Continuous EEG Randomized Trial in Adults

Coma Clinical Trial

— CERTA  

Official title:

Impact on Clinical Outcome of Continuous Video-electroencephalography (cEEG) Monitoring in Patients With Disorders of Consciousness: A Randomized Controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03129438
• Other study ID #: 2017_00268
• Status: Completed
• Phase: N/A
• Start date: April 25, 2017
• Est. completion date: May 13, 2019

Study information

• Verified date: July 2019
• Source: Centre Hospitalier Universitaire Vaudois
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 404
• Est. completion date: May 13, 2019
• Est. primary completion date: May 13, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Coma
• EEG With Abnormally Slow Frequencies
• EEG With Periodic Abnormalities
• Outcome, Fatal

Intervention

Diagnostic Test:
• continuous EEG (cEEG)
differential use of continuous versus routine EEG
• routine EEG (rEEG)
differential use of continuous versus routine EEG

Locations

Country	Name	City	State
Switzerland	Universitätsspital	Basel
Switzerland	Inselspital	Bern
Switzerland	Centre Hospitalier Universitaire Vaudois (CHUV)	Lausanne	Vaud
Switzerland	Hôpital du Valais - Site Hôpital de Sion	Sion	Valais

Sponsors (1)

Lead Sponsor	Collaborator
Andrea Rossetti, MD

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mortality	Fatality rate	6 months
Secondary	Functional outcome 1	Functional outcome using the modified Rankin Scale (mRS) (ordinal)	4 weeks, 6 months
Secondary	Functional outcome 2	Functional outcome using the Cerebral Performance Categories (CPC) (ordinal)	4 weeks, 6 months
Secondary	Work/School	Assessment of ability to go back to work/school if previously working/at school (proportion)	4 weeks, 6 months
Secondary	Seizure detection rate	Seizure detection rate (proportion)	within 60 hours
Secondary	Status Epilepticus detection rate	Status Epilepticus detection rate (proportion)	within 60 hours
Secondary	Time to detection of seizure	Time to detection of seizure after the start of EEG recording (continuous variable)	within 60 hours
Secondary	Time to detection of status epilepticus	Time to detection of status epilepticus after the start of EEG recording (continuous variable)	within 60 hours
Secondary	Presence of clinical signs of seizures	Presence of clinical signs of seizures (continuous variable)	within 60 hours
Secondary	Detection of interictal epileptiform features	Detection of interictal epileptiform features (categorical)	within 60 hours
Secondary	Rate of Infections	Rate of in-hospital infections requiring antibiotic treatment at 4 weeks after first EEG (proportion)	4 weeks
Secondary	Need of mechanical ventilation	Need of mechanical ventilation after first EEG (proportion variable)	4 weeks
Secondary	Duration of mechanical ventilation	Duration of mechanical ventilation after first EEG (continuous variable)	4 weeks
Secondary	Duration of ICU and hospital stay	Duration of ICU and hospital stay (continuous variable)	4 weeks, 6 months
Secondary	Patient destination	Patient destination after acute facility (home, rehab, nursing home, other; categorical)	4 weeks, 6 months
Secondary	Change in clinical patients' management	Change in clinical patient management (i.e., antiepileptic drugs (AED) introduced or stopped, AED increased or decreased, brain imaging procedure order) occurring during the 60 hours following the start of the first EEG (categorical).	60 hours
Secondary	Correlation between quantitative EEG and primary outcome	Correlation between quantitative EEG and primary outcome	6 months
Secondary	Hospitalization costs	Global hospitalization costs intended as amount billed for each patient's acute hospital stay, assessed through the billing department of each hospital (continuous variable - stratified by site)	6 months