Reversal of Residual Neuromuscular Blockade at Train-of-four Ratio 0.3 With Sugammadex and Neostigmine

• ClinicalTrials.gov Identifier: NCT03656614
• Recruitment Status: Completed
• First Posted: September 4, 2018
• Last Update Posted: August 11, 2020
• Sponsor: Guangzhou General Hospital of Guangzhou Military Command
• Information provided by (Responsible Party): bo xu, Guangzhou General Hospital of Guangzhou Military Command

Study Description

Brief Summary:

The aim of this study is to estimate the optimal dose of sugammadex and neostigmine reversal of a vecuronium-induced residual neuromuscular block at train-of-four ratio 0.3.

Condition or disease	Intervention/treatment
Neuromuscular Blockade	Drug: Sugammadex; Drug: Neostigmine; Drug: Saline 0.9%

Detailed Description:

Sugammadex is a modified γ-cyclodextrin compound that reverses the neuromuscular blockade produced by steroidal nondepolarizing muscle relaxants such as rocuronium,vecuronium and pipecuronium by encapsulating them, making them unavailable to interact with the nicotinic acetylcholine receptors at the neuromuscular junction.However, residual neuromuscular blocks between reappearance of T4 and train-of-four ratio (TOFR)=0.5 are more frequent in clinical practice compared with profound or deep blocks and have not been investigated for sugammadex previously.

Unlike neostigmine, sugammadex is efficacious in reversing profound (no responses to either train-of-four (TOF) or posttetanic count stimulation) or deep (posttetanic count of 1 or 2) neuromuscular block (NMB) in doses of 16 and 4 mg/kg, respectively. However, shallow neuromuscular blocks are more frequent in clinical practice compared with profound or deep blocks and have not been investigated for sugammadex previously.

Study Design

• Study Type: Observational [Patient Registry]
• Actual Enrollment: 121 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Target Follow-Up Duration: 1 Day
• Official Title: Dose Finding Study for Reversal of Vecuronium-induced Neuromuscular Blockade at Train-of-four Ratio 0.3 With Sugammadex and Neostigmine
• Actual Study Start Date: July 26, 2018
• Actual Primary Completion Date: June 28, 2019
• Actual Study Completion Date: June 30, 2019

