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

Neuromuscular Blockade Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00751179
• Other study ID #: P05700
• Secondary ID: 19.4.319
• Status: Completed
• Phase: Phase 3
• First received: September 10, 2008
• Last updated: June 3, 2015
• Start date: November 2008
• Est. completion date: December 2009

Study information

• Verified date: June 2015
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 161
• Est. completion date: December 2009
• Est. primary completion date: December 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Neuromuscular Blockade

Intervention

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.
• 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.
• 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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

References & Publications (1)

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. 20 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Primary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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)	Yes
Secondary	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)	Yes