Safety and Efficacy of Topiramate in Neonates With Hypoxic Ischemic Encephalopathy Treated With Hypothermia (NeoNATI)
|Hypoxic Ischemic Encephalopathy||Drug: Topiramate in newborns with hypoxic ischemic encephalopathy treated with therapeutic hypothermia||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Safety and Efficacy of Oral Topiramate in Neonates With Hypoxic Ischemic Encephalopathy Treated With Hypothermia: a Pilot Study of the Neonatal Neuroprotection of Asphyxiated Tuscan Infants (NeoNATI) Network|
- The primary aim is to evaluate the neurological outcome at 6, 12, 18 months of life [ Time Frame: 18 months of life ]
- The secondary aim is to evaluate the efficacy of treatment with topiramate for improving neuroradiological outcome at 3 and 12 months of life [ Time Frame: 12 months of life ]
|Study Start Date:||February 2010|
|Study Completion Date:||December 2013|
|Primary Completion Date:||December 2013 (Final data collection date for primary outcome measure)|
Newborns with hypoxic ischemic encephalopathy treated with mild hypothermia and topiramate
Drug: Topiramate in newborns with hypoxic ischemic encephalopathy treated with therapeutic hypothermia
TPM 10 mg/kg once a day will be administered with an orogastric tube as enteric-coated granules mixed with water on arrival in the NICU, when the cooling will be begun (T0), once a day for the first 3 days of life, for a total of 3 doses per patient.
No Intervention: Control
Newborns with hypoxic ischemic encephalopathy treated with mild hypothermia
Neonatal hypoxic-ischemic encephalopathy, due to perinatal asphyxia, is one of the leading causes of cerebral palsy, whose incidence, despite improvements in perinatal practice and neonatal care, has remained essentially unchanged over the recent past decades. It occurs approximately in 2-3 newborns every 1000 live births with a mortality rate of 10% for mild degrees and 60% for severe degrees. About 30% of survivors with mild hypoxic-ischemic encephalopathy and 100% with severe hypoxic-ischemic encephalopathy exhibit variable degrees of neurological disability.
Several studies have demonstrated the therapeutic effects of whole-body or selective head cooling to treat neonates with hypoxic-ischemic encephalopathy. Mild hypothermia, (rectal or esophageal temperature 33-34°C), started within 6 h after birth and protracted for 48-72 h, can significantly improve primary outcome measures such as death or disability at 18 months or improve the neurological outcome in survivors. Consequently, mild hypothermia is at present recommended for the treatment of moderate degrees of encephalopathy.
Topiramate an anticonvulsant agent widely used in adults and children, has been demonstrated to posses neuroprotective properties against hypoxic ischemic brain damage, both in vitro and in animal models and has been included in neuroprotective strategies for ischemic stroke and neonatal hypoxic-ischemic cerebral injury. Recently, topiramate treatment in asphyxiated newborns has been reported safe.
Aim of the present study is to confirm the safety and to evaluate whether the association of topiramate enhances the neuroprotective properties of hypothermia for the treatment of neonatal hypoxic-ischemic encephalopathy.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01241019
|Neonatal Intensive Care Unit - Azienda Ospedaliero-Universitaria Meyer|
|Florence, Italy, I-50139|
|Neonatal Intensive Care Unit - Azienda Ospedaliero-Universitaria Pisana|
|Pisa, Italy, I-56100|
|Principal Investigator:||Luca Filippi, MD||Azienda Ospedaliero-Universitaria A. Meyer, Firenze, Italy|