Age-Based Seizure Protocol for Pediatric Seizures

(PediDOSE Trial)

Recruiting at 20 trial locations

Overseen By Leonard Basobas, MS

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Stanford University

Disqualifiers: Benzodiazepine allergy, Pregnancy, Growth restriction

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

6700 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method for paramedics to treat seizures in children during ambulance rides. Currently, paramedics calculate doses of midazolam, a medication used to stop seizures, which can cause delays. The study examines whether administering fixed doses based on age, either as an injection or nasal spray, is more effective and safe than the current method. Children experiencing seizures while receiving emergency services in participating cities may qualify to join. The goal is to determine if this new approach helps more children stop seizing before reaching the hospital. As a Phase 3 trial, this treatment is in the final step before FDA approval, offering a chance to contribute to a potentially groundbreaking improvement in emergency seizure care for children.

Will I have to stop taking my current medications?

The trial information does not specify whether participants need to stop taking their current medications.

What prior data suggests that this seizure protocol is safe for children?

Research shows that using a standard method with age-specific doses of midazolam is likely safe for children. Previous studies found that midazolam nasal spray is safe and effective for treating seizures in kids. Some hospitals and clinics already use this method.

Studies also suggest that quicker response times with standard seizure treatments can improve safety and results. Midazolam in forms like nasal spray has proven safe in many cases, helping to stop seizures without major side effects. However, like any medication, risks exist. Excessive midazolam can cause breathing problems, but the standard method aims to prevent this by adjusting the dose based on age.

Overall, current evidence supports that this approach is as safe as, or even safer than, current methods. The study aims to confirm these findings and possibly make treatment more effective and easier to use in emergencies. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the Age-Based Seizure Protocol for pediatric seizures because it offers a new, standardized approach that could lead to better outcomes for young patients. Unlike the conventional protocols used by emergency medical services, which can vary widely, this standardized protocol is designed to be more consistent and specifically tailored to different age groups. This could potentially reduce the time to treatment and improve the accuracy of interventions during critical moments when a child is experiencing a seizure. By streamlining the process, the protocol aims to enhance efficacy and safety, potentially setting a new standard in emergency pediatric seizure care.

What evidence suggests that this age-based seizure protocol is effective for pediatric seizures?

Research has shown that using midazolam in set doses can effectively stop seizures in children. In studies, seizures stopped in about 80% of children who received the correct dose of midazolam. In this trial, participants in the intervention arm will follow a standardized seizure protocol using midazolam, administered either as a shot in the muscle or as a nasal spray. This method often acts faster than intravenous administration, helping to stop seizures sooner and simplifying use for paramedics. The goal is to avoid mistakes and delays in administering the medicine, which often occur with current methods. Overall, evidence suggests that using age-based set doses is both effective and safe for treating seizures in children. ^{2 3 4 6 7}

Who Is on the Research Team?

Manish I Shah, MD, MS

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

The PediDOSE trial is for children actively seizing when paramedics arrive, under their care, and transported by an EMS agency in the study. It excludes kids with known pregnancy, benzodiazepine allergy, or severe growth restriction as judged by the paramedic.

Inclusion Criteria

You were brought to the study location by an ambulance service that is involved in the study.

A paramedic saw you having a seizure, no matter how long it lasted or what type it was.

Currently being treated by a paramedic.

Exclusion Criteria

Known or presumed pregnancy

The paramedic believes that the person's growth is severely restricted.

You have had an allergic reaction to benzodiazepine before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Intervention

Paramedics administer age-based standardized doses of midazolam to treat seizures in children on ambulances

Up to 1 hour

On-scene and during transport

Emergency Department Assessment

Participants are assessed for seizure cessation and other outcomes upon arrival at the emergency department

Up to 24 hours

Emergency department visit

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 hours

What Are the Treatments Tested in This Trial?

Interventions

• Conventional seizure protocol
• Standardized seizure protocol

Trial Overview PediDOSE tests if age-based doses of midazolam given via muscle injection or nasal spray are more effective than current calculation-based methods at stopping seizures before reaching the hospital. The study changes protocols across 20 cities to compare outcomes.

