Dose Finding Study for Remimazolam in Children

Effective Dose of Remimazolam for Loss of Consciousness in Children: A Prospective Dose Finding Study

This study aims to find effective dose of remimazolam for inducing loss of consciousness in children aged 2 to 8 years old. We will explore ED90 of remimazolam for loss of consciousness in 2 minutes after intravenous injection, via a up-and-down method with biased-coin design.

Study Overview

• Status: Recruiting
• Conditions: Drug Effect
• Intervention / Treatment: Drug: Remimazolam besylate

Detailed Description

We will administer remimazolam intravenously to the study participants. Remimazolam will be infused in 30 seconds to the participants, and we will wait for 2 minutes for the participants be sedated.

When a participant was not sedated in 2 minutes, dose of remimazolam in the next participant will be escalated by 0.05mg/kg. When a participant was sedated in 2 minutes, dose of remimazolam in the next participant will be decreased by 0.05mg/kg or maintained as same. The probability of decrement and maintenance will be 90% and 10% respectively. The dose of remimazolam in the first participant of the study will be 0.05mg/kg.

We will collect the results and obtain ED90 of remimazolam for loss of consciousness in children aged 2 to 8 years old.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Sang-Hwan Ji, M.D., Ph.D.; Phone Number: 82-2-2072-3661; Email: jsh1@snu.ac.kr

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Recruiting
    • Seoul National University Hospital
    • Contact: Sang-Hwan Ji, M.D., M.S.; Phone Number: +82-2-2072-3661; Email: taepoongshin@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Children scheduled to undergo general anesthesia or sedation
• American Society of Anesthesiologist Physical Status of 1 or 2

Exclusion Criteria:

• Presence of Upper respiratory tract infection or any pulmonary disease
• Presence of subglottic stenosis, laryngomalacia, or tracheomalacia
• History of hypersensitivity to benzodiazepines or propofol
• History of hypersensitivity to beans or peanut
• History of seizure
• Presence of arrhythmia, tachycardia, or bradycardia
• Presence of acute closed-angle glaucoma
• Patients with unstable vital sign
• Presence of sleep apnea
• Presence of galactose intolerance, Lapp lactase deficiency, or glucose-galactose absorption disorder
• History of hypersensitivity to dextran 40
• Refusal to enroll by one or more parents or legal guardian
• Other conditions the researchers regarded as inappropriate to enroll

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Study group; Remimazolam administration and evaluation of sedative effect	Drug: Remimazolam besylate; Intravenous administration of predetermined dose of Byfavo for 30 seconds; Other Names: Byfavo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Loss of consciousness	Score 3 or more in the University of Michigan Sedation Scale in less than 2 minutes after administration of remimazolam besylate	From start of remimazolam administration to 2 minute after end of administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Heart rate	Serial measurement of heart rate	From start of remimazolam administration to 2 minute after end of administration
Pulse oximetry	Serial measurement of pulse oximetry	From start of remimazolam administration to 2 minute after end of administration
Noninvasive mean blood pressure	Serial measurement of noninvasive mean blood pressure	From start of remimazolam administration to 2 minute after end of administration
Anesthetic depth	Serial measurement of electroencephalogram-based anesthetic depth monitoring	From start of remimazolam administration to 2 minute after end of administration
Apnea	Incidence of apnea after administration of remimazolam besylate	From start of remimazolam administration to 2 minute after end of administration
UMSS (University of Michigan Sedation Scale)	Serial measurement of University of Michigan Sedation Scale	From start of remimazolam administration to 2 minute after end of administration

Collaborators and Investigators

• Sponsor: Seoul National University Hospital
• Investigators: Principal Investigator: Jin-Tae Kim, M.D., Ph.D., Seoul National University Hospital

Publications and helpful links

General Publications

• Antonik LJ, Goldwater DR, Kilpatrick GJ, Tilbrook GS, Borkett KM. A placebo- and midazolam-controlled phase I single ascending-dose study evaluating the safety, pharmacokinetics, and pharmacodynamics of remimazolam (CNS 7056): Part I. Safety, efficacy, and basic pharmacokinetics. Anesth Analg. 2012 Aug;115(2):274-83. doi: 10.1213/ANE.0b013e31823f0c28. Epub 2011 Dec 20.
• Gorges M, Zhou G, Brant R, Ansermino JM. Sequential allocation trial design in anesthesia: an introduction to methods, modeling, and clinical applications. Paediatr Anaesth. 2017 Mar;27(3):240-247. doi: 10.1111/pan.13088. Epub 2017 Feb 17.
• Kilpatrick GJ, McIntyre MS, Cox RF, Stafford JA, Pacofsky GJ, Lovell GG, Wiard RP, Feldman PL, Collins H, Waszczak BL, Tilbrook GS. CNS 7056: a novel ultra-short-acting Benzodiazepine. Anesthesiology. 2007 Jul;107(1):60-6. doi: 10.1097/01.anes.0000267503.85085.c0.

Study record dates

Study Major Dates

• Study Start (Actual): November 16, 2023
• Primary Completion (Estimated): October 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: July 27, 2023
• First Submitted That Met QC Criteria: July 27, 2023
• First Posted (Actual): August 3, 2023

Study Record Updates

• Last Update Posted (Estimated): November 22, 2023
• Last Update Submitted That Met QC Criteria: November 20, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Children; Dose; Remimazolam
• Other Study ID Numbers: 2306-198-1445

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes