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

NCT01241019 | Completed Phase 2

• 1 other identifier: EudraCT: 2010-018627-25
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 2

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.

Conditions

Hypoxic Ischemic Encephalopathy

Keywords

asphyxia neonatorum, hypothermia, neuroprotection

Outcome Measures

Primary Outcomes (1)

• The primary aim is to evaluate the neurological outcome at 6, 12, 18 months of life

  18 months of life

Secondary Outcomes (1)

• 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

Study Arms (2)

Topiramate

EXPERIMENTAL

Newborns with hypoxic ischemic encephalopathy treated with mild hypothermia and topiramate

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

Control

NO INTERVENTION

Newborns with hypoxic ischemic encephalopathy treated with mild hypothermia

Interventions

Topiramate in newborns with hypoxic ischemic encephalopathy treated with therapeutic hypothermia 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.

Topiramate

Eligibility Criteria

• Age: 36 Weeks+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• 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.
• abnormal aEEG

You may not qualify if:

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

Sponsors & Collaborators

• Meyer Children's Hospital IRCCS: lead
• Azienda Ospedaliero, Universitaria Pisana: collaborator

Study Sites (2)

Neonatal Intensive Care Unit - Azienda Ospedaliero-Universitaria Meyer

Florence, I-50139, Italy

Location

Neonatal Intensive Care Unit - Azienda Ospedaliero-Universitaria Pisana

Pisa, I-56100, Italy

Location

Related Publications (4)

• 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.

  PMID: 19744111 BACKGROUND

• 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.

  PMID: 20553846 BACKGROUND

• 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.

  PMID: 24524452 DERIVED

• 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.

  PMID: 22950861 DERIVED

Related Links

• Drug information

MeSH Terms

Conditions

Hypoxia-Ischemia, Brain; Asphyxia Neonatorum; Hypothermia

Interventions

Topiramate; Hypothermia, Induced

Condition Hierarchy (Ancestors)

Brain Ischemia; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hypoxia, Brain; Vascular Diseases; Cardiovascular Diseases; Hypoxia; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Body Temperature Changes

Intervention Hierarchy (Ancestors)

Fructose; Hexoses; Monosaccharides; Sugars; Carbohydrates; Ketoses; Cryotherapy; Therapeutics

Study Officials

• Luca Filippi, MD

  Azienda Ospedaliero-Universitaria A. Meyer, Firenze, Italy

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr. Luca Filippi

Study Record Dates

• First Submitted: November 10, 2010
• First Posted: November 16, 2010
• Study Start: February 1, 2010
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: December 13, 2013

Record last verified: 2013-12

Locations

IT (2)