Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 59 of 185 for:    GLYCOPYRROLATE

Comparison of Sugammadex (MK-8616/Org 25969) With Neostigmine Administered at 1-2 Post-tetanic Counts (PTCs) After Administration of Rocuronium or Vecuronium (19.4.302/P05945/MK-8616-025)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00473694
Recruitment Status : Completed
First Posted : May 15, 2007
Results First Posted : March 7, 2019
Last Update Posted : March 19, 2019
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Brief Summary:
The purpose of the trial is to demonstrate a faster recovery from neuromuscular block (NMB) induced with rocuronium or vecuronium after reversal by 4.0 mg/kg of Org 25969 compared with reversal by 70 μg/kg of neostigmine in combination with 14 μg/kg glycopyrrolate.

Condition or disease Intervention/treatment Phase
Anesthesia, General Drug: sugammadex Drug: neostigmine Drug: vecuronium Drug: rocuronium Drug: glycopyrrolate Phase 3

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 182 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Parallel Group Comparative, Active-Controlled, Safety-assessor Blinded. Phase IIIa, Pivotal Trial in Adult Subjects Comparing Org 25969 With Neostigmine as Reversal Agent of a Neuromuscular Block Induced by Maintenance Dosing of Rocuronium or Vecuronium at 1-2 PTCs
Actual Study Start Date : November 28, 2005
Actual Primary Completion Date : November 6, 2006
Actual Study Completion Date : January 29, 2007


Arm Intervention/treatment
Experimental: rocuronium+sugammadex
Participants received a single bolus dose of 0.60 mg/kg rocuronium prior to intubation. The neuromuscular block was maintained with 0.15 mg/kg rocuronium if needed. At 1-2 post-tetanic counts (PTC) and after the last dose of rocuronium, a single bolus dose of 4.0 mg/kg sugammadex was administered.
Drug: sugammadex
Administered as an intravenous (IV) infusion
Other Names:
  • Org 25969
  • MK-8616
  • BRIDION®

Drug: rocuronium
Administered as an IV infusion
Other Name: ZEMURON®

Active Comparator: rocuronium+neostigmine
Participants received a single bolus dose of 0.60 mg/kg rocuronium prior to intubation. The neuromuscular block was maintained with 0.15 mg/kg rocuronium if needed. At 1-2 PTC and after the last dose of rocuronium, a single bolus dose of 70.0 μg/kg neostigmine (up to a maximum dose of 5 mg) was administered in combination with 14.0 μg/kg glycopyrrolate.
Drug: neostigmine
Administered as an IV infusion
Other Name: PROSTIGMIN®

Drug: rocuronium
Administered as an IV infusion
Other Name: ZEMURON®

Drug: glycopyrrolate
Administered as an IV infusion
Other Name: ROBINUL®

Experimental: vecuronium+sugammadex
Participants received a single bolus dose of 0.1 mg/kg vecuronium prior to intubation. The neuromuscular block was maintained with 0.015 mg/kg vecuronium if needed. At 1-2 PTC and after the last dose of vecuronium, a single bolus dose of 4.0 mg/kg sugammadex was administered.
Drug: sugammadex
Administered as an intravenous (IV) infusion
Other Names:
  • Org 25969
  • MK-8616
  • BRIDION®

Drug: vecuronium
Administered as an IV infusion
Other Name: NORCURON®

Active Comparator: vecuronium+neostigmine
Participants received a single bolus dose of 0.1 mg/kg vecuronium prior to intubation. The neuromuscular block was maintained with 0.015 mg/kg vecuronium if needed. At 1-2 PTC and after the last dose of vecuronium, a single bolus dose of 70.0 μg/kg neostigmine (up to a maximum dose of 5 mg) was administered in combination with 14.0 μg/kg glycopyrrolate.
Drug: neostigmine
Administered as an IV infusion
Other Name: PROSTIGMIN®

Drug: vecuronium
Administered as an IV infusion
Other Name: NORCURON®

Drug: glycopyrrolate
Administered as an IV infusion
Other Name: ROBINUL®




Primary Outcome Measures :
  1. Time From Start of Administration of Sugammadex or Neostigmine to Recovery of the T4/T1 Ratio to 0.9 After Neuromuscular Block (NMB) Induced by Rocuronium [ Time Frame: Up to approximately 3 hours after administration of study drug ]
    Mean time from start of sugammadex or neostigmine administration to recovery of T4/T1 ratio to 0.9 was assessed 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 represented the greater the recovery from NMB; with a value of 0.0 representing no recovery and 1.0 representing full recovery. Reduced recovery time of the T4/T1 ratio to 0.9 indicated faster recovery from NMB. Mean time was collected in minutes and seconds but converted to and presented in minutes only. The analysis included a procedure for the imputation of missing recovery times.