How Is the Trial Designed?

Group I: Intervention Experimental Treatment 1 Intervention

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

Group II: Control Active Control 1 Intervention

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

Conventional seizure protocol is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Midazolam for:

• Seizures
• Anesthesia
• Anxiety disorders

Approved in United States as Midazolam for:

• Seizures
• Anesthesia
• Anxiety disorders

Approved in Canada as Midazolam for:

• Seizures
• Anesthesia
• Anxiety disorders

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Baylor College of Medicine

Collaborator

Trials

1,044

Recruited

6,031,000+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

University of Utah

Collaborator

Trials

1,169

Recruited

1,623,000+

Published Research Related to This Trial

Buccolam(®), a licensed midazolam oromucosal solution, is more cost-effective than both rectal diazepam and unlicensed buccal midazolam for treating prolonged, acute convulsive seizures in children, showing a cost reduction of £2,939 compared to standard care.

The use of Buccolam(®) not only saves costs but also improves quality-adjusted life-years (QALYs) by 0.025 to 0.082, indicating it is a beneficial treatment option for children with epilepsy in the community setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The cost effectiveness of licensed oromucosal midazolam (Buccolam(®)) for the treatment of children experiencing acute epileptic seizures: an approach when trial evidence is limited. Lee, D., Gladwell, D., Batty, AJ., et al.[2021]

In a study of 124 pediatric patients experiencing seizures, those treated with intranasal midazolam using a Mucosal Atomization Device (MAD) had significantly shorter seizure durations (11 minutes) compared to those treated with rectal diazepam (30 minutes).

Patients receiving rectal diazepam were more likely to experience severe outcomes, including ongoing seizures in the emergency department, intubation, and higher rates of hospital admissions, indicating that IN-MAD midazolam is a more effective and safer option for prehospital seizure management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prehospital intranasal midazolam for the treatment of pediatric seizures. Holsti, M., Sill, BL., Firth, SD., et al.[2013]

In a study involving 175 patients with seizure clusters, the nasal spray formulation of midazolam (MDZ-NS) was effective, achieving seizure termination in 55% of episodes after a single dose and 80.2% after a second dose, indicating strong efficacy in an outpatient setting.

The treatment was generally well tolerated, with 40.4% of patients experiencing treatment-emergent adverse events, primarily nasal discomfort and somnolence, but no serious safety concerns like respiratory depression or signs of drug dependence were reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of midazolam nasal spray in the outpatient treatment of patients with seizure clusters: An open-label extension trial. Wheless, JW., Meng, TC., Van Ess, PJ., et al.[2020]

Midazolam nasal spray (MDZ-NS) has been shown to be effective in treating seizure clusters, with a significant success rate in terminating seizures within 10 minutes and maintaining seizure-free status for at least six hours, compared to placebo.

The 5 mg dose of MDZ-NS was found to be as safe as a placebo, indicating that it is a well-tolerated option for patients aged 12 years and older experiencing seizures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Evaluation of the Efficacy and Safety of Midazolam Nasal Spray in Patients With Seizure Clusters: A Systematic Review and Meta-Analysis. Niraj, N., Mahajan, S., Prakash, A., et al.[2023]

In a study of 2,034 pediatric patients, intranasal (IN) midazolam was found to require redosing in 25% of cases, compared to only 14% for intravenous (IV) or intramuscular (IM) routes, indicating that the IN route may be less effective at the standard dose of 0.1 mg/kg.

The results suggest that the current dose for IN midazolam may be too low for effective seizure termination in children, as it was associated with a higher likelihood of needing additional doses compared to other administration methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effectiveness of Intranasal Midazolam for the Treatment of Prehospital Pediatric Seizures: A Non-inferiority Study. Whitfield, D., Bosson, N., Kaji, AH., et al.[2022]

In a study involving 34 children with status epilepticus unresponsive to diazepam, intravenous midazolam showed an impressive seizure cessation rate of 88% after an initial bolus dose, indicating its efficacy as a first-line treatment.

