Age-Based Seizure Protocol for Pediatric Seizures (PediDOSE Trial)
Palo Alto (17 mi)Overseen byManish I Shah, MD, MS
Age: < 18
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: Stanford University
No Placebo Group
Pivotal Trial (Near Approval)
Prior Safety Data
Trial Summary
What is the purpose of this trial?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.
Do I have to stop my current medications for this trial?The protocol does not specify if you need to stop your current medications. However, the trial focuses on optimizing midazolam dosing during seizures, so it might not require changes to your regular medications.
Is the drug used in the Age-Based Seizure Protocol for Pediatric Seizures a promising treatment?Yes, the drug, which includes midazolam, is promising because it is easy to use, works quickly to stop seizures, and can be given by non-medical people, making it very accessible and effective for treating seizures in children.13458
What safety data exists for the treatment of pediatric seizures using midazolam?Several studies have evaluated the safety of midazolam for treating pediatric seizures. A simple linear midazolam-based protocol has been shown to be safe for managing impending status epilepticus in children. The intranasal formulation, Nayzilam, is FDA-approved and has been proven safe and effective for acute seizures in children, offering a user-friendly alternative to intravenous administration. A systematic review and meta-analysis found that midazolam nasal spray is as safe as a placebo and effective in treating seizure clusters. Buccal midazolam has also been demonstrated to be safe and acceptable for pediatric convulsive seizures, providing a viable alternative when intravenous access is challenging.246810
What data supports the idea that Age-Based Seizure Protocol for Pediatric Seizures is an effective drug?The available research shows that the Age-Based Seizure Protocol, which includes midazolam, is effective for treating pediatric seizures. One study highlights that an intranasal form of midazolam, Nayzilam, is easy to use and quickly stops seizures, making it a good alternative to rectal diazepam, which has been the standard treatment. Another study found that buccal midazolam is effective, safe, and well-accepted by children and their caregivers. However, a study on intranasal midazolam in prehospital settings noted that it required more frequent redosing compared to other methods, suggesting the dose might be too low. Overall, midazolam is shown to be effective, but the method of delivery and dosage are important factors to consider.24789
Eligibility Criteria
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.Treatment Details
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.
2Treatment groups
Experimental Treatment
Active Control
Group I: InterventionExperimental Treatment1 Intervention
This arm will be exposed to the study intervention: a standardized seizure protocol.
Group II: ControlActive Control1 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, Australia 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
🇦🇺 Approved in Australia as Midazolam for:
- Seizures
- Anesthesia
- Anxiety disorders
Find a clinic near you
Research locations nearbySelect from list below to view details:
University of WashingtonSeattle, WA
Cincinnati Children's Hospital Medical CenterCincinnati, OH
University of Texas SouthwesternDallas, TX
University of UtahSalt Lake City, UT
More Trial Locations
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Who is running the clinical trial?
Stanford UniversityLead Sponsor
Baylor College of MedicineCollaborator
National Institute of Neurological Disorders and Stroke (NINDS)Collaborator
University of UtahCollaborator
References
Prehospital intranasal midazolam for the treatment of pediatric seizures. [2013]The local emergency medical services (EMS) council implemented a new pediatric treatment protocol using a Mucosal Atomization Device (MAD) to deliver intranasal (IN) midazolam for seizure activity.
Buccal midazolam for pediatric convulsive seizures: efficacy, safety, and patient acceptability. [2021]Prolonged seizures and status epilepticus are a common acute neurological presentation in pediatric practice. As a result, there is a need for effective and safe medications that can be delivered to convulsing children to effect rapid seizure termination both in hospital and community settings. The challenges of achieving intravenous access, particularly in young children, mandate alternative routes of administration for these drugs. Over the last ten years, midazolam delivered via the buccal mucosa has been demonstrated to be efficacious, safe, and acceptable to children and their caregivers, and a formulation has recently been licensed for use in Europe. The aim of this article is to review the clinical pharmacology with respect to these issues.
The cost effectiveness of licensed oromucosal midazolam (Buccolam(®)) for the treatment of children experiencing acute epileptic seizures: an approach when trial evidence is limited. [2021]In the UK, two treatment options are used for acute epileptic seizures in the community-rectal diazepam and unlicensed buccal midazolam. In practice, the former is rarely used, with unlicensed buccal midazolam being widely recommended and prescribed by physicians. In September 2011, Buccolam(®) (licensed midazolam oromucosal solution) became the first medicine to receive a Paediatric-Use Marketing Authorization (PUMA) and it is indicated for the treatment of prolonged, acute, convulsive seizures by caregivers in the community for children (aged 6 months to
Quality assurance evaluation of a simple linear protocol for the treatment of impending status epilepticus in a pediatric emergency department 2 years postimplementation. [2019]To evaluate the efficacy and safety of a simple linear midazolam-based protocol for the management of impending status epilepticus in children up to 18 years of age.
Efficacy, safety, and pharmacokinetics of intravenous midazolam in Japanese children with status epilepticus. [2019]No dosing regimen has been established for the initial treatment of pediatric status epilepticus with intravenous midazolam. We therefore evaluated the efficacy, safety, and pharmacokinetics of bolus and continuous midazolam infusion.
Safety and efficacy of midazolam nasal spray in the outpatient treatment of patients with seizure clusters: An open-label extension trial. [2020]To evaluate safety- and seizure-related outcomes with repeated intermittent use of a novel formulation of midazolam administered as a single-dose nasal spray (MDZ-NS) in the outpatient treatment of patients experiencing seizure clusters (SCs).
