Clinical trial NCT05975255: Dose Finding Study for Remimazolam in Children
Official title: Effective Dose of Remimazolam for Loss of Consciousness in Children: A Prospective Dose Finding Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Drug Effect
Keywords: Remimazolam
Children
Dose
Lead sponsor: Seoul National University Hospital
Sponsor class: OTHER
First posted: 2023-08-03
Enrollment: 50
Sex: ALL
Minimum age (years): 2
Maximum age (years): 8
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: Sequential allocation to drug dosage according to result of previous participant
Primary purpose: SUPPORTIVE_CARE

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Loss of consciousness
timeFrame: From start of remimazolam administration to 2 minute after end of administration
Secondary outcomes:
measure: UMSS (University of Michigan Sedation Scale)
timeFrame: From start of remimazolam administration to 2 minute after end of administration
measure: Heart rate
timeFrame: From start of remimazolam administration to 2 minute after end of administration
measure: Pulse oximetry
timeFrame: From start of remimazolam administration to 2 minute after end of administration
measure: Noninvasive mean blood pressure
timeFrame: From start of remimazolam administration to 2 minute after end of administration
measure: Anesthetic depth
timeFrame: From start of remimazolam administration to 2 minute after end of administration
measure: Apnea
timeFrame: From start of remimazolam administration to 2 minute after end of administration
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
Study officials:
affiliation: Seoul National University Hospital
name: Jin-Tae Kim, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.