org 25969
Active Comparator: Succinylcholine; Succinylcholine 1.0 mg/kg	Drug: succinylcholine; A single bolus intubation dose of 1.0 mg/kg succinylcholine will be administered following induction of anesthesia and the subject is allowed to recover spontaneously from the neuromuscular blockade.; Other Names: Quelicin® (succinylcholine chloride injection United States Pharmacopeia [USP])

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Plasma Potassium Levels at 5 Minutes After Treatment With Rocuronium or Succinylcholine	Change from baseline = 5 minutes post dose value - baseline value. Baseline levels were obtained prior to rocuronium or succinylcholine dose. Only data post rocuronium dose are included for "rocuronium - sugammadex" group. The change from baseline interval included most or all of the intubation/surgical period for sugammadex analysis (since sugammadex was administered at the end of the surgical procedure) but not for succinylcholine or rocuronium analyses (since these were administered immediately after the baseline measurement just prior to intubation/commencement of the surgical period).	Baseline and 5 minutes post dose
Change From Baseline in Plasma Potassium Levels at 5 Minutes After Treatment With Sugammadex	Change from baseline = 5 minutes post dose value - baseline value. Baseline levels were obtained prior to rocuronium dose. Only data post sugammadex dose are included for "rocuronium - sugammadex" group. The change from baseline interval included most or all of the intubation/surgical period for sugammadex analysis (since sugammadex was administered at the end of the surgical procedure) but not for succinylcholine or rocuronium analyses (since these were administered immediately after the baseline measurement just prior to intubation/commencement of the surgical period).	Baseline and 5 minutes post dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Plasma Potassium Levels at 2 Minutes After Treatment With Rocuronium or Succinylcholine	Change from baseline = 2 minutes post dose value - baseline value. Baseline levels were obtained prior to rocuronium or succinylcholine dose. Only data post rocuronium dose are included for "rocuronium - sugammadex" group. The change from baseline interval included most or all of the intubation/surgical period for sugammadex analysis (since sugammadex was administered at the end of the surgical procedure) but not for succinylcholine or rocuronium analyses (since these were administered immediately after the baseline measurement just prior to intubation/commencement of the surgical period).	Baseline and 2 minutes post dose
Change From Baseline in Plasma Potassium Levels at 2 Minutes After Treatment With Sugammadex	Change from baseline = 2 minutes post dose value - baseline value. Baseline levels were obtained prior to rocuronium dose. Only data post sugammadex dose are included for "rocuronium - sugammadex" group. The change from baseline interval included most or all of the intubation/surgical period for sugammadex analysis (since sugammadex was administered at the end of the surgical procedure) but not for succinylcholine or rocuronium analyses (since these were administered immediately after the baseline measurement just prior to intubation/commencement of the surgical period).	Baseline and 2 minutes post dose
Change From Baseline in Plasma Potassium Levels at 10 Minutes After Treatment With Rocuronium or Succinylcholine	Change from baseline = 10 minutes post dose value - baseline value. Baseline levels were obtained prior to rocuronium or succinylcholine dose. Only data post rocuronium dose are included for "rocuronium - sugammadex" group. The change from baseline interval included most or all of the intubation/surgical period for sugammadex analysis (since sugammadex was administered at the end of the surgical procedure) but not for succinylcholine or rocuronium analyses (since these were administered immediately after the baseline measurement just prior to intubation/commencement of the surgical period).	Baseline and 10 minutes post dose
Change From Baseline in Plasma Potassium Levels at 10 Minutes After Treatment With Sugammadex	Change from baseline = 10 minutes post dose value - baseline value. Baseline levels were obtained prior to rocuronium dose. Only data post sugammadex dose are included for "rocuronium - sugammadex" group. The change from baseline interval included most or all of the intubation/surgical period for sugammadex analysis (since sugammadex was administered at the end of the surgical procedure) but not for succinylcholine or rocuronium analyses (since these were administered immediately after the baseline measurement just prior to intubation/commencement of the surgical period).	Baseline and 10 minutes post dose
Change From Baseline in Plasma Potassium Levels at 15 Minutes After Treatment With Rocuronium or Succinylcholine	Change from baseline = 15 minutes post dose value - baseline value. Baseline levels were obtained prior to rocuronium or succinylcholine dose. Only data post rocuronium dose are included for "rocuronium - sugammadex" group. The change from baseline interval included most or all of the intubation/surgical period for sugammadex analysis (since sugammadex was administered at the end of the surgical procedure) but not for succinylcholine or rocuronium analyses (since these were administered immediately after the baseline measurement just prior to intubation/commencement of the surgical period).	Baseline and 15 minutes post dose
Change From Baseline in Plasma Potassium Levels at 15 Minutes After Treatment With Sugammadex	Change from baseline = 15 minutes post dose value - baseline value. Baseline levels were obtained prior to rocuronium dose. Only data post sugammadex dose are included for "rocuronium - sugammadex" group. The change from baseline interval included most or all of the intubation/surgical period for sugammadex analysis (since sugammadex was administered at the end of the surgical procedure) but not for succinylcholine or rocuronium analyses (since these were administered immediately after the baseline measurement just prior to intubation/commencement of the surgical period).	Baseline and 15 minutes post dose
Number of Participants With at Least One Adverse Event (AE) in Rocuronium - Sugammadex and Succinylcholine Treatment Groups	Only AEs which occurred following administration of sugammadex or succinylcholine are included. AEs in the rocuronium - sugammadex group occurring after rocuronium but before sugammadex administration are considered "pretreatment" events and are not included. The AE reporting interval included the entire intubation/surgical period for the succinylcholine group (since succinylcholine was administered just prior to intubation/commencement of surgery) but not for the rocuronium - sugammadex group (since sugammadex was administered at the end of the surgical procedure).	Up to 7 days post dose
Time to Recovery of the Fourth Twitch/First Twitch (T4/T1) Ratio to 0.9 Following Administration of 4.0 mg/kg of Sugammadex After Neuromuscular Blockade Induced by Rocuronium	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. Nerve stimulation continued until the ratio of the magnitude of the fourth twitch (T4) to first twitch (T1) reached at least 0.9. The greater the T4/T1 ratio the greater the recovery from neuromuscular blockade, with a value of 1.0 representing full recovery.	Start of administration of sugammadex to recovery from neuromuscular blockade (Up to approximately 6 minutes)
Time to Recovery of T1 to 90% of Baseline Following Neuromuscular Blockade Induced by Succinylcholine	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. Nerve stimulation continued until recovery of T1 of 90% of baseline and full recovery of neuromuscular function occurred as determined by the anesthesiologist as per routine clinical practice.	Start of administration of succinylcholine to recovery from neuromuscular blockade (Up to approximately 18 minutes)

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Soto R, Jahr JS, Pavlin J, Sabo D, Philip BK, Egan TD, Rowe E, de Bie J, Woo T. Safety and Efficacy of Rocuronium With Sugammadex Reversal Versus Succinylcholine in Outpatient Surgery-A Multicenter, Randomized, Safety Assessor-Blinded Trial. Am J Ther. 2016 Nov/Dec;23(6):e1654-e1662. doi: 10.1097/MJT.0000000000000206.
• Sabo D, Jahr J, Pavlin J, Philip B, Shimode N, Rowe E, Woo T, Soto R. The increases in potassium concentrations are greater with succinylcholine than with rocuronium-sugammadex in outpatient surgery: a randomized, multicentre trial. Can J Anaesth. 2014 May;61(5):423-32. doi: 10.1007/s12630-014-0128-7. Epub 2014 Apr 8.

Study record dates

Study Major Dates

• Study Start: November 1, 2008
• Primary Completion (Actual): December 1, 2009
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: September 10, 2008
• First Submitted That Met QC Criteria: September 10, 2008
• First Posted (Estimate): September 11, 2008

Study Record Updates

• Last Update Posted (Estimate): June 30, 2015
• Last Update Submitted That Met QC Criteria: June 3, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Peripheral Nervous System Agents; Anticonvulsants; Neuromuscular Agents; Neuromuscular Nondepolarizing Agents; Neuromuscular Blocking Agents; Neuromuscular Depolarizing Agents; Bromides; Rocuronium; Succinylcholine
• Other Study ID Numbers: P05700; 19.4.319

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No