Clinical trial NCT05374824: Comparative Effectiveness of Palliative Surgery Versus Additional Anti-Seizure Medications for Lennox-Gastaut Syndrome
Official title: Comparative Effectiveness of Palliative Surgery Versus Additional Anti-Seizure Medications for Lennox-Gastaut Syndrome - PCORI
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Lennox Gastaut Syndrome
Keywords: epilepsy
seizure
Lead sponsor: Ann & Robert H Lurie Children's Hospital of Chicago
Sponsor class: OTHER
Collaborators: name: Patient-Centered Outcomes Research Institute
name: Nationwide Children's Hospital
name: University of Colorado, Denver
name: University of Michigan
name: University of Pittsburgh
name: Seattle Children's Hospital
name: St. Louis Children's Hospital
name: University of Cincinnati
name: Nemours Children's Health System
name: Stanford University
name: Monroe Carell Jr. Children's Hospital at Vanderbilt
name: University of North Carolina
name: Duke University
name: Indiana University
name: Johns Hopkins University
name: Nicklaus Children's Hospital f/k/a Miami Children's Hospital
First posted: 2022-05-16
Enrollment: 4680
Sex: ALL
Maximum age (years): 26
Standard ages: CHILD
ADULT
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: For Aim 1a, 928 patients up to age 30 years with a chart-review validated diagnosis of Lennox-Gastaut Syndrome between 1/1/2016 and 12/31/2021 will be identified from 7 principal pediatric hospitals. For Aim 1b, a subset of half of those 928 patients (N=464) will be recruited. Analyses for Aim 2 will be based on ≥4000 patients with LGS ICD-10 codes from 18 pediatric hospitals (representing 5 PCORnet CRNs).

Brief summary: Lennox-Gastaut syndrome is a serious and rare form of epilepsy that begins in infancy and early childhood. Seizures and their consequences need medical attention, emergency encounters, and hospitalizations. Seizures disrupt home life for the patient and for family. Lennox-Gastaut syndrome is typically accompanied by disabilities in motor, communication, eating, and other skills needed for daily function.

Lennox-Gastaut syndrome (LGS) has no cure. Although current treatments may help reduce the number of seizures, none are expected to eliminate them entirely; these treatments are palliative. The main treatments include anti-seizure medications and some surgical approaches, including the implantation of a vagus nerve stimulator (a pacemaker-like generator implanted in the chest wall and programmed by a physician to stimulate the vagus nerve in the neck) and corpus callosotomy (cutting through the band of fibers that connect the two sides of the brain). While both types of treatment (medications and surgeries) produce some benefit by reducing how often the seizures occur, both also have some risks. All medications can, in some patients, produce moderate to severe side effects. This is true of anti-seizure medications. Most patients with LGS take several anti-seizure medications at a time. Surgeries can also have associated risks and is additionally stressful for parents and family members. Currently, there is no strong evidence to support parents and physicians in deciding which type of treatment (more medicines or surgery) will be most successful for a child with LGS, and whether one or the other approach may lessen the toll that seizures take on a child's development and ability to function.

This study has two components. It will engage a network of seven pediatric hospitals in the United States where children with Lennox-Gastaut syndrome are cared for and determine whether seizure-related emergency department visits and hospitalizations are more likely to be reduced following the use of additional medications or adding palliative surgery to existing medications. The investigators will determine whether medical versus surgical treatment is more likely to lessen some of the developmental and functional difficulties that affect patients with LGS. The study will also determine whether starting therapies at a younger versus older age makes a difference.

The second component of the study will provide a description of the use of surgical versus medical treatment approaches across 18 pediatric hospitals in the United States (seven plus 11 centers). The investigators will describe how treatments differ across hospitals and over time.

The results from this study will help parents and providers make more informed choices about treatment for children with Lennox-Gastaut syndrome and will highlight areas for improvement in providing the best possible health care for this severe, lifelong disorder.

Detailed description: Background and Significance: Lennox-Gastaut Syndrome (LGS) is a rare developmental-epileptic encephalopathy characterized by life-long refractory seizures which result in frequent utilization of emergency healthcare resources and also contribute to the severe developmental and functional impairment ubiquitously seen in affected patients. Current treatment pathways are the addition of anti-seizure medication treatment or palliative surgical procedures (including neurostimulation), both of which have strong evidence supporting their effectiveness in reducing seizure frequency, but without cures. No evidence exists about the comparative effectiveness of these two pathways. Until such evidence is developed, parents and physicians will continue to struggle with difficult and daunting decisions about whether to add anti-seizure medications or to pursue palliative surgery, and when to do so.

Study Aims: Determine the comparative effectiveness of adding palliative surgery versus adding an LGS-approved medication (Aim 1a) for decreasing utilization of seizure-related emergency health care and (Aim 1b) for limiting the impairment of functional abilities. (Aim 2) Describe the frequency and patterns of utilization of the two therapy pathways at 18 PCORnet sites for variation over time and across sites as well as by patient features - age, medical fragility, race, ethnicity, and insurance type. In addressing these aims, the study will assess and improve PCORnet infrastructure and will enhance methods for future studies of LGS and other rare epilepsies.

Study Description: (Aim 1a) Observational retrospective cohort study of emergency health-care utilization and (Aim 1b) cross sectional study of the impact of treatment pathways on functional outcomes. (Aim 2) Retrospective open cohort study of frequency and patterns (by race, ethnicity, insurance, age) of utilization of the two treatment pathways.

Eligibility criteria: Inclusion Criteria:

Patients with the diagnosis of Lennox Gastaut syndrome with medical records at the seven plus eleven pediatric centers

Exclusion Criteria:

Patients without Lennox Gastaut Syndrome

Primary outcomes:
measure: Seizure-related emergency health care utilization
timeFrame: 2 years
Secondary outcomes:
measure: Parent-reported Clinical Outcome Assessments
timeFrame: 2 years
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Ann Arbor
country: United States
facility: C.S. Mott Children's Hospital
state: Michigan
city: Saint Louis
country: United States
facility: St. Louis Children's Hospital
state: Missouri
city: Columbus
country: United States
facility: Nationwide Children's
state: Ohio
Study officials:
affiliation: Ann and Robert H. Lurie Children's Hospital of Chicago
name: Sandi Lam, MD MBA
role: PRINCIPAL_INVESTIGATOR
References: