Topiramate in Neonates Receiving Whole Body Cooling for Hypoxic Ischemic Encephalopathy

Kristin R Hoffman

Status and phase: Terminated; Phase 2; Phase 1

Conditions: Hypoxic Ischemic Encephalopathy

Treatments: Drug: Placebo; Drug: Topiramate

Study type: Interventional

Funder types: Other

Identifiers

NCT01765218

1182678

Details and patient eligibility

About

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.

Full 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

Enrollment: 34 patients

Sex: All

Ages: Under 6 hours old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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34 participants in 2 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Subjects will receive the standard of care intervention for HIE at our institution (whole body cooling for 72h followed by gradual rewarming)

Treatment:

Drug: Placebo

Topiramate

Active Comparator group

Description:

In addition to whole body cooling, 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.

Treatment:

Drug: Topiramate