Neonatal SeizuresEAGLETNCT05079971
EAGLET: EEG vs aEEG to Improve the Diagnosis of neonataL Seizures and Epilepsy
A study testing Group B: aEEG with concurrent multichannel (full) continuous cEEG review by clinical neurophysiology in people with Neonatal Seizures, run by Cambridge University Hospitals NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
The current project undertakes a prospective multicentre randomised controlled trial to evaluate whether full or continuous electroencephalography (cEEG) is superior to amplitude-integrated electroencephalography (aEEG) in the real time evaluation and diagnosis of neonatal seizures and in reducing time to treatment. Read more about this study
- Who is it for?
- Ages 32 weeks and older
- Conditions the study is for
- Neonatal Seizures
- What is being tested?
- Group B: aEEG with concurrent multichannel (full) continuous cEEG review by clinical neurophysiology
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 140 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 1 Jul 2023to Dec 2024
- Phase
- Interventional
- 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 32 weeks and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Term or preterm neonate, born at post-menstrual age (PMA) 32-44 weeks;
- And at least one of the following:
- (2.1) Neonate with any clinical event suspicious of seizures (2.2) Neonate at high-risk of seizures with confirmed or suspected: (2.2.1) Hypoxic ischaemic encephalopathy (moderate to severe, or deemed eligible for therapeutic hypothermia) (2.2.2) Cerebral vascular insult (e.g., perinatal arterial ischaemic stroke, cerebral venous sinus thrombus) (2.2.3) Meningitis / encephalitis - Inflammatory (2.2.4) Inborn error of metabolism (2.2.5) Brain malformation (2.2.6) Large intraventricular haemorrhage (III-IV)
- Infant is up to 28 days of age
- Written informed parental consent can be obtained.
Who cannot join
- No parental consent
- Poor prognosis of immediate survival
- Any contraindication to perform EEG (e.g. structural pathologies interfering with EEG electrode placement, such as cephalohematoma or subgaleal haemorrhage).
- Infants born at less than 31+6 weeks PMA and infants who are or are suspected to be experiencing or are at high-risk of seizures when aged 29 days or older.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site, 1 recruiting
- Recruiting
Cambridge University Hospitals NHS Foundation Trust
Cambridge
Topun Austin
About this study
Official title: The EAGLET Project: EEG vs aEEG to Improve the Diagnosis of neonataL Seizures and Epilepsy - a Randomised Trial
The current project undertakes a prospective multicentre randomised controlled trial to evaluate whether full or continuous electroencephalography (cEEG) is superior to amplitude-integrated electroencephalography (aEEG) in the real time evaluation and diagnosis of neonatal seizures and in reducing time to treatment. At-risk new-born infants will be recruited on the participating neonatal intensive care units (NICUs) by trained specialist staff and will have 24 hours of EEG monitoring.
Read the detailed description
Seizures are the most common neurological emergency in the neonatal period, affecting over 2000 infants per year in the UK. Although neonatal seizures usually result from acute brain insults, about 10-15% represent genetic forms of epilepsy which are often diagnosed late, thus limiting the timely use of targeted therapies. Lack or delayed initiation of treatment results in a high seizure burden which is independently associated with worse clinical outcomes.
Diagnosing neonatal seizures is challenging because most have only subtle or no clinical manifestation. The gold standard for seizure detection is continuous electroencephalography (cEEG). cEEG can assist with establish the aetiology of seizures, and their management. However, this capability is lacking in most neonatal intensive care units (NICU) due to lack of on-site specialist support. The more common amplitude-integrated EEG (aEEG) uses a limited number of electrodes and is easier to apply and interpret but has been shown to miss a significant number of seizures. It is unclear how often seizure treatment is missed or delayed due to lack of cEEG access. Although studies have compared the diagnostic value of aEEG and cEEG retrospectively, the measured sensitivity of aEEG ranges widely (25-85%), likely due to poor design (retrospective, lack of adequate control group, no power calculations).
The current project undertakes a prospective multicentre randomised controlled trial to evaluate whether cEEG is superior to aEEG in the real time evaluation and diagnosis of neonatal seizures and in reducing time to treatment. At-risk neonates will be recruited on the NICU by trained specialist staff and will have 24 hours of EEG monitoring.
