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Topiramate in Neonates Receiving Whole Body Cooling for Hypoxic Ischemic Encephalopathy

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2013 by University of California, Davis
Sponsor:
Information provided by (Responsible Party):
University of California, Davis
ClinicalTrials.gov Identifier:
NCT01765218
First received: January 7, 2013
Last updated: June 4, 2013
Last verified: June 2013

January 7, 2013
June 4, 2013
February 2013
February 2015   (final data collection date for primary outcome measure)
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.
Seizures [ Time Frame: At 4w 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.
Complete list of historical versions of study NCT01765218 on ClinicalTrials.gov Archive Site
  • 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
  • HIE score [ Time Frame: At 4w 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 4w 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 9m, 18m and 27m of age ] [ 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
Not Provided
Not Provided
 
Topiramate in Neonates Receiving Whole Body Cooling for Hypoxic Ischemic Encephalopathy
TOPIRAMATE AS AN ADJUVANT TO THERAPEUTIC HYPOTHERMIA FOR INFANTS WITH 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 (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

Interventional
Phase 1
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Hypoxic Ischemic Encephalopathy
  • 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.
    Other Names:
    • Topamax
    • Topiragen
  • Drug: Placebo
    A placebo identical in appearance to the active agent (topiramate)
  • 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)
    Intervention: Drug: Placebo
  • 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.
    Intervention: Drug: Topiramate
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
42
February 2018
February 2015   (final data collection date for primary outcome measure)

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
Both
up to 6 Hours
No
Contact: Ian J Griffin, MD 916-703-5015 ijgriffin@ucdavis.edu
Contact: Majid Mirmiran majid.mirmiran@ucdmc.ucdavis.edu
United States
 
NCT01765218
2012_05_17_UCD
Yes
University of California, Davis
University of California, Davis
Not Provided
Principal Investigator: Ian J Griffin, MD UC Davis
University of California, Davis
June 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP