Improving Status Epilepticus Treatment Times (QuITT-SE)

Quality Improvement in Time to Treatment of Status Epilepticus

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.

Study Overview

• Status: Recruiting
• Conditions: Status Epilepticus
• Intervention / Treatment: Other: Quality improvement bundle; Other: Quality improvement bundle and local PDSA cycles with central support; Other: Quality improvement bundle and local PDSA cycles without central support

Detailed Description

The overall study design is a stepped-wedge cluster randomized trial. A stepped-wedge is a unidirectional crossover design in which clusters switch treatments at different time points, enabling statistically rigorous assessment of interventions while reducing ethical and resource limitations for quality improvement studies.[1] Seven centers will be randomly assigned to implement the QI bundle at staggered 1-month intervals after a baseline period. Only the timing of the dissemination visit will be randomized; all sites will receive the same materials and perform the same activities (e.g. focus group, process map development, simulations).

This study is an effectiveness-implementation hybrid study. The effectiveness-implementation hybrid design is ideal for assessing both clinical interventions and implementation.17 Importantly, our interventions have strong face-validity, are evidence-based, low-risk and low-cost. For instance, the price to change BZD formulations is nominal (~$1 per dose), and other QI bundle interventions are primarily focused on frontline staff process changes. While testing the effect of the QI bundle on time to BZD treatment, we will utilize this framework and mixed methods analysis to measure implementation and identify barriers and facilitators. Thus, this proposal is of high-value, as it will provide randomized multicenter efficacy data while providing understanding for broad implementation following study end.

For the effectiveness component, we will utilize a stepped-wedge cluster randomized design. Based on our preliminary data, the intraclass correlation coefficient is estimated around 0.5, an overall sample size of 60 episodes will be adequate to achieve powers greater than 90%. A potential pitfall of the stepped wedge design is the potential confounding effects of temporal trends. We will mitigate this by tracking data at the primary site, which will be in the sustain phase throughout the study entirety. We reduce temporal effects of site enrollment (e.g., staffing changes, temporal trends in hospital admissions) by enrolling sites at different times throughout the calendar year.

The implementation component was designed utilizing the Practical, Robust Implementation and Sustainability Model (PRISM).[2] PRISM provides a scientifically rigorous and structured approach to implementation strategy development through domains focusing on (1) program, (2) external environment, (3) implementation and sustainability infrastructure and (4) recipients.[2] These elements are addressed as follows:

Program. Organizational readiness across the study sites will be critical for success. Our proposal is based on evidence derived from a successful single-center study. The QI bundle is low-cost and all interventions are currently FDA-approved. Our innovative de-implementation of time-consuming, low-value workflows (e.g. IV medication administration) will decrease care complexity in the initial stages of SE treatment. The QI bundle components are trialable, adaptable and reversible. Treatment results are immediately observable by stakeholders through individual outcomes (SE cessation) and shared measure and feedback data reports. We highlight improved outcomes and safety as organizational, caregiver, and patient priorities to achieve broad buy-in.

External Environment. Regulatory and professional organization priorities support our area of study and primary efficacy outcomes. Rapid treatment of SE has been identified as a quality measure by the AAN11, and guidelines for such care have been published by the AES.[3] Additionally, our study proposal further aligns with NAEC, which mandates a focus on rapid treatment of SE through pathway requirements across 260 hospitals. Data from our proposal will serve as a framework for accomplishing the goal of rapid SE treatment, which is inconsistently met at present.[4]

Implementation and sustainability infrastructure. Our infrastructure will utilize proven features associated with successful implementation projects.[5,6] Co-investigators experienced in working within pSERG will provide a bridge to the local QI and clinical teams, engaging stakeholders at all 3 organizational levels (frontline staff, mid-level management and senior administration). Measure and feedback will be emphasized through control chart data and implementation reports. Furthermore, the adaptable protocol allows for site-specific implementation strategies for the QI bundle as well as iterative PDSA development in the Sustain and Independent phases in order to address local drivers.

Recipients. Positive organizational characteristics are supported by LOS from senior hospital administrators and nurse managers. Furthermore, the co-investigators have previously collaborated with pSERG from their respective centers. Each site has access to data through Export, Transform, Load (ETL) data queries and EHR. The diverse demographics of patients is aided through intentional site selection and inclusion of nearly all ages of children. Importantly, our proposed interventions of performing basic seizure first aid and using non-IV forms of BZD aligns with those of patients and families in the ambulatory setting.[7]

• Study Type: Interventional
• Enrollment (Estimated): 450
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Adam Ostendorf, MD; Phone Number: 614-722-5145; Email: adam.ostendorf@nationwidechildrens.org

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43205
      • Recruiting
      • Nationwide Children's Hospital
      • Contact: Adam P Ostendorf, MD; Phone Number: 614-722-5145; Email: adam.ostendorf@nationwidechildrens.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• SE episode occurs in a male or female child aged between > 30 days to < 19 years