- Conditions
- Neonatal Seizures
- Being tested
- Group B: aEEG with concurrent multichannel (full) continuous cEEG review by clinical neurophysiology
- Keywords
- Neonatal Seizures, cEEG, aEEG, Epilepsy
- Medical subject headings
- Epilepsy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Group B: aEEG with concurrent multichannel (full) continuous cEEG review by clinical neurophysiologyDiagnostic test
In group B, the standart-care equivalent aEEG review is undertaken by NICU staff via a 2-channel display. In addition to the standard care, concurrent full EEG is reviewed remotely with regular feedback by a specialist trained clinical neurophysiologist. The clinical neurophysiology reports only on seizure burden, no information or direction is provided regarding clinical management.
| Study group | Role | What they receive |
|---|---|---|
| Group A is a control group with aEEG monitoring only, and with retrospective cEEG review | Active comparator | Not described Receives: Diagnostic Test: Group B: aEEG with concurrent multichannel (full) continuous cEEG review by clinical neurophysiology |
| Group B is undergoing aEEG monitoring with concurrent full EEG review | Experimental | Not described Receives: Diagnostic Test: Group B: aEEG with concurrent multichannel (full) continuous cEEG review by clinical neurophysiology |
What is being measured
The primary outcome is the main question the study is designed to answer.
Seizure detection yield of aEEG compared to full EEG
The primary outcome measure for the study is the difference in the number of correctly identified seizures by NICU staff in real time with (full EEG) or without (aEEG only) the support of clinical neurophysiology.
Measured: Each participant will be assessed in Group A (aEEG review only) or Group B (a+cEEG) for 24 hours.
Secondary outcomes (4)
Time from first recorded seizure to first recognised seizure and to treatment.
Their time to treatment and time to discharge will also be noted.
Measured: Each participant's seizure burden, treatment and discharge timelines will be recorded up until their discharge from the hospital, or for up to 6 months, whichever came first.
Number of false positive seizure detections clinically and/or by aEEG
Measured: Followed until their discharge from hospital, or for up to 6 months, whichever came first.
Off-line seizure burden (min/hr) detected by aEEG vs detected by cEEG
Measured: Followed until their discharge from hospital, or for up to 6 months, whichever came first.
Parental and staff acceptance of EEG monitoring (combined cohort) using questionnaire.
Measured: Parents may fill in the questionnaire online after their infant's discharge from hospital, the questionnaire will take a maximum of 10 minutes to complete.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Oct 2021
- Study start1 Jul 2023
- Primary completionSep 2024 (estimated)
- Study completionDec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Neonatal SeizuresStudies 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 N/A
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 140 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Cambridge University Hospitals NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Collaborators
- Norfolk and Norwich University Hospitals NHS Foundation Trust, Luton and Dunstable Hospital NHS Foundation Trust, Infant, University College Cork, Ireland, Guy's and St Thomas' NHS Foundation Trust, University Hospital Southampton NHS Foundation Trust
- Responsible party
- Principal investigator, Ronit Pressler, Cambridge University Hospitals NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05079971
- Sponsor's protocol ID
- A 096043
- Acronym
- EAGLET
- Status last verified
- Aug 2023
- First submitted
- 13 Sep 2021
- Last updated
- 14 Aug 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Pinchefsky EF, Hahn CD. Outcomes following electrographic seizures and electrographic status epilepticus in the pediatric and neonatal ICUs. Curr Opin Neurol. 2017 Apr;30(2):156-164. doi: 10.1097/WCO.0000000000000425.
PubMed 28118303Malone A, Ryan CA, Fitzgerald A, Burgoyne L, Connolly S, Boylan GB. Interobserver agreement in neonatal seizure identification. Epilepsia. 2009 Sep;50(9):2097-101. doi: 10.1111/j.1528-1167.2009.02132.x. Epub 2009 Jun 1.
PubMed 19490044Boylan GB, Kharoshankaya L, Mathieson SR. Diagnosis of seizures and encephalopathy using conventional EEG and amplitude integrated EEG. Handb Clin Neurol. 2019;162:363-400. doi: 10.1016/B978-0-444-64029-1.00018-7.
PubMed 31324321Pellegrin S, Munoz FM, Padula M, Heath PT, Meller L, Top K, Wilmshurst J, Wiznitzer M, Das MK, Hahn CD, Kucuku M, Oleske J, Vinayan KP, Yozawitz E, Aneja S, Bhat N, Boylan G, Sesay S, Shrestha A, Soul JS, Tagbo B, Joshi J, Soe A, Maltezou HC, Gidudu J, Kochhar S, Pressler RM; Brighton Collaboration Neonatal Seizures Working Group. Neonatal seizures: Case definition & guidelines for data collection, analysis, and presentation of immunization safety data. Vaccine. 2019 Dec 10;37(52):7596-7609. doi: 10.1016/j.vaccine.2019.05.031. No abstract available.
PubMed 31783981Gossling L, Alix JJP, Stavroulakis T, Hart AR. Investigating and managing neonatal seizures in the UK: an explanatory sequential mixed methods approach. BMC Pediatr. 2020 Jan 28;20(1):36. doi: 10.1186/s12887-020-1918-4.
PubMed 31992265Rakshasbhuvankar A, Paul S, Nagarajan L, Ghosh S, Rao S. Amplitude-integrated EEG for detection of neonatal seizures: a systematic review. Seizure. 2015 Dec;33:90-8. doi: 10.1016/j.seizure.2015.09.014. Epub 2015 Sep 26.
