Hypoxic Ischemic EncephalopathyPhase 2NeoNATINCT01241019
Safety and Efficacy of Topiramate in Neonates With Hypoxic Ischemic Encephalopathy Treated With Hypothermia
A Phase 2 study testing Topiramate in newborns with hypoxic ischemic encephalopathy treated with therapeutic hypothermia in people with Hypoxic Ischemic Encephalopathy, run by Meyer Children's Hospital IRCCS at 2 sites in Italy.
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. Read more about this study
- Who is it for?
- Ages 36 weeks and older
- Conditions the study is for
- Hypoxic Ischemic Encephalopathy
- What is being tested?
- Topiramate in newborns with hypoxic ischemic encephalopathy treated with therapeutic hypothermia
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 64 participants
- Where
- 2 sitesItaly
- Study dates
- Feb 2010to Dec 2013
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 36 weeks and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- congenital abnormalities, congenital viral infections or evidence encephalopathy other than HIE.
- -
Trial locations and contacts
2 sites in 1 country.
Italy2 sites
Neonatal Intensive Care Unit - Azienda Ospedaliero-Universitaria Meyer
Florence, I-50139
Neonatal Intensive Care Unit - Azienda Ospedaliero-Universitaria Pisana
Pisa, I-56100
About this study
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 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.
Read the 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
- Being tested
- Topiramate in newborns with hypoxic ischemic encephalopathy treated with therapeutic hypothermia
- Keywords
- asphyxia neonatorum, hypothermia, neuroprotection
- Medical subject headings
- Hypoxia-Ischemia, Brain, Asphyxia Neonatorum, Hypothermia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Topiramate in newborns with hypoxic ischemic encephalopathy treated with therapeutic hypothermiaDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Topiramate | Experimental | Newborns with hypoxic ischemic encephalopathy treated with mild hypothermia and topiramate Receives: Drug: Topiramate in newborns with hypoxic ischemic encephalopathy treated with therapeutic hypothermia |
| Control | No intervention | Newborns with hypoxic ischemic encephalopathy treated with mild hypothermia |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary aim is to evaluate the neurological outcome at 6, 12, 18 months of life
Measured: 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
Measured: 12 months of life
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Nov 2010 (estimated)
- Study startFeb 2010
- Primary completionDec 2013
- Study completionDec 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Hypoxic Ischemic EncephalopathyStudies of the same condition, open and under way.
- More trials run by Meyer Children's Hospital IRCCSThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 64 participants (actual)
Sponsor and investigators
- Lead sponsor
- Meyer Children's Hospital IRCCS
- Sponsor type
- University, hospital or other
- Collaborators
- Azienda Ospedaliero, Universitaria Pisana
- Responsible party
- Principal investigator, Luca Filippi, Meyer Children's Hospital IRCCS
- Investigators
- Luca Filippi, MD, Principal investigator, Azienda Ospedaliero-Universitaria A. Meyer, Firenze, Italy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01241019
- Sponsor's protocol ID
- EudraCT: 2010-018627-25
- Acronym
- NeoNATI
- Status last verified
- Dec 2013
- First submitted
- 10 Nov 2010
- Last updated
- 13 Dec 2013
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 19744111Filippi 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.
PubMed 20553846Shankaran 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.
PubMed 24524452Filippi 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.
PubMed 22950861
Study at a glance
From the registry record, last updated by the sponsor on 13 Dec 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01241019
- Acronym / sponsor ID
- NeoNATI / EudraCT: 2010-018627-25
- Conditions
- Hypoxic Ischemic Encephalopathy
- Keywords
- asphyxia neonatorum, hypothermia, neuroprotection
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 64 participants (actual)
- Lead sponsor
- Meyer Children's Hospital IRCCSUniversity, hospital or other
- Collaborators
- Azienda Ospedaliero, Universitaria Pisana
- Study start
- Feb 2010
- Primary completion
- Dec 2013 (actual)
- Study completion
- Dec 2013 (actual)
- First posted
- 16 Nov 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Topiramate | Experimental | Drug: Topiramate in newborns with hypoxic ischemic encephalopathy treated with therapeutic hypothermiaNewborns with hypoxic ischemic encephalopathy treated with mild hypothermia and topiramate |
| Control | No intervention | –Newborns with hypoxic ischemic encephalopathy treated with mild hypothermia |
Who may qualify
- Ages
- 36 weeks and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (2 listed)
- congenital abnormalities, congenital viral infections or evidence encephalopathy other than HIE.
- -
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Topiramate in newborns with hypoxic ischemic encephalopathy treated with therapeutic hypothermiaTPM 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. | Drug | Topiramate |
Primary outcome
The primary aim is to evaluate the neurological outcome at 6, 12, 18 months of life
Time frame: 18 months of life
1 secondary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Dec 2013.
- Background: PubMed 19744111Filippi 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.
- Background: PubMed 20553846Filippi 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.
- Derived from this study: PubMed 24524452Shankaran 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.
- Derived from this study: PubMed 22950861Filippi 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.
- Drug informationLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Luca Filippi, MD principal investigator
Azienda Ospedaliero-Universitaria A. Meyer, Firenze, Italy
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Topiramate in newborns with hypoxic ischemic encephalopathy treated with therapeutic hypothermia in people with Hypoxic Ischemic Encephalopathy, run by Meyer Children's Hospital IRCCS at 2 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Dec 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The primary aim is to evaluate the neurological outcome at 6, 12, 18 months of life (time frame: 18 months of life). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01241019, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Dec 2013.