Topiramate in Neonates Receiving Whole Body Cooling for Hypoxic Ischemic Encephalopathy
We wish to see whether topiramate (an anti-epileptic agent) improves the outcome of babies with neonatal hypoxic encephalopathy who are receiving whole body cooling.
Hypoxic Ischemic Encephalopathy
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||TOPIRAMATE AS AN ADJUVANT TO THERAPEUTIC HYPOTHERMIA FOR INFANTS WITH HYPOXIC ISCHEMIC ENCEPHALOPATHY|
- Seizures [ Time Frame: At 4 weeks post-natal age or the time of hospital discharge (whichever is earlier) ] [ Designated as safety issue: No ]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.
- HIE score [ Time Frame: At 4 weeks post-natal age or the time of hospital discharge (whichever is earlier) ] [ Designated as safety issue: No ]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
- Normalization of aEEG [ Time Frame: At 4 weeks post-natal age or the time of hospital discharge (whichever is earlier) ] [ Designated as safety issue: No ]The time for normalization of aEEG voltages will be compared in the two groups.
- S100-beta levels [ Time Frame: Day of life 1, 3 and 7 ] [ Designated as safety issue: No ]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)
- MRI score [ Time Frame: On day 5-7 of life ] [ Designated as safety issue: No ]The MRI score on day 5 to 7 of life will be compared in the two groups.
- Developmental Outcome [ Time Frame: At 9, 18 and 27 months ] [ Designated as safety issue: No ]Bayley scales of infant development III will be compared in the two groups at 9, 18 and 27m of age
|Study Start Date:||February 2013|
|Estimated Study Completion Date:||February 2018|
|Estimated Primary Completion Date:||February 2017 (Final data collection date for primary outcome measure)|
Placebo Comparator: Placebo
Subjects will receive the standard of care intervention for HIE at our institution (whole body cooling for 72h followed by gradual rewarming)
A placebo identical in appearance to the active agent (topiramate)
Active Comparator: Toprimate
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.
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.
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 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 4w post-natal age (which ever is earlier) will be significantly reduced in the topiramate group compared to the control group
Please refer to this study by its ClinicalTrials.gov identifier: NCT01765218
|Contact: Ian J Griffin, MDfirstname.lastname@example.org|
|Contact: Majid Mirmiranemail@example.com|
|United States, California|
|UC Davis Medical Center||Recruiting|
|Sacramento, California, United States, 95822|
|Contact: Ian J Griffin, MD 916-703-5015 firstname.lastname@example.org|
|Contact: Kristen Hoffmann, MD|
|Principal Investigator: Ian J Griffin, MD|
|Principal Investigator:||Ian J Griffin, MD||UC Davis|