The Impact of Electroencephalographic (EEG) Seizure Treatment in Neonatal Encephalopathy

The Impact of Electroencephalographic (EEG) Seizure Treatment in Near Term ≥ 36 Weeks Gestation and Term Infants With Neonatal Encephalopathy

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).

Study Overview

• Status: Completed
• Conditions: Seizures; Encephalopathy
• Intervention / Treatment: Other: EEG monitoring and treatment of EEG seizures

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.

• Study Type: Interventional
• Enrollment (Actual): 69
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • St. Louis Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 hour to 3 days (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: EEG seizure treatment group; EEG data available to physicians. Treatment based on EEG seizures. Treatment will be dictated by the detailed treatment protocol. Standard antiepileptic medications will be used.	Other: EEG monitoring and treatment of EEG seizures; Seizures will prompt treatment with loading doses of phenobarbital (20mg/kg), fosphenytoin (20mg/kg),and midazolam (0.05mg/kg bolus and .15mg/kg/hr infusion tapered over 48 hours)in that order for persisting seizures.; Other Names: EEG monitoring; Anti-epileptic drugs
No Intervention: Clinical Seizure treatment Group; Seizure treatment in this group will be based on standard care - treating clinical seizures only. While EEG data will be collected in this group, the data will not be available to the treating physicians. A one-hour EEG report will be available to the treating team. Continuous EEG monitoring and treatment will only be allowed if the initial EEG shows status.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Seizure burden	2 to 3 years
Presence of a single combined event: death in the first two years of life or moderate or severe disability at 18-24 months	first two years of life; 18-24 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Time to seizure cessation	2 to 3 years
Number, duration of anticonvulsants used and cumulative dose	2 to 3 years
EEG background state	2 to 3 years
Time to all per oral feeding	2 to 3 years
Duration of hospital stay	2 to 3 years
MRI measures from the Day #7-10 MRI in survivors	2 to 3 years

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Investigators: Principal Investigator: Amit Mathur, Washington University in Saint Louis

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: January 1, 2010
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: December 8, 2009
• First Submitted That Met QC Criteria: December 8, 2009
• First Posted (Estimate): December 9, 2009

Study Record Updates

• Last Update Posted (Estimate): December 10, 2015
• Last Update Submitted That Met QC Criteria: December 8, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: Neonatal Seizures; Neonatal encephalopathy
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Seizures; Brain Diseases; Anticonvulsants
• Other Study ID Numbers: 08-0888