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

Sponsor

Columbia University (Other)

Overall Status

Recruiting

CT.gov ID

NCT04586504

Collaborator

Emergency Medicine Foundation (Other), Mailman School of Public Health (Other)

150

Enrollment

Location

Arms

12.7

Anticipated Duration (Months)

11.8

Patients Per Site Per Month

Study Details

Study Description

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 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.

Condition or Disease	Intervention/Treatment	Phase
Procedural Anxiety	Drug: Intranasal midazolam	Phase 1/Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

150 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Sequential selection procedureSequential selection procedure

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Sep 8, 2021

Anticipated Primary Completion Date :

Oct 1, 2022

Anticipated Study Completion Date :

Oct 1, 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

Pediatric Sedation State Scale Score [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).
Time to onset of minimal sedation [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).

Secondary Outcome Measures

Time to recovery [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.
Incidence of adverse events [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).
OSBD-R Scale Score [From study drug administration until procedure finished (approximately 60 minutes)]
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).
UMSS Scale Score [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

6 Months to 7 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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