Topiramate in Neonates Receiving Whole Body Cooling for Hypoxic Ischemic Encephalopathy - Full Text View

Purpose

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.

Condition	Intervention	Phase
Hypoxic Ischemic Encephalopathy	Drug: Topiramate Drug: Placebo	Phase 1 Phase 2

Study Type:	Interventional
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

Resource links provided by NLM:

MedlinePlus related topics: Hypothermia

Drug Information available for: Topiramate

U.S. FDA Resources

Further study details as provided by University of California, Davis:

Primary Outcome Measures:

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.

Secondary Outcome Measures:

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

Estimated Enrollment:	42
Study Start Date:	February 2013
Estimated Study Completion Date:	February 2018
Estimated Primary Completion Date:	February 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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)	Drug: Placebo 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.	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

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 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

Eligibility

Ages Eligible for Study:	up to 6 Hours
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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

Be near term (typically ≥34wks gestation) and be aged < 6h old
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)
Have signs of moderate or severe encephalopathy based on either clinical examination or on amplitude integrated aEEG assessment

Exclusion Criteria:

Known congenital myopathy
Known congenital neuropathy

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01765218

Contacts

Contact: Ian J Griffin, MD	916-703-5015	ijgriffin@ucdavis.edu
Contact: Majid Mirmiran		majid.mirmiran@ucdmc.ucdavis.edu

Locations

United States, California
UC Davis Medical Center	Recruiting
Sacramento, California, United States, 95822
Contact: Ian J Griffin, MD 916-703-5015 ijgriffin@ucdavis.edu
Contact: Kristen Hoffmann, MD
Principal Investigator: Ian J Griffin, MD

Sponsors and Collaborators

University of California, Davis

Investigators

Principal Investigator:

Ian J Griffin, MD

UC Davis

More Information

No publications provided

Responsible Party:	University of California, Davis
ClinicalTrials.gov Identifier:	NCT01765218 History of Changes
Other Study ID Numbers:	2012_05_17_UCD
Study First Received:	January 7, 2013
Last Updated:	June 4, 2013
Health Authority:	United States: Institutional Review Board United States: Food and Drug Administration

Keywords provided by University of California, Davis:

Hypoxic ischemic encephalopathy
HIE
Perinatal depression
Whole body cooling
Therapeutic hypothermia

Additional relevant MeSH terms:

Brain Ischemia
Hypothermia
Ischemia
Brain Damage, Chronic
Delirium
Encephalitis
Hepatic Encephalopathy
Neurotoxicity Syndromes
Hypoxia-Ischemia, Brain
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases

Body Temperature Changes
Signs and Symptoms
Pathologic Processes
Confusion
Neurobehavioral Manifestations
Neurologic Manifestations
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Central Nervous System Viral Diseases
Virus Diseases
Central Nervous System Infections
Liver Failure
Hepatic Insufficiency
Liver Diseases
Digestive System Diseases

ClinicalTrials.gov processed this record on June 17, 2013