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

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ClinicalTrials.gov Identifier: NCT04586504
Recruitment Status : Recruiting
First Posted : October 14, 2020
Last Update Posted : September 10, 2021
Sponsor:
Collaborators:
Emergency Medicine Foundation
Mailman School of Public Health
Information provided by (Responsible Party):
Daniel S Tsze, MD, MPH, Columbia University

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Sequential 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 : September 8, 2021
Estimated Primary Completion Date : October 2022
Estimated Study Completion Date : October 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Anxiety

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 Name: 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 Name: 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 Name: 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 Name: IN midazolam




Primary Outcome Measures :
  1. Pediatric Sedation State Scale Score [ 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).

  2. 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).


Secondary Outcome Measures :
  1. 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.

  2. Incidence 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).

  3. OSBD-R Scale Score [ Time Frame: 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).

  4. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   6 Months to 7 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04586504


Contacts
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Contact: Daniel S Tsze, MD, MPH 212-305-9825 dst2141@cumc.columbia.edu
Contact: Raquel Shrager 212-305-4687 rs3823@cumc.columbia.edu

Locations
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United States, New York
NewYork Presbyterian Morgan Stanley Children's Hospital Recruiting
New York, New York, United States, 10032
Contact: Daniel S Tsze, MD, MPH    212-305-9825    dst2141@cumc.columbia.edu   
Contact: Raquel Shrager    212-305-4687    rs3823@cumc.columbia.edu   
Principal Investigator: Daniel S Tsze, MD, MPH         
Sub-Investigator: Peter S Dayan, MD, MSc         
Sub-Investigator: Hilary A Woodward, MS, CCLS         
Sub-Investigator: Cheng-Shiun Leu, PhD         
Sponsors and Collaborators
Columbia University
Emergency Medicine Foundation
Mailman School of Public Health
Investigators
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Principal Investigator: Daniel S Tsze, MD, MPH Columbia University
Publications:
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.

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Responsible Party: Daniel S Tsze, MD, MPH, Associate Professor of Emergency Medicine, Dept of Pediatrics, Columbia University
ClinicalTrials.gov Identifier: NCT04586504    
Other Study ID Numbers: AAAS7996
First Posted: October 14, 2020    Key Record Dates
Last Update Posted: September 10, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Keywords provided by Daniel S Tsze, MD, MPH, Columbia University:
Intranasal
Midazolam
Pediatric
Laceration repair
Sedation
Anxiolysis
Adaptive trial design
Dose finding
Additional relevant MeSH terms:
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Midazolam
Adjuvants, Anesthesia
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action