  2. Time From Start of Administration of Sugammadex or Neostigmine to Recovery of the T4/T1 Ratio to 0.9 After Neuromuscular Block (NMB) Induced by Vecuronium [ Time Frame: Up to approximately 6 hours after administration of study drug ]
    Mean time from start of sugammadex or neostigmine administration to recovery of T4/T1 ratio to 0.9 was assessed 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 represented the greater the recovery from NMB; with a value of 0.0 representing no recovery and 1.0 representing full recovery. Reduced recovery time of the T4/T1 ratio to 0.9 indicated faster recovery from NMB. Mean time was collected in minutes and seconds but converted to and presented in minutes only. The analysis included a procedure for the imputation of missing recovery times.


Secondary Outcome Measures :
  1. Time From Start of Administration of Sugammadex or Neostigmine to Recovery of the T4/T1 Ratio to 0.7 After Neuromuscular Block (NMB) Induced by Rocuronium [ Time Frame: Up to approximately 2 hours after administration of study drug ]
    Mean time from start of sugammadex or neostigmine administration to recovery of T4/T1 ratio to 0.7 was assessed 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 0.7. The greater the T4/T1 ratio represented the greater the recovery from NMB; with a value of 0.0 representing no recovery and 1.0 representing full recovery. Reduced recovery time of the T4/T1 ratio to 0.7 indicated faster recovery from NMB. Mean time was collected in minutes and seconds but converted to and presented in minutes only. The analysis included a procedure for the imputation of missing recovery times.

  2. Time From Start of Administration of Sugammadex or Neostigmine to Recovery of the T4/T1 Ratio to 0.7 After Neuromuscular Block (NMB) Induced by Vecuronium [ Time Frame: Up to approximately 4 hours after administration of study drug ]
    Mean time from start of sugammadex or neostigmine administration to recovery of T4/T1 ratio to 0.7 was assessed 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 0.7. The greater the T4/T1 ratio represented the greater the recovery from NMB; with a value of 0.0 representing no recovery and 1.0 representing full recovery. Reduced recovery time of the T4/T1 ratio to 0.7 indicated faster recovery from NMB. Mean time was collected in minutes and seconds but converted to and presented in minutes only. The analysis included a procedure for the imputation of missing recovery times.

  3. Time From Start of Administration of Sugammadex or Neostigmine to Recovery of the T4/T1 Ratio to 0.8 After Neuromuscular Block (NMB) Induced by Rocuronium [ Time Frame: Up to approximately 3 hours after administration of study drug ]
    Mean time from start of sugammadex or neostigmine administration to recovery of T4/T1 ratio to 0.8 was assessed 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 0.8. The greater the T4/T1 ratio represented the greater the recovery from NMB; with a value of 0.0 representing no recovery and 1.0 representing full recovery. Reduced recovery time of the T4/T1 ratio to 0.8 indicated faster recovery from NMB. Mean time was collected in minutes and seconds but converted to and presented in minutes only. The analysis included a procedure for the imputation of missing recovery times.

  4. Time From Start of Administration of Sugammadex or Neostigmine to Recovery of the T4/T1 Ratio to 0.8 After Neuromuscular Block (NMB) Induced by Vecuronium [ Time Frame: Up to approximately 5 hours after administration of study drug ]
    Mean time from start of sugammadex or neostigmine administration to recovery of T4/T1 ratio to 0.8 was assessed 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 0.8. The greater the T4/T1 ratio represented the greater the recovery from NMB; with a value of 0.0 representing no recovery and 1.0 representing full recovery. Reduced recovery time of the T4/T1 ratio to 0.8 indicated faster recovery from NMB. Mean time was collected in minutes and seconds but converted to and presented in minutes only. The analysis included a procedure for the imputation of missing recovery times.

  5. Number of Participants Awake and Oriented After Anesthesia (Clinical Assessment of Level of Consciousness) [ Time Frame: Up to 24 hours ]
    The number of participants who were awake and oriented was assessed as part of an overall assessment of the clinical level of consciousness by the investigator. The clinical level of consciousness was used as a measure of recovery from NMB at 2 timepoints: prior to transfer to the recovery room after extubation and prior to discharge from the recovery room. Attempts were made to arouse participants every 15 minutes with mild prodding, mild shaking, and asking questions regarding name, location, and day of the week. The assessment ended once the participant was awake and fully orientated, 24 hours, or discharged from the hospital if discharge occurs before 24 hours; whichever occurred first. Participants were given a level of consciousness based on what type of stimulation they responded to. Participants who were not cooperative with the examination were not included in the assessment.

