Clinical trial NCT03943888: Pharmacokinetic-pharmacodynamic Analysis of Sugammadex in Children
Official title: Pharmacokinetic-pharmacodynamic Analysis of Reversal of Rocuronium-induced Neuromuscular Blockade by Sugammadex in Children
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Anesthesia, General
Neuromuscular Blockade
Keywords: sugammadex
pharmacokinetics
pharmacodynamics
pediatric anesthesia
Lead sponsor: Seoul National University Hospital
Sponsor class: OTHER
Collaborators: name: Ministry of Food and Drug Safety, Korea
First posted: 2019-05-09
Enrollment: 40
Sex: ALL
Minimum age (years): 2
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.

Detailed description: This study enrolls pediatric patients undergoing surgery under general anesthesia with need for early 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. 15 minutes after rocuronium administration, 2 or 4 or 8mg/kg of sugammadex sodium or conventional neuromuscular reversal agent is administered according to randomization table.

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Neuromuscular Recovery
timeFrame: up to 30 minutes to 1 hour
Secondary outcomes:
measure: Plasma Concentrations
timeFrame: From anesthetic induction to 480 minutes after sugammadex administration
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: SNUH
state: Jongro Gu
Study officials:
affiliation: Seoul National University Hospital
name: Hee-Soo Kim, M.D, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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. doi: 10.1097/00000542-200604000-00009.
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. doi: 10.1097/01.anes.0000265152.78943.74.
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.
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.