Safety & Efficacy of Intranasal Dexmedetomidine, Fentanyl & Midazolam in the Pediatric Emergency Room

A Double-blinded, Randomized Trial Comparing the Safety & Efficacy of Intranasal Dexmedetomidine, Intranasal Fentanyl & Intranasal Midazolam in the Pediatric Emergency Room

The hypothesis is that intranasal dexmedetomidine will provide significantly more effective analgesia and anxiolysis for subjects undergoing a simple laceration repair when compared to either intranasal fentanyl or intranasal midazolam.

Additional hypotheses include that there will be 1) no significant increase in adverse effects between drugs and 2) significantly higher satisfaction rates for both subject experience and ease of laceration repair based on structured, proceduralist feedback.

Study Overview

• Status: Not yet recruiting
• Conditions: Pain; Anxiety; Acute Stress Disorder
• Intervention / Treatment: Drug: Intranasal Dexmedetomidine (4 mcg/kg); Drug: Intranasal Fentanyl (2 mcg/kg); Drug: Intranasal Midazolam (5 mg/kg)

Detailed Description

Intranasal medications are rapidly gaining popularity as agents for analgesia and anxiolysis in the pediatric hospital setting. One of the primary reasons for the popularity of intranasal medications is ease of administration combined with favorable pharmacokinetics. It has been well established that children identify venipuncture as one of the most painful and anxiety-producing procedures during time spent in the hospital, and these experiences have been shown to have a more lasting impact, producing increased anxiety and fear at subsequent visits. Although oral and rectal administration of analgesics are also non-invasive, bioavailability, time to onset, and half-lives are significantly longer with these routes of administration in comparison to intranasal administration. Multiple studies have shown that intranasal fentanyl, midazolam, and dexmedetomidine have similar pharmacokinetics to intravenous preparations and reach adequate serum levels in both the blood and cerebrospinal fluid. In the pediatric emergency room setting, intranasal fentanyl and midazolam have been shown to provide effective analgesia and anxiolysis for a variety of settings, including pain management (e.g. pain associated with long bone fractures, burns, incision and drainage) and pre-procedural sedation/anxiolysis (e.g. radiological imaging).Numerous studies have examined the safety and efficacy of intranasal fentanyl and midazolam, and several studies have examined the efficacy of intranasal dexmedetomidine for non-painful procedural sedation. To date, two studies have compared the use of intranasal dexmedetomidine and intranasal midazolam or intranasal dexmedetomidine, intranasal fentanyl, and intranasal midazolam for anxiolysis in painful procedural sedations. However, as of 2020, no previous studies have compared the use of intranasal dexmedetomidine, intranasal fentanyl, and intranasal midazolam for painful procedures in the pediatric emergency setting.

• Study Type: Interventional
• Enrollment (Anticipated): 180
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jonathan Chang, MD; Phone Number: 501-364-1050; Email: jchang3@uams.edu

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Arkansas Children's Hospital
      • Contact: Jonathan Chang, MD; Phone Number: 501-364-1050; Email: jchang3@uams.edu
      • Principal Investigator: Jonathan Chang, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 6 years (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Primary complaint of "laceration"
• 2 years to 6 years of age (inclusive)
• Initial presentation at the Arkansas Children's Hospital (ACH) Emergency Department

Exclusion Criteria:

• Prior allergic reaction to fentanyl or midazolam or dexmedetomidine
• Prior major adverse reaction to fentanyl or midazolam (e.g. seizure-like activity, paradoxical reaction, hallucinations)
• Nasal injury/deformity
• Potential for altered pain perception (e.g. autism, severe sensory-neural disturbances)
• History of adverse reaction to sedation/anesthesia
• History of cardiac arrhythmia
• History of liver dysfunction
• Concurrent injuries that would necessitate higher levels of care (e.g. inpatient admission, immediate evaluation in the operating room (OR), etc.)
• Complex (multi-layer) lacerations or those requiring subspecialty consultation for repair
• American Society of Anesthesiology (ASA) score ≥ 3
• Use of analgesics (with the exception of ibuprofen or acetaminophen) or anxiolytics in the immediate pre-examination period (within 4 hours)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intranasal Dexmedetomidine (4 mcg/kg); Dexmedetomidine 100 mcg/mL (concentration of 200 mcg/2 mL) will be atomized for intranasal administration at a dose of 4 mcg/kg (0.04 mL/kg) according to a weight-based dosing chart. The maximum dose will be 200 mcg.	Drug: Intranasal Dexmedetomidine (4 mcg/kg); Dexmedetomidine 100 mcg/mL (concentration of 200 mcg/2 mL) will be atomized for intranasal administration at a dose of 4 mcg/kg (0.04 mL/kg) according to a weight-based dosing chart prior to laceration repair. The maximum dose will be 200 mcg.; Other Names: Precedex
Experimental: Intranasal Fentanyl (2 mcg/kg); Fentanyl 50 mcg/mL (concentration of 100 mcg/2 mL) will be atomized for intranasal administration at a dose of 2 mcg/kg (0.04 mL/kg) according to a weight-based dosing chart. The maximum dose will be 100 mcg.	Drug: Intranasal Fentanyl (2 mcg/kg); Fentanyl 50 mcg/mL (concentration of 100 mcg/2 mL) will be atomized for intranasal administration at a dose of 2 mcg/kg (0.04 mL/kg) according to a weight-based dosing chart prior to laceration repair. The maximum dose will be 100 mcg.; Other Names: Fentanyl Citrate
Experimental: Intranasal Midazolam (5 mg/kg); Midazolam 5 mg/mL (concentration of 10 mg/2 mL) will be atomized for intranasal administration at a dose of 0.3 mg/kg (0.06 mL/kg) according to a weight-based dosing chart. The maximum dose will be 10 mg	Drug: Intranasal Midazolam (5 mg/kg); Midazolam 5 mg/mL (concentration of 10 mg/2 mL) will be atomized for intranasal administration at a dose of 0.3 mg/kg (0.06 mL/kg) according to a weight-based dosing chart prior to laceration repair. The maximum dose will be 10 mg.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain using the Face, Legs, Activity, Cry, Consolability (FLACC) scale	Analgesia in subjects undergoing simple laceration repair will be compared across the three investigational drug products (intranasal dexmedetomidine, intranasal fentanyl, and intranasal midazolam) using the FLACC scale.	through the procedure, an average of 1 day
Anxiety using the modified Yale Preoperative Anxiety Scale (mYPAS) behavior observation tool	Anxiolysis in subjects undergoing simple laceration repair will be compared across the three investigational drug products (intranasal dexmedetomidine, intranasal fentanyl, and intranasal midazolam) using the modified Yale Preoperative Anxiety Scale (mYPAS) behavior observation tool.	through the procedure, an average of 1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Satisfaction rates for subject experience across the three study drugs based on parent/legally authorized representative (LAR) survey	Parent/LAR will be asked to complete a follow-up survey so that parent/LAR can provide feedback on the level of satisfaction with the laceration repair experience.	within 1 week of the laceration repair, average of 5 days
Satisfaction rates for surgical repair across the three study drugs based on proceduralist survey	Proceduralist will be asked to complete a follow-up survey to provide feedback on the level of satisfaction with the laceration repair experience.	within 1 week of the laceration repair, average of 5 days

Collaborators and Investigators

• Sponsor: University of Arkansas
• Investigators: Principal Investigator: Jonathan Chang, MD, University of Arkansas

Study record dates

Study Major Dates

• Study Start (Anticipated): October 1, 2022
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: September 15, 2021
• First Submitted That Met QC Criteria: September 15, 2021
• First Posted (Actual): September 27, 2021

Study Record Updates

• Last Update Posted (Actual): July 12, 2022
• Last Update Submitted That Met QC Criteria: July 11, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Disease Attributes; Trauma and Stressor Related Disorders; Stress Disorders, Traumatic; Emergencies; Stress Disorders, Traumatic, Acute; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Analgesics, Opioid; Narcotics; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Fentanyl; Midazolam; Dexmedetomidine
• Other Study ID Numbers: 261081

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No