Comparison of Sugammadex Administered at 1-2 Post Tetanic Counts (PTCs) or Better With Neostigmine Administered as Per Standard of Care to Reverse Rocuronium-Induced Neuromuscular Blockade in Adults Undergoing Elective Open Abdominal Procedure (19.4.334) (P05774)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00675792
First received: May 7, 2008
Last updated: May 12, 2014
Last verified: May 2014
  Purpose

The primary purpose of this study is to compare the incidence of

residual neuromuscular blockade at the time of tracheal extubation after reversal of rocuronium bromide-induced neuromuscular blockade by 4 mg/kg sugammadex with that of 50 µg/kg neostigmine. Residual neuromuscular blockade is defined as the fourth twitch to first twitch (T4/T1) ratio of

< 0.90.


Condition Intervention Phase
Anesthesia
Drug: Sugammadex
Drug: Neostigmine
Drug: Rocuronium
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multi-center, Randomized, Parallel Group, Comparative, Active Controlled, Safety-assessor Blinded, Anesthesiologist-TOF-Watch® SX Blinded Trial Comparing T4/T1 Ratio at Time of Tracheal Extubation Using 4 mg/kg Sugammadex Administered at 1-2 PTCs or Better After the Last Dose of Rocuronium Bromide to 50 µg/kg Neostigmine Administered as Per Standard of Care in Adult Subjects Undergoing Elective Open Abdominal Procedures Requiring Neuromuscular Blockade Reversal

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Residual Neuromuscular Blockade Evidenced by T4/T1 Ratio at the Time of Tracheal Extubation [ Time Frame: Up to the first 24 hours after tracheal extubation ] [ Designated as safety issue: No ]
    Neuromuscular function 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 with a TOF-Watch® SX. The magnitudes (heights) of the first and fourth twitches (T1 and T4) were used to calculate the T4/T1 ratio, where a higher T4/T1 ratio indicates a greater recovery from neuromuscular blockade, with a value of 1.0 indicating complete recovery. After anesthesia, when neuromuscular function was expected to be fully recovered, tracheal extubation was performed, at which time the T4/T1 ratio was measured, with any missing recovery times imputed.


Secondary Outcome Measures:
  • Number of Participants With Post-operative Complications [ Time Frame: Up to 7 days after surgery ] [ Designated as safety issue: Yes ]
    Post-operative complications include any of the following: procedural pain, nausea, vomiting, incision-site pain, constipation, headache, pyrexia, dizziness and pruritus.

  • Number of Participants With Evidence of Possible Interaction of Sugammadex With Endogenous Compounds or Exogenous Compounds Other Than Rocuronium Bromide [ Time Frame: Up to 7 days after surgery ] [ Designated as safety issue: Yes ]
    Evidence of adverse events due to a possible interaction of sugammadex with exogenous compounds or endogenous compounds other than rocuronium was recorded.

  • Time From Start of Administration of Investigational Medicinal Product (IMP) to Recovery of the T4/T1 Ratio to 0.9 [ Time Frame: Up to 1 hour after treatment ] [ Designated as safety issue: No ]
    Neuromuscular function was monitored by applying repetitive TOF electrical stimulations to the ulnar nerve every 15 seconds, and assessing T1 and T4 twitch response at the adductor pollicis muscle with a TOF-Watch® SX. Nerve stimulation was continued until the T4/T1 ratio, which indicates the extent of recovery from neuromuscular blockade, achieved a ratio of 0.9, with imputed data included.

  • Time From Start of Administration of IMP to Recovery of the T4/T1 Ratio to 0.8 [ Time Frame: Up to 1 hour after treatment ] [ Designated as safety issue: No ]
    Neuromuscular function was monitored by applying repetitive TOF electrical stimulations to the ulnar nerve every 15 seconds, and assessing T1 and T4 twitch response at the adductor pollicis muscle with a TOF-Watch® SX. Nerve stimulation was continued until the T4/T1 ratio, which indicates the extent of recovery from neuromuscular blockade, achieved a ratio of 0.8, with imputed data included.

  • Time From Start of Administration of IMP to Recovery of the T4/T1 Ratio to 0.7 [ Time Frame: Up to 1 hour after treatment ] [ Designated as safety issue: No ]
    Neuromuscular function was monitored by applying repetitive TOF electrical stimulations to the ulnar nerve every 15 seconds, and assessing T1 and T4 twitch response at the adductor pollicis muscle with a TOF-Watch® SX. Nerve stimulation was continued until the T4/T1 ratio, which indicates the extent of recovery from neuromuscular blockade, achieved a ratio of 0.7, with imputed data included.


