Quality Improvement Bundle for Epileptic Seizures

(QuITT-SE Trial)

Overseen By Adam Ostendorf, MD

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: Nationwide Children's Hospital

Must be taking: Benzodiazepines

Disqualifiers: Infantile spasms, Electrographic-only seizures

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

Compensation: Varies

Number of Visits: Unknown

450 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a stepped-wedge cluster randomized effectiveness-implementation hybrid study aimed at determining the effect of dissemination of a QI bundle on the time to treatment of SE among hospitalized, non-critically ill children. The primary study endpoint is to decrease the time from the SE diagnosis to treatment with the first dose of a benzodiazepine (BZD) as measured during hospitalization, which will decrease chances of morbidity and mortality.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug Ativan for treating epileptic seizures?

Research shows that Ativan (lorazepam) is effective in controlling status epilepticus, a severe form of epileptic seizure, in most patients. It has been found to control seizures longer than diazepam, another common treatment, with minimal side effects. ^{1 2 3 4 5}

Is the Quality Improvement Bundle for Epileptic Seizures safe for humans?

The safety of treatments like Ativan (lorazepam) and diazepam nasal spray, which are used for seizures, has been studied. These treatments are generally considered safe, but they can have side effects, and their safety has been evaluated in various studies, including those involving children and adolescents. ^{1 6 7 8 9}

How does the Quality Improvement Bundle for Epileptic Seizures differ from other treatments?

The Quality Improvement Bundle for Epileptic Seizures is unique because it combines a structured approach to improving care with local Plan-Do-Study-Act (PDSA) cycles, which are iterative processes for testing changes in real-world settings, and may include central support to enhance implementation. This approach focuses on quality improvement rather than just medication, making it different from standard drug treatments like benzodiazepines, which are typically used for immediate seizure control. ^{1 8 10 11 12}

Research Team

Adam Ostendorf, MD

Principal Investigator

Nationwide Children's Hospital and The Ohio State University

Eligibility Criteria

This trial is for hospitalized, non-critically ill children diagnosed with status epilepticus (SE). It aims to improve the time it takes to treat SE by using a quality improvement bundle. The main goal is to reduce the time from diagnosis to first benzodiazepine dose.

Inclusion Criteria

I have had long or repeated seizures without normal recovery.

Exclusion Criteria

My child has had spasms as a baby.

My child has seizures that show only on EEG, with no other symptoms except brain dysfunction.

Timeline

Baseline

Sites provide routine care before implementing the QI bundle

1 month

Adoption

Following the dissemination visit, sites actively work to implement the bundle of interventions

1 month

Sustain

Sites actively work to sustain the implemented interventions and develop site-specific plan-do-study-act cycles

Duration not specified

Independent

Sites continue to sustain the implemented interventions and develop site-specific plan-do-study-act cycles without central support

Duration not specified

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Quality improvement bundle
• Quality improvement bundle and local PDSA cycles with central support
• Quality improvement bundle and local PDSA cycles without central support

Trial Overview The study tests how well different strategies help in treating SE quickly. Hospitals will use a quality improvement bundle alone or combined with local Plan-Do-Study-Act (PDSA) cycles, either with or without central support, and compare treatment times.

Participant Groups

Group I: Sustain phase Experimental Treatment 1 Intervention

During this arm, sites will actively work to sustain the implemented interventions and will be allowed to develop site-specific plan-do-study-act cycles in order to address site-specific key drivers with central data and methodological support.

Group II: Independent phase Experimental Treatment 1 Intervention

During this arm, sites will continue to sustain the implemented interventions and develop site-specific plan-do-study-act cycles in order to address site-specific key drivers without central data and methodological support.

Group III: Adoption phase Experimental Treatment 1 Intervention

Following the dissemination visit, sites will actively work to implement the bundle of interventions.

Group IV: Baseline phase Active Control 1 Intervention

During this arm, sites will provide routine care.

Quality improvement bundle is already approved in United States, European Union for the following indications:

Approved in United States as Ativan for:

• Status epilepticus

Approved in European Union as Ativan for:

• Status epilepticus

Who Is Running the Clinical Trial?

