NCT02207673

Brief Summary

Epilepsy occurs in 0.5-0.7% of the population, of which 25% are children. 30% Of patients with focal epilepsy do not respond well to medication and half of them are eligible for epilepsy surgery. In recent years, the importance of early epilepsy surgery has been stressed, as successful surgery may lead seizure and medication freedom and improved social and cognitive development, especially in children. The current success rate of epilepsy surgery is around 65%; During surgery intracranial electrocorticography (acute ECoG, aECoG) is recorded in some medical centers. The presence of epileptiform brian activity, spikes, identified by clinical neurophysiologists, is used to guide the neurosurgeon in the extent of the brain tissue that needs to be resected. Spikes are considered markers of the presence of epilepsy. High Frequency Oscillations (HFOs, \>80-500Hz) in the ECoG have recently been identified as a new biomarker for epileptogenic tissue. Retrospective research shows that their local presence strongly relates to the seizure onset, and removal of tissue with HFOs could predict a better surgical outcome. The area showing HFOs usually overlaps with, but is smaller than the area with spikes, and HFOs do not tend to propagate to distant sites as spikes do. The identification of HFOs is more objective than of spikes and automatic detection software exists. A pilot study is performed to test the hypothesis : The intra-operative use of HFOs to delineate the epileptogenic cortex does not yield significantly worse outcome in seizure freedom than the current method based on spikes. Study design is a single blinded multi-center randomized controlled trial. In two Dutch centers, the VU medical center ( Amsterdam) and University Medical Center Utrecht. The study population (sample size 78) consists of patients of all ages with refractory epilepsy undergoing epilepsy surgery with aECoG to guide the extent of the resection. Eligible patients are randomised, after informed consent, into group 1 (HFOs) in whom a resection guided by HFOs in the aECoG (new), or into group 2 (spikes) in whom a resection is guided by epileptiform spikes in the aECoG (current standard). Ictiform spike patterns will always be resected. Main study endpoint is outcome after epilepsy surgery after 1 year of follow-up dichotomized in total seizure freedom (Engel Ia\&b) vs. seizure recurrence (Engel Ic-IV).

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
78

participants targeted

Target at P50-P75 for not_applicable

Timeline
Completed

Started Nov 2014

Longer than P75 for not_applicable

Geographic Reach
1 country

2 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 31, 2014

Completed
4 days until next milestone

First Posted

Study publicly available on registry

August 4, 2014

Completed
3 months until next milestone

Study Start

First participant enrolled

November 1, 2014

Completed
6.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2021

Completed
4 months until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2021

Completed
Last Updated

November 4, 2020

Status Verified

November 1, 2020

Enrollment Period

6.3 years

First QC Date

July 31, 2014

Last Update Submit

November 3, 2020

Conditions

Refractory Localization-related Epilepsy

Keywords

epilepsy surgerybiomarkerhigh frequency oscillations (HFOs)acute electrocorticography (aECoG)

Outcome Measures

Primary Outcomes (1)

  • Post-surgical outcome

    To simplify analysis outcome scores will be dichotomized in two categories, total seizure freedom (Engel Ia+Ib) versus seizure recurrence (Engel Ic-IV).To enable interim analysis of the outcome in terms of seizures, we will determine preliminary post-surgical outcomes at 6-8 weeks and 6 months. A final outcome will be determined after 12 months. This will require the patients to fill in an additional short questionnaire on their seizure frequency at pre-surgical baseline (after singing informed consent), at 6-8 weeks, 6 and 12 months post- operatively (by telephone/email). So called 'running down' seizures, seizures that occur in the first 2 weeks after surgery are not considered as seizure recurrence.

    12 months after surgery

Secondary Outcomes (6)

  • Volume of resected tissue

    3 months after surgery a post-resection MRI is made

  • Neurological deficits

    baseline + post operative before discharge, 6-8 weeks, 6 and 12 months

  • Cognitive functioning

    pre- vs. post surgery (6 or 12 months)

  • Health related Quality of life (HRQOL)

    pre- vs. post-operative (6 or 12 months)

  • Procedure duration

    intraoperative

  • +1 more secondary outcomes

Study Arms (2)

Spikes as biomarker

ACTIVE COMPARATOR

In arm " spikes" the resection of epileptogenic tissue is guided by epileptiform spikes in the aECoG (current standard). (Independent of the randomisation ictiform spike patterns will always be resected.)

Procedure: Tailoring of the resection based on biomarker in aEcoG during epilepsy surgery

HFOs as biomarker

EXPERIMENTAL

In arm "HFOs" resection of epileptogenic tissue is guided by HFOs in the aECoG (new). (Independent of the randomisation ictiform spike patterns will always be resected.)

Procedure: Tailoring of the resection based on biomarker in aEcoG during epilepsy surgery

Interventions

Tailoring of the resection based on biomarker in aEcoG during epilepsy surgeryPROCEDURE
HFOs as biomarkerSpikes as biomarker

Eligibility Criteria

Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • Patients of all ages with:
  • Refractory Focal Epilepsy; at least ≥2 experienced seizures in the past 24 months, in spite of 2 or more different anti-epileptic drugs tried.
  • Planned neurosurgery with aECoG, with the goal of tailoring the resection.
  • Command of Dutch language of the patient/parents/legal representatives and capability of completing the questionnaires (by email or phone).

You may not qualify if:

  • Patients who underwent chronic ECoG monitoring preceding epilepsy surgery (grids). This is a biased population, since the results of the extensive pre-surgical work-up as well as the results of the cECoG monitoring period are included in the final decision making regarding the resection, and a precise seizure onset zone as well as spike and HFO area are known.
  • Patients with an occipital focus undergoing aECoG. Currently, it is not possible to discriminate between pathological or physiological occipital HFOs, and thus unsafe to perform HFO guided resections in patients with a presumed occipital focus.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

VU University medical center

Amsterdam, 1081 HV, Netherlands

Location

University Medical Center Utrecht

Utrecht, 3584 CG, Netherlands

Location

Related Publications (2)

  • van 't Klooster MA, Leijten FS, Huiskamp G, Ronner HE, Baayen JC, van Rijen PC, Eijkemans MJ, Braun KP, Zijlmans M; HFO study group. High frequency oscillations in the intra-operative ECoG to guide epilepsy surgery ("The HFO Trial"): study protocol for a randomized controlled trial. Trials. 2015 Sep 23;16:422. doi: 10.1186/s13063-015-0932-6.

    PMID: 26399310RESULT

  • Zweiphenning W, Klooster MAV', van Klink NEC, Leijten FSS, Ferrier CH, Gebbink T, Huiskamp G, van Zandvoort MJE, van Schooneveld MMJ, Bourez M, Goemans S, Straumann S, van Rijen PC, Gosselaar PH, van Eijsden P, Otte WM, van Diessen E, Braun KPJ, Zijlmans M; HFO study group. Intraoperative electrocorticography using high-frequency oscillations or spikes to tailor epilepsy surgery in the Netherlands (the HFO trial): a randomised, single-blind, adaptive non-inferiority trial. Lancet Neurol. 2022 Nov;21(11):982-993. doi: 10.1016/S1474-4422(22)00311-8.

    PMID: 36270309DERIVED

Related Links

MeSH Terms

Conditions

Epilepsies, Partial

Condition Hierarchy (Ancestors)

EpilepsyBrain DiseasesCentral Nervous System DiseasesNervous System Diseases

Study Officials

  • Maeike Zijlmans, MD, PhD

    University Medical Center Utrecht, the Netherlands

    PRINCIPAL INVESTIGATOR

  • Maryse van 't Klooster, MSc.

    University Medical Center Utrecht, the Netherlands

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
PARTICIPANT
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
MD, PhD

Study Record Dates

First Submitted

July 31, 2014

First Posted

August 4, 2014

Study Start

November 1, 2014

Primary Completion

February 1, 2021

Study Completion

June 1, 2021

Last Updated

November 4, 2020

Record last verified: 2020-11

Locations

NL(2)