Groups and Cohorts

Group/Cohort	Intervention/treatment
sugammadex 0.125; Sugammadex group: sugammadex 0.125 mg/kg IV once at the reappearance of TOF 0.3	Drug: Sugammadex; At the end of surgical procedure at a depth of neuromuscular blockade at the reappearance of train-of-four 0.3, single intravenous injection of either : Sugammadex 0.125 mg/kg (sugammadex 0.125) Sugammadex 0.25 mg/kg (sugammadex 0.25) Sugammadex 0.5 mg/kg (sugammadex 0.5) Sugammadex 1.0 mg/kg (sugammadex 1.0) Sugammadex 2.0 mg/kg (sugammadex 2.0); Other Names: Bridion; Org 25969
Sugammadex 0.25; Sugammadex group: sugammadex 0.25 mg/kg IV once at the reappearance of TOF 0.3	Drug: Sugammadex; At the end of surgical procedure at a depth of neuromuscular blockade at the reappearance of train-of-four 0.3, single intravenous injection of either : Sugammadex 0.125 mg/kg (sugammadex 0.125) Sugammadex 0.25 mg/kg (sugammadex 0.25) Sugammadex 0.5 mg/kg (sugammadex 0.5) Sugammadex 1.0 mg/kg (sugammadex 1.0) Sugammadex 2.0 mg/kg (sugammadex 2.0); Other Names: Bridion; Org 25969
Sugammadex 0.5; Sugammadex group: sugammadex 0.5 mg/kg IV once at the reappearance of TOF 0.3	Drug: Sugammadex; At the end of surgical procedure at a depth of neuromuscular blockade at the reappearance of train-of-four 0.3, single intravenous injection of either : Sugammadex 0.125 mg/kg (sugammadex 0.125) Sugammadex 0.25 mg/kg (sugammadex 0.25) Sugammadex 0.5 mg/kg (sugammadex 0.5) Sugammadex 1.0 mg/kg (sugammadex 1.0) Sugammadex 2.0 mg/kg (sugammadex 2.0); Other Names: Bridion; Org 25969
Sugammadex 1.0; Sugammadex group: sugammadex 1.0 mg/kg IV once at the reappearance of TOF 0.3	Drug: Sugammadex; At the end of surgical procedure at a depth of neuromuscular blockade at the reappearance of train-of-four 0.3, single intravenous injection of either : Sugammadex 0.125 mg/kg (sugammadex 0.125) Sugammadex 0.25 mg/kg (sugammadex 0.25) Sugammadex 0.5 mg/kg (sugammadex 0.5) Sugammadex 1.0 mg/kg (sugammadex 1.0) Sugammadex 2.0 mg/kg (sugammadex 2.0); Other Names: Bridion; Org 25969
Sugammadex 2.0; Sugammadex group: sugammadex 2.0 mg/kg IV once at the reappearance of TOF 0.3	Drug: Sugammadex; At the end of surgical procedure at a depth of neuromuscular blockade at the reappearance of train-of-four 0.3, single intravenous injection of either : Sugammadex 0.125 mg/kg (sugammadex 0.125) Sugammadex 0.25 mg/kg (sugammadex 0.25) Sugammadex 0.5 mg/kg (sugammadex 0.5) Sugammadex 1.0 mg/kg (sugammadex 1.0) Sugammadex 2.0 mg/kg (sugammadex 2.0); Other Names: Bridion; Org 25969
Neostigmine 10; Neostigmine group: neostigmine 10 µg/kg IV once at the reappearance of TOF 0.3	Drug: Neostigmine; At the end of surgical procedure at a depth of neuromuscular blockade at the reappearance of train-of-four 0.3, single intravenous injection of either : Neostigmine 10 µg/kg (Neostigmine 10) Neostigmine 25 µg/kg (Neostigmine 25) Neostigmine 40 µg/kg (Neostigmine 40) Neostigmine 55 µg/kg (Neostigmine 55) Neostigmine 70 µg/kg (Neostigmine 70) Atropine will be administered with Neostigmine at a half dose of Neostigmine administered through an intravenous line with brisk flow.; Other Name: Prostigmin
Neostigmine 25; Neostigmine group: neostigmine 25 µg/kg IV once at the reappearance of TOF 0.3	Drug: Neostigmine; At the end of surgical procedure at a depth of neuromuscular blockade at the reappearance of train-of-four 0.3, single intravenous injection of either : Neostigmine 10 µg/kg (Neostigmine 10) Neostigmine 25 µg/kg (Neostigmine 25) Neostigmine 40 µg/kg (Neostigmine 40) Neostigmine 55 µg/kg (Neostigmine 55) Neostigmine 70 µg/kg (Neostigmine 70) Atropine will be administered with Neostigmine at a half dose of Neostigmine administered through an intravenous line with brisk flow.; Other Name: Prostigmin
Neostigmine 40; Neostigmine group: neostigmine 40 µg/kg IV once at the reappearance of TOF 0.3	Drug: Neostigmine; At the end of surgical procedure at a depth of neuromuscular blockade at the reappearance of train-of-four 0.3, single intravenous injection of either : Neostigmine 10 µg/kg (Neostigmine 10) Neostigmine 25 µg/kg (Neostigmine 25) Neostigmine 40 µg/kg (Neostigmine 40) Neostigmine 55 µg/kg (Neostigmine 55) Neostigmine 70 µg/kg (Neostigmine 70) Atropine will be administered with Neostigmine at a half dose of Neostigmine administered through an intravenous line with brisk flow.; Other Name: Prostigmin
Neostigmine 55; Neostigmine group: neostigmine 55 µg/kg IV once at the reappearance of TOF 0.3	Drug: Neostigmine; At the end of surgical procedure at a depth of neuromuscular blockade at the reappearance of train-of-four 0.3, single intravenous injection of either : Neostigmine 10 µg/kg (Neostigmine 10) Neostigmine 25 µg/kg (Neostigmine 25) Neostigmine 40 µg/kg (Neostigmine 40) Neostigmine 55 µg/kg (Neostigmine 55) Neostigmine 70 µg/kg (Neostigmine 70) Atropine will be administered with Neostigmine at a half dose of Neostigmine administered through an intravenous line with brisk flow.; Other Name: Prostigmin
Neostigmine 70; Neostigmine group: neostigmine 70 µg/kg IV once at the reappearance of TOF 0.3	Drug: Neostigmine; At the end of surgical procedure at a depth of neuromuscular blockade at the reappearance of train-of-four 0.3, single intravenous injection of either : Neostigmine 10 µg/kg (Neostigmine 10) Neostigmine 25 µg/kg (Neostigmine 25) Neostigmine 40 µg/kg (Neostigmine 40) Neostigmine 55 µg/kg (Neostigmine 55) Neostigmine 70 µg/kg (Neostigmine 70) Atropine will be administered with Neostigmine at a half dose of Neostigmine administered through an intravenous line with brisk flow.; Other Name: Prostigmin
Placebo; Placebo group: Saline 0.9% IV once at the reappearance of TOF 0.3	Drug: Saline 0.9%; At the end of surgical procedure at a depth of neuromuscular blockade at the reappearance of train-of-four 0.3, single intravenous injection of saline 0.9%.; Other Name: Placebo

