Pharmacokinetic-pharmacodynamic Analysis of Sugammadex for Conventional Reversal in Children

Neuromuscular Blockade Clinical Trial

Official title:

Pharmacokinetic-pharmacodynamic Analysis of Conventional Reversal of Rocuronium-induced Neuromuscular Blockade by Sugammadex in Children

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04347486
• Other study ID #: 2002-148-1105
• Status: Completed
• Phase: Phase 2
• Start date: April 29, 2020
• Est. completion date: December 7, 2021

Study information

• Verified date: February 2022
• Source: Seoul National University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study administers sugammadex sodium to pediatric patients under general anesthesia with rocuronium. Pharmacokinetic and pharmacodynamic analysis are performed based on plasma concentration of sugammadex sodium and monitoring of neuromuscular blockade.

Description:

This study enrolls pediatric patients undergoing surgery under general anesthesia with need for reversal of neuromuscular blockade, aged between 2 and 18 years old.

After routine anesthetic induction with 1% propofol and 0.6mg/kg of rocuronium, maintenance of anesthesia with total intravenous anesthesia is commenced. For neuromuscular monitoring, train-of-four (TOF) count and T4/T1 ratio are monitored, with recording of the time to recovery of the T4/T1 ratio to 0.7, 0.8 and 0.9.

On reappearance of T2 after rocuronium administration , 2 or 4 or 8mg/kg of sugammadex sodium or conventional neuromuscular reversal agent is administered according to randomization table.

For pharmacokinetic analysis, patient blood sample is obtained before / 2 min after rocuronium administration, before / 2min / 5min / 15min / 60min / 120min / 240min / 480min after sugammadex administration. Plasma concentration of rocuronium and sugammadex sodium are analyzed via high-performance liquid chromatography with mass spectrometric detection.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: December 7, 2021
• Est. primary completion date: December 7, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 17 Years

Eligibility

Inclusion Criteria:

• All of below Pediatric patients undergoing surgery under general anesthesia with requirement of early reversal of neuromuscular blockade Aged between 2 and 17 American Society of Anesthesiologists Physical Status Classification 1 and 2

Exclusion Criteria:

• Any of below One or more legal guardian declines to enroll in the study History of hypersensitivity to any anesthetic agents including rocuronium Presence of underlying cardiovascular or genitourinary disease Under usage of neuromuscular blocking agents before surgery Under usage of drugs influencing the effect of neuromuscular blocking agents History of malignant hyperthermia Anticipation of massive hemorrhage during surgery

Related Conditions & MeSH terms

• Anesthesia, General
• Neuromuscular Blockade

Intervention

Drug:
• Sugammadex Injection 2mg/kg
Intravenous injection of 2mg/kg of sugammadex sodium on reappearance of T2
• Sugammadex Injection 4mg/kg
Intravenous injection of 4mg/kg of sugammadex sodium on reappearance of T2
• Sugammadex Injection 8mg/kg
Intravenous injection of 8mg/kg of sugammadex sodium on reappearance of T2
• Neuromuscular reversal agent injection
Intravenous injection of 0.02mg/kg of atropine and 0.03mg/kg of neostigmine

Locations

Country	Name	City	State
Korea, Republic of	SNUH	Seoul	Jongro Gu

Sponsors (2)

Lead Sponsor	Collaborator
Seoul National University Hospital	Ministry of Food and Drug Safety, Korea

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (5)

Gijsenbergh F, Ramael S, Houwing N, van Iersel T. First human exposure of Org 25969, a novel agent to reverse the action of rocuronium bromide. Anesthesiology. 2005 Oct;103(4):695-703. — View Citation

Ploeger BA, Smeets J, Strougo A, Drenth HJ, Ruigt G, Houwing N, Danhof M. Pharmacokinetic-pharmacodynamic model for the reversal of neuromuscular blockade by sugammadex. Anesthesiology. 2009 Jan;110(1):95-105. doi: 10.1097/ALN.0b013e318190bc32. — View Citation

Sorgenfrei IF, Norrild K, Larsen PB, Stensballe J, Ostergaard D, Prins ME, Viby-Mogensen J. Reversal of rocuronium-induced neuromuscular block by the selective relaxant binding agent sugammadex: a dose-finding and safety study. Anesthesiology. 2006 Apr;104(4):667-74. — View Citation

Sparr HJ, Vermeyen KM, Beaufort AM, Rietbergen H, Proost JH, Saldien V, Velik-Salchner C, Wierda JM. Early reversal of profound rocuronium-induced neuromuscular blockade by sugammadex in a randomized multicenter study: efficacy, safety, and pharmacokinetics. Anesthesiology. 2007 May;106(5):935-43. — View Citation

Won YJ, Lim BG, Lee DK, Kim H, Kong MH, Lee IO. Sugammadex for reversal of rocuronium-induced neuromuscular blockade in pediatric patients: A systematic review and meta-analysis. Medicine (Baltimore). 2016 Aug;95(34):e4678. doi: 10.1097/MD.0000000000004678. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Neuromuscular recovery	Time to recovery of train-of-four T4/T1 ratio to 90% after sugammadex sodium or neuromuscular reversal agent administration up to 30 minutes to 1 hour.	up to 30 minutes to 1 hour
Secondary	Plasma concentrations	Plasma concentrations of rocuronium and sugammadex sodium	From anesthetic induction to 480 minutes after sugammadex administration