Safety and Efficacy of Topiramate in Neonates With Hypoxic Ischemic Encephalopathy Treated With Hypothermia (NeoNATI)

Azienda Ospedaliero, Universitaria Meyer

Status and phase: Completed; Phase 2

Conditions: Hypoxic Ischemic Encephalopathy

Treatments: Drug: Topiramate in newborns with hypoxic ischemic encephalopathy treated with therapeutic hypothermia

Study type: Interventional

Funder types: Other

Identifiers

NCT01241019

EudraCT: 2010-018627-25

Details and patient eligibility

About

The purpose of this study is to determine whether the administration of topiramate to newborns with hypoxic-ischemic encephalopathy potentiates the neuroprotective effect of treatment with hypothermia.

Full description

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.

Enrollment: 64 patients

Sex: All

Ages: 36+ weeks old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Gestational age > 36 weeks and birth weigh > 1800 g with at least 1 of the following: a) Apgar score < 5 at 10 minutes; b) persisting need for resuscitation, including endotracheal intubation or mask ventilation 10 minutes after birth; c) acidosis (pH <7.0, base deficit >-16 mmol/L in umbilical cord blood or arterial, venous or capillary blood) within 60 minutes from birth;
2. moderate to severe encephalopathy, consisting of altered state of consciousness (irritability, lethargy, stupor, or coma) and > 1 of the following sings: a) hypotonia, b) abnormal reflexes, including oculomotor or pupil abnormalities, c) absent or weak suck, d) clinical seizures.
3. abnormal aEEG

Exclusion criteria

congenital abnormalities, congenital viral infections or evidence encephalopathy other than HIE.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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64 participants in 2 patient groups

Topiramate

Experimental group

Description:

Newborns with hypoxic ischemic encephalopathy treated with mild hypothermia and topiramate

Treatment:

Drug: Topiramate in newborns with hypoxic ischemic encephalopathy treated with therapeutic hypothermia

Control

No Intervention group

Description:

Newborns with hypoxic ischemic encephalopathy treated with mild hypothermia