Diagnostic Subdural EEG-electrode And Subdural hEmatoma (DISEASE)

Diagnostic Subdural EEG-electrode And Subdural hEmatoma (DISEASE): Study Protocol for Prospective Non-randomized Controlled Trial

Epileptic seizures are one of the frequent complications in patients with traumatic brain injury; the incidence lies approximately at 20%. Particularly, acute subdural hematoma (aSDH) is one of the most important predictors for epileptic seizures, which is besides other parameters like age, preoperative Glasgow coma scale, cerebral herniation, hematoma volume and time to operation, associated with worse neurological outcome. In a recent systematic review, the mean incidence of epileptic seizures in aSDH was 28%, whereas one retrospective study focusing on EEG-diagnostic reported very high incidence of epileptiform abnormalities on surface EEG in 87% of patients with aSDH, wherefore the question rises, if the incidence of epileptic seizures is underestimated.

Despite successful evacuation of subdural hematoma, approximately one third of patients show no clinical improvement without medical explanation. Routinely, surface spot EEG is performed to detect epileptic seizures; however the sensitivity is limited due to the skin-bone barrier and the short duration of recording. Furthermore, surface EEG is not always available, for example during the night or at weekends, which is an additional limitation for the loss of treatment timing as well. Spot surface EEG will record for only 20 to 30 minutes in contrast to continuous EEG recordings that are performed for hours or days.

Due to the clinical relevance of epileptic seizures, several studies investigated the benefit of prophylactic antiepileptic treatment. To date, there is only one recommendation from the Brain Trauma Foundation at evidence class II to treat patients with severe traumatic brain injury with prophylactic antiepileptic treatment during the first week. Beyond the interval; there was no clinical benefit for patients selected. Still, there are some limitations´wherefore the clinical use of prophylactic antiepileptic treatment varies between clinicians and countries. At that time, the standard medication was phenytoin which has several side effects, but to date, there are several new intravenous antiepileptic drugs with comparable effect but better safety profile. On the other hand, there was no sifferentiation made between high-risked seizure prone patients, like patients with aSDH, and low-risked patients which is one of the limiting factors to support a general recommendation. Therefore the role of prophylactic antiepileptic treatment is still questionable.

In the clinical routine, invasive EEG-electrodes are commonly used to detect epileptic focus. The benefit of those electrodes is the real time analysis in case of seizure occurrence compared to surface EEG. Moreover, therapeutic effect is directly visible through the monitoring. Therefore the idea of this study was to make a real time analysis possible for patient with TBI, particularly aSDH, to have diagnostic and therapeutic real time monitoring detecting subclinical seizures.

Study Overview

• Status: Unknown
• Conditions: Seizures; Subdural Hematoma
• Intervention / Treatment: Device: invasive subdural grid electrode; Other: Control arm

• Study Type: Interventional
• Enrollment (Anticipated): 110
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sae-Yeon Won, MD; Phone Number: +496963015295; Email: sae-yeon.won@kgu.de
• Study Contact Backup: Name: Juergen Konczalla, MD PhD; Phone Number: +496963015982; Email: J.konczalla@med.uni-frankfurt.de

Study Locations

• Germany
  • Frankfurt/Main, Germany
    • Recruiting
    • Goethe University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult patients (aged ≥18 years)
• Symptomatic aSDH needing operative treatment via craniotomy or craniectomy
• Informed consent

Exclusion Criteria:

• Patients with infaust prognosis
• Asymptomatic patients with conservative treatment
• aSDH as a secondary diagnosis
• Concurrent enrollment in any other trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Invasive subdural arm; Implantation of invasive subdural electrode in patients after surgical treatment of acute subdural hematoma	Device: invasive subdural grid electrode; A subdural EEG-electrode (PLATIN 1x4 or 1x6; Ad-Tech Medical Instrument Corporation, Oak Creek, WI, USA, Figure 1) will be implanted in the subdural space frontotemporal intraoperatively and diverted separately from the wound area. Afterwards, invasive Monitoring will be performed for 7 days and the grid will be removed simply by pulling out.
SHAM_COMPARATOR: Standard treatment arm; Patients with acute subdural hematoma who underwent surgical Treatment and receive Standard medical treatment	Other: Control arm; Standard Treatment based on Brain Trauma Foundation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time-to-Seizure	The time until seizure occurrence will be compared between both arms.	up to 14 days
Incidence of seizure	Incidence of seizures will be compared between both arms.	1-7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Modified rankin scale at discharge and follow-up	Modified Rankin Scale: 0 - No symptoms.; - No significant disability.; - Slight disability.; - Moderate disability.; - Moderately severe disability.; - Severe disability.; - Dead.	3-6 months
Glasgow outcome scale at discharge and follow-up	Glasgow Outcome scale: Death; Persistent vegetative state; Severe disability; Moderate disability; Low disability	3-6months

Collaborators and Investigators

• Sponsor: University Clinic Frankfurt

Publications and helpful links

General Publications

• Won SY, Freiman TM, Reif PS, Dubinski D, Hattingen E, Herrmann E, Seifert V, Rosenow F, Strzelczyk A, Konczalla J. DIagnostic Subdural EEG electrodes And Subdural hEmatoma (DISEASE): a study protocol for a prospective nonrandomized controlled trial. Neurol Res Pract. 2020 Dec 15;2:50. doi: 10.1186/s42466-020-00096-8. eCollection 2020.

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): December 20, 2019
• Primary Completion (ANTICIPATED): December 20, 2020
• Study Completion (ANTICIPATED): December 30, 2020

Study Registration Dates

• First Submitted: December 18, 2019
• First Submitted That Met QC Criteria: December 24, 2019
• First Posted (ACTUAL): December 26, 2019

Study Record Updates

• Last Update Posted (ACTUAL): December 26, 2019
• Last Update Submitted That Met QC Criteria: December 24, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: functional outcome; invasive grid electrode; predictors for seizures
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Wounds and Injuries; Hemorrhage; Craniocerebral Trauma; Trauma, Nervous System; Intracranial Hemorrhages; Intracranial Hemorrhage, Traumatic; Seizures; Hematoma; Hematoma, Subdural
• Other Study ID Numbers: DISEASE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: email contact.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No