Clinical trial NCT01027715: The Impact of Electroencephalographic (EEG) Seizure Treatment in Neonatal Encephalopathy
Official title: The Impact of Electroencephalographic (EEG) Seizure Treatment in Near Term ≥ 36 Weeks Gestation and Term Infants With Neonatal Encephalopathy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Seizures
Encephalopathy
Keywords: Neonatal Seizures
Neonatal encephalopathy
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
First posted: 2009-12-09
Enrollment: 69
Sex: ALL
Minimum age (years): 1
Maximum age (years): 72
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a prospective, randomized, single-center pilot trial of term and near term (≥ 36 weeks gestation) infants with encephalopathy or seizures comparing a "EEG Seizure Treatment Group" or ESG with a "Clinical Seizure Treatment Group" or CSG.

The investigators hypothesize that the accurate detection and treatment of EEG seizures will decrease the seizure burden and improve outcomes in newborn infants with seizures and/or hypoxic-ischemic encephalopathy (HIE).

Detailed description: This is a prospective, randomized, pilot trial of term and near term (≥ 36 weeks gestation) infants with encephalopathy or seizures comparing a "EEG Seizure Treatment Group" or ESG with a "Clinical Seizure Treatment Group" or CSG. Eligibility is based on clinical criteria for moderate/severe encephalopathy or seizures. We will recruit near term or term infants (≥ 36 weeks gestation) with a diagnosis of seizures or encephalopathy admitted to the neonatal intensive care unit (NICU) at St. Louis Children's Hospital within the first 72 hours of life. Infants will be randomized into an EEG Seizure Treatment Group (ESG) or a Clinical Seizure Treatment Group (CSG) (n=20 in each group). Patients in both groups will have EEG monitoring. While treating physicians will have access to EEG data in the ESG, no EEG data in the CSG will be available to the clinician for treatment of seizures. AED treatment will be initiated/escalated using stringent EEG seizure criteria (EST) or clinical criteria (CST) with the goal being seizure cessation. The specific AED, dosage, and duration of treatment is standardized in both groups. Monitoring will continue for a period of upto 96 hours in both arms. Other than the anticonvulsant drugs, treatment thresholds and dosing schedules, treatment in both arms will be at the discretion of the bedside physician.All infants will undergo an assessment of neuromotor disability and neurodevelopmental evaluation at 18 to 24 months.

Eligibility criteria: Inclusion Criteria:

* Term or near term infants ≥ 36 weeks gestation admitted to the neonatal intensive care unit
* ≤ 72 hours of age
* Screening for the "at risk" infant by the clinical team to include any one of the following:

  * Apgar score \<5 at 5 min
  * Cord blood or postnatal gas with pH \<7.0 or BE \> -12
  * Need for respiratory support at 10 min of life
  * Suspected or definite seizures
  * Encephalopathy defined by recognition of altered neurological behavior
* Infants identified in the above screen will be examined by the research team and will be eligible if they satisfy at least one of the following:

  * Moderate-severe neonatal encephalopathy (3 out of 6 criteria)
  * Suspected or definite neonatal seizures

Exclusion criteria:

* Infants \< 36 weeks gestation
* \> 72 hours of age
* Infants with congenital anomalies of the central nervous system
* Moribund infants for whom no further aggressive treatment is planned
* Metabolic disorders or documented CNS infection
* Neuro-muscular blockade

Primary outcomes:
measure: Seizure burden
timeFrame: 2 to 3 years
measure: Presence of a single combined event: death in the first two years of life or moderate or severe disability at 18-24 months
timeFrame: first two years of life; 18-24 months
Secondary outcomes:
measure: Time to seizure cessation
timeFrame: 2 to 3 years
measure: Number, duration of anticonvulsants used and cumulative dose
timeFrame: 2 to 3 years
measure: EEG background state
timeFrame: 2 to 3 years
measure: Time to all per oral feeding
timeFrame: 2 to 3 years
measure: Duration of hospital stay
timeFrame: 2 to 3 years
measure: MRI measures from the Day #7-10 MRI in survivors
timeFrame: 2 to 3 years
Other outcomes:
Locations:
city: St. Louis
country: United States
facility: St. Louis Children's Hospital
state: Missouri
Study officials:
affiliation: Washington University in Saint Louis
name: Amit Mathur
role: PRINCIPAL_INVESTIGATOR
References:
citation: Srinivasakumar P, Zempel J, Trivedi S, Wallendorf M, Rao R, Smith B, Inder T, Mathur AM. Treating EEG Seizures in Hypoxic Ischemic Encephalopathy: A Randomized Controlled Trial. Pediatrics. 2015 Nov;136(5):e1302-9. doi: 10.1542/peds.2014-3777. Epub 2015 Oct 19.