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

Seizures Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01027715
• Other study ID #: 08-0888
• Status: Completed
• Phase: N/A
• First received: December 8, 2009
• Last updated: December 8, 2015
• Start date: January 2010
• Est. completion date: December 2015

Study information

• Verified date: December 2015
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 69
• Est. completion date: December 2015
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 72 Hours

Eligibility

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 Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain Diseases
• Encephalopathy
• Seizures

Intervention

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.

Locations

Country	Name	City	State
United States	St. Louis Children's Hospital	St. Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Washington University School of Medicine

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Seizure burden		2 to 3 years	No
Primary	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	No
Secondary	Time to seizure cessation		2 to 3 years	No
Secondary	Number, duration of anticonvulsants used and cumulative dose		2 to 3 years	No
Secondary	EEG background state		2 to 3 years	No
Secondary	Time to all per oral feeding		2 to 3 years	No
Secondary	Duration of hospital stay		2 to 3 years	No
Secondary	MRI measures from the Day #7-10 MRI in survivors		2 to 3 years	No