PubMed 26456517
Study at a glance
From the registry record, last updated by the sponsor on 14 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The EAGLET Project: EEG vs aEEG to Improve the Diagnosis of neonataL Seizures and Epilepsy - a Randomised Trial
- ClinicalTrials.gov ID
- NCT05079971
- Acronym / sponsor ID
- EAGLET / A 096043
- Conditions
- Neonatal Seizures
- Keywords
- Neonatal Seizures, cEEG, aEEG, Epilepsy
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 140 participants (estimated)
- Lead sponsor
- Cambridge University Hospitals NHS Foundation TrustUniversity, hospital or other
- Collaborators
- Norfolk and Norwich University Hospitals NHS Foundation Trust, Luton and Dunstable Hospital NHS Foundation Trust, Infant, University College Cork, Ireland, Guy's and St Thomas' NHS Foundation Trust, University Hospital Southampton NHS Foundation Trust
- Study start
- 1 Jul 2023 (actual)
- Primary completion
- Sep 2024 (estimated)
- Study completion
- Dec 2024 (estimated)
- First posted
- 15 Oct 2021 (actual)
- 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 current project undertakes a prospective multicentre randomised controlled trial to evaluate whether full or continuous electroencephalography (cEEG) is superior to amplitude-integrated electroencephalography (aEEG) in the real time evaluation and diagnosis of neonatal seizures and in reducing time to treatment. At-risk new-born infants will be recruited on the participating neonatal intensive care units (NICUs) by trained specialist staff and will have 24 hours of EEG monitoring.
Detailed description
Seizures are the most common neurological emergency in the neonatal period, affecting over 2000 infants per year in the UK. Although neonatal seizures usually result from acute brain insults, about 10-15% represent genetic forms of epilepsy which are often diagnosed late, thus limiting the timely use of targeted therapies. Lack or delayed initiation of treatment results in a high seizure burden which is independently associated with worse clinical outcomes.
Diagnosing neonatal seizures is challenging because most have only subtle or no clinical manifestation. The gold standard for seizure detection is continuous electroencephalography (cEEG). cEEG can assist with establish the aetiology of seizures, and their management. However, this capability is lacking in most neonatal intensive care units (NICU) due to lack of on-site specialist support. The more common amplitude-integrated EEG (aEEG) uses a limited number of electrodes and is easier to apply and interpret but has been shown to miss a significant number of seizures. It is unclear how often seizure treatment is missed or delayed due to lack of cEEG access. Although studies have compared the diagnostic value of aEEG and cEEG retrospectively, the measured sensitivity of aEEG ranges widely (25-85%), likely due to poor design (retrospective, lack of adequate control group, no power calculations).
The current project undertakes a prospective multicentre randomised controlled trial to evaluate whether cEEG is superior to aEEG in the real time evaluation and diagnosis of neonatal seizures and in reducing time to treatment. At-risk neonates will be recruited on the NICU by trained specialist staff and will have 24 hours of EEG monitoring.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group A is a control group with aEEG monitoring only, and with retrospective cEEG review | Active comparator | Diagnostic Test: Group B: aEEG with concurrent multichannel (full) continuous cEEG review by clinical neurophysiology |
| Group B is undergoing aEEG monitoring with concurrent full EEG review | Experimental | Diagnostic Test: Group B: aEEG with concurrent multichannel (full) continuous cEEG review by clinical neurophysiology |
Who may qualify
- Ages
- 32 weeks and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- Term or preterm neonate, born at post-menstrual age (PMA) 32-44 weeks;
- And at least one of the following:
- (2.1) Neonate with any clinical event suspicious of seizures (2.2) Neonate at high-risk of seizures with confirmed or suspected: (2.2.1) Hypoxic ischaemic encephalopathy (moderate to severe, or deemed eligible for therapeutic hypothermia) (2.2.2) Cerebral vascular insult (e.g., perinatal arterial ischaemic stroke, cerebral venous sinus thrombus) (2.2.3) Meningitis / encephalitis - Inflammatory (2.2.4) Inborn error of metabolism (2.2.5) Brain malformation (2.2.6) Large intraventricular haemorrhage (III-IV)
- Infant is up to 28 days of age
- Written informed parental consent can be obtained.
Key exclusion criteria (4 listed)
- No parental consent
- Poor prognosis of immediate survival
- Any contraindication to perform EEG (e.g. structural pathologies interfering with EEG electrode placement, such as cephalohematoma or subgaleal haemorrhage).
- Infants born at less than 31+6 weeks PMA and infants who are or are suspected to be experiencing or are at high-risk of seizures when aged 29 days or older.
