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Continuous EEG Randomized Trial in Adults (CERTA)

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ClinicalTrials.gov Identifier: NCT03129438
Recruitment Status : Completed
First Posted : April 26, 2017
Last Update Posted : July 25, 2019
Sponsor:
Information provided by (Responsible Party):
Andrea Rossetti, MD, Centre Hospitalier Universitaire Vaudois

Tracking Information
First Submitted Date  ICMJE April 17, 2017
First Posted Date  ICMJE April 26, 2017
Last Update Posted Date July 25, 2019
Actual Study Start Date  ICMJE April 25, 2017
Actual Primary Completion Date May 13, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 25, 2017)
Mortality [ Time Frame: 6 months ]
Fatality rate
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03129438 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 25, 2017)
  • Functional outcome 1 [ Time Frame: 4 weeks, 6 months ]
    Functional outcome using the modified Rankin Scale (mRS) (ordinal)
  • Functional outcome 2 [ Time Frame: 4 weeks, 6 months ]
    Functional outcome using the Cerebral Performance Categories (CPC) (ordinal)
  • Work/School [ Time Frame: 4 weeks, 6 months ]
    Assessment of ability to go back to work/school if previously working/at school (proportion)
  • Seizure detection rate [ Time Frame: within 60 hours ]
    Seizure detection rate (proportion)
  • Status Epilepticus detection rate [ Time Frame: within 60 hours ]
    Status Epilepticus detection rate (proportion)
  • Time to detection of seizure [ Time Frame: within 60 hours ]
    Time to detection of seizure after the start of EEG recording (continuous variable)
  • Time to detection of status epilepticus [ Time Frame: within 60 hours ]
    Time to detection of status epilepticus after the start of EEG recording (continuous variable)
  • Presence of clinical signs of seizures [ Time Frame: within 60 hours ]
    Presence of clinical signs of seizures (continuous variable)
  • Detection of interictal epileptiform features [ Time Frame: within 60 hours ]
    Detection of interictal epileptiform features (categorical)
  • Rate of Infections [ Time Frame: 4 weeks ]
    Rate of in-hospital infections requiring antibiotic treatment at 4 weeks after first EEG (proportion)
  • Need of mechanical ventilation [ Time Frame: 4 weeks ]
    Need of mechanical ventilation after first EEG (proportion variable)
  • Duration of mechanical ventilation [ Time Frame: 4 weeks ]
    Duration of mechanical ventilation after first EEG (continuous variable)
  • Duration of ICU and hospital stay [ Time Frame: 4 weeks, 6 months ]
    Duration of ICU and hospital stay (continuous variable)
  • Patient destination [ Time Frame: 4 weeks, 6 months ]
    Patient destination after acute facility (home, rehab, nursing home, other; categorical)
  • Change in clinical patients' management [ Time Frame: 60 hours ]
    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).
  • Correlation between quantitative EEG and primary outcome [ Time Frame: 6 months ]
    Correlation between quantitative EEG and primary outcome
  • Hospitalization costs [ Time Frame: 6 months ]
    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)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Continuous EEG Randomized Trial in Adults
Official Title  ICMJE Impact on Clinical Outcome of Continuous Video-electroencephalography (cEEG) Monitoring in Patients With Disorders of Consciousness: A Randomized Controlled Trial
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Masking Description:
Blind assessment of secondary outcomes at 6 months
Primary Purpose: Diagnostic
Condition  ICMJE
  • EEG With Periodic Abnormalities
  • EEG With Abnormally Slow Frequencies
  • Coma
  • Outcome, Fatal
Intervention  ICMJE
  • Diagnostic Test: continuous EEG (cEEG)
    differential use of continuous versus routine EEG
  • Diagnostic Test: routine EEG (rEEG)
    differential use of continuous versus routine EEG
Study Arms  ICMJE
  • Experimental: continuous EEG (cEEG)
    Patients randomized to continuous EEG will be recorded with at least 21 electrodes placed according to the international 10-20 system; occasionally, a reduced montage will be allowed in patients with extensive neurosurgical scars, according to good common practice. Recordings will last a minimum of 30 and a maximum of 48 hours. During this time, one interruption to a maximum of two hours for diagnostic purposes will be allowed. Reactivity testing using auditory and nociceptive stimuli will be performed at least twice during the recording time. Recordings will be visually interpreted by certified electroencephalographers (i.e., interpretation of the automated algorithm only won't be allowed) using the 2013 American Clinical neurophysiology nomenclature; interpretations will be communicated within two hours of their completion to the treating team.
    Intervention: Diagnostic Test: continuous EEG (cEEG)
  • Active Comparator: routine EEG (rEEG)
    Patients randomized to routine EEG will be recorded with at least 21 electrodes placed according to the international 10-20 system; occasionally, a reduced montage will be allowed in patients with extensive neurosurgical scars, according to good common practice. Recordings will last between 20 and 30 minutes; two recordings will take place over a period of 24 to 48 hours. Reactivity testing using auditory and nociceptive stimuli will be performed once per recording. Recordings will be visually interpreted by certified electroencephalographers using the 2013 American Clinical neurophysiology nomenclature, as for the experimental intervention, and the interpretation will be communicated within two hours of its completion to the treating team.
    Intervention: Diagnostic Test: routine EEG (rEEG)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 13, 2018)
404
Original Estimated Enrollment  ICMJE
 (submitted: April 25, 2017)
350
Actual Study Completion Date  ICMJE May 13, 2019
Actual Primary Completion Date May 13, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Switzerland
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03129438
Other Study ID Numbers  ICMJE 2017_00268
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Andrea Rossetti, MD, Centre Hospitalier Universitaire Vaudois
Study Sponsor  ICMJE Andrea Rossetti, MD
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Andrea O Rossetti, MD Centre Hospitalier Universitaire Vaudois
PRS Account Centre Hospitalier Universitaire Vaudois
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP