EncephalitisENCEPHALITICANCT02906631
Epidemiology and Prognosis of Encephalitis in Intensive Care
An observational study of Encephalitis, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
Introduction: Acute encephalitis (AE) is a severe neurological disorder associated with significant morbidity and mortality. Approximately 50% of patients with AE require ICU admission because of coma, seizures or acute respiratory failure. Determinants of neurological prognosis in these patients are not known. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Encephalitis
- How many people
- 350 participants
- Where
- 1 siteFrance
- Study dates
- 27 Oct 2017to 1 Dec 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients admitted to ICU for a suspicion of AE (acute encephalopathy and CSF pleocytosis > 5 cells / microliter) will be eligible for inclusion.
Who may be able to join
- Altered mental status, delirium, or personality changes for a duration > or = 24 h
- At least 2 of the following: 1) fever (>38°C) within 72 hours before or following hospital admission; 2) new-onset seizures; 3) new-onset focal signs; 4) CSF pleocytosis > 5 cell / microl; 5) brain parenchyma abnormalities on neuroimaging compatible with the diagnosis of encephalitis; 6) EEG abnormalities compatible with the diagnosis of encephalitis.
- Altered mental status with a GCS < or =13 without sedation, or GCS < or =13 before sedation administration in sedated patients
- CSF analysis performed
- Brain imaging performed (CT/MRI)
- Age >18
Who cannot join
- Time between the first hospitalization for neurologic symptoms in relation with encephalitis and ICU admission > 21 days
- Purulent bacterial meningitis diagnosed by direct examination or CSF analysis
- Isolated brain abscess.
- Febrile encephalopathy associated with another diagnosis
- Predicted time in ICU < or = 24 hours
- Opposition of close-of-kin, if present at the inclusion, for patient participation in research.
Trial locations and contacts
1 site in 1 country.
About this study
Introduction: Acute encephalitis (AE) is a severe neurological disorder associated with significant morbidity and mortality. Approximately 50% of patients with AE require ICU admission because of coma, seizures or acute respiratory failure. Determinants of neurological prognosis in these patients are not known.
Objectives:
Read more
Main objective: To identify determinants of outcome in adult patients admitted to the ICU; Secondary objectives: a) To study the impact of diagnostic studies (Brain MRI, CSF analysis, EEG) on neurologic outcome; b) to describe the epidemiology of patients admitted to the ICU with AE; c) to study the impact of early appropriate therapy on neurologic outcomes; d) to describe morbidity and mortality associated with AE at 90 days and 1 year following diagnosis.
Methods: prospective observational multicenter study in French ICUs. All patients admitted to the ICU for probable or confirmed AE (2013 IDSA criteria)with a Glasgow coma scale score < or =to 13 will be eligible for inclusion. Factors associated with a poor prognosis at 90 days will be identified by multivariable logistic regression analysis.
Duration of study: 30 months (recruitment 18 months, follow-up 12 months).
Patients: 300 patients
Endpoints:
- Primary endpoint: The primary endpoint is the modified Rankin scale score 90 days following onset of abnormal status (GCS < or =13). This score will be determined by contacting the patient. A poor outcome will be defined as a mRS >2 at 90 days.
- Secondary endpoints: a) neurological findings within 7 days following onset of altered mental status; b) abnormal findings on diagnostic studies (MRI, EEG, CSF analysis) within7 days following onset of altered mental status; c) Time between onset of altered mental status and completion of diagnostic studies; d)Time between onset of altered mental status and start of appropriate specific therapy; e) neurologic outcomes at 1 year mRS score and extended Glasgow outcome scale (GOS); f) causes of death in non-survivors at 1 year; g) quality of life and posttraumatic stress at 1 year: IADL and SF36 scales;
Read the detailed description
Acute encephalitis (AE) is a serious condition associated with significant morbidity and mortality. Patients require ICU admission in 60 % of cases, mainly because of neurological symptoms (coma, seizures) or acute respiratory failure.
The etiological profile of AE has changed considerably in recent years, with the emergence of new pathogens and the description of new immune-mediated causes (acute disseminated encephalomyelitis (ADEM), autoimmune limbic encephalitis) that require urgent specific therapies. Furthermore, despite extensive investigations, the proportion of cases of unknown cause remains high.
In-ICU care of patients with AE is a difficult task, given the diversity of etiologies and clinical presentations. Furthermore, additional studies such as magnetic resonance imaging (MRI) can be challenging to obtain in this population. Finally, there are no specific recommendations on the management and prognostic assessment of patients admitted to the ICU with AE.
