Clinical trial NCT04586504: Dose-Finding Study of Intranasal Midazolam for Procedural Sedation in Children
Official title: Dose-Finding Study of Intranasal Midazolam for Procedural Sedation in Children
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Procedural Anxiety
Keywords: Intranasal
Midazolam
Pediatric
Laceration repair
Sedation
Anxiolysis
Adaptive trial design
Dose finding
Lead sponsor: Columbia University
Sponsor class: OTHER
Collaborators: name: Emergency Medicine Foundation
name: Mailman School of Public Health
First posted: 2020-10-14
Enrollment: 101
Sex: ALL
Minimum age (years): 6
Maximum age (years): 7
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Sequential selection procedure
Primary purpose: TREATMENT

Brief summary: Dose-finding study to compare intranasal midazolam doses of 0.2, 0.3, 0.4 and 0.5 mg/kg in children undergoing laceration repair to achieve the following aims:

Specific Aim #1: To determine the most effective dose of intranasal midazolam for producing adequate sedation state associated with each dose.

Specific Aim #2: To determine the time to recovery and describe the adverse events associated with each dose.

Detailed description: Intranasal midazolam is a common and effective sedative whose use in children presenting to emergency departments has been described. However, the doses of intranasal midazolam used have varied greatly, with no identified optimal dose. Doses most commonly described in literature reviews, research studies, and clinical guidelines range from 0.2 to 0.5 mg/kg. There is only one study, retrospective, that compares doses and suggests that clinical efficacy is improved with higher doses, without any clear difference in safety. There is a need for a rigorously-conducted trial to determine the dose of intranasal midazolam that optimizes the adequacy of sedation state without leading to adverse events or compromising emergency department-centric outcomes such as time to onset of sedation and time to recovery. To fill this important and persistent gap in knowledge, the investigator will conduct a dose-finding study using an adaptive trial design to compare intranasal midazolam doses of 0.2, 0.3, 0.4, and 0.5 mg/kg in children undergoing laceration repairs, one of the most common types of minor trauma treated in emergency departments.

Eligibility criteria: Inclusion Criteria:

* Ages 6 months to 7 years old (i.e. before their 8th birthday)
* Simple laceration
* Attending physician has decided intranasal midazolam indicated to facilitate repair

Exclusion Criteria:

* Repair using tissue adhesive (e.g. Dermabond) or staples
* Known or confirmed developmental delay
* Baseline motor neurological abnormality (e.g. motor deficit, cerebral palsy)
* Autism spectrum disorder
* Illness associated with chronic pain
* Known allergy to midazolam or any other benzodiazepine
* Eyelid laceration
* Tongue or intraoral lacerations
* Nasal obstruction that cannot be easily cleared
* Does not speak English or Spanish
* Foster children, wards of the state

Primary outcomes:
measure: Number of Children Who Achieved PSSS Score 2, 3, or 4 for 95% or Greater of the Scored Procedure
timeFrame: From study drug administration until procedure finished (approximately 60 minutes)
Secondary outcomes:
measure: Time to Recovery
timeFrame: From study drug administration until patient discharge (approximately 120 minutes)
measure: Number of Adverse Events
timeFrame: From study drug administration until patient discharge (approximately 120 minutes)
measure: Time to Onset of Minimal Sedation
timeFrame: From study drug administration until procedure finished (approximately 60 minutes)
measure: UMSS Scale Score
timeFrame: From study drug administration until procedure finished (approximately 60 minutes)
Other outcomes:
Locations:
city: New York
country: United States
facility: NewYork Presbyterian Morgan Stanley Children's Hospital
state: New York
Study officials:
affiliation: Columbia University
name: Daniel S. Tsze, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tsze DS, Ieni M, Fenster DB, Babineau J, Kriger J, Levin B, Dayan PS. Optimal Volume of Administration of Intranasal Midazolam in Children: A Randomized Clinical Trial. Ann Emerg Med. 2017 May;69(5):600-609. doi: 10.1016/j.annemergmed.2016.08.450. Epub 2016 Nov 4.
citation: Cravero JP, Askins N, Sriswasdi P, Tsze DS, Zurakowski D, Sinnott S. Validation of the Pediatric Sedation State Scale. Pediatrics. 2017 May;139(5):e20162897. doi: 10.1542/peds.2016-2897.
citation: Mellion SA, Bourne D, Brou L, Brent A, Adelgais K, Galinkin J, Wathen J. Evaluating Clinical Effectiveness and Pharmacokinetic Profile of Atomized Intranasal Midazolam in Children Undergoing Laceration Repair. J Emerg Med. 2017 Sep;53(3):397-404. doi: 10.1016/j.jemermed.2017.05.029.
citation: Leu C-S, Levin B. On the probability of correct selection in the Levin-Robbins sequential elimination procedure. Stat Sin 1999;9(3):879-91.
citation: Malviya S, Voepel-Lewis T, Tait AR, Merkel S, Tremper K, Naughton N. Depth of sedation in children undergoing computed tomography: validity and reliability of the University of Michigan Sedation Scale (UMSS). Br J Anaesth. 2002 Feb;88(2):241-5. doi: 10.1093/bja/88.2.241.
citation: Bhatt M, Kennedy RM, Osmond MH, Krauss B, McAllister JD, Ansermino JM, Evered LM, Roback MG; Consensus Panel on Sedation Research of Pediatric Emergency Research Canada (PERC) and the Pediatric Emergency Care Applied Research Network (PECARN). Consensus-based recommendations for standardizing terminology and reporting adverse events for emergency department procedural sedation and analgesia in children. Ann Emerg Med. 2009 Apr;53(4):426-435.e4. doi: 10.1016/j.annemergmed.2008.09.030. Epub 2008 Nov 20.
citation: Elliott CH, Jay SM, Woody P. An observation scale for measuring children's distress during medical procedures. J Pediatr Psychol. 1987 Dec;12(4):543-51. doi: 10.1093/jpepsy/12.4.543. No abstract available.