The ED95 of Single Intravenous Bolus Remimazolam Besylate in Pediatric Patients During General Anesthesia Induction

The ED95 of Single Intravenous Bolus Remimazolam Besylate in Pediatric Patients During General Anesthesia Induction:a Randomised,Double-blind Clinical Trial

Due to the incomplete development of systems and low pain thresholds in the pediatric population, good general anesthesia is required during the perioperative period to ensure the smooth progress of the surgery.Propofol is often used for anesthesia induction in clinical work, which can achieve good anesthesia effects. However, this drug has obvious injection pain and is prone to significant inhibition of blood circulation, and may even lead to adverse conditions such as respiratory depression in children. For the pediatric population, maintaining appropriate anesthesia depth and stable circulation during the induction period of general anesthesia has always been a focus of attention and research by anesthesiologists.Remimazolam besylate is a new type of water-soluble ultra short acting benzodiazepine drug that is hydrolyzed and metabolized by plasma esterase in the body, independent of liver and kidney function, and the metabolite zolam propionic acid has no pharmacological activity; Rapid onset and failure, short sedation recovery time; Has little impact on respiration and circulation; And there is no injection pain.Remazolam besylate is highly suitable for children due to its characteristics, and some studies have demonstrated the safety of intravenous injection of Remazolam besylate. However, there is limited research on its dosage exploration, which to some extent limits its clinical application in children.This study aims to explore the 95% effective dose (ED95) of single intravenous injection of remidazolam besylate in children of different age groups, providing a theoretical basis for the use of remidazolam besylate in pediatric anesthesia.

Study Overview

• Status: Completed
• Conditions: Sedation; General Anesthesia; Pediatric; ED95
• Intervention / Treatment: Drug: Remimazolam besylate; Drug: Remimazolam besylate

Detailed Description

This experiment was divided into three groups based on the age of the children, namely 1-3 years old, 4-6 years old, 7-12 years old, with an initial dose of 0.2mg/kg. The time of consciousness loss in the children was evaluated after injection of ramazolam besylate to determine whether sedation had been achieved. The next dose was adjusted to 0.05mg/kg according to biased coin design,to further explore the ED95 of a single intravenous injection of ramazolam in children of different age groups.

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Wenzhou, Zhejiang, China
      • The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. with American Society of Anesthesiologists (ASA) physical status I or II；
2. aged 1-12 years；
3. children with weight for age within the normal range；
4. were scheduled general anesthesia surgery

Exclusion Criteria:

1. Children who had gastrointestinal,Cardiovascular or endocrine dysfunction;
2. contraindication to preoperative sedation or had a known allergy or hypersensitive reaction to remimazolam;
3. recently respiratory infection, mental disorder;
4. other reasons that researchers hold it is not appropriate to participate in this trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1-3years old; single intravenous bolus remimazolam about 5min before general anesthesia induction	Drug: Remimazolam besylate; initial dose is 0.2mg/kg；adjust dosage is 0.05mg/kg; Other Names: single intravenous bolus remimazolam according to biased coin design; Drug: Remimazolam besylate; initial dose is based on the findings from the school-age group；adjust dosage is 0.05mg/kg; Other Names: single intravenous bolus remimazolam according to biased coin design
Experimental: 3-6years old; single intravenous bolus remimazolam about 5min before general anesthesia induction	Drug: Remimazolam besylate; initial dose is 0.2mg/kg；adjust dosage is 0.05mg/kg; Other Names: single intravenous bolus remimazolam according to biased coin design; Drug: Remimazolam besylate; initial dose is based on the findings from the school-age group；adjust dosage is 0.05mg/kg; Other Names: single intravenous bolus remimazolam according to biased coin design
Experimental: 6-12years old; single intravenous bolus remimazolam about 5min before general anesthesia induction	Drug: Remimazolam besylate; initial dose is 0.2mg/kg；adjust dosage is 0.05mg/kg; Other Names: single intravenous bolus remimazolam according to biased coin design; Drug: Remimazolam besylate; initial dose is based on the findings from the school-age group；adjust dosage is 0.05mg/kg; Other Names: single intravenous bolus remimazolam according to biased coin design

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the time of the loss of consciousness(LOC)	Modified Observers Assessment of Alertness/Sedation (MOAA/S) score of 1 or deeper within 1 minute, and maintained until the end of the 5-minute observation period.	during anaesthetic induction

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
BIS	BIS values range from 0 to 100. A value of 0 represents the absence of brain activity, and 100 represents the awake state. BIS values between 60 to 80 represent sedation; BIS values between 40 to 60 represent adequate general anesthesia for a surgery; values less than 40 represent a deep hypnotic state.	Every 1 minutes after single intravenous bolus remimazolam
Number of children with adverse effects	Number of children with adverse effects: １、Bradycardia and/or hypotension need for hemodynamic support; 2、Desaturation is defined as Oxygen desaturation <90%; 3、Nausea and vomiting; 4、Any adverse effects requiring interventions.	Up to 24 hours including preoperative, intraoperative, and postoperative periods
Recovery time	The time from discontinuation of sevoflurane to the first open eye of the children and to achieve the modified aldrete scole ≥9. then the aldrete scole's minimum value is 0 and maximum value is 10, and higher scores mean a better or outcome. The modified aldrete scole consists of five items. Each item is scored 0-2 yielding a total between 0 and 10.	Within up to 30 minutes after child's first eye opening in the postoperative period
Rate of Pediatric anesthesia emergence delirium	The pediatric anesthesia emergence delirium scale consists of five items. Each item is scored 0-4 yielding a total between 0 and 20. The degree of emergence delirium increased directly with the total score. pediatric anesthesia emergence delirium scale ≥12 at any time indicates presence of emergence delirium.	Within up to 15-30 minutes after child's first eye opening in the postoperative period
Modified observer's assessment of alertness／sedation（MOAA/S）scale	5-Subject responds readily to name spoken in a normal tone; 4 -Lethargic response of a subject to a name spoken in a normal tone; 3 -The subject responds only after a name is called loudly and repeatedly; 2 -The subject responds only after mild prodding or shaking; 1 -The subject responds only after a painful trapezius squeeze; 0 -The subject does not respond to painful trapezius squeeze. MOAA/S score ≤ 1 points represent successful sedation	Every 1 minutes after single intravenous bolus remimazolam

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital of Wenzhou Medical University
• Investigators: Principal Investigator: Huacheng Liu, Second Affiliated Hospital of Wenzhou Medical University; Principal Investigator: Yuhang Cai, Second Affiliated Hospital of Wenzhou Medical University; Principal Investigator: Leqi Dong, Second Affiliated Hospital of Wenzhou Medical University

Study record dates

Study Major Dates

• Study Start (Actual): October 6, 2023
• Primary Completion (Actual): February 27, 2024
• Study Completion (Actual): February 27, 2024

Study Registration Dates

• First Submitted: September 24, 2023
• First Submitted That Met QC Criteria: September 24, 2023
• First Posted (Actual): September 29, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 4, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: remimazolam
• Other Study ID Numbers: SAHoWMU-CR2023-03-107

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No