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

NCT04586504 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: AAAS7996
• Study Type: interventional
• Target: 101
• Locations: 1 country
• Sites: 1

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.

Conditions

Procedural Anxiety

Keywords

Intranasal; Midazolam; Pediatric; Laceration repair; Sedation; Anxiolysis; Adaptive trial design; Dose finding

Outcome Measures

Primary Outcomes (1)

• Number of Children Who Achieved PSSS Score 2, 3, or 4 for 95% or Greater of the Scored Procedure

  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)

Secondary Outcomes (4)

• Time to Recovery

  From study drug administration until patient discharge (approximately 120 minutes)

• Number of Adverse Events

  From study drug administration until patient discharge (approximately 120 minutes)

• Time to Onset of Minimal Sedation

  From study drug administration until procedure finished (approximately 60 minutes)

• UMSS Scale Score

  From study drug administration until procedure finished (approximately 60 minutes)

Study Arms (4)

0.2 mg/kg

EXPERIMENTAL

Children in a single urban pediatric emergency department (ED) randomized to receive IN midazolam at 0.2 mg/kg.

Drug: Intranasal midazolam

0.3 mg/kg

EXPERIMENTAL

Children in a single urban pediatric emergency department (ED) randomized to receive IN midazolam at 0.3 mg/kg.

Drug: Intranasal midazolam

0.4 mg/kg

EXPERIMENTAL

Children in a single urban pediatric emergency department (ED) randomized to receive IN midazolam at 0.4 mg/kg.

Drug: Intranasal midazolam

0.5 mg/kg

EXPERIMENTAL

Children in a single urban pediatric emergency department (ED) randomized to receive IN midazolam at 0.5 mg/kg.

Drug: Intranasal midazolam

Interventions

Intranasal midazolam DRUG

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

Also known as: IN midazolam

0.2 mg/kg; 0.3 mg/kg; 0.4 mg/kg; 0.5 mg/kg

Eligibility Criteria

• Age: 6 Months - 7 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Columbia University: lead
• Emergency Medicine Foundation: collaborator
• Mailman School of Public Health: collaborator

Study Sites (1)

NewYork Presbyterian Morgan Stanley Children's Hospital

New York, New York, 10032, United States

Location

Related Publications (8)

• 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.

  PMID: 27823876 BACKGROUND

• 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.

  PMID: 28557732 BACKGROUND

• 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.

  PMID: 28992870 BACKGROUND

• 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.

  BACKGROUND

• 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.

  PMID: 11878656 BACKGROUND

• 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.

  PMID: 19026467 BACKGROUND

• 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.

  PMID: 3430286 BACKGROUND

• Tsze DS, Woodward HA, McLaren SH, Leu CS, Venn AMR, Hu NY, Flores-Sanchez PL, Stefan BR, Shen ST, Ekladios MJ, Cravero JP, Dayan PS. Optimal Dose of Intranasal Midazolam for Procedural Sedation in Children: A Randomized Clinical Trial. JAMA Pediatr. 2025 Sep 1;179(9):979-986. doi: 10.1001/jamapediatrics.2025.2181.

  PMID: 40720114 RESULT

MeSH Terms

Interventions

Midazolam

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Daniel Tsze MD MPH
• Organization: Columbia University

dst2141@cumc.columbia.edu

212-317-0997

Study Officials

• Daniel S. Tsze, MD, MPH

  Columbia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Pediatrics in Emergency Medicine

Model Details: Sequential selection procedure

Study Record Dates

• First Submitted: October 12, 2020
• First Posted: October 14, 2020
• Study Start: September 8, 2021
• Primary Completion: May 14, 2024
• Study Completion: May 14, 2024
• Last Updated: August 6, 2025
• Results First Posted: June 12, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)