The Effectiveness of Intranasal Midazolam for the Treatment of Prehospital Pediatric Seizures: A Non-inferiority Study. [2022]Background: Intranasal (IN) midazolam allows for rapid, painless treatment of pediatric seizures in the prehospital setting and may be a preferred administration route if determined to be non-inferior to intravenous (IV) or intramuscular (IM) routes. We sought to evaluate the effectiveness of IN midazolam for terminating prehospital pediatric seizures compared to midazolam administered by alternate routes. Methods: We performed a retrospective, non-inferiority analysis using data from a regional Emergency Medical Services (EMS) database. We included pediatric patients ≤ 14 years treated with midazolam (0.1 mg/kg) by EMS for non-traumatic seizures. The primary outcome was the proportion of patients requiring redosing of midazolam after initial treatment with IN midazolam compared to those that received IV or IM midazolam. We established a priori a risk difference of 6.5% as the non-inferiority margin. Results: We evaluated outcomes from 2,034 patients (median age 6 years [interquartile range 3 - 10 years], 55% male). Initial administration routes were 461 (23%) IN, 547 (27%) IM, 1024 (50%) IV, and 2 (0.1%) intraosseous (IO). Midazolam redosing occurred in 116 patients (25%) who received IN midazolam versus 222 patients (14%) treated initially with midazolam via alternate routes (risk difference 11% [95%CI 7 - 15%]). The age-adjusted odds ratio for redosing midazolam after intranasal administration compared to alternate route administration was 2.0 (95% CI 1.6 - 2.6). Conclusion: Prehospital treatment of pediatric seizure with intranasal midazolam was associated with increased frequency of redosing compared to midazolam administered by other routes, suggesting that 0.1 mg/kg is a subtherapeutic dose for intranasal midazolam administration.
Midazolam nasal spray to treat intermittent, stereotypic episodes of frequent seizure activity: pharmacology and clinical role, a comprehensive review. [2022]An intranasal formulation of midazolam, Nayzilam, has been FDA-approved to treat intermittent, stereotypic episodes of frequent seizure activity. Nayzilam is easy to administer and can quickly treat seizures that occur outside of the hospital. The intra-nasal route of administration allows non-medical personal to administer the drug which makes it more accessible and user-friendly in the event of a seizure. Many studies have indicated quick cessation of seizures with Nayzilam compared to rectal diazepam, which has been the standard of care treatment. Nayzilam has been proven to be safe and effective for acute seizures in children, deeming it a revolutionary alternative in times where intravenous administration is not possible.
Rescue Treatments for Seizure Clusters. [2022]Treatment of seizure clusters endeavors to prevent additional seizures and avoid progression to conditions such as prolonged seizures and status epilepticus. Rescue therapies are key components of seizure action plans (SAPs) for individuals with seizure clusters. Three rescue therapies are approved in the United States for the treatment of seizure clusters: diazepam rectal gel, midazolam nasal spray, and diazepam nasal spray. Diazepam rectal gel is an effective rescue therapy for seizure clusters, though adults and adolescents may have social reservations regarding its administration. Intranasal delivery of midazolam or diazepam is a promising alternative to rectal administration because these formulations offer easy, socially acceptable administration exhibit a rapid onset, and allow for the possibility of self-administration. Off-label benzodiazepines, such as orally disintegrating lorazepam and intranasal use of an intravenous (IV) formulation of midazolam via nasal atomizer, are less well characterized regarding bioavailability and tolerability compared with approved agents.
The Evaluation of the Efficacy and Safety of Midazolam Nasal Spray in Patients With Seizure Clusters: A Systematic Review and Meta-Analysis. [2023]Midazolam nasal spray (MDZ-NS) is a new emerging rescue medication that suppresses epileptic seizures. Until now, few studies, pharmacokinetic (PK) and pharmacodynamic (PD) profiles, and clinical trials have shown that midazolam nasal spray could become an effective and promising alternative to conventional routes (intravenous {IV}/rectal). Therefore, we thought of conducting a systematic review and meta-analysis of midazolam (MDZ) to assess its potential outcomes. The analysis was also evaluated based on the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of midazolam nasal spray. A systematic literature search was carried out through various databases to identify studies of accounted outcomes of midazolam nasal spray (MDZ-NS). Randomized and other studies of patients (12 years or older) with seizure clusters (SCs) were included. A total of three full-text articles were considered for systematic review and meta-analysis as per the inclusion and exclusion criteria. The 5 mg MDZ-NS was observed to be equally safe as a placebo, and the risk ratio (RR) was 1.01 (95% confidence interval (CI): 0.67-1.53). After the administration of MDZ-NS, either the patients remained seizure-free for six hours or more or the seizure was terminated within 10 minutes and had no recurrence between 10 minutes and six hours. The risk ratio (RR) obtained was 1.54 (95% CI: 1.25-1.91). The result was statistically significant as a higher success rate was observed with the use of 5 mg midazolam nasal spray compared to placebo (p < 0.0001). Heterogeneity was not observed in the results of the included studies (inconsistency index {I2}: 0%). The present systematic review and meta-analysis demonstrated that 5 mg midazolam nasal spray was efficacious in treating patients with seizure clusters and is well-tolerated. Also, its use is relatively safe.