Outcome Measures

Primary Outcome Measures :

1. Time to TOF 0.9 after the administration of reversal agent [ Time Frame: the general anesthesia time 1 hour at least ]
   The time to achieve TOF (Train of Four stimulation) ratio to 0.9 following the investigational drug or placebo administration.

Secondary Outcome Measures :

1. incidence of reparalysis [ Time Frame: approximately 1 hour ]
   Determining whether patients receiving reversal agent will have a train-to-four ratio <0.8 during total recovery time (from TOF reach 0.9 first time to post-anaesthesia care unit (PACU) departure)
2. incidence of adverse event [ Time Frame: the general anesthesia and recovery time 2 hours at least ]
   Documenting whether patients will have some adverse events(such as hypoxia bradycardia nausea and vomiting) from anesthesia commence to PACU departure.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Probability Sample

Study Population

people scheduled for elective surgery

Criteria

Inclusion Criteria:

• 1 age of 18 to 65 yr,
• 2 body mass index 18.5 to 25.0 kg/m2,
• 3 American Society of Anesthesiologists physical status I to III
• 4 scheduled for elective surgery with an expected duration of at least 60min under general anesthesia with intubation of the trachea or laryngeal mask
• 5 patients having given informed consent to the study

Exclusion Criteria:

• 1 patients who had participated in another clinical trial within 1 month
• 2 Patients with suspected difficult airway, bronchial asthma, chronic obstructive pulmonary disease
• 3 known neuromuscular disease
• 4 suspected malignant hyperthermia
• 5 hepatic or renal dysfunction
• 6 glaucoma
• 7 allergy to the medication that used in this trial
• 8 taking medicaments that might influence the effect of NMB agents
• 9 pregnant, or breastfeeding state
• 10 taking medication known to alter the effect of neuromuscular blocking agents( toremifene .etc)

Contacts and Locations

Locations

China, Guangdong

Guangzhou Military Region General Hospital, Department of Anesthesiology

Guangzhou, Guangdong, China, 510010

Sponsors and Collaborators

Guangzhou General Hospital of Guangzhou Military Command

More Information

Additional Information:

Publications:

Pongrácz A, Szatmári S, Nemes R, Fülesdi B, Tassonyi E. Reversal of neuromuscular blockade with sugammadex at the reappearance of four twitches to train-of-four stimulation. Anesthesiology. 2013 Jul;119(1):36-42. doi: 10.1097/ALN.0b013e318297ce95.

Schaller SJ, Fink H, Ulm K, Blobner M. Sugammadex and neostigmine dose-finding study for reversal of shallow residual neuromuscular block. Anesthesiology. 2010 Nov;113(5):1054-60. doi: 10.1097/ALN.0b013e3181f4182a.

Kaufhold N, Schaller SJ, Stäuble CG, Baumüller E, Ulm K, Blobner M, Fink H. Sugammadex and neostigmine dose-finding study for reversal of residual neuromuscular block at a train-of-four ratio of 0.2 (SUNDRO20)†,. Br J Anaesth. 2016 Feb;116(2):233-40. doi: 10.1093/bja/aev437.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

He J, He H, Li X, Sun M, Lai Z, Xu B. Required dose of sugammadex or neostigmine for reversal of vecuronium-induced shallow residual neuromuscular block at a train-of-four ratio of 0.3. Clin Transl Sci. 2022 Jan;15(1):234-243. doi: 10.1111/cts.13143. Epub 2021 Nov 2.

• Responsible Party: bo xu, Clinical Professor, Guangzhou General Hospital of Guangzhou Military Command
• ClinicalTrials.gov Identifier: NCT03656614
• Other Study ID Numbers: Reversal Neuromuscular Block
• First Posted: September 4, 2018
• Last Update Posted: August 11, 2020
• Last Verified: August 2020

Keywords provided by bo xu, Guangzhou General Hospital of Guangzhou Military Command:

sugammadex neostigmine

Additional relevant MeSH terms:

Neostigmine; Cholinesterase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Neurotransmitter Agents; Physiological Effects of Drugs; Parasympathomimetics; Autonomic Agents; Peripheral Nervous System Agents