Clinical trial NCT03129438: Continuous EEG Randomized Trial in Adults
Official title: Impact on Clinical Outcome of Continuous Video-electroencephalography (cEEG) Monitoring in Patients With Disorders of Consciousness: A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: EEG With Periodic Abnormalities
EEG With Abnormally Slow Frequencies
Coma
Outcome, Fatal
Keywords: continuous EEG
routine EEG
prognosis
Lead sponsor: Centre Hospitalier Universitaire Vaudois
Sponsor class: OTHER
First posted: 2017-04-26
Enrollment: 404
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: Continuous video-EEG monitoring (cEEG) significantly improves seizure or status epilepticus detection in patients in intensive care units (ICUs), and is recommended for patients with consciousness impairment. cEEG is time- and resource consuming as compared to routine EEG (rEEG, lasting 20-30 minutes). While centers in North America have been using it increasingly, most European hospitals still do not have resources to comply with these guidelines. In addition, only one population-based study based on discharge diagnoses suggested that cEEG may improve patients' outcome. Current guidelines are thus based upon weak evidence and expert opinions.

Aim of the study is to assess if cEEG in adults with consciousness impairment is related to an improvement of functional outcome, and to address the prognostic role of quantitative network EEG analyses.

In this multicenter randomized controlled trial, adults with GCS inferior or equal to 11 or FOUR score inferior or equal to 12 will be randomized 1:1 to cEEG for 30-48 hours or two rEEG within 48 hours. The primary outcome will be mortality at 6 months. Secondary outcomes will blindly assess functional outcome, seizure/status epilepticus detection rate, duration of ICU stay, change in patient management (antiepileptic drug introduced, increased, or stopped, brain imaging), and reimbursement. Additionally, quantitative EEG will be assessed towards the primary outcome. 350 patients are planned to be included.

Detailed description: Background: Continuous video-EEG monitoring (cEEG) is a non-invasive tool to monitor the electrical brain function; it significantly improves seizure or status epilepticus detection in comatose patients in intensive care units (ICUs), which often do not show any specific clinical correlates. Recently, the European Society of Intensive Care Medicine published guidelines regarding the use of cEEG in the ICUs, recommending it for most patients with consciousness disorders. cEEG is time- and resource consuming as compared to routine spot EEG (rEEG, typically lasting 20-30 minutes). While centers in North America have been using it increasingly, most European - and all Swiss - hospitals still do not have enough resources to comply with these guidelines. In addition, while the superiority of cEEG to detect non-convulsive seizures or status epilepticus is proven, only one population-based study based on discharge diagnoses suggested that cEEG may improve patients' outcome. Current guidelines are thus based upon weak evidence and expert opinions. If cEEG leads to improved patients' care remains elusive. Moreover, little attention has been drawn towards quantitative EEG information beyond visual analysis, and the impact of such information on diagnosis, treatment, and outcome remains unclear.

Aim: To assess whether the use of cEEG in patients with consciousness impairment is related to an improvement of functional outcome, and to address the prognostic role of quantitative network EEG analyses in this cohort. Also, a cost analysis will be performed.

Methods: In this multicenter randomized controlled trial, adults with a Glasgow Coma Score (GCS) inferior or equal to 11 or a FOUR score inferior or equal to 12, regardless of etiologies, will be randomized 1:1 to cEEG for 30-48 hours or two rEEG within 48 hours, interpreted in a standardized way. Patients with detected seizures in the last 36h or status epilepticus in the last 96h will be excluded, as cEEG may represent the standard of care. Demographics, etiology, Charlson Comorbidity Index, GCS, diagnosis leading to EEG, mechanical ventilation, and subsequent use of rEEG/cEEG will be collected. The primary outcome will be mortality at 6 months. Secondary outcomes will blindly assess functional outcome at 4 weeks and 6 months, as well as seizure/status epilepticus detection rate and time to detection, infections rate, duration of ICU stay, change in patient management (antiepileptic drug introduced, increased, or stopped, brain imaging), and reimbursement. Analyses will compare the two interventional groups (intention to diagnose) regarding outcome, as a whole and stratified according to etiological subgroups, and other variables of interest. Additionally, lope cross correlation and horizontal visibility graphs will be applied to compute a weighted adjacency matrix consisting of all the pairwise interdependences between EEG signals, in order to characterize the integrative and segregative characteristics of the underlying functional brain networks and compare their relationship with the primary outcome. According to a previous estimate, patients with consciousness disorders undergoing cEEG have a 75% survival rate; while patients w/o cEEG 61%. Using a power of 0.8, an α error of 0.05, and a 2-side approach, 2x174 patients would be needed to detect this significant difference in survival.