Present available data on the prognosis of patients with AE include both adult and pediatric cases, and focuses only on AE with identified causes. Prognosis of encephalitis in adult patients requiring ICU admission has been previously described only in retrospective single centre cohorts. To date, no prospective multicenter study on AE has been conducted in the specific population of adult critically ill patients. Furthermore, data on the diagnostic and prognostic contributions of magnetic resonance imaging (MRI) and electroencephalography studies in these patients are lacking The development of guidelines for standardized care in critically ill AE patients is needed, and will include management of early life support, prompt and exhaustive etiologic investigations, early administration of specific treatments and assessment of neurological prognosis. This study, which will focus on prognostic evaluation of severe AE in adults, appears crucial to support the development of such guidelines.
Patients admitted to ICU for a suspicion of AE (acute encephalopathy and CSF pleocytosis > 5 cells / microliter) will be eligible for inclusion.
Patients admitted to ICU for a suspicion of AE (acute encephalopathy and CSF pleocytosis > 5 cells / microliter) will be eligible for inclusion. Eligible patients will be included if they fulfil the IDSA 2013 diagnostic criteria for ""probable"" or ""confirmed"" encephalitis (see inclusion criteria). In patients without an obvious etiological diagnosis, an algorithm will be suggested to investigators to guide etiological investigations, according to the most recent recommendations (IDSA 2013). Aetiology of encephalitis will be described according to a priori-defined categories: 1) viral causes, 2) immune-mediated-causes, 3) bacterial or fungal meningitis with secondary encephalitic features, 4) undetermined causes. For each included patient, CSF and plasma samples will be stored at -80°C. A biobank will be created for subsequent analyses (etiological diagnosis, prognostic biomarkers). Outcomes will be assessed at 90 days and 365 days by contacting the patient or his relatives. The primary outcome is the score on the modified Rankin scale, which will be assessed 90 days after inclusion. Independent predictors of functional outcomes will be determined by multivariate logistic regression analysis.
- Conditions
- Encephalitis
- Keywords
- encephalitis,, neurologic outcomes of all-cause encephalitis in intensive care unit, outcome, intensive care unit
- Medical subject headings
- Encephalitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| patients admitted to the ICU for AE | Adult patients with all-cause encephalitis admitted to an intensive care unit. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Neurological status on the modified Rankin scale
The primary outcome measure is the modified Rankin scale score 90 days following onset of abnormal status (defined by a GCS score< or =13). This score will be determined by contacting the patient or his relatives. A poor outcome will be defined as a mRS >2 at 90 days.
Measured: 90 days
Secondary outcomes (23)
Biological data within 7 days following onset of altered mental status
Measured: 7 days
State of consciousness defined by the Glasgow Coma Scale within 7 days following onset of altered mental status
Measured: 7 days
Patient's comorbidity measured by Charlson Comorbidity Index
Measured: 7 days
Presence of focal neurological deficit within 7 days following onset of altered mental status
Measured: 7 days
Presence of thermal dysregulation within 7 days following onset of altered mental status
Measured: 7 days
Presence of seizures within 7 days following onset of altered mental status
Measured: 7 days
Magnetic resonance imaging anomalies within 7 days following onset of altered mental status
Measured: 7 days
Electrophysiologic anomalies within 7 days following onset of altered mental status
Measured: 7 days
Time between onset of altered mental status and cerebrospinal fluid analysis
Measured: one year
Time between onset of altered mental status and brain magnetic resonance imaging study
Measured: one year
Time between onset of altered mental status and electroencephalogram study
Measured: one year
Time between onset of altered mental status and completion of diagnostic studies (CSF analysis, MRI, EEG)
Measured: one year
Number of patients with primitive acute encephalitis (AE)
Number of patients with infectious causes leading to primitive AE
Measured: 7 days
Number of patients with infectious causes leading to meningitis with secondary encephalitic features
Measured: 7 days
Number of patients with immune-mediated causes of encephalitis
Measured: 7 days
Number of patients with other infectious causes of encephalitis
Measured: 7 days
Proportion of patients with appropriate specific therapy
Measured: 7 days
Time between onset of altered mental status and appropriate specific therapy
Measured: one year
Neurological status on the modified Rankin scale
This score will be determined by contacting the patient or his relatives.