Nationwide Children's Hospital

Lead Sponsor

Trials

354

Recruited

5,228,000+

Children's Hospital of Philadelphia

Collaborator

Trials

749

Recruited

11,400,000+

Boston Children's Hospital

Collaborator

Trials

801

Recruited

5,584,000+

Emory University

Collaborator

Trials

1,735

Recruited

2,605,000+

Children's National Research Institute

Collaborator

Trials

227

Recruited

258,000+

Seattle Children's Hospital

Collaborator

Trials

319

Recruited

5,232,000+

Children's Hospital and Health System Foundation, Wisconsin

Collaborator

Trials

56

Recruited

93,300+

UVA Children's Hospital

Collaborator

Trials

2

Recruited

610+

Phoenix Children's Hospital

Collaborator

Trials

78

Recruited

5,014,000+

UVA Children's Hospital

Collaborator

Trials

2

Recruited

610+

Findings from Research

In a study involving 175 patients with seizure clusters, diazepam nasal spray demonstrated a favorable safety profile, with low rates of treatment-emergent adverse events (15.2%) after a second dose.

Only 48.5% of patients required a second dose within 24 hours, indicating that the initial dose of diazepam nasal spray was effective in managing seizures for most patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of second doses of Valtoco® (diazepam nasal spray) across 24 hours after the initial dose for out-of-hospital seizure clusters: Results from a phase 3, open-label, repeat-dose safety study. Sperling, MR., Wheless, JW., Hogan, RE., et al.[2022]

In patients with high-grade glioma, seizures are common during the end-of-life phase, and traditional oral anti-epileptic drugs may become ineffective due to swallowing difficulties.

The proposed treatment includes buccal clonazepam for maintenance and intranasal midazolam for acute seizure management, which can help improve the quality of life for these patients during their final stages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Gliomas: fighting until the end against epilepsy; administration of antiepileptic drugs in the end-of-life phase]. Koekkoek, JA., Boddaert, MS., Taphoorn, M.[2018]

Long-acting rescue therapies, such as diazepam and midazolam, are crucial for managing seizure clusters in people with epilepsy, especially since these clusters can lead to medical emergencies if untreated.

The analysis of three studies showed that the need for a second dose of rescue therapy was significant, with less than 40% of clusters controlled at 6 hours and less than 13% at 24 hours, highlighting the potential for second doses to reduce hospitalizations and improve health-care utilization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Implications of Seizure-Cluster Treatment on Healthcare Utilization: Use of Approved Rescue Medications. Rabinowicz, AL., Faught, E., Cook, DF., et al.[2022]

In a study of 25 patients with status epilepticus, intravenous lorazepam effectively controlled seizures in 22 patients, demonstrating its efficacy as an anticonvulsant with minimal respiratory and circulatory side effects.

Lorazepam provided longer seizure control compared to diazepam, with most patients achieving effective plasma drug levels between 30 and 100 ng/mL, and only one case of transient respiratory arrest reported, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lorazepam in status epilepticus. Walker, JE., Homan, RW., Vasko, MR., et al.[2013]

Status epilepticus is a critical medical emergency that requires prompt treatment to prevent serious complications, with benzodiazepines being the first-line therapy for out-of-hospital management.

For refractory cases, where seizures persist despite standard treatments, additional interventions such as surgical options and advanced pharmacological therapies are necessary, highlighting the importance of timely and effective management strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of status epilepticus. Misra, S., Singh, NN.[2007]

Resuming home antiseizure drugs (ASDs) alone after ictal SPECT injection is equally effective for localizing seizure onset zones compared to adding scheduled intravenous lorazepam, based on a study of 22 patients with temporal and extratemporal epilepsy.

The group that received lorazepam reported significantly higher rates of dizziness and sedation, indicating that avoiding lorazepam may lead to fewer treatment-emergent adverse events and lower costs without compromising localization efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Injection of prophylactic lorazepam versus antiseizure drugs on the localization value of ictal SPECT studies and treatment-emergent adverse events: A single-center prospective study. Rao, CK., Tatum, WO., Brinkmann, BH., et al.[2021]

The implementation of a Medical Control Guideline (MCG) with a standardized formulary significantly reduced pediatric midazolam dosing errors from 18.5% to 14.1% in a large EMS system, indicating improved safety in emergency treatment for seizures.

Paramedics reported decreased anxiety and increased confidence in administering midazolam after the formulary was introduced, suggesting that standardized protocols can enhance provider performance and patient care in high-pressure situations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Standardized Formulary to Reduce Pediatric Medication Dosing Errors: A Mixed Methods Study. Bosson, N., Kaji, AH., Gausche-Hill, M.[2022]

In a study of 163 pediatric patients aged 6 to 17 years, diazepam nasal spray (Valtoco) was found to have a consistent safety profile, with no serious treatment-related adverse events reported, indicating it is a safe option for managing seizure clusters.