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 |
|---|---|---|
| Group B: aEEG with concurrent multichannel (full) continuous cEEG review by clinical neurophysiologyIn group B, the standart-care equivalent aEEG review is undertaken by NICU staff via a 2-channel display. In addition to the standard care, concurrent full EEG is reviewed remotely with regular feedback by a specialist trained clinical neurophysiologist. The clinical neurophysiology reports only on seizure burden, no information or direction is provided regarding clinical management. | Diagnostic test | Group A is a control group with aEEG monitoring only, and with retrospective cEEG review, Group B is undergoing aEEG monitoring with concurrent full EEG review |
Primary outcome
Seizure detection yield of aEEG compared to full EEG
Time frame: Each participant will be assessed in Group A (aEEG review only) or Group B (a+cEEG) for 24 hours.
The primary outcome measure for the study is the difference in the number of correctly identified seizures by NICU staff in real time with (full EEG) or without (aEEG only) the support of clinical neurophysiology.
4 secondary outcomes
Time from first recorded seizure to first recognised seizure and to treatment.
Time frame: Each participant's seizure burden, treatment and discharge timelines will be recorded up until their discharge from the hospital, or for up to 6 months, whichever came first.
Number of false positive seizure detections clinically and/or by aEEG
Time frame: Followed until their discharge from hospital, or for up to 6 months, whichever came first.
Off-line seizure burden (min/hr) detected by aEEG vs detected by cEEG
Time frame: Followed until their discharge from hospital, or for up to 6 months, whichever came first.
Parental and staff acceptance of EEG monitoring (combined cohort) using questionnaire.
Time frame: Parents may fill in the questionnaire online after their infant's discharge from hospital, the questionnaire will take a maximum of 10 minutes to complete.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Aug 2023.
- Background: PubMed 28118303Pinchefsky EF, Hahn CD. Outcomes following electrographic seizures and electrographic status epilepticus in the pediatric and neonatal ICUs. Curr Opin Neurol. 2017 Apr;30(2):156-164. doi: 10.1097/WCO.0000000000000425.
- Background: PubMed 19490044Malone A, Ryan CA, Fitzgerald A, Burgoyne L, Connolly S, Boylan GB. Interobserver agreement in neonatal seizure identification. Epilepsia. 2009 Sep;50(9):2097-101. doi: 10.1111/j.1528-1167.2009.02132.x. Epub 2009 Jun 1.
- Background: PubMed 31324321Boylan GB, Kharoshankaya L, Mathieson SR. Diagnosis of seizures and encephalopathy using conventional EEG and amplitude integrated EEG. Handb Clin Neurol. 2019;162:363-400. doi: 10.1016/B978-0-444-64029-1.00018-7.
- Background: PubMed 31783981Pellegrin S, Munoz FM, Padula M, Heath PT, Meller L, Top K, Wilmshurst J, Wiznitzer M, Das MK, Hahn CD, Kucuku M, Oleske J, Vinayan KP, Yozawitz E, Aneja S, Bhat N, Boylan G, Sesay S, Shrestha A, Soul JS, Tagbo B, Joshi J, Soe A, Maltezou HC, Gidudu J, Kochhar S, Pressler RM; Brighton Collaboration Neonatal Seizures Working Group. Neonatal seizures: Case definition & guidelines for data collection, analysis, and presentation of immunization safety data. Vaccine. 2019 Dec 10;37(52):7596-7609. doi: 10.1016/j.vaccine.2019.05.031. No abstract available.
- Background: PubMed 31992265Gossling L, Alix JJP, Stavroulakis T, Hart AR. Investigating and managing neonatal seizures in the UK: an explanatory sequential mixed methods approach. BMC Pediatr. 2020 Jan 28;20(1):36. doi: 10.1186/s12887-020-1918-4.
- Background: PubMed 26456517Rakshasbhuvankar A, Paul S, Nagarajan L, Ghosh S, Rao S. Amplitude-integrated EEG for detection of neonatal seizures: a systematic review. Seizure. 2015 Dec;33:90-8. doi: 10.1016/j.seizure.2015.09.014. Epub 2015 Sep 26.
- Individual participant dataSharing planned: Undecided
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Group B: aEEG with concurrent multichannel (full) continuous cEEG review by clinical neurophysiology in people with Neonatal Seizures, run by Cambridge University Hospitals NHS Foundation Trust at 1 site in United Kingdom.
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 5 inclusion and 4 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: status not confirmed, as of the sponsor's last update on 14 Aug 2023. 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 Kingdom. 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.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Ronit M Pressler, Phd MD MRCPCH (07737333607 ext. +44, r.pressler@ucl.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Seizure detection yield of aEEG compared to full EEG (time frame: Each participant will be assessed in Group A (aEEG review only) or Group B (a+cEEG) for 24 hours.). 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 NCT05079971, which also lists 6 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 14 Aug 2023.