Topiramate in Neonates Receiving Whole Body Cooling for Hypoxic Ischemic Encephalopathy

Hypoxic Ischemic Encephalopathy Clinical Trial

Official title:

Topiramate as an Adjuvant to Therapeutic Hypothermia for Infants With Hypoxic Ischemic Encephalopathy

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01765218
• Other study ID #: 1182678
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: February 2013
• Est. completion date: January 27, 2022

Study information

• Verified date: November 2023
• Source: University of California, Davis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal is to see whether topiramate (an anti-epileptic agent) improves the outcome of babies with neonatal hypoxic encephalopathy who are receiving whole body cooling.

Description:

Hypoxic ischemic encephalopathy (HIE) is a devastating and unexpected disease in newborns that affects 1.5-2.6 per 1000 live births. Hypoxic ischemic encephalopathy has a mortality rate of up to 30% and survivors are at significant risk for adverse long-term outcomes, including seizures, cerebral palsy, and developmental delay. The investigators propose a randomized controlled study comparing therapeutic hypothermia alone, or therapeutic hypothermia combined with topiramate. The investigators hypothesize that adjuvant therapy with topiramate will reduce short term severity of HIE including seizures (the primary outcome), a composite HIE severity score, and reduce the time of normalization of the amplitude integrated EEG (aEEG). The investigators further hypothesize, that it will improve longer term outcomes such as developmental outcome. The primary hypothesis is that seizures before hospital discharge (or before 4 weeks post-natal age (which ever is earlier)) will be significantly reduced in the topiramate group compared to the control group

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 34
• Est. completion date: January 27, 2022
• Est. primary completion date: January 27, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 6 Hours

Eligibility

Inclusion Criteria:

In order to be eligible for cooling the baby must meet all three of the following sets of criteria

1. Be near term (typically =34wks gestation) and be aged < 6h old

2. Have signs of early perinatal depression (EITHER 10 minute Apgar score < 5, OR pH < 7.00 within 60mins of age, OR Base Excess < -12 within 60mins of age, OR need respiratory support at 10min of age due to respiratory depression)

3. Have signs of moderate or severe encephalopathy based on either clinical examination or on amplitude integrated aEEG assessment

Exclusion Criteria:

1. Known congenital myopathy

2. Known congenital neuropathy

Related Conditions & MeSH terms

• Brain Diseases
• Brain Ischemia
• Hypoxia
• Hypoxia-Ischemia, Brain
• Hypoxic Ischemic Encephalopathy
• Ischemia

Intervention

Drug:
• Topiramate
Infants assigned to the topiramate group will receive 5mg/kg of topiramate daily enterally for a total of 5 doses. The first dose will be administered as soon as possible on admission.
• Placebo
A placebo identical in appearance to the active agent (topiramate)

Locations

Country	Name	City	State
United States	UC Davis Medical Center	Sacramento	California

Sponsors (1)

Lead Sponsor	Collaborator
Kristin R Hoffman

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Seizures	Clinical or electrical seizures occuring before hospital discharge or before 4w post-natal age (which ever is earlier) will be compared between the topiramate and control groups.	At 4 weeks post-natal age or the time of hospital discharge (whichever is earlier)
Secondary	HIE score	Differences in daily HIE score between the two groups will be compared from birth to day-5, and from birth to the time of discharge from hospital	At 4 weeks post-natal age or the time of hospital discharge (whichever is earlier)
Secondary	Normalization of aEEG	The time for normalization of aEEG voltages will be compared in the two groups.	At 4 weeks post-natal age or the time of hospital discharge (whichever is earlier)
Secondary	S100-beta levels	Serum and urine S100beta levels (a marker of neuronal injury) will be compared in the two groups at three time points (on day of life 1, 3, and 7)	Day of life 1, 3 and 7
Secondary	MRI score	The MRI score on day 5 to 7 of life will be compared in the two groups.	On day 5-7 of life
Secondary	Developmental Outcome	Bayley scales of infant development III will be compared in the two groups at 9, 18 and 27m of age	At 9, 18 and 27 months