Pediatric Dose Optimization for Seizures in Emergency Medical Services

Seizures Clinical Trial

— PediDOSE  

Official title:

Pediatric Dose Optimization for Seizures in EMS (PediDOSE)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05121324
• Other study ID #: BCM H-49824
• Secondary ID: U01NS114042
• Status: Recruiting
• Phase: Phase 3
• Start date: August 8, 2022
• Est. completion date: August 31, 2026

Study information

• Verified date: May 2023
• Source: Baylor College of Medicine
• Contact: Manish I Shah, MD, MS
• Phone: 832-824-6703
• Email: mxshah[@]texaschildrens.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 6000
• Est. completion date: August 31, 2026
• Est. primary completion date: July 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 13 Years

Eligibility

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

Related Conditions & MeSH terms

• Seizures

Intervention

Drug:
• Standardized seizure protocol
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).
• Conventional seizure protocol
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).

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	Emory University	Atlanta	Georgia
United States	University of Colorado	Aurora	Colorado
United States	University at Buffalo	Buffalo	New York
United States	Mecklenburg EMS	Charlotte	North Carolina
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	University of Texas Southwestern	Dallas	Texas
United States	Baylor College of Medicine	Houston	Texas
United States	Indiana University	Indianapolis	Indiana
United States	Children's Hospital of Los Angeles	Los Angeles	California
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	Oregon Health and Sciences University	Portland	Oregon
United States	University of California, Davis	Sacramento	California
United States	University of Utah	Salt Lake City	Utah
United States	University of California, San Francisco	San Francisco	California
United States	University of Washington	Seattle	Washington
United States	University of Arizona	Tucson	Arizona
United States	Children's National Hospital	Washington	District of Columbia

Sponsors (3)

Lead Sponsor	Collaborator
Baylor College of Medicine	National Institute of Neurological Disorders and Stroke (NINDS), University of Utah

Country where clinical trial is conducted

United States, 

References & Publications (3)

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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Time to seizure cessation in the emergency department	For participants who are seizing upon emergency department arrival, this is the time in minutes that it takes for the seizure to stop, as determined by the rapid response electroencephalogram (preferred) or clinical judgement (alternative)	From emergency department arrival until emergency department departure, assessed up to 24 hours after emergency department arrival
Other	Dose/route adherence	A binary assessment of receiving midazolam in the prehospital setting by both the preferred route (intranasal or intramuscular) and correct dose [within 30% of 0.2 mg/kg (=0.14-0.26 mg/kg)], based on a calculation from weight measured in the emergency department	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	Life-threatening hypotension	A binary assessment of whether or not the patient had a systolic blood pressure in mm Hg that persisted below the following age-based thresholds despite receiving a 20 ml/kg isotonic fluid bolus: 6-11 months (<60 mm Hg); 1-10 years {< [(age in years)x2] + 70 mm Hg}; >10 years: (<90 mm Hg)	Between paramedic midazolam administration and hospital discharge, assessed up to 24 hours
Other	Life-threatening cardiac arrhythmia	A binary assessment of whether or not the patient's heart rhythm changed to require intervention with chest compressions, pacing, defibrillation, or the use of an anti-arrhythmic agent or procedure.	Between paramedic midazolam administration and hospital discharge, assessed up to 24 hours
Other	Depressed level of consciousness	Glasgow coma score <8 that persists more than 4 hours after emergency department arrival	Between paramedic midazolam administration and 4 hours after emergency department arrival
Primary	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	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
Secondary	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