Clinical trial NCT05121324: Pediatric Dose Optimization for Seizures in Emergency Medical Services
Official title: Pediatric Dose Optimization for Seizures in EMS (PediDOSE)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Seizures
Keywords: Child
Emergency Medical Services
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: National Institute of Neurological Disorders and Stroke (NINDS)
name: University of Utah
name: Baylor College of Medicine
First posted: 2021-11-16
Enrollment: 6000
Sex: ALL
Minimum age (years): 6
Maximum age (years): 13
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Seizing on emergency department arrival
timeFrame: Between arrival to the emergency department and 10 minutes after arrival
Secondary outcomes:
measure: Respiratory failure
timeFrame: Between paramedic arrival on scene until 30 minutes after emergency department arrival
measure: Time to first midazolam administration
timeFrame: 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
Other outcomes:
measure: Time to seizure cessation in the emergency department
timeFrame: From emergency department arrival until emergency department departure, assessed up to 24 hours after emergency department arrival
measure: Dose/route adherence
timeFrame: 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
measure: Life-threatening hypotension
timeFrame: Between paramedic midazolam administration and hospital discharge, assessed up to 24 hours
measure: Life-threatening cardiac arrhythmia
timeFrame: Between paramedic midazolam administration and hospital discharge, assessed up to 24 hours
measure: Depressed level of consciousness
timeFrame: Between paramedic midazolam administration and 4 hours after emergency department arrival
Locations:
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
city: Los Angeles
country: United States
facility: Children's Hospital of Los Angeles
state: California
city: Sacramento
country: United States
facility: University of California, Davis
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Washington
country: United States
facility: Children's National Hospital
state: District of Columbia
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Buffalo
country: United States
facility: University at Buffalo
state: New York
city: Charlotte
country: United States
facility: Mecklenburg EMS
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Sciences University
state: Oregon
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Dallas
country: United States
facility: University of Texas Southwestern
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: Stanford University
name: Manish I Shah, MD, MS
role: PRINCIPAL_INVESTIGATOR
References:
citation: Shah MI, Ostermayer DG, Browne LR, Studnek JR, Carey JM, Stanford C, Fumo N, Lerner EB. Multicenter Evaluation of Prehospital Seizure Management in Children. Prehosp Emerg Care. 2021 Jul-Aug;25(4):475-486. doi: 10.1080/10903127.2020.1788194. Epub 2020 Jul 17.
citation: Carey JM, Studnek JR, Browne LR, Ostermayer DG, Grawey T, Schroter S, Lerner EB, Shah MI. Paramedic-Identified Enablers of and Barriers to Pediatric Seizure Management: A Multicenter, Qualitative Study. Prehosp Emerg Care. 2019 Nov-Dec;23(6):870-881. doi: 10.1080/10903127.2019.1595234. Epub 2019 May 13.
citation: Shah MI, Macias CG, Dayan PS, Weik TS, Brown KM, Fuchs SM, Fallat ME, Wright JL, Lang ES. An Evidence-based Guideline for Pediatric Prehospital Seizure Management Using GRADE Methodology. Prehosp Emerg Care. 2014;18 Suppl 1:15-24. doi: 10.3109/10903127.2013.844874. Epub 2013 Dec 3.