Pediatric Dose Optimization for Seizures in Emergency Medical Services

NCT ID: NCT05121324

Last Updated: 2025-09-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

6700 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-08-08

Study Completion Date

2026-09-30

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.

Detailed Description

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Conditions

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Seizures

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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 Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors
Neurologists will assess the primary outcome of seizing on emergency department arrival using a rapid response electroencephalogram (RR-EEG) that is applied to the patient's scalp upon arrival. Site-specific identifiers will not be available to the neurologist when reading the RR-EEG, so they will be masked to whether the patient was treated under the conventional or standardized protocol.

Since the participants' parents will likely see how the paramedics select the midazolam dose and may share that with the participant, they will not be masked to the intervention. The paramedics are the care providers, and they will not be masked to the intervention since their medical director must inform them when their seizure treatment protocol switches from the conventional to the standardized protocol. The investigators will not be masked because they will conduct the training of the paramedic trainers at each site between randomization and implementation of the intervention.

Study Groups

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Intervention

This arm will be exposed to the study intervention: a standardized seizure protocol.

Group Type EXPERIMENTAL

Standardized seizure protocol

Intervention Type DRUG

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).

Control

This arm will be exposed to the emergency medical services (EMS) agency's existing seizure protocol; this is the control arm

Group Type ACTIVE_COMPARATOR

Conventional seizure protocol

Intervention Type DRUG

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).

Interventions

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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).

Intervention Type DRUG

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).

Intervention Type DRUG

Other Intervention Names

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midazolam midazolam

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
Minimum Eligible Age

6 Months

Maximum Eligible Age

13 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role collaborator

University of Utah

OTHER

Sponsor Role collaborator

Baylor College of Medicine

OTHER

Sponsor Role collaborator

Stanford University

OTHER

Sponsor Role lead

Responsible Party

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Manish Shah

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Manish I Shah, MD, MS

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

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University of Arizona

Tucson, Arizona, United States

Site Status RECRUITING

Children's Hospital of Los Angeles

Los Angeles, California, United States

Site Status RECRUITING

University of California, Davis

Sacramento, California, United States

Site Status RECRUITING

University of California, San Francisco

San Francisco, California, United States

Site Status RECRUITING

University of Colorado

Aurora, Colorado, United States

Site Status RECRUITING

Children's National Hospital

Washington D.C., District of Columbia, United States

Site Status RECRUITING

Emory University

Atlanta, Georgia, United States

Site Status RECRUITING

Indiana University

Indianapolis, Indiana, United States

Site Status RECRUITING

University of Michigan

Ann Arbor, Michigan, United States

Site Status RECRUITING

University at Buffalo

Buffalo, New York, United States

Site Status RECRUITING

Mecklenburg EMS

Charlotte, North Carolina, United States

Site Status RECRUITING

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Site Status RECRUITING

Nationwide Children's Hospital

Columbus, Ohio, United States

Site Status RECRUITING

Oregon Health and Sciences University

Portland, Oregon, United States

Site Status RECRUITING

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status RECRUITING

University of Texas Southwestern

Dallas, Texas, United States

Site Status RECRUITING

Baylor College of Medicine

Houston, Texas, United States

Site Status RECRUITING

University of Utah

Salt Lake City, Utah, United States

Site Status RECRUITING

University of Washington

Seattle, Washington, United States

Site Status RECRUITING

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Manish I Shah, MD, MS

Role: CONTACT

650-723-3319

Leonard Basobas, MS

Role: CONTACT

773-504-5963

Facility Contacts

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Joshua B Gaither, MD

Role: primary

520-626-1670

Todd P Chang, MD, MAcM

Role: primary

323-361-2109

Daniel Nishijima, MD, MAS

Role: primary

916-734-3884

Nicolaus Glomb, MD, MPH

Role: primary

415-476-3345

Kathleen Adelgais, MD, MPH

Role: primary

303-724-2595

Kathleen Brown, MD

Role: primary

202-476-4177

Claudia R Morris, MD

Role: primary

404-727-5500

Gregory W Faris, MD

Role: primary

317-962-3886

Stacey Noel, MD

Role: primary

734-763-7488

Brian Clemency, MD

Role: primary

716-645-9726

Douglas Swanson, MD

Role: primary

704-355-2000

Lauren Riney, DO

Role: primary

513-803-2969

Julie Leonard, MD, MPH

Role: primary

614-722-4384

Matthew Hansen, MD, MCR

Role: primary

503-494-7551

Sylvia Owusu-Ansah, MD, MPH

Role: primary

412-692-7692

Geoffrey Lowe, MD

Role: primary

214-456-1359

Kathryn M Kothari, MD

Role: primary

832-824-5497

Maija Holsti, MD, MPH

Role: primary

801-587-7450

Andrew Latimer, MD

Role: primary

206-521-1588

Lorin Browne, DO

Role: primary

414-266-2625

References

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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.

Reference Type BACKGROUND
PMID: 32589502 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30917730 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24298939 (View on PubMed)

Johnson AR, Riches NO, VanBuren JM, Corona AE, Jacobsen K, Yang S, Shah MI; Pediatric Emergency Care Applied Research Network (PECARN) PediDOSE Study Investigators. Measuring the efficacy of community consultation in a pediatric exception from informed consent trial. Acad Emerg Med. 2025 May;32(5):506-515. doi: 10.1111/acem.15073. Epub 2024 Dec 29.

Reference Type RESULT
PMID: 40365924 (View on PubMed)

Kornblith AE, Singh C, Innes JC, Chang TP, Adelgais KM, Holsti M, Kim J, McClain B, Nishijima DK, Rodgers S, Shah MI, Simon HK, VanBuren JM, Ward CE, Counts CR. Analyzing patient perspectives with large language models: a cross-sectional study of sentiment and thematic classification on exception from informed consent. Sci Rep. 2025 Feb 20;15(1):6179. doi: 10.1038/s41598-025-89996-w.

Reference Type RESULT
PMID: 39979559 (View on PubMed)

Ward CE, Adelgais KM, Holsti M, Jacobsen KK, Simon HK, Morris CR, Gonzalez VM, Lerner G, Ghaffari K, VanBuren JM, Lerner EB, Shah MI; Pediatric Emergency Care Applied Research Network (PECARN) PediDOSE Study Group. Public support for and concerns regarding pediatric dose optimization for seizures in emergency medical services: An exception from informed consent (EFIC) trial. Acad Emerg Med. 2024 Jul;31(7):656-666. doi: 10.1111/acem.14884. Epub 2024 Mar 7.

Reference Type RESULT
PMID: 38450918 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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U01NS114042

Identifier Type: NIH

Identifier Source: secondary_id

View Link

BCM H-49824

Identifier Type: OTHER

Identifier Source: secondary_id

73018

Identifier Type: -

Identifier Source: org_study_id

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