Measured: 365 days
Hospital anxiety and depression scale (HAD)
Measured: 365 days
Quality of life measured by SF36 scale
Measured: 365 days
INSTRUMENTAL ACTIVITIES OF DAILY LIVING SCALE (IADL)
Measured: 365 days
Neurological prognosis on the extended Glasgow outcome scale
Measured: 365 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Sep 2016 (estimated)
- Study start27 Oct 2017
- Primary completion20 Apr 2023
- Study completion1 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for EncephalitisStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 350 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Romain Sonneville, M.D. Ph.D., Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02906631
- Sponsor's protocol ID
- AOR 15096
- Acronym
- ENCEPHALITICA
- Status last verified
- Mar 2024
- First submitted
- 1 Sep 2016
- Last updated
- 20 Mar 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 20 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Epidemiology and Prognosis of Encephalitis in Intensive Care
- ClinicalTrials.gov ID
- NCT02906631
- Acronym / sponsor ID
- ENCEPHALITICA / AOR 15096
- Conditions
- Encephalitis
- Keywords
- encephalitis,, neurologic outcomes of all-cause encephalitis in intensive care unit, outcome, intensive care unit
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 350 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 27 Oct 2017 (actual)
- Primary completion
- 20 Apr 2023 (actual)
- Study completion
- 1 Dec 2023 (actual)
- First posted
- 20 Sep 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Introduction: Acute encephalitis (AE) is a severe neurological disorder associated with significant morbidity and mortality. Approximately 50% of patients with AE require ICU admission because of coma, seizures or acute respiratory failure. Determinants of neurological prognosis in these patients are not known.
Objectives:
Main objective: To identify determinants of outcome in adult patients admitted to the ICU; Secondary objectives: a) To study the impact of diagnostic studies (Brain MRI, CSF analysis, EEG) on neurologic outcome; b) to describe the epidemiology of patients admitted to the ICU with AE; c) to study the impact of early appropriate therapy on neurologic outcomes; d) to describe morbidity and mortality associated with AE at 90 days and 1 year following diagnosis.
Methods: prospective observational multicenter study in French ICUs. All patients admitted to the ICU for probable or confirmed AE (2013 IDSA criteria)with a Glasgow coma scale score < or =to 13 will be eligible for inclusion. Factors associated with a poor prognosis at 90 days will be identified by multivariable logistic regression analysis.
Duration of study: 30 months (recruitment 18 months, follow-up 12 months).
Patients: 300 patients
Endpoints:
- Primary endpoint: The primary endpoint is the modified Rankin scale score 90 days following onset of abnormal status (GCS < or =13). This score will be determined by contacting the patient. A poor outcome will be defined as a mRS >2 at 90 days.
- Secondary endpoints: a) neurological findings within 7 days following onset of altered mental status; b) abnormal findings on diagnostic studies (MRI, EEG, CSF analysis) within7 days following onset of altered mental status; c) Time between onset of altered mental status and completion of diagnostic studies; d)Time between onset of altered mental status and start of appropriate specific therapy; e) neurologic outcomes at 1 year mRS score and extended Glasgow outcome scale (GOS); f) causes of death in non-survivors at 1 year; g) quality of life and posttraumatic stress at 1 year: IADL and SF36 scales;
Detailed description
Acute encephalitis (AE) is a serious condition associated with significant morbidity and mortality. Patients require ICU admission in 60 % of cases, mainly because of neurological symptoms (coma, seizures) or acute respiratory failure.
The etiological profile of AE has changed considerably in recent years, with the emergence of new pathogens and the description of new immune-mediated causes (acute disseminated encephalomyelitis (ADEM), autoimmune limbic encephalitis) that require urgent specific therapies. Furthermore, despite extensive investigations, the proportion of cases of unknown cause remains high.
In-ICU care of patients with AE is a difficult task, given the diversity of etiologies and clinical presentations. Furthermore, additional studies such as magnetic resonance imaging (MRI) can be challenging to obtain in this population. Finally, there are no specific recommendations on the management and prognostic assessment of patients admitted to the ICU with AE.
Present available data on the prognosis of patients with AE include both adult and pediatric cases, and focuses only on AE with identified causes. Prognosis of encephalitis in adult patients requiring ICU admission has been previously described only in retrospective single centre cohorts. To date, no prospective multicenter study on AE has been conducted in the specific population of adult critically ill patients. Furthermore, data on the diagnostic and prognostic contributions of magnetic resonance imaging (MRI) and electroencephalography studies in these patients are lacking The development of guidelines for standardized care in critically ill AE patients is needed, and will include management of early life support, prompt and exhaustive etiologic investigations, early administration of specific treatments and assessment of neurological prognosis. This study, which will focus on prognostic evaluation of severe AE in adults, appears crucial to support the development of such guidelines.
Patients admitted to ICU for a suspicion of AE (acute encephalopathy and CSF pleocytosis > 5 cells / microliter) will be eligible for inclusion.
