Pharmacokinetic-pharmacodynamic Analysis of Sugammadex in Children

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Anesthesia, General, Neuromuscular Blockade

Intervention / Treatment
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* Drug: Sugammadex Injection 2mg/kg
* Drug: Sugammadex Injection 4mg/kg
* Drug: Sugammadex Injection 8mg/kg
* Drug: Neuromuscular reversal agent injection


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sugammadex 2mg<br>Administer 2mg/kg of sugammadex 15 minutes after rocuronium administration | Drug: Sugammadex Injection 2mg/kg<br>* Intravenous injection of 2mg/kg of sugammadex sodium 15 minutes after rocuronium administration<br>* Other names: Bridion 2mg/kg;|
| Experimental: Sugammadex 4mg<br>Administer 4mg/kg of sugammadex 15 minutes after rocuronium administration | Drug: Sugammadex Injection 4mg/kg<br>* Intravenous injection of 4mg/kg of sugammadex sodium 15 minutes after rocuronium administration<br>* Other names: Bridion 4mg/kg;|
| Experimental: Sugammadex 8mg<br>Administer 8mg/kg of sugammadex 15 minutes after rocuronium administration | Drug: Sugammadex Injection 8mg/kg<br>* Intravenous injection of 8mg/kg of sugammadex sodium 15 minutes after rocuronium administration<br>* Other names: Bridion 8mg/kg;|
| Active Comparator: Conventional reversal<br>Administer conventional neuromuscular reversal agent (0.02mg/kg of atropine and 0.03mg/kg of neostigmine) 15 minutes after rocuronium administration | Drug: Neuromuscular reversal agent injection<br>* Intravenous injection of 0.02mg/kg of atropine and 0.03mg/kg of neostigmine<br>* Other names: Atropine and neostigmine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma Concentrations | Plasma concentrations of rocuronium and sugammadex sodium | From anesthetic induction to 480 minutes after sugammadex administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sugammadex, pharmacokinetics, pharmacodynamics, pediatric anesthesia