The majority of patients (88%) reported satisfaction with the treatment, and the dosing guidelines based on age and weight were supported by the findings, with similar rates of treatment-emergent adverse events across different age subgroups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Diazepam Nasal Spray in Children and Adolescents With Epilepsy: Results From a Long-Term Phase 3 Safety Study. Tarquinio, D., Dlugos, D., Wheless, JW., et al.[2022]

A retrospective study of 1516 children with seizure activity showed that reducing the diazepam dose from 0.2-0.5 mg/kg to 0.05-0.1 mg/kg significantly decreased the intubation rate from 19 cases in the higher dose group to just 1 case in the lower dose group, indicating improved safety with the lower dose.

The lower diazepam dose was effective in terminating seizures without increasing adverse events, and it also resulted in a lower hospital admission rate, suggesting that the new protocol is both effective and safer for children experiencing seizures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The short-term outcome of seizure management by prehospital personnel: a comparison of two protocols. Galustyan, SG., Walsh-Kelly, CM., Szewczuga, D., et al.[2019]

Benzodiazepines are the first-line treatment for acute repetitive seizures and status epilepticus due to their rapid onset and effectiveness, helping to reduce emergency department visits when administered timely.

The new intravenous formulation of valproate offers a valuable option for children experiencing breakthrough seizures from low oral valproate levels, ensuring they receive necessary treatment even when oral administration is not feasible.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Additional modalities for treating acute seizures in children: overview. Bebin, EM.[2017]

In a 12-month safety study involving 72 adults with seizure clusters, treatment with diazepam nasal spray (Valtoco®) led to stable or improved quality of life scores, particularly in areas related to Seizure Worry and Social Functioning.

The results indicate that patients with refractory epilepsy experienced meaningful improvements in their quality of life while using diazepam nasal spray, suggesting that intermittent rescue therapy may enhance patient functioning and warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality-of-life results in adults with epilepsy using diazepam nasal spray for seizure clusters from a long-term, open-label safety study. Cramer, JA., Faught, E., Davis, C., et al.[2022]

In a study of 120 children aged 6 months to 14 years, all three benzodiazepines (Lorazepam, Midazolam, and Diazepam) were found to be equally effective in stopping seizures, with no significant differences in the time to seizure cessation.

However, Diazepam was associated with a higher rate of complications, requiring more patients to receive a second dose for seizure control and causing more excessive somnolence compared to Lorazepam and Midazolam.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous diazepam, midazolam and lorazepam in acute seizure control. Gathwala, G., Goel, M., Singh, J., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Use of second doses of Valtoco® (diazepam nasal spray) across 24 hours after the initial dose for out-of-hospital seizure clusters: Results from a phase 3, open-label, repeat-dose safety study. [2022]

2. Netherlands pubmed.ncbi.nlm.nih.gov

[Gliomas: fighting until the end against epilepsy; administration of antiepileptic drugs in the end-of-life phase]. [2018]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Implications of Seizure-Cluster Treatment on Healthcare Utilization: Use of Approved Rescue Medications. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Lorazepam in status epilepticus. [2013]

5. India pubmed.ncbi.nlm.nih.gov

Management of status epilepticus. [2007]

6. United States pubmed.ncbi.nlm.nih.gov

Injection of prophylactic lorazepam versus antiseizure drugs on the localization value of ictal SPECT studies and treatment-emergent adverse events: A single-center prospective study. [2021]

7. England pubmed.ncbi.nlm.nih.gov

A Standardized Formulary to Reduce Pediatric Medication Dosing Errors: A Mixed Methods Study. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Safety of Diazepam Nasal Spray in Children and Adolescents With Epilepsy: Results From a Long-Term Phase 3 Safety Study. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

The short-term outcome of seizure management by prehospital personnel: a comparison of two protocols. [2019]

10. United States pubmed.ncbi.nlm.nih.gov

Additional modalities for treating acute seizures in children: overview. [2017]

11. United States pubmed.ncbi.nlm.nih.gov

Quality-of-life results in adults with epilepsy using diazepam nasal spray for seizure clusters from a long-term, open-label safety study. [2022]

12. India pubmed.ncbi.nlm.nih.gov

Intravenous diazepam, midazolam and lorazepam in acute seizure control. [2021]