  6. Number of Participants Aroused With Minimal Stimulation After Anesthesia (Clinical Assessment of Level of Consciousness) [ Time Frame: Up to 24 hours ]
    The number of participants aroused with minimal stimulation was assessed as part of an overall assessment of the clinical level of consciousness by the investigator. The clinical level of consciousness was used as a measure of recovery from NMB at 2 timepoints: prior to transfer to the recovery room after extubation and prior to discharge from the recovery room. Attempts were made to arouse participants every 15 minutes with mild prodding, mild shaking, and asking questions regarding name, location, and day of the week. The assessment ended once the participant was awake and fully orientated, 24 hours, or discharged from the hospital if discharge occurs before 24 hours; whichever occurred first. Participants were given a level of consciousness based on what type of stimulation they responded to. Participants who were not cooperative with the examination were not included in the assessment.

  7. Number of Participants Responsive Only to Tactile Stimulation After Anesthesia (Clinical Assessment of Level of Consciousness) [ Time Frame: Up to 24 hours ]
    The number of participants responsive only to tactile stimulation was assessed as part of an overall assessment of the clinical level of consciousness by the investigator. The clinical level of consciousness was used as a measure of recovery from NMB at 2 timepoints: prior to transfer to the recovery room after extubation and prior to discharge from the recovery room. Attempts were made to arouse participants every 15 minutes with mild prodding, mild shaking, and asking questions regarding name, location, and day of the week. The assessment ended once the participant was awake and fully orientated, 24 hours, or discharged from the hospital if discharge occurs before 24 hours; whichever occurred first. Participants were given a level of consciousness based on what type of stimulation they responded to. Participants who were not cooperative with the examination were not included in the assessment.

  8. Number of Participants Able to Perform a 5-second Head Lift [ Time Frame: Up to 24 hours ]
    The number of participants who were able to lift their head for 5 seconds was assessed by the investigator as a measure of recovery from NMB at 2 timepoints: prior to transfer to the recovery room after extubation and prior to discharge from the recovery room. The assessment was performed every 15 minutes until the first successful 5-second head lift was achieved. Participants who were not cooperative with the examination were not included in the assessment.

  9. Number of Participants Experiencing General Muscle Weakness [ Time Frame: Up to 24 hours ]
    The number of participants experiencing general muscle weakness was assessed by the investigator as a measure of recovery from NMB at 2 timepoints: prior to transfer to the recovery room after extubation and prior to discharge from the recovery room. The assessments were performed every 15 minutes until the absence of general muscle weakness. A standardized examination form was used to determine the presence or absence of muscle weakness in various muscle groups. Participants who were not cooperative with the examination were not included in the assessment.



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • American Society of Anesthesiologists (ASA) Class 1 to 4
  • 18 years or older
  • Scheduled to undergo an elective surgical procedure under general anesthesia requiring the use of rocuronium or vecuronium for endotracheal intubation and maintenance of neuromuscular block
  • Scheduled for surgery in supine position
  • Given written informed consent

Exclusion Criteria:

  • Participants in whom a difficult intubation is expected due to anatomical malformations
  • Known or suspected to have neuromuscular disorders impairing neuromuscular blockade and/or significant renal dysfunction
  • Known or suspected to have a (family) history of malignant hyperthermia
  • Known or suspected to have an allergy to narcotics, muscle relaxants, or other medications used during surgery
  • Receiving medication known to interfere with neuromuscular blocking agents such as anticonvulsants, antibiotics, and magnesium (Mg2+)
  • Participants in whom the use of neostigmine and/or glycopyrrolate may be contraindicated
  • Female participants who are pregnant or breast-feeding
  • Females participants of childbearing potential not using an acceptable method of birth control [condom or diaphragm with spermicide, vasectomized partner (> 6 months), IUD, abstinence]
  • Participants who had already participated in an Org 25969 trial
  • Participants who had participated in another clinical trial, not pre-approved by Organon, within 30 days of entering into Protocol 19.4.302

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00473694


Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Layout table for investigator information
Study Director: Medical Director Merck Sharp & Dohme Corp.

Additional Information:
Study Data/Documents: CSR Synopsis  This link exits the ClinicalTrials.gov site

Publications of Results:
Layout table for additonal information
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00473694     History of Changes
Other Study ID Numbers: P05945
19.4.302 ( Other Identifier: Organon Protocol Number )
P05945 ( Other Identifier: Schering-Plough Protocol Number )
MK-8616-025 ( Other Identifier: Merck Protocol Number )
First Posted: May 15, 2007    Key Record Dates
Results First Posted: March 7, 2019
Last Update Posted: March 19, 2019
Last Verified: March 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Glycopyrrolate
Rocuronium
Vecuronium Bromide
Neostigmine
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
Adjuvants, Anesthesia
Muscarinic Antagonists
Cholinergic Antagonists
Nicotinic Antagonists