• Seizures meeting AT LEAST ONE of the following criteria:

  1. continuous clinically apparent seizure lasting greater than 5 minutes
  2. continuous clinically apparent seizure of any duration receiving BZD
  3. repeated seizures without return to neurological baseline within 5 minutes

Exclusion Criteria:

• SE episode occurs in a child with infantile spasms
• SE episode occurs in a child with electrographic-only seizures without clinical signs other than encephalopathy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Baseline phase; During this arm, sites will provide routine care.
Experimental: Adoption phase; Following the dissemination visit, sites will actively work to implement the bundle of interventions.	Other: Quality improvement bundle; (1) standardizing BZD default to intranasal or buccal midazolam; (2) targeting initial BZD treatment within 10 minutes of seizure onset; (3) relocating and bundling all administration items needed to the hospital unit medication room; (4) utilizing basic seizure first aid in the initial patient assessment; (5) developing and implementing SE-specific EHR documentation; (6) multidisciplinary QI teams
Experimental: Sustain phase; 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.	Other: Quality improvement bundle and local PDSA cycles with central support; Sites will implement both the standard QI bundle as well as site-specific PDSA cycles with central data and methods support.
Experimental: Independent phase; 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.	Other: Quality improvement bundle and local PDSA cycles without central support; Sites will implement both the standard QI bundle as well as site-specific PDSA cycles without central data or methods support.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time from the SE diagnosis to first dose of BZD	Time in minutes from SE diagnosis to treatment with the first dose of a benzodiazepine (BZD) as measured during hospitalization, which will decrease chances of morbidity and mortality	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cost of hospitalization	Cost of hospitalization will be calculated as follows: cost per SE type x LOS	30 days
ICU transfer rate	Percent of SE episodes resulting in transfer to the ICU within 6 hours of the episode as well as at any point during the admission.	30 days
Change in PCPC score	Change in PCPC score from admission to discharge	30 days

Collaborators and Investigators

• Sponsor: Nationwide Children's Hospital
• Collaborators: Children's Hospital of Philadelphia; Boston Children's Hospital; Emory University; Seattle Children's Hospital; Children's National Research Institute; Children's Hospital and Health System Foundation, Wisconsin; Phoenix Children's Hospital; UVA Children's Hospital
• Investigators: Principal Investigator: Adam Ostendorf, MD, Nationwide Children's Hospital and The Ohio State University

Publications and helpful links

General Publications

• Hussey MA, Hughes JP. Design and analysis of stepped wedge cluster randomized trials. Contemp Clin Trials. 2007 Feb;28(2):182-91. doi: 10.1016/j.cct.2006.05.007. Epub 2006 Jul 7.
• Solberg LI, Brekke ML, Fazio CJ, Fowles J, Jacobsen DN, Kottke TE, Mosser G, O'Connor PJ, Ohnsorg KA, Rolnick SJ. Lessons from experienced guideline implementers: attend to many factors and use multiple strategies. Jt Comm J Qual Improv. 2000 Apr;26(4):171-88. doi: 10.1016/s1070-3241(00)26013-6.
• Feldstein AC, Glasgow RE. A practical, robust implementation and sustainability model (PRISM) for integrating research findings into practice. Jt Comm J Qual Patient Saf. 2008 Apr;34(4):228-43. doi: 10.1016/s1553-7250(08)34030-6.
• Bradley EH, Holmboe ES, Mattera JA, Roumanis SA, Radford MJ, Krumholz HM. A qualitative study of increasing beta-blocker use after myocardial infarction: Why do some hospitals succeed? JAMA. 2001 May 23-30;285(20):2604-11. doi: 10.1001/jama.285.20.2604.
• O'Hara KA. First aid for seizures: the importance of education and appropriate response. J Child Neurol. 2007 May;22(5 Suppl):30S-7S. doi: 10.1177/0883073807303066.
• Ostendorf AP, Loddenkemper T, Morgan LA, Appavu B, Farias-Moeller R, Harrar D, Press C, Abend NS, Gaillard WD, Bai S, Eisner M, McHenry L, Kroshus E, Vannatta K, Goodkin HP. Treating seizures faster: The Quality Improvement in Time to Treat Status Epilepticus (QuITT-SE) multicenter randomized stepped wedge clinical trial protocol. Contemp Clin Trials. 2025 Apr;151:107831. doi: 10.1016/j.cct.2025.107831. Epub 2025 Feb 8.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2024
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): March 31, 2027

Study Registration Dates

• First Submitted: December 22, 2023
• First Submitted That Met QC Criteria: December 22, 2023
• First Posted (Actual): January 8, 2024

Study Record Updates

• Last Update Posted (Actual): April 1, 2026
• Last Update Submitted That Met QC Criteria: March 27, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Status Epilepticus; Quality Improvement; Interventions
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Seizures; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Status Epilepticus
• Other Study ID Numbers: STUDY00003386

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No