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

Hypoxic Ischemic Encephalopathy Clinical Trial

— NeoNATI  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01241019
• Other study ID #: EudraCT: 2010-018627-25
• Status: Completed
• Phase: Phase 2
• First received: November 10, 2010
• Last updated: December 12, 2013
• Start date: February 2010
• Est. completion date: December 2013

Study information

• Verified date: December 2013
• Source: Azienda Ospedaliero, Universitaria Meyer
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Ethics CommitteeItaly: National Monitoring Centre for Clinical Trials - Ministry of Health
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 64
• Est. completion date: December 2013
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 36 Weeks and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain Diseases
• Brain Ischemia
• Hypothermia
• Hypoxia-Ischemia, Brain
• Hypoxic Ischemic Encephalopathy
• Ischemia

Intervention

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.

Locations

Country	Name	City	State
Italy	Neonatal Intensive Care Unit - Azienda Ospedaliero-Universitaria Meyer	Florence
Italy	Neonatal Intensive Care Unit - Azienda Ospedaliero-Universitaria Pisana	Pisa

Sponsors (2)

Lead Sponsor	Collaborator
Azienda Ospedaliero, Universitaria Meyer	Azienda Ospedaliero, Universitaria Pisana

Country where clinical trial is conducted

Italy, 

References & Publications (2)

Filippi L, la Marca G, Fiorini P, Poggi C, Cavallaro G, Malvagia S, Pellegrini-Giampietro DE, Guerrini R. Topiramate concentrations in neonates treated with prolonged whole body hypothermia for hypoxic ischemic encephalopathy. Epilepsia. 2009 Nov;50(11):2355-61. doi: 10.1111/j.1528-1167.2009.02302.x. Epub 2009 Sep 10. — View Citation

Filippi L, Poggi C, la Marca G, Furlanetto S, Fiorini P, Cavallaro G, Plantulli A, Donzelli G, Guerrini R. Oral topiramate in neonates with hypoxic ischemic encephalopathy treated with hypothermia: a safety study. J Pediatr. 2010 Sep;157(3):361-6. doi: 10.1016/j.jpeds.2010.04.019. Epub 2010 May 31. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary aim is to evaluate the neurological outcome at 6, 12, 18 months of life		18 months of life	No
Secondary	The secondary aim is to evaluate the efficacy of treatment with topiramate for improving neuroradiological outcome at 3 and 12 months of life		12 months of life	No

External Links

•   Drug information