Maryse A van 't Klooster1, Frans S S Leijten2, Geertjan Huiskamp3, Hanneke E Ronner4, Johannes C Baayen5, Peter C van Rijen6, Martinus J C Eijkemans7, Kees P J Braun8, Maeike Zijlmans9,10. 1. Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, University Medical Center Utrecht, PO Box 85500, 3504, Utrecht, GA, The Netherlands. m.a.vanhetklooster-2@umcutrecht.nl. 2. Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, University Medical Center Utrecht, PO Box 85500, 3504, Utrecht, GA, The Netherlands. F.S.S.Leijten@umcutrecht.nl. 3. Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, University Medical Center Utrecht, PO Box 85500, 3504, Utrecht, GA, The Netherlands. G.J.M.Huiskamp@umcutrecht.nl. 4. Department of Clinical Neurophysiology and Magnetoencephalography Center, VU University Medical Center, Amsterdam, The Netherlands. HE.Ronner@vumc.nl. 5. Neurosurgical Center Amsterdam, VU University Medical Center Amsterdam, Amsterdam, The Netherlands. jc.baaijen@vumc.nl. 6. Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, University Medical Center Utrecht, PO Box 85500, 3504, Utrecht, GA, The Netherlands. P.v.Rijen@umcutrecht.nl. 7. Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. M.J.C.Eijkemans@umcutrecht.nl. 8. Department of Child Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands. K.Braun@umcutrecht.nl. 9. Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, University Medical Center Utrecht, PO Box 85500, 3504, Utrecht, GA, The Netherlands. G.J.M.Zijlmans@umcutrecht.nl. 10. SEIN-Stichting Epilepsie Instellingen Nederland, Heemstede, The Netherlands. G.J.M.Zijlmans@umcutrecht.nl.
Abstract
BACKGROUND: Intra-operative electrocorticography, based on interictal spikes and spike patterns, is performed to optimize delineation of the epileptogenic tissue during epilepsy surgery. High frequency oscillations (HFOs, 80-500 Hz) have been identified as more precise biomarkers for epileptogenic tissue. The aim of the trial is to determine prospectively if ioECoG-tailored surgery using HFOs, instead of interictal spikes, is feasible and will lead to an equal or better seizure outcome. METHODS\ DESIGN: We present a single-blinded multi-center randomized controlled trial "The HFO Trial" including patients with refractory focal epilepsy of all ages who undergo surgery with intra-operative electrocorticography. Surgery is tailored by HFOs (arm 1) or interictal spikes (arm 2) in the intra-operative electrocorticography. Primary outcome is post-operative outcome after 1 year, dichotomized in seizure freedom (Engel 1A and 1B) versus seizure recurrence (Engel 1C-4). Secondary outcome measures are the volume of resected tissue, neurologic deficits, surgical duration and complications, cognition and quality of life. The trial has a non-inferiority design to test feasibility and at least equal performance in terms of surgical outcome. We aim to include 78 patients within 3 years including 1 year follow-up. Results are expected in 2018. DISCUSSION: This trial provides a transition from observational research towards clinical interventions using HFOs. We address methodological difficulties in designing this trial. We expect that the use of HFOs as a biomarker for tailoring will increase the success rate of epilepsy surgery while reducing resection volume. This may reduce neurological deficits and yield a better quality of life. Future technical developments, such as validated automatic online HFO identification, could, together with the attained clinical knowledge, lead to a new objective tailoring approach in epilepsy surgery. TRIAL REGISTRATION: This trial is registered at the US National Institutes of Health (ClinicalTrials.gov) #NCT02207673 (31 July 2014) and the Central Committee on Research Involving Human Subjects, The Netherlands #NL44257.041.13 (18 March 2014).
RCT Entities:
BACKGROUND: Intra-operative electrocorticography, based on interictal spikes and spike patterns, is performed to optimize delineation of the epileptogenic tissue during epilepsy surgery. High frequency oscillations (HFOs, 80-500 Hz) have been identified as more precise biomarkers for epileptogenic tissue. The aim of the trial is to determine prospectively if ioECoG-tailored surgery using HFOs, instead of interictal spikes, is feasible and will lead to an equal or better seizure outcome. METHODS\ DESIGN: We present a single-blinded multi-center randomized controlled trial "The HFO Trial" including patients with refractory focal epilepsy of all ages who undergo surgery with intra-operative electrocorticography. Surgery is tailored by HFOs (arm 1) or interictal spikes (arm 2) in the intra-operative electrocorticography. Primary outcome is post-operative outcome after 1 year, dichotomized in seizure freedom (Engel 1A and 1B) versus seizure recurrence (Engel 1C-4). Secondary outcome measures are the volume of resected tissue, neurologic deficits, surgical duration and complications, cognition and quality of life. The trial has a non-inferiority design to test feasibility and at least equal performance in terms of surgical outcome. We aim to include 78 patients within 3 years including 1 year follow-up. Results are expected in 2018. DISCUSSION: This trial provides a transition from observational research towards clinical interventions using HFOs. We address methodological difficulties in designing this trial. We expect that the use of HFOs as a biomarker for tailoring will increase the success rate of epilepsy surgery while reducing resection volume. This may reduce neurological deficits and yield a better quality of life. Future technical developments, such as validated automatic online HFO identification, could, together with the attained clinical knowledge, lead to a new objective tailoring approach in epilepsy surgery. TRIAL REGISTRATION: This trial is registered at the US National Institutes of Health (ClinicalTrials.gov) #NCT02207673 (31 July 2014) and the Central Committee on Research Involving Human Subjects, The Netherlands #NL44257.041.13 (18 March 2014).
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