Safety and Efficacy of Topiramate in Neonates With Hypoxic Ischemic Encephalopathy Treated With Hypothermia (NeoNATI)
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
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 |
- 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 ]
- 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 ]
| Estimated Enrollment: | 60 |
| Study Start Date: | February 2010 |
| Estimated Study Completion Date: | August 2013 |
| Estimated Primary Completion Date: | February 2012 (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 |
Inclusion Criteria:
- 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
Exclusion Criteria:
congenital abnormalities, congenital viral infections or evidence encephalopathy other than HIE.
-
Contacts and Locations| Contact: Luca Filippi, MD | ++ 39-(0)55-5662434 | l.filippi@meyer.it |
| Italy | |
| Neonatal Intensive Care Unit - Azienda Ospedaliero-Universitaria Meyer | Recruiting |
| Florence, Italy, I-50139 | |
| Contact: Luca Filippi, MD ++ 39-(0)55-5662434 l.filippi@meyer.it | |
| Sub-Investigator: Patrizio Fiorini, MD | |
| Sub-Investigator: Renzo Guerrini, MD | |
| Sub-Investigator: Serena Catarzi, MD | |
| Sub-Investigator: Tiziana Pisano, MD | |
| Sub-Investigator: Melania Falchi, MD | |
| Sub-Investigator: Sara Savelli, MD | |
| Sub-Investigator: Maria Luce Cioni, MD | |
| Sub-Investigator: Filomena Paternoster, MD | |
| Sub-Investigator: Giancarlo la Marca, Pharm Sc | |
| Sub-Investigator: Sabrina Malvagia, BSc | |
| Neonatal Intensive Care Unit - Azienda Ospedaliero-Universitaria Pisana | Recruiting |
| Pisa, Italy, I-56100 | |
| Contact: Laura Bartalena, MD ++39 (0)50/992529 l.bartalena@ao-pisa.toscana.it | |
| Sub-Investigator: Antonio Boldrini, MD | |
| Sub-Investigator: Giovanni Cioni, MD | |
| Sub-Investigator: Francesca Tinelli, MD | |
| Sub-Investigator: Rosa Teresa Scaramuzzo, MD | |
| Sub-Investigator: Massimiliano Ciantelli, MD | |
| Sub-Investigator: Emilio Sigali, MD | |
| Sub-Investigator: Marco Vuerich, MD | |
| Sub-Investigator: Roberta Battini, MD | |
| Sub-Investigator: Rosario Federico, MD | |
| Sub-Investigator: Andrea Guzzetta, MD | |
| Sub-Investigator: Simona Fiori, MD | |
| 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: | January 22, 2012 |
| 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:
|
Hepatic Encephalopathy Brain Ischemia Hypothermia Ischemia Brain Damage, Chronic Delirium Encephalitis Neurotoxicity Syndromes Hypoxia-Ischemia, Brain Cerebrovascular Disorders Brain Diseases Central Nervous System Diseases Nervous System Diseases Vascular Diseases Cardiovascular Diseases |
Body Temperature Changes Signs and Symptoms Pathologic Processes Confusion Neurobehavioral Manifestations Neurologic Manifestations Delirium, Dementia, Amnestic, Cognitive Disorders Mental Disorders Central Nervous System Viral Diseases Virus Diseases Central Nervous System Infections Liver Failure Hepatic Insufficiency Liver Diseases Digestive System Diseases |
ClinicalTrials.gov processed this record on May 16, 2013