Enrollment: 100
Study Start Date: May 2008
Study Completion Date: September 2008
Primary Completion Date: September 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sugammadex
4 mg/kg sugammadex
Drug: Sugammadex
Participants received 4 mg/kg sugammadex at 1-2 Post Tetanic Counts (PTCs) or better after the last dose of rocuronium bromide.
Other Names:
  • Org 25969
  • SCH 900616
  • MK-8616
  • Bridion®
Drug: Rocuronium
Participants received a single intubation bolus dose of 0.6 mg/kg rocuronium bromide, followed if necessary to maintain neuromuscular blockade by one or more single bolus dose(s) of 0.15 mg/kg rocuronium bromide.
Other Names:
  • Rocuronium bromide
  • Esmeron®
Active Comparator: Neostigmine
50 µg/kg neostigmine
Drug: Neostigmine
Participants received 50 µg/kg neostigmine combined with 10 µg/kg glycopyrrolate after the last dose of rocuronium bromide as per standard of care.
Other Name: Prostigmin®
Drug: Rocuronium
Participants received a single intubation bolus dose of 0.6 mg/kg rocuronium bromide, followed if necessary to maintain neuromuscular blockade by one or more single bolus dose(s) of 0.15 mg/kg rocuronium bromide.
Other Names:
  • Rocuronium bromide
  • Esmeron®

Detailed Description:

Undetected residual neuromuscular blockade is common in the post-anesthesia care

unit (PACU). In fact, 16%-42% of patients receiving intermediate-acting muscle

relaxants in the operating room have T4/T1 ratios <0.7-0.8 in the PACU. Respiratory and pharyngeal muscle function can be adversely affected during minimal neuromuscular blockade. Studies in awake volunteers and surgical patients have demonstrated that T4/T1 ratios of 0.7 - 0.9 are associated with impaired airway protective reflexes, upper airway obstruction, a decreased hypoxic ventilatory response, and post-operative hypoxemia. The incidence and severity of residual neuromuscular blockade at the time of tracheal extubation will be evaluated to determine how these influence the length of stay in the operating room and PACU.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • male or females who are >= 18 and <= 65 years of age
  • classified by the American Society of Anesthesiologists (ASA) as Class 1 or 2 or 3;
  • Body Mass Index (BMI) of <35 kg/m^2;
  • is scheduled to undergo an elective open abdominal surgical procedure under general anesthesia requiring neuromuscular relaxation using rocuronium bromide (maintenance of neuromuscular blockade if required) for endotracheal intubation and requiring neuromuscular blockade reversal;
  • is scheduled to undergo a surgical procedure in a position that does not interfere with the use of TOF-Watch® SX;
  • is scheduled to undergo an elective open abdominal procedure expected to last <=4 hours (from start of skin incision to end of last stitch of the skin);
  • have given written informed consent.

Exclusion Criteria:

  • participants for whom a difficult intubation is expected because of anatomical malformations;
  • is known or suspected to have neuromuscular disorders that may impair neuromuscular blockade;
  • is known or suspected to have significant renal dysfunction (e.g., creatinine clearance < 30 mL/min) ;
  • is known or suspected to have significant hepatic dysfunction;
  • is known or suspected to have a (family) history of malignant hyperthermia;
  • is known or suspected to have an allergy to opioids, muscle relaxants or other medications used during general anesthesia;
  • participants for whom the use of neostigmine and/or glycopyrrolate may be contraindicated;
  • participants for whom a pre-established need for postoperative intensive care admission is expected;
  • pregnant or breast-feeding females;
  • have participated in a previous sugammadex clinical trial;
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00675792     History of Changes
Other Study ID Numbers: P05774, 19.4.334
Study First Received: May 7, 2008
Results First Received: May 21, 2013
Last Updated: May 12, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Bromides
Rocuronium
Neostigmine
Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Neuromuscular Nondepolarizing Agents
Neuromuscular Blocking Agents
Neuromuscular Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Cholinesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Cholinergic Agents
Neurotransmitter Agents
Parasympathomimetics
Autonomic Agents

ClinicalTrials.gov processed this record on September 22, 2014