Expected impact: This study will clarify if cEEG monitoring has a significant impact on functional outcome and define its cost effectiveness, and if network EEG analysis has a role in outcome prognostication. The results of this study will have a considerable potential to influence clinical practice regarding EEG and treatment of patients with altered levels of consciousness. If results will indicate that cEEG contributes to improve outcome, this will lead to the urgent need for implementation of cEEG with consecutive substantial impact on health care and resource allocation in larger Swiss and European hospitals.

Eligibility criteria: Inclusion Criteria:

* In-patients aged ≥18 years, treated in an ICU or intermediate care unit
* Alteration of mental state of any etiology (i.e., primarily cerebral or not), with Glasgow-coma scale inferior or equal to 11 or FOUR score inferior or equal to 12.
* Need of an EEG to exclude seizures or SE, or to evaluate prognosis as per the treating physician or the consulting neurologist.
* Informed consent obtained for research in emergency situation according to Human Research Act (HRA) art 30-31 at the time of inclusion

Exclusion Criteria:

* Clinical and/or electrographic status epilepticus \< 96h before randomization
* Clinical and/or electrographic seizure \< 36h before randomization
* Palliative care situation, in which detection of SE or seizures would not have any impact on the patient's care.
* High likelihood of needing a surgical intervention or an invasive diagnostic procedure within the next 48 hours according to the treating physician (as this would require cEEG removal).

Primary outcomes:
measure: Mortality
timeFrame: 6 months
Secondary outcomes:
measure: Functional outcome 1
timeFrame: 4 weeks, 6 months
measure: Functional outcome 2
timeFrame: 4 weeks, 6 months
measure: Work/School
timeFrame: 4 weeks, 6 months
measure: Seizure detection rate
timeFrame: within 60 hours
measure: Status Epilepticus detection rate
timeFrame: within 60 hours
measure: Time to detection of seizure
timeFrame: within 60 hours
measure: Time to detection of status epilepticus
timeFrame: within 60 hours
measure: Presence of clinical signs of seizures
timeFrame: within 60 hours
measure: Detection of interictal epileptiform features
timeFrame: within 60 hours
measure: Rate of Infections
timeFrame: 4 weeks
measure: Need of mechanical ventilation
timeFrame: 4 weeks
measure: Duration of mechanical ventilation
timeFrame: 4 weeks
measure: Duration of ICU and hospital stay
timeFrame: 4 weeks, 6 months
measure: Patient destination
timeFrame: 4 weeks, 6 months
measure: Change in clinical patients' management
timeFrame: 60 hours
measure: Correlation between quantitative EEG and primary outcome
timeFrame: 6 months
measure: Hospitalization costs
timeFrame: 6 months
Other outcomes:
Locations:
city: Sion
country: Switzerland
facility: Hôpital du Valais - Site Hôpital de Sion
state: Valais
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois (CHUV)
state: Vaud
city: Basel
country: Switzerland
facility: Universitätsspital
city: Bern
country: Switzerland
facility: Inselspital
Study officials:
affiliation: Centre Hospitalier Universitaire Vaudois
name: Andrea O Rossetti, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Urbano V, Alvarez V, Schindler K, Ruegg S, Ben-Hamouda N, Novy J, Rossetti AO. Continuous versus routine EEG in patients after cardiac arrest: Analysis of a randomized controlled trial (CERTA). Resuscitation. 2022 Jul;176:68-73. doi: 10.1016/j.resuscitation.2022.05.017. Epub 2022 May 30.
citation: Urbano V, Novy J, Alvarez V, Schindler K, Ruegg S, Rossetti AO. EEG recording latency in critically ill patients: Impact on outcome. An analysis of a randomized controlled trial (CERTA). Clin Neurophysiol. 2022 Jul;139:23-27. doi: 10.1016/j.clinph.2022.04.003. Epub 2022 Apr 18.
citation: Urbano V, Novy J, Schindler K, Ruegg S, Alvarez V, Zubler F, Oddo M, Lee JW, Rossetti AO. Continuous versus routine EEG in critically ill adults: reimbursement analysis of a randomised trial. Swiss Med Wkly. 2021 Mar 16;151:w20477. doi: 10.4414/smw.2021.20477. eCollection 2021 Mar 15.
citation: Guinchard M, Warpelin-Decrausaz L, Schindler K, Ruegg S, Oddo M, Novy J, Alvarez V, Rossetti AO. Informed consent in critically ill adults participating to a randomized trial. Brain Behav. 2021 Feb;11(2):e01965. doi: 10.1002/brb3.1965. Epub 2020 Dec 3.
citation: Rossetti AO, Schindler K, Sutter R, Ruegg S, Zubler F, Novy J, Oddo M, Warpelin-Decrausaz L, Alvarez V. Continuous vs Routine Electroencephalogram in Critically Ill Adults With Altered Consciousness and No Recent Seizure: A Multicenter Randomized Clinical Trial. JAMA Neurol. 2020 Oct 1;77(10):1225-1232. doi: 10.1001/jamaneurol.2020.2264.