EAGLET: EEG vs aEEG to Improve the Diagnosis of neonataL Seizures and Epilepsy

NCT ID: NCT05079971

Last Updated: 2023-08-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

140 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-07-01

Study Completion Date

2024-12-31

Brief Summary

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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

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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

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Neonatal Seizures

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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Group A is a control group with aEEG monitoring only, and with retrospective cEEG review

Group Type ACTIVE_COMPARATOR

Group B: aEEG with concurrent multichannel (full) continuous cEEG review by clinical neurophysiology

Intervention Type DIAGNOSTIC_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.

Group B is undergoing aEEG monitoring with concurrent full EEG review

Group Type EXPERIMENTAL

Group B: aEEG with concurrent multichannel (full) continuous cEEG review by clinical neurophysiology

Intervention Type DIAGNOSTIC_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.

Interventions

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Group B: aEEG with concurrent multichannel (full) continuous cEEG review by clinical neurophysiology

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.

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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Inclusion Criteria

1. Term or preterm neonate, born at post-menstrual age (PMA) 32-44 weeks;
2. 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)
3. Infant is up to 28 days of age
4. Written informed parental consent can be obtained.

Exclusion Criteria

1. No parental consent
2. Poor prognosis of immediate survival
3. Any contraindication to perform EEG (e.g. structural pathologies interfering with EEG electrode placement, such as cephalohematoma or subgaleal haemorrhage).
4. 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.
Minimum Eligible Age

32 Weeks

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Norfolk and Norwich University Hospitals NHS Foundation Trust

OTHER

Sponsor Role collaborator

Luton and Dunstable Hospital NHS Foundation Trust

UNKNOWN

Sponsor Role collaborator

Infant, University College Cork, Ireland

UNKNOWN

Sponsor Role collaborator

Guy's and St Thomas' NHS Foundation Trust

OTHER

Sponsor Role collaborator

University Hospital Southampton NHS Foundation Trust

OTHER

Sponsor Role collaborator

Cambridge University Hospitals NHS Foundation Trust

OTHER

Sponsor Role lead

Responsible Party

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Ronit Pressler

Dr (Clinical Neurophysiology)

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Cambridge University Hospitals NHS Foundation Trust

Cambridge, , United Kingdom

Site Status RECRUITING

Countries

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United Kingdom

Central Contacts

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Ronit M Pressler, Phd MD MRCPCH

Role: CONTACT

07737333607 ext. +44

Topun Austin, MD MRCP MRCPCH PhD

Role: CONTACT

01223217677 ext. +44

Facility Contacts

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Topun Austin

Role: primary

References

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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.

Reference Type BACKGROUND
PMID: 28118303 (View on PubMed)

Malone 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.

Reference Type BACKGROUND
PMID: 19490044 (View on PubMed)

Boylan 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.

Reference Type BACKGROUND
PMID: 31324321 (View on PubMed)

Pellegrin 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.

Reference Type BACKGROUND
PMID: 31783981 (View on PubMed)

Gossling 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.

Reference Type BACKGROUND
PMID: 31992265 (View on PubMed)

Rakshasbhuvankar 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.

Reference Type BACKGROUND
PMID: 26456517 (View on PubMed)

Other Identifiers

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A 096043

Identifier Type: -

Identifier Source: org_study_id

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