The treatment was generally safe, with only mild adverse events reported, including one case of respiratory depression, suggesting that midazolam can be administered with careful monitoring in pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy, safety, and pharmacokinetics of intravenous midazolam in Japanese children with status epilepticus. Hamano, SI., Sugai, K., Miki, M., et al.[2019]

Nayzilam, an intranasal formulation of midazolam, is FDA-approved for treating intermittent seizures and is user-friendly, allowing non-medical personnel to administer it quickly during a seizure episode.

Studies show that Nayzilam effectively stops seizures faster than the traditional rectal diazepam, making it a safe and revolutionary option for treating acute seizures, especially in children when intravenous access is not available.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Midazolam nasal spray to treat intermittent, stereotypic episodes of frequent seizure activity: pharmacology and clinical role, a comprehensive review. Cornett, EM., Nemomsa, MA., Turbeville, B., et al.[2022]

In a study of 128 children with seizure disorders, a midazolam-based protocol effectively terminated seizures in 67.6% of cases, with 86.3% of those treated successfully responding to one or two doses.

The protocol demonstrated safety, with only a small number of complications, including a few cases requiring advanced airway management, indicating it can be a reliable option for managing impending status epilepticus in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality assurance evaluation of a simple linear protocol for the treatment of impending status epilepticus in a pediatric emergency department 2 years postimplementation. Tourigny-Ruel, G., Diksic, D., Mok, E., et al.[2019]

Midazolam, when delivered through the buccal mucosa, has been shown to be an effective and safe treatment for prolonged seizures and status epilepticus in children, addressing the challenges of intravenous access.

A new formulation of buccal midazolam has been licensed for use in Europe, highlighting its acceptability to both children and caregivers in emergency situations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Buccal midazolam for pediatric convulsive seizures: efficacy, safety, and patient acceptability. Anderson, M.[2021]

Three approved rescue therapies for treating seizure clusters in the U.S. are diazepam rectal gel, midazolam nasal spray, and diazepam nasal spray, with diazepam rectal gel being effective but potentially socially uncomfortable for adults and adolescents.

Midazolam and diazepam nasal sprays offer a rapid and socially acceptable alternative to rectal administration, allowing for easier self-administration during seizure clusters.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rescue Treatments for Seizure Clusters. Kotloski, RJ., Gidal, BE.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12034653/

Midazolam infusions for therapeutic management of pediatric ... In 15 studies, seizures cessed in 321/399 (80%) children at mean effective doses of 2.0–5.0 μg/kg/min (13, 24–27, 29–32, 34–36, 38, 39, 41, 42).

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05121324

NCT05121324 | Pediatric Dose Optimization for Seizures ... The investigators believe that a standardized seizure protocol with age-based doses is more effective than current practice. Another aim of PediDOSE is to ...

3. annemergmed.com annemergmed.com/article/S0196-0644(22)00363-8/fulltext

Real-World Midazolam Use and Outcomes With Out-of- ... Our findings suggest that the intranasal administration of midazolam is less effective and the intravenous administration of midazolam more ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1059131125002080

Effectiveness and safety of midazolam versus lorazepam ... Primary outcomes included treatment success and failure rates, time to seizure cessation from drug administration, and safety outcomes (respiratory depression ...

5. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1111/epi.17940

Association of midazolam route of administration and need ... Another study among 150 children with active seizures in the ED, however, reported that a higher proportion of children given IM midazolam (61%) ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8006203/

A Standardized Protocol to Improve Acute Seizure ... Responses to acute seizures were faster, and nursing confidence increased. CONCLUSIONS: A collaborative quality improvement effort between physicians and nurses ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9560890/

Midazolam nasal spray to treat intermittent, stereotypic ... Nayzilam has been proven to be safe and effective for acute seizures in children, deeming it a revolutionary alternative in times where ...