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

NCT ID: NCT01027715

Last Updated: 2015-12-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 69 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-01-31
• Study Completion Date: 2015-12-31

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.

Conditions

Seizures; Encephalopathy

Keywords

Neonatal Seizures; Neonatal encephalopathy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

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.

Group Type: EXPERIMENTAL

EEG monitoring and treatment of EEG seizures

Intervention Type: OTHER

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.

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.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

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.

Intervention Type: OTHER

Other Intervention Names

EEG monitoring; Anti-epileptic drugs

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

• Minimum Eligible Age: 1 Hour
• Maximum Eligible Age: 72 Hours
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Washington University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Amit Mathur

Role: PRINCIPAL_INVESTIGATOR

Washington University in Saint Louis

Locations

St. Louis Children's Hospital

St Louis, Missouri, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 26482675 (View on PubMed)

Other Identifiers

08-0888

Identifier Type: -

Identifier Source: org_study_id