Patients admitted to ICU for a suspicion of AE (acute encephalopathy and CSF pleocytosis > 5 cells / microliter) will be eligible for inclusion. Eligible patients will be included if they fulfil the IDSA 2013 diagnostic criteria for ""probable"" or ""confirmed"" encephalitis (see inclusion criteria). In patients without an obvious etiological diagnosis, an algorithm will be suggested to investigators to guide etiological investigations, according to the most recent recommendations (IDSA 2013). Aetiology of encephalitis will be described according to a priori-defined categories: 1) viral causes, 2) immune-mediated-causes, 3) bacterial or fungal meningitis with secondary encephalitic features, 4) undetermined causes. For each included patient, CSF and plasma samples will be stored at -80°C. A biobank will be created for subsequent analyses (etiological diagnosis, prognostic biomarkers). Outcomes will be assessed at 90 days and 365 days by contacting the patient or his relatives. The primary outcome is the score on the modified Rankin scale, which will be assessed 90 days after inclusion. Independent predictors of functional outcomes will be determined by multivariate logistic regression analysis.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| patients admitted to the ICU for AE | – | –Adult patients with all-cause encephalitis admitted to an intensive care unit. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients admitted to ICU for a suspicion of AE (acute encephalopathy and CSF pleocytosis > 5 cells / microliter) will be eligible for inclusion.
Key inclusion criteria (6 listed)
- Altered mental status, delirium, or personality changes for a duration > or = 24 h
- At least 2 of the following: 1) fever (>38°C) within 72 hours before or following hospital admission; 2) new-onset seizures; 3) new-onset focal signs; 4) CSF pleocytosis > 5 cell / microl; 5) brain parenchyma abnormalities on neuroimaging compatible with the diagnosis of encephalitis; 6) EEG abnormalities compatible with the diagnosis of encephalitis.
- Altered mental status with a GCS < or =13 without sedation, or GCS < or =13 before sedation administration in sedated patients
- CSF analysis performed
- Brain imaging performed (CT/MRI)
Key exclusion criteria (6 listed)
- Time between the first hospitalization for neurologic symptoms in relation with encephalitis and ICU admission > 21 days
- Purulent bacterial meningitis diagnosed by direct examination or CSF analysis
- Isolated brain abscess.
- Febrile encephalopathy associated with another diagnosis
- Predicted time in ICU < or = 24 hours
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Neurological status on the modified Rankin scale
Time frame: 90 days
The primary outcome measure is the modified Rankin scale score 90 days following onset of abnormal status (defined by a GCS score< or =13). This score will be determined by contacting the patient or his relatives. A poor outcome will be defined as a mRS >2 at 90 days.
23 secondary outcomes
Biological data within 7 days following onset of altered mental status
Time frame: 7 days
State of consciousness defined by the Glasgow Coma Scale within 7 days following onset of altered mental status
Time frame: 7 days
Patient's comorbidity measured by Charlson Comorbidity Index
Time frame: 7 days
Presence of focal neurological deficit within 7 days following onset of altered mental status
Time frame: 7 days
Presence of thermal dysregulation within 7 days following onset of altered mental status
Time frame: 7 days
Presence of seizures within 7 days following onset of altered mental status
Time frame: 7 days
Magnetic resonance imaging anomalies within 7 days following onset of altered mental status
Time frame: 7 days
Electrophysiologic anomalies within 7 days following onset of altered mental status
Time frame: 7 days
Time between onset of altered mental status and cerebrospinal fluid analysis
Time frame: one year
Time between onset of altered mental status and brain magnetic resonance imaging study
Time frame: one year
Time between onset of altered mental status and electroencephalogram study
Time frame: one year
Time between onset of altered mental status and completion of diagnostic studies (CSF analysis, MRI, EEG)
Time frame: one year
Number of patients with primitive acute encephalitis (AE)
Time frame: 7 days
Number of patients with infectious causes leading to meningitis with secondary encephalitic features
Time frame: 7 days
Number of patients with immune-mediated causes of encephalitis
Time frame: 7 days
Number of patients with other infectious causes of encephalitis
Time frame: 7 days
Proportion of patients with appropriate specific therapy
Time frame: 7 days
Time between onset of altered mental status and appropriate specific therapy
Time frame: one year
Neurological status on the modified Rankin scale
Time frame: 365 days
Hospital anxiety and depression scale (HAD)
Time frame: 365 days
Quality of life measured by SF36 scale
Time frame: 365 days
INSTRUMENTAL ACTIVITIES OF DAILY LIVING SCALE (IADL)
Time frame: 365 days
Neurological prognosis on the extended Glasgow outcome scale
Time frame: 365 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Mar 2024.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Romain Sonneville, M.D. Ph.D. principal investigator
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Encephalitis, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Neurological status on the modified Rankin scale (time frame: 90 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Mar 2024.