Hypoxic Ischemic EncephalopathyPhase 1/2NCT01765218
Topiramate in Neonates Receiving Whole Body Cooling for Hypoxic Ischemic Encephalopathy
A Phase 1/2 study testing Topiramate in people with Hypoxic Ischemic Encephalopathy, run by Kristin R Hoffman at 1 site in United States.
Trial summary
The goal is to see whether topiramate (an anti-epileptic agent) improves the outcome of babies with neonatal hypoxic encephalopathy who are receiving whole body cooling. Read more about this study
- Who is it for?
- Ages Up to 6 hours
- Conditions the study is for
- Hypoxic Ischemic Encephalopathy
- What is being tested?
- Topiramate
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 34 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2013to 27 Jan 2022
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 Up to 6 hours
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- In order to be eligible for cooling the baby must meet all three of the following sets of criteria
- Be near term (typically ≥34wks gestation) and be aged < 6h old
- Have signs of early perinatal depression (EITHER 10 minute Apgar score < 5, OR pH < 7.00 within 60mins of age, OR Base Excess < -12 within 60mins of age, OR need respiratory support at 10min of age due to respiratory depression)
- Have signs of moderate or severe encephalopathy based on either clinical examination or on amplitude integrated aEEG assessment
Who cannot join
- Known congenital myopathy
- Known congenital neuropathy
Trial locations and contacts
1 site in 1 country.
United States1 site
UC Davis Medical Center
Sacramento, California, 95822
About this study
Official title: Topiramate as an Adjuvant to Therapeutic Hypothermia for Infants With Hypoxic Ischemic Encephalopathy
The goal is to see whether topiramate (an anti-epileptic agent) improves the outcome of babies with neonatal hypoxic encephalopathy who are receiving whole body cooling.
Read the detailed description
Hypoxic ischemic encephalopathy (HIE) is a devastating and unexpected disease in newborns that affects 1.5-2.6 per 1000 live births. Hypoxic ischemic encephalopathy has a mortality rate of up to 30% and survivors are at significant risk for adverse long-term outcomes, including seizures, cerebral palsy, and developmental delay. The investigators propose a randomized controlled study comparing therapeutic hypothermia alone, or therapeutic hypothermia combined with topiramate. The investigators hypothesize that adjuvant therapy with topiramate will reduce short term severity of HIE including seizures (the primary outcome), a composite HIE severity score, and reduce the time of normalization of the amplitude integrated EEG (aEEG). The investigators further hypothesize, that it will improve longer term outcomes such as developmental outcome. The primary hypothesis is that seizures before hospital discharge (or before 4 weeks post-natal age (which ever is earlier)) will be significantly reduced in the topiramate group compared to the control group
- Conditions
- Hypoxic Ischemic Encephalopathy
- Being tested
- Topiramate, Placebo
- Keywords
- Hypoxic ischemic encephalopathy, HIE, Perinatal depression, Whole body cooling, Therapeutic hypothermia
- Medical subject headings
- Hypoxia-Ischemia, Brain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TopiramateDrug
Also called Topamax, Topiragen
Infants assigned to the topiramate group will receive 5mg/kg of topiramate daily enterally for a total of 5 doses. The first dose will be administered as soon as possible on admission.
PlaceboDrug
A placebo identical in appearance to the active agent (topiramate)
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Subjects will receive the standard of care intervention for HIE at our institution (whole body cooling for 72h followed by gradual rewarming) Receives: Drug: Placebo |
| Topiramate | Active comparator | In addition to whole body cooling, infants assigned to the topiramate group will receive 5mg/kg of topiramate daily enterally for a total of 5 doses. The first dose will be administered as soon as possible on admission. Receives: Drug: Topiramate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patients With Seizures
Clinical or electrical seizures occuring before hospital discharge or before 4w post-natal age (which ever is earlier) will be compared between the topiramate and control groups.
Measured: At 4 weeks post-natal age or the time of hospital discharge (whichever is earlier)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jan 2013 (estimated)
- Study startFeb 2013
- Primary completion27 Jan 2022
- Study completion27 Jan 2022
Why it stopped: The study was stopped early due to changes in the UC Davis guidelines on who qualified for therapeutic hypothermia and significant difficulty in recruitment of patients following the COVID19 pandemic.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Hypoxic Ischemic EncephalopathyStudies of the same condition, open and under way.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kristin R Hoffman
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Kristin R Hoffman, University of California, Davis
- Investigators
- Kristin R Hoffman, MD, Principal investigator, UC Davis
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01765218
- Sponsor's protocol ID
- 1182678
- Status last verified
- May 2024
- First submitted
- 7 Jan 2013
- Last updated
- 11 Jun 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 11 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Topiramate as an Adjuvant to Therapeutic Hypothermia for Infants With Hypoxic Ischemic Encephalopathy
- ClinicalTrials.gov ID
- NCT01765218
- Acronym / sponsor ID
- 1182678
- Conditions
- Hypoxic Ischemic Encephalopathy
- Keywords
- Hypoxic ischemic encephalopathy, HIE, Perinatal depression, Whole body cooling, Therapeutic hypothermia
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was stopped early due to changes in the UC Davis guidelines on who qualified for therapeutic hypothermia and significant difficulty in recruitment of patients following the COVID19 pandemic.
- Enrolment
- 34 participants (actual)
- Lead sponsor
- Kristin R HoffmanUniversity, hospital or other
- Study start
- Feb 2013 (actual)
- Primary completion
- 27 Jan 2022 (actual)
- Study completion
- 27 Jan 2022 (actual)
- First posted
- 10 Jan 2013 (estimated)
- Results
- Posted 11 Jun 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal is to see whether topiramate (an anti-epileptic agent) improves the outcome of babies with neonatal hypoxic encephalopathy who are receiving whole body cooling.
Detailed description
Hypoxic ischemic encephalopathy (HIE) is a devastating and unexpected disease in newborns that affects 1.5-2.6 per 1000 live births. Hypoxic ischemic encephalopathy has a mortality rate of up to 30% and survivors are at significant risk for adverse long-term outcomes, including seizures, cerebral palsy, and developmental delay. The investigators propose a randomized controlled study comparing therapeutic hypothermia alone, or therapeutic hypothermia combined with topiramate. The investigators hypothesize that adjuvant therapy with topiramate will reduce short term severity of HIE including seizures (the primary outcome), a composite HIE severity score, and reduce the time of normalization of the amplitude integrated EEG (aEEG). The investigators further hypothesize, that it will improve longer term outcomes such as developmental outcome. The primary hypothesis is that seizures before hospital discharge (or before 4 weeks post-natal age (which ever is earlier)) will be significantly reduced in the topiramate group compared to the control group
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboSubjects will receive the standard of care intervention for HIE at our institution (whole body cooling for 72h followed by gradual rewarming) |
| Topiramate | Active comparator | Drug: TopiramateIn addition to whole body cooling, infants assigned to the topiramate group will receive 5mg/kg of topiramate daily enterally for a total of 5 doses. The first dose will be administered as soon as possible on admission. |
Who may qualify
- Ages
- Up to 6 hours
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- In order to be eligible for cooling the baby must meet all three of the following sets of criteria
- Be near term (typically ≥34wks gestation) and be aged < 6h old
- Have signs of early perinatal depression (EITHER 10 minute Apgar score < 5, OR pH < 7.00 within 60mins of age, OR Base Excess < -12 within 60mins of age, OR need respiratory support at 10min of age due to respiratory depression)
- Have signs of moderate or severe encephalopathy based on either clinical examination or on amplitude integrated aEEG assessment
Key exclusion criteria (2 listed)
- Known congenital myopathy
- Known congenital neuropathy
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 |
|---|---|---|
| TopiramateAlso: Topamax, TopiragenInfants assigned to the topiramate group will receive 5mg/kg of topiramate daily enterally for a total of 5 doses. The first dose will be administered as soon as possible on admission. | Drug | Topiramate |
| PlaceboA placebo identical in appearance to the active agent (topiramate) | Drug | Placebo |
Primary outcome
Number of Patients With Seizures
Time frame: At 4 weeks post-natal age or the time of hospital discharge (whichever is earlier)
Clinical or electrical seizures occuring before hospital discharge or before 4w post-natal age (which ever is earlier) will be compared between the topiramate and control groups.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jun 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Hypoxic Ischemic Encephalopathy
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The PROTECT-HIE Pilot Trial
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Neuro-MoD: Neuroplasticity With Motor Development
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A Dose Escalation Study of Levetiracetam in the Treatment of Neonatal Seizures
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Pediatric Influence of Cooling Duration on Efficacy in Cardiac Arrest Patients (P-ICECAP)
Cardiac Arrest, Out-Of-Hospital, Hypothermia, Induced
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.
Kristin R Hoffman, MD principal investigator
UC Davis
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Topiramate in people with Hypoxic Ischemic Encephalopathy, run by Kristin R Hoffman at 1 site in United States.
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 4 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: stopped early, as of the sponsor's last update on 11 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Yes. Results are posted in the registry (first posted 11 Jun 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Patients With Seizures (time frame: At 4 weeks post-natal age or the time of hospital discharge (whichever is earlier)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 11 Jun 2024.