Dose-Finding Study of Intranasal Midazolam for Procedural Sedation in Children

Procedural Anxiety Clinical Trial

Official title:

Dose-Finding Study of Intranasal Midazolam for Procedural Sedation in Children

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04586504
• Other study ID #: AAAS7996
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: September 8, 2021
• Est. completion date: May 14, 2024

Study information

• Verified date: May 2024
• Source: Columbia University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 and time to onset of minimal sedation associated with each dose.

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 101
• Est. completion date: May 14, 2024
• Est. primary completion date: May 14, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 7 Years

Eligibility

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

Related Conditions & MeSH terms

• Procedural Anxiety

Intervention

Drug:
• Intranasal midazolam
5 mg/mL concentration of midazolam. Maximum dose = 10 mg. Administered using a mucosal atomization device.

Locations

Country	Name	City	State
United States	NewYork Presbyterian Morgan Stanley Children's Hospital	New York	New York

Sponsors (3)

Lead Sponsor	Collaborator
Columbia University	Emergency Medicine Foundation, Mailman School of Public Health

Country where clinical trial is conducted

United States, 

References & Publications (7)

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. — View 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. — View 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. — View 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.

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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pediatric Sedation State Scale Score	The Pediatric Sedation State Scale (PSSS) is scored from 0 to 5, representing a continuum of sedation that spans from over-sedation associated with changes in vital signs (0) to inadequate sedation (5).	From study drug administration until procedure finished (approximately 60 minutes)
Primary	Time to onset of minimal sedation	Time (in minutes) from administration of intranasal midazolam until a University of Michigan Sedation State (UMSS) score of 1 is achieved. The UMSS represents a spectrum of depth of sedation ranging from unarousable (4) to awake and alert (0).	From study drug administration until procedure finished (approximately 60 minutes)
Secondary	Time to recovery	Time (in minutes) from procedure completion until a Simplified Aldrete Score (SAS) of at least 6 is achieved. The score ranges from 0 (lowest) to 8 (highest). If a patient already fulfills criteria for recovery at procedure start, then time to recovery is 0.	From study drug administration until patient discharge (approximately 120 minutes)
Secondary	Incidence of adverse events	Adverse events will be defined using the Pediatric Emergency Research Canada and Pediatric Emergency Care Applied Research Network Consensus-Based Recommendations. These adverse events include oxygen desaturation; apnea (central, obstructive, laryngospasm); clinically apparent pulmonary aspiration; retching/vomiting; bradycardia; hypotension; excitatory movements; paradoxical response to sedation; unpleasant recovery reactions; and permanent complications (including death).	From study drug administration until patient discharge (approximately 120 minutes)
Secondary	OSBD-R Scale Score	Procedural pain and distress will be measured using the Observational Scale of Behavioral Distress - Revised (OSBD-R). Each 15-second interval is scored from 0 (no pain or distress) to 23.5 (maximal pain and distress).	From study drug administration until procedure finished (approximately 60 minutes)
Secondary	UMSS Scale Score	Depth of sedation will be measured using the University of Michigan Sedation Scale (UMSS). This sedation scale ranges from zero to four with higher numbers indicating deeper sedation.	From study drug administration until procedure finished (approximately 60 minutes)