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

This study has been completed.
Sponsor:
Collaborator:
Azienda Ospedaliero, Universitaria Pisana
Information provided by (Responsible Party):
Luca Filippi, Azienda Ospedaliero, Universitaria Meyer
ClinicalTrials.gov Identifier:
NCT01241019
First received: November 10, 2010
Last updated: December 12, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
Hypoxic Ischemic Encephalopathy
Drug: Topiramate in newborns with hypoxic ischemic encephalopathy treated with therapeutic hypothermia
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (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

Resource links provided by NLM:


Further study details as provided by Azienda Ospedaliero, Universitaria Meyer:

Primary Outcome Measures:
  • The primary aim is to evaluate the neurological outcome at 6, 12, 18 months of life [ Time Frame: 18 months of life ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Enrollment: 64
Study Start Date: February 2010
Study Completion Date: December 2013
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Topiramate
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

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.

  Eligibility

Ages Eligible for Study:   36 Weeks and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

-

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01241019

Locations
Italy
Neonatal Intensive Care Unit - Azienda Ospedaliero-Universitaria Meyer
Florence, Italy, I-50139
Neonatal Intensive Care Unit - Azienda Ospedaliero-Universitaria Pisana
Pisa, Italy, I-56100
Sponsors and Collaborators
Azienda Ospedaliero, Universitaria Meyer
Azienda Ospedaliero, Universitaria Pisana
Investigators
Principal Investigator: Luca Filippi, MD Azienda Ospedaliero-Universitaria A. Meyer, Firenze, Italy
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Luca Filippi, Dr. Luca Filippi, Azienda Ospedaliero, Universitaria Meyer
ClinicalTrials.gov Identifier: NCT01241019     History of Changes
Other Study ID Numbers: EudraCT: 2010-018627-25
Study First Received: November 10, 2010
Last Updated: December 12, 2013
Health Authority: Italy: Ethics Committee
Italy: National Monitoring Centre for Clinical Trials - Ministry of Health

Keywords provided by Azienda Ospedaliero, Universitaria Meyer:
asphyxia neonatorum, hypothermia, neuroprotection

Additional relevant MeSH terms:
Brain Ischemia
Hypothermia
Ischemia
Brain Diseases
Hypoxia-Ischemia, Brain
Cerebrovascular Disorders
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Body Temperature Changes
Signs and Symptoms
Pathologic Processes
Hypoxia, Brain
Topiramate
Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Neuroprotective Agents
Protective Agents
Physiological Effects of Drugs
Anti-Obesity Agents

ClinicalTrials.gov processed this record on July 31, 2014