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

NCT ID: NCT01241019

Last Updated: 2013-12-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 64 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-02-28
• Study Completion Date: 2013-12-31

Brief 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.

Detailed 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.

Conditions

Hypoxic Ischemic Encephalopathy

Keywords

asphyxia neonatorum, hypothermia, neuroprotection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Topiramate

Newborns with hypoxic ischemic encephalopathy treated with mild hypothermia and topiramate

Group Type: EXPERIMENTAL

Topiramate in newborns with hypoxic ischemic encephalopathy treated with therapeutic hypothermia

Intervention Type: DRUG

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.

Control

Newborns with hypoxic ischemic encephalopathy treated with mild hypothermia

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

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.

Intervention Type: DRUG

Eligibility Criteria

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.

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• Minimum Eligible Age: 36 Weeks
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Azienda Ospedaliero, Universitaria Pisana

OTHER

Sponsor Role: collaborator

Meyer Children's Hospital IRCCS

OTHER

Sponsor Role: lead

Responsible Party

Luca Filippi

Dr. Luca Filippi

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Luca Filippi, MD

Role: PRINCIPAL_INVESTIGATOR

Azienda Ospedaliero-Universitaria A. Meyer, Firenze, Italy

Locations

Neonatal Intensive Care Unit - Azienda Ospedaliero-Universitaria Meyer

Florence, , Italy

Neonatal Intensive Care Unit - Azienda Ospedaliero-Universitaria Pisana

Pisa, , Italy

Countries

Italy

References

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.

Reference Type: BACKGROUND

PMID: 19744111 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 20553846 (View on PubMed)

Shankaran S. Outcomes of hypoxic-ischemic encephalopathy in neonates treated with hypothermia. Clin Perinatol. 2014 Mar;41(1):149-59. doi: 10.1016/j.clp.2013.10.008.

Reference Type: DERIVED

PMID: 24524452 (View on PubMed)

Filippi L, Fiorini P, Daniotti M, Catarzi S, Savelli S, Fonda C, Bartalena L, Boldrini A, Giampietri M, Scaramuzzo R, Papoff P, Del Balzo F, Spalice A, la Marca G, Malvagia S, Della Bona ML, Donzelli G, Tinelli F, Cioni G, Pisano T, Falchi M, Guerrini R. Safety and efficacy of topiramate in neonates with hypoxic ischemic encephalopathy treated with hypothermia (NeoNATI). BMC Pediatr. 2012 Sep 5;12:144. doi: 10.1186/1471-2431-12-144.

Reference Type: DERIVED

PMID: 22950861 (View on PubMed)

Related Links

http://druginfo.nlm.nih.gov/

Drug information

Other Identifiers

EudraCT: 2010-018627-25

Identifier Type: -

Identifier Source: org_study_id