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

July 28, 2025 updated by: Daniel S Tsze, MD, MPH, Columbia University

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

101

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10032
        • NewYork Presbyterian Morgan Stanley Children's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

6 months to 7 years (Child)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 0.2 mg/kg
Children in a single urban pediatric emergency department (ED) randomized to receive IN midazolam at 0.2 mg/kg.
Drug: Intranasal midazolam
5 mg/mL concentration of midazolam. Maximum dose = 10 mg. Administered using a mucosal atomization device.
Other Names:
  • IN midazolam
Experimental: 0.3 mg/kg
Children in a single urban pediatric emergency department (ED) randomized to receive IN midazolam at 0.3 mg/kg.
Drug: Intranasal midazolam
5 mg/mL concentration of midazolam. Maximum dose = 10 mg. Administered using a mucosal atomization device.
Other Names:
  • IN midazolam
Experimental: 0.4 mg/kg
Children in a single urban pediatric emergency department (ED) randomized to receive IN midazolam at 0.4 mg/kg.
Drug: Intranasal midazolam
5 mg/mL concentration of midazolam. Maximum dose = 10 mg. Administered using a mucosal atomization device.
Other Names:
  • IN midazolam
Experimental: 0.5 mg/kg
Children in a single urban pediatric emergency department (ED) randomized to receive IN midazolam at 0.5 mg/kg.
Drug: Intranasal midazolam
5 mg/mL concentration of midazolam. Maximum dose = 10 mg. Administered using a mucosal atomization device.
Other Names:
  • IN midazolam

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Children Who Achieved PSSS Score 2, 3, or 4 for 95% or Greater of the Scored Procedure
Time Frame: From study drug administration until procedure finished (approximately 60 minutes)
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
UMSS Scale Score
Time Frame: From study drug administration until procedure finished (approximately 60 minutes)
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)
Time to Recovery
Time Frame: From study drug administration until patient discharge (approximately 120 minutes)
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)
Number of Adverse Events
Time Frame: From study drug administration until patient discharge (approximately 120 minutes)
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)
Time to Onset of Minimal Sedation
Time Frame: From study drug administration until procedure finished (approximately 60 minutes)
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). Note: This outcome was initially listed as a primary outcome, but was changed to a secondary outcome in the IRB-approved protocol and prior to enrollment of the first patient.
From study drug administration until procedure finished (approximately 60 minutes)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Columbia University

Collaborators

Emergency Medicine Foundation
Mailman School of Public Health

Investigators

  • Principal Investigator: Daniel S. Tsze, MD, MPH, Columbia University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 8, 2021

Primary Completion (Actual)

May 14, 2024

Study Completion (Actual)

May 14, 2024

Study Registration Dates

First Submitted

October 12, 2020

First Submitted That Met QC Criteria

October 12, 2020

First Posted (Actual)

October 14, 2020

Study Record Updates

Last Update Posted (Actual)

August 6, 2025

Last Update Submitted That Met QC Criteria

July 28, 2025

Last Verified

July 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AAAS7996

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

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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