Pediatric Dose Optimization for Seizures in Emergency Medical Services

Study Overview
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Brief Summary
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The Pediatric Dose Optimization for Seizures in Emergency Medical Services (PediDOSE) study is designed to improve how paramedics treat seizures in children on ambulances. Seizures are one of the most common reasons why people call an ambulance for a child, and paramedics typically administer midazolam to stop the seizure. One-third of children with active seizures on ambulances arrive at emergency departments still seizing. Prior research suggests that seizures on ambulances continue due to under-dosing and delayed delivery of medication. Under-dosing happens when calculation errors occur, and delayed medication delivery occurs due to the time required for dose calculation and placement of an intravenous line to give the medication. Seizures stop quickly when standardized medication doses are given as a muscular injection or a nasal spray. This research has primarily been done in adults, and evidence is needed to determine if this is effective and safe in children. PediDOSE optimizes how paramedics choose the midazolam dose by eliminating calculations and making the dose age-based. This study involves changing the seizure treatment protocols for ambulance services in 20 different cities, in a staggered and randomly-assigned manner. One aim of PediDOSE is to determine if using age to select one of four standardized doses of midazolam and giving it as a muscular injection or nasal spray is more effective than the current calculation-based method, as measured by the number of children arriving at emergency departments still seizing. The investigators believe that a standardized seizure protocol with age-based doses is more effective than current practice. Another aim of PediDOSE is to determine if a standardized seizure protocol with age-based doses is just as safe as current practice, since either ongoing seizures or receiving too much midazolam can interfere with breathing. The investigators believe that a standardized seizure protocol with age-based doses is just as safe as current practice, since the seizures may stop faster and these doses are safely used in children in other healthcare settings. If this study demonstrates that standardized, age-based midazolam dosing is equally safe and more effective in comparison to current practice, the potential impact of this study is a shift in the treatment of pediatric seizures that can be easily implemented in ambulance services across the United States and in other parts of the world.

Official Title
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Pediatric Dose Optimization for Seizures in EMS (PediDOSE)

Conditions
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Seizures

Intervention / Treatment
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* Drug: Standardized seizure protocol
* Drug: Conventional seizure protocol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Witnessed by the paramedic to be actively seizing, regardless of seizure type or duration; AND Under the care of a paramedic; AND Transported by an EMS agency participating in the study Exclusion Criteria: A prior history of a benzodiazepine allergy; OR Known or presumed pregnancy; OR Severe growth restriction based on the paramedic's subjective assessment

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 13 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a stepped-wedge, cluster-randomized trial. Every 2 months, 1 of the 20 sites will transition, in a staggered manner, from the control (conventional protocol with calculation-based dosing) to the intervention (standardized protocol with age-based dosing), such that all 20 sites will ultimately implement the intervention during the 4-year enrollment period.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br>This arm will be exposed to the study intervention: a standardized seizure protocol. | Drug: Standardized seizure protocol<br>* The intervention is a standardized seizure protocol for paramedics that prioritizes administration of only intramuscular (IM) or intranasal (IN) midazolam, up to 2 doses given 5 minutes apart, with age-based dosing as follows: 6-16 months (1.25 mg); 17 months-5 years (2.5 mg); 6-11 years (5 mg); 12-13 years (10 mg).<br>* Other names: midazolam;|
| Active Comparator: Control<br>This arm will be exposed to the emergency medical services (EMS) agency's existing seizure protocol; this is the control arm | Drug: Conventional seizure protocol<br>* The control is the EMS agency's current seizure protocol, based on conventional calculation-based dosing. These vary from one EMS agency to the other with respect to recommended midazolam doses ranging from 0.05-0.3 mg/kg and with multiple route choices listed, including intravenous, intraosseous, intramuscular, intranasal, and rectal. for paramedics that prioritizes administration of only intramuscular (IM) or intranasal (IN) midazolam, up to 2 doses given 5 minutes apart, with age-based dosing as follows: 6-16 months (1.25 mg); 17 months-5 years (2.5 mg); 6-11 years (5 mg); 12-13 years (10 mg).<br>* Other names: midazolam;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seizing on emergency department arrival | Binary assessment of whether the participant is seizing or not upon arrival to the emergency department, as measured by either a rapid response electroencephalogram (preferred) or clinical judgement (alternative). | Between arrival to the emergency department and 10 minutes after arrival | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Respiratory failure | A binary assessment of insufficient breathing at any point during EMS care or within 30 minutes of emergency department arrival, defined as having received bag valve mask ventilation, bi-level positive airway pressure, placement of a supraglottic airway or endotracheal intubation. | Between paramedic arrival on scene until 30 minutes after emergency department arrival | 
| Time to first midazolam administration | Time in minutes from paramedic arrival to the scene until the paramedic administers midazolam to the patient | From paramedic arrival to the scene until emergency department arrival, assessed up to 1 hour after paramedic scene arrival or 1 minute after emergency department arrival, whichever occurs last | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Child, Emergency Medical Services