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Pediatric Dose Optimization for Seizures in Emergency Medical Services (PediDOSE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05121324
Recruitment Status : Not yet recruiting
First Posted : November 16, 2021
Last Update Posted : November 16, 2021
Sponsor:
Collaborators:
National Institute of Neurological Disorders and Stroke (NINDS)
University of Utah
Information provided by (Responsible Party):
Manish Shah, MD, Baylor College of Medicine

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.


Condition or disease Intervention/treatment Phase
Seizures Drug: Standardized seizure protocol Drug: Conventional seizure protocol Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 4840 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: This is a stepped-wedge, cluster-randomized trial. Every 4 months, 2 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 (Outcomes Assessor)
Masking Description:

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.

Primary Purpose: Treatment
Official Title: Pediatric Dose Optimization for Seizures in EMS (PediDOSE)
Estimated Study Start Date : May 2022
Estimated Primary Completion Date : April 2026
Estimated Study Completion Date : July 2026

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Intervention
This arm will be exposed to the study intervention: a standardized seizure protocol.
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).
Other Name: midazolam

Active Comparator: Control
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

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).

Other Name: midazolam




Primary Outcome Measures :
  1. Seizing on emergency department arrival [ Time Frame: Between arrival to the emergency department and 10 minutes after 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).


Secondary Outcome Measures :
  1. Respiratory failure [ Time Frame: Between paramedic arrival on scene until 30 minutes after emergency department arrival ]
    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.

  2. Time to first midazolam administration [ Time Frame: 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 ]
    Time in minutes from paramedic arrival to the scene until the paramedic administers midazolam to the patient


Other Outcome Measures:
  1. Time to seizure cessation in the emergency department [ Time Frame: From emergency department arrival until emergency department departure, assessed up to 24 hours after emergency department arrival ]
    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)

  2. Dose/route adherence [ Time Frame: 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 ]
    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

  3. Life-threatening hypotension [ Time Frame: Between paramedic midazolam administration and hospital discharge, assessed up to 24 hours ]
    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)

  4. Life-threatening cardiac arrhythmia [ Time Frame: Between paramedic midazolam administration and hospital discharge, assessed up to 24 hours ]
    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.

  5. Depressed level of consciousness [ Time Frame: Between paramedic midazolam administration and 4 hours after emergency department arrival ]
    Glasgow coma score <8 that persists more than 4 hours after emergency department arrival



Information from the National Library of Medicine

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Ages Eligible for Study:   6 Months to 13 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

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): NCT05121324


Contacts
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Contact: Manish I Shah, MD, MS 832-824-6703 mxshah@texaschildrens.org
Contact: Victor M Gonzalez, MD 832-824-5977 vmgonzal@bcm.edu

Locations
Show Show 20 study locations
Sponsors and Collaborators
Baylor College of Medicine
National Institute of Neurological Disorders and Stroke (NINDS)
University of Utah
Investigators
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Principal Investigator: Manish I Shah, MD, MS Baylor College of Medicine
Publications:
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Responsible Party: Manish Shah, MD, Associate Professor, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT05121324    
Other Study ID Numbers: BCM H-49824
U01NS114042 ( U.S. NIH Grant/Contract )
First Posted: November 16, 2021    Key Record Dates
Last Update Posted: November 16, 2021
Last Verified: November 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

After subject enrollment and follow up have been completed, the Data Coordinating Center (DCC) for the study will prepare a final study database for analysis. A releasable database will be produced and completely de-identified in accordance with the definitions provided in the Health Insurance Portability and Accountability Act (HIPAA). Namely, all identifiers specified in HIPAA will be recoded in a manner that will make it impossible to deduce or impute the specific identity of any participant. The database will not contain institutional identifiers.

The DCC will also prepare a data dictionary that provides a concise definition of every data element included in the database. If specific data elements have idiosyncrasies that might affect interpretation or analysis, this will be discussed in the dictionary document. In accordance with policies determined by the investigators and funding sponsors, the releasable database will be provided to users in electronic form.

Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Manish Shah, MD, Baylor College of Medicine:
Child
Emergency Medical Services
Additional relevant MeSH terms:
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Seizures
Neurologic Manifestations
Nervous System Diseases
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