Hypoxic Ischemic Encephalopathy
Conditions
Keywords
Hypoxic ischemic encephalopathy, HIE, Perinatal depression, Whole body cooling, Therapeutic hypothermia
Brief 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.
Detailed 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
Interventions
DRUGTopiramate
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.
DRUGPlacebo
A placebo identical in appearance to the active agent (topiramate)
Sponsors
Kristin R Hoffman
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
No minimum to 6 Hours
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Seizures | At 4 weeks post-natal age or the time of hospital discharge (whichever is earlier) | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Subjects will receive the standard of care intervention for HIE at our institution (whole body cooling for 72h followed by gradual rewarming)
Placebo: A placebo identical in appearance to the active agent (topiramate) | 17 |
| Topiramate 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.
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. | 17 |
| Total | 34 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 1 | 2 |
Baseline characteristics
| Characteristic | Placebo | Topiramate | Total |
|---|---|---|---|
| Age, Customized Gestational Age | 39.12 Weeks | 38.88 Weeks | 39 Weeks |
| Birth Weight (g) | 3236.14 grams | 3159.24 grams | 3197.46 grams |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 6 Participants | 8 Participants | 14 Participants |
| Race (NIH/OMB) White | 5 Participants | 5 Participants | 10 Participants |
| Sex: Female, Male Female | 10 Participants | 5 Participants | 15 Participants |
| Sex: Female, Male Male | 7 Participants | 12 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 17 | 0 / 17 |
| other Total, other adverse events | 2 / 17 | 4 / 17 |
| serious Total, serious adverse events | 1 / 17 | 0 / 17 |
Outcome results
Primary
Number of Patients With 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.
Time frame: At 4 weeks post-natal age or the time of hospital discharge (whichever is earlier)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Patients With Seizures | 3 Participants with Seizures |
| Topiramate | Number of Patients With Seizures | 1 Participants with Seizures |