Pharmacokinetic-pharmacodynamic Analysis of Sugammadex for Conventional Reversal in Children

NCT04347486 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: 2002-148-1105
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Anesthesia, General; Neuromuscular Blockade

Keywords

Sugammadex; Pharmacokinetics; Pharmacodynamics; Pediatric anesthesia

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Plasma concentrations

  From anesthetic induction to 480 minutes after sugammadex administration

Study Arms (4)

Sugammadex 2mg

EXPERIMENTAL

Administer 2mg/kg of sugammadex on reappearance of T2 by Train-of-Four stimulation

Drug: Sugammadex Injection 2mg/kg

Sugammadex 4mg

EXPERIMENTAL

Administer 4mg/kg of sugammadex on reappearance of T2 by Train-of-Four stimulation

Drug: Sugammadex Injection 4mg/kg

Sugammadex 8mg

EXPERIMENTAL

Administer 8mg/kg of sugammadex on reappearance of T2 by Train-of-Four stimulation

Drug: Sugammadex Injection 8mg/kg

Conventional reversal

ACTIVE COMPARATOR

Administer conventional neuromuscular reversal agent (0.02mg/kg of atropine and 0.03mg/kg of neostigmine) on reappearance of T2 by Train-of-Four stimulation

Drug: Neuromuscular reversal agent injection

Interventions

Sugammadex Injection 2mg/kg DRUG

Intravenous injection of 2mg/kg of sugammadex sodium on reappearance of T2

Also known as: Bridion 2mg/kg

Sugammadex 2mg

Sugammadex Injection 4mg/kg DRUG

Intravenous injection of 4mg/kg of sugammadex sodium on reappearance of T2

Also known as: Bridion 4mg/kg

Sugammadex 4mg

Sugammadex Injection 8mg/kg DRUG

Intravenous injection of 8mg/kg of sugammadex sodium on reappearance of T2

Also known as: Bridion 8mg/kg

Sugammadex 8mg

Neuromuscular reversal agent injection DRUG

Intravenous injection of 0.02mg/kg of atropine and 0.03mg/kg of neostigmine

Also known as: Atropine and neostigmine

Conventional reversal

Eligibility Criteria

• Age: 2 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Seoul National University Hospital: lead
• Ministry of Food and Drug Safety, Korea: collaborator

Study Sites (1)

SNUH

Seoul, Jongro Gu, 15710, South Korea

Location

Related Publications (6)

• 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. doi: 10.1097/00000542-200510000-00007.

  PMID: 16192761 BACKGROUND

• 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. doi: 10.1097/00000542-200604000-00009.

  PMID: 16571960 BACKGROUND

• 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. doi: 10.1097/01.anes.0000265152.78943.74.

  PMID: 17457124 BACKGROUND

• 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.

  PMID: 19104176 BACKGROUND

• 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.

  PMID: 27559972 BACKGROUND

• Ji SH, Huh KY, Oh J, Jeong HJ, Jang YE, Kim EH, Lee JH, Kim JT, Kim HS. Conventional reversal of rocuronium-induced neuromuscular blockade by sugammadex in Korean children: pharmacokinetics, efficacy, and safety analyses. Front Pharmacol. 2023 Apr 13;14:1127932. doi: 10.3389/fphar.2023.1127932. eCollection 2023.

  PMID: 37124204 DERIVED

MeSH Terms

Interventions

Sugammadex; Atropine; Neostigmine

Intervention Hierarchy (Ancestors)

gamma-Cyclodextrins; Cyclodextrins; Macrocyclic Compounds; Polycyclic Compounds; Dextrins; Starch; Glucans; Polysaccharides; Carbohydrates; Atropine Derivatives; Tropanes; Azabicyclo Compounds; Aza Compounds; Organic Chemicals; Belladonna Alkaloids; Solanaceous Alkaloids; Alkaloids; Heterocyclic Compounds; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring; Phenylammonium Compounds; Quaternary Ammonium Compounds; Amines; Onium Compounds

Study Officials

• Hee-Soo Kim, M.D., Ph.D.

  Seoul National University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD, Professor

Study Record Dates

• First Submitted: April 13, 2020
• First Posted: April 15, 2020
• Study Start: April 29, 2020
• Primary Completion: December 7, 2021
• Study Completion: December 7, 2021
